Complications as a Mediator of the Perioperative Frailty–Mortality Association

BACKGROUND Preoperative frailty is strongly associated with postoperative complications and mortality. However, the pathways between frailty, postoperative complications, and mortality are poorly described. The authors hypothesized that the occurrence of postoperative complications would mediate a substantial proportion of the total effect of frailty on mortality after elective noncardiac surgery. METHODS Following protocol registration, the authors conducted a retrospective cohort study of intermediate- to high-risk elective noncardiac surgery patients (2016) using National Surgical Quality Improvement Program data. The authors conducted Bayesian mediation analysis of the relationship between preoperative frailty (exposure, using the Risk Analysis Index), serious complications (mediator), and 30-day mortality (outcome), comprehensively adjusting for confounders. The authors estimated the total effect of frailty on mortality (composed of the indirect effect mediated by complications and the remaining direct effect of frailty) and estimated the proportion of the frailty-mortality association mediated by complications. RESULTS The authors identified 205,051 patients; 1,474 (0.7%) died. Complications occurred in 20,211 (9.9%). A 2 SD increase in frailty score resulted in a total association with mortality equal to an odds ratio of 3.79 (95% credible interval, 2.48 to 5.64), resulting from a direct association (odds ratio, 1.76; 95% credible interval, 1.34 to 2.30) and an indirect association mediated by complications (odds ratio, 2.15; 95% credible interval, 1.58 to 2.96). Complications mediated 57.3% (95% credible interval, 40.8 to 73.8) of the frailty-mortality association. Cardiopulmonary complications were the strongest mediators among complication subtypes. CONCLUSIONS Complications mediate more than half of the association between frailty and postoperative mortality in elective noncardiac surgery. EDITOR’S PERSPECTIVE