Summary of the paper
In the February issue of the Annals of Internal Medicine, Meurin and the colleagues from the French Society of Cardiology [9] have published results of their randomized trial on the NSAIDs Treatment for Postoperative Pericardial Effusion, performed in 5 French postoperative cardiac rehabilitation centres. They evaluated 196 patients at high risk for tamponade because of moderate to large persistent pericardial effusion (grade 2, 3, or 4 on a scale of 0 to 4, as measured by echocardiography) more than 7 days after cardiac surgery. The patients were randomly assigned at each site in blocks of 4 to diclofenac, 50 mg, or placebo twice daily for 14 days. The main end point was change in effusion grade after 14 days of treatment. Secondary end points included frequency of late cardiac tamponade. The initial mean pericardial effusion grade was 2.58 (SD, 0.73) for the placebo group and 2.75 (SD, 0.81) for the diclofenac group. The 2 groups showed similar mean decreases from baseline after treatment (-1.08 grades [SD, 1.20] for the placebo group vs. -1.36 (SD, 1.25) for the diclofenac group). The mean difference between groups was -0.28 grade (95% CI, -0.63 to 0.06 grade; P=0.105). Eleven cases of late cardiac tamponade occurred in the placebo group and 9 in the diclofenac group (P=0.64). These differences persisted after adjustment for grade of pericardial effusion at baseline, treatment site, and type of surgery. Therefore, in this trial, the use of diclofenac, 100 mg/d, did not significantly reduce the size of pericardial effusions or the risk for late cardiac tamponade. Moreover, this study confirms that moderate to large pericardial effusion (grade 2, 3, or 4) occurring 7 to 30 days after cardiac surgery is a severe condition because 10.2% of these patients required pericardiocentesis in the 14 days after they enrolled in the study.
Discussion
Therapy with NSAIDs has been previously considered useful for postoperative pericardial effusions that persist after the first postoperative week. Pericardial effusions and tamponade that occur early after surgery are usually related to surgical bleeding; however, late effusions and tamponade (which are much more frequent) have multiple causal mechanisms, and inflammation seems to play an important role. Postpericardiotomy syndrome may include fever, friction rubs, chest pain, pleuritis, and pericardial effusion. Therefore, use of an NSAID to treat late postoperative pericardial effusions seems logical, and it is common in daily practice (up to 77% of patients in several surveys [2,3,10]). However, patients who have valvular surgery routinely receive oral anticoagulants, and the combination of these agents with an NSAID could provoke gastrointestinal haemorrhage. In addition, use of an NSAID after CABG could promote atherothrombotic complications. Diclofenac was selected for this study because it is widely used and seems not to antagonize the irreversible platelet inhibition induced by aspirin [11], which is usually prescribed for these patients. However, the main limitation of the study is that it was underpowered to detect small beneficial effects from diclofenac or to evaluate adverse clinical events from the drug, because only 95 patients received the drug.
Although postoperative pericardial effusion is frequent and potentially severe, few randomized, controlled trials have examined treatment for this condition. Recommendation given in the ESC Guidelines to treat postoperative pericardial effusion with NSAIDs was based on the results of the double-blind, placebo-controlled, randomized study by Horneffer et al. [6] applying a 10-day course of ibuprofen or indomethacin. Of 1019 adult patients undergoing cardiac operations during a 14-month period, a diagnosis of postpericardiotomy syndrome was made in 187, and 149 were enrolled in the study. Diagnosis was based on the presence of at least two of the following: fever, anterior chest pain, and friction rub. Drug efficacy was defined as the resolution of at least two of these criteria within 48 hours of drug initiation. Ibuprofen and indomethacin were 90.2% and 88.7% effective, respectively, and both were significantly more effective than placebo (62.5%, p = 0.003).
The occurrence of side effects, including nausea, vomiting, renal failure, and fluid retention, was low in all groups (13.1% for ibuprofen, 16.1% for indomethacin, and 16.7% for placebo [p = not significant). Length of hospital stay, incidence of ischemic events, and accumulation of significant pericardial effusions were similar in all groups. The results of this study suggested that both ibuprofen and indomethacin provide safe and effective symptomatic treatment for postpericardiotomy syndrome.
Aspirin [12] and diclofenac [13] were tested in clinical trials that examined prevention of the postcardiotomy syndrome (not treatment), but these trials included rather limited number of patients. A prospective, randomized, double-blind on primary prevention of postpericardiotomy syndrome was performed by Finkelstein et al [14] in 163 patients who underwent cardiac surgery in two centres in Israel between. On the 3rd postoperative day, the patients were randomly assigned to receive colchicine (1.5 mg/day) or placebo for 1 month. All were evaluated monthly for the first 3 postoperative months for development of postpericardiotomy syndrome. Of the 111 patients who completed the study, 47 (42.3%) received colchicine and 64 (57.7%) placebo. There was no statistically significant difference between the groups in clinical or surgical characteristics. The postpericardiotomy syndrome was diagnosed in 19 patients (17.1%), 5/47 cases (10.6%) in the colchicine group and 14/64 (21.9%) in the placebo group. However the study was underpowered and the difference showed only a trend toward statistical significance (p < 0.135). Therefore, colchicine is further being tested in an ongoing prevention trial of prevention (COPPS) [15].
Conclusion:
In conclusion, the study of Meuring et al. is one step further in introduction of evidence-based medicine in the management of pericardial diseases and suggests that, until we have further data, clinicians should avoid the routine use of NSAIDs [9]. This is most probably especially true, in the absence of evidence of inflammation, such as elevated C-reactive protein levels or other symptoms. Furthermore, in the postoperative setting, corticosteroids plus colchicine may be the favoured choice to avoid negative interactions between NSAID and oral anticoagulant therapy [16]. However, careful monitoring of postoperative pericardial effusions is warranted, especially for large effusions. Redo surgery and pericardiectomy are very rarely needed. Primary prevention of postperiocardiotomy syndrome using short-term perioperative steroid treatment, intrapericardial treatment or colchicine should be also further evaluated.
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