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, CLASS-II, AND CLASS-III INPATIENTS

Study Objective: To compare the clinical efficacy and safety of sevofl urane and isoflurane when used for the maintenance of anesthesia in ad ult ASA I, II, and III inpatients undergoing surgical procedures of at least 1 hour's duration. Design: Phase III, randomized, open-label cl inical trial. Setting: 12 international surgical units. Patients: 555 consenting inpatients undergoing surgeries of intermediate duration. I nterventions: Subjects received either sevoflurane (n = 272) or isoflu rane (n = 283) as their primary anesthetic drug, each administered in nitrous oxide (N2O) (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 resp onse to clinical variables was permitted. Comparison of efficacy was b ased on observations made of the rapidity and ease of recovery from an esthesia and the frequency of untoward effects for the duration of ane sthesia to the return of orientation. Safety was evaluated by monitori ng adverse experiences, hematologic and non-laboratory testing, and ph ysical 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 ma intenance, at the end of anesthesia, and at 1, 2, 4, 8, 12, 24, 48, an d 72 hours postoperatively. Measurements and Main Results: Emergence, response to commands, orientation, and the first request for postopera tive analgesia were all more rapid following discontinuation of sevofl urane than following discontinuation of isoflurane (sevoflurane, 11.0 +/- 0.6, 12.8 +/- 0.7, 17.2 +/- 0.9, 46.1 +/- 3.0 minutes, respectivel y, 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 i n the sevoflurane group had no untoward effects versus 39% in the isof lurane group. Three patients who received sevoflurane had serum inorga nic fluoride levels 50 mu M/L or greater though standard tests indicat ed no evidence of associated renal dysfunction. Conclusion: Sevofluran e anesthesia, as compared with isoflurane, may be advantageous in prov iding a smoother clinical course with a more rapid recovery. (C) 1996 by Elsevier Science Inc.