Cardiovascular manifestations of acute antibiotic toxicity during E coli endotoxin shock in anesthetized dogs

Surgically instrumented, pentobarbital-anesthetized dogs were used to examine the acute cardiovascular activities of gentamicin, tobramycin, sodium penicillin-G, and sodium cephalothin during a control state and during experimental circulatory shock induced by E coli endotoxin. Intravenous administration of 2.5, 5, 10, and 20 mg/kg gentamicin or tobramycin resulted in a transient (5--20-minute) state of cardiovascular depression, as reflected by dose-related decreases of systemic blood pressure, cardiac output, left ventricular pressure, dP/dt max, left ventricular contractile force, and dF/dt max; heart rate was affected little. Endotoxin produced a persistent state of circulatory depression characterized by hypotension, decreased cardiac output, arterial acidemia, and reduced indices of cardiac function. During endotoxin shock, the cardiovascular effects of gentamicin and tobramycin were relatively more pronounced (sometimes more than doubled) than effects observed during the control state. Equally large doses of penicillin or cephalothin, however, had no discernible circulatory effects in either control dogs or dogs subjected to endotoxin shock. Present data indicate that the cardiovascular toxicities of the aminoglycoside antibiotics gentamicin and tobramycin were augmented during experimental circulatory shock, and suggest the need for specific hemodynamic surveillance when intravenous administration of cardioactive antibiotics is required in patients with pre-existing circulatory dysfunction.