Effectiveness of Fludrocortisone Plus Hydrocortisone versus Hydrocortisone Alone in Septic Shock: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Rationale: The use of hydrocortisone in adult patients with septic shock is controversial, and the effectiveness of adding fludrocortisone to hydrocortisone remains uncertain. Objectives: To assess the comparative effectiveness and safety of fludrocortisone plus hydrocortisone, hydrocortisone alone, and placebo or usual care in adults with septic shock. Methods: A systematic review and a Bayesian network meta-analysis of peer-reviewed randomized trials were conducted. The primary outcome was all-cause mortality at last follow-up. Treatment effects are presented as relative risks (RRs) with 95% credible intervals (CrIs). Placebo or usual care was the reference treatment. Measurements and Main Results: Among 7,553 references, we included 17 trials (7,688 patients). All-cause mortality at last follow-up was lowest with fludrocortisone plus hydrocortisone (RR, 0.85; 95% CrI, 0.72-0.99; 98.3% probability of superiority, moderate-certainty evidence), followed by hydrocortisone alone (RR, 0.97; 95% CrI, 0.87-1.07; 73.1% probability of superiority, low-certainty evidence). The comparison of fludrocortisone plus hydrocortisone versus hydrocortisone alone was based primarily on indirect evidence (only two trials with direct evidence). Fludrocortisone plus hydrocortisone was associated with a 12% lower risk of all-cause mortality compared with hydrocortisone alone (RR, 0.88; 95% CrI, 0.74-1.03; 94.2% probability of superiority, moderate-certainty evidence). Conclusions: In adult patients with septic shock, fludrocortisone plus hydrocortisone was associated with lower risk of all-cause mortality at last follow-up than placebo and hydrocortisone alone. The scarcity of head-to-head trials comparing fludrocortisone plus hydrocortisone versus hydrocortisone alone led our network meta-analysis to rely primarily on indirect evidence for this comparison. Although we undertook several sensitivity analyses and assessments, these findings should be considered while also acknowledging the heterogeneity of included trials.

Evaluation of Etomidate Use and Association with Mortality Compared with Ketamine Among Critically Ill Patients.

RATIONALE: Uncertainty remains regarding the risks associated with single dose use of etomidate. OBJECTIVES: To assess use of etomidate in critically ill patients and compare outcomes for patients who received etomidate versus ketamine. METHODS: We assessed patients who received invasive mechanical ventilation (IMV), admitted to an ICU in the Premier Healthcare Database, 2008-2021. The exposure was receipt of etomidate on the day of IMV initiation and the main outcome was hospital mortality. Using multivariable regression we compared patients who received IMV within the first two days of hospitalization who received etomidate with propensity-score matched patients who received ketamine. We also assessed whether receipt of corticosteroids in the days after intubation modified the association between etomidate and mortality. MEASUREMENTS AND MAIN RESULTS: Of 1,689,945 patients who received IMV, nearly half (738,855; 43.7%) received etomidate. Among those who received IMV in the first two days of hospitalization, we established 22,273 matched pairs given either etomidate or ketamine. In the primary analysis, receipt of etomidate was associated with greater hospital mortality relative to ketamine (21.6% vs 18.7%; absolute risk difference: 2.8%, 95% CI 2.1%, 3.6%; adjusted odds ratio: 1.28, 95% CI 1.21,1.34). This was consistent across subgroups and sensitivity analyses. We found no attenuation of the association with mortality with receipt of corticosteroids in the days following etomidate use. CONCLUSIONS: Use of etomidate on the day of IMV initiation is common and associated with a higher odds of hospital mortality compared with ketamine. This finding is independent of subsequent treatment with corticosteroids.

An Update on Management of Adult Patients with Acute Respiratory Distress Syndrome: An Official American Thoracic Society Clinical Practice Guideline.

Background: This document updates previously published Clinical Practice Guidelines for the management of patients with acute respiratory distress syndrome (ARDS), incorporating new evidence addressing the use of corticosteroids, venovenous extracorporeal membrane oxygenation, neuromuscular blocking agents, and positive end-expiratory pressure (PEEP). Methods: We summarized evidence addressing four "PICO questions" (patient, intervention, comparison, and outcome). A multidisciplinary panel with expertise in ARDS used the Grading of Recommendations, Assessment, Development, and Evaluation framework to develop clinical recommendations. Results: We suggest the use of: 1) corticosteroids for patients with ARDS (conditional recommendation, moderate certainty of evidence), 2) venovenous extracorporeal membrane oxygenation in selected patients with severe ARDS (conditional recommendation, low certainty of evidence), 3) neuromuscular blockers in patients with early severe ARDS (conditional recommendation, low certainty of evidence), and 4) higher PEEP without lung recruitment maneuvers as opposed to lower PEEP in patients with moderate to severe ARDS (conditional recommendation, low to moderate certainty), and 5) we recommend against using prolonged lung recruitment maneuvers in patients with moderate to severe ARDS (strong recommendation, moderate certainty). Conclusions: We provide updated evidence-based recommendations for the management of ARDS. Individual patient and illness characteristics should be factored into clinical decision making and implementation of these recommendations while additional evidence is generated from much-needed clinical trials.

Variation in Use of Medications for Opioid Use Disorder in Critically Ill Patients Across the United States.

OBJECTIVES: To describe practice patterns surrounding the use of medications to treat opioid use disorder (MOUD) in critically ill patients. DESIGN: Retrospective, multicenter, observational study using the Premier AI Healthcare Database. SETTING: The study was conducted in U.S. ICUs. PATIENTS: Adult (≥ 18 yr old) patients with a history of opioid use disorder (OUD) admitted to an ICU between 2016 and 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 108,189 ICU patients (658 hospitals) with a history of OUD, 20,508 patients (19.0%) received MOUD. Of patients receiving MOUD, 13,745 (67.0%) received methadone, 2,950 (14.4%) received buprenorphine, and 4,227 (20.6%) received buprenorphine/naloxone. MOUD use occurred in 37.9% of patients who received invasive mechanical ventilation. The median day of MOUD initiation was hospital day 2 (interquartile range [IQR] 1-3) and the median duration of MOUD use was 4 days (IQR 2-8). MOUD use per hospital was highly variable (median 16.0%; IQR 10-24; range, 0-70.0%); admitting hospital explained 8.9% of variation in MOUD use. A primary admitting diagnosis of unintentional poisoning (aOR 0.41; 95% CI, 0.38-0.45), presence of an additional substance use disorder (aOR 0.66; 95% CI, 0.64-0.68), and factors indicating greater severity of illness were associated with reduced odds of receiving MOUD in the ICU. CONCLUSIONS: In a large multicenter, retrospective study, there was large variation in the use of MOUD among ICU patients with a history of OUD. These results inform future studies seeking to optimize the approach to MOUD use during critical illness.

Two Weeks Versus One Week of Maximal Patient-Intensivist Continuity for Adult Medical Intensive Care Patients: A Two-Center Target Trial Emulation.

OBJECTIVES: To compare outcomes for 2 weeks vs. 1 week of maximal patient-intensivist continuity in the ICU. DESIGN: Retrospective cohort study. SETTING: Two U.S. urban, teaching, medical ICUs where intensivists were scheduled for 2-week service blocks: site A was in the Midwest and site B was in the Northeast. PATIENTS: Patients 18 years old or older admitted to a study ICU between March 1, 2017, and February 28, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We applied target trial emulation to compare admission during an intensivist's first week (as a proxy for 2 wk of maximal continuity) vs. admission during their second week (as a proxy for 1 wk of maximal continuity). Outcomes included hospital mortality, ICU length of stay, and, for mechanically ventilated patients, duration of ventilation. Exploratory outcomes included imaging, echocardiogram, and consultation orders. We used inverse probability weighting to adjust for baseline differences and random-effects meta-analysis to calculate overall effect estimates. Among 2571 patients, 1254 were admitted during an intensivist's first week and 1317 were admitted during a second week. At sites A and B, hospital mortality rates were 25.8% and 24.2%, median ICU length of stay were 4 and 2 days, and median mechanical ventilation durations were 3 and 3 days, respectively. There were no differences in adjusted mortality (odds ratio [OR], 1.01 [95% CI, 0.96-1.06]) or ICU length of stay (-0.25 d [-0.82 d to +0.32 d]) for 2 weeks vs. 1 week of maximal continuity. Among mechanically ventilated patients, there were no differences in adjusted mortality (OR, 1.00 [0.87-1.16]), ICU length of stay (+0.06 d [-0.78 d to +0.91 d]), or duration of mechanical ventilation (+0.37 d [-0.46 d to +1.21 d]) for 2 weeks vs. 1 week of maximal continuity. CONCLUSIONS: Two weeks of maximal patient-intensivist continuity was not associated with differences in clinical outcomes compared with 1 week in two medical ICUs.

A novel measure to summarize blood transfusion practice during critical illness.

BACKGROUND: Large-scale observational studies have summarized transfusion practice using traditional measures of central tendency (e.g., the mean hemoglobin concentration at the time of transfusion). However, the mean hemoglobin concentration fails to identify specific hemoglobin concentration thresholds that drive practice. In the following brief report, we propose a novel measure of "practice discontinuity" that identifies specific practice-defining hemoglobin thresholds. STUDY DESIGN AND METHODS: We used the PINC AI Database (2016-2022) to identify adult patients admitted to an intensive care unit with at least one hemoglobin concentration measurement. For each day that hemoglobin was measured, we identified whether the patient received a red blood cell transfusion using hospital charge codes. We defined the "practice discontinuity" measure as the hemoglobin concentration at which there was the largest increase in transfusion use going from a higher to an incrementally lower hemoglobin concentration. We also calculated the mean and median pretransfusion hemoglobin concentrations. RESULTS: We identified 1,298,367 patients and 4,905,839 patient-days for inclusion. RBC transfusion occurred in a total of 530,654 (10.8%) patient-days. The overall pre-transfusion mean and median hemoglobin concentrations were 8.4 and 8.0 g/dL, respectively. The practice discontinuity measure identified 7.0 g/dL as the hemoglobin concentration at which transfusion use increased the most, from 46.6% of patient-days at a concentration of 7.0 g/dL to 74.8% of patient-days at a concentration of 6.9 g/dL. DISCUSSION: We propose that future studies of red blood cell transfusion practice consider inclusion of the practice discontinuity measure to more fully summarize clinical practice.

Discharge Disposition and Loss of Independence Among Survivors of COVID-19 Admitted to Intensive Care: Results From the SCCM Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS).

OBJECTIVES: To describe incidence and risk factors of loss of previous independent living through nonhome discharge or discharge home with health assistance in survivors of intensive care unit (ICU) admission for coronavirus disease 2019 (COVID-19). DESIGN: Multicenter observational study including patients admitted to the ICU from January 2020 till June 30, 2021. HYPOTHESIS: We hypothesized that there is a high risk of nonhome discharge in patients surviving ICU admission due to COVID-19. SETTING: Data were included from 306 hospitals in 28 countries participating in the SCCM Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 registry. PATIENTS: Previously independently living adult ICU survivors of COVID-19. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was nonhome discharge. Secondary outcome was the requirement of health assistance among patients who were discharged home. Out of 10 820 patients, 7101 (66%) were discharged alive; 3791 (53%) of these survivors lost their previous independent living status, out of those 2071 (29%) through nonhome discharge, and 1720 (24%) through discharge home requiring health assistance. In adjusted analyses, loss of independence on discharge among survivors was predicted by patient age ≥ 65 years (adjusted odds ratio [aOR] 2.78, 95% confidence interval [CI] 2.47-3.14, P < .0001), former and current smoking status (aOR 1.25, 95% CI 1.08-1.46, P = .003 and 1.60 (95% CI 1.18-2.16), P = .003, respectively), substance use disorder (aOR 1.52, 95% CI 1.12-2.06, P = .007), requirement for mechanical ventilation (aOR 4.17, 95% CI 3.69-4.71, P < .0001), prone positioning (aOR 1.19, 95% CI 1.03-1.38, P = .02), and requirement for extracorporeal membrane oxygenation (aOR 2.28, 95% CI 1.55-3.34, P < .0001). CONCLUSIONS: More than half of ICU survivors hospitalized for COVID-19 are unable to return to independent living status, thereby imposing a significant secondary strain on health care systems worldwide.

WITHDRAWN: Update in Critical Care 2021.

Ahead of Print article withdrawn by publisher.

National Trends in Timing of Death Among Patients With Septic Shock, 1994-2014.

OBJECTIVES: To assess trends in timing of mortality among patients with septic shock. DESIGN: Retrospective cohort study. SETTING: Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project's National Inpatient Sample, 1994-2014. PATIENTS: Hospitalized adults (≥ 18 yr) with International Classification of Diseases, 9th Edition, Clinical Modification codes consistent with septic shock; secondary analysis: adults with International Classification of Diseases, 9th Edition, Clinical Modification codes consistent with acute respiratory failure receiving invasive mechanical ventilation and patients with both septic shock and acute respiratory failure receiving invasive mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: From 1994 to 2014, 48-hour mortality rates decreased among patients with septic shock (21.2% to 10.8%) and septic shock with acute respiratory failure receiving invasive mechanical ventilation (19.1% to 13.4%) but increased among patients with acute respiratory failure receiving invasive mechanical ventilation (7.9% to 9.8%; p value for all trends, < 0.001). Three-to-14-day mortality decreased among patients with septic shock (22.1% to 15.5%), septic shock with acute respiratory failure receiving invasive mechanical ventilation (28.7% to 22.4%) and acute respiratory failure receiving invasive mechanical ventilation (16.8% to 15.0%; p value for all trends, < 0.001). Mortality after 14 days decreased among all groups (septic shock: 12.6% to 6.7%; septic shock with acute respiratory failure receiving invasive mechanical ventilation: 20.3% to 11.3%; and acute respiratory failure receiving invasive mechanical ventilation: 12.7% to 5.8%; p value for all trends, < 0.001). Cox proportional hazard ratio for declining risk in mortality per year (adjusted for patient and hospital characteristics) was 0.96 (95% CI, 0.96-0.96) for septic shock, 0.97 (0.97-0.97) for acute respiratory failure receiving invasive mechanical ventilation and septic shock, and 0.99 (0.99-0.99) for acute respiratory failure receiving invasive mechanical ventilation. CONCLUSIONS: Septic shock 48-hour, 3-14-day and greater than 14-day mortality declined markedly over two decades; in contrast, patients with acute respiratory failure only experienced marked decreases in greater than 14-day in-hospital mortality rates.

Patient Outcomes After the Introduction of Statewide ICU Nurse Staffing Regulations.

OBJECTIVES: To assess whether Massachusetts legislation directed at ICU nurse staffing was associated with improvements in patient outcomes. DESIGN: Retrospective cohort study; difference-in-difference design to compare outcomes in Massachusetts with outcomes of other states (before and after the March 31, 2016, compliance deadline). SETTING: Administrative claims data collected from medical centers across the United States (Vizient). PATIENTS: Adults between 18 and 99 years old who were admitted to ICUs for greater than or equal to 1 day. INTERVENTIONS: Massachusetts General Law c. 111, § 231, which established 1) maximum patient-to-nurse assignments of 2:1 in the ICU and 2) that this determination should be based on a patient acuity tool and by the staff nurses in the unit. MEASUREMENTS AND MAIN RESULTS: Nurse staffing increased similarly in Massachusetts (n = 11 ICUs, Baseline patient-to-nurse ratio 1.38 ± 0.16 to Post-mandate 1.28 ± 0.15; p = 0.006) and other states (n = 88 ICUs, Baseline 1.35 ± 0.19 to Post-mandate 1.31 ± 0.17; p = 0.002; difference-in-difference p = 0.20). Massachusetts ICU nurse staffing regulations were not associated with changes in hospital mortality within Massachusetts (Baseline n = 29,754, standardized mortality ratio 1.20 ± 0.04 to Post-mandate n = 30,058, 1.15 ± 0.04; p = 0.11) or when compared with changes in hospital mortality in other states (Baseline n = 572,952, 1.15 ± 0.01 to Post-mandate n = 567,608, 1.09 ± 0.01; difference-in-difference p = 0.69). Complications (Massachusetts: Baseline 0.68% to Post-mandate 0.67%; other states: Baseline 0.72% to Post-mandate 0.72%; difference-in-difference p = 0.92) and do-not-resuscitate orders (Massachusetts: Baseline 13.5% to Post-mandate 15.4%; other states: Baseline 12.3% to Post-mandate 14.5%; difference-in-difference p = 0.07) also remained unchanged relative to secular trends. Results were similar in interrupted time series analysis, as well as in subgroups of community hospitals and workload intensive patients receiving mechanical ventilation. CONCLUSIONS: State regulation of patient-to-nurse staffing with the aid of patient complexity scores in intensive care was not associated with either increased nurse staffing or changes in patient outcomes.