European Journal of Cardiovascular Medicine

The field of anaesthesia has seen major progress with the introduction of neuromuscular blocking agents (NMBAs) and drugs used to reverse their effects. These agents are crucial for enabling smooth endotracheal intubation and maintaining ideal surgical conditions by ensuring adequate muscle relaxation. However, if neuromuscular blockade is not adequately or promptly reversed, patients may experience residual muscle weakness, postoperative respiratory compromise, aspiration risk, and delayed recovery.

This highlights the critical importance of having reliable and effective reversal agents in clinical practice. Neostigmine has long been the conventional drug of choice for reversing non-depolarizing neuromuscular blockade. It acts by inhibiting acetylcholinesterase, the enzyme responsible for breaking down acetylcholine at the neuromuscular junction. As a result, acetylcholine levels rise, enabling it to outcompete neuromuscular blocking agents at nicotinic receptors and thereby re-establish normal muscle function. Although neostigmine is effective in reversing neuromuscular blockade, its use is often limited by undesirable side effects, including bradycardia, bronchospasm, excessive salivation, gastrointestinal upset, and postoperative nausea and vomiting (PONV).

To counteract these cholinergic reactions, it is usually given along with an anticholinergic such as glycopyrrolate; however, this combination does not fully prevent the occurrence of such complications.[1]

The practice of anaesthesia has greatly improved after the emergency of drug sugammadex which is selective relaxant binding agent. Structurally derived from modified γ-cyclodextrin, it works by enclosing steroidal neuromuscular blocking agents such as rocuronium and vecuronium within its molecular cavity.

This encapsulation blocks their ability to bind to acetylcholine receptors at the neuromuscular junction, allowing for a rapid and complete reversal of paralysis without relying on acetylcholinesterase inhibition.[2]

Studies based on sugammdex has highlighted that it its reverses the neuromuscular blockade completely, safely and rapidly as compared to neostigmine. sugammdex works effectively even when patient is in deeper plane of anaesthesia. [3,4]

Incidence post operative nausea and vomiting [PONV]is very less with sugammdex as compared to neostigmine. This property of drug makes it superior to other drugs and the drug of choice in all high-risk cases including paediatric. [5,6]

Adenotonsillectomy is among the most common surgical procedure performed in paediatric age group. Desaturation, nausea, vomiting and airway obstruction are most encountered medical complication post-surgery so extubation becomes challenging. Hence, achieving quick recovery and safe extubation is essential to reduce complications and support early discharge.

Post operative outcome depends on choice of reversal agent and its effect on body. Neostigmine is associated with few complications such as dry mouth, anaphylaxis, bradycardia and PONV.Sugammdex is associated with less complication, rapid and complete recovery from muscle relaxant. [7,8,9]

While global research strongly supports the safety and effectiveness of sugammadex, evidence from the Indian paediatric population remains scarce. Given the variations in healthcare practices, resource availability, and demographic characteristics, evaluating the role of sugammadex in Indian children undergoing adenotonsillectomy is particularly important.

The present aims to address this gap by prospectively assessing recovery indices, time to extubation [TOE], and postoperative parameters including nausea, vomiting, bradycardia, and hypotension, hypertension, anaphylaxis reaction, hyperthermia and agitation while comparing sugammadex with neostigmine.

Through the assessment of these parameters, this dissertation aims to provide meaningful evidence to improve anaesthetic management in paediatric adenotonsillectomy. Demonstrating the superiority of sugammadex as a safer and more effective reversal drug could enhance perioperative safety, lower postoperative complications, and promote better patient outcomes, thereby reinforcing its role in contemporary paediatric anaesthesia practice. Recent international studies have strengthened the evidence supporting sugammadex in paediatric anaesthesia. Liu et al. reported that sugammadex achieves faster reversal and fewer adverse effects in children, confirming its superiority over neostigmine [10]. Similarly, Won et al. found that the mean recovery time to a train-of-four (TOF) ratio ≥ 0.9 was 1.6 minutes with sugammadex versus 7.5 minutes with neostigmine (p < 0.0001) [11]. Furthermore, a pooled meta-analysis by Herring et al. demonstrated a mean reversal time difference of –26.36 minutes favouring sugammadex, with a significantly reduced rate of PONV [12].

Despite extensive global data, evidence from the Indian paediatric population remains limited. Given the variability in clinical practices and patient profiles, assessing sugammadex’s role in Indian children undergoing adenotonsillectomy is essential.

The present study was designed to compare recovery indices, time to extubation, and postoperative complications (nausea, vomiting, bradycardia, hypotension, hypertension, anaphylaxis, hyperthermia, and agitation) between sugammadex and neostigmine. This work aims to contribute to improving paediatric anaesthetic care by demonstrating that sugammadex offers a faster, safer, and more reliable reversal profile, potentially setting a new standard for clinical practice.

STUDY DESIGN AND PARTICIPENTS:

This prospective, randomized, double-blinded controlled trial was conducted between February 2024 and June 2025 in the Department of Anaesthesiology, Shri B.M. Patil Medical College, Hospital and Research Centre, Vijayapura, Karnataka. A total of 128 paediatric patients, aged 3 to 17 years and classified as ASA physical status I or II, scheduled for elective adenotonsillectomy under general anaesthesia were enrolled. Participants were randomly assigned to one of two groups: Group S received sugammadex (2 mg/kg), and Group N received neostigmine (0.05–0.09 mg/kg) combined with glycopyrrolate (0.008–0.15 mg/kg) for reversal of neuromuscular blockade. Written informed consent was obtained from parents or legal guardians prior to participation.

INCLUSION AND EXCLUSION CRITERIA:

 Inclusion criteria:

1. Paediatric patient undergoing adenotonsillectomy
2. Age group – 3-17 years
3. ASA grade I and II

Exclusion criteria:

1. Any cardiovascular and hepatic impairment
2. Creatinine clearance <30 mg/ml

Sample size calculation:

The sample size was calculated using G*Power software version 3.1.9.7 based on a previous study comparing extubation times between sugammadex and neostigmine. Considering the mean ± SD of extubation time as 2.0 ± 0.8 minutes in the sugammadex group and 4.3 ± 1.9 minutes in the neostigmine group, a power of 80% and a significance level of 5% (two-tailed) were used to detect a significant difference between the two groups. The required minimum sample size was 128 patients, with 64 participants in each group, to ensure adequate statistical validity.

Randomization and group allocation:

Patients were randomized using a computer-generated sequence in a 1:1 ratio into two groups. Allocation was concealed using sealed opaque envelopes to avoid selection bias. The envelopes were prepared by an independent anaesthesiologist not involved in the study. Group S received sugammadex (2 mg/kg), and Group N received neostigmine (0.05–0.09 mg/kg) with glycopyrrolate (0.008–0.15 mg/kg) for reversal of neuromuscular blockade. The envelope was opened only after induction of anaesthesia, and both the observer and patient caregivers were blinded to group assignment.

study protocol:

All patients underwent a thorough pre-anaesthetic assessment, including medical history, airway evaluation (Mallampati grading), and baseline vital recording. Routine investigations such as CBC, RFT, RBS, ECG, and coagulation profile were performed. Premedication included midazolam (0.03 mg/kg), ondansetron (0.15 mg/kg), and glycopyrrolate (0.008 mg/kg) with oxygen at 5 L/min. Induction was done using propofol (2–4 mg/kg), fentanyl (1–2 µg/kg), and succinylcholine (1–1.5 mg/kg), followed by intubation. Anaesthesia was maintained with sevoflurane (1–2%), oxygen-nitrous oxide (50:50), and vecuronium (0.08–0.12 mg/kg). Reversal was achieved using group S sugammadex (2 mg/kg) or group N neostigmine (0.05–0.09 mg/kg) with glycopyrrolate (0.008–0.15 mg/kg). Extubation was performed after confirming adequate spontaneous breathing, airway reflexes, hemodynamic stability, and GCS ≥13, and the recovery time was recorded.

Ethical Consideration:

Informed written consent was taken from parents or the legal guardians before participants enrolled into the study. The study received approval from the Institutional Ethics Committee of Shri B.M. Patil Medical College, Hospital and Research Centre, Vijayapura (Ref. No: BLDE(DU)/IEC-SBMPMC/079/2023-24, dated 10/02/2024). The trial was prospectively registered with the Clinical Trials Registry of India (CTRI/2024/07/071709; Ref. No: REF/2024/07/087867). All procedures were conducted in accordance with the Declaration of Helsinki and institutional ethical guidelines for human research.

Statistical Analysis:

Data were analysed using IBM SPSS Statistics version 26.0. Continuous variables were presented as mean ± standard deviation (SD) and compared using the independent t-test, while categorical variables were analysed using the Chi-square or Fisher’s exact test. A p-value < 0.05 was considered statistically significant. The primary outcome was extubation time, and secondary outcomes included recovery indices and postoperative complications.

A total of 128 paediatric patients participated in the study, with no significant difference in demographic variables between the two groups (p > 0.05). The mean extubation time was markedly shorter in the sugammadex group (2.6 ± 0.7 minutes) than in the neostigmine group (7.0 ± 1.8 minutes; p < 0.001). Both groups maintained stable hemodynamic parameters, though postoperative stability was slightly better with sugammadex (p < 0.05). Postoperative nausea and vomiting occurred exclusively in the neostigmine group (p < 0.001). No major adverse events were recorded in either group. Overall, sugammadex resulted in quicker recovery, smoother extubation, and fewer postoperative complications compared with neostigmine in paediatric adenotonsillectomy cases.

Figure 1: comparison of mean extubation time

Fig.1: Comparison of mean extubation time between groups. The mean extubation time was significantly shorter in the sugammadex group (2.6 ± 0.7 minutes) than in the neostigmine group (7.0 ± 1.8 minutes; p < 0.001)

Table 1: Comparison of Mean Extubation Time

Figure 2: comparison of mean arterial pressure [MAP] baseline, intraoperative and postoperative.

Figure 2: Comparison of mean arterial pressure at various intervals. The sugammadex group maintained better hemodynamic stability compared to the neostigmine group throughout the perioperative period (p < 0.05).

Figure 3: incidence of post operative nausea and vomiting

Table 2:

Figure 3: comparison of nausea and vomiting parameter

Figure 3: Incidence of postoperative nausea and vomiting between groups. No PONV was observed in the sugammadex group, whereas the neostigmine group had higher incidences of nausea (40.6%) and vomiting (12.5%) (p < 0.001).

Table 3:

Our study evaluated and compared the recovery indices and postoperative outcomes of sugammadex versus neostigmine in paediatric patients in the age group of 3-17 years undergoing adenotonsillectomy. The results indicated that sugammadex ensured a more rapid and consistent reversal of neuromuscular blockade compared with neostigmine. paediatric patients who received sugammadex as a reversal agent at the end of the surgery they experienced lesser incidence of nausea, vomiting and bradycardia with shorter extubation time and complete recovery from muscle relaxation. These observations are in line with previously published literature, which has consistently emphasized the advantages of sugammadex over acetylcholinesterase inhibitors in the paediatric population.

The mechanism of sugammadex is distinctive. As a modified γ-cyclodextrin, it binds directly to steroidal neuromuscular blocking drugs such as rocuronium and vecuronium, forming an inactive complex that is rapidly excreted. Unlike neostigmine, its reversal action is not dependent on acetylcholinesterase inhibition, which significantly reduces the risk of residual neuromuscular blockade or postoperative residual curarization (PORC).[4]

In our study, the shorter extubation times with sugammadex are comparable to the findings of Ammar et al., who reported a faster and more complete recovery when sugammadex was used in paediatric anaesthesia.[3]

An additional observation in this study was the reduction in postoperative nausea and vomiting (PONV) in the sugammadex group. This is an important outcome in adenotonsillectomy, where PONV can delay recovery, increase discomfort, and sometimes lead to secondary complications such as dehydration or bleeding. Similar reductions in PONV were reported by Nik Mat et al., who demonstrated that sugammadex use resulted in fewer gastrointestinal side effects compared with neostigmine–atropine reversal.[5]

Another notable advantage of sugammadex in this study was greater cardiovascular stability. Neostigmine, particularly when administered with glycopyrrolate, is often associated with fluctuations in heart rate & blood pressure due to its cholinergic effects. In contrast, patients receiving sugammadex showed fewer hemodynamic changes. These results are in line with Khuenl-Brady et al., who documented more stable cardiovascular responses following sugammadex administration compared with neostigmine.[9]

However, rare adverse cardiac events, such as transient bradycardia or arrhythmias, have been reported with sugammadex.[1] though none occurred in our cohort.

The clinical relevance of these findings is considerable, especially in paediatric adenotonsillectomy, where airway protection is critical. By providing rapid and predictable reversal of muscle relaxation, sugammadex may help reduce the risk of postoperative airway obstruction and hypoxia, both of which are associated with incomplete neuromuscular recovery. This is consistent with Ghoneim and El Beltagy’s findings in paediatric neurosurgical patients, where sugammadex provided a safe and effective reversal, ensuring earlier restoration of airway reflexes.[7]

Although the present study demonstrates distinct advantage of sugammadex, certain limitations must be noted. As the study was conducted in single centre and included only children aged 3-17 years, the extent to which these findings can be generalized to other populations may be limited. Moreover, the cost of sugammadex remains significantly higher than neostigmine, which may limit its widespread adoption in low-resource settings despite its safety and efficacy advantages. Larger multicentre trials involving infants and high-risk paediatric groups are needed to better define its role in routine practice.

In summary, this study supports the growing body of literature indicating that sugammadex offers faster recovery, fewer adverse effects, and improved safety compared with neostigmine in paediatric adenotonsillectomy. Although its higher cost is a limiting factor, the clinical benefits suggest that sugammadex could become the preferred reversal agent in paediatric anaesthesia when rapid and reliable recovery is essential.

Sugammadex has been shown to be more effective than neostigmine in reversing vecuronium induced neuromuscular blockade. It enables rapid and complete recovery from muscle relaxation leading to significant shorter extubation time and very smooth emergence from general anaesthesia. The incidence of post operative nausea and vomiting was lower in the sugammadex group compared to neostigmine group. Mild agitation was observed in some patient after administration of sugammadex whereas this was not reported with neostigmine. Additionally, the incidence of dry mouth and bradycardia were less observed in sugammadex group compared to neostigmine.

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