The study was prospective, randomized, comparative, and double-blind. There were no changes in methods after the eligibility criteria.
The number of participants was calculated using the SPSS17® program. A difference of 3 in pain intensity was considered significant at 80% power and a 95% confidence interval. Based on a preliminary evaluation,9 the estimated standard deviation of the pain intensity score within the groups was 2.2, and a sample size of 20 patients per group was calculated for a power of 0.95 and α = 0.05.
Participants were randomly drawn and allocated to one of the groups. The randomization was performed by the Randomizer® program. The drawings for allocation in the groups were made by numbers placed in an envelope. On the day of surgery before the onset of anesthesia, the pharmacist opened the participant’s envelope and prepared the solution according to the draw with esmolol or saline solution.
The anesthesiologist and the evaluator did not know which group the participant belonged to until the end of the study. In case of an emergency, the anesthesiologist caring for the patient could break protocol and see the group assignment.
After approval from the Ethics Committee (CAAE No 83115117.5.0000.5450) and signing the Consent Form, 40 patients aged 18–50 years, of both genders, physical status I or II by American Society of Anesthesiology (ASA), submitted to laparoscopic bypass gastroplasty were included in the stud. This study was conducted in accordance with the Declaration of Helsinki.
Patients with drug allergy; respiratory, renal, hepatic, cardiovascular or psychiatric disease; cognitive alteration; use of beta-adrenergic antagonists; or use of illicit drugs were excluded.
Monitoring was performed with a cardioscope, capnograph, pulse oximeter, noninvasive blood pressure, and neuromuscular blockade device.
Anesthesia was with fentanyl (5ug/kg), propofol (2–4mg/kg) and rocuronium (0.6mg/kg and as required), 50% oxygen (without nitrous oxide) and 2% sevoflurane. Remifentanil intraoperatively (0.05 to 0.2ug/kg/min) was given if the heart rate was greater than 15% and the systolic blood pressure was greater than 20% of the baseline values. The baseline heart rate and systolic blood pressure was defined as the mean of the two lowest measurements recorded during the 3- to 5-minute interval prior to anesthetic induction. In case of hypotension, defined as systolic blood pressure less than 80 mmHg or mean arterial pressure lower than 60 mmHg, a bolus of ephedrine (0.5mg IV) was administered; in case of bradycardia, defined as heart rate <50, a bolus of atropine was administered (0.5mg).
Before extubation, sugammadex (2 mg/kg) was administered; if necessary, an additional dose (2 mg/kg) was given. Patients were kept in the recovery unit and received oxygen (5 L/min), until saturation was greater than 92% in ambient air for 10 min. Side effects and complications were noted. Patients with heart rate < 45bpm or mean blood pressure <60 mmHg were withdrawn from the study and treated.
Participants were divided into two groups. Group 1 patients received a 0.5mg/kg bolus of esmolol in 30 mL of saline before induction of anesthesia, followed by infusion of 15 µg/kg/min until end of surgery; group 2 received a 30mL bolus of saline and infusion of the same volume as G1.
The study was retrospectively registered at Brazilian Clinical Trials Registry (ReBec–9w3k77). The data were collected at IGESP hospital, São Paulo, Brazil.
Postoperative pain was treated with venous morphine (5mg per dose) as required.
The following were evaluated: consumption of intra-operative remifentanil; time to supplementation; intensity of pain by numerical scale from 0 to 10 after extubation (T0) and 30 minutes,1h, 2h, 6h, 12h and 24h; morphine dose over 24h; and side effects
The primary outcome was pain intensity reduction. The secondary outcomes were need of analgesic complementation, and adverse effects. No change in outcome was made after the trial commenced.
The results were submitted to statistical analysis by SPSS® program. The following tests were used: Wilcoxon for age, weight, height, body mass index, duration of surgery, remifentanil, time to recovery, time to first supplementation, dose of morphine in 24h, and pain intensity; chi-square test for number of participants requiring remifentanil and morphine supplementation; and Fisher’s test for side effects. The level of statistical significance was p<0.05.