Cardiac surgery has seen remarkable advancements over the years, yet differences in postoperative outcomes between men and women remain a significant clinical concern. Studies suggest that biological sex may influence the body’s response to surgical trauma, particularly in terms of inflammation. This research examines how systemic inflammatory response syndrome (SIRS) differs between male and female patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Understanding these differences may help improve postoperative care and mitigate the risks women face following surgery.
This study retrospectively analyzed data from 1,005 patients who underwent cardiac surgery at Santa Maria Hospital in Italy between 2018 and 2020. Among these patients, 299 (29.8%) were women. The primary aim was to determine whether sex played a role in the incidence of SIRS and subsequent postoperative complications. SIRS was defined using established criteria, including changes in body temperature, heart rate, respiratory rate, and white blood cell count. The study also examined a composite outcome that included mortality, stroke, renal failure requiring dialysis, major bleeding, the need for extracorporeal membrane oxygenation (ECMO) or intra-aortic balloon pump (IABP) support, and prolonged ICU stays.
The results highlighted a significant disparity in inflammatory response and postoperative outcomes between men and women. Women experienced SIRS at a much higher rate (41.8% vs. 22.8%) and had a greater likelihood of experiencing complications. The analysis showed that female sex was independently associated with SIRS (OR 1.56, 95% CI 1.12-2.18, p=0.009) and with the composite outcome (OR 1.72, 95% CI 1.10-2.69, p=0.017). This suggests that the increased inflammatory response observed in women played a substantial role in their higher complication rates.
Further statistical modeling revealed that SIRS mediated more than half (50.8%) of the effect of female sex on adverse outcomes. In other words, a significant portion of the difference in complications between men and women was attributable to the heightened inflammatory response in women. Additionally, SIRS mediated 30.9% of the effect of intraoperative hyperlactatemia and 17.0% of the effect of preexisting left ventricular dysfunction on postoperative complications. These findings point to systemic inflammation as a key factor in the poorer outcomes observed in women undergoing cardiac surgery.
Several physiological mechanisms could explain why women experience a more pronounced inflammatory response after surgery. One likely factor is the difference in baseline hemoglobin levels between men and women. The study found that women had significantly lower preoperative hemoglobin (12.8 g/dL vs. 14.0 g/dL) and intraoperative hemoglobin nadir (8.6 g/dL vs. 9.8 g/dL). Anemia has been shown to exacerbate inflammation, and lower hemoglobin levels may contribute to the increased inflammatory burden in female patients. Furthermore, women were more likely to receive intraoperative blood transfusions (22.1% vs. 9.9%), a factor that has also been linked to higher levels of systemic inflammation.
Intraoperative hyperlactatemia was another important factor influencing outcomes. Elevated lactate levels indicate impaired oxygen delivery and tissue hypoxia, which can trigger a strong inflammatory response. The study found that intraoperative lactate peaks were more common in women, and this metabolic disturbance significantly increased their risk of developing SIRS. Given that hyperlactatemia is modifiable through improved perfusion strategies and fluid management, addressing this issue could be a potential avenue for reducing inflammation and improving outcomes in female patients.
Beyond physiological factors, differences in immune response between men and women also play a role. Research suggests that women tend to have a more robust immune reaction, partly due to hormonal influences. Estrogen has been shown to enhance immune system activity, leading to stronger inflammatory responses. While this heightened immune response can be beneficial in fighting infections, it may also lead to excessive inflammation following major surgical interventions such as cardiac surgery. This could explain why women were more likely to develop SIRS, which in turn contributed to their worse postoperative outcomes.
The clinical implications of these findings are significant. Given that inflammation appears to be a central mechanism driving sex differences in cardiac surgery outcomes, targeted interventions to reduce inflammatory burden may help bridge this gap. One potential strategy is optimizing preoperative hemoglobin levels in female patients through iron supplementation or erythropoietin therapy. Ensuring that women enter surgery with adequate red blood cell counts could help reduce the need for transfusions and mitigate inflammatory responses.
Another important consideration is intraoperative management. Efforts to minimize hyperlactatemia through improved oxygen delivery, perfusion techniques, and careful fluid management may reduce the inflammatory burden. Closer intraoperative monitoring of lactate levels, particularly in female patients, could help identify those at higher risk of developing SIRS, allowing for early intervention.
Postoperatively, anti-inflammatory therapies may also play a role in improving outcomes. Corticosteroids and other immune-modulating treatments have been explored in the context of cardiac surgery, and future research could investigate whether these interventions are particularly beneficial for female patients. Additionally, closer postoperative monitoring of inflammatory markers, including white blood cell count and C-reactive protein, could help identify patients at risk of developing complications, allowing for more personalized care.
Despite its valuable insights, the study does have limitations. It is a retrospective, single-center study, which may limit the generalizability of the findings. Additionally, while the SIRS criteria used in the study are well-established, they were originally developed for sepsis rather than postoperative inflammation, which may affect their applicability in the context of cardiac surgery. Future prospective studies are needed to confirm these findings and explore more refined definitions of postoperative inflammation.
This study provides compelling evidence that female patients undergoing cardiac surgery are at higher risk of developing SIRS and experiencing worse postoperative outcomes. The findings suggest that systemic inflammation is a key mediator of this increased risk, with factors such as anemia and hyperlactatemia playing important roles. By identifying inflammation as a potential target for intervention, this research paves the way for future studies aimed at improving outcomes for female patients through tailored perioperative management strategies. Addressing sex-based differences in inflammation may be a crucial step in reducing disparities and enhancing the overall quality of cardiac surgical care.
Study Ranking = 4.5 (High Quality) This study is based on a robust dataset of 1,005 patients and employs multivariable regression and mediation analysis. However, its single-center retrospective design limits generalizability.
