Improving Outcomes in Patients Undergoing Neuromuscular ...mededicus.com/downloads/Neuromuscular_Blockade_Mongraph.pdfneuromuscular blockade (RNMB) 2 Select neuromuscular blocking

Release Date: March 8, 2016 Expiration Date: March 8, 2017Estimated Time To Complete Activity: 1 hourTarget Audience: This activity intends to educate anesthesiologists, anesthesiologist assistants, certified registered nurse anesthetists, and registered nurses.Learning ObjectivesUpon completion of this activity, participants will have improved their ability to:1 Identify risk factors for complications from residual

neuromuscular blockade (RNMB)2 Select neuromuscular blocking agents based on iden-

tified risk factors for RNMB3 Debate the rationale for objective monitoring of

depth of neuromuscular blockade in patients under-going general anesthesia

4 Compare efficacy and safety profiles of neuromuscu-lar blockade reversal agents to identify appropriate use in patients

5 Compare the dose adjustments required for special populations of patients

6 Collaborate with surgical suite colleagues to improve patient safety and outcomes

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Sorin J. Brull, MD, has had a financial agreement or affiliation during the past year with the follow-ing commercial interest in the form of Contracted Research: Merck & Co., Inc.Steven B. Greenberg, MD, has had a financial agree-ment or affiliation during the past year with the fol-lowing commercial interest in the form of Consulting Fees (e.g., advisory boards): CAS Medical Systems, Inc.; and Contracted Research: Cadence, Inc.Richard Prielipp, MD, MBA, FCCM, has had a financial agreement or affiliation during the past year with the following commercial interest in the form of Fees for Non-CME/CE Services Received Directly from a Commercial Interest or their Agents (e.g., speakers’ bureaus): Merck & Co., Inc.Mark Welliver, DNP, CRNA, ARNP, has had a financial agreement or affiliation during the past year with the following commercial interest in the form of Consulting Fees (e.g., advisory boards): Merck & Co., Inc; Fees for Non-CME/CE Services Received Directly from a Commercial Interest or their Agents (e.g., speakers’ bureaus): Merck & Co., Inc.The planners and managers reported the following financial relationships or relationships to products or devices they or their spouse/life partner have with commercial interests related to the content of this CME/CE activity:The following PIM planners and managers, Trace Hutchison, PharmD, Samantha Mattiucci, PharmD, CHCP, Judi Smelker-Mitchek, RN, BSN, and Jan Schultz, RN, MSN, CHCP, hereby state that they or their spouse/life partner do not have any financial relationships or relationships to products or devices with any commercial interest related to the content of this activity of any amount during the past 12 months.The following MedEdicus planners and managers, Kerry Grimberg, Diane McArdle, PhD, and Cynthia Tornallyay, RD, MBA, CHCP, have no real or appar-ent conflicts of interest to report.

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Improving Outcomes in Patients Undergoing Neuromuscular Blockade

The content of this activity was developed by the faculty indicated herein under the supervision of Postgraduate Institute for Medicine and assistance from MedEdicus LLC. Applied Clinical Education (ACE) is responsible for graphic design and distribution of

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Distributed via Anesthesiology News and CMEZone.com

© 2016 MedEdicus LLC

Moderator

Richard Prielipp, MD, MBA, FCCMProfessor, Department of AnesthesiologyAnesthesiology AdministrationMinneapolis, Minnesota

Faculty

Sorin J. Brull, MDProfessor of AnesthesiologyDepartment of AnesthesiologyMayo Clinic, College of MedicineJacksonville, Florida

Steven B. Greenberg, MDClinical Associate ProfessorDepartment of AnesthesiologyNorthShore Medical GroupEvanston, Illinois

Mark Welliver, DNP, CRNA, ARNPAssociate Professor of Professional Practice School of Nurse AnesthesiaHarris College of Nursing & Health SciencesTexas Christian UniversityFort Worth, Texas

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Introduction

Over the course of the 234 million surgeries performed worldwide each year that necessitate general anesthesia,1 many patients receive neuromuscular blocking agents (NMBAs) to facilitate tracheal intu-bation and maintain optimal surgical conditions.2 In the United States alone, more than 100 million doses of NMBAs are adminis-tered annually.3 However, residual neuromuscular blockade (RNMB) and subsequent pulmonary complications4,5—muscular weakness, prolonged stay in the postanesthesia care unit (PACU) and hospital, and delayed extubation6-8—may occur in approximately 30% or more of surgical cases involving NMBAs.7,9-11 The risk for complications from RNMB increases with certain patient characteristics, comor-bidities, and types of surgery, including older age, female sex, obe-sity, myasthenia gravis, and upper abdominal or thoracic surgery.12-17

Use of NMBAs that generate active metabolites (eg, vecuronium) in patients in these high-risk groups may further increase the risk for RNMB.16,18,19 On the basis of these data, the American Society of Anesthesiologists recommends that “assessment of neuromuscu-lar function should be performed during emergence and recovery for patients who have received nondepolarizing neuromuscular blocking agents or who have medical conditions associated with neuromuscu-lar dysfunction.”20 Despite this evidence, RNMB remains unrecog-nized or underrecognized by clinicians and, therefore, is a significant problem for patients after surgery.11,21

Selection of Neuromuscular Blocking Agents

For patients at high risk for aspiration, those having an impend-ing loss of airway, or in patients with severely impaired gas exchange requiring mechanical ventilation, rapid-sequence induction and intu-bation is often performed.22,23 To achieve rapid-sequence intuba-tion, optimal pharmacotherapy should have a rapid onset of action, short duration of action, negligible hemodynamic effects, minimal side-effect profile, and be quickly reversible.23 Several factors should be considered when selecting the appropriate NMBA. Patients with neurologic disorders (eg, myasthenia gravis or Lambert-Eaton myasthenic syndrome) may require dose adjustments or avoid-ance of nondepolarizing NMBAs (eg, rocuronium or vecuronium) for safety reasons.23 Succinylcholine, a depolarizing NMBA, is metabolized by pseudocholinesterases and therefore should also be avoided in patients with pseudocholinesterase deficiency, advanced liver or renal disease, and other comorbidities due to the risk for pro-longed paralysis, for up to 8 hours. Increased potassium concentra-tions have been associated with succinylcholine administration in patients undergoing surgery.24 In overweight patients with a body mass index (BMI) of 25 to 30 kg/m2, succinylcholine use was associ-ated with a significantly more rapid desaturation (P = .01) and longer recovery of oxygen saturation (P = .002) than was rocuronium dur-ing rapid-sequence induction.25 Rocuronium is not recommended in patients who may be difficult to bag-mask ventilate because of its longer duration of action. An additional consideration when select-ing an NMBA is the desired time to recovery from blockade. Spon-taneous recovery from succinylcholine has been shown to be as long as 8 to 11 minutes22,26; this is likely too long to avoid desaturation in a “cannot intubate, cannot ventilate” emergency.

Monitoring of Neuromuscular Blockade

Repeated administration of NMBAs and intraoperative use of a high-dose NMBA can cause significant morbidity and mortality.7 The use of neuromuscular monitors in the operating room, however, remains inconsistent.21,27,28 Subjective monitoring of neuromuscular blockade (NMB) focuses on qualitative clinical signs, such as visual and tactile observations, and clinical signs, such as head lift, handgrip, and tidal volume, and is of limited value and can be performed only on awake patients.29 Subjective qualitative monitoring can also be achieved via visual/tactile twitch assessments, such as with peripheral nerve stimulation (PNS), which relies on an externally applied elec-trical stimulus to a peripheral nerve to elicit a corresponding muscle contraction (ie, twitch). One of the most commonly used, and accu-rate, sites is the ulnar nerve to assess the adductor pollicis (thumb) muscle contraction. The train-of-four (TOF) count (TOFc), the most frequently used mode, requires the user to count the number of responses representing the degree of NMB.30 However, this method is inherently subjective and there are levels at which clinicians cannot detect the presence of fade.30 Furthermore, different muscle groups demonstrate varying sensitivities to NMBAs, so a PNS at a single recording site may not accurately reflect the depth of NMB or its recovery everywhere.29

In contrast, acceleromyography and kinemyography are objective methods of monitoring based on accelerometry and are more reliable than PNS.8 With acceleromyography, an accelerometer is fixed to the patient’s thumb and an electrical signal based on changes in acceler-ation is produced whenever the thumb moves in response to stimu-lation of the ulnar nerve.31 For kinemyography, a mechanosensor is placed between the thumb and forefinger. Movement of the thumb deforms the piezoelectric polymer, generating a small current pro-portional to the amount of stretching or bending.32 Electromyogra-phy, another objective method, is a good option when the arm is not accessible. Electromyography records the evoked electrical response from a stimulating electrode placed on the ulnar nerve as for acceler-ometry and a sensor over the motor point of the muscle, usually the thenar or hypothenar eminence of the hand.33

Reversal of Residual Neuromuscular Blockade

The use of NMBAs might be associated with postoperative resid-ual weakness, leading to additional significant complications4-11; therefore, appropriate timing, dosing, and monitoring of reversal of NMB are essential. Cholinesterase inhibitors have been recom-mended to antagonize RNMB since 1948,34 and by the mid-1950s, neostigmine became the drug of choice.35 The common dosage for neostigmine is 0.03 to 0.07 mg/kg and its onset of action is within several minutes, although the peak effect is variable (10-30 minutes). The use of neostigmine is contraindicated in patients with known hypersensitivity to the drug and in those with mechanical bowel or urinary tract obstruction. The most common adverse events associ-ated with neostigmine are bradycardia, nausea, and vomiting. How-ever, there are several limitations associated with cholinesterase inhibitors: they are not reliable for reversing deep or even moder-ate levels of NMB (TOFc 0/4 and 1-2/4, respectively); they have a

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ceiling effect; and they may cause serious side effects, including bradycardia, hypotension, bronchoconstriction, and gastrointesti-nal hypermotility.36-41

In December 2015, the US Food and Drug Administration (FDA) approved sugammadex, a selective relaxant-binding agent, for reversal of the NMB induced by rocuronium or vecuronium in adults who received either NMBA during surgery. There is a large body of clinical trial literature with sugammadex.42 Hyper-sensitivity reactions to sugammadex, ranging from isolated skin reactions to serious systemic reactions (eg, anaphylaxis and ana-phylactic shock), have rarely been observed43-46; therefore, sugammadex is contraindicated in patients with a known hyper-sensitivity to the agent or to any of its components.47 In data pooled from phase 1 to 3 clinical trials, the frequency of hyper-sensitivity reactions was low.48 Among 3519 patients treated with sugammadex, hypersensitivity reactions occurred in 0.26%, with no cases of anaphylaxis. The estimated risk for anaphylaxis was calculated at ≤ 0.1%. Several large studies have consistently dem-onstrated significantly shorter times to recovery (P < .0001) in patients receiving sugammadex compared with those receiving the standard reversal agent, neostigmine, for reversal of NMB (Table 1).49-52 A systematic review of 17 randomized controlled trials of 1553 patients found that sugammadex significantly reduced all signs of RNMB, including residual postoperative paralysis (P = .0004), minor respiratory events (P = .0034), and drug-related side effects (P = .02).53

Reversal Agents: Dosing and Dose Adjustments for Patients With Comorbidities

The pharmacokinetics of sugammadex is known to be affected by age, renal function, body weight, and race.54 Three differ-ent doses are currently approved.47 The labeling recommends a

single 2- or 4-mg/kg bolus injection, with the timing and dose dependent on the patient’s response to TOF stimulation, and a 16-mg/kg bolus if the patient received a single 1.2-mg/kg dose of rocuronium for rapid-sequence induction and intubation, and the clinical need arises for reversal of NMB within 3 minutes (eg, “cannot ventilate, cannot intubate” rescue). For the use of neostigmine, caution is recommended in patients with renal insufficiency, hepatic impairment, or older age, but no specific guidance on dose adjustment is given in the product label.55

To mitigate the increased risk for RNMB in patients with var-ious comorbidities, dosing and dose adjustments are warranted. Altered pharmacokinetics and dynamics, changes in receptor sen-sitivity, and impairment of the body’s normal homeostatic mech-anisms in elderly patients56 may contribute to altered duration of action and decreased elimination of certain NMBAs.57-59 Time to recovery of the TOF ratio to 0.9 has been shown to increase with increasing age with administration of sugammadex 2.0 mg/kg. The average time to recovery for patients aged 75 years or older (n = 40; 3.6 minutes) was significantly longer than in younger adults aged 18 to 64 years (n = 48; 2.3 minutes).60 Similar results were found after administration of sugammadex 4.0 mg/kg dur-ing deep NMB (posttetanic count of 1 or 2) with rocuronium; there was a 3-fold longer recovery in patients aged 70 years or older (n = 15; 3.6 minutes) compared with younger adults (n = 15; 1.3 minutes).61 A recent study in patients aged 70 years or older (n = 22) found that a significantly higher dose of sugammadex is needed to provide adequate recovery to a TOF ratio of 0.9 within a 2-minute window.62

Patients with comorbidities, such as renal, cardiac, or pulmo-nary disease, or obese patients may also require dose adjustments for NMB reversal agents.63 Several multicenter studies and indi-vidual case reports have examined the utility of administering a higher dose of sugammadex (4.0 mg/kg) in these subpopulations (Table 2).64-68 Three studies examined the effects of sugammadex

Table 1. Summary of Phase 3 Trials of Sugammadex Versus Neostigmine in Recovery From Neuromuscular Blockade

NMBA

Time to Recovery to TOF Ratio of 0.9, Geometric Mean, min

ReferenceNeostigminea Sugammadexb

Rocuronium50.4 2.9 Jones49

18.6 1.5 Blobner50

Vecuronium66.2 4.5 Lemmens51

17.9 2.7 Khuenl-Brady52

a Plus glycopyrrolate (10 or 14 mg/kg).b P < .001.


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2.0 mg/kg and 4.0 mg/kg, respectively, for patients with end-stage renal disease (creatinine clearance [CLCR] < 30 mL/min) compared with controls with normal renal function.64-66 Time to recovery from rocuronium-induced deep NMB was similar for sugammadex 2.0 mg/kg in the experimental and control arms despite poor CLCR rates, neuromuscular monitoring via accelero-myography, and administration of sugammadex at the reappearance of the second twitch of the TOF.64 Two recent studies compar-ing the 4 mg/kg dose in patients with CLCR < 30 mL/min versus those with a normal renal function showed a significantly lon-ger time to recover for patients with renal insufficiency; however, there were no serious adverse events in either group.65,66 Dahl and colleagues67 demonstrated the safety and efficacy of sugammadex 2.0 mg/kg and 4.0 mg/kg in patients with cardiac disease (ischemic heart disease, chronic heart failure, or arrhythmia) (N = 76), with no significant differences observed in corrected QT interval, com-pared with those treated with placebo. In obese patients, there is a risk for incomplete reversal of NMB when sugammadex is under-dosed; therefore, dosing recommendations are based on total body weight.47 Carron and colleagues68 have published case reports that further support the benefit of sugammadex 4.0 mg/kg in obese patients and in patients with cardiac disease (total NMB reversal within 100 seconds). Patients with pulmonary diseases are at an increased risk for complications when undergoing general anes-thesia69-75; therefore, rapid and safe reversal is essential. In a phase 3, randomized, multicenter, parallel-group, comparative safety assessor-blinded study of patients with a history of pulmonary

disease, including asthma, chronic obstructive pulmonary disease, and bronchitis, sugammadex 2.0 mg/kg and 4.0 mg/kg demon-strated similar times to recovery to a TOF ratio ≥ 0.9.76 Safety was comparable between the doses, but 2 cases of bronchospasm in patients with asthma were reported in the higher-dose group.

Incidence and Effects of Residual Neuromuscular Blockade in Ambulatory Surgery

RNMB occurs significantly more frequently in inpatient sur-geries than in ambulatory surgeries.77 However, with incidences of 47% and 38%, respectively, the effect on patients undergoing either ambulatory or inpatient surgery is considerable. Interme-diate NMBAs significantly increase the risk for critical respira-tory events, including reintubation and unplanned intensive care admissions. This was also true in patients undergoing shorter operations (< 2 hours), of particular significance to ambula-tory surgery.3 In the ambulatory setting, there is an expectation of rapid patient movement to the next recovery phase. RNMB results in delayed patient recovery and decreased the efficiency of the ambulatory care center.25 A recent multicenter, randomized safety assessor-blinded trial study of patients undergoing outpa-tient surgery demonstrated a 10-fold faster recovery to a TOF ratio ≥ 0.9 in the rocuronium-sugammadex 4.0-mg/kg group than in the succinylcholine group (1.8 minutes vs 10.8 minutes, respectively), with no fewer adverse events.26

Table 2. Summary of Sugammadex in Recovery From Neuromuscular Blockade in High-risk Patients

Reference Patient Characteristics

Time to Recovery to TOF Ratio of 0.9, min

P ValueSugammadex 2.0 mg/kg Sugammadex 4.0 mg/kg

Staals64Renal failurea (n = 15) 2.0b –

P = NSControl (n = 15) 1.65b –

Panhuizen65Renal failure (n = 35) – 3.1c

P = .0002Control (n = 32) – 1.9c

De Souza66Renal failure (n = 20) – 5.6b

P = .003Control (n = 20) – 2.7b

Dahl67 Heart failured (N = 76) 1.7b 1.4b P = NS

Amao76 Pulmonary disease (N = 77) 2.1b 1.8b P = NR

NR, not reported; NS, nonsignificant a Creatinine clearance < 30 mL/min.b Mean time to recovery of TOF ratio to 0.9.c Median time to recovery of TOF ratio to 0.9.d New York Heart Association class II and III.


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Case Studies

Case 1: Video-Assisted Thoracoscopic Surgery From the files of Sorin J. Brull, MD

• 69-year-old male• Height: 6 ft 4 in, weight: 248 lb, BMI: 30.2 m/kg2

• Active gastroesophageal reflux disease (GERD): twice daily omeprazole

• Hypertension: losartanMetabolic syndrome

− Fasting plasma glucose: 136 mg/dL − Hypertriglyceridemia − Low serum high-density lipoprotein

• Family history of prolonged paralysis after succinylcholine• Airway examination

− Class III upper lip bite test (lower incisors unable to touch mucosa of upper lip)

− Mallampati class III• Surgeon requires single-lung ventilation during the video-

assisted thorascopic surgery (VATS)

Commentary

This challenging case presents multiple management concerns, of which obesity and airway examination are the most challeng-ing. The airway upper lip bite test and a Mallampati class III are predictive of a difficult intubation, with indicators for a diffi-cult airway and an anterior larynx anatomy. Patients with obesity have higher oxygen consumption and lower functional residual capacity, which can lead to a faster desaturation, compared with patients with a normal BMI.78 The history of GERD could result in pulmonary aspiration of gastric content. The surgeon’s request

for “single-lung ventilation” further complicates the case because it indicates the need for a double-lumen tracheal tube in the set-ting of rapid-sequence induction. According to the family history, it appears that the patient has pseudocholinesterase deficiency; therefore, succinylcholine is contraindicated as an option for rapid-sequence induction.79 Rocuronium is appealing because it can be given in doses up to 3 to 4 times higher than ED95 to up to 1.2 mg/kg. It is well known that neostigmine cannot reverse a deep block. The recent FDA approval of sugammadex makes this new agent more appealing because the dose of the reversal agent is dependent on the depth of block; sugammadex dosing provides that flexibility. Therefore, high-dose rocuronium block can be antagonized in less time than spontaneous recovery from succinylcholine.22

Considerations

• Proper anesthesia management includes a thorough history• In patients with obesity, consider competing issues: the need

for a rapid-sequence induction and intubation vs a potentially difficult airway

• Continuous neuromuscular monitoring intraoperatively is essential; if you are at a known level of NMB, you can be assured that you have not overdosed the patient leading to a prolonged recovery

• Compared with sugammadex, neostigmine cannot rapidly or reliably reverse deep levels of NMB52

Case 2: Residual Neuromuscular Blockade From the files of Steven B. Greenberg, MD

• 78-year-old male• Height: 5 ft 8 in, weight: 260 lb, BMI: 39.5 m/kg2

• 60-pack-year smoker, drinks 2 beers daily• Type 2 diabetes mellitus (DM): metformin 2000 mg daily,

insulin glargine injection 40 U subcutaneously once daily at bedtime

• Obstructive sleep apnea: does not wear continuous positive airway pressure (CPAP) mask

• Hypertension: once daily lisinopril 10 mg, metoprolol XL 100 mg, amlodipine 5 mg

• Vital signs − Blood pressure (BP): 165/89 mm Hg − Heart rate (HR): 65 beats per minute − Pulse oximetry: 94% room air

• Patient requires lung VATS

• Anesthesia induction − Propofol 200 mg − Fentanyl 100 mg − Lidocaine 30 mg − Rocuronium 50 mg − Mask ventilation and 37 french left-sided double lumen tube

with glidescope• 15 minutes prior to end of case, surgeon requests anesthesia to

“relax the patient” and says he is moving − Rocuronium 10 mg is given − No twitch count measured

• End of surgery − Peripheral nerve stimulator shows 1 strong twitch only

• Neostigmine 5 mg• Glycopyrrolate 0.8 mg


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− TOFc 4/4 − Vital capacity > 50 cc/kg − Negative inspiratory force > 20 cm H2O − Head lift for 5 seconds − Extubation

• Bilateral twitching of upper extremities• Oxygen saturation drops to 85%• Mask ventilation initiated with 100% fraction of inspired

oxygen• After 15 minutes, O2 saturation continues to fall to 80%

− Patient was reintubated in PACU• After 2 hours, patient is extubated again

• 3 days later, patient continues to have oxygenation problems − Chest x-ray has a right lower lobe infiltrate − White blood cell count is 12,000 per µL, and patient com-

plains of a productive cough − Patient is diagnosed with pneumonia and successfully treated

with antibiotics − Hospital length of stay is prolonged for 7 days

Commentary

This case probably represents a scenario in which a lack of NMB monitoring resulted in several postoperative compli-cations in a patient with multiple comorbidities. In this case,

intubation and redosing of rocuronium occurred in the absence of any reported NMB monitoring. The majority of respondents to a 2010 survey of current management of NMB stated that nei-ther conventional nerve stimulators nor quantitative TOF moni-tors should be part of minimum monitoring standards.21 As many as 20% of European and 10% of US survey respondents stated that they never use neuromuscular monitors. When they are used, monitoring of recovery at the facial muscles has been shown to result in a significantly higher incidence of residual block. The adductor pollicis is the most appropriate site for monitoring.80,81 If this site is inaccessible during surgery, it may be prudent to switch to the adductor pollicis site to confirm adequate recovery of NMB prior to extubation. Failure to confirm adequate recovery might lead to significant risks, including increased length of stay in the PACU, hospital length of stay, other pulmonary complica-tions, and potentially fatal outcomes.

Considerations

• RNMB occurs in 30% to 60% of all surgical cases• Qualitative monitoring may not be sufficient to detect depth of

NMB or presence of RNMB• Communication and collaboration with surgical suite colleagues

is essential for successful case management; engage, educate, and discuss need for NMB and subsequent monitoring

Case 3: Roux-en-Y Anastomosis Gastric Bypass From the files of Mark Welliver, DNP, CRNA, ARNP

• 33-year-old female• Height: 5 ft 5 in, weight: 106 kg, recently lost 30 kg• Insulin-dependent DM: neutral protamine hagedorn insulin

25 U 3 times per day• Obstructive sleep apnea: uses (CPAP) mask nightly• Hypertension: benazepril 40 mg orally once daily; hydrochloro-

thiazide 25 mg orally twice daily• Anxiety disorder• Occasional GERD• Vital signs

− BP: 135/90 mm Hg − HR: 88 beats per minute − Respiratory rate 24 breaths per minute − Arterial oxygen saturation: 97% room air − Morning blood sugar 150 mg/dL − Electrocardiogram sinus rhythm with occasional premature

atrial contraction, left ventricular hypertrophy• Airway examination

− Mallampati class III• Anesthesia induction

− Lidocaine 100 mg − Propofol 200 mg − Fentanyl 100 mg − Succinylcholine 100 mg − Intubated with 7.0 endotracheal tube stylet

• Intraoperative maintenance − Rocuronium 10 mg bolus every 30 to 40 minutes − Fentanyl 50 to 100 mg as needed − TOFc monitored at ulnar nerve maintained at 1/4

Surgeon complains of diaphragmatic excursions − Curare clefts noted on EtCO2 waveform − TOFc 2/4 − Additional 10 mg of rocuronium and 100 mg of fentanyl

administered − Anastomosis leak found during intraoperative endoscopic

leak test, intraoperative movement suspected cause• End of surgery

− TOFc 4/4, with fade at ulnar nerve − Neostigmine 3 mg with intravenous glycopyrrolate 0.6 mg − Extubated to FiO2 facemask

• In PACU − No TOF monitoring − Morphine sulfate as needed − Arterial oxygen saturation in low 90s − Patient appeared weak − Neostigmine 2 mg with glycopyrrolate 0.4 mg − Airway occlusion at rest − CPAP mask required − PACU stay: 4 hours


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Commentary

This case also presents the need for objective monitoring of NMB from induction all the way through to and including the PACU. In this case, a rapid sequence induction of anesthesia was needed and, as such, the benefits and risks of monitoring during induction must be evaluated. In some instances, it would be use-ful to verify that the TOFc is absent before inserting the endo-tracheal tube, especially when using rocuronium, which is not as reliable as succinylcholine. Evaluation in the PACU often relies on clinical signs, which are highly unreliable.82,83 The American Association of Nurse Anesthetists (AANA) Standard 5e requires neuromuscular monitoring of patients whenever NMBAs are used.84 Recently, The Association of Anaesthetists of Great Brit-ain & Ireland published updated monitoring guidelines that call for PNS and recommend use of depth of anesthesia monitors whenever NMBAs are used.85 The diaphragm is one of the most resistant of all muscles to NMBAs and requires up to 2 times more muscle relaxant than the adductor pollicis for an identi-cal degree of blockade.29 Monitoring with accelerometry31 will

become more relevant as patient populations continue to be older, heavier, and have more comorbidities. A significantly lower fre-quency of RNMB in the PACU was observed in patients random-ized to intraoperative acceleromyographic monitoring than in those followed with qualitative TOF monitoring.8 A department-wide implementation of universal electromyographic-based quantita-tive NMB monitoring in an academic center resulted in a signif-icant reduction in the incidence of incompletely reversed patients in the PACU, with no cases of NMB-related reintubations over a 2-year period.28

Considerations

• Appropriate location of neuromuscular monitoring is critical; PNS on the ulnar nerve will show blockage prior to the dia-phragm or the laryngeal musculature

• Monitoring with accelerometry will become more relevant as patients become older, heavier, and have more comorbidities

• Sugammadex may be used to rescue suspected residual paralysis after neostigmine

Case 4: Ambulatory Ventral Hernia Repair From the files of Richard Prielipp, MD, MBA, FCCM

• 58-year-old female• Weight: 77 kg• Chronic renal insufficiency: creatinine 1.95 mg/dL• Hepatitis C: 3 years post–liver transplantation• Vital signs

− Ejection fraction: 55%• Airway examination

− Class I• Anesthesia induction

− Propofol − Rocuronium 50 mg

• 15 minutes after induction − TOFc of 4/4 at the orbicularis oculi muscle using facial nerve

stimulation 15 minutes after induction − Rocuronium 10 mg

• Postoperative recovery − Period of mechanical ventilation for spontaneous recovery − Neostigmine

Commentary

This case probably represents an inappropriate redose of rocuronium because of inaccurate use and misinterpretation of the

nerve stimulator used on the orbicularis muscle. The patient was given an additional 20% of the induction dose, which is at least 2 times greater than what was needed, therefore leading to pro-longed blockade. In addition, with chronic renal insufficiency, it is well established that rocuronium clearance may be attenuated,86 likely also contributing to the prolonged blockade in this patient. This case supports the optimal placement for the PNS on the ulnar nerve. Complications, such as that which occurred in this ambu-latory case, are disruptive not only to the patient, but also to the recovery room nurse staff. Ultimately, these complications also result in increased costs.87

Considerations

• Objective monitoring and correct interpretation are essential to minimize RNMB

• Monitoring of NMB should ideally be determined at the ulnar nerve

• In patients with organ dysfunction, NMB dosing might be needed

• Sugammadex is known to be effective, even in patients with renal dysfunction; sugammadex, rocuronium, and encapsulated rocuronium are all removed via dialysis

Summary

Anesthesiologists, certified registered nurse anesthetists, and anesthesiology assistants are the primary providers for periopera-tive care of patients undergoing general anesthesia with NMBAs, such as rocuronium. The current US population is trending older, with more obesity and other comorbidities, such as obstructive

sleep apnea. In the absence of definitive guidelines on monitoring NMB and managing RNMB, a multidisciplinary approach with all team members possessing a greater understanding of how NMBAs work in these special populations, is needed. Indeed, interprofes-sional communication and coordination of care is integral to the


8

National Quality Strategy, and is aimed at improving quality of patient care and health care outcomes.

Take-home points of this review include the following:• RNMB should be a primary clinical concern

− Between 30% and 60% of patients arrive at the recovery room with RNMB (TOF ratio < 0.9)

• Proper anesthesia management always includes a thorough his-tory, including possible airway issues, and continuous team communication

• Definitive neuromuscular monitoring is a professional standard (AANA84 and The Association of Anaesthetists of Great Brit-ain & Ireland85) and should be used whenever NMBAs are used

• There are multiple barriers to routine monitoring: − Lack of detailed knowledge of neuromuscular blockers

− Common erroneous assumption that rocuronium is an inter-mediate acting drug that can easily be reversed with neostig-mine from any depth of block

− Failure to recognize limitations of clinical signs of NMB recovery

− Lack of quantitative monitoring equipment at all anesthetiz-ing sites (eg, accelerometry)

− Lack of universal monitoring standards within the United States

• Sugammadex is a novel FDA-approved steroid-specific NMBA reversal agent that rapidly (less than 3 minutes) and completely reverses NMB induced by rocuronium and vecuronium from any depth of blockade

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52. Khuenl-Brady KS, Wattwil M, Vanacker BF, Lora-Tamayo JI, Rietbergen H, Alvarez-Gómez JA. Sugammadex provides faster reversal of vecuronium-induced neuromuscular blockade compared with neostigmine: a multicenter, randomized, controlled trial. Anesth Analg. 2010;110(1):64-73.

53. Abad-Gurumeta A, Ripollés-Melchor J, Casans-Francés R, et al; Evidence Anaesthesia Review Group. A systematic review of sugammadex vs neostigmine for reversal of neuromuscular blockade. Anaesthesia. 2015;70(12):1441-1452.

54. Kleijn HJ, Zollinger DP, van den Heuvel MW, Kerbusch T. Population pharmacoki-netic-pharmacodynamic analysis for sugammadex-mediated reversal of rocuronium-induced neuromuscular blockade. Br J Clin Pharmacol. 2010;72(3):415-433.

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60. McDonagh DL, Benedict PE, Kovac AL, et al. Efficacy, safety, and pharmaco-kinetics of sugammadex for the reversal of rocuronium-induced neuromuscular blockade in elderly patients. Anesthesiology. 2011;114(2):318-329.

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66. de Souza CM, Tardelli MA, Tedesco H, et al. Efficacy and safety of sugammadex in the reversal of deep neuromuscular blockade induced by rocuronium in patients with end-stage renal disease: a comparative prospective trial. Eur J Anaesthesiol. 2015;32(10):681-686.

67. Dahl V, Pendeville PE, Hollmann MW, Heier T, Abels EA, Blobner M. Safety and efficacy of sugammadex for the reversal of rocuronium-induced neuromuscu-lar blockade in cardiac patients undergoing noncardiac surgery. Eur J Anaesthesiol. 2009;26(10):874-884.

68. Carron M, Gasparetto M, Vindigni V, Foletto M. Laparoscopic surgery in a mor-bidly obese, high-risk cardiac patient: the benefits of deep neuromuscular block and sugammadex. Br J Anaesth. 2014;113(1):186-187.

69. Sakai RL, Abrao GM, Ayres JF, VIanna PT, Carvalho LR, Castiglia YM. Prog-nostic factors for perioperative pulmonary events among patients undergoing upper abdominal surgery. Sao Paulo Med J. 2007;125(6):315-321.

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74. Smetana GW. Preoperative pulmonary evaluation. N Engl J Med. 1999;340(12): 937-944.

75. Chetta A, Tzani P, Marangio E, Carbognani P, Bobbio A, Olivieri D. Respiratory effects of surgery and pulmonary function testing in the preoperative evaluation. Acta Biomed. 2006;77(2):69-74.

76. Amao R, Zornow MH, Cowan RM, Cheng DC, Morte JB, Allard MW. Use of sugammadex in patients with a history of pulmonary disease. J Clin Anesth. 2012;24(4):289-297.

77. Cammu G, De Witte J, De Veylder J, et al. Postoperative residual paralysis in out-patients versus inpatients. Anesth Analg. 2006;102(2):426-429.

78. Parameswaran K, Todd DC, Soth M. Altered respiratory physiology in obesity. Can Respir J. 2006;13(4):203-210.

79. Leadingham CL. A case of pseudocholinesterase deficiency in the PACU. J Perianesth Nurs. 2007;22(4):265-271.

80. Thilen SR, Hansen BE, Ramaiah R, Kent CD, Treggiari MM, Bhananker SM. Intraoperative neuromuscular monitoring site and residual paralysis. Anesthesiology. 2012;117(5):964-972.

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11

Post-Test

1. Which of the following factors would most likely increase the risk for residual weakness after use of NMB drugs in the operating room?a. Lack of quantitative TOF monitoring in the operating room

b. Inexperienced anesthesia provider (compared with an experi-enced provider)

c. Failure to confirm full reversal with a 5-second head lift

d. Testing TOF response at the wrist (ulnar nerve response) rather than at the face (orbicularis oculi response)

2. Pair the clinical factor with the correct corresponding NMB drug interaction:a. Reversibility with sugammadex, cisatracurium

b. Pseudocholinesterase deficiency, rocuronium

c. Reversibility with sugammadex, vecuronium

d. Hypokalemia, succinylcholine

3. Limitations of subjective monitoring using a peripheral nerve stimulator to assess recovery from NMB drugs include all of the following EXCEPT:a. Confirmatory clinical signs (eg, head lift) must be assessed in

awake patients.

b. Presence of fade can be missed with routine TOF monitoring.

c. Even experienced practitioners are often inaccurate in assess-ing T4/T1 ratios.

d. PNS monitoring cannot be performed intraoperatively.

4. The efficacy of sugammadex in patients with comorbidities has been explored in multiple trials. Based on these stud-ies, which of the following statements regarding a 4-mg/kg dose versus a 2-mg/kg dose for times to recovery from NMB of TOF ratio ≥ 0.9 is TRUE?a. There was no significant difference between the 2 doses in

patients with pulmonary disease, but bradycardia was more fre-quent at the higher dose.

b. The 4-mg/kg dose was significantly better for patients with car-diac disease, but this dose was associated with prolongation of the corrected QT interval.

c. At the 4-mg/kg dose, recovery was similar for patients with a creatinine clearance rate of < 30 mL/min compared with con-trols, with no differences in serious adverse events.

d. Recovery for obese patients is similar for both doses.

5. According to the prescribing information for neostigmine and sugammadex, what are the contraindications and other safety considerations for their use?a. Both are contraindicated in patients with a known hypersensitiv-

ity to the drugs.

b. Neostigmine may cause complications in patients with a mechanical bowel obstruction or perforation.

c. Both drugs may be associated with bradycardia.

d. Common adverse events associated with sugammadex are vomiting, pain, nausea, hypotension, and headache.

e. All the above

6. Which of the following is the optimal unifying strategy to improve outcomes and safety in patients who require muscle relaxation during surgery?a. Total avoidance of NMB drugs

b. Maintenance of only very shallow levels of NMB blockade (TOFc of 3-4/4) throughout surgery

c. Effective communication among all members of the periopera-tive team, highlighting surgical needs for muscle relaxation dur-ing various phases of the operation

d. Increasing the dose of reversal agents based on total body weight

12 95

MM163

Evaluation Form Activity ID: 11331-EJ-42

Improving Outcomes in Patients Undergoing Neuromuscular BlockadePlease complete the following evaluation questions to receive your certificate.

1. What degree best describes you?❑ MD/DO ❑ PA/PA-C ❑ NP❑ RN ❑ PharmD/RPh ❑ PhD❑ Other, please specify:

2. What is your area of specialization?❑ Anesthesiology ❑ Colorectal❑ Orthopedic surgery ❑ Surgery, general❑ Surgery, vascular ❑ Surgery, other❑ Other, please specify:

3. Which of the following best describes your primary practice setting?❑ Solo practice ❑ Group practice❑ Government ❑ University/teaching system❑ Community hospital ❑ HMO/managed care❑ Nonprofit/community ❑ I do not actively practice❑ Other, please specify:

4. How long have you been in practice?❑ More than 20 years ❑ 11-20 years❑ 6-10 years ❑ 1-5 years❑ Less than 1 year ❑ I do not directly provide care

5. Approximately how many patients do you see each week?❑ Less than 50 ❑ 50-99 ❑ 100-149❑ 150-199 ❑ 200 or more❑ I do not directly provide care

6. In how many patients do you use neuromuscular blockade drugs?❑ Fewer than 5 ❑ 5-15 ❑ 16-25❑ 26-35 ❑ 36-45 ❑ 46-55❑ 56 or more ❑ I do not directly provide care

7. Please select the extent to which you agree/disagree that the activity supported the achievement of each learning objective

StronglyAgree

Agree Neutral Disagree Strongly Disagree

Identify risk factors for complications from RNMB 5 4 3 2 1

Select NMBAs based on identified risk factors for RNMB 5 4 3 2 1Debate the rationale for objective monitoring of depth of NMB in patients undergoing general anesthesia 5 4 3 2 1

Compare efficacy and safety profiles of NMB reversal agents to identify appropriate use in patients 5 4 3 2 1

Compare the dose adjustments required for special populations of patients 5 4 3 2 1

Collaborate with surgical suite colleagues to improve patient safety and outcomes 5 4 3 2 1

8. Please select the extent to which you agree/disagree that the activity achieved the following:

StronglyAgree

Agree Neutral Disagree Strongly Disagree

The faculty were effective in presenting the material 5 4 3 2 1The content was evidence based 5 4 3 2 1The educational material provided useful informa-tion for my practice 5 4 3 2 1

The activity enhanced my current knowledge base 5 4 3 2 1The activity provided appropriate and effective opportunities for active learning (eg, case studies, discussion, Q&A, etc)

5 4 3 2 1

The opportunities provided to assess my own learn-ing were appropriate (eg, questions before, during, or after the activity)

5 4 3 2 1

9. Based upon your participation in this activity, do you intend to change your practice behavior? (Choose only one of the following options)❑ I do plan to implement changes in my practice based on the

information presented❑ My current practice has been reinforced by the information

presented❑ I need more information before I will change my practice

10. Thinking about how your participation in this activity will influence your patient care, how many of your patients are likely to benefit? Please use a number (eg, 250): __________

11. If you plan to change your practice behavior, what type of changes do you plan to implement? (Check all that apply)❑ Apply latest guidelines❑ Choice of treatment/management approach❑ Change in pharmaceutical therapy❑ Change in current practice for referral❑ Change in nonpharmaceutical therapy❑ Change in differential diagnosis❑ Change in diagnostic testing ❑ Other, please specify: ____________________________________

12. How confident are you that you will be able to make your intended changes?❑ Very confident ❑ Somewhat confident ❑ Unsure ❑ Not very confident

13. Which of the following do you anticipate will be the primary barrier to implementing these changes?❑ Formulary restrictions ❑ Insurance/financial issues❑ Time constraints ❑ Lack of multidisciplinary support❑ System constraints ❑ Treatment-related adverse events❑ Patient adherence/compliance❑ Other, please specify: _____________________________________

14. Was the content of this activity fair, balanced, objective, and free of bias?❑ Yes ❑ No, please explain: ______________________________

15. Please list any clinical issues/problems within your scope of practice you would like to see addressed in future educa-tional activities: ____________________________________________

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*Valid email address required for receipt of your certificate.You will receive your certificate from [email protected].

For Physicians Only❑ I participated in the entire activity and claim 1.0 credit.❑ I participated in only part of the activity and claim _____ credit.