How strong is the evidence for the use of perioperative β blockers in non-cardiac surgery? Systematic review and meta-analysis of randomised controlled trials

Abstract Objective To determine the effect of perioperative β blocker treatment in patients having non-cardiac surgery. Design Systematic review and meta-analysis. Data sources Seven search strategies, including searching two bibliographic databases and hand searching seven medical journals. Study selection and outcomes We included randomised controlled trials that evaluated β blocker treatment in patients having non-cardiac surgery. Perioperative outcomes within 30 days of surgery included total mortality, cardiovascular mortality, non-fatal myocardial infarction, non-fatal cardiac arrest, non-fatal stroke, congestive heart failure, hypotension needing treatment, bradycardia needing treatment, and bronchospasm. Results Twenty two trials that randomised a total of 2437 patients met the eligibility criteria. Perioperative β blockers did not show any statistically significant beneficial effects on any of the individual outcomes and the only nominally statistically significant beneficial relative risk was 0.44 (95% confidence interval 0.20 to 0.97, 99% confidence interval 0.16 to 1.24) for the composite outcome of cardiovascular mortality, non-fatal myocardial infarction, and non-fatal cardiac arrest. Methods adapted from formal interim monitoring boundaries applied to cumulative meta-analysis showed that the evidence failed, by a considerable degree, to meet standards for forgoing additional studies. The individual safety outcomes in patients treated with perioperative β blockers showed a relative risk for bradycardia needing treatment of 2.27 (95% CI 1.53 to 3.36, 99% CI 1.36 to 3.80) and a nominally statistically significant relative risk for hypotension needing treatment of 1.27 (95% CI 1.04 to 1.56, 99% CI 0.97 to 1.66). Conclusion The evidence that perioperative β blockers reduce major cardiovascular events is encouraging but too unreliable to allow definitive conclusions to be drawn.

[1]  C. Jakobsen,et al.  Effect of metoprolol and diazepam on pre‐operative anxiety , 1990, Anaesthesia.

[2]  A. Wallace,et al.  Prophylactic Atenolol Reduces Postoperative Myocardial Ischemia , 1998, Anesthesiology.

[3]  Jeroen J. Bax,et al.  The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group. , 1999, The New England journal of medicine.

[4]  Jeroen J. Bax,et al.  The Effect of Bisoprolol on Perioperative Mortality and Myocardial Infarction in High-Risk Patients Undergoing Vascular Surgery , 2000 .

[5]  D. Massel,et al.  Propranolol for the prevention of postoperative arrhythmias in general thoracic surgery. , 1999, The Annals of thoracic surgery.

[6]  C. Jakobsen,et al.  Preoperative metoprolol improves cardiovascular stability and reduces oxygen consumption after thoracotomy , 1997, Acta anaesthesiologica Scandinavica.

[7]  R. Martineau,et al.  Bolus administration of esmolol for controlling the haemodynamic response to tracheal intubation: the canadian multicentre trial , 1991, Canadian journal of anaesthesia = Journal canadien d'anesthesie.

[8]  R. Martineau,et al.  Bolus administration of esmolol for controlling the hemodynamic response to laryngoscopy and intubation: Efficacy and effects on myocardial performance , 1990 .

[9]  D. Reich,et al.  Beneficial effects from beta-adrenergic blockade in elderly patients undergoing noncardiac surgery. , 1999, Anesthesiology.

[10]  J. Leslie,et al.  Attenuation of the hemodynamic responses to endotracheal intubation with preinduction intravenous labetalol. , 1989, Journal of clinical anesthesia.

[11]  How Strong Is the Evidence for the Use of Perioperative &bgr; Blockers in Noncardiac Surgery? Systematic Review and Meta-Analysis of Randomized Controlled Trials , 2005 .

[12]  M. Jacka,et al.  More conclusive large-scale trials necessary before recommending use of beta blockade in patients at risk. , 2004, Anesthesia and analgesia.

[13]  E. Antman,et al.  ACC/AHA Guideline Update for Perioperative Cardiovascular Evaluation for Noncardiac Surgery—Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1996 Guidelines on Perioperative Cardiovascular Evaluati , 2002, Journal of the American College of Cardiology.

[14]  Prophylactic Atenolol Reduces Postoperative Myocardial Ischemia , 1998 .

[15]  Gries,et al.  Perioperative catecholamine changes in cardiac risk patients , 1999, European journal of clinical investigation.

[16]  R. Stevens,et al.  Pharmacologic Myocardial Protection in Patients Undergoing Noncardiac Surgery: A Quantitative Systematic Review , 2003, Anesthesia and analgesia.

[17]  allace,et al.  EFFECT OF ATENOLOL ON MORTALITY AND CARDIOVASCULAR MORBIDITY AFTER NONCARDIAC SURGERY , 2000 .

[18]  R. Peto,et al.  Beta blockade during and after myocardial infarction: an overview of the randomized trials. , 1985, Progress in cardiovascular diseases.

[19]  Dwight Lemon,et al.  Randomised trial of intravenous atenolol among 16,027 cases of suspected acute myocardial infarction: ISIS-1 , 1987 .

[20]  D. Cullen,et al.  Effect of labetalol or lidocaine on the hemodynamic response to intubation: a controlled randomized double-blind study. , 1989, Journal of clinical anesthesia.

[21]  R. Matteo,et al.  Evaluation of esmolol in controlling increases in heart rate and blood pressure during endotracheal intubation in patients undergoing carotid endarterectomy. , 1986, Anesthesiology.

[22]  C. Weissman The Metabolic Response to Stress: An Overview and Update , 1990, Anesthesiology.

[23]  J. Bird,et al.  Timolol: a non-sedative anxiolytic premedicant for day cases. , 1989, BMJ.

[24]  M. Davies,et al.  Prevention of Tachycardia with Atenolol Pretreatment for Carotid Endarterectomy Under Cervical Plexus Blockade , 1992, Regional Anesthesia & Pain Medicine.

[25]  Fach,et al.  Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in-Congestive Heart Failure (MERIT-HF) , 1999, The Lancet.

[26]  B. Covino,et al.  Esmolol for control of increases in heart rate and blood pressure during tracheal intubation after thiopentone and succinylcholine , 1986, Canadian Anaesthetists' Society journal.

[27]  J. Sear,et al.  Myocardial Ischemia in Untreated Hypertensive Patients: Effect of a Single Small Oral Dose of a Beta‐Adrenergic Blocking Agent , 1988, Anesthesiology.

[28]  A Whitehead,et al.  A general parametric approach to the meta-analysis of randomized clinical trials. , 1991, Statistics in medicine.

[29]  D. Reich,et al.  Beneficial Effects from β-Adrenergic Blockade in Elderly Patients Undergoing Noncardiac Surgery , 1999 .

[30]  C. Furberg,et al.  Improving cardiac outcomes after noncardiac surgery. , 2003, Anesthesia and analgesia.

[31]  H. Priebe Triggers of perioperative myocardial ischaemia and infarction. , 2004, British journal of anaesthesia.

[32]  W. Pearce,et al.  Sequential changes in coagulation and platelet function following femorotibial bypass. , 1984, Journal of vascular surgery.

[33]  ISIS-1 Collaborative Group RANDOMISED TRIAL OF INTRAVENOUS ATENOLOL AMONG 16 027 CASES OF SUSPECTED ACUTE MYOCARDIAL INFARCTION: ISIS-1 , 1986, The Lancet.

[34]  M. Packer,et al.  Clinical effects of beta-adrenergic blockade in chronic heart failure: a meta-analysis of double-blind, placebo-controlled, randomized trials. , 1998, Circulation.

[35]  C. Jakobsen,et al.  Metoprolol decreases the amount of halothane required to induce hypotension during general anaesthesia. , 1986, British journal of anaesthesia.

[36]  L. Burgos,et al.  A technique of laryngoscopy for difficult intubation. , 1986, Anesthesiology.

[37]  W. Flinn,et al.  Antithrombin III deficiency as a reflection of dynamic protein metabolism in patients undergoing vascular reconstruction. , 1984, Journal of vascular surgery.

[38]  M. Müllner,et al.  C-reactive protein and mortality in patients with acute aortic disease , 2002, Intensive Care Medicine.

[39]  S. Yusuf,et al.  Cumulating evidence from randomized trials: utilizing sequential monitoring boundaries for cumulative meta-analysis. , 1997, Controlled clinical trials.

[40]  C. Jordan,et al.  Cardiovascular responses to anaesthesia , 1980, Anaesthesia.

[41]  T. H. Lee,et al.  Reducing cardiac risk in noncardiac surgery. , 1999, The New England journal of medicine.

[42]  D. Altman,et al.  Measuring inconsistency in meta-analyses , 2003, BMJ : British Medical Journal.

[43]  CIBIS-II Investigators and Committees The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial , 1999, The Lancet.

[44]  Farris K. Timimi,et al.  The effect of heart rate control on myocardial ischemia among high-risk patients after vascular surgery. , 1999, Anesthesia and analgesia.

[45]  Homer Yang,et al.  The effects of perioperative β-blockade: Results of the Metoprolol after Vascular Surgery (MaVS) study, a randomized controlled trial , 2006 .

[46]  N. Laird,et al.  Meta-analysis in clinical trials. , 1986, Controlled clinical trials.

[47]  M. Breslow,et al.  The Effects of Different Anesthetic Regimens on Fibrinolysis and the Development of Postoperative Arterial Thrombosis , 1993, Anesthesiology.

[48]  S. Yusuf,et al.  Overcoming the limitations of current meta-analysis of randomised controlled trials , 1998, The Lancet.

[49]  S. Black,et al.  Esmolol for the control of hypertension after neurologic surgery , 1988, Clinical pharmacology and therapeutics.

[50]  P. Grayburn,et al.  Cardiac Events in Patients Undergoing Noncardiac Surgery: Shifting the Paradigm from Noninvasive Risk Stratification to Therapy , 2003, Annals of Internal Medicine.

[51]  P. Kligfield,et al.  Postoperative Prophylactic Administration of &bgr;-Adrenergic Blockers in Patients at Risk for Myocardial Ischemia , 2000, Anesthesia and analgesia.

[52]  A S Detsky,et al.  Perioperative Assessment and Management of Risk from Coronary Artery Disease , 1997, Annals of Internal Medicine.

[53]  M. Breslow,et al.  Catecholamine and cortisol responses to lower extremity revascularization: correlation with outcome variables. Perioperative Ischemia Randomized Anesthesia Trial Study Group. , 1995, Critical care medicine.

[54]  O. Werner,et al.  Haemodynamic effects of pretreatment with metoprolol in hypertensive patients undergoing surgery. , 1986, British journal of anaesthesia.

[55]  L. Goldman,et al.  beta-Blockers and reduction of cardiac events in noncardiac surgery: scientific review. , 2002, JAMA.