RECENT EVIDENCE AND PROGNOSTIC FACTORS OF POSTOPERATIVE SEPSIS-INDUCED ARDS IN ADULT SURGICAL PATIENTS

SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 10 OCTOBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 162 RECENT EVIDENCE AND PROGNOSTIC FACTORS OF POSTOPERATIVE SEPSIS-INDUCED ARDS IN ADULT SURGICAL PATIENTS R.A. Ibadov1, S.Kh. Ibragimov2 State Institution "Republican Specialized Scientific and Practical Medical Center of Surgery named after academician V. Vakhidov", Tashkent, Uzbekistan1,2 https://doi.org/10.5281/zenodo.17502267 Abstract. Postoperative sepsis-induced acute respiratory distress syndrome (ARDS) remains a major contributor to morbidity and mortality among critically ill surgical patients. Despite advances in perioperative care, this complication continues to pose significant therapeutic challenges due to its complex and multifactorial pathogenesis. Current evidence highlights the pivotal role of systemic inflammation, endothelial injury, and intraoperative hemodynamic and ventilatory stress in the development of postoperative ARDS following septic complications. Recent studies emphasize that the severity of organ dysfunction, impaired oxygenation at onset, metabolic acidosis, excessive positive fluid balance, and delayed initiation of targeted antimicrobial therapy are key predictors of poor outcomes. Conversely, early goal-directed resuscitation, lung-protective ventilation, and restrictive transfusion strategies are associated with improved survival and reduced duration of mechanical ventilation. In this article, we emphasize that postoperative sepsis-induced ARDS requires an integrated management approach that targets both infectious and host-response components. Optimization of perioperative strategies, early recognition of sepsis, and precision-guided respiratory support remain critical to improving patient prognosis and reducing postoperative mortality. Keywords: acute respiratory distress syndrome, postoperative sepsis, critical care, mortality, prognostic factors, perioperative management. Introduction Postoperative sepsis with acute respiratory distress syndrome (ARDS) is a serious complication in surgical ICU patients. ARDS occurs in about 10% of ICU admissions and carries a high mortality (40% in hospital). Sepsis is a leading cause of ARDS, and up to one-third of septic patients are postoperative cases [1, 2]. Major surgery itself predisposes to ARDS – for instance, emergency abdominal operations and post-surgical pneumonia or intra-abdominal infections are frequent precipitating factors [1, 3, 4]. However, literature specifically on postoperative sepsisinduced ARDS has been relatively scarce until recent years. Here we review studies since 2018 that shed light on prognostic biomarkers, severity scores, and outcomes in this population, including comparisons to non-surgical sepsis, and we highlight heterogeneity in findings across cohort studies, meta-analyses, and reviews. Prognostic Biomarkers for ARDS and Mortality in Sepsis Elevated blood lactate is a well-established marker of illness severity in sepsis, and recent data confirm its prognostic value for ARDS. In a 2024 cohort of postoperative sepsis patients, those who went on to develop ARDS had a significantly higher lactate at sepsis diagnosis (median 4.6 vs 2.3 mmol/L). Lactate was also higher in non-survivors compared to survivors (3.7 vs 2.2) [1, 5]. Prior studies similarly noted that hyperlactatemia is an independent risk factor for ARDS in SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 10 OCTOBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 163 septic patients. These findings align with lactate indicating poor perfusion and aggressive systemic inflammation, which predispose the lungs to injury. Procalcitonin (PCT), a marker of bacterial infection, has shown promise in signaling sepsis severity and potentially ARDS risk. In the above postoperative sepsis cohort, ARDS patients had markedly higher PCT levels than non-ARDS patients (median 21.5 vs 4.8 ng/mL). Likewise, PCT was elevated in those who died versus survivors (7.8 vs 4.5) [1]. High PCT may reflect an uncontrolled infection that can trigger or exacerbate ARDS. Notably, another study comparing surgical vs. non-surgical sepsis found higher PCT in non-surgical patients, paralleling their greater organ dysfunction [3, 6]. This suggests PCT correlates with overall severity. However, while PCT is often higher in ARDS cases, it has not consistently emerged as an independent predictor of mortality once general severity (e.g. SOFA score) is accounted for [1, 5, 7]. This indicates that PCT’s prognostic value may overlap with broader measures of organ failure. Lactate Dehydrogenase (LDH) is released during tissue damage and has gained attention as a biomarker of lung injury severity. Recent evidence suggests LDH is strongly associated with ARDS outcomes. In the postoperative sepsis cohort, an elevated LDH was independently linked to higher 60-day mortality (OR 1.7 per unit increase). ARDS patients had higher LDH on admission than those without ARDS, and higher LDH was observed in non-survivors. In fact, LDH is among the biomarkers most strongly tied to ARDS mortality in various studies [8, 9]. For example, a COVID-19 ARDS series found mean LDH 373 U/L in ARDS vs 298 U/L without ARDS (p=0.015) [Figueira Gonçalves 2022]. Elevated LDH likely reflects the extent of cell injury in the lungs and other organs. Clinically, a rising LDH in septic patients may warn of developing ARDS or worse prognosis. Inflammatory markers such as C-reactive protein (CRP) and D-dimer have been explored, especially in virus-associated ARDS, but their utility in sepsis-induced ARDS is variable [10, 11]. Some novel protein and genomic markers (e.g. sRAGE, angiopoietin-2, certain gene expression profiles) have been studied with mixed results [12, 13]. Overall, traditional biomarkers like lactate, PCT, and LDH currently have the most practical prognostic value for identifying high-risk patients, though they are non-specific. The heterogeneity of biomarker findings across studies underscores the complex pathophysiology of ARDS. It also motivates ongoing research into multibiomarker panels and “omics” approaches to improve early prediction [13]. Predictive Value of Severity Scores (SOFA and APACHE II) Standard ICU severity scores – particularly the Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) – are useful for assessing the risk of ARDS and outcomes in septic patients. A recent meta-analysis (15 studies, >40,000 patients) confirmed that higher APACHE II and SOFA scores are significant risk factors for developing ARDS among septic patients [14, 15]. This makes intuitive sense: the more severe the organ dysfunction at sepsis onset, the more likely acute lung injury will occur. Correspondingly, in a 2024 prospective surgical ICU study, patients who developed ARDS had higher baseline scores than those who did not (median SOFA 9 vs 8; APACHE II 17 vs 15) [1, 3]. Both scores showed independent predictive power for ARDS in multivariate analysis, with each 1-point SOFA increase raising ARDS odds by 10% [1]. Elevated scores often reflect shock and multi-organ failure, which predispose the lungs to ARDS. Beyond ARDS risk, these scores correlate with mortality in sepsis-associated ARDS. In the postoperative sepsis cohort, non-survivors had significantly higher SOFA and APACHE II on admission [1, 5, 16]. An APACHE II >16 was independently associated with ~2.7-fold higher 60- SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 10 OCTOBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 164 day mortality. Notably, SOFA might be especially informative: a dedicated study of surgical sepsis patients found the SOFA score at ICU admission was the only independent predictor of in-hospital death (OR 1.24 per point) when compared to many variables including APACHE II [1, 5]. In that study, a SOFA >8 on admission was a clear cutoff distinguishing high-risk patients – mortality was significantly higher with SOFA >8 vs ≤8. The authors observed that SOFA outperformed APACHE II in prognosticating surgical sepsis outcomes, possibly because SOFA more directly quantifies organ failures (including respiratory and coagulation parameters relevant to ARDS). Similarly, serial SOFA trends during the first week of sepsis have been shown to track prognosis better than a one-time APACHE II [1, 5, 8]. In summary, high SOFA and APACHE II scores signal a septic patient at elevated risk for ARDS and death. These scoring tools are thus quite informative in sepsis-induced ARDS: they help identify patients who might benefit from early aggressive support. However, it’s worth noting that they are general severity indices. Their cutoffs and prognostic accuracy can vary by setting. The literature shows some heterogeneity – e.g. one cohort found SOFA was superior to APACHE in surgical patients, while other analyses consider both useful [9, 11, 16]. This likely reflects differences in patient populations and timing of score assessment. Regardless, both SOFA and APACHE II remain valuable for risk stratification in current practice. ARDS Impact on 28-Day and 60-Day Mortality in Surgical Patients ARDS substantially worsens outcomes in septic surgical patients. Multiple studies have documented that when postoperative patients with sepsis develop ARDS, their likelihood of survival drops significantly. For instance, Bardají-Carrillo et al. (2024) reported a 60-day mortality of 55.6% in post-op sepsis patients with ARDS, compared to 27.4% in those without ARDS [1, 5]. In adjusted analysis, ARDS conferred ~2.7-fold higher odds of 60-day death (95% CI 1.1–6.3) [frontiersin.org]. Similarly, an earlier multicenter study found sepsis-related ARDS had an unadjusted 60-day mortality of 38%, about 1.7 times higher than ARDS from non-septic causes [9, 17]. ARDS not only increases the fraction of patients who die, but also appears to hasten death: in the surgical cohort, ARDS patients died on average ~12 days sooner within the 60-day period than those without ARDS [1, 5]. These findings highlight the acute lethality of ARDS superimposed on sepsis. Shorter-term mortality (28-day or in-hospital) is likewise elevated. In one analysis of ARDS among septic ICU patients (a Chinese multicenter cohort), ARDS was found to be an independent predictor of 30-day mortality, even after matching patients on other factors [7]. The attributable mortality of ARDS in that sepsis population was estimated at 11.9% at 30 days – meaning roughly that proportion of deaths could be directly attributed to the development of ARDS. Moreover, the severity of ARDS matters: mild ARDS had a lower impact (adjusted HR 1.3), while severe ARDS nearly doubled the hazard of death (HR 1.95) [7]. This dose-response reinforces that the physiological burden of ARDS (e.g. refractorily low oxygenation in severe cases) drives mortality risk in sepsis beyond the underlying infections. It is important to note that some of the mortality risk associated with ARDS overlaps with how sick the patient was to begin with (confounding by indication). Indeed, earlier studies suggested that once you control for illness severity and comorbidities, ARDS per se may not independently quadruple mortality as raw numbers suggest [11, 13, 17]. For example, a 2010 analysis found the higher mortality in sepsis-related ARDS vs non-sepsis ARDS was largely explained by higher baseline APACHE scores and comorbid conditions in the sepsis patients [17 In modern cohorts, however, even after adjustments, ARDS remains a significant independent SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 10 OCTOBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 165 contributor to death [7, 18]. This likely reflects that despite improvements in supportive care, ARDS adds an extra physiologic insult (refractory hypoxemia, ventilator-associated complications, etc.) on top of sepsis. For surgical patients, the development of ARDS can be viewed as a turning point that often portends a poor 4-week and 8-week outcome. Therefore, preventing ARDS or mitigating its severity (through lung-protective ventilation, early sepsis source control, etc.) is critical to improving survival in postoperative sepsis. Surgical vs. Non-Surgical Sepsis: How Do Outcomes Differ? An interesting question is whether septic ARDS in surgical patients has different outcomes compared to sepsis in medical (non-surgical) patients. Recent data suggest that surgical sepsis patients may fare slightly better, likely due to differences in patient profiles and management. A 2023 retrospective stud y of 737 ICU sepsis cases compared those with prior surgery (mostly abdominal, vascular, etc.) to those without [3]. The non-surgical sepsis group had significantly higher 90-day mortality (37% vs 30% in surgical sepsis, p=0.046). Non-surgical patients also had more severe organ failure: their average SOFA score was higher and they more frequently required ventilation, vasopressors, and dialysis. Notably, serum procalcitonin was higher in non-surgical sepsis as well, reflecting a greater inflammatory burden [3]. These findings suggest that surgical sepsis patients, who often have a clear infection source amenable to surgical control, might experience somewhat less prolonged organ dysfunction than medical sepsis patients. Focusing specifically on ARDS, a new large-scale analysis from Spain provides valuable insight. Bardají-Carrillo et al. (2025) examined over 93,000 ARDS cases in a national database, of which 40,601 (44%) were postoperative/surgical ARDS [5]. Historically (2000–2015), postoperative ARDS patients had a slightly lower hospital mortality than medical ARDS patients (47.0% vs 49.9%, p<0.001). In recent years (2017–2022), outcomes converged, with mortality 43% in both groups (no significant difference). This convergence may reflect overall improvements in critical care and ARDS management that benefited both populations. Interestingly, despite similar mortality rates now, the resource use was higher for surgical ARDS: postoperative ARDS cases had longer hospital stays and about 1.5× higher healthcare costs compared to medical ARDS. One possible explanation is that surgical patients who develop ARDS often have undergone major operations and may face additional surgical complications, prolonging their hospitalization. Additionally, the Spanish study noted a higher incidence of abdominal (digestive tract) infections in the postoperative ARDS group, indicating that intra-abdominal sepsis is a common driver of ARDS in surgical patients [5]. Overall, while surgical sepsis-associated ARDS was historically thought to have a slightly better survival than medical sepsis ARDS, recent data suggest outcomes are now comparable. Non-surgical sepsis patients still present a more severe organ failure profile on average, which could be due to factors like advanced age or comorbidities in medical patients. Surgical patients, in contrast, might benefit from timely source control (e.g. an abscess drainage or removal of infected tissue) which can improve sepsis outcomes. These differences highlight the heterogeneity within “sepsis” and ARDS populations [5]. When comparing studies, one must account for the case mix: a cohort dominated by emergency surgical sepsis might have different ARDS rates and outcomes than one of medical ICU patients with pneumonia. The literature suggests that baseline patient factors (comorbidities, infection source, etc.) largely drive mortality, rather than the surgical vs. medical label by itself [17]. In practical terms, this means that prognostic models should perhaps incorporate whether an infection source was operatively controlled, rather than simply classifying patients by surgical history. SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 10 OCTOBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 166 Evidence from Recent Cohort Studies, Meta-Analyses, and Reviews The insights above are drawn from a range of study designs, each contributing pieces to the puzzle of postoperative sepsis and ARDS: The Frontiers 2024 study of 454 post-surgery sepsis patients exemplifies a single-center prospective cohort [1]. It provided granular data on risk factors (like lactate, SOFA) and outcomes (60-day mortality) in a well-defined surgical population. Its findings (10% incidence of ARDS, 2.7× mortality risk) form a baseline for understanding this subgroup. Similarly, Chinese multicenter cohorts (2014–2015) tracked sepsis patients prospectively to quantify ARDSattributable mortality with robust adjustments [7]. Large database studies and single-center retrospectives have extended these observations. The 2025 Spanish nationwide analysis (MBDS registry) retrospectively identified trends over two decades [5]. Another retrospective study (Mewes et al. 2023) used ICU records to directly compare surgical vs. non-surgical sepsis outcomes [3]. While retrospective data can be limited by documentation and selection biases, they excel in sheer size and “real-world” diversity, helping to confirm that the small prospective studies are generalizable. Notably, the retrospective studies show consistency with prospective ones on key points (e.g. the importance of organ failure severity, the proportion of ARDS in surgical sepsis). Recent reviews have synthesized available evidence to identify common risk factors for ARDS in sepsis. Two independent teams (Cureus 2023 and Heliyon 2024) reviewed dozens of studies [15]. They consistently found that pulmonary infection, septic shock, and pancreatitis are among the strongest predictors of ARDS in sepsis patients. Importantly, they highlighted that high APACHE II/SOFA scores are associated with ARDS development across multiple settings – reinforcing that our earlier points hold across heterogeneous studies. These meta-analyses also note what factors were not universally predictive: for example, patient sex or smoking status did not show a significant association with ARDS risk in sepsis [15]. By pooling data, such reviews handle between-study variability and provide more robust estimates. However, they also reported substantial heterogeneity (I² statistics often high), meaning results differed notably between studies. This heterogeneity likely stems from differences in definitions (Berlin vs. AECC criteria for ARDS), timing (early-onset ARDS vs ARDS developing days into ICU stay), and population (surgical ICU, medical ICU, mixed) in the included studies. Systematic reviews therefore urge caution: while general risk factors are clear, the exact magnitude of risk or mortality attributable to ARDS can vary. Different studies occasionally report divergent results, and understanding why is crucial. For instance, one cohort found an almost four-fold crude mortality increase with ARDS in sepsis, whereas another, after careful matching, estimated the ARDS-attributable increase to be 12% [1, 7]. Such discrepancies arise from study design differences. Unadjusted analyses inflate ARDS’ apparent impact because patients who develop ARDS are usually those already critically ill. Modern studies applying propensity matching or multivariable adjustment tend to show a more modest (but still significant) independent effect of ARDS [17]. Additionally, outcome timing matters: 28-day mortality vs. 90-day mortality might differ if some ARDS survivors later succumb to complications. For example, surgical ARDS patients might have slightly lower 28-day mortality than medical ARDS (perhaps due to healthier baseline), but by 90 days this difference could diminish as longer-term factors play in [5]. Another source of heterogeneity is evolving clinical practice. SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 10 OCTOBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 167 The management of ARDS (e.g. use of low tidal volumes, proning, ECMO referrals) has improved over the last decade, improving survival. Indeed, the Spanish registry noted declining mortality in both surgical and medical ARDS from 2000s to recent years [5]. Thus older studies may report higher fatality rates than newer ones. Finally, each study’s inclusion criteria (postoperative definition, sepsis criteria, etc.) can differ. Some include only septic shock, others any sepsis; some define “postoperative” as within 30 days of surgery, others use different windows. These nuances can lead to variable patient cohorts and outcomes. In light of these factors, clinicians and researchers should interpret any single study with context. The overall evidence since 2018 converges on a few key principles despite the noise: (1) Patients with severe sepsis (high lactate, shock, multi-organ failure) are at greatest risk of ARDS. (2) If ARDS develops, it approximately doubles short-term mortality in contemporary ICU settings. (3) Robust predictors of poor outcome in sepsis-related ARDS include some biomarkers (like LDH) and especially organ failure scores (SOFA/APACHE). (4) Postoperative (surgical) sepsis patients form a large subset of ARDS cases and, when appropriately managed, have survival rates now comparable to other ARDS patients– though their hospital stays and costs are higher. Conclusion Postoperative sepsis-associated ARDS in adults remains a life-threatening complication with high morbidity and mortality. Recent publications have advanced our understanding in several ways. First, they affirm the prognostic value of biomarkers: for example, early lactate elevation and procalcitonin surges can flag patients likely to develop ARDS or deteriorate, while LDH levels correlate with the degree of lung injury and death risk. Second, widely used severity scores (SOFA, APACHE II) are validated as important risk stratification tools in this context – high scores should alert clinicians to the need for aggressive support and possibly ARDS prevention strategies. Third, ARDS significantly impacts outcomes: it roughly doubles 28or 60day mortality in surgical sepsis patients, even if modern care has attenuated this impact compared to historical data. We now recognize that a surgical patient with sepsis who progresses to ARDS has a far worse prognosis than one who does not, emphasizing the importance of early intervention to prevent lung injury (e.g. prompt infection control, judicious fluids, lung-protective ventilation). Fourth, comparisons between surgical and medical sepsis populations show that while baseline characteristics differ (non-surgical sepsis often more severe), outcome gaps have narrowed in recent years. This suggests that critical care improvements benefit all, but also that surgical sepsis patients should not be underestimated – they too require careful monitoring for ARDS and organ failures. Finally, we must acknowledge the heterogeneity in study findings and the reasons behind it. Outcomes in “sepsis-ARDS” can vary depending on patient mix, definition of ARDS, and advances in care. Discrepancies in the literature – such as varying reported mortality rates or differing significance of certain biomarkers – often trace back to these factors rather than true contradictions. Thus, an analytical approach is needed when applying evidence to practice. Emerging research is exploring composite predictors (e.g. combining clinical scores with biomarker panels or genomic indicators) to improve early identification of patients at risk. While no single predictive system is foolproof yet, the trajectory is toward more personalized risk assessment. In the meantime, critical care teams should leverage the known prognostic markers SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 10 OCTOBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 168 and scores to guide therapy and consider early aggressive measures in high-risk postoperative sepsis patients (for instance, those with lactate >4 mmol/L, PCT >10 ng/mL, or SOFA ≥8). 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