Prone Positioning During Extracorporeal Membrane Oxygenation in Patients With Severe ARDS: The PRONECMO Randomized Clinical Trial.

Importance: Prone positioning may improve outcomes in patients with severe acute respiratory distress syndrome (ARDS), but it is unknown whether prone positioning improves clinical outcomes among patients with ARDS who are undergoing venovenous extracorporeal membrane oxygenation (VV-ECMO) compared with supine positioning. Objective: To test whether prone positioning vs supine positioning decreases the time to successful ECMO weaning in patients with severe ARDS supported by VV-ECMO. Design, Setting, and Participants: Randomized clinical trial of patients with severe ARDS undergoing VV-ECMO for less than 48 hours at 14 intensive care units (ICUs) in France between March 3, 2021, and December 7, 2021. Interventions: Patients were randomized 1:1 to prone positioning (at least 4 sessions of 16 hours) (n = 86) or to supine positioning (n = 84). Main Outcomes and Measures: The primary outcome was time to successful ECMO weaning within 60 days following randomization. Secondary outcomes included ECMO and mechanical ventilation-free days, ICU and hospital length of stay, skin pressure injury, serious adverse events, and all-cause mortality at 90-day follow-up. Results: Among 170 randomized patients (median age, 51 [IQR, 43-59] years; n = 60 women [35%]), median respiratory system compliance was 15.0 (IQR, 10.7-20.6) mL/cm H2O; 159 patients (94%) had COVID-19-related ARDS; and 164 (96%) were in prone position before ECMO initiation. Within 60 days of enrollment, 38 of 86 patients (44%) had successful ECMO weaning in the prone ECMO group compared with 37 of 84 (44%) in the supine ECMO group (risk difference, 0.1% [95% CI, -14.9% to 15.2%]; subdistribution hazard ratio, 1.11 [95% CI, 0.71-1.75]; P = .64). Within 90 days, no significant difference was observed in ECMO duration (28 vs 32 days; difference, -4.9 [95% CI, -11.2 to 1.5] days; P = .13), ICU length of stay, or 90-day mortality (51% vs 48%; risk difference, 2.4% [95% CI, -13.9% to 18.6%]; P = .62). No serious adverse events were reported during the prone position procedure. Conclusions and Relevance: Among patients with severe ARDS supported by VV-ECMO, prone positioning compared with supine positioning did not significantly reduce time to successful weaning of ECMO. Trial Registration: ClinicalTrials.gov Identifier: NCT04607551.

Lung morphology impacts the association between ventilatory variables and mortality in patients with acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) patients with different lung morphology have distinct pulmonary mechanical dysfunction and outcomes. Whether lung morphology impacts the association between ventilatory variables and mortality remains unclear. Moreover, the impact of a novel combined ventilator variable [(4×DP) + RR] on morality in ARDS patients needs external validation. METHODS: We obtained data from the Chinese Database in Intensive Care (CDIC), which included adult ARDS patients who received invasive mechanical ventilation for at least 24 h. Patients were further classified into two groups based on lung morphology (focal and non-focal). Ventilatory variables were collected longitudinally within the first four days of ventilation. The primary outcome was 28-day mortality. Extended Cox regression models were employed to explore the interaction between lung morphology and longitudinal ventilatory variables on mortality. FINDINGS: We included 396 ARDS patients with different lung morphology (64.1% non-focal). The overall 28-day mortality was 34.4%. Patients with non-focal lung morphology have more severe and persistent pulmonary mechanical dysfunction and higher mortality than those with focal lung morphology. Time-varying driving pressure (DP) was more significantly associated with 28-day mortality in patients with non-focal lung morphology compared to focal lung morphology patients (P for interaction = 0.0039). The impact of DP on mortality was more significant than that of respiratory rate (RR) only in patients with non-focal lung morphology. The hazard ratio (HR) of mortality for [(4×DP) + RR] was significant in patients with non-focal lung morphology (HR 1.036, 95% CI 1.027-1.045), not in patients with focal lung morphology (HR 1.019, 95% CI 0.999-1.039). INTERPRETATION: The association between ventilator variables and mortality varied among patients with different lung morphology. [(4×DP) + RR] was only associated with mortality in patients with non-focal lung morphology. Further validation is needed.

The relationship between immature granulocyte count and mortality in ARDS Due to COVID-19.

Background: Acute phase reactants and inflammation biomarkers such as ferritin, procalcitonin, C-reactive protein (CRP), and complete blood count parameters (White blood cell, platelet count) are usually used to evaluate and monitor the disease severity and treatment response of systemic inflammatory diseases. In addition to these parameters, Immature granulocytes (IG) that increase during systemic infection, hematological malignancy, and drug treatments (such as chemotherapy and glucocorticoids) are important parameters for evaluating systemic inflammation. The sensitivity and specificity of IG are as high as the abovementioned inflammatory biomarkers for monitoring disease severity and treatment response. Aim: The aim of the study is to evaluate the relationship between IG count and the need for mechanical ventilation and mortality in patients hospitalized in the intensive care unit (ICU) due to coronavirus disease 2019 (COVID-19). Patients and Methods: The medical records of the 401 patients who were followed up in the ICU due to COVID-19-related acute respiratory distress syndrome between October 2020 and February 2021 were retrospectively reviewed. On the day of admission to the ICU complete blood count (CBC), arterial blood gas analysis, coagulation parameters (fibrinogen, D-dimer) are recorded. CRP, procalcitonin, and ferritin levels are also recorded at the day of admission. During the follow-up period, the survival status and mechanical ventilation status of the patients were recorded and the relation between IG count and these parameters was evaluated. Results: The mean IG at the admission was 0.2 ± 0.4 109/L. The IG level of the intubated patients at the time of intubation was 0.3 ± 0.5 109/L. There was a significant positive correlation between mortality and IG levels at admission and at the time of intubation (IG admission; P = 0.001, r = 0.347 and IG at intubation; P = 0.001, r = 0.228). Conclusion: IG levels in CBC data could be a potential practical biomarker. This issue requires further research and the development of therapies targeting IG cells is needed.

Predictors of in-hospital mortality of COVID-19 patients and the role of telemetry in an internal medicine ward during the third phase of the pandemic.

OBJECTIVE: The first pandemic phase of COVID-19 in Italy was characterized by high in-hospital mortality ranging from 23% to 38%. During the third pandemic phase there has been an improvement in the management and treatment of COVID-19, so mortality and predictors may have changed. A prospective study was planned to identify predictors of mortality during the third pandemic phase. PATIENTS AND METHODS: From 15 December 2020 to 15 May 2021, 208 patients were hospitalized (median age: 64 years; males: 58.6%); 83% had a median of 2 (IQR,1-4) comorbidities; pneumonia was present in 89.8%. Patients were monitored remotely for respiratory function and ECG trace for 24 hours/day. Management and treatment were done following the timing and dosage recommended by international guidelines. RESULTS: 79.2% of patients necessitated O2-therapy. ARDS was present in 46.1% of patients and 45.4% received non-invasive ventilation and 11.1% required ICU treatment. 38% developed arrhythmias which were identified early by telemetry and promptly treated. The in-hospital mortality rate was 10%. At multivariate analysis independent predictors of mortality were: older age (R-R for≥70 years: 5.44), number of comorbidities ≥3 (R-R 2.72), eGFR ≤60 ml/min (RR 2.91), high d-Dimer (R-R for≥1,000 ng/ml:7.53), and low PaO2/FiO2 (R-R for <200: 3.21). CONCLUSIONS: Management and treatment adherence to recommendations, use of telemetry, and no overcrowding appear to reduce mortality. Advanced age, number of comorbidities, severe renal failure, high d-Dimer and low P/F remain predictors of poor outcome. The data help to identify current high-risk COVID-19 patients in whom management has yet to be optimized, who require the greatest therapeutic effort, and subjects in whom vaccination is mandatory.

Outcomes of patients with COVID-19 acute respiratory distress syndrome requiring invasive mechanical ventilation admitted to an intensive care unit in South Africa.

BACKGROUND: Up to 32% of patients with COVID-19 pneumonia may require intensive care unit (ICU) admission or mechanical ventilation. Data from low- and middle-income countries on COVID-19 acute respiratory distress syndrome (ARDS) are limited. Groote Schuur Hospital in Cape Town, South Africa, expanded its intensive care service to support patients with COVID-19 ARDS requiring invasive mechanical ventilation (IMV). OBJECTIVES: To report on patients' characteristics and outcomes from the first two pandemic waves. METHODS: All patients with COVID-19 ARDS admitted to the ICU for IMV were included in this prospective cohort study. Data were collected from 5 April 2020 to 5 April 2021. RESULTS: Over the 12-month study period, 461 patients were admitted to the designated COVID-19 ICU. Of these, 380 met the study criteria and 377 had confirmed hospital discharge outcomes. The median (range) age of patients was 51 (17 - 71) years, 50.5% were female, and the median (interquartile range (IQR)) body mass index was 32 (28 - 38) kg/m2. The median (IQR) arterial oxygen partial pressure to fractional inspired oxygen (P/F) ratio was 97 (71 - 128) after IMV was initiated. Comorbidities included diabetes (47.6%), hypertension (46.3%) and HIV infection (10.5%). Of the patients admitted, 30.8% survived to hospital discharge with a median (IQR) ICU length of stay of 19.5 (9 - 36) days. Predictors of mortality after adjusting for confounders were male sex (odds ratio (OR) 1.74), increasing age (OR 1.04) and higher Sequential Organ Failure Assessment (SOFA) score (OR 1.29). CONCLUSIONS: In a resource-limited environment, the provision of IMV support in the ICU achieved 30.8% hospital survival in patients with COVID-19 ARDS. The ability to predict survival remains difficult given this complex disease.

Acute respiratory distress syndrome readmissions: A nationwide cross-sectional analysis of epidemiology and costs of care.

BACKGROUND: Acute Respiratory Distress Syndrome affects approximately 10% of patients admitted to intensive care units internationally, with as many as 40%-52% of patients reporting re-hospitalization within one year. RESEARCH QUESTION/AIM: To describe the epidemiology of patients with acute respiratory distress syndrome who require 30-day readmission, and to describe associated costs. STUDY DESIGN AND METHODS: A cross-sectional analysis of the 2016 Healthcare Cost and Utilization Project's Nationwide Readmission Database, which is a population-based administrative database which includes discharge data from U.S. hospitals. Inclusion criteria: hospital discharge records for adults age > 17 years old, with a diagnosis of ARDS on index admission, with associated procedure codes for endotracheal intubation and/or invasive mechanical ventilation, who were discharged alive. Primary exposure is adult hospitalization for meeting criteria as described. The primary outcome measure is 30-day readmission rate, as well as patient characteristics and time distribution of readmissions. RESULTS: Nationally, 25,170 admissions meeting criteria were identified. Index admission mortality rate was 37.5% (95% confidence interval [CI], 36.2-38.8). 15,730 records of those surviving hospitalization had complete discharge information. 30-day readmission rate was 18.4%, with 14% of total readmissions occurring within 2 calendar days of discharge; these early readmissions had higher mortality risk (odds ratio 1.82, 95% CI 1.05-6.56) compared with readmission in subsequent days. For the closest all-cause readmission within 30 days, the mean cost was $26,971, with a total national cost of over $75.6 million. INTERPRETATION: Thirty-day readmission occurred in 18.4% of patients with acute respiratory distress syndrome in this sample, and early readmission is strongly associated with increased mortality compared to late readmission. Further research is needed to clarify whether the rehospitalizations or associated mortalities are preventable.

Randomized, double-blind, controlled trial of human anti-LIGHT monoclonal antibody in COVID-19 acute respiratory distress syndrome.

BACKGROUNDSevere coronavirus disease 2019 (COVID-19) is associated with a dysregulated immune response, which can result in cytokine-release syndrome and acute respiratory distress syndrome (ARDS). Patients with COVID-19-associated ARDS have elevated free serum levels of the cytokine lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells (LIGHT; also known as TNFSF14). Such patients may benefit from LIGHT-neutralization therapy.METHODSThis randomized, double-blind, multicenter, proof-of-concept trial enrolled adults hospitalized with COVID-19-associated pneumonia and mild to moderate ARDS. Patients received standard of care plus a single dose of a human LIGHT-neutralizing antibody (CERC-002) or placebo. The primary endpoint was the proportion of patients receiving CERC-002 who remained alive and free of respiratory failure through day 28. Safety was assessed via adverse event monitoring.RESULTSFor most of the 83 enrolled patients, standard of care included systemic corticosteroids (88.0%) or remdesivir (57.8%). A higher proportion of patients remained alive and free of respiratory failure through day 28 after receiving CERC-002 (83.9%) versus placebo (64.5%; P = 0.044), including in patients 60 years of age or older (76.5% vs. 47.1%, respectively; P = 0.042). Mortality rates were 7.7% (CERC-002) and 14.3% (placebo) on day 28 and 10.8% and 22.5%, respectively, on day 60. Treatment-emergent adverse events were less frequent with CERC-002 than placebo.CONCLUSIONFor patients with COVID-19-associated ARDS, adding CERC-002 to standard-of-care treatment reduces LIGHT levels and might reduce the risk of respiratory failure and death.TRIAL REGISTRATIONClinicalTrials.gov NCT04412057.FUNDINGAvalo Therapeutics.

Mortality Rates of Severe Dengue Viral Infection Before and After Implementation of a Revised Guideline for Severe Dengue.

OBJECTIVES: To compare the mortality rate of severe dengue (SD) before and after implementation of a revised SD guideline. METHODS: Medical records of SD patients <15 years of age hospitalized during 1998-2020 were reviewed. The revised SD guidelines were implemented in 2016, including intensive monitoring of vital signs and intra-abdominal pressure, the release of intra-abdominal pressure in cases of abdominal compartment syndrome (ACS) and the use of N-acetyl cysteine in cases of acute liver failure. RESULTS: On initial admission, organ failure including severe bleeding, acute respiratory failure, acute kidney injury and acute liver failure was not significantly different between 78 and 23 patients treated in the pre- and postrevised guideline periods, respectively. After hospitalization, the proportions of patients who developed profound shock (68.8% vs. 41.2%), multiorgan failures (60.4% vs. 73.3%), ACS (37.2% vs. 26.1%) and fatal outcome (33.3% vs. 13.0%) were also not significantly different between the pre- and postrevised guideline periods, respectively. In subgroup analysis, the mortality rates in patients with multiorgan failure (44.1% vs. 15.8%), acute respiratory failure and active bleeding (78.1% vs. 37.5%) and ACS (82.8% vs. 33.3%), respectively, were significantly higher in the pre- than the postrevised guideline periods. The durations of time before the liver function tests returned to normal levels, and the mortality rates in acute liver failure patients treated with and without N-acetyl cysteine were not significantly different. CONCLUSIONS: Although following the revised guidelines could not prevent organ failure, the mortality rates in patients with multiorgan failure and/or ACS decreased significantly when following the revised guidelines.

High-Flow Nasal Oxygen for Severe Hypoxemia: Oxygenation Response and Outcome in Patients with COVID-19.

Rationale: The "Berlin definition" of acute respiratory distress syndrome (ARDS) does not allow inclusion of patients receiving high-flow nasal oxygen (HFNO). However, several articles have proposed that criteria for defining ARDS should be broadened to allow inclusion of patients receiving HFNO. Objectives: To compare the proportion of patients fulfilling ARDS criteria during HFNO and soon after intubation, and 28-day mortality between patients treated exclusively with HFNO and patients transitioned from HFNO to invasive mechanical ventilation (IMV). Methods: From previously published studies, we analyzed patients with coronavirus disease (COVID-19) who had PaO2/FiO2 of ⩽300 while treated with ⩾40 L/min HFNO, or noninvasive ventilation (NIV) with positive end-expiratory pressure of ⩾5 cm H2O (comparator). In patients transitioned from HFNO/NIV to invasive mechanical ventilation (IMV), we compared ARDS severity during HFNO/NIV and soon after IMV. We compared 28-day mortality in patients treated exclusively with HFNO/NIV versus patients transitioned to IMV. Measurements and Main Results: We analyzed 184 and 131 patients receiving HFNO or NIV, respectively. A total of 112 HFNO and 69 NIV patients transitioned to IMV. Of those, 104 (92.9%) patients on HFNO and 66 (95.7%) on NIV continued to have PaO2/FiO2 ⩽300 under IMV. Twenty-eight-day mortality in patients who remained on HFNO was 4.2% (3/72), whereas in patients transitioned from HFNO to IMV, it was 28.6% (32/112) (P < 0.001). Twenty-eight-day mortality in patients who remained on NIV was 1.6% (1/62), whereas in patients who transitioned from NIV to IMV, it was 44.9% (31/69) (P < 0.001). Overall mortality was 19.0% (35/184) and 24.4% (32/131) for HFNO and NIV, respectively (P = 0.2479). Conclusions: Broadening the ARDS definition to include patients on HFNO with PaO2/FiO2 ⩽300 may identify patients at earlier stages of disease but with lower mortality.

Comparative outcomes between COVID-19 and influenza patients placed on veno-venous extracorporeal membrane oxygenation for severe ARDS.

BACKGROUND: ECMO is an established supportive adjunct for patients with severe, refractory ARDS from viral pneumonia. However, the exact role and timing of ECMO for COVID-19 patients remains unclear. METHODS: We conducted a retrospective comparison of the first 32 patients with COVID-19-associated ARDS to the last 28 patients with influenza-associated ARDS placed on V-V ECMO. We compared patient factors between the two cohorts and used survival analysis to compare the hazard of mortality over sixty days post-cannulation. RESULTS: COVID-19 patients were older (mean 47.8 vs. 41.2 years, p = 0.033), had more ventilator days before cannulation (mean 4.5 vs. 1.5 days, p < 0.001). Crude in-hospital mortality was significantly higher in the COVID-19 cohort at 65.6% (n = 21/32) versus 36.3% (n = 11/28, p = 0.041). The adjusted hazard ratio over sixty days for COVID-19 patients was 2.81 (95% CI 1.07, 7.35) after adjusting for age, race, ECMO-associated organ failure, and Charlson Comorbidity Index. CONCLUSION: ECMO has a role in severe ARDS associated with COVID-19 but providers should carefully weigh patient factors when utilizing this scarce resource in favor of influenza pneumonia.

Red Cell Distribution Width at Admission Predicts the Frequency of Acute Kidney Injury and 28-Day Mortality in Patients With Acute Respiratory Distress Syndrome.

OBJECTIVES: To determine the association of red cell distribution width (RDW) at admission with frequency of acute kidney injury (AKI) and 28-day mortality in acute respiratory distress syndrome (ARDS) patients. METHODS: Two hundred fifty-eight ARDS patients were investigated in retrospective and prospective studies. The primary outcome was frequency of AKI. The secondary outcome was 28-day mortality. RESULTS: The retrospective study included 193 ARDS patients, of which 67 (34.7%) were confirmed AKI and 76 (39.4%) died within 28 days. The RDW level in the AKI group was significantly higher than in the non-AKI group ([15.15 ±â€Š2.59]% vs. [13.95 ±â€Š1.89]%). Increased RDW was a significant predictor of frequency of AKI (odds ratio: 1.247, 95% confidence interval [CI]: 1.044, 1.489). The area under the receiver operating characteristic curve of RDW for predicting AKI was 0.687 (95%CI: 0.610, 0.764) and the cut-off value was 14.45 (sensitivity, 56.7%; specificity, 72.8%). In addition, the proportion of patients with RDW ≥ 14.45% in the non-survival group was notably higher compared with the survival group (48.7% vs. 29.1%). Furthermore, cox regression analysis revealed that RDW ≥ 14.45% was associated with 28-day mortality (hazard ratio: 1.817, 95%CI: 1.046, 3.158), while Kaplan-Meier analysis showed patients with RDW ≥ 14.45% had a significantly lower survival rate than those with RDW < 14.45%. The prospective study, on the other hand, included 65 ARDS patients, with frequency of AKI and 28-day mortality in the RDW ≥ 14.45% group significantly higher than in RDW < 14.45%. CONCLUSION: RDW was a significant, independent predictor for frequency of AKI and 28-day mortality in ARDS patients.

Use of Airway Pressure Release Ventilation in Patients With Acute Respiratory Failure Due to COVID-19: Results of a Single-Center Randomized Controlled Trial.

OBJECTIVES: Airway pressure release ventilation is a ventilatory mode characterized by a mandatory inverse inspiratory:expiratory ratio with a very short expiratory phase, aimed to avoid derecruitment and allow spontaneous breathing. Recent basic and clinical evidence suggests that this mode could be associated with improved outcomes in patients with acute respiratory distress syndrome. The aim of this study was to compare the outcomes between airway pressure release ventilation and traditional ventilation targeting low tidal volume, in patients with severe coronavirus disease 2019. DESIGN: Single-center randomized controlled trial. SETTING: ICU of a Mexican referral center dedicated to care of patients with confirmed diagnosis of coronavirus disease 2019. PATIENTS: Ninety adult intubated patients with acute respiratory distress syndrome associated with severe coronavirus disease 2019. INTERVENTIONS: Within 48 hours after intubation, patients were randomized to either receive ventilatory management with airway pressure release ventilation or continue low tidal volume ventilation. MEASUREMENTS AND MAIN RESULTS: Forty-five patients in airway pressure release ventilation group and 45 in the low tidal volume group were included. Ventilator-free days were 3.7 (0-15) and 5.2 (0-19) in the airway pressure release ventilation and low tidal volume groups, respectively (p = 0.28). During the first 7 days, patients in airway pressure release ventilation had a higher Pao2/Fio2 (mean difference, 26 [95%CI, 13-38]; p < 0.001) and static compliance (mean difference, 3.7 mL/cm H2O [95% CI, 0.2-7.2]; p = 0.03), higher mean airway pressure (mean difference, 3.1 cm H2O [95% CI, 2.1-4.1]; p < 0.001), and higher tidal volume (mean difference, 0.76 mL/kg/predicted body weight [95% CI, 0.5-1.0]; p < 0.001). More patients in airway pressure release ventilation had transient severe hypercapnia, defined as an elevation of Pco2 at greater than or equal to 55 along with a pH less than 7.15 (42% vs 15%; p = 0.009); other outcomes were similar. Overall mortality was 69%, with no difference between the groups (78% in airway pressure release ventilation vs 60% in low tidal volume; p = 0.07). CONCLUSIONS: In conclusion, when compared with low tidal volume, airway pressure release ventilation was not associated with more ventilator-free days or improvement in other relevant outcomes in patients with severe coronavirus disease 2019.

Autopsy-Based Pulmonary and Vascular Pathology: Pulmonary Endotheliitis and Multi-Organ Involvement in COVID-19 Associated Deaths.

BACKGROUND: Findings from autopsies have provided evidence on systemic microvascular damage as one of the underlying mechanisms of Coronavirus disease 2019 (CO-VID-19). The aim of this study was to correlate autopsy-based cause of death in SARS-CoV-2, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients with chest imaging and severity grade of pulmonary and systemic morphological vascular pathology. METHODS: Fifteen SARS-CoV-2 positive autopsies with clinically distinct presentations (age 22-89 years) were retrospectively analyzed with focus on vascular, thromboembolic, and ischemic changes in pulmonary and in extrapulmonary sites. Eight patients died due to COVID-19 associated respiratory failure with diffuse alveolar damage in various stages and/or multi-organ failure, whereas other reasons such as cardiac decompensation, complication of malignant tumors, or septic shock were the cause of death in 7 further patients. The severity of gross and histopathological changes was semi-quantitatively scored as 0 (absent), 1 (mild), and 3 (severe). Severity scores between the 2 groups were correlated with selected clinical parameters, initial chest imaging, autopsy-based cause of death, and compared using Pearson χ2 and Mann-Whitney U tests. RESULTS: Severe pulmonary endotheliitis (p = 0.031, p = 0.029) and multi-organ involvement (p = 0.026, p = 0.006) correlated significantly with COVID-19 associated death. Pulmonary microthrombi showed limited statistical correlation, while tissue necrosis, gross pulmonary embolism, and bacterial superinfection did not differentiate the 2 study groups. Chest imaging at hospital admission did not differ either. CONCLUSIONS: Extensive pulmonary endotheliitis and multi-organ involvement are characteristic autopsy features in fatal CO-VID-19 associated deaths. Thromboembolic and ischemic events and bacterial superinfections occur frequently in SARS-CoV-2 infection independently of outcome.

Impact of Clinical Sepsis Phenotypes on Mortality and Fluid Status in Critically Ill Patients.

BACKGROUND: Sepsis is associated with high rates of in-hospital mortality, despite being the focus of medical research and public health initiatives for several years. The primary objective of this study was to determine the influence of septic phenotypes on rates of in-hospital mortality throughout intensive care unit (ICU) admission. PATIENTS AND METHODS: Retrospective, single-center cohort study. Medical ICU of an academic medical center. Medical ICU patients admitted between January 2016 and August 2019 with a "sepsis alert" were screened for admitting diagnosis of "sepsis" or "septic shock." Patients were classified into one of four clinical sepsis phenotypes: multi-organ failure (MOF), respiratory dysfunction (RD), neurologic dysfunction (ND), or other patients (OP). RESULTS: An analysis of 320 patients was completed. In-hospital mortality was different between groups (P < 0.001). Patients with the MOF phenotype had the highest rate of mortality (48.4%), followed by the ND phenotype (39.7%), RD phenotype (20.8%), and OP phenotype (13.7%). There were differences in volume balances between phenotypes at 48 h (P = 0.001), 72 h (P < 0.001), and 96 h (P < 0.001) after hospital presentation, with the MOF and ND phenotypes having the largest volume balances at these time points. Ventilator-free days (P < 0.001) and ICU length of stay (LOS) (P = 0.030) were different between groups. There was no difference in hospital LOS (P = 0.479). CONCLUSIONS: This data supports the presence of marked intra-disease differences in septic patient presentation and correlation with clinical outcomes including mortality. Additionally, significantly more positive fluid balances were observed between survivors and non-survivors in some patient subsets. Using pragmatic clinical variables readily available to providers to classify patients into septic phenotypes has the propensity to guide treatment strategies in the future.

Neuromuscular Blocker Use in Critically Ill Children: Assessing Mortality Risk by Propensity Score-Weighted Analysis.

OBJECTIVES: We aim to describe the use of continuous infusion of neuromuscular blocking agents in mechanically ventilated critically ill children and to test its association with in-hospital mortality. DESIGN: Multicenter, registry-based, observational, two-cohort-comparison retrospective study using prospectively collected data from a web-based national registry. SETTING: Seventeen PICUs in Italy. PATIENTS: We included children less than 18 years who received mechanical ventilation and a neuromuscular blocking agent infusion from January 2010 to October 2017. A propensity score-weighted Cox regression analysis was used to assess the relationship between the use of neuromuscular blocking agents and in-hospital mortality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 23,227 patients admitted to the PICUs during the study period, 3,823 patients were included. Patients who received a continuous infusion of neuromuscular blocking agent were more likely to be younger (p < 0.001), ex-premature (p < 0.001), and presenting with less chronic respiratory insufficiency requiring home mechanical ventilation (p < 0.001). Reasons for mechanical ventilation significantly differed between patients who received a continuous infusion of neuromuscular blocking agent and patients who did not receive a continuous infusion of neuromuscular blocking agent, with a higher frequency of respiratory and cardiac diagnosis among patients who received neuromuscular blocking agents compared with other diagnoses (all p < 0.001). The covariates were well balanced in the propensity-weighted cohort. The mortality rate significantly differed among the two cohorts (patients who received a continuous infusion of neuromuscular blocking agent 21% vs patients who did not receive a continuous infusion of neuromuscular blocking agent 11%; p < 0.001 by weighted logistic regression). Patients who received a continuous infusion of neuromuscular blocking agent experienced longer mechanical ventilation and PICU stay (both p < 0.001 by weighted logistic regression). A weighted Cox regression analysis found the use of neuromuscular blocking agents to be a significant predictor of in-hospital mortality both in the unadjusted analysis (hazard ratio, 1.7; 95% CI, 1.3-2.2) and in the adjusted one (hazard ratio, 1.6; 95% CI, 1.2-2.1). CONCLUSIONS: Thirteen percent of mechanically ventilated children in PICUs received neuromuscular blocking agents. When adjusting for selection bias with a propensity score approach, the use of neuromuscular blocking agent was found to be a significant predictor of in-hospital mortality.

Maintenance of low driving pressure in patients with early acute respiratory distress syndrome significantly affects outcomes.

BACKGROUND: Driving pressure (∆P) is an important factor that predicts mortality in acute respiratory distress syndrome (ARDS). We test the hypothesis that serial changes in daily ΔP rather than Day 1 ΔP would better predict outcomes of patients with ARDS. METHODS: This retrospective cohort study enrolled patients admitted to five intensive care units (ICUs) at a medical center in Taiwan between March 2009 and January 2018 who met the criteria for ARDS and received the lung-protective ventilation strategy. ∆P was recorded daily for 3 consecutive days after the diagnosis of ARDS, and its correlation with 60-day survival was analyzed. RESULTS: A total of 224 patients were enrolled in the final analysis. The overall ICU and 60-day survival rates were 52.7% and 47.3%, respectively. ∆P on Days 1, 2, and 3 was significantly lower in the survival group than in the nonsurvival group (13.8 ± 3.4 vs. 14.8 ± 3.7, p = 0.0322, 14 ± 3.2 vs. 15 ± 3.5, p = 0.0194, 13.6 ± 3.2 vs. 15.1 ± 3.4, p = 0.0014, respectively). The patients were divided into four groups according to the daily changes in ∆P, namely, the low ∆P group (Day 1 ∆P < 14 cmH2O and Day 3 ∆P < 14 cmH2O), decrement group (Day 1 ∆P ≥ 14 cmH2O and Day 3 ∆P < 14 cmH2O), high ∆P group (Day 1 ∆P ≥ 14 cmH2O and Day 3 ∆P ≥ 14 cmH2O), and increment group (Day 1 ∆P < 14 cmH2O and Day 3 ∆P ≥ 14 cmH2O). The 60-day survival significantly differed among the four groups (log-rank test, p = 0.0271). Compared with the low ΔP group, patients in the decrement group did not have lower 60-day survival (adjusted hazard ratio 0.72; 95% confidence interval [CI] 0.31-1.68; p = 0.4448), while patients in the increment group had significantly lower 60-day survival (adjusted hazard ratio 1.96; 95% CI 1.11-3.44; p = 0.0198). CONCLUSIONS: Daily ∆P remains an important predicting factor for survival in patients with ARDS. Serial changes in daily ΔP might be more informative than a single Day 1 ΔP value in predicting survival of patients with ARDS.