Timing of Beta Blocker Administration Post–Cardiac Surgery Explored

Administration of beta blockers after cardiac surgery provides a significant protective effect against postoperative atrial fibrillation, but the timing of administration does not seem to affect the incidence of the sometimes devastating adverse event, a study has concluded. The researchers thereforerecommended use of the agents on either postoperative day 1 or 2, in appropriate patient populations.

“Most anesthesiologists understand that postoperative atrial fibrillation is common and associated with worse outcomes after cardiac surgery,” said Nathan Waldron, MD, MHS, a cardiothoracic anesthesiology fellow at Duke University Health System, in Durham, N.C. “While beta blockers have been shown repeatedly to prevent postoperative atrial fibrillation when administered postoperatively, it’s not known if the timing of administration matters.

“In a basic view, it would make sense that the earlier you could give someone a protective medication, the better,” Dr. Waldron continued. “But given that patients are a little bit more hemodynamically precarious in the early postoperative period, there is a significant proportion of patients who are not getting their beta blockers until much later in the postoperative recovery phase, after their risk of [postsurgical] atrial fibrillation has risen substantially … or even after they’ve developed it.”

Patient Acuity

To examine the effect of beta blocker timing on the development of postoperative atrial fibrillation, Dr. Waldron and his colleagues evaluated the records of 972 patients undergoing coronary artery bypass graft (CABG) surgery (with or without valvular surgery) using cardiopulmonary bypass. The researchers used propensity-weighted models and multivariable logistic regression to determine the influence of timing on the ability of postoperative beta blockers to prevent postoperative atrial fibrillation. Early administration was considered to be on or before postoperative day 1, while late was on or after postoperative day 2.

“When we began the study, we had some thought that maybe earlier administration would be better,” Dr. Waldron said. “I don’t think that is an unreasonable first assumption. Nevertheless, our results did not support this conclusion.”

As reported at the 2017 annual meeting of the Society of Cardiovascular Anesthesiologists (abstract SCA163), postoperative atrial fibrillation occurred in 300 patients (30.9%). Of the 745 patients who received the agents prior to the occurrence of postoperative atrial fibrillation, there were 586 (78.7%) who received beta blockers early and 159 (21.3%) who received them late. Patients who developed postoperative atrial fibrillation were significantly older, had an increased comorbidity burden, were more likely to be affected by postoperative complications, required more postoperative inotropes, and had more recent surgeries than their counterparts who did not develop postoperative atrial fibrillation.

Early and Late Efficacy

Inverse probability of treatment weighting models found that both early (odds ratio [OR], 0.57; 95% CI, 0.44-0.73; P<0.0001) and late (OR, 0.52; 95% CI, 0.38-0.71; P<0.0001) beta blocker use gave similar protection against postoperative atrial fibrillation, compared with no use or subsequent use (after development of the adverse event).

“Patients who received early postoperative beta blockers saw a 43% reduction in their odds of atrial fibrillation, after accounting for other factors that would impact that risk,” Dr. Waldron said in an interview with Anesthesiology News. “Similarly, patients who received late postoperative beta blockers had about a 48% reduction in their odds of postoperative atrial fibrillation.”

Regardless of timing, the investigators recommended judicious use of the agents in cardiac surgery patients, although they noted some circumstances when their use is not recommended. “Beta blockers are one of the most protective things you can do to prevent postoperative atrial fibrillation, when appropriate.

“However, how do we adequately ‘prophylax’ for postoperative atrial fibrillation in patients with very poor intrinsic cardiac function or who are on mechanical circulatory support? I think the early use of postoperative beta blockers would be controversial in these individuals. So, our group is trying to come up with novel solutions to help prevent postoperative atrial fibrillation that may be either better tolerated or not have some of the potential hemodynamic downsides of postoperative beta blockers.”

John F. Butterworth IV, MD, called the findings provocative, but also brought to light the shortcomings of retrospective analyses. “These types of retrospective studies are hypothesis generating, not hypothesis testing; a proper randomized trial would not need to adjust for differences between groups,” he said, a professor and chair of anesthesiology at Virginia Commonwealth University, in Richmond.

“There may very well be between-group differences that cannot be accounted for by statistical adjustments,” Dr. Butterworth pointed out. “Just think about purported cardiac benefits of hormone replacement therapy in postmenopausal women, which were supported by all sorts of animal research and retrospective studies, but nevertheless rejected by one proper clinical trial.”