Activity presentations are considered intellectual property These - - PowerPoint PPT Presentation

Activity presentations are considered intellectual property

These slides may not be published or posted online without permission from Vindico Medical Education (cme@vindicocme.com). Please be respectful of this request so we may continue to provide you with presentation materials.

Optimal Neuromuscular Blockade Management

• J. Ross Renew, MD, FASA, FASE

Assistant Professor of Anesthesiology Mayo Clinic Jacksonville, FL

AP = adductor pollicis muscle; PTC = post-tetanic count; TOFC = train-of-four count; TOFR = train-of-four ratio. Adapted from: Naguib M, et al. Anesth Analg. 2018;127(1):71-80.

Nomenclature

Level of Blockade Depth Objective Measurement at AP Subjective Evaluation With PNS at AP 5 Complete block No PTC No PTC 4 Deep block PTC > 1, no TOFC

PTC ≥ 1, no TOFC

3 Moderate block TOFC = 1-3 TOFC = 1-3 2b Shallow block TOFR < 0.4 TOFC = 4 with fade detected 2a Minimal block TOFR = 0.4-0.9 TOFC = 4 with no fade detected 1 Acceptable recovery

TOFR ≥ 0.9

Unable to detect

PPV = positive predictive value. Cammu G, et al. Anesth Analg. 2006;102(2):426-429.

Nomenclature

Clinical assessment:

• Inability to smile, swallow, speak; PPV = 0.47
• General weakness; PPV= 0.51
• Inability to lift head for 5 seconds; PPV= 0.51
• Inability to lift leg for 5 seconds; PPV= 0.50
• Inability to sustain hand grip for 5 seconds; PPV= 0.51
• Inability to perform sustained tongue depressor test 5 seconds; PPV= 0.52

Viby-Mogensen J, et al. Anesthesiology. 1985;63(4):440-443.

Nomenclature

Peripheral nerve stimulator:

• Tactile assessment slightly more sensitive than visual
• Inexperienced anesthesiologists cannot detect fade when TOFR > 0.3
• Majority cannot detect fade when TOFR > 0.4

Murphy GS, et al. Anesthesiology. 2008;109(3):389-398.

Objective Monitoring

• Hand-held versus monitoring incorporated

into anesthesia workstation

• Monitors:

– Acceleromyography (AMG) – Kinemyography (KMG) – Electromyography (EMG)

ACh = acetylcholine; IV = intravenous. Neostigmine methylsulfate. Product information. American Reagent. 2017.

Neostigmine

• Acetylcholinesterase inhibitor that prevents breakdown of

ACh to overwhelm postsynaptic nicotinic receptors

• Requires co-administration with antimuscarinic agent
• 0.2 mg glycopyrrolate IV for each 1 mg neostigmine IV

(similar onset time)

• Edrophonium (0.5 to 1 mg/kg) + atropine (7 to 14 µg/kg IV)

Naguib M, et al. Anaesthesia. 2017;72(Suppl 1):16-37.

Neostigmine (cont’d)

• TOFC > 2

Recommend 70 µg/kg

• TOFC = 4

Recommend 20-50 µg/kg

• Ceiling effect at 5 mg

Kim KS, et al. Anesth Analg. 2004;99(4):1080-1085.

Neostigmine (cont’d)

• Recommend administration with at least TOFC = 3
• Median time to recovery with TOFC = 3 is 15.6 minutes

(7.3 to 43.9)

• Median time to recovery with TOFC = 4 is 9.7 minutes

(5.1 to 26.4)

• Can be prolonged with inhalation anesthesia, hypothermia,

acidosis, electrolyte disturbances, hypercarbia, and patient age

NMBA = neuromuscular blocking agent. Debaene B, et al. Anesthesiology. 2003;98(5):1042-1048; Goldhill DR, el al. Anaesthesia. 1989;44(4):293-299; Murphy G, et al. Anesthesiology. 2018;128(1):27-37.

Spontaneous Recovery

• Unpredictable response to NMBA
• 37% of patients had residual weakness 2 hours after

intubating dose of intermediate-acting NMBA

• Do not omit NMBA antagonism if one cannot demonstrate

adequate recovery (quantitative monitoring)

• Neostigmine administered in the absence of NMB can cause

paradoxical reduction in TOFR

• 40 µg/kg after spontaneous recovery had no increase in

adverse events (it actually had less diplopia)

ICU = intensive care unit; PACU = post-anesthesia care unit. Berg H, et al. Acta Anaesthesiol Scan. 1997;41(9):1095-1103. Murphy GS. Minerva Anesthesiol. 2006;72(3):97-109. Murphy GS, et al. Anesth Analg. 2008;107(1):130-137.

Residual Neuromuscular Blockade

• Subjective feelings of weakness
• Oropharyngeal dysfunction
• Prolonged PACU stay
• Postoperative pulmonary complications
• Respiratory collapse requiring reintubation/ICU care

RNMB = residual neuromuscular block. Brull SJ, et al. Anesthesiology. 2017;126(1):173-190.

Strategies to Avoid RNMB

• Use of short- or intermediate-acting NMBA
• Use quantitative monitoring to guide redosing and confirm

adequate recovery

• Administer NMBA antagonists at appropriate depth of blockade
• Extubate the trachea once adequate recovery has been confirmed

Current and Emerging Neuromuscular Blockade (NMB) Reversal Agents

Anthony L. Kovac, MD

Kasumi Arakawa Professor of Anesthesiology University of Kansas Medical Center Kansas City, KS

Objectives: Agents for Rapid Recovery of Deep Neuromuscular Blockade (NMB)

• New class  selective relaxant binding agents (SRBA):

–

Selectively binds & terminates non-depolarizing NMB relaxants

• Sugammadex  efficacy and safety data  benefits and risks
• I mpact/ utility of rapid recovery on surgical practice:

A.

Reverse deep and intense NMB

B.

Improves patient safety, intubation time, postop residual curarization, muscle recovery, OR efficiency

• Preclinical/ clinical data of emerging agents: gantacurium, CW002, and CW0011, calabadion

OR = operating room.

Slide courtesy of AL Kovac, MD.

1.

Deep NMB useful during:

–

Laparoscopy

–

Robotic surgery

–

Microscopic surgery

–

Bariatric surgery

2.

I mprovement of:

–

Patient safety

–

Muscle strength

–

Postoperative intubation time

–

Risk of respiratory complications

–

Postoperative residual curarization

–

OR efficiency: turnover times

I mpact/ Utility of Rapid Recovery

• n Surgical Practice

Heerdt PM, et al. Anesthesiology. 2015;28(4):403-410. Hunter JM. Br J Anaesth. 2017;119(suppl_1):i53-i62.

• Acetylcholinesterase inhibitors  reverse low levels of NMB

(neostigmine)

• Encapsulating agents  reverse all levels of NMB

– Sugammadex  reverses steroid NMB agents – Calabadion  reverses steroid and benzylisoquinoline NMB agents

• L-Cysteine adduction  reverses gantacurium and CW002

Agents for Reversal of Nondepolarizing NMB

Block Depth: I ntense

TOF = 0 PTC = 0

Deep

TOF = 0

PTC = ≥1

Moderate

TOF = 1-3

PTC = ≥1

Recovery

TOF = T4/T1

Levels of Block After a Normal I ntubating Dose of a Non-depolarizing NMB Agent

PTC = post-tetanic count; TOF = train of four. Fuchs-Buder T, et al. Acta Anaesthesiol Scand. 2009;51(7):789-808.

Naguib M. Anesth Analg. 2007:104(3):575-581. Google Patents: Sugammadex sodium. Filed January 23, 2017. Accessed October 9, 2020. https://patents.google.com/patent/WO2018136013A1/en

Cyclodextrin Characteristics

• Encapsulating agents

(sugammadex)

• Interior lipophilic (OH)
• Interior hydrophobic

Exterior hydrophilic (COO) Allows strong binding to hydrophobic molecules to stabilize or solubilize

Rocuronium and Sugammadex Complex Radiograph Crystal Structure

Gijsenbergh F, et al. Anesthesiology. 2005:103(4);695-703. Reprinted With Permission. https://pubs.asahq.org/anesthesiology

+ =

Rocuronium Sugammadex

Naguib M. Anesth Analg. 2007:104(3);575-581.

Sugammadex Characteristics

• Binds at 1:1 ratio
• Reduces amount of NMB agent to bind to nicotinic receptor
• Affinity for steroidal non-depolarizing NMB agents
• Affinity: rocuronium > vecuronium
• No affinity for succinylcholine, cisatracurium
• Half life = 100 minutes
• Renal excretion; no metabolism
• Over 24 hours, 60%-80% excreted in urine

Sugammadex Reversal Doses at Different NMB

• Light to moderate block: TOF ≥ 1  2 mg/kg
• Deep block: TOF = 0, PTC ≥ 1

 4 mg/kg

• Intense block: TOF = 0, PTC = 0  16 mg/kg

Naguib M. Anesth Analg. 2007:104(3):575-581. Hristovska AM, et al. Cochrane Database Syst Review. 2017;8(8):CD012763.

Gijsenbergh F, et al. Anesthesiology. 2005:103(4);695-703. Reprinted With Permission. https://pubs.asahq.org/anesthesiology

Sugammadex Rapidly Reverses NMB

TOF tracings after rocuronium 0.6 mg/kg and placebo Or Sugammadex 4.0 mg/kg; deep NMB TOF=0, PTC=1

0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 10 20 30 40 50 60 70 80 90

Rocuronium + sugammadex Vecuronium + sugammadex Rocuronium + neostigmine Vecuronium + neostigmine Rocuronium + placebo

Kaplan–Meier curves showing time to recovery to train-of-four ratio of 0.9 after study drug administration at reappearance of second twitch (T2), by treatment group and neuromuscular blocking agent (intent-to-treat population). Gray vertical dotted line represents recovery time of 5 minutes.

Time to Recovery (minutes) Cumulative Recovery Rate

Adapted from: Herring WJ, et al. J Clin Anesth. 2017;41:84-91. Vecuronium + placebo

Sugammadex Efficacy for Reversal of Rocuronium- and Vecuronium- induced NMB: Pooled Analysis

• f 26 Studies

Sugammadex

16 mg/ kg Dosing After Rocuronium 1.2 mg/ kg I ntense NMB TOF = 0, PTC = 0

Roc = rocuronium. Naguib M. Anesth Analg. 2007:104(3):575-581. Reprinted With Permission. https://journals.lww.com/anesthesia-analgesia

Sugammadex: Benefits

• Rapidly encapsulates rocuronium > vecuronium, reverses deep

and intense block

• Well tolerated
• Effective & safe in elderly, pediatric, cardiac, renal, and pulmonary

disease patients; no bronchospasm

• Helps improve surgical conditions  optimize surgical space conditions

during laparoscopic surgery

• Helps minimize postoperative complications  reduces inadequate

reversal (residual paralysis)

Naguib M. Anesth Analg. 2007:104(3):575-581. Bruintjes MH, et al. Br J Anaesth. 2017;118(6):834-842.

Sugammadex: Possible Risks at High Doses (16 mg/ kg)

• Hypotension
• Bradycardia
• QT interval prolongation
• Drug interaction(s) with steroid compounds (estrogens)
• Anticoagulation
• Anaphylaxis
• Hypersensitivity reactions

Honing G, et al. Expert Opin Drug Saf. 2019;18(10);883-891.

• Asymmetric alpha-chlorofumarate
• Ultra-short nondepolarizing NMB
• Onset = 90 seconds
• Ultra-short duration = 10 minutes
• Minimal or no hemodynamic effects
• No histamine release
• Inactivation by L-Cysteine adduction
• Organ independent metabolism

Preclinical/ Clinical Data of Emerging Agents: Gantacurium

Heerdt PM, et al. Anesthesiology. 2015;28(4):403-410. Hunter JM. Br J Anaesth. 2017;119(suppl_1):i53-i62.

• Amino acid with thiol side chain
• Targets are the novel isoquinoliniums 

gantacurium, CW002 & CW0011

• Adducts to fumarate moiety 

Reversal at any time with same dose

L-Cysteine

Heerdt PM, et al. Anesthesiology. 2015;28(4):403-410. Hunter JM. Br J Anaesth. 2017;119(suppl_1):i53-i62.

Cysteine Gantacurium

Gantacurium Reversal

Heerdt PM, et al. Anesthesiology. 2015;28(4):403-410.

Gantacurium – L-cysteine Adduct

Preclinical/ Clinical Data of Emerging Agents: CW002 and CW0011

• Symmetric alpha-chlorofumarate
• Structure similar to gantacurium, except no chlorine atom at the

fumarate double bond

• Intermediate nondepolarizing NMB (greater potency than gantacurium)
• Onset = 90 seconds, intermediate duration = 40 to 60 minutes
• Minimal or no hemodynamic effects
• No histamine release
• Inactivation by L-cystine adduction
• Organ independent metabolism

Heerdt PM, et al. Anesthesiology. 2015;28(4):403-410. Hunter JM. Br J Anaesth. 2017;119(suppl_1):i53-i62.

Adapted from: Savarase JJ, et al. Anesthesiology. 2010;113(1):58-73.

Gantacurium CW002

Comparison of Gantacurium, CW0011, CW002, and L-cysteine Adduction of CW002

CW0011 NB 1043-10 L-cysteine Adduct of CW002

Acyclic cucurbituril  binds to all NMB quaternary amines

Heerdt PM, et al. Anesthesiology. 2015;28(4):403-410. Hunter JM. Br J Anaesth. 2017;119(suppl_1):i53-i62. Image: Czarnetzki C. Dissertation. University of Geneva; 2017. Accessed October 9, 2020. https://www.researchgate.net/publication/325205759_Drug_interactions_in_the_context_of_neuromuscular_blockade_clinical_implications_and_safety_issues

Preclinical/ Clinical Data of Emerging Agents: Calabadion 1 and 2

I mportance of a Multidisciplinary Approach

• Teams versus tribes…
• The basic obstacle to a multidisciplinary approach…
• Territoriality and organizational obstacles

Components of a Multidisciplinary Approach

• Surgical team—office staff, house staff, surgeons
• Anesthesia team—anesthesiologists, nurse anesthetists,

residents, technicians

• OR nursing team
• Preoperative holding
• PACU
• Day stay or inpatient unit (where applicable)

PACU = post-anesthesia care unit.

Epstein NE. Surg Neurol Int. 2014;5(Suppl 7):295-303.

Advantages of a Multidisciplinary Approach to Perioperative Care

• Minimizes the risks of errors
• Is more efficient
• Improves outcomes
• Is essential for “enhanced recovery after surgery” (ERAS)

pathways

• Because of the standardization associated with this

approach, it creates a superior teaching environment

VTE = venous thromboembolism. Whiteman AR, et al. Br J Anaesth. 2015;116(3):311-314. Image created by Arafat Uddin from the Noun Project.

I mportance of Effective Communication Within the Team

• This should seem obvious and intuitive
• Efficiency
• Safety—minimizes risk of errors
• Improved outcomes
• As one reviews the factors contributing to

surgical complications (particularly VTE and wound complications), the need for communications, standardization, and a team approach becomes apparent

Improving Outcomes and Decreasing Complications

Examples of a Successful Team Approach

• Large paraesophageal hernias—listed separately because of the

need for diaphragmatic relaxation

• Specimen extraction following laparoscopic appendectomy,

colectomy, sleeve gastrectomy, and distal pancreatectomy

• Laparoscopic inguinal and ventral hernia
• These are all examples of cases which quickly

transition into wound closure Case Conclusion After Deep Neuromuscular Blockade

Image created by Arafat Uddin from the Noun Project.

MIS = minimally invasive surgery. Staehr-Rye AK, et al. Anesth Analg. 2014;119(5):1084-1092.

The Specific Challenge of Low Pressure MI S

• As a topic this has been discussed but inadequately researched;

it is most likely procedure specific

• Many studies address “working space” in pelvic MIS
• Definitely a “tribal-biased” posture in the literature
• Physiology—perfusion and high intra-abdominal pressure, hypercarbia: impacts upon pH,

cardiopulmonary performance, and renal function; impact upon postoperative pain

• Risk of high pressure aerosol in COVID transmission

Maintaining an Intra-abdominal Pressure of 8 mm Hg or Less

The Goals of I ntegration

• How can newer and emerging reversal agents be

integrated into a team approach?

• Can these agents impact the specific challenges of

low pressure MIS?

• Can these agents improve outcomes, patient safety,
• perating room efficiency, and positively impact costs?
• Should these agents be integrated into the concept of

ERAS pathways?

The Goals of I ntegration

• How can newer and emerging reversal agents be

integrated into a team approach?

• Can these agents impact the specific challenges of

low pressure MIS?

• Can these agents improve outcomes, patient safety,
• perating room efficiency, and positively impact costs?
• Should these agents be integrated into the concept of

ERAS pathways?

The Goals of I ntegration

• How can newer and emerging reversal agents be

integrated into a team approach?

• Can these agents impact the specific challenges of

low pressure MIS?

• Can these agents improve outcomes, patient safety,
• perating room efficiency, and positively impact costs?
• Should these agents be integrated into the concept of

ERAS pathways?

The Goals of I ntegration

• How can newer and emerging reversal agents be

integrated into a team approach?

• Can these agents impact the specific challenges of

low pressure MIS?

• Can these agents improve outcomes, patient safety,
• perating room efficiency, and positively impact costs?
• Should these agents be integrated into the concept of

ERAS pathways?