Ketanserin and hypertension in cardiac surgery

Abstract

Ketanserin and hypertension in cardiac surgery P.J.A. van der Starre, Maastricht: State University of Limburg, 26 February 1988. Promoter: Prof. Dr. R.S. Reneman (Maastricht). Referees: Prof. Dr. J.G. Bovill (Leiden) and Prof. Dr. S. de Lange (Maastricht). An important problem for the anaesthesiologist is the prevention and treatment of hypertension during and following cardiac surgery. A distinction is made between the type of hypertension which develops before the start of cardiopulmonary bypass, during cardiopulmonary bypass, in the period immediately following the termination of cardiopulmonary bypass and postoperatively, in the first hours after arrival in the intensive-care unit. The treatment of hypertension is particularly important in the period before cardiopulmonary bypass because it can cause myocardial damage, increased blood loss and possibly cerebral haemorrhage, especially in the elderly patient. Hypertension in this period is mainly caused by the stress of laryngoscopy, intubation, sternotomy and sternal spread. During these manipulations pressor effects occur leading to a significant increase in the plasma levels of catecholamines, vasopressin as well as renin and angiotensin. Increased plasma serotonin levels may play a role. Hypertension during cardiopulmonary bypass has other causes. The concentrations of catecholamines in the plasma increase, particularly under the influence of haemodilution, hypothermia, hypotension and the application of non-pulsatile flow. During cardiopulmofiary bypass damage of blood pl~itelets occurs, leading to the release of beta-thromboglobulin, platelet factor-4, thromboxane B2 arLd possibly serotonin. In the period immediately following cardiopulmonary bypass, hypertension rarely occurs because the heart has to recover from the ischemic insult resulting from aortic clamping during cardiopulmonary bypass. At this stage hypertension may develop only in the presence of severe peripheral vasoconstriction. In the early postoperative phase in the intensive-care unit hypertension often develops (40-60% of the coronary-bypass patients). Factors like the maintained elevated plasma levels of catecholamines and the diminishing efficacy of the pre-operative beta-blockade may be responsible for this hypertension. The patient's arousal during this period may lead to intolerance of the endotracheal tube which may also cause hypertension. It is unclear whether serotonin plays a role in this process. In this phase hypertension may cause the same complications as in the period before cardiopulmonary bypass. In addition it is assumed that hypertension may contribute to early closure of coronary bypass grafts. Serotonin is synthesized in the chromaffine cells of the gastro-intestinal tract. After release the compound is almost completely metabolized in the liver. The residual serotonin is taken up by endothelial cells, especially in the lung. Small amounts of serotonin, which pass the lung, are stored in platelets, resulting in very small amounts of serotonin in plasma. Serotonin may cause vasodilatation as well as vasoconstriction, depending on the type of blood vessel and the basic vascular tone. Serotonin is liberated from aggregating platelets, causing, for example, vasoconstriction in arteries, an effect mediated by S2-serotonergic receptors. Serotonin dilates arterioles probably via S~serotonergic yeceptors, an effect in which 'endothelium-derived relaxing factors' may play a role. Serotonin. also amplifies vasoconstriction, as induced by vasoconstricting agents like catecholamines and angiotensin. Especially through this mechanism serotonin is believed to play a role in the origin of hypertension. In pathological conditions like atheroscterosis, pulmonary hypertension, endotoxic schock and ecclampsia, an increased activity of serotonin has been demonstrated. Perioperative hypertension is generally treated by means of vasodilators, of which sodium nitroprusside and nitroglycerin are most commonly used. Recently antihyperten: sive compounds like urapidil, adenosine and ketanserin were developed. The latter is a S2serotonergic receptor antagonist with ~adrenergic receptor blocking properties. The compound is devoid of Sl-serotonergic receptorblocking properties. It is a quinazoline derivative with a half-life of 15 h. Ketanserin is mainly metabolized in the liver into non-active metabolites. The most important application is its use as an antihypertensive agent, especially in patients with essential hypertension, preecclampsia, pulmonary hypertension and neurogenic hypertension. It is also administered in patients with peripheral vascular disease like Raynaud's disease, Burger's disease and diabetes mellitus. In a double-blind prospective clinical study ketanserin or the solvent of ketanserin were administered perand postoperatively as a continuous infusion in patients undergoing coronary artery bypass surgery. Changes in Dr. P.J.A. van der Starre: Department of Anaesthesiology, Medical Center De Klokkenberg, Postbus 90108, 4800 RA Breda, the Netherlands.