Ankara, Turkey - A new study suggests that the administration of sodium nitroprusside during coronary artery bypass graft (CABG) surgery might be an option to reduce the risk of atrial fibrillation following surgery, with the incidence of postoperative atrial fibrillation one-third that observed in patients given a placebo [1]. Investigators suggest that nitroprusside, a nitric-oxide (NO) donor, reduces inflammation, which in turn reduces postoperative atrial fibrillation risk, as C-reactive protein (CRP) levels were significantly reduced among those treated with nitroprusside.

The small pilot study, conducted by lead investigator Dr Raif Cavolli (Umut Heart Hospital, Ankara, Turkey) and colleagues, is published in the July 15, 2008 issue of Circulation.

Atrial tachyarrhythmia—usually atrial fibrillation or atrial flutter—is a common complication following cardiac surgery and is associated with hemodynamic deterioration, stroke, other thromboembolic events, a prolongation of hospital stay, and increased costs. Postsurgical atrial fibrillation occurs in 20% to 40% of CABG patients, write Cavolli and colleagues, but the exact mechanism behind its development is unknown.

In this investigation of sodium nitroprusside, a NO donor believed to limit the amount of reperfusion injury during surgery, Cavolli and colleagues included patients undergoing CABG surgery but excluded those undergoing CABG plus valve repair or replacement. Fifty patients received placebo, and 50 patients were treated with sodium nitroprusside after the release of the cross-clamp and before rewarming had been started. Nitroprusside was administered as a continuous infusion at 0.5 µg/kg per minute, and all patients were monitored with telemetry for five days.

During the study period, 12% of patients treated with sodium nitroprusside developed atrial fibrillation, compared with 36% in the control arm (p=0.005). During the study, the average postoperative CRP levels increased in both treatment arms, but patients who received nitroprusside had significantly lower CRP levels throughout the entire postoperative period than those in control arm.

Cavolli and colleagues write there is evidence that NO function is disrupted because of ischemia-reperfusion injury during cardiac surgery. They note that in addition to preventing reperfusion injury, nitroprusside has anti-inflammatory and antistunning effects, in addition to inhibiting apoptosis.

Commenting on the study for heartwire, Dr Joseph Mathew (Duke University Medical Center, Durham, NC) said it was an interesting hypothesis, as it "makes sense to test the theory that NO donation would ameliorate reperfusion injury." However, from his own observational experience, his group uses sodium nitroprusside in the rewarming process, and it does not appear to have an effect on the incidence of postoperative atrial fibrillation.

He noted that the study was small, and patients were relatively healthy, with normal ejection fractions, as would be expected in a pilot study. He pointed out, however, that Cavolli and colleagues did not adjust for medications given in the postoperative period, agents such as beta blockers, ACE inhibitors, statins, or withdrawal of these drugs, important confounders that have been shown to modulate postoperative atrial fibrillation. He noted that the study should have adjusted for the use of statins prior to surgery, especially since CRP is an outcomes measure.

In 2004, Mathew, the lead author of the Multicenter Study of Perioperative Ischemia Research Group, published a paper in the Journal of the American Medical Association that established a risk index for atrial fibrillation after cardiac surgery [2]. Risk factors associated with the arrhythmia were advanced age, history of atrial fibrillation or chronic obstructive pulmonary disease, valve surgery, and the postoperative withdrawal of a beta blocker or an ACE inhibitor. Reduced risk was associated with postoperative administration of beta blockers, ACE inhibitors, potassium supplementation, and nonsteroidal anti-inflammatory drugs.

Attempts to reduce the incidence of atrial fibrillation after cardiac surgery have been under investigation in numerous trials, many of which have been reported by heartwire. One small, randomized clinical trial suggested that corticosteroids given after cardiac surgery could significantly reduce the risk of developing postsurgical atrial fibrillation, while another, the PAPABEAR study, showed that the use of prophylactic amiodarone therapy reduced the risk of atrial tachyarrhythmias after cardiac surgery. Digoxin, beta blockers, magnesium, and L-arginine, the precursor of NO, have also been studied.