Cardiovascular Responses to Diazepam and Midazolam Maleate in the Dog

Abstract

Previous clinical studies establishing the efficacy of midazolam maleate (RO 21-3981), a new water-soluble benzodiazepine for induction of anesthesia, have not critically evaluated the effects of this agent on the cardiovascular system. The present study compares the cardiovascular effects of midazolam maleate and diazepam in conscious dogs. Systemic arterial, pulmonary arterial and central venous pressures, cardiac output, LVmax dP/dt (maximum change in left ventricular pressure with time), heart rate and regional coronary blood flow were measured 3 min after i.v. administration of diazepam (0.5, 1.0 and 2.5 mg/kg) or midazolam maleate (0.25, 1.0 and 10.0 mg/kg). Midazolam maleate increased heart rate 10-20% with all 3 doses and decreased mean arterial blood pressure .apprx. 10-20% at 1.0 and 10 mg/kg. Cardiac output was increased 10-12% with all 3 doses of midazolam maleate, and LVmax dP/dt was decreased 13-16% at the 2 higher doses. Diazepam at all 3 doses did not alter heart rate or mean arterial blood pressure. Diazepam, 1.0 and 2.5 mg/kg, produced significant (17%) decreases in LVmax dP/dt, and 2.5 mg/kg produced a significant (10%) increase in cardiac output. Neither drug in any dosage altered regional coronary blood flow, systemic or coronary vascular resistance, stroke volume or stroke work. Maximum changes in cardiovascular variables occurred with doses of midazolam maleate that are 10-15 times the recommended clinical induction dosage. Apparently in concentrations necessary for induction of anesthesia midazolam maleate has minimal effects on cardiovascular function.