Volume 6, No. 1 • Spring 1991

Safety of Various Types of Anesthetics Tied to Risk Factors

James B. Forrest, M.D., Ph.D.

Large Multi-Center Trial Evaluates Drugs, Adverse Outcomes

Potential risk factors for adverse outcomes of general anesthesia include, among others, the health status of the patient, the type of surgery, and the anesthetic drugs used. Unfortunately, very few studies have examined these risk factors in sufficient detail to assist the anesthesiologist in everyday practice. In our large study, we hoped originally to test two hypotheses. (1) that there are no significant differences in the risks of death, myocardial infarction, and stroke with the use of enflurane, fentanyl, halothane, or isoflurane, and (2) that there are differences for other adverse outcomes, such as arrhythmias, hypotension, or vomiting with these four anesthetics. To test the first hypothesis would require 230,000 patients to be studied and we therefore decided to focus on the second hypothesis.

A prospective randomized clinical trial of these four anesthetics was done involving 17,201 patients in 15 university teaching hospitals in the United States and Canada. (1) Adult patients were studied before, during and up to seven days after general anesthesia with 66 types of adverse outcomes recorded. In this study most patients were healthy (90.7%) but there were 1,607 patients ASA Physical Status 3 or 4. The most common types of surgery were musculoskeletal, abdominal and gynecologic and about two thirds of the patients were female. Nineteen patients in the study died and in seven of these, the anesthetic may have been a contributing factor. (2)

The rates of 16 of 66 types of adverse outcomes differed among the four study anesthetics. Thus atrial, nodal, and ventricular arrhythmias were more common with halothane; tachycardia was more common with isoflurane; bradycardia and hypertension were more common and hypotension less common with fentanyl. Cough, laryngospasm, and secretions were equity common with the three volatile anesthetics whereas bronchospasm was more common with fentanyl. Postanesthetic nausea and vomiting were more common but shivering was less common with fentanyl. Most of these adverse outcomes were minor but severe ventricular arrhythmia was more common with halothane, severe hypertension and bronchospasm were more common with fentanyl, and severe tachycardia was more common with isoflurane.

Risk Factors Studied

The next stage of our analysis was a detailed computation of the risks and predictors of severe perioperative adverse outcomes in the 17,201 patients in the study.’ One hundred potential risk factors, such as preoperative diseases, surgical procedures, age, gender, obesity, smoking status, ASA Physical Status and the four study anesthetics were tested for each of the 66 types of severe perioperative outcomes. lndependentpixActorsforsevewcardiovascularoutcomesincludedpreoperativecardiovasculardisease, cardiothoracic surgery, ASA Physical Status 3 or 4, age over 60 years as well as the study anesthetics. We found most predictors confirmed the overall clinical experience of the practicing anesthesiologist. However, some were less important than expected, for example preoperative diabetes, COPD, or asthma carried only relatively small risks of severe perioperative outcomes.

The clinical implications of the Multicenter Study of General Anesthesia relate to the prediction of the risks of a wide range of severe perioperative adverse outcomes which can be computed for an individual patient. This provides the anesthesiologist with a guide to the appropriate selection of the anesthetic as well as highlights those preoperative conditions and types of surgery that have the potential for serious risk for that patient.

Dr. Forrest, McMaster University, Hamilton, Ontario, is organizer and lead author of the comparison studies of different anesthetics.


1. Forrest JB, Rehder K, Goldsmith CH, Cahalan MK, et al: Multicenter Study of General Anesthesia. I. Design and Patient Demography. Anesthesiology. 72:252-261,1990.

2. Forrest JB, Cahalan MK, Rehder K, Goldsmith CH, et a]: Multicenter Study of General Anesthesia. 11. Results. Anesthesiology 72:262-268, 1990.

3. Forrest JB, Rehder K, Cahalan MK, Goldsmith CH: Multicenter Study of General Anesthesia. Ill. Predictors of Severe Perioperative Adverse Outcomes (submitted for publication).