file.qums.ac.irfile.qums.ac.ir/repository/sd/pazhohesh/Library/E... · are immunocompromised. The usual oral dosage for amoxicillin with clavulanate is 1,000-mg loading dose followed

are immunocompromised. The usual oral dosage foramoxicillin with clavulanate is 1,000-mg loading dosefollowed by 500 mg every 8 hours. An alternate dosageis 875 mg every 12 hours.

Erythromycin has traditionally been the alternativechoice for patients allergic to penicillin, but it is noteffective against anaerobes associated with endodonticinfections. Clarithromycin and azithromycin aremacrolides like erythromycin, with some advantagesover the latter. They have a spectrum of antimicrobialactivity that includes facultative bacteria and someanaerobic bacteria associated with infections of endo-dontic origin. They also have less gastrointestinal upsetthan erythromycin. The oral dosage for clarithromycinis a 500-mg loading dose followed by 250 mg every 12hours. The oral dosage for azithromycin is a 500-mgloading dose followed by 250 mg once a day.

Clindamycin is effective against both facultativeand strict anaerobic bacteria associated with endo-dontic infections. It is well distributed throughoutthe body, especially to bone, where its concentrationapproaches that of plasma. Both penicillin and clin-damycin have been shown to produce good results intreating odontogenic infections.4,5,20 Clindamycin israpidly absorbed even in the presence of food in thestomach.21 The oral adult dosage for serious endo-dontic infections is a 600-mg loading dose followedby 300 mg every 6 hours.

Metronidazole is a nitroimidazole that is activeagainst parasites and anaerobic bacteria. However, itis ineffective against facultative bacteria.4,5,22 It is avaluable antimicrobial agent in combination withpenicillin when penicillin alone has been ineffective.22

The usual oral dosage for metronidazole is a 1,000-mgloading dose followed by 500 mg every 6 hours. Con-sultation with, and referral to other specialists in themanagement of facial infections, is indicated forsevere or persistent infections.

Cephalosporins are usually not indicated for thetreatment of endodontic infections. First-generationcephalosporins do not have activity against the anae-robes usually involved in endodontic infections.Second-generation cephalosporins have some efficacyfor anaerobes, however, there is a possibility of cross-allergenicity of cephalosporins with penicillin.

Doxycycline occasionally may be indicated when theabove antibiotics are contraindicated. However, many strainsof bacteria have become resistant to the tetracyclines.

Ciprofloxacin is a quinilone antibiotic that is noteffective against anaerobic bacteria usually found inendodontic infections. With a persistent infection, itmay be indicated if culture and sensitivity testsdemonstrated the presence of susceptible organisms.

PROPHYLACTIC ANTIBIOTICSFOR MEDICALLY COMPROMISEDPATIENTSProphylactic antibiotic coverage may be indicatedfor medically compromised patients requiring endo-dontic treatment. The American Heart Association(AHA) and the American Academy of OrthopaedicSurgeons have made guidelines for prophylactic anti-biotic coverage.23,24 The guidelines are meant to aidpractitioners but are not intended as the standard ofcare or as a substitute for clinical judgment. Theincidence of endocarditis following most procedureson patients with underlying cardiac disease is low (seeChapter 7 ‘‘Microbiology of Endodontic Disease’’).

A reasonable approach for prescribing prophylacticantibiotics considers the degree to which the underlyingdisease creates a risk for endocarditis, the apparent riskfor producing a bacteremia, adverse reactions to theprophylactic antibiotic, and the cost-benefit aspect ofthe regimen.23 Antibiotic prophylaxis is employed toprevent surgical infections or their postoperative seque-lae, to prevent metastatic bacteremias, and to preventaccusation that ‘‘all was not done for the patient.’’25 It issuspected that antibiotic prophylaxis is often prescribedto prevent malpractice claims.25

How antibiotics quickly kill bacteria in the blood isdifficult to answer when many antibiotics are onlyeffective with actively dividing bacteria. It is speculatedthat antibiotics may reduce metastatic infections bypreventing adhesion of bacteria to tissues or inhibitinggrowth after attachment.26 The principles of antibioticprophylaxis state that the antibiotic must be in thesystem prior to an invasive procedure. If a patient hasnot taken the prescribed antibiotic, he or she should berescheduled or wait an hour after administration of theantibiotic for treatment. However, there is data tosupport the use of an antibiotic up to 2 hours afterthe onset of bacteremia.25

The incidence of bacteremia has been shown to below during root canal therapy. A transient bactere-mia can result from the extrusion of microorganismsfrom the root canal to the periapical tissues of thetooth.27–31 In addition, positioning rubber damclamps and accomplishing other dental proceduresmay produce bleeding and can lead to a bacteremia.Medically compromised dental patients who are atrisk of infection should receive a regimen of antibio-tics that either follows the recommendations of theAHA or an alternate regimen determined in consul-tation with the patients’ physicians.23 Chapter 24gives the antibiotic regimens recommended fordental procedures. It is believed that amoxicillin,

Chapter 21 / Treatment of Endodontic Infections, Cysts, and Flare-ups / 695

ampicillin, and penicillin V are equally effectiveagainst alpha-hemolytic streptococci; however,amoxicillin is recommended because it is betterabsorbed from the gastrointestinal tract and provideshigher and more sustained serum levels.23

For cardiac conditions associated with endocarditis,prophylaxis is recommended for both non-surgicaland surgical endodontic procedures.23 Antibiotic pro-phylaxis is recommended for cardiac conditions asso-ciated with endocarditis at a high or moderate riskcategory (see Chapter 24). Dental procedures forwhich antibiotic prophylaxis is recommended (seeChapter 24) include endodontic instrumentationbeyond the apex or surgery, but not intracanal endo-dontic treatment, post-placement and buildup.23

From a practical standpoint, it is difficult to deter-mine with certainty that endodontic instruments donot pass beyond the apical foramen. Also included forprophylaxis antibiotics is intraligamentary period-ontal ligament (PDL) local anesthetic injections, butnot non-intraligamentary ones.23

In 2003, a joint committee of the American DentalAssociation and American Academy of OrthopaedicSurgeons published their first advisory statement onantibiotic prophylaxis for patients with prostheticjoints. The dental procedures of concern and theantibiotic regimens are the same as for endocarditisChapter 24. Patients of potential increased risk ofhaving a hematogenous total joint infection includeall patients during the first 2 years following jointreplacement, immunocompromised/immunosuppressedpatients, and patients with comorbidities as shown inChapter 24.32

COLLECTION OF A MICROBIAL SAMPLEAdjunctive antibiotic therapy for endodontic infec-tions is most often prescribed empirically based onknowledge of the bacteria most often associatedwith endodontic infections. At times, culturingmay provide valuable information to better selectthe appropriate antibiotic regimen. For example, animmunocompromised/immunosuppressed patient(not immunocompetent) or patients at high riskof developing infections (e.g., history of infectiveendocarditis) following a bacteremia require closemonitoring. These patients may have an infectioncaused by bacteria usually not associated with theoral cavity. Other examples include a seeminglyhealthy patient who has persistent or progressivesymptoms following surgical or non-surgical endo-dontic treatment. An aseptic microbial samplefrom a root canal is collected by first isolating the

tooth with a rubber dam and disinfecting the toothsurface and rubber dam with sodium hypochloriteor other disinfectant. Sterile burs and instrumentsmust be used to gain access to the root canal system.Intracanal irrigation should not be used until afterthe microbial sample has been taken. If there isdrainage from the canal, it may be sampled with asterile paper point or aspirated into a sterile syringewith a sterile 18- to 25-gauge needle, depending onthe viscosity of the exudate. The aspirate shouldeither be taken immediately to a microbiologylaboratory in the syringe or injected into pre-reduced transport media. To sample a dry rootcanal, a sterile syringe should be used to place somepre-reduced transport medium into the canal. Asterile endodontic instrument is then used to scrapethe walls of the canal to suspend microorganismsinto the medium.

To prevent contamination by the normal oral flora,a microbial sample from a soft tissue swelling shouldbe obtained before making an I&D. Once profoundanesthesia is achieved, the surface of the mucosashould be dried and disinfected with an iodophorswab. A sterile 16- to 20-gauge needle and syringe isused to aspirate the exudate. The aspirate should behandled as described above. A sample can be collectedon a swab after the I&D has been made, but great caremust be taken to prevent microbial contaminationwith normal oral flora. After collecting the specimenon a swab, it should be quickly placed in pre-reducedmedium for transport to the laboratory.

Good communication with the laboratory personnelis important. The sample should be Gram-stained todemonstrate which types of microorganisms predomi-nate. The culture results should show the prominentisolated microorganisms and not just be identified as‘‘normal oral flora.’’ Antibiotics can usually be chosento treat endodontic infections based on the identifica-tion of the prominent microorganisms in the culture.With persistent infections, susceptibility testing can beundertaken to establish which antibiotics are the mosteffective against resistant microbial isolates. At present,it may take 1 to 2 weeks to identify anaerobes usingconventional methods. Some laboratories may havemolecular methods available to rapidly detect andidentify known opportunistic bacteria.

CORTICAL TREPHINATIONCortical trephination is defined as the surgical perfora-tion of the alveolar cortical plate to release accumulatedtissue exudates.1 Its use is indicated for patients withsevere pain of endodontic origin without intraoral or

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extraoral swelling and when drainage cannot be accom-plished through the root canal, for example, in thepresence of posts, filling material, or ledging. Corticaltrephination involves exposing the cortical bone, makingan opening in the bone, and making a pathway throughthe cancellous bone to the root end.33–40 Occasionally,an instrument may be used to penetrate the mucosa andcortical plate without an incision (Figure 10A,B). Severalstudies have demonstrated that a patient with severeperiapical pain without swelling will have significantrelief following trephination.34,41–43 A technique for tre-phination recommended by Henry and Fraser41 involvesa submarginal horizontal full thickness flap to access the

alveolar bone, the use of a surgical high speed round burto access the involved root apex and abscessed area, andthe placement of a sutured drain.

Some studies have shown cortical trephination maynot be predictable in relieving periapical pain.36–38 Aprospective randomized blinded clinical trial raisedconcern about the assumed clinical effectiveness oftrephination.38 In that study, pain logs were evaluatedafter non-surgical endodontic treatment and either realor simulated trephination. It was found that the rou-tine use of trephination for the reduction of pain orswelling in symptomatic necrotic pulps in teeth withperiapical radiolucencies was not predictable. A sys-tematic review of the literature concerning the emer-gency management of acute apical periodontitis in thepermanent dentition also concluded that routine cor-tical trephination did not show significant benefit.44

While there is no higher level of evidence justifyingthe routine use of surgical trephination, there are lim-ited instances in which it is a reasonable treatmentalternative. Patients with severe periapical pain ofendodontic origin without swelling may benefit fromthe procedure.

DECOMPRESSION: ASPIRATIONAND IRRIGATIONThe terms decompression and marsupialization areoften used interchangeably. Decompression is the sur-gical exposure of a cyst wall and insertion of a tube orother type of drain to decompress the lesion duringhealing.1 It is not uncommon for chronic periapicalpathosis to remain clinically asymptomatic and developa bony defect of significant size. If left undiagnosed anduntreated, periapical pathosis may develop into self-perpetuating entities that erode osseous supportingstructures and encroach on adjacent teeth, sinus cav-ities, neurovascular bundles, and even the nasal cavity.Bony lesions radiographically exceeding 200 mm2 havea higher statistical chance of being cystic.45 There areradicular cysts that may have progressed to the extentthat they are truly independent, and non-surgical endo-dontic treatment may no longer be enough to result inbony healing.46,47 When non-surgical endodontics doesnot resolve apical pathosis, surgical intervention is analternative treatment recommendation.

Surgical treatment, including the enucleation ofextensive bony lesions, may involve unintentionalinterruption of periapical vascular and neural struc-tures, development of soft tissue defects, and damageto adjacent anatomic structures. Decompression is amore conservative treatment option that allows theprogressive reduction in lesion size and may eliminate

A

B

Figure 10 A, Trephination using a #3 spreader. B, Radiograph showingtip of a #3 spreader near root end. Courtesy Dr. Craig Baumgartner.


the necessity for surgical enucleation. Decompression isintended to disrupt the integrity of the lesion wall,reduce the internal osmotic pressure, and permit oss-eous regeneration (Figure 11).

In 1982, Suzuki48 suggested treating jaw cystsusing an irrigational technique. In that study, thecontents of 36 cysts were irrigated weekly for monthsand even years. This irrigation method involved theuse of Ringer’s solution, glucose, and antibiotics. Thefluids aspirated from the cysts were quantitativelyanalyzed for electrolytes, inorganic substances, pro-teins, and lipids. Irrigation of the lesions eventuallyresulted in the reduction in the volume and size ofthe cysts. The irrigation method is effective for thetreatment of cysts in jaws.48 Large cysts have beendecompressed using acrylic stents, obturators, andtubing that extends into the lesion.49–53 Acrylicstents or tubing was often left in for months withirrigation of the lesion. Neaverth and Berg52

described several cases of large lesion decompressionthat lasted from several weeks to more than a year.The method used radiopaque tubing in conjunctionwith water irrigation by the patient. The tube wasremoved once there was evidence of elimination ofthe cystic lesion.

A surgical technique was described in case seriesformat by Wong54 in 1991. After flap reflection, asurgical fenestration was used to obtain some tissuefor biopsy, but the majority of bony defect was leftintact. Copious drainage was accomplished and thedefect irrigated with saline prior to suturing. Thissurgical treatment was effective in producing healingwhile avoiding potential complications.54 Rees55 in1997 reviewed and highlighted the treatment of largemaxillary cysts by root canal treatment and subse-quent decompression. The described technique useda drain made from surgical suction tubing. This seemsto be the consensus treatment sequence currently inthe dental literature. Figure 12 shows the radiographicand clinical appearance of decompression tube thatwas left in position for 1 week and the 6-monthfollow-up radiograph after non-surgical root canalfilling.

A 20-patient cohort study of decompressionresults by Enislidis et al.56 is perhaps the best evi-dence of the technique’s effectiveness. The authorsdescribed the advantages as ease of treatment, con-firmed diagnosis with biopsy, low morbidity, andlow incidence of complications. The quickest evi-dence of successful decompression was related byLoushine et al.57 in 1991. This case report relatedthe removal of the decompression tube after only 2days with follow-up examinations showing progres-

sive osseous repair at 3, 6, and 12 months. The use ofdecompression to treat odontogenic keratocyst(OKC) has been reported by August et al.58 A pedia-tric nasal airway was modified and placed in 14OKCs for an average of 8.4 months. They were irri-gated twice a day with chlorhexidine. At the time ofcystectomy, 9 of 14 no longer showed histologicalfeatures of OKCs. The epithelium had dedifferen-tiated and lost cytokeratin 10 production in 64% ofthe patients.

Mejia et al.59 reported, in a case series format,the use of a vacuum system within the root canalsystem. The technique produced a vacuum effectcapable of removing copious amounts of exudateand inflammatory fluids. Perhaps, the removal ofthe rather high osmolarity fluid and disruption ofthe bony defect lining is the impetus for subse-quent healing.

The combination of aspiration and irrigation asan alternative to surgical endodontic treatment wasreported by Hoen et al.60 in 1990. This case seriesdemonstrated successful outcomes using a single-visit aspiration and saline irrigation of non-healingbony lesions associated with previously endodonti-cally treated teeth. Following profound anesthesia,mucosa disinfection and aspiration of the cyst con-tents was accomplished using a 16- or 18-gaugeneedle attached to a syringe. Several milliliters ofviscous aspirate was routinely obtained. The aspi-rates were submitted for aerobic and anaerobic cul-turing, Gram-staining, and immunoglobulin quanti-fication. The level of immunoglobulin (Ig) G wassignificantly elevated in each specimen. Above nor-mal levels of IgG have been shown to be consistentwith cyst fluid.61 It has also been shown there is ahigh level of albumin and globulin in cysts com-pared to ‘‘granulomas’’.62 No bacteria were seen orcultured from any of the aspirates. At the 1-yearfollow-up appointments, the patients were asympto-matic and significant bony healing was seen onradiographs. It is important to develop a clear dif-ferential diagnosis and to have timely re-evaluationsof the patient’s signs and symptoms to determine iffurther treatment is needed.60

An additional use of aspiration is to obtain a biopsysample. August et al.58 concluded that the use ofneedle aspiration for biopsy is a useful techniqueto distinguish between malignant and benignintraosseous jaw lesions. The described techniqueinvolved the use of a 10-mL syringe containing 1 or2 mL of air attached to 23- or 25-gauge needles. Oncewithin the lesion, suction was applied and severalquick passes were performed to obtain cellular

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A B

C D

E

Figure 11 A, Surgical window into cyst. B, Healed surgical window. C, Acrylic stint in place for decompression. D, Biopsy from window consistentwith radicular cyst. E, Palatal radiographs showing loss of bone on left and bone fill after 3 months of decompression. Courtesy Dr. CraigBaumgartner.


material. The specimens were then placed on glassslides for smear preparation. The authors suggestedthat aspiration may be the diagnostic tool of choice ina hospital setting due to its simplicity, suitability as anoutpatient procedure, rapidity of interpretation, andminimal morbidity.63 The accuracy of fine-needleaspiration biopsy of head and neck tumors has beenreviewed in 218 patients.64 The technique was deter-mined to be a useful modality for the diagnosis ofhead and neck tumors. The use of such a techniquerequires coordination with a pathologist familiar withneedle biopsy specimens.

Endodontic Flare-ups

The American Association of Endodontics’ Glossary ofEndodontic Terms offers the following definition: ‘‘Aflare-up is an acute exacerbation of an asymptomaticpulp/or periapical pathosis after the initiation or con-tinuation of root canal treatment.’’1 Treating similarteeth in patients with comparable medical and dentalhistories is no assurance of a common outcome. Whileone patient remains asymptomatic, another may have aflare-up. The contrasting clinical outcomes may seem tooccur in a random manner or lead to erroneous

B

A C

Figure 12 A, A 20-mm piece of nasogastric tubing in cyst for decompression. B, Tubing used next to ruler was in place for 1 week. C, Six-month follow-up after non-surgical root canal filling. Courtesy Dr. Craig Baumgartner.

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conclusions about the cause–effect relationship of endo-dontic procedures to the flare-up. The development ofmoderate to severe inter-appointment pain, with orwithout swelling, is an infrequent but challengingproblem. The severe pain and swelling associated withflare-ups represent the clinical manifestation of complexpathologic changes occurring at a cellular level. There isincreasing evidence pointing to multiple complex factorsinvolved in producing a flare-up. These factors includemechanical, microbial, chemical, immunological, gen-der, and psychological components. The regulation ofperiapical inflammation is highly complex and isanother factor in patients’ response to endodonticprocedures.22,65–70

The reported incidence of inter-appointmentemergencies ranges from 1.4 to 19%.66,69–74 Whileone study found pain and swelling occurred in asmany as 20 to 40% of patients,75 the incidence ofsevere pain conditions is most frequently reported atless than 5%.65,70,76,77 Variations in the findings arethe result of a number of factors. For example, dif-ferences exist in the definition of a flare-up. Someinvestigators have used swelling as the sole criteriafor a flare-up after treating asymptomatic teeth withpulp necrosis and chronic apical periodontitis.71

Others have used broader definitions of a flare-upwhich do not require swelling.65,66,69,70 Some inves-tigators used a retrospective approach in theirresearch,69,73 while others used prospective meth-odologies.65,66,70 There have also been variations insample size, treatment procedures, number of visits,endodontic medications, and other variables that areneither well-defined nor controlled.

AGE OF PATIENTThere is a lack of agreement concerning the influenceof age on the incidence of flare-ups. Prospectivestudies assessing the incidence of flare-ups in endo-dontic patients found no correlation between flare-ups and the age of the patient.70 However, a largeretrospective study reached a different conclusion.Records of 2,000 patients were examined, and it wasdetermined that when age was evaluated (20–39,40–59, over age 60), a significant difference wasfound among age groups (p = 0.0001). Patients inthe 40- to 59-year range had the most flare-ups andthose under the age of 20 had the least.69 Conflictingconclusions regarding the influence of age on theincidence of flare-ups can be attributed to variationsin research methodologies, definitions, sample size,and clinical procedures.

GENDER AND FLARE-UPSAn extensive review concerning gender variation inclinical pain experience reported that women aremore likely than men to experience a variety of recur-rent pain.78 In most studies, women have reportedmore severe levels of pain, more frequent pain, andpain of longer duration than men.79 While a numberof studies found a significantly higher percentage offemales than males had postoperative pain,69,70,75,80

others have not found gender to be a significantfactor.66,81 It should be noted that there are consider-able variations between different types of clinicalpain.82 Experimental pain, produced under controlledconditions by brief, noxious stimuli, differs from pro-cedural and post-surgical pain. These differencesmake the study of pain more complex.79

SYSTEMIC CONDITIONSIt seems reasonable to assume that host resistance,for example, medical status of the patient, is animportant variable in the occurrence of flare-ups.Unfortunately, there is little conclusive evidenceconcerning the relationship between host resistanceand flare-ups. One study found a highly significantassociation between flare-ups and the presence ofallergies to various substances (sulfa medication,pollen, dust, and foodstuffs) and the frequency ofinter-appointment pain.69 It was suggested that thiscould have been due to an immediate hypersensitiv-ity reaction occurring in the periapical tissues inresponse to the egress of antigens from the rootcanal. Although the components of the immediatehypersensitivity reactions (IgE, mast cells, and mastcell-derived mediators) have been found in periapi-cal lesions, evidence is lacking as to whether thesereactions actually occur in the periapical tissues andare responsible for inter-appointment pain.68 Anassociation between allergy and inter-appointmentpain has not been confirmed.70

ANATOMIC LOCATIONExamining the incidence of flare-ups by tooth groupsor between arches (maxillary versus mandibular) hasusually shown no significant difference.66,70,80 Anexception was a retrospective study of 2,000 patientswho had received root canal treatment for necroticpulps. Mandibular teeth were associated with moreinter-appointment emergencies than their maxillarycounterparts (p = 0.0247). Mandibular premolarsfollowed by mandibular incisors were the most


problematic teeth after cleaning and shaping of theirroot canals.69

ANXIETYA high incidence of fear and anxiety among patientsconcerning an endodontic procedure may have amarked effect on the patient’s intra-operative andpostoperative response to treatment. It has beenshown that if a patient expects pain to occur duringdental treatment, this increases the likelihood of painbeing perceived.83 An anxious patient with a previousmemory of dental pain is more likely to expect painduring subsequent treatment. The slightest pressureon the tooth can be interpreted as pain and initiate apain reaction. Anxiety may also lead to increasedsympathetic activity and muscle tension that maycause more pain.79 Patients’ descriptions of their paincan be influenced by their level of anxiety and com-plicate the diagnostic process.79

A multivariate analysis of the effectiveness of localanesthesia in pediatric patients indicated anxiety asthe strongest predictor of poor pain control.84 A largeretrospective study noted an association betweenapprehension and postoperative pain.72 The dentalprocedures causing the highest levels of stress andanxiety are oral surgery and endodontics. There is ahigh probability that endodontic patients are anxiousand expect to experience pain during treatment79 (seeChapter 22).

PREOPERATIVE HISTORYOF THE TOOTHMost studies have found a highly significant relation-ship between the presence of preoperative pain and/or swelling and the incidence of inter-appointmentemergencies.65,66,69,70 Studies have also shown astatistically significant higher incidence of flare-upsin patients taking analgesics and anti-inflammatorydrugs.66,70 It is reasonable to assume that patientstaking those drugs were having preoperative pain.

PULP/PERIAPICAL STATUSThere is no universal agreement concerning the influ-ence of pulp status and/or the presence of a periapicallesion on the incidence of inter-appointment emergen-cies. A prospective study found that teeth with vitalpulps resulted in relatively few flare-ups, with an over-all percentage of 1.3%.66,70 In contrast, pulp necrosiscorrelated to an incidence of flare-ups of 6.5%, a sta-tistically significant increase when compared to vitalpulps. A low number of flare-ups following root canal

treatment of teeth with vital pulps is consistent withfindings in other studies.73,74

The periapical diagnosis of acute apical abscess wasalso related to significantly greater incidence of flare-ups when compared with less symptomatic or lesssevere apical pathosis.70 As one might expect, thepresence of a sinus tract did not correlate with flare-ups.69,70 Investigators found the presence of a peri-apical radiolucency was significantly related tointer-appointment flare-ups.65,66,71,74 These findingsare in contrast to others who found a higher incidenceof inter-appointment emergencies in teeth withoutapical radiolucencies.69,81,85,86 The differences infindings may be attributable to variations in researchmethodologies, sample size, clinical procedures,patients studied, and definition of flare-ups.

NUMBER OF TREATMENT VISITSA number of studies have determined that less post-operative pain results from a single-visit approach toendodontics than a multi-visit course of treat-ment.66,87,88 Other investigators concluded that little orno difference occurred between single- and multiple-visit endodontic therapy.70,89–91 Significant variablesexist among the studies that may account for thedifferent conclusions.

CAUSES OF INTER-APPOINTMENT PAINInter-appointment pain is caused by mechanical,chemical, and/or microbial injury to the pulp orperiapical tissues that are induced or exacerbatedduring endodontic treatment.68,69,92 The cause ofinjury may vary, but the intensity of the inflammatoryresponse is usually directly proportional to the inten-sity of tissue injury.93 Mechanical and chemicalinjuries are often associated with iatric factors, butmicrobial-induced injury is a major cause of inter-appointment pain.68,92,94 Microbial factors may becombined with iatric factors to cause inter-appoint-ment pain. Even when endodontic procedures areperformed within accepted guidelines, microbes cancause a flare-up.68 Development of pain precipitatedby microbial factors can depend on the interrelation-ship of several factors that are discussed in Chapter 7.

TREATMENT OF TEETH WITH VITAL ANDNON-VITAL PULPSTreatment of teeth with vital (pulpitis) and non-vital(necrotic) pulps represent pathological conditions thatrequire different approaches to therapy.95 It has beensuggested that if the pulp is free of infection, the

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endodontic treatment should be completed in one visitif other factors permit. Temporization after removal ofa vital pulp entails the risk of micro-leakage and con-tamination of the canal.95 A high level of asepsis dur-ing pulpectomy and subsequent obturation is anessential part of treatment. Although asepsis is alsoan important part of treating a tooth with a non-vitalpulp, the principle concern is the presence of bacteriain the root canal system. Infected canals may contain10 to 100 million bacterial cells.95–97 Clinicians arefaced with the challenge of disinfecting the canal sys-tem through instrumentation, irrigation, and medica-tion without pushing debris into the periapical tissues.

RE-TREATMENT CASESRe-treatment cases, in most studies, have had asignificantly higher incidence of flare-ups than conven-tional cases 69,70 (Figure 13). One study found an extre-mely high incidence of flare-ups (13.6%) in re-treatmentteeth with apical periodontitis.77 It can be hypothesizedthat re-treatment cases are often technically difficult totreat, and there is a tendency to push remnants of gutta-percha, solvents, and other debris into the periapicaltissues. Microbes may also be pushed apically duringthe re-treatment process. Extrusion of infected debrisor solvents into the periapical tissues during preparationof the canals is allegedly one of the principal causes ofpostoperative pain.92,96,98 Re-treatment cases are usuallyassociated with a persistent or secondary root canalinfection by therapy-resistant microorganisms thatmay be more difficult to eradicate when compared toprimary infections.67,98,99 In contrast, others have found

no statistical significance in the relation of re-treatmentto flare-ups.70

WORKING LENGTHThe apical portion of the root canal system has beenconsidered the most critical anatomic area with regard tothe need for cleaning, disinfection, and sealing.67,100

Overextension should be avoided as it can result inpostoperative pain.67 Teeth with non-vital (necrotic)pulps associated with a periapical lesion, as well asroot-filled teeth with recalcitrant lesions, represents adifferent biological challenge.67 In these cases, micro-organisms may be at or near the apical foramen andaccessory foramina that are in close contact with theperiapical tissues.67,101–104 Thus, correct working lengthin infected teeth is essential.67,105 Inaccurate workinglength or inadvertent over- or under-instrumentationcan result in negative outcomes for the patient.Over-instrumentation may force infected debris intothe periapical tissues eliciting a severe inflammatoryresponse and pain. Under-instrumentation will leavemicroorganisms in close proximity to the apicalforamina where they or their virulence factors can gainaccess to the periapical tissues67,106 (see Chapter 7).Incomplete instrumentation can disrupt the balancewithin the microbial flora and allow previously inhib-ited species to overgrow.107 If those strains of bacteriaare virulent and/or reach sufficient numbers, damageto the periapical tissues may be intensified and resultin an exacerbation of the lesion. Furthermore, environ-mental changes, induced by incomplete debridement,have the potential to activate virulence genes.68

Figure 13 Swelling associated with flare-up following revision of previous endodontic treatment. Courtesy Dr. Paul Rosenberg.


A change in host resistance or microbial virulence mayallow a previously asymptomatic situation to becomesymptomatic.68 Clinical studies, however, have notlinked incomplete canal preparation to flare-ups.70,91,108,109

OBTURATIONOverfilling can cause postoperative pain particularlywhen a substantial amount of filling material extrudesthrough the apical foramen. Gross overfilling involvesthe introduction of excess sealer (and its cytotoxiccomponents) into the periapical tissues causing tissuedamage and inflammation.67 A recent study foundthat overfilling was significantly associated withincreased rate of pain and percussion sensitivity in1-week follow-up examinations in comparison withteeth not overfilled.110 Scheduling of the obturationvisit in relation to instrumentation may be anotherimportant factor. Obturation in the presence of acuteapical periodontitis can be considered to be a predic-tor of postoperative pain. In order to avoid increasedpostoperative pain, patients who present for obtura-tion but have significant acute apical periodontitisshould have the procedure postponed until the toothis more comfortable. Relief of pain can be achieved bytreatment directed at reducing tissue levels of factorsthat stimulate peripheral terminals of nociceptors orby reducing mechanical stimulation of sensitizednociceptors (e.g., occlusal adjustment). Thusby deferring obturation of a tooth with pericementitis,further stimulation of sensitized nociceptors isavoided.111,112

Strategies to Prevent Flare-ups

ANXIETY REDUCTIONThe causes of endodontic flare-ups are varied, and aneffective preventive strategy must be multifaceted(see Chapter 23). There is a well-documented rela-tionship between anxiety, pain threshold, and post-operative pain.72,79,83,84

BEHAVIORAL INTERVENTIONIn preoperative patients, high levels of stress, anxiety,or pessimism predict poor outcomes in measures thatrange from speed of wound healing to duration ofhospital stay. Over 200 studies indicate that preemp-tive behavioral intervention, to decrease anxiety

before and after surgery, reduces postoperative painintensity and intake of analgesics improves treatmentcompliance, cardiovascular and respiratory indices,and accelerates recovery.113 In a landmark study, itwas found that preoperative discussion of likely post-surgical treatments and associated discomfort halvedthe requirement for postoperative morphine andreduced time to discharge. Patients in that study alsoreceived instructions in a relaxation technique.114

Providing information about the procedure is animportant step in preparing patients for endodontictreatment. Information about profound dentalanesthesia and preventive pain strategies is an impor-tant anxiety reduction technique. Perhaps mostimportantly, the dentist should assure the patient thatpain prevention is a primary concern. It was deter-mined that patients given a running commentaryconcerning procedures and associated sensationsrated themselves as less anxious and experiencing lesspain than a normal control group.115 Informationabout sensations experienced during treatment as wellas a description of procedures appears to have a sig-nificant impact in reducing patient anxiety.115

Patients should not be allowed to watch surgical pro-cedures in a mirror.

OCCLUSAL REDUCTIONOcclusal reduction is a valuable pain preventive strat-egy in appropriate cases.116,117 Some earlier studiesraised questions concerning the value of prophylacticocclusal reduction as a pain preventive mea-sure.118,119 The results of a more recent study indi-cated that occlusal reduction should result in lesspost-treatment pain in patients whose teeth exhibitpulp vitality, preoperative pain, percussion pain, orabsence of a periapical radiolucency.120 While thepresence of all four conditions is the strongestpredictor, the presence of any one or more of theconditions is enough to indicate the need for occlusalreduction (Figure 14).

Occlusal reduction when performed in appropriatecases is a highly predictable, simple strategy for theprevention of postoperative pain and relief of paindue to acute apical periodontitis. There is a biologicrationale for the relief of pain provided by theocclusal reduction. Mechanical allodynia (i.e., sensi-tivity to percussion or biting forces) is due to tissuelevels of mediators that stimulate peripheral term-inals of nociceptors. Occlusal adjustment, in eitherarch, reduces mechanical stimulation of sensitizednociceptors.120,121

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Pharmacologic Strategies for Flare-ups

ANTIBIOTICSAntibiotics are frequently prescribed to endodonticpatients without a rational biologic basis.122,123 Anevidence-based review determined that the use of sys-temic antibiotics for the prevention of post-treatmentendodontic pain should be discouraged.124 Antibiotictreatment is generally not recommended for healthypatients with localized endodontic infections. Systemicantibiotics should be considered if there is a spreadinginfection that indicates failure of local host responses tocontrol bacterial irritants or the patient has a medicalcondition that compromises defense mechanisms andcould expose the patient to higher systemic risks.124

NSAIDS AND ACETOMINOPHENNonsteroidal anti-inflammatory drugs (NSAIDs) havebeen shown to be effective for managing pulpal andperiapical pain.111,125 However, due to the renaleffects of NSAIDs as well as interactions with manyanti-hypertensive drugs, acetaminophen should beconsidered for post-treatment pain in patients withknown sensitivity to NSAIDs or aspirin. Acetamino-phen should also be considered for those with thefollowing disorders: ulcers, ulcerative colitis, asthma,or hypertension. Pretreatment with NSAIDs or acet-aminophen has also been shown to be effective forreducing postoperative pain.68,121 Pretreatment withNSAIDs for irreversible pulpitis should have the effectof reducing pulpal levels of the inflammatory media-tor prostaglandin E2 (PGE2).68,71

It is advisable to have endodontic patients taketheir analgesics ‘‘by the clock’’ rather than on an‘‘as needed basis’’.121 Patients should take anNSAID or acetaminophen just prior to, or imme-diately after, treatment. If they wait to take medi-cation until after the onset of pain, there is usuallya delay of up to 1 hour before they experience painrelief. It has been suggested that instructingpatients to take their analgesics by the clock forthe first few days provides a more consistent bloodlevel of the drug and may contribute to moreconsistent pain relief.121 The combination of ibu-profen and acetaminophen taken together has beenshown to produce additive analgesia when treatingdental pain.111,121,126–128 Opioids may be addedwhen indicated (see Chapter 22).

LONG-ACTING LOCAL ANESTHETICSLong-acting local anesthetics (e.g., bupivicaine) canprovide an increased period of post-treatment analge-sia beyond the usual duration of anesthesia.129,130 Byblocking the activation of unmyelinated C-fiber noci-ceptors, the anesthetic decreases the potential forcentral sensitization.121 Long-acting local anestheticscan provide a period of analgesia for up to 8 to 10hours following block injections and may reducepain even 48 hours later.121,129 Use of long-actinglocal anesthetics is a valuable biologically based strat-egy that provides analgesia during the immediatepostoperative period.121 Endodontic treatment byitself can be expected to provide significant pain relief(see Chapter 22).

Treatment of Endodontic Flare-ups

Selecting the appropriate treatment after an endodon-tic flare-up is dependent upon understanding itsbiological cause. For example, the clinician mustdetermine if a flare-up is primarily iatrogenic in nat-ure, as in the case of inaccurate measurement control,or microbiologically based, as in an infected necroticsituation.

DIAGNOSIS AND DEFINITIVETREATMENTHistory of the onset of pain is important in deter-mining if the pain is spontaneous or provoked bya specific stimulus. For example, if a tooth had ahistory of acute apical periodontitis and its occlu-sion had not been reduced, that could be identifiedas a probable cause of postoperative pain,

Figure 14 Effect of occlusal reduction on pain. Courtesy Dr. PaulRosenberg.


appropriate treatment should be provided.120 Incontrast, a complaint of swelling, pressure, andthrobbing in the interproximal area might suggesta periodontal component of the problem thatshould be explored. If inaccurate measurement con-trol was used or proper measurement not main-tained, the clinician must determine if the canalwas under- or over-instrumented. Working lengthshould be reconfirmed, patency to the apical fora-men obtained, and thorough debridement withcopious irrigation completed. Remaining tissue,microorganisms and their products, and extrusionbeyond the apex are major factors responsible forpost-treatment symptoms.94 Pain relief in the over-instrumented case is often dependent on an analge-sic strategy. The under-instrumented case mayrequire further instrumentation to the correct mea-surement, as well as the use of analgesics.

Drainage Through the Coronal Access

Opening

A cardinal principle in the treatment of suppurativelesions is the establishment of drainage (Figure 15).Drainage, upon access to the pulp cavity, releasespurulent or hemorrhagic exudate from the periapicaltissues and may reduce periapical pressure in sympto-matic teeth with radiolucent areas.131 Obtaining

drainage through the coronal access opening has beenadvocated as a means of reducing pain followingtreatment in some necrotic cases.132 Interestingly, aretrospective study examined the effect of drainageupon access on postoperative endodontic pain andswelling in symptomatic necrotic teeth. It was deter-mined that drainage upon access (average of 1.85minutes) did not significantly (p > 0.05) reduce pain,percussion pain, swelling, or the number of analgesicmedications taken, for symptomatic teeth with peria-pical radiolucencies.131 It is possible that pre-existentapical periodontitis was a factor in the cases studiedand was not addressed by the establishment of drai-nage. Occlusal relief may also have been required toaddress that symptom.

I&DThe goal of emergency treatment for an endodonticflare-up with a swelling is to achieve drainage.132 Theobject of drainage is to evacuate exudate from theperiapical spaces (Figure 16). Drainage is bestachieved through a combination of canal instrumen-tation and I&D. Even in cases where an I&D is to beimplemented, the canal should be accessed, instru-mented, irrigated, medicated, and closed as soon asactive drainage stops. Systemic antibiotics can beexpected to be more effective once the canal has beendebrided, medicated, and closed.133,134

Figure 15 Purulent drainage upon access to the pulp cavity. Courtesy Dr. Craig Baumgartner.

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INSTRUMENTATIONAfter considering the biological cause of the flare-up,the clinician may decide to re-enter the symptomatictooth. Profound local anesthesia is necessary beforere-entry. Enhanced magnification and illuminationare helpful in reassessing the chamber morphologyfor canals that might have been missed at the priorvisit.135–137 Working lengths should be reconfirmed,patency to the apical foramen obtained, and a thor-ough debridement with copious irrigation per-formed.68 Remaining necrotic tissue, microorganisms,and toxic products are important factors responsiblefor flare-ups.94 Enlarging the apical constriction hasbeen advocated to encourage drainage.138 Others havefound that instrumenting through the apical foramendoes not ensure drainage of periapical exudation.68,138

In some cases, however, drainage may be establishedthrough the root canal system upon instrumentation.Drainage allows for exudate to be released from theperiapical tissues thus reducing localized tissue pressureand pain.131 Leaving a tooth open after drainage iscomplete will result in re-infection from oralmicrobes.73,94

TREPHINATIONAs discussed earlier in the chapter, trephination is thesurgical perforation of the alveolar cortical plate overthe root end, to release accumulated tissue exudatethat is causing pain.1 It may be indicated for patientswith a flare-up when there is exquisite pain, no swel-ling, and drainage cannot be accomplished throughthe tooth.

COMPLEX DIAGNOSESThe clinician must be sensitive to the potential of non-odontogenic pain being confused with a flare-up. Forexample, the words ‘‘tingling’’ or ‘‘burning’’ when usedas descriptors of pain are signals of non-odontogenicpain rather than a flare-up. Similarly, although rare, itis possible for a tooth, other than one undergoingendodontic treatment, to suddenly become painfuland confuse the diagnosis. A previously undetectedperiodontal component may also pose a diagnosticproblem.

Bacterial Factors Associated

with Flare-ups

Bacteria are capable of acting as irritants and inducenon-specific innate or specific adaptive immuneresponses in the host.139,140 The host’s responses to abacterial challenge depend largely on virulence factorsand the numbers of pathogens, as well as the host’sinnate and adaptive immunity. If the host’s defensemechanisms are capable of overcoming a bacterialchallenge, bacteria will be eliminated. In contrast, ifthe bacterial challenge overwhelms the host’s defensemechanisms, an inflammatory response, as a resultof innate or adaptive immunity, will occur. Micro-organisms have been suggested as the major causativeagents of flare-ups.68,92,94 Unlike elsewhere in the body,bacteria in the root canal system are well protectedfrom the host’s immune defenses and antimicrobialagents. The microbes and virulence factors associatedwith pulpal and periapical infections are discussed inChapter 7 ‘‘Microbiology of Endodontic Disease.’’

The bacterial community in an infected root canal isclosely related to the nutrient supply, bacterial interac-tion, and oxidation–reduction potential.107 Endodonticprocedures cause changes in the root canal environment,favoring growth of some pathogens remaining in theincompletely instrumented canals, thus predisposing thepatient to a flare-up.94 Some bacterial species may, undercertain conditions such as changes in oxidation-reductionpotential, bacterial interaction, or environmental stresses,become more virulent and induce higher concentrationsof inflammatory molecules and/or cytokines fromdamaged periapical tissues, thus intensifying the inflam-matory response.68,94 This is exemplified in some asymp-tomatic infected teeth with pulpal and/or periapicalpathosis, as well as some asymptomatic re-treatment caseswith periapical pathosis. After initiation or continuationof root canal treatment, those cases suddenly develop aflare-up. Preoperative symptomatic teeth have been

Figure 16 Purulent drainage following incision of a fluctuant abscessinvolving a mandibular anterior tooth (Courtesy Dr. John Ingle).


shown to produce a higher incidence of flare-ups thanasymptomatic teeth,69,70 although the mechanism is notclear. It is possible, in teeth that are symptomatic, thecanals are dominated by pathogens often found asso-ciated with pain or an acute periapical abscess. Therefore,these cases are predisposed to flare-up if the canals are notcompletely debrided or critical numbers of pathogens areforced into the apical tissues to overwhelm the host’sdefenses. A shift in the microbial community in the rootcanal may occur before the appearance of a flare-up.94

Therapeutically, it is easier to reduce the intracanalbacterial count than to control specific pathogens in theinfected root canals. Mechanical instrumentation andantiseptic irrigation have been shown to greatly reducebacterial count in infected root canals.141 Intracanalmedication between visits with calcium hydroxide mayfurther reduce the bacterial count.97,142 However, studieshave not demonstrated an ability to eliminate allbacteria in infected root canals using contemporaryendodontic procedures. Usually, the pathogenicity ofmicroorganisms is related to their virulence factors andnumbers. Although complete chemo-mechanical pre-paration, in combination with intracanal medication,may not eliminate specific pathogens and their virulencefactors, the procedures will significantly reduce the intra-canal bacterial count and the nutrient supply, thus pos-sibly preventing critical numbers of pathogens fromcausing a flare-up. Many species of bacteria have beendemonstrated in teeth with clinical signs and symptoms;however, the cause of a flare-up by a specific species ofbacteria or combinations of bacteria requires furtherclarification. The presence of specific species of bacteriain teeth with clinical symptoms does not necessarilyimply they are the cause of a flare-up.

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113. Carr D, Goudas L. Acute pain. Lancet 1999;353:2051–8.

114. Egbert A, Bettit G, Welch C, Barttett M. Reducation ofpostoperative pain by encouragement and instruction ofpatients. N Engl J Med 1964;270:825–7.

115. Wardle J. Psychological management of anxiety and pain dur-ing dental treatment. J Psychosom Res 1983;27:399–402.

116. Natkin E. Treatment of endodontic emergencies. Dent ClinNorth Am 1974;18:243–55.

117. Antrim D, Bakland L, Parker M. Treatment of endodonticurgent care cases. Dent Clin North Am 1986;30:549–72.

118. Creech J, Walton R, Kaltenbach R. Effect of occlusion relief onendodontic pain. J Am Dent Assoc 1984;109:64–7.

119. Jostes J, Holland G. The effect of occlusal reductionafter canal preparation on patient comfort. J Endod1984;10:34–7.

120. Rosenberg P, Babick P, Schertzer L, Leung A. The effect ofocclusal reduction on pain after endodontic instrumenta-tion. J Endod 1998;24:492–6.

121. Keiser K, Hargreaves K. Building effective strategies forthe management of endodontic pain. Endod Topics2002;3:93–105.

122. Whitten B, Gardiner D, Jeansonne B, Lemon R. Currenttrends in endodontic treatment: report of a national survey.J Am Dent Assoc 1996;127:1333–14.

123. Yingling N, Byrne B, Hartwell G. Antibiotic use bymembers of the American Association of Endodontists inthe year 2000: report of a national survey. J Endod2002;28:396–404.

124. Fouad A. Are antibiotics effective for endodontic pain?Endod Topics 2002;3:52–6.

125. Holstein A, Hargreaves K, Niederman R. Evaluation ofNSAIDs for treating post-endodontic pain: a systemicreview. Endod Topics 2002;3:3–13.

126. Wright CI, Antal E, Gillespie W, Albert K. Ibuprofen andacetaminophen kinetics when taken concurrently. Clin Phar-macol Ther 1983;34:707–10.

127. Cooper S. The relative efficacy of ibuprofen in dental pain.Compend Contin Educ Dent 1986;7–11.

128. Breivik E, Barkvoll P, Skovlund E. Combining diclofinacwith acetaminophen-codeine after oral surgery: a rando-mized, double blind single dose study. Clin Pharmacol Ther1999;66:625–35.


129. Cout R, Koraido G, Moore P. A clinical trial of long-actingabesthetics for periodontal surgery. Anesth Prog 1990;37:194–9.

130. Gordon S, Dionne R, Brahim J, et al. Blockage of periapicalneuronal barrage reduced post-operative pain. Pain1997;709:209–15.

131. Nusstein J, Reader A, Beck M. Effect of drainage upon accesson postoperative endodontic pain and swelling in sympto-matic necrosis teeth. J Endod 2002;28:584–8.

132. Harrington G, Natkin E. Midtreatment flare-ups. Dent ClinNorth Am 1992;36:409–23.

133. Baumgartner J, Hutter J. Endodontic microbiology andtreatment of infection. In: Pathways of the pulp. Cohen, S.and Hargreaves, K. 8th ed. St. Louis: Mosby; 2002.

134. Hutter J. Facial space infections of odontogenic origin.J Endod 1991;17:422.

135. Schwarze T, Baethge C, Stecher T, Guertsen W. Identifica-tion of second canals in the mesiobuccal root of maxillaryfirst and second molars using magnifying loupes or anoperating microscope. Aust Endod J 2002;28:57–60.

136. Wolcott J, Ishley D, Kennedy W, et al. Clinical investigationof second mesiobuccal canals in endodontically treated andretreated maxillary molars. J Endod 2002;28:477–9.

137. Buhrley L, Barrows M, BeGole E, Wenckus C. Effect ofmagnification on location the MB2 canal in maxillarymolars. J Endod 2002;28:324–7.

138. Weine F. Endodontic therapy. 2nd ed. St. Louis: Mosby; 1976.

139. Mims C, Playfair J, Roitt I, et al. Medical microbiology. 2nded. Philadelphia: Mosby; 1999.

140. Abbas A, Lichtman A, Pober J. Cellular and molecularimmunology. 4th ed. Philadelphia: WB Saunders; 2000.

141. Bystrom A, Sundqvist G. Bacteriologic evaluation of theefficacy of mechanical root canal instrumentation inendodontic therapy. Scand J Dent Res 1981;89:321–8.

142. Bystrom A, Claesson R, Sundqvist G. The antibacterialeffect of camphorated paramonochlorophenol, campho-rated phenol and calcium hydroxide in the treatmentof infected root canals. Endod Dent Traumatol1985;1:170–5.

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CHAPTER 22

PHARMACOLOGIC MANAGEMENT

OF ENDODONTIC PAIN

KENNETH M. HARGREAVES, AL READER, JOHN M. NUSSTEIN, J. GORDON MARSHALL, JENNIFER L. GIBBS

The management of pain represents both a challenge andan opportunity for the endodontist. It is a challenge dueto pharmacological (e.g., reduced anesthetic success),behavioral (e.g., patient apprehension), and practicemanagement (e.g., relationship with referring practi-tioner) issues. Many of these factors can increase thestress of providing high-quality clinical care to ourpatients. However, effective pain management also repre-sents a unique opportunity to integrate pharmacological,procedural, and behavioral skills in providing outstand-ing pain control to grateful patients. A tremendousincrease in our knowledge of the pain system and itsdynamic plasticity in response to tissue inflammationoccurred over the last decade (Chapter 10, ‘‘Mechanismsof Odontogenic and Non-Odontogenic Pain’’ and Chap-ter 11, ‘‘Non-Odontogenic Toothache and Chronic Headand Neck Pains’’). Equally important, a commensurateincrease in analgesic clinical trials provides the clinicianwith a unique opportunity to develop biologically andevidence-based strategies for effectively treating endo-dontic pain patients. This chapter contributes to thatskillset by comprehensively reviewing this clinical litera-ture and formulating strategies based on the latest resultsfrom clinical research. To accomplish this goal, the chap-ter will sequentially review major drug classes available tothe practitioner and then use this information to sum-marize evidence-based approaches for pain control.

Local Anesthesia

Profound pain control starts with effective local anesthe-sia. In addition to the obvious ethical and moral obligationof providing appropriate high-quality care, the technicalchallenges of endodontic procedures are greatly increasedwithout effective anesthesia. Background reviews on local

anesthetic techniques and pharmacology should bereviewed as needed by the reader. This section providesan evidence-based rationale of various local anestheticagents and primary and supplemental routes of adminis-tration, with an emphasis on clinical implications.

Before reviewing the clinical trial literature, sev-eral preliminary factors should be considered. First,subjective approaches for assessing the depth ofanesthesia (‘‘are you numb?’’) are fraught with alack of sensitivity and specificity.1–4 Instead, testingfor pulpal responses in vital teeth, by an applicationof a cold refrigerant or by using an electric pulptester (EPT), are effective methods for evaluatinganesthesia in pain-free5–9 or symptomatic vitalteeth5,9–11 in nearly5,9,10 all patients. Simply put,the lack of profound anesthesia after an initialinjection becomes a major indication for supple-mental injection of local anesthetic solutions. Sec-ond, a prior history of incomplete anesthesia oftenpredicts subsequent problems with obtaining com-plete anesthesia.12 This issue should be consideredwhen reviewing the patient’s dental history. Third,preoperative pain is a risk factor for incompletelocal anesthesia, with up to an eight-fold increase inthe prevalence of incomplete anesthesia observed inpatients with irreversible pulpitis.13 Although themechanism(s) mediating this clinical problem isincompletely understood, several hypotheses havebeen advanced including (1) ion trapping of localanesthetic molecules due to lower pH (only possiblefor infiltration injections; block injections are notlikely to involve acidotic tissue); (2) altered membraneexcitability of peripheral nociceptors14,15; (3) increasedactivity of the tetrodotoxin-resistant (TTXr) class ofsodium channels that may also be resistant to theaction of local anesthetics16; (4) increased overall

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expression of sodium channels in pulps diagnosed withirreversible pulpitis17; and/or (5) central sensitizationthat amplifies peripheral input from afferent neurons.Importantly, supplemental techniques such as intraoss-eous9,10,18,19 or periodontal ligament (PDL)11 injec-tions have been demonstrated to increase anestheticefficacy when an inferior alveolar nerve (IAN) blockfails to provide effective anesthesia. Fourth, preopera-tive apprehension, possibly due to previous dentalprocedures including injections,20–22 may contributeto patient management issues. Topical anestheticshave been reported to be effective in reducing injectiondiscomfort in some,23–26 but not all,27–29 studies, andboth pharmacological and psychological componentsmay contribute to the effectiveness of topical anes-thetics.29 Fifth, a slow rate of injection (60 versus15 seconds) reduces patient discomfort30 and can beaccomplished either manually or by a computer-controlled anesthetic delivery system. Automated anes-thetic delivery systems have been shown to produce lesspain in some studies,31–36 or either no difference orgreater pain in other studies37,38; at least some discomforthas been noted in most studies.32–38 Sixth, epinephrine-containing local anesthetics, with their associated low-ered pH, are thought to be associated with more injectiondiscomfort in some39,40 but not all41 studies. As noted inChapter 10, ‘‘Mechanisms of Odontogenic and Non-Odontogenic Pain,’’ the TRPV1 ‘‘capsaicin receptor’’ isexpressed on pain neurons and is profoundly activated bypH solutions of <6.0, which might provide a biologicalbasis for this observation. Seventh, permanent damage tothe lingual nerve and IANs are very rare, with a calculatedincidence of about 0.0006 to 0.3%.42 Of these reportedinjuries, the lingual nerve is affected ~70 to 79%, while theIAN is affected ~21 to 30% of these cases.42,43 In one caseseries, the lingual nerve was affected in 18 out of 12,104patients (~0.1%), with 17 of these 18 cases resolved within6 months.44 Collectively, these general principles of localanesthesia provide foundation knowledge when using thisimportant class of drugs.

Mandibular Anesthesia

Numerous studies have evaluated pulpal anesthesiausing a standardized testing protocol involvingrepeated application of an EPT using a 0–80 scale ofcurrent.1–4,45–49 This method permits controlled clin-ical trials in which either normal healthy control sub-jects or odontogenic pain patients using the samedependent measure for study outcome. In these stu-dies, anesthetic success is defined as the percentage ofsubjects who achieve two consecutive 80 readings

(EPT) within 15 minutes and continuously demon-strate a lack of responsiveness for 60 minutes. Conver-sely, anesthetic failure is defined as the percentage ofsubjects who never achieved two consecutive 80 EPTreadings at any observation time. In general, studiesperforming IAN block injections with one cartridge of2% lidocaine with 1:100,000 epinephrine report differ-ent proportions of anesthetic success/failure for themandibular first molar (53% success/17% failure), firstpremolar (61%/11%), and the lateral incisor (35%/32%)1–4,45–49 (Figure 1). It is important to note, how-ever, that 100% of the subjects1–4,45–49 reported pro-found lip numbness. Therefore, this outcome has nopredictable value for determining the depth of pulpalanesthesia. Although the presence of lip sign does notindicate effective pulpal anesthesia, the absence of a lipsign indicates a failed IAN block injection and shouldprompt a second injection of local anesthetic beforetreatment begins.

Several local anesthetics have been compared inclinical trials using designs similar to that describedabove. As summarized in Table 1, these studies havedemonstrated that many local anesthetics producesimilar levels of anesthesia for IAN block injections.In particular, the equivalency of 3% mepivacaine and2% lidocaine with 1:100,000 epinephrine, in patientswith irreversible pulpitis, is an important finding. Itprovides a vasoconstrictor-free alternative when med-ical conditions or drug therapies suggest caution inadministering epinephrine-containing solutions.

Mepivacaine is available in a formulation containinglevonordefrin, an adrenergic agonist with 75% a

Figure 1 Time–response curve for the development of pulpal anesthesia(defined as no response on Analytical Technologies EPT at setting = 80) ofmandibular first molars following inferior alveolar nerve (IAN) block injection of1.8 mL of 2% lidocaine with 1:100,000 epinephrine. Data courtesy of Dr. A.Reader et al.

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activity and only 25% b activity, making it seem moreattractive than epinephrine (50% a activity and 50% bactivity).50 However, levonordefrin is marketed as a1:20,000 concentration in dental cartridges.50 Clinically,the higher concentration of levonordefrin makes itequipotent to epinephrine in clinical and systemiceffects.4,51 Therefore, 1:20,000 levonordefrin offers noclinical advantage over 1:100,000 epinephrine.

Articaine is available in the United States as a 4%solution containing 1:100,000 and 1:200,000 epi-nephrine.52 Articaine is an amide anesthetic thatcontains a thiophene ring and an ester linkage unlikeother amide local anesthetics.52 The extra ester link-age is susceptible to hydrolysis by plasma esterases.52

Several studies have reported that articaine is safewhen used in appropriate doses.52–60 Although lido-caine and articaine have the same maximum 500 mgdose for the adult patient,50 the manufacturer’srecommended maximum dose for a healthy 70 kgadult would be 7 cartridges of 4% articaine solutioncompared to 13 cartridges of 2% lidocaine solu-tion.50 Articaine, like prilocaine, has the potentialto cause methemoglobinemia and neuropathies.52

While the incidence of methemoglobinemia is rare,dentists should be aware of this complication inpatients who are at an increased risk of developingthis condition.61 The incidence of neuropathies(involving the lip and/or the tongue), associatedwith articaine and prilocaine, is approximately fivetimes more than that found with either lidocaine ormepivacaine.62,63 In one retrospective study, theincidence of paresthesia was approximately one in785,000 injections.62 Therefore, while the paresthe-sia incidence is statistically higher for articaine andprilocaine, it is a clinically rare event that never-theless imposes some medicolegal implications.Available literature indicates that articaine isequally effective when statistically compared toother local anesthetics,60,64–71 with relatively fewstudies demonstrating a statistical superiority ofarticaine over lidocaine for nerve blocks. Recent

studies have reported that articaine was signifi-cantly better than lidocaine for anesthesia afterbuccal infiltration of the mandibular first molar,with articaine producing a success rate of about64 to 87%.72,73

Long-acting local anesthetics, including bupiva-caine and etidocaine, have been advocated for pro-longed pain control, with support from several clinicaltrials.74–79 Recently, etidocaine has been withdrawnfrom the market by Dentsply Pharmaceuticals.Although bupivacaine exhibits sustained anesthesiaand pain control, patients should be informed ofprolonged soft tissue anesthesia (lip sign) since thismay preclude their willingness to use this drug.75

Bupivacaine has a somewhat slower onset than 2%lidocaine but almost twice the duration of pulpalanesthesia (approximately 4 hours) in the mandible48

(Figure 2).Ropivacaine is a structural homologue of bupiva-

caine that appears to have a lower potential for central

Figure 2 Time–response curve for the development of pulpal anesthe-sia (defined as no response on Analytical Technologies EPT at setting =80) of mandibular first molars following inferior alveolar nerve (IAN)block injection of either 1.8 mL of 2% lidocaine with 1:100,000 epi-nephrine or 1.0 mL of 0.5% bupivacaine with 1:200,000 epinephrine.Data courtesy of Dr. A. Reader et al.

Table 1 Comparison of Local Anesthetics for Inferior Alveolar Nerve Anesthesia

Local Anesthetic I Local Anesthetic II Patient Population Finding Reference

3% Mepivacaine plain 2% Lidocaine with 1:100,000 epinephrine Healthy volunteer subjects I = II 2

3% Mepivacaine plain 2% Lidocaine with 1:100,000 epinephrine Irreversible pulpitis I = II 11

2% Mepivacaine with 1:20,000 levonordefrin 2% Lidocaine with 1:100,000 epinephrine Healthy volunteer subjects I = II 4

4% Prilocaine plain 2% Lidocaine with 1:100,000 epinephrine Healthy volunteer subjects I = II 2

4% Prilocaine with 1:200,000 epinephrine 2% Lidocaine with 1:100,000 epinephrine Healthy volunteer subjects I = II 4

4% Articaine with 1:100,000 epinephrine 2% Lidocaine with 1:100,000 epinephrine Healthy volunteer subjects I = II 71

4% Articaine with 1:100,000 epinephrine 2% Lidocaine with 1:100,000 epinephrine Irreversible pulpitis I = II 72

4% Articaine with 1:100,000 epinephrine 4% Articaine with 1:200,000 epinephrine Healthy volunteer subjects I = II 73

Chapter 22 / Pharmacologic Management of Endodontic Pain / 715

nervous system (CNS) and cardiovascular toxiceffects.80 Anesthesia from injection of 0.5% ropivacainewith 1:200,000 epinephrine was equivalent to 0.5%bupivacaine with 1:200,000 epinephrine. One studyfound that 0.5 and 0.75% concentrations of ropivacainewithout epinephrine were effective for IAN blocks.81

IAN block injections are not always successful. Asnoted above, patients with preoperative pain are atrisk for reduced rates of successful anesthesia. How-ever, even in patients without pain, the IAN blockinjection is not always successful. Several hypotheseshave been advanced for this lack of complete suc-cess.69 First, the mylohyoid nerve has been suggestedto provide accessory innervation that might contri-bute to the clinical failure of IAN block injec-tions.82,83 However, clinical studies in which IANblock injections were compared to an IAN block aswell as with mylohyoid nerve block failed to demon-strate any increase in anesthetic success. This led tothe conclusion that the mylohyoid nerve is not amajor contributor to failed IAN block injections.84 Sec-ond, it is possible that inaccurate positioning of theneedle might contribute to IAN block failures; however,confirming the needle position with either a medicalultrasound device45 or radiographs85,86 failed toincrease success rates of IAN injections. Third, it ispossible that needle deflection might be a cause forIAN block failures.87–89 However, neither a bidirec-tional rotation method, using the Wand (CompuDent,Milestone Scientific Inc., Deerfield, IL),89 nor insertionwith the needle bevel oriented away from the mandib-ular ramus (so the needle would deflect toward themandibular foramen)90,91 substantially improved anes-thetic success. Fourth, it is possible that the contralateralIAN provides an accessory path for innervation. Cross-innervation occurs in mandibular incisors92,93 but likelydoes not contribute to most cases of IAN block failures.Fifth, it is very possible that anesthetic failure of man-dibular anterior teeth might be due to the anatomicalorganization of the IAN where the ‘‘central core’’ ofaxons supplies the distal anterior teeth and the outerlayer of axons supplies the posterior teeth.94,95 The well-described failure of the IAN block to anesthetize ante-rior teeth1–4,45–49,96 might be simply due to the lack ofsufficient drug concentrations to block voltage-gatedsodium channels (VGSC) in the central core axons. Ofcourse, this hypothesis does not explain the failure toblock posterior mandibular teeth. Collectively, thesefindings have prompted much research to increase thesuccess of IAN nerve block injections.

Several procedures have been evaluated for increasingthe rate of successful anesthesia of the IAN block. First,

increasing the volume of 2% lidocaine with epinephrine(from 1.8 to 3.6 mL) does not increase anestheticsuccess.1,49,84,97,98 Second, increasing epinephrine con-centration (from 1:100,000 to 1:50,000) does not appearto increase anesthetic success in normal teeth.46,99

Third, hyaluronidase, an enzyme that reduces tissueviscosity100 with favorable anesthetic enhancementproperties,101,102 was not found to improve the successof lidocaine anesthesia in a recent double-blind, rando-mized clinical study.103 Fourth, carbonated solutions arethought to trap the anesthetic within the nerve as well asimpose a direct depressant action on nerves.3 Lidocainehydrocarbonate, however, was no more effective foranesthetic success.3 Fifth, diphenhydramine, an antihis-tamine with reported local anesthetic properties,104,105

did not improve lidocaine anesthesia when injected as acombined solution.106 Sixth, meperidine, an opioidanalgesic with demonstrated anesthetic properties,107

did not improve the success of lidocaine anesthesia aftercoinjection.107,108 Although these experimental appr-oaches using pharmacological methods were not success-ful in improving IAN block anesthesia, other studiesevaluating alternative methods of drug delivery provedmore successful in addressing this problem.

Alternative or supplemental injections are indicatedwhen IAN block is not successful. One alternativeapproach is to reduce the speed of injection for an IANblock. A slow IAN block injection (60 seconds) signifi-cantly increases anesthesia success rates (electric pulptesting), compared to a rapid injection (15 seconds).30

There are three supplemental routes of injection that willbe discussed in the following sections, ‘‘The intraliga-mentary injection,’’ ‘‘The intraosseous injection,’’ and‘‘The intrapulpal injection.’’ They are included in thesection under ‘‘Mandibular anesthesia’’ because this isthe major, though not exclusive, area for their clinicalapplication.

THE SUPPLEMENTALINTRALIGAMENTARY INJECTIONThe technique of intraligamentary anesthesia can bereviewed in other published papers or textbooks. Stu-dies have reported that about 0.2 mL of solution isdelivered with each mesial and distal injection using atraditional or pressure syringe, that different needlegauges (25, 27, or 30 gauge) are equally effective,109,110

and that standard syringes are as effective as specialligamental syringes.110–112 Several studies have shownthat the intraligamentary injection produces initial suc-cess rates of about 63 to 74% and that, if needed, reinjec-tions produce an overall success rate of about 92 to

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96%.11,110–113 The intraligamentary injection will not besuccessful in mandibular anterior teeth.114,115 This routeof injection should be considered a type of intraosseousinjection since the solutions are forced throughthe cribriform plate into the marrow spaces aroundthe tooth116–120 and not via the PDL. Although back-pressure upon injection is the most important factorfor anesthetic success,116,118 this simply reflects forcesnecessary to penetrate the cribriform plate and does notproduce pressure anesthesia121,122 like the intrapulpalinjection.123,124 The presence of a vasoconstrictor signif-icantly increases the efficacy of intraligamentary injec-tion,122,125–128 and anesthetic solutions with reducedvasoconstrictor concentrations (e.g., bupivacaine with1:200,000 epinephrine) are not very effective with thistechnique.128,129 The onset of anesthesia is immedi-ate110–112,114,121,122 and if anesthesia is still not adequate,reinjection is indicated. Since the duration of pulpalanesthesia in asymptomatic cases following the IANnerve block plus supplemental intraligamentary injec-tions is only about 23 minutes,113 the operator mustwork fairly quickly and be prepared to reinject if pro-found anesthesia is lost. Although it has been reportedthat the intraligamentary injection can be used in thedifferential diagnosis of pulpally involved teeth,130,131

experimental studies have demonstrated that adjacentteeth also become anesthetized with the intraligamentaryinjection of a single tooth.114,121,122 Therefore, the intra-ligamentary PDL injection should not be used for differ-ential diagnosis.

Several studies have evaluated potential adverseeffects that may occur with the intraligamentary routeof injection. First, intraligamentary injections are morepainful when anesthetizing teeth with irreversible pul-pitis, as compared to normal teeth,5,111,114,122 and thismay be due to the mechanical allodynia that oftenoccurs in cases of irreversible pulpitis.132 The patientshould be made aware of this possibility. Second, intra-ligamentary injections typically produce mild postinjec-tion pain in the majority of patients for 14 to 72 hoursafter injection,111,114,122 and this would be additive toany postendodontic pain. Third, about 40% of thepatients will report that their tooth feels high in occlu-sion.114,122 Fourth, although a letter to the editorreported avulsion of a tooth following intraligamentaryinjections,133 no clinical or experimental study hasreported avulsion or loosening of teeth with this tech-nique,114,121,122 and therefore, avulsion should not bea concern when using the intraligamentary injectiontechnique. Fifth, initial studies in dogs reported cardio-vascular responses to intraligamentary injection of epi-nephrine-containing solutions134; however, this has notbeen confirmed in clinical studies evaluating tachycar-

dia.135,136 Sixth, minor damage to the periodontiumdoes occur, but only at the site of needle penetrationand this subsequently undergoes repair in nearly allcases. In very rare instances, periodontal abscesses anddeep pocket formation113,114 or root resorption137,138

have occurred after intraligamentary injections.Seventh, clinical and animal studies have shown noeffect on the pulp following intraligamentary injec-tions114,121,122,138–140 other than a rapid and prolongeddecrease in pulpal blood flow caused by epinephrine.127

No histological induction of pulpal inflammation hasbeen observed in studies comparing restorative proce-dures to restorative procedures combined with intrali-gamentary injections.141 Therefore, intraligamentaryinjections are unlikely to cause pulpal necrosis.Eighth, the intraligamentary injection of primaryteeth may cause enamel hypoplasia of the developingpermanent teeth.142 However, the effect was not dueto the injection itself but due to the anesthetic agentsused. The same effect would seemingly be producedby an infiltration injection next to the developingtooth. Ninth, intraligamentary injection has beenreported to be safe in the presence of mild to mod-erate gingival inflammation or incipient periodonti-tis.143 Taken together, the intraligamentary route ofinjection provides a useful supplemental route forincreasing anesthesia success with minimal adverseevents reported in the great majority of studies.

A recent modification of the intraligamentary sup-plemental injection is the computer-assisted localanesthetic delivery system such as the Wand orCompuDent (CompuDent, Milestone ScientificInc.) that accommodates a standard local anestheticcartridge that is linked by sterile microtubing to adisposable, pen-like handpiece with a Luer-Lok nee-dle attached to the end. The device is activated by afoot control that automates the infusion of localanesthetic solution at a controlled rate. A slow orfast flow rate may be initiated and maintained by afoot pedal control. A 1.4-mL aliquot of solution isdelivered in 1 minute in the fast mode and in about4 minutes and 45 seconds in the slow mode. Theslow rate is used for the intraligamentary injection.

A recent study,144 using experimental subjects,demonstrated that the Wand method of primaryintraligamentary injection of 1.4 mL of 4% articainewith 1:100,000 epinephrine, versus injection of 1.4 mLof 2% lidocaine with 1:100,000 epinephrine, producedsimilar rates of successful anesthesia of the mandibularfirst molar (86 versus 74%, respectively, using EPT).The duration of anesthesia (31–34 minutes) was muchlonger than that reported previously using a pressuresyringe and 0.4 mL of a lidocaine solution


(10 minutes).114 Another study evaluated patientswith irreversible pulpitis and a failed IAN block. Suc-cess of the intraligamentary injection (none or mildpain upon endodontic access or initial instrumenta-tion) was obtained in only 56% of the patients.145 Theresults were somewhat disappointing because thecomputer-controlled anesthetic delivery systemshould have been capable of delivering approximately1.4 mL of anesthetic solution via intraligamentaryinjection by consistently maintaining a precise flowrate. Thus, other supplemental injection proceduresmay be indicated in patients with irreversible pulpitis.

INTRAOSSEOUS ANESTHESIAA second route for supplemental injection is theintraosseous injection. There are three intraosseoussystems in the commercial market, including the Sta-bident system (Fairfax Dental Inc., Miami, FL), theX-tip system (Dentsply, Tulsa, OK), the IntraFlow(IntraVantage, Plymouth, MN). However, to date,most published clinical trials have used either theStabident or X-tip systems. The Stabident system iscomprised of a slow-speed handpiece-driven perfora-tor, a solid 27-gauge wire with a beveled end that,when activated, drills a small hole through the corti-cal plate. The anesthetic solution is delivered to thecancellous bone through the 27-gauge ultra-shortinjector needle placed into the hole made by theperforator; the modified nonbevel needle is recom-mended for ease of negotiation. The X-tip anesthesiadelivery system consists of a special hollow needlethat serves as the drill penetrating the cortical plate,whereupon it is separated and withdrawn. The guidesleeve is designed to accept a 27-gauge needle to injectthe anesthetic solution and is removed after injection(Figure 3).

Several characteristics are similar among the studiedintraosseous delivery systems. First, anesthetic successis improved following injection into a site distal ratherthan mesial to the selected tooth.19,51,146–152 Theexception to this rule is the maxillary and mandibularsecond molars where the mesial site should beselected.19,51,146–152 Second, the onset of anesthesiais essentially immediate.19,51,146–153 Third, manufac-turer’s instructions locate the perforation site inattached gingival, where the cortical bone is oftenthinner and one can inject at a site equidistant betweenadjacent root structures. However, two studies havesuccessfully used the X-tip system, with its guide sleevedesign, in alveolar mucosa at a more apical loca-tion,19,148 providing a potential clinical advantage over

the Stabident system when apical injections are con-sidered.

As described above, a regular IAN block oftenprovides poor anesthetic success in patients with irre-versible pulpitis (i.e., only 19 to 56% of patientsreport no/mild pain upon access).9–11,19,71,153 Thus,several studies have evaluated whether supplementalintraosseous injections improve anesthetic successafter IAN nerve block in odontogenic pain patients.

Several studies have evaluated the Stabident systemin patients with irreversible pulpitis in mandibularposterior molars after failed conventional IAN nerveblock injections. In general, these trials have demon-strated that a Stabident injection of 2% lidocaine with1:100,000 epinephrine produced 79% anesthetic suc-cess at a volume of 0.45 to 0.9mL18 and 91% successrate at an intraosseous injection volume of 1.8 mL.9

The intraosseous injection was more successful thanthe PDL injection,113 probably due to the greateramount of anesthetic solution delivered with theintraosseous injection. Other studies using a similarpatient population and experimental design havedemonstrated that supplemental intraosseous injectionof 3% mepivacaine produced 80% success after onecartridge and 98% success following a second intraoss-eous injection.10 Another study demonstrated that asupplemental intraosseous injection of 1.8 mL of 4%articaine with 1:100,000 epinephrine was 87% success-ful after the failure of IAN blocks for posterior teethdiagnosed with irreversible pulpitis.153 Two conclu-sions are evident from this analysis. First, a supplemen-tal intraosseous injection after a failed IAN nerve blocksignificantly improves anesthetic success. Second, itappears that an intraosseous injection of one cartridgeof 3% mepivacaine plain may not be as efficacious as onecartridge of 2% lidocaine with 1:100,000 epinephrine.However, as noted below, an advantage of mepivacaineis that 3% mepivacaine does evoke the tachycardia typi-cally observed with epinephrine-containing anestheticsolutions.

Parallel studies have evaluated the X-Tip system inpatients with irreversible pulpitis in mandibular pos-terior molars after failed conventional IAN nerveblock injections. In one study evaluating apical posi-tioning of the perforator, the X-tip injection site was 3to 7 mm apical to the mucogingival junction of themandibular molar or premolar tooth, and 1.8 mL of2% lidocaine with 1:100,000 epinephrine was admi-nistered.19 The authors reported that in the absence ofthe backflow of anesthetic solution into the oral cav-ity, the success rate was 82%, but that in the presenceof a backflow, the success rate dropped to 18%.19

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Several clinical implications can be derived fromthese studies. First, given the relatively high failurerate of IAN blocks in patients with irreversible pulpi-tis, it would be prudent to consider using thesecombined methods in all patients with irreversiblepulpitis. Second, anesthetic success requires deposi-tion of the solution into the cancellous bone. If

backflow occurs, the clinician should consider reper-foration at the same or another site. A second intraoss-eous injection of 1.4 mL of 2% lidocaine with1:100,000 epinephrine 30 minutes after the initialintraosseous injection provided an additional 15 to20 minutes of pulpal anesthesia.154 Third, in studiesusing either the Stabident or the X-tip system, the

A

C

B

D

Figure 3 Intraosseous anesthesia delivery system X-tip. A, The X-tip system comes in two parts: the drill and the guide sleeve and special injectionneedle. First, anesthetize the mucobuccal fold and select a site 2 to 4 mm apical to the alveoli crest and between the roots. B, Place the X-tip drill in aslow-speed handpiece (15,000 to 20,000 rpm) and drill at maximum speed at 90� to the bone. In 2 to 4 seconds the drill will perforate the cortical boneinto the cancellous bone. C, Hold the guide sleeve in place and withdraw the drill. D, Insert the special short needle into the hole in the guide sleeve andslowly inject a few drops of anesthetic solution. In the event, additional anesthesia is needed later; the guide sleeve can be left in place until the end oftreatment.


duration of anesthesia was sufficient for the entiredebridement appointment.9,19,153 Fourth, no clinicalstudy has reported the anesthetic success rate oradverse events of supplemental intraosseous injectionin painful teeth with necrotic pulps and periradicularradiolucencies. Therefore, no evidence-based clinicalrecommendations for necrotic cases can be made dueto this lack of data. This is an area for future research.

Several studies have evaluated potential adverseeffects that may occur with intraosseous injections.First, pain may occur during perforation and solutiondeposition when using the Stabident system, althoughthe incidence of even a moderate transient pain is lowin asymptomatic patients.146–151 In symptomatic teethwith irreversible pulpitis, the incidence of transientmoderate–severe pain is about 0 to 16% during Stabi-dent perforation and about 5 to 31% during injectionof the anesthetic solution.9,10,153 For the X-tip systemin patients with irreversible pulpitis, there is a 48%incidence of moderate to severe pain with perforationand a 27% incidence with injection of anesthetic.19

Second, it has been estimated that about 1% of per-forators ‘‘separate’’ during use, requiring removal witha hemostat.19,146–151 Third, a transient tachycardia (12to 32 bpm) can occur for about 4 minutes in 46 to 93%of patients after Stabident or X-tip intraosseous injec-tion of epinephrine- and levonordefrin-containingsolutions.9,19,51,146–150,152,153,155 No significant changein diastolic, systolic, or mean arterial blood pressurehas been observed with the intraosseous injection of2% lidocaine with 1:100,000 epinephrine.155,156 In onestudy, a slow intraosseous injection (over 4 minutes45 seconds using a computer-assisted local anestheticdelivery system) was compared to a ‘‘fast’’ injection(45 seconds) of 2% lidocaine with 1:100,000 epinephr-ine. The slow infusion produced a significantly loweredmagnitude of tachycardia (12 versus 25 bpm).157

Although transient tachycardia is noticeable to thepatient, it is thought to be not clinically significantin otherwise healthy patients.155 Importantly, there isno significant increased tachycardia when 3% mepi-vacaine is used for intraosseous anesthesia.155,158 Thisrepresents an alternative approach for patientswhose medical condition (moderate-to-severe cardi-ovascular disease) or drug therapies (patients takingtricyclic antidepressants or nonselective b-adrenergicblocking agents) suggest caution in administeringepinephrine- or levonordefrin-containing solutions.Based upon these considerations, the intraosseousinjection of 1.8 mL of 3% mepivacaine without a vaso-constrictor (e.g., 3% Carbocaine) could be recom-mended as a local anesthetic of first choice. This is notbased on the potential cardiovascular risks associated

with a vasoconstrictor-containing anesthetic solutions,but instead is based on the avoidance of a transienttachycardia combined with its reasonably effectiveanesthesia.155,158 Fourth, the traditional long-actinglocal anesthetic (e.g., bupivacaine) did not demonstrateprolonged anesthesia after intraosseous or maxillaryinfiltration anesthesia.152,159–161 Given concerns aboutits potential for cardiotoxicity,162 bupivacaine shouldnot be used for intraosseous anesthesia. Fifth, someauthors have cautioned that administration of an overlylarge volume of local anesthetic with an intraosseousinjection could lead to overdose reactions.163 However,venous plasma levels of lidocaine were the same formaxillary anterior intraosseous and infiltration injec-tions of 2% lidocaine with 1:100,000 epinephrine.164

Therefore, the intraosseous technique should not beconsidered an intravascular injection. Sixth, about 2to 15% of patients receiving Stabident injection havereported moderate pain on a postoperative day,51,146,

149,150,155 although this is less than that reported afterintraligamentary injection.122 Gallatin et al.165 foundthat significantly more males experienced postoperativepain with the X-tip system than with the Stabidentsystem. They felt that this was related to a denser andmore mineralized bone in the posterior mandible inmales and the fact that the X-tip perforating systemdiameter is larger than the Stabident perforator result-ing in the generation of more frictional heat duringperforation. Seventh, other postinjection problemscan occur, including swelling and/or exudate at the siteof perforations in <5% of patients after Stabident andpossibly a slightly greater prevalence after X-tip injec-tions.51,146,149,150,155,165 These slow-healing perforationsites may be due to overheating of the bone caused bypressure during perforation, warranting a slow gentleapproach during perforation. To date, all such reportedcases have healed without incidence.

THE INTRAPULPAL INJECTIONIn about 5 to 10% of mandibular posterior teeth withirreversible pulpitis, supplemental intraosseous injec-tions, even when repeated, do not produce profoundanesthesia; pain persists when the pulp is entered. Thisis an indication for an intrapulpal injection. Theadvantage of the intrapulpal injection is that it workswell for profound anesthesia if given under backpres-sure.123,124 Onset will be immediate and no specialsyringes or needles are required. The major drawbackof the technique is that needle placement and injectionare directly into a vital and very sensitive pulp; theinjection may be moderately to severely painful andthe patient should be warned of this potentiality.9

720 / Endodontics

Maxillary Anesthesia

Descriptions of conventional techniques for maxillaryanesthesia are available for review in numerous articlesand textbooks. Clinically, maxillary anesthesia is moresuccessful than mandibular anesthesia and the infiltrationroute is by far the dominant approach.12 Numerous stu-dies have demonstrated that infiltration injection of anes-thetics such as 2% lidocaine with 1:100,000 epinephrineresults in 90 to 95% successful pulpal anesthesia (obtain-ing an 80 reading) in anterior and posterior maxillaryteeth.67,68,160,166–169 Although the onset of infiltrationanesthesia usually occurs within 5 to 7 minutes, the dura-tion is fairly short in both anterior (20 to 30 minutes) andposterior (30 to 45 minutes) maxillary teeth.160,166–169

This may require additional anesthetic injections depend-ing on the length of the procedure. For maxillary infiltra-tion injections, increasing the volume of 2% lidocainewith 1:100,000 epinephrine to 3.6 mL will increase theduration of pulpal anesthesia.167 As with mandibularanesthesia, pulpal anesthesia does not last as long as softtissue anesthesia.160,166–169 The infiltration injection of 4%prilocaine (1:200,000 epinephrine) is similar in action toan infiltration injection using 2% lidocaine (1:100,000epinephrine).169 In most,65–68 but not all,170 studies, max-illary infiltration injections of articaine with 1:100,000epinephrine were equivalent to both prilocaine and lido-caine with epinephrine. Although bupivacaine provideslong-acting anesthesia in the mandible, it does not pro-vide prolonged pulpal anesthesia in maxillary infiltrationinjections.80,159,160 The infiltration injection of anestheticswithout vasoconstrictors, 3% mepivacaine plain and 4%prilocaine plain, produce a brief duration (15 to 20 min-utes) of pulpal anesthesia and accordingly are generallyused only for brief procedures.168,169

Since many endodontic procedures are done onone tooth at a time, the infiltration route is mostcommonly employed. However, for the sake of com-pleteness, major maxillary block injections that areeffective for anesthetizing multiple teeth will be brieflyreviewed. The posterior superior alveolar (PSA) nerveblock anesthetizes some first molars, and all secondand third molars.7 Generally, to ensure patient com-fort for the first molar, an additional buccal infiltrationinjection after the PSA block may be needed. Theinfraorbital nerve block injection will anesthetizethe first and second premolars and the lip, but notthe central or lateral incisors.171,172 The second divisionnerve block will successfully anesthetize the pulps ofmolar teeth and about 50% of the second premo-lars.173,174 The high tuberosity approach is preferredover the greater palatine approach because the successrate is similar and it is less painful.173 The palatal-

anterior superior alveolar (P-ASA) injection depositsthe anesthetic solution into the incisive canal andderives its name from the injection’s ability to suppo-sedly anesthetize both the right and the left anteriorsuperior alveolar nerves leading to bilateral anesthesiaof maxillary incisors and canines.175 However, needleinsertion results in 54 to 58% of the subjects reportingmoderate/severe pain following needle placement.34,176

The anterior middle superior alveolar (AMSA) injectionis a new route for anesthetizing the maxillary centraland lateral incisors, canines, and first and second pre-molars.177–179 The AMSA injection site is located pala-tally at a point that bisects the premolars and isapproximately halfway between the midpalatine rapheand the crest of the free gingival margin. However,studies evaluating the AMSA route have reportedrather modest to low success rates,180,181 and 32% to38% incidence of moderate injection pain.35

Non-Narcotic Analgesics: Nonsteroidal

Anti-Inflammatory Analgesics

and Acetaminophen

The major analgesic drug class for treating endodonticpain is the non-narcotic drugs, consisting of the non-steroidal anti-inflammatory analgesics (NSAIDs) andacetaminophen. The reader is referred to basic phar-macology texts for an overview of these drugs. Thepresent review will instead focus on newer evidencesand clinical implications from controlled clinicaltrials. The NSAID class of drugs are thought to pro-duce their analgesic and anti-inflammatory effects bythe inhibition of cyclooxygenase (COX).182 Othermechanisms such as inhibition of cell signaling mole-cules (e.g., NFkB) have also been proposed.183 Twomajor isotypes of COX have been described,184,185 andNSAID drugs can be classified based upon their pre-ference for blocking COX1 or COX2. NSAIDs such asibuprofen should be considered ‘‘mixed COX’’ inhibi-tors since they can inhibit both enzymes at clinicaldosages. Moreover, a recent study has reported thatthe analgesic efficacy of ibuprofen depends upon thegenetic mutation of COX1, with patients having certainpolymorphisms of COX1 displaying significantly betteranalgesic responses than patients having other poly-morphisms.186 If confirmed, then variations in patientresponses to NSAIDs might be due to variations in themutations on the gene encoding the COX1 enzyme.Blockade of COX1 is associated with increased risk forgastrointestinal side effects such as ulcers, whereasblockade of COX2 is associated with increased


cardiovascular risk such as thrombotic events.187

Instead of a bimodal classification, the NSAIDs shouldbe viewed as having an inhibitory continuum,187 wheredrugs can have varying efficacy for inhibiting COX1versus COX2, and accordingly would be expected tovary in their clinical side effect profile (Figure 4). Basedupon findings demonstrating rapid upregulation ofprothrombic enzymes188 and cardiac events,189,190 ithas been suggested that most patients would be bestmanaged with the non-COX2-selective NSAIDs such asibuprofen.191

Several systematic reviews have been publisheddescribing the efficacy and adverse effect profile ofNSAIDs for treating both postsurgical pain192–194 andpostendodontic pain.195 In general, these studies havedemonstrated that NSAIDs produce excellent analgesicresponses in patients who can tolerate this class ofdrugs. For example, in a meta-analysis of >14,000 thirdmolar patients,192 several NSAIDs were shown toproduce a dose-related analgesic effect (defined as>50% pain relief). These data are summarized inTable 2. Since many clinicians were originally taughtthat acetaminophen/codeine combinations providesuperior pain control, it is worth carefully reviewingthese data. The lowest studied dose of ibuprofen(200 mg) actually has about the same analgesic responseas acetaminophen 600 to 650 mg/codeine 60 mg. More-over, the 400 mg and 600 mg doses of ibuprofen pro-duce substantially greater levels of analgesia. Equally

important, only the acetaminophen/codeine combina-tion was associated with any significant increase inadverse effects.192 Fortunately, these findings mirrorthe responses of endodontists published in a recentsurvey196 where non-narcotics, especially ibuprofen600 mg, were dominantly selected for pain control overthe acetaminophen/opiate combination drugs.

Other studies have evaluated the analgesic benefit ofNSAIDs for treating pain after nonsurgical endodonticprocedures.197–215 In general, the randomized placebo-controlled endodontic studies have demonstratedsignificant analgesic benefits for patients treated withflurbiprofen,202 flurbiprofen/tramadol,197 intracanalketorolac,198 IM ketorolac,208 intraoral ketorolac(in some,201,207 but not all216 studies), piroxicam,210

mefanamic acid,211 aspirin,211 diclofenac,209 ketoprofen(in some,199,209 but not all200 studies), ibuprofen,199,204

and ibuprofen/acetaminophen.204

Interestingly, ibuprofen 600 mg produced only amodest/moderate analgesic effect in several postendo-dontic studies.217–220 It is not clear if this modest analge-sic effect reflects a non-COX pain mechanism inendodontic pain patients reflective of chronic inflamma-tory conditions (e.g., cytokines), or whether it representsa ‘‘floor effect’’ where nonsurgical root canal treatmentby itself reduces pain to the extent that it is difficult todetect further reduction by the addition of an analgesic.This latter point has been observed in many endodontictrials where non-surgical root canal treatment (NS-RCT) plus a placebo pill resulted in a 50 to 80% painreduction, 24 to 48 hours after treatment.197,199 How-ever, the overall interpretation of these data providestrong support for the use of NSAIDs as a primary classof analgesics for treating acute inflammatory pain due toeither surgical or nonsurgical procedures.

As noted in Chapter 10, ‘‘Mechanisms of Odonto-genic and Non-Odontogenic Pain,’’ the VGSC playthe dominant role in the signaling of nociceptor

Figure 4 Schematic illustration of the relationship between risk foradverse side effect profile of non-narcotic analgesics based on the relativeinhibition of COX1 versus COX2. Adapted from FitzGerald GA.187

Table 2 Meta-Analysis of Non-Narcotic Analgesics for Reliefof Postoperative Pain

Drug

Percentage of Patients

with ‡50% pain relief

N (No. of

patients)

Ibuprofen 200 mg 46 1,194

Ibuprofen 400 mg 56 3,402

Ibuprofen 600 mg 79 203

Diclofenac 50 mg 50 367

Diclofenac 100 mg 70 204

Acetaminophen 600–650 mg 36 1,265

Acetaminophen 600–650 mg

plus codeine 60 mg

48 911

Placebo ~13 6,497

Data adapted from Barden J et al.192

722 / Endodontics

activity from the periphery to the CNS. In particular,the TTX-resistant class of VGSCs expressed on noci-ceptors is relatively resistant to lidocaine and is sensi-tized by prostaglandins.16,221,222 One interpretation ofthese basic science findings is that NSAIDs would beexpected to increase the effectiveness of local anes-thetics by virtue of their ability to reduce prostaglan-din levels in inflamed tissue. A preemptive approachto improve anesthesia in patients with irreversiblepulpitis is to give ibuprofen 1 hour before anestheticadministration. A recent study223 evaluated ibuprofengiven before local anesthetic injection in patients withirreversible pulpitis. It concluded that it significantlyimproved the depth of anesthesia using an EPT testingparadigm. Another study pretreated patients witheither a placebo or with acetaminophen 650 mg orthe combination of ibuprofen 600 mg with acetami-nophen 650 mg. They concluded that the odds ratiofor the combination group tended to favor successfulanesthesia in the active groups as compared to theplacebo.224 However, both of the studies have fairlysmall sample sizes, and further research is needed onthis potentially important clinical finding.

Acetaminophen represents the second major mem-ber of the non-narcotic class of analgesics. Its utility islargely based on the finding that its side effect profileis less adverse than the NSAIDs, and that the drug canbe used in patients for whom NSAIDs are contra-indicated.225 Although acetaminophen has been usedfor nearly 100 years, its mechanism of action remainsmostly unknown. Acetaminophen does inhibit per-ipheral COX activity in inflamed tissues but only atdoses of about 1,000 mg.226 Recent studies have sug-gested additional mechanisms by which acetamino-phen may act by metabolic conversion to a compoundpreviously called AM404, which is a cannabinoid-likeanalgesic.227 Indeed, acetaminophen antinociception isreversed in mice by pretreatment with a cannabinoidreceptor antagonist.228 However, other potentialmechanisms have been proposed including modulationof the serotonin receptor 5HT1A.229

In humans, acetaminophen inhibits central sensitiza-tion under conditions that exclude a potential periph-eral site of action,230 suggesting that this drug also has aCNS site of action. Interestingly, animal studies demon-strate that acetaminophen produces synergistic effectswith a variety of NSAIDs (i.e., ibuprofen, diclofenac,ketoprofen, meloxicam, metamizol, naproxen, nimesu-lide, parecoxib, and piroxicam) using a mouse model oftissue hyperalgesia.231 This finding appears to have clin-ical implications since acetaminophen/NSAID combi-nations appear to be very effective for pain controlfollowing surgical232,233 or endodontic204 procedures.

Steroids

Various classes of drugs have been studied for themanagement of endodontic posttreatment pain.197

These include non-narcotic analgesics comprisingNSAIDs and acetaminophen, opioids and glucocorti-coids (steroids). This section will consider the use ofglucocorticoids for the management of endodonticpain. For an in-depth description of the pharmacology,pharmacodynamics, mechanisms and sites of action, aswell as their anti-inflammatory actions, the reader isdirected to review articles.198,199,234–238

The potent anti-inflammatory properties of glucocor-ticoids were first appreciated and utilized as an adjunctto endodontic therapy more than 50 years ago.239–241

Steroids have been used as a pulp-capping agent,242 asan intracanal medicament either alone or in combina-tion with antibiotics/antihistamines,198,240,241,243–247

and systemically199,248,234–236,239,249–253 as a means todecrease pain and inflammation in endodontic patients.

In critically evaluating the literature, it must be keptin mind that the most powerful conclusions are gen-erated from studies that are prospective, randomized,double-blind, and placebo-controlled. However, noneof the endodontic reports on the use of corticoster-oids published prior to 1984 meets these criteria, andthe results therefore should be considered as lowerlevels of evidence. Results from studies that usedcorticosteroids in combination with other agents(antibiotics and/or antihistamines) are also difficultto interpret, as results ascribed to one of the agentsmay reflect the activity of the combination.199,200

Equally difficult to interpret are results from studiesusing intracanal steroid delivery.198,240,241,243–247 Themethodology in these studies cannot account foreither the dosage or the delivery period of the intra-canal medicament to reach the site of action (peria-pical tissues). In these studies, very small dosages ofthe steroid are placed into the canal(s). Even assumingapical patency of unknown size, the steroid must passthrough the apical foramen via passive diffusion alonga concentration gradient, and this may be opposed bya potential backpressure from periapical transudate orexudate. For a critical assessment of these studies, thereader is directed to review an article by Marshall.238

Studies evaluating the systemic administration of cor-ticosteroid as the sole agent, in a known dose, are thecritical ones in evaluating the efficacy of the steroid’sability to decrease endodontic posttreatment pain.

In a randomized, prospective, double-blind, placebo-controlled study, Marshall and Walton235 evaluatedthe effect of the intramuscular injection of dexametha-sone on posttreatment endodontic pain when compared


to a placebo. After endodontic instrumentation and/or obturation, patients received an IM injection of1.0 mL of either dexamethasone (4 mg/mL) or sterilesaline. Pain levels of none, mild, moderate, or severewere recorded preoperatively at 4, 24, and 48 hoursposttreatment. Teeth with vital and necrotic pulps aswell as retreatment cases were included. No antibio-tics were taken by the patients and no postoperativeinfections were reported. The amount of additionalpostoperative pain medication required was notrecorded. Results indicated that dexamethasone sig-nificantly reduced both pain incidence and severity at4 hours posttreatment. At 24 hours posttreatment,patients in the corticosteroid group showed a trendtoward less pain.

Another double-blind study evaluated the effect oforal dexamethasone on posttreatment pain.252 Fiftypatients presenting for endodontic treatment werestudied. Retreatment cases and patients presentingwith purulent drainage or cellulitis were excluded.Teeth were instrumented and closed with no intraca-nal medication. Pretreatment, 8, and 24 hours post-treatment pain levels were recorded on a visual analogscale (0–100). Patients randomly received dexametha-sone (0.75-mg tablet) or a placebo, with instructionsto take three tablets immediately and then one tabletevery 3 hours until bedtime for a total of seven tablets.Results showed that patients receiving dexamethasonehad significantly less pain at 8 and 24 hours whencompared to those receiving the placebo (p<0.01)

A third study250 evaluated the effect of oral dexa-methasone on endodontic interappointment pain, butat a much higher dosage than the preceding study.252

Forty patients with ‘‘asymptomatic vital inflamed’’pulps were evaluated. After endodontic instrumenta-tion and temporization, alternate patients were giveneither dexamethasone (4 mg per tablet) or a placebo.Instructions were to take one tablet immediately andthen one tablet at 4 and 8 hours posttreatment for atotal dose of 12 mg in the dexamethasone group. Painwas recorded on a visual analog scale at 8, 24, and48 hours posttreatment. Patients receiving dexametha-sone had a statistically significant reduction in pain atall post treatment periods.

Liesinger et al.234 in a double-blind, randomized,prospective, placebo-controlled study evaluated theeffect of four different dosages of dexamethasone onposttreatment endodontic pain. All patients (N=106)presented with pretreatment pain. Pulp status wasrecorded (vital and necrotic cases were included).Endodontic instrumentation and/or obturation wasperformed after which patients randomly received a1.0-mL intraoral injection of either a placebo (sterile

saline) or dexamethasone (2, 4, 6, 8 mg/mL). The injec-tion was given into the masseter, internal ptyergoid, orbuccinator muscle; preference was given to introoralmuscles anesthetized for treatment. Patients recordedtheir pain levels on a 0 to 9 scale. Pretreatment andposttreatment (4, 8, 24, 48, and 72 hours) pain levelswere recorded. The type and the amount of posttreat-ment analgesics taken were also recorded. No antibioticswere given at any time. Results showed patients receiv-ing dexamethasone had significantly less severe pain at 4and 8 hours postoperatively (p<0.05) and took signifi-cantly less pain medication compared to the placebo(dexamethasone mean, 1.98 tablets; placebo mean,4.64 tablets). When evaluated on a milligram per kilo-gram dosage basis, patients who received 0.07 to0.09 mg/kg of IM dexamethasone had significantly lesspain at 8 hours and required significantly less post-operative pain medication when compared to the IMplacebo.

Kaufman et al.254 were the first to evaluate theeffect of the intraligamentary delivery of dexametha-sone on endodontic posttreatment pain. Forty-fivepatients were randomly assigned to one of threeexperimental groups. Endodontic treatment was com-pleted in one appointment on both vital and necroticpulps, with and without periapical radiolucencies.After the administration of local anesthesia, but priorto endodontic treatment, patients in Group 1 received4 to 8 mg of slow-release methylprednisolone (Depo-Medrol) via an intraligamentary syringe. Single-rooted teeth received 4 mg, and multirooted teethreceived 8 mg. Group 2 received a PDL injection of3% mepivacaine in a similar fashion to Group 1.Patients in Group 3 received no PDL injection.Pretreatment pain levels were not recorded. Patientswere telephoned at 24 hours posttreatment andreported their pain intensity on a 1–10 scale. Theresults showed a significant decrease in postoperativepain in the methylprednisolone group compared tothe active and passive placebo groups (p<0.05).

Gallatin et al.248 evaluated pain reduction in patientswith untreated irreversible pulpitis using an intraoss-eous injection of methylprednisolone. Forty patientswith a clinical diagnosis of irreversible pulpitis activelyassociated with moderate–severe pain participated inthis prospective double-blind study. The involvedtooth was anesthetized followed by an intraosseousinjection of 1 mL of either methylprednisolone(Depo-Medrol 40 mg/mL) or saline. The blinded solu-tions were administered using the Stabident system(Fairfax Dental Inc.). No endodontic treatment wasperformed at this time. Patients were given a 7-day paindiary as well as analgesic medication. Over the 7-day

724 / Endodontics

observation period, patients who received Depo-Medrolreported significantly less pain (p<0.05) compared to aplacebo while taking significantly fewer analgesics(p<0.05).

Bramy et al.236 evaluated the intraosseous admin-istration of corticosteroid for pain reduction insymptomatic necrotic teeth. Thirty-eight patientswith a clinical diagnosis of pulpal necrosis withassociated periapical radiolucency participated inthe study. All patients experienced moderate–severepain at the time of presentation with mild or noclinical swelling. After complete canal debridement,patients in a double-blind fashion randomlyreceived an intraosseous injection of 1 mL of eithermethylprednisolone (Depo-Medrol 40 mg/mL) orsterile saline. All subjects received ibuprofen andTylenol #3 (with codeine) and were instructed totake the medication as needed for pain. Patientsrecorded their pain levels and the type and amountof pain medications taken for 7 days postopera-tively. The results showed that the steroid grouphad significantly less postoperative pain and tooksignificantly less pain medication over the 7 dayswhen compared to the placebo group (p<0.05). Noantibiotics were taken by patients at any time.

In a follow-up study, Claffey et al.249 evaluated painreduction in symptomatic teeth with necrotic pulpsusing an oral dose regimen of methylprednisolone. Thematerials and methods were nearly identical to Bramyet al.236 except that no patient had clinical swelling, andafter canal debridement, patients randomly receivedeither oral methylprednisolone (48 mg/day for 3 days)or an oral placebo (lactose 48 mg/day for 3 days) in adouble-blind fashion. All patients received ibuprofenand Tylenol #3 and a diary to record pain, percussionpain, swelling, and number and type of pain medicationtaken. Clinical success was defined as any patient whoexperienced only none–mild pain, none–mild percus-sion pain, none–mild swelling, and did not take anyTylenol #3. No antibiotics were prescribed or taken.The results showed that patients who received methyl-prednisolone had a significantly higher level of clinicalsuccess when compared to the placebo (p<0.05).

Ouyang et al.253 evaluated the effect of submuco-sally injected dexamethasone on both the incidenceand the severity of endodontic interappointmentpain. Teeth with a diagnosis of asymptomatic pulpalnecrosis were endodontically treated in one appoint-ment. Eighty patients received a submucosal injec-tion of 5 mg dexamethasone; the control group of80 patients had endodontic treatment performedbut no submucosal injection. Pain incidence andseverity was evaluated for 3 days postoperatively.

Results indicated that the patients in the dexa-methasone group had a statistically significantdecreased incidence and severity of endodonticinterappointment pain.

Prior to interpreting these studies,248,234–236,249–

251,253 it is critical to remember that endodontictreatment has a major effect in reducing posttreat-ment pain regardless of pharmacologic intervention.As stated by Hargreaves,255 ‘‘ This reduction in post-treatment pain, combined with variable levels ofpreoperative pain, reduces the statistical power ofendodontic clinical trials for detecting active analge-sics over time in all patient groups (the so-calledfloor effect). This limitation is a problem in inter-preting clinical studies in general and may explainwhy some endodontic clinical trials fail to detectanalgesic treatment or only detect it in those patientswith moderate/severe pain.’’ This has been shown byTorabinejad et al.199 and Rogers et al.198 where var-ious agents including corticosteroid significantlyreduced posttreatment pain but only in thosepatients who presented for treatment with at leastmoderate/severe pretreatment pain. It would seemthat the systemic administration of a corticosteroidto ameliorate endodontic posttreatment pain wouldbe appropriate only for those patients who presentwith at least moderate levels of preoperative pain.Three independent studies234,236,249 meet the criteriaof being prospective, randomized, double-blind, pla-cebo-controlled with no drug combinations, andincluding patients who presented with the requiredlevel of pretreatment pain. Importantly, these studiesshowed that the systemic administration of corticos-teroid not only significantly reduces posttreatmentpain at various times but also significantly reducesthe amount of additional pain medication required.

Interestingly, the reports by Bramy et al.236 andClaffey et al.249 show significant pain relief with theadministration of a steroid for up to 7 days posttreat-ment, in contrast to Liesinger et al.234who found sig-nificant differences in pain reduction only in the first8 hours. It is possible that these findings are due todifferences in dosages of different corticosteroids ordue to the routes of administration. This is probablynot the case, as dexamethasone is approximately fivetimes as potent as methylprednisolone. The 6 to 8 mgintramuscular dosage used by Liesinger et al.234 wouldbe equivalent to 30 to 40 mg of methylprednisolone.Intraosseous 40 mg of methylprednisolone was thedosage used by Bramy et al.236 It may be speculatedthat these differences in the duration of action mightbe related to differences in the preoperative pulpal andperiapical status of the patient populations of these


studies. All of the patients in the studies by Bramyet al.236 and Claffey et al.249 presented for treatmentwith necrotic pulps, associated periapical radiolucen-cies, and either mild or no swelling. The majority ofpatients in the study by Liesinger et al.234 had a pre-operative diagnosis of irreversible pulpitis and acuteapical periodontitis. Those patients with necroticpulps had no associated periapical radiolucencies. Itis plausible that corticosteroids may be more effica-cious in attenuating the pain associated with pulpalnecrosis and an associated radiolucency compared topain associated with irreversible pulpitis. Necrosis/radi-olucency is associated with a more complex chronicinflammatory process. Thus the efficacy of corticoster-oids, in endodontic pain patients, may be related tovariations in the periapical immunological/inflamma-tory dynamics of teeth with irreversibly inflamed pulpscompared to necrotic pulps.

On the basis of the work of Bramy et al.236 andClaffey et al.,249 it is plausible that corticosteroidswould have efficacy in cases of endodontic flare-upthat result after treatment of previously asympto-matic teeth with necrotic pulps with or withoutassociated periapical radiolucencies. This premisehas not been investigated. The low incidence of thistype of flare-up256 would require a multicenterstudy over a period of years to achieve an adequatesample size.

It appears that the route of systemic administrationof a steroid is not a determinant in the efficacy ofaction.234,236,249 When given in equivalent dosages,agents such as dexamethasone and methylprednisoloneappear to be interchangeable. If a systemic steroid is tobe administered, an intraoral IM injection or anintraosseous injection would seem to be preferable overan extraoral IM injection. Clinicians are familiar withintraoral and intraosseous injections, and the site ofinjection is already anesthetized. Intraoral injection ofsteroid would be preferable to a written prescriptionfor glucocorticoid as no assumption to patient com-pliance is required. An injection dosage of 6 to 8 mg ofdexamethasone or 40 mg of methylprednisoloneappears to be appropriate for the adult patient. If anoral route is chosen, 48 mg of methylprednisolone perday for 3 days and by extrapolation 10 to 12 mg ofdexamethasone per day for 3 days should provide sig-nificant posttreatment pain relief.

It has been stated that antibiotics must be given inconjunction with steroids to prevent an infectionsecondary to a decrease in the inflammatoryresponse.239,257–259 The implication is that suppres-sion of inflammation also means a decrease in localdefenses permitting unchecked proliferation of

pathogenic microorganisms. None of the studiespublished since 1984 supports this premise, includ-ing those cases with a diagnosis of pulpal necrosiswith periapical radiolucency where the potential fordissemination of an infectious process might beexpected.236,249 Antibiotics were not given or neededat any time during these studies nor were the steroidsassociated with any increase in infection rate comparedto the control groups. It can be concluded that anti-biotics are not routinely required or recommended inconjunction with corticosteroids for the managementof endodontic posttreatment pain in the otherwisehealthy patient.

Opioid Analgesics

Because opioids are not anti-inflammatory, nonopioidswith anti-inflammatory efficacy (e.g., aspirin, ibupro-fen) are the analgesics of first choice for endodonticpain.260 It has been shown that codeine in a 30 mgdose provides no more analgesia than a placebo.261,262

However, a 60 mg dose of codeine produces signifi-cantly more analgesia than a placebo. Thus, opioids inthe appropriate dosage may be of benefit when addi-tional pain control in needed. For example, if anNSAID is not controlling a patient’s discomfort, anopioid combination such as acetaminophen/hydroco-done may be prescribed in addition to the NSAID.Opioids in combination with an NSAID produce addi-tional analgesia beyond the ceiling effect of the NSAID.Opioid analgesics activate mu receptors that inhibit thetransmission of nociceptive signals from the trigeminalnucleus to the higher brain centers and activate periph-eral receptors to reduce pain.263,264 Although opioidanalgesics may be effective for the relief of moderate tosevere pain, their use is limited by adverse side effectsthat include nausea, vomiting, drowsiness, dizziness,constipation, and respiratory depression. In addition,chronic use is associated with tolerance and depen-dence. Because of the numerous side effects, opioidsare usually used in combination with other analgesicsto manage endodontic pain. Table 3 has a list of opioids

Table 3 Opioid Analgesic Combinations

Opioid Combination Usual Dose

Acetaminophen (300 mg) and codeine (30 mg) 2 tablets q4h

Aspirin (325 mg) and codeine (30 mg) 2 tablets q4h

Acetaminophen (500 mg) and hydrocodone (5 mg) 1-2 tablets q6h

Acetaminophen (325/500 mg) and oxycodone (5 mg) 1 tablet q6h

Aspirin (325 mg) and oxycodone (5 mg) 1 tablet q6h

Ibuprofen (200 mg) and hydrocodone (7.5 mg) 1 tablet q6h

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in combination with aspirin, acetaminophen, and ibu-profen that may be used to alleviate pain of endodonticorigin. Clinicians must be aware of drug-seekingpatients who request a specific opioid.

Conclusions

A thorough knowledge of the biological (Chapter 10,‘‘Mechanisms of Odontogenic and Non-OdontogenicPain’’) and pharmacological aspects of odontogenicpain reveals several important conclusions that aresummarized as follows:

• There is no single magic bullet for treating pain.Clinicians need to develop skills for differentialdiagnoses of pain disorders, delivering positivebehavioral management strategies, identifying riskfactors for postprocedural pain, effective intraoss-eous injection of local anesthetics (particularly incases of painful mandibular teeth, especially irre-versible pulpitis), using combinations of an NSAIDwith acetaminophen (in patients who can toleratethese drugs), delivering effective and appropriatedental treatment, and following up all patients toensure their appropriate response.

• The intensity of preoperative pain is a useful predic-tor of post-endodontic pain,199,202,265 and this riskfactor should be considered when developing thepain treatment plan before treatment commences.

• Preoperative pain in a mandibular tooth is a riskfactor for anesthetic failure of IAN block injections.The best evidence to date, which balances efficacywith minimal adverse effects, would support treat-ing patients with an irreversible pulpitis of a man-dibular tooth first with an IAN block injection,followed immediately by an intraosseous injectionof 3% mepivacaine. Little is known about benefits/risks of an intraosseous injection of symptomaticmandibular teeth with pulpal necrosis and periapi-cal radiolucencies.

• Emerging clinical evidence provides qualitative sup-port that a preoperative NSAID would be expectedto enhance the magnitude of anesthesia, althoughadditional research is needed.

• In patients who can tolerate the drug classes, thereis strong preclinical and clinical trial data demon-strating that the combination of an NSAID withacetaminophen provides effective pain control inboth postsurgical and postendodontic patients. Onepossible strategy to treat patients in moderate-to-severe pain would be to consider combinationsof up to ibuprofen 600 mg and acetaminophen

1,000 mg, four times a day for no more than 2 to3 days after the procedure. This combination ofanalgesics provides a useful alternative to the classi-cal use of narcotic-containing analgesic drugs.

• It is our belief that the integration of high-qualityclinical research findings together with the clini-cian’s own skills, the patient’s desires and the par-ticulars of each case, represents the highest level ofclinical care. From this perspective, this chapterrepresents an important contribution, but is onlyone source of information on the pharmacology ofpain control. Clinicians must supplement thisinformation and evaluate its application to anyparticular clinical case.

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CHAPTER 23

ANXIETY AND FEAR IN THE ENDODONTIC

PATIENT

STANLEY F. MALAMED

Fear and anxiety is far from being a uniquely endo-dontic problem; it is, however, a more significantproblem within because of the commonplace natureof the patients’ underlying problem: pain. Dentistryconsistently appears in lists of our most common fearsalong with fear of heights, flying, mice, and publicspeaking.1 Common dental fears include fear of theunknown, fear of pain, and, perhaps most commonly,fear of the ‘‘shot.’’

Studies over the years have evaluated the incidenceof dental phobia (odontophobia) in the general popu-lation.2–4 They indicate that between 10 and 30% ofthe adult population suffer from moderately severe toextreme odontophobia. Chanpong et al.4 in a survey(n = 1101) of Canadian adults found 7.6% statingthey had ‘‘missed, cancelled or avoided a dentalappointment because of fear or anxiety.’’ In responseto the question ‘‘How would you assess your feelingstowards having dental treatment done?’’, 5.5%assessed themselves as either ‘‘very afraid’’ (2.0%) or‘‘terrified’’ (3.5%). In this ‘‘high fear’’ group, 49.2%had missed, cancelled, or avoided a dental appoint-ment because of fear or anxiety compared with only5.2% of the ‘‘low or no fear’’ group.

Enkling et al.5 reported that in 67% of odontopho-bic patients a prior painful dental or medical experi-ence was the primary cause of their fear, followed byfear of needles (33%).

Dental fear is real and it hurts. For the patient, it ispalpable. For the doctor and office staff, it stands as abarrier to the delivery of quality dental care. Withinthe realm of endodontics, many patients requiringtreatment do so as a result of their extreme odonto-phobia. The first endodontic appointment, duringwhich access will be gained and pulpal tissuesremoved, provides the greatest challenge to the

endodontist, confronted with a patient who is inpain and having possibly been in pain for severalmonths, and who is fearful not just of the localanesthetic injection but of ‘‘root canal work’’ itself.

Other chapters have information on the managementof endodontic infection (Chapter 20, ‘‘Treatment ofEndodontic Infections, Cysts, and Flare-Ups’’) and endo-dontic pain (Chapter 10, ‘‘Mechanisms of Odontogenicand Nonodontogenic Pain’’) and pain of nonendodonticorigin (Chapter 11, ‘‘Nonodontogenic Toothache andChronic Head and Neck Pains’’).

Fear and pain are a potent combination capable ofprovoking some of the most catastrophic situationsimaginable in the dental office, such as cardiac arrest.Surveying the incidence of medical emergencies in thedental environment, Malamed6 found that 54.9%occurred during the administration of the local anes-thetic with an additional 22.0% occurring duringdental treatment. When a medical emergency aroseduring dental treatment, 65.8% occurred either duringextirpation of the pulp (26.9%) or extraction of thetooth (38.9%).7 Over three-quarters of medical emer-gencies seen in dentistry are stress-related. Potentiallystress-related medical emergencies include syncope,angina pectoris, bronchospasm, seizures, hyperventi-lation, and the so-called ‘‘epinephrine reaction.’’

Recognition of Fear and Anxiety

Recognition of dental fear should not be left until thepatient is seated in the dental chair. Quite often thereceptionist is asked revealing questions by patients,such as ‘‘Is the doctor gentle?’’, ‘‘Does the doctor givegood shots?’’ Patients in the reception area may con-verse amongst themselves, discussing their upcoming

737

treatment, perhaps in lurid ways. This invaluable infor-mation must be relayed to chair-side personnel who cannow act to prevent a ‘‘problem’’ from developing.

Once seated in the dental chair, the patient’s fearsusually become more obvious. Fearful patients simplydo not ‘‘look’’ comfortable. Legs remain crossed andfingers clutch the armrest of the dental chair, theso-called ‘‘white-knuckle syndrome.’’ The patient clo-sely watches everything, not wanting to be ‘‘snuck upon’’ by the doctor. Responses to questions are unu-sually prompt; speech is rapid. Perspiration may beobserved on the patient’s forehead, upper lip, andperhaps underarms.

If any of the above is noted, it is important for thedoctor to confront the patient, asking them ‘‘if any-thing about the upcoming procedure bothers them.’’Once the patient admits to having fears and once thefears are out in the open, the ‘‘problem’’ should bemanageable.

Management problems occurring during the localanesthetic administration can be almost entirely pre-vented by taking a patient’s ‘‘feelings’’ about receiving‘‘shots’’ into consideration. Most people do not relishthe thought of receiving intraoral local anesthetic injec-tions as demonstrated by the high incidence of adversereactions occurring at this time. Fifty-five percent of allmedical emergencies reported by Malamed6 were faint-ing, and over 54% of all emergencies occurred duringadministration of the local anesthetic. Syncopeaccounted for 61.1% of dental office medical emergen-cies reported during a 1-year period in New Zealand.8

Fainting during injection is preventable by following afew simple steps aimed at making all local anestheticinjections as comfortable (atraumatic) as possible: (1)placing the patient about to receive an intraoral injec-tion into a supine position prior to injection, (2) slowadministration of the local anesthetic solution, and(3) use of sedation, if warranted, prior to the adminis-tration of the local anesthetic.

Management of Fear and Anxiety

The concept behind the successful use of sedation is thatfearful patients are overly focused on everything thathappens around them, and to them, in the dental envir-onment. Administration of a central nervous system(CNS)-depressant drug lessens the patients’ awareness,moving their minds away from the dental chair. They nolonger over-respond to stimulation. They no longer careabout the procedure and, in effect, become more ‘‘nor-mal’’ patients. Stated even more simply, sedation is aboutdistraction.

DEFINITIONSSedation occurs as a result of depression of the CNS.Although various levels of CNS depression will be dis-cussed, one is in fact dealing with a continuum, from theearliest manifestations of a drug’s action, anxiolysis,through the controlled loss of consciousness, generalanesthesia. As most jurisdictions require a licensed den-tist to obtain a permit before being allowed to administerCNS-depressant drugs via various routes and to varyinglevels of CNS depression, a number of dental (and med-ical) organizations have published guidelines for the safeand effective use of these drugs.9–11

When describing, and defining, the various levels ofCNS depression, the precise wording of the definitionmay vary slightly from state to state and organization toorganization, but the essence of the definitions is thesame. The reader is strongly advised to adhere to thosedefinitions that have been established in the jurisdictionin which he/she is licensed. Until recently, the termsused to describe the levels of CNS depression were (inorder of increasing levels of depression): anxiolysis !conscious sedation! deep sedation! general anesthe-sia. New definitions, first proposed by the AmericanSociety of Anesthesiologists, describe the degree ofCNS depression ultimately achieved (Table 1).12 Thedefinitions that follow are taken from the American

Table 1 Continuum of Depth of Sedation: Definition of General Anesthesia and Levels of Sedation/Analgesia

Minimal Sedation(Anxiolysis)

Moderate Sedation/Analgesia(Conscious Sedation) Deep Sedation/Analgesia General Anesthesia

Responsiveness Normal response to

verbal stimulation

Purposeful* response

to verbal or tactile stimulation

Purposeful* response

after repeated or painful

stimulation

Unarousable, even

with painful stimulus

Airway Unaffected No intervention required Intervention may be required Intervention often

required

Spontaneous ventilation Unaffected Adequate May be inadequate Frequently inadequate

Cardiovascular function Unaffected Usually maintained Usually maintained May be impaired

*Source: American Society of Anesthesiologists Task Force on Sedation and Analgesia by Non-Anesthesiologists.12

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Dental Association’s (ADA’s) Guidelines for the Use ofSedation and General Anesthesia by Dentists.11

Minimal SedationMinimal sedation was previously associated withanxiolysis—a minimally depressed level of conscious-ness that retains the patient’s ability to independentlyand continuously maintain an airway and respondappropriately to physical stimulation or verbal com-mand, and that is produced by a pharmacologic ornonpharmacologic method or a combination thereof.Although cognitive function and coordination may bemodestly impaired, ventilatory and cardiovascularfunctions are unaffected.11–12 In accord with this par-ticular definition, the drug(s) and/or techniques usedshould carry a margin of safety wide enough to renderunintended loss of consciousness unlikely. Further-more, patients whose only response is a reflexive with-drawal from repeated painful stimuli would not beconsidered to be in a state of minimal sedation.

When the intent is minimal sedation for adults, theappropriate dosing of enteral drugs is no more thanthe maximum recommended dose of a single drugthat can be prescribed for unmonitored home use.

Nitrous oxide/oxygen (N2O–O2) when used incombination with sedative agents may produce mini-mal, moderate, or deep sedation or general anesthesia.

The following definitions apply to administrationof minimal sedation:

Maximum recommended therapeutic dose (MRTD):maximum FDA-recommended dose of a drugapproved for unmonitored home use. Incrementaldosing: administration of multiple doses of a druguntil a desired effect is reached, but not to exceedthe MRTD. Titration: administration of incrementaldoses of a drug until a desired effect is reached.Knowledge of each drug’s time of onset, peakresponse, and duration of action is essential.Although the concept of titration of a drug toeffect is critical, when the intent is minimalsedation, one must know whether the previousdose has taken full effect before administering anadditional drug dose.

Moderate SedationThis was previously associated with conscious seda-tion—a drug-induced depression of consciousnessduring which patients respond purposefully to verbalcommands, either alone or accompanied by lighttactile stimulation. No interventions are required tomaintain a patent airway, and spontaneous ventilat-ion is adequate. Cardiovascular function is usually

maintained.11,12 In accord with this particular defini-tion, the drugs and/or techniques used should carry amargin of safety wide enough to render unintendedloss of consciousness unlikely. Repeated dosing of anagent before the effects of previous dosing can be fullyappreciated may result in a greater alteration of thestate of consciousness than is the intent of the dentist.Furthermore, a patient whose only response is a reflex-ive withdrawal from a painful stimulus is not consid-ered to be in a state of moderate sedation.

Deep SedationThis is a drug-induced depression of consciousnessduring which patients cannot be easily aroused butrespond purposefully following repeated or painfulstimulation. The ability to independently maintainventilatory function may be impaired. Patients mayrequire assistance in maintaining a patent airway, andspontaneous ventilation may be inadequate. Cardio-vascular function is usually maintained.11,12

General AnesthesiaThis is a drug-induced loss of consciousness duringwhich patients are not arousable, even by painfulstimulation. The ability to independently maintainventilatory function is often impaired. Patients oftenrequire assistance in maintaining a patent airway, andpositive pressure ventilation may be required becauseof depressed spontaneous ventilation or drug-induceddepression of neuromuscular function. Cardiovascu-lar function may be impaired.11,12 Because sedationand general anesthesia are a continuum, it is notalways possible to predict how an individual patientwill respond. Hence, practitioners intending to pro-duce a given level of sedation should be able todiagnose and manage the physiologic consequences(rescue) for patients whose level of sedation becomesdeeper than initially intended.12

For all levels of sedation, the practitioner must havethe training, skills, and equipment to identify andmanage such an occurrence until either assistancearrives (emergency medical service) or the patientreturns to the intended level of sedation without air-way or cardiovascular complications.

REGULATIONThrough the 1960s, upon receiving a dental degreeand a license to practice dentistry, the dentists wereallowed to administer any form of anesthesia (fromlocal anesthesia to sedation to general anesthesia).No prohibitions, except for common sense, existed.As no formal training had been received in thesetechniques (aside from local anesthesia) in dental

Chapter 23 / Anxiety and Fear in the Endodontic Patient / 739

school, most new doctors prudently avoided theiruse, managing fearful patients as best they could.Some, however, felt that they could easily administeranesthesia (in the broad sense) to their patients.Although some were successful, a large enoughnumber became involved in serious untowardevents, leading to death or severe neurologicdamage, that governmental agencies (state dentalboards and/or legislatures) began to seriously ques-tion whether dentists should be allowed to performthese techniques.

In the early 1970s, an Alaskan dentist had severaldeaths occur under halothane general anesthesia. Asthis dentist had little or no formal training in generalanesthesia, Alaska became the first state to ban theadministration of general anesthesia in the dentaloffice. In 1974, in response to four patient deathsunder general anesthesia in a short span of time inthe office of an untrained dentist, Ohio became thefirst state to limit the use of general anesthesia todentists who could prove adequate training, eitherthrough an oral surgery program or a 1-year anesthe-siology residency13 (J. Weaver, personal communica-tion, January 2006).

As of 21 December 2006, all 50 states have enactedregulation governing the administration of generalanesthesia and deep sedation in dental offices.14 Deepsedation, by virtue of the fact that the patient’s venti-latory status and ability to maintain an airway may beimpaired, requires a level of training equal to that ofgeneral anesthesia. Education and training in generalanesthesia requires a minimum of a 1-year or 2-year,full-time residency in anesthesiology.

Some dentists, untrained and now unable to admin-ister general anesthesia, began administering CNS-depressant drugs parenterally, either intramuscularly orintravenously, as these techniques had not yet been regu-lated. Not surprisingly, a number of deaths occurred,as well as other serious morbidities over the ensuingyears. And also, not surprisingly, legislative bodiesbegan to regulate parenteral sedation. All 50 statesnow regulate the administration of parenteral con-scious sedation.15 (Intranasal [IN] sedation, a relativelynew approach to CNS-depressant drug administrationin dentistry, is classified as a parenteral route of drugadministration.)

The oral route, the least effective and least control-lable common mode of drug delivery, had alwaysenjoyed a somewhat limited use in dentistry. As otherroutes of drug delivery and levels of sedation encoun-tered increased scrutiny and regulation, interest bur-geoned in this, as yet, unregulated mode of drugadministration.

Orally administered drugs had always been animportant management technique within the specialtypractice of pediatric dentistry, with chloral hydrate,hydroxyzine, and promethazine forming a triad ofoft-used drugs. In 1985 the American Academy ofPediatric Dentistry developed guidelines for the useof sedation by pediatric dentists who received ade-quate clinical and didactic experience in this techni-que during their residencies. These guidelines havebeen reevaluated several times with the most recentversion accepted and published in 2006.16

Unfortunately, some untrained nonpediatric den-tists (e.g., general dentists), now unable to administerdrugs parenterally, began using oral sedative drugs toachieve more profound levels of CNS depression, withpredictable results: death and severe morbidity (e.g.,brain damage). Legislation to require permits for oralconscious sedation (OCS) in children appeared inthe late 1990s. Enacted in 2000, California’s legisla-tion requires a permit for OCS in patients less than13 years of age.17 At present, 11 states require advancededucation and awarding of a permit for a licenseddentist to administer OCS to a pediatric patent.15

OCS for adult dental patients had an increase inpopularity in the mid-1990s, which continues today.Although many oral drugs are available, one, triazo-lam, has proven the most popular.18,19

And now, for the first time, state dental boards haveacted proactively rather than reactively, as in the past,enacting legislation mandating continuing dental educa-tion (CDE) and a permit to administer OCS to the adultdental patient. As of December 2006, 19 states haverequirements for CDE and a permit for adult OCS.15

One route of drug administration has yet to be dis-cussed: inhalation. In contrast to the oral route, theinhalation route represents the most controllable tech-nique of drug administration. In dentistry in the UnitedStates, the combination of N2O and O2 is available andused, with varying frequency, in approximately 35% ofdental offices.20 The ADA, in concert with manufac-turers of inhalation sedation units, mandated the inclu-sion of safety features into these machines. The goal ofthese safety features is to make it close to impossible theadministration of levels of O2 less than 21% (ambientair) to a patient.21 Deaths and serious morbidity asso-ciated with N2O–O2 inhalation sedation in dentistryhave not occurred in recent years due primarily to theaddition of these safety features and the requirement ofthe ADA’s Commission on Dental Accreditation that allgraduating dental students be trained to proficiencyin inhalation sedation.22 As of December 2006, onlya handful of states require a permit for the use ofinhalation sedation.

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SEDATION: NONDRUG TECHNIQUES(IATROSEDATION)Management of a patient’s dental fear begins as soonas the patient enters the office. The environment, theambiance of the office, establishes a mood either ofquiet relaxation or of a hurried, frenetic pace. Thedental staff should be alert to any tell-tale signs ofdental fear and, if noted, report it to the dentistimmediately. ‘‘Forewarned is forearmed.’’ Relaxationof a patient by the doctor’s behavior has been termediatrosedation, a term formulated by Dr. Nathan Fried-man, for many years chairman of the Section ofHuman Behavior at the University of Southern Cali-fornia, School of Dentistry.23 The word is derivedfrom the Greek prefix iatro, ‘‘pertaining to the doc-tor,’’ and sedation, ‘‘the relief of anxiety.’’

The concept on which iatrosedation is based is ratherbasic: that the behavior of the doctor and staff has aprofound influence on the behavior of the patient.Other terms applied to this concept include sugges-tion, chairside/bedside manner, and the laying on ofhands. The underlying premise of all these techniquesis similar: that one can use nonchemical means to aidin relaxing the patient. For a more in-depth discus-sion of nondrug techniques of sedation, the reader isreferred to Sedation: a guide to patient management.24

Examples of iatrosedative techniques include hypno-sis, acupuncture, audioanalgesia, and biofeedback.

Iatrosedation forms the building block for all seda-tion techniques requiring drug administration. Simplyput, a patient who remains fearful, perhaps with dis-trust of the doctor, is less likely to ‘‘allow’’ their CNS-depressant drug to work. Although true for all routesof drug administration, it is especially relevant with theoral and inhalation routes.

Consider the patients’ frame of mind in the dentaloffice: afraid that something/everything is going to bepainful. Their dentist is telling them, nonverbally, to‘‘trust me.’’ ‘‘Allow me, a stranger, to give you a drugthat will decrease your level of consciousness so thatyou are less aware of what is happening around you.’’ ‘‘Iwill take good care of you.’’ The doctor who establishesa bond of trust with their patients will have them sitback in the dental chair and ‘‘let the drug work.’’ Con-versely, where the doctor–patient relationship isstrained or uncomfortable, patients are much less likelyto surrender to the clinical effects of the drug, notwanting to ‘‘lose control’’ of the situation. The leveldefined as minimal sedation is highly unlikely to suc-ceed in this situation. Moderate sedation would have asomewhat greater success rate but still with a signifi-cant, perhaps unacceptably high, failure rate (Table 2).

SEDATION: DRUG TECHNIQUES(PHARMACOSEDATION)In dentistry, CNS-depressant drugs are administeredby four routes: commonly by oral and inhalation, andless commonly by intravenous (IV) and intramuscular(IM). IN drug administration is a relatively recentaddition to this armamentarium, primarily employedto provide moderate sedation in children.25

The following is a brief overview of these routes ofCNS-depressant drug administration in dentistry. It isnot meant to substitute for a complete course in pharma-cology or in the safe and effective technique of drugadministration. The doctor wishing to administer drugsby any of these routes should check with their state Boardof Dental Examiners for specific education and permitrequirements for each technique or level of sedation.

INHALATION SEDATION (N2O–O2)Inhalation sedation with N2O–O2 represents the mostcontrollable technique of sedation available. Inhala-tion sedation possesses a number of compelling clin-ical properties that serve to increase its success rateand its safety, including (1) rapid onset of action(~20–30 seconds); (2) a level of CNS depression thatcan rapidly be increased, if necessary; (3) the level ofCNS depression that can be rapidly decreased, ifneeded—a significant factor in increasing the safetyof inhalation sedation; (4) complete recovery follow-ing the delivery of 100% O2 at the conclusion of theprocedure, permitting almost all N2O–O2 patients tobe discharged from the dental office unescorted, andwith no prohibitions on their postinhalation sedation

Table 2 Efficacy of Sedation by Routes ofDrug Administration

TechniqueRoute

Titrateto Effect

RapidReversal

ExpectedSuccessRate(%)

Intravenous Yes Yes* 90Inhalation Yes Yes 80IntramuscularIntranasal

No No 67

Oral (adult) No No 50–60Oral (child) No No Older: 50–60

Younger: 35–40General anesthesia† Yes Yes# 0

*Opioids, benzodiazepines.†General anesthesia is not a sedation technique. It is included forcomparative purposes only.#Dependent on route of administration and drug.


activities. No other route of drug administrationoffers this significant advantage. Because of its rapidonset, inhalation sedation with N2O–O2 may betitrated. The ability to titrate increases both the suc-cess and safety of the technique.

In order for a drug to be titrated, it must enter intothe cardiovascular system rapidly. When possible,titration allows the doctor to individualize the dosageof the drug for each patient, negating the so-called‘‘bell-shaped’’ or ‘‘normal distribution’’ curve.

The technique of inhalation sedation with N2O–O2

possesses very few significant disadvantages. One fac-tor, common to it and several other techniques, is thatof patient cooperation. The patient breathes the gassesthrough a small mask placed on the nose, the nasalhood. Uncooperative patients, usually odontophobicyounger children, or any patient who is claustropho-bic, might not allow the nasal hood to be placed,condemning the inhalation route to failure. Personsunable to breathe through their nose, for whateverreason, will be unable to receive inhalation sedationin a dental office. A recommended technique ofadministration of N2O–O2 is outlined in Table 3.

Inhalation sedation with N2O–O2 may be employedto provide minimum to moderate sedation. It may alsobe used, in conjunction with drugs administered byother routes, to supplement the CNS depression theyprovide. N2O–O2 when used in combination with seda-tive agents may produce minimal, moderate, or deepsedation or general anesthesia.11

The use of N2O–O2 inhalation sedation in endodonticsshould become more common given the positive attri-butes of the technique. A common complaint from endo-dontists is that the nasal hood is in the way (Figure 1).Once experience is gained in the technique, this ceases tobe a concern. Inhalation sedation with N2O–O2 has asuccess rate of approximately 80% in adult patients.

ORAL CONSCIOUS SEDATIONThe oral route of drug administration is the least con-trollable route of drug administration. A number offactors work against an orally administered drug beingeffective, including a slow onset of action (~1 hour formost drugs); erratic absorption of the drug from thegastrointestinal (GI) tract; and, for some drugs, a signif-icant hepatic first-pass effect. For these reasons, titrationof the drug to clinical effect is not possible, eliminatingthe most important safety factor in drug administration.

Once administered, the level of CNS depressionreached by oral drugs is not easily increased (providingdeeper sedation) or decreased (lighter sedation).

The duration of CNS depression from orally admi-nistered drugs greatly exceeds the typical length of thedental visit so these patients will always require anescort on being discharged from the office. This escort

Table 3 Technique of Administration of Inhalation Sedationwith N2O–O2

1. Prior to placing nasal hood, start a flow of 5 to 6 LPM (liters per

minute) of O2.

2. Have patient assist in proper placement and securing of the nasal

hood.

3. Determine if patient can ‘‘breathe comfortably’’ with 100% oxygen (‘‘Is

the flow volume adequate?’’). Increase the flow, if necessary.

4. Start titration of N2O by increasing its flow to 1 LPM, decreasing the

O2 flow by 1 LPM.

5. After 1 minute determine what, if any, signs and symptoms the patient

may be experiencing.

6. If needed, increase N2O by 0.5 LPM, decreasing O2 0.5 LPM.

7. Repeat steps 5 and 6 until the patient reaches the desired level of

sedation.

8. Administer local anesthesia as would be done if the patient were not

receiving N2O–O2.

9. At the conclusion of the procedure, increase the O2 flow to the level

determined in step 3 and return the N2O to 0 LPM.

10. Permit the patient to breathe 100% O2 for not less than 3 to 5

minutes before considering removal of the nasal hood.

11. Assess recovery from sedation. If considered recovered, remove nasal

hood before terminating the flow of O2.

12. Permit the patient to leave dental chair. Have a staff person close to

the patient so as to prevent any possible injury when standing, due

to postural hypotension.

13. Document treatment in the patient’s chart.

Figure 1 N2O–O2 nasal hood.

742 / Endodontics

should be a responsible adult who has a vested interestin the health and safety of the patient.

The only advantages associated with the oral routeof drug administration are that it is easier for both thedoctor and the patient.

Having just described a technique that seems quitemediocre compared with other routes of administra-tion, it must be stated that there is a legitimate placefor orally administered CNS depressants in dentistry.

Odontophobic patients, especially when faced withthe fear of root canal treatment, frequently requiremanagement with CNS depressants (1) the night priorto the planned appointment, in order for the patient toexperience a restful night’s sleep, and (2) in the morn-ing, 1 hour prior to the scheduled dental visit, to assistthem in overcoming any last minute increase in theiranxiety.

In the absence of other sedation techniques in adental office, the oral route may also be used for intra-operative sedation. However, owing to the lack of con-trol maintained over this technique by the doctor, thegoal in administering oral CNS depressants should belimited to minimal to moderate CNS depression.

Many excellent oral preparations are currently avail-able for administration. Table 4 presents some com-monly used drugs and their recommended dosages.26,27

When used alone, and in recommended dosages,orally administered drugs will have only an approxi-mately 50 to 60% success rate with adult patients. Thissuccess rate is even lower in younger children.

INTRAVENOUS CONSCIOUS SEDATIONCNS-depressant drugs administered intravenously inthe dorsum of the hand reach the brain in approxi-mately 20 seconds. With this rapid onset, IV drugadministration allows patients to be titrated to adesired level of CNS depression, thereby increasingcontrol over the effect of the administered drug and,ultimately, the safety of the technique. Other advan-tages of IV drug administration include the ability torapidly increase the level of sedation, if needed, and thereversibility of many intravenously administered drugs(benzodiazepines and opioids).

Disadvantages associated with intravenously admi-nistered CNS depressants include the requirement of

Table 4 Common Orally Administered CNS Depressants

Generic Name Proprietary Name Availability (mg)

Usual Dental

Dosage

Benzodiazepines

Alprazolam Niravam, Xanax Tab: 0.25, 0.5, 1.0, 2.0 0.25–0.5 (max 4 mg/day)

Diazepam Valium Tab: 2, 5, 10 2–10 mg bid-qid

Flurazepam Dalmane Cap: 15, 30 15–30 mg at bedtime

Lorazepam Ativan 0.5, 1.0, 2.0 2–3 mg/day given bid-tid

Midazaolam Versed Syr: 2 mg/mL Pediatrics: 0.25–1.0 mg/kg single dose

Oxazepam Serax Cap: 10, 15, 30

Tab: 15

Adults (Anxiety): mild to moderate:

severe: 15–30 tid-qid

Triazolam Halcion Tab: 0.125, 0.25 0.25 qhs, max 0.5

Miscellaneous, non-benzodiazepine anxiolytics, sedatives

Eszopiclone Lunesta Tab: 1.0, 2.0, 3.0 Initial: 2mg qhs

Zaleplon Sonata Cap: 5, 10 Insomnia: 10 qhs

Zolpidem Ambien Tab: 5, 10 Adult: usual 10 mg qhs

Miscellaneous sedative-hypnotic

Chloral hydrate n/a Syr: 500 mg/5ml Adults: 500 mg – 1gr 15–30 mg hs;

max 2 g/day

Hydroxyzine HCl Atarax Syr: 10 mg/5mL Tab: 25, 50, 100 Adults (Sedation): 50–100 mg

Hydroxyzine pamoate Vistaril Cap: 25, 50, 100 Sus: 25 mg/5mL

Tab = Tablet; Syr = Syrup; Cap = Capsule; Sus = Suspension.

Sources: (1) ADA/PDR Guide to Accepted Dental Therapeutics26.

(2) www.ePocrates.com27


fasting prior to the procedure (NPO status); an inabil-ity to quickly lessen the level of CNS depression; aninability to reverse the clinical actions of some drugs(e.g., barbiturates); and prolonged clinical recoverywith an attendant need for an adult escort for thepatient when discharged from the dental office.

Venipuncture is a learned skill and, though nor-mally quite easy to achieve, represents the most diffi-cult part of the entire IV sedation procedure. Oncevenous access is obtained, titration to the desired levelof CNS depression is normally accomplished easily.

Many CNS-depressant drugs are available for IVadministration, but those most often employed arethe benzodiazepines, midazolam (Versed), and diaze-pam (Valium).

State requirements for a permit to employ IV con-scious sedation (also termed ‘‘parenteral sedation’’ or‘‘moderate sedation’’) most often mandate 60 hours ofdidactics and either 10 or 20 cases of IV sedation admi-nistered by the doctor in a supervised environment.15

Variation may exist from jurisdiction to jurisdiction, soit is strongly advised that specific state dental boardregulations be consulted.

Basic IV sedation techniques have evolved over the pastthree decades. The combination of pentobarbital (Nem-butal), meperidine (Demerol), and scopolamine repre-sented the original IV technique introduced in the 1950sby Dr. Neils Bjorn Jorgensen at Loma Linda University.28

As described by Jorgensen, the drugs were injected directlyinto the vein via the syringe that was then removed.29 TheJorgensen technique provided a duration of CNS depres-sion of approximately 2 hours, a function of the barbitu-rate, a pentobarbital. With the introduction in the early1960s of the benzodiazepine diazepam, a shorter durationof CNS depression became possible.30 An additional ben-efit of diazepam was a brief period (approximately 10minutes) of retrograde amnesia, permitting potentiallytraumatic procedures to be done with a likelihood of thepatient not having any recall. For the patient this meant, inessence, that the fearful event (e.g., local anesthetic injec-tion) never happened.

IV conscious sedation with a benzodiazepine hasbecome the most popular technique in dentistry. IVbenzodiazepine sedation meets the needs of contem-porary dental practice, that is, sedation for approxi-mately 1 hour. Introduced in the United States in1986, midazolam (Versed) has now supplanted diaze-pam (Valium) as the most used IV benzodiazepine inthe area of 1-hour IV conscious sedation. Midazolam,

unlike diazepam, is water soluble, thus capable ofbeing administered intramuscularly and intranasally(see following discussions of these techniques). Theamnestic properties of midazolam are considerablygreater than diazepam’s, providing lack of recall formost, if not all, of the dental appointment. Clinicalsedation, however, from the dentist’s perspective, isnot quite as good with midazolam compared withdiazepam. Both drugs, with one titrating dose, providethe doctor with approximately 1 hour of working time.

Direct injection of a drug into a vein, followed byremoval of the syringe at the start of the dental pro-cedure, gave way to the continuous IV infusion, inwhich venous access is maintained for the duration ofthe procedure. Initially, winged needles, also knownas ‘‘scalp vein’’ and ‘‘butterfly needles,’’ were used(Figure 2). Easy to insert, the winged needle has thedisturbing propensity to perforate the vein during thedental procedure, leading to loss of venous accessand formation of a hematoma. In recent years, theindwelling catheter has become increasing popular.

Figure 2 IV needles.

744 / Endodontics

Once inserted and secured in a vein, the 300 plasticcatheter is unlikely to accidentally become dislodged(Figure 3).

Opioids, specifically the short-acting fentanyl, havealso been used in IV conscious sedation with increasedfrequency. When the primary goal of IV drug admin-istration is management of fear, there is usually little orno need for opioid administration. Indeed, in the vastmajority of successful IV sedation cases, the onlydrug(s) administered are either midazolam and/or dia-zepam. However, in situations in which surgery orother dental procedures that may prove painful areplanned, or in which successful pain control may notbe easily achieved with local anesthesia alone, opioidadministration may be justified.

When administered carefully via titration, successrates of 90% may be achieved with IV sedation. TheIV route can be used to achieve moderate and deepsedation, as well as general anesthesia.

INTRAMUSCULARIM, like IV, is a parenteral route of administration, inwhich the drug by-passes the GI tract, being absorbeddirectly into the systemic (venous) circulation. Thehepatic first-pass effect is negated, leading to morereliable absorption and more rapid onset of action(~10–20 minutes) than with enterally administereddrugs. However, titration is not possible, as the onsetis not rapid enough, thus denying the IM route a

major safety benefit and thereby limiting its indica-tions for use in sedation in dentistry.

Doses of IM drugs are primarily determined on aweight (e.g., mg/kg) basis. Given the appropriatedosage, approximately 70% of patients should be CNSdepressed to the desired level of sedation. However,another 15% will likely be undersedated with that samedose, whereas the remaining 15% are CNS depressed toa level beyond that which is being sought. This lattergroup, hyperresponders to the drug, may be CNSdepressed to a level beyond which the doctor is ableto safely manage them. For example, an IM drug isadministered to a patient to achieve a level of moderatesedation (formerly termed ‘‘conscious sedation’’).However, the resultant level of CNS depression is deepsedation. At this level, patients are unable to adequatelymaintain their airway without assistance (e.g., head-tilt,chin-lift). Dental care would, of course, need to bepostponed as the doctor is required to ‘‘rescue’’patients from this unintended level of CNS depression.Airway management and, possibly, ventilatory assis-tance are continued until the level of CNS depressionlightens, a process that could require several hours.

Along with the inability to titrate IM drugs, it is alsonot possible to rapidly lessen or deepen the level ofsedation. Reversal of intramuscularly administereddrugs, if possible, by intravenously administered fluma-zenil or naloxone, would be somewhat successful for aperiod of time. However, as a reservoir of the IM drugexists within the muscle into which it was injectedpreviously, the drug will continue to be absorbed overseveral hours leading to the likelihood of a reboundsedation effect occurring as the action of the intrave-nously administered reversal agent diminishes. IMadministration of the reversal agent is generally notrecommended as its onset, 10 to 20 minutes, is too slowto provide any immediate relief in the event of over-sedation. Additionally, the degree of the intramuscularlyadministered reversal agent’s effectiveness would be lessthan that seen following its administration IV.

IM drugs are not as controllable as intravenouslyadministered drugs. Sedation should therefore be lim-ited to a moderate level, with the doctor trained torecognize and manage (e.g., rescue) the patientsshould they inadvertently enter deep sedation.Patients receiving IM drugs for sedation must alsomaintain NPO status prior to sedation.

Recovery from IM drugs is prolonged; thus, thepatient must have an adult escort when being dis-charged from the office. This being said, it would seemthat IM drugs have few indications in dentistry. How-ever, used judiciously by the doctor trained in parent-eral conscious sedation (IV, IM, IN), the technique

Figure 3 Indwelling catheter.


can be employed with a likelihood of success of about67%. Midazolam is the most commonly employed IMCNS-depressant drug in conscious sedation.

INTRANASALThe IN administration of CNS-depressant drugs is rela-tively new within medicine and dentistry, though it hasbeen used for many years by drug abusers (e.g., cocaine)and for the administration of nasal decongestants.

Nasal mucosa is highly vascular; therefore, absorp-tion of drugs instilled into the nares is more rapidthan for other routes of administration. Lam et al.25

compared the efficacy, in children, of IN midazolamwith that of its IM administration, finding the levelof sedation to be comparable. IN midazolam hasalso been adopted in emergency medicine in themanagement of acute seizures in pediatric patients.31

Primosch32 compared nasal drops versus nasal sprayas a technique of IN drug administration and foundthat although the effectiveness of conscious sedationwas not influenced by the method of nasal adminis-tration, spray administration produced significantlyless aversive behavior than administering drops in2- to 3-year-old dental patients of similar behavioralcharacteristics.

Most studies and clinical usage of the IN route ofdrug administration appear in pediatrics, there beingfew reports of the use of this technique, and of itseffectiveness, in adults, thereby limiting its utility inmost endodontic cases.

The advantages of IN drug administration include itsmore rapid onset of action (compared with enteralroutes) and the lack of need for injection and theaccompanying trauma, both psychological and physical,associated with it.

Disadvantages of IN drug administration are simi-lar to those of IM. IN drugs cannot be titrated.Dosages are based on weight (mg/kg). Along withthe inability to titrate IN drugs, it is also not possibleto rapidly lessen or deepen the level of the resultantCNS depression. Reversal of intranasally administereddrugs, if possible, by intravenously administered flu-mazenil or naloxone, would be somewhat successful.IM or IN administration of a reversal agent is gener-ally not recommended as its onset, 10 to 20 minutes,is too slow to provide any immediate relief in theevent of oversedation. Additionally, the efficacy ofan IM or IN reversal agent would be less than thatseen with its IV administration.

IN drugs are not as controllable as intravenouslyadministered drugs. The level of CNS depressionsought should, therefore, be limited to moderate, withthe doctor trained to recognize and manage (e.g., res-

cue) the patients should they enter into deep sedation.Patients receiving IN drugs for sedation must alsomaintain NPO status prior to sedation.

Recovery from IN drugs is prolonged, thus therequirement for an adult escort for the patient whendischarged from the office.

Techniques of conscious sedation will enable theendodontist to manage the dental fears of the over-whelming majority of odontophobic patients. Table 6illustrates the possible uses of the techniques of con-scious sedation in endodontic practice. Unfortunately,not all fears can be successfully managed with con-scious sedation techniques. For these few patients,general anesthesia is required.

GENERAL ANESTHESIAGeneral anesthesia is the controlled loss of consciousness,the final step in our continuum of CNS depression thatstarted with minimal sedation. The success rates of thesedation techniques described above, along with theamnestic properties of some of the drugs employed,specifically the benzodiazepines midazolam and triazo-lam, has decreased the need for general anesthesia as amethod of managing significant numbers of odontopho-bic patients.

All 50 states regulate the use of general anesthesia indentistry.14 A residency in anesthesiology of either 1- or2-year duration usually represents the educationalrequirement. As of November 2007, seven residenciesin anesthesiology for dentists were accredited by theAmerican Dental Board of Anesthesiology.33

Doctors who have completed accredited residen-cies, dentist anesthesiologists, provide anesthesia ser-vices for other dentists either (1) by establishing afree-standing outpatient surgical center, in which theendodontist (or any other dentist) brings the odonto-phobic patient to the surgical center to carry out thescheduled procedures while the patient receives gen-eral anesthesia provided by the dentist anesthesiolo-gist, or (2) by traveling to the office of the dentist whowill be managing the dental needs of the fearfulpatient, wherein dentist anesthesiologists bring alongall of their anesthesia drugs, equipment, and expertise.

Once general anesthesia has been induced by thedentist anesthesiologist, the dentist can then proceedwith the endodontic procedure on a now more nearly‘‘ideal’’ patient.

SUMMARYDental fears exist and are a fact of life, especially in thespecialty of endodontics. The primary obstacles to suc-cessful endodontic treatment are the presence of dual

746 / Endodontics

problems: pain and fear. To ignore fear, in the best ofcircumstances, will complicate dental treatment unne-cessarily, as the patient remains an unwilling partici-pant throughout the procedure. Fear lowers the painreaction threshold, with odontophobic patients being

unable to sit still during their treatment, adding to thefrustration of the treating doctor. Fear increases cate-cholamine release into the cardiovascular system with aresultant rise in the incidence and severity of medicalemergency situations.

Table 5 Comparison of Routes of Drug Administration

Route of Drug

Administration Onset of Action

Titrate

Yes–

No Advantages Disadvantages

Inhalation Rapid (~20 seconds) Yes Patient need not be NPO; rapid onset;

titration; rapidly increase

or decrease level of CNS depression;

full recovery in most patients; no

prohibitions of postoperative functions

Patient cooperation required; ineffective

if unable to breathe through nose

Oral Slow (~ 1 hour for

maximal

clinical effect)

No Easy for patient; easy for doctor Patient cooperation needed; slow onset;

inability to titrate; erratic absorption from

GI tract; significant hepatic 1st-pass effect for

some drugs; no control over ultimate level of

CNS depression; inability to quickly increase

or decrease level of CNS depression; inability

to reverse CNS depression; prolonged recovery;

requirement for escort for patient on leaving

dental office

Parenteral:

Intramuscular

Intermediate

(10–20 minutes)

No More reliable absorption than

oral; minimal patient cooperation

required

Patient must be NPO; potential needle injury;

relatively slow onset; inability to titrate; no

control over ultimate level of CNS depression;

inability to quickly increase or decrease level of

CNS depression; inability to reverse CNS depression;

prolonged recovery; requirement for escort for

patient on leaving dental office

Parenteral:

Intravenous

Rapid (~20 seconds) Yes Rapid onset; titration; rapidly

increase level of CNS depression;

most drugs reversible

Venipuncture is learned technique; patient

must be NPO; inability to quickly decrease level of

CNS depression; prolonged recovery; requirement

for escort for patient on leaving dental office

Parenteral:

Intranasal

Intermediate

(10–20 minutes)

No More reliable absorption than

oral; minimal patient cooperation

required

Unpleasant (bitter) taste if liquid enters oral cavity;

may irritate nasal mucosa; inability to titrate; no

control over ultimate level of CNS depression;

inability to quickly increase or decrease level of

CNS depression; inability to reverse CNS depression;

prolonged recovery; requirement for escort for patient

on leaving dental office

Table 6 Techniques of Conscious Sedation—Summary

Preoperative PerioperativeAbility to

Titrate

CNS DepressionLevel WhenUsed Alone

CNS DepressionLevel Used inCombination

Night priorto treatment

Morning oftreatment

Oral sedation Yes Yes Yes No Min, mod Min, mod, deep, GAInhalation Yes Yes Mod Mod, deep, GAIV Yes Yes Mod, deep, GA Mod, deep, GAIM/IN Yes No Mod, deep, GA Mod, deep, GA

Min = minimal sedation; Mod = moderate sedation; Deep = deep sedation; GA = general anesthesia.


The recognition of fear, and its management,removes the primary obstacle to the delivery of healthcare. Once fear is eliminated, clinically adequate paincontrol is normally accomplished quite readily. AsPeter Milgrom wrote, ‘‘Deal with the fear first, thenpain will be a minor problem.’’5,34

References

1. Our most common fears. Dental Health Advisor, Spring 1987.

2. Dionne DA, Gordon SM, McCullagh LM, Phero JC. Assessingthe need for anesthesia and sedation in the general popula-tion. J Am Dent Assoc 1998;129(2):167–73.

3. Gatchel RJ, Ingersoll BD, Bowman L, et al. The prevalence ofdental fear and avoidance: a recent survey study. J Am DentAssoc 1983;107(4):609–10.

4. Chanpong B, Haas DA, Locker D. Need and demand for seda-tion or general anesthesia in dentistry: a national survey of theCanadian population. Anesth Prog 2005;52(1):3–11.

5. Enkling N, Martwinski G, Johren P. Dental anxiety in arepresentative sample of residents of a large German city. ClinOral Investig 2006;10(1):84–91.

6. Malamed SF. Beyond the basics: emergency medicine in den-tistry, J Am Dent Assoc 1997;128(7):843–54.

7. Matsuura H. Analysis of systemic complications and deathsduring dental treatment in Japan. Anesth Prog 1990;36:219–28.

8. Broadbent JM, Thomson WM. The readiness of New Zealandgeneral dental practitioners for medical emergencies. NZDent J 2001;97:82–6.

9. American Association of Oral and Maxillofacial Surgeons.Parameters of care for oral and maxillofacial surgery: a guidefor practice, monitoring and evaluation, Rosemont, Ill: TheAssociation of Oral and Maxillofacial Surgeons; 1995.

10. Academy Report: The use of conscious sedation by period-ontists. J Periodontol 2003;74:933.

11. American Dental Association. Guidelines for the use of sedationand general anesthesia by dentists. Draft 11 November 2006.

12. American Society of Anesthesiologists Task Force on Sedationand Analgesia by Non-Anesthesiologists. Practice guidelinesfor sedation and analgesia by non-anesthesiologists. Anesthe-siology 2002;96(4):1004–17.

13. Ohio State Dental Board, Ohio State Dental Board Law andRules, Columbus, Ohio, 1974.

14. Department of State Government Affairs, 30a Statutory Require-ments for general anesthesia/deep sedation, American DentalAssociation, December 21, 2006, Chicago, IL.

15. Department of State Government Affairs, 30b ConsciousSedation Permit Requirement, American Dental Association,December 21, 2006, Chicago, IL.

16. American Academy of Pediatrics. American Academy of PediatricDentistry. Cote CJ, Wilson S. Work Group on Sedation. Guide-lines for monitoring and management of pediatric patients duringand after sedation for diagnostic and therapeutic procedures: anupdate. Pediatrics 2006;118(6):2587–602.

17. Dental Board of California, Chapter 2, Article 5.5. Oral con-scious sedation. Dental Board of California, Sacramento, [email protected] 2000 accessed 9 Febuary 2007.

18. Feck AS. Goodchild JH. The use of anxiolytic medications tosupplement local anesthesia in the anxious patient. CompendContin Educ Dent 2005;26(3):183–6, 188, 190.

19. Dionne RA, Yagiela JA, Cote CJ, et al. Balancing efficacy andsafety in the use of oral sedation in dental outpatients. J AmDent Assoc 2006;137(4):502–13.

20. Clark M, Brunick A. Handbook of nitrous oxide and oxygensedation. 2nd ed. St. Louis: C.V. Mosby; 2003.

21. American Dental Association Seal of Acceptance Program.www.ada.org/ada/seal/index.asp accessed 9 Febuary 2007.

22. Commission on Dental Accreditation, Accreditation standard23, American Dental Association, Chicago, IL 2006.

23. Friedman N. Iatrosedation. In: McCarthy FM, editor. Emer-gencies in dental practice. 3rd ed. Philadelphia: WB Saunders;1979.

24. Malamed SF. Iatrosedation. In: Malamed SF, editor. Sedation:a guide to patient management. 4th ed. St. Louis: CV Mosby;2002.

25. Lam C, Udin RD, Malamed SF, et al. Midazolam premedica-tion in children: a pilot study comparing intramuscular andintranasal administration. Anesth Prog 2005;52(2):56–61.

26. Byrne BE, Tibbetts LS, editors. Conscious sedation and agentsfor the control of anxiety. In: ADA/PDR guide to accepteddental therapeutics, 4th ed. Chicago, IL: ADA PublishingDivision; 2006, pp. 23–51.

27. www.ePocrates.com

28. Jorgensen NB, Leffingwell FE. Premedication in dentistry. JSouth Calif Dent Assoc 1953;21:25.

29. Jorgensen NB, Hayden J Jr. Premedication, local and generalanesthesia in dentistry. Philadelphia: Lea amp; Febiger; 1967.

30. O’Neill R, Verrill PJ, Aellig WH, et al. Intravenous diazepamin minor oral surgery. Br Dent J 1970;128:15.

31. Harbord MG, Kyrkou NE, Kyrkou MR, et al. Use of intranasalmidazolam to treat acute seizures in paediatric community set-tings. J Paediatr Child Health 2004;40(9–10):556–8.

32. Primosch RE, Guelmann M. Comparison of drops versusspray administration of intranasal midazolam in two- andthree-year-old children for dental sedation. Pediatr Dent2005;27(5):401–8.

33. www.asdahq.org/training.html accessed 23 November 2007.

34. Milgrom P, Weinstein P, Getz T. Treating fearful dental patients:a patient management handbook. 2nd ed. Seattle, WA: Univer-sity of Washington Continuing Dental Education; 1995.12

748 / Endodontics

CHAPTER 24

THE MEDICALLY COMPLEX ENDODONTIC

PATIENT

BRADFORD R. JOHNSON, DENA J. FISCHER, JOEL B. EPSTEIN

One of the challenges faced by dental specialists today isin the assessment and management of patients withincreasingly complex medical conditions. Not only hasthe average life expectancy increased dramatically overthe past 50 years, but our geriatric patients are muchmore likely to be at least partially dentulous and have acomplex medical history with multiple medical problemsand the use of multiple medications.1 Approximately25% of patients aged 65 to 74 and 35% of patients aged75 and older have a medical condition that wouldplace them in the ASA (American Society of Anesthesiol-ogists’ Health Classification System) category III or IV(Figure 1).2 An aging population with both the desireand resources to preserve their natural dentition willdrive the demand for root canal therapy for patients withcomplex medical conditions. Even in a typical popula-tion of younger and presumably healthier patients,approximately 50% of patients referred to a dental speci-alty practice can be expected to report at least one posi-tive finding on their health history questionnaire.1,3 Sincemedical complexity is often an indication for referral to adental specialist,4,5 endodontists should be prepared toaccurately evaluate medically complex patients and iden-tify situations that require a modification of normaltreatment procedures and identify oral and systemicconditions requiring diagnosis and management.

The purpose of this chapter is to serve as a briefoverview of common medical conditions that requiresome modification of the treatment protocol toensure safe endodontic treatment in an ambulatorydental setting. It is not intended as a substitute forcase-specific clinical judgment or consultation withmedical experts. For the purposes of this chapter, amedically complex patient will be defined as anypatient requiring modification of the usual treatmentprocedure.

MEDICAL HISTORY AND PATIENTINTERVIEW

‘‘Never Treat a Stranger’’ (Attributed to SirWilliam Osler)The value of a thorough medical history and patientinterview cannot be overemphasized. Recognition of amedical condition that requires treatment modifica-tion prior to treatment can avert significant treatmentcomplications. Approximately 25 to 30% of patientsseeking treatment in a dental office can be expected toreport at least one medical condition that has poten-tial relevance to dental treatment, although not all ofthese conditions will require treatment modifica-tion.6,7 An adverse outcome, due to failure to recog-nize a known risk factor and modify treatmentaccordingly, is a major predictor of a successful liabi-lity claim.8 Cardiovascular disease, drug allergies, dia-betes, and concerns about the safety of vasoconstrictoruse are some of the most common medical reasonsfor referral to a specialist.1,9,10 This is consistent withan analysis of the most common medical emergenciesin the dental office: angina, hypoglycemia, adversereaction to local anesthetics, and seizures.11

A standard health history questionnaire should coverall common medical conditions (both treated anduntreated), surgeries, hospitalizations, medications, andallergies. Although many standard forms are readily avail-able and are usually convenient and easy to complete,most of these forms do not clearly lead to a specificdetermination of risk for dental treatment. More usefulmedical risk assessment models are under developmentand will be briefly discussed later in this section. Thewritten health history questionnaire should always besupplemented with a patient interview to help decrease

749

false-positive and false-negative findings and to furtherexplore positive findings.12 The clinician should reviewany positive findings with the patient and determine thepatient’s level of compliance with medical treatmentrecommendations. For example, a compliant patient withwell-managed hypertension presents a relatively low riskcompared to a patient who refuses to take prescribedmedications or does so erratically. Unfortunately, for avariety of reasons, the reliability of self-reported informa-tion in the health history may be less than ideal. Patientsmay simply forget to report important medical informa-tion, but it has also been shown that some patients willintentionally omit relevant information due to concernsover privacy or failure to understand how the informationcould be relevant to dental practice.13,14

MEDICATIONS AND ALLERGIESThe list of medications and allergies should be con-sistent with the disclosed medical conditions and can

alert the clinician to unlisted medical conditions aswell as potential drug interactions. Relevant medicalconditions and severity of systemic disease can oftenbe determined by a careful analysis of the patient’slist of medications.15 Allergies to materials used inendodontic treatment are covered later in this chap-ter and drug interactions are covered in Chapter 25,‘‘Drug Interactions and Laboratory Tests.’’

Herbs, dietary supplements, vitamins, and otherover the counter medications can contribute to com-plications in the dental setting, although patientsoften fail to report the use of these substances in theinitial evaluation.16 In a recent survey of surgicalpatients, approximately one-third reported the useof a nonprescription medication that could poten-tially inhibit coagulation or interact with anes-thetics.17 In particular, Ginkgo biloba, ginger, garlic,ginseng, feverfew, and vitamin E all inhibit plateletaggregation and can increase the risk of bleeding.18

Ingredients in over-the-counter (OTC) weight loss

ASA physical

classification Description

Therapy modifications (McCarthy and

Malamed, 1979)

ASA 1 A normal healthy patient None (stress reduction as indicated)

ASA 2 A patient with mild

systemic disease

Possible stress reduction and other

modifications as needed

ASA 3 A patient with a severe

systemic disease that

limits activity, but is not

incapacitating

Possible strict modifications; stress

reduction and medical consultation are

priorities

ASA 4 A patient with an

incapacitating systemic

disease that is a constant

threat to life

Minimal emergency care in office (may

consist of pharmacologic management

only); hospitalize for stressful elective

treatment; medical consultation urged

ASA 5 A moribund patient who

is not expected to survive

without the operation

Treatment in the hospital is limited to life

support only; for example, airway and

hemorrhage management

ASA 6 A declared brain-dead

patient whose organs are

being removed for donor

purposes

Not applicable

Figure 1 American Society of Anesthesiologists’ (ASA) health classification system and suggested treatment modifications. Adapted from Tables 1 and 2,Goodchild J and Glick M.27

750 / Endodontics

products can potentiate the effect of epinephrine andincrease cardiac stress, although the most obviousexample of this phenomenon, ephedra, has beenremoved from the US market by FDA order.

PREVIOUS DENTAL TREATMENTA standard screening question for all patients shouldenquire about any problems with previous dental treat-ment. This line of questioning serves several importantfunctions. First, it allows the patient to discuss anyprevious negative dental experiences as well as expresspossible anxiety related to the proposed treatment. Areport of difficulty in achieving profound local anesthe-sia is a common finding, especially for root canaltherapy. This provides an opportunity to demonstrateconcern for your patient and discuss how you plan toavoid a repeat of the previous experience. Second,potential adverse reactions to dental materials or drugsmay emerge in response to this question. Finally, sincethis question is designed at least in part to help developrapport with your patient, it can serve as a good leadinto other important but potentially more sensitivequestions (e.g., use of oral contraceptives, history ofhuman immunodeficiency virus (HIV))

PHYSICAL EXAM: VITAL SIGNSIn addition to the mandatory health history ques-tionnaire and patient interview, vital signs (bloodpressure, heart rate, respiratory rate, temperature,height, and weight) should be recorded prior todental treatment whenever possible. In particular,blood pressure, heart rate, and respiratory rate pro-vide the essential risk assessment baseline informa-tion for all patients. Temperature may be routinelyrecorded but is specifically indicated in the presenceof infection or signs of generalized malaise or toxi-city. Height and weight can usually be obtained fromthe patient or the guardian, and this information isparticularly important in determining appropriatedrug dosages in pediatric and geriatric patients andin assessing unexplained changes in weight.

RELATIVE STRESS OF THE PLANNEDPROCEDURE AND BEHAVIORALCONSIDERATIONSA patient’s ability to tolerate the stress of dental treat-ment depends on the procedure planned, timerequired to complete the procedure, physical healthstatus, and psychological factors. Anticipation of astressful dental procedure can increase the heart rate

and endogenous secretion of epinephrine in otherwisehealthy adults.19,20 In fact, even anticipation of aroutine dental checkup can result in increased bloodpressure in some patients.21 Most changes in heartrate and blood pressure are within the normal phy-siological range, although more significant changeshave been observed before administration of localanesthetic, during subgingival scaling and duringextractions.22 Since there are no specific guidelinesfor assigning stress levels to various dental procedures,clinical judgment is essential in determining whetheror not stress-reducing treatment modifications shouldbe employed. Dental specialists, by virtue of addi-tional training and experience, should be expected toprovide treatment in a shorter time period and shouldbe better prepared to manage perioperative complica-tions than a general practitioner.

Endodontic treatment in general is often consid-ered a high-stress dental visit, especially amongpatients with no prior endodontic treatment experi-ence or patients who have had a previous negativeexperience with endodontic treatment. For many,the perception of the treatment often differs fromthe reality that most current endodontic treatment isminimally invasive, relatively comfortable, efficientand very well tolerated by the majority of patientswhen skillfully performed. In a study that measuredsalivary cortisol levels in patients undergoing a vari-ety of dental procedures, root canal treatment was nodifferent than a routine dental exam, prophylaxis, orrestorative treatment, and only tooth extractionresulted in a significant increase in salivary corti-sol.23 Surgical root canal procedures, the presenceof acute pain, self-reported dental anxiety, or diffi-culty with previous treatment, and lengthy proce-dures would all be expected to increase the level ofstress.22,24 If any of these conditions are present inaddition to significant systemic disease, treatmentmodification including a stress reduction protocolshould be considered (see Chapter 23, ‘‘Anxietyand Fear in Endodontics’’).

PHYSICAL HEALTH STATUSThe American Society of Anesthesiologists’ (ASA)Health Classification System is the most widely usedsystem for assessing physical health status and helpsto determine the potential need for medical consul-tation and treatment modifications prior to dentaland medical procedures (see Figure 1). In general,ASA I status represents a healthy patient who doesnot require any treatment modification. An ASA IIpatient presents with well-controlled systemic

Chapter 24 / The Medically Complex Endodontic Patient / 751

disease and usually will not require significant treat-ment modification, although stress reduction may beindicated. Patients in the ASA III category or abovewill almost always require medical consultation andpossible treatment modifications. However, the ASAclassification system has several significant limita-tions and should be used only as a general guidefor determining peri- and postoperative risk. Evenexperienced anesthesiologists exhibit differences ofopinion in the classification of cases.25,26 In addition,when used alone, the ASA system is not a goodpredictor of operative risk.27 Various authors haveproposed a medical risk assessment process thatfocuses more clearly on medical conditions specifi-cally relevant to dental practice.2,6,27,28 Cliniciansmay want to consider health history questionnairesand verbal questions that focus primarily on medicalconditions that would, when present, elevate thepatient to ASA II status or above. That is, any posi-tive response to one of the health history questionswould automatically classify the patient as at leastASA II and further exploration would be necessary todetermine the extent of systemic disease. de Jonget al.12,28,29 have developed and validated a patientquestionnaire consisting of approximately 30 questionsfor use in assessing the risk for dental treatment.

MEDICAL CONSULTATIONSApproximately one-third of patients referred for a med-ical consultation result in recommendations for somemodification of treatment procedures.9 A request forconsultation may occur by phone or letter and eachapproach has certain advantages and disadvantages. Aphone conversation is immediate and may allow for thediscovery of additional useful information. However,the lack of a written letter from the physician increasesthe risk for potential misunderstanding and provides alower level of documentation from a medicolegal stand-point. The substance of all medical consultation con-versations should be documented in the patient’s recordand, whenever possible, a letter detailing the physician’srecommendations should be requested. A letter pro-vides more formal documentation of the communica-tion between health care providers.

When requesting a medical consultation, the clini-cian should be specific and concise. The medical con-dition in question should be identified and the natureof dental procedure planned should be described (e.g.,a brief description of the procedure, the type of anes-thetic planned, the potential for bleeding, the expectedlength of procedure). The clinician should specificallyask the physician if the patient’s medical condition

requires any modification in the usual treatment pro-tocol and, if so, what modifications are recommended.Since the ultimate responsibility for providing safetreatment rests with the dentist, any concerns aboutrecommended treatment modifications should beresolved with the physician prior to treatment.

Assessing the Need for Treatment

Modifications

MULTIDIMENSIONAL RISK ASSESSMENTMODEL (MD-RAM)Systemic disease can result in the loss of reserve capa-city to handle stress.15 A patient’s ability to handlestress decreases in direct relation to the extent of sys-temic disease. The three primary components of riskassessment for dental treatment are physical healthstatus (reserve capacity), emotional or psychologicalstatus, and type of dental procedure planned.30

Lapointe et al.15 proposed a two-dimensional riskassessment model that correlated the severity of diseaseand procedural stress. However, this model presentedonly two specific medical conditions as examples(ischemic heart disease and chronic obstructive pul-monary disease (COPD)) and did not explicitly con-sider patient anxiety as a variable. Dental anxiety canincrease sympathetic activity and for some patients canpotentially precipitate a medical emergency.31

We propose a new model, the MultidimensionalRisk Assessment Model (MD-RAM; Figures 2 and 3),that incorporates the three primary aspects of riskassessment into a unified approach for evaluatingperioperative risk related to treatment for the ambu-latory dental patient. In this model, the dental patientis assigned a score ranging from 1 to 4 in each of thethree domains: physical health status (using the ASAclassification system); procedural stress (type ofprocedure, length of time to complete the procedure,and clinician expertise—Figure 4); and psychologicalstatus (self-reported dental anxiety—Figure 5). Aswith any model, the output is only as good as theinformation input.

This model may provide a general guide for patientassessment and is not intended to be all inclusive or asubstitute for case-specific clinical judgment. Theprimary purpose of this model is to assist cliniciansin determining if treatment modification, often astress reduction protocol, may be indicated prior todental treatment. Disease-specific recommendationswill be discussed later in the chapter.

752 / Endodontics

Figure 2 Multidimensional Risk Assessment Model (MD-RAM).

MD-RAM score Interpretation

3-5 No treatment modification usually

indicated

6-7 Possible medical consultation and

treatment modification

8-9 Medical consultation often indicated and

probable treatment modification

10-12 Medical consultation strongly advised;

may require treatment in a hospital or

specially equipped out-patient facility

Figure 3 Interpretation of MD-RAM score.


Cardiovascular Disease

HYPERTENSIONHypertension is one of the most common medicalconditions likely to be encountered in a dental office.Hypertensive patients are defined as those receivingtreatment for hypertension or those with a mean systo-lic blood pressure (SBP) of 140 mg Hg or greater and/ora mean diastolic blood pressure (DBP) of 90 mg Hg orgreater. By this definition, approximately 24% of theadult population of the United States is hypertensivewith about half of this group untreated and only one-

quarter receiving successful treatment for hyperten-sion.32 The goal for patients with diabetes or renaldisease is to maintain blood pressure below SBP of130 and DBP of 80. Since hypertension is typicallyasymptomatic, approximately one-third of patientswith high blood pressure are unaware of their condi-tion.33 Even patients with normal blood pressure at theage of 55 to 65 years have an almost 90% risk of devel-oping hypertension by the age of 80 to 85 years.34

Patients with untreated or inadequately treated hyper-tension are at significantly increased risk for acute com-plications such as myocardial infarction (MI) andstroke and chronic complications of hypertension.

Dental anxiety scale Verbal descriptor

1 No anxiety

2 Mild anxiety

3 Moderate anxiety

4 Severe anxiety

Figure 5 Behavioral scale—patient’s self-reported dental anxiety.

Procedural stress scale Examples*

1 Denture adjustment; non-invasive oral

exam; radiographs

2 Procedures requiring local anesthesia;

prophylaxis with sub-gingival scaling;

simple restorative procedures;

uncomplicated non-surgical root canal

treatment

3 Patients with acute pain and/or significant

infection; extractions; surgical root canal;

periodontal surgery

4 Bony impactions; trauma surgery

* = The clinician should consider possible upgrading if procedure is lengthy and move either up or down depending on clinician’s experience.

Figure 4 Estimating procedural stress. Adapted in part from Lapointe HJ et al.15

754 / Endodontics

The clinical significance to the dental practitioner isclear—since at least 15% of all adult dental patients haveeither untreated or inadequately treated hypertension,initial blood pressure measurement is an essential screen-ing tool prior to dental treatment. In addition, it isappropriate to measure blood pressure at least annuallyduring recall visits for all patients and at every visit forpatients when an invasive dental procedure is planned.

Guidelines for the classification of blood pressurewere recently revised in the seventh report of the JointNational Committee on Prevention, Detection, Eva-luation, and Treatment of High Blood Pressure (JNC7, 2003) (Figure 6). The JNC 7 report added a newcategory, prehypertension, for patients with SBP of120 to 139 and/or DBP of 80 to 89 in recognition ofthe fact that this group was at greater risk for devel-oping hypertension and should receive lifestyle mod-ification advice and subsequent monitoring. Thereport also combined the previous Stage 2 and Stage3 categories into a new Stage 2 category for patientswith SBP greater than or equal to 160 and/or DBPgreater than or equal to 100. From a practical stand-point, patients with well-controlled hypertension orSBP below 160 and DBP below 100 should tolerate allroutine dental procedures,35 although referral for eva-luation by the patient’s physician is appropriate dueto the well-documented benefits of maintaining bloodpressure in the normal range. Patients with SBPbetween 160 and 180 or DBP between 100 and 110should also be able to tolerate most dental procedureswithout significantly increased risk of perioperativecardiovascular complications; however, complexityand stress of the planned treatment should be care-fully considered with attention given to stress reduc-

tion strategies prior to treatment.36 Although clearguidelines for establishing a cutoff point for dentaltreatment (emergency or routine) are lacking, it isgenerally accepted that patients with SBP greater than180 and/or DBP greater than 110 should be referredfor medical consultation and treatment prior to den-tal treatment and only emergency management ofpain or acute infection should be considered.36

Patients with SBP above 210 and/or DBP above 120should be referred for emergent medical evaluation.

VASOCONSTRICTOR USE IN PATIENTSWITH CARDIOVASCULAR DISEASEVasoconstrictors are used routinely in endodontictherapy as a component of local anesthetics and oftenas a hemostatic agent during periapical surgery. Localanesthetic with a vasoconstrictor, most commonlylidocaine with 1:100,000 epinephrine, is the usualanesthetic of choice for root canal therapy, althoughmany nonsurgical procedures can be performed usinglocal anesthetics without vasoconstrictor.37 When avasoconstrictor is indicated, epinephrine is preferredover norepinephrine or levonordefrin due to adecreased potential for alpha-1 receptor stimulation.Surgical procedures typically require greater quanti-ties of local anesthetic with a vasoconstrictor thannonsurgical root canal treatment. In particular,patients with advanced cardiovascular disease, geria-tric patients, and patients taking certain medications(e.g., MAO inhibitors and nonselective beta blockers)may have a reduced tolerance for vasoconstrictor-containing local anesthetics. Since local anestheticswith vasoconstrictors are very helpful in obtaining

ClassificationSystolic Blood Pressure

(SBP) in mm HgDiastolic Blood Pressure

(DBP) in mm Hg

Normal < 120 and < 80

Prehypertension 120-139 or 80-89

Stage 1 Hypertension* 140-159 or 90-99

Stage 2 Hypertension ≥ 160 or ≤ 100

* For patients with diabetes or renal disease, the goal is to maintain blood pressure less than 130/80 mm Hg.

Figure 6 Blood pressure classification for adult patients. Adapted from Herman WW et al.36


adequate hemostasis and visibility during periapicalsurgery, it may be difficult to perform the procedureusing anesthetics without vasoconstrictors.38

The use of local anesthetics with vasoconstrictors inpatients with cardiovascular disease has been some-what controversial and was addressed by the JNC 7report. While the general goal should be to minimizethe use of vasoconstrictors in patients with cardiovas-cular disease, the benefit of greater depth and dura-tion of anesthesia when local anesthetics with avasoconstrictor are used is a significant argument infavor of their use. Adequate pain control is an essen-tial component of endodontic therapy since pain-related stress could stimulate the release of significantquantities of endogenous catecholamines. Differentkinds of stress can increase the release of endogenousepinephrine by as much as 20 to 40 times over base-line values.39 Pooled results from six studies ofpatients undergoing extraction or other minor oralsurgery procedure demonstrated an average increasein SBP and DBP of 11.7 and 3.3 mm Hg, respectively,as well as an increase in heart rate of 4.7 beats perminute (bpm). The use of local anesthetics containingepinephrine for these procedures resulted in an addi-tional relatively minor increase in SBP of 4 mm Hgand 6 bpm.32 Careful aspiration and use of adequategauge needle to facilitate aspiration during injection isrequired to minimize the chance of intravascularinjection. Most authors feel that 0.036 to 0.054 mgof epinephrine (approximately two to three cartridgesof local anesthetic with 1:100,000 epinephrine) shouldbe safe for all patients except those with severe cardi-ovascular disease or other specific risk factors, andthose with SBP requiring urgent medical atten-tion.36,40,41 Local anesthetics with vasoconstrictorsshould be avoided or used with extreme caution inpatients with the following cardiovascular conditions:severe or poorly controlled hypertension, arrhythmiasthat are refractory to treatment, MI within the pastmonth, stroke within the past 6 months, coronaryartery bypass graft within the past 3 months, anduncontrolled congestive heart failure (CHF).30

An important exception to this general rule regard-ing vasoconstrictors is the choice of local anestheticfor intraosseous (IO) injections in patients with car-diovascular disease. IO injections are most commonlyused as a supplemental anesthetic technique for teeththat are otherwise difficult to anesthetize. A transientincrease in heart rate can be expected in about two-thirds of patients receiving an IO injection usinglidocaine with 1:100,000 epinephrine, although heartrate returns to near baseline within 4 minutes afterinjection.42 No increase in heart rate was found

in patients receiving an IO injection with a 3% mepi-vacaine solution. Although in this study no signifi-cant change in blood pressure was found in eithergroup, the authors recommended 3% mepivacainewithout vasoconstrictor for patients with any medicalcondition that could reduce their tolerance forepinephrine.

Although most experts agree that the use of gingivalretraction cord containing epinephrine should beavoided in patients with significant cardiovascular dis-ease,36,40 some uncertainty exists over the use of racemicepinephrine-impregnated pellets as recently advocatedfor improved hemostasis during periapical surgery.38,43

In two clinical studies, no significant changes wereobserved in blood pressure or heart rate when epinephr-ine pellets (either cotton or collagen) were placed in thebony crypt to improve hemostasis during periapicalsurgery.44,45 It is unlikely that a patient healthy enoughto tolerate two or three cartridges of local anestheticwith 1:100,000 epinephrine would experience anyuntoward effects from the proper use of epinephrine-impregnated pellets during periapical surgery. Regard-less, other alternative topical hemostatic agents areavailable and should be considered for patients withsignificant cardiovascular disease.

ISCHEMIC HEART DISEASEWhen coronary atherosclerotic heart disease becomessufficiently advanced to produce symptoms, it isreferred to as ischemic heart disease. Ischemic heartdisease is relatively common in the general popula-tion, especially with increasing age, and typicallypresents as angina or heart failure.46 In most cases,diminished blood perfusion of the myocardium dueto coronary artery disease (atherosclerosis) is theunderlying cause with hypertension as a commoncontributing factor in heart failure. CHF and enlarge-ment of the heart result from weakening of thedamaged heart muscle.

Chest pain secondary to ischemic heart disease resultswhen the oxygen demand of the myocardium exceedsthe oxygen supply. Transient pain is referred to asangina pectoris and is often described as an aching,squeezing sensation or tightness in the middle of thechest. Angina is often precipitated by physical activity orstress and may radiate to the arm or jaw and maypresent as facial or dental pain. Fear and anxiety asso-ciated with dental treatment may be a precipitatingfactor for angina in some patients.46 Sublingual or otherforms of nitrates are the standard treatment for anginaand should result in rapid reversal of symptoms.Patients should always be instructed to bring their usual

756 / Endodontics

antianginal medicine with them for dental appoint-ments. If symptoms are not relieved with oral nitratesand suspension of stress-inducing activity, then MIshould be suspected and immediate emergency treat-ment should be initiated. Since angina is usually atransient event, patients with progressive pain or painat rest are considered to have unstable angina and pre-sent a significant perioperative risk for MI.30 Thesepatients are usually categorized as ASA IV. Chest painthat is manageable with rest or medication and rela-tively unchanged in duration, frequency, or severityover time is termed stable angina and represents a betterprognosis and somewhat lower risk level than unstableangina. Typically, patients with stable angina would beclassified as ASA II or ASA III.

Compared to other surgical procedures, most dentaland oral surgery procedures are considered relativelylow risk.47,48 However, a history of significant cardiacdisease can be a major predictor of perioperative risk,even for procedures with relatively low procedural stress.Recent MI (less than 1 month), unstable angina, past MIwith significant residual damage, decompensated CHF,significant arrhythmias, and severe valvular disease areall considered major predictors of increased periopera-tive cardiovascular risk, and these patients would usuallybe classified as ASA IV. Patients with stable angina, pasthistory of MI (greater than 1 month) with minimalresidual myocardial damage, compensated CHF, ordiabetes mellitus (DM) should be considered at inter-mediate risk and would usually be classified as ASA II orASA III.30,47 The presence of multiple risk factors createsan additive increase in the overall perioperative risk.49

Even patients with a history of recent MI or unstableangina should be able to tolerate routine dental proce-dures with local anesthesia, although medical consulta-tion is required and conscious sedation with monitoringis often recommended.48,50

Treatment modification considerations for patientswith ischemic heart disease should include morningappointments, short appointments, oral premedica-tion with an anxiolytic drug and/or nitrous oxide/oxygen sedation, limited use of vasocontrictors (aspreviously discussed), adequate pain management(during and after the dental appointment), and pos-sible cardiac monitoring.30 Sedation with a short act-

ing oral benzodiazepine (e.g., triazolam or ativan)and/or nitrous oxide can reduce the stress of a dentalprocedure and increase the effectiveness of localanesthesia.31 Clinicians must be aware of the medicalneed and legal requirements that include special train-ing, permits, and monitoring when anxiolysis crossesover into conscious sedation. If conscious sedation isrequired, it is best performed by a trained provider ofanesthesia/sedation and with another operator pro-viding the dental care.

HEART MURMURS AND VALVULARDISEASEPatients with valvular disease present two primaryconsiderations for dental treatment: potential risk forinfective endocarditis and risk of excessive bleedingin patients on anticoagulant therapy.46 Managementconsiderations for patients on anticoagulant therapy arediscussed later in this chapter. Most heart valve abnorm-alities affect either the aortic or the mitral valve andrepresent partial obstruction of blood flow (stenosis) orvalve incompetence (regurgitation). Heart murmurs arecommon and may be benign or signify major underlyingdiseases such as degenerative valve disorders (e.g., aorticstenosis), rheumatic heart disease, congenital valvelesions, prosthetic valves, atrial fibrillation, or CHF.51

Two other conditions that place patients at increased riskfor infective endocarditis are systemic lupus erythemato-sus and certain medications used for weight reduction(dexfenfluramine and fenfluramine–phentermine).51,52

Dental management requires evaluation of the type ofheart condition and the risk of bacteremia from theplanned dental procedure. New guidelines for the pre-vention of infective endocarditis were published in 2007and represent a significant change from previous Amer-ican Heart Association guidelines.53 For example, anti-biotic prophylaxis is no longer recommended for patientswith a history of mitral valve prolapse (with or withoutregurgitation), rheumatic heart disease, bicuspid valvedisease, aortic stenosis, and certain congenital heartconditions. Antibiotic prophylaxis is now recommendedonly for patients with valvular disease associated with thehighest risk of adverse outcomes from infective endocar-ditis. For patients in the highest risk category, antibiotic


prophylaxis is recommended for dental procedures thatinvolve manipulation of gingival tissues or the periapicalregion of teeth or perforation of the oral mucosa. For allother patients with valvular disease, the risks associatedwith routine antibiotic prophylaxis are greater thanpotential benefits.53 Figures 7 and 8 list the specific heartvalve abnormalities and dental procedures that are con-sidered highest risk for infective endocarditis. In general,procedures associated with nonsurgical root canal treat-ment such as local anesthetic injection, placement of therubber dam, and instrumentation when contained withinthe canal system do not place the patient at significant

risk for infective endocarditis.54 The incidence andmagnitude of bacteremia when canal instrumentationdoes not extend into the periapical tissues is very low,and almost all bacteria are eliminated from the bloodwithin 10 minutes.55,56 Canal instrumentation beyondthe apex, intraligamentary and IO injections, and peria-pical surgery can all be expected to result in a higher riskfor transient bacteremia. In these situations, antibioticpremedication is recommended for patients in thehighest risk disease categories. Infective endocarditis isonly rarely directly linked to dental procedures and theefficacy of the recommended antibiotic regimen is

Antibiotic prophylaxis recommended

Highest risk of adverse outcome from infective endocarditis:

Prosthetic heart valve

Previous infective endocarditis

Congenital heart disease (CHD)*

Unrepaired cyanotic CHD, including palliative shunts and conduits

Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or catheter, during the first six months after the procedure

Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device

Cardiac transplantation recipients who develop cardiac valvulopathy

* antibiotic prophylaxis is not recommended for other forms of CHD

Figure 7 Recommendations for antibiotic prophylaxis based on risk stratification for infective endocarditis. Adapted from Wilson W et al.53

Antibiotic prophylaxis recommended only for patients at highest risk for adverse

outcome from infective endocarditis (Figure 24-7):

All dental procedures that involve manipulation of gingival tissue or the periapical

region of teeth or perforation of the oral mucosa (does not include routine local

anesthetic injections through noninfected tissue)

Figure 8 Risk of dental procedures. Adapted from Wilson W et al.53

758 / Endodontics

questionable.53,57–61 The current regimen and drugs ofchoice for antibiotic prophylaxis are presented in Figure 9.

According to Lessard et al., some patients with sig-nificant heart murmurs may have dyspnea, fatigue anddifficulty in breathing when reclined in the dentalchair51 and therefore the dental procedure may need

to be performed with the chair in a more uprightposition. They also suggest that the use of a rubberdam may be contraindicated for some of these patientsdue to restriction of air flow; however, this may beovercome with careful application of the rubber dam.Failure to use the rubber dam is considered below the

Standard oral regimen Adults: 2.0g Amoxicillin

Children: 50mg/kg

Alternative oral regimen for patients allergic to penicillin orpatients who are currently taking a penicillin class antibiotic

Adults: 2.0g Cephalexin or other 1st or 2nd generation cephalosporin in equivalent dosage* OR600mg ClindamycinOR500mg Azithromycin or clarithromycin

Children:50mg/kg Cephalexin or other 1st or 2nd generation cephalosporin in equivalent dosage* OR20mg/kg ClindamycinOR15mg/kg Azithromycin or clarithromycin

Patients unable to take oral medications

Adults:2.0g IM or IV Ampicillin OR1.0g IM or IV Cefazolin or ceftriaxone*

Children: 50mg/kg IM or IV AmpicillinOR50mg/kg IM or IV Cefazolin or ceftriaxone*

Alternative IM/IV regimen for patients allergic to penicillin and unable to take oral medications

Adults: 1.0g IM or IV Cefazolin or ceftriaxone* OR600mg IM or IV Clindamycin

Children:50mg/kg IM or IV Cefazolin or ceftriaxone*OR20mg/kg IM or IV Clindamycin within 30 minutes before the procedure

* = Cephalosporins should be used with caution in patients reporting an allergy to penicillin since approximately 5%–15% of patients who are allergic to penicillin will demonstrate cross reactivity with cephalosporins, especially first and second generation cephalosporins.

Figure 9 Antibiotic prophylaxis for dental procedures—all regimens are a single dose given 30 to 60 minutes before the procedure. Adapted fromWilson W et al.53


standard of care for root canal therapy and extractionmay be the only option for these patients if a rubberdam cannot be used.

ANTICOAGULANT THERAPYAND BLEEDING DISORDERSManagement of patients on anticoagulant therapydepends on the type of anticoagulant, the reason for antic-oagulant therapy, and the type of procedure planned.Warfarin (Coumadin—DuPont Pharmaceuticals,Wilmington, DE) anticoagulants are commonly pre-scribed for the treatment or the prevention of thromboem-bolic events. This category of anticoagulant works byblocking the formation of prothrombin and other clottingfactors. The international normalized ratio (INR) value isthe accepted standard for measuring prothrombin time(PT). The desired therapeutic range for INR is usuallybetween 2 and 3.5, depending on the underlying medicalindication for anticoagulant therapy.

Limited oral surgery procedures, defined as simpleforceps extraction of one to three teeth, may be safelyperformed on patients with INR values within thenormal therapeutic range.62–64 Nonsurgical root canaltreatment does not usually require modification ofanticoagulant therapy, although it is important toascertain that the patient’s INR is within the thera-peutic range, especially if a nerve block injection isrequired. Periapical surgery may present a greaterchallenge for hemostasis even for patients well main-tained within the therapeutic range. The clear fieldvisibility normally required for proper surgical man-agement of the root end may not be possible inpatients on anticoagulant therapy. Consultation withthe patient’s physician is required to assist in devel-oping an appropriate treatment plan. Some patientsmay be able to tolerate discontinuation of warfarintherapy 2 days prior to a planned surgical procedureto allow for the INR to ‘‘drift’’ downward. In a pro-spective cohort study, Russo et al.65 report that sus-pension of warfarin 2 days prior to a surgical proce-dure resulted in no bleeding problems and nothromboembolic events. They found that the averagetime spent at an INR less than 2.0 (critical value) was28 hours and that 90% of the patients returned to thedesired therapeutic INR value within 7 days. How-ever, this strategy may place certain patients at greaterrisk for a thromboembolic event and in these casesdiscontinuation of anticoagulant therapy would notbe recommended.

In general, patients on warfarin anticoagulant ther-apy should present minimal risk for significant bleedingduring or after oral surgery and local measures to

control bleeding should be adequate.66,67 Jeske andSuchko,68 in a review prepared for the American DentalAssociation Council on Scientific Affairs and Divisionof Science, recommend against routine discontinuationof anticoagulant therapy prior to dental procedures,including surgical procedures. Regardless of the man-agement approach selected, consultation with thepatient’s physician and an INR test on the day of surgeryare strongly recommended. Hospitalization and conver-sion to heparin therapy may be considered in specialcases, but the patient, physician, and surgeon mustcarefully weigh the potential risks against the expectedoutcome and benefits. A new category of heparin antic-oagulant, low molecular weight heparins (LMWHs),allows for patient self-administration and may presenta viable alternative for some patients who need toremain at a high level of anticoagulation but wish toreduce the cost and time associated with traditionalheparin conversion therapy.

Low-dose aspirin therapy is known to increasebleeding time by irreversibly inhibiting platelet aggre-gation. No treatment modifications should be neces-sary for nonsurgical root canal procedures. However,surgical procedures require evaluation of the reasonfor and the necessity of aspirin therapy. It has been acommon practice to advise patients to discontinueaspirin therapy for 7 to 10 days prior to an oralsurgical procedure.69 At low-dose therapeutic levels(<100 mg/day), aspirin may increase bleeding timeand potentially complicate surgical procedures. How-ever, Ardekian et al.69 concluded that low-doseaspirin therapy (<100 mg/day) should not be discon-tinued prior to oral surgery procedures and thatbleeding could be controlled by local measures.Higher dose therapy may present a greater risk forbleeding either during or after surgery. Even though apatient on aspirin therapy may not be at high risk forsignificant intra- or postoperative bleeding, a concernfor periapical surgery is the visibility problemscreated by oozing blood. Consultation with thepatient’s physician is advised to determine the med-ical reason for aspirin therapy and to weigh the risksand benefits of discontinuing aspirin prior to theproposed surgery. It should be possible to performperiapical surgery without discontinuing aspirin ther-apy if necessary, but the visibility during the proce-dure may be compromised and the prognosis maydecrease accordingly.38

Nonsteroidal anti-inflammatory drugs (NSAIDs)also have an antiplatelet effect but, unlike aspirin,the effect is reversible when discontinued and plateletactivity should be expected to return to normal withinapproximately three half-lives of the drug. Other

760 / Endodontics

commonly prescribed antiplatelet drugs includedipyridamole, ticlopidine, clopidogrel, abciximab,integrelin, tyrafiban, and lamifiban. Heavy alcoholconsumption, liver disease, and certain medicationscan increase the risk of perioperative bleeding inpatients taking antiplatelet medications. Medicalconsultation is advised prior to surgical proceduresand lab tests to determine platelet count and function(PFA-100 and Ivy BT) may be indicated. Some herbsand dietary supplements may also affect bleeding risk.

Patients with inherited or acquired bleeding disordersare also at risk for excessive bleeding during and afterperiapical surgery procedures and may be at risk fromlocal anesthetic injections particularly when using nerveblock injections. Impaired liver function secondary topast or current alcohol or drug abuse may also predis-pose a patient to excessive bleeding during surgery. Amedical consultation, usually with a hematologist, isrequired prior to dental treatment for patients withserious bleeding disorders such as thrombocytopenia,hemophilia, and von Willebrand’s disease. Replacementof deficient coagulation factors or platelet transfusionmay be required prior to dental treatment,70 particularlyif an inferior alveolar nerve block is required or a surgi-cal treatment is planned. If non-surgical root canaltreatment can be performed with only infiltration localanesthesia, replacement may not be necessary.71 How-ever, this decision must be reached in consultation withthe patient’s hematologist.

ARRHYTHMIAS AND CARDIACPACEMAKERSCardiac arrhythmias are a heterogeneous group ofconditions defined as any disturbance in the normalrate or rhythm of the heartbeat. Arrhythmias are theresult of abnormal impulse generation, impulse con-duction, or both and can range from harmless to lifethreatening.46 The overall prevalence of cardiacarrhythmias in the general dental patient populationis 15% to 17% with approximately 2 to 4% represent-ing serious, potentially life-threatening arrhythmias.30

Although arrhythmias are not uncommon in normal,healthy adults, the possibility of underlying cardiovas-cular disease, systemic disease, or medication-inducedarrhythmia should be carefully evaluated prior todental treatment. Anxiety associated with dental treat-ment may induce arrhythmias in susceptible patients.In addition, patients with cardiovascular disease aremore prone to arrhythmias during oral surgery pro-cedures with local anesthesia.72 Patients takingdigoxin for atrial fibrillation or CHF are especially atrisk for arrhythmias during oral surgery procedures.73

Medications are usually the first line of treatmentfor cardiac arrhythmias, although many of these havea narrow therapeutic safety range (e.g., digoxin) andmust be carefully monitored. Surgery, cardioversion,and pacemakers are also used to treat arrhythmias. Itis common for patients with atrial fibrillation to betreated with an anticoagulant (typically warfarinsodium—management considerations discussed pre-viously in this chapter). A history of cardiac arrhyth-mia is often disclosed in the medical history. Inaddition to the medical history, patients with anirregular pulse, unusually rapid or slow pulse,reports of syncope, palpitations, dizziness, angina,or dyspnea should be referred to a physician forevaluation prior to dental treatment. Once the nat-ure of arrhythmia and the stability of the conditionhave been determined, most dental treatment can besafely performed using the same stress reductiontreatment modifications listed in the discussion ofischemic heart disease. As always, the clinician andstaff should be prepared to manage a medical emer-gency if necessary.

Electrical interference from certain dental devices is apotential concern for patients with implanted cardiacpacemakers or cardioverter/defibrillators. In particular,electronic apex locators (EAL) and electric pulp testers(EPT) are commonly used in root canal therapy. Man-ufacturers of EAL and EPT devices warn against the useof these devices in patients with cardiac pacemakers.However, current cardiac pacemakers are very wellshielded from external electrical fields and the possibi-lity for electrical interference seems to be very low.A recent clinical study supports previous in vitroresearch and a case report in concluding that EAL andEPT devices should be safe to use in patients withcardiac pacemakers and cardioverter/defibrillators.74–76

One caveat from this study is that a mucosal lip clip wasused to complete the circuit with the EPT device insteadof the common clinical practice of having the patienthold the EPT wand in their hand. This lip clip techniqueis recommended if one elects to use an EPT device on apatient with a cardiac pacemaker, since the practice ofusing the patient’s hand to complete the circuit mayallow for electrical current to pass through an area of thebody in closer proximity to the pacemaker. The safety ofthis variation of the EPT technique has not yet beentested.

CONGESTIVE HEART FAILURECHF is the fourth most common medical diagnosis inall age groups and represents the end-stage of othercommon cardiovascular diseases such as coronary


artery disease, hypertension, cardiomyopathy, andvalvular heart disease.30 CHF results in an inabilityof the heart to efficiently pump blood that can involveone or both ventricles. Patients with CHF typicallypresent with significantly diminished reserve capacityfor handling stress (including dental treatment) andare often taking multiple medications with the poten-tial for drug interactions.

Patients with well-managed CHF should tolerateroutine dental treatment with possible minor treatmentmodifications, similar to those recommended forpatients with ischemic heart disease. In addition, theunderlying causes (coronary artery disease, hyperten-sion, valve disease, etc.) and medications should beconsidered and managed appropriately. Patients withmoderate to advanced CHF may require a moreupright chair position due to the presence of pulmon-ary edema. The clinician should be alert for orthostatichypotension when making adjustments in chair posi-tion. Uncompensated, advanced CHF requires medicalconsultation prior to dental treatment and vasocon-strictors should be avoided. These patients may require

treatment in special care facilities or hospital-basedclinics. The New York Heart Association (NYHA) hasdeveloped a classification system for CHF that can beadapted to assist in assessing risk for dental treatment(Figure 10).

Diabetes

Diabetes mellitus (DM) is a complex metabolic dis-order characterized by abnormalities in carbohydrate,fat, and protein metabolism resulting either from adeficiency of insulin (type 1) or from target tissueresistance to its cellular metabolic effects (type 2).Hyperglycemia is the most clinically important meta-bolic aberration in DM and the basis for its diagnosis.Chronic hyperglycemia is associated with ophthalmic,renal, cardiovascular, cerebrovascular, and peripheralneurological complications. DM is defined as a fastingblood glucose level greater than 125 mg/dL and thenormal fasting blood glucose level is considered to beless than 110 mg/dL. Patients with fasting plasma

New York Heart

Association CHF

classification Signs and symptoms considerations

Class I No limitations on physical activity;

no dyspnea, fatigue, or palpitations

with ordinary physical activity

Should be able to tolerate routine

dental treatment; stress reduction

protocol as needed

Class II Slight limitation on physical

activity; comfortable at rest but

may experience fatigue,

palpitations, and dyspnea with

ordinary physical activity

Should be able to tolerate routine

dental treatment; stress reduction

protocol as needed; possible

medical consultation

Class III Significant limitation of activity;

comfortable at rest but even minor

activity results in symptoms

Medical consultation; consider

treatment in hospital dental clinic

or similar facility; avoid

vasoconstrictors

Class IV Symptoms present at rest;

symptoms exacerbated by any

physical activity

Medical consultation; conservative

treatment only; treatment in

hospital dental clinic; avoid

vasoconstrictors

Dental management

Figure 10 New York Heart Association’s classification system for patients with congestive heart failure (CHF) and dental management considerations.Adapted from Little JW et al.30

762 / Endodontics

glucose levels greater than 110 mg/dL but less than126 mg/dL represent a transitional condition betweennormal and DM and are considered to have impairedglucose tolerance.77 Identification of patients at thisstage can allow for earlier preventive interventionsand possibly delay or prevent progression to DM.There are 20.8 million children and adults in theUnited States, or 7% of the population, who haveDM. While an estimated 14.6 million have been diag-nosed with DM, 6.2 million people (or nearly one-third) are unaware that they have the disease.78 Theepidemic of obesity in the United States is anticipatedto result in an increase in the prevalence of diabetes.

When reviewing medical histories, the clinicianshould be aware of cardinal symptoms of DM, suchas polydipsia, polyuria, polyphagia, weight loss, andweakness, and should be referred to a physician fordiagnosis and treatment.30 In diabetic patients, theclinician should ascertain how well controlled thecondition may be. Dental appointment schedulingshould take into account the importance of nutri-tional consistency and the avoidance of appointmentsthat will overlap with or prevent scheduled meals.Symptoms of hypoglycemia may range from mild,such as anxiety, sweating, tachycardia, to severe, suchas mental status changes, seizure, and coma. Severehypoglycemic episodes are a medical emergency andshould promptly be treated with 15 g of oral carbo-hydrate, such as 6 oz orange juice, three to four teas-poons of table sugar, five Life Savers, or three glucoseor dextrose tablets. If a patient is unable to cooperateor swallow, 1 mg glucagon may be administered bysubcutaneous or intramuscular injection. Side effectsof glucagon include nausea, vomiting, and headache.

It has been well established that hyposalivation,gingivitis, periodontitis, and periodontal bone lossare associated with DM, especially when poorly con-trolled.79,80 The well-controlled diabetic is at nogreater risk of postoperative infection than is thenondiabetic.81 Therefore, surgical procedures in well-controlled diabetics do not require prophylacticantibiotics. However, when surgery is necessary inthe poorly controlled diabetic, prophylactic antibioticsshould be considered due to the altered function ofneutrophils in diabetics. Surgery may also increaseinsulin resistance such that a diabetic may becomehyperglycemic in the postoperative period. Preopera-tive antibiotics should be administered in theseinstances.82 Furthermore, delayed alveolar healingfollowing dentoalveolar surgery should raise the suspi-cion of osteomyelitis, for which prompt surgicalconsultation should be arranged. Finally, patients withDM may present with systemic complications, each of

which should be taken into account prior to dentalprocedures.

Pulmonary Disorders: Asthma, COPD,

and Tuberculosis

Asthma is a chronic inflammatory respiratory diseasewith recurrent episodes of chest tightness, coughing,dyspnea, and wheezing resulting from hyperrespon-siveness and inflammation of bronchiole tissue. Overtattacks may be provoked by allergens, upper respira-tory tract infections, genetic and environmental fac-tors, certain medications, and highly emotional statessuch as anxiety, stress, and nervousness.

The endodontist should obtain a good history todetermine the severity and stability of disease. Patientsshould be instructed to bring their inhalers (broncho-dilators) to each appointment and inform the endo-dontist of the earliest sign or symptom of an asthmaattack. During dental treatment, the most likely timesfor an acute exacerbation of asthma are during andimmediately after local anesthetic administration andwith stimulating procedures such as pulp extirpa-tion.83 Because stress is implicated as a precipitatingfactor in asthma attacks, sedation may be beneficial.While nitrous oxide may be used in patients withmild-to-moderate asthma, its use is contraindicatedin patients with severe asthma due to its potential tocause airway irritation.84 Alternatively, oral premedi-cation may be accomplished with small doses of ashort-acting benzodiazepine. In patients taking theo-phylline, macrolide antibiotics should be avoided, asthey have the potential to develop toxic levels oftheophylline. In addition, it is important to note thataspirin and other NSAIDs may trigger asthma attacksin a proportion of patients.85

COPD is a term for pulmonary disorders character-ized by chronic irreversible obstruction of airflow fromthe lungs and represents the fourth most common causeof death in the United States.86 The three most commonforms of COPD are chronic bronchitis, emphysema, andbronchial asthma. Patients with pulmonary diseases typi-cally present with one or more of the following symp-toms: cough, dyspnea, sputum, hemoptysis, wheezing, orchest pain.87 Patients should be placed in a semisupineposition. Since the use of a rubber dam may induce afeeling of airway constriction, careful application of therubber dam and administration of humidified low-flowoxygen, generally between 2 and 3 L/min, may be con-sidered. Nitrous oxide should not be used in patientswith severe COPD.


Tuberculosis (TB) is an infectious disease that isspread by way of bacilli-containing airborne droplets,typically by coughing, sneezing, or talking. The signaturelesion of TB is the tubercle, a granuloma formed by thecontinuing ingress of macrophages and lymphocytes tothe site of infection.88 In the lung, tuberculous granulo-mas are frequently associated with regions of tissuenecrosis, termed caseous necrosis due to its gross appear-ance. After the infection is established, symptomaticindividuals will show pulmonary manifestations of thedisease, often limited to the periphery of the middle andlower regions of the lung,88 though reactivated disease ismost commonly found in the lung apices.89 Oral tuber-cular infections are rare, occurring in 0.05 to 5% ofpatients with TB, though when lesions are present, theytypically consist of ulcers, fissures, or swellings on thedorsum of the tongue.90 Despite the declining incidenceof TB in the United States, health care workers includingendodontists and their staff remain at high risk for con-tracting the disease. It is imperative for the endodontistto educate office staff about TB prevention and recogni-tion of symptoms and oral manifestations of the diseaseto protect the staff and other patients from becominginfected. A thorough medical history should be obtained,and any elective dental procedures on a patient withestablished or suspected active TB should be delayeduntil the individual can be treated and subsequentlyproved noninfectious. Routine dental treatment isappropriate after it has been established that the patienthas been adequately treated and there are no signs orsymptoms of active disease. The clinician should beaware of potential drug interactions when managingdental patients undergoing antitubercular treatment. Inpatients taking medications such as rifampin and isonia-zid, acetominophen should be avoided due to the poten-tial for liver damage. The use of aspirin and musclerelaxants is discouraged in those individuals taking strep-tomycin due to a heightened risk of ototoxicity andrespiratory paralysis, respectively.91 Streptomycin is alsoknown to cause facial paresthesia and pancytopenia.

Central Nervous System: Stroke,

Seizure Disorders, and Hydrocephalic

Shunts

Cerebrovascular accident or stroke is defined as theacute onset of neurologic deficits persisting for at least24 hours. Strokes are subclassified into ischemic insults,occurring secondary to thrombosis or embolization, orhemorrhagic, which usually indicate an arterial process.The lack of blood flow leads to deprivation of oxygen

and glucose in a localized area of the brain. The endo-dontist should be aware of how to identify the patienthaving a stroke in his/her office. Regardless of the pro-cedure, a patient’s blood pressure should be checkedbefore treatment to identify a patient whose bloodpressure is elevated and who might be at risk for a strokeif subjected to stress. Slurred speech, loss of motorcontrol over a portion of the body, unilateral facialdroop, unilateral visual changes, and unilateral severeheadache are all potential signs of a stroke or a transientischemic attack. Should any of these events occur, thepatient should have his/her vital signs checked, beplaced in a supine position, have vital signs monitored,and be transported to an emergency facility immedi-ately, as treatment must be activated in a timely manner.Patients with a history of stroke may be at risk foraspiration due to swallowing abnormalities, so theyshould be positioned in a semisupine position, andrubber dams should be carefully applied and shouldalways be used. Poststroke patients may be on oralanticoagulants; so if surgical intervention is planned,the endodontist should contact the physician to deter-mine whether or not the risk of a thromboembolic eventoutweighs the benefits of postoperative hemostasis(please refer to section ‘‘Anticoagulant therapy andbleeding disorders’’). The endodontist should also beaware that the poststroke patient may experience emo-tional problems, including depression and behaviorinappropriate to the situation.

Seizures are one of the most commonly encoun-tered neurological disorders and can manifest as anisolated incident with unknown etiology or as a symp-tom of a condition that requires long-term treatment.A seizure is a temporary involuntary disturbance ofbrain function that results in synchronous, excessive,abnormal electrical discharges of the neurons in thecentral nervous system.92 This manifestation can takethe form of motor disturbances, altered feelings, orchanges in the patient’s level of consciousness. Thetwo main categories of seizure classification are partialand generalized. Most people who have seizures havegood control and are capable of receiving routinedental care. The endodontist should be aware of thepatient’s seizure medications, since many antibioticsare contraindicated. Should a seizure occur in thedental office, the procedure should be stopped imme-diately and all instruments should be removed fromthe oral cavity. The patient should be placed in asupine position and low to the ground. Basic lifesupport should begin immediately, including openingthe airway, obtaining vital signs such as heart rate andblood pressure, and contacting emergency medicalservices.

764 / Endodontics

The risk of shunt infection following invasive dentaltreatment for patients with hydrocephalic shunts (ven-triculoperitoneal and ventriculoatrial) is believed to beabout 3.0 to 5.0% and because of this there is a lack ofconsensus regarding the need for antibiotic prophy-laxis.93 The authors of this study found that pediatricdentists were more likely to be concerned about strep-tococcal microorganisms and neurosurgeons weremore concerned about staphylococcal microorganismsin shunt infection. The majority of both groups recom-mended penicillin prophylaxis, although there aremore appropriate antibiotics if staphylococcal micro-organisms are presumed to be responsible for mostshunt infections (please refer to the discussion in sec-tion ‘‘Prosthetic joints and other prosthetic devices’’).Consultation with the patient’s neurosurgeon isadvised and close attention to any changes in prophy-laxis guidelines is important.

Renal Disease and Dialysis

Chronic renal failure is a slowly progressive conditioncharacterized by an irreversible reduction in the glo-merular filtration rate. The progression of this diseasebegins with an asymptomatic decrease in the kidneyfunction and eventually results in end-stage renal dis-ease (ESRD). Throughout the decline in function,multiple systems are affected, directly related to thekidney dysfunction. ESRD is potentially fatal unlessthe patient undergoes dialysis or kidney transplanta-tion (please see section ‘‘Solid Organ Transplanta-tion’’ regarding kidney transplantation). Dialysismay take the form of hemodialysis, which represents90% of dialysis treatment,94 or peritoneal dialysis.This treatment removes fluid and wastes and equili-brates electrolytes and acid–bases via diffusion andosmosis across a semipermeable membrane.

The clinician should be aware of the ESRD patient’stype and days of dialysis treatment as well as comor-bid conditions such as hypertension and/or diabetes.Mechanical trauma to platelets and anticoagulantssuch as heparin used during hemodialysis mayincrease the renal patient’s tendency for bleeding.While it is recommended that dental procedures beperformed on nondialysis days, typically the day afterdialysis,95 the endodontist should be aware thatabnormal platelet function may cause a greater riskof bleeding during surgical procedures. In addition,patients with ESRD require aggressive treatment ofodontogenic infections. Antibiotic premedication hasalso been recommended for hemodialysis patientswith shunts who undergo invasive dental proce-

dures,96–98 and other authors have recommendedantibiotic prophylaxis for all hemodialysis patientsundergoing procedures that cause mucosal bleedingto prevent vascular access infections, bacteremia, andinfective endocarditis.97 Renal osteodystrophy andsecondary hyperparathyroidism may occur in late-stage disease due to disorders in calcium, phosphor-ous, and abnormal vitamin D metabolism. Such amanifestation may predispose renal patients to jawfracture during surgical procedures.

Because many drugs are metabolized via the kidney,renal dosing should account for the drug’s extendedhalf-life by lengthening the interval between medicationdoses. In particular, antibiotic medications should beadjusted for renal dosing. NSAIDs should be avoidedin patients with renal insufficiency due to their nephro-toxic effects, but no longer need to be avoided when thepatient has ESRD.

Cancer Chemotherapy and Radiation

Therapy

Oropharyngeal cancer encompasses a variety of malig-nant diseases. More than 90% of oral cancers aresquamous cell cancers, 9% are salivary gland tumors,sarcomas and lymphomas, and the remaining 1% aremetastatic cancers originating in other parts of thebody.99 In the year 2006, the American Cancer Societyreported 31,000 people with newly diagnosed orophar-yngeal cancers and 7800 deaths from this disease.100

Numerous risk factors have been implicated in theetiology of oropharyngeal cancer, including tobacco,excessive alcohol, ultraviolet light exposure, immuno-suppression, and viruses. Oral cancer has a variableappearance, including white or red patches, an exophy-tic mass, an ulceration, a granular raised lesion, asubmucosal mass, or a combination thereof. Treatmentof oropharyngeal cancer is composed of surgical inter-vention, radiation treatment, and chemotherapy andfor systemic cancers possibly hematopoietic stem celltransplantation (HSCT). Multimodality therapy is nowmore commonly used for oropharyngeal cancer inorder to obtain increased survival rates.

Cancers that are amenable to surgery and do notaffect the oral cavity require few treatment plan mod-ifications. However, oropharyngeal cancer treatmentsand complications may cause significant changes inthe oral cavity. Preceding cancer treatment, all sourcesof inflammation and potential infection should beeliminated. Whenever possible, nonrestorable teethand teeth with a poor long-term periodontal


prognosis (i.e., not expected to be retained for thepatient’s lifetime) within the field of high-dose radia-tion should be extracted more than 2 weeks prior toradiation therapy. Symptomatic nonvital teeth can beendodontically treated at least 1 week before initiationof head and neck radiation or chemotherapy althoughdental treatment of asymptomatic teeth even withperiapical involvement can be delayed, particularly iftreatment can be limited to intracanal therapy. Manycancer patients have indwelling catheters that may besusceptible to infection and, while controversial, theAmerican Heart Association (AHA) regimen for anti-biotic prophylaxis (see Figure 9) has been recom-mended before invasive dental procedures.101 If anindividual is receiving chemotherapy, the endodontistshould be familiar with the patient’s white bloodcount (WBC) count and platelet status. Endodonticprocedures can be performed if the neutrophil countis greater than 2000 cells per cubic millimeter andplatelets are greater than 50,000 cells per cubic milli-meter. Postradiation osteonecrosis (PRON) resultsfrom radiation-induced changes in the jaws, may arisein bones exposed to high-dose radiation, and is char-acterized by asymptomatic or painful bone exposure.Protocols to reduce the risk of osteonecrosis includeselection of endodontic therapy over extraction,expert atraumatic surgical procedures, consideringthe use of nonlidocaine local anesthetics that containno or low concentration of epinephrine, and prophy-lactic antibiotics plus antibiotics during the week ofhealing.102

BISPHOSPHONATE-ASSOCIATEDOSTEONECROSIS OF THE JAWSBisphosphonates are bone resorption inhibitor medica-tions that are commonly used in conjunction with can-cer chemotherapy and the prevention or treatment ofosteoporosis. Recent reports have suggested thatbisphosphonates (e.g., pamidronate, zoledronic acid)may cause osteonecrosis of the maxillary and mandib-ular bones, either spontaneously or following dentalsurgical procedures or oral trauma.103–107 Althoughthe mechanism of action is unknown, it is suggestedthat a decrease in bone cellularity and antiangiogeniceffects and decreased blood flow resulting from bispho-sphonate therapy could lead to a generalized impair-ment in bone remodeling.105 There appears to be adose–response relationship in that patients taking IVformulations appear to be at greater risk for bispho-sphonate-associated osteonecrosis (BON).108 There arecurrently no scientific data to support any specific treat-ment protocol for the management of patients with

BON, though minimally invasive procedures have beenrecommended.106 Before initiation of bisphosphonatetherapy, aggressive preventive treatment should be per-formed including oral hygiene, caries control, andextraction of teeth with a poor long-term prognosis.For patients who have been taking bisphosphonatemedication, preventive care for high-risk patients isimportant to reduce the risk of developing BON. Non-surgical endodontic treatment of teeth that wouldotherwise be extracted should be considered. Teeth withextensive carious lesions might be treated by nonsurgi-cal endodontic therapy possibly followed by crownresection and restoration similar to preparing an over-denture abutment.109 For patients at higher risk ofdeveloping BON, surgical procedures including surgicalendodontic procedures should be avoided if possible.Informed consent for endodontic procedures shouldinvolve a discussion of risks, benefits, and alternativetreatments with the patient.

Bone Marrow and Solid Organ

Transplantation

HEMATOPOIETIC STEM CELLTRANSPLANTATIONHSCT may be indicated in patients with hematologi-cal malignancy, nonhematological malignancy, andsome nonmalignant disorders. Patients may undergoan autologous (self) or an allogeneic (nonself) trans-plantation, each of which has its own pros and cons.The goal is to treat bone marrow disease or to inten-sify therapy that would destroy the bone marrow,following which the patient is ‘‘rescued’’ by the infu-sion of previously stored autologous hematopoieticstem cells or hematopoietic stem cells from a matcheddonor. Prior to transplantation, patients shouldundergo a thorough dental examination and treat-ment to permit adequate healing before the HSCT.Pretreatment endodontic therapy should be com-pleted at least 10 days prior to initiation of cancertherapy. Teeth with poor prognoses should beextracted, utilizing the 10-day window as a guide.The current AHA protocol for antibiotic prophylaxisprior to invasive oral procedures may be warranted inpatients who have indwelling catheters (e.g., Hickmancatheter). Prophylactic antibiotics are also recom-mended in patients who are neutropenic (<1,000neutrophils per cubic millimeter).

During and following high-dose chemotherapy/HSCT, aggressive oral hygiene measures should be

766 / Endodontics

instituted. Numerous oral complications may develop,including mucositis, graft-versus-host disease, infec-tion, taste changes, and bleeding. Patients should notresume routine dental treatment, including dental scal-ing and polishing, until adequate immunologicalreconstitution has taken place; this typically occurs noless than 1 year posttransplant. The aerosolization ofdebris and bacteria during the use of high-speed rotarycutting instruments can put the patient at risk foraspiration pneumonia; additionally, bacteremias occuras a result of dental treatment and can cause seriousoutcomes. Should treatment be deemed necessarywithin 1 year posttransplant, the endodontist mustconsult with the oncologist to determine appropriatetreatment.

SOLID ORGAN TRANSPLANTATIONIt is important to reduce the risk of infection in theimmunosuppressed recipient of a transplant.110 Pre-transplant patients should undergo eradication ofdental disease, including endodontic procedures aswarranted to remove any potential sources of infec-tion, and deferral of any elective treatments. Ofcourse, the endodontist should take into accountthe underlying condition for which the transplant isrequired. In the immediate posttransplant period,emergency dental procedures may be necessary. Atthis stage, patients are highly immunosuppressedto prevent organ rejection, so the AHA regimen ofantibiotic prophylaxis with possible postoperative

antibiotics may be recommended for invasive proce-dures. Further, patients may have indwelling cathetersthat may lead to a recommendation for antibioticprophylaxis. Should a patient experiences transplantrejection, dental care provided should be limitedto emergency care only until stabilization is againachieved. After the posttransplantation patient hasstabilized, indicated dental procedures may be per-formed after consultation with the patient’s transplantteam. Postoperative guidelines regarding prophylacticantibiotics have not been established but, if recom-mended, AHA guidelines may be used.110 Finally, theendodontist should be aware that posttransplant reci-pients will likely be on immunosuppressant therapy,regardless of the length of time posttransplant.

Prosthetic Joints and Other

Prosthetic Devices

Patients with prosthetic joints may be at increasedrisk for developing a hematogenous joint infectionfollowing dental procedures. Since the necessity ofprophylactic antibiotics in this group of patients iscontroversial, consultation with the patient’s ortho-pedic surgeon is advised. Current recommendationsinclude antibiotic coverage with higher risk dentalprocedures (see Figure 8) within 2 years followingprosthetic joint surgery, for those who have had pre-vious hematogenous prosthetic joint infections andfor those with some medical conditions (Figure 11).111

All patients during first two years following total joint replacement

Immunocompromised/immunosuppressed patients

Inflammatory arthropathies such as rheumatoid arthritis, systemic lupus erythematosus

Drug- or radiation-induced immunosuppression

Patients with medical comorbidities

Previous prosthetic joint infections

Malnourishment

Hemophilia

HIV infection

Type 1 diabetes

Malignancy

Figure 11 Patients at potential increased risk of experiencing hematogenous total joint infection. Adapted from ADA, AAOS Advisory statement.111


The selection of antibiotic and dosage regimen differsslightly from the commonly accepted regimen forprevention of bacterial endocarditis since differentmicroorganisms are more commonly associated withlate joint infections (Figure 12). These guidelines sug-gest prophylaxis for recently placed large joint pros-theses even though there is little evidence that oralflora account for many infections in joint prostheses.These guidelines will be continually reviewed andcurrent guidelines must be followed for medicolegalpurpose.

Antibiotic prophylaxis is not indicated for dentalpatients with pins, plates, screws, and penile or breastimplants, nor is it routinely indicated for dentalpatients 2 years after total joint replacements. Apatient with a total joint replacement or other surgi-cally placed prosthesis with acute orofacial infectionshould be aggressively treated as any other patient toeliminate the source of infection, and appropriateantibiotics should be administered as warranted.

Pregnancy

Few procedures are contraindicated during pregnancy.There is no contraindication to using necessary diag-nostic procedures, such as appropriate radiographs, aslong as normal safety precautions are followed. If dentalcaries is the source of pain or infection, invasive caresuch as endodontic therapy should be provided regard-

less of the patient’s phase of pregnancy.112 Elective den-tal procedures may often be performed in the secondtrimester, when the pregnancy is mostly devoted tomaturation. While some medications may be harmfulto the fetus, safe alternatives are often available. Lido-caine and prilocaine local anesthetics have an FDAcategory B rating and consequently should be first-linechoices for use with pregnant women. A commonmisconception is concern over the use of local anes-thetics containing epinephrine. Local anesthetics con-taining epinephrine should be relatively safe for useduring pregnancy113 and allow for greater depth andduration of anesthesia as well as reduction of any poten-tial systemic effect of lidocaine. In addition, the onlycommonly available alternative to local anesthetics witha vasoconstrictor is 3% mepivicaine, an FDA category Cdrug. If antibiotics are warranted, many first-linechoices are rated by the FDA as category B for pregnancyrisk. Pregnant women may be more susceptible to infec-tion,114 which may be partly due to physiologicalchanges as well as alterations in pharmacokinetics.

Human Immunodeficiency Virus

HIV is a blood-borne retrovirus infection transmittedprimarily by blood and bodily fluids by intimate sexualcontact and parenteral means. Upon infection, a viralenzyme reverse transcriptase allows the virus to inte-grate its own DNA into the genome of an infected cell

Patient Type Suggested Drug Regimen

Patients not allergic to

penicillin

Cephalexin, cephradine or

amoxicillin

2 grams orally 1 hour prior

to dental procedure

Patients not allergic to

penicillin and unable to take

oral medications

Cefazolin or ampicillin Cefazolin 1g or ampicillin

2g intramuscularly or

intravenously 1 hour prior

to the dental procedure

Patients allergic to

penicillin

Clindamycin Clindamycin 600 mg orally

1 hour prior to the dental

procedure

Patients allergic to

penicillin and unable to take

oral medications

Clindamycin 600mg intravenously 1 hour

prior to the dental procedure

Figure 12 Suggested antibiotic prophylaxis regimens for patients with total joint replacement. Adapted from ADA, AAOS Advisory statement.111

768 / Endodontics

and replicate using the infected cell’s ribosomes andprotein synthesis. Initially, immune seroconversionwith antiviral antibody production occurs followed bya significant decrease in CD4+ lymphocytes over a per-iod of up to years. The most effective management inthe progression of HIV infection and AIDS is a combi-nation of antiviral agents known as highly active anti-retroviral therapies (HAART), which has significantlyincreased the lifespan and the quality of life of indivi-duals infected with HIV. Upon initial assessment of anHIV-infected individual, the patient’s physician shouldbe contacted to determine CD4+ counts as well as base-line kidney and liver function. It is safe and desirable toassure that comprehensive dental care is available toHIV-positive patients. No modification of irreversibleprocedures or surgical treatment is recommendedunless patients have reduced platelet count (<50,000cells per milliliter) or neutrophil counts <1,000 cellsper milliliter, at which time a patient may require anti-biotic prophylaxis. Routine antibiotic use is contraindi-cated. The prognosis for successful healing of necroticteeth with chronic apical periodontitis following rootcanal treatment is essentially the same for HIV-positivepatients as for noninfected patients.115,116 The endo-dontist should examine oral tissues, as oral conditionsassociated with HIV may identify a person who isunknowingly infected with HIV, may be used in stagingand classification, and/or may denote progression toAIDS. Surgically treated teeth do not show delayedhealing. Antibiotics are used only if warranted by theclinical infection, and in a neutropenic patient.

Sickle Cell Anemia

Sickle cell anemia (SCA) affects approximately 1 in400 African-Americans and as much as 30% of thepopulation of some Central and West African coun-tries. Clinical concerns in endodontic practice includethe propensity for painful vasoocclusive episodes andbacterial infections.117 Since patients with SCA may beconsidered immunocompromised and infections cantrigger a sickle cell crisis, these patients usually requireaggressive treatment of infections, including the use ofsystemic antibiotics.117 The vasoocclusive aspects of thedisease can result in tissue and bone necrosis andpulpal necrosis in an otherwise intact and healthytooth.118 Since teeth with asymptomatic necrotic pulpscan become infected, patients with SCA require carefulpulpal evaluation. Nonsurgical root canal treatment ofasymptomatic necrotic teeth prior to the developmentof acute symptoms and infection is indicated. There isa lack of consensus regarding the value of prophylactic

antibiotics for patients with SCA, although the major-ity of pediatric dentistry program directors and pedia-tric hematologists recommend antibiotic coverage forinvasive procedures such as extraction or other surgicalprocedures.119 The use of a local anesthetic with novasoconstrictor (or minimal vasoconstrictor) may beadvisable for nonsurgical procedures since the micro-vasculature is often already compromised by SCA.Osteomyelitis is much more common in patients withSCA117 and the risk/benefit ratio for surgical endodon-tic procedures should be carefully considered forpatients with SCA.

Liver Disease

End-stage chronic liver disease (cirrhosis) is the result ofhepatocellular injury and necrosis that leads to fibrosisand nodular regeneration. Cirrhosis may be asympto-matic for long periods of time and may be undiagnoseduntil systemic signs are apparent. Ultimately, chronicliver disease affects multiple body systems. For moreinformation on the preliver transplant patient, pleasesee section ‘‘Solid organ transplantation’’ earlier in thischapter.

Performing any surgery in the preliver transplantpatient involves the risk of severe hemorrhage due tothrombocytopenia or reduced hepatic synthesis ofcoagulation factors. Preoperative evaluation shouldinclude a complete blood count with platelet count,PT or INR, and partial thromboplastin time to ensurean intact coagulation system. Patients with cirrhosishave an increased susceptibility to infection. Odonto-genic infections should be treated aggressively withappropriate antibiotic treatment. Antibiotic prophy-laxis prior to dental procedures is recommended onlyif the patient has a history of spontaneous bacterialperitonitis (SBP), ascites (accumulation of excess fluidin the abdomen), another medical indication for anti-biotic prophylaxis, or whose medical condition woulddrastically deteriorate should SBP develop. Whenantibiotic prophylaxis is indicated in the patient withend-stage liver disease, a recommended oral regimenis 2.0 g of amoxicillin plus 500 mg of metronidazole1 hour before the dental procedure, or patients maybe given 2.0 g of ampicillin plus 500 mg of metroni-dazole intravenously 1 hour before the procedure.120

Finally, the pharmacokinetics of drugs commonlyused in dentistry can be altered in patients with end-stage liver disease. Alteration of medication dosagebased upon hepatic compromise, additional medica-tions, and site of metabolism of the medication mayrequire consultation with the patient’s physician.


Adrenal Suppression and Long-Term

Steroid Use

The adrenal cortex produces mineralocorticoids, suchas aldosterone, and glucocorticoids, such as cortisol,which are important in maintaining fluid volume. Adre-nocortical insufficiency may result primarily from Addi-son’s disease, an autoimmune condition, or secondarilyfrom hypothalamic or pituitary disease or from theadministration of exogenous corticosteroids (30 mgper day or more of cortisol equivalent [about 5 mgprednisone]). Supplemental steroids are often recom-mended before and possibly following surgery to pre-vent adrenal crisis in patients who receive chronic dailysteroid therapy.121 In these patients, for minor surgicalprocedures such as routine endodontic surgeries, theglucocorticoid target is about 25 mg of hydrocortisoneequivalent (5 mg of prednisone) on the day of surgery. Ifa moderate risk surgery is to be performed, the gluco-corticoid target is about 50 to 75 mg per day of hydro-cortisone equivalent on the day of surgery and for onepostoperative day. Nonsurgical dental procedures,including nonsurgical root canal treatment, generallyrequire no supplementation; however, this should bereviewed on a case-by-case basis and considerationgiven to the anticipated procedural stress and patienttolerance for dental treatment.121 As a rule of thumb, apatient who recently discontinued the use of exogenouscorticosteroids should wait 2 weeks before undergoingsurgical procedures. Patients on alternate day steroidsdo not likely require steroid supplementation. Efforts tocontrol pain and infection can decrease the risk of anadrenal crisis.

Allergy to Materials Used in

Endodontic Therapy

The prevalence of allergies and allergy-related diseaseshas increased significantly in recent years.122 Approxi-mately 15 to 20% of dental patients report some formof allergy on their medical history questionnaire andapproximately 5% report allergy to one or moredrugs.123 In fact, allergy is the single most commonpositive finding on the medical history questionnaire.2

Fortunately, with the exceptions of latex and certainantibiotics, the majority of reported allergies are tosubstances not typically used in dental treatment. Evenso, many materials used in root canal therapy have thepotential for eliciting an allergic reaction. The medicalhistory questionnaire serves as the first stage in screen-ing for allergies but should always be supplemented

with direct patient questioning about the history ofallergic reactions to any drugs or substances. Trueallergic reactions are characterized by one or more ofthe following signs and symptoms: skin rash, swelling,urticaria, chest tightness, shortness of breath, rhinor-rhea, and conjunctivitis.123

Type I (immediate or anaphylactic, IgE-mediated)and Type IV (delayed, cell-mediated) are the two typesof allergic reactions most likely to be encountered as aresult of exposure to a substance used in endodontictreatment. Type I hypersensitivity requires previousexposure to the antigen and can occur after a singleprior exposure or multiple prior exposures to the aller-gen. The reaction occurs shortly after exposure and canrapidly progress to life-threatening anaphylaxis. TypeIV hypersensitivity typically appears 48 to 72 hours afterexposure and is mediated by T lymphocytes in contrastto the humoral immune system (antibody)-mediatedType I reaction. Contact dermatitis is a classic Type IVreaction. When materials used in endodontic treatmentcome in contact with the periapical tissues (eitherintentionally or inadvertently), there is the potentialfor a delayed Type IV hypersensitivity reaction. Theallergic potential of various materials commonly usedin endodontic treatment is summarized in Figure 13.

LOCAL ANESTHETICSTrue Type I allergy to an amide local anesthetic isextremely rare. Nevertheless, patients reporting a his-tory of allergic reaction to a local anesthetic requirethorough evaluation prior to proceeding with treat-ment (assuming that a local anesthetic is needed forroot canal treatment) since true allergic reactions havebeen reported.124–133 Perhaps the most commonresponse elicited upon exploration of the presumedallergic reaction is a report of tachycardia, syncope orgeneral uneasiness following local anesthetic injection.Such a response almost certainly represents a psycho-genic reaction rather than true allergy.132,134 Carefulaspiration during injection can help prevent an inad-vertent intravascular injection and subsequentincreased toxicity and potential for adverse reaction.

In a recent prospective study of 5,018 dental patientswho received a local anesthetic, 25 (0.5%) adverse reac-tions were recorded.124 Twenty-two of the reactionswere mild, quickly reversible, and considered to be psy-chogenic in nature. Only two of the reactions wereinitially viewed as possible allergic reactions and bothof these were excluded as true allergic reactions afterprovocative challenge tests. In another study of 236patients who experienced an adverse reaction after injec-tion of local anesthetic, all tested negative following

770 / Endodontics

intradermal injection of local anesthetic containingepinephrine and preservative.135

Both sulfite preservatives used in local anestheticscontaining epinephrine and latex allergen released intothe anesthetic solution from the vial stopper are poten-

tial causes of allergic reactions. Although reaction to thesulfite preservative is also believed to be rare,135 allergicreactions to preservatives used in local anesthetics havebeen reported.136–138 Since preservatives are used onlyin local anesthetics containing a vasoconstrictor, the risk

Category Material Allergic potential

Barriers Natural rubber latex +

Vinyl (polyvinyl chloride) –*

Nitrile (acrylonitrile and butadiene)

Polychloroprene (Neoprene)

Irrigating solutions and disinfectants

Sodium hypochlorite (0.5%–6%)

+

Hydrogen peroxide (3%–30%)

–

Chlorhexidine (0.2%–2%)

+

+

Ethylenediamine tetraacetic acid (EDTA) (10%–17%)

–

Citric acid (10%–50%)

–

MTAD (mixture of tetracycline, citric acid and detergent)

?

Intracanal medications Phenols +

Aldehydes +

Calcium hydroxide –

Iodine containing pastes +

Sealers and filling materials ZnOE materials (various sealers and temporary filling materials)

+

Epoxy resins +

Glass ionomers –

Composite resins ?

Mineral trioxide aggregate (MTA)

–

Calcium chelate/polyvinyl resin –

Gutta percha (trans 1,4-isoprene polymer)

?

* = Type I allergic reactions are generally not seen with use of these synthetic materials; however, chemicals used in processing and powders in gloves may still cause Type IV reactions in sensitive individuals? = allergic potential is uncertain or unknown but probably low; allergy to one of the components is possible.

Iodine Potassium iodide(2%–5%)

–*

–*

Figure 13 Allergic potential of materials commonly used in endodontic treatment. Adapted in part from Hensten A and Jacobsen N,158 and Zehnder M.151


of allergic reaction from this potential source can beeliminated by using an anesthetic without vasoconstric-tor and preservative (e.g., 3% mepivicaine). Local anes-thetic cartridges contain two potential sources of latexallergen that could possibly leach into the anestheticsolution—the rubber stopper and the diaphragm. Arecent review of the literature found no case reports orcontrolled studies demonstrating that the latex presentin a dental local anesthetic cartridge could cause anallergic reaction.139 However, the same review foundseveral case reports of allergic reactions attributed totrace amounts of latex found in other medication vialstoppers and intravenous tubing. Even though there isno strong evidence to support the avoidance of localanesthetic cartridges in patients with a known latexallergy, experts in the area have recommended usinglocal anesthetic from glass-enclosed vials to avoid anypotential risk of exposure to latex allergens.140,141 If itcan be determined that the local anesthetic cartridgecontains non-latex materials for the diaphragm andstopper, then there is no need for concern.

It should also be noted that a documented allergy toone type of amide local anesthetic does not necessarilyimply allergy to all amide local anesthetics and often areadily available alternative can be found after test-ing.128,132 As a practical matter, patients referred forallergy testing should be given sample cartridges of atleast two different local anesthetics so that the allergistcan test with the same solution that will be used fordental treatment. Options for patients with a docu-mented allergy to all commonly used local anestheticsinclude sedation, general anesthesia, electronic anesthe-sia,132,142 and injectable diphenhydramine. A solutionof 1% diphenhydramine with 1:100,000 epinephine canbe compounded by a local pharmacist and used forinfiltration or mandibular block injections. The dosageshould be limited to a maximum of 50 mg at eachappointment.123

LATEXOf the many materials used in the dental office with thepotential for initiating an allergic reaction, natural rub-ber latex (NRL) is the most common.143 Reports ofallergic reactions to NRL began in 1987 coincident withthe widespread adoption of universal precautions,including the use of latex gloves for practically all med-ical and dental procedures.144,145 Type IV sensitivity isthe most common type and is related to the variouschemicals used in processing NRL. The potentially muchmore serious Type I sensitivity to NRL is a reaction toproteins found in NRL. Approximately 6% of the gen-eral population is believed to have Type I sensitivity to

NRL and this number increases to as much as 17% forhealth care workers.146 Urticaria is the most commoninitial finding in Type I sensitivity reaction to NRL.144

Patients with a history of multiple surgeries (especiallyspina bifida) or atopy (multiple allergies) and healthcare workers all have an increased risk of sensitivity toNRL. Some food allergies (e.g., avocado and banana) areassociated with an increased risk of latex allergy. Con-sidering the multiple potential sources of exposure toNRL in the dental office (e.g., rubber dam material,gloves, local anesthetic cartridges, rubber mouth props,rubber tubing, and even some blood pressure cuffs),history of allergy to NRL requires special treatmentmodifications. In addition, clinicians who treat patientswith known or suspected sensitivity to NRL should beprepared to provide initial management of an acuteallergic reaction if necessary.

Consultation with the patient’s primary care physicianor allergist is advised to help assess the degree of risk,previous reactions and treatment, and possible premedi-cation with a corticosteroid. All potential sources of NRLexposure in the dental office should be considered. Non-latex gloves and rubber dam materials are now readilyavailable from commercial sources, and these items maybe easily substituted for NRL-containing products. Sincelatex allergens can be transferred by contact with powderfrom latex gloves and other sources, it may be prudent toschedule the patient as the first of the day to decrease thechance of contact with residual latex allergens on envir-onmental surfaces, clothing, and room air.147 The poten-tial for cross-reaction with gutta-percha in NRL-sensitivepatients has not been demonstrated although cautionshould be exercised to avoid extrusion of any fillingmaterial beyond the confines of the root canal space(for more on this subject, please refer to section ‘‘Intra-canal medications, cements, and filling materials’’). Also,as previously discussed, the potential for reaction to latexallergens present in the local anesthetic cartridge stopperor diaphragm should be considered.

ANTIBIOTICS AND ANALGESICSAllergy to penicillin is one of the most common drugallergies and affects approximately 2.5 million peoplein the United States.123 Although many reportedallergic reactions cannot be confirmed unless thepatient is willing to undergo testing to rule outallergy to penicillin, it is safest to assume the allergyis real and select an alternative antibiotic. In the caseof allergy to penicillin, it should be presumed thatthe patient is also allergic to the synthetic penicillins.In addition, cephalosporins show cross-reactivity inapproximately 5% to 10% of penicillin allergic

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patients.123 Clindamycin is an appropriate alterna-tive to penicillin for treatment of endodontic infec-tions and bacterial endocarditis prophylaxis.54,148

Clarithromycin is another medication that can beconsidered. More information about antibiotic selec-tion and dosage is found in Chapter 21, ‘‘Treatmentof Endodontic Infections, Cysts, and Flare-Ups.’’

NSAIDs are the usual drugs of first choice formanagement of endodontic-related pain and are tol-erated well by most patients. However, caution shouldbe used in prescribing NSAIDs in patients withasthma and/or known allergy or sensitivity to aspirin.Reports of allergy to codeine are most commonlyrelated to gastrointestinal side effects rather than trueallergy, although allergy to opioid analgesics doesoccur. If the patient’s history suggests an adversereaction related to gastrointestinal distress (includingnausea, emesis, or constipation), an alternative syn-thetic narcotic or a combination pain medicine maybe considered. Analgesics are discussed in more detailin Chapter 22, ‘‘Management of Endodontic Pain.’’

IRRIGATING SOLUTIONSSodium hypochlorite, in concentrations varying from0.5% to 6%, is currently the most commonly usedcanal disinfectant and irrigating solution in endodon-tics.149–151 Sodium hypochlorite not only possessesexcellent tissue solvent and antimicrobial propertiesbut also demonstrates concentration-related tissuetoxicity. Although an allergic reaction and/or hyper-sensitivity to sodium hypochlorite when used as anendodontic irrigating solution is rare, several cases havebeen reported.150,152,153 It has been suggested that somepatients may be sensitized by exposure to householdbleaching products.150 Alternatives to sodium hypo-chlorite include sterile saline or water, chlorhexidine(0.2% to 2%), iodine potassium iodide (2% to 5%),hydrogen peroxide (3%), ethylenediamine tetraaceticacid (EDTA, 10% to 17%), citric acid (10%), and arecently introduced material, MTAD.151,154–157 Ofthese alternatives, iodine potassium iodide and chlor-hexidine possess the potential for stimulating anallergic reaction. A recent review article provides anexcellent overview of the relative advantages and dis-advantages of these selected irrigating solutions.151

INTRACANAL MEDICATIONS, CEMENTS,AND FILLING MATERIALSIntracanal medications such as formocresol, formal-dehyde, eugenol, camphorated phenols, and cresatinare all known to be potential allergens.158,159 Fortu-nately, these canal medications are not frequently

used in current endodontic therapy. Calcium hydro-xide paste, a commonly used intra-appointment med-ication, is not allergenic. Temporary filling materialscontaining zinc oxide and eugenol (ZnOE) have thepotential for allergic reactions and, unlike materialscontained exclusively within the confines of the rootcanal space, are likely to have contact with mucosaltissues.160

Zinc oxide and eugenol, a potential allergen, is a com-mon component of many root canal sealers and twocommon root-end filling materials (IRM and SuperEBA). Sealers containing formaldehyde or paraformal-dehyde (such as N2 paste and Endometazone), especiallywhen extruded beyond the apex, have been demon-strated to stimulate often severe allergic reactions.161–164

Resin-based sealers such as AH26 and AHPlus also havethe potential to stimulate an allergic response,158

although this is believed to be rare. Calcium hydroxide-based sealers such as Sealapex or glass ionomer sealerssuch as Ketac-Endo could be reasonable alternatives forpatients with known allergy to any of the components ofZnOE or resin-based sealers. As always, one should care-fully read the list of ingredients since at least one sealermarketed as a calcium hydroxide-based sealer contains asignificant ZnOE component.

Dentin-bonded resin-type root-end filling materialshave demonstrated excellent biocompatibility in long-term clinical studies with no evidence of allergic reac-tions in treatment failures.165–167 However, the choice ofresin filling material is important since some resins areknown to release formaldehyde when setting. Mineraltrioxide aggregate (MTA), a relatively new material usedfor root-end fillings, apexification, perforation repair,and pulp capping, has demonstrated excellent biocom-patibility and no suspected allergic potential.168–170

Although there have been case reports of suspectedallergic reactions to gutta-percha in patients who wereallergic to NRL,171,172 the possibility that the reactionswere due to another material used in root canal treat-ment could not be ruled out. In fact, cross-reactivitybetween commercially available gutta-percha and NRLhas not been demonstrated.173,174 In addition, gutta-percha is normally well contained within the confinesof the root canal space and therefore should not have thepotential to elicit an immune response. Gutta-perchamanufactured for root canal treatment contains otheringredients such as barium sulfate, zinc oxide, waxes, andcoloring agents; so potential allergy to any of these mate-rials should be considered, especially if there is a potentialfor extrusion of filling material. Newer non-gutta-perchafilling materials (e.g., Resilon) show promise but couldbe expected to contain many of the same added ingre-dients as commercially available gutta-percha. In patients


with multiple allergies (atopy) and suspected allergy toany of the components of gutta-percha, consultationwith the patient’s physician is advised. If safe use of thestandard obturating material cannot be confirmed, onealternative is to fill the root canal space with MTA. Thistechnique presents some technical challenges, especiallyin smaller canals, but should be manageable by an experi-enced clinician. MTA has a relatively long setting time(about 4 hours) but once final hardening has occurred,removal of the filling material through an orthogradeapproach is extremely difficult and is possible only inlarge, straight canals.

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117. Kelleher M, Bishop K, Briggs P. Oral complications asso-ciated with sickle cell anemia: a review and case report. OralSurg Oral Med Oral Pathol Oral Radiol Endod1996;82(2):225–8.

118. Andrews CH, England MC, Jr., Kemp WB. Sickle cell ane-mia: an etiological factor in pulpal necrosis. J Endod1983;9(6):249–52.

119. Tate AR, Norris CK, Minniti CP. Antibiotic prophylaxis forchildren with sickle cell disease: a survey of pediatric den-tistry residency program directors and pediatric hematolo-gists. Pediatr Dent 2006;28(4):332–5.

120. Douglas LR, Douglass JB, Sieck JO, Smith PJ. Oral manage-ment of the patient with end-stage liver disease and the livertransplant patient. Oral Surg Oral Med Oral Pathol OralRadiol Endod 1998;86(1):55–64.

121. Miller CS, Little JW, Falace DA. Supplemental corticoster-oids for dental patients with adrenal insufficiency: reconsi-deration of the problem. J Am Dent Assoc2001;132(11):1570–9; quiz 1596–7.

122. Kay AB. Allergy and allergic diseases. First of two parts.N Engl J Med 2001;344(1):30–7.

123. Little JA, Falace DA, Miller CS, Rhodus NL. Dental manage-ment of the medically compromised patient. St. Louis, MO:Mosby; 2002. pp. 314–27.

124. Baluga JC, Casamayou R, Carozzi E, et al. Allergy to localanaesthetics in dentistry. Myth or reality? Allergol Immuno-pathol (Madr) 2002;30(1):14–19.

125. El-Qutob D, Morales C, Pelaez A. Allergic reaction caused byarticaine. Allergol Immunopathol (Madr) 2005;33(2):115–16.

126. Finder RL, Moore PA. Adverse drug reactions to localanesthesia. Dent Clin North Am 2002;46(4):747–57, x.


127. Brown RS, Paluvoi S, Choksi S, et al. Evaluating a dentalpatient for local anesthesia allergy. Compend Contin EducDent 2002;23(2):125–8, 131–2, 134 passim; quiz 140.

128. Malanin K, Kalimo K. Hypersensitivity to the localanesthetic articaine hydrochloride. Anesth Prog 1995;42(3–4):144–5.

129. Bosco DA, Haas DA, Young ER, Harrop KL. An anaphylac-toid reaction following local anesthesia: a case report. AnesthPain Control Dent 1993;2(2):87–93.

130. MacColl S, Young ER. An allergic reaction following injec-tion of local anesthetic: a case report. J Can Dent Assoc1989;55(12):981–4.

131. Ravindranathan N. Allergic reaction to lignocaine. A casereport. Br Dent J 1975;138(3):101–2.

132. Ball IA. Allergic reactions to lignocaine. Br Dent J1999;186(5):224–6.

133. Seng GF, Kraus K, Cartwright G, et al. Confirmed allergicreactions to amide local anesthetics. Gen Dent 1996;44(1):52–4.

134. Rood JP. Adverse reaction to dental local anaestheticinjection—‘allergy’ is not the cause. Br Dent J 2000;189(7):380–4.

135. Berkun Y, Ben-Zvi A, Levy Y, et al. Evaluation of adversereactions to local anesthetics: experience with 236 patients.Ann Allergy Asthma Immunol 2003;91(4):342–5.

136. Campbell JR, Maestrello CL, Campbell RL. Allergic responseto metabisulfite in lidocaine anesthetic solution. Anesth Prog2001;48(1):21–6.

137. Schwartz HJ, Sher TH. Bisulfite sensitivity manifesting asallergy to local dental anesthesia. J Allergy Clin Immunol1985;75(4):525–7.

138. Seng GF, Gay BJ. Dangers of sulfites in dental local anes-thetic solutions: warning and recommendations. J Am DentAssoc 1986;113(5):769–70.

139. Shojaei AR, Haas DA. Local anesthetic cartridges andlatex allergy: a literature review. J Can Dent Assoc2002;68(10):622–6.

140. Malamed SF. Medical emergencies in the dental office. 5thed. St. Louis, MO: Mosby; 2000. p. 394.

141. Roy A, Epstein J, Onno E. Latex allergies in dentistry:recognition and recommendations. J Can Dent Assoc1997;63(4):297–300.

142. Malamed SF, Quinn CL. Electronic dental anesthesia in apatient with suspected allergy to local anesthetics: report ofcase. J Am Dent Assoc 1988;116(1):53–5.

143. Scully C, Ng Y-L, Gulabivala K. Systemic complications due toendodontic manipulations. Endod Top 2003;4:60–8.

144. Huber MA, Terezhalmy GT. Adverse reactions to latex pro-ducts: preventive and therapeutic strategies. J Contemp DentPract 2006;7(1):97–106.

145. Hamann CP, DePaola LG, Rodgers PA. Occupation-relatedallergies in dentistry. J Am Dent Assoc 2005;136(4):500–10.

146. Clarke A. The provision of dental care for patients withnatural rubber latex allergy: are patients able to obtain safecare? Br Dent J 2004;197(12):749–52; discussion 746.

147. Kosti E, Lambrianidis T. Endodontic treatment in cases ofallergic reaction to rubber dam. J Endod 2002;28(11):787–9.

148. Baumgartner JC, Xia T. Antibiotic susceptibility of bacteriaassociated with endodontic abscesses. J Endod2003;29(1):44–7.

149. Johnson BR, Remeikis NA. Effective shelf-life of preparedsodium hypochlorite solution. J Endod 1993;19(1):40–3.

150. Kaufman AY, Keila S. Hypersensitivity to sodium hypo-chlorite. J Endod 1989;15(5):224–6.

151. Zehnder M. Root canal irrigants. J Endod 2006;32 (5):389–98.

152. Caliskan MK, Turkun M, Alper S. Allergy to sodium hypo-chlorite during root canal therapy: a case report. Int Endod J1994;27(3):163–7.

153. Dandakis C, Lambrianidis T, Boura P. Immunologic evalua-tion of dental patient with history of hypersensitivity reac-tion to sodium hypochlorite. Endod Dent Traumatol2000;16(4):184–7.

154. Torabinejad M, Khademi AA, Babagoli J, et al. A new solu-tion for the removal of the smear layer. J Endod2003;29(3):170–5.

155. Shabahang S, Pouresmail M, Torabinejad M. In vitro anti-microbial efficacy of MTAD and sodium hypochlorite. JEndod 2003;29(7):450–2.

156. Beltz RE, Torabinejad M, Pouresmail M. Quantitative ana-lysis of the solubilizing action of MTAD, sodium hypochlor-ite, and EDTA on bovine pulp and dentin. J Endod2003;29(5):334–7.

157. Vianna ME, Gomes BP, Berber VB, et al. In vitro evaluationof the antimicrobial activity of chlorhexidine and sodiumhypochlorite. Oral Oral Surg Oral Med Oral Pathol OralRadiol Endod 2004;97(1):79–84.

158. Hensten A, Jacobsen N. Allergic reactions in endodonticpractice. Endod Top 2005;12:44–51.

159. Gawkrodger DJ. Investigation of reactions to dental materi-als. Br J Dermatol 2005;153(3):479–85.

160. Hensten-Pettersen A, Jacobsen N. Perceived side effects ofbiomaterials in prosthetic dentistry. J Prosthet Dent1991;65(1):138–44.

161. Forman GH, Ord RA. Allergic endodontic angio-oedema inresponse to periapical endomethasone. Br Dent J 1986;160(10):348–50.

162. Kunisada M, Adachi A, Asano H, Horikawa T. Anaphylaxisdue to formaldehyde released from root-canal disinfectant.Contact Dermititis 2002;47(4):215–18.

163. Haikel Y, Braun JJ, Zana H, et al. Anaphylactic shock duringendodontic treatment due to allergy to formaldehyde in a rootcanal sealant. J Endod 2000;26(9):529–31.

778 / Endodontics

164. Braun JJ, Zana H, Purohit A, et al. Anaphylactic reactionsto formaldehyde in root canal sealant after endodontictreatment: four cases of anaphylactic shock and three ofgeneralized urticaria. Allergy 2003;58(11):1210–15.

165. Rud J, Rud V, Munksgaard EC. Long-term evaluation ofretrograde root filling with dentin-bonded resin composite.J Endod 1996;22(2):90–3.

166. Rud J, Rud V, Munksgaard EC. Periapical healing of man-dibular molars after root-end sealing with dentine-bondedcomposite. Int Endod J 2001;34(4):285–92.

167. Andreasen JO, Munksgaard EC, Fredebo L, Rud J. Period-ontal tissue regeneration including cementogenesis adjacentto dentin-bonded retrograde composite fillings in humans.J Endod 1993;19(3):151–3.

168. Torabinejad M, Chivian N. Clinical applications of mineraltrioxide aggregate. J Endod 1999;25(3):197–205.

169. Torabinejad M, Hong CU, Pitt Ford TR, Kaiyawasam SP.Tissue reaction to implanted super-EBA and mineral trioxide

aggregate in the mandible of guinea pigs: a preliminary report.J Endod 1995;21(11):569–71.

170. Koh ET, McDonald F, Pitt Ford TR, TorabinejadM. Cellular response to mineral trioxide aggregate. J Endod1998;24(8):543–7.

171. Gazelius B, Olgart L, Wrangsjo K. Unexpected symptoms toroot filling with gutta-percha. A case report. Int Endod J1986;19(4):202–4.

172. Boxer MB, Grammer LC, Orfan N. Gutta-percha allergy in ahealth care worker with latex allergy. J Allergy Clin Immunol1994;93(5):943–4.

173. Costa GE, Johnson JD, Hamilton RG. Cross-Reactivity stu-dies of gutta-percha, gutta-balata, and natural rubber latex(Hevea brasiliensis). J Endod 2001;27(9):584–7.

174. Hamann C, Rodgers PA, Alenius H, et al. Cross-reactivitybetween gutta-percha and natural rubber latex:assumptions vs. reality. J Am Dent Assoc 2002;133(10):1357–67.


CHAPTER 25

DRUG INTERACTIONS AND LABORATORY

TESTS

PAUL D. ELEAZER

Drug Interactions

Drug interaction discussions are often exhaustive,but may not be directed to probabilities of interac-tions clinicians are more likely to experience.Drug–drug interactions as well as some food–drugand herbal medicine–drug interactions that arelikely to occur will be considered in this chapter.While dentists are not obliged to treat everypatient, they cannot deny treatment based on apatient’s disability, such as a medical condition.Therefore, it is important to be prepared to treatpatients taking multiple drugs by becoming awareof dangerous drug interactions.

The drug interaction information in this chapteris derived from the work of a panel of pharmacolo-gists who factor likelihood of an interaction withseverity of the possible reaction to arrive at a level ofclinical significance.1 Some less likely reactions withserious potential adverse results are also included.Certainly new reactions, some serious, will be dis-covered as more knowledge accumulates. On-lineresources are available for updated information.2,3

Principles of pharmacology and history taking canhelp the clinician determine probable risk for indivi-dual patients. Drug interactions can be classed aspharmacokinetic or pharmacodynamic. Pharmacoki-netic reactions include changes of rate or extent ofabsorption, distribution, metabolism, or excretion.Pharmacodynamic drug interactions involve achange in the patient’s response without a change indrug plasma level.

An example of a pharmacokinetic absorption isthe anti-diarrheal Kao-Pectate (kaolin and pectin)which decreases absorption of tetracycline antibio-tics. An example of pharmacokinetic drug interac-

tion of distribution is epinephrine and b-blockerdrugs competing for the same binding site onalbumin. Metabolism-type pharmacokinetic inter-actions include the macrolide family of antimicro-bials competing for the breakdown liver enzymepathway with drugs such as Tagamet (cimetidine).Elimination drug reactions include the competi-tion of methotrexate and nonsteroidal anti-inflammatory drugs (NSAIDs) for removal by thekidney.

An example of pharmacodynamic reaction isethanol and a benzodiazepine combining to increasecentral nervous system (CNS) sedation without adetectable difference in plasma levels in either ofthe drugs from their levels if administered alone.

Interviewing the patient may provide valuableclues about possible drug reactions or interactions.When drug action is plotted against response in alarge patient population, the graph is almost alwaysa bell-shaped curve, meaning that a few patientsdevelop an exaggerated response and some showvery little effect. Most people have the expectedresponse. If a patient has a history of over- orunder-response to a drug, the clinician should bealert to a similar response. Drug interactions formembers of the same drug class are likely tobe analogous, but there are exceptions. A secondmajor consideration in history taking is thepossibility of inaccurate reporting by the patient.Such may be the case with a patient who deniesa medical problem based on a sense of bravado orone who vainly wants to postpone admission ofthe encroachment of age. Furthermore, patientsmay simply forget important details of their drugsor dosages. Also, many lay persons who are notwell versed in medical conditions may not grasp

780

the importance of reporting all their specific con-ditions or chronic medications.

Some authors have suggested that generic medi-cations may not be as effective as brand namedrugs, especially for certain categories of drugs. Anexample of this is illustrated by the discovery ofimperfections with enteric coatings that would notprotect the medication from adverse effects ofacidic stomach contents.4

The prudent practitioner should observe druginteraction reports for newly introduced drugs andbe cautions about prescribing these drugs until suffi-cient time has elapsed to elucidate all reactions.Often, drug interactions are discovered after a drug isintroduced to the market, even though many lab tests,animal tests, and human trials were performed beforerelease of the drug for sale. An example of such asituation is the drug ketorolac (Toradol). It was foundvery effective in controlling postoperative dental painand was widely prescribed before being associated withstomach and kidney problems that eventually lead towithdrawal of the oral form from the market, exceptfor brief follow-up to parenteral use.5

Dentists are fortunate in that they seldom need toprescribe drugs for chronic use. Brief exposure limitsdrug interactions and side effects compared to long-term use. Even so, some important drug interactionsoccur rapidly.

For many drug interactions, the net result issimply a change in reaction to one or both drugs.The change can be an increased response or adecreased effect. Sometimes, a combination ofdrugs results in an unexpected interaction. Anexample of a surprising increased drug effect occurswhen administering benzodiazepine drugs topatients taking the calcium channel blocker diltia-zem (Cardizem). The combination causes littlechange to diltiazem action, but results in a rapidincrease in benzodiazepine sedation, apparentlybecause the calcium channel blocker decreasesmetabolic breakdown of the benzodiazepine. Inone study, the area under the curve of drug con-centration over time for a benzodiazepine wasnearly tripled.6

Individual variation plays an important role inmuch of what we know about drug interactions.Generally, those affected more are the elderly,whose metabolic systems are less robust. Often,those with chronic systemic disease, and those tak-ing multiple medicines, are more likely to havedrug interactions, perhaps because unknown reac-tions may be at work. Patients taking herbal med-

icines and those on atypical diets also may be morelikely to have an unexpected drug reaction.

Some patients may not be greatly affected by adrug interaction and might not report it to theirprescribing doctor. Even among observant patients,the number of dramatic drug interactions thataffect every patient every time is probably verylow. This inconsistency of effect may allow thepractitioner to gain confidence in prescribing drugsif they see their patients having no problems. Evenfor a specific individual, past experience with com-bining drugs is no guarantee of safety.

The most serious reactions of concern to den-tists are listed in Tables 1–12. With theophylline,the margin between therapeutic dose and toxiclevel is narrow. With international travel now com-monplace, drugs removed from the market in onecountry may be brought in from another, makingthe need to know overseas trade names as wellas the generic labels. Such is the case with non-sedating antihistamines astemizole (Hismanal) andterfenadine (Seldane), which can cause life-threa-tening torsades de pointes cardiac arrhythmias ifcombined with macrolide antibiotics.

Systemic epinephrine can adversely affect apatient without drug interaction by increasinganxiety and causing frightening tachycardia.Keeping the local anesthetic in the local area mini-mizes the possibility of drug interaction. However,Lipp et al.7 experimented with labeled epinephrineand found a 22% incidence of intravascular injec-tion without positive aspiration, meaning that theclinician should not derive a false sense of securityfrom a lack of aspiration of blood during ananesthetic injection. Avoidance of systemic inter-action can best be assured by slow injection withobservation of the patient for signs of systemicinjection of epinephrine, such as pallor, tachycar-dia, and anxiety.

The concept of decreased drug effect of oral con-traceptives by orally administered antibiotics hasreceived attention in the lay press. Careful researchhas led to the belief that antibacterial drugs com-monly used by dentists are very unlikely to causea failure in oral contraception. Research suggeststhat the antifungal drug ketoconazole and the anti-tuberculosis drug rifampin may have an effecton oral contraceptives. It is prudent for clinicians tosuggest alternative methods of contraception tofemale patients of childbearing age because birthcontrol pills are not 100% effective and because ofthe misinformation in the lay press.

Chapter 25 / Drug Interactions and Laboratory Tests / 781

Over-the-counter drugs can cause drug interac-tions of concern to the dentist. Herbals can alsocause drug interaction problems. One problem withherbals is that many patients consider them to bedietary supplements and fail to report that they aretaking an herbal. Recent study has elucidated manydrug interactions with herbals.

Dentists commonly use antimicrobial drugs,pain relievers, and local anesthetics. Antimicrobialdrugs have eliminated many risks of life. The firsttrue antibiotic, penicillin, came into common useamong dentists following World War II. Becauseso many patients have taken antibiotics, it is a littlewonder that many drug interactions have beenidentified.

Tetracyclines were developed after penicillin. Asthey were gaining in popular usage, penicillin drugswere undergoing structural changes to offer differ-ent forms to counter antimicrobial resistance. Ery-thromycin, the original macrolide antibiotic, wasintroduced after tetracyclines. For a time, erythro-mycin was widely popular among dentists, whochose it because there was no risk of anaphylacticreaction and because antibiotic resistance to thisdrug originally seemed to be a limited problem.While severe allergic problems have not arisen,bacterial resistance and serious drug interactionshave limited use of erythromycin and its congeners,clarithromycin (Biaxin) and azithromycin (Zithro-max). The many drugs now known to interact withmacrolides do so because of shared metabolic path-ways that delay metabolism. Higher levels of one orboth drugs commonly result in severe cardiacrhythm problems, some life-threatening. Surpris-ingly, even anti-arrhythmic drugs may cause sucharrhythmias when administered with macrolides.One should note that combinations do not alwayscause a predictable reaction, meaning that prescrib-ing a certain dose for a particular individual with-out untoward reaction does not guarantee a similarresult for subsequent prescriptions.

Severe muscle wasting serious reactions mayoccur with macrolides when combined with ‘‘sta-tin’’ drugs, very commonly used for lowering cho-lesterol. These drugs inhibit HMG-CoA reductase,a key enzyme in the production pathway of the‘‘bad’’ or low density cholesterol. Muscle achesare among the first symptoms that can occur withthe drug alone, but occur much more often whenthe macrolide antibiotic effectively increases itsconcentration by impeding metabolism throughtheir common liver pathway. The symptoms may

take a few days to appear. Damaged muscle leads toincreased creatine phosphokinase enzyme levels,which are typically used to confirm a clinician’ssuspicion of this potentially very serious drug inter-action. Early reports question whether rosuvastatin(Crestor) is subject to this interaction.8

Ergot derivatives, which mitigate vascular head-aches, may interact with macrolide antibiotics,inducing peripheral ischemia secondary to vasos-pasm. Not all patients respond to reversal therapyfor this drug interaction, making this a very seriouspotential problem.

Yet another category of classic interaction withdrugs slowing metabolic pathways occurs withmacrolides. To reach therapeutic levels, theophyl-line is often administered in doses close to the toxicthreshold. When paired with erythromycin, thedecreased elimination may push the concentrationof the bronchodilator into the danger zone.Obviously, the higher the patient’s therapeuticdose, the greater the risk. Early studies indicateazithromycin probably acts similarly, while clari-thromycin may not.9,10

Table 1 contains more serious and more prob-able reactions of drugs with macrolide antibiotics.Dentists who prescribe macrolides should maintainvigilance for signs of any interaction.

Table 2 ranks potential reactions to metronida-zole (Flagyl), a drug many dentists prescribe. Thisdrug’s antibacterial spectrum is for obligate anae-robes, but some obligate anaerobes are resistant.Clinicians often use this DNA impeding agent witha penicillin or cephalosporin bactericidal drug.Research has shown that most endodontic infec-tions contain multiple organisms, characteristicallywith many facultative microbes.11 Outcome analy-sis of microbial susceptibilities of cultures fromendodontic infections shows that metronidazolealone is not effective for these infections.12

Metronidazole shares the adverse interaction ofanticoagulant drugs with all antibiotics. By killingnormal gut flora, the production of vitamin Kdecreases, thus altering the balance between thenormal clotting enhancing vitamin and the clot-preventing anticoagulant. The result is that a clin-ical bleeding problem is more likely. Metronidazolehas an additional interaction of importance to theclotting balance. It further increases bleeding pro-clivity by a direct inhibition of metabolism ofwarfarin (Coumadin).13

Also of note, metronidazole shows interactionwith ethanol, just like with disulfram (Antabuse),

782 / Endodontics

resulting in nausea and vomiting in many patients.The clinician should caution patients to avoid etha-nol while taking metronidazole and for 1 full daythereafter to ensure no untoward drug interaction.Another drug interaction of metronidazole is, whencombined with Antabuse, patients taking metroni-dazole have experienced acute psychotic reactions.

Except for potentially fatal allergic reactions(anaphylaxis), the penicillin family of antibiotics,and the cephalosporins, have remained relativelyfree of serious drug interactions (Table 3). Thepenicillins are very effective against common endo-dontic pathogens.12 Most cephalosporins are not

Table 1 Potential Reactions between Macrolide* Antibiotics and All Drugs

Rapid Reactions Delayed Reactions

Very significant

Established reaction Established reactions

s Carbamazepine (Tegretol) (! toxicity) (76b) s Cisapride (Propulcid) (! arrhythmia) (192)

s Digoxin (! toxicity) (285a)

Probable reaction Probable reactions

Ergot derivatives (! peripheral ischemia) (315a) s Anticoagulants (! bleed) (79)

s Statins (! myopathy) (rhabdomyolysis) (368hb)

s Primozide (Orap) antipsychotic (! cardiotoxicity) (575d)

Suspected reactions

s Antiarrhythmics (! arrhythmia) (36a)

s Eplerenone (hyperkalemia) (! arrhythmia) (312c)

Grapefruit = s absorption (! toxicity) (479f)

Some quinolones = (! arrhythmia) (479h)

Verapamil, s macrolide (! cardiotoxicity (759)

Somewhat less significant Established reactions

s Theophylline (! toxicity) (714a)

s Corticosteroid (! possible toxicity) (221)

s Cyclosporine = (! nephrotoxicity amp; neurotoxicity) (236a)

Probable reaction

Rifampin (! t antibacterial/s gut effects) (479i)

Suspected reaction Suspected reactions

s Benzodiazepines (! sedation) (131a) Tacrolimus (Prograf) (! s tacrolimus toxicity) (685d)

Repag. (Prandin) (! s Repag = t blood glucose) (613b)

Numbers indicate page number in Facts and Comparisons, Drug Interactions.1

*Macrolides share liver metabolic pathways with many other drugs, generally resulting in delayed metabolism of both drugs, which increases drug levels.

t Drug action is probably diminished.

s Drug action is probably increased.

Table 2 Metronidazole* (Flagyl) and All Drugs


Very significant s Anticoagulants (bleed) (82)

Somewhat less significant Suspected reactions

Suspected reaction

Ethanol (! disulfram

reaction) (335)

Barbiturates speed metabolism of

metronidazole (! t antibacterial)

(512), Disulfram (! acute psychosis)

(304)

Numbers in brackets indicate page number in Facts and Comparisons,Drug Interactions.1

*This antibiotic decreases metabolism of warfarin. It also may cause

nausea if combined with ethanol or disulfram (Antabuse), but reaction

is inconsistent.



Table 3 Penicillins/Cephalosporins and All Drugs

Delayed Reactions

Suspected reactions

Tetracyclines (! cidal drug) (560)

Methotrexate (! toxicity) (496c)

Somewhat less significant

Suspected reactions

Allopurinol (Zyloprim) (! rash) (555)

Food decreases ! absorption (559)

Beta-blockers (t antihypertensive + antianginal) (155)

Warfarin, s bleeding (51)

Aminoglycosides, inactivated by parenteral Penicillin (PCN) (22)

Aminoglycosides + cephalosporin (! nephrotoxicity) (18)

Numbers in brackets indicate page number in Facts and ComparisonsDrug Interactions.1




effective against the strict anaerobes found in endo-dontic infections. There may be cross-allergenicitybetween penicillins and cephalosporins.

Methotrexate, a powerful anti-metabolite forsome types of cancer and for refractory arthritispatients, combined with penicillin has causedsevere toxicity, including renal failure, myelosup-pression, neutropenia, thrombocytopenia, and skinulcers. Cephalosporins have not been reported tocause this drug interaction.

Quinolone antibiotics have potential to causesevere interactions with several drugs (Table 4).As with macrolides, quinolones cause serious car-diac rhythm problems in the presence of manyother drugs. The macrolide–quinolone combina-tion is one of the drug interactions that can causefatal arrhythmias. Macrolides or quinolones plus

cisapride (Propulcid) may interrupt normalnerve impulse conduction within the heart thatmay threaten life. Yet another problem that qui-nolones have is the drug interaction with theo-phylline. The shared metabolic pathway similarlycauses theophylline concentrations to increase totoxic levels. These similarities occur even thoughthe molecular structures of the two drug classesare quite different.

Coumadin plus a quinolone may produce a car-diac rhythm problem.14 All antibiotics can causebleeding problems for patients taking anticoagu-lants because the antibiotic kills gut flora that pro-duce vitamin K, a natural substance that enhancesclotting. Lack of this balance means patient takeslonger to clot. When healthy patients take an anti-biotic, the reduction in vitamin K causes no clini-cally apparent change in clotting parameters. Thewell-informed dentist should be able to evaluateblood clotting tests such as bleeding time andInternational Normalized Ratio (INR) with thepatient’s physician.

Tetracyclines have seen resurgence in popularityamong dentists because of their actions againstcollagenase and their effectiveness against period-ontal pathogens, many shared with endodonticdiseases. Both of these advantages carry over intoendodontics. While there is a long list of drugs thatinteract with tetracyclines, the reactions tendto be inconsistent and are rarely life-threatening(Table 5). The digoxin–tetracycline interactionarguably has the most serious potential. In a smallportion of the population, the gut flora metabol-izes a significant percentage of their digoxindose, meaning that they need a fairly high doseto achieve the proper steady-state digoxin level.

Table 4 Quinolone* Antibiotics and All Drugs


Very significant Probable reaction

Anticoagulants s bleed (92)

Suspected reactions

Serious arrhythmias with:

phenothiazines (573);

Cisapride (Propulsid) (610b);

Macrolide antibiotics (479h);

Tricyclic antidepressants (750a);

Ziprasidone (Geodon) (773e);

Antiarrhythmics (36b)


Antacids, t Quinolone absorption

(610)

Suspected reactions

Cyclosporine, nephrotoxicity (238j)

Theophylline s Theo ! toxicity

(716)

Probable reactions

Sulcralfate (Carafate) = t

Quinolone absorption (610j)

Heavy metal salts = t

Quinolone absorption (610f)

Suspected reactions

Sevelamer (Ranagel) = t

Quinolone absorption (610i)

Tizanidine (Zanaflex) = t

Tizanidine metabolism ! t

oxicity (735 ab)

Food = t Quinolone absorption

(610d)

Numbers in brackets indicate page number in Facts and Comparisons DrugInteractions.1

*Note that serious psychotic reactions can occur with these drugs. Such

reactions may persist long after the drug is discontinued.



Table 5 Tetracycline and All Drugs

Delayed Reactions

Suspected reactions

Pens/Cephs, cidal/ static (560)

Digoxin, s dig. (295)


Suspected reactions

Activated charcoal, absorbs (182)

Heavy metal salts = chelation (686) (687) (688) (693) (696)

Retinoids (Accutane) risk of (614) benign intracranial hypertension




784 / Endodontics

Tetracyclines can induce significant microflorachanges, such that greater digoxin absorption leadsto toxic levels. As noted above, macrolides interactwith digoxin in a different way, inhibiting renalexcretion of digoxin, also reaching potentially toxiclevels, and this change can last for many days aftermacrolide is stopped.

While it may be nice to contemplate treatingendodontic patients without antibiotics, such isan unrealistic dream. No antibiotic is withoutpotential interaction with other drugs. The rapiddiscovery of new interactions mandates that thosewho treat infected patients keep abreast of contem-porary information.

Pain control drugs fall into a similar situation.Certainly, modern endodontic techniques and bet-ter appreciation of the value of ‘‘not’’ harmingtissues adjacent to root canals have helped reducethe need for pain-relieving drugs. Yet, postopera-tive pain will remain a factor in treating someendodontic maladies. Clinical experience of manydentists reinforces the experimental observationsthat NSAIDs are effective pain relievers. Most prac-titioners find NSAIDs as effective as codeine orhydrocodone for most patients. Chronic NSAIDuse has revealed stomach and kidney problems,especially among the elderly, but only a few pro-blems have been associated with short-term use.

Serious drug interactions with NSAIDs are rela-tively rare (Table 6). The effect of Coumadin ispotentiated by NSAIDs. The prescription ofNSAIDs for only a few doses limits the clinicalappearance of this interaction. But a very serious

NSAID reaction is with methotrexate, resulting inkidney failure. This reaction is more likely withhigh-dose methotrexate, typically used for anti-neoplastic therapy, as opposed to the lower dosesused for rheumatoid arthritis refractory to lesspowerful drugs.

Patients taking b-blockers may experiencehypertension breakthrough when taking NSAIDs.Sulindac (Clinoril) apparently does not have thepropensity to cause this reaction.15

Lithium toxicity induced by adding NSAIDs hasoccurred. The decrease of lithium metabolism hasnot resulted in clinical problems in healthypatients.16

NSAIDs and the very popular antidepressantsthat work by selective serotonin re-uptake inhibi-tion (SSRI) drugs within brain synapses can interactadversely. Increased gastrointestinal (GI) bleedinghas been reported, although the problem has alsooccurred when an SSRI drug was used alone.17

Narcotic pain relievers will continue to play auseful role for dentists, albeit less necessary becauseof improved understanding and better instrumentsand techniques. Demerol (meperidine) is the mosttroublesome for potential interactions. The mostserious, sometimes resulting in death, is less likelynow because oxidase inhibitors are rarely pre-scribed. Other reactions are listed in Table 7.

Control of intra-operative pain is a standard bywhich patients judge their endodontic caregiver.Pilots are judged by how smoothly they can landa plane even though this is a small part of a pilot’sskill. Similarly, patients judge us by our skill atgiving an ‘‘easy shot.’’

There are two separate drug interaction consid-erations with local anesthetics, the anesthetic itselfTable 6 Nonsteroidal Anti-inflammatory Drugs and All

Drugs

Delayed Reactions

Very significant

Probable reaction

Anticoagulants s bleed (86a, 86b)

Suspected reaction

Methotrexate s Methotrexate (! toxicity) (496)


Probable reaction

Beta-blockers = t antihypertensive (154)

Suspected reactions

Aminoglycosides, s antibiotic (21)

s Lithium (! Li toxicity) (464)

SSRI, s gut bleed (548)

SSRI, selective serotonin re-uptake inhibition. Numbers in brackets

indicate page number in Facts and Comparisons Drug Interactions.1



Table 7 Narcotics* and All Drugs


Very significant

Demerol and Mao inhibitors (488)


Probable reaction Suspected reaction

Demetrol + Phenothiazines (488a) Demetrol + Ritonavir

(Norvir) (488b)

Suspected reaction

Barbiturates (112)

Numbers in brackets indicate page number in Facts and Comparisons

Drug Interactions.1

Note that death has been reported from giving Demerol to Manomine

oxidase (MAO) inhibitor patients.

*Most reactions are due to additive central nervous system effects.


and the vasoconstrictor. Epinephrine is very rapidlymetabolized, so any drug interaction is rapidlyapparent (Table 8). Tolerance of the vasoconstric-tor in one dose means that an additional dose afterabout 5 minutes can be given with similar result,given that neither is injected systemically.

Hypertensive events have been documented inpatients taking b-blockers, Furazolidone (Furox-one) tricyclic antidepressants, methyl dopa, andthe anti-hypertensive drugs guanethedine (Ismelin)and Rauwolfia alkaloids. Beta-blocker interact-ions are potentially the most serious. It is advisableto take a preoperative blood pressure reading toestablish a baseline for that patient. Furthermore,intravascular injection occurs without a positiveaspiration of blood.7

The anesthetic itself does not cause any knownvery serious drug interactions (Table 9). The pro-blem with the anesthetic is that repeated injec-tions build to overdose levels because, unlike thevery rapidly metabolized vasoconstrictor, theanesthetic agent is metabolized over hours. Thisis especially important for pediatric patientswhose body mass cannot tolerate as much anes-thetic as an adult.

Beta-blockers may interact with lidocaine, low-ering the number of doses to reach the toxic range.This drug interaction is believed to be via inhibi-tion of hepatic metabolic enzymes.18

Cimetidine (Tagamet) increases lidocaine levelstoo, probably by the same general effect on liver

enzymes. Yet, the reaction does not occur everytime the drugs are combined.19 Research on otherhistamine H2 antagonists failed to show this inter-action.

Benzodiazepine reactions are typically one of theincreased drug effects and can be accounted for bybeginning with a lower dose, perhaps a half pill,until the patient’s own reaction is defined. Theprotease inhibitor reactions however have beenreported to induce severe sedation and respiratorydepression. As noted in Table 10, no drug interac-tions with benzodiazepines have been ranked in thevery significant category.

Table 11 lists drugs that may be used by dentiststhat interact with Coumadin (warfarin). Thisextensive list calls for careful consideration by the

Table 10 Benzodiazepine* and All Drugs

Rapid Reaction Delayed Reaction


Established reactions Suspected reactions

Ethanol (325) Carbamazepine (Tegretol) (123a)

Azole antifungals (122b) Hydantoins (Dilantin) (375)

Modafinil (Provigil) (131b)

Non-nucleoside reverse

transcriptase (131d)

Inhibitors

Protease inhibitors (133)

St. John’s Wort (136a)

Macrolide antibiotics (131a)

Rifampin (136)

Probable reactions

Diltiazem (Cardizem) (128)

Food (129b)


*In most reactions, benzodiazepine effect is increased, but decreased

with Rifampin. Generally, titration of dosage is indicated.

Table 8 Epinephrine*-Containing Local Anesthetics andAll Drugs

Rapid Reactions

Very significant

Established reaction

Beta Blockers ! hypertension then bradycardia (312)

Suspected reaction

Furazolidone (Furozone) antibiotic ! hypertension (674a)



Tricyclic antidepressants ! hypertension (683)

Suspected reactions

Rauwolfia alkaloids ! hypertension (682)

Methyldopa ! hypertension (680)

Guanethidine ! hypertension (354)

Numbers in brackets indicate page number in Facts and ComparisonsDrug Interactions.1Epinephrine is rapidly metabolized, so delayed

reactions do not occur.

*Minimize risk by injecting slowly and watching patient reaction.

Table 9 Local Anesthetics and All Drugs

Rapid Reaction


Established reactions

Beta blockers [! (Lido. toxicity)] (450a)

Histamine H2 Antagonists (Tagamet) (! Lido. toxicity) (451)

Suspected reaction

Succinylcholine, s succinylcholine half-life (636)




786 / Endodontics

dentist and alerting the patient to watch for signs ofbleeding. Notably, the rapid reaction category isempty, indicating that short-term use carries lessharmful potential.

Drug Interactions with Food

and Herbals

Many patients are now taking herbal medicines, yetconsider them as harmless food supplements. Table 12lists more serious interactions with prescriptiondrugs that should be reviewed (the table is derivedfrom the panel of experts described in the beginningof this chapter). Facts and comparisons herbal sup-plements and food publication ranks potential inter-actions into only three categories, of which the moreserious two are included.20 However, many new druginteractions with herbals and food are currentlyunder study and the fact that more people are nowtaking herbals means that more interactions will beelucidated.

Grapefruit–drug absorption interactions accountfor many newly discovered drug level changes.

Apparently, this citrus fruit speeds absorption farmore than other similar fruits. The result can bedamagingly high levels of drug, even in the absenceof other drugs. This action contradicts the typicalfinding that food binds with drugs to decreaseabsorption, or at least slows drug absorption.

Khat is a stimulant plant from East Africa that isusually chewed. It has been imported into theUnited States and other counties as a recreationaleuphoric agent. It sometimes is smoked to achievehigher concentrations, which may induce hallucina-tions. Khat has been shown to decrease absorptionof amoxicillin and its close congener, ampicillin.This may lead to persistence of an infection. A smallstudy demonstrated the maximum decrease to occur2 hours after chewing khat.21 Other potential druginteractions with khat have not been investigatedthoroughly.

Ginkgo biloba, which is commonly used as amemory enhancer, interacts with salicylates andNSAIDs to increase bleeding. The apparentmechanism is by lowered platelet aggregation.

Table 12 Drugs Prescribed by Dentist That May Interactwith Herbal Medicines

Significance

levels

1 Amoxicillin + Khat ! t amoxicillin (85, 86)

1 ASA or NSAIDs + Ginkgo biloba ! bleed by platelet

aggregation) (19, 20)

1 Benzodiazepines + Kava ! s benzo levels (sedation)

(84)

Benzodiazepine + St. John’s Wort !t Benzodiazepine (sedation)

2 Corticosteroids + Licorice ! s corticosteroid (87)

1 Ciprofloxacin + Calcium-supplemented orange juice !s Cipro (95a) # antibiotic absorption

1 Cipro + Zinc ! s Cipro (154ba) # antibiotic

absorption

1 Acetaminophen + Ethyl Alcohol ! Hepatotoxic

Metabolite (14e)

1 Macrolide antibiotics + Grapefruit ! s absorption of

macrolide (toxicity) (44a)

2 Tetracycline + Zinc ! s tetracycline # antibiotic

absorption

1 Tetracycline + dairy products ! # Tetracycline due to

chelation (12a–12d)

Levofloxacin + orange juice (plain or with ca++) ! #Levoflox (95f)


Significance level 1 = herbal drug should not be combined. Significance

level 2 = herbal drug may be continuously allowed.



Table 11 Drugs Prescribed by Dentists That MayInteract with Warfarin Anticoagulant

Delayed Reactions

Very significant

Established reactions

Sulfonamides, bleed (98)

Metronidazole, bleed (82)

Vitamin E, bleed *(197a)

Aspirin (ASA), bleed (94)

Probable reaction

NSAIDs/(86a) CoX2 inhibitors (86b) = bleed

Quinolones = bleed (92)

Macrolides = bleed (79)



Suspected reactions

Acetaminophen = s vitamin K, thus t bleed (39)

Carbamazepine (Tegretol), t bleed (50)

Vitamin K = t bleed (109)

Most antibiotics kill vitamin K bacteria = bleed (51, 89, 92, 47,

82, 93, 98)

NSAIDs, nonsteroidal anti-inflammatory drugs. Numbers in brackets

indicate page number in Facts and Comparisons Drug Interactions.1 Most

drug interactions result in increased bleeding. Tylenol, Tegretol, rifampin,

and vitamin K increase bleeding. The Tylenol reaction is apparently not

consistent and, if reported, exceeded six doses/week. Vitamin K reverses

the action of warfarin. However, there is currently no antidote for Plavix.




Kava, an herbal drug from the South Pacific plantof the same name, is drunk as a tea or now available inpill form to relieve stress and produce a sense of well-being. A single, but serious drug interaction-inducedcoma has been reported. While the reaction occurredwhen combined with alprazolam (Xanax), expertsanticipate that the danger likely extends to the entirebenzodiazepam family.22

Another herbal anxiolytic–benzodiazepine interac-tion has been anticipated, but not yet reported,between a benzodiazepine and the weed-derivedSt. John’s Wort. Experimental evidence demonstratedthat the combination of the herbal and clonazepam(Klonapin) decreased the benzodiazepine levels.23

Licorice has been shown to alter levels of corticos-teroids, either increasing or decreasing the drug.24

The interaction would be more serious in patients onhigh-dose steroid. No evidence exists yet as to exactmechanism of the interaction or about any potentialproblems with natural steroid drugs or overall actionon inflammation or healing.

Orange juice, particularly when calcium-fortified,lowers the levels of the fluoroquinones Cipro(ciprofloxacin) and Levaquin (levofloxacin). Whilethe exact mechanism is unknown, the suspicion isthat the orange juice and the drug compete fortransportation across the intestinal membrane.25

Cipro absorption is also diminished in the pre-sence of zinc, as are tetracycline concentrations.This essential heavy metal additive is common inmultivitamin preparations. The net result of theinteractions is lowering of antibiotic levels in the25 to 40% range.26,27

Tetracycline absorption is also hindered by dairyproducts, which all contain the heavy metal ioncalcium. Doxycycline is the least affected of the tetra-cycline family to bind with heavy metal ions, a pro-cess called chelation.28

Ethyl alcohol is discussed in ‘‘Drug Interactions’’,but there is a brief review in here.20 Perhaps, becauseit is so often used or abused among patients, alcoholis sometimes considered a food. Generally, its inter-actions are to increase action of drugs that act on theCNS. It delays gastric emptying, so can delay absorp-tion of almost any drug taken by mouth. It specifi-cally interacts with metronidazole in a disulfram classreaction, inducing nausea and vomiting. All theabove reactions are dose related, so the astuteclinician should caution patients accordingly. Theinteraction with Tylenol (acetaminophen) is differentand potentially lethal. Chronic use of ethyl alcoholincreases the enzyme that metabolizes acetamino-

phen, resulting in the rapid metabolism of acetami-nophen with consequent high levels of a toxicacetaminophen metabolite, known as NAPQI,N-acetyl-p-benzoquinone.

Lab Tests of Potential Importance

in Endodontics

Dentists may be uncomfortable in orderinglaboratory tests. Referral to a physician is alwaysappropriate, but there is no reason for a dentistto be intimidated by the process. Dentists are oftenthe first healthcare provider to identify systemicdisease. Frequently, this is the case because oraltissues are the first to be affected. Also, manypatients do not regularly visit their physician, ormany receive only cursory information on subtletiesof oral changes from disease. Leukemia, bacterialendocarditis-induced oral petechiae, bleeding disor-ders, various cancers, and many other diseases arefirst suspected in the dental office. Ordering alaboratory test to confirm or rule-out suspicionsis perfectly appropriate for any dentist. Cultureand sensitivity testing for identification of thecause of an infection and the most likely effectiveantimicrobial should be in every dentist’s arma-mentarium.

Laboratory tests are commonly helpful to dentists.The list of lab tests commonly helpful to dentists isnot exhaustive, and dentists should not be limited tothose tests listed below. Disorders of inflammation,perhaps related to a chronic dental infection, maycause an increased erythrocyte sedimentation rate.Blood tests can be helpful in identifying blooddyscrasias from cellular imbalances to inflammatorysystem evaluation and to clotting factors. Most clas-sic hemophiliacs are diagnosed early in life and canprovide the dentist with important information byhistory. Every dentist should be aware of the risksassociated with altered blood clotting profiles of theirpatients. Newly identified risk assessment studieshave shown the mortality and morbidity of decreas-ing anti-clotting parameters. The dentist should becomfortable in interpreting these tests to determine ifa patient is a candidate for a surgical procedure.

The prothrombin time test has been largelyreplaced by the INR, which uses a standardizedcontrol and expresses the result in a percent ofnormal clotting time. This test evaluates the extrinsicclotting mechanism. With an INR of 1 being the

788 / Endodontics

normal level, minor dental-alveolar surgery can becarried out to an INR level <3.5 with local methodsof hemostasis sufficing. For other than minor sur-gery, consultation should be obtained with consid-eration for modification of the anticoagulation orhospitalization.

The partial thromboplastin time test remainsvaluable to determine the intrinsic clotting path-way, which is the clotting factors in blood plasma.

Bleeding time, the number of minutes requiredfor a standard wound to clot, may help diagnoselater onset problems of importance to the dentistsuch as von Willebrand’s disease, where the intrin-sic factor VIII is diminished by this hereditarydefect. Also, bleeding time identifies disorders ofthe platelet system, including those induced bysalicylates or NSAIDs.

Complete blood counts enumerate platelets,different white blood cells, and red blood cellsand can confirm or rule out many suspiciousfindings. An increased number of red cells, poly-cythemia vera, can reveal itself as darker gingival,because of the engorgement of the vascular sys-tem. Bleeding gingival can be seen in many formsof leukemia. Petechiae due to sickle cell anemiacan be diagnosed by the occasional characteristicshaped red blood cells.

While it is easier to direct patients and staff who areaccidentally exposed to blood-borne pathogens tosomeone trained in counseling for such risks, testsfor such infectious agents may be ordered by thedentist who suspects a disease.

Patients with unexplained radiolucencies of theirjaws may need testing for certain disorders. Forexample, a multiple myeloma patient will have theabnormal Bence Jones protein in their urine. Apatient with hyperparathyroidism-caused boneradiolucencies will have elevated blood calciumand decreased blood phosphorus. Urine levels ofcalcium may be lower, with increased urine phos-phorus. Serum alkaline phosphatase is elevated inhyperparathyroidism, although not as markedly aswith Paget’s disease.

Diabetes mellitus has broad implications in heal-ing. Blood or urine glucose elevations can be theimpetus needed to send a patient for medical care.

Allergies can make life unpleasant for many.They may stem from food allergies which can causenutritional imbalances which may be suggested bychanges in oral tissues. They may include dentalmaterials, such as nickel or eugenol, making thepatient less likely to have a favorable treatment

outcome. The dentist who suspects such a problemwill probably refer the patient to an allergist forskin or other tests and then help manage the dentalaspects of the patient’s care.

Summary

There is a limited understanding of drug interactionincidence because of under-reporting. Also, animalstudies may not transfer directly to the human.Animals cannot express mood changes effectivelyand there are some metabolic differences betweenanimals and man.

The astute clinician should explain possibleadverse or undesirable reactions with patients sothat they may watch for an adverse outcome. Thischapter emphasizes drug reactions that are poten-tially very serious and/or very likely to occur. Somepractitioners will see interactions of drugs beyondthose covered here. It is important to report sus-pected drug interactions to the Food and DrugAdministration (FDA) for evaluation. The FDAperiodically sends information about newly discov-ered serious drug interactions to practitionersregistered by state license to practice dentistry.Furthermore, the reader should remember thatinformation about drug interactions is constantlychanging, mostly with newly discovered interactionreports.

References

1. Tatro DS, editor. Facts and comparisons, drug interactionsfacts. St. Louis: Wolters Klewer Health; 2006.

2. Lexi-Comp, Inc. http://www.lexi.com.

3. Epocrates, Inc. http://www.epocrates.com.

4. Agyilirah GA, Banker GS. Polymers for enteric coatingapplications. In: Tarcha PJ, editor. Polymers for controlleddrug delivery. Cleveland, OH: CRC Press; 1990.

5. Fick DM, Cooper JW, Wade WE, et al. Updating the Beerscriteria for potentially inappropriate medication use inolder adults. Arch Intern Med 2003;163:2716–24.

6. Bachman JT, Olkkola KT, Aranko K, et al. Dose of mid-azolam should be reduced during diltiazem and verapamiltreatments. Br J Clin Pharmacol 1994;37:221–5.

7. Lipp M, Dick W, Daublander M, et al. Exogenous and endo-genous plasma levels of epinephrine during dental treatmentunder local anesthesia. Reg Anesth 1993;18(1):6–12.


8. Cooper KJ, Martin PD, Dane AL, et al. The effect oferythromycin on the pharmacokinetics of rosuvastatin.Eur J Clin Pharmacol 2003;59:51–6.

9. Gillum GJ, Israel DS, Scott RB, et al. Effect of combinationtherapy with ciprofloxacin and clarithromycin on theo-phylline pharmacokinetics in healthy volunteers. Antimi-crob Agents Chemother 1996;40:1715–16.

10. Pollak TP, Slayter KL. Reduced serum theophylline concen-trations after discontinuation of azithromycin: evidence foran unusual interaction. Pharmacotherapy 1997;17(4):827–9.

11. Munson MA, Pitt-Ford T, Chong B, et al. Molecular andcultural analysis of the microflora associated with endo-dontic infections. J Dent Res 2002;81(11):761–6.

12. Baumgartner JC, Xia T. Antibiotic susceptibility of bacteriaassociated with endodontic abscesses. J Endod 2002:29:44–7.

13. Yacobi A, Lai C, Levy G. Pharmacokinetic and pharmaco-dynamic studies of acute interaction between warfarinenantiomers and metronidazole in rats. J Pharmacol ExpTher 1984;231:72–9.

14. Linville T, Matani D. Norfloxacin and warfarin. AnnIntern Med 1989;110:751–2.

15. Pope JE, Anderson JJ, Felson DT. A meta-analysis of theeffects of nonsteroidal anti-inflammatory drugs on bloodpressure. Arch Intern Med 1993;153:477–84.

16. Levin GM, Grum C, Eisele G. Effect of over-the-counterdosages of naproxen sodium and acetaminophen onplasma lithium concentrations in normal volunteers.J Clin Psychopharmacol 1998;18:237–40.

17. Dalton SO, Johansen C, Mellemkjaer L, et al. Use ofselective serotonin reuptake inhibitors and risk of up-per gastrointestinal tract bleeding. Arch Intern Med2003;163:59–64.

18. Bax NDS, Al-Asady LD, Deacon CS, et al. Inhibition ofdrug metabolism by b -adrenoceptor antagonists. Drugs1983;26(Suppl 2):121–6.

19. Jackson JE, Bentley JB, Glass SJ, et al. Effects of histamine-2 receptor blockade on lidocaine kinetics. Clin PharmacolTher 1985;37:544–8.

20. Tatro DS, editor. Facts and comparisons, drug interactionsfacts, Herbal supplements and food. St. Louis: WoltersKlewer Health; 2006.

21. Attef OA, Ali AA, Ali HM Effect of khat chewing on thebioavailability of ampicillin and amoxicillin. J AntimicrobChemother 1997;39:523–5.

22. Almeida JC, Grimsley EW. Coma from the health foodstore: interaction between kava and alprazolam. AnnIntern Med 1996;125:940–1.

23. Wang Z, Gorski JC, Hamman MA, Huang SM, Lesko LJ,Hall SD. The effects of St. John’s Wort (Hypericum perfor-atum) on human Cytochrome P450 activity. Clin Pharma-col Ther 2001;70:317–26.

24. Homma M, Oka K, Ikeshima K, Takahashi N, Nitsuma T,Fukudu T, Itah H. Different effects of traditional Chinesemedicines containing similar herbal constituents onprednisolone pharmacokinetics. J Pharm Pharmacol1995;47:687–92.

25. Wallace AW, Victory JM, Amsden GW. Lack of bioequiva-lence when levofloxacin and calcium-fortified orange juiceare coadministered to healthy volunteers. J Clin Pharmacol2003;43:539–44.

26. Polk RE, Healy DP, Sahai J, Drwal L, Racht E. Effect offerrous sulfate and multivitamins with zinc on absorptionof ciprofloxacin in normal volunteers. Antimicrob AgentsChemother 1989;33:1841–4.

27. Penttila O, Hurme H, Neuvonen PJ. Effect of zinc sulfateon the absorption of tetracycline and doxycycline in man.Eur J Clin Pharmacol 1975;9:131–4.

28. Matilla MJ, et al. Interference of iron preparations andmilk with the absorption of tetracyclines. Excerpta MedicaInternational Congress Series No. 254. Toxicological Pro-blems of Drug Combinations. 1927:128–33.

790 / Endodontics

CHAPTER 26

ENDODONTICS INSTRUMENTS

AND ARMAMENTARIUM

A. DENTAL DAM AND ITS APPLICATION

WILLIAM G. SCHINDLER

It may be difficult, if not impossible, to achieve a sterilefield in endodontics; however, every effort should be madeto work as much as possible in a bacteria-free field. Thatbeing said, the use of dental dam is absolutely essentialduring nonsurgical endodontic therapy. For root canaltreatment, rapid, simple, and effective methods of damapplications have been developed. In all but the mostunusual circumstances, the dental dam can be placed onthe tooth being treated in less than a minute. Its routineuse will enhance every aspect of endodontic therapy.

Although the modern nonsurgical endodonticapproach to the use of dental dam has changed, theimportance and purposes of the dam remain the same:

1. It provides a dry, clean, and disinfected operatingfield removed from saliva and blood.

2. It protects the patient from possible aspiration orswallowing of tooth debris, restorative materials,bacteria, necrotic pulp tissue, and instruments1–3

(Figure 1).3. It protects the adjacent soft tissues (tongue, lips,

cheek) by retracting them out of the way.4. It protects the patient’s soft tissues from irritating

irrigating solutions and drugs that may be usedduring treatment.

5. Visibility and efficiency are improved.6. Its routine use protects the clinician from litiga-

tion related to instrument aspiration or swallow-ing. Even swallowing diluted sodium hypochloritecan be dangerous in addition to it having anunpleasant taste.4 Use of dental dam for nonsurgi-cal endodontics is the standard of care.5

The clinician should be aware that there may be rareinstances when coronal access to root canals might be

made prior to the placement of the dental dam.Examples of this situation may include severe tippingof teeth, extreme calcification of the canal system, andorientation difficulties related to coronal restoration.However, once the chamber or canals have been locatedand before instruments or irrigating solutions havebeen used, the dental dam must be placed.

Equipment

DAM MATERIALDental dam is available in a variety of thicknesses,colors, sizes, and material. The medium-weight thick-ness is highly recommended for general all-arounduse. It has the advantage of nicely adapting to thecervical area of the tooth, providing a fluid seal with-out the use of floss or ligature ties around each tooth.Also, it does not tear easily and provides more protec-tion from injury to the adjacent soft tissues andincreased visibility than does the thinner material.There are, however, some advantages in the use ofthin-weight dam material on mandibular anteriorteeth and partially erupted posterior teeth. These teethhave very little bulk of contour and the thinner mate-rial will exert less dislodging force on the clamp. Thedisadvantage is that it is easily torn.

Dam materials may be purchased in precut 5˝ � 5˝(127 mm � 127 mm) or 6˝ � 6˝ (152 mm � 152mm) sheets. The choice of light- or dark-coloredmaterial is largely up to the practitioner. Darker mate-rial provides a contrasting color as a background forthe light-colored tooth.

791

Dental dam is available in latex or non-latex mate-rial. With the apparent increasing incidence ofpatients allergic to latex, non-latex dental dam mustbe available in all offices.6,7 Latex-free dams are avail-able (Coltene Whaledent, Inc., Cuyahoga Falls, OH)and supplied in a powder-free, 6˝ � 6˝, mediumthickness. In an emergency, non-latex glove materialcan also be used (Figure 2).

PUNCHAny dental dam punch that is convenient for theoperator and creates a sharp, clean hole in the dammaterial is satisfactory. All too often the punch has

not been correctly centered over the hole, and a‘‘nick’’ on the cutting margin results, producing anincomplete jagged cut in the dam material. Thisresults in a poor seal at the time of placement andmay make the dam susceptible to tearing.

FRAMESIn addition to supporting the dam, frames should beradiolucent to prevent obstruction of an importantarea on radiographs that are taken during treatment.There are a variety of dental dam frames that meetthis requirement. The U-shaped Young’s frame ismade of radiolucent plastic for endodontic

A

B

Figure 1 A, Swallowed endodontic file ended up in the appendix resulting in acute appendicitis. B, Specimen shows file in the appendix removed byappendectomy. Use of dental dam would have prevented this complication. C, Dental burs can sometimes disengage from hand pieces and beswallowed, as shown here. This is also preventable with dental dam. (A and B, Reproduced with permission from Thomsen LC, Appleton SS, EngstromHI. Appendicitis induced by an endodontic file. Gen Dent 1989;37:50.)

792 / Endodontics

applications. It is easily manipulated and is usedwidely (Figure 3). The Nygaard-Østby (N-Ø) dentaldam frame (Coltene Whaledent, Inc.) is shield-shaped to

fit the face, is made of radiolucent nylon, and may be inplace while a tooth is subjected to X-rays without interfer-ing with the radiographic image.

Figure 2 Latex-free barrier dams must be used for patients sensitive to latex; in this case a latex-free glove was cut up and used as a barrier.

Figure 3 The U-shaped Young’s dental dam frame is an example of commonly used frames.

Chapter 26 / Endodontics Instruments and Armamentarium / 793

An articulated frame developed to facilitate endo-dontic radiography (Figure 4) is also curved to fit theface. It is hinged in the middle to fold back, allowingeasier access for film and sensor placement. Derma-Frame (Ultradent Products, Inc., South Jordan, UT) isa soft metal frame that may be formed to fit the

patient’s face. The frame retains its configurationbut may then be reshaped after use.

Recently, several dental companies have introduceddisposable, single-use, pre-framed dental dams. TheHandiDam (Figure 5) and the InstaDam (Zirc Co.,Buffalo, NY) allow the clinician to quickly apply the

Figure 5 Frame and dam combinations such as the HandiDam (Aseptico, Inc., Woodinville, WA) allow convenient placement of a dental dam barrier forsingle teeth; the material is available both in latex and latex-free.

A B

Figure 4 Hinged dental dam frame. A, In closed position, frame is curved to fit face. B, Open position, from either side, allows passage of radiographic film holder.

794 / Endodontics

dam without the addition of a conventional frame. Bothof these innovative devices are available in latex andlatex-free versions.

CLAMPSThe dental dam clamp secures the dam to the toothand helps in soft-tissue retraction. Although the selec-tion of five to seven clamps will permit the clinician toisolate the majority of teeth treated, the experiencedoperator will expand that number. Teeth that arerotated, partially erupted, fractured, unusual in crownform, or with severe carious involvement all presentproblems requiring special clamps or clamping techni-ques. There are a variety of clamps available to meetany clinical situation that may arise (Figure 6). Table 1lists a suggested assortment of metal clamps for variousteeth.

For endodontic treatment particularly, the use ofclamps with wings allows a more rapid, efficientmeans of applying the dental dam. The wings allowthe dentist to place the clamp, dam, and frame in oneoperation (Figure 7). In addition, the wings cause abroader buccal–lingual deflection of the dam from theisolated tooth, thus allowing increased access. Onedisadvantage of the use of winged clamps is that thewings may occasionally interfere with radiographicinterpretation of file or master cone positioning.

Plastic clamps (Moyco/Union Broach, York, PA)are also available in two sizes, large and small, andare used in selected cases. When metal clamp obstruc-tion is a problem, radiolucent plastic clamps allow foran unobstructed film-view of the tooth.

FORCEPSEither the Ash- or Ivory-style clamp forceps is accep-table. One advantage of the Ivory forceps, however, is

Figure 6 There are a variety of clamps available for all situations, including plastic clamps.

Table 1 Dental Dam Clamp Selection

Clamps

Maxillary teeth

Central incisor 6, 9, 210, 212Lateral incisor 6, 9, 210, 00Canine 6, 9, 210Premolars 0, 2, 2A, W2AMolars 3, W3, W8A, 14, 14A

Mandibular teeth

Incisors 6, 9, 210, 212Canine 6, 9, 210Premolars 0, 00, 2, W2AMolars 3, W3, W8A, 14, 14A


the projections from the engaging beaks. These allowthe clinician the opportunity to exert a gingivallydirected force, which is often necessary to direct theclamp beyond the bulk of contour and into proximalundercuts. The Ash-style forceps beaks, however,afford a fulcrum point for posterior or anterior rota-tion of the clamp.

ADJUNCTS TO DENTAL DAM PLACEMENTIn addition to the previously mentioned materials,several other items will be of benefit for the efficientapplication of the dental dam.

A plastic or cement instrument can be used to shedthe dental dam off the wings of the clamp once theclamp has been positioned. It is also used, along witha stream of air, to invert or ‘‘tuck’’ the edges of thedam into the gingival sulcus, thus ensuring a fluid-proof seal. This is particularly necessary in multi-tooth applications.

Dental floss is an essential adjunct to dam place-ment, even for endodontic therapy. Floss can be usedfor testing of contacts prior to dam application andfor passing the dam material through the contactsafter placement. It is recommended that the operatorrelease the lingual grasp of the floss after passing itthrough the contact and pulling it out to the buccal,rather than back through the contact. Another pro-duct that may help with the stabilization of the inter-proximal dam is the Wedjets stabilizing cord (ColteneWhaledent, Inc.) (Figure 8). Small strips of the cord

can be wedged into the interproximal space over thedam to fix the dam in place.

Even with proper techniques of placement of thedental dam, there will still be clinical situations inwhich some small amount of leakage of fluids can beanticipated. Adjustments can be made including repo-sitioning of the clamp and closer attention to inver-sion of the dam material around the tooth. Whenthose techniques are ineffective, leakage can usuallybe effectively controlled by the placement of a ‘‘patch-ing’’ material at the interface of the tooth and the dammaterial. Orabase, rubber base adhesive, Cavit, a mix-ture of Super Poly-Grip Denture Adhesive with zincoxide powder, and periodontal packing have beenused in the past with limited success.8 Currently, theapplication of OraSeal Caulking (Ultradent Products,Inc.) seems to provide a quick, easy-to-apply solutionto the problem of seepage of fluids around the dentaldam (Figure 9).

Techniques of Application

ROUTINE TECHNIQUESTwo techniques of dental dam application that can beused routinely are next described, followed by examplesof special situations that may complicate the process.

Prior to application of the dental dam, it is sug-gested that the patient should rinse for 30 secondswith an effective antibacterial agent. A mouth rinse of

Figure 8 Wedjets cord (Coltene Whaledent, Inc.) can help stabilize theinterproximal area of the dental dam.

Figure 7 Winged clamp, dental dam, and frame ready for placement ontooth. Bow of clamp is oriented to the distal.

796 / Endodontics

0.12% chlorhexidine gluconate, such as Peridex(Proctor & Gamble, Cincinnati, OH), will reduce thenumber of microorganisms in the mouth prior todam placement.9

SINGLE MOTION TECHNIQUEThis is the most efficient endodontic dam applicationtechnique through the use of winged clamps resultingin the dam, clamp, and frame being taken to the toothto be isolated in a single motion (see Figure 7).

1. Select the clamp to be used.2. Punch one appropriate-sized hole just off center

of a 6˝ � 6˝ piece of dam material.3. Stretch the dam over the frame and fit the clamp

through the punched hole so that the wings retainthe clamp.

4. Place the clamp over the tooth with the accom-panying frame and dam attached so the clamp isseated over the bulk of contour of the tooth.

5. Use a plastic or cementing instrument to flick thedam off of the wings of the clamp. The dammaterial should be positioned on the tooth belowthe clamp.

6. Use floss to aid in passing the dam through con-tacts.

DOUBLE MOTION TECHNIQUEThis technique is still very efficient, requires the use ofa winged or wingless clamp, and involves a seven-steps procedure.

1. Select the clamp to be used.2. Punch one appropriate-sized hole just off center

of a 6˝ � 6˝ piece of dam material.3. Loosely attach the dam material to the four cor-

ners of the frame.4. Place the clamp over the bulk of contour of the

tooth to be isolated and ensure the clamp issecure.

5. Stretch the dam over the clamp so the dam mate-rial is seated under the clamp and hugging thecervical area of the tooth.

6. Completely stretch the dental dam onto allprongs of the frame.

7. Use floss to aid in passing the dam through con-tacts.

Regardless of the technique used, the surface of thetooth and dental dam should be disinfected with anappropriate disinfectant (i.e., 2.5% sodium hypo-chlorite, 10% iodine tincture, 2% chlorhexidine) priorto access of the root canal system.10

REMOVAL OF DAM

1. For single-tooth applications, simply remove theclamp with the forceps and remove the dam.

2. For multiple-tooth applications, first remove theclamp, then place a finger under the dam in thevestibule, and stretch the dam to the facial, awayfrom the teeth. Cut the stretched interproximaldam with scissors and then remove the dam.After removal, it is essential that the dam be

A B

Figure 9 A, Partially erupted first molar clamped with a W8A with leakage toward the lingual and distal. B, Leakage controlled with Oraseal (UltradentProducts, Inc.).


inspected to ensure that no interproximal damhas been left between the teeth.

Techniques for Special Situations

MULTIPLE ADJACENT TEETH REQUIRINGTREATMENT OR EXTREME MOBILITY OFTHE TOOTH BEING TREATEDThe posterior tooth is clamped normally whereas asecond clamp is reversed (with the bow pointingmesially) on the most anterior tooth (Figure 10). Or,the most posterior tooth is clamped normally,whereas the anterior portion of the dam is retainedwithout a clamp. A strip of dental dam, a piece offloss, or a Wedjets cord can be placed interproximallyto hold the anterior portion of the dam in place.

INSUFFICIENT TOOTH STRUCTUREOR PORCELAIN CROWNS OF VENEERSWHERE AN INTACT POSTERIOR TOOTH ISIN PLACEThe split-dam technique can be effectively used utiliz-ing a clamped tooth posterior to the tooth to betreated (Figure 11). Two holes can be punched, one

for the clamped tooth and one for the tooth anteriorto the tooth to be treated. The dam between the twoholes can be cut with iris scissors. Once the clamp isplaced on the posterior tooth, the dam can be placedon the clamped tooth and stretched mesially to ante-rior tooth and held in place with a Wedjets cord, floss,or a cut piece of dental dam. A cotton role can be

Figure 10 The posterior tooth is clamped normally whereas a secondclamp is reversed (with the bow pointing mesially) on the more anteriortooth.

Figure 11 The split-dam technique can be effectively used by clamping a tooth posterior to the one to be treated and stretching over a tooth anteriorly.

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placed under the lip or cheek in the mucobuccal foldover the tooth to be treated.

BRIDGE ABUTMENTS, SPLINTS,AND ORTHODONTICS WITH WIRESPunch a larger-than-normal hole in the dam. PlaceOraSeal around the punched hole on the underside ofthe dam. Clamp the tooth in the normal manner. Ifleakage is a problem, add more Oraseal around theabutment at the site of leakage.

TOOTH WITH CALCIFIED PULP CHAMBERAND CANAL(S)Use the three-tooth dental dam isolation techniquepreviously described in the multiple adjacent teethrequiring treatment technique. The involved tooth iswithout a clamp, allowing the clinician to bettervisualize the Cemento Enamel Junction (CEJ) regionof the tooth. A periodontal probe can be traced alongthe root surface to orientate oneself to the crown–rootangulations during difficult access cavity preparations.

TERMINAL TOOTH WITH INSUFFICIENTTOOTH STRUCTUREIf insufficient tooth structure is present to allow aclamp from being placed on the tooth and the toothis the terminal tooth in an arch, the clinician must firstdetermine whether the tooth is sufficiently periodon-tally sound and restorable. If the tooth is determinedto be retainable, perhaps a clamp with prongs extend-ing apically can be used to effectively engage and holdon the tooth, followed by dam placement. If that isunsuccessful, the tooth may require coronal build-uprestoration with pin-retained restorative materials sothe retainer can be properly placed. Additionally, theterminally positioned tooth can undergo periodontalcrown lengthening to expose more tooth structure toallow for clamp placement11 (see Chapter 18, ‘‘Endo-dontic–Periodontic Differentiation’’).

Summary

Clinicians will find endodontic procedures morerewarding and less frustrating as their mastery ofdental dam applications increases. The use of simpli-fied techniques, improved materials, and organizedprocedures, as well as patience and practice, will has-ten this mastery. Endodontists have long recognizedthat the use of dental dam is imperative in the practiceof endodontics.

References

1. Goultschin J, Heling B. Accidental swallowing of an endo-dontic instrument. Oral Surg Oral Med Oral Pathol OralRadiol Endod 1971;32:621–2.

2. Govila CP. Accidental swallowing of an endodontic instru-ment. A report of two cases. Oral Surg Oral Med Oral PatholOral Radiol Endod 1979;48:269–71.

3. Lambrianidis T, Beltes P. Accidental swallowing of endodonticinstruments. Endod Dent Traumatol 1996;12:301–4.

4. The Dentist Insurance Company, California Dental Associa-tion. Rubber dam it. Liability Lifeline 2004;80:1–7.

5. Cohen S, Schwartz, S. Endodontic complications and the law.J Endod 1987;13:191–7.

6. de Andrade ED, Ranali J, Volpato MC, de Oliveira MM.Allergic reaction after rubber dam placement. J Endod2000;26:182–3.

7. Kosti E, Lambrianidis T. Endodontic treatment in cases ofallergic reaction to rubber dam. J Endod 2002;28:787–9.

8. Weisman MI. Remedy for dental dam leakage problems.J Endod 1991;17:88–9.

9. Miller CH. Infection control. Dent Clin North Am1996;40:437–56.

10. Ng Y, Spratt D, Sriskantharajah S, Gulabivala K. Evaluation ofprotocols for field decontamination before bacterial samplingof root canals for contemporary microbiology techniques. JEndod 2006;29:317–20.

11. Lovdahl PE, Gutmann JL. Periodontal and restorative con-siderations prior to endodontic therapy. Gen Dent1980;28:38–45.


B. INTRODUCTION OF NICKEL–TITANIUM ALLOY

TO ENDODONTICS

WILLIAM A. BRANTLEY

Prior to the prescient review article by Civjan et al.1

on the potential uses of nickel–titanium alloys fordentistry, pioneering feasibility studies for orthodon-tics were performed by George Andreasen et al.2,3

This work led to the commercial development ofthe first NiTi alloy for orthodontics (Nitinol) bythe Unitek Corporation (now 3M Unitek, Monrovia,CA). The mechanical properties of this alloy, alongwith its notable clinical applications, were presentedin a classic article by Andreasen and Morrow.4 Par-ticularly important were the very low elastic modulusand very wide elastic working range of the NiTi alloy,compared with stainless steel, which was the majororthodontic wire alloy for clinical use at that time.

Subsequently, Harmeet Walia thought that thisnickel–titanium (NiTi: see next section) alloy mighthave enormous potential for endodontic files, becauseits very low elastic modulus would permit the nego-tiation of curved root canals with much greater facil-ity than stainless steel instruments available at thetime. Using special large-diameter orthodontic wirescontributed by the Unitek Corporation, Quality Den-tal Products (Johnson City, TN) fabricated the firstprototype NiTi hand files by machining rather thanthe conventional manner of twisting the taperedstainless steel wire blanks. The properties of these firstNiTi files in bending and torsion were compared withthose for stainless steel hand files of the same sizemanufactured by a similar machining process. Thehighly promising initial results of these pioneeringlaboratory studies were first presented by Waliaet al.5 at the annual meeting of the InternationalAssociation for Dental Research in 1987, and a morecomplete description of this work was publishedthe next year in a seminal article in the Journal ofEndodontics.6 Subsequently, more information about

torsional ductility, which was superior to that formachined stainless steel instruments,5,6 and cuttingability of the NiTi hand files, was reported by Waliaet al.7 at the 1989 annual meeting of the AmericanAssociation for Endodontists.

Based on these promising research results, innova-tive dental manufacturers began to market NiTiendodontic instruments in the 1990s. A major imp-etus was the merger of Quality Dental Products withTulsa Dental Products (now Dentsply Tulsa Dental,Tulsa, OK), and this latter company introduced Pro-File NiTi rotary files in 1993. Subsequently, manyother manufacturers introduced NiTi rotary instru-ments for endodontics, and studies of the propertiesand performance of these instruments became anintensive area for endodontics research. In January2007, PubMed listed over 350 articles dealing withvarious aspects of the NiTi endodontic instrumentssince their inception.

Mechanical Behavior and NiTi Phases for

Nickel–Titanium Alloys

The NiTi alloy used in orthodontics and endodonticswas developed by Buehler and associates. This alloywas termed ‘‘Nitinol’’ from nickel, titanium, and theNaval Ordnance Laboratory, the site of this develop-ment work that is described in a classic review articleby Buehler and Wang.8 The alloy is based on the NiTiintermetallic compound and can exhibit superelasticbehavior (termed ‘‘pseudoelastic’’ in materials science)and shape memory with appropriate processing condi-tions.9 Because of the difference in atomic weights ofnickel and titanium, the equiatomic NiTi alloy compo-sition is 55 wt% Ni and 45 wt% Ti.

800

When a superelastic NiTi wire is loaded in tension,normal elastic behavior initially occurs. With furthertensile loading, the elastic stress reaches a certain levelat which there is an extended horizontal region ofelastic strain (upper superelastic plateau). Up toabout 10% elastic strain can occur in a superelasticNiTi orthodontic wire at this constant stress.10 Duringsubsequent tensile unloading, the alloy will exhibit ahorizontal region of elastic strain at a lower stress(lower superelastic plateau) on the stress–strain plot.With further unloading, the strain reaches the end ofthe lower superelastic plateau, and the final portion onthe stress–strain plot again corresponds to the linearelastic unloading.

Khier et al.11 compared the bending properties ofsuperelastic and nonsuperelastic NiTi orthodonticwires. For elastic bending of superelastic NiTi ortho-dontic wires having clinically relevant test spans, theupper and lower superelastic plateaus are less welldefined (Figure 1), because stress varies linearly overthe cross-section. The regions on the bending plotsthat correspond to these plateaus have greater slopesfor nonsuperelastic NiTi wires, such as the original 3MUnitek Nitinol orthodontic wire (Figure 2). If the

superelastic alloy is loaded in tension to a value ofstrain beyond the upper plateau region, there willbe some permanent strain after unloading. Thispermanent strain will be greater for a nonsuperelasticNiTi wire having the same dimensions and loaded tothe same overall strain as the superelastic wire. Bycontrast, a NiTi wire alloy that exhibits shape memorybehavior in the oral environment will have no residualpermanent strain after unloading from beyond theupper plateau region; the wire will completely returnto its initial dimensions before loading.9

The mechanical behavior of the superelastic, non-superelastic, and shape memory NiTi alloys arisesfrom the nature and proportions of their microstruc-tural phases, which has been discussed by Brantley12

for orthodontic NiTi wires. There are three NiTiphases in these alloys.9 Austenitic NiTi (austenite)has a complex body-centered cubic structure, andexists at higher temperatures and lower stresses.

Figure 1 Cantilever bending plots for 6 mm test spans of four differentsizes of the superelastic NiTi alloy Nitinol SE (3M Unitek). Reprintedfrom Khier et al.11 with permission from the American Association ofOrthodontists.

Figure 2 Cantilever bending plots for 6 mm test spans of four differentsizes of the nonsuperelastic NiTi alloy Nitinol (3M Unitek). Reprintedfrom Khier et al.11 with permission from the American Association ofOrthodontists.


Martensitic NiTi (martensite) has a complex structuredescribed as monoclinic, and exists at lower tempera-tures and higher stresses. Transformation between aus-tenite and martensite occurs by a twinning process atthe atomic level, and the reversibility of this twinningis the origin of shape memory.9,12 During tensile load-ing, the upper superelastic plateau corresponds to thestress-induced transformation from the initial austeni-tic structure to martensite, and the lower superelasticplateau corresponds to reverse transformation frommartensite to austenite.

The R-phase is an intermediate phase with a rhom-bohedral structure that can form during forward trans-formation from martensite to austenite on heating andreverse transformation from austenite to martensite oncooling.9 Formation of R-phase is favored by the pre-sence of dislocations and precipitates in the NiTialloy.13 A substantial density of dislocations is expectedin NiTi orthodontic wires and endodontic instruments,because the alloy experiences considerable permanentdeformation during the manufacturing processes.Because of the relatively narrow range of the equia-tomic NiTi phase field in the nickel–titanium phasediagram at low temperatures, Ti2Ni and Ni3Ti precipi-tates are expected in Ti-rich and Ni-rich alloys, respec-tively.14 Oxide particles also form during processing ofthe NiTi alloy by manufacturers.9 Such nickel–titaniumoxide precipitates have been observed by Alapati et al.15

on the cutting tip of a rotary instrument (Figure 3)and were presumably elongated during the manufac-turing process for the starting wire blank.

Several phase transformation temperatures areimportant: As, the starting temperature for transfor-mation to austenite; Af, the temperature at whichtransformation to austenite is finished; Ms, the start-ing temperature for transformation to martensite;and Mf, the temperature at which transformation tomartensite is finished. The Rs and Rf temperaturesfor transformations involving the R-phase aredefined in a similar manner.

If a NiTi orthodontic wire or endodontic instrumentis cooled to a sufficiently low temperature (shown inlater differential scanning calorimetry [DSC] plots), itwill consist entirely of martensite. Upon heating, mar-tensite will start transforming to R-phase at the Rs tem-perature, and this transformation will be finished at theRf temperature. With further heating, R-phase startstransforming to austenite at the As temperature, andtransformation is finished at the Af temperature. Alter-natively, if the NiTi orthodontic wire or endodonticinstrument is heated above the Af temperature, it willbe converted entirely to austenite. Then, upon cooling tosufficiently lower temperature, the alloy starts transform-ing from austenite to R-phase at the Rs temperature, andthis transformation will be finished at the Rf tempera-ture. With further cooling, R-phase starts transformingto martensite at the Ms temperature, and transformationis finished at the Mf temperature. These transformationprocesses are summarized in Figure 4.

Use of Differential Scanning Calorimetry

to Study Nickel–Titanium Alloys

DSC can be used to easily determine the transforma-tion temperature ranges (TTRs) for NiTi phases and

Forward transformation sequence

M →

→ →

→R A (Heating)

Reverse transformation sequence

A R M (Cooling)

Figure 4 Structural transformations in NiTi alloys for orthodontic wiresand endodontic instruments: M, martensite; R, R-phase; A, austenite.Beginning with martensite at low temperatures, starting temperaturesare Rs and As for forward transformations on heating, which are finishedat Rf and Af temperatures. Beginning with austenite at high tempera-tures, starting temperatures are Rs and Ms for reverse transformationson cooling, which are finished at Rf and Mf temperatures. Starting andfinishing temperatures for the same transformation can be different forheating and cooling.

Figure 3 SEM photograph of the cutting tip for a LightSpeed instrumentafter one simulated clinical use, showing elongated nickel-titanium oxideprecipitates and flattening of the rollover. Scale bar length is 5 mm.Reprinted from Alapati et al.15 with permission from the AmericanAssociation of Endodontists.

802 / Endodontics

enthalpy changes in NiTi alloys.16,17 A test sample isheated or cooled at the same rate (typically 10�C/min)as an inert control material. The difference in thermalenergy to heat both materials at this rate is plotted asheat flow per unit sample weight (W/g) as a functionof temperature. Bradley et al.18 used DSC to comparesuperelastic, nonsuperelastic, and shape memory NiTiorthodontic wires.

In their first published article on the use of DSC toinvestigate NiTi rotary instruments, Brantley et al.19

compared ProFile (Dentsply Tulsa Dental) and Light-Speed (LightSpeed Technology, San Antonio, TX)instruments in the as-received condition. Figure 5 pre-sents heating and cooling DSC plots for a test sampleconsisting of several segments from an as-received Pro-File instrument. The temperature range from –75�C to75�C is shown. The lower curve is for the initial heatingcycle and the upper curve is for the subsequent coolingcycle. Exothermic reactions are represented by peaks inthe upward direction. The two endothermic peaks onthe heating curve correspond to initial transformationfrom martensite to R-phase (M fi R), followed bytransformation from R-phase to austenite (R fi A).This latter transformation is completed at an Af tem-perature of approximately 25�C, so the as-receivedinstrument will be in the superelastic condition at37�C, which Thompson reported to be desired by man-

ufacturers.20 (Some investigators determine the Af tem-perature from the intersection of a tangent line to theright side of the peak with an extension of the adjacentbaseline, which gives a lower value.) A single exothermicpeak is observed on the cooling curve, because the peaksassociated with the reverse transformations of A fi Rfollowed by R fi M could not be resolved.

Figure 6 presents DSC plots for the tip segment fromanother as-received ProFile instrument (DentsplyTulsa Dental) in a subsequent study by Brantleyet al.,21 investigating instruments subjected to simu-lated clinical use. This test sample was also in thesuperelastic condition, but the Af temperature on theheating curve was less than 0�C. The endothermic peakon the heating curve corresponds to the M fi R trans-formation, followed by R fi A, which could not beresolved as two separate peaks. The weaker broadexothermic peak over the same temperature range onthe cooling curve corresponds to the reverse transfor-mations of A fi R, followed by R fi M. The broadlow-temperature peak has been reported by Brantleyet al.22 to arise from twinning within martensite, andsimilar low-temperature peaks have been observed byBrantley et al.23,24 in NiTi orthodontic wires, usingtemperature-modulated DSC.

Figure 7 presents DSC plots for the tip segment of aProFile instrument, from the same batch as the

Figure 5 Differential scanning calorimetry (DSC) heating (lower) and cooling (upper) curves for a test sample of several segments from one as-receivedProFile NiTi instrument. Reprinted from Brantley et al.19 with permission from the American Association of Endodontists.


Figure 6 Differential scanning calorimetry (DSC) heating (lower) and cooling (upper) curves for the tip segment from another as-received ProFileinstrument. Reprinted from Brantley et al.21 with permission from the American Association of Endodontists.

Figure 7 Differential scanning calorimetry (DSC) heating (lower) and cooling (upper) curves for the tip segment from a ProFile instrument subjected toone simulated clinical use. Reprinted from Brantley et al.21 with permission from the American Association of Endodontists.

804 / Endodontics

instrument for Figure 6, which had been subjected toone simulated clinical use.21 Similar DSC plots wereobtained for tip segments from other ProFile instru-ments in this batch, which had been subjected to threeand five simulated clinical uses. After one, three, andfive simulated clinical uses, the tip segments stillremained in the superelastic condition, with the Af

temperature on the heating curve less than 0�C. Thus,DSC was unable to detect effects from up to fivesimulated clinical uses on the tip segments of theseinstruments.

Figure 8 shows DSC plots for the tip segment froma LightSpeed NiTi rotary instrument that had beensubjected to one simulated clinical use.21 This tipsegment is also in the superelastic condition, becausethe Af temperature on the heating DSC curve is lessthan 25�C. There were minimal differences comparedwith Figure 8 for the DSC plots from tip segments ofother LightSpeed instruments from the same batchthat were subjected to three and five simulated clinicaluses, as well as with DSC plots from the tip segmentof an as-received LightSpeed instrument.21 Interest-ingly, the DSC plots for a test sample consisting ofseveral segments for a LightSpeed instrument from adifferent batch were similar to Figure 5 for an as-received ProFile instrument.19

These two DSC studies by Brantley et al.19,21

showed that there are substantial differences in thecharacter of the NiTi phases for segments taken fromdifferent portions of the same rotary NiTi instru-ment. Moreover, evident batch effects were observedin the DSC plots for instruments from the samemanufacturer. The DSC results also indicated thatthe stresses experienced by a rotary instrument dur-ing manufacturing vary with position along its axisand that there may be differences in the manufactur-ing procedure and starting NiTi alloy. Nevertheless,regardless of the considerably different character ofthe various DSC plots,19,21 test samples from theProFile and LightSpeed instruments, in either theas-received condition or after simulated clinical use,always displayed superelastic behavior at 37�C,although there were relatively large differences inthe Af values for test samples.

From these DSC studies,19,21 it is tempting toassume that the optimum microstructure for super-elastic NiTi rotary instruments would have the max-imum amount of austenite that could reversiblytransform to martensite, with a large enthalpy change(peak area). When there is substantial stable work-hardened martensite in the microstructure, the enth-alpy change for reversible transformation to austenite is

Figure 8 Differential scanning calorimetry (DSC) heating (lower) and cooling (upper) curves for the tip segment from a LightSpeed instrument subjectedto one simulated clinical use. Reprinted from Brantley et al.21 with permission from the American Association of Endodontists.


much smaller.18,23 However, further research is neededto test this hypothesis and its relevance to the clinicalperformance of NiTi instruments.

In a contemporary DSC study, Kuhn and Jordan25

analyzed ProFile (Dentsply Maillefer, Baillagues,Switzerland) and Hero NiTi rotary instruments hav-ing different ISO (International Organization forStandardization) sizes and tapers. Both as-receivedand clinically used instruments were selected, andtest samples were obtained from portions of theinstruments that would be active or inactive duringcutting. Their observations were in good agreementwith the results by Brantley et al.19,21. The DSC plotsfor as-received Hero instruments with differenttapers were similar to Figure 5, and plots for activeand inactive portions of the same instrument weredifferent. The Af temperature of 20�C on heating forHero instruments was lower than the Af temperatureof 35�C for ProFile instruments. Transformationtemperatures were decreased after clinical use of theinstruments.

Kuhn and Jordan25 also studied the effects of heattreatments at six temperatures from 350� to 700�C.Whereas only single peaks were observed on the heat-ing and cooling DSC plots for as-received instruments(interpreted as direct transformations of M fi A andA fi M, respectively), the DSC plots were altered forannealed test samples. Heat treatments below 510�Cresulted in two DSC peaks during heating (M fi Rfollowed by R fi A) and two peaks during cooling(A fi R followed by R fi M). After heat treatmentsabove 510�C, one peak was observed during heating(interpreted as M fi A) and one peak during cooling(interpreted as A fi M). Heat treatment shifted themartensite transformation to lower temperatures.When heat treatment was performed at 600�C, recrys-tallization of the NiTi microstructure occurred in theinstruments, as previously found for NiTi orthodonticwires.12 Kuhn and Jordan25 observed that heat treat-ments below 600�C caused test samples to haveincreased bending flexibility, whereas flexibility wasdecreased by heat treatments above 600�C. Theyrecommended that heat treatment at 400�C, corre-sponding to the recovery annealing stage beforerecrystallization,12 be utilized by manufacturers priorto machining the NiTi instruments to decrease thework hardening of the alloy.

Alapati et al.26 have recently reported the first useof temperature-modulated DSC to investigate heat-treated NiTi rotary instruments. This technique pro-vides much greater resolution about the complexstructural transformations in the NiTi orthodonticwires than is possible with conventional DSC,23,24

and it should be extensively employed for futureinvestigations on NiTi instruments. Future researchshould also include the use of X-ray diffraction andtransmission electron microscopy, along with scan-ning electron microscopy and measurements ofmechanical properties, to determine the NiTi phasesand their characteristics in as-received, heat-treated,and clinically-used instruments.

X-ray diffraction provides information about theNiTi phases in a test sample, and Iijima et al.27 havereported the use of a new micro-X-ray diffractiontechnique to determine the NiTi phases at differentlocations on a NiTi instrument. Although preparationof the very thin foil specimens is challenging, trans-mission electron microscopy can be used to obtaininsight at the nanometer to submicron level intocauses of fatigue behavior and provide informationabout the NiTi phases and dislocation configurationsdue to manufacturer processing or clinical use of theinstruments.28–30 Scanning electron microscopic(SEM) observations of polished and etched test sam-ples can show whether the rotary instrument has aconventional wrought microstructure or provide evi-dence of heat treatment that caused recrystallizationto yield equiaxed grains.12 Vickers hardness measure-ments can be used to verify whether the NiTi instru-ment is in the superelastic condition and to investi-gate the extent of work hardening.12,31

As another example of combining experimentaltechniques, Miyai et al.32 recently investigated tor-sional and bending properties of EndoWave, Hero642, K3, ProFile .06, and ProTaper instruments andfound that their functional properties (particularlyflexible bending load level) were related to phasetransformation behavior determined by DSC.Transformation temperatures for Hero and K3instruments were significantly lower than for Endo-Wave, ProFile, and ProTaper instruments. How-ever, the clinical significance and predictabilityfrom such DSC results for performance of the NiTiinstruments remain to be established in futureresearch.

Effects of Heat Sterilization on Properties

of Nickel–Titanium Instruments

There have been numerous laboratory studies ofNiTi instruments subjected to multiple heat steriliza-tion cycles. Repeated sterilization has been found bySilvaggio and Hicks33 and Canalda-Sahli et al.34 tocause changes in torsion and bending properties, and

806 / Endodontics

by Rapisarda et al.35 and Schafer36 to affect cuttingefficiency. However, Hilt et al.37 found no effects onthe torsional properties, hardness, and microstructureof NiTi files from the number of sterilization cyclesand the type of autoclave sterilization.

Whereas Mize et al.38 found that repeated heatsterilization did not affect the number of cycles forfatigue failure, Chaves Craveiro de Melo et al.39 andViana et al.40 reported that repeated heat sterilizationcaused substantial increases in the number of cyclesfor failure. These observations indicate the necessityof having a standard technique for evaluation of thefatigue behavior of NiTi instruments.

Recent DSC studies by Alexandrou et al.41 haveshown that after 11 sterilization cycles, ProFile andFlexmaster instruments had the completely austeniticstructure needed for superelastic behavior in the oralenvironment. Alexandrou et al.42 also found that after11 sterilization cycles, the Mani NRT instrumentswere either austenite or a mixture of austenite andR-phase at 37�C and concluded that these instrumentsare also capable of superelastic behavior under clinicalconditions.

In future studies, it would be worthwhile to com-pare etched microstructures of the NiTi alloy forinstruments subjected to multiple heat sterilizationcycles with etched microstructures for as-receivedinstruments to determine whether changes occurredin the original wrought structure due to the steriliza-tion cycles. Comparison of the X-ray diffraction pat-terns and Vickers hardness for sterilized and as-received instruments would reveal12,27,31 whether ster-ilization caused relief of the residual stresses present inthe as-received instruments from the manufacturingprocess. Such residual stresses may contribute to theclinical failure of the NiTi instruments.

Failure of Nickel–Titanium Instruments

and Failure Mechanisms

The manufacturing process of machining the NiTirotary instruments from starting wire blanks20 resultsin rollover at the edges of the flutes6 and a variety ofsurface defects.6,43–45 Machining grooves, microcracks,and surface debris are evident when as-received instru-ments are examined with a scanning electron micro-scope, and instrument fracture generally occurs atsurface defects.

Recent extensive clinical studies by Knowles et al.46

for LightSpeed instruments and by Di Fiore et al.47 forProFile, ProTaper, ProFile GT, and K3 Endo instru-ments reported separation (fracture) rates of less than1.5% and much less than 1%, respectively. No statis-tically significant difference in incidence of fracturewas found for the ProFile, ProTaper, ProFile GT, andK3 Endo instruments.47 Although these rates are verylow and justify the widespread use of rotary NiTi instru-ments, clinical failures are sources of anguish for boththe patient and endodontist. Accordingly, there havebeen substantial research efforts to characterize theinstrument failures and determine their origins andto develop new instruments that would minimize theoccurrence of failures.

One contributing mechanism for clinical failure ofNiTi instruments, reported by Alapati et al.,48 may bethe widening of surface machining grooves by tena-cious dentin debris deposits. The SEM photograph inFigure 9 shows an example of this phenomenon for aclinically fractured ProTaper instrument. The poten-tial role of dentin debris for failure of rotary NiTiinstruments requires further study.

Alapati et al.49 have also performed an extensiveSEM study of clinically failed NiTi rotary instrumentsto characterize the major aspects of their fractureprocesses. Instruments generally appeared to exhibit

Figure 9 SEM photograph of a clinically fractured ProTaper instrumentshowing a widened machining groove containing dentin debris that wasclose to the area in which the fracture occurred. Scale bar length is22 mm. Reprinted from Alapati et al.48 with permission from the Amer-ican Association of Endodontists.


ductile fracture, rather than brittle fracture, as shownin Figure 10 of a clinically fractured ProTaper instru-ment,49 where the surface has the characteristicdimpled appearance for ductile fracture.50,51 SEMobservations at high magnification show that thesedimples are nucleated at secondary phase particles inthe microstructure, such as nickel–titanium oxides.9

The volume fraction of such particles may indicatethe quality of the starting NiTi wire alloy used formanufacturing the instruments.

An example of a more complex fracture surfaceis shown for a clinically failed ProFile GT instru-ment in Figure 11.49 Transgranular fractureoccurred across the fine grains in this microstruc-ture, as well as intergranular fracture along somegrain boundaries. Voids or regions of separationbetween some grains can also be seen in Figure 11and suggest the loss of small grains, subgrains, orsecondary phase particles during the fracture pro-cess.49 Although this rotary instrument may haveexperienced overall ductile fracture during clinicalfailure, the features in Figure 11 do not resemblethose for ductile fracture in Figure 10.

Two other major failure processes, excessive tor-sional deformation without separation and axial frac-ture, were observed by Alapati et al.49 for these clini-cally retrieved NiTi rotary instruments. Permanent

torsional deformation, giving an ‘‘unfluted appear-ance,’’ and permanent bending deformation withoutinstrument separation, as well as instruments thatfractured in these modes, under clinical conditions,have been observed by other investigators.44,52–56 Theaxial fracture mode for clinically retrieved instru-ments49 involved crack propagation in a directionapproximately parallel to the flutes that connectedpitted regions on the surface. These pits may havebeen former sites of secondary phase particles.

Alapati et al.49 did not observe the characteristicstriations50,51 for cyclic fatigue on the fracture sur-faces of clinically failed NiTi instruments, presum-ably because the instrumentation time before frac-ture of the retrieved instruments was insufficientlylong. These investigators concluded that separationof the used instruments, retrieved for their study,was generally caused by a single overload event thatresulted in ductile fracture. By contrast, Cheunget al.55 observed striations indicative of fatigue fail-ure for numerous ProTaper instruments that hadfractured during clinical use, and these authors con-cluded that fatigue failure is an important mode ofseparation during clinical instrumentation. Anexample of the fine-scale striations is shown in Fig-ure 12 from a laboratory study by Luebke et al.57 of

Figure 10 Secondary electron image of the fracture surface of aProTaper rotary instrument that failed during clinical use, showingelongated dimples indicative of ductile fracture and secondary phaseparticles that may be nickel-titanium oxides. Scale bar length is 6 mm.Reprinted from Alapati et al.49 with permission from the AmericanAssociation of Endodontists.

Figure 11 SEM photograph of the fracture surface of a ProFile GTinstrument that failed during clinical use, showing transgranular (clea-vage) fracture and intergranular fracture along grain boundaries. Scalebar length is 3 mm. Reprinted from Alapati et al.49 with permission fromthe American Association of Endodontists.

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NiTi Gates Glidden drills subjected to cyclic cantile-ver bending.

In summary, numerous studies have shown thatNiTi alloys for rotary instruments can possesssignificant ductility in bending and torsion, withoutexperiencing separation in certain clinical cases, wherethe canals have substantial curvature or where rota-tion of the tip is hindered. Fracture initiation oftenappears to occur at machining grooves, with a possi-ble role from retained dentin debris in these grooves.Retrieved instruments, which failed during clinicaluse, may fracture from cyclic fatigue after longerperiods of use or from single overload events afterrelatively brief periods of use. Clearly, the manufac-turing process for NiTi rotary instruments and theneed for a starting NiTi wire alloy of high metallurgi-cal quality are major factors for reducing the inci-dence of clinical failure of these instruments.

Strategies for Improved Nickel–Titanium

Instruments

Several strategies have been employed to developNiTi instruments that should have improved clinicalperformance. These strategies have included electro-polishing the machined surfaces, ion implantationto create harder surfaces, and use of special sur-face coatings. Research has also suggested that heat

treatment of these instruments may yield beneficialresults.

Tripi et al.58 recently compared the effects of instru-ment design and surface treatment on the cyclic fati-gue of ProFile, RaCe, K3, Hero, and Mtwo instru-ments. While the best fatigue resistance was foundfor the ProFile instruments, the electropolishing sur-face treatment for RaCe instruments increased theirfatigue resistance by reducing the presence of micro-cracks, surface debris, and other machining damage.

Lee et al.59 first proposed the application of ionimplantation to NiTi instruments. They reported thatboron-ion implantation more than doubled the surfacehardness of Nitinol at the nanoindentation depth of0.05 mm, yielding a hardness value greater than that ofstainless steel.

Rapisarda et al.60 subsequently employed both athermal nitriding technique and nitrogen-ion implan-tation to increase the wear resistance of NiTi instru-ments. The ion-implanted samples had a higher N:Tiratio, which suggested the presence of a titaniumnitride layer. Both the thermal-nitrided and nitro-gen-ion-implanted instruments had higher wear resis-tance and increased cutting ability in acrylic blockscompared with control instruments without surfacemodifications. An SEM study of nitrogen-ion-implanted instruments by these investigators61

revealed the absence of surface wear and morphologychanges that occurred in control instruments after thesame period of simulated clinical use.

Schafer36 used a physical vapor deposition (PVD)process to create a TiN surface coating on NiTi instru-ments. Surface-coated instruments had greater cuttingefficiency (penetration into plastic samples withcylindrical canals) compared with control instruments,and their cutting efficiency was not altered by repeatedautoclave or sodium hypochlorite sterilization.

Lastly, use of heat treatments for the NiTi instru-ments, or general modifications in proprietary ther-momechanical processing procedures for the startingwire blanks, may provide other strategies.62 It hasbeen noted that Kuhn and Jordan25 explored theuse of heat treatments at temperatures ranging from350� to 700�C. They concluded that annealing around400�C yields a suitable proportion of NiTi micro-structural phases and a beneficial effect (limitingbrittleness) on the mechanical properties of theseinstruments. Previous research on NiTi orthodonticwires has shown that heat treatment at 400�C doesnot affect the bending properties of superelastic wires,whereas heat treatment at 600�C causes loss of super-elastic behavior.10,11 Heat treatment for 10 minutes at500�C had minimal effect on the cantilever bending

Figure 12 SEM photomicrograph of the in vitro fracture surface of aNiTi Gates Glidden drill tested to failure in bending fatigue, showing finestriations that form during fatigue crack propagation. Scale bar length is0.7 mm. Reprinted from Luebke et al.57 with permission from the Amer-ican Association of Endodontists.


plots, but 2 hours of heat treatment at this tempera-ture decreased the average superelastic bendingmoment during unloading of the wire test span.

Heat treatment can alter the phase transformationtemperatures for the NiTi alloy, such as reduction ofthe Ms temperature to subambient levels to yield acompletely austenitic structure at room temperature.12

Heat treatment within only the recovery annealingstage for the NiTi alloy would reduce residual stressesof potential importance for fracture behavior withoutaltering the microstructure. Presumably, heat treat-ment at temperatures of 600�C and higher, causingrecrystallization of the wrought microstructure,12,25

should be avoided for the rotary instruments. Giventhe special nature of the NiTi alloy phases and theirtransformations,9 one can envision the future devel-opment of complex thermomechanical processingcycles to optimize the starting NiTi wire blanks ornew heat treatments to improve the cutting efficiencyand fatigue resistance of the instruments after machin-ing from these blanks.

References

1. Civjan S, Huget EF, DeSimon LB. Potential applications of cer-tain nickel-titanium (Nitinol) alloys. J Dent Res 1975;54:89–96.

2. Andreasen GF, Brady PR. A use hypothesis for 55 nitinol wirefor orthodontics. Angle Orthod 1972;42:172–7.

3. Andreasen GF, Hilleman TB. An evaluation of 55 cobaltsubstituted nitinol wire for use in orthodontics. J Am DentAssoc 1971;82:1373–5.

4. Andreasen GF, Morrow RE. Laboratory and clinical analysesof nitinol wire. Am J Orthod 1978;73:142–51.

5. Walia H, Brantley W, Gerstein H, Arpaio J. New metallurgyroot canal files. J Dent Res 1987;66(Special Issue):349,Abstract No. 1943.

6. Walia H, Brantley WA, Gerstein H. An initial investigation ofthe bending and torsional properties of Nitinol root canalfiles. J Endod 1988;14:346–51.

7. Walia H, Costas J, Brantley W, Gerstein H. Torsional ductilityand cutting efficiency of the Nitinol file. J Endod 1989;15:174[Abstract 22].

8. Buehler WJ, Wang FE. A summary of recent research on thenitinol alloys and their potential application in ocean engi-neering. Ocean Eng 1968;1:105–20.

9. Duerig TW, Melton KN, Stockel D, Wayman CM, editors.Engineering aspects of shape memory alloys. London: Butter-worth-Heinemann; 1990. pp. 3–45, 369–93.

10. Miura F, Mogi M, Ohura Y, Hamanaka H. The super-elasticproperty of the Japanese NiTi alloy wire for use in orthodontics.Am J Orthod Dentofacial Orthop 1986;90:1–10.

11. Khier SE, Brantley WA, Fournelle RA. Bending properties ofsuperelastic and nonsuperelastic nickel-titanium orthodonticwires. Am J Orthod Dentofacial Orthop 1991;99:310–128.

12. Brantley WA. Orthodontic wires. In: Brantley WA, Eliades T,editors. Orthodontic materials: scientific and clinical aspects.Stuttgart: Thieme; 2001. pp. 15–21, 84–97.

13. Miyazaki S, Otsuka K. Development of shape memory alloys.Iron Steel Inst Jpn Int 1989;29:353–77.

14. Goldstein D, Kabacoff L, Tydings J. Stress effects on nitinolphase transformations. J Metals 1987;39:19–26.

15. Alapati SB, Brantley WA, Svec TA, et al. Scanning electronmicroscope observations of new and used nickel-titaniumrotary files. J Endod 2003;29:667–9.

16. Todoroki T, Tamura H. Effect of heat treatment after coldworking on the phase transformation in TiNi alloy. Trans JpnInst Metals 1987;28:83–94.

17. Yoneyama T, Doi H, Hamanaka H, et al. Super-elasticity andthermal behavior of Ni-Ti alloy orthodontic arch wires. DentMater J 1992;11:1–10.

18. Bradley TG, Brantley WA, Culbertson BM. Differential scan-ning calorimetry (DSC) analyses of superelastic and nonsu-perelastic nickel-titanium orthodontic wires. Am J OrthodDentofacial Orthop 1996;109:589–97.

19. Brantley WA, Svec TA, Iijima M, et al. Differential scanningcalorimetric studies of nickel titanium rotary endodonticinstruments. J Endod 2002;28:567–72.

20. Thompson SA. An overview of nickel-titanium alloys used indentistry. Int Endod J 2000;33:297–310.

21. Brantley WA, Svec TA, Iijima M, et al. Differential scanningcalorimetric studies of nickel-titanium rotary endodonticinstruments after simulated clinical use. J Endod2002;28:774–8.

22. Brantley WA, Guo WH, Clark WAT, Iijima M. TEM confir-mation of low-temperature martensite transformation innickel-titanium orthodontic wire. J Dent Res 2003;82(SpecialIssue A): Abstract No. 1535.

23. Brantley WA, Iijima M, Grentzer TH. Temperature-modulated DSC study of phase transformations in nickel-titanium orthodontic wires. Thermochimica Acta2002;392–3:329–37.

24. Brantley WA, Iijima M, Grentzer TH. Temperature-modulated DSC provides new insight about nickel-titaniumwire transformations. Am J Orthod Dentofacial Orthop2003;124:387–94.

25. Kuhn G, Jordan L. Fatigue and mechanical properties of nickel-titanium endodontic instruments. J Endod 2002;28:716–20.

26. Alapati SB, Brantley WA, Schricker SR, et al. Investigation oftransformations in used and heat-treated nickel-titaniumendodontic instruments. J Dent Res 2006;85(Special IssueA): Abstract No. 38.

27. Iijima M, Brantley WA, Alapati SB, Nusstein JM. Micro-XRDstudy of nickel-titanium rotary endodontic instruments after

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clinical use. J Dent Res 2005;84(Special Issue A): Abstract No.1479.

28. Guo WH, Brantley WA, Li D, et al. Fatigue studies of high-palladium dental casting alloys: Part II. Transmission electronmicroscopic observations. J Mater Sci: Mater Med2002;13:369–74.

29. Guo WH, Brantley WA, Clark WAT, et al. Transmissionelectron microscopic investigation of a Pd-Ag-In-Sn dentalalloy. Biomaterials 2003;24:1705–12.

30. Guo WH, Brantley WA, Clark WAT, et al. Transmissionelectron microscopic studies of deformed high-palladiumdental alloys. Dent Mater 2003;19:334–40.

31. Alapati SB, Brantley WA, Nusstein JM, et al. Vickers hardnessinvestigation of work-hardening in used NiTi rotary instru-ments. J Endod 2006;32:1191–3.

32. Miyai K, Ebihara A, Hayashi Y, et al. Influence of phasetransformation on the torsional and bending properties ofnickel-titanium rotary endodontic instruments. Int Endod J2006;39:119–26.

33. Silvaggio J, Hicks ML. Effect of heat sterilization on thetorsional properties of rotary nickel-titanium endodonticfiles. J Endod 1997;23:731–4.

34. Canalda-Sahli C, Brau-Aguade E, Sentis-Vilalta J. The effectof sterilization on bending and torsional properties of K-filesmanufactured with different metallic alloys. Int Endod J1998;31:48–52.

35. Rapisarda E, Bonaccorso A, Tripi TR, Condorelli GG. Effect ofsterilization on the cutting efficiency of rotary nickel-titaniumendodontic files. Oral Surg Oral Med Oral Pathol Oral RadiolEndod 1999;88:343–7.

36. Schafer E. Effect of sterilization on the cutting efficiency ofPVD-coated nickel-titanium endodontic instruments. IntEndod J 2002;35:867–72.

37. Hilt BR, Cunningham CJ, Shen C, Richards N. Torsionalproperties of stainless-steel and nickel-titanium filesafter multiple autoclave sterilizations. J Endod 2000;26:76–80.

38. Mize SB, Clement DJ, Pruett JP, Carnes DL Jr. Effect ofsterilization on cyclic fatigue of rotary nickel-titanium endo-dontic instruments. J Endod 1998;24:843–7.

39. Chaves Craveiro de Melo M, Guiomar de Azevedo Bahia M,Lopes Buono VT. Fatigue resistance of engine-driven rotarynickel-titanium endodontic instruments. J Endod2002;28:765–9.

40. Viana ACD, Gonzalez BM, Buono VTL, Bahia MGA. Influ-ence of sterilization on mechanical properties and fatigueresistance of nickel-titanium rotary endodontic instruments.Int Endod J 2006;39:709–15.

41. Alexandrou GB, Chrissafis K, Vasiliadis LP, et al. SEM obser-vations and differential scanning calorimetric studies of newand sterilized nickel-titanium rotary endodontic instruments.J Endod 2006;32:675–9.

42. Alexandrou G, Chrissafis K, Vasiliadis L, et al. Effect of heatsterilization on surface characteristics and microstructure ofMani NRT rotary nickel-titanium instruments. Int Endod J2006;39:770–8.

43. Eggert C, Peters O, Barbakow F. Wear of nickel-titaniumLightspeed instruments evaluated by scanning electron micro-scopy. J Endod 1999;25:494–7.

44. Sattapan B, Nervo GJ, Palamara JEA, Messer HH. Defects inrotary nickel-titanium files after clinical use. J Endod2000;26:161–5.

45. Tripi TR, Bonaccorso A, Tripi V, et al. Defects in GT rotaryinstruments after use: an SEM study. J Endod 2001;27:782–5.

46. Knowles KI, Hammond NB, Biggs SG, Ibarrola JL. Incidenceof instrument separation using LightSpeed rotary instru-ments. J Endod 2006;32:14–16.

47. Di Fiore PM, Genov KA, Komaroff E, et al. Nickel-titaniumrotary instrument fracture: a clinical practice assessment. IntEndod J 2006;39:700–8.

48. Alapati SB, Brantley WA, Svec TA, et al. Proposed role ofembedded dentin chips for the clinical failure of nickel-titanium rotary instruments. J Endod 2004;30:339–41.

49. Alapati SB, Brantley WA, Svec TA, et al. SEM observationsof nickel-titanium rotary endodontic instruments that frac-tured during clinical use. J Endod 2005;31:40–3.

50. Dieter GE. Mechanical metallurgy. 3rd ed. New York:McGraw-Hill; 1986. pp. 254–6, 262–4, 394–8.

51. Kerlins V, Phillips A. Modes of fracture. In: Metals handbook.Vol 12. 9th ed. Fractography. Metals Park, OH: ASM Inter-national; 1987. pp. 12–71.

52. Tygesen YA, Steiman HR, Ciavarro C. Comparison of distor-tion and separation utilizing ProFile and Pow-R nickel-tita-nium rotary files. J Endod 2001;27:762–4.

53. Arens FC, Hoen MM, Steiman HR, Dietz GC Jr. Evaluation ofsingle-use rotary nickel-titanium instruments. J Endod2003;29:664–6.

54. Parashos P, Gordon I, Messer HH. Factors influencing defectsof rotary nickel-titanium endodontic instruments after clin-ical use. J Endod 2004;30:722–5.

55. Cheung GSP, Peng B, Bian Z, et al. Defects in ProTaper S1instruments after clinical use: fractographic examination. IntEndod J 2005;38:802–9.

56. Shen Y, Cheung GSP, Bian Z, Peng B. Comparison of defectsin ProFile and ProTaper systems after clinical use. J Endod2006;32:61–5.

57. Luebke NH, Brantley WA, Alapati SB, et al. Bending fatiguestudy of nickel-titanium Gates Glidden drills. J Endod2005;31:523–5.

58. Tripi TR, Bonaccorso A, Condorelli GG. Cyclic fatigue of differ-ent nickel-titanium endodontic rotary instruments. Oral SurgOral Med Oral Pathol Oral Radiol Endod 2006;102:E106–14.


59. Lee DH, Park B, Saxena A, Serene TP. Enhanced surfacehardness by boron implantation in Nitinol alloy. J Endod1996;22:543–6.

60. Rapisarda E, Bonaccorso A, Tripi TR, et al. The effect ofsurface treatments of nickel-titanium files on wear and cut-ting efficiency. Oral Surg Oral Med Oral Pathol Oral RadiolEndod 2000;89:363–8.

61. Rapisarda E, Bonaccorso A, Tripi TR, et al. Wear of nickel-titanium endodontic instruments evaluated by scanning electronmicroscopy: effect of ion implantation. J Endod 2001;27:588–92.

62. Alapati SB. An investigation of phase transformation mechan-isms for nickel-titanium rotary endodontic instruments (PhDdissertation). Columbus, OH: The Ohio State University,2006.

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C. INSTRUMENTS FOR CLEANING AND SHAPING

TIMOTHY A. SVEC

Instrumentation of the root canal system requiresboth hand and rotary files. No canal system can orshould be instrumented with rotary files alone. Thedevelopment of hand and engine-driven files will bediscussed with an emphasis on nickel–titanium rotaryfiles.

Basic Endodontic Instruments

After the introduction of standardized instruments,1

about the only changes made were the universal use ofstainless rather than carbon steel and the addition ofsmaller (Nos. 6 and 8) and larger (Nos. 110–150) sizesas well as color coding. It was not until 1976 that thefirst approved specification for root canal instrumentswas published (ADA Specification No. 28).

ENDODONTIC INSTRUMENTSTANDARDIZATIONIn 1959, a new line of standardized instruments andfilling material was introduced to the profession:2

1. A formula for the diameter and taper in each sizeof instrument and filling material was agreed on.

2. A formula for a graduated increment in size fromone instrument to the next was developed.

3. A new instrument numbering system based oninstrument metric diameter was established.

This numbering system, last revised in 2002,3 usingnumbers from 6 to 140, is based on the diameter ofthe instruments in hundredths of a millimeter at thebeginning of the tip of the blades, a point called D0(diameter 1 mm) (Figure 1), and extending up theblades to the most coronal part of the cutting edge atD16 (diameter 2–16 mm in length). Additional revi-sions are under way to cover instruments constructedwith new materials, designs, and tapers greater than0.02 mm/mm.

Instruments with a taper greater than the ISO (Inter-national Standards Organization) standard of 0.02 mm/mm have become popular: 0.04, 0.06, 0.08, 0.10, and0.12. This means that for every millimeter gain in thelength of the cutting blade, the width (taper) of theinstrument increases in size by 0.04, 0.06, 0.08, 0.10, or0.12 of a millimeter rather than the ISO standard of0.02 mm/mm. These new instruments allow for greatercoronal flaring than the 0.02 instruments.

Figure 1 Original recommendation for standardized instruments. Cuttingblades 16 mm in length are of the same size and numbers as standar-dized filling points. The number of the instrument is determined bydiameter size at D1 in hundredths of millimeters. Diameter 2 (D2) isuniformly 0.32 mm greater than D1, a gain of 0.02 mm/1 mm of cuttingblades. Reproduced with permission from Ingle JI. In Grossman, LI,editor. Transactions of the Second International Conference on Endo-dontics. Philadelphia: University of Pennsylvania; 1958. p. 123.

813

The full extent of the shaft, up to the handle, comes inthree lengths: standard, 25 mm; long, 31 mm; and short,21 mm. The long instruments are often necessary whentreating canines over 25 mm long. Shorter instrumentsare helpful in second and third molars or in the patientwho cannot open widely. Other special lengths areavailable.

Ultimately, to maintain these standards, the Amer-ican Association of Endodontists (AAE) urged theAmerican Dental Association (ADA) and the UnitedStates Bureau of Standards to appoint a committee forendodontic instrument standardization. A committeewas formed and produced a specification package thatslightly modified Ingle’s original standardization.1

Then a worldwide committee was formed: ISO, con-sisting of the Federation Dentaire International, theWorld Health Organization, and the ADA InstrumentCommittee. The ISO has now formulated interna-tional specifications using the ADA proposal as amodel.

ANSI (American National Standards Institute)/ADA standards have also been set for other instru-ments and filling materials: No. 58, Hedstroem files;No. 63, rasps and barbed broaches; No. 71, spreadersand condensers; No. 95, root canal enlargers; as wellas No. 57, filling materials; No. 73, absorbent points;and No. 78, obturating points. Committee work iscontinuing to make these standards comparable withISO standards.

The relevant standards have tolerances for sizemaintenance (both diameter and taper), surface deb-ris, cutting flute character, torsional properties, stiff-ness, cross-sectional shape, cutting tip design, andtype of metal. Variations from these tolerances havebeen noted4–9 (Figure 2). More recently, Stenman and

Spangberg10 noted that few brands are within accep-table dimensional standards.

Cormier et al.6 have warned of the importance ofusing only one brand of instruments because of dis-crepancies in instrument size among manufacturers.Seto et al.7 noted that grinding the flutes in files ratherthan twisting them ‘‘does not improve the strength orductility of the instrument . . . (and) may also createmore undesirable fluting defects.’’ Since then, however,grinding has improved and gained importance becausemost nickel–titanium instruments must be machined,not twisted. Several recent studies have indicated thatthis type of manufacturing does not weaken instru-ments. In fact, most studies indicate that both manu-facturing processes produce files that meet or exceedISO standards.11–13

It has also been found that autoclaving has nosignificant deleterious effects on stainless steel ornickel–titanium endodontic instruments.14,15 Nowmade universally of nickel–titanium and stainless steelrather than carbon steel, K-type instruments are pro-duced using one of two techniques. The more tradi-tional is produced by grinding graduated sizes ofround wire into various shapes such as square, trian-gular, or rhomboid. A second grinding operationproperly tapers these pieces. To give the instrumentsthe spirals that provide the cutting edges, the squareor triangular stock is then grasped by a machine thattwists it counterclockwise a programed number oftimes—tight spirals for files, loose spirals for reamers.The cutting blades that are produced are the sharpedges of either the square or the triangle. In anyinstrument, these edges are known as the ‘‘rake’’ ofthe blade. The more acute the angle of the rake, thesharper the blade. There is approximately twice the

814 / Endodontics

file.qums.ac.irfile.qums.ac.ir/repository/sd/pazhohesh/Library/E... · are immunocompromised. The usual oral dosage for amoxicillin with clavulanate is 1,000-mg loading dose followed

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