Postoperative anaemia increases unplanned readmission: an international prospective cohort study of patients undergoing major abdominal surgery

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Preoperative anaemia is observed in one-third of patients who present for surgery, and is associated with increased postoperative complications, length of stay, poorer quality of life and delayed recovery1,2. In the last decade, there has been a focus on the detection and management of anaemia, prevention of bleeding and appropriate blood transfusion practices, collectively termed patient blood management (PBM)3. Implementation of PBM programmes is associated with reduced blood transfusion use and shorter hospital stay4,5. In surgical patients, preoperative anaemia can be exacerbated by blood loss at the operation and repeated blood testing during and after the procedure. As iron deficiency is the commonest underlying cause of anaemia, the use of intravenous (IV) iron is a plausible and attractive therapeutic option to improve haemoglobin levels6. However, two recent large RCTs on the use of preoperative IV iron in major abdominal surgery, PREVENTT and FIT, did not show benefit in the immediate perioperative period on blood transfusion rates, complications or length of stay. However, an interesting finding in both trials was that the greatest treatment effect was increased haemoglobin levels at 6–8 weeks after surgery, which was associated with a reduction in unplanned hospital readmissions7,8. The association of postoperative anaemia and worse patient recovery was also observed in a large database analysis of patients undergoing surgery9. In a reanalysis of a large perioperative clinical trial, postoperative anaemia was associated with an increased risk of death and disability at 90 days10. The mechanism of postoperative anaemia leading to delayed postoperative recovery is possibly due to the symptoms associated with the condition, including impaired mental function and reduced physical exercise capacity11. In the elderly, anaemia is associated with functional loss and increased risk for developing frailty12–15. The prospective international POST-operative Variability in anaemia treatmenT and Transfusion (POSTVenTT) cohort study aimed to determine whether postoperative anaemia was associated with poorer recovery after surgery, with an increased rate of readmissions. The POSTVenTT study was a prospective, multicentre, international observational cohort study involving sites across Australia, Aotearoa New Zealand, Europe, North Africa and the Middle East. The POSTVenTT study was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12621001517864; 8 November 2021). The trial protocol was approved by the South Metropolitan Health Service (Western Australia) Health Research Ethics Committee (EC00265), the Western Australia Research Governance System (RCG 4477), with local ethics and governance confirmed at each site before patient recruitment16. Sites were recruited utilizing collaborative research networks such as TASMAN and EuroSurg. This study is reported in concordance with the STROBE statement17. POSTVenTT was conducted by utilizing existing student- and trainee-led collaborative research models18. An advisory board of surgical trialists supported by the Western Australia Clinical Trials Unit oversaw a student- and trainee-led project management group. Data was collected over two 2-week periods during July 2021 at sites across Australia and Aotearoa New Zealand, and additionally in October 2021 at sites in Europe, North Africa and the Middle East. Each site was responsible for a 30-day prospective follow-up after discharge. All consecutive adult patients aged 18 years or above undergoing major emergency or elective abdominal surgery were eligible. Major abdominal surgery was defined as any operation with an incision into the abdominal cavity (open, laparoscopic, or robotic surgery) and an anticipated duration of more than 1 h. Patients were recruited upon booking for an eligible procedure and upon procedure completion the operation report was reviewed for eligibility. Patients with planned readmissions were included due to the existing potential for unplanned readmission. Full details of eligible procedures and eligibility criteria are listed in the study protocol16. Anaemia was defined using the WHO sex-specific cut-off haemoglobin values (<130 g/l for men, <120 g/l for non-pregnant women)19. Mild anaemia was defined as a haemoglobin >100 g/l, and moderate to severe anaemia <100 g/l. The primary outcome was the rate of unplanned readmission to the hospital within 30 days after initial discharge. Secondary outcomes included clinical frailty score, length of postoperative hospital stay, postoperative complications (defined by the Clavien–Dindo classification), packed red blood cell (pRBC) transfusion and the prevalence of anaemia at discharge and 30 days post-discharge. Frailty was defined according to the CSHA Clinical Frailty score, and further classified as ‘Not Frail’ (1–3), ‘Mild Frailty’ (4–5), and ‘Moderate to Severe Frailty’ (≥6)20,21. Prolonged length of hospital stay was defined as a postoperative hospital admission greater than that of the 75th centile of patients in the study. R version 3.6.1 (R Foundation for Statistical Computing, Vienna, Austria) was used for all analyses. It was prespecified that data would only be included from hospitals with >95% data completeness as per the study protocol.16 Categorical data were presented as numbers and percentages, analysed using the chi-square test. Continuous data were presented as means with standard deviations or medians with interquartile ranges as appropriate and analysed using the independent samples t-test or Kruskal–Wallis test. Time to readmission within 30 days from discharge was analysed as a time-to-event variable, using multivariable Cox regression models, reported as adjusted hazard ratios (aHR) with associated 95% confidence intervals). To analyse postoperative changes in frailty, this outcome was dichotomized as ‘more frail’ versus ‘unchanged/less frail’ at 30 days follow-up compared with preoperative frailty, and this was analysed using multivariate logistic regression models, reported with adjusted odds ratios (aOR) and 95% c.i. These models were adjusted for age, sex, ASA, cardiac history, diabetes mellitus, preoperative frailty, operative urgency, operative procedure, wound contamination, postoperative complications, postoperative pRBC transfusion and country of treatment. Adjusted restricted cubic spline models were used to investigate the effect of haemoglobin at discharge as a continuous variable, for both readmission and frailty outcomes. For these models, splines were placed at the 5th, 25th, 75th and 95th percentiles. Multiple imputations with the mice (Multivariate Imputations by Chained Equations) package were used to generate 10 imputed data sets, and these were pooled to conduct the analyses described above. A sensitivity analysis was also performed with non-imputed data and pairwise exclusion of patients with missing data. A post-hoc sensitivity analysis was performed excluding patients undergoing cholecystectomy, as although defined as major surgery, cholecystectomy is often performed as a day-case procedure and is associated with lower risks of bleeding and anaemia. In total, 5266 patients undergoing major abdominal surgery at 101 hospitals across 13 countries, with a median of 47 patients (i.q.r. 21–77) per hospital were included, of whom 5143 (97.7%) were discharged before the end of the study. Data were complete for 99.3% of all data fields. Of those discharged prior to the end of the study, 30-day follow-up data were completed for 5050 patients (98.2%). Only patients with 30-day follow-up were included in the analysis. The mean age was 55.6 (s.d. 16.8) years, and 2944 (58.3%) were women (Table 1). Demographic and preoperative clinical data, by readmission within 30 days of discharge Demographic and preoperative clinical data, by readmission within 30 days of discharge The most common operations were hepatopancreatobiliary (38.4%), color

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