A randomized multicenter double-blind comparison of urapidil and ketanserin in hypertensive patients after coronary artery surgery.

OBJECTIVES: To compare the hemodynamic responses, safety, and efficacy of urapidil and ketanserin in hypertensive patients after coronary artery surgery. DESIGN: Randomized double-blind study. SETTING: Multi-institutional. PARTICIPANTS: One hundred twenty-two patients undergoing elective coronary artery surgery. INTERVENTIONS: When hypertension (defined as mean arterial pressure > 85 mmHg) developed within the first 2 hours after arrival in the intensive care unit, patients received urapidil (n = 62) or ketanserin (n = 60) to reach a mean arterial pressure between 65 and 75 mmHg. Urapidil was administered by repeated bolus injections (25 to 125 mg) followed by a continuous infusion of maximally 50 micrograms/kg/min. Ketanserin was administered by repeated bolus injections (10 to 50 mg) followed by a continuous infusion of maximally 4.0 micrograms/kg/min. MEASUREMENTS AND MAIN RESULTS: A complete hemodynamic profile was determined at baseline and at 30 and 60 minutes after start of study medication. In the urapidil group, mean arterial pressure (+/-SD) decreased significantly from 100.6 +/- 12.4 mmHg at baseline to 74.6 +/- 12.1 mmHg at 30 minutes and 73.5 +/- 13.8 mmHg at 60 minutes. In the ketanserin group, mean arterial pressure decreased significantly from 98.7 +/- 10.7 mmHg at baseline to 83.5 +/- 16.8 mmHg at 30 minutes and 83.1 +/- 15.3 mmHg at 60 minutes. Between the groups, there was a significant difference in the degree of lowering mean arterial pressure at 30 and 60 minutes. Heart rate increased significantly by 5.8 +/- 12.7 (30 minutes) and 8.6 +/- 16.5 (60 minutes) beats/min in the ketanserin group. In the urapidil group, no changes in heart rate occurred. Cardiac output increased to the same extent (0.7 L/min) in both groups. Within and between the groups, there were no relevant changes in pulmonary filling pressures. The number of patients not responding adequately to the study medication (mean arterial pressure > 85 mmHg after 30 minutes despite the maximum doses of study medication) was comparable in both groups (9 [U] v 13 [K]). Adverse events attributable to the study medication occurred to a similar degree in both groups. In the patients treated with urapidil, a significantly higher incidence (32.3%) of hypotension (mean arterial pressure < or = 65 mmHg for more than 10 minutes) occurred after 60 minutes of continuous infusion. CONCLUSIONS: In contrast to ketanserin, urapidil did not increase heart rate. Urapidil was more effective in lowering arterial blood pressure than ketanserin. However, one third of the patients treated with urapidil developed hypotension after 60 minutes of continuous infusion.

Intermittent antegrade/selective cerebral perfusion during circulatory arrest for repair of the aortic arch.

If the aortic arch requires repair or replacement due to an aneurysm or dissection, conventional cardiopulmonary bypass (CPB) is not possible during the period in which the aortic arch is excluded from the circulation. This creates a situation in which there is no cerebral circulation. The brain needs adequate protection from this ischaemic insult. Hypothermic circulatory arrest (HCA), antegrade/selective cerebral perfusion (ASCP) and retrograde cerebral perfusion (RCP) are reported to exhibit their cerebral protective capabilities during procedures involving the aortic arch. HCA can provide adequate protection in procedures of short duration and avoids the complications associated with cerebral perfusion techniques. The main disadvantage of HCA is that the 'safe' duration of circulatory arrest is not clearly defined. Topical cooling of the head may enhance cerebral hypothermia and provide additional protection. If longer periods of circulatory arrest are anticipated or occur unexpectedly, we suggest that ASCP can offer improved cerebral protection by providing adequate brain perfusion and improved cerebral cooling. By using a coronary sinus perfusion catheter as a carotid artery cannula, it is not necessary to snare or clamp the carotid arteries. This technique minimizes the chance of damaging the carotid arteries. In this report, we describe our set-up and ASCP perfusion protocol for the surgical repair of an aortic arch aneurysm.

Ketanserin in the treatment of protamine-induced pulmonary hypertension.

The reversal of heparin by protamine may cause severe hemodynamic deterioration, characterized by systemic hypotension, pulmonary hypertension, and bronchoconstriction. A case report is presented concerning the administration of ketanserin in the treatment of pulmonary vasoconstriction and right ventricular failure following the infusion of protamine in a patient undergoing coronary artery bypass surgery and mitral valve replacement. The potential role of serotonin in the development of this serious complication is discussed.

The role of serotonin blockers in cardiac anesthesia.

In the complex setting of cardiac surgery and cardiopulmonary bypass, several potent mediators are released that by interacting may cause clinical syndromes like coronary ischemia, systemic hypertension, pulmonary hypertension, and renal failure. One of the mediators is serotonin, released from aggregating platelets, and causing vasoconstriction by activating S2-serotonergic receptors, particularly in patients with an impaired endothelial function, as in atherosclerosis. The most important available specific S2-serotonergic receptor antagonist is ketanserin. If administered during or after cardiac surgery, ketanserin lowers systemic and pulmonary blood pressure, and improves peripheral and pulmonary perfusion without causing reflex tachycardia or an increase in pulmonary shunt fraction.

Pharmacokinetics of pancuronium in patients undergoing coronary artery surgery with and without low dose dopamine.

Pancuronium is frequently used in coronary artery surgery, but its pharmacokinetics in these patients are still unknown. It is possible that dopamine, administered to prevent renal impairment induced by the surgery, might promote the elimination of pancuronium. Therefore, the pharmacokinetics of a bolus dose of pancuronium were studied in 2 groups of coronary artery surgery patients, with and without dopamine 2 micrograms/kg/min, administered during and after cardiopulmonary bypass. Dopamine in the administered dose did not influence the systemic haemodynamics. The pharmacokinetic variables in both groups did not differ from those found in an earlier study in healthy normothermic patients. Total renal clearance was not influenced by dopamine, due to post-bypass rebound hyperperfusion in the control group. Pancuronium was shown to be subject to considerable tubular reabsorption, and its elimination was found to be increased during hypothermia. Dopamine increases pancuronium elimination by an increase in glomerular filtration rate. The dopamine-induced decrease in tubular solute reabsorption did not enhance the elimination of pancuronium.

Serotonin and acute cardiovascular disorders.

In this survey the possible role of serotonin in such acute disorders as systemic and pulmonary hypertension following cardiac surgery is discussed. Although platelets are activated during cardiopulmonary bypass, the increase in serotonin plasma levels is limited because the serotonin released is taken up by normal platelets and endothelial cells. This does not imply that serotonin is not involved in the origin of systemic hypertension during and after cardiac surgery, because subthreshold or threshold doses of this amine amplify the vasoconstrictive effect of, for example, epinephrine and norepinephrine, the levels of which are significantly elevated under these circumstances. That serotonin plays a role through its amplifying effect is supported by the finding that ketanserin, a specific S2-serotonergic receptor antagonist with alpha 1-adrenergic receptor blocking properties, effectively lowers arterial blood pressure in patients with systemic postoperative hypertension by combined blockade of these receptors. The compound is also effective in the treatment of pulmonary hypertension after valve replacement, indicating that serotonin plays a role in the origin of this disorder. This idea is supported by the experimental finding that serotonin induces pulmonary hypertension. It is an interesting observation that, unlike such compounds as nitroprusside, ketanserin does not affect intrapulmonary shunting in patients with systemic hypertension and even reduces the intrapulmonary shunt fraction in patients with pulmonary hypertension. These findings indicate that this compound dilates the resistance vessels in well-ventilated, but not in poorly ventilated areas, and may dilate constricted bronchi.(ABSTRACT TRUNCATED AT 250 WORDS)

Ketanserin in the treatment of systemic hypertension during and following coronary artery bypass surgery.

One of the most important problems during cardiac surgery is the prevention and treatment of hypertension, occurring in 40-60% of the patients following coronary artery bypass surgery (CABS). Hypertension should be avoided to prevent myocardial damage, neurologic complications, increased blood loss, and premature graft closure due to intimal damage. During and following cardiac surgery hypertension is routinely treated with vasodilating agents, which generally induce reflex tachycardia and increased intrapulmonary shunting. The results obtained with ketanserin, a specific S2-serotonergic receptor blocker with alpha 1-adrenergic receptor blocking properties, in the prevention and treatment of hypertension in patients undergoing cardiac surgery, are presented. Ketanserin effectively lowers blood pressure by decreasing systemic vascular resistance but does not completely prevent perioperative and postoperative hypertension when administered as a continuous infusion from the start of anesthesia. In contrast to sodium nitroprusside, ketanserin does not induce reflex tachycardia in the treatment of postoperative systemic hypertension following CABS. The compound improves diuresis and perfusion of the skin perioperatively. Ketanserin is devoid of rebound phenomena after its administration is stopped. It is postulated that the antihypertensive effect of ketanserin can be explained by its property of simultaneously blocking alpha 1-adrenergic and S2-serotonergic receptors.

Ketanserin in the treatment of pulmonary hypertension after valvular surgery: a comparison with sodium nitroprusside.

In a prospective randomized trial in patients with a history of preoperative pulmonary hypertension who were undergoing surgery for valvular replacement or annuloplasty, the effects of ketanserin (KET) (12 patients) and sodium nitroprusside (SNP) (14 patients) on the systemic and pulmonary circulation and pulmonary shunt fraction (Qsp/Qt) were studied in the immediate postoperative period. The agents were administered at the moment that pulmonary arterial pressure (PAP) tended to rise and cardiac output started to decrease. After administration, systemic arterial BP, PAP, systemic and pulmonary (PVR) vascular resistance, and right ventricular stroke work (RVSW) decreased significantly in both groups. The decrease in mean pulmonary arterial pressure (p less than .01), PVR (p less than .01), and RVSW (p less than .05) was significantly more pronounced in the KET than in the SNP group. Qsp/Qt significantly (p less than .001) increased in the SNP group, but significantly (p less than .05) decreased in the KET group; the response was significantly different between the two groups (p less than .001). In six patients, SNP converted pacemaker-dependent heart rate into a spontaneous rhythm, whereas this occurred in only one patient in the KET group. We concluded that KET, as opposed to SNP, reduces PVR without increasing Qsp/Qt in the lung, which is particularly advantageous in patients after valvular surgery.

Dopexamine hydrochloride after coronary artery bypass grafting.

Dopexamine hydrochloride, a dopamine analog with specific beta 2 adrenergic and DA1 dopaminergic receptor activity, was evaluated in a prospective study including 20 patients undergoing coronary artery bypass grafting. Shortly after admission to the intensive care unit, increasing doses of dopexamine hydrochloride (1.0, 2.0, 4.0, 6.0, 8.0 and 10.0 micrograms/kg/min) were administered as continuous infusion at 20-minute intervals. Hemodynamic monitoring revealed that dopexamine hydrochloride causes a significant decrease in systemic vascular resistance and a significant increase in cardiac output and heart rate, even at lower dose levels (1.0 micrograms/kg/min). At higher dose levels (greater than or equal to 2.0 micrograms/kg/min), adverse effects such as systolic hypertension and tachycardia were observed. Shunt fraction increased significantly during dopexamine hydrochloride administration, probably due to the increase in cardiac output. It is concluded that dopexamine hydrochloride is a potent vasodilating agent at lower dose levels and is of potential benefit to patients with compromised myocardial function after coronary artery bypass grafting. Higher dose levels may cause unwanted side effects, which might be explained by various mechanisms such as norepinephrine uptake inhibition.

Comparative study between two prophylactic antibiotic regimens of cefamandole during coronary artery bypass surgery.

In two groups of patients undergoing coronary artery bypass grafting (CABG), two different regimens of antibiotic prophylaxis with cefamandole nafate were compared. In Group 1, 30 mg per kilogram of body weight was administered intravenously during induction of anesthesia. In Group 2, a second dose of 15 mg/kg was administered intravenously shortly before cannulation. Serum and tissue levels in the right atrium, the pericardium, and the sternum were determined using high-pressure liquid chromatography. The results showed that in Group 2 the serum levels were significantly higher from 48 minutes onward after induction and remained at an acceptable level during CABG. The tissue levels in the sternum and pericardium were also significantly higher in Group 2 compared with Group 1. It is concluded that a second dose of cefamandole (15 mg/kg) shortly before the beginning of cardiopulmonary bypass is recommended, particularly for high-risk patients.

The alpha-adrenergic receptor blocking effect of ketanserin and the interaction between alpha-adrenergic and S2-serotonergic receptor blockade.

The alpha 1-adrenergic receptor blocking effect of ketanserin, the blocking properties of this compound for nonspecific stimulation with angiotensin II, and the alpha-adrenergic receptor blocking properties and the blood pressure lowering effect of phentolamine, ritanserin, and the combination of both compounds were studied in patients on cardiopulmonary bypass (constant flow rate, mild hypothermia) undergoing coronary artery bypass grafting. Phenylephrine was used as alpha 1-adrenergic agonist. Ketanserin reduces the alpha 1-agonistic effect of phenylephrine on blood pressure in a dose-dependent manner up to a dose of 10 mg. Ketanserin did not block the nonspecific vasoconstriction, as induced by angiotensin II. The moderate blood pressure lowering effect of phentolamine was substantially potentiated by ritanserin, which in itself did not affect blood pressure. The findings in this study indicate that the blood pressure lowering activity of ketanserin results from a combined blockade of alpha 1-adrenergic and S2-serotonergic receptors.

Peripheral vascular effects of ketanserin and nifedipine during cardiopulmonary bypass.

Ketanserin, a selective S2-serotonergic receptor antagonist with alpha 1-adrenergic receptor-blocking properties, as well as nifedipine, a classic calcium channel blocker, is used as an antihypertensive agent during and following cardiac surgery. In a double-blind prospective study, using hypothermic cardiopulmonary bypass as a study model, ketanserin (10 mg i.v.) and nifedipine (2 mg i.v.) were evaluated with respect to their effects on the peripheral circulation. The results showed that ketanserin and nifedipine dilate the arterial side of the vasculature, but that ketanserin, unlike nifedipine, also dilates the venous capacitance vessels; nifedipine even caused a short-lasting venous vasoconstriction. Since venous tone is increased during and following cardiopulmonary bypass, antihypertensive treatment with ketanserin might be advantageous under these circumstances.

Use of an arterial pH catheter immediately after coronary artery bypass grafting.

An arterial pH catheter was inserted into a femoral artery of 15 patients immediately after coronary artery bypass grafting. Catheter pH measurements correlated well with conventional blood gas measurements during the first 12 h postsurgery, and revealed rapid pH changes during weaning and bronchial suctioning. This device is a promising step in the development of a complete on-line blood gas analyzer.

Nitroprusside and ketanserin in the treatment of postoperative hypertension following coronary artery bypass grafting: a haemodynamic and ventilatory comparison.

Postoperative hypertension following coronary artery bypass grafting is usually treated with vasodilating agents like nitroprusside. In recent studies ketanserin, a 5-hydroxytryptamine type 2 antagonist, appeared to be effective in the treatment of this clinical syndrome. In 20 patients, divided into two comparable groups, nitroprusside and ketanserin were compared with respect to their haemodynamic and ventilatory profiles. The study showed that both agents were equally effective in decreasing the raised systolic blood pressure, but that ketanserin was more advantageous with respect to the absence of reflex tachycardia and the unchanged shunt fraction.