Abstract
BACKGROUND: To evaluate the association between tramadol use and short-term outcomes, including 28-day mortality, intensive care unit (ICU) mortality, and ICU length of stay, in critically ill patients undergoing cardiac surgery. METHODS: This retrospective cohort study included 3,544 participants from the MIMIC-IV database. A comprehensive analytical approach was employed, including multivariate Cox regression, subgroup analysis, propensity score matching (PSM), inverse probability weighting (IPW), doubly robust estimation, and E-value calculation. Receiver operating characteristic (ROC) curves and the DeLong test were used to compare the predictive performance of different opioids, and SHAP analysis was employed for model interpretation. RESULTS: Tramadol use was consistently associated with a significant reduction in 28-day mortality across all models. The hazard ratios (HR) ranged from 0.305 to 0.341 after rigorous adjustment and matching (all P < 0.05). Subgroup analyses demonstrated the robustness of this protective association, and a significant interaction was observed with respect to surgery type after PSM. Furthermore, tramadol demonstrated superior predictive performance for 28-day mortality (AUC = 0.603) compared to other opioids, including fentanyl, hydromorphone, morphine, and oxycodone AUC range: 0.523-0.597). However, no significant association was found with secondary outcomes like ICU mortality or length of stay. CONCLUSION: Tramadol administration is independently associated with a significantly lower risk of 28-day mortality in cardiac surgery patients, showing better predictive utility than other common opioids, which may inform postoperative analgesic strategies.