Increased Mortality After Lower Extremity Amputation in a Danish Nationwide Cohort: The Mediating Role of Postoperative Complications

Anna Trier Heiberg Brix,1,2 Tanja Gram Petersen,3 Tine Nymark,1,2 Hagen Schmal,1,4 Martin Lindberg-Larsen,1,2 Katrine Hass Rubin2,3 1Department of Orthopedic Surgery and Traumatology, Odense University Hospital, Odense, Denmark; 2Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 3Research Unit OPEN, Odense University Hospital and University of Southern Denmark, Odense, Denmark; 4Department of Orthopedics and Traumatology, University Medical Center Freiburg, Freiburg, GermanyCorrespondence: Anna Trier Heiberg Brix, Department of Orthopedic Surgery and Traumatology, Odense University Hospital, J. B. Windsløws vej 4, Odense, 5000, Denmark, Tel +45 3027 2862, Email [email protected]: Patients who undergo major lower extremity amputation (MLEA) have the highest postoperative mortality among orthopedic patient groups. The comorbidity profile for MLEA patients is often extensive and associated with elevated postoperative mortality. This study primarily aimed to investigate the increased short- and long-term mortality following first and subsequent major lower extremity amputation. Secondarily, to examine the mediation role of post-amputation complications.Study Design and Setting: With data from the Danish National Patient Registry, 11,695 first-time MLEAs in patients aged ≥ 50 years were identified between January 1, 2010, and December 31, 2021, along with 58,466 unamputated persons matched 1:5 by year of birth, sex, and region of residence. Mediators were identified through diagnosis codes (ICD-10) present in 6 months following MLEA.Results: The increased mortality following MLEA was highest in the month following MLEA, hazard ratio (HR) 38.7 (95% confidence interval (CI) 30.5– 48.9) in women and HR 55.7 (CI 44.3– 70.2) in men compared to a matched unamputated cohort. Subsequent amputation resulted in an increased mortality the month after a subsequent amputation (overall HR 3.2 (CI 2.8– 3.7) in women and HR 3.2 (CI 2.8– 3.6) in men) and almost normalized after the first year. The proportion of the mortality risk that potentially could be reduced by preventing sepsis was 16% (CI 11.7– 20.3) for women and 17% (CI 13.4– 20.4) for men. For pneumonia, it was 10.5% (CI 7.1– 13.9) in women and 14.9% (11.6– 18.2) in men.Conclusion: We observed an increased mortality in the month following MLEA, which remained elevated for years compared to the matched unamputated cohort. A subsequent amputation results in increased mortality in the following year, but declined and normalized after the first year. Sepsis and pneumonia arising after the amputation appeared to be important factors that contributed to the increased postoperative mortality.Keywords: major lower extremity amputation, registry study, mediator analysis, mortality, nationwide