This randomized controlled trial (registration number: ChiCTR2000034105) included 390 children who received internal inguinal ring ligation at the Baoding Children’s Hospital between March 2019 and May 2019. This study was conducted in agreement with the GCP standards and Declaration of Helsinki, and approved by the Ethics Committee of the Baoding Children’s Hospital (approval number: 201829). The parents of all children provided informed consent.

The inclusion criteria were: (1) Children aged 1-3 years and weighing 10-20 kg; (2) Received elective laparoscopic unilateral internal inguinal ring ligation; (3) American Society of Anesthesiologists (ASA) scores of I-II; (4) Usage of a continuous constant speed intravenous analgesia pump (CCIA) immediately after surgery; and (5) In agreement with the ethics requirements, children volunteered to participate in the study, and their parents provided informed consent. The exclusion criteria were: (1) Neurological disorders or cognitive impairments, such as epilepsy, depression, and dementia; (2) History of using psychotropic drugs; (3) Vital organ (such as the liver, heart, and kidney) dysfunction; (4) Vasoactive drugs received during the surgery; (5) Allergy to sufentanil or dexmededomide; and (6) Participated in other clinical trials within the last 3 mo.

The randomization strategy was designed by an independent third-party that has not participated in this study. According to the random number table generated with SPSS 22.0 software (SPSS Inc., Chicago, IL), the 390 children were 1:1:1 randomized into a dexmededomide group (D group), a dexmededomide + sufentanil group (DS group), and a sufentanil group (S group). The protocol of randomization was also managed by an independent third-party that has not participated in this study. The personnel in charge of drug preparation confirmed the randomization results of the children, then labeled the corresponding syringes with the number 1, 2, or 3 according to the protocols, and after that contacted the investigator in charge of the randomization to pass the ID numbers and names of the children. Then, the investigator in charge of the randomization informed the personnel in charge of drug preparation regarding the randomization numbers and groups of children. After confirming the groups of children, the drugs were prepared according to the study protocols, and the randomization numbers of the children were attached to the corresponding syringes.

Double-blind approach was adopted in this study, in which children (guardians), personnel in charge of drug preparation, and data collectors were independent from each other. All the children (guardians) and data collectors were masked from the randomization results, and the only personnel in charge of drug preparation knew the groups of the children. After the surgery of internal inguinal ring ligation was completed, the anesthesia was stopped, and the children were equipped with a CCIA. The packages of all the analgesics were masked by a white envelope. After the CCIA was equipped and the child restored satisfactory autonomous respiration, the laryngeal mask was removed and the child was transferred to the recovery room, and then transferred back to the ward after awakening. The postoperative data were collected by an investigator not participating in drug management and blinded to the randomization results. The anesthetists were strictly isolated from the data collector in the study. In addition, the statistical analyses of data were also performed by statisticians from an independent third-party that has not participated in this study. The preparation and management of all the drugs in this study were performed by the same personnel. All the surgeries were performed by the same group of surgeons. The study processes were supervised by two supervisors.

The children were routinely fasted from food for 8 h, and not allowed to drink water for 2 h. After transfer to the operating room, the vital signs of the children were monitored. The induction strategy included 3 mg/kg propofol, 0.1 mg/kg cisatracurium besylate, and 2 μg/kg remifentanil. After the requirements of tracheal intubation were met, the laryngeal mask was applied and the mechanical ventilator was connected to manage the respiration. The respiratory parameters were adjusted to maintain the EtCO₂ at 35-40 mmHg. Afterwards, 0.35 μg/kg/min remifentanil and 2% sevoflurane was applied for anesthesia maintenance. After the surgery ended, the anesthesia was stopped, and the children were equipped with a CCIA. According to the randomization results, the drugs were prepared as follows: (1) D group: Normal saline was added to 1.5 μg/kg dexmededomide until the volume was 100 mL. The background infusion rate was 2 mL/h, and the drug was pumped in the CIAA for 48 h; (2) DS group: Normal saline was added to 1.5 μg/kg dexmededomide and 1.5 μg/kg sufentanil until the volume was 100 mL. The background infusion rate was 2 mL/h, and the drug was pumped in the CIAA for 48 h; and (3) S group: Normal saline was added to 1.5 μg/kg sufentanil until the volume was 100 mL. The background infusion rate was 2 mL/h, and the drug was pumped in the CIAA for 48 h.

The study was completed 48 h after surgery. After the data collection, for the children in D group or S group with a Face, Legs, Activity, Cry, and Consolability (FLACC) pain score ≥ 7 points, one other analgesic drug was added to combination for alleviating the pain.

General characteristics, including age, sex, height, body weight, vital signs, diagnosis, previous histories, allergic histories, pre-operative examination results, and combined drug therapies, were collected.

The primary endpoint was the percentage of children with an FLACC analgesia score ≤ 3 points at 2 h after surgery. The secondary endpoints included the FLACC analgesia score, pediatric anesthesia emergence delirium score, Ramsay sedation score, Cole 5-point scale score, and safety treatment.

The FLACC scale was used for the evaluation of analgesia success. The FLACC score is a useful tool for the evaluation of postoperative pain in children aged from 2 mo to 7 years, which includes five items. The data collectors were required to observe the children for 1-15 min, and then scores were assigned for the children according to the findings and the descriptions in the scale. The scores for each item ranged from 0-2 points, and the scores of each item were added to acquire the total score, which ranged from 0-10 points. The score of 0 indicated relaxed and comfort, 1-3 points indicated mild discomfort, 4-6 points indicated moderate pain, and 7-10 points indicated severe pain, discomfort, or both. In this study, FLACC scale evaluation was performed at 2, 4, 6, 8, and 12 h after the equipment of CIAA, and the corresponding data were collected.

Sedation evaluation was evaluated using the PAED scale, Ramsay sedation score, and Cole 5-point scale score (CPS). PAED is a scale for the evaluation of agitation in the recovery period that has been proven effective, which could be used to evaluate the agitation of children after surgery. This scale evaluates the agitation from the following five aspects: Eye contact; aware of the surroundings; purposeful actions; restless, confused, or delirium; and inconsolable crying. The score for each item ranges from 0-4, and the total score of the scale is 20. Children with a score > 12 points were considered with agitation in recovery period. Higher scores indicated more severe agitation of children. The Ramsay sedation score is commonly used for patients receiving continuous intravenous sedation, with a total score ranging from 1 to 6 points: 1 point = restless and agitated; 2 points = co-operative and tranquil; 3 points = asleep and responding to commands; 4 points = asleep, and could be waked; 5 points = asleep, with sluggish responses; and 6 points = could not be waked. The scores of 2-3 indicated satisfactory sedation. The total score of CPS is 5 points, with 1 point indicating asleep, 2 indicating awake and tranquil, 3 indicating agitated and crying, 4 indicating inconsolable and crying, and 5 indicating severe agitation and disorientation. The scores of 2 points or higher indicated satisfactory sedation. In this study, the sedation scale evaluation was performed at 2, 4, 6, 8, 12, and 24 h after the equipment of CCIA, and the corresponding data were collected.

This study was a non-inferiority designed randomized controlled trial, which aimed to investigate whether or not dexmededomide monotherapy is not inferior to the combined use of sufentanil and dexmededomide for postoperative analgesia in children who received laparoscopic unilateral internal inguinal ring ligation. According to the results of preliminary experiments and previous studies, the percentage of children with an FLACC analgesia score ≤ 3 points at 3 h after surgery was 80% after the combined application of sufentanil and dexmededomide. We assumed that the effects of using dexmededomide alone are not inferior to the combined use of sufentanil and dexmededomide. The non-inferiority margin (δ) of this study was set at 15%, α was 0.025 (one-sided), and power (1-β) was 0.8. The sample sizes of the three groups (N1 = N2 = N3) were equal. PASS 11 software showed that the sample size was 112 for all the three groups. After the drop-off rate of 20% was considered, 130 children were planned to be included in each group.

All the data were managed with Epidata3.0 software. The data input was performed independently by two investigators, with following checks and modifications to ensure the accuracy of the data. SAS 9.4 (SAS Institute Inc, Cary, North Carolina) was used for the statistical analyses of data. The baseline data, including age, sex, body weight, vital signs, surgeries, initiate sedation, and sedation scores, were compared by one-way analysis of variances (ANOVA) or non-parametric tests, and are described as the mean ± SD. Paired t-test was performed for the comparisons within groups, while for the data not following a normal distribution or with unequal variances, non-parametric test was performed. One-way ANOVA or non-parametric test was performed for the comparison of data among the three groups, and LSD test was further performed for the pair-wise comparison. P ≤ 0.05 was considered statistically significant.

A total of 390 children satisfied the inclusion criteria in this study, of which nine did not complete the study, and four were excluded due to low compliance. Finally, 377 children were included, of which 125, 126, and 126 were in the D group, DS group, and S group, respectively (Figure 1). Statistical analyses showed that the three groups were comparable with regard to baseline data, including age, sex, body weight, vital signs, initial sedation, and sedation scores (P > 0.05) (Table 1).

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Figure 1 Study flow chart.

The FLACC pain scores of children at 2, 4, 6, 8, 12, and 24 h after surgery are shown in Table 2. The percentages of children with an FLACC analgesia score ≤ 3 points at 2 h after surgery were not different between groups (P > 0.05). The comparisons of the data in the three groups showed that the FLACC scores at different time points were not significantly different among the three groups (P > 0.05).

The pair-wise comparison of PAED scores among the three groups showed that the PAED score in the D group was significantly lower than that in the S group at 4 and 6 h after surgery (P < 0.05). The PAED score was also significantly lower in the DS group than in the S group at 2 and 4 h after surgery (P < 0.05), and significantly lower in the D group than in the DS group at 6 h after surgery (P < 0.05) (Table 3).

Statistical analysis of the satisfactory degree to Ramsay sedation score at different time points (sedation scores of 2 or 3 points were considered satisfactory) showed that more children in the D group and DS group were satisfactory to the sedation at 2-6 h after surgery than those in the S group (P < 0.05); however, the difference was not statistically significant between the D group and DS group (P > 0.05) (Table 4).

The pair-wise comparison of satisfactory degree to CPS sedation score (CPS score > 2 points indicated satisfactory) at different time points after surgery among the three groups showed that more children in the D group and DS group were satisfactory to the sedation at 2 h after surgery than those in the S group (P < 0.05); however, the difference was not statistically significant between the D group and DS group (P > 0.05) (Table 5).

The comparison of postoperative incidence of nausea and vomiting showed that the incidence was significantly lower in the D group than in the S group and DS group (P < 0.05). Four (3.1%), 18 (14.3%), and 10 (7.9%) of children in the D group, S group, and DS group, respectively, demonstrated symptoms of nausea after surgery. In addition, 0, 8 (6.3%), and 2 (1.6%) of children in the D group, S group, and DS group, respectively, demonstrated symptoms of vomiting after surgery (Table 6).

Pediatric inguinal hernia is common in children. Safe and effective analgesia strategy remains one of the priorities for pediatric inguinal hernia treatment.

Search for safe and effective analgesia strategy is one of the priorities for inguinal hernia treatment in pediatric practice.

Our aim was to explore the safety and efficacy of dexmededomidine monotherapy for postoperative analgesia in children who received laparoscopic unilateral internal inguinal ring ligation.

This randomized single-center controlled trial included children (aged 1-3 years, ASA grade I-II), randomly divided into the D group, DS group, and S group. The analgesia effect, sedative effects, and complications were compared.

Finally, 377 children were included, of which 125, 126, and 126 were in a dexmededomidine group (D group), a dexmededomidine + sufentanil group (DS group), and a sufentanil group (S group), respectively. The analgesia effect showed no difference among the three groups. The sedative effects were significantly better in the D group than in the S group, but not significantly different from that in the DS group. The incidence of nausea and vomiting was significantly lower in the D group than in the S group and DS group.

Analgesic effects of dexmededomidine monotherapy were comparable with those of sufentanil alone or in combination with dexmededomidine for children who underwent laparoscopic unilateral internal inguinal ring ligation, with better sedative effects and a lower incidence of adverse events.

Dexmededomidine for analgesia and sedation is worth to be applied in pediatric inguinal hernia treatment. Pediatric inguinal hernia is common in children.