Ethical approval for this study was provided by the Ethical Committee of Anhui Medical University, Hefei, Anhui (approval number:20160104). All patients provided written informed consent. The trial was registered before patient enrollment at clinicaltrials.gov (NCT02673723, Principal investigator: Erwei Gu, Date of registration: February 4, 2016). We conducted the study according to the principles of the Helsinki Declaration and the International Conference on Harmonization guidelines for Good Clinical Practice, at the First Affiliated Hospital of Anhui Medical University.
The study examined 480 adult patients scheduled at five hospitals in China for general anesthesia tracheal intubation between March 2016 and December 2018. Included study participants were aged 18-65 years, with an American Society of Anesthesiologists (ASA) physical status classification of I-II. Exclusion criteria included: severe bradycardia or any type of electrocardiogram conduction block, use of an α agonist or antagonist within two weeks; opioid use within 24 hours; serious heart, liver, kidney, or cerebrovascular disease; allergy to the drugs used in this study; predictably difficult airway; three instances of intubation failure or the patient unable to bear intubation; any respiratory illness; obstacles in language communication; or a person of unsound mind.
Patients were randomly divided into a dezocine group and a saline group. Dezocine was dosed in kilograms of body weight. The specific method of random grouping is as follows: the patients in each center entered the test groups according to the order of enrollment and the random number (scratch card) generated by the statistical software. Randomization results were concealed in opaque envelopes until informed consent had been given. Patients and perioperative period observers were blind to the patient’s assigned group.
Anesthesia and research procedure
Baseline vital signs were recorded immediately before the procedure. All patients received supplemental oxygen intranasally (6L/min) and underwent continuous monitoring of heart rate (three-lead electrocardiography), oxygen saturation (pulse oximetry), blood pressure (automated blood pressure cuff, serial measurements every 3 minutes). The respiratory rate and end-tidal CO2 were also recorded. Dezocine (5 mg/mL; Yangtze River Pharmaceutical, Co., Jiangsu, China) was diluted with normal saline to one mg/mL and was administered with one bolus of dezocine 0.05 mg/kg (D0.05 group), 0.10 mg/kg (D0.1 group), 0.15 mg/kg (D0.15 group), or an equal volume of 0.9% normal saline (saline group) intravenously three to five seconds before anesthesia induction. Sufentanil (Yichang Humanwell Pharmaceutical Co., Hubei, China) was diluted with normal saline from its original concentration of 50 μg/mL to a concentration of 5 μg/mL. Two minutes later, all patients received 0.4 μg/kg sufentanil over three seconds. Five minutes after sufentanil injection, the anesthesiologist used a laryngoscope to expose the glottis, and topical anesthesia was performed with two mL 2% lignocaine via the larynx. Two minutes later, the anesthesiologist exposed the glottis for tracheal intubation.
Immediately after injection, an anesthetic registrar recorded the occurrence of cough as ‘yes’ or ‘no’. Depending on the number of coughs observed, the cough severity was graded as mild (one to two), moderate (three to five), or severe (> five). Blood pressure and heart rate (HR) were recorded before sufentanil injection(T0-s), one minute (T1-s), three minutes (T3-s), and five minutes (T5-s) after sufentanil injection. Blood pressure and HR were recorded during intubation (T1), and at one minute (T2) and three minutes (T3) after intubation, and the patient’s intubation response were observed in terms of five variables [10,11]
- Ease of intubation: 1 - very easy, 2 - easy, 3 - general, 4 - difficult, 5 - very difficult.
- Intubation comfort score: 1 - no reaction, 2 - slight grimacing, 3 - heavy grimacing, 4 - verbal objection, and 5 - defensive movement of head or hands.
- Limb movement: 1 - none, 2 - slight, 3 - moderate, and 4 - severe.
- Glottis exposure:1- full exposure, 2- partial exposure, and 3 - no exposure.
- Patient Satisfaction:1- very satisfied, 2-satisfied, 3- no opinion, 4-dissatisfied, -very dissatisfied.
If patients experienced adverse reactions such as hypertension, hypotension, tachycardia, bradycardia, or respiratory depression during the experiment, we had corresponding unified treatment measures.
The primary outcome of our study was to observe the incidence of respiratory depression. Respiratory depression was considered to be significant when SpO2 was 90%, end-tidal CO2 was >50 mmHg at any time, respiratory rate was <6 breaths/minute, or when airway obstruction with the cessation of gas exchange was observed at any time (noted by an absent end-tidal CO2 waveform).
Secondary outcomes included the success rate of intubation, ease of intubation, intubation comfort score, sore throat, hoarseness, lethargy, limb movement, glottis exposing, and the satisfaction of patients during intubation. Hemodynamic changes were recorded after sufentanil injection and awake intubation. The patients' memories, throat pain, and hoarseness were followed up 24 hours after the operation.
According to the results of our preliminary experiment, this study required at least 88 patients per group to attain appropriate power (a = 0.05 [two-tailed]; β = 0.2). The sample size was increased to 120 patients per group to account for any dropouts. Data are expressed as mean ± standard deviation (SD) or as the number or percentage of patients. Patient characteristics and the hemodynamic variables between the groups were compared using unpaired two-tailed t-tests. The incidence and severity of cough, gender proportions, and ASA class were assessed using Chi-squared tests and Fisher’s exact test with Bonferroni correction. P < 0.05 was defined significance. A Bonferroni correction would be used if the difference between groups was P < 0.05. P < 0.0083 was used to define significance to reduce the risk of type I error due to multiple analyses or for subgroup interactions. All analyses were performed using SPSS 16.0.