The vasoactive inotropic score (VIS) is calculated as a weighted sum of all administered vasopressor and inotropic medications and quantifies the amount of pharmacological cardiovascular support in patients with the most severe combined cardiopulmonary failure supported with extracorporeal membrane oxygenation (ECMO). This study evaluated (1) whether VIS prior to the initiation of ECMO is an independent predictor of survival in these patients and (2) whether VIS might guide the selection of the appropriate extracorporeal cannulation modality (Veno-Venous ‘V-V’ or Veno-VenoArterial ‘V-VA’). In this study, 39 V-VA and 182 V-V ECMO runs were retrospectively analyzed. VIS immediately prior to ECMO initiation (pre-ECMO) was 40 (10/113) in all patients, 30 (10/80) in patients with V-V ECMO and 207 (60/328) in patients with V-VA ECMO. Pre-ECMO VIS was an independent predictor of survival in univariate (AUC = 0.68, p = 0.001) and multi-variable analyses (p = 0.02). Pre-ECMO VIS was clearly associated with mortality (p = 0.001) in V-V ECMO group; however, V-VA ECMO disrupted this association (p = 0.18). Therefore, in conjunction with echocardiography, VIS might assist in selecting the appropriate ECMO cannulation strategy as patients with a pre-ECMO VIS ≥ 61.4 had significantly lower odds of survival compared to those with lower VIS.

Timely and reliable distinction of sepsis from non-infectious systemic inflammatory response syndrome (SIRS) supports adequate antimicrobial therapy and saves lives but is clinically challenging. Blood transcriptional profiling promises to deliver insights into the pathomechanisms of SIRS and sepsis and to accelerate the discovery of urgently sought sepsis biomarkers. However, suitable reference genes for normalizing gene expression in these disease conditions are lacking. In addition, variability in blood leukocyte subtype composition complicates gene profile interpretation. Here, we aimed to identify potential reference genes in natural killer (NK) cells and granulocytes from patients with SIRS and sepsis on intensive care unit (ICU) admission. Discovery by a two-step probabilistic selection from microarray data followed by validation through branched DNA assays in independent patients revealed several candidate reference genes in NK cells including AKIRIN1, PPP6R3, TAX1BP1, and ADRBK1. Initially, no candidate genes could be validated in patient granulocytes. However, we determined highly similar AKIRIN1 expression also in SIRS and sepsis granulocytes and no change by in vitro LPS challenge in granulocytes from healthy donors. Inspection of external neutrophil transcriptome datasets further support unchanged AKIRIN1 expression in human systemic inflammation. As a potential new reference gene in NK cells and granulocytes in infectious and inflammatory diseases, AKIRIN1 may improve our pathomechanistic understanding of SIRS and sepsis and help identifying new sepsis biomarkers.

A common final pathway of pathogenetic mechanisms in septic organ dysfunction and death is a lack or non-utilization of oxygen. Plasma concentrations of lactate serve as surrogates for the oxygen-deficiency-induced imbalance between energy supply and demand. As S-adenosylhomocysteine (SAH) was shown to reflect tissue hypoxia, we compared the ability of SAH versus lactate to predict the progression of inflammatory and septic disease to septic organ dysfunction and death. Using univariate and multiple logistic regression, we found that SAH but not lactate, taken upon patients’ inclusion in the study close to ICU admission, significantly and independently contributed to the prediction of disease progression and death. Due to the stronger increase in SAH in relation to S-adenosylmethionine (SAM), the ratio of SAM to SAH, representing methylation potential, was significantly decreased in patients with septic organ dysfunction and non-survivors compared with SIRS/sepsis patients (2.8 (IQR 2.3–3.9) vs. 8.8 (4.9–13.8); p = 0.003) or survivors (4.9 (2.8–9.5) vs. 8.9 (5.1–14.3); p = 0.026), respectively. Thus, SAH appears to be a better contributor to the prediction of septic organ dysfunction and death than lactate in critically ill patients. As SAH is a potent inhibitor of SAM-dependent methyltransferases involved in numerous vital biochemical processes, the impairment of the SAM-to-SAH ratio in severely critically ill septic patients and non-survivors warrants further studies on the pathogenetic role of SAH in septic multiple organ failure.

Viral pneumonia is frequently complicated by bacterial co- or superinfection (c/s) with adverse effects on patients’ outcomes. However, the incidence of c/s and its impact on the outcomes of patients might be dependent on the type of viral pneumonia. We performed a retrospective observational study in patients with confirmed COVID-19 pneumonia (CP) or influenza pneumonia (IP) from 01/2009 to 04/2022, investigating the incidence of c/s using a competing risk model and its impact on mortality in these patients in a tertiary referral center using multivariate logistic regressions. Co-infection was defined as pulmonary pathogenic bacteria confirmed in tracheal aspirate or bronchoalveolar lavage within 48 h after hospitalization. Superinfection was defined as pulmonary pathogenic bacteria detected in tracheal aspirate or bronchoalveolar lavage 48 h after hospitalization. We examined 114 patients with CP and 76 patients with IP. Pulmonary bacterial co-infection was detected in 15 (13.2%), and superinfection was detected in 50 (43.9%) of CP patients. A total of 5 (6.6%) co-infections (p = 0.2269) and 28 (36.8%) superinfections (p = 0.3687) were detected in IP patients. The overall incidence of c/s did not differ between CP and IP patients, and c/s was not an independent predictor for mortality in a study cohort with a high disease severity. We found a significantly higher probability of superinfection for patients with CP compared to patients with IP (p = 0.0017).

Data on sepsis in patients with a subarachnoid hemorrhage (SAH) are scarce. We assessed the impact of different sepsis criteria on the outcome in an SAH cohort. Adult patients admitted to our ICU with a spontaneous SAH between 11/2014 and 11/2018 were retrospectively included. In patients developing an infection, different criteria for sepsis diagnosis (Sepsis-1, Sepsis-3_original, Sepsis-3_modified accounting for SAH-specific therapy, alternative sepsis criteria compiled of consensus conferences) were applied and their impact on functional outcome using the modified Rankin Scale (mRS) on hospital discharge and in-hospital mortality was evaluated. Of 270 SAH patients, 129 (48%) developed an infection. Depending on the underlying criteria, the incidence of sepsis and septic shock ranged between 21–46% and 9–39%. In multivariate logistic regression, the Sepsis-1 criteria were not associated with the outcome. The Sepsis-3 criteria were not associated with the functional outcome, but in shock with mortality. Alternative sepsis criteria were associated with mortality for sepsis and in shock with mortality and the functional outcome. While Sepsis-1 criteria were irrelevant for the outcome in SAH patients, septic shock, according to the Sepsis-3 criteria, adversely impacted survival. This impact was higher for the modified Sepsis-3 criteria, accounting for SAH-specific treatment. Modified Sepsis-3 and alternative sepsis criteria diagnosed septic conditions of a higher relevance for outcomes in patients with an SAH.

Background: Intestinal ischemia is a common complication with obscure pathophysiology in critically ill patients. Since insufficient delivery of oxygen is discussed, we investigated the influence of oxygen delivery, hemoglobin, arterial oxygen saturation, cardiac index and the systemic vascular resistance index on the development of intestinal ischemia. Furthermore, we evaluated the predictive power of elevated lactate levels for the diagnosis of intestinal ischemia. Methods: In a retrospective case-control study data (mean oxygen delivery, minimum oxygen delivery, systemic vascular resistance index) of critical ill patients from 02/2009–07/2017 were analyzed using a proportional hazard model. General model fit and linearity were tested by likelihood ratio tests. The components of oxygen delivery (hemoglobin, arterial oxygen saturation and cardiac index) were individually tested in models. Results: 59 out of 874 patients developed intestinal ischemia. A mean oxygen delivery less than 250ml/min/m² (LRT vs. null model: p = 0.018; LRT for non-linearity: p = 0.012) as well as a minimum oxygen delivery less than 400ml/min/m² (LRT vs null model: p = 0.016; LRT for linearity: p = 0.019) were associated with increased risk of the development of intestinal ischemia. We found no significant influence of hemoglobin, arterial oxygen saturation, cardiac index or systemic vascular resistance index. Receiver operating characteristics analysis for elevated lactate levels, pH, CO₂ and central venous saturation was poor with an area under the receiver operating characteristic of 0.5324, 0.52, 0.6017 and 0.6786. Conclusion: There was a significant correlation for mean and minimum oxygen delivery with the incidence of intestinal ischemia for values below 250ml/min/m² respectively 400ml/min/m². Neither hemoglobin, arterial oxygen saturation, cardiac index, systemic vascular resistance index nor elevated lactate levels could be identified as individual risk factors.