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.
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.


METHODS
Phase III, randomized, open-label clinical trial.


METHODS
12 international surgical units.


METHODS
555 consenting inpatients undergoing surgeries of intermediate duration.


METHODS
Subjects received either sevoflurane (n = 272) or isoflurane (n = 283) as their primary anesthetic drug, each administered in nitrous oxide (N2O) (up to 70%) and oxygen (O2) 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 variable was permitted. Comparison of efficacy was based on observations made of the rapidly and ease of recovery from anesthesia and the frequency of untoward effects for the duration of anesthesia in 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 171 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.


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 on the sevoflurane group had no untoward effect versus 39% in the isoflurane group. Three patients who received sevoflurane had serum inorganic fluoride levels 50 microM/I. or greater though standard tests indicated no evidence of associated renal dysfunction.


CONCLUSIONS
Sevoflurane anesthesia, as compared with isoflurane, may be advantageous in providing a smoother clinical course with a more rapid recover.
Department of Anesthesia, Indiana University School of Medicine, University Medical Center, Indianapolis, USA.
C
C
Campbell
M
M
Andreen
M F
MF
Battito
E M
EM
Camporesi
M E
ME
Goldberg
R M
RM
Grounds
J
J
Hobbhahn
P
P
Lumb
J M
JM
Murray
D R
DR
Solanki
S O
SO
Heard
P
P
Coriat
D000328:Adult; D000368:Aged; D000698:Analgesia; D000762:Anesthesia Recovery Period; D000769:Anesthesia, Inhalation; D018685:Anesthetics, Inhalation / Q000008:administration & dosage* / Q000009:adverse effects; D018686:Anesthetics, Intravenous / Q000008:administration & dosage; D004987:Ethers / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage; D005459:Fluorides / Q000097:blood; D005500:Follow-Up Studies; D006801:Humans; D007530:Isoflurane / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008738:Methyl Ethers; D008875:Middle Aged; D009609:Nitrous Oxide / Q000008:administration & dosage; D009949:Orientation / Q000187:drug effects; D010100:Oxygen / Q000008:administration & dosage; D012449:Safety; D000077149:Sevoflurane; D013874:Thiopental / Q000008:administration & dosage; D014851:Wakefulness / Q000187:drug effects
D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D004987:Ethers; D008738:Methyl Ethers; D000077149:Sevoflurane; D007530:Isoflurane; D013874:Thiopental; D009609:Nitrous Oxide; D005459:Fluorides; D010100:Oxygen; D005283:Fentanyl