Associations between intraoperative nociceptive and early postoperative C-reactive protein levels in patients undergoing non-cardiac surgery under general anesthesia

Abstract Background: Early detection of postoperative increase in C-reactive protein (CRP) predicts complications after surgery. The preoperative and intraoperative factors associated with postoperative CRP changes are potentially significant in the prophylactic management of postoperative complications. Although ongoing nociception during surgery under general anesthesia is one of potential candidates for these factors, it has not been evaluated with the unavailability of valid nociception measures in clinical practice. Then we adopted averaged values of nociceptive response (NR) throughout surgery as intraoperative nociceptive levels, being examined the association between perioperative factors, early changes in postoperative CRP levels, and postoperative complications Material and Methods: Data from 174 adult patients undergoing elective non-cardiac surgery under general anesthesia on perioperative variables, including age, sex, BMI, American Society of Anesthesiologists-physical status (ASA-PS), duration of surgery, mean NR during surgery as intraoperative nociceptive level, CRP levels before and after surgery on postoperative day (POD) 1, and postoperative complications using the extended Clavien-Dindo classification were retrospectively obtained in a training cohort. Multivariate regression analysis was performed to determine the independent factor of CRP levels on POD1and to develop a prediction model. In two validation cohorts, both 75 patients undergoing mastectomy (validation cohort A) and 139 patients undergoing laparoscopic or open abdominal surgery (validation cohort B) were separately selected, and retrospectively utilized to evaluate the value of the prediction model. Results: CRP levels on POD1 in the training cohort significantly increased in the order of Clavien-Dindo grades. Multivariate regression analysis selected mean NR, BMI, and duration of surgery to set up the prediction model of CRP level on POD1, which showed significant correlation with the measured CRP in both two validation cohorts. To confirm associations between mean NR, postoperative CRP, and major complications (Clavien-Dindo grade ≥ IIIa), we performed a propensity score matching in the validation cohort B, using age, BMI, ASA-PS, and duration of operations, finding that both mean NR and CRP levels on POD1 were significantly higher in patients with major complications than those without major complications. Conclusion: Increases in the intraoperative nociceptive level likely associated with early increases in CRP level after surgery. Keywords: C-reactive protein, Postoperative complications, Nociception.