Comparison of sedation and general anaesthesia for transcatheter aortic valve implantation on cerebral oxygen saturation and neurocognitive outcome†.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a treatment strategy for patients with severe aortic stenosis. Although general anaesthesia (TAVI-GA) and sedation (TAVI-S) have previously been described for TAVI, the difference in safety and efficacy of both methods has not been studied in a randomized trial. METHODS: The INSERT trial was a single centre, controlled parallel-group trial with balanced randomization. Sixty-six patients (68-94 yr) with acquired aortic stenosis undergoing transfemoral CoreValve™ were assigned to TAVI-GA or TAVI-S. Comparable operative risk was determined from risk-scores (EUROscore, STS-Score). Monitoring and anaesthetic drugs were standardized. Near-Infrared-Spectroscopy was used to monitor cerebral-oxymetry blinded. Primary outcome was the perioperative cumulative cerebral desaturation. As secondary outcomes, changes in neurocognitive function and respiratory and haemodynamic adverse events were evaluated. RESULTS: Of 66 included patients, 62 (TAVI-GA: n=31, TAVI-S: n=31) were finally analysed. Baseline characteristics were comparable. In 24 patients (39%) cerebral desaturation was observed. Cumulative cerebral desaturation was comparable (TAVI-GA:(median [IQR]) (0[0/1308] s%) vs. TAVI-S:(0[0/276] s%); P=0.505) between the groups. Neurocognitive function did not change within and between groups. Adverse events were more frequently observed in TAVI-S patients (P<0.001). Bradypnoea (n=16, 52%) and the need for airway manoeuvres (n=11, 36%) or bag-mask-ventilation (n=6, 19%) were the most common respiratory adverse events. CONCLUSIONS: Cerebral desaturation occurred in both patient groups, but there was no significant difference between the two groups. Based on primary outcome, both methods were shown to be comparable. Neurocognitive outcome was similar. The higher incidence of adverse events in the sedation group suggests a potential advantage of general anaesthesia. CLINICAL TRIAL REGISTRATION: NCT 01251328.

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.

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.

Inhibition of the hypotensive effect of plasma protein solutions by C1 esterase inhibitor.

The hypotensive effect of stable plasma protein solution (SPPS) is a well-known phenomenon, causing serious problems in surgical patients and patients supported by cardiopulmonary bypass. Kinins are believed to be responsible. A study was made to prevent this hypotension by adding C1 esterase inhibitor to the SPPS and comparing this with 5% human albumin. The results shows a significant difference between the effects of SPPS and SPPS plus C1 esterase inhibitor infusion on bypass. Five percent human albumin did not cause hypotension. Possible sequelae are discussed.

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.

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.

Prevention and treatment of supraventricular tachycardia shortly after coronary artery bypass grafting: a randomized open trial.

Supraventricular arrhythmias continue to complicate the postoperative course of patients following coronary artery bypass grafting. In a randomized, open, controlled trial we assessed the value of two different beta-blocking agents in the prevention and treatment of these arrhythmias. Of 151 consecutive patients undergoing coronary artery surgery, 39 were treated with metoprolol and 41 were treated with sotalol (a beta blocker with class III antiarrhythmic properties). Fifty patients served as a control group and received no prophylactic therapy. Twenty-one patients were eliminated from the study for various reasons, making a final total of 130 in the study group. In the metoprolol group 15.3% of patients developed supraventricular tachycardia SVT after coronary artery surgery, which was significantly less (p less than 0.05) than the incidence observed in the control group. However, in the group of patients receiving sotalol, 2.4% developed SVT (p less than 0.01 compared with the control group). Of 18 patients in the control group who developed SVT after randomization, 10 received sotalol and 4 metoprolol to terminate the arrhythmia. The mean time of termination of SVT after drug administration was 2.4 +/- 1.8 hours for treatment with sotalol and 13.6 +/- 9.8 hours for treatment with metoprolol. We conclude that sotalol significantly reduces the incidence of supraventricular tachycardia in the early period after coronary artery bypass surgery.

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.

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.

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.

Humoral changes during and following coronary bypass surgery: relationship to postoperative blood pressure.

In this study we investigated the role of the renin-angiotensin system and the adrenergic system in the hypertensive response during and following coronary bypass surgery. Arterial blood samples for measurement of active renin, angiotensin II, aldosterone and catecholamines were drawn before, during and in the first period after coronary artery grafting. Both noradrenaline and adrenaline rose significantly during extracorporeal circulation and remained elevated afterwards, the rise in adrenaline preceding that of noradrenaline. During cardiopulmonary bypass renin also increased while angiotensin II increased after an initial fall. Postoperatively, renin tended to return to control levels. However, angiotensin II fell in some patients but remained elevated in others. The latter group had significantly lower blood pressure during cardiopulmonary bypass, but higher pressure thereafter. Aldosterone levels were markedly reduced during cardiopulmonary bypass. The results suggest that low pressure during extracorporeal circulation may trigger enhanced formation of angiotensin II, apparently involving extrapulmonary converting enzyme. This mechanism may, when acting in concert with an activated sympathetic nervous system, produce significant blood pressure elevation postoperatively.

The Treonic Haemoheater: a new blood warming device.

A new blood warming apparatus, the Treonic Haemoheater, is described. The blood circulates through a disposable warming bag situated between two electrically heated panels containing two types of thermostat. The apparatus appears to be electrically safe and exhibits a high capacity for the transference of heat. Haemolysis is not caused and the device is simple to use.

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.

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.

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)

The use of ketanserin, a 5-hydroxytryptamine receptor antagonist, for treatment of postoperative hypertension following coronary artery bypass surgery.

In patients developing hypertension following coronary artery bypass surgery (CABG) the possible role of 5-hydroxytryptamine (5-HT; serotonin) was investigated by injecting ketanserin, a specific 5-HT2-receptor antagonist. Ketanserin was administered intravenously when intraarterial systolic blood pressure (SAP) exceeded 150 mm Hg either as a 10-mg bolus (group 1, N = 15), or as a 10-mg bolus followed by infusion of 4 mg/h for either 2.5 h (group 2, N = 15) or for 1 h (group 3, N = 10). In 33 patients (82.5%), SAP and diastolic arterial pressure decreased significantly within 5 min after the 10-mg bolus. In group 1, SAP gradually increased after 30-50 min but in groups 2 and 3 SAP remained normal. The triple index (TI) decreased significantly in all groups. Heart rate decreased slightly but significantly in groups 2 and 3. Central venous and left atrial pressures did not change substantially in any of the three groups. Cardiac output increased significantly (0.51 +/- 0.158 L/min); hence, systemic vascular resistance (SVR) decreased significantly (452.1 +/- 50.57 dyn . s . cm-5--group 3). No rebound increase in SAP occurred after terminating the infusions (groups 2 and 3). These findings indicate that 5-HT plays a role in the majority of patients who develop hypertension following CABG. The decrease of SVR without reflex tachycardia is a favorable effect of ketanserin.

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.