Rocuronium is a non-depolarizing neuromuscular blocker used in surgery as an adjunct to general anesthesia to induce muscle relaxation.[i] Contrary to some other neuromuscular blockers, rocuronium is fast-acting and reversible. As a result, it is commonly used to facilitate endotracheal intubation by paralyzing the airway muscles and provide skeletal muscle relaxation during mechanical ventilation and surgery.[ii] At normal doses, rocuronium does not affect heart rate or blood pressure, though cases of rocuronium-induced anaphylaxis have been documented.[iii] The drug was introduced in 1994 and is marketed under the brand names Zemuron and Esmeron.1
Non-depolarizing neuromuscular blockers are competitive antagonists for the neurotransmitter acetylcholine (ACh) and bind to nicotinic receptors on the postsynaptic membrane of the neuromuscular junction.[iv] Muscular impulses are normally transmitted via the diffusion of ACh across the synaptic membrane and their subsequent binding to the alpha subunits of nicotinic receptors. This allows for the influx of sodium ions into the membrane and the creation of an action potential, which is propagated along the sarcolemma (the sheath that houses muscle fibers) until the release of calcium ions that triggers muscle contraction.[v] Neuromuscular blockers like rocuronium bind directly to the nicotinic receptors, preventing the binding of ACh and leading to muscular paralysis.
Neuromuscular blockers can be divided into two categories based on their molecular structures: steroidal and the benzylisoquinolinium class.2 While the two categories have the same mechanism of action, steroidal blockers are said to have more vagolytic activity, which means they inhibit the action of the vagus nerve on the heart, gastrointestinal tract, and other organs.4 Rocuronium is only mildly vagolytic at high doses.[vi] Due to its limited lipid solubility, rocuronium does not pass the blood-brain barrier and other lipid barriers, and therefore does not affect the central nervous system.2
Rocuronium has a dosing range of 0.6 to 1.2 mg/kg, and intubating conditions are generally reached within one to two minutes of administration.1 The paralyzing effects generally last approximately 30 minutes after administration, though higher concentrations can be used to achieve a longer duration of action. Contraindications to rocuronium include an allergic reaction to the drug, renal or hepatic dysfunction, and residual neuromuscular blockade, a condition where the effects of the neuromuscular block persist into the postoperative period.[vii]
To monitor the effects of rocuronium both during and after surgery, anesthesiologists typically use peripheral nerve stimulation. Electrodes are placed adjacent to a superficial nerve, typically the ulnar or facial nerve, and the stimulator provides four consecutive electrical impulses.[viii] The “train-of-four” method, used in conjunction with nerve stimulation, dictates that a response of two muscular twitches indicates adequate muscle relaxation while one twitch is a sign of good intubating conditions.8 If all four twitches are lost, clinicians will not administer any further rocuronium until twitches are detected.
Two subgroups of drugs can be used to reverse the effects of rocuronium. Anticholinesterases prevent the metabolism of ACh by inhibiting the action of cholinesterase, which allows ACh to bind the nicotinic receptors instead of rocuronium. Alternatively, sugammadex, a novel drug of the cyclodextrin family, reverses neuromuscular blockade by encapsulating free rocuronium molecules to form a stable complex.[ix] For both, dosage will depend on the number of twitches detected. Despite the occasional case of an adverse effect due to rocuronium, its safety and that of its reversal are well-established.
References
[i] “Rocuronium.” DrugBank Online, go.drugbank.com/drugs/DB00728.
[ii] Jain A, Wermuth HR, Dua A, et al. Rocuronium. [Updated 2021 Apr 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK539888/
[iii] Takazawa T, Mitsuhata H, Mertes PM. Sugammadex and rocuronium-induced anaphylaxis. J Anesth. 2016 Apr;30(2):290-7. doi: 10.1007/s00540-015-2105-x. Epub 2015 Dec 8. PMID: 26646837; PMCID: PMC4819478.
[iv] Clar DT, Liu M. Non-depolarizing Neuromuscular Blockers. [Updated 2021 Apr 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK534828/
[v] “Anatomy and Physiology I.” Lumen, Carnegie Mellon University, courses.lumenlearning.com/cuny-csi-ap-1/chapter/neuromuscular-junctions-and-muscle-contractions/.
[vi] Appiah-Ankam, J., and J. M Hunter. “Pharmacology of Neuromuscular Blocking Drugs.” Continuing Education in Anaesthesia Critical Care & Pain, vol. 4, no. 1, 2004, pp. 2–7., doi:10.1093/bjaceaccp/mkh002.
[vii] Murphy, G. S., and S. J. Brull. “Residual Neuromuscular Block.” Anesthesia & Analgesia, vol. 111, no. 1, 2010, pp. 120–128., doi:10.1213/ane.0b013e3181da832d.
[viii] “How to Monitor with Train-of-Four.” Anesthesiology Hub, Abbvie, www.anesthesiologyhub.com/nimbex/ICU/train-of-four.html.
[ix] Singh, D.R., et al. “Sugammadex: A Revolutionary Drug in Neuromuscular Pharmacology.” Anesthesia: Essays and Researches, vol. 7, no. 3, 2013, p. 302., doi:10.4103/0259-1162.123211.