Preventing Residual Paralysis, with or without Sugammadex

Stephan Thilen, MD, MSDecember 9, 2018

DisclosuresI have no relevant financial relationship with any commercial interest.

OBJECTIVESAt the end of this lecture, the audience participants will be able to: 1. Define residual neuromuscular blockade 2. Explain fundamental concepts of recovery and reversal from

neuromuscular blockade3. List the important risk factors for residual paralysis4. Apply evidence-based practices related to neuromuscular

management that are useful towards decreasing the incidence ofresidual neuromuscular block.

sthilen@uw.edu

Sugammadex

Neostigmine

Onset Intense Block Deep Block Moderate Block Shallow Block

MinimalBlock

Injection of NMBA

PTC Stimulation During Deep Block

Classic neuromuscular block

Use of Peripheral Nerve Stimulator

“The Zone of Blind Paralysis”

Plaud et al, Anesthesiology 2010; 112:1013–22

We are unable to detect TOF fade visually or manually when the actual TOFR exceeds 0.4

Mechanomyography – The Gold Standard

The Acceleration Transducer

Bild 2

Newer EMG monitors

Kirkegaard et al, Anesthesiology 2002;96:45-50.

TOFR ≥ 70%

TOFR ≥ 70%

10 minutes after reversal

Kirkegaard et al, Anesthesiology 2002;96:45-50.

Fuchs-Buder et al, Anesthesiology 2010; 112: 34-40.

Neostigmine reversal from TOF ratio 0.4(NO subjective fade, “4 equal witches”)

Donati F, CJA 2013; 60: 714-29

(TOF count = 1)

(TOF count = 4)

Reversal at 1 twitch

Reversal at 4 twitches

PREFERRED Site

AVOID this site

Anesthesiology (Nov) 2012; 117:968

Donati, Anesthesiology Nov 2012.

“In practice, reversal and recovery should be guided by adductor pollicis response, and if needed, a switch from facial to ulnar nerve stimulation should be accomplished at the end of the surgical procedure.”

Summary – monitoring site

• The adductor pollicis is the gold standard and the preferred site

• Be aware of the potentially great discrepancy in twitch response between facial muscles and the adductor pollicis

• Always obtain the pre-reversal assessment from the adductor pollicis.

Interpatient variability

Debaene et al, Anesthesiology 2003; 98:1042-8

Dose adjustment for age and gender

Time to T1=25%after Roc 0.6 mg/kg

Mencke et al, Anaesthesist 2000;49:609-12Adamus et al, Biomed Pap Med 2011;155:347-54Xue et al, A&A 1997; 85:667-71Murphy et al, Anesthesiology 2015;123:1322-36

Baykara et al, JCA 2003; 15: 328-33Arain et al, Acta Anaesth Scand; 2005: 312-5Bevan et al, CJA 1993; 40: 127-32Matteo et al, A&A 1993; 77: 1193-7

Anesthesiology (Nov) 2012; 117:968

Roc and Vec Need to Be Dose- Adjusted with High BMI

Clinical Consequences of Residual Paralysis

Database

studies

Volunteer

studies

Clinical

studies

Outcomes and Residual ParalysisVolunteer studies

• Inability to swallow and to protect upper airwayPavlin, et al., Anesthesiology 1989; 70:381-5Sundman, et al., Anesthesiology 2000; 92: 977-84

• Impairs upper airway dimensions and functionEikermann, et al., Anesthesiology 2003; 98: 1333-7Eikermann, et al., AJRCCM 2007; 175: 9-15

Effect on the Genioglossus Muscle

Eikermann et al, Am J Respir Crit Care Med 2007; 175: 9-15

TOFR=0.5 0.8

1.0 1.0 + 15 min

Baseline

Outcomes and Residual ParalysisClinical studies

• POPC –RCT, 691 patientsBerg, et al. Acta Anaesthesiol Scand 1997: 41:1095-1103

• Critical respiratory eventsMurphy, et al. Anesth Analg 2008 ;107:130-7Murphy, et al. Anesthesiology 2008 Sep;109(3):389-98

• Longer PACU stay with residual paralysisButterly, et al. British J of Anaesthesia 2010; 105: 304-9

• Lower satisfaction with early recoveryMurphy, et al. Anesth Analg 2013; 117: 133-141

Database Studies

• Beecher and Todd, 1954- Mortality rate with NMBDs (1:370) 6x higher

- Majority of excess deaths w. NMBDs – respiratoryBeecher HK, Todd DP, Ann Surg 1954; 104:2-35

• Dose-dependent Association NMBD and Readmission Thevathasan et al, BJA Sep 2017

Beecher HK, Todd DP, Ann Surg 1954; 104:2-35

Neostigmine or Sugammadex?

More or less muscle relaxant?

Deep Block

www.medscape.org/viewarticle/870640_3www.cmezone.com/activities/CU172/2425

Deep Block

Madsen et al, Acta Anaesthesiol Scand 2015;1:1-16Kopman et al, Anesth Analg 2015;120:51-8

Cost of Reversal Drugs(my hospital in Seattle)

Neostigmine1 mg/ml 5 ml $12.92

Glycopyrrolate0.2/ml 1 ml vial $ 2.93

Sugammadex100 mg/ml 2 ml $88.92100 mg/ml 5 ml $162

Reversal with neostigmine <20% of sugammadex

Interpatient variability

Debaene et al, Anesthesiology 2003; 98:1042-8

Patients who are slow are…slow

Dubois et al, Acta Anaesth Scand 2012; 56:76-82

Caldwell et al, Anesth & Analg 1995;80: 1168-74

Weakness from Neostigmine

Protocol for Rocuronium + Neostigmine + PNS

• Intubation 0.6 mg/kg IBW• 15% reduction for females• 1% reduction for each yr >55 yrs• Incremental doses 25% of intubation dose• Monitor AP, avoid redose last 30 mins• Prereversal assessment always at adductor pollicis• Confirm TOF count of 4• TOF count 4 with fade: 40 mcg/kg IBW

TOF count 4 w/o fade 15-25 mcg/kg IBW• Minimum 10 minutes before extubation

Protocol for Rocuronium + Neostigmine + PNS

• Intubation 0.6 mg/kg IBW• 15% reduction for females• 1% reduction for each yr >55 yrs• Incremental doses 25% of intubation dose• Monitor AP, avoid redose last 30 mins• Prereversal assessment always at adductor pollicis• Confirm TOF count of 4• TOF count 4 with fade: 40 mcg/kg IBW

TOF count 4 w/o fade 15-25 mcg/kg IBW• Minimum 10 minutes before extubation

Protocol for Rocuronium + Neostigmine + PNS

• Intubation 0.6 mg/kg IBW• 15% reduction for females• 1% reduction for each yr >55 yrs• Incremental doses 25% of intubation dose• Monitor AP, avoid redose last 30 mins• Prereversal assessment always at adductor pollicis• Confirm TOF count of 4• TOF count 4 with fade: 40 mcg/kg IBW

TOF count 4 w/o fade 15-25 mcg/kg IBW• Minimum 10 minutes before extubation

Protocol for Rocuronium + Neostigmine + PNS

• Intubation 0.6 mg/kg IBW• 15% reduction for females• 1% reduction for each yr >55 yrs• Incremental doses 25% of intubation dose• Monitor AP, avoid redose last 30 mins• Prereversal assessment always at adductor pollicis• Confirm TOF count of 4• TOF count 4 with fade: 40 mcg/kg IBW

TOF count 4 w/o fade 15-25 mcg/kg IBW• Minimum 10 minutes before extubation

Results

Results

Sequential ID number

Raw

TO

F Ra

tio a

t PAC

U

Conclusions

• The protocol was associated with less residual paralysis• Significantly less severe residual paralysis• Important how residual paralysis is defined • Although challenging to follow, this protocol does not eliminate all

residual paralysis

An Example to Follow

Baillard et al, BJA 2005;95 :622-6

Another Example to Follow – Univ of Iowa

Todd M et al, Anesth Analg 2015; 121:836-8

Sugammadex

Sugammadex

•Cyclodextrin•True reversal agentreceptor-distant mechanism

•Efficacy if reversing rocuronium and vecuronium, and given in proper dose

Sugammadex w/o monitoring

Kotake et al, A&A 2013; 117:354-51

Sugammadex – monitoring site

Acta Anaesthesiol Scand 2015;59:892-901

When will we need sugammadex?

• In cannot intubate cannot ventilate16 mg/kg

• Deep paralysis and need an efficient reversal. PTC 1 or 2 4mg/kg• When we have TOF<4 and need a prompt reversal?• For outliers with unusual duration of NMBD• When neostigmine reversal has failed, but need quantitative

monitoring to identify this failure.• Only rocuronium or vecuronium reversal

When will sugammadex be used?

• When succinylcholine is contraindicated- e.g. Roc used for RSI and short case

• In myasthenia gravis• For high-risk patients, COPD, OSA, Morbid obesity, extremes of age• In anaphylactic reactions to rocuronium?• Potential to restore safety margin?• Is routine use cost-effective?

Recurarization with Sugammadex

Eleveld et al, A&A 2007; 104: 582-4

Bradycardia and Hypotension

• BradycardiaPlacebo 1%Sugammadex 2 mg/kg 1%

4 mg/kg 1%16 mg/kg 5%

• HypotensionPlacebo 4%Sugammadex 2 mg/kg 4%

4 mg/kg 5%16 mg/kg 13%

Caveats - Sugammadex

• Monitor properly, dose properly, and don’t underdose

• Re-paralyze with benzylisoquinolones• Not recommended with Cr Clearance <30 ml/min• Slower in very elderly, 3.6 vs 2.2 minutes• Use actual body weight• Potential displacement interactions with toremifene

Example of discharge instructions that patients will receivewhen you submit order in EMR