Mechanisms and causes of death after abdominal surgery in low-income and middle-income countries: a secondary analysis of the FALCON trial.

Background: Death after surgery is devasting for patients, families, and communities, but remains common in low-income and middle-income countries (LMICs). We aimed to use high-quality data from an existing global randomised trial to describe the causes and mechanisms of postoperative mortality in LMICs. To do so, we developed a novel framework, learning from both existing classification systems and emerging insights during data analysis.

Methods: This study was a preplanned secondary analysis of the FALCON trial in 54 hospitals across seven LMICs (Benin, Ghana, India, Mexico, Nigeria, Rwanda, and South Africa). FALCON was a pragmatic, 2 × 2 factorial, randomised controlled trial that compared the effectiveness of two types of interventions for skin preparation (10% aqueous povidone-iodine vs 2% alcoholic chlorhexidine) and sutures (triclosan-coated vs uncoated). Patients who did not have surgery or were lost to follow-up were excluded (n=231). The primary outcomes of the present analysis were the mechanism and cause of death within 30-days of surgery, determined using a modified verbal autopsy strategy from serious adverse event reports. Factors associated with mortality were explored in a mixed-effects Cox proportional hazards model. The FALCON trial is registered with ClinicalTrials.gov, NCT03700749.

Findings: This preplanned secondary analysis of the FALCON trial included 5558 patients who underwent abdominal surgery, of whom 4248 (76·4%) patients underwent surgery in tertiary, referral centres and 1310 (23·6%) underwent surgery in primary referral (ie, district or rural) hospitals. 3704 (66·7%) of 5558 surgeries were emergent. 306 (5·5%) of 5558 patients died within 30 days of surgery. 226 (74%) of 306 deaths were due to circulatory system failure, which included 173 (57%) deaths from sepsis and 29 (9%) deaths from hypovolaemic shock including bleeding. 47 (15%) deaths were due to respiratory failure. 60 (20%) of 306 patients died without a clear cause of death: 45 (15%) patients died with sepsis of unknown origin and 15 (5%) patients died of an unknown cause. 46 (15%) of 306 patients died within 24 h, 111 (36%) between 24 h and 72 h, 57 (19%) between >72 h and 168 h, and 92 (30%) more than 1 week after surgery. 248 (81%) of 306 patients died in hospital and 58 (19%) patients died out of hospital. The adjusted Cox regression model identified age (hazard ratio 1·01, 95% CI 1·01-1·02; p<0·0001), ASA grade III-V (4·93, 3·45-7·03; p<0·0001), presence of diabetes (1·47, 1·04-2·41; p=0·033), being an ex-smoker (1·59, 1·10-2·30; p=0·013), emergency surgery (2·08, 1·45-2·98; p<0·0001), cancer (1·98, 1·42-2·76; p<0·0001), and major surgery (3·94, 2·30-6·75; p<0·0001) as risk factors for postoperative mortality INTERPRETATION: Circulatory failure leads to most deaths after abdominal surgery, with sepsis accounting for almost two-thirds. Variability in timing of death highlights opportunities to intervene throughout the perioperative pathway, including after hospital discharge. A high proportion of patients without a clear cause of death reflects the need to improve capacity to rescue and cure by strengthening perioperative systems.

Funding: National Institute for Health and Care Research Global Health Research Unit.