Effect of nonsteroidal anti-inflammatory drug selection for preventive analgesia on the severity of postoperative cognitive dysfunction: a prospective, comparative study

BACKGROUND: Postoperative cognitive dysfunction is a common complication, with neuroinflammation recognized as one of its key pathogenetic mechanisms. Despite extensive evidence supporting the use of nonsteroidal anti-inflammatory drugs for preventive analgesia, comparative studies evaluating their effects on blood–brain barrier injury markers and cognitive outcomes remain limited and do not allow for definitive conclusions.

AIM: This study aimed to compare the effects of preventive administration of ibuprofen and ketoprofen on the level of neuroinflammation and the severity of early postoperative cognitive dysfunction in patients undergoing elective surgery under general anesthesia.

METHODS: A single-center, randomized, prospective study was conducted. A total of 45 patients were enrolled and randomly assigned into two groups. Thirty minutes before anesthesia induction, patients in group 1 (n = 23) received intravenous ibuprofen 800 mg, whereas patients in group 2 (n = 22) received intravenous ketoprofen 100 mg. Biochemical markers (S100B, C-reactive protein, fibrinogen, and D-dimer) and cognitive test results (MoCA, TMT, MMSE) were assessed over time.

RESULTS: The groups were comparable in baseline characteristics. On postoperative day 1, S100B concentration in the ibuprofen group was significantly lower than in the ketoprofen group: 0.117 ng/mL vs. 0.164 ng/mL, respectively (p = 0.046). By postoperative day 3, this difference was no longer observed. No statistically significant intergroup differences were found in the trends of cognitive test results or in the levels of C-reactive protein, fibrinogen, and D-dimer. None of the patients demonstrated cognitive impairment meeting the predefined criterion (deviation ≥ 2 points on cognitive tests).

CONCLUSION: Preventive administration of ibuprofen was associated with a less pronounced increase in S100B levels in the early postoperative period compared with ketoprofen, which may indicate a stronger inhibitory effect on neuroinflammation. However, this difference resulted only in a statistically non-significant reduction in the incidence of postoperative cognitive dysfunction. The main limitations of the study include the small sample size and the short duration of postoperative cognitive follow-up.