Bleeding complications in cardiothoracic surgery and extracorporeal membrane oxygenation treatment

<p dir="ltr">Background</p><p dir="ltr">Bleeding is a common complication in cardiothoracic surgical procedures and creates the need for blood transfusions and reexploration. After cardiac surgery and lung resections it has been associated with other postoperative complications and increased mortality. The long-term effects of bleeding complications on survival are less studied, and the impact on graft patency after coronary artery bypass grafting (CABG) is unknown. In patients on extracorporeal membrane oxygenation (ECMO), bleeding occurs even more frequently due to long exposure to antithrombotic heparin treatment and coagulopathy induced by both the circuit and underlying pathological processes. Major iatrogenic bleeding events have been reported in patients on ECMO support from both chest tube treatment and vascular cannulation, but the true incidence of these complications remains uncertain.</p><p dir="ltr">This thesis investigates the incidence and both short- and long-term effects of bleeding in CABG, lung resection, and chest tube treatment during ECMO. It also compares complications between minimally invasive and standard techniques for both aortic valve replacement (AVR) and ECMO femoral cannulation.</p><p dir="ltr">Methods and results</p><p dir="ltr">Study I - Within the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registry, all isolated CABG operations using a single internal mammary artery and saphenous vein grafts in patients aged 40 to 80 years between year 2005 and 2015 were included. Patients who underwent reexploration for bleeding within 24 hours of the operation were identified and their future incidence of coronary angiographies, coronary reinterventions, and mortality were compared to patients not reexplored. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using multivariable Cox regression and adjusted for confounding variables associated to graft patency. Angiography events were analysed separately as early and late (within and beyond one year).</p><p dir="ltr">Of 27 957 CABG patients, 1071 (3.8%) underwent reexploration. Ninety-day mortality was higher in reexplored patients. Mean follow-up was 6.5 ± 3.1 years, and within 1 year, the cumulative incidence of coronary angiography was 7.8% in reexplored versus 4.8% in non-reexplored patients (adjusted HR 1.64; 95% CI 1.31-2.06), and need for coronary reintervention within 1 year was 4.9% vs 2.6% respectively (adjusted HR 1.91; 95% CI 1.43-2.56). No statistically significant differences were seen beyond 1 year.</p><p dir="ltr">Study II - In this randomised trial, 100 patients scheduled for AVR due to aortic stenosis were randomised in a 1:1 ratio to undergo either full sternotomy or ministernotomy. The primary composite outcome was severe or massive bleeding defined as at least one of the following criteria: delayed sternal closure; postoperative chest tube output >1000 mL, transfusion of >4 units of packed red blood cells or plasma, administration of recombinant activated factor VII or reexploration. Secondary outcomes included transfusion rates, chest tube output, and reexploration.</p><p dir="ltr">Three patients in each group (6%) met the criteria for severe or massive bleeding (p=1.00). Mean 12-hour chest tube output was 350 ± 220 mL in the full sternotomy group and 270 ± 190 mL in the ministernotomy group (p=0.08). Packed red blood cell transfusion was administered in 28% of cases in the full sternotomy group vs 36% in the ministernotomy group (p=0.39). Two patients per group required reexploration.</p><p dir="ltr">Study III - This was a nationwide cohort study including adult patients who underwent lung resections for malignant and non-malignant diagnoses between 2013 and 2021. All data were obtained from the Swedish National Registry for Thoracic Surgery (ThoR). Patients with and without bleeding complications, defined as requiring reexploration or receiving any blood transfusions, were compared regarding incidence of postoperative complications and long-term survival. Full matching was performed, and Cox regression was used for survival analysis.</p><p dir="ltr">The cohort comprised 15 617 adult patients, of whom 646 (4.1%) had bleeding complications. The unadjusted 90-day mortality was 9.4% in patients with a bleeding complication versus 1.0% in the non-bleeding group. After matching, the odds ratio (OR) for 90-day mortality in the bleeding group was 3.66 (95% CI 2.17-6.17). Long-term overall survival was lower among patients in the bleeding group, with an adjusted HR of 1.47 (95% CI 1.29-1.69). Other postoperative complications were also more common (OR 3.00; 95% CI 2.38-3.79), including infections (OR 2.80; 95% CI 1.86-4.20). Bleeding complication rates declined during the study period (p<0.001).</p><p dir="ltr">Study IV - This was a retrospective study of ECMO patients with iatrogenic bleeding events related to chest tube treatment. All consecutive paediatric and adult patients treated at the Karolinska University Hospital ECMO Centre from 2010 to 2024 with chest tubes for pneumothorax or pleural effusion during ECMO were included. Major bleeding was defined by the chest tube output (e.g. 800 mL/24 h for adult patients), transfusion requirement, or need for intervention with thoracotomy or angiography to stop the haemorrhage.</p><p dir="ltr">A total of 168 out of 1158 ECMO patients (14.5%) underwent chest tube treatment for pneumothorax or pleural effusion, with a total of 279 chest tubes. Major bleeding occurred in 12.5% of patients (n=21) and from 8.1% of individual chest tubes. Emergency thoracotomy to control the blood loss was required in 14 patients. Bleeding occurred more frequently from tubes inserted during ECMO than with those inserted before ECMO (11.3% vs 4.7%, p=0.036). Patients with major chest tube-related bleeding had longer ECMO durations (median 42 vs 17 days, p=0.003) and lower in-hospital survival (47.6% vs 71.4%, p=0.043). No associations to ECMO mode or chest tube characteristics, including size and placement technique, were found.</p><p dir="ltr">Study V - This was a retrospective cohort study of 384 consecutive adult venoarterial (VA) ECMO patients treated at the Karolinska University Hospital Cardiothoracic Unit between 2007 and 2022, comparing percutaneous (n=181) and surgical (n=203) femoral cannulation. Complications including bleeding, infection, and limb ischaemia were analysed. Cannulation-site bleeding was defined as requiring blood transfusion or resulting in at least one of the following: conversion to surgical cut-down, change in cannulation strategy, vascular repair, cannula relocation, or use of a mechanical compression device. Logistic regression was used for multivariable adjustment.</p><p dir="ltr">Bleeding complications occurred in 29.3% of percutaneously and 40.9% of surgically cannulated patients (p = 0.02), while infections were observed in 8.3% and 31.0% of patients, respectively (p < 0.001). Rates of limb ischaemia were 11.6% vs 15.3% (p=0.29). Surgical cannulation independently predicted bleeding (OR 2.39; 95% CI 1.43-3.98) and infection (OR 5.47; 95% CI 2.47-12.12). Use of the percutaneous technique increased over the study period.</p><p dir="ltr">Conclusions</p><p dir="ltr">The results of these studies confirm that bleeding complications are common and clinically significant adverse events in cardiothoracic procedures. Reexploration after CABG is associated with increased mortality and with a higher need for coronary reintervention within the first year. Minimally invasive aortic valve surgery via ministernotomy did not reduce bleeding compared to full sternotomy in a randomised trial. In lung resections, reexploration and blood transfusions are strongly associated with worse short- and long-term survival. In ECMO patients, chest tube-related major bleeding is common and often severe enough to require emergency thoracotomy for haemostasis. For ECMO femoral cannulation, local complications were common, and percutaneous access was associated with fewer bleeding events and infections than surgical cut-down.</p><p dir="ltr">In summary, these findings support minimising perioperative bleeding to potentially reduce complications and improve survival. They also underscore the challenges in evaluating outcomes for new surgical methods, such as ministernotomy and percutaneous cannulation. Finally, knowing the incidence of bleeding for a procedure is useful for individualised risk-benefit assessments in clinical decision-making, for example, whether to place a chest tube or when selecting a cannulation method for an ECMO patient.</p><h3>List of scientific papers</h3><p dir="ltr">I. Re-exploration for bleeding associated with increased incidence of the need for reintervention after coronary artery bypass graft surgery. <b>Dimberg A,</b> Alström U, Janiec M. Interactive cardiovascular and thoracic surgery. 2019;28:214-21. <a href="https://doi.org/10.1093/icvts/ivy245" rel="noreferrer" target="_blank">https://doi.org/10.1093/icvts/ivy245</a></p><p dir="ltr">II. Bleeding in minimally invasive versus conventional aortic valve replacement. Bratt S, <b>Dimberg A,</b> Kastengren M, Lilford RD, Svenarud P, Sartipy U, Franco-Cereceda A, Dalén M. Journal of cardiothoracic surgery. 2024;19:349. <a href="https://doi.org/10.1186/s13019-024-02667-1" rel="noreferrer" target="_blank">https://doi.org/10.1186/s13019-024-02667-1</a></p><p dir="ltr">III. Bleeding and long-term survival after lung resections: nationwide observational cohort study. <b>Dimberg A,</b> Dalén M, Sartipy U. Journal of thoracic disease. 2024;16:4409-16. <a href="https://doi.org/10.21037/jtd-24-502" rel="noreferrer" target="_blank">https://doi.org/10.21037/jtd-24-502</a></p><p dir="ltr">IV. Bleeding complications from chest tube treatment in patients on extracorporeal membrane oxygenation support. <b>Dimberg A,</b> Dalen M, Broman L M, Sartipy U, Larsson M. [Submitted]</p><p dir="ltr">V. Percutaneous cannulation for femoral veno-arterial ECMO associated with lower rates of cannulation site bleeding and infection than open surgical cut-down technique. <b>Dimberg A,</b> Dalén M, Franco-Cereceda A, Fux T. [Submitted]</p>