A single dose of dezocine suppresses emergence agitation in preschool children anesthetized with sevoflurane-remifentanil

Preschool children undergoing laparoscopic repair of an inguinal hernia by high ligation of the hernia sac at our institution between December 2014 and November 2016 were eligible for this study. Inclusion criteria were 1) American Society of Anesthesiologists (ASA) score I or II; and 2) scheduled for elective laparoscopic repair of an inguinal hernia by high ligation of the hernia sac under sevoflurane-remifentanil anesthesia. Exclusion criteria were 1) psychiatric or neurological disease; 2) sleep apnea; 3) treatment with sedative or opioid two weeks prior to surgery and 4) body mass index (BMI) ≥40 kg/m². Study participants were randomly allocated into Group C (control group, n = 50) and Group D (dezocine group, n = 50) using a computer generated table of random numbers.

This study was approved by the Ethics Committee of Huai’an First People’s Hospital, affiliated with Nanjing Medical University, China (Approval # HA141001S). Written informed consent was obtained from the patients’ parents or legal guardians.

Children were fasted for ≥4 h before induction of anesthesia and received no premedication. Upon arrival in the operating room, heart rate (HR), pulse oximetry (SpO2) and non-invasive blood pressure (BP) monitoring were applied. One experienced anesthesiologist administered anesthesia, performed tracheal intubation, and assessed intubation. Anesthesia was induced with 8% sevoflurane in oxygen flowing at 6 L/min through a pediatric anesthesia breathing circuit with a 1.5 L re-breathable bag. Initially, spontaneous respiration was assisted; subsequently, respiration was manually controlled. An intravenous cannula was sited after disappearance of the eyelash reflex. Dexamethasone 0.2 mg/kg and ondansetron 0.15 mg/kg were administered through the cannula. The concentration of sevoflurane was decreased to 1.3 minimum alveolar concentration (MAC). Tracheal intubation was attempted using a tracheal tube (size formula: internal diameter = 4 + yr./4), the muscle relaxant atracurium 1.0 mg/kg, and fentanyl 1 μg/kg. Anesthesia was maintained with 0.8–1.2 MAC sevoflurane in combination with remifentanil (0.5 μg/kg/h), BP and HR within 20% of the baseline value, and bispectral index (BIS) values between 40 and 60. Ventilation was controlled to maintain end tidal carbon dioxide (ETCO2) levels between 35 and 40 mmHg and oxygen flow at 2 L/min.

Skilled surgeons performed the operations. All incisions were infiltrated with 0.25% ropivacaine before surgery. At the completion of the surgery, remifentanil was discontinued and fentanyl 1 μg/kg was administered. Atropine 0.01 mg/kg and neostigmine 0.04 mg/kg were used to reverse residual neuromuscular blockade. Patients in Group C received 10 mL Ringer’s lactate; patients in Group D received dezocine 0.1 mg/kg (Yangzi River Co., Jiangsu, China) in 10 mL Ringer’s lactate. Concurrently, sevoflurane was terminated and controlled ventilation with 8 L/min of oxygen was instituted. Extubation was performed when the cough reflex and regular respiration were regained. After extubation, subjects were transferred to the post-anesthesia care unit (PACU). Oxygen (6 L/min) was administrated via a face-mask in the PACU.

Primary outcomes of the study were the incidence and severity of EA in the PACU. Secondary outcomes of the study were time to extubation, emergence time, Children and Infants Postoperative Pain Scale (CHIPPS) score, incidence of rescue drug administration, time in the PACU, and Ramsay sedation score.

Emergence time after extubation was defined as time to eye opening or purposeful movement in the PACU. Consciousness after emergence was evaluated using the Ramsay sedation scale [13]. In the PACU, a study investigator blinded to the study groups simultaneously assessed the incidence of postoperative EA defined as a score ≥ 3 on Aono’s four point scale or Pediatric Anesthesia Emergence Delirium (PAED) PAED score ≥ 10, and the severity of postoperative EA was described by the distribution of EA scores on the PAEDscale [1, 14]; a score ≥ 13 was classified as severe EA and a score ≥ 10 - <13 was classified as moderate EA. Postoperative pain was assessed by the CHIPPS [15]. A bolus of fentanyl 1 μg/kg was injected as a rescue medication for severe EA or a CHIPPS pain score > 5. Propofol 1 mg/kg was administered if EA was not attenuated within 5 min. Patients were discharged from the PACU to the ward when they recovered from anesthesia, defined as an Aldrete score < 9 [16].

Statistical analyses were conducted using IBM SPSS Statistics for Windows Version 20.0 (IBM Corp., Armonk, NY, USA). Based on a previous study in children undergoing cleft lip surgery under sevoflurane anesthesia that reported a 25% decrease in the incidence of EA as clinically significant [17], the sample size for the current study was calculated as 50 patients in each group (alpha value, 0.05; beta-value, 0.80).

Continuous variables were analyzed with Student’s t-test. Categorical variables including gender, ASA, and incidence of EA are reported as frequency, percentage, and risk ratios (RRs) with corresponding 95% confidence interval (CIs) and were compared using chi-square test and correction or Fisher’s exact probability test. A P value less than 0.05 was considered statistically significant.

This study included a consecutive sample of 100 pediatric patients (55 male/23 female; mean age 4.6 ± 1.9 years, range 1–6 years) (Fig. 1). All surgeries were successful. Two cases were lost to follow-up, one in Group C that experienced serious laryngospasm after extubation requiring the use of a muscle relaxant and one in Group D who suffered from bilateral inguinal hernia. The final analysis included 49 patients in Group C (29 male/20 female; mean age 4.9 ± 1.6 years, range 1–6 years) and 49 patients in Group D (26 male/23 female, mean age 4. 2 ± 2.1 years, range, 1–6 years). Patients’ baseline demographic and clinical characteristics are shown in Table 1. There were no significant differences between groups.

Primary and secondary outcome data are shown in Table 2 and Fig. 2. Incidence of EA in the PACU (10% vs. 76% and 27% vs. 86%, P < 0.05), the percentage of patients with severe EA (88% vs. 46%, P < 0.05), and the percentage of patients with moderate EA (12% vs. 54%, P < 0.05) were significantly lower in Group D compared to Group C. There were no significant differences in mean time to extubation and mean emergence time between groups. Mean CHIPPS score was significantly lower in Group D compared to Group C (1.2 ± 0.5 vs. 5.2 ± 0.6; P < 0.05). Patients need for fentanyl (18% vs. 4%) or propofol rescue (20% vs. 0%) was significantly greater in Group C compared to Group D. There was no significant difference in mean time to discharge from the PACU between groups. There were no significant differences in the incidence of postoperative events including desaturation, headache, nausea, and vomiting between the two groups.

There was no significant difference in mean Ramsey sedation score between groups. However, more patients in Group C were evaluated as level 1, which indicates they were anxious, agitated or restless, compared to Group D, while more patients in Group D were evaluated as level 2 (cooperative, orientated, tranquil) or level 3 (responsive to commands only) compared to Group C (Fig. 3).