This randomized clinical study has been performed in Ain Shams University Hospitals between October 2021 and February 2022. The identification code in the ClinicalTrials.gov database is NCT 05097508. This study has been permitted by the Research Ethical Committee of Ain Shams University under the number. Every patient provided written informed consent prior to enrollment. This study adheres to CONSORT guidelines.
Forty male patients aged between 20 and 50 years with American Society of Anesthesiologists physical status (ASA) I to II.
Patients receiving any neuropsychiatric medications, undergoing neurosurgical operation, BMI above 40, or had any drug addiction were excluded from this study.
Patients’ recruitment and randomization
Randomization was performed using computer-generated random number tables in opaque, sealed envelopes prepared by an anesthesiologist who was not part of the study. The randomization was performed in a 1:1 ratio. Group assignments were enclosed in sealed, opaque, sequentially numbered envelopes by a junior anesthesiologist not involved in the study. All the attending anesthesiologists, the patients, and the data collectors were blinded to group assignments throughout the entire study period. On the scheduled day of operation, the junior anesthesiologist opened each envelope just before induction of general anesthesia, prepared the induction dose and the infusion solution of muscle relaxants, and handled it to anesthesiologist, who was then planning to collect the perioperative data. At the end of our study, the anesthesiologist was informed about the nature of the muscle relaxant needed to complete the operation safely including maintenance and reversal drugs.
Forty patients were randomly divided into 2 equal groups by a computer-generated random numbers table, each consisting of 20 patients, namely group A and group R.
No premedication was given. After the patients were admitted to the operating room, a venous cannula was inserted. Data from standard monitoring, including noninvasive arterial blood pressure, oxygen saturation, end-tidal oxygen concentration (ETO2), and end-tidal carbon dioxide concentration (ETCO2) were gathered. Neuromuscular blockade was constantly evaluated by acceleromyograph using the train-of-four-watch SX system (made in Ireland), starting when the patients were unconscious. RE and SE were monitored using a Datex Ohmeda Entropy Module (M-Entropy) and the Entropy Sensor system (made in Finland). Baseline RE and SE were recorded. Anesthesia was induced with propofol (doses of 2–3 mg/kg) and fentanyl as analgesia (doses of 1–2 mg/kg). Tracheal intubation was promoted with rocuronium (0.6 mg/kg) or atracurium (0.5 mg/kg) after an acceleromyograph count of 0. Anesthesia was sustained with isoflurane in an air-O2 mixture (FiO2 0.6, 2 L/min). Mechanical ventilation was sustained at a tidal volume of 5–7 ml/kg. Ventilator frequency was aligned for the preservation of an ETCO2 of 35–40 mmHg. After reaching equilibrium for 30 min, SE, RE, and the difference between them were recorded at MAC 0.8 and MAC 1 at two levels of muscle relaxation assessed by TOF values of 50% and 100%. Rocuronium (dose 0.01–0.012 mg/kg/min) or atracurium (dose 0.005–0.01 mg/kg/min) was continually infused and adjusted until 50% and 100% depression of T1 (first twitch by acceleromyograph) was noticed. In case of hypotension (drop in blood pressure 20% of baseline reading), 10–30 mg of ephedrine will be given intravenously by titration, and in case of bradycardia (heart rate less than 60 bpm), when it is accompanied by hypotension or any evidence of reduced perfusion, 0.01–0.02 mg/kg of atropine will be administered. The whole experiment ended prior to the start of surgery.
The primary outcome was to evaluate the correlation between SE and RE, including the RE-SE difference, at different degrees of neuromuscular block (at TOF 50% and 100%) during different MACs of isoflurane anesthesia (MAC 0.8% and 1%).
Using PASS 11 program for sample size calculation and according to Kawaguchi et al. (Kawaguchi et al. 2009) and Aho et al. (Aho et al. 2011), the expected spectral entropy among study groups = 52 ± 6.5 and 62 ± 10, sample size of 20 patients can detect the difference between two groups regarding spectral entropy after surgery with power 90% and x-error 0.05.
Data were analyzed using Statistical Package for Social Science (SPSS) version 22.0. Quantitative data were expressed as mean ± standard deviation (SD). Qualitative data were expressed as frequency and percentage. The following tests were used. Independent-sample t-test of significance was used when comparing between two means. Chi-square (χ2) test of significance was used to compare proportions between two qualitative parameters. Pearson’s correlation coefficient to analyze the degree of association between two parametric variables and the confidence interval was set to 95%, and the margin of error accepted was set to 5%. The P-value was considered significant when P-value < 0.05 and highly significant when P-value < 0.001. P-value > 0.05 was considered non-significant.