Adverse Effects Due to Morphine Sulfate Challenge to Previous Clinical Doctrine CLAY F. SEMENKOVICH, M.D. ALLAN S. JAFFE, M.D. St. Louis, Missouri From the Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri, This work was supported in pat-l by the Specialized Centers of Research in lschemic Heart Disease, Grant HL-17646 from the National Institutes of Health, and Multicenter Investigation of the Limi- tation of Infarct Size Grant HL-17460 (this is an “ancillary study” of the MILIS grant). Requests for reprints should be addressed to Dr. Allan S. Jaffe, Washington University School of Medicine, Car- diovascular Division, 660 South Euclid Avenue, St. Louis, Missouri 63110. Manuscript accepted December 19, 1984. Despite a lack of clinical data in this area, conventional wisdom holds that morphine sulfate induces vagally mediated conduction defects, especially in patients with inferior myocardial infarction. To assess the accuracy of this “clinical pearl,” the records of 244 patients admitted to the Barnes Hospital Cardiac Care Unit with suspected acute myocardial infarction were reviewed to determine the frequency of deleterious cardiovascular effects related to the administration of morphine sulfate. Of 184 patients (156 subse- quently documented to have infarction) who received morphine sulfate, four patients had symptomatic hypotension temporally as- sociated with morphine sulfate administration. This represented a frequency of 2.2 percent for all patients treated with morphine sulfate and a frequency of 2.6 percent in those with proved infarction. In each instance, the heart rate response was inappropriate, i.e., de- creased or less markedly accelerated than might be expected given the reduced blood pressure, suggesting a vagal mechanism for the adverse effects. Only one of the four patients had inferior infarction, and in three of four instances, the adverse effect occurred after the first dose. All patients subsequently received morphine sulfate without evidence of toxicity. No case of narcotic-induced conduction abnormality was identified. This series, which is the most extensive evaluation of the topic, documents that adverse cardiovascular effects due to morphine sulfate are rare and do not conform to preconceived clinical doctrine. They consist of inappropriate heart rate responses to hypotension rather than conduction defects and are not particularly associated with inferior myocardial infarc- tion. Despite cautions concerning potential detrimental effects of morphine sulfate when it is used for analgesia in patients with myocardial in- farction [I], there is surprisingly little well-derived clinical information concerning adverse effects. Accordingly, we utilized the extensive data bank from our clinical center in the Multicenter Investigation of the Limitation of Infarct Size (MILIS) Study, to evaluate the types, in- cidences, and severity of morphine sulfate toxicity in a large group of patients admitted to a coronary care unit with suspected myocardial infarction. PATIENTS AND METHODS Washington University was one of the participating institutions in the MILIS Study. Patients presenting to Barnes Hospital with suspected infarction and at least 30 minutes of chest pain and ST segment depression or elevation, September 1985 The American Journal of Medicine Volume 79 325