Search

Infectious complications are common during extracorporeal membrane oxygenation (ECMO) and may negatively impact outcomes. However, there is considerable variation in the reported rates of incidence, which hampers the use of infections as a quality benchmark for ECMO centers. To assess the contributing role of poor interrater agreement, three independent raters reviewed medical records from all intensive care unit (ICU) patients who received ECMO for >24 h in our tertiary center between October 2019 and October 2021 for suspected episodes of infection, which were rated based on their date of onset and presumed site/diagnosis. To establish a gold standard, any discrepancies were resolved using an expert panel consisting of two intensivists/infectious disease specialists. During 83 ECMO-runs in 77 patients, we observed a total of 62 adjudicated infectious episodes (incidence rate 62, 95% CI: 48–80, per 1000 days at risk). Among 81 episodes suspected by at least one observer, 66 (81%) were identified by two, and only 44 (54%) by all three raters, resulting in Fleiss’ kappa of 0.10 (95% CI: 0.00–0.19; slight agreement). However, if raters concurred regarding infection onset, subsequent agreement on infection site was good (concordance 89%; kappa 0.85, 95% CI: 0.72–0.98; near perfect agreement). In conclusion, adjudication of infectious episodes during ECMO is associated with poor interrater agreement regarding occurrence—but not site—of infection. This finding might partially explain the significant disparities observed in reported infection rates during ECMO, emphasizing the need for caution when interpreting infection data in this particular population due to the potential for inherent measurement error.

Background:Aims of this study were to investigate the prevalence and incidence of catheter-related infection, identify risk factors, and determine the relation of catheter-related infection with mortality in critically ill COVID-19 patients. Methods:This was a retrospective cohort study of central venous catheters (CVCs) in critically ill COVID-19 patients. Eligible CVC insertions required an indwelling time of at least 48 hours and were identified using a full-admission electronic health record database. Risk factors were identified using logistic regression. Differences in survival rates at day 28 of follow-up were assessed using a log-rank test and proportional hazard model. Results:In 538 patients, a total of 914 CVCs were included. Prevalence and incidence of suspected catheter-related infection were 7.9% and 9.4 infections per 1,000 catheter indwelling days, respectively. Prone ventilation for more than 5 days was associated with increased risk of suspected catheter-related infection; odds ratio, 5.05 (95% confidence interval 2.12–11.0). Risk of death was significantly higher in patients with suspected catheter-related infection (hazard ratio, 1.78; 95% confidence interval, 1.25–2.53). Conclusions:This study shows that in critically ill patients with COVID-19, prevalence and incidence of suspected catheter-related infection are high, prone ventilation is a risk factor, and mortality is higher in case of catheter-related infection.

Staphylococcus aureusis a major human pathogen, yet the immune factors that protect against infection remain elusive. High titers of opsonic IgG antibodies, achieved in preclinical animal immunization studies, have consistently failed to provide protection in humans. Here, we investigate antibody responses to the conserved S. aureussurface glycan wall teichoic acid (WTA) and detect the presence of WTA-specific IgM and IgG antibodies in the plasma of healthy individuals. Functionally, WTA-specific IgM outperforms IgG in opsonophagocytic killing of S. aureusand protects against disseminated S. aureusbacteremia through passive immunization. In a clinical setting, patients with S. aureusbacteremia have significantly lower WTA-specific IgM but similar IgG levels compared to healthy controls. Importantly, low WTA-IgM levels correlate with disease mortality and impaired bacterial opsonization. Our findings may guide risk stratification of hospitalized patients and inform future design of antibody-based therapies and vaccines against serious S. aureusinfection.

Transfusion of red blood cells (RBCs) from female donors has been associated with increased risk of mortality. This study aims to investigate the associations between donor-recipient sex and posttransfusion mortality and morbidity in critically ill patients who received RBC transfusions from either male-only donors or from female-only donors (unisex-transfusion cases). Survival analysis was used to compare 4 groups: female-to-female, female-to-male, male-to-female, and male-to-male transfusion. Multivariate logistic model was used to evaluate the association between donor sex and intensive care unit (ICU) mortality. Associations between transfusion and acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), and nosocomial infections were assessed. Of the 6992 patients included in the original cohort study, 403 patients received unisex-transfusion. Survival analysis and the logistic model showed that transfusion of female RBCs to male patients was associated with an increased ICU mortality compared with transfusion of female RBCs to female patients (odds ratio, 2.43; 95% confidence interval, 1.02-5.77; P < .05). There was a trend toward increased ARDS in patients receiving RBC from female donors compared with those receiving blood from males (P = .06), whereas AKI was higher in donor-recipient sex-matched transfusion groups compared with sex-mismatched groups (P = .05). This was an exploratory study with potential uncontrolled confounders that limits broad generalization of the findings. Results warrant further studies investigating biological mechanisms underlying the association between donor sex with adverse outcomes as well as studies on the benefit of matching of blood between donor and recipient.

Pulmonary embolism (PE) occurs in one‐third of critically‐ill COVID‐19 patients. Although prior studies identified several pathways contributing to thrombogenicity, it is unknown whether this is COVID‐19‐specific or also occurs in ARDS patients with another infection.

Pulmonary embolism (PE) occurs in one‐third of critically‐ill COVID‐19 patients. Although prior studies identified several pathways contributing to thrombogenicity, it is unknown whether this is COVID‐19‐specific or also occurs in ARDS patients with another infection. To compare pathway activity among patients having COVID‐19 with PE (C19PE+), COVID‐19 without PE (C19PE‐), and influenza‐associated ARDS (IAA) using a targeted proteomics approach. We exploited an existing biorepository containing daily plasma samples to carefully match C19PE+ cases to C19PE‐ and IAA controls on mechanical ventilation duration, PEEP, FiO2, and cardiovascular‐SOFA (n= 15 per group). Biomarkers representing various thrombosis pathways were measured using proximity extension‐ and ELISA‐assays. Summed z‐scores of individual biomarkers were used to represent total pathway activity. We observed no relevant between‐group differences among 22 biomarkers associated with activation of endothelium, platelets, complement, coagulation, fibrinolysis or inflammation, except sIL‐1RT2 and sST2, which were lower in C19PE‐ than IAA (log2‐Foldchange −0.67, p= .022 and −1.78, p= .022, respectively). However, total pathway analysis indicated increased activation of endothelium (z‐score 0.2 [−0.3–1.03] vs. 0.98 [−2.5–−0.3], p= .027), platelets (1.0 [−1.3–3.0] vs. −3.3 [−4.1–−0.6], p= .023) and coagulation (0.8 [−0.5–2.0] vs. −1.0 [−1.6–1.0], p= .023) in COVID‐19 patients (C19PE+/C19PE‐ groups combined) compared to IAA. We observed only minor differences between matched C19PE+, C19PE‐, and IAA patients, which suggests individual biomarkers mostly reflect disease severity. However, analysis of total pathway activity suggested upregulation of some distinct processes in COVID‐19 could be etiologically related to increased PE‐risk.

Supplemental Digital Content is available in the text

A prolonged prothrombin time (PT) is a common feature in sepsis indicating consumptive coagulopathy.

A prolonged prothrombin time (PT) is a common feature in sepsis indicating consumptive coagulopathy. To determine the association between a prolonged PT and aberrations in other host response mechanisms in sepsis. Patients admitted to the intensive care unit with sepsis were divided in quartiles according to the highest PT value measured within 24 h after admission. The host response was evaluated by measuring 19 plasma biomarkers reflecting pathways implicated in sepsis pathogenesis and by blood leukocyte gene expression profiling. Of 1524 admissions for sepsis, 386 (25.3%) involved patients with a normal PT (≤12.7 s); the remaining quartiles entailed 379 (24.9%) patients with a slightly prolonged PT (12.8 ≤ PT ≤ 15.0 s), 383 (25.1%) with an intermediately prolonged PT (15.1 ≤ PT ≤ 17.2 s), and 376 (24.7%) with an extremely prolonged PT (≥17.3 s). While patients with an extremely prolonged PT showed an increased crude mortality up to 1 year after admission, none of the prolonged PT groups was independently associated with 30‐day adjusted mortality. Comparison of the host response between patients with a normal PT or an extremely prolonged PT matched for baseline characteristics including severity of disease showed that an extremely prolonged PT was associated with impaired anticoagulant mechanisms, a more disturbed endothelial barrier integrity and increased systemic inflammation, and blood leukocyte transcriptomes indicating more prominent metabolic reprogramming and protein catabolism. A prolonged PT is associated with stronger anomalies in pathways implicated in the pathogenesis of sepsis, suggesting that activation of coagulation impacts other host response mechanisms.

Little is known about the practice of ventilation management in patients with COVID-19. We aimed to describe the practice of ventilation management and to establish outcomes in invasively ventilated patients with COVID-19 in a single country during the first month of the outbreak.

Poor neuropsychiatric outcomes are common in survivors of critical illness but it is unclear what patient groups to target for interventions to improve mental health. We compared anxiety, depression, and post-traumatic stress disorder (PTSD) symptoms and health-related quality of life (HrQoL) across different subgroups of Intensive Care Unit (ICU) survivors.

SeptiCyte LAB measures the expression of four host-response RNAs in peripheral blood to distinguish sepsis from sterile inflammation. This study evaluates whether sequential monitoring of this assay has diagnostic utility in patients after esophageal surgery.

To describe the characteristics and procedural outcomes of source control interventions among Intensive Care Unit (ICU) patients with severe intra-abdominal-infection (IAI).

To assess the reliability of physicians' prognoses for intensive care unit (ICU) survivors with respect to long-term survival and health related quality of life (HRQoL).

Host responses during sepsis are highly heterogeneous, which hampers the identification of patients at high risk of mortality and their selection for targeted therapies. In this study, we aimed to identify biologically relevant molecular endotypes in patients with sepsis.

IMPORTANCE: Cellulitis is a commonly occurring skin and soft tissue infection and one of the most frequently seen dermatological diseases in the intensive care unit (ICU). However, clinical characteristics of patients with cellulitis requiring intensive care treatment are poorly defined. Necrotizing fasciitis is often confused for cellulitis at initial presentation and is considered to be more severe and thus has previously been described in more detail. OBJECTIVE: To describe the clinical presentation and outcomes of patients with ICU-necessitating cellulitis and to compare them with patients with necrotizing fasciitis. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study includes all ICU admissions from 2 tertiary hospitals in the Netherlands. Of 2562 sepsis admissions, 101 had possible, probable, or definite cellulitis or soft tissue infections. Retrospective review identified severe cellulitis was the reason for ICU admission in 23 patients, necrotizing fasciitis in 31 patients, and other diagnoses in 47 patients. MAIN OUTCOMES AND MEASURES: Patient and disease characteristics, cultured pathogens, lengths of stay, and short-term and long-term mortality. RESULTS: Overall, 54 patients with cellulitis (n = 23; mean [SD] age, 57.2 [17.7] years) or necrotizing fasciitis (n = 31; mean [SD] age, 54.3 [13.5]) were included in this study. Patients with cellulitis were found to be less severely ill than patients with necrotizing fasciitis. This is reflected in rates of shock (7 [30.4%] vs 19 [61.3%]; P = .03), need for mechanical ventilation (12 [52.2%] vs 19 [93.5%]; P = .003) and slightly lower mean Sequential Organ Failure Assessment scores (8 vs 10; P = .046). Median (interquartile range [IQR]) Acute Physiology and Chronic Health Evaluation IV scores did not differ significantly (82 [75-98] vs 76 [70-96]; P = .16). Patients with cellulitis had more chronic comorbidities than patients with necrotizing fasciitis (20 [87.0%] vs 17 [54.8%]; P = .02), especially cardiovascular insufficiencies (10 [43.5%] vs 4 [12.9%]; P = .02) and immunodeficiencies (9 [39.1%] vs 3 [9.7%]; P = .02). Among patients with cellulitis and patients with patients with necrotizing fasciitis, Staphylococcus aureus (10 [43.5%] vs 4 [12.9%]; P = .02), Streptococcus pyogenes (2 [8.7%] vs 19 [61.3%]; P &lt; .001) and Escherichia coli (4 [17.4%] vs 5 [16.2%]; P = .90) were the most frequently observed pathogens. Median (IQR) length of ICU stay was shorter for patients with cellulitis vs patients with necrotizing fasciitis (3 [2-5] vs 5 [3-11]; P = .01), while median (IQR) hospital length of stay did not differ significantly (22 [10.25-32] vs 36 [14.25-40]; P = .16); and the in-hospital mortality rate (26.1% vs 22.6%, P > .99) and 90-day mortality rate (30.4% vs 22.6%; P = .54) were similar. CONCLUSIONS AND RELEVANCE: Patients with cellulitis patients are seldom admitted to the ICU. However, while these patients are less critically ill on admission than patients with necrotizing fasciitis, they have more chronic comorbidities and most notably similar short-term and long-term mortality. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01905033

Preclinical studies have suggested that platelets influence the host response during sepsis. We sought to assess the association of admission thrombocytopenia with the presentation, outcome, and host response in patients with sepsis. Nine hundred thirty-one consecutive sepsis patients were stratified according to platelet counts (very low <50 × 109/L, intermediate-low 50 × 109 to 99 × 109/L, low 100 × 109 to 149 × 109/L, or normal 150 × 109 to 399 × 109/L) on admission to the intensive care unit. Sepsis patients with platelet counts <50 × 109/L and 50 × 109 to 99 × 109/L presented with higher Acute Physiology and Chronic Health Evaluation scores and more shock. Both levels of thrombocytopenia were independently associated with increased 30-day mortality (hazard ratios with 95% confidence intervals 2.00 [1.32-3.05] and 1.72 [1.22-2.44], respectively). To account for baseline differences besides platelet counts, propensity matching was performed, after which the association between thrombocytopenia and the host response was tested, as evaluated by measuring 17 plasma biomarkers indicative of activation and/or dysregulation of pathways implicated in sepsis pathogenesis and by whole genome blood leukocyte expression profiling. In the propensity matched cohort, platelet counts < 50 × 109/L were associated with increased cytokine levels and enhanced endothelial cell activation. All thrombocytopenic groups showed evidence of impaired vascular integrity, whereas coagulation activation was similar between groups. Blood microarray analysis revealed a distinct gene expression pattern in sepsis patients with <50 × 109/L platelets, showing reduced signaling in leukocyte adhesion and diapedesis and increased complement signaling. These data show that admission thrombocytopenia is associated with enhanced mortality and a more disturbed host response during sepsis independent of disease severity, thereby providing clinical validity to animal studies on the role of platelets in severe infection.

Preclinical studies have suggested that platelets influence the host response during sepsis. We sought to assess the association of admission thrombocytopenia with the presentation, outcome, and host response in patients with sepsis. Nine hundred thirty-one consecutive sepsis patients were stratified according to platelet counts (very low <50 × 109/L, intermediate-low 50 × 109to 99 × 109/L, low 100 × 109to 149 × 109/L, or normal 150 × 109to 399 × 109/L) on admission to the intensive care unit. Sepsis patients with platelet counts <50 × 109/L and 50 × 109to 99 × 109/L presented with higher Acute Physiology and Chronic Health Evaluation scores and more shock. Both levels of thrombocytopenia were independently associated with increased 30-day mortality (hazard ratios with 95% confidence intervals 2.00 [1.32-3.05] and 1.72 [1.22-2.44], respectively). To account for baseline differences besides platelet counts, propensity matching was performed, after which the association between thrombocytopenia and the host response was tested, as evaluated by measuring 17 plasma biomarkers indicative of activation and/or dysregulation of pathways implicated in sepsis pathogenesis and by whole genome blood leukocyte expression profiling. In the propensity matched cohort, platelet counts < 50 × 109/L were associated with increased cytokine levels and enhanced endothelial cell activation. All thrombocytopenic groups showed evidence of impaired vascular integrity, whereas coagulation activation was similar between groups. Blood microarray analysis revealed a distinct gene expression pattern in sepsis patients with <50 × 109/L platelets, showing reduced signaling in leukocyte adhesion and diapedesis and increased complement signaling. These data show that admission thrombocytopenia is associated with enhanced mortality and a more disturbed host response during sepsis independent of disease severity, thereby providing clinical validity to animal studies on the role of platelets in severe infection.

The acute phase of sepsis is characterized by a strong inflammatory reaction. At later stages in some patients, immunoparalysis may be encountered, which is associated with a poor outcome. By transcriptional and metabolic profiling of human patients with sepsis, we found that a shift from oxidative phosphorylation to aerobic glycolysis was an important component of initial activation of host defense. Blocking metabolic pathways with metformin diminished cytokine production and increased mortality in systemic fungal infection in mice. In contrast, in leukocytes rendered tolerant by exposure to lipopolysaccharide or after isolation from patients with sepsis and immunoparalysis, a generalized metabolic defect at the level of both glycolysis and oxidative metabolism was apparent, which was restored after recovery of the patients. Finally, the immunometabolic defects in humans were partially restored by therapy with recombinant interferon-γ, which suggested that metabolic processes might represent a therapeutic target in sepsis.

Transfusion of red blood cell (RBC) from female donors has been associated with increased risk of mortality. This study aims to investigate the associations between donor-recipient sex and post-transfusion mortality and morbidity in critically ill patients who received RBC transfusions from either male only donors or from female only donors (unisex-transfusion cases). Survival analysis was used to compare 4 groups: female-to-female, female-to-male, male-to-female, and male-to-male transfusion. Multivariate logistic model was used to evaluate the association between donor sex and ICU mortality. Associations between transfusion and acute kidney injury (AKI), acute respiratory distress syndrome (ARDS) and nosocomial infections were assessed. Of the 6992 patients included in the original cohort study, 403 patients received unisex-transfusion. Survival analysis and the logistic model showed that transfusion of female RBCs to male patients was associated with an increased ICU mortality compared to transfusion of female RBCs to female patients (OR 2.43; 95% CI 1.02- 5.77; p-value< 0.05). There was a trend towards increased ARDS in patients receiving RBC from female donors compared to those receiving blood from males (p-value= 0.06) while AKI was higher in donor-recipient sex-matched transfusion groups compared to sex-mismatched groups (p-value= 0.05). This was an exploratory study with potential uncontrolled confounders that limits broad generalization of the findings. Results warrant further studies investigating biological mechanisms underlying the association between donor sex with adverse outcomes as well as studies on the benefit of matching of blood between donor and recipient.

Although humans can produce billions of IgG1 variants through recombination and hypermutation, the diversity of IgG1 clones circulating in human blood plasma has largely eluded direct characterization. Here, we combined several mass-spectrometry-based approaches to reveal that the circulating IgG1 repertoire in human plasma is dominated by a limited number of clones in healthy donors and septic patients. We observe that each individual donor exhibits a unique serological IgG1 repertoire, which remains stable over time but can adapt rapidly to changes in physiology. We introduce an integrative protein- and peptide-centric approach to obtain and validate a full sequence of an individual plasma IgG1 clone de novo. This IgG1 clone emerged at the onset of a septic episode and exhibited a high mutation rate (13%) compared with the closest matching germline DNA sequence, highlighting the importance of de novosequencing at the protein level. A record of this paper’s transparent peer review process is included in the supplemental information.

The propofol infusion syndrome is a rare condition characterized by the occurrence of lactic acidosis, rhabdomyolysis and cardiovascular collapse following high-dose propofol infusion over prolonged periods of time. Patients with traumatic brain injury are particularly at risk of developing this complication because large doses of propofol are commonly used to control intracranial pressure, whereas vasopressors are administered to augment cerebral perfusion pressure. In this review, we provide an update on the literature with particular emphasis on patients with traumatic brain injury.

A prognostic model for head trauma patients is useful only if it predicts clinically relevant outcomes accurately on new subjects in various settings. Most existing models consider only dichotomous outcome and have not been tested externally. We developed and validated a rule for prediction of three functional outcome states after severe head injury, using information from day 1.

Supplemental Digital Content is available in the text.

Supplemental Digital Content is available in the text.

Supplemental Digital Content is available in the text.

ObjectiveTo determine the attributable mortality caused by delirium in critically ill patients.DesignProspective cohort study.Setting32 mixed bed intensive care unit in the Netherlands, January 2011 to July 2013.Participants1112 consecutive adults admitted to an intensive care unit for a minimum of 24 hours.ExposuresTrained observers evaluated delirium daily using a validated protocol. Logistic regression and competing risks survival analyses were used to adjust for baseline variables and a marginal structural model analysis to adjust for confounding by evolution of disease severity before the onset of delirium.Main outcome measureMortality during admission to an intensive care unit.ResultsAmong 1112 evaluated patients, 558 (50.2%) developed at least one episode of delirium, with a median duration of 3 days (interquartile range 2-7 days). Crude mortality was 94/558 (17%) in patients with delirium compared with 40/554 (7%) in patients without delirium (P<0.001). Delirium was significantly associated with mortality in the multivariable logistic regression analysis (odds ratio 1.77, 95% confidence interval 1.15 to 2.72) and survival analysis (subdistribution hazard ratio 2.08, 95% confidence interval 1.40 to 3.09). However, the association disappeared after adjustment for time varying confounders in the marginal structural model (subdistribution hazard ratio 1.19, 95% confidence interval 0.75 to 1.89). Using this approach, only 7.2% (95% confidence interval −7.5% to 19.5%) of deaths in the intensive care unit were attributable to delirium, with an absolute mortality excess in patients with delirium of 0.9% (95% confidence interval −0.9% to 2.3%) by day 30. In post hoc analyses, however, delirium that persisted for two days or more remained associated with a 2.0% (95% confidence interval 1.2% to 2.8%) absolute mortality increase. Furthermore, competing risk analysis showed that delirium of any duration was associated with a significantly reduced rate of discharge from the intensive care unit (cause specific hazard ratio 0.65, 95% confidence interval 0.55 to 0.76).ConclusionsOverall, delirium prolongs admission in the intensive care unit but does not cause death in critically ill patients. Future studies should focus on episodes of persistent delirium and its long term sequelae rather than on acute mortality.Trial registrationClinicaltrials.gov NCT01905033.