Sugammadex, the first noncompetitive antagonist developed for the reversal of neuromuscular blockade (NMB) [1], is one of the few drugs that has revolutionized anesthetic practice. Because of its rapid and predictable action in reversing NMB, it is now preferred over traditional acetylcholinesterase inhibitors. While effective, acetylcholinesterase inhibitors have a slower onset and are associated with a wide range of side effects, including bradycardia, increased secretions, and the need for concomitant anticholinergic drugs to mitigate these effects [2]. While sugammadex was approved for adults in the United States in 2015, its use in children (2 to 17 years) was not approved until 2021. Although the precision and reliability of NMB reversal by sugammadex are of great benefit in pediatric anesthesia, several important questions remain regarding the use of sugammadex in young patients.

A recent meta-analysis suggesting the superiority of sugammadex over acetylcholinesterase inhibitors also highlighted the need for additional high-quality randomized trials owing to the general low quality and heterogeneity of previous studies [3]. Therefore, there is a need to further explore and understand the use of sugammadex in children. For example, the pharmacokinetics and pharmacodynamics of sugammadex in pediatric patients can differ significantly from those in adults, necessitating age-specific considerations of dosing and administration. The long-term safety and efficacy of sugammadex in the pediatric population also require further research.

In this brief narrative review, our aim is to address several practical concerns that anesthesiologists often face when using sugammadex in pediatric patients, drawing from the existing literature to provide a comprehensive overview of key considerations and potential challenges. Our focus is not on comparing the efficacy of sugammadex and acetylcholinesterase inhibitors, as this has been extensively reviewed elsewhere [3,4]. Instead, we focus on particular issues that anesthesiologists often face when using sugammadex in pediatric anesthesia.

Although the risk of overdosing with sugammadex remains unclear [5], underdosing poses a definite risk because of the possibility of residual blockade. Therefore, the dosage should be adjusted according to the degree of NMB using appropriate NMB monitoring techniques.

In adults, the recommended dose of sugammadex is 2-16 mg/kg. The routine reversal dose is 4 mg/kg when the post-tetanic count (PTC) is 1-2 or there are no twitch responses to train-of-four (TOF) stimulation (deep block), and 2 mg/kg when there is reappearance of the second twitch (T2) in response to TOF stimulation (moderate block). A dose of 16 mg/kg is used for immediate reversal of rocuronium-induced NMB [6]. In pediatric patients, the recommended routine reversal dose is the same as that in adults. However, measuring the degree of NMB itself can be challenging in young pediatric patients, making it more difficult to select the appropriate reversal dose. In cases of accidental large doses of rocuronium, the administration of additional rocuronium just before the end of surgery, or continuous rocuronium infusion, insufficient sugammadex dosing without NMB monitoring can lead to residual blockade and subsequent respiratory complications. Therefore, careful selection of the sugammadex dosage is essential.

In a recent randomized clinical trial using NMB monitoring, the authors showed that in pediatric patients aged 2-17 years, there was no difference in recovery time (1.3, 0.9 and 0.6 min, respectively) and dose-dependent side effects between different dosages of sugammadex (2, 4, and 8 mg/kg) when administered at a TOF count of 2 [7].These results suggest that a dose of 2 mg/kg should be sufficient in situations where NMB monitoring can be employed. However, caution is warranted when NMB monitoring cannot be employed, as residual block or recurarization has been frequently documented and the use of higher doses may be considered. We address this issue in more detail below.

Although formal research on immediate reversal in pediatric patients is limited, several successful cases have been documented. For example, Wooszczuk-Gbicka et al. [8] reported a 10-month-old infant who had difficulty ventilating with a mask after receiving 0.1 mg/kg of vecuronium but returned to spontaneous ventilation after the administration of an 8 mg/kg dose of sugammadex. Similarly, Wakimoto et al. [9] described a newborn weighing 1.77 kg at 34 weeks of gestation who experienced ventilation difficulties after administration of 1 mg/kg of rocuronium and subsequently resumed spontaneous breathing after receiving 8 mg/kg of sugammadex. The patients successfully returned to spontaneous ventilation within 25 s and 1-2 min, respectively. Recently, Ji et al. [10] reported that in patients aged 2-7 years who received 1 mg/kg rocuronium, effective reversal was achieved within 3 min following the administration of 8 mg/kg sugammadex at the moment of intense NMB (PTC of 0) without adverse events. In a "cannot ventilate, cannot intubate" situation in a pediatric patient, sugammadex use may be considered, though with caution [11].

In pediatric patients, owing to their smaller capacity compared to adults, the presence of residual blockade or recurarization can be extremely dangerous and life-threatening [12]. Even in adults, 0.2% of patients experience recurrence of NMB despite the use of the recommended dose, and this incidence can increase to 4.62% when doses lower than the recommended amount are administered. Therefore, careful consideration is necessary when selecting the appropriate dose.

Most research findings suggest that sugammadex can be used safely in pediatric patients; however, previous reports have frequently documented cases of residual blockade or recurarization in these children. These incidents have been associated with the prolonged use of neuromuscular blocking agents (NMBAs) [13] or administration of lower than the recommended doses of sugammadex [14]. However, recurrence of NMB, even when using recommended doses, can occur due to the redistribution of NMBAs or potential interactions with other medications [15]. Cases have been documented in which difficulties in reversal were encountered despite using doses greater than 4 mg/kg, and instances of recurarization occurred as late as 52 min after surgery [16]. Cates et al. [17] also suggested that younger age and lower body weight are associated with an increased risk of residual weakness. Therefore, meticulous monitoring up to one hour after surgery should be considered in pediatric patients despite the use of the recommended doses. This is especially true in pediatric patients who receive vecuronium, as the affinity for sugammadex is 3.1 times lower than that for rocuronium [18].

Most studies indicate that sugammadex is well tolerated in children, with adverse effects that are usually mild and self-limiting, such as nausea/vomiting and pain. However, studies also suggest the importance of maintaining awareness, particularly regarding the signs of allergic reactions, bradycardia, and laryngospasm.

Neonates and infants under 2 years of age are particularly sensitive to NMBAs owing to underdeveloped neuromuscular junctions and immature clearance systems. This can prolong the effects of the drugs and increase the risk of residual neuromuscular blockade after surgery [47,48]. Furthermore, their immature respiratory systems render them more susceptible to complications from residual paralysis such as respiratory failure. Therefore, precise dosing and use of sugammadex, which provides more complete reversal, might be beneficial [49].

While currently approved for children aged 2 years and older, emerging data support the use of sugammadex in patients under 2 years (Table 1). A recent retrospective cross-sectional observational study found that anesthesiologists may prefer to use sugammadex in children under the age of 2 years [50]. Although its safety and efficacy in this age group have not been conclusively established, the limited data do not show any unique side effects of sugammadex in infants and neonates compared to those in older children. Franz et al. [51] reported the use of sugammadex in 331 patients under two years of age, including 53 neonates, with the youngest patient being two days old. The doses of sugammadex used were 2 mg/kg in 223 infants, 4 mg/kg in 98 infants, and 16 mg/kg in 10 infants. No adverse effects were observed in any of the patients [51]. Other studies have reported similar results in neonates and infants with no adverse effects of sugammadex (2-16 mg/kg) [9,52-57]. One of these case reports included the successful use of sugammadex in a preterm infant weighing 850 g [52]. The infant received 1.2 mg/kg of rocuronium and experienced ventilation difficulties. The infant recovered spontaneous ventilation after receiving 16 mg/kg sugammadex. A recent meta-analysis, although stating the need for additional studies, also demonstrated rapid recovery without any significant increase in adverse effects when using sugammadex (2 or 4 mg/kg) in neonates and infants [3].

Compared with older children, the optimal dose required for neonates and infants has not been clearly established. One prospective trial enrolled infants aged 28 days to 23 months to receive one of four doses of sugammadex (0.5, 1, 2, or 4 mg/kg) but did not specify whether dosing differed from the older pediatric groups [58]. Another study reported rapid recovery without significant side effects when using a fixed dose of 4 mg/kg sugammadex to reverse deep NMB in 34 children aged 2 months to 8 years [59]. A recent randomized clinical trial conducted in pediatric patients under 2 years of age with congenital heart diseases also reported similar results [60].

Based on the limited data, it is possible that the use of doses previously approved for older pediatric patients may also be appropriate for neonates and infants. However, additional research is still needed on sugammadex dosing and safety profile, specifically in this youngest age group.

Recent evidence also supports the use of sugammadex in infants and children with neuromuscular disorders (NMDs) or congenital heart disease.

Drawing a definitive conclusion on the use of sugammadex in pediatric patients is challenging owing to the wide age spectrum. Although approved for patients over 2 years of age, anesthesiologists must be aware of the potential risks of sugammadex in young patients. Importantly, despite not being approved, recent studies have indicated that the efficacy and safety of sugammadex are not significantly different in neonates and infants. However, most studies on safety and efficacy in this age group are retrospective, case-based, or observational, and have inherent limitations. Therefore, further prospective studies are crucial to establish the safety and efficacy of sugammadex.