Circulatory Shock Following Intravenous Propoxyphene Poisoning. An Experimental Study of Cardiac Function and Metabolism in Pentobarbital‐Anesthetized Pigs

Abstract

The effects of continuously administered intravenous propoxyphene chloride (15 mg X min-1) on ECG, systemic, pulmonary and coronary circulations and myocardial oxygenation were investigated in eight pentobarbital-anesthetized pigs. Circulatory shock, defined as a systolic blood pressure below 60 mmHg (8.0 kPa) and a cardiac output of approximately 2.0 l X min-1 X m-2, occurred after 675 to 2025 mg propoxyphene chloride. At the time when shock occurred plasma concentrations of propoxyphene ranged from 9.6 to 15.3 micrograms X ml-1 which is within the range of the lethal concentration observed in man. Statistically significant decreases were observed for the following variables: maximum rate of rise of left ventricular pressure dP/dt (-90%), mean arterial pressure (-73%), heart rate (-46%), cardiac index (-58%), stroke volume index (-22%), left ventricular stroke work index (-85%), right ventricular stroke work index (-63%) and systemic vascular resistance (-50%). Mean pulmonary arteriolar occlusion pressure increased (+42%), whereas mean right atrial pressure and pulmonary vascular resistance remained unchanged. The arteriovenous oxygen difference increased (+53%) and total body oxygen consumption decreased (-35%). The following coronary variables decreased: coronary sinus blood flow (-57%), coronary vascular resistance (-65%), myocardial oxygen consumption (-68%), myocardial oxygen extraction (-26%) and myocardial lactate extraction (-28%). Prolongation of the ECG PQ and QRS intervals were recorded shortly before shock appeared, and all animals were in sinus rhythm till the last minute before death. The results indicate that intravenously administered propoxyphene besides being a powerful negative inotropic and chronotropic agent, is also a potent systemic and coronary vasodilator.

The Effects of Dopamine on Central Hemodynamics and Myocardial Metabolism in Experimental Propoxyphene‐Induced Shock

“…However, plasma concentrations below 1 pg*ml-'may cause death ( l ) , but this parameter is a poor measure of toxicity (13,17). The tissue concentrations found post mortem are consistent with previous observations of a high affinity of propoxyphene for heart muscle and less penetrability of norpropoxyphene into the brain (4,15). As dopamine infusion was decreased and stopped before shock reappeared, the death of the animals resembled acute propoxyphene poisoning, giving a plasma propoxyphene/norpropoxyphene ratio of 6: 1 (15,18).…”

“…Eight unpremedicated pigs, weight [4][5] kg, were used for the investigation. Anesthesia was induced with pentobarbital 900 mg i.v.…”

“…The incidence of cardiovascular complications in propoxyphene overdose is high and cardiac failure is the main cause of death (1, 2). The detrimental effects of propoxyphene on cardiovascular function have been demonstrated in experimental studies (3,4). Propoxyphene has strong negative inotropic and chronotropic properties and is a potent vasodilatator (4):…”

“…The increase in coronary blood flow far exceeded myocardial oxygen requirements. The coronary vasodilatation during extremely high infusion rates of dopamine may be due to an initial, direct action of propoxyphene paralyzing the regulation of coronary vascular tonus (4). Inhibition of cellular oxidative processes, leading to tissue hypoxia in spite of sufficient O?-delivery, may also account for the dilatation.…”

Severe acute propoxyphene overdose: plasma concentrations of propoxyphene and norpropoxyphene and the effect of dopamine on circulatory failure

“…Studies on pentobarbital-anaesthetized pigs have demonstrated that intravenously administered propoxyphene possesses negative inotropic and chronotropic effects, while dilating both the systemic and the coronary vascular bed (12). The shock state in these experiments could, however, be reversed by dopamine infusion, while naloxone had no effects (13,14).…”