Timing of β-Blocker Reintroduction and the Occurrence of Postoperative Atrial Fibrillation After Cardiac Surgery

A Prospective Cohort Study

Camille Couffignal, Pharm.D.; Julien Amour, M.D., Ph.D.; Nora Ait-Hamou, M.D.; Bernard Cholley, M.D., Ph.D.; Jean-Luc Fellahi, M.D., Ph.D.; Xavier Duval, M.D., Ph.D.; Yolande Costa De Beauregard, Pharm.D.; Patrick Nataf, M.D.; Marie-Pierre Dilly, M.D.; Sophie Provenchère, M.D.; Philippe Montravers, M.D., Ph.D.; France Mentré, M.D., Ph.D.; Dan Longrois, M.D., Ph.D.

Disclosures

Anesthesiology. 2020;132(2):267-279. 

In This Article

Abstract and Introduction

Abstract

Background: For cardiac surgery patients under chronic β-blocker therapy, guidelines recommend their early postoperative reintroduction to decrease the incidence of postoperative atrial fibrillation. The authors hypothesized that the timing of β-blocker reintroduction affects their effectiveness on the incidence of postoperative atrial fibrillation.

Methods: This multicenter prospective French cohort study included patients on β-blockers (more than 30 days before surgery) in sinus rhythm without a pacemaker. The primary outcome, time sequence of β-blocker reintroduction, was analyzed for 192 h after surgery. The secondary outcome, relationship between the occurrence of postoperative atrial fibrillation and timing of β-blocker reintroduction, was analyzed based on pre- and intraoperative predictors (full and selected sets) according to landmark times (patients in whom atrial fibrillation occurred before a given landmark time were not analyzed).

Results: Of 663 patients, β-blockers were reintroduced for 532 (80%) but for only 261 (39%) patients in the first 48 h after surgery. Median duration before reintroduction was 49.5 h (95% CI, 48 to 51.5 h). Postoperative atrial fibrillation or death (N = 4) occurred in 290 (44%) patients. After performing a landmark analysis to take into account the timing of β-blocker reintroduction, the adjusted odds ratios (95% CI) for predictor full and selected (increased age, history of paroxysmal atrial fibrillation, and duration of aortic cross clamping) sets for the occurrence of postoperative atrial fibrillation were: adjusted odds ratio (full) = 0.87 (0.58 to 1.32; P = 0.517) and adjusted odds ratio (selected) = 0.84 (0.58 to 1.21; P = 0.338) at 48 h; adjusted odds ratio (full) = 0.64 (0.39 to 1.05; P = 0.076) and adjusted odds ratio (selected) = 0.58 (0.38 to 0.89; P = 0.013) at 72 h; adjusted odds ratio (full) = 0.58 (0.31 to 1.07; P = 0.079) and adjusted odds ratio (selected) = 0.53 (0.31 to 0.91; P = 0.021) at 96 h.

Conclusions: β-Blockers were reintroduced early (after less than 48 h) in fewer than half of the cardiac surgery patients. Reintroduction decreased postoperative atrial fibrillation occurrence only at later time points and only in the predictor selected set model. These results are an incentive to optimize (timing, doses, or titration) β-blocker reintroduction after cardiac surgery.

Introduction

Many patients who undergo surgical procedures receive chronic cardiovascular medication that must be managed during the perioperative period. For patients under chronic β-blocker therapy, reintroduction of β-blockers as soon as possible after cardiac[1] and noncardiac[2] surgeries is a grade 1 recommendation and is followed by many institutions and clinicians.[3] Early reintroduction of β-blockers is supposed to attenuate the deleterious effects of excessive sympathetic nervous system activation after surgery.[4]

In cardiac surgery, postoperative reintroduction of β-blockers is one of the few modifiable risk factors to prevent the occurrence of transient postoperative atrial fibrillation that concerns up to 47% of patients.[5] Prevention of transient postoperative atrial fibrillation is important because its occurrence is independently associated with increased morbidity (namely, stroke), length of stay, and mortality in the immediate postoperative period.[5] Similar statistical associations between transient postoperative atrial fibrillation and morbidity/mortality have been found in noncardiac surgery.[3] Interestingly, transient postoperative atrial fibrillation is also associated with long-term mortality,[6] despite the fact that fewer than 2% of the patients with transient postoperative atrial fibrillation included in a trial were discharged from the hospital with persistent atrial fibrillation.[7]

The relationship between postoperative reintroduction of β-blockers after cardiac surgery and the risk of postoperative atrial fibrillation was investigated in several studies. Mathew et al.[8] showed that β-blocker withdrawal after cardiac surgery increased the risk of postoperative atrial fibrillation (odds ratio = 1.91; 95% CI, 1.52 to 2.4). In a more recent article from the same group, similar findings were reported.[9]

Guidelines stipulate that reintroduction of β-blockers should respect contraindications[1] but make no specific statements on the timing of the reintroduction other than "as early as possible." In the majority of published studies, the time sequence of reintroduction was not explicitly addressed; the reintroduction of β-blockers (oral route) may have a delayed effect related to the much lower postoperative bioavailability of oral as compared with intravenous β-blockers.[10] Furthermore, the nonreintroduction of β-blockers could be explained by the use of catecholamines that have been shown to be independently associated with an increased risk of postoperative atrial fibrillation;[11] other contraindications to β-blocker reintroduction may exist. Finally, side effects of β-blocker reintroduction, such as arterial hypotension with the associated risk of stroke, have to be considered.[12]

Given the widely accepted guidelines-based reintroduction of β-blockers after cardiac surgery but the persistent issues such as those enumerated above, we investigated several aspects of the β-blocker reintroduction after cardiac surgery. We hypothesized that the effectiveness of β-blocker reintroduction in preventing transient postoperative atrial fibrillation may be dependent on the temporal relationship between β-blocker reintroduction and postoperative atrial fibrillation occurrence in the first 192 h after cardiac surgery.

The main goals of this study were to describe the time sequence of β-blocker reintroduction after cardiac surgery with the reason for delayed reintroduction and also to identify potential predictive factors of postoperative atrial fibrillation occurrence with the estimated association between timing of β-blocker reintroduction and postoperative atrial fibrillation occurrence.

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