Hemodynamic effects of high dose naloxone in congestive heart failure

Abstract

In humans, the salutary properties of the opioid agonist morphine in the treatment of acute pulmonary edema and chronic congestive heart failure (CHF) are well known. These are thought to be the result of vasodilatation and concomitant afterload reduction caused by binding with central 1–3 and peripheral 4 opioid receptors. This clinical pharmacologic observation suggests that the endogenous opioid peptides have the potential to contribute favorably to the regulation of the hemodynamic response to acute and chronic CHF. However, contrary to the expectation based on the therapeutic efficacy of morphine, the endogenous opioids may actually exert a deleterious effect on the hemodynamic response to cardiogenic shock and the syndrome of CHF. 5,6 Case reports describe dramatic hemodynamic improvement after the administration of low doses of the narcotic antagonist naloxone to patients suffering cardiogenic shock in the setting of an acute myocardial infarction. 7 The hemodynamic effects of therapeutic (0.02 mg/kg) or maximal (1 mg/kg) doses of naloxone have not been studied in patients with CHF. In normal volunteers naloxone at doses up to 1 mg/kg causes little alteration in blood pressure, heart rate or respiration. 8 If endogenous opioids do play a role in the regulation of the hemodynamic response to chronic myocardial failure, alterations in resting hemodynamics after the administration of an opioid antagonist to patients with CHF should be identified. We report the first study defining the hemodynamic consequences of a graded naloxone infusion in patients with CHF.