Evidence-Based Perspectives on Pain and Anxiety Control in ...

Evidence-Based Perspectives on Pain

and Anxiety Control in Dentistry

Dr. Arthur Jeske

[email protected]

Utah Dental Association, 2/15/08

Today’s Course Topics…Today’s Course Topics…• Fundamentals of anxiety managementFundamentals of anxiety management• Current guidelines (conscious/minimal sedation)Current guidelines (conscious/minimal sedation)• Enteral (oral) sedativesEnteral (oral) sedatives• Nitrous oxide/oxygen inhalation sedationNitrous oxide/oxygen inhalation sedation• Basic emergency drugsBasic emergency drugs• Contemporary perspectives on local anestheticsContemporary perspectives on local anesthetics• Contemporary perspectives on oral analgesicsContemporary perspectives on oral analgesics

DisclaimersDisclaimersThe opinions expressed in this course The opinions expressed in this course

are those of the speaker and not are those of the speaker and not necessarily those of the Utah Dental necessarily those of the Utah Dental

Association.Association.

The opinions expressed in this course The opinions expressed in this course should not be construed as advice for should not be construed as advice for

the care of specific patients.the care of specific patients.

The drugs and techniques contained in The drugs and techniques contained in this course must be based on the this course must be based on the clinical judgment of the individual clinical judgment of the individual

practitioner.practitioner.

American Dental AssociationAmerican Dental AssociationGUIDELINES FOR TEACHING GUIDELINES FOR TEACHING

PAIN CONTROL AND SEDATION PAIN CONTROL AND SEDATION TO DENTISTS AND DENTAL TO DENTISTS AND DENTAL

STUDENTSSTUDENTSAs adopted by the October 2007 ADA As adopted by the October 2007 ADA

House of Delegates House of Delegates www.ada.orgwww.ada.org

Minimal Sedation

A minimally depressed level of consciousness produced by a pharmacologic

method that retains the patient’s ability to independently and continuously maintain an

airway and respond normally to tactile stimulation and verbal command. Although

congnitive function may be modestly impaired, ventilatory and cardiovascular

functions are unaffected.

Other ADA Guideline Excerpts• Nitrous oxide may be used with “a single enteral drug”• Initial oral dose is “no more than MRD for unmonitored

home use”• Combination of nitrous and oral agents “may produce

minimal, moderate or deep sedation or general anesthesia”

• “Supplemental dosing is a single additional dose” for “prolonged procedures” and “should not exceed ½ the initial dose” (not until the “clinical half-life of the initial dose has passed”)

• “total aggregate dose must not exceed 1.5 MRD”

Conscious Sedation

Guidelineshttp://www.ncbi.nih.gov/pubmed/

17187034?ordinalpos

Balancing Efficacy and Balancing Efficacy and Safety in the Use of Oral Safety in the Use of Oral

Sedation in Dental Sedation in Dental OutpatientsOutpatients

Dionne RA et al. JADA Dionne RA et al. JADA 2006;137:502-132006;137:502-13

http://jada.ada.orghttp://jada.ada.org

““ENTERAL ADMINISTRATION OF ENTERAL ADMINISTRATION OF Benzodiazepines safe but poorly Benzodiazepines safe but poorly documented in the office setting”documented in the office setting”

Conscious sedation, including Conscious sedation, including incremental triazolam, necessitates…incremental triazolam, necessitates…monitoring, documentation, facilities monitoring, documentation, facilities

equipment and personnel as described equipment and personnel as described in ADA and AAPD guidelines”in ADA and AAPD guidelines”

Consensus (Dionne et al., 2006)Consensus (Dionne et al., 2006)

• Oral sedative = wide margin of safety in Oral sedative = wide margin of safety in ADULTSADULTS

• Most serious events = Most serious events = respiratory respiratory depressiondepression

• State regulation required to ensure safetyState regulation required to ensure safety

• More research needed for “incremental More research needed for “incremental dosing” techniquesdosing” techniques

• 0.25 mg triazolam X 2 >>0.5 mg single dose0.25 mg triazolam X 2 >>0.5 mg single dose

Sedation Modifications. Sedation Modifications. How Will the Proposed How Will the Proposed Guidelines Affect Your Guidelines Affect Your

Practice?Practice?

Lynch, K. AGD Impact July 2007;48-54Lynch, K. AGD Impact July 2007;48-54

AGD White Paper at:AGD White Paper at:http://www.agd.org/members_only/advocacy/priority_issues/ConsciousSedation.dochttp://www.agd.org/members_only/advocacy/priority_issues/ConsciousSedation.doc

Here’s What You Thought (AGD Here’s What You Thought (AGD Impact July 2007)Impact July 2007)

• 74% use N74% use N22O O

• 53% combine nitrous oxide and a BZ53% combine nitrous oxide and a BZ

• 67% have patient take sedative at home67% have patient take sedative at home

• 43% administer sedative in the office43% administer sedative in the office

• 90% never had an untoward reaction90% never had an untoward reaction

• 48% totally understand the difference 48% totally understand the difference between minimal and moderate sedtionbetween minimal and moderate sedtion

Conscious Sedation Guidance

Coulthard, P. J. Evid. Based Dent., 2006;7(4):90-91

www.scottishdental.org/cep/guidance/dentalsedation.htm

The Scottish Dental Clinical Effectiveness Programme

Coulthard, 2006

• 48 recommendations total

• To be updated 2008• Included general

systematic reviews (Cochrane Library) and specific studies (Medline, Embase & Cochrane Library)

Recommendations: Referral

• Discuss alternative methods of anxiety management with patient

• Ensure that definition of “conscious sedation” is met

Recommendations: Assessment and Record Keeping

• Discuss all aspects of sedation procedure with patient

• Provide written instructions

• Obtain informed consent

• Maintain and update patient records

Recommendations: Environment and Facilities

• Ensure that environment is safe

• Correct equipment and drugs

• Emergency drugs and equipment immediately available

Recommendations: Training

• All members of team are correctly trained• Training includes monitoring techniques

and emergency interventions• “For oral and transmucosal” sedation,

“sedationist” trained in other titratable sedation techniques and venipuncture

• Teams should provide sedation for patient groups they are experienced in treating

Recommendations: Techniques

• “Titrated dose of nitrous oxide”

• Oral, transmucosal and i.v. “require” pulse oximetry and BP monitoring

Recommendations: Aftercare

• Monitor patients during recovery

• Dismiss patient into care of a responsible adult (who also has written instructions)

• Nitrous oxide sedation “might not” required adult escort during recovery

Recommendations: Further Research Required For…

• Fasting before conscious sedation

• Pediatric conscious sedation

• Drug combinations

• Conscious sedation methods

• Cognitive & behavioural effects of sedation

• Interaction of pharmacological and nonpharmacologic anxiety management

Utah Dentist and Dental Utah Dentist and Dental Hygienist Practice Act Rules Hygienist Practice Act Rules

R156-69-601R156-69-601

Scope of Practice—Anesthesia and Scope of Practice—Anesthesia and Analgesia PermitAnalgesia Permit

Conscious Sedation for Conscious Sedation for Dental AnxietyDental Anxiety

(Protocol)(Protocol)

Cochrane Database of Systematic Cochrane Database of Systematic ReviewsReviews

2007, Issue 12007, Issue 1

Primary Outcomes To Be Primary Outcomes To Be AssessedAssessed

• Changes in anxiety scoresChanges in anxiety scores

• Reliability and validity of anxiety Reliability and validity of anxiety measurement instruments/scalesmeasurement instruments/scales

AnxietyAnxiety

An internal, emotional response; An internal, emotional response; a specific unpleasurable sense a specific unpleasurable sense state of tension which indicates state of tension which indicates the presence of some dangerthe presence of some danger

ANTICIPATEDANTICIPATED

FearFear::A short-lived feeling that something A short-lived feeling that something

terrible is going to happen; terrible is going to happen; accompanied by physiologic accompanied by physiologic

changes (increased HR, changes (increased HR, perspiration) and overt behavior perspiration) and overt behavior

signs (jitteriness, shaking)signs (jitteriness, shaking)“Fight or Flight”“Fight or Flight”

IMMEDIATE THREATIMMEDIATE THREAT

Conscious SedationConscious Sedation

• Drugs and/or techniques used should Drugs and/or techniques used should carry a margin of safety wide enough to carry a margin of safety wide enough to render loss of consciousness UNLIKELYrender loss of consciousness UNLIKELY

• Patients who are SLEEPING and whose Patients who are SLEEPING and whose only reponse to stimuli is reflex only reponse to stimuli is reflex withdrawal would NOT be considered withdrawal would NOT be considered to be in a state of conscious sedationto be in a state of conscious sedation

“Bottom-Line” Requirements for Minimal/Conscious Sedation

• Comfort

• Consciousness

• Cooperation

AdultAdult Preferences for Sedation or Preferences for Sedation or General Anesthesia (Survey of 1,101 General Anesthesia (Survey of 1,101

Canadian Adults)Canadian Adults)• Routine cleaning: 7.2%Routine cleaning: 7.2%• Fillings/crowns: 18%Fillings/crowns: 18%• Tooth extraction: 47%Tooth extraction: 47%• Endodontic procedure: 55%Endodontic procedure: 55%• Periodontal surgery: 68%Periodontal surgery: 68%• From Chanpong, Haas & Locker, Anesth. Prog. From Chanpong, Haas & Locker, Anesth. Prog.

2005;52(1):3-112005;52(1):3-11• http://apt.allenpress.com/perlserv http://apt.allenpress.com/perlserv

Clinical ConsiderationsClinical Considerations

• Physician consultation recommended for Physician consultation recommended for ASA III & IV patientsASA III & IV patients

• One member of assistant staff should be One member of assistant staff should be present (in addition to dentist)present (in addition to dentist)

• Direct supervisionDirect supervision• Monitoring required for oxygenation, Monitoring required for oxygenation,

ventilation and circulationventilation and circulation• Time-oriented anesthetic recordTime-oriented anesthetic record

Advantages of Oral SedationAdvantages of Oral Sedation

• Universal acceptabilityUniversal acceptability• Ease of administrationEase of administration• Low co$tLow co$t• Incidence of adverse reactions less than Incidence of adverse reactions less than

some other techniquessome other techniques• No needles, syringes or special techniquesNo needles, syringes or special techniques• Various drugs, dosage forms availableVarious drugs, dosage forms available• Allergic reactions less severe than seen in Allergic reactions less severe than seen in

parenteral administration parenteral administration

Disadvantages of Oral SedationDisadvantages of Oral Sedation

• Reliance on Reliance on patient compliancepatient compliance• Prolonged, variable onsetProlonged, variable onset of action of action• Unreliable absorptionUnreliable absorption of drug from G.I. tract of drug from G.I. tract• INABILITY TO TITRATE: INABILITY TO TITRATE: WHAT???WHAT???• Prolonged durationProlonged duration of action of action• IneffectiveIneffective in anxiety levels > mild in anxiety levels > mild• Adverse interactionsAdverse interactions of sedative drugs of sedative drugs

IdiosyncrasyIdiosyncrasy

An unexpected, unpredictable An unexpected, unpredictable adverse or undesirable drug adverse or undesirable drug

actionaction

Indications for Oral SedationIndications for Oral Sedation

• Mild to moderate dental Mild to moderate dental anxietyanxiety

• To assist with restful sleep on To assist with restful sleep on night before dental night before dental appointmentappointment

ContraindicationsContraindications to Oral to Oral SedationSedation

• SevereSevere dental anxiety & fear dental anxiety & fear• High probability of High probability of adverse drug interactionadverse drug interaction• Poor past experiencePoor past experience with oral sedation with oral sedation• AllergyAllergy to drug being used to drug being used• Other drug contraindications (Other drug contraindications (pregnancy, pregnancy,

glaucoma, etc.)glaucoma, etc.)• Need for rapid onset and/or rapid recoveryNeed for rapid onset and/or rapid recovery

What causes the sudden

death of a patient?• Respiratory arrest with or without airway

obstruction• Cellular hypoxia without respiratory

depression (CN, CO)• Severe hypotension (hypovolemic, etc.)• Lethal cardiac dysrhythmias• Post-seizure complications (pulmonary

aspiration, hypoxia, brain damage)• Organ damage (e.g., APAP/liver)• Behavior aberrations (motor vehicle

accidents)

Oral Sedation: “Unfilled Expectations”

• Pain control, reduced need for local anesthesia• Control of defiant behavior, mentally-

challenged patients• Amnesia• Lack of adverse effects• Consistency from appointment to appointment• “A good night’s sleep” the night before the

dental procedure

Sedation should NOT be Sedation should NOT be used to control pain and used to control pain and does NOT substitute for does NOT substitute for good local anesthesiagood local anesthesia

Enteral SedationEnteral Sedation

Light to mild conscious Light to mild conscious sedation administered not sedation administered not for analgesic effect, but for analgesic effect, but primarily for behavioral primarily for behavioral

management (drug management (drug absorbed through GI tract or absorbed through GI tract or

oral mucosa)oral mucosa)

Factors Influencing Oral Drug Factors Influencing Oral Drug AbsorptionAbsorption

• Lipid solubilityLipid solubility• pH of gastric tissuespH of gastric tissues• Mucosal surface areaMucosal surface area• Gastric emptying timeGastric emptying time• Dosage form of drugDosage form of drug• Drug inactivation (“first pass effect”)Drug inactivation (“first pass effect”)• Presence of food in stomachPresence of food in stomach• Bioavailability of drugBioavailability of drug• GeneticsGenetics

Alpha Distribution PhaseAlpha Distribution Phase

The phase in which sedative The phase in which sedative activity is initiated & ended, by activity is initiated & ended, by

entry into and removal from entry into and removal from the CNSthe CNS

Beta Elimination Phase Beta Elimination Phase

The phase in which a sedative The phase in which a sedative drug is inactivated by hepatic drug is inactivated by hepatic

metabolism & excretionmetabolism & excretion

Margin of SafetyMargin of Safety

The difference between the The difference between the effective therapeutic dose and the effective therapeutic dose and the dose that produces severe or life-dose that produces severe or life-

threatening adverse effectsthreatening adverse effects

Reasons NOT to used BZs…Reasons NOT to used BZs…

• AllergyAllergy

• Narrow angle glaucomaNarrow angle glaucoma

• Chronic BZ ingestion…???Chronic BZ ingestion…???

• Tricyclic antidepressant therapy…???Tricyclic antidepressant therapy…???

• Adversely interactive drugs (e.g., azole Adversely interactive drugs (e.g., azole antifungals/triazolam)antifungals/triazolam)

Characteristics of Characteristics of BenzodiazepinesBenzodiazepines

• Facilitate binding of Facilitate binding of GABAGABA (endogenous (endogenous inhibitory transmitter)inhibitory transmitter)

• More More favorable therapeuticfavorable therapeutic index than older index than older agentsagents

• Can produce anterograde Can produce anterograde amnesiaamnesia• Agents Agents differ in onset, duration & metabolismdiffer in onset, duration & metabolism • Agents Agents differdiffer in regard to in regard to sedation vs. sedation vs.

hypnosishypnosis

Boxed Warning: BZs“sleep driving” (with no memory)

“severe allergic reactions”http://www.fda.gov/bbs/topics/NEWS/2007/NEW01587.html

Pharmacokinetics and Clinical Effects of Pharmacokinetics and Clinical Effects of Multidose Sublingual Triazolam in Healthy Multidose Sublingual Triazolam in Healthy

Volunteers. Jackson DL et al. J. Clin. Volunteers. Jackson DL et al. J. Clin. Psychopharmacol. 2006;26(1):4-8Psychopharmacol. 2006;26(1):4-8

• 10 human volunteers10 human volunteers

• 0.25 mg followed by 0.25 mg at 60 mins 0.25 mg followed by 0.25 mg at 60 mins and 0.25 mg at 90 minsand 0.25 mg at 90 mins

• Evaluated by observed, bispectral index Evaluated by observed, bispectral index and plasma triazolam levelsand plasma triazolam levels

• 8 subjects met criteria for deep sedation or 8 subjects met criteria for deep sedation or general anesthesia at later time point general anesthesia at later time point

Advantages of BenzodiazepinesAdvantages of Benzodiazepines

• Specificity of effectSpecificity of effect

• Well absorbed by the oral routeWell absorbed by the oral route

• High margin of safety/therapeutic indexHigh margin of safety/therapeutic index

• Effective as single agentsEffective as single agents

• Specific reversal agent available Specific reversal agent available (flumazenil)(flumazenil)

Classification of BenzodiazepinesClassification of Benzodiazepines

• Alprazolam: antianxietyAlprazolam: antianxiety

• Diazepam: antianxietyDiazepam: antianxiety

• Lorazepam: antianxiety/sedative-hypnoticLorazepam: antianxiety/sedative-hypnotic

• Midazolam: sedative/hypnoticMidazolam: sedative/hypnotic

• Oxazepam: antianxietyOxazepam: antianxiety

• Triazolam: sedative/hypnoticTriazolam: sedative/hypnotic

DiazepamDiazepam (VALIUM (VALIUM))

• Usual dose range: Usual dose range: 2 - 20 mg2 - 20 mg, 1 h before , 1 h before appointment (adults)appointment (adults)

• Onset: 1 hr (peak levels in 2 hrs)Onset: 1 hr (peak levels in 2 hrs)• Duration: Duration: 1 - 3 hrs1 - 3 hrs• Contraindications: allergy, narrow-angle & Contraindications: allergy, narrow-angle &

untreated open-angle glaucomauntreated open-angle glaucoma• Precautions: sedation intensified by Precautions: sedation intensified by

several CYP inhibitors (3A4, 2C19)several CYP inhibitors (3A4, 2C19)

DiazepamDiazepam

• Active Active metabolites? Yesmetabolites? Yes

• Pregnancy Pregnancy category Dcategory D

• Availability: 2-, 5- Availability: 2-, 5- & 10-mg tabs, 5 & 10-mg tabs, 5 mg/ml liquid, rectal mg/ml liquid, rectal gel 5 mg/mlgel 5 mg/ml

LorazepamLorazepam (ATIVAN (ATIVAN))

• Usual dose range: Usual dose range: 2 - 4 mg2 - 4 mg 1 hr before 1 hr before appointment (adults)appointment (adults)

• Onset: 1 hr (peak levels in 2 hrs)Onset: 1 hr (peak levels in 2 hrs)• Duration: Duration: 2 - 4 hrs (use for longer 2 - 4 hrs (use for longer

procedures)procedures)• Contraindications: allergy, narrow-angle Contraindications: allergy, narrow-angle

glaucomaglaucoma• Precautions: greater likelihood of excessive Precautions: greater likelihood of excessive

sedation than with other agents, do not use in sedation than with other agents, do not use in cases of depressive disorder/psychosiscases of depressive disorder/psychosis

LorazepamLorazepam

• Active Active metabolites? Nometabolites? No

• Pregnancy Pregnancy category Dcategory D

• Availability: 0.5-, 1 Availability: 0.5-, 1 and 2-mg tabsand 2-mg tabs

OxazepamOxazepam (SERAX) (SERAX)

• Usual dose range: Usual dose range: 10 – 30 mg10 – 30 mg, 1 hr , 1 hr before appointment (adults)before appointment (adults)

• Onset: 1 hr (peak levels in 1 – 4 hrs)Onset: 1 hr (peak levels in 1 – 4 hrs)

• Duration: Duration: 2 – 4 hrs2 – 4 hrs

• Contraindications: allergyContraindications: allergy

• Precautions: same as for other agentsPrecautions: same as for other agents

• Active metabolites? No Active metabolites? No

OxazepamOxazepam• Pregancy Pregancy category Dcategory D

• Availability: 10-, Availability: 10-, 15- & 30-mg 15- & 30-mg caps, 15-mg tabs caps, 15-mg tabs

TriazolamTriazolam (HALCION (HALCION))

• Usual dose range: Usual dose range: 0.25 – 0.50.25 – 0.5 mg, 1 hr before mg, 1 hr before appointment (adults)appointment (adults)

• Onset: 1.3 hrs (peak levels in 0.5 – 4 hrs)Onset: 1.3 hrs (peak levels in 0.5 – 4 hrs)• Duration: Duration: 1 hr1 hr• Contraindications: allergy, pregnancy, do not Contraindications: allergy, pregnancy, do not

administer with potent CYP 3A4 inhibitors (e.g., administer with potent CYP 3A4 inhibitors (e.g., azole antifungals)azole antifungals)

• Precautions: anterograde amnesia, excessive Precautions: anterograde amnesia, excessive sedation (especially elderly)sedation (especially elderly)

TriazolamTriazolam

• Active metabolites? NoActive metabolites? No

• Pregnancy category XPregnancy category X

• Availability: 0.125- & 0.25-mg tabsAvailability: 0.125- & 0.25-mg tabs

Triazolam DosesTriazolam Doses

Short-term management of insomniaShort-term management of insomnia

0.25mg PO hs0.25mg PO hs

Max: 0.5 mg PO hs;Max: 0.5 mg PO hs;

Alternative: 0.125 mg PO hs if elderly, hepatic Alternative: 0.125 mg PO hs if elderly, hepatic impairmentimpairment

TriazolamTriazolam

Onset:Onset:

Peak effect:Peak effect:

Duration:Duration:

1 hr.1 hr.

1.3 hrs.1.3 hrs.

2 – 3 hrs.2 – 3 hrs.

AlprazolamAlprazolam (XANAX)(XANAX)

• Usual dose range: Usual dose range: 0.25 – 1 mg0.25 – 1 mg 1 hr before 1 hr before appointment (adults)appointment (adults)

• Onset: 1 hr (peak levels in 1 – 2 hrs)Onset: 1 hr (peak levels in 1 – 2 hrs)• Duration: Duration: 1 – 2 hrs1 – 2 hrs• Contraindications: allergy, narrow- and untreated Contraindications: allergy, narrow- and untreated

open-angle glaucoma, potent CYP 3A4 inhibitors open-angle glaucoma, potent CYP 3A4 inhibitors (e.g., azole antifungals)(e.g., azole antifungals)

• Precautions: sedation intensified by CYP 3A4 Precautions: sedation intensified by CYP 3A4 inhibitors, produces little or no amnesia or inhibitors, produces little or no amnesia or somnolencesomnolence

AlprazolamAlprazolam• Active metabolites? Active metabolites?

NoNo• Pregnancy category Pregnancy category

DD• Availability: 0.25-, Availability: 0.25-,

0.5, 1- & 2-mg tabs, 0.5, 1- & 2-mg tabs, 0.5- and 1 mg/ml 0.5- and 1 mg/ml liquid liquid

MidazolamMidazolam

• ALL BRAND NAME FORMS (VERSED) ALL BRAND NAME FORMS (VERSED) DISCONTINUED BY ROCHE MAY, 2002DISCONTINUED BY ROCHE MAY, 2002

• Now available from Ranbaxy Pharmaceuticals Now available from Ranbaxy Pharmaceuticals as 2 mg/ml cherry syrup (Princeton, NJ)as 2 mg/ml cherry syrup (Princeton, NJ)

• Usual dosage range: Usual dosage range: 0.25 – 0.5 mg/kg0.25 – 0.5 mg/kg single single dose up to a total maximum of 20 mg (children)dose up to a total maximum of 20 mg (children)

• Onset: 10 – 20 minOnset: 10 – 20 min• Duration: Duration: 30 – 60 min30 – 60 min• Contraindications: allergy, narrow-angle Contraindications: allergy, narrow-angle

glaucomaglaucoma

MidazolamMidazolam

• Precautions: may cause intense Precautions: may cause intense CNS/respiratory depression, use with CNS/respiratory depression, use with caution with potent CYP 3A4 inhibitors caution with potent CYP 3A4 inhibitors (e.g., azole antifungals) (e.g., azole antifungals) NOT TO BE NOT TO BE ADMINISTERED AT PATIENT’S HOMEADMINISTERED AT PATIENT’S HOME

• Active metabolites? NoActive metabolites? No• Pregnancy category DPregnancy category D• Availability: 2 mg/ml syrupAvailability: 2 mg/ml syrup

Oral BZ Biovailability & Half-livesOral BZ Biovailability & Half-lives

• Diazepam: 100%, 43 Diazepam: 100%, 43 ± 13 hrs± 13 hrs

• Oxazepam: 97%, 8 ± 2.4 hrsOxazepam: 97%, 8 ± 2.4 hrs

• Lorazepam: 90%, 12 ± hrsLorazepam: 90%, 12 ± hrs

• Alprazolam: 88%, 12 ± 2 hrsAlprazolam: 88%, 12 ± 2 hrs

• Triazolam: 44%, 2.9 ± 1 hrsTriazolam: 44%, 2.9 ± 1 hrs

• Midazolam: 44%, 1.9 ± 0.6 hrsMidazolam: 44%, 1.9 ± 0.6 hrs

Non-BZ BZ Receptor Agonists

• Eszopiclone (LUNESTA)

• Zaleplon (SONATA)

• Zolpidem (AMBIEN)

Melatonin Receptor Agonist: Ramelteon (ROZEREM)

• MT1 & MT2 receptor agonist

• Simulates melatonin (“circadian rhythm)

• 8 mg

• Rapid onset, Tmax = 45 min

• Low bioavailability, 70% protein-bound

• CYP 1A2 (fluvoxamine caution)

• Not controlled substance

Zolpidem (AMBIEN)Zolpidem (AMBIEN)

• Usual dose range: 5 – 10 mg, 1/2 hr Usual dose range: 5 – 10 mg, 1/2 hr before appointmentbefore appointment

• Onset: 0.5-1 hr (peak levels in 1.6 hrs)Onset: 0.5-1 hr (peak levels in 1.6 hrs)(use when rapid onset needed)(use when rapid onset needed)

• Duration: 2 – 3 hrsDuration: 2 – 3 hrs• Contraindications: allergyContraindications: allergy• Precautions: reduce dosage in elderlyPrecautions: reduce dosage in elderly• Active metabolites? NoActive metabolites? No

ZolpidemZolpidem

• Pregnancy category BPregnancy category B• Availability: 5- and Availability: 5- and

10-mg tabs10-mg tabs

Hydroxyzine (ATARAX, VISTARIL)Hydroxyzine (ATARAX, VISTARIL)

• Usual dose range: 50 – 100 mg, 1 hr before Usual dose range: 50 – 100 mg, 1 hr before appointment (adults), 1.1 – 2.2 mg/kg (children)appointment (adults), 1.1 – 2.2 mg/kg (children)

• Onset: 30 min (peak effect 2 hrs)Onset: 30 min (peak effect 2 hrs)• Duration: 3 – 4 hrsDuration: 3 – 4 hrs• Contraindications: allergyContraindications: allergy• Precautions: same as for benzodiazepines, Precautions: same as for benzodiazepines,

more anticholinergic actions (glaucoma, more anticholinergic actions (glaucoma, respiratory disease)respiratory disease)

HydroxyzineHydroxyzine• Active metabolites? NoActive metabolites? No• Pregnancy category DPregnancy category D• Availability: 10-, 25-, 50- & Availability: 10-, 25-, 50- &

100-mg tabs; 10mg/5 ml 100-mg tabs; 10mg/5 ml syrup (ATARAX); 25-, 50-, syrup (ATARAX); 25-, 50-, & 100-mg caps and & 100-mg caps and 25mg/5 ml oral suspension 25mg/5 ml oral suspension (VISTARIL)(VISTARIL)

• Non-controlled substanceNon-controlled substance

PromethazinePromethazine (PHENERGAN) (PHENERGAN)

• Usual dose range: Usual dose range: 25 – 50 mg25 – 50 mg, 1 hr before , 1 hr before appointment (adults), 2.2 mg/kg (children, when appointment (adults), 2.2 mg/kg (children, when used as SOLE sedative agent)used as SOLE sedative agent)

• Onset: 1 hr (peak effect 2 hrs)Onset: 1 hr (peak effect 2 hrs)• Duration: Duration: 3 – 4 hrs3 – 4 hrs (may be (may be up to 12 hrsup to 12 hrs))• Contraindications: allergy, conditions worsened Contraindications: allergy, conditions worsened

by anticholinergic actionsby anticholinergic actions• Precautions: same as for other sedatives, also Precautions: same as for other sedatives, also

seizure disordersseizure disorders

PromethazinePromethazine• Active metabolites? NoActive metabolites? No• Pregnancy category CPregnancy category C• Availability: 12.5-, 25- & Availability: 12.5-, 25- &

50-mg tabs; 6.25 mg/5 50-mg tabs; 6.25 mg/5 ml syrup; 25 mg/5 ml ml syrup; 25 mg/5 ml syrup fortissyrup fortis

• Not a controlled Not a controlled substance substance

Agents NOT Recommended Agents NOT Recommended (Adults)(Adults)

• AlcoholAlcohol

• Chloral hydrateChloral hydrate

• OpioidsOpioids

• Multi-Drug CocktailsMulti-Drug Cocktails

Nitrous Oxide

Advantages of Nitrous Oxide

• Rapid onset (almost equal to that of iv)

• Titratable (up AND down)

• Depth of sedation readily altered

• Flexible duration of action

• Rapid recovery from sedation

• Safe

Advantages of Nitrous Oxide

• No injection required

• Very few side effects

• No adverse effects on vital organs

• May substitute for local anesthesia in selected circumstances (e.g., soft tissue procedures)

Disadvantages of Nitrous Oxide

• Initial co$t of cumbersome equipment is high

• Continuing co$ts of gases high

• Equipment takes up operatory space

• Lack of potency

• Requires constant patient cooperation

• Chronic exposure of office personnel

Indications for Inhalation Sedation

• Mild to moderate dental anxiety

• Medically compromised patients

• Gagging (impressions, radiographs)

Relative Contraindications to Inhalation Sedation

• Severe dental anxiety & fear

• Compulsive personalities

• Poor past experience with oral sedation

• Claustrophobia

• Pregnancy

• URI, COPD

Concentration EffectThe higher the concentration

of inhaled gas, the more rapidly the blood level of the

gas increases

Diffusion Hypoxia (?)When the flow of nitrous oxide

is stopped, nitrous oxide rapidly leaves the blood and

dilutes the oxygen in the alveoli of lungs

Prevention of Diffusion Hypoxia

Administer 100% oxygen for 3 to 5 minutes at the termination

of the sedation procedure

CNS Effects of Nitrous Oxide

• All senses are slightly depressed or altered (perioral numbness, etc.)

• Amnesia does NOT occur

• Mild depression of cerebral cortex

• Produces mild sedation, analgesia

• Lacks direct respiratory depression

Nitrous Oxide Does NOT...

• Obtund sharp pain impulses

• Substitute for good local anesthesia

• Sedate agitated or extremely anxious patients

• Produce loss of consciousness when used correctly

Why Nitrous Oxide is Associated with Nausea

• Not titrated

• All patients are given “fixed” concentrations (usually 50%)

• Signs and symptoms of impending nausea and vomiting are not recognized

• Patients are not given appropriate pre-treatment instructions

Other Effects of Nitrous Oxide

• Cardiovascular: no clinically significant effects at recommended concentrations

• Cutaneous vasodilation (flush, warmth)

• Respiratory: no clinically significant depression at recommended concentrations

• G.I. Tract: no effects liver)

Other Effects of Nitrous Oxide

• Kidneys: no effect

• Blood: inhibition of vitamin B-12 metabolism (chronic administration)

• Skeletal muscle: no direct effect (relaxation secondary to sedative effect)

Contraindications to Nitrous Oxide

• Pregnancy (1st trimester)

• Upper respiratory tract infection

• Nasal hood unacceptable (claustrophobia, allergy, etc.)

• Previous “bad experience”

• Drug abuse

• Chronic environmental exposure

Effects of Pathologic Conditions on Inhalation Sedation

• Emphysema: decreased total surface area of alveoli

• Pneumonia: alveolar walls thickened

• Asthma: increased thickness of bronchial secretions

• Anemia/Methemoglobinemia: decreased oxygen-carrying capacity of blood

Physiologic EquivalentsPhysiologic Equivalents

• Total gas flow (LPM) = minute respiratory Total gas flow (LPM) = minute respiratory volumevolume

• Excursion of reservoir = tidal volumeExcursion of reservoir = tidal volume• Excursions of reservoir bag/min = Excursions of reservoir bag/min =

respiratory rate = respiratory center “firings”respiratory rate = respiratory center “firings”• Collapse of reservoir bag with maximum Collapse of reservoir bag with maximum

inhalation = inspiratory reserve capacityinhalation = inspiratory reserve capacity

Complications and Chronic Toxicity

Excessive Perspiration

• Etiology: peripheral vasodilation

• Management: decrease nitrous oxide concentration (5% per min)

Expectoration

• Etiology: fluid removal problems, diminished patient coordination and cooperation

• Management: efficient vacuum operation, rubber dam

Behavioral Problems

• Etiology: authoritarian patient, excessive nitrous oxide concentrations

• Management: decrease nitrous oxide concentration, allow controlled mouth breathing if necessary

Nausea

• Etiology: excessive length and/or depth of sedation, over-emotional patient, over-eating, frequent changes in patient position (esp. pediatrics), frequent changes in nitrous oxide concentration

• Management: avoid etiologic factors, premedicate with anti-emetic drug

Vomiting

• Etiology: same as for nausea

• Management: remove nasal hood, turn patient’s head to assistant, change gas mixture to 100% oxygen, apply 100% oxygen for at least 5 min and inform patient

Pre-Operative Instructions

• 1. Take pre-operative medications (if indicated)

• 2. No heavy meals (or no food intake at all) for 4 hrs prior to sedation

• 3. Require an escort (if indicated or otherwise required)

Chronic Exposure to Nitrous Oxide

Mutagenicity of Nitrous Oxide?

• Negative in Salmonella microsome assays

• Negative in cultured hamster lung fibroblasts

• negative in hamster ovarian cells

• negative in Drosophila melanogaster

• No human studies

Carcinogenicity of Nitrous Oxide?

• Negative results in mice

• Human studies generally negative

Teratogenicity of Nitrous Oxide

• Definite teratogenicity in rats

• male rodents show chromosomal damage (not heritable, significance?)

• INCREASED RISK OF SPONTANEOUS ABORTION IN HUMANS

• Effects require chronic exposure

Dental Office Exposure to Nitrous

Oxide

Sources of Environmental N2O

• Normal gas flow to patients

• Patient (talking, “washout” during recovery)

• Equipment (leaks)

• Air conditioning (recirculation)

Office Levels of N2O Depend on

• Frequency of use

• Size of operatory

• Ventilation of operatory

• Type of operatory (open vs. closed)

Detection of Office N2O

• Visual inspection (rubber goods, connections)

• Application of soapy water

• Air analysis (by outside service company) (infrared spectroscopy)

• Monitoring cartridges (Porter “Peace of Mind” cartridges)

Minimizing Office N2O

Effects of Scavenging

Systems

Nitrous Oxide Levels (ppm) of Breathing Zones in Offices Without & With Scavenging Systems (from

Whitcher et al., JADA, 1977) • WITHOUT • General dentist: 775

(+/- 63)• Pedodontist: 940 (+/-

92)• Oral Surgeon: 1000

(+/-130)

• WITH• General dentist: 21

(+/-2)• Pedodontists: 33 (+/-

4)• Oral Surgeon: 36 (+/-

4)

Abuse of Nitrous Oxide

Mechanism of Chronic Toxicity

• Oxidation of vitamin B-12 (cobalamin; bound co-factor for methionine synthetase and methylmalonyl CoA mutase)

• Interferes with folate metabolism and DNA synthesis (decreased thymidine)

Clinical Effects of Chronic Toxicity

• Bone marrow suppression, anemia, leukopenia

• Suppression of neutrophil chemotaxis

• Alterations in reproductive cells

• Peripheral neuropathy with subacute degeneration of spinal cord

• Layzer, R.B. Lancet 2:1227, 1978

FlumazenilFlumazenil (ROMAZICON) (ROMAZICON)

• Competes with benzodiazepine for Competes with benzodiazepine for receptor sitereceptor site

• Used to reverse CNS depressant effects Used to reverse CNS depressant effects of overdose and to decrease recovery timeof overdose and to decrease recovery time

• REVERSAL OF RESPIRATORY REVERSAL OF RESPIRATORY DEPRESSION NOT PREDICTABLEDEPRESSION NOT PREDICTABLE

• Short half-life (readministration often Short half-life (readministration often required)required)

Sublingual Injection of Flumazenil?Sublingual Injection of Flumazenil?

• Average time to reversal with IV route = 2 Average time to reversal with IV route = 2 minutesminutes

• Average time to reversal with SL route = Average time to reversal with SL route = 4.33 minutes4.33 minutes

FlumazenilFlumazenil

• Only BZ antagonist availableOnly BZ antagonist available• Can produce agitation, confusion, dizziness & Can produce agitation, confusion, dizziness &

nauseanausea• Can precipitate withdrawal syndrome (chronic BZ Can precipitate withdrawal syndrome (chronic BZ

use)use)• Can produce seizures & cardiac arrhythmias in Can produce seizures & cardiac arrhythmias in

patients taking tricyclic antidepressantspatients taking tricyclic antidepressants• Usual dose: Usual dose: 0.2 mg iv in 15 secs, evaluate in 45 0.2 mg iv in 15 secs, evaluate in 45

secs. Add additional 0.2 mg if neededsecs. Add additional 0.2 mg if needed• Repeat q. 5 min until recovery or total dose of 1 Repeat q. 5 min until recovery or total dose of 1

mgmg

Fundamentals of Emergency Fundamentals of Emergency PreparationPreparation

• 1. Training (BLS, ACLS, PALS, TSBDE-1. Training (BLS, ACLS, PALS, TSBDE-approved courses)approved courses)

• 2. Development and implementation of an 2. Development and implementation of an emergency plan emergency plan

• 3. Purchase and maintenance of 3. Purchase and maintenance of emergency equipment and drugsemergency equipment and drugs

• 4. Periodic mock emergency drills4. Periodic mock emergency drills• 5. Training new staff members5. Training new staff members

What Your EMS Personnel Want What Your EMS Personnel Want and NEED!and NEED!

• An An accurate medical historyaccurate medical history of the of the patient/victimpatient/victim

• A concise A concise description of everythingdescription of everything that that happenedhappened

• Doctor remains with patient/victimDoctor remains with patient/victim

Pre-Emptive Strategies for Dental Office Pre-Emptive Strategies for Dental Office Emergency Preparation and ManagementEmergency Preparation and Management

• Painstakingly detailed health history Painstakingly detailed health history

• Medical risk classifcationMedical risk classifcation

• Avoid potential drug interactionsAvoid potential drug interactions

• Calculate dental drug dosages carefullyCalculate dental drug dosages carefully

• Monitor, monitor, monitor!!!Monitor, monitor, monitor!!!

• IMPLEMENT AN OFFICE EMERGENCYN IMPLEMENT AN OFFICE EMERGENCYN PLANPLAN

A General Paradigm for A General Paradigm for Assessing and Managing ASA II-IV PatientsAssessing and Managing ASA II-IV Patients

• Monitor vital signs at every appointmentMonitor vital signs at every appointment• Know patient’s medications and why they Know patient’s medications and why they

are taking themare taking them• Consult the physician to determine degree Consult the physician to determine degree

of disease control, compliance and ability of disease control, compliance and ability of patient to tolerate dental procedureof patient to tolerate dental procedure

• Utilize the stress-reduction protocolUtilize the stress-reduction protocol• Plan for likely emergenciesPlan for likely emergencies

Stress-Reduction Protocol Stress-Reduction Protocol (Medically Compromised Patients)(Medically Compromised Patients)

• 1. Recognize medical risk1. Recognize medical risk• 2. Consult patient’s physician(s)2. Consult patient’s physician(s)• 3. Pharmacosedation, as indicated3. Pharmacosedation, as indicated• 4. Short appointments4. Short appointments• 5. Morning appointments5. Morning appointments• 6. Excellent intraoperative pain control6. Excellent intraoperative pain control• 7. Minimize waiting room time7. Minimize waiting room time• 8. Excellent post-operative pain control 8. Excellent post-operative pain control

Range of Dental Office Range of Dental Office EmergenciesEmergencies

• SyncopeSyncope• Nausea, vomitingNausea, vomiting• HyperventilationHyperventilation• Acute bronchial constriction/asthmaAcute bronchial constriction/asthma• SeizuresSeizures• Acute elevations in BP and HRAcute elevations in BP and HR• Acute depressions in BP and HRAcute depressions in BP and HR• HypoglycemiaHypoglycemia• Acute CNS/respiratory depressionAcute CNS/respiratory depression• Swallowing/aspirating foreign objectSwallowing/aspirating foreign object

Adverse events associated with Adverse events associated with outpatient anesthesia in outpatient anesthesia in

MassachusettsMassachusetts

D’eramo EM, Bookless SJ, Howard JBD’eramo EM, Bookless SJ, Howard JBJ. Oral Maxillofac. Surg. 2003;61:793-J. Oral Maxillofac. Surg. 2003;61:793-

800800

Methods and Outcomes from Methods and Outcomes from D’Eramo et al.D’Eramo et al.

• Morbidity data from 157 oral surgeons for Morbidity data from 157 oral surgeons for year 1999year 1999

• Syncope was most common complication Syncope was most common complication (1 in 160 patients receving local (1 in 160 patients receving local anesthesia)anesthesia)

Types of Emergency Drugs and Types of Emergency Drugs and Drug KitsDrug Kits

• None (or expired)None (or expired)

• Custom (“homemade”)Custom (“homemade”)

• Pre-assembled, commercial Pre-assembled, commercial

• Complete medical emergency “crash Complete medical emergency “crash carts”carts”

• Published listsPublished lists

• ACLS “Core Drugs”ACLS “Core Drugs”

Office Emergencies and Office Emergencies and Emergency KitsEmergency Kits

ADA Council on Scientific AffairsADA Council on Scientific Affairs

JADA 2002;133(3):364-365JADA 2002;133(3):364-365

““Proprietary emergency drug kits Proprietary emergency drug kits are available, but none of these are available, but none of these kits is compatible with the needs kits is compatible with the needs

of all practitioners.”of all practitioners.”

ADA Council on Scientific Affairs ADA Council on Scientific Affairs

20022002

MinimumMinimum Emergency Drugs Emergency Drugs Recommended by ADA CSARecommended by ADA CSA

• Epinephrine 1:1,000Epinephrine 1:1,000• Injectable antihistamineInjectable antihistamine• 100% oxygen with positive-pressure ventilation100% oxygen with positive-pressure ventilation• Nitroglycerin (sublingual/aerosol)Nitroglycerin (sublingual/aerosol)• Bronchodilator (inhaler)Bronchodilator (inhaler)• ““Sugar” (or glucose)Sugar” (or glucose)• Others “as training and needs mandate”Others “as training and needs mandate”

““Essential” Emergency Drugs (Haas, Dent. Essential” Emergency Drugs (Haas, Dent. Clin. N. Am., 2002:46:815-830)Clin. N. Am., 2002:46:815-830)

• OxygenOxygen

• EpinephrineEpinephrine

• NitroglycerinNitroglycerin

• AntihistamineAntihistamine

• Beta agonist (bronchodilator)Beta agonist (bronchodilator)

• AspirinAspirin

““Supplementary” Emergency DrugsSupplementary” Emergency Drugs(Haas, 2002)(Haas, 2002)

• GlucagonGlucagon• AtropineAtropine• EphedrineEphedrine• HydrocortisoneHydrocortisone• Morphine (or nitrous oxide)Morphine (or nitrous oxide)• NaloxoneNaloxone• Lorazepam or midazolam (seizures)Lorazepam or midazolam (seizures)• FlumazenilFlumazenil

““Proprietary emergency drug kits Proprietary emergency drug kits are available, but none of these are available, but none of these kits is compatible with the needs kits is compatible with the needs of all practitioners. The Council of all practitioners. The Council

on Scientific Affairs does not on Scientific Affairs does not recommend any specific recommend any specific

proprietary drug kit.”proprietary drug kit.”

JADA 2002;133(3):364-365JADA 2002;133(3):364-365

Oxygen Cylinders and VolumesOxygen Cylinders and Volumes

• E: 625 litersE: 625 liters

• H: 6,909 liters H: 6,909 liters

Time Available at 15 L/min Flow Time Available at 15 L/min Flow Rate (from 2,000 psi fill)Rate (from 2,000 psi fill)

• E cylinder = 41 minutesE cylinder = 41 minutes

• H cylinder = 460 minutesH cylinder = 460 minutes

• Reduce times by ½ at 1,000 psiReduce times by ½ at 1,000 psi

Appropriate Use of OxygenAppropriate Use of Oxygen

• Any suspected cardiopulmonary Any suspected cardiopulmonary emergency emergency

• Complaints of shortness of breath and Complaints of shortness of breath and suspected ischemic painsuspected ischemic pain

• For patients with suspected stroke or For patients with suspected stroke or unknown blood oxygenationunknown blood oxygenation

• May be administered to patients who are May be administered to patients who are not hypoxemicnot hypoxemic

Precautions: OxygenPrecautions: Oxygen

• Observe closely when using with patients Observe closely when using with patients known to be dependent on hypoxic drive known to be dependent on hypoxic drive (COPD; very rare)(COPD; very rare)

• Pulse oximetry may provide a useful Pulse oximetry may provide a useful method of assessing oxygenation (may be method of assessing oxygenation (may be inaccurate in low cardiac output, with inaccurate in low cardiac output, with vasoconstriction or with CO poisoning)vasoconstriction or with CO poisoning)

Oxygen Flow Requirments (ACLS)Oxygen Flow Requirments (ACLS)

• Nasal cannula: 1-6 L/min, 21-44%Nasal cannula: 1-6 L/min, 21-44%• Venturi mask: 4-12 L/min, 24-50%Venturi mask: 4-12 L/min, 24-50%• Partial rebreather mask: 6-10 L/min, 35-Partial rebreather mask: 6-10 L/min, 35-

60%60%• Nonrebreather mask with reservoir: 6-15 Nonrebreather mask with reservoir: 6-15

L/minL/min• Bag-mask with nonrebreather “tail”: 15 Bag-mask with nonrebreather “tail”: 15

L/min, 95-100%L/min, 95-100%

Positive-Pressure VentilationPositive-Pressure Ventilation

A nitrous oxide nasal hood CAN A nitrous oxide nasal hood CAN NOT provide positive-pressure NOT provide positive-pressure

ventilationventilation

Supplementary Oxygen vs. Supplementary Oxygen vs. Positive-Pressure Ventilation with Positive-Pressure Ventilation with

100% Oxygen100% Oxygen

EpinephrineEpinephrine

• Only injectable agent which should be available Only injectable agent which should be available in ALL dental officesin ALL dental offices

• Use pre-loaded syringes (not ampuls)Use pre-loaded syringes (not ampuls)• Use 1:1,000 by sublingual or I.M. route only Use 1:1,000 by sublingual or I.M. route only • Adult dose = 0.3 mg, q. 5-10 min & monitor CV Adult dose = 0.3 mg, q. 5-10 min & monitor CV

status before re-dosingstatus before re-dosing• Produces bronchodilation, cardiac stimulation Produces bronchodilation, cardiac stimulation

and vasoconstrictionand vasoconstriction

Epinephrine PrecautionsEpinephrine Precautions

• Elevations of BP and increased HR may Elevations of BP and increased HR may cause ischemia, increased O2 demand cause ischemia, increased O2 demand and dysrhythmiasand dysrhythmias

• Avoid accidental injection of rescuerAvoid accidental injection of rescuer

Whenever epinephrine or another Whenever epinephrine or another emergency drug is administered, emergency drug is administered,

medical assistance must be medical assistance must be summonedsummoned

Other BronchodilatorsOther Bronchodilators

• Beta-2 AgonistsBeta-2 Agonists

• TerbutalineTerbutaline

Beta-2 Adrenergic AgonistsBeta-2 Adrenergic Agonists

• Albuterol (VENTOLIN)(first choice)Albuterol (VENTOLIN)(first choice)

• Metaproterenol (ALUPENT)Metaproterenol (ALUPENT)

• Terbutaline (BRETHAIRE)Terbutaline (BRETHAIRE)

• Peak onset = 30-60 minutesPeak onset = 30-60 minutes

Albuterol (PROVENTIL, Albuterol (PROVENTIL, VENTOLIN)VENTOLIN)

• Use by inhalation route for emergency Use by inhalation route for emergency airway constrictionairway constriction

• May produce sympathomimetic CV effects May produce sympathomimetic CV effects (tachycardia, palpitations, elevated BP)(tachycardia, palpitations, elevated BP)

• May be ineffective or partially effective if May be ineffective or partially effective if patient taking beta blockerspatient taking beta blockers

NitroglycerinNitroglycerin

• Available in 0.4 mg sublingual tabsAvailable in 0.4 mg sublingual tabs

• Decreases cardiac work load Decreases cardiac work load

• Administer 1 tab q. 5 min up to 3 times Administer 1 tab q. 5 min up to 3 times

• Also available in spray form (more stable)Also available in spray form (more stable)(1-2 sprays q. 5 min up to 3 sprays)(1-2 sprays q. 5 min up to 3 sprays)

• May produce hypotension (do not use if May produce hypotension (do not use if hypotension present) hypotension present)

Nitroglycerin PrecautionsNitroglycerin Precautions

• Avoid in patients taking drugs for EDAvoid in patients taking drugs for ED

• May cause excessive decrease in BP with May cause excessive decrease in BP with syncope (patient should be in sitting or syncope (patient should be in sitting or reclined position when taking)reclined position when taking)

Aromatic Spirits of AmmoniaAromatic Spirits of Ammonia

• Irritates respiratory mucosa, causes Irritates respiratory mucosa, causes muscle contractions, improves muscle contractions, improves venous returnvenous return

• Dose = inhaled vapors of one Dose = inhaled vapors of one crushed ampul crushed ampul

• Supplied as 0.3 ml “vaporole”Supplied as 0.3 ml “vaporole”

Glucose/SucroseGlucose/Sucrose

• Acceptable forms of sucrose include Acceptable forms of sucrose include soft drinks, orange juice & candy barssoft drinks, orange juice & candy bars

• Glucose also available Glucose also available • Do not use oral dose forms in Do not use oral dose forms in

unconscious patientunconscious patient • Long onset (10 min)Long onset (10 min)

AntihistaminesAntihistamines

• Diphenhydramine (BENADRYL) (50 Diphenhydramine (BENADRYL) (50 mg/ml)mg/ml)

• Chlorpheniramine (CHLOR-TRIMETON) Chlorpheniramine (CHLOR-TRIMETON) (10 mg/ml)(10 mg/ml)

• DO NOT subsitute for epinephrine in DO NOT subsitute for epinephrine in anaphylaxisanaphylaxis

AspirinAspirin

• Indicated in all patients with ACSIndicated in all patients with ACS• Any person with symptoms of “pressure, Any person with symptoms of “pressure,

“heavy weight”, “squeezing”, or “crushing” “heavy weight”, “squeezing”, or “crushing” (suggestive of ischemia)(suggestive of ischemia)

• DO NOT administer in aspirin-allergic DO NOT administer in aspirin-allergic patientspatients

• Relatively contraindicated in ulcer disease Relatively contraindicated in ulcer disease or asthmaticsor asthmatics

Aspirin DosageAspirin Dosage

• 160 – 325 mg non-enteric coated tablets 160 – 325 mg non-enteric coated tablets ASAPASAP

• Chewing is preferredChewing is preferred

• May use rectal suppository form (if May use rectal suppository form (if available)available)

AtropineAtropine

• Indicated for bradycardiaIndicated for bradycardia

• Rapid onset, short durationRapid onset, short duration

• 0.5 mg i.m. q. 3-5 min up to total of 3 mg0.5 mg i.m. q. 3-5 min up to total of 3 mg

• Avoid excessive reductions of heart rate Avoid excessive reductions of heart rate and use in patients susceptible to adverse and use in patients susceptible to adverse anticholinergic effectsanticholinergic effects

• Also used for organophosphate poisoningAlso used for organophosphate poisoning

ReferencesReferences• Malamed, Malamed, Sedation: A Guide to patient Sedation: A Guide to patient

management, 4management, 4thth edition, 2003 edition, 2003

• Jackson & Johnson, Jackson & Johnson, Conscious sedation Conscious sedation for dentistry: risk management and patient for dentistry: risk management and patient selection, selection, Dent. Clin. N. Am. Vol. 46, 2002Dent. Clin. N. Am. Vol. 46, 2002

• American Dental Association, American Dental Association, Guidelines Guidelines for the use of conscious sedation, deep for the use of conscious sedation, deep sedation and general anesthesia, 2007. sedation and general anesthesia, 2007.

Local Anesthetic DosagesLocal Anesthetic Dosages

• ALWAYS calculated on basis of body ALWAYS calculated on basis of body weight (mg/kg)weight (mg/kg)

• Absolute maximum dosage reached at Absolute maximum dosage reached at body weight of 70 kg (150 lbs)body weight of 70 kg (150 lbs)

• Apply to a single appointmentApply to a single appointment

• Adjusted downward to compensate for Adjusted downward to compensate for drug interactions, medical conditionsdrug interactions, medical conditions

Maximum Doses of Selected Local Maximum Doses of Selected Local AnestheticsAnesthetics

• Lidocaine (4.4 mg/kg, 300 mg absolute)Lidocaine (4.4 mg/kg, 300 mg absolute)• Mepivacaine (4.4 mg/kg, 300 mg absolute)Mepivacaine (4.4 mg/kg, 300 mg absolute)• Prilocaine (6 mg/kg, 400 mg absolute)Prilocaine (6 mg/kg, 400 mg absolute)• Articaine (7 mg/kg, 500 mg absolute)Articaine (7 mg/kg, 500 mg absolute)• Bupivacaine (1.3 mg/kg, 90 mg absolute)Bupivacaine (1.3 mg/kg, 90 mg absolute)

Other Informational ResourcesOther Informational Resources

• Mosby’s Drug Consult, Mosby’s Drug Consult, 800-545-2522800-545-2522• Mosby’s Dental Drug ReferenceMosby’s Dental Drug Reference, ,

www.elsevierhealth.comwww.elsevierhealth.com• Drug Interaction FactsDrug Interaction Facts, Facts & , Facts &

Comparisons, 800-223-0554Comparisons, 800-223-0554• www.rxlist.comwww.rxlist.com• www.drugfacts.comwww.drugfacts.com• www.med.umich.edu/1lib/aha/umherb01www.med.umich.edu/1lib/aha/umherb01

Local Anesthetics

Approaches to Failed IABs…

• Reinject (if lower lip not numb)?• Increase local anesthetic concentration

(prilocaine, articaine)?• Increase the vasoconstrictor

concentration?• Wait?• Apply the “Volume Rule”?• Apply the “Real Estate Rule”?

How long should you wait?

Varies with anesthetic and tissueLip = 5-7 minutes

Pulps = 10-15 minutes>15 minutes (~1 in 4 patients)>30 minutes (~1 in 10 patients)Longer-acting anesthetics have

longer onsets (Marcaine)

Malamed et al., JADA 2000, 2001

• 2% lidocaine with 1:100K epi vs. 4% articaine with 1:100K epi

• 882/443 articaine/lidocaine subjects• Used “simple” (single extractions, etc) and “complex”

(alveolectomies, etc) for evaluations• Articaine “is an efffective agent acting in the standard

lidocaine-mepivacaine range”• Clinical performance not sufficiently different to

qualify it as a replacement for lidocaine

Articaine vs. Other Agents

• Absolute max dose (carts) < lidocaine (7.3 vs. 8.3)

• Pregnancy category C (lidocaine B)

• Available with 1:100,000 and 1:200,000 epinephrine

Anesthetic Efficacy of Articaine for IABs in

Patients with Irreversible Pulpitis

Claffey E. et al. J. Endo. 2004;30:568-71

Claffey et al./Articaine

• 72 cases of irreversible pulpitis• Compared 4% articaine 2.2 ml vs. 2%

lidocaine with 1:100K epi 2.2 ml• All patients had “numb lips”• Endo access started 15 min post

numbness• Success rates = 24% for articaine &

23% for lidocaine

Results from Nusstein et al., J. Endo. 2003

Review of Intraosseous Injection Systems: ADA Professional

Product Review, Volume 2, Issue 1, Winter 2006

• Stabident• X-Tip• Intraflow (not evaluated)• “Clinical performance” best feature• X-Tip easiest to use• Tachycardia most common concern

Results from Replogle et al. (1999)

• 67% of ASA I patients receiving IO injections of lidocaine 2% with 1:100K epi experienced significantly increased HR

• Tachycardia averaged 28 bpm & lasted average of 4-5 min

• Systolic & diastolic BP unchanged• No increased HR observed with 3%

mepivacaine

Paresthesia

“An altered sensation of numbness, burning or pricking that may reflect an alteration in

the sensation of pain in the distribution of a specific sensory

nerve.”

Proposed Causes of Paresthesia

• Direct nerve trauma by needle• Barbed needles (“fish hook effect”)• Intraneural hematoma• Chemical toxicity of local

anesthetics/high concentration local anesthetic (4%)

• Surgical procedures following local anesthetic injection

• Neural ischemia (vasoconstrictor???)

“An inferior alveolar nerve block can cause occasional

peripheral nerve damage. The exact mechanism is unknown

and there is no known prevention or treatment.”

Pogrel MA, Thamby S. JADA 2000;131:901-907

Haas, D. J. Am. Coll. Dent. 2006

• Focused on NON-SURGICAL cases• Evaluated in vitro and human clinical outcomes• All agents have potential for neurotoxicity,

probably dose (concentration)-dependent• Nerves with fewer fasicles may be more

susceptible (e.g., lingual)• RCTs not likely to discriminate differences

between various local anesthetics

Summary of Findings in IAB-Related Paresthesias

• ~50% of patients experience “electric shock” sensation

• 85-94% of cases recover in 8 wks or less• Tongue (79%) and lower lip most frequently

affected• No difference between right and left sides• Nerve damage cannot be visualized or corrected

surgically• Overall incidence of permanent paresthesia =

1:785,000

Conclusions of Haas (2006)

• Data are “strongly suggestive” that paresthesia more likely with 4% agents

• “Concentration, not drug per se” cause

• Cited Royal College of Dental Surgeons (Ontario, 2005) (risks may outweigh benefits of 4% solutions for inferior alveolar and lingual blocks)

Avoiding Paresthesia…

• Use the lowest practical anesthetic and vasoconstrictor concentrations

• Use the atraumatic injection technique• Check your cartridges• Don’t subject your cartridges to temperature

extremes• Avoid operative neural trauma (careful use of

forceps, elevators, rubber dam clamps, etc.)

New Perspectives on Pain Control in Patients With Cardiovascular

Disease

E-References, Antiplatelet Drugs

• Antman EM et al. Use of Nonsteroidal Antiinflammatory Drugs. An Update for Clinicians. A Scientific Statement from the American Heart Association. Circulation, February 26, 2007

• http://www.circ.ahajournals.org/cgi/content/full/115/6/813

NSAID Classes

• Salicylic acid derivatives (diflunisal/DOLOBID)• P-Aminophenols (acetaminophen/TYLENOL)• Indole acetic acids (etodolac/LODINE)• Aryl acetic acids (diclofenac/VOLTAREN,

ketorolac/TORADOL)• Propionic acids (ibuprofen/MOTRIN,

naproxen/ANAPROX, ketoprofen/ORUDIS, flurbiprofen/ANSAID)

• Fenamates (mefenamic acid/PONSTEL)• Alkanones (nabumetone/RELAFEN)• Diarylheterocycles (selective COX-2 inhibitors)

Beneficial Effects of NSAIDs

• Analgesic (relieve pain)

• Antipyretic (reduce fever)

• Anti-inflammatory

• Available OTC

The Oxford League Table of Analgesic Efficacy

www.jr2.ox.ac.uk/bandolier/booth/painpag/Acutrev/

Analgesics/lftab.html

Oxford League Table of Analgesic Efficacy/NNTs (

www.jr2.ox.ac.uk/bandolier)(moderate-severe pain)

• Valdecoxib 40 mg: 1.6• Ibuprofen 800 mg: 1.6• Ketorolac 20 mg/60 mg: 1.8• Diclofenac 100 mg: 1.9• Rofecoxib 50 mg: 1.9• APAP 1,000 mg + codeine 60 mg: 2.2• APAP 500 mg + oxycodone 5 mg: 2.2• Naproxen 440 mg: 2.3 • Ibuprofen 600 mg: 2.4 • Ibuprofen 400 mg: 2.4 • Morphine 10 mg i.m.: 2.9

Relative Efficacy of Oral Analgesics After Third Molar

Extraction

Barden J, Edwards, JE, McQuay HJ, Wiffen PJ, Moore RA

British Dental Journal 2004;197:407-411

NNTs from Barden et al.

• Valdecoxib 40 mg (BEXTRA): 1.6• Diclofenac 100 mg (VOLTAREN): 1.6• Ibuprofen 400 mg: 4.7• Ibuprofen 200 mg: 4.6• Ibuprofen 600 mg: 1.9 • Celecoxib (CELEBREX): 4.8 • APAP 1,000 mg: 3.8 • APAP 600 mg + codeine 60 mg: 2.5 • APAP 300 mg + codeine 30 mg: 3.3

Contraindications to NSAIDs

• Stomach problems• Aspirin Allergy• Bleeding • Pregnancy• Kidney disease• CARDIOVASCULAR

DISEASE/RISK OF THROMBOEMBOLISM

Conditions With Risk for NSAID-Induced Nephropathy

• Volume depletion/dehydration (diarrhea, vomiting)

• Renal insufficiency

• Heart failure

• Diabetes

• Advanced age

• Kharasch, E. Anesth. Analg. 2004;98:1-3

COX-2-Selective Inhibitors

Selecting new drugs for pain control: evidence-based

decision or clinical impression?Jeske, AH. JADA 2002;133:1052-6

Conclusions

• VIOXX = 400 mg ibuprofen

• VIOXX has 50% “rescue” rate within 24 hrs

• Ibuprofen = VIOXX G.I. problems for 30 days

• VIOXX not OTC

Single dose oral celecoxib for postoperative pain (Barden J et al.

Cochrane Review: Issue 3, 2004)**

Similar in efficacy to aspirin 650 mg and APAP 1,000 mg

Evaluated 200-mg dose (more studies needed for 400-mg dose)

Moderate to Severe Post-Op Pain4-6 Hours

The Use of COX-2 Inhibitors for Acute Dental Pain: A

Second LookHuber, MA and Terezhalmy, GT.

JADA 2006;137:480-7

Unresolved Issues: NSAIDs

• COX-2 constitutively expressed in some tissues (brain, kidney, ovary & uterus)

• COX-2-synthesized PGs are pro-inflammatory early, may reduce inflammation & promote healing later

• Is opioid-sparing effect significant?

• Cardiovascular side effects? (prostacyclin vs. thromboxane A-2, salt and water retention)

COX-2 inhibitors

• Celecoxib (CELEBREX)

• Rofecoxicb (VIOXX)

• Etoricoxib (ARCOXIA)

• Lumiracoxib (PREXIGE) (Thromboxane antagonist???)

• Valdecoxib (BEXTRA)

Effects of NSAIDs on Platelet Aggregation

• Thromboxane A2 = vasoconstrictor, promotes platelet aggregation

• PG I2 = Vasodilator, inhibits platelet aggregation

• COX-2 inhibitors prevent synthesis of PG I2 but have no effect on TX A2, resulting in a prothrombotic state

Use of NSAIDs. An update for clinicians. A Scientific Statement

from the American Heart Association

Antman, E. M. et al.

Circulation

February 26, 2007

AHA Recommendations 2007 for Patients With Cardiovascular Disease

• Acetaminophen, aspirin and opioid analgesics (incl. tramadol) preferred for short-term pain management

• If NSAID is needed, naproxen “appears to be the preferred choice”

• Prescribe at lowest effective doses for shortest possible period of time

• Diclofenac not recommended as NSAID in this group of patients

• Ibuprofen should be given 30 mins AFTER low-dose aspirin or 8 hrs before (if use concomitantly)

PRECISION…coming to a journal near

you!Prospective Randomized

Evaluation of Celecoxib Integrated Safety vs Ibuprofen or Naproxen

www.clinicaltrials.gov No. NCT00346216

Single Dose Oral Acetaminophen for Postoperative Pain (Barden J et al., Cochrane Review, Issue 3, 2004)**

325 mg, 500 mg, 650 mg, 975-1,000 & 1,500 mg doses vs. placebo

1,000 mg = 1,500 mg (NNT 3.8 vs. 3.7)

Adverse Effects of 975-1,000 mg = placebo (!)

Preferred Oral Opioid Analgesics

• Tylenol with codeine #2: (2 or 3 q. 4 h.)

• Hydrocodone 2.5 or 5 mg with 500 mg APAP (1 or 2 q. 4 - 6 h.)

• Oxycodone 5 mg with 500 mg APAP (e.g., TYLOX) (1 or 2 q. 4 - 6 h.)

• Oxycodone 5 mg with 400 mg ibuprofen (COMBUNOX)**

Other Oral Opioid Analgesics

• Tramadol (ULTRAM): 50 - 100 mg q.4 -6 h. (now available with APAP as ULTRACET, 35/325)

• VICOPROFEN: 1 tab q. 4 – 6 h. • Pentazocine (TALWIN

COMPOUND, TALACEN)• Propoxyphene (DARVON

COMPOUND, DARVOCET)• VOPAC (650 mg APAP + 30 mg

codeine)

MAGNACET® (March, 2007)

• Oxycodone + acetaminophen 400 mg (?)

• 2.5, 5, 7.5 and 10 mg oxycodone (?)

• Schedule II

• “Moderate to moderately-severe pain”

• “Gives physicians flexibility”

• Compare with PERCOCET, TYLOX & COMBUNOX

Results from Dionne, R. J. Oral Max. Surg. 57:673, 1999

• Compared 400 mg ibuprofen + 2.5, 5 and 10 mg oxycodone

• Only 10 mg oxycodone was superior to 400 mg ibuprofen alone

• Opioid adverse effects were dose-related• 65% drowsy, 20% nauseated & 16%

vomited at 10 mg oxycodone