Beneficial effect of continuation of propranolol through coronary bypass surgery

Boudoulas, Harisios; Lewis, Richard P.; Snyder, Gary L.; Karayannacos, Panayotis E.; Vasko, John S.

doi:10.1002/clc.4960020202

Cited by 26 publications

(6 citation statements)

References 29 publications

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“…Forty-one patients undergoing elective coronary artery bypass surgery were randomly assigned to receive timolol (21 patients) or placebo (20 patients) in a double-blind manner for 7 days after surgery. Patients with the following contraindications to taking /3-adrenoceptor-blocking agents were not eligible for inclusion: (1) second-or third-degree atrioventricular block, (2) resting sinus bradycardia less than 56 beats/min. (3) diabetes mellitus requiring insulin or oral hypoglycemic agents, (4) history of attacks of spontaneous hypoglycemia, (5) allergic rhinitis, (6) bronchospasm of any cause, or (7) chronic obstructive pulmonary disease.…”

Section: Methodsmentioning

confidence: 99%

Efficacy and safety of timolol for prevention of supraventricular tachyarrhythmias after coronary artery bypass surgery.

White¹,

Antman²,

Glynn³

et al. 1984

Circulation

158

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Forty-one patients undergoing coronary artery bypass grafting were randomly assigned to receive prophylactic timolol or placebo, given in a double-blind fashion. /3-Adrenoceptor-blocking therapy was stopped at least one half-life before surgery. Three to 7 hr after surgery (304 + 56 min), 0.5 mg of timolol or placebo was given intravenously twice daily in a double-blind manner. When oral medications were resumed postoperatively, 10 mg of timolol twice daily or placebo was continued orally. Continuous electrocardiograms were recorded for 24 hr before and for 7 days after surgery with a standard cassette recorder. No patient received digoxin. Both groups were comparable for frequency of preoperative supraventricular arrhythmias, left ventricular ejection fraction, duration of cardiopulmonary bypass, aortic cross-clamp time, number of bypass grafts, and total duration of monitoring. Analysis of arrhythmias was done by hand counts, and supraventricular arrhythmias were divided into supraventricular tachycardia and atrial fibrillation and/or flutter. Timolol decreased the frequency of supraventricular tachycardia (581 episodes placebo vs 84 timolol; p < .05) and of atrial fibrillation and/ or flutter (291 episodes placebo vs five timolol; p < .05). Timolol decreased the number of patients with severe (heart rate > 200 beats/min, duration > 50 beats) episodes of supraventricular tachycardia (four placebo vs 0 timolol; p < .05) and also decreased the number of episodes of severe (heart rate > 200 beats/min, duration > 5 min) atrial fibrillation and/or flutter (16 placebo vs one timolol; p < .005). There were no differences in the durations of supraventricular arrhythmias. All 1 1 episodes of supraventricular tachycardia and 11 episodes of atrial fibrillation and/or flutter with heart rates over 200 beats/min occurred in the placebo group (p < .005). Four patients on placebo and one patient on timolol required treatment for symptomatic supraventricular arrhythmias. Two patients in the timolol group were nauseated and one patient developed wheezing while on placebo. The results of this study demonstrate that prophylactic use of timolol after coronary bypass surgery is effective and safe therapy for decreasing the frequency and severity of supraventricular arrhythmias. Circulation 70, No. 3, 479-484, 1984. SUPRAVENTRICULAR arrhythmias are common after coronary artery bypass surgery, occurring in 20% to 54% of patients. -110 These arrhythmias may be associated with excessively rapid ventricular rates that jeopardize hemodynamic stability; in such cases urgent treatment is required to slow the heart rate or restore sinus rhythm. On occasion, when antiarrhythmic drug therapy is ineffective, it is even necessary to

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Section: Methodsmentioning

confidence: 99%

Efficacy and safety of timolol for prevention of supraventricular tachyarrhythmias after coronary artery bypass surgery.

White¹,

Antman²,

Glynn³

et al. 1984

Circulation

158

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“…After the studies of Boudoulas et al (7,22), the maintenance of preoperative β-blocker therapy became a routine procedure, since it does not modify myocardial performance during the pre-and posthypothermic CPB period. Furthermore, due to the markedly increased adrenergic M.J.C.…”

Section: Discussionmentioning

confidence: 99%

“…Preoperative β-blocker therapy has also been shown to reduce the incidence of intraoperative ischemic events related to increases in heart rate and hemodynamic responses to surgical stimulation during coronary artery bypass graft (CABG) (5,6). Administration of a β-blocker before coronary bypass and its postoperative reinstitution is considered safe and beneficial (7,8), whereas an abrupt with-Propranolol and atenolol pharmacokinetics alterations by CPB www.bjournal.com.br drawal of the drug has been associated with myocardial ischemia, hypertension, and arrhythmia secondary to a β-blockade-induced increase in β-receptor density (9).…”

Section: Introductionmentioning

confidence: 99%

Effect of cardiopulmonary bypass on the pharmacokinetics of propranolol and atenolol

Carmona

Pereira

Auler

et al. 2009

Braz J Med Biol Res

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The pharmacokinetics of some β-blockers are altered by cardiopulmonary bypass (CPB). The objective of this study was to compare the effect of coronary artery bypass graft (CABG) surgery employing CPB on the pharmacokinetics of propranolol and atenolol. We studied patients receiving oral propranolol with doses ranging from 80 to 240 mg (N = 11) or atenolol with doses ranging from 25 to 100 mg (N = 8) in the pre-and postoperative period of CABG with moderately hypothermic CPB (32°C). On the day before and on the first day after surgery, blood samples were collected before β-blocker administration and every 2 h thereafter. Plasma levels were determined using high-performance liquid chromatography and data were treated by pharmacokinetics-modelling. Statistical analysis was performed using ANOVA or the Friedman test, as appropriate, and P < 0.05 was considered to be significant. A prolongation of propranolol biological half-life from 5.41 ± 0.75 to 11.46 ± 1.66 h (P = 0.0028) and an increase in propranolol volume of distribution from 8.70 ± 2.83 to 19.33 ± 6.52 L/kg (P = 0.0032) were observed after CABG with CPB. No significant changes were observed in either atenolol biological half-life (from 11.20 ± 1.60 to 11.44 ± 2.89 h) or atenolol volume of distribution (from 2.90 ± 0.36 to 3.83 ± 0.72 L/kg). Total clearance was not changed by surgery. These CPBinduced alterations in propranolol pharmacokinetics may promote unexpected long-lasting effects in the postoperative period while the effects of atenolol were not modified by CPB surgery. . .. .

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“…Eighteen hours after surgery, on the first postoperative day after the patients were allowed to drink water, a postoperative baseline blood sample was collected and 10 mg propranolol was administered per os. For postoperative pharmacokinetics, blood samples were collected at 2,4,6,8,12, and 24 h. EDTA tubes containing blood samples were centrifuged at 1500 g for 10 min and stored at a temperature of -70ºC (-158ºF) until the time for the drug assay.…”

Section: Study Protocol and Propranolol Measurementsmentioning

confidence: 99%

“…Preoperative ß-blocker therapy has been shown to reduce the incidence of intraoperative ischemic events related to increases in heart rate (4,5) and hemodynamic responses to surgical stimulation during revascularization of the myocardium. Administration of a ß-blocker before coronary bypass and its immediate reinstitution afterwards is considered to be safe and beneficial (6,7), whereas an abrupt withdrawal of the drug has been associated with myocardial ischemia, hypertension, and tachydysrhythmias secondary to a ß-blockade-induced increase in ß-receptor density (8).…”

Section: Introductionmentioning

confidence: 99%

Cardiopulmonary bypass alters the pharmacokinetics of propranolol in patients undergoing cardiac surgery

Carmona

Malbouisson

Pereira

et al. 2005

Braz J Med Biol Res

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The pharmacokinetics of propranolol may be altered by hypothermic cardiopulmonary bypass (CPB), resulting in unpredictable postoperative hemodynamic responses to usual doses. The objective of the present study was to investigate the pharmacokinetics of propranolol in patients undergoing coronary artery bypass grafting (CABG) by CPB under moderate hypothermia. We evaluated 11 patients, 4 women and 7 men (mean age 57 ± 8 years, mean weight 75.4 ± 11.9 kg and mean body surface area 1.83 ± 0.19 m 2 ), receiving propranolol before surgery (80-240 mg a day) and postoperatively (10 mg a day). Plasma propranolol levels were measured before and after CPB by highperformance liquid chromatography. Pharmacokinetic Solutions 2.0 software was used to estimate the pharmacokinetic parameters after administration of the drug pre-and postoperatively. There was an increase of biological half-life from 4.5 (95% CI = 3.9-6.9) to 10.6 h (95% CI = 8.2-14.7; P < 0.01) and an increase in volume of distribution from 4.9 (95% CI = 3.2-14.3) to 8.3 l/kg (95% CI = 6.5-32.1; P < 0.05), while total clearance remained unchanged 9.2 (95% CI = 7.7-24.6) vs 10.7 ml min -1 kg -1 (95% CI = 7.7-26.6; NS) after surgery. In conclusion, increases in drug distribution could be explained in part by hemodilution during CPB. On the other hand, the increase of biological half-life can be attributed to changes in hepatic metabolism induced by CPB under moderate hypothermia. These alterations in the pharmacokinetics of propranolol after CABG with hypothermic CPB might induce a greater myocardial depression in response to propranolol than would be expected with an equivalent dose during the postoperative period.

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Beneficial effect of continuation of propranolol through coronary bypass surgery

Cited by 26 publications

References 29 publications

Efficacy and safety of timolol for prevention of supraventricular tachyarrhythmias after coronary artery bypass surgery.

Efficacy and safety of timolol for prevention of supraventricular tachyarrhythmias after coronary artery bypass surgery.

Effect of cardiopulmonary bypass on the pharmacokinetics of propranolol and atenolol

Cardiopulmonary bypass alters the pharmacokinetics of propranolol in patients undergoing cardiac surgery

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