A phase III, multicenter, open-label, randomized, comparative study evaluating the effect of sevoflurane versus isoflurane on the maintenance of anesthesia in adult ASA class I, II, and III inpatients

Abstract

Study Objective: To compare the clinical efficacy and safety of sevoflurane and isoflurane when used for the maintenance of anesthesia in adult ASA I, II, and III inpatients undergoing surgical procedures of at least 1 hour's duration. Design: Phase III, randomized, open-label clinical trial. Setting: 12 international surgical units. Patients: 555 consenting inpatients undergoing surgeries of intermediate duration. Interventions: Subjects received either sevoflurane (n = 272) or isoflurane (n = 283) as their primary anesthetic drug, each administered in nitrous oxide (N 2O) (up to 70%) and oxygen (O 2) after an intravenous induction using thiopental and low-dose fentanyl. The concentration of volatile drug was kept relatively constant but some titration in response to clinical variables was permitted. Comparison of efficacy was based on observations made of the rapidity and ease of recovery from anesthesia and the frequency of untoward effects for the duration of anesthesia to the return of orientation. Safety was evaluated by monitoring adverse experiences, hematologic and non-laboratory testing, and physical assessments. In 25% of patients (all patients in both treatment groups at selected investigational sites), plasma inorganic fluoride concentrations were determined preoperatively, every 2 hours during maintenance, at the end of anesthesia, and at 1, 2, 4, 8, 12, 24, 48, and 72 hours postoperatively. Measurements and Main Results: Emergence, response to commands, orientation, and the first request for postoperative analgesia were all more rapid following discontinuation of sevoflurane than following discontinuation of isoflurane (sevoflurane, 11.0 ± 0.6, 12.8 ±0.7, 17.2 ± 0.9, 46.1 ± 3.0 minutes, respectively, versus isoflurane, 16.4 ± 0.6, 18.4 ± 0.7, 24.7 ± 0.9, 55.4 ± 3.2 minutes). The incidence of adverse experiences was similar for sevoflurane and isoflurane patients. Forty-eight percent of patients in the sevoflurane group had no untoward effects versus 39% in the isoflurane group. Three patients who received sevoflurane had serum inorganic fluoride levels 50 μM/L or greater though standard tests indicated no evidence of associated renal dysfunction. Conclusion: Sevoflurane anesthesia, as compared with isoflurane, may be advantageous in providing a smoother clinical course with a more rapid recovery.