Enalaprilat in the treatment of hypertension and heart failure in critical care

Abstract

Abstract: Neurosurgical patients are particularly vulnerable to uncontrolled hypertension. If the patient has an unclipped cerebral arterial aneurysm, sudden increases in arterial pressure, as may be induced by laryngoscopy and tracheal intubation, may lead to rupture or rebleeding. During the immediate postoperative period after cerebrovascular surgery and intracranial neurosurgery, blood pressure elevation may lead to postoperative hemorrhage and cerebral edema.Left ventricular (LV) dysfunction is common in acute myocardial infarction (AMI). After open heart surgery, LV dysfunction may follow a perioperative AMI or mobilization of peripheral edema. Preceding ischemic cardiomyopathy and a stunned or hibernating myocardium may predispose to postoperative heart failure. In severe forms of heart failure, conventional therapy with inotropes, nitrates and diuretics may prove inadequate, and there is a need to further reduce raised preload and afterload.The present series of studies was carried out in order to assess the effects of pharmacological inhibition of angiotensin converting enzyme (ACE) on the hemodynamics, systemic oxygenation and hormonal regulation of the blood circulation in patients subjected to anesthesia due to neurosurgery or intensive care due to neurosurgery or heart failure complicating AMI or open heart surgery. Oral enalapril premedication or intravenous (i.v.) enalaprilat was either compared to inert placebo or used in five before‐after designed studies with a total of 40 neurosurgical patients and 26 heart failure patients.Oral enalapril premedication (0.1 mg/kg) was effective in preventing a blood pressure increase in response to tracheal intubation in patients subjected to cerebrovascular surgery. At a dose of 0.015 mg/kg, i.v. enalaprilat effectively controlled the postoperative hypertension of patients subjected to intracranial surgery. In patients with heart failure complicating AMI or open heart surgery, the addition of i.v. enalaprilat to conventional therapy (median doses 0.3 mg, 0.9 mg, and 2.0 mg in the three studies) relieved left ventricular filling pressure while maintaining cardiac function and systemic oxygenation. Further, enalaprilat had potentially beneficial hormonal effects in patients with severe heart failure, e.g. by lowering plasma levels of endothelin.Thus, ACE inhibition may expand our armamentarium of drugs to treat hypertension and heart failure in the intensive care unit and to prevent hypertension associated with tracheal intubation.