Nondepolarizing Neuromuscular Blocking Agents

Table 1. Commonly used nondepolarizing NMBAs. Adapted from Butterworth JF, Mackey DC, Wasnick JD. Morgan and Mikhail’s Clinical Anesthesiology, 7th Edition. McGraw Hill; 2022.
a Doses of 1-1.2 mg/kg IV provide intubating conditions comparable to succinylcholine for rapid sequence intubation.
b IM administration of 1 mg/kg (infants) or 1.8 mg/kg (children) produces intubating conditions in 2.5-3 minutes.
c The amount of NMBA required to reduce twitch height by 95%

Aminosteroids tend not to cause histamine release but their metabolism is organ dependent.

• Chronic administration of anticonvulsants can lead to resistance to the effects of aminosteroid NMBAs due to stimulation of hepatic microsomal enzymes and upregulation of ACh receptors.

Pancuronium

• Dosing: 0.1-0.15 mg/kg produces intubating conditions in 90-120 seconds (0.06-0.1 mg/kg 2-3 min) with a duration of action of 40-80 minutes.
• Long-acting
• Adverse effects: Vagolytic effect may cause a transient increase in heart rate and blood pressure. This may result in atrial tachyarrhythmias.
• Elimination/Metabolism: primarily renal elimination (80%)
  • Hepatic metabolism via hydroxylation to an active 3-OH metabolite (50% neuromuscular blocking effects) with dependence on renal excretion
  • Chronic renal failure (CRF) increases pancuronium’s elimination half-life by 97%.

  Vecuronium

  • Dosing: 0.1-0.15 mg/kg results in intubating conditions in 80-90 seconds with a duration of 30-40 minutes.
    • 0.3 mg/kg shortens the onset to 60-75 seconds while increasing the duration of action to 60-90 minutes.
    • The primary metabolite 3-desacetylvecuronium has 80% neuromuscular blocking activity.
    • 20-30% excreted by the kidneys unchanged.
    • Duration of action is prolonged in patients with liver failure and in neonates and young infants due to immature hepatic microsomal enzymes.
    • Elimination half time is increased by 24-56% in patients with CRF resulting in a prolonged and variable duration of action.

    Rocuronium

    • Dosing: 0.6-1.2 mg/kg IV results in intubating conditions in less than 2 minutes with a duration of action of 20-90 minutes.
      • Doses of 1-1.2 mg/kg provide rapid intubating conditions comparable to succinylcholine for rapid sequence induction.
      • Doses of 0.3-0.45 mg/kg IV produce intubating conditions in neonates and young infants within 45-60 seconds. 3
      • IM deltoid administration of 1 mg/kg for infants or 1.8 mg/kg for children provides intubating conditions in 2.5 to 3 min with duration of action of 90-120 min. 4
        • IM administration is reserved for the treatment of laryngospasm in patients without IV access and in whom succinylcholine is contraindicated due to prolonged duration of neuromuscular blockade.
        • Currently no studies address the reversal of IM rocuronium with sugammadex.
        • Hepatic and renal disease prolong the effects of rocuronium but to a lesser degree than with vecuronium or pancuronium.
        • Elimination half time is increased by approximately 37% in CRF without significant effect on duration of action.
        • Alterations in clearance are also seen in neonates and infants due to immature microsomal enzyme system; clearance rates approach adult levels by 6-12 months.

        Rapacuronium

        • Nondepolarizer with onset and duration is similar to succinylcholine but without associated hyperkalemia, myalgias, or MH risk. 3
        • It was removed from the market in 2001 due to its association with severe and potentially fatal bronchospasm. 5,6

        Benzylisoquinoliniums: cause histamine release to varying degrees but metabolism is organ independent

        Atracurium

        • Dosing: 0.6 mg/kg produces intubating conditions in 2 to 3 minutes with a duration of action of 40 to 60 minutes.
        • Intermediate-acting
        • Adverse effects: histamine release may cause hypotension in adult patients at larger doses. Atracurium should be avoided in asthma patients.
        • Metabolism: spontaneous degradation via Hoffman elimination and ester hydrolysis
          • Laudanosine (a metabolic byproduct of Hoffman elimination) has been shown to cause seizures in animals and patients with renal failure have increased levels, but no clinical effects have been documented in humans.
          • Recovery time is prolonged with hypothermia as Hoffman elimination is temperature dependent.

          Cisatracurium

          • A stereoisomer of atracurium devoid of clinically significant histamine release or cardiovascular effects that is four times more potent.
          • Dosing: 0.2 mg/kg provides intubating conditions in approximately 2 minutes.
          • Intermediate-acting
          • Dosing requirement increases over time with prolonged infusions.
          • Recovery time is shorter after cisatracurium infusion when compared with vecuronium.
          • Metabolism: Hoffman elimination
            • As with atracurium, laudanosine is a byproduct and hypothermia prolongs recovery time.

            Mivacurium

            • Dosing: 0.2 mg/kg produces intubating conditions in 2 to 3 minutes with a duration of around of 10 minutes.
            • The shortest acting of the nondepolarizers
            • Adverse effects: Mivacurium can cause histamine release.
            • It was unavailable in the United States from 2006-2016.
            • It does not require reversal with neostigmine and may be use useful in patients with neuromuscular disorders due to its short duration of action.
            • Metabolism: Nonspecific plasma cholinesterase
              • Inactive metabolites are renally excreted. 3
              • Acquired or congenital deficiencies of butyrylcholinesterase can cause prolonged blockade similar to succinylcholine. 7
              • As with succinylcholine, mivacurium should be avoided in patients with a personal or family history of pseudocholinesterase deficiency.
              1. Gash MC, Varacallo M. Physiology, Muscle Contraction. In: StatPears (Internet). Treasure Island (FL); StatPearls Publishing; 2023. PubMed
              2. Butterworth JF, Mackey DC, Wasnick JD. Neuromuscular blocking agents. In: Morgan and Mikhail’s Clinical Anesthesiology, 7th Edition. McGraw Hill; 2022.
              3. Tobias JD. Neuromuscular blocking agents. In: Fuhrman BP, Zimmerman JJ (eds). Fuhrman & Zimmerman’s Pediatric Critical Care. Elsevier; 2022. 1567-82.
              4. Reynolds LM, Lau M, Brown R, et al. Intramuscular rocuronium in infants and children. Dose ranging and tracheal intubation conditions. Anesthesiology. 1996;85(2):231-9. PubMed
              5. Tobias JD, Johnson JO, Sprague K, et al. Effects of rapacuronium on respiratory function during general anesthesia. Anesthesiology. 2001;95(4):908-12. PubMed
              6. Rajchert DM, Pasquariello CA, Watcha MF, et al. Rapacuronium and the risk of bronchospasm in pediatric patients. Anesth Analg. 2002;94(3):488-93. PubMed
              7. Rosenberg MK, Lebenbom-Mansour M. Markedly prolonged paralysis after mivacurium in a patient apparently heterozygous for the atypical and usual pseudocholinesterase alleles by conventional biochemical testing. Anesth Analg. 1997;84(2):457-60. PubMed

              Copyright Information

              
              This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.