The cortisol stress response induced by surgery: A systematic review and meta-analysis

Objective: Surgery is a stressor that can be categorized by duration and severity and induces a systemic stress response that includes increased adrenal cortisol production. However, the precise impact of surgical stress on the cortisol response remains to be defined. Design: We performed a systematic review and meta-analysis to assess the cortisol stress response induced by surgery and to stratify this response according to different parameters. Methods: We conducted a comprehensive search in several databases from 1990 to 2016. Pairs of reviewers independently selected studies, extracted data and evaluated the risk of bias. Cortisol concentrations were standardized, pooled in meta-analysis and plotted over time. Results: We included 71 studies reporting peri-operative serum cortisol measurements in 2953 patients. The cortisol response differed substantially between moderately/highly invasive and minimally invasive surgical procedures. Minimally invasive procedures did not show a peri-operative cortisol peak, whereas more invasive surgeries caused a cortisol surge that was more pronounced in older subjects, women and patients undergoing open surgery and general anaesthesia. The duration of the procedure and the use of etomidate for induction of anaesthesia did not affect the cortisol response. Conclusions: The peri-operative cortisol stress response is dynamic and influenced by patient-specific, surgical and anaesthetic features. However, the available evidence is derived from highly heterogeneous studies, with only two of 71 studies measuring cortisol by mass spectrometry, which currently prevents a precise and reproducible definition of this response.