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A novel urinary biomarker predicts 1-year mortality after discharge from intensive care

期刊: CRITICAL CARE, 2020; 24 (1)

Rationale The urinary proteome reflects molecular drivers of disease. Objectives To construct a urinary proteomic biomarker predicting 1-year post-ICU mortality. Methods In 1243 patients, the urinary proteome was measured on ICU admission, using capillary electrophoresis coupled with mass spectrometry along with clinical variables, circulating biomarkers (BNP, hsTnT, active ADM, and NGAL), and urinary albumin. Methods included support vector modeling to construct the classifier, Cox regression, the integrated discrimination (IDI), and net reclassification (NRI) improvement, and area under the curve (AUC) to assess predictive accuracy, and Proteasix and protein-proteome interactome analyses. Measurements and main results In the discovery (deaths/survivors, 70/299) and test (175/699) datasets, the new classifier ACM128, mainly consisting of collagen fragments, yielding AUCs of 0.755 (95% CI, 0.708-0.798) and 0.688 (0.656-0.719), respectively. While accounting for study site and clinical risk factors, hazard ratios in 1243 patients were 2.41 (2.00-2.91) for ACM128 (+ 1 SD), 1.24 (1.16-1.32) for the Charlson Comorbidity Index (+ 1 point), and >= 1.19 (P <= 0.022) for other biomarkers (+ 1 SD). ACM128 improved (P <= 0.0001) IDI (>= + 0.50), NRI (>= + 53.7), and AUC (>= + 0.037) over and beyond clinical risk indicators and other biomarkers. Interactome mapping, using parental proteins derived from sequenced peptides included in ACM128 and in silico predicted proteases, including/excluding urinary collagen fragments (63/35 peptides), revealed as top molecular pathways protein digestion and absorption, lysosomal activity, and apoptosis. Conclusions The urinary proteomic classifier ACM128 predicts the 1-year post-ICU mortality over and beyond clinical risk factors and other biomarkers and revealed molecular pathways potentially contributing to a fatal outcome.

Effects of endovascular and surface cooling on resuscitation in patients with cardiac arrest and a comparison of effectiveness, stability, and safety: a systematic review and meta-analysis

期刊: CRITICAL CARE, 2020; 24 (1)

Objectives This study conducted a meta-analysis to assess the effectiveness, stability, and safety of mild therapeutic hypothermia (TH) induced by endovascular cooling (EC) and surface cooling (SC) and its effect on ICU, survival rate, and neurological function integrity in adult CA patients. Methods We developed inclusion criteria, intervention protocols, results, and data collection. The results included outcomes during target temperature management as well as ICU stay, survival rate, and neurological functional integrity. The characteristics of the included population and each study were analyzed. Results Four thousand nine hundred thirteen participants met the inclusion criteria. Those receiving EC had a better cooling efficiency (cooling rates MD = 0.31[0.13, 0.50], p < 0.01; induced cooling times MD = - 90.45[- 167.57, - 13.33], p = 0.02; patients achieving the target temperature RR = 1.60[1.19, 2.15], p < 0.01) and thermal stability during the maintenance phase (maintenance time MD = 2.35[1.22, 3.48], p < 0.01; temperature fluctuation MD = - 0.68[- 1.03, - 0.33], p < 0.01; overcooling RR = 0.33[0.23, 0.49], p < 0.01). There were no differences in ICU survival rate (RR = 1.22[0.98, 1.52], p = 0.07, I-2 = 0%) and hospital survival rate (RR = 1.02 [0.96, 1.09], p = 0.46, I-2 = 0%), but EC reduced the length of stay in ICU (MD = - 1.83[- 3.45, - 0.21], p = 0.03, I-2 = 49%) and improved outcome of favorable neurological function at discharge (RR = 1.15[1.04, 1.28], p < 0.01, I-2 = 0%). EC may delay the hypothermia initiation time, and there was no significant difference between the two cooling methods in the time from the start of patients' cardiac arrest to achieve the target temperature (MD = - 46.64[- 175.86, 82.58]). EC was superior to non-ArcticSun in terms of cooling efficiency. Although there was no statistical difference in ICU survival rate, ICU length of stay, and hospitalization survival rate, in comparison to non-ArcticSun, EC improved rates of neurologically intact survival (RR = 1.16 [1.01, 1.35], p = 0.04, I-2 = 0%). Conclusions Among adult patients receiving cardiopulmonary resuscitation, although there is no significant difference between the two cooling methods in the time from the start of cardiac arrest to achieve the target temperature, the faster cooling rate and more stable cooling process in EC shorten patients' ICU hospitalization time and help more patients obtain good neurological prognosis compared with patients receiving SC. Meanwhile, although EC has no significant difference in patient outcomes compared with ArcticSun, EC has improved rates of neurologically intact survival.

Efficacy and safety of early prone positioning combined with HFNC or NIV in moderate to severe ARDS: a multi-center prospective cohort study

期刊: CRITICAL CARE, 2020; 24 (1)

Background Previous studies suggest that prone positioning (PP) can increase PaO2/FiO(2) and reduce mortality in moderate to severe acute respiratory distress syndrome (ARDS). The aim of our study was to determine whether the early use of PP combined with non-invasive ventilation (NIV) or high-flow nasal cannula (HFNC) can avoid the need for intubation in moderate to severe ARDS patients. Methods This prospective observational cohort study was performed in two teaching hospitals. Non-intubated moderate to severe ARDS patients were included and were placed in PP with NIV or with HFNC. The efficacy in improving oxygenation with four support methods-HFNC, HFNC+PP, NIV, NIV+PP-were evaluated by blood gas analysis. The primary outcome was the rate of intubation. Results Between January 2018 and April 2019, 20 ARDS patients were enrolled. The main causes of ARDS were pneumonia due to influenza (9 cases, 45%) and other viruses (2 cases, 10%). Ten cases were moderate ARDS and 10 cases were severe. Eleven patients avoided intubation (success group), and 9 patients were intubated (failure group). All 7 patients with a PaO2/FiO(2) < 100 mmHg on NIV required intubation. PaO2/FiO(2) in HFNC+PP were significantly higher in the success group than in the failure group (125 +/- 41 mmHg vs 119 +/- 19 mmHg, P = 0.043). PaO2/FiO(2) demonstrated an upward trend in patients with all four support strategies: HFNC < HFNC+PP <= NIV < NIV+PP. The average duration for PP was 2 h twice daily. Conclusions Early application of PP with HFNC, especially in patients with moderate ARDS and baseline SpO(2) > 95%, may help avoid intubation. The PP was well tolerated, and the efficacy on PaO2/FiO(2) of the four support strategies was HFNC < HFNC+PP <= NIV < NIV+PP. Severe ARDS patients were not appropriate candidates for HFNC/NIV+PP.

The impact of high frequency oscillatory ventilation on mortality in paediatric acute respiratory distress syndrome

期刊: CRITICAL CARE, 2020; 24 (1)

Background High-frequency oscillatory ventilation (HFOV) use was associated with greater mortality in adult acute respiratory distress syndrome (ARDS). Nevertheless, HFOV is still frequently used as rescue therapy in paediatric acute respiratory distress syndrome (PARDS). In view of the limited evidence for HFOV in PARDS and evidence demonstrating harm in adult patients with ARDS, we hypothesized that HFOV use compared to other modes of mechanical ventilation is associated with increased mortality in PARDS. Methods Patients with PARDS from 10 paediatric intensive care units across Asia from 2009 to 2015 were identified. Data on epidemiology and clinical outcomes were collected. Patients on HFOV were compared to patients on other modes of ventilation. The primary outcome was 28-day mortality and secondary outcomes were 28-day ventilator- (VFD) and intensive care unit- (IFD) free days. Genetic matching (GM) method was used to analyse the association between HFOV treatment with the primary outcome. Additionally, we performed a sensitivity analysis, including propensity score (PS) matching, inverse probability of treatment weighting (IPTW) and marginal structural modelling (MSM) to estimate the treatment effect. Results A total of 328 patients were included. In the first 7 days of PARDS, 122/328 (37.2%) patients were supported with HFOV. There were significant differences in baseline oxygenation index (OI) between the HFOV and non-HFOV groups (18.8 [12.0, 30.2] vs. 7.7 [5.1, 13.1] respectively; p < 0.001). A total of 118 pairs were matched in the GM method which found a significant association between HFOV with 28-day mortality in PARDS [odds ratio 2.3, 95% confidence interval (CI) 1.3, 4.4, p value 0.01]. VFD was indifferent between the HFOV and non-HFOV group [mean difference - 1.3 (95%CI - 3.4, 0.9); p = 0.29] but IFD was significantly lower in the HFOV group [- 2.5 (95%CI - 4.9, - 0.5); p = 0.03]. From the sensitivity analysis, PS matching, IPTW and MSM all showed consistent direction of HFOV treatment effect in PARDS. Conclusion The use of HFOV was associated with increased 28-day mortality in PARDS. This study suggests caution but does not eliminate equivocality and a randomized controlled trial is justified to examine the true association.

Facilitating ventilator weaning through rib fixation combined with video-assisted thoracoscopic surgery in severe blunt chest injury with acute respiratory failure

期刊: CRITICAL CARE, 2020; 24 (1)

Background Severe blunt chest injury sometimes induces acute respiratory failure (ARF), requiring ventilator use. We aimed to evaluate the effect of performing rib fixation with the addition of video-assisted thoracoscopic surgery (VATS) on patients with ARF caused by blunt thoracic injury with ventilator dependence. Methods This observational study prospectively enrolled patients with multiple bicortical rib fractures with hemothorax caused by severe blunt chest trauma. All patients received positive pressure mechanical ventilation within 24 h after trauma because of ARF. Some patients who received rib fixation with VATS were enrolled as group 1, and the others who received only VATS were designated as group 2. The length of ventilator use was the primary clinical outcome. Rates of pneumonia and length of hospital stay constituted secondary outcomes. Results A total of 61 patients were included in this study. The basic demographic characteristics between the two groups exhibited no statistical differences. All patients received operations within 6 days after trauma. The length of ventilator use was shorter in group 1 (3.19 +/- 3.37 days vs. 8.05 +/- 8.23, P = 0.002). The rate of pneumonia was higher in group 2 (38.1% vs. 75.0%, P = 0.005). The length of hospital stay was much shorter in group 1 (17.76 +/- 8.38 days vs. 24.13 +/- 9.80, P = 0.011). Conclusion Rib fixation combined with VATS could shorten the length of ventilator use and reduce the pneumonia rate in patients with severe chest blunt injury with ARF. Therefore, this operation could shorten the overall length of hospital stay.

Defining persistent critical illness based on growth trajectories in patients with sepsis

期刊: CRITICAL CARE, 2020; 24 (1)

Background Persistent critical illness is common in critically ill patients and is associated with vast medical resource use and poor clinical outcomes. This study aimed to define when patients with sepsis would be stabilized and transitioned to persistent critical illness, and whether such transition time varies between latent classes of patients. Methods This was a retrospective cohort study involving sepsis patients in the eICU Collaborative Research Database. Persistent critical illness was defined at the time when acute physiological characteristics were no longer more predictive of in-hospital mortality (i.e., vital status at hospital discharge) than antecedent characteristics. Latent growth mixture modeling was used to identify distinct trajectory classes by using Sequential Organ Failure Assessment score measured during intensive care unit stay as the outcome, and persistent critical illness transition time was explored in each latent class. Results The mortality was 16.7% (3828/22,868) in the study cohort. Acute physiological model was no longer more predictive of in-hospital mortality than antecedent characteristics at 15 days after intensive care unit admission in the overall population. Only a minority of the study subjects (n = 643, 2.8%) developed persistent critical illness, but they accounted for 19% (15,834/83,125) and 10% (19,975/198,833) of the total intensive care unit and hospital bed-days, respectively. Five latent classes were identified. Classes 1 and 2 showed increasing Sequential Organ Failure Assessment score over time and transition to persistent critical illness occurred at 16 and 27 days, respectively. The remaining classes showed a steady decline in Sequential Organ Failure Assessment scores and the transition to persistent critical illness occurred between 6 and 8 days. Elevated urea-to-creatinine ratio was a good biochemical signature of persistent critical illness. Conclusions While persistent critical illness occurred in a minority of patients with sepsis, it consumed vast medical resources. The transition time differs substantially across latent classes, indicating that the allocation of medical resources should be tailored to different classes of patients.

The global survival rate among adult out-of-hospital cardiac arrest patients who received cardiopulmonary resuscitation: a systematic review and meta-analysis

期刊: CRITICAL CARE, 2020; 24 (1)

BackgroundTo quantitatively summarize the available epidemiological evidence on the survival rate of out-of-hospital cardiac arrest (OHCA) patients who received cardiopulmonary resuscitation (CPR).MethodsWe systematically searched the PubMed, Embase, and Web of Science databases, and the references of retrieved articles were manually reviewed to identify studies reporting the outcome of OHCA patients who received CPR. The overall incidence and outcome of OHCA were assessed using a random-effects meta-analysis.ResultsA total of 141 eligible studies were included in this meta-analysis. The pooled incidence of return of spontaneous circulation (ROSC) was 29.7% (95% CI 27.6-31.7%), the rate of survival to hospital admission was 22.0% (95% CI 20.7-23.4%), the rate of survival to hospital discharge was 8.8% (95% CI 8.2-9.4%), the pooled 1-month survival rate was 10.7% (95% CI 9.1-13.3%), and the 1-year survival rate was 7.7% (95% CI 5.8-9.5%). Subgroup analysis showed that survival to hospital discharge was more likely among OHCA patients whose cardiac arrest was witnessed by a bystander or emergency medical services (EMS) (10.5%; 95% CI 9.2-11.7%), who received bystander CPR (11.3%, 95% CI 9.3-13.2%), and who were living in Europe and North America (Europe 11.7%; 95% CI 10.5-13.0%; North America: 7.7%; 95% CI 6.9-8.6%). The survival to discharge (8.6% in 1976-1999 vs. 9.9% in 2010-2019), 1-month survival (8.0% in 2000-2009 vs. 13.3% in 2010-2019), and 1-year survival (8.0% in 2000-2009 vs. 13.3% in 2010-2019) rates of OHCA patients who underwent CPR significantly increased throughout the study period. The Egger's test did not indicate evidence of publication bias for the outcomes of OHCA patients who underwent CPR.ConclusionsThe global survival rate of OHCA patients who received CPR has increased in the past 40years. A higher survival rate post-OHCA is more likely among patients who receive bystander CPR and who live in Western countries.

Association between furosemide administration and outcomes in critically ill patients with acute kidney injury

期刊: CRITICAL CARE, 2020; 24 (1)

Background Although current guidelines for AKI suggested against the use of furosemide in AKI management, the effect of furosemide on outcomes in real-world clinical settings remains uncertain. The aim of the present study was to investigate the association between furosemide administration and outcomes in critically ill patients with AKI using real-world data. Methods Critically ill patients with AKI were identified from the Medical Information Mart for Intensive Care (MIMIC)-III database. Propensity score (PS) matched analysis was used to match patients receiving furosemide to those without diuretics treatment. Linear regression, logistic regression model, and Cox proportional hazards model were used to assess the associations between furosemide and length of stay, recovery of renal function, and in-hospital and 90-day mortality, respectively. Results A total of 14,154 AKI patients were included in the data analysis. After PS matching, 4427 pairs of patients were matched between the patients who received furosemide and those without diuretics treatment. Furosemide was associated with reduced in-hospital mortality [hazard ratio (HR) 0.67; 95% CI 0.61-0.74; P < 0.001] and 90-day mortality [HR 0.69; 95% CI 0.64-0.75; P < 0.001], and it was also associated with the recovery of renal function [HR 1.44; 95% CI 1.31-1.57; P < 0.001] in over-all AKI patients. Nevertheless, results illustrated that furosemide was not associated with reduced in-hospital mortality in patients with AKI stage 0-1 defined by UO criteria, AKI stage 2-3 according to SCr criteria, and in those with acute-on-chronic (A-on-C) renal injury. Conclusions Furosemide administration was associated with improved short-term survival and recovery of renal function in critically ill patients with AKI. Furosemide was especially effective in patients with AKI UO stage 2-3 degree. However, it was not effective in those with AKI SCr stage 2-3 and chronic kidney disease. The results need to be verified in randomized controlled trials.

Effects of a national quality improvement program on ICUs in China: a controlled pre-post cohort study in 586 hospitals

期刊: CRITICAL CARE, 2020; 24 (1)

Introduction Patient safety and critical care quality remain a challenging issue in the ICU. However, the effects of the national quality improvement (QI) program remain unknown in China. Methods A national ICU QI program was implemented in a controlled cohort of 586 hospitals from 2016 to 2018. The effects of the QI program on critical care quality were comprehensively investigated. Main results A total of 81,461,554 patients were enrolled in 586 hospitals, and 1,587,724 patients were admitted to the ICU over 3 years. In 2018, there was a significantly higher number of ICU beds (2016 vs. 2018: 10668 vs. 13,661, P = 0.0132) but a lower doctor-to-bed ratio (2016 vs. 2018: 0.64 (0.50, 0.83) vs. 0.60 (0.45, 0.75), P = 0.0016) and nurse-to-bed ratio (2016 vs. 2018: 2.00 (1.64, 2.50) vs. 2.00 (1.50, 2.40), P = 0.031) than in 2016. Continuous and significant improvements in the ventilator-associated pneumonia (VAP) incidence rate, microbiology detection rate before antibiotic use and deep vein thrombosis (DVT) prophylaxis rate were associated with the implementation of the QI program (VAP incidence rate (per 1000 ventilator-days), 2016 vs. 2017 vs. 2018: 11.06 (4.23, 22.70) vs. 10.20 (4.25, 23.94) vs. 8.05 (3.13, 17.37), P = 0.0002; microbiology detection rate before antibiotic use (%), 2016 vs. 2017 vs. 2018: 83.91 (49.75, 97.87) vs. 84.14 (60.46, 97.24) vs. 90.00 (69.62, 100), P < 0.0001; DVT prophylaxis rate, 2016 vs. 2017 vs. 2018: 74.19 (33.47, 96.16) vs. 71.70 (38.05, 96.28) vs. 83.27 (47.36, 97.77), P = 0.0093). Moreover, the 6-h SSC bundle compliance rates in 2018 were significantly higher than those in 2016 (6-h SSC bundle compliance rate, 2016 vs. 2018: 64.93 (33.55, 93.06) vs. 76.19 (46.88, 96.67)). A significant change trend was not found in the ICU mortality rate from 2016 to 2018 (ICU mortality rate (%), 2016 vs. 2017 vs. 2018: 8.49 (4.42, 14.82) vs. 8.95 (4.89, 15.70) vs. 9.05 (5.12, 15.80), P = 0.1075). Conclusions The relationship between medical human resources and ICU overexpansion was mismatched during the past 3 years. The implementation of a national QI program improved ICU performance but did not reduce ICU mortality.

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