Is neuromuscular blocker needed in children undergoing inguinal herniorrhaphy?: A prospective, randomized, and controlled trial.

BACKGROUND: Intraoperative neuromuscular blocker is widely used, but is known to be associated with postoperative residual paralysis, which is known to be associated with increased risk of pulmonary complications. Hence, its use should be individualized and restricted to procedures where it is mandatory. We examined whether not using a neuromuscular blocker affects the surgical conditions in children undergoing inguinal herniorrhaphy.
METHODS: Anesthesia was induced and maintained with sevoflurane in 60% nitrous oxide, and the airway was maintained using an I-gel. In total, 66 children aged 1 to 6 years were randomized to receive rocuronium (rocuronium group, n = 33) or saline (control group, n = 33); 61 children of them finished the study. A single surgeon who performed the operation rated the surgical condition of each patient on a 4-point scale (1 = poor, 2 = acceptable, 3 = good, and 4 = excellent). Intraoperative patient movement, recovery time, emergence agitation, and postoperative pain scores were evaluated.
RESULTS: One patient in control group and no patient in rocuronium group showed intraoperative movement. When noninferiority test was done for intraoperative patient movement, with the noninferiority margin of 20%, the difference of absolute risk was 3.3% (95% confidence interval -8.0% to 16.7%) and saline group was noninferior to rocuronium group. All of the patients showed good to excellent surgical conditions, and no difference was found between the 2 groups. The recovery time was shorter in the control group than in the rocuronium group (4.5 ± 1.8 vs 5.6 ± 2.2 minutes, respectively; P = .028).
CONCLUSION: In children aged 1 to 6 years undergoing inguinal herniorhaphy under sevoflurane anesthesia using an I-gel, not using neuromuscular blocker showed similar intraoperative condition and shortened recovery time compared with using neuromouscular blocker.

RCT Entities:   Population Interventions Outcomes

Introduction

A neuromuscular blocker is widely used in anesthesia practice as a component of balanced anesthesia. It is used to facilitate endotracheal intubation and to maintain intraoperative surgical relaxation. However, the use of a neuromuscular blocker is not without complications, and vigilance is required for its full reversal at the end of surgery. Up to 50% of patients show postoperative residual curarization even after the use of intermediate-acting neuromuscular blockers.[ Postoperative residual curarization is associated with postoperative respiratory complications.[ The only way to confirm the full recovery of neuromuscular function is the qualitative monitoring of neuromuscular function, but the reality is not ideal. In addition, the intraoperative use of a neuromuscular blocker is a risk factor for accidental awareness during general anesthesia.[ In this regard, the use of an intraoperative neuromuscular blocker should be done cautiously and be confined to the procedure necessitating a neuromuscular blockade.

Concerning pediatric inguinal herniorrhaphy, the procedure may be performed using supraglottic airways, and a neuromuscular blockade for endotracheal intubation is not mandatory. Additionally, the surgical procedure is brief and would be completed before spontaneous recovery from the induction dose of the neuromuscular blocker. However, neuromuscular blockers are still used in some institutions for the purpose of improving the surgical condition and assist intraoperative mechanical ventilation. In this study, we tried to find if not using neuromuscular blocker affects the surgical condition in children undergoing inguinal herniorrhaphy, by using noninferiority test.

Materials and methods

The study protocol was approved by the Ethical Committee of the Institutional Review Board on human research of Seoul National University Bundang Hospital (Seongnam, Korea) on August 2013 with the approval code of B-1307/212–002. It was also registered at cris.nih.go.kr (KCT0000991). Written informed parental consent was obtained from all of the patients. Written informed consent from patients was exempted by our Institutional Review Board, because they were preschool-aged young children. Patients aged 1 to 6 years with an American Society of Anesthesiologists Physical Status classification of 1 to 2, who were scheduled to undergo elective inguinal herniorrhaphy, were included. The exclusion criteria were a body mass index >25 m/kg2, allergies to any of the study drugs, general conditions impairing neuromuscular function, a history of admission to the neonatal intensive care unit due to prematurity or other causes, and an upper airway infection. Sixty-six children were randomly allocated to receive rocuronium (rocuronium group, n = 33) or saline (control group, n = 33) using Random Allocation Software (version 2.0). The random table was kept in a sealed envelope and opened immediately before the induction of anesthesia. Both the anesthesiologist and surgeon assessing the outcome variables were blinded to the patient group. The drugs were prepared by an anesthesiology nurse who was not involved in either patient care or data collection.

All of the patients were transported to the operating room with their parents. After attaching standard monitoring devices for noninvasive blood pressure measurement, electrocardiography, and pulse oximetry, anesthesia was induced by the inhalation of sevoflurane in 60% nitrous oxide. After the loss of consciousness, intravenous access was performed, and rocuronium (0.45 mg/kg) or saline prepared in the same volume was injected. After 60 seconds, a single skilled anesthesiologist inserted the I-gel device (Intersurgical Ltd., Wokingham, Berkshire, UK) according to the manufacturer's instructions and assessed the insertion conditions (coughing, gagging, gross purposeful movements, laryngospasm, or trauma). Anesthesia was maintained with 2% to 3% sevoflurane in 60% nitrous oxide, and the lungs were ventilated to maintain an end-tidal carbon dioxide level of 4 to 4.6 kPa. Alfentanil (10 μg/kg) was administered 1 to 2 minutes before the skin incision, and an additional dose of alfentanil (5 μg/kg) was administered as needed according to the hemodynamic changes in the patients. Before the closure of the skin, regional anesthesia using 0.5% bupivacaine HCl on the ilio-inguinal and ilio-hypogastric nerves was done by the surgeon. The surgeon was allowed to request a neuromuscular blockade if needed. When the surgery was completed, neostigmine (0.04 mg/kg) and glycopyrrolate (0.01 mg/kg) in the rocuronium group and the same volume of saline in the control group were injected. The I-gel was removed when spontaneous breathing and purposeful movements were observed. The time from the cessation of sevoflurane administration to removal of the I-gel was recorded as the recovery time.

A single surgeon who performed the surgery rated the surgical condition scores on a 4-point scale as follows: 1 = poor, surgery cannot proceed because of muscle contractions or gross patient movement; 2 = acceptable, muscle contractions causing some interference in the surgical procedure; 3 = good, only a few muscle contractions that do not affect the surgical procedure; and 4 = excellent, no muscle contractions at all. In addition, the I-gel insertion conditions, intraoperative movement or spontaneous breathing, and time from the cessation of inhalational agent administration to removal of the I-gel (recovery time) were evaluated. In the postanesthesia care unit (PACU), postoperative pain and anxiety scores (at arrival and before discharge from the PACU), additional opioids used, adverse effects, and duration of the PACU stay were recorded. Postoperative pain was evaluated using the pediatric Face, Legs, Activity, Cry, and Consolability (FLACC) pain scale (Table 1),[ and postoperative anxiety was evaluated using a 5-point agitation scale as follows: 1 = sleeping; 2 = awake, calm; 3 = irritable, crying; 4 = inconsolable, crying; and 5 = severe restlessness, disorientation.[ Fentanyl (1 μg/kg) was administered as needed when severe pain or agitation was observed in the PACU. The surgical complications including the recurrence of hernia were observed until 1 year after surgery.

Table 1

The Face, Legs, Activity, Cry, Consolability pain scale.

Statistical analysis

The sample size calculation for noninferiority trial was performed according to the priori study. Based on the 6% incidence of movement in the rocuronium group, the sample size to test the noninferiority was 30 patients per group with α = 0.05, power = 0.90, and the noninferiority margin of the absolute risk of 20%. Considering the dropout rate of 10%, 33 patients per group were recruited.[ All data are expressed as the mean ± SD, and number (% incidence). Patient characteristics and other clinical data were compared using Student t test, the chi-square test, and Fischer exact test, as appropriate. All P values were 2-sided and were deemed to indicate statistical significance at P = 0.05. A statistical analysis of the data was performed using IBM SPSS Statistics (version 22.0; IBM Corp., Armonk, NY).

Results

In all, 88 patients were screened, 66 were enrolled, and 61 were analyzed (Fig. 1). One child from the rocuronium group was excluded from the study because of refusing to participate and 2 children from the control group were also excluded due to changing surgery plan. Also, 1 child in each group was excluded due to laryngeal spasm requiring intubation. No difference in patient characteristics was detected between the groups (Table 2). One patient in control group and no patient in rocuronium group showed intraoperative movement. When noninferiority test was done for intraoperative patient movement, with the noninferiority margin of 20%, the difference of absolute risk was 3.3% (95% confidence interval [CI] −8.0% to 16.7%) and saline group was noninferior to rocuronium group. There was no intraoperative additional request from the surgeon for a neuromuscular blocker. All of the patients were rated good to excellent on a surgical rating scale and were not different between the groups (Fig. 2). The recovery time was significantly longer in the rocuronium group than in the control group (5.6 ± 2.2 vs 4.5 ± 1.8 minutes, respectively; P = .028). Other intraoperative and postoperative variables such as the operation time, anesthesia time, PACU stay time, and postoperative anxiety and pain scores were not different between the groups. A few patients needed intraoperative or postoperative additional opioids, but did not show a difference between the groups (Tables 3 and 4). One patient in the rocuronium group showed symptoms of postoperative residual curarization in the PACU and had a delayed discharge from the PACU—45 minutes compared with an average time of 23.8 minutes. One patient in the control group showed testicular torsion 2 days after surgery, and no patient showed recurrence of inguinal hernia until 1 year ager surgery.

Figure 1

A CONSORT diagram.

Table 2

Patient characteristics.

Figure 2

The distribution of a surgical condition score. 1 = poor, 2 = acceptable, 3 = good, 4 = excellent (P = .570).

Table 3

Intraoperative characteristics.

Table 4

Postoperative characteristics.

Discussion

The main finding of this study is that the use of a neuromuscular blocker did not influence the incidence of intraoperative patient movement or the surgical condition in children undergoing inguinal herniorrhaphy using an I-gel. There was also no difference in postoperative surgical complications including recurrence of hernia. Additionally, the recovery times were longer in the rocuronium group than in the control group. The difference was only approximately 1 minute; however, considering the instability of the patients’ condition during this period, the difference is meaningful. Because of the short duration of the procedure, we reduced the dose of rocuronium and only used 0.45 mg/kg (1.5 × ED95) instead of 0.6 mg/kg (2 × ED95). Had we used the full intubating dose of rocuronium, the difference in recovery time might have been greater.

We were able to find only a few studies regarding the necessity of neuromuscular blockers in specific surgical procedures, and the studies were concerned exclusively with adults. One concerned radical retropubic prostatectomy, in which significantly more patients showed good to excellent surgical conditions with neuromuscular blockers than patients without them.[ However, the authors concluded that the routine use of neuromuscular blockers in adequately anesthetized patients undergoing this process might not be indicated because two-thirds of patients without the use of neuromuscular blockers showed a good to excellent surgical condition. The other study concerned laparoscopic gynecological surgery[; the authors concluded that a neuromuscular blockade was not necessary in general anesthesia using ProSeal laryngeal mask airway (LMA) for this process. They reported that the insertion conditions for ProSeal LMA and surgical conditions were comparable with or without neuromuscular blockers, and that the recovery time was shorter in the group without the neuromuscular blocker. Our study is different from previous ones in that we studied young children aged 1 to 6 years, and the surgical procedure was limited to inguinal herniorrhaphy. However, our results are in line with those of previous studies in that the insertion conditions for the I-gel and surgical conditions were comparable between the groups, whereas the recovery time was prolonged in the group that received a neuromuscular blocker.

Although neuromuscular blockers are valuable components of general anesthesia, there are several undesirable effects. First, postoperative residual curarization is the most common complication. With a train-of-four ratio <0.9, the reported incidence of postoperative residual curarization is as high as 50% after the use of an intermediate-duration neuromuscular blocker, with the highest incidence reported after short surgical procedures.[ In children, however, recovery from a neuromuscular blockade is quicker and postoperative residual curarization is rarer than in adults.[ Nevertheless, caution should be used to prevent residual curarization in patients recovering from a neuromuscular blockade. Indeed, 1 of our patients in the rocuronium group had a delayed discharge from the PACU due to symptoms of residual curarization. Second, neuromuscular blockers are the leading cause of perioperative anaphylaxis. Although the incidence of perioperative anaphylaxis is not high, it is a serious life-threatening complication, with a reported mortality of 3% to 9%.[ Third, neuromuscular blocker is 1 of the factors increasing the risk of accidental awareness during general anesthesia.[ Of the patients who had recall of intraoperative events, all of the paralyzed patients had pain, anxiety, or delayed neurotic symptoms compared with none of the nonparalyzed patients.[ In this regard, the routine use of neuromuscular blockers during general anesthesia should be reconsidered and should be confined to procedures with an obvious gain.

Our study has several limitations. First, we used sevoflurane for the maintenance of anesthesia, despite the fact that inhalational anesthetics have some degree of muscle-relaxant properties. It remains to be elucidated what would be the outcome under intravenous anesthesia. Second, our study population was limited to very young children, aged 1 to 6 years, whose muscle power is relatively weak and could be easily controlled. Our results cannot be extended to older children or adults. Third, we did not use intraoperative neuromuscular monitoring and cannot rule out the possibility of postoperative residual curarization in patients who received rocuronium, which might affect the recovery time or postoperative agitation score. However, most of our patients recovered well; only 1 patient in the rocuronium group showed symptoms of residual curarization in the PACU, but fully recovered without complication.

Conclusions

In conclusion, not using neuromuscular blocker in children aged 1 to 6 years undergoing inguinal herniorhaphy under sevoflurane anesthesia using an I-gel does not affect the surgical condition and results in faster recovery from anesthesia.