Nonsteroidal Antiinflammatory Drugs Used in Cardiac Surgery: A Survey of Practices and New Insights for Future Studies

We would like to share the results from our survey on non-steroidal anti-inflammatory drugs (NSAIDs) use during cardiac surgery. Acute postoperative pain management remains a primary concern after cardiac surgery as it may impair full recovery, delay rehabilitation and lead to chronic pain1. Multimodal pain management based on association of several drugs, including paracetamol, nefopam and others, allows a reduction in pain and opioids consumption (and the related side-effects). NSAIDs are parts of these multimodal strategies and are widely used for reduction of pain and opioids consumption in non-cardiac surgery, and thus they may also play a role during cardiac surgery2. To date, few studies have assessed their use in this setting. Nevertheless, the experts from the Enhanced Recovery After Surgery Society guidelines did not recommend their use regarding its potential for kidney dysfunction3. This position was based on a single-center randomized study using high doses of ibuprofen, with a slight and transient increase in acute kidney injury (AKI)4. Other studies did not show such effects5,6. In the light of these conflicting data and guidelines, we wanted to describe the habits of French anesthesiologists regarding their use of NSAIDs in cardiac surgery, allowing to drive future clinical trials on this topic. We conducted a prospective declarative survey during a 2-month period in 2021. The survey was sent electronically to the members of thoracic and vascular surgery anesthesiologist society (ARCOTHOVA) via the online software SurveyMonkey®. The survey was anonymous and responders were able to skip some questions at their discretion. The complete survey is available in the Supplementary File 1. It was divided in three parts: 1) general questions about respondents, 2) questions about the use (or not) of NSAIDs in cardiac surgery, 3) details of the practice concerning NSAID in cardiac surgery (indications, dose, contraindications etc.). Data are presented as absolute numbers or percentages and medians with interquartile ranges, as appropriate. The survey was sent to 560 caregivers and 74 answered to the survey (response rate 13.2%): 68 senior physicians and 6 junior physicians with a median experience of 7 [3-12] years in the specialty (Table 1). Only 10 % (n=7) declared to never use NSAIDs, 85% (n=63) frequently and 5% (n=4) always (Figure 1). Among the 7 physicians who did not use NSAID, the main reasons to avoid NSAIDs were the risks of kidney injury (4/7), bleeding (3/7) and gastric injury (2/7).Table 1Respondents demographical characteristics. ICU: intensive care unit; OR: operating roomVariablesRespondentsN=74Age; years39 [35-48]Male gender; n (%)43 (58)Professional status; n (%)Attending physician, public53 (72)Assistant Professor6 (8)Professor5 (7)Physicians (private exercise)10 (13)Specialty; n (%)Anesthesiologist72 (98)Others2 (2)Activity location; n (%)Public hospital2 (3)University hospital62 (84)Private clinic9 (12)Other1 (1)Experience; years6.5 [3.0-12.0]Type of ward; n (%)ICU exclusively6 (8)OR exclusively7 (9)Both61 (83) Open table in a new tab Among respondents, 81% (n=57) declared using NSAIDs for coronary artery bypass graft (with cardiopulmonary bypass), 87% (n=61) for valvular surgery, 67% (n=47) for combined surgery, 40% (n=28) for redo surgery, 44% (n=31) for aortic root surgery and only 9% (n=6) for transcatheter aortic valve replacement (TAVR). In the majority of cases (84%, n=64), NSAIDs were not considered for procedures with deep hypothermia (<30°C). Respondents suggested ketoprofen (99%) and sometimes ibuprofen (6%) administration. Diclofenac and naproxen were suggested by only 1% of respondents. Doses of ketoprofen ranged from 50 mg every 8 hours to 100 mg every 8 hours. The use of NSAIDs was a part of a multimodal analgesia approach, including a regular use of nefopam (97%), morphine (90%) and tramadol (74%). Physicians declared to also regularly use ketamine (91%) and dexamethasone (61%) in the operating room. Concerning contraindications, only 51% of physicians did not consider NSAIDs in elderly, above 75 [70-80] years old. Only 10% avoided NSAIDs in patients under single antiplatelet therapy (aspirin or clopidogrel), but 57% considered the association of dual or more antiplatelet therapy as a contraindication, and 30% did not consider NSAIDs for patients under curative anticoagulant therapy. In patients with a past history of arterial thrombosis (cerebral or cardiac stroke, peripheral ischemia or other), only 14% avoided NSAIDs. The most striking finding in our survey is the use of NSAIDs among 90% of respondents despite current guidelines not recommending them3. The absence of a strong evidence for a harmful effect of NSAIDs may explain this discrepancy. Nevertheless, the absence of evidence does not mean the absence of effect, and some points must be discussed. First, NSAIDs may enhance renal failure because of its vasoconstrictive effects on renal vascularization. The risk of AKI may greatly differ according to patient and surgical risk factors. Thus, a rational approach may be the use of NSAIDs in patient at low risk of AKI, in association with a close monitoring of postoperative renal function and fluid administration. Second, bleeding or gastrointestinal injuries were reported to be a concern for respondents. Cardiac surgery is at high risk for bleeding and because NSAIDs may disturb platelet function, their use may be questionable in high-risk situations. Nevertheless, no current evidence for a higher incidence of bleeding and/or transfusion has been documented in cardiac surgery, despite studies have not been designed for this purpose, and therefore we cannot conclude definitively4,7. While no significant increase in gastrointestinal damages was observed in these studies, the risk and benefits of NSAIDs should be weighed in patients and/or situations at high risk of gastrointestinal or systemic bleeding. Indeed, more than 50% of respondents avoided NSAIDs in redo, aortic root or deep hypothermia surgeries. In the same way, 57% of respondents do not consider NSAIDs in cases of a double antiplatelet therapy, which is consistent with the excess risk of bleeding identified in the literature. Third, NSAIDs have been described as increasing the risk of myocardial infarction, notably at high doses and long-lasting exposure8. Nevertheless, the use of NSAIDs in the perioperative period of cardiac surgery has not been associated with myocardial injuries. Our study presents limitations related to its declarative nature: respondent selection bias, reporter bias linked to the purely declarative nature of the survey, difficulty in generalizing data to actual practice and to other healthcare systems, etc. In addition, the number of respondents was relatively low, with a response rate of only 13%. Nevertheless, it demonstrated that physicians declare to use NSAIDs during cardiac perioperative settings. Because of the lack of robust trials on this particular topic, this survey emphasizes the need to perform further prospective studies, to explore the safety, efficacy, risks and benefits of NSAIDs use in the cardiac surgical population. OA: original draft writing; supervision; conceptualization MY: original draft writing MD: original draft review; conceptualization PM: original draft review and editing SP: original draft review and editing JF: original draft review and editing EB: original draft writing; supervision; conceptualization; formal analysis 1Lahtinen P, Kokki H, Hynynen M: Pain after cardiac surgery: a prospective cohort study of 1-year incidence and intensity. Anesthesiology 105:794–800, 20062Moote C: Efficacy of Nonsteroidal Anti-Inflammatory Drugs in the Management of Postoperative Pain: Drugs 44:14–30, 19923Engelman DT, Ben Ali W, Williams JB, et al: Guidelines for Perioperative Care in Cardiac Surgery: Enhanced Recovery After Surgery Society Recommendations. JAMA Surg 154:755–66, 20194Qazi SM, Sindby EJ, Nørgaard MA: Ibuprofen - a Safe Analgesic During Cardiac Surgery Recovery? A Randomized Controlled Trial. J Cardiovasc Thorac Res 7:141–8, 20155Hynninen MS, Cheng DC, Hossain I, et al: Non-steroidal anti-inflammatory drugs in treatment of postoperative pain after cardiac surgery. Can J Anaesth 47:1182–7, 20006Bainbridge D, Cheng DC, Martin JE, et al: NSAID-analgesia, pain control and morbidity in cardiothoracic surgery. Can J Anaesth 53:46–59, 20067Kulik A, Ruel M, Bourke M, et al: Postoperative naproxen after coronary artery bypass surgery: a double-blind randomized controlled trial. European Journal of Cardio-Thoracic Surgery 26:694–700, 20048Bally M, Dendukuri N, Rich B, et al: Risk of acute myocardial infarction with NSAIDs in real world use: bayesian meta-analysis of individual patient data. BMJ 357:j1909, 2017 The authors declare no conflict of interest with the present subject This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.