Elsevier

The Lancet

Volume 372, Issue 9654, 6–12 December 2008, Pages 1962-1976
The Lancet

Articles
Perioperative β blockers in patients having non-cardiac surgery: a meta-analysis

https://doi.org/10.1016/S0140-6736(08)61560-3Get rights and content

Summary

Background

American College of Cardiology and American Heart Association (ACC/AHA) guidelines on perioperative assessment recommend perioperative β blockers for non-cardiac surgery, although results of some clinical trials seem not to support this recommendation. We aimed to critically review the evidence to assess the use of perioperative β blockers in patients having non-cardiac surgery.

Methods

We searched Pubmed and Embase for randomised controlled trials investigating the use of β blockers in non-cardiac surgery. We extracted data for 30-day all-cause mortality, cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, heart failure, and myocardial ischaemia, safety outcomes of perioperative bradycardia, hypotension, and bronchospasm.

Findings

33 trials included 12 306 patients. β blockers were not associated with any significant reduction in the risk of all-cause mortality, cardiovascular mortality, or heart failure, but were associated with a decrease (odds ratio [OR] 0·65, 95% CI 0·54–0·79) in non-fatal myocardial infarction (number needed to treat [NNT] 63) and decrease (OR 0·36, 0·26–0·50) in myocardial ischaemia (NNT 16) at the expense of an increase (OR 2·01, 1·27–3·68) in non-fatal strokes (number needed to harm [NNH] 293). The beneficial effects were driven mainly by trials with high risk of bias. For the safety outcomes, β blockers were associated with a high risk of perioperative bradycardia requiring treatment (NNH 22), and perioperative hypotension requiring treatment (NNH 17). We recorded no increased risk of bronchospasm.

Interpretation

Evidence does not support the use of β-blocker therapy for the prevention of perioperative clinical outcomes in patients having non-cardiac surgery. The ACC/AHA guidelines committee should soften their advocacy for this intervention until conclusive evidence is available.

Funding

None.

Introduction

The 2007 update on perioperative β blocker therapy in the American College of Cardiology and American Heart Association (ACC/AHA) guidelines for perioperative cardiovascular assessment for non-cardiac surgery recommends β blockers for patients already on therapy or who are having vascular surgery and have ischaemia on preoperative testing (class I) and for those having vascular surgery or intermediate or high-risk non-vascular surgery with high risk for coronary disease or those with established disease (class II).1 Consequently, the Physicians Consortium for Performance Improvement and the Surgical Care Improvement Project both recommend perioperative β blockade.2

Some randomised trials do not support recommendations in the guidelines and have shown no beneficial effect of perioperative β blockade.3, 4, 5 Despite these findings, the most recent ACC/AHA guideline update in 2007 states that “although many of the randomised controlled trials of β blocker therapy are small, the weight of evidence—especially in aggregate—suggests a benefit to perioperative β blockade during non-cardiac surgery in high-risk patients”.1 In the recently published, landmark POISE (perioperative ischaemic evaluation) trial,6 perioperative metoprolol was associated with a 30% reduction in non-fatal myocardial infarction at the expense of 33% increased risk of all-cause mortality and a 117% increased risk of stroke.

We aimed to critically review the evidence for perioperative β blockers in patients undergoing non-cardiac surgery.

Section snippets

Search strategy and selection criteria

We searched Pubmed, Embase, and the Cochrane Library with the terms “β adrenergic blockers”, “adrenergic β antagonist”, “β blockers”, “perioperative”, “preoperative”, and “intraoperative”. We restricted our search to studies in human beings from January, 1966, to May, 2008. We checked the reference lists of identified articles, previous meta-analyses, and original studies identified by the electronic search to find other potentially eligible studies. There was no language restriction for the

Results

We identified 112 randomised controlled trials, of which 73 were retrieved for detailed assessment (figure 1). We excluded 40 trials—36 of which did not evaluate outcomes of interest, one that was a small subgroup analysis from a larger non surgical cohort,18 and three that were multiple publications from the same dataset19, 20, 21—leaving 33 trials that fulfilled our inclusion criteria.

Table 1 and the webtable summarise the baseline characteristics, and quality assessment, respectively. The 33

Discussion

Our meta-analysis of randomised controlled trials in patients having non-cardiac surgery showed no clear benefit of perioperative β blockers compared with control for the prevention of cardiovascular outcomes. For the overall cohort, we estimate that treatment of 1000 patients with β blockers results in 16 fewer non-fatal myocardial infarctions in survivors but at the expense of three disabling strokes, 45 patients with clinically significant perioperative bradycardia, 59 with hypotension, and

References (54)

  • JG Stone et al.

    Risk of myocardial ischaemia during anaesthesia in treated and untreated hypertensive patients

    Br J Anaesth

    (1988)
  • D Miller et al.

    Bolus administration of esmolol for controlling the hemodynamic response to laryngoscopy and intubation: efficacy and effects on myocardial performance

    J Cardiothorac Anesth

    (1990)
  • JM Burns et al.

    Effects of nadolol on arrhythmias during laparoscopy performed under general anaesthesia

    Br J Anaesth

    (1988)
  • E Inada et al.

    Effect of labetalol or lidocaine on the hemodynamic response to intubation: a controlled randomized double-blind study

    J Clin Anesth

    (1989)
  • JB Leslie et al.

    Attenuation of the hemodynamic responses to endotracheal intubation with preinduction intravenous labetalol

    J Clin Anesth

    (1989)
  • H Magnusson et al.

    Methohexitone anaesthesia for microlaryngoscopy: circulatory modulation with metoprolol and dihydralazine

    Br J Anaesth

    (1986)
  • EO McFalls et al.

    The influence of perioperative myocardial infarction on long-term prognosis following elective vascular surgery

    Chest

    (1998)
  • LH Lindholm et al.

    Should beta blockers remain first choice in the treatment of primary hypertension? A meta-analysis

    Lancet

    (2005)
  • LA Fleisher et al.

    ACC/AHA 2006 guideline update on perioperative cardiovascular evaluation for noncardiac surgery: focused update on perioperative beta-blocker therapy: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery)

    Circulation

    (2006)
  • AR Brady et al.

    Perioperative beta-blockade (POBBLE) for patients undergoing infrarenal vascular surgery: results of a randomized double-blind controlled trial

    J Vasc Surg

    (2005)
  • AB Juul et al.

    Effect of perioperative beta blockade in patients with diabetes undergoing major non-cardiac surgery: randomised placebo controlled, blinded multicentre trial

    BMJ

    (2006)
  • Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial

    Lancet

    (2008)
  • J Higgins et al.

    Cochrane handbook for systematic reviews of interventions version 5.0.0 edn

    (2008)
  • MJ Bradburn et al.

    Sbe24: metan—an alternative meta-analysis command

    Stata Technical Bull Reprints

    (1998)
  • RF Galbraith

    A note on graphical presentation of estimated odds ratios from several clinical trials

    Stat Med

    (1988)
  • MJ Bradburn et al.

    Much ado about nothing: a comparison of the performance of meta-analytical methods with rare events

    Stat Med

    (2007)
  • MJ Sweeting et al.

    What to add to nothing? Use and avoidance of continuity corrections in meta-analysis of sparse data

    Stat Med

    (2004)
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