enalaprilat-anhydrous and Postoperative-Complications

Perioperative hypertension is commonly encountered in patients that undergo surgery. While attempts have been made to standardize the method to characterize the intraoperative hemodynamics, these methods still vary widely. In addition, there is a lack of consensus concerning treatment thresholds and appropriate therapeutic targets, making absolute recommendations about treatment difficult. Nevertheless, perioperative hypertension requires careful management. When treatment is necessary, therapy should be individualized for the patient. This paper reviews the pharmacologic agents and strategies commonly used in the management of perioperative hypertension.

Topics: Adrenergic beta-Antagonists; Antihypertensive Agents; Enalaprilat; Fenoldopam; Hemodynamics; Humans; Hydralazine; Hypertension; Incidence; Labetalol; Nicardipine; Nitroglycerin; Nitroprusside; Perioperative Care; Postoperative Complications; Propanolamines; Pyridines; Surgical Procedures, Operative; Vascular Resistance; Vasodilator Agents

Hypertension in pediatric patients after surgical repair of coarctation of the aorta can be difficult to control and may lead to morbidity. The renin-angiotensin system mediates at least part of this hypertension. Enalaprilat, the only intravenous angiotensin-converting enzyme inhibitor, is used to treat hypertension in pediatric patients in other settings. However, its effect on postoperative hypertension during the early postoperative period in patients undergoing surgical repair of coarctation of the aorta is unknown.. Prospective, randomized, double-blind study.. Operating room and the pediatric intensive care unit.. Fourteen consecutive pediatric patients between the ages of 1 and 18 yrs scheduled to undergo surgical repair of coarctation of the aorta.. Patients were randomized to receive enalaprilat or saline placebo. Infusions were begun intraoperatively within 15 mins of aortic repair and repeated every 6 hrs.. Plasma renin activity was measured at baseline and on postoperative day 1. Blood pressure was determined at 30 mins and at 2, 4, and 6 hrs after infusion and scored relative to the preoperative blood pressure. The blood pressure in the enalaprilat group was consistently lower at 30 mins, 2 hrs, and 4 hrs after infusion (p <.05), but not at 6 hrs. Plasma renin activity was significantly lower in the placebo group on postoperative day 1. Length of stay in the pediatric intensive care unit trended shorter in the treated group.. Conclusions are limited by a small cohort. Angiotensin-converting enzyme inhibitor therapy resulted in improved blood pressure control after coarctation repair. Further improvement of blood pressure control may be achievable by use of a larger dose of enalaprilat or a 4-hr enalaprilat-dosing interval.

Topics: Adolescent; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Aortic Coarctation; Blood Pressure Monitoring, Ambulatory; Child; Child, Preschool; Cohort Studies; Double-Blind Method; Enalaprilat; Female; Humans; Hypertension; Infant; Infusions, Intravenous; Intensive Care Units, Pediatric; Length of Stay; Male; Monitoring, Physiologic; Placebos; Postoperative Complications; Prospective Studies; Renin; Renin-Angiotensin System; Statistics, Nonparametric; Thoracotomy; Time Factors

The efficacy of intravenous enalaprilat in lowering postoperative hypertension.. Prospective, randomized, controlled, single blind trial.. Surgical ICT in a university hospital (tertiary care center).. 18 neurosurgical patients subjected to the extirpation of a supratentorial intracerebral tumour were studied after detection of postoperative hypertension. This was defined as a constant elevation of systolic arterial pressure over 160 mmHg or diastolic arterial pressure over 95 mmHg.. Enalaprilat 0.015 mg kg-1 was injected within 5 min to 9 patients.. Central haemodynamics and systemic oxygenation were assessed at baseline before enalaprilat injection, and repeatedly during four hours after the injection. The statistical analysis was performed with analysis of variance for repeated measurements. As compared to control patients, the blood pressure lowering effect of enalaprilat became evident within 15 min and lasted for over four hours (p = 0.008). It was mainly due to the reduced systemic vascular resistance. Enalaprilat also induced a small decline in myocardial perfusion pressure. Cardiac performance, preload, heart rate and systemic oxygenation were not affected by enalaprilat.. We found intravenous enalaprilat effective and safe in lowering postoperative hypertension following neurosurgery as assessed by it's effects on central haemodynamics and systemic oxygenation.

Topics: Adult; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Cardiac Output; Enalaprilat; Female; Heart Function Tests; Hemodynamics; Humans; Hypertension; Middle Aged; Oxygen Consumption; Postoperative Complications; Prospective Studies; Single-Blind Method; Statistics, Nonparametric; Supratentorial Neoplasms

1. Cardiorespiratory effects of long-term, continuous i.v. administration of the ACE inhibitor enalaprilat were studied. 2. Forty-five consecutive critically patients suffering from trauma or postoperative complications were randomly separated into three groups (15 patients in each group) receiving either 0.25 mg h-1 or 0.50 mg h-1 enalaprilat, respectively, or saline solution as placebo (= control group). The infusion was continued for 5 days. 3. Haemodynamic and respiratory parameters were intensively monitored on admission to the intensive care unit (= 'baseline' values) and daily during the next 5 days. 4. Mean arterial blood pressure (MAP) decreased significantly only in the enalaprilat-treated patients, whereas heart rate (HR) remained unchanged in these patients. 5. Pulmonary capillary wedge pressure (PCWP) and pulmonary artery pressure (PAP) were decreased by enalaprilat (0.50 mg h-1: PAP (mean +/- s.d.) decreased from 28.0 +/- 4.1 to 24.0 +/- 3.0 mm Hg) and remained significantly lower than in the control group. In the untreated control group, cardiac index (CI), oxygen consumption (VO2I) and oxygen delivery (DO2I) significantly decreased, which was blunted by enalaprilat infusion. Oxygen extraction (O2-extr) increased in both enalaprilat groups (0.25 mg h-1: from 26.1 +/- 5.5 to 30.4 +/- 4.0%; 0.50 mg h-1: 25.2 +/- 5.6 to 30.9 +/- 4.4%) and decreased in the control patients. 6. Right ventricular haemodynamics improved by enalaprilat infusion (0.50 mg h-1: RVEF increased from 40.0 +/- 3.5 to 45.5 +/- 4.0%). Lactate plasma concentrations decreased in the group with 0.50 mg h-1 enalaprilat (from 1.9 +/- 1.0 to 1.3 +/- 0.3 mg dl-1) and increased in the control patients. 7. Continuous infusion of the ACE inhibitor enalaprilat exerted beneficial cardiorespiratory effects in the critically ill. The widespread common risk of altered perfusion with decreased CI, DO2, VO2, O2-extr and increased lactate concentration was blunted by enalaprilat infusion. 8. Although 0.5 mg h-1 enalaprilat was most effective, a dose of 0.25 mg h-1 also showed beneficial haemodynamic effects in the critically ill.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Critical Care; Enalaprilat; Female; Hemodynamics; Humans; Infusions, Intravenous; Male; Middle Aged; Oxygen; Postoperative Complications; Respiratory Distress Syndrome; Wounds and Injuries

The purpose of this study was to study the effect of the angiotensin-converting enzyme inhibitor, enalaprilat, on blood pressure and splanchnic perfusion after cardiac surgery.. Sixteen patients were studied after coronary artery bypass grafting. After admission to the intensive care unit, a 30-minute baseline measurement of systemic hemodynamics, oxygen transport, and gastric tonometry was performed. In 6 of 10 patients receiving enalaprilat and in each of 6 control patients, regional (splanchnic and leg) blood flows were measured also. After the baseline measurement period, 10 patients received a 0.5 mg bolus of enalaprilat and thereafter an incremental infusion of enalaprilat up to a total dose of 10 mg (mean 8.3; range 4 to 10 mg) was continued to reduce the mean arterial pressure (MAP) to 70 to 80 mm Hg. A 30-minute measurement period was repeated 2 to 3 hours after the first measurement period. In the control group, the second measurement was performed at corresponding time points.. Though MAP decreased in the enalaprilat group (enalaprilat 99 +/- 14 mm Hg v 89 +/- 21 mm Hg, P < .05; control 95 +/- 13 mm Hg v82 +/- 10 mm Hg, P = NS) in only 4 of 10 patients was the targeted MAP reduction achieved. No significant changes were observed either in systemic or regional blood flows. Systemic, pulmonary, and femoral vascular resistance indices decreased significantly in both groups. Gastric-arterial PCO2 difference did not change in either groups. Angiotensin-converting enzyme activity decreased in the enalaprilat group (10.0 +/- 2.3 v 1.3 +/- 0.3 U x l(-1), P < .01), but plasma renin and endothelin-1 concentrations did not change in either group.. The effect of enalaprilat on blood pressure was poor and it had no beneficial effects on splanchnic circulation. Renin-angiotensin activation is not a major factor in hypertension and splanchnic perfusion after cardiac surgery.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Coronary Artery Bypass; Critical Care; Dose-Response Relationship, Drug; Drug Administration Schedule; Enalaprilat; Female; Gastric Mucosa; Humans; Hypertension; Infusions, Intravenous; Male; Middle Aged; Monitoring, Physiologic; Postoperative Complications; Splanchnic Circulation; Vascular Resistance