Brull, Sorin J.

Abstract Purpose Sugammadex rapidly and effectively reverses aminosteroidal neuromuscular blocking agents and has largely replaced neostigmine in perioperative practice. Although its use is associated with faster recovery and a lower rate of residual neuromuscular blockade, clinically important limitations exist. This review summarizes the literature describing incomplete reversal, recurrence of neuromuscular blockade, adverse effects, drug interactions, and challenges in special populations, with a focus on the role of quantitative neuromuscular monitoring and pharmacist-led activities to optimize sugammadex use. Summary While sugammadex substantially reduces the risk of residual neuromuscular blockade compared to neostigmine, incomplete reversal and recurrence of neuromuscular blockade continue to occur, particularly when dosing is not guided by quantitative neuromuscular monitoring. Underdosing, redistribution of neuromuscular blocking agents, and altered pharmacokinetics can all contribute to inconsistent responses. Quantitative neuromuscular monitoring, rather than choice of reversal agent, is the main determinant of reliable neuromuscular recovery and reduced occurrence of postoperative complications. Sugammadex is associated with rare but potentially serious adverse effects, including hypersensitivity reactions and cardiovascular instability, highlighting the need for careful monitoring. Patent expiration and generic availability may expand access to sugammadex, and these limitations warrant continued attention. Conclusion Sugammadex represents a major advance in neuromuscular blockade reversal but remains an imperfect agent. Safe and effective use requires individualized dosing guided by quantitative neuromuscular monitoring and vigilance for adverse effects. Pharmacists are well positioned to lead education, dosing protocol development, and monitoring strategies that optimize patient safety while supporting adoption of quantitative neuromuscular monitoring.

Background/Objectives: The aim of this observational study was to collect hand measurements and anthropometric data in children aged 1–15 years of age to help the design of a pediatric skin electrode for electromyography-based neuromuscular monitoring. Methods: Data collection was performed at the Pediatric Department of the University of Debrecen Medical Centre between 1 December 2019 and 31 January 2021. After gaining written informed consent from the parents or legal representatives and verbal acceptance from age-appropriate (12–35 months) patients, a total of 153 children were enrolled. The following parameters were recorded: demographics (age, sex, weight, height, and hand dominance) and hand size parameters, defined as the distance between the following reference points: the ulnar groove and the midpoint of the hypothenar eminence (A); the midpoint of the hypothenar eminence and the first interphalangeal joint of the 5th finger (B); the ulnar groove and the midpoint of the thenar eminence (C); the midpoint of the thenar eminence and the interphalangeal joint of the thumb (D); the midpoint of the wrist crease and the tip of the third finger; wrist circumference (E); and forearm length. All measurements were made in centimeters (cm). Results: The children were divided into 4 groups (12–23 months, 2–5 years, 6–11 years and 12+ years). The number of children in the groups ranged between 6 and 16. The hand size parameters increased according to the children’s age (A: 4.3 ± 0.4, 5.0 ± 0.7, 6.3 ± 0.6, and 6.9 ± 1.0 cm; B: 3.2 ± 0.4, 4.1 ± 0.7, 5.0 ± 0.6, and 5.9 ± 0.6 cm; C: 3.0 ± 0.3, 3.6 ± 0.7, 4.1 ± 0.6, and 4.9 ± 0.6 cm; D: 4.1 ± 0.4, 4.8 ± 0.8, 6.2 ± 0.8, and 7.2 ± 0.9 cm; E: 10.1 ± 0.6, 12.0 ± 1.1, 15.3 ± 1.3, and 17.7 ± 1.7 cm, respectively, in the four groups, [mean ± SD]). The height of the children showed a closer correlation with hand size parameters (Pearson’s correlation coefficients: 0.702–0.961) than with age (0.665–0.904) or weight (0.675–0.863). The correlation was weaker when data were examined in prespecified age groups. Conclusions: The current pediatric hand size database provides previously unavailable information that was used in one manufacturer’s design, which may help with the future design of pediatric electrodes of electromyography-based neuromuscular monitors; this information may facilitate adoption of quantitative neuromuscular monitoring in routine pediatric anesthesia practice.

Background: There is little data available in infants on the extent to which inhalational anesthetics prolong the effects of neuromuscular blocking agents compared with intravenous agents. Here, we assessed the differences between the neuromuscular blocking effects (duration and recovery time) of a single dose of rocuronium during propofol vs. sevoflurane anesthesia. Methods: The prospective study enrolled 20 infants (4–12 months of age) scheduled for craniosynostosis surgery, randomly assigned to receive general anesthesia maintenance with sevoflurane or propofol. All patients received 0.6 mg/kg rocuronium as a single bolus dose to facilitate tracheal intubation and surgery. Primary study endpoint was the clinical duration of rocuronium, from administration until spontaneous recovery to a train-of-four ratio (TOFR) > 0.90. Secondary endpoints were times for reappearance of the first, second, third, and fourth twitches of the TOF (T1, T2, T3 and T4, respectively) in the two patient groups. Results: There were no differences in the infants’ age (sevoflurane maintenance: 5.8 ± 2.4 months; propofol maintenance: 6.7 ± 3.1 months, p = 0.47) or weight (sevoflurane: 7722 ± 1644 g; propofol: 7433 ± 1782 g, p = 0.71). Rocuronium onset time was 101.0 ± 55.0 s in the sevoflurane group and 83.4 ± 47.9 s in the propofol group (p = 0.46). Total duration of anesthesia was comparable in the sevoflurane (122.0 ± 23.8 min) and propofol (107.7 ± 25.2 min, p = 0.18) groups. Rocuronium recovery to TOFR > 0.9 required 136 min (CI: 123.7–149.5 min) in the sevoflurane group and 61.5 min (CI: 58.0–101.0 min) in the propofol group (p < 0.001). Conclusions: In infants, sevoflurane maintenance enhances the neuromuscular blocking effect of a single, 0.6 mg/kg BW dose of rocuronium as compared to propofol maintenance. After discontinuation of sevoflurane, additional time is necessary to reach the acceptable TOFR >0.9 needed before tracheal extubation. The present study further underscores the importance of objective (quantitative) neuromuscular monitoring in infants to guide intraoperative management and prevent residual neuromuscular block.

Background: Tracheal intubation and mechanical ventilation are facilitated by neuromuscular blocking agents. We investigated the effectiveness of subjective clinical evaluation of neuromuscular function on retroglossal area size, since it determines spontaneous ventilation adequacy following tracheal extubation. Secondarily, we correlated changes in retroglossal area and depth of neuromuscular block assessed during both respiratory phases using quantitative neuromuscular monitoring. Methods: Once mechanical ventilation was no longer needed, antagonists were used to reverse the neuromuscular block in 21 consenting patients; adequacy of reversal was assessed subjectively by delivering a sequence of four rapid (2 Hz) electrical stimuli (train-of-four, TOF) to a peripheral nerve and assessing attainment of four equal muscle contractions (TOF ratio = 1.0), signifying normal neuromuscular function. Retroglossal area during both inhalation and exhalation were measured pharyngoscopically at various phases of neuromuscular recovery, including at baseline after anesthesia induction but before neuromuscular block onset and at recovery before tracheal extubation; area changes were correlated with depth of quantitatively measured neuromuscular block. Results: Clinicians’ subjective evaluation of readiness for tracheal extubation failed to identify significant residual block in most patients who required rescue antagonism. Markedly decreased retroglossal areas (inhalation: 39.5% of baseline; exhalation: 20.1% of baseline) were present at extubation, and 11 out of 21 (52.4%) patients needed rescue antagonism. In contrast, in patients with neuromuscular recovery to the currently recommended threshold determined quantitatively (TOF ratio > 0.90), retroglossal areas were only 80% recovered but returned to near baseline values when the TOF ratio ≥ 0.95. Conclusions: Quantitative monitoring should guide the timing of tracheal extubation. Current definitions of the minimal threshold for adequate neuromuscular recovery (TOF ratio > 0.90) after mechanical ventilation in postoperative patients should be re-evaluated. A TOF ratio > 0.95 better correlates with return to normal (baseline) retroglossal area during both inhalation and exhalation.

BACKGROUND: Peripheral nerve stimulation with a train-of-four (TOF) pattern can be used intraoperatively to evaluate the depth of neuromuscular block and confirm recovery from neuromuscular blocking agents (NMBAs). Quantitative monitoring can be challenging in infants and children due to patient size, equipment technology, and limited access to monitoring sites. Although the adductor pollicis muscle is the preferred site of monitoring, the foot is an alternative when the hands are unavailable. However, there is little information on comparative evoked neuromuscular responses at those 2 sites. METHODS: Pediatric patients undergoing inpatient surgery requiring NMBA administration were studied after informed consent. Electromyographic (EMG) monitoring was performed simultaneously in each participant at the hand (ulnar nerve, adductor pollicis muscle) and the foot (posterior tibial nerve, flexor hallucis brevis muscle). RESULTS: Fifty patients with a mean age of 3.0 ± standard deviation (SD) 2.9 years were studied. The baseline first twitch amplitude (T1) of TOF at the foot (12.46 mV) was 4.47 mV higher than at the hand ( P <.0001). The baseline TOF ratio (TOFR) before NMBA administration and the maximum TOFR after antagonism with sugammadex were not different at the 2 sites. The onset time until the T1 decreased to 10% or 5% of the baseline value (T1) was delayed by approximately 90 seconds (both P =.014) at the foot compared with the hand. The TOFR at the foot recovered (TOFR ≥0.9) 191 seconds later than when this threshold was achieved at the hand ( P =.017). After antagonism, T1 did not return to its baseline value, a typical finding with EMG monitoring, but the fractional recovery (maximum T1 at recovery divided by the baseline T1) at the hand and foot was not different, 0.81 and 0.77, respectively ( P =.68). The final TOFR achieved at recovery was approximately 100% and was not different between the 2 sites. CONCLUSIONS: Although this study in young children demonstrated the feasibility of TOF monitoring, interpretation of the depth of neuromuscular block needs to consider the delayed onset and the delayed recovery of TOFR at the foot compared to the hand. The delay in achieving these end points when monitoring the foot may impact the timing of tracheal intubation and assessment of adequate recovery of neuromuscular block to allow tracheal extubation (ie, TOFR ≥0.9).