Addressing residual neuromuscular blockade: A key to achieving ERAS goals in cardiac surgery
Year: 2025
Type: article
Abstract: As Enhanced Recovery After Cardiac Surgery (ERACS) protocols evolve, the goals of early extubation, reduced intensive care unit (ICU) stays, and lower complication rates have come into focus principles.[1] Fast tracking after cardiac surgery aims at achieving extubation in the first 6 h while ultrafast tracking aims at extubation within 1 h or sometime on operating table at the end of surgical procedure. Risk factors for fast-track failure have been identified and include EUROSCORE II and transfusion of blood product.[2] Within this framework, one crucial yet often underestimated aspect is the complete, timely, and safe recovery from neuromuscular blockade (NMB). This is particularly relevant in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB), where residual NMB remains a common postoperative concern. The challenge is further compounded by hypothermia, frequently employed during CPB, which alters the pharmacokinetics (PK) and pharmacodynamics (PD) of neuromuscular blocking agents (NMBAs), resulting in delayed metabolism and clearance. During hypothermic CPB, muscle relaxation is often achieved using intermittent boluses of rocuronium or continuous infusions of cis-atracurium. The literature has largely favored infusion strategies for providing steady-state muscle relaxation. However, concerns remain about dose adjustments, individual variability, incomplete reversal, and postoperative residual neuromuscular blockade all of which can delay extubation and prolong ICU stay, ultimately undermining ERAS goals.[3] A recent prospective randomized double-blind trial, published in this issue, sheds light on this important subject.[4] The study underscores the need to reevaluate NMBA selection, dosing, and monitoring practices in the context of CPB, particularly under hypothermic conditions. Rocuronium, a steroidal nondepolarizing NMBA with rapid onset and intermediate duration of action, is widely used due to its favorable intubating conditions.[5] However, during hypothermic CPB (typically at 28°C–32°C), the hepatic metabolism, the primary route of rocuronium elimination, is significantly impaired. Reduced hepatic blood flow and cytochrome P450 enzyme activity prolong its duration of action. Furthermore, hypothermia may increase the plasma protein binding of rocuronium, further reducing the free (active) fraction and contributing to inter-patient variability.[6] Cis-atracurium, a benzylisoquinolinium-based, intermediate-acting nondepolarizing NMBA, is eliminated via organ-independent Hofmann degradation, theoretically providing more predictable PD. Hofmann elimination is both temperature- and pH-dependent; hence, hypothermia during CPB can also slow its degradation, though generally to a lesser extent than the impairment seen with rocuronium metabolism.[7,8] Cammu et al. demonstrated that under hypothermic CPB, the duration of action of cis-atracurium is more consistent and less variable than that of rocuronium.[9,10] Multiple studies have highlighted the implications of these altered PK and PD. McEwin et al. reported that patients receiving rocuronium had better train-of-four (TOF) ratios than those given pancuronium, yet 40% still had TOF ratios below 0.7 at ICU admission, a level associated with impaired pharyngeal and laryngeal function, leading to airway complications.[11] Cammu et al. also showed that both rocuronium and cis-atracurium required reduced dosing during hypothermic CPB, but rocuronium exhibited greater variability and prolongation due to its hepatic dependence. More recently, Cammu et al. emphasized that even intermediate-acting agents can lead to residual NMB in the ICU, especially when neuromuscular monitoring is absent and clinicians rely solely on assumed spontaneous recovery.[9,10] The pivotal study by Cammu et al. demonstrated that cis-atracurium infusion rates should be halved during CPB due to hypothermia-induced reduction in metabolism, while rocuronium exhibited a smaller, statistically insignificant reduction.[9,10] Similarly, Withington et al., in pediatric patients, showed that cis-atracurium infusion rates could be reduced by around 60% during moderate hypothermia.[12] However, these findings also highlight interpatient variability and the operational challenges of adjusting infusion rates in real time. Using large, single-bolus doses before CPB initiation with subsequent titration based on neuromuscular monitoring may simplify intraoperative management. Cammu et al. compared bolus and infusion regimens and found bolus dosing to be safe.[10] Still, from a practical standpoint, bolus dosing paired with TOF monitoring ensures flexibility, allows for correction of unexpected under- or over-relaxation, and circumvents the difficulties of adjusting infusions during temperature transitions on bypass. The risk of residual NMB necessitates vigilant monitoring and timely reversal strategies. Quantitative TOF monitoring should be considered standard practice during both intraoperative and postoperative phases and must be integrated into ERACS protocols.[13] Sugammadex offers a reliable and rapid reversal of rocuronium-induced blockade but remains prohibitively expensive in many resource-limited settings. In such scenarios, a strategy combining dose minimization, temperature-adjusted pharmacologic planning, and neostigmine-based reversal (guided by TOF ratios) becomes essential. Continuous neuromuscular monitoring is essential throughout the perioperative period, as hypothermia alters nerve conduction and muscle response, making clinical assessment unreliable.[10] During surgery, dosing should be guided by TOF monitoring, with a target of ~ 15% T1/T0 during CPB.[10,14] Postoperatively, patients should not be shifted to ICU without confirming full recovery (TOF ratio ≥ 0.9), and ICU teams must be trained to continue monitoring and administer reversal agents when needed.[15] In summary, instituting formal protocols that define NMBA selection, dosing adjustments for hypothermia, routine TOF monitoring, and reversal strategies is essential. These protocols should be reinforced through regular audits and education to ensure consistency across providers and cases. While continuous infusion of NMBAs remains an option, bolus dosing with vigilant neuromuscular monitoring offers a simpler and potentially safer approach during hypothermic CPB. However, regardless of the method chosen, routine and continuous neuromuscular transmission monitoring is nonnegotiable. Furthermore, neuromuscular management must be fully integrated into ERAS cardiac protocols, extending into the postoperative ICU period. Treating neuromuscular recovery as a vital endpoint, rather than a passive outcome, aligns with the broader goals of ERACS and perioperative patient safety.
Source: The Indian Anaesthetists Forum
Authors: Anita Chouhan, Sadik Mohammed, Rakesh Kumar
Institution: All India Institute of Medical Sciences Jodhpur
Language: English
Subfield: Anesthesiology and Pain Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4411852503