Author: Michael Vlessides
Absent or delayed beta-blocker administration after the fifth postoperative day is associated with increased rates of postoperative atrial fibrillation in patients who underwent coronary artery bypass graft (CABG) surgery, valve surgery, or combined CABG and valve surgeries, according to new research.
In addition, in these patient groups, absent or delayed beta-blocker administration was associated with immediate postoperative prolonged mechanical ventilation or reintubation.
“We wanted to know if administering beta-blockers before postoperative day 5 correlates with lower rates of postoperative atrial fibrillation and improves such outcomes as time on ventilator, mortality, renal failure and need for dialysis,” said Emily Chanan, MD, an assistant professor of anesthesiology and critical care at NYU Langone Health, in New York City.
“We used postoperative day 5 as the benchmark because our cardiac surgeons felt it was the cutoff for when a patient was fast-tracked and doing well, versus somebody who had a more complicated length of stay.”
Looking for Rebound Effect
As part of the retrospective cohort study, Dr. Chanan and her colleagues identified patients who had CABG, valve, or combined CABG and valve surgeries. They then separated patients who received beta-blockers before postoperative day 5 from those who either received the agents after that day or did not receive them at all (Table 1). “Most patients come in with pretty good heart function, with an average preoperative ejection fraction of 60,” Dr. Chanan said in an interview with Anesthesiology News.
|Table 1. Clinical Characteristics of Patients|
|Clinical Characteristic||N=2,526 Patients, n (% or interquartile range)|
|Preoperative beta-blocker use||1,671 (66)|
|Age, years||66 (58-74)|
|Sex, male||1,714 (68)|
|Type of surgery|
|Chronic lung disease||100 (4.0)|
|Cerebrovascular disease||235 (9.3)|
|Average presurgery blood creatinine, mg/dL||0.9 (0.8-1.1)|
|Preoperative hemodialysis||64 (2.5)|
|Preoperative cardiogenic shock||55 (2.2)|
|Preoperative inotrope||64 (2.5)|
|Intra-aortic balloon pump||83 (3.3)|
|Postoperative tamponade||3 (0.12)|
|Postoperative cardiac arrest||36 (1.4)|
|CABG, coronary artery bypass graft|
The study involved 3,617 patients who underwent cardiac surgery at the institution between Jan. 1, 2013 and Sept. 30, 2017. Of these, 2,526 patients (mean age, 66 years; 68% men) underwent CABG, valve or combined surgeries. Preoperative beta-blockade was given to 1,671 patients in the 24 hours prior to surgery.
As Dr. Chanan reported at the 2019 annual meeting of the International Anesthesia Research Society (abstract D39), 1,695 patients (67%) received beta-blockers in the first five days after surgery (Table 2). Conversely, 831 patients (33%) did not receive beta-blockers or received them after postoperative day 5.
|Table 2. Results in All Patients by Time of Beta-Blocker Administration|
|Outcome||Early Continuation Of Beta-Blockers, POD 0-5 (n=1,695)||Absent or Delayed Beta-Blockers After POD 5 (n=831)||Adjusted OR (95% CI)||Adjusted P Value|
|Mortality at discharge||10 (0.59%)||19 (2.3%)||1.4 (0.63-3.3)||0.41|
|Postoperative cerebrovascular event||15 (0.88%)||27 (3.2%)||1.9 (0.94-4.2)||0.08|
|Postoperative atrial fibrillation||276 (16%)||196 (24%)||1.5 (1.2-1.9)||<0.001|
|Prolonged mechanical ventilation or reintubation||57 (3.4%)||115 (14%)||2.5 (1.7-3.7)||<0.001|
|Renal failure or new need for dialysis||5 (0.29%)||14 (1.7%)||2.5 (0.8-9.2)||0.12|
|OR, odds ratio; POD, postoperative day|
Similar percentages were found in the 1,671 patients who received preoperative beta-blockade: 1,086 (65%) received the agents during the first to fifth postoperative days, and 585 (35%) were given them after postoperative day 5 or not at all (Table 3).
|Table 3. Results in Patients Receiving Preoperative Beta-Blockers|
|Outcome||Early Continuation Of Beta-Blockers, POD 0-5 (n=1,086)||Absent or Delayed Beta-Blockers After POD 5 (n=585)||Adjusted OR (95% CI)||Adjusted P Value|
|Mortality at discharge||8 (0.74%)||5 (0.85%)||1.5 (0.43-5.9)||0.53|
|Postoperative cerebrovascular event||9 (0.83%)||20 (3.4%)||2.0 (0.89-5.0)||0.11|
|Postoperative atrial fibrillation||171 (16%)||146 (25%)||1.7 (1.3-2.3)||<0.001|
|Prolonged mechanical ventilation or reintubation||41 (3.8%)||84 (14%)||2.5 (1.6-3.9)||<0.001|
|Renal failure or new need for dialysis||3 (0.28%)||7 (1.2%)||5.0 (0.81-97)||0.14|
|OR, odds ratio; POD, postoperative day|
“In this population, we were interested in seeing if there was some sort of rebound or withdrawal effect in patients who got beta-blockers before surgery,” Dr. Chanan said.
Causality Not Demonstrated
The study found that patients who had absent or delayed administration of beta-blockers showed significantly increased risk for both new-onset postoperative atrial fibrillation (odds ratio [OR], 1.5; 95% CI, 1.2-1.9; P<0.001) and prolonged mechanical ventilation or reintubation (OR, 2.5; 95% CI, 1.7-3.7; P<0.001).
Despite this risk, these patients were not found to have significantly increased odds of mortality at discharge (OR, 1.4; 95% CI, 0.63-3.3; P=0.41), postoperative stroke (OR, 1.9; 95% CI, 0.94-4.2; P=0.08), or renal failure or new need for dialysis (OR, 2.5; 95% CI, 0.8-9.2; P=0.12).
“We looked at postoperative stroke because of the POISE study [Lancet 2008;371(9627):1839-1847] in the noncardiac surgical population, which showed an increased rate of stroke with atenolol,” Dr. Chanan explained. “But we did not find that.”
Similar results were seen in patients who were given beta-blockers within 24 hours of cardiac surgery. In this group, absent or delayed administration of postoperative beta-blockers was associated with increased odds of new-onset postoperative atrial fibrillation (OR, 1.7; 95% CI, 1.3-2.3; P<0.001) and prolonged mechanical ventilation or reintubation (OR, 2.5; 95% CI, 1.6-3.9; P<0.001).
The following end points were not significantly associated with absent or delayed administration of postoperative beta-blockers: mortality at discharge (OR, 1.5; 95% CI, 0.43-5.9; P=0.53), postoperative stroke (OR, 2.0; 95% CI, 0.89-5.0; P=0.11), renal failure, or new need for dialysis (OR, 5.0; 95% CI, 0.81-97; P=0.14).
As Dr. Chanan pointed out, the study does not demonstrate causality. “What’s interesting to us,” she concluded, “is that the study shows that there is some association with a better outcome if you get your beta-blockers earlier. So perhaps we need to think about timing. If we can, we should push administration to before postoperative day 5, because that may be beneficial for these patients.”
The findings did not come as a surprise to Sasha K. Shillcutt, MD, MS, a professor of anesthesiology and the vice chair of strategy and innovation at the University of Nebraska Medical Center, in Omaha. “The most hemodynamically challenging period after cardiac surgery is within the first five days, and the half-life of most beta-blockers given in the preoperative period has been exceeded,” she said.
Yet as Dr. Shillcutt went on to discuss, beta-blockers are not for all cardiac surgery patients. “The study primarily included patients with normal LV [left ventricle] function, and did not show the same results in patients with severe heart failure after cardiac surgery. Beta-blocker use may be contraindicated in high-risk surgery patients with significant LV dysfunction or bradycardia, and thus we don’t know about the benefits of use in those populations.” She also noted that beta-blockers can worsen respiratory function in patients with asthma.
“We try to start beta-blockers immediately after surgery, or continue beta-blocker use in patients currently taking them prior to surgery,” Dr. Shillcutt said.