In terms of why we need to consider rocuronium over succinylcholine, there are number of pharmacologic, physiologic, and even clinical factors that make using depolarizing agents less desirable. For instance, succinylcholine’s nicotinic effects are well recognized, such as increased intracranial, intraocular, and even intra-gastric pressure (JAMA 2019;322:2303-12). Furthermore, the hyperkalemic risk, especially in patients who present with pathologic upregulation of its target receptor, further preclude its use (Anesthesiology 2006;104:158-69). Not to mention the postoperative myalgias and the rare but significant risk of malignant hyperthermia, which also contribute to hesitation with its use. Actually, there is recent data to suggest that the use of succinylcholine was associated with an increase in postoperative pulmonary complications due to residual paralysis (Br J Anaesth 2020;125:629-36; Br J Anaesth 2020;125:423-5). The finding was more common at higher doses (>2 mg/kg) and for procedures less than two hours in duration (Br J Anaesth 2020;125:423-5).
Now, despite all of the previous indictments levied against succinylcholine, it remains the gold standard for rapid sequence induction (RSI), mainly due to its ability to provide excellent intubating conditions reliably and expeditiously (<50 seconds) (BMC Anesthesiology 2020;20:54). However, given the concerns with succinylcholine-related adverse effects, use of high-dose rocuronium has been recommended as an alternative (Anaesthesia 2017;72:765-77). A prospective randomized controlled trial reported that the incidence of failed intubation attempts and qualitative scores of intubation conditions after RSI did not differ between succinylcholine versus rocuronium in the intensive care setting (Crit Care 2011;15:R199). Furthermore, the differences in onset times between the two groups were also not clinically relevant. The authors noted that only at higher rocuronium doses (1.2 mg/kg) will it come closer to approximating succinylcholine. Evidence, however, suggests superior intubating conditions with succinylcholine versus rocuronium (BMC Anesthesiology 2020;20:54; Cochrane Database Syst Rev 2015;CD002788; Cochrane Database Syst Rev 2003;CD002788; Acad Emerg Med 2002;9:813-23). Consequently, there have been studies evaluating even higher doses of rocuronium (2 mg/kg) to increase the probability of perfect conditions for tracheal intubation (Anesth Analg 2000;90:175-9). While increasing the dose of rocuronium can shorten the onset time, it can also considerably prolong the duration of action and increase the concerns of postoperative residual paralysis and its consequences (J Intensive Care 2020;8:37).
Perhaps the more important question should be: Is the onset of rocuronium we are using in our clinical practice reliable? Perhaps the perceived need to give more to get more is just an unnecessary consequence of using a drug that is not optimally potent. This issue of potency and neuromuscular blocking drugs is not inconsequential in terms of their onset.
There is an inverse correlation between the molar potency and speed of onset (Anesthesiology 2000;92:1507). Given the low potency of rocuronium, there appears to be a significant variability in its onset and duration (Br J Anaesth 2000;84:43-7; Anesth Analg 1995;80:1249). Incidentally, the onset time of succinylcholine also appears to be compatible with this relationship as well. Another factor that can influence the onset of rocuronium is the need for refrigeration. Manufacturers of rocuronium recommend that it be stored in a refrigerator at 36° F to 46° F (Korean J Anesthesiol 2007;52:386-91). Upon removal from the refrigerator to room temperature conditions (~77° F), it should be used within 60 days.
A prospective randomized controlled trial evaluated the effects of storage temperature on rocuronium’s intubating conditions and clinical duration (Korean J Anesthesiol 2007;52:386-91). The first cohort consisted of those who received rocuronium refrigerated up until the time of administration, while the second cohort received rocuronium stored at room temperature. The onset times to twitch depression of 0% in the room temperature group were statistically significantly prolonged compared to the refrigerated group (means 152 seconds and 137 seconds, respectively). Also, the intubating conditions were poor with rocuronium at room temperature. Interestingly, the clinical durations were also statistically significantly shortened in room temperature group (means 24 minutes vs. 33 minutes) (Korean J Anesthesiol 2007;52:386-91). This temperature-related variability compounds the fact that rocuronium has inherently unpredictable pharmacokinetics. It bears mentioning that the impact of temperature is not exclusive to rocuronium. Succinylcholine, with its variable pharmacokinetics, is also subject to storage temperature-based alterations. Nevertheless, monitoring the eye muscles (corrugator supercilii) at induction should also help confirm that we have acceptable intubating conditions because the upper airway muscles are particularly sensitive to neuromuscular agents (Br J Anaesth 2009;102:869-74). In contrast, monitoring of the adductor pollicis is recommended to assess recovery from neuromuscular blockade (Anesthesiology 2012;117:964-72).
In summary, we pose several important questions. For instance, how certain are we that the rocuronium we utilize is stored in the appropriate conditions (i.e., as recommended by the manufacturer)? In addition, if the recommendations are not being met, what impact does that potentially have on clinical efficacy? Also, if there is a negative impact on its effectiveness, what impact if any could this have on airway manipulation-related trauma, particularly when used for rapid-sequence intubation? Given the low potency and the concerns of effects of temperature control, should we stop using a prerequisite time for tracheal intubation? Finally, we need to continue our pursuit for a reliable ultra-rapid-acting non-depolarizing neuromuscular blocking drug that would replace succinylcholine.
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