Critical care explorations最新文献

Objectives: This study evaluated whether the established efficacy of tocilizumab, an interleukin-6 (IL-6) receptor antagonist, differs between the hypoinflammatory and hyperinflammatory subphenotypes.

Design: Retrospective analysis of data from three biobanks.

Setting: ICUs of three university teaching hospitals in the Netherlands.

Patients: Mechanically ventilated patients with COVID-19.

Interventions: Tocilizumab administration vs. no administration.

Measurements and main results: A total of 561 patients were included. Based on a classifier model incorporating IL-6, tumor necrosis factor receptor 1, and bicarbonate, 95% were classified as Hypoinflammatory and 5% as Hyperinflammatory. Tocilizumab was associated with a significant reduction in 30-day mortality in the overall cohort, even after adjustment for confounders (p = 0.014). However, there was no evidence that treatment effectiveness differed between the two subphenotypes (p = 0.59).

Conclusions: In this cohort, tocilizumab significantly reduced 30-day mortality overall. Although the number of Hyperinflammatory patients was low, there was no evidence that its efficacy differed between inflammatory subphenotypes. These findings underscore the importance of including both subphenotypes in future trials evaluating the differential effects of tocilizumab.

Objectives: This study aimed to determine the decrease in opioid and benzodiazepine doses associated with the development of withdrawal in children.

Setting: Electronic health record data.

Intervention: None.

Patients: Four hundred and seven children who received invasive mechanical ventilation (IMV) between January 1, 2012 and January 1, 2022 with Withdrawal Assessment Tool-1 (WAT-1) scores during their IV opioid wean were included.

Measurements and main results: The primary outcome was development of withdrawal, defined as a WAT-1 score greater than or equal to 3, during the IV opioid weaning phase. Descriptive data included age, weight, insurance, race, ethnicity, language, comorbidities, length of stay, and IMV duration. WAT-1 scores were recorded, and the cumulative IV and enteral opioids, benzodiazepines, and A2As were calculated. Recent changes in IV opioid and benzodiazepine doses were assessed in the 16 hours before each WAT-1 score divided into 4-hour periods. Doses were compared across 4-hour periods, and a multivariable mixed-effects model was used to assess their association with withdrawal. The presence of greater than or equal to 2 pediatric complex chronic condition classification system version 2 (CCC-V2) diagnosis categories (odds ratio [OR] 3.35; 95% CI, 2.61-5.15) was associated with withdrawal. Heart disease, prematurity, and IV opioid class switching did not qualify for model inclusion. Cumulative IV opioid dose and a decrease in opioid exposure between 16-12 and 4-0 hours before the WAT-1 score were associated with withdrawal (OR 1.02; 95% CI, 1.01-1.03; OR 1.92; 95% CI, 1.38-3.16). Morphine was associated with increased odds of withdrawal compared with fentanyl and hydromorphone (OR 1.48; 95% CI, 1.37-1.81). The model did not establish an association between cumulative IV benzodiazepine exposure or IV benzodiazepine dose decrease and withdrawal.

Conclusions: Patients with a higher cumulative IV opioid dose, an IV opioid wean in the preceding 8-12 hours, and greater than or equal to 2 CCC-V2 categories had the highest odds of withdrawal in this single-center study. Morphine was associated with increased odds of withdrawal as well.

Importance: Inflammation, endothelial dysfunction, and complement activation are associated with COVID-19 acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).

Objectives: We hypothesized that higher levels of inflammation, endothelial dysfunction, and complement activation implicated in more severe COVID-19 ALI/ARDS are associated with post-acute sequelae of COVID-19 (PASC) phenotypes in the 3 years after hospitalization.

Design, setting, and participants: A single-center prospective cohort of 150 adult survivors of severe and critical COVID-19 from the first wave of the pandemic with sampling weighted to include 50% survivors of mechanical ventilation.

Main outcomes and measures: Eleven serum biomarkers at hospital discharge, 4 months, 15 months, and 3 years, and symptoms and physical function at 15 months and 3 years. PASC presence was defined using the 12 symptoms and scoring from the Researching COVID to Enhance Recovery (RECOVER) definition. We tested associations of biomarkers with PASC and symptom phenotypes of post-exertional malaise, fatigue, and brain fog while adjusting for age, sex, body mass index, comorbidities, and days since COVID-19 diagnosis.

Results: The mean (sd) age of the cohort was 56 years (13); 67% were Hispanic and 25% were Black. PASC was present in 26% of participants at both 15 months and 3 years. PASC and symptom phenotypes at 15 months and 3 years were consistently associated with higher frailty phenotype category, worse short physical performance battery scores, and shorter 6-minute walk distance. Biomarkers of inflammation, including interleukin-6 and soluble tumor necrosis factor receptor-1, endothelial function, including angiopoietin, and complement, including C2, C4b, and C5, were not associated with PASC or symptom phenotypes in cross-sectional or longitudinal analyses.

Conclusions and relevance: PASC persists for 3 years after acute COVID-19 ALI/ARDS, is associated with frailty, but not associated with persistently higher levels of inflammatory, endothelial, and complement biomarkers implicated in worse short-term outcomes in acute COVID-19, non-COVID-19 ARDS, and sepsis. Future studies should employ multiomics to elucidate potential mechanisms of PASC.

Objectives: To summarize the effectiveness of critical care ultrasonography (CCUS) in adult patients with cardiogenic shock vs. standard of care without CCUS on patient-relevant outcomes.

Design: We performed a scoping review across MEDLINE, Embase, CENTRAL, World Health Organization, International Clinical Trials Registry, ClinicalTrials.gov, and published and unpublished sources from inception until February 2024.

Setting: The emergency department, ward, or ICU.

Patients: We included randomized clinical trials (RCTs) and observational studies comparing CCUS to non-CCUS care in adult patients with cardiogenic shock. We included any type of ultrasound measure for the intervention in adult patients (≥ 18 yr old).

Interventions: CCUS.

Measurements and main results: We included two RCTs (n = 573 patients) and one observational study (n = 30 patients). RCT data suggested that CCUS, with transesophageal echocardiography in particular, in adult patients with cardiogenic shock may shorten time to resolution of hemodynamic instability at 72 hours (subhazard ratio [SHR], 1.26; 95% CI, 1.02-1.55) but failed to influence mortality (risk difference, -0.03; 95% CI, -0.1 to 0.05), time to resolution of hemodynamic instability within 6 days (SHR, 1.20; 95% CI, 0.98-1.46), ICU length of stay (LOS; p = 0.87), hospital LOS (p = 0.91), duration of mechanical ventilation (p = 0.73), or duration of renal replacement therapy (RRT; p = 0.68).

Conclusions: In adult patients with cardiogenic shock, CCUS does not impact mortality, time to resolution of hemodynamic instability within 6 days, ICU and hospital LOS, nor mechanical ventilation or RRT duration. Notably, CCUS may hasten resolution of hemodynamic instability at 72 hours, but such evidence is limited by imprecision and indirectness.

Importance: Venous congestion contributes to multiple organ dysfunction and mortality in critically ill patients. The venous excess ultrasound (VExUS) and lung ultrasound scores have been shown to reflect cardiac filling pressures, but their ability to track hemodynamic changes during decongestion in critically ill patients remains unclear.

Objectives: To determine the correlation of lung ultrasound and VExUS scores with intracardiac filling pressures before and after decongestion in critically ill patients with acute decompensated heart failure.

Design, setting, and participants: We conducted a prospective single-center observational pilot study of adults admitted to the cardiac intensive care and who underwent pulmonary artery catheter placement for hemodynamic-guided decongestion. We performed paired measurements of VExUS grade, simplified lung ultrasound (sLUS) scores, and calculated the renal venous stasis index (RVSI) before and after decongestion and assessed for changes and correlation with right atrial pressure (RAP) and pulmonary artery occlusion pressure (PAOP).

Measurements and main results: Twenty patients underwent 40-paired assessments. After decongestion, a significant reduction in RAP (-9.2 mm Hg; 95% CI, -12.4 to -5.9 mm Hg; p ≤ 0.0001) and PAOP (-12.8 mm Hg; 95% CI, -16.6 to -9.1 mm Hg; p ≤ 0.0001) mirrored reductions in VExUS grades (-1.3; 95% CI, -1.8 to -0.7; p = 0.0002), portal vein pulsatility fraction (-19.9%; 95% CI, -34.1 to -5.6; p = 0.0075), RVSI (-0.19; 95% CI, -0.38 to 0; p = 0.04), and sLUS (-11 points; 95% CI, -14.2 to -8.5; p ≤ 0.0001). VExUS grades and portal vein pulsatility fraction correlated with RAP both before (p = 0.02 and p ≤ 0.003) and after (p = 0.01 and p = 0.001) decongestion, but neither correlated with PAOP. sLUS correlated with PAOP at baseline (ρ = 0.82; p < 0.001) and following decongestion (ρ = 0.59; p = 0.05), while showing no significant correlation with RAP pre-decongestion.

Conclusions and relevance: In critically ill patients with acute decompensated heart failure, we observed changes in VExUS and sLUS scores with decongestion which mirrored changes in intracardiac pressures. The portal vein pulsatility fraction had the higher reproducibility of the VExUS subcomponents. These findings support the role of VExUS and sLUS in hemodynamic monitoring of decongestion in critically ill patients with acute decompensated heart failure.

Context: Sedation and pain management are core strategies used to manage discomfort, anxiety, and pain in intensive care; however, strategies to improve this practice are inconsistently implemented with differential effect.

Objectives: We describe the development and psychometric testing of the Optimizing ContExt in Assessing sedatioN in ICU (OCEAN-ICU) instrument intended for use in intensive care to guide development of change strategies to optimize sedation. We also provide descriptive results.

Methods and models: A prospective instrument development study was undertaken in the United Kingdom. Clinical staff who self-identified as responsible for prescribing, administering, and/or advising on sedation to invasively mechanically ventilated intensive care patients participated. Developed from previous interviews and refined during pilot testing, the draft instrument incorporated 68 statements aligned with the theoretical domains framework. Interested clinicians completed an online survey. Item responses were summed descriptively. Congruence between rankings of agreement and importance were assessed descriptively. Construct validity was assessed using confirmatory factor analysis.

Results: 252 usable responses were received from U.K.-based critical care clinicians (53 medical doctors, 149 nurses, 25 pharmacists, 16 physiotherapists, and nine other healthcare professionals). After refining, 39 items were retained with an overall internal consistency of 0.81 and construct validity of χ²/degrees of freedom = 1.86, comparative fit index = 0.73, and root mean square error of approximation = 0.058.

Interpretation: Areas of practice with high levels of agreement and perceived importance focused on the value of light sedation and the lack of progress in sedation minimization. Conflict between importance and agreement was reported in the effective assessment and management of pain, delirium, and agitation.

Conclusions: The OCEAN-ICU instrument has been developed to determine barriers and facilitators to improving sedation practice in local intensive care contexts. Further validation is required before testing whether the development of change strategies based on identified barriers and facilitators are effective in optimizing sedation practice.

Objectives: To evaluate the agreement between transcranial ultrasound (TUS) and CT measurements of third ventricle diameter in critically ill children.

Design: Prospective observational cohort study.

Setting: PICU of the Children's Hospital of Rabat, Morocco.

Patients: Children 1 month to 15 years old admitted with acute neurologic distress who underwent brain CT.

Interventions: TUS was performed within 1 hour of CT using a phased-array probe through bilateral transtemporal windows.

Measurements and main results: Of 150 screened patients, 148 were included (median age 5 yr; 68% male). Feasibility was high, with bilateral acoustic windows obtained in 98.6% of cases. The median third ventricle diameter was 3.6 mm by both CT and TUS. Bland-Altman analysis demonstrated good agreement between TUS and CT: mean bias 0.11 mm (limits of agreement, -0.78 to 1.01 mm) on the right side and 0.16 mm (-0.81 to 1.13 mm) on the left. Agreement was highest for smaller third ventricle diameters, which accounted for most measurements. No patients had a midline shift or had undergone decompressive craniectomy at the time of imaging.

Conclusions: TUS provides reproducible bedside measurements of third ventricle diameter in children, with good agreement compared with CT in patients without midline shift or major surgical alterations. While not a substitute for comprehensive neuroimaging, TUS may serve as a nonirradiating adjunct for serial ventricular monitoring, particularly for monitoring for the development of hydrocephalus and during external ventricular drain management. Further research should evaluate interoperator reproducibility, applicability in patients with mass effect, and integration into clinical workflows.

Heart rate variability (HRV) reflects autonomic nervous system function and has emerged as a potential noninvasive biomarker for early detection of physiologic deterioration in critical illness. HRV-based prediction models show promise; however, translation into routine ICU practice has been limited. A major barrier is the insufficient characterization of medication effects on HRV. Pharmacologic agents commonly used in critical care, including vasopressors, steroids, and antiarrhythmics, can directly or indirectly alter autonomic tone, yet existing studies rarely account for these influences. As a result, medication-induced HRV changes may represent meaningful therapeutic response or misleading confounding noise, complicating interpretation. Current studies do not adequately account for medication exposure when evaluating HRV in critical illness. We outline research priorities focused on quantifying medication effects, integrating medication exposure into predictive modeling, evaluating HRV as a marker of treatment response, and determining the utility of HRV as a treatment target.

Objectives: Critically ill patients have a high risk for delirium, which may result from inadequate cerebral perfusion. One resuscitation goal for adult critically ill patients is maintaining mean arterial pressure (MAP) greater than 65 mm Hg, regardless of diagnosis or patient characteristics. Recent data suggest a high degree of individual variability in optimal MAP (MAPopt) due, in part, to whether autoregulation is intact or absent. The overall objective of this study was to evaluate the feasibility of maintaining critically ill patients within an individualized MAPopt range identified noninvasively with near-infrared spectroscopy, a technology that measures regional cerebral oxygen saturation (rSo2).

Design: Pilot interventional feasibility study.

Setting: Mixed ICU at a tertiary hospital.

Patients: Sixteen adult critically ill patients were enrolled within 24 hours of ICU admission. Exclusion criteria included expected survival less than 24 hours, neurologic or neurosurgical diagnoses, absence of an arterial catheter, or pregnancy.

Interventions: MAP and rSo2 data were recorded for 24 hours and processed through a custom algorithm. A running correlation coefficient between MAP and rSo2 was generated. Periods where there was zero or negative correlation between MAP and rSo2 reflected intact autoregulation. The MAP range where this correlation was near zero was determined to be the MAPopt. Vasoactive medications were used to maintain patients within that target range for the next 48 hours.

Measurements and main results: The enrollment rate was 0.5 patients/mo (goal 1/mo). MAPopt was successfully identified in 12 patients (75%) and maintained for 61% ± 17% of the follow-up period. The proportion of time spent within MAPopt strongly correlated with the width of the MAPopt range (r = 0.729; p = 0.017). There were no adverse events associated with the intervention.

Conclusions: Although enrollment was lower than expected, MAPopt was calculated in the majority of patients. Maintaining patients within individualized MAPopt ranges was challenging, particularly when this range was narrow.