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Neuromuscular Blocking Agents Neuromuscular Blocking Agents Summary Neuromuscular blocking agents (NMBAs) are used to facilitate endotracheal intubation and provide skeletal muscle relaxation during surgery or mechanical ventilation. NMBAs do not provide sedation, analgesia, or amnesia; administer only after unconsciousness has been induced and maintain adequate amnesia and analgesia throughout paralysis. NMBA selection depends on clinical application and patient factors; consider the onset and duration of action, adverse effects, and metabolism/excretion of each agent. Pharmacology Neuromuscular blocking agents (NMBAs) cause skeletal muscle relaxation by blocking acetylcholine, and therefore, the transmission of nerve impulses at the neuromuscular junction. Depolarizing NMBAs bind to and activate cholinergic receptor sites, making the muscle fiber refractory to the action of acetylcholine. Nondepolarizing NMBAs competitively antagonize cholinergic receptors. Nondepolarizing NMBAs are divided into 2 broad structural classes: aminosteroidal and benzylisoquinolinium agents. Differences in chemical structure reflect little but variance in drug elimination pathways.[52452][52486] [65358][65369][65389] Neuromuscular Blocking Agent General Pharmacology[65358][65369] Metabolism/ Drug Mechanism Class Elimination plasma esterase/ Atracurium Nondepolarizing Benzylisoquinolinium Hofmann elimination plasma esterase/ Cisatracurium Nondepolarizing Benzylisoquinolinium Hofmann elimination* Mivacurium Nondepolarizing Benzylisoquinolinium plasma cholinesterase Pancuronium Nondepolarizing Aminosteroidal renal > hepatic Rocuronium Nondepolarizing Aminosteroidal renal < hepatic Succinylcholine Depolarizing Acetylcholine-like plasma cholinesterase Vecuronium Nondepolarizing Aminosteroidal renal <= hepatic *Less than 20% of elimination occurs via renal and hepatic pathways combined Onset and Duration of Action of Neuromuscular Blocking Agents[52452][52486][65358][65369][65389] Drug Onset (minutes) Duration (minutes) Succinylcholine 0.5 to 1.5 5 to 10 Short-acting Mivacurium 2 to 3 10 to 20 Atracurium 3 to 5 20 to 35 Cisatracurium 2 to 5 20 to 60 Intermediate-acting Rocuronium 1 to 2 20 to 35 Vecuronium 3 to 5 20 to 45 Long-acting Pancuronium 2 to 5 60 to 100 Pharmacodynamics of Neuromuscular Blocking Agents[42613][52452][65345] [65358][65369] Histamine Ganglionic/Vagal Drug Muscarinic Receptor Effect Prolonged Blockade Release Blockade Atracurium low to minimal none minimal to none rare Cisatracurium minimal to none none none rare Mivacurium low to minimal none none rare Pancuronium minimal to none moderate blockade yes yes Rocuronium minimal to none minimal blockade at high doses no Succinylcholine minimal stimulation none with reduced plasma cholinesterase activity Vecuronium none none at high doses yes Therapeutic Use Therapeutic Use Table Export to CSV (Excel) Atracurium Cisatracurium Mivacurium Pancuronium Rocuronium Succinylcholine Vecuronium Indications Besylate Besylate Chloride Bromide Bromide Chloride Bromide Renal Impairment Yes Yes Yes Yes Dosing Adjustment Hepatic Impairment Yes Yes Yes Dosing Adjustment endotracheal Yes Yes Yes Yes Yes Yes Yes intubation neuromuscular blockade during Yes Yes Yes Yes Yes Yes mechanical ventilation neuromuscular blockade Yes Yes Yes Yes Yes Yes Yes during surgery rapid- sequence Yes † Yes Yes Yes † intubation Yes – Labeled Yes † – Off-label, Recommended NR – Off-label, Not Recommended Neuromuscular blocking agent (NMBA) selection depends on clinical application and patient factors; consider the onset and duration of action, adverse effects, and metabolism/elimination of each agent. Succinylcholine is the NMBA of choice for rapid-sequence intubation (RSI) due to its rapid onset and short duration; it can also be given intramuscularly in patients without venous access. Several adverse effects (i.e., hyperkalemia, malignant hyperthermia, increased intraocular and intracranial pressures) limit its use.[44868][52452][65345] Aminosteroidal NMBAs depend on organ function for metabolism and excretion; they tend not to cause histamine release, making them preferred NMBAs in patients with asthma. Rocuronium and vecuronium are considered preferred NMBAs in patients with cardiac conditions or hemodynamic instability due to their cardiovascular stability. Rocuronium is an attractive alternative for RSI due to its relatively short onset.[44868][52441][52452][65345] Pancuronium may cause significant tachycardia and hypertension. Due to its long duration, intermittent doses can be considered as an alternative to continuous infusions of shorter-acting NMBAs in patients requiring sustained paralysis.[52443] Benzylisoquinolinium NMBAs undergo organ-independent degradation; they lack vagolytic activity but are more likely to cause histamine release.[52452] Atracurium and cisatracurium are attractive for continuous infusion use in critically ill patients, as their metabolism is largely unrelated to hepatic or renal function.[65358] A short course (48 hours or less) of NMBA by continuous infusion is recommended for patients with early acute respiratory distress syndrome (ARDS) with a PaO2/FiO2 less than 150 mmHg.[61770] [62859] Comparative Efficacy Succinylcholine is considered the neuromuscular blocking agent (NMBA) of choice for rapid- sequence intubation (RSI) due to its rapid onset and shorter duration; however, adverse effects limit its use. Rocuronium is an attractive alternative.[44868][52452][65345] Both agents offer similar safety and efficacy for RSI when used in various patient populations. [65441][65442][65443] When dosed at 0.9 to 1.2 mg/kg, rocuronium's onset of action is similar to succinylcholine with a longer duration.[65442] Neuromuscular Blocking Agent Comparative Efficacy Trials for Rapid-Sequence Intubation (RSI) Citation Design/Regimen Results Conclusion Marsch SC, et Randomized, controlled, single-blind trial comparing Incidence of Incidence and severity of oxygen al. Crit Care succinylcholine 1 mg/kg IV (n = 208) vs. rocuronium oxygen desaturations, quality of intubation 2011;15:R199. 0.6 mg/kg IV (n = 208) for rapid-sequence intubation desaturation, conditions, and incidence of failed intubation [65441] in critically ill adults. Patients were premedicated with defined as a attempts did not differ between fentanyl 1 mcg/kg IV, and etomidate 0.2 mg/kg IV or decrease in succinylcholine and rocuronium in critically ill propofol 1 mg/kg IV were used for induction. oxygen adults. The mean intubation sequence was saturation of 14 seconds shorter after succinylcholine 5% or more: compared to rocuronium. Hemodynamic effects of intubation were similar in both Succinylcholine: groups. 37% Rocuronium: 34% (p = 0.67) Incidence of severe oxygen desaturation, resulting in a saturation value of 80% or less: Succinylcholine: 10% Rocuronium: 10% (p = 1) Duration of intubation sequence: Succinylcholine: 81 +/- 38 seconds Rocuronium: 95 +/- 48 seconds (p = 0.002) Incidence of failed first intubation attempt: Succinylcholine: 16% Rocuronium: 18% (p = 0.4) Intubation conditions (maximal score = 9): Succinylcholine: 8.3 +/- 0.8 Rocuronium: 8.2 +/- 0.9 (p = 0.7) Magorian T, et Randomized, controlled trial comparing rocuronium Mean onset of Onset of action for rocuronium 0.9 and 1.2 al. 0.6, 0.9, or 1.2 mg/kg IV, vecuronium 0.1 mg/kg IV, or action: mg/kg was similar to succinylcholine. Anesthesiology succinylcholine 1 mg/kg IV (total n = 50) for rapid- Rocuronium's duration of action was 1993;79:913- sequence induction of anesthesia in adult patients Rocuronium 0.6 prolonged compared to succinylcholine at mg/kg: 918. [65442] who were ASA physical status 1 thru 3. Patients were these doses; duration of action with premedicated with midazolam 0.02 to 0.05 mg/kg IV, rocuronium 1.2 mg/kg was significantly 89 seconds and incremental doses of thiopental 1 to 2 mg/kg IV longer compared to all other agents/doses. were given before neuromuscular blockade. Rocuronium 0.9 Recovery index was significantly shorter for mg/kg: succinylcholine but similar for all other agents/doses. 75 seconds Rocuronium 1.2 mg/kg: 55 seconds Vecuronium 0.1 mg/kg: 144 seconds Succinylcholine 1 mg/kg: 50 seconds Mean duration of action: Rocuronium 0.6 mg/kg: 37 minutes Rocuronium 0.9 mg/kg: 53 minutes Rocuronium 1.2 mg/kg: 73 minutes Vecuronium 0.1 mg/kg: 41 minutes Succinylcholine 1 mg/kg: 9 minutes Mean recovery index: Rocuronium 0.6 mg/kg: 14 minutes Rocuronium 0.9 mg/kg: 22 minutes Rocuronium 1.2 mg/kg: 24 minutes Vecuronium 0.1 mg/kg: 20 minutes Succinylcholine 1 mg/kg: 2 minutes April MD, et al. International, multicenter, observational series Incidence of First-pass intubation success, glottic view, Ann Emerg comparing succinylcholine (n = 2,275; mean dose: first-pass and incidence of adverse effects did not Med 1.8 mg/kg IV) and rocuronium (n = 1,800; mean intubation differ between succinylcholine and 2018;72:645- dose: 1.2 mg/kg IV) for rapid-sequence intubation in success: rocuronium during emergency department 653. [65443] the emergency department in patients older than 14 intubation. years. Sedation agents included etomidate, Succinylcholine ketamine, and propofol. 87% Rocuronium 87.5% (risk difference 0.5%; 95% CI -1.6% to 2.6%) Cormack- Lehane grade 1 or 2 view: Succinylcholine: 88.5% Rocuronium: 89% Incidence of adverse events: Succinylcholine: 14.7% Rocuronium: 14.8% Adverse Reactions / Side Effects Top 20 Adverse Reactions / Side Effects Table Export to CSV (Excel) Adverse Atracurium Cisatracurium Mivacurium Pancuronium Rocuronium Succinylcholine Vecuronium Reaction
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