Effect of Sodium Nitroprusside on the Occurrence of Atrial Fibrillation After Cardiothoracic Surgery

Scott Bolesta PharmD; Timothy D Aungst PharmD; Fanhui Kong PhD


The Annals of Pharmacotherapy. 2012;46(6):785-792. 

In This Article

Abstract and Introduction


Background: Postoperative atrial fibrillation (POAF) is a frequent complication following cardiothoracic surgery and is associated with an increase in morbidity, mortality, and cost. One small prospective study of patients undergoing isolated coronary artery bypass graft surgery has demonstrated a decrease in the risk of POAF with the use of sodium nitroprusside.
Objective: To determine whether there is an association between intraoperative sodium nitroprusside use and the incidence of POAF.
Methods: A retrospective cohort of 1025 patients aged 18 years and older who underwent any cardiac surgery between April 2007 and July 2010 was evaluated at Regional Hospital of Scranton. Patients with a history of atrial fibrillation, those who had undergone cardiothoracic surgery, or those undergoing surgical treatment for atrial fibrillation were excluded. The primary outcome was the odds of developing POAF given the utilization of sodium nitroprusside during cardiothoracic surgery. POAF was defined according to the Society of Thoracic Surgeons Adult Cardiac Surgery Database version 2.61 as a new onset of atrial fibrillation/flutter requiring treatment that was not present preoperatively. Data on use of intraoperative sodium nitroprusside were obtained from the pharmacy department's billing database.
Results: The final analysis included 699 patients; 473 received sodium nitroprusside. The incidence of POAF was 25.4% in the sodium nitroprusside group and 27.9% in the control group. Univariate analysis demonstrated no association of sodium nitroprusside with POAF (OR 0.880; 95% CI 0.615 to 1.257). Multivariate analysis also showed no significant difference in the odds of POAF with sodium nitroprusside (OR 0.827; 95% CI 0.565 to 1.210). Repeating the analysis in 276 propensity score–matched patients also failed to demonstrate any association (OR 0.774; 95% CI 0.454 to 1.319).
Conclusions: There was no significant association between the use of sodium nitroprusside during cardiothoracic surgery and POAF.


Postoperative atrial fibrillation (POAF) occurs in approximately 10–90% of patients undergoing cardiothoracic surgery.[1–5] The incidence varies widely based on several factors, including type of procedure, patient demographics, and even geographic location. Although 70% of events occur within 4 days of the surgical procedure,[3] it is also a leading cause for readmission.[6] Development of POAF has been associated with an increase in postoperative myocardial infarction, congestive heart failure, renal insufficiency, infection, and prolonged mechanical ventilation.[2–5] In addition, patients are 2–3 times more likely to experience a cerebrovascular accident[1–4] and more than twice as likely to die.[4,5,7] There is also an added burden placed on the health care system from POAF resulting from an increased length of stay and added cost.[2,3,5,7,8]

The most widely recommended therapy for the prevention of POAF is the use of a β-adrenergic antagonist to decrease sympathetic stimulation.[9–12] However, more recent evidence suggests that inflammation and oxidative stress play a role in the development of POAF.[13] Therefore, medications that have antiinflammatory or antioxidant effects have been evaluated for their utility in the prevention of POAF.[13] Among them is sodium nitroprusside, a relatively inexpensive and moderately safe drug, with a quick onset of action and short half-life. In the perioperative period, sodium nitroprusside is thought to counteract vascular inflammation and donate nitric oxide (NO), decreased levels of which are associated with uncontrolled conduction in cardiac myocytes.[14–16]

Based on these findings, Cavolli and colleagues conducted a prospective, double-blind, randomized pilot study to determine whether sodium nitroprusside decreased the incidence of POAF.[17] They found a statistically significant decrease in the incidence of POAF between patients who received intraoperative sodium nitroprusside and those who did not. However, the study has been criticized for several reasons.[18,19] It was relatively small, with only 50 patients in each group. The use of additional therapies found to reduce the incidence of POAF, such as statins, corticosteroids, and antiangiotensin agents, was not reported. Investigators also did not report the preoperative occurrence of atrial fibrillation of patients in each group. Finally, only patients undergoing elective coronary artery bypass graft (CABG) surgery were included, excluding patients undergoing procedures with a higher risk of POAF.

Our study sought to address some of the limitations of the pilot study by Cavolli and colleagues. Specifically, it accounts for additional perioperative medications known to affect the incidence of POAF. Also, it includes a cohort of patients undergoing procedures that would better represent the POAF risk of the general cardiothoracic surgical population. The objective of this study was to determine whether there was an association between the utilization of intraoperative sodium nitroprusside and the incidence of POAF. The working hypothesis was that use of sodium nitroprusside during cardiothoracic surgery would be associated with a decreased incidence of POAF.


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