This study was approved by the Ethics Committee of Affiliated Hospital of Chengde Medical College (22029). This prospective, randomized, controlled, double-blinded study was performed from September 2015 to September 2016, and the hospitalization time of patients before operation was less than 1 week in the burn unit of our hospital. The total burn areas ranged from 31–50% of total body surface area (TBSA), with full-thickness burn surface area (FTBSA) 11–20% of the area. After voluntarily signed informed consents from patients or their legal representative, forty patients with severe burns, aged 18 to 65 years, ASA II or III, scheduled to receive elective general anesthesia with endotracheal intubation were included in the study. All patients were randomly assigned into etomidate group (Group E) (2 mg/mL, Jiangsu Nhwa Pharmaceutical, Xuzhou, China) and propofol group (Group P) (10 mg/mL, Fresenius Kabi Pharmaceutical Co. Ltd, Beijing, China) using web-based randomization software method. Exclusion criteria included: allergies to any of the study drugs; patients with epilepsy; body mass index (BMI) < 13 kg/m2 or > 30 kg/m2; history of heart, lung, liver or kidney dysfunction and adrenocortical insufficiency; airway abnormalities; administration of sedative or opioids within 24 hours; history of general anaesthesia within 7 days; pregnancy and mental disease.
All patients fasted for more than 8 hours before surgery and did not receive any premedication. On arrival at the operating room, the standard monitors consisted of heart rate (HR), electrocardiogram (ECG), pulse oximetry (SpO2), invasive arterial pressure (IBP), end-tidal carbon dioxide (PETCO2) and bispectral index (BIS) (BISTM XP sensor). In the meantime, an indwelling cannula was inserted into a large vein by nurse. Anesthesia was induced after ensuring that the blood pressure and HR were constant. Then, the patients were preoxygenated via a face mask and induction of anaesthesia intravenously was performed with midazolam 0.05 mg/kg, fentanyl 4ug/kg, etomidate 0.3 mg/kg or propofol 2 mg/kg with 20 s injecting time, respectively. After palpebral reflex loss, the BIS value reached to 50, a single dose of rocuronium 0.6 mg/kg was given and 1 min later the patient was orotracheally intubated. Continuous infusion of propofol 6–10 mg/kg/h or etomidate 0.6-1 mg/kg/h and remifentanil 0.1 µg/kg/min-0.3 µg /kg/min maintained anesthesia. The BIS value was used as a guide to adjust the infusion rate of propofol or etomidate and that was maintained between 40 and 50. Ventilation was adjusted to maintain PETCO2 between 35–45 mmHg. To avoid the effects of diurnal changes in cortisol secretion, each study began between 8 AM to 9AM.
The patient characteristics (age, sex, weight, total burn areas, third-degree burns area), operation time and recovery time (time from drug stopping to orientation recovery (min)) of the two groups were recorded. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), HR and BIS were measured and recorded immediately at 7 different time points: the baseline (t0), before anesthesia induction (t1), 1, 3, 5, and 30 min following the intubation (t2–5), and the end of the surgery (t6). The remifentanil hydrochloride dosage was recorded during anesthesia maintenance in the two groups.
The number of patients with significant hemodynamic changes during the whole operation were recorded in the two groups: SBP or HR increases or decreases baselines by more than 30%, SBP < 90 mmHg or > 140 mmHg; HR < 50 beats/min or > 100 beats/min. Changes in MAP and HR fluctuated within 30% of the baseline values. Beyond this range, vasoactive drugs would be used for treatment (including ephedrine and atropine, etc.).
The clinical grade of myoclonic intensity was determined by the following scales for a period of two minutes: 0, no myoclonus; 1, mild myoclonus (short limb movements, such as fingers or wrists); 2, Moderate myoclonus (light movements of two different muscles, such as the face and arms); 3, Severe myoclonus (intense clonic movement of two two or more muscle groups, rapid adduction of limbs). 
Before induction of anesthesia, and at 30 min, 2 h, 24 h, and 48 h after end of surgery, artery blood (2 ml) was collected and placed in the PE tube (T0, T1, T2, T3 and T4). These samples were stored at -20℃ after centrifugation. Radioimmunoassay was used for quantifying serum concentrations of ACTH, Cor and ALD after all the samples were obtained.
All the patients were randomly assigned into Group E and Group P using web-based randomization software. One researcher sealed envelopes in which had sequential study numbers, and they were opened just before anesthesia induction.
Another researcher performed total anesthesia according to the trial protocol and randomized table.
The study was s a double-blind trial, the data collectors were blinded to which group each patient belong to and another study personnel gave the drugs intravenously. The patients also did not know which group they belong to.
Data are expressed as mean ± standard deviation (SD) or number, as appropriate.
SPSS statistical software was used for data analysis (SPSS 16.0, SPSS, Inc., Chicago, IL, USA). Kolmogorov-Simonov was used to test the normal distribution of data.
T test was used for comparison between the two groups. Repeated measures analysis of variance (RM-ANOVA) was used to compare the difference within the group and post hoc tests (Least Significant Difference, LSD). Count data were analyzed by Chi-square test. A P value of < 0.05 was considered statistically significant.
The study was designed to be a non-inferiority trial, and the aim of that was to assess whether etomidate is superior to propofol in severe burn patients. When calculating the sample size, the maximum risk was 5% and the significance level was 5%. According to the previous results, we determined that the sample size for each group should be 20 for proper reproducibility.