Critical Care Medicine最新文献

Objectives: The study investigates the prognostic impact of right bundle branch block (RBBB) and left bundle branch block (LBBB) in patients with cardiogenic shock (CS) compared with no bundle branch block (BBB). In patients with heart failure, existence of RBBB and LBBB has influence on prognosis.

Design: Prospective registry-study.

Setting: ICU of a tertiary academic hospital in Germany.

Patients: Adult patients with CS.

Interventions: None.

Measurements and main results: Consecutive patients with CS were included. The prognostic impact of RBBB and LBBB on 30-day all-cause mortality was tested within the entire cohort and in the subgroup of CS patients with cardiac arrest at admission. The final study cohort comprised 248 patients. Patients with RBBB showed the highest 30-day all-cause mortality followed by LBBB and no BBB (72.5% vs. 52.9% vs. 50.0%; log-rank p = 0.015). These findings were consistent even after solely including CS patients with cardiac arrest (90.0% vs. 73.3% vs. 62.2%; log-rank p = 0.008). After adjustment for lactate, norepinephrine, troponin I, Acute Physiology Score, Society of Cardiovascular Angiography & Interventions shock stage, and heart rate in a multivariable Cox regression analysis, RBBB still revealed a negative impact on 30-day all-cause mortality (hazard ratio [HR], 1.807; 95% CI, 1.107-2.947; p = 0.018), whereas LBBB was not associated with 30-day all-cause mortality. In this multivariable Cox regression model lactate (HR, 1.065; 95% CI, 1.018-1.115; p = 0.006), troponin I (HR, 1.003; 95% CI, 1.001-1.005; p = 0.001), and Acute Physiology Score (HR, 1.033; 95% CI, 1.001-1.066; p = 0.041) were as well associated with 30-day all-cause mortality. Finally, no association of RBBB was found with the incidence of liver or severe renal failure.

Conclusions: Besides the Acute Physiology Score, lactate, and troponin levels, RBBB was associated with an increased 30-day all-cause mortality in consecutive CS patients with and without cardiac arrest, whereas LBBB showed no prognostic impact.

Objectives: Pulmonary ventilation/perfusion (V/Q) mismatch measured by electrical impedance tomography (EIT) is associated with the outcome of patients with the acute respiratory distress syndrome (ARDS), but the underlying pathophysiological mechanisms have not been fully elucidated. The present study aimed to verify the correlation between relevant pathophysiological markers of ARDS severity and V/Q mismatch.

Design: Prospective observational study.

Setting: General ICU of a university-affiliated hospital.

Patients: Deeply sedated intubated adult patients with ARDS under controlled mechanical ventilation.

Interventions: Measures of V/Q mismatch by EIT, respiratory mechanics, gas exchange, lung imaging, and plasma biomarkers.

Measurements and main results: Unmatched V/Q units were assessed by EIT as the fraction of ventilated nonperfused plus perfused nonventilated lung units. At the same time, plasma biomarkers with proven prognostic and mechanistic significance for ARDS (carbonic anhydrase 9 [CA9], hypoxia-inducible factor 1 [HIF1], receptor for advanced glycation endproducts [RAGE], angiopoietin 2 [ANG2], gas exchange, respiratory mechanics, and quantitative chest CT scans were measured. Twenty-five intubated ARDS patients were included with median unmatched V/Q units of 37.1% (29.2-49.2%). Unmatched V/Q units were correlated with plasma levels of CA9 (rho = 0.47; p = 0.01), HIF1 (rho = 0.40; p = 0.05), RAGE (rho = 0.46; p = 0.02), and ANG2 (rho = 0.42; p = 0.03). Additionally, unmatched V/Q units correlated with plateau pressure (r = 0.38; p = 0.05) and with the number of quadrants involved on chest radiograph (r = 0.73; p < 0.01). Regional unmatched V/Q units were correlated with the corresponding fraction of poorly aerated lung tissue (r = 0.62; p = 0.01) and of lung tissue weight (rho: 0.51; p = 0.04) measured by CT scan.

Conclusions: In ARDS patients, unmatched V/Q units are correlated with pathophysiological markers of lung epithelial and endothelial dysfunction, increased lung stress, and lung edema. Unmatched V/Q units could represent a comprehensive marker of ARDS severity, reflecting the complex organ pathophysiology and reinforcing their prognostic significance.

Objectives: To explore associations between the physical, cognitive, and mental post-intensive care syndrome (PICS) health domains with changes in health-related quality of life (HRQoL) following ICU admission.

Design: A longitudinal prospective multicenter cohort study.

Setting/patients: Patients (n = 4092) from seven Dutch ICUs.

Interventions: None.

Measurements and main results: At ICU admission, 3 and 12 months post-ICU, patients completed validated questionnaires regarding physical health problems, cognitive health problems, mental health problems, and HRQoL. Composite scores were created for the physical health domain (physical problems and fatigue) and mental health domain (anxiety, depression, and post-traumatic stress disorder). Adjusted multivariable linear regression analyses were performed, including covariables (e.g., patient characteristics, disease severity, pre-ICU HRQoL, etc.) to explore associations between the physical, cognitive, and mental health domains of PICS and changes in HRQoL at 3 and 12 months post-ICU. At 3 months (n = 3368), physical health problems (β = -0.04 [95% CI, -0.06 to 0.02]; p < 0.001), cognitive health problems (β = -0.05 [95% CI, -0.09 to -0.02]; p < 0.001), and mental health problems (β = -0.08 [95% CI, -0.10 to -0.05]; p < 0.001) were negatively associated with changes in HRQoL. Also, at 12 months (n = 2950), physical health problems (β = -0.06 [95% CI, -0.08 to -0.03]; p < 0.001), cognitive health problems (β = -0.04 [95% CI, -0.08 to -0.01]; p < 0.015), and mental health problems (β = -0.06 [95% CI, -0.08 to -0.03]; p < 0.001) were negatively associated with changes in HRQoL.

Conclusions: PICS symptoms in the physical, cognitive, and mental domains are all negatively associated with changes in HRQoL at 3 and 12 months post-ICU. At 3 months, PICS symptoms in the mental domain seem to have the largest negative associations. At 12 months, the associations of PICS in the mental and physical domains are the same. This implies that daily ICU care and follow-up care should focus on preventing and mitigating health problems across all three PICS domains to prevent a decrease in HRQoL.

Objectives: The optimal approach for resuscitation in septic shock remains unclear despite multiple randomized controlled trials (RCTs). Our objective was to investigate whether previously uncharacterized variation across individuals in their response to resuscitation strategies may contribute to conflicting average treatment effects in prior RCTs.

Design: We randomly split study sites from the Australian Resuscitation of Sepsis Evaluation (ARISE) and Protocolized Care for Early Septic Shock (ProCESS) trials into derivation and validation cohorts. We trained machine learning models to predict individual absolute risk differences (iARDs) in 90-day mortality in derivation cohorts and tested for heterogeneity of treatment effect (HTE) in validation cohorts and swapped these cohorts in sensitivity analyses. We fit the best-performing model in a combined dataset to explore roles of patient characteristics and individual components of early goal-directed therapy (EGDT) to determine treatment responses.

Setting: Eighty-one sites in Australia, New Zealand, Hong Kong, Finland, Republic of Ireland, and the United States.

Patients: Adult patients presenting to the emergency department with severe sepsis or septic shock.

Interventions: EGDT vs. usual care.

Measurements and main results: A local-linear random forest model performed best in predicting iARDs. In the validation cohort, HTE was confirmed, evidenced by an interaction between iARD prediction and treatment (p < 0.001). When patients were grouped based on predicted iARDs, treatment response increased from the lowest to the highest quintiles (absolute risk difference [95% CI], -8% [-19% to 4%] and relative risk reduction, 1.34 [0.89-2.01] in quintile 1 suggesting harm from EGDT, and 12% [1-23%] and 0.64 [0.42-0.96] in quintile 5 suggesting benefit). Sensitivity analyses showed similar findings. Pre-intervention albumin contributed the most to HTE. Analyses of individual EGDT components were inconclusive.

Conclusions: Treatment response to EGDT varied across patients in two multicenter RCTs with large benefits for some patients while others were harmed. Patient characteristics, including albumin, were most important in identifying HTE.

Critical care physicians are rich sources of innovation, developing new diagnostic, prognostic, and treatment tools they deploy in clinical practice, including novel software-based tools. Many of these tools are validated and promise to actively help patients, but physicians may be unlikely to distribute, implement, or share them with other centers noncommercially because of unsettled ethical, regulatory, or medicolegal concerns. This Viewpoint explores the potential barriers and risks critical care physicians face in disseminating device-related innovations for noncommercial purposes and proposes a framework for risk-based evaluation to foster clear pathways to safeguard equitable patient access and responsible implementation of clinician-generated technological innovations in critical care.

Objectives: Appropriate resuscitation from hemorrhagic shock is critical to restore tissue perfusion and to avoid over-resuscitation. The objective of this study was to test the ability of a closed-loop diagnosis and resuscitation algorithm called resuscitation from shock using functional hemodynamic monitoring using invasive monitoring (ReFit1) and minimally invasive monitoring (ReFit2) to identify, treat, and stabilize a porcine model of severe hemorrhagic shock.

Design: We created a ReFit algorithm using dynamic hemodynamic parameters of pulse pressure variation (PPV), stroke volume variation (SVV), dynamic arterial elastance (Eadyn = PPV/SVV), driven by mean arterial pressure (MAP), mixed venous oxygen saturation, and heart rate targets to define the need for fluids, vasopressors, and inotropes.

Setting: University-based animal laboratory.

Subjects: Twenty-seven female pigs.

Interventions: Anesthetized, intubated, and ventilated (8 mL/kg) pigs were bled at 10 mL/min until a MAP of less than 40 mm Hg, held for 30 minutes, then resuscitated. The ReFit algorithm used the above dynamic parameters to drive computer-controlled infusion pumps to deliver blood, lactated Ringer's solution, norepinephrine, and in ReFit1 dobutamine. In four animals, after initial resuscitation from hemorrhagic shock, the ability of the ReFit1 algorithm to treat acute air embolism-induced pulmonary hypertension and right heart failure was also tested.

Main results: In 10 ReFit1 and 17 ReFit2 animals, the time to stabilization from shock was not dissimilar to open controlled resuscitation performed by an expert physician (52 ± 12, 50 ± 13, and 60 ± 15 min, respectively) with similar amounts of fluids and norepinephrine needed. In four ReFit1 animals after initial stabilization, the algorithm successfully resuscitated the animals after inducing an acute air embolism right heart failure, with all animals recovering stability within 30 minutes.

Conclusions: Our physiologically based functional hemodynamic monitoring-centered closed-loop resuscitation system can effectively diagnose and treat cardiovascular shock due to hemorrhage and air embolism.

Objectives: Acute kidney injury (AKI) predicts death after cardiac and vascular surgery. Higher preoperative high-density lipoprotein (HDL) concentrations are associated with less postoperative AKI. In animals, HDL's anti-inflammatory capacity to suppress endothelial cell adhesion molecule expression reduces kidney damage due to ischemia and hemorrhagic shock. The objective of this study is to evaluate the statistical relationship between HDL anti-inflammatory capacity and AKI after major cardiac and vascular surgery.

Design: Prospective observational study.

Setting: Quaternary medical center.

Patients: One hundred adults with chronic kidney disease on long-term statin therapy undergoing major elective cardiac and vascular surgery.

Interventions: None.

Measurements and main results: Apolipoprotein B-depleted serum collected at anesthetic induction was incubated with tumor necrosis factor alpha stimulated human endothelial cells. Reverse transcriptase-polymerase chain reaction was used to measure intercellular adhesion molecule-1 (ICAM-1) messenger RNA. Enzyme-linked immunosorbent assay assays were used to measure apolipoprotein A-I and postoperative soluble ICAM-1 concentrations in patient plasma. HDL concentration did not correlate with HDL ICAM-1 suppression capacity (Spearman R = 0.05; p = 0.64). Twelve patients (12%) were found to have dysfunctional, pro-inflammatory HDL. Patients with pro-inflammatory HDL had a higher rate of postoperative AKI than patients with anti-inflammatory HDL (p = 0.046). After adjustment for AKI risk factors, a higher preoperative HDL capacity to suppress endothelial ICAM-1 was independently associated with lower odds of AKI (odds ratio, 0.88; 95% CI, 0.80-0.98; p = 0.016). The association between HDL anti-inflammatory capacity and postoperative AKI was independent of HDL concentration (p = 0.018). Further, a higher long-term statin dose was associated with higher HDL capacity to suppress endothelial ICAM-1 (p = 0.045).

Conclusions: Patients with chronic kidney disease undergoing cardiac and vascular surgery who have dysfunctional, pro-inflammatory HDL have a higher risk of postoperative AKI compared with patients with anti-inflammatory HDL. Conversely, a higher HDL anti-inflammatory capacity is associated with a lower risk of postoperative AKI, independent of HDL concentration. Higher long-term statin dose is associated with higher HDL anti-inflammatory capacity.

Objectives: Explore whether extracorporeal cardiopulmonary resuscitation (ECPR) mortality differs by in-hospital cardiac arrest location and whether moving patients for cannulation impacts outcome.

Design: Retrospective cohort study.

Setting: ECPR hospitals that report data to the Extracorporeal Life Support Organization (ELSO).

Patients: Patients having ECPR for in-hospital cardiac arrest between 2020 and 2023 with data in the ELSO registry.

Interventions: None.

Measurements and main results: Patient demographics, comorbidities, pre-cardiac arrest conditions, pre-ECPR vasopressor use, cardiac arrest details, ECPR cannulation information, major complications, and in-hospital mortality were recorded. Multivariable logistic regression model was used to examine the associations between in-hospital mortality and 1) cardiac arrest location and 2) moving a patient for ECPR cannulation. A total of 2515 patients met enrollment criteria. The adjusted odds ratio (aOR) for mortality was increased in patients who had a cardiac arrest in the ICU (aOR, 1.85; 95% CI, 1.45-2.38; p < 0.001) and in patients who had a cardiac arrest in an acute care bed (aOR, 1.68; 95% CI, 1.09-2.58; p = 0.02) compared with the cardiac catheterization laboratory. Moving a patient for cannulation had no association with mortality (aOR, 0.70; 95% CI, 0.18-2.81; p = 0.62). Advanced patient age was associated with increased mortality. Specifically, patients 60-69 and patients 70 years old or older were more likely to die compared with patients younger than 30 years old (aOR, 1.71; 95% CI, 1.17-2.50; p = 0.006 and aOR, 2.27; 95% CI, 1.49-3.48; p < 0.001, respectively).

Conclusions: ECPR patients who experienced cardiac arrest in the ICU and in acute care hospital beds had increased odds of mortality compared with other locations. Moving patients for ECPR cannulation was not associated with improved outcomes.

Objectives: COVID-19 treatment guidelines recommend baricitinib or tocilizumab for the management of hospitalized patients with COVID-19. We compared the effectiveness of baricitinib vs. tocilizumab on mortality and clinical outcomes among hospitalized patients with COVID-19.

Design: Multicenter, retrospective, propensity-weighted cohort study using a target trial emulation approach.

Setting: The National COVID Cohort Collaborative (N3C), which is the largest electronic health records data on COVID-19 in the United States. The setting included 75 hospitals.

Patients: Adults who were hospitalized for COVID-19.

Interventions: Newly initiated on baricitinib or tocilizumab.

Measurements and main results: Our primary outcome was 28-day mortality. We used propensity scores with inverse probability of treatment weights (IPTWs) to control bias and confounding while comparing treatments. Among 10,661 individuals included in the study, 6,229 (58.4%) received baricitinib and 4,432 (41.6%) tocilizumab. Overall, the mean age of the cohort was 60.0 ± 15.1 years, 6429 (60.3%) were male, and 19.2% received invasive mechanical ventilation. After IPTW adjustment, baricitinib use was associated with lower 28-day mortality (odds ratio [OR], 0.91; 95% CI, 0.85-0.98) and hospital (OR, 0.88; 95% CI, 0.82-0.94) mortality compared with tocilizumab. Baricitinib was also associated with shorter hospital length of stay (incident rate ratio, 0.92; 95% CI, 0.90-0.94) and lower rates of hospital-acquired infections (OR, 0.86; 95% CI, 0.75-0.99), although no difference in ICU length of stay was noted between the two groups.

Conclusions: In this large, diverse cohort of U.S. hospitalized adults with COVID-19, baricitinib was associated with significantly lower 28-day mortality, hospital mortality, shorter hospital length of stay, and less hospital-acquired infections compared with tocilizumab.

Objectives: Neurocritically ill patients are at high risk for developing delirium, which can worsen the long-term outcomes of this vulnerable population. However, existing delirium assessment tools do not account for neurologic deficits that often interfere with conventional testing and are therefore unreliable in neurocritically ill patients. We aimed to determine the accuracy and predictive validity of the Fluctuating Mental Status Evaluation (FMSE), a novel delirium screening tool developed specifically for neurocritically ill patients.

Design: Prospective validation study.

Setting: Neurocritical care unit at an academic medical center.

Patients: One hundred thirty-nine neurocritically ill stroke patients (mean age, 63.9 [sd, 15.9], median National Institutes of Health Stroke Scale score 11 [interquartile range, 2-17]).

Interventions: None.

Measurements and main results: Expert raters performed daily Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition-based delirium assessments, while paired FMSE assessments were performed by trained clinicians. We analyzed 717 total noncomatose days of paired assessments, of which 52% (n = 373) were rated by experts as days with delirium; 53% of subjects were delirious during one or more days. Compared with expert ratings, the overall accuracy of the FMSE was high (area under the curve [AUC], 0.85; 95% CI, 0.82-0.87). FMSE scores greater than or equal to 1 had 86% sensitivity and 74% specificity on a per-assessment basis, while scores greater than or equal to 2 had 70% sensitivity and 88% specificity. Accuracy remained high in patients with aphasia (FMSE ≥ 1: 82% sensitivity, 64% specificity; FMSE ≥ 2: 64% sensitivity, 84% specificity) and those with decreased arousal (FMSE ≥ 1: 87% sensitivity, 77% specificity; FMSE ≥ 2: 71% sensitivity, 90% specificity). Positive FMSE assessments also had excellent accuracy when predicting functional outcomes at discharge (AUC, 0.86 [95% CI, 0.79-0.93]) and 3 months (AUC, 0.85 [95% CI, 0.78-0.92]).

Conclusions: In this validation study, we found that the FMSE was an accurate delirium screening tool in neurocritically ill stroke patients. FMSE scores greater than or equal to 1 indicate "possible" delirium and should be used when prioritizing sensitivity, whereas scores greater than or equal to 2 indicate "probable" delirium and should be used when prioritizing specificity.