Critical care explorations最新文献

Objectives background: Monocyte anisocytosis (monocyte distribution width [MDW]) has been previously validated to predict sepsis and outcome in patients presenting in the emergency department and mixed-population ICUs. Determining sepsis in a critically ill surgical/trauma population is often difficult due to concomitant inflammation and stress. We examined whether MDW could identify sepsis among patients admitted to a surgical/trauma ICU and predict clinical outcome.

Design: Secondary analysis of three prospective observational clinical studies.

Setting: Single institution ICU.

Patients/subjects: Two hundred thirty-eight participants were included in this study: 107 patients who were admitted to the ICU and adjudicated to have sepsis, 80 patients who were considered critically ill nonseptic (CINS), and 51 healthy control participants.

Interventions: MDW was measured among hospitalized patients admitted to the ICU with the diagnosis of sepsis or CINS patients at risk of developing sepsis. Blood samples were collected at admission and at intervals during ICU admission.

Measurements and main results: MDW significantly differed between septic and CINS patients on ICU admission (26.4, interquartile range [IQR, 23.5-30.8] vs. 20.1 [IQR, 17.9-21.9]; p < 0.001) and could discriminate with an area under the receiver operating characteristic curve of 0.85 (95% CI, 0.79-0.91; p < 0.001). An MDW of greater than 22.0 at admission to the ICU could identify sepsis with a 78% specificity and a 90% sensitivity but could not discriminate in-hospital, 30-day, or 90-day mortality.

Limitations: Small sample size from a single institution. Our analysis did not include other relevant biomarkers such as procalcitonin, C-reactive protein, and interleukin-6. In the imputation of missing values, linear mixed-effect models were used, risking model misspecification and the violation of the missing-at-random assumption.

Conclusions: Among surgical/trauma ICU patients, MDW can discriminate between sepsis and nonseptic inflammation, but it is a weak predictor of mortality.

Importance: Sepsis remains a leading cause of death in infectious cases. The heterogeneity of immune responses is a major challenge in the management and prognostication of patients with sepsis. Identifying distinct immune response subphenotypes using parsimonious classifiers may improve outcome prediction, particularly in resource-limited settings.

Objectives: This study aimed to evaluate whether classification of the immune response can serve as a predictor of mortality.

Design, setting, and participants: This prospective cohort study was conducted in the emergency department, inpatient wards, and ICU of a tertiary hospital. Adult patients diagnosed with sepsis within the previous 24 hours were included. Exclusion criteria were history of RBC transfusion, major thalassemia, decompensated cirrhosis, hematologic malignancy, or use of immunosuppressive or chronic corticosteroid therapy. Demographic, clinical, and laboratory data-including serum ferritin and monocyte human leukocyte antigen-DR/Human Leukocyte Antigen-DR) (mHLA-DR) levels-were collected.

Main outcomes and measures: Subjects were classified into the following immune subphenotypes: macrophage activation-like syndrome (MALS) (if ferritin > 4420 ng/mL), immunoparalysis (if mHLA-DR < 10,000 receptors/cell and ferritin ≤ 4420 ng/mL), and unclassified (if they did not meet the criteria for either MALS or immunoparalysis). The primary outcome was in-hospital mortality.

Results: Of the 200 subjects recruited, 54 (27%) were classified into the MALS group, 19 (9.5%) into the immunoparalysis group, and the remainder into the unclassified group. The in-hospital mortality rates for the MALS, immune paralysis, and unclassified groups were 83.3%, 68.4%, and 51.1%, respectively. The proportional hazards assumption was met between the MALS and unclassified groups (crude hazard ratio [HR] 2.3; 95% CI, 1.56-3.35) but not between the immunoparalysis and unclassified groups (crude HR 1.4; 95% CI, 0.76-2.50). After adjusting for confounding variables, MALS's adjusted HR was 1.7 (95% CI, 1.13-2.49; p = 0.01).

Conclusions and relevance: The MALS subphenotype is an independent predictor of in-hospital mortality in sepsis.

Objective: Vitamin C has been linked to alterations in platelet count and aggregation behavior. Given recent findings suggesting an association between vitamin C and adverse outcomes in patients with septic shock, we aimed to investigate whether vitamin C influences mortality in septic patients through its impact on platelets.

Design: Post hoc analysis of the Lessening Organ Dysfunction With Vitamin C (LOVIT) randomized trial (clinicaltrials.gov NCT03680274).

Setting: Multicenter international study.

Patients: Patients were included with an ICU stay of more than 24 hours, confirmed or suspected infection, vasopressor requirement, and availability of platelet count data.

Intervention: Vitamin C (50 mg/kg body weight) every 6 hours for 4 days, or placebo.

Measurements and main results: Of the 863 patients enrolled in the LOVIT trial, 859 had available platelet count data at any time. Although the longitudinal trajectory of platelet count was significantly associated with 28-day mortality (hazard ratio 0.97 per 10 × 10⁹/L increase, 95% CI, 0.96-0.98), there was no interaction between the effect of vitamin C on mortality and either platelet count at baseline or over time.

Conclusions: These results do not support the hypothesis that vitamin C administration increases mortality risk by affecting platelet count.

Mean airway pressure, a monitored variable continuously available on the modern ventilator, is the pressure measured at the airway opening averaged over the time needed to complete the entire respiratory cycle. Mean airway pressure is well recognized to connect three key physiologic processes in mechanical ventilation: physical stretch, cardiovascular dynamics, and pulmonary gas exchange. Although other parameters currently employed in adults to determine "safe" ventilation are undoubtedly valuable for daily practice, all have limitations for continuous monitoring of ventilation hazard. The purpose of this communication is to explore the often-underappreciated link between mean airway pressure and the mechanical power (cumulative inflation energy/min) that helps determine the adverse consequences of invasive ventilation (ventilator-induced lung injury).

Importance: Propofol is a first-line sedative for adults receiving invasive mechanical ventilation (IMV). However, it can contribute to hemodynamic instability, especially during intubation. The magnitude, timing, risk factors, and variability of sedation-associated mean arterial pressure (MAP) changes remain poorly characterized in ICU settings.

Objectives: To quantify MAP changes following propofol sedation, identify risk factors for hemodynamic instability, and characterize associated interventions.

Design: Retrospective cohort study. The primary outcome was MAP change within 2 hours following sedation. Secondary outcomes included vasopressor use and hypotension (MAP ≤ 60 mm Hg). Mixed-effects modeling was used to account for individual patient differences.

Setting and participants: Adults (≥ 18 yrs old) who required IMV and received greater than or equal to 6 consecutive hours of propofol infusion, between May 5th, 2018, and July 31st, 2024, in 11 ICUs across the Mayo Clinic, spanning 5 hospitals in 4 states.

Main outcomes and measures: The primary outcome was the change in MAP within 2 hours following the initiation of propofol-based sedation.

Results: Across 16,418 patients, 25.2% were on vasopressors before sedation initiation. Among the remaining 12,281 patients, 40.3% required vasopressors and 7.7% experienced hypotension within 2 hours of sedation. Propofol-based sedation was associated with a MAP reduction within the first 30 minutes (-6.58 mm Hg; 95% CI, -6.85 to -6.32; p < 0.001). There was substantial interpatient variability in both baseline MAP, and MAP decline after sedation (9.5 and 40.9% between-patient differences, respectively). Higher Sequential Organ Failure Assessment (SOFA) scores (-0.31 mm Hg/point), older age (-0.04 mm Hg/yr), and male sex (-0.47 mm Hg) were associated with lower MAP. Patients with higher illness severity experienced progressively greater MAP decline over time (-0.20 mm Hg/hr/SOFA point; p < 0.001).

Conclusions and relevance: Propofol-based sedation was associated with clinically significant hemodynamic effects requiring intervention in the early post-intubation period. The marked interpatient variability in hemodynamic responses highlights the importance of personalized management approaches, including risk stratification based on age, sex, and illness severity.

Mean airway pressure, a monitored variable continuously available on the modern ventilator, is the pressure measured at the airway opening averaged over the time needed to complete the entire respiratory cycle. Mean airway pressure is well recognized to connect three key physiologic processes in mechanical ventilation: physical stretch, cardiovascular dynamics, and pulmonary gas exchange. Although other parameters currently employed in adults to determine "safe" ventilation are undoubtedly valuable for daily practice, all have limitations for continuous monitoring of ventilation hazard. The purpose of this communication is to explore the often-underappreciated link between mean airway pressure and the mechanical power (cumulative inflation energy/min) that helps determine the adverse consequences of invasive ventilation (ventilator-induced lung injury).

Objective: To identify distinct phenotypes of acute respiratory distress syndrome (ARDS) developing after hematopoietic cell transplantation (HCT), using routinely available clinical data at ICU admission.

Design: Multicenter retrospective cohort study using latent class analysis.

Setting: ICUs across three Mayo Clinic campuses (Minnesota, Florida, and Arizona).

Patients: A total of 166 adult patients who developed ARDS within 120 days following HCT (96 allogeneic, 70 autologous).

Intervention: None.

Measurements and main results: Model selection was based on multiple metrics including Bayesian information criteria, entropy, and Vuong-Lo-Mendell-Rubin Likelihood Ratio testing. A two-class model optimally described the cohort. Class 1 (n = 81) was characterized by worse hypoxemia (P/F ratio 157 vs. 210, p = 0.002), higher Pco2 (41 vs. 36 mm Hg, p < 0.001), and higher bilirubin (1.4 vs. 0.9 mg/dL, p < 0.001) compared with class 2 (n = 85). Both classes included a mix of transplant types, transcending a simple autologous/allogeneic dichotomy, although class 1 had more allogeneic recipients (70.4% vs. 45.9%, p = 0.001). Although time-from-transplant was not a class-defining variable, class 1 occurred later after transplant (30.0 vs. 11.9 d, p < 0.001) with higher frequency of idiopathic pneumonia syndrome (14.8% vs. 2.4%, p = 0.004). Class 2 had more frequent neutropenia (leukocytes 0.4 vs. 5.9 × 109, p < 0.001) and higher frequency of peri-engraftment respiratory distress syndrome (29.4% vs. 9.9%, p = 0.005). Outcomes were significantly worse for class 1 (90-d mortality: 72.8% vs. 48.2%, p = 0.001). An exploratory parsimonious model had good classification accuracy (0.90) using just six variables: leukocyte count, platelet count, bilirubin, Pco2, body mass index, and temperature.

Conclusions: ARDS after HCT comprises two distinct phenotypes with distinct clinical characteristics and outcomes. These phenotypes align with recognized post-HCT lung injury syndromes and may reflect different underlying biological processes. This framework provides a foundation for investigating targeted therapeutic approaches.

Objective: This post hoc study of the Progesterone for Traumatic Brain Injury, Experimental Clinical Treatment (ProTECT) III trial investigates whether improving traumatic brain injury (TBI) classification, using serum biomarkers (glial fibrillary acidic protein [GFAP] and ubiquitin carboxyl-terminal esterase L1 [UCH-L1]) and algorithmically assessed total lesion volume, could identify a subset of responders to progesterone treatment, beyond broad measures like the Glasgow Coma Scale (GCS) and Glasgow Outcome Scale-Extended (GOS-E), which may fail to capture subtle changes in TBI recovery.

Design: Brain lesion volumes on CT scans were quantified using Brain Lesion Analysis and Segmentation Tool for CT. Patients were classified into true-positive and true-negative groups based on an optimization scheme to determine a threshold that maximizes agreement between radiological assessment and objectively measured lesion volume. True-positives were further categorized into low (> 0.2-10 mL), medium (> 10-50 mL), and high (> 50 mL) lesion volumes for analysis with protein biomarkers and injury severity. Correlation analyses linked Rotterdam scores (RSs) with biomarker levels and lesion volumes, whereas Welch's t-test evaluated biomarker differences between groups and progesterone's effects.

Setting: Forty-nine level 1 trauma centers in the United States.

Patient: Patients with moderate-to-severe TBI.

Interventions: Progesterone.

Measurements and main results: GFAP and UCH-L1 levels were significantly higher in true-positive cases with low to medium lesion volume. Only UCH-L1 differed between progesterone and placebo groups at 48 hours. Both biomarkers and lesion volume in the true-positive group correlated with the RS. No sex-specific or treatment differences were found.

Conclusions: This study reaffirms elevated levels of GFAP and UCH-L1 as biomarkers for detecting TBI in patients with brain lesions and for predicting clinical outcomes. Despite improved classification using CT-imaging segmentation and serum biomarkers, we did not identify a subset of progesterone responders within 24 or 48 hours of progesterone treatment. More rigorous and quantifiable measures for classifying the nature of injury may be needed to enable development of therapeutics as neither serum markers nor algorithmic CT analysis performed better than the older metrics of Rotterdam or GCS metrics.

Importance: The relationship between endotoxin activity, organ failure, and mortality is not well understood.

Objective: To test whether the combination of endotoxin activity and organ failure identifies patients at higher risk of death from sepsis and determine the relationship to previously described sepsis phenotypes.

Design, setting, and participants: Prospective observational study in four ICUs enrolling critically ill patients with septic shock.

Main outcomes and measures: Endotoxin activity assay (EAA) results, Sequential Organ Failure Assessment (SOFA), and multiple organ dysfunction (MODS) and 28-day mortality.

Results: We enrolled 90 patients aged 25-95 years and set an EAA cutoff of greater than or equal to 0.6 together with SOFA greater than 11 or MODS greater than 9 to define endotoxic septic shock (ESS). At baseline mean EAA was 0.64 (sd = 0.19), whereas mean SOFA and MODS were 10.3 (sd 3.2) and 5.8 (sd 3.1), respectively. EAA greater than or equal to 0.6 and SOFA greater than 11 were present in 20 patients (23.3%) and these patients had 60% mortality. EAA greater than or equal to 0.6 and SOFA less than or equal to 11 occurred in 31 (36.0%) with mortality 12.9%. Of the 35 remaining patients with EAA less than 0.6, 29 (33.7%) had SOFA less than or equal to 11 and 5 of them (17.2%) died. Only six patients (7.0%) had EAA less than 0.6 and SOFA greater than 11 and none died (p < 0.001). All patients with MODS greater than 9 also had EAA greater than or equal to 0.6 (12 patients) with 75% mortality. EAA greater than or equal to 0.6 with MODS less than or equal to 9 occurred in 39 patients with 17.9% mortality (p < 0.001). ESS (EAA ≥ 0.6 together with SOFA > 11 or MODS > 9) occurred in 21 patients and they had significantly higher mortality (57.1% vs. 15.9%, p < 0.001) compared with non-ESS, with a relative risk for death of 3.58 (95% CI, 1.86-6.91). Among ESS patients, 7 (33.3%) had δ phenotype, whereas only 4 (5.8%) had δ among non-ESS (p = 0.001).

Conclusions and relevance: ESS compromises patients with the highest mortality rate from sepsis. Such patients are most appropriate for trials testing anti-endotoxin therapy for improving survival.