Critical care explorations最新文献

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.

Importance: Accurate and reliable sedation assessment is crucial to improving patient outcomes in the ICU.

Objective: To evaluate the inter-rater agreement and reliability of Richmond Agitation Sedation Scale (RASS) assessments between bedside nurses and trained investigators in patients receiving mechanical ventilation in the ICU.

Design, setting, and participants: An assessor triad, comprising an ICU nurse providing direct patient care and two trained investigators, simultaneously performed RASS assessments during 79 encounters with 62 unique patients receiving mechanical ventilation at two ICUs at a tertiary care academic hospital in Colorado. A total of 58 nurses participated in the study.

Main outcomes and measures: The inter-rater reliability of RASS assessments was evaluated with the intraclass correlation coefficient (ICC) and weighted kappa (κ), and inter-rater agreement was evaluated with percentage agreement and Bland-Altman analysis.

Results: Acute respiratory failure (55%) and altered mental status (21%) were the most common reasons for mechanical ventilation. Most patients were receiving one (interquartile range, 0.5-2) continuous sedative during the assessment. The inter-rater reliability of RASS assessments between the nurses and investigators (ICC, 0.728-0.779; weighted κ, 0.62-0.63) was lower than between the two investigators (ICC, 0.891; weighted κ, 0.80). The assessor triad agreed on the same RASS values in only 35% of observations. The average differences in RASS were greater between the investigators and nurses, ranging from -0.658 to -0.544, compared with 0.114 between the two investigators. Compared with the mean of the two investigators, RASS values recorded by nurses were more likely to be higher (52% of observations), indicating a lighter sedation level. In 16% of observations, at least one assessor commented on uncertainty or ambiguity with the RASS.

Conclusions and relevance: The inter-rater reliability of RASS assessments was high. However, we observed variations in the degree of agreement by assessor category. Further studies are necessary to explore how factors such as assessor characteristics, ICU environment, and patient conditions influence the inter-rater agreement of the RASS in contemporary ICU practices.

Objectives: We sought to estimate the association between chronic use of renin-angiotensin system inhibitors and acute kidney injury requiring renal replacement therapy in critically ill adult patients with sepsis.

Design: Population-based cohort study in Ontario, Canada.

Setting: ICUs in Ontario, Canada, between April 2008 and March 2019.

Patients: Elderly patients admitted to an ICU with a sepsis diagnosis; we excluded patients with established indications of renin-angiotensin system inhibitors.

Interventions: The prior use (i.e., within 100 d of hospitalization) of an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker served as the main exposure of interest; the active comparator was the prior use of calcium channel blockers.

Measurements and main results: Acute kidney injury requiring renal replacement therapy was the primary outcome. Septic shock and all-cause mortality at 30 days served as secondary outcomes. We fitted multivariable modified Poisson regression models to adjust for potential confounders; associations were reported as risk ratios (RRs) alongside 95% CIs. We included 8621 patients, of whom 81% received a renin-angiotensin system inhibitor; mean age was 78 years. Renal replacement therapy was performed in 3.2% of patients; compared with the prior use of a calcium channel blocker, prior use of a renin-angiotensin system inhibitor was associated with a higher risk of acute kidney injury and renal replacement therapy (RR, 1.57; 95% CI, 1.10-2.24), septic shock (RR, 1.18; 95% CI, 1.04-1.33), but not all-cause mortality at 30 days (RR, 0.93; 95% CI, 0.88-1.01). Our results were robust across sensitivity analyses.

Conclusions: Chronic use of a renin-angiotensin system inhibitor is associated with a higher risk of renal replacement therapy and septic shock in adult patients with sepsis.

Importance: Vasopressin is used in one-third of patients with septic shock to augment hemodynamics and reduce overall catecholamine exposure. However, the optimal clinical context in which to initiate vasopressin is unknown.

Objectives: To determine the association between norepinephrine-equivalent dose, lactate concentration, and time duration from shock onset at vasopressin initiation with in-hospital mortality.

Design, setting, and participants: Retrospective, observational evaluation utilizing Medical Information Mart for Intensive Care-IV and electronic ICU Collaborative Research Database databases of adult patients with septic shock based on modified Sepsis-3 criteria receiving continuous infusion catecholamines.

Main outcomes and measures: The associations of norepinephrine-equivalent dose, lactate concentration, and time duration from shock onset at vasopressin initiation with in-hospital mortality were evaluated with multivariable regression models.

Results: In total, 1409 patients from 209 hospitals were included. At vasopressin initiation patients had a median (interquartile range) norepinephrine-equivalent dose 28.4 µg/min (16.4-42.6 µg/min), lactate concentration 3.7 mmol/L (2.5-6.2 mmol/L), and 5.6 hours (2.0-13.5 hr) had elapsed since shock onset. All three variables of interest were associated with in-hospital mortality. Three restricted cubic spline knots were identified where the relationship between norepinephrine-equivalent dose and in-hospital mortality changed substantially: 9, 28, and 72 µg/min. The odds of in-hospital mortality increased by 90% and 3.9-fold when comparing vasopressin initiation at norepinephrine-equivalent doses of 28 µg/min and 72 µg/min to 9 µg/min, respectively (adjusted odds ratio [OR], 1.90 [95% CI, 1.49-2.41] and 3.93 [95% CI, 2.74-5.64]). The odds of in-hospital mortality increased by 16% for every mmol/L in the lactate concentration at vasopressin initiation (adjusted OR, 1.16 [95% CI, 1.11-1.21]). Finally, the odds of in-hospital mortality increased by 3% for every hour in the time duration from shock onset to vasopressin initiation (adjusted OR, 1.03 [95% CI, 1.01-1.04]).

Conclusions and relevance: Earlier adjunctive vasopressin initiation may decrease mortality in patients with septic shock.