Postoperative serum interleukin-6 level as a risk factor for development of hyperactive delirium with agitation after head and neck surgery with free tissue transfer reconstruction

Objective: Occurrence of hyperactive postoperative delirium (POD) with agitation after head and neck surgery with free tissue transfer reconstruction (HNS-FTTR) is associated with the risk of life-threatening complications. The relationships between occurrence of hyperactive POD after HNS-FTTR and inflammatory markers reflecting the surgical stress response, represented by postoperative interleukin-6 levels, are not fully understood. Methods: A retrospective study was conducted on 221 consecutive patients who underwent HNS-FTTR at our department between September 2016 and December 2021. Potential risk factors for POD were examined, including age, operation time, intraoperative blood loss, and postoperative serum levels of blood parameters such as interleukin-6, C-reactive protein, and neutrophil-to-lymphocyte ratio. Results: Hyperactive POD with agitation was observed in 54 subjects (24.4%). The postoperative hospital stay in the POD group was significantly longer than that in the non-POD group (median: 32.5 days vs. 28 days; p=0.0129). Multivariate logistic regression analysis identified age (in years) (odds ratio: 1.102; p<0.0001), operation time (min) (odds ratio: 1.004; p=0.0359), and postoperative serum interleukin-6 level (pg/mL) (odds ratio: 1.005; p=0.0384) as significant risk factors for development of POD. In a receiver operating characteristic curve and area under the curve analysis, the cut-off value for postoperative serum interleukin-6 level to predict POD development was 82.5 pg/mL. The postoperative serum interleukin-6 ≥82.5 pg/mL group developed hyperactive POD with agitation significantly more often than the postoperative serum IL-6 <82.5 pg/mL group (odds ratio: 4.400; p<0.0001). The postoperative serum IL-6 ≥82.5 pg/mL group also had significantly longer postoperative hospital stay (41.58 ± 33.42 days vs. 31.73 ± 22.89 days; p=0.0151), older age (68.60 ± 9.99 years vs. 64.30 ± 12.58 years; p=0.0054), and longer operation time (625.4 ± 114.05 min vs. 575.5 ± 98.73 min; p=0.0009) than the postoperative serum IL-6 <82.5 pg/mL group. Conclusion: Postoperative serum interleukin-6 level, as well as age and operation time, were identified as significant independent risk factors for development of hyperactive POD with agitation after HNS-FTTR. Inflammation is a potential target for the prevention and treatment of POD after HNS-FTTR.