Forecasting disease trajectories in critical illness: comparison of probabilistic dynamic systems to static models to predict patient status in the intensive care unit.

OBJECTIVE: Conventional prediction models fail to integrate the constantly evolving nature of critical illness. Alternative modelling approaches to study dynamic changes in critical illness progression are needed. We compare static risk prediction models to dynamic probabilistic models in early critical illness. DESIGN: We developed models to simulate disease trajectories of critically ill COVID-19 patients across different disease states. Eighty per cent of cases were randomly assigned to a training and 20% of the cases were used as a validation cohort. Conventional risk prediction models were developed to analyse different disease states for critically ill patients for the first 7 days of intensive care unit (ICU) stay. Daily disease state transitions were modelled using a series of multivariable, multinomial logistic regression models. A probabilistic dynamic systems modelling approach was used to predict disease trajectory over the first 7 days of an ICU admission. Forecast accuracy was assessed and simulated patient clinical trajectories were developed through our algorithm. SETTING AND PARTICIPANTS: We retrospectively studied patients admitted to a Cleveland Clinic Healthcare System in Ohio, for the treatment of COVID-19 from March 2020 to December 2022. RESULTS: 5241 patients were included in the analysis. For ICU days 2-7, the static (conventional) modelling approach, the accuracy of the models steadily decreased as a function of time, with area under the curve (AUC) for each health state below 0.8. But the dynamic forecasting approach improved its ability to predict as a function of time. AUC for the dynamic forecasting approach were all above 0.90 for ICU days 4-7 for all states. CONCLUSION: We demonstrated that modelling critical care outcomes as a dynamic system improved the forecasting accuracy of the disease state. Our model accurately identified different disease conditions and trajectories, with a <10% misclassification rate over the first week of critical illness.

Sotatercept for Pulmonary Arterial Hypertension in the Inpatient Setting.

Patients with pulmonary arterial hypertension (PAH) who are admitted to the hospital pose a challenge to the multidisciplinary healthcare team due to the complexity of the pathophysiology of their disease state and PAH-specific medication considerations. Pulmonary arterial hypertension is a progressive disease that may lead to death as a result of right ventricular (RV) failure. During acute on chronic RV failure it is critical to decrease the pulmonary vascular resistance with the goal of improving RV function and prognosis; therefore, aggressive PAH-treatment based on disease risk stratification is essential. Pulmonary arterial hypertension treatment for acute on chronic RV failure can be impacted by end-organ damage, hemodynamic instability, drug interactions, and PAH medications dosage and delivery. Sotatercept, a first in class activin signaling inhibitor that works on the bone morphogenetic protein/activin pathway is on track for Food and Drug Administration approval for the treatment of PAH based on results of recent trials in where the medication led to clinical and hemodynamic improvements, even when added to traditional PAH-specific therapies. The purpose of this review is to highlight important considerations when starting or continuing sotatercept in patients admitted to the hospital with PAH.

Impact of Sedation Practices on Mortality in COVID-19-Associated Adult Respiratory Distress Syndrome Patients: A Multicenter Retrospective Descriptive Study.

Background: Reduction in sedation exposure is an important metric in intensive care unit (ICU) patients. However, challenges arose during the coronavirus disease-2019 (COVID-19) pandemic in adhering to this practice, driven by concerns on transmission and disease severity issues. Accordingly, diverse sedation approaches emerged, although the effect on mortality has not been studied thoroughly. Methods: Retrospective cohort study in the medical ICU of seven hospitals within a major Health System in Northeast Ohio. We included all adult patients admitted with COVID-19 requiring invasive mechanical ventilation (IMV) from March 2020 to December 2021. Results: Study included 2394 COVID-19 patients requiring IMV. Across waves, sample included 55-63% male subjects, with an average age of 61-68 years (P < 0.001), Acute Physiologic and Chronic Health Evaluation (APACHE)-III score 65.8-68.9 (P = 0.37), median IMV duration 8-10 days (P = 0.14), and median ICU duration 9.8-11.6 days (P = 0.084). Propofol remained the primary sedative (84-92%; P = 0.089). Ketamine use increased from the first (9.7%) to fourth (19%) wave (P = 0.002). Midazolam use decreased from the first (27.4%) to third (9.4%) wave (P = 0.001). Dexmedetomidine use declined from 35% to 27-28% (P = 0.002) after the first wave. A multivariable regression analysis indicated clinical variables explained 34% of the variation in hospital mortality (R2). Factors associated with higher mortality included age [aOR = 1.059 (95% CI 1.049-1.069); P < 0.001], COVID-19 wave, especially fourth wave [aOR = 2.147, (95% CI 1.370-3.365); P = 0.001], and higher number of vasopressors [aOR = 31.636, (95% CI 17.603-56.856); P < 0.001]. Addition of sedative medications to a second model led to an increase in the R2 by only 1.6% to 35.6% [aOR = 1 (95% CI 1-1); P > 0.05] for propofol, ketamine, and midazolam. Dexmedetomidine demonstrated a decrease in the odds of mortality [aOR = 0.96 (95% CI 0.94-0.97); P < 0.001]. Conclusion: Mortality in critical COVID-19 patients was mostly driven by illness severity, and the choice of sedation might have minimal impact when other factors are controlled.

Antipsychotic Use for ICU Delirium and Associated Inflammatory Markers.

Purpose: We sought to evaluate critically ill patients with delirium to evaluate inflammatory cytokine production and delirium progression and the role of antipsychotics. Materials and Methods: Adult critically ill patients with confirmed delirium according to a positive CAM-ICU score were included and IL-6 and IL-8 levels were trended for 24 h in this single-center, prospective, observational cohort study. Results: A total of 23 patients were consented and had blood samples drawn for inclusion. There was no difference in IL-6 and IL-8 levels at baseline, 4 to 8 h, and 22 to 28 h after enrollment when comparing patients based on antipsychotic exposure. We identified 2 patient clusters based on age, APACHE III, need for mechanical ventilation, and concomitant infection. In cluster 1, 5 (33.3%) patients received antipsychotics versus 5 (62.5%) patients in cluster 2 (P = .18). Patients in cluster 1 had more co-inflammatory conditions (P < .0001), yet numerically lower baseline IL-6 (P = .18) and IL-8 levels (P = .80) compared to cluster 2. Patients in cluster 1 had a greater median number of delirium-free days compared to cluster 2 (17.0 vs 6.0 days; P = .05). Conclusions: In critically ill patients with delirium, IL-6 and IL-8 levels were variable and antipsychotics were not associated with improvements in delirium or inflammatory markers.

Evaluation of Dolutegravir- and Bictegravir-Based Antiretroviral Regimen Utilization in Patients who Cannot Take Medications by Mouth.

A retrospective review of patients unable to take medications by mouth showed short interruptions of therapy for most patients. In a secondary analysis, our data showed maintenance and/or achievement of viral suppression for most patients. A retrospective review of intensive care patients unable to take antiretrovirals by mouth showed 56.6% of patients experiencing a transient interruption in therapy. Additionally, our case series further supports previous literature on crushing dolutegravir and bictegravir regimens to maintain and achieve viral suppression.

Inhaled Prostacyclins for Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis.

Studies evaluating inhaled prostacyclins for the management of acute respiratory distress syndrome (ARDS) have produced inconsistent results regarding their effect on oxygenation. The purpose of this systematic review and meta-analysis was to evaluate the change in the Pao2/Fio2 ratio after administration of an inhaled prostacyclin in patients with ARDS. DATA SOURCES: We searched Ovid Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane, Scopus, and Web of Science. STUDY SELECTION: We included abstracts and trials evaluating administration of inhaled prostacyclins in patients with ARDS. DATA EXTRACTION: Change in the Pao2/Fio2 ratio, Pao2, and mean pulmonary artery pressure (mPAP) were extracted from included studies. Evidence certainty and risk of bias were evaluated using Grading of Recommendations Assessment, Development, and Evaluation and the Cochrane Risk of Bias tool. DATA SYNTHESIS: We included 23 studies (1,658 patients) from 6,339 abstracts identified by our search strategy. The use of inhaled prostacyclins improved oxygenation by increasing the Pao2/Fio2 ratio from baseline (mean difference [MD], 40.35; 95% CI, 26.14-54.56; p < 0.00001; I2 = 95%; very low quality evidence). Of the eight studies to evaluate change in Pao2, inhaled prostacyclins also increased Pao2 from baseline (MD, 12.68; 95% CI, 2.89-22.48 mm Hg; p = 0.01; I2 = 96%; very low quality evidence). Only three studies evaluated change in mPAP, but inhaled prostacyclins were found to improve mPAP from baseline (MD, -3.67; 95% CI, -5.04 to -2.31 mm Hg; p < 0.00001; I2 = 68%; very low quality evidence). CONCLUSIONS: In patients with ARDS, use of inhaled prostacyclins improves oxygenation and reduces pulmonary artery pressures. Overall data are limited and there was high risk of bias and heterogeneity among included studies. Future studies evaluating inhaled prostacyclins for ARDS should evaluate their role in ARDS subphenotypes, including cardiopulmonary ARDS.

Potential Impact of Subphenotyping in Pharmacologic Management of Acute Respiratory Distress Syndrome.

Background: Acute respiratory distress syndrome (ARDS) is an acute inflammatory process in the lungs associated with high morbidity and mortality. Previous research has studied both nonpharmacologic and pharmacologic interventions aimed at targeting this inflammatory process and improving ventilation. Hypothesis: To date, only nonpharmacologic interventions including lung protective ventilation, prone positioning, and high positive end-expiratory pressure ventilation strategies have resulted in significant improvements in patient outcomes. Given the high mortality associated with ARDS despite these advancements, interest in subphenotyping has grown, aiming to improve diagnosis and develop personalized treatment approaches. Data Collection: Previous trials evaluating pharmacologic therapies in heterogeneous populations have primarily demonstrated no positive effect, but hope to show benefit when targeting specific subphenotypes, thus increasing their efficacy, while simultaneously decreasing adverse effects. Results: Although most studies evaluating pharmacologic therapies for ARDS have not demonstrated a mortality benefit, there is limited data evaluating pharmacologic therapies in ARDS subphenotypes, which have found promising results. Neuromuscular blocking agents, corticosteroids, and simvastatin have resulted in a mortality benefit when used in patients with the hyper-inflammatory ARDS subphenotype. Therapeutic Opinion: The use of subphenotyping could revolutionize the way ARDS therapies are applied and therefore improve outcomes while also limiting the adverse effects associated with their ineffective use. Future studies should evaluate ARDS subphenotypes and their response to pharmacologic intervention to advance this area of precision medicine.

Evaluation of anticoagulation with bivalirudin for heparin-induced thrombocytopenia during extracorporeal membrane oxygenation.

INTRODUCTION: Unfractionated heparin is the most commonly utilized anticoagulant in extracorporeal membrane oxygenation (ECMO) due to clinician familiarity, ease of reversal, and low cost compared to alternative agents. However, heparin's anticoagulant effect can be unpredictable and its use accompanies a risk of heparin induced thrombocytopenia (HIT). Successful use of bivalirudin as an alternative to heparin in non-HIT ECMO patients has previously been described. However, there is a paucity of data regarding its utilization in patients with confirmed HIT on ECMO. METHODS: This single-center retrospective chart review at Cleveland Clinic Main Campus included 12 ECMO patients who were managed with bivalirudin for a new diagnosis of HIT. Descriptive statistical analyses were performed utilizing median with interquartile range and number with percent as appropriate. RESULTS: Of the 12 patients included, median ECMO duration was 328.5 (218.8-502.1) h and venoarterial ECMO was the most common configuration. No patients experienced the primary outcome of in-circuit thrombosis while on bivalirudin. One patient developed a deep vein thrombosis 22.5 h after switching from heparin to bivalirudin. Major bleeding occurred during bivalirudin therapy in 8 (66.7%) patients. CONCLUSIONS: Overall, our study results suggest that bivalirudin is effective for the management of HIT and did not show evidence of in-circuit thrombosis. A high incidence of major bleeding was observed with bivalirudin use within this study. Clinicians should view bivalirudin as an acceptable agent for the treatment of HIT in the ECMO population, but must consider bleeding risk given the lack of effective reversal agents.

Delirium prediction in the ICU: designing a screening tool for preventive interventions.

Introduction: Delirium occurrence is common and preventive strategies are resource intensive. Screening tools can prioritize patients at risk. Using machine learning, we can capture time and treatment effects that pose a challenge to delirium prediction. We aim to develop a delirium prediction model that can be used as a screening tool. Methods: From the eICU Collaborative Research Database (eICU-CRD) and the Medical Information Mart for Intensive Care version III (MIMIC-III) database, patients with one or more Confusion Assessment Method-Intensive Care Unit (CAM-ICU) values and intensive care unit (ICU) length of stay greater than 24 h were included in our study. We validated our model using 21 quantitative clinical parameters and assessed performance across a range of observation and prediction windows, using different thresholds and applied interpretation techniques. We evaluate our models based on stratified repeated cross-validation using 3 algorithms, namely Logistic Regression, Random Forest, and Bidirectional Long Short-Term Memory (BiLSTM). BiLSTM represents an evolution from recurrent neural network-based Long Short-Term Memory, and with a backward input, preserves information from both past and future. Model performance is measured using Area Under Receiver Operating Characteristic, Area Under Precision Recall Curve, Recall, Precision (Positive Predictive Value), and Negative Predictive Value metrics. Results: We evaluated our results on 16 546 patients (47% female) and 6294 patients (44% female) from eICU-CRD and MIMIC-III databases, respectively. Performance was best in BiLSTM models where, precision and recall changed from 37.52% (95% confidence interval [CI], 36.00%-39.05%) to 17.45 (95% CI, 15.83%-19.08%) and 86.1% (95% CI, 82.49%-89.71%) to 75.58% (95% CI, 68.33%-82.83%), respectively as prediction window increased from 12 to 96 h. After optimizing for higher recall, precision and recall changed from 26.96% (95% CI, 24.99%-28.94%) to 11.34% (95% CI, 10.71%-11.98%) and 93.73% (95% CI, 93.1%-94.37%) to 92.57% (95% CI, 88.19%-96.95%), respectively. Comparable results were obtained in the MIMIC-III cohort. Conclusions: Our model performed comparably to contemporary models using fewer variables. Using techniques like sliding windows, modification of threshold to augment recall and feature ranking for interpretability, we addressed shortcomings of current models.

Retrospective evaluation of a delirium order set utilizing nonpharmacologic and pharmacologic interventions for the treatment of delirium in medical intensive care unit patients.

PURPOSE: To describe the use of a medical intensive care unit (MICU) delirium order set pilot and its associated impact on utilization of nonpharmacologic and pharmacologic interventions, pharmacologic continuation at transitions of care, and resolution of ICU delirium. METHODS: This was a retrospective cohort analysis of MICU patients who received delirium management using an order set pilot compared to standard care. Patients 18 years of age or older admitted to the MICU between May 2019 and January 2020 who received an antipsychotic or valproic acid for the treatment of delirium were included. RESULTS: Pharmacologic treatment continuation past ICU discharge occurred in 30% of patients in the pilot cohort (n = 50) compared to 54% of patients receiving standard care (n = 50; P = 0.027). On treatment days 1 through 7, utilization of deliriogenic medications was significantly lower in the pilot cohort (78% vs 96%, P = 0.007). No differences were observed between the groups in delirium resolution, delirium recurrence, hospital and ICU length of stay, or mortality. CONCLUSION: A MICU order set prioritizing nonpharmacologic management and limiting the duration of pharmacologic agents for delirium may aid providers in the management of ICU delirium and reduce exposure to pharmacologic interventions.

A Review of Pulmonary Arterial Hypertension Treatment in Extracorporeal Membrane Oxygenation: A Case Series of Adult Patients.

BACKGROUND: Little data is published describing the use of medications prescribed for pulmonary arterial hypertension (PAH) in patients receiving extracorporeal membrane oxygenation (ECMO). Even though many patients with PAH may require ECMO as a bridge to transplant or recovery, little is reported regarding the use of PAH medications in this setting. METHODS: This retrospective case series summarizes the clinical experience of 8 patients with PAH receiving ECMO and reviews medication management in the setting of ECMO. RESULTS: Eight PAH patients, 5 of whom were female, ranging in age from 21 to 61 years old, were initiated on ECMO. Veno-arterial (VA) ECMO was used in 4 patients, veno-venous (VV) ECMO and hybrid ECMO configurations in 2 patients respectively. Common indications for ECMO included cardiogenic shock, bridge to transplant, and cardiac arrest. All patients were on intravenous (IV) prostacyclin therapy at baseline. Refractory hypotension was noted in 7 patients of whom 5 patients required downtitration or discontinuation of baseline PAH therapies. Three patients had continuous inhaled epoprostenol added during their time on ECMO. In patients who were decannulated from ECMO, PAH therapies were typically resumed or titrated back to baseline dosages. One patient required no adjustment in PAH therapy while on ECMO. Two patients were not able to be decannulated from ECMO. CONCLUSION: The treatment of critically ill PAH patients is challenging given a variety of factors that could affect PAH drug concentrations. In particular, PAH patients on prostacyclin analogues placed on VA ECMO appear to have pronounced systemic vasodilation requiring vasopressors which is alleviated by temporarily reducing the intravenous prostacyclin dose. Patients should be closely monitored for potential need for rapid titrations in prostacyclin therapy to maintain hemodynamic stability.

Mortality associated with acute respiratory distress syndrome, 2009-2019: a systematic review and meta-analysis.

Background: Acute respiratory distress syndrome (ARDS) occurs commonly in intensive care units. The reported mortality rates in studies evaluating ARDS are highly variable. Objective: To investigate mortality rates due to ARDS from before the 2009 H1N1 influenza pandemic began until the start of coronavirus disease 2019 (COVID-19) pandemic. Design: We performed a systematic search and then ran a proportional meta-analysis for mortality. We ran our analysis in three ways: for randomised controlled trials only, for observational studies only, and for randomised controlled trials and observational studies combined. Data sources: MEDLINE and Embase, using a highly sensitive criterion and limiting the search to studies published from January 2009 to December 2019. Review methods: Two of us independently screened titles and abstracts to first identify studies and then complete full text reviews of selected studies. We assessed risk of bias using the Cochrane RoB-2 (a risk-of-bias tool for randomised trials) and the Cochrane ROBINS-1 (a risk-of-bias tool for non-randomised studies of interventions). Results: We screened 5844 citations, of which 102 fully met our inclusion criteria. These included 34 randomised controlled trials and 68 observational studies, with a total of 24 158 patients. The weighted pooled mortality rate for all 102 studies published from 2009 to 2019 was 39.4% (95% CI, 37.0-41.8%). Mortality was higher in observational studies compared with randomised controlled trials (41.8% [95% CI, 38.9-44.8%] v 34.5% [95% CI, 30.6-38.5%]; P = 0.005). Conclusions: Over the past decade, mortality rates due to ARDS were high. There is a clear distinction between mortality in observational studies and in randomised controlled trials. Future studies need to report mortality for different ARDS phenotypes and closely adhere to evidence-based medicine. PROSPERO registration: CRD42020149712 (April 2020).

Effectiveness and Safety of Twice Daily Versus Thrice Daily Subcutaneous Unfractionated Heparin for Venous Thromboembolism Prophylaxis at a Tertiary Medical Center.

BACKGROUND: The direct comparison of twice daily (BID) and thrice daily (TID) dosing of subcutaneous low dose unfractionated heparin (LDUH) for venous thromboembolism (VTE) prophylaxis in a mixed inpatient population is not well-studied. OBJECTIVE: This study evaluated the effectiveness and safety of BID compared to TID dosing of LDUH for prevention of VTE. METHODS: Retrospective, single-center analysis of patients who received LDUH for VTE prophylaxis between July and September 2015. Outcomes were identified by ICD-9 codes. A matched cohort was created using propensity scores and multivariate analysis was conducted to identify independent risk factors for VTE. The primary outcome was incidence of symptomatic VTE. RESULTS: In the full cohort, VTE occurred in 0.71% of patients who received LDUH BID compared to 0.77% of patients who received LDUH TID (p = 0.85). There was no difference in major (p = 0.85) and minor (p = 0.52) bleeding between the BID and TID groups. For the matched cohort, VTE occurred in 1.4% of BID patients and 2.1% of TID patients (p = 0.32). Major bleed occurred in 0.36% of BID patients and 0.52% of TID patients (p = 0.7), while a minor bleed was seen in 3.4% of BID patients and 2.1% of TID patients (p = 0.13). Personal history of VTE (p = 0.002) and weight (p = 0.035) were independently associated with increased risk of VTE. CONCLUSION: This study did not demonstrate a difference in effectiveness or safety between BID and TID dosing of LDUH for VTE prevention.

Antibody-Mediated Rejection Management Following Lung Transplantation.

BACKGROUND: Although antibody-mediated rejection (AMR) is described in other solid organ transplant populations, the literature describing the management following lung transplantation is limited. OBJECTIVE: The purpose of this study is to evaluate the management strategies of AMR in lung transplant recipients. METHODS: This single-center, retrospective study described the management of AMR in adult lung transplant recipients who received treatment with rabbit antithymocyte globulin, bortezomib, rituximab, intravenous immune globulin (IVIG), and/or plasmapheresis between September 2015 and June 2019. RESULTS: A total of 270 medication orders for 55 patient admissions were included in the primary outcome analysis. The most commonly used regimen consisted of IVIG, plasmapheresis, and rituximab (49.1%; n = 27), followed by IVIG and plasmapheresis alone (27.3%, n = 15). A total of 51 patients (93%) received plasmapheresis as part of their AMR treatment, with a median of 4 [3, 5] sessions per encounter; 86% of patients with positive donor-specific antibodies (DSAs) had a reduction in DSAs following AMR treatment. Overall, 23.5% of patients had noted allograft failure or need for retransplantation. A total of 10 patients died during the AMR treatment hospital admission, and an additional 11 patients died within 1 year of the initial encounter. CONCLUSION AND RELEVANCE: This represents the largest report describing management strategies of AMR in lung transplant recipients. Although practice varied, the most commonly used regimen consisted of plasmapheresis, IVIG, and rituximab.

Critically ill patients with severe immune checkpoint inhibitor related neurotoxicity: A multi-center case series.

PURPOSE: Serious immune checkpoint inhibitor (ICI)-related neurotoxicity is rare. There is limited data on the specifics of care and outcomes of patients with severe neurological immune related adverse events (NirAEs) admitted to the Intensive Care Unit (ICU). MATERIALS AND METHODS: Retrospective study of patients with severe NirAEs admitted to the ICU at 3 academic centers between January 2016 and December 2018. Clinical data collected included ICI exposure, type of NirAE (central [CNS] or peripheral nervous system [PNS) disorders), and patient outcomes including neurological recovery and mortality. RESULTS: Seventeen patients developed severe NirAEs. Eight patients presented with PNS disorders; 6 with myasthenia gravis (MG), 1 had a combination of MG and polyneuropathy and 1 had Guillain-Barre syndrome. Nine patients had CNS disorders (6 seizures and 5 had concomitant encephalopathy. During ICU admission, 65% of patients required mechanical ventilation, 35% vasopressors, and 18% renal replacement therapy. The median ICU and hospital length of stay were 7 (2-36) and 18 (4-80) days, respectively. Hospital mortality was 29%. At hospital discharge, 18% of patients made a full neurologic recovery, 41% partial recovery, and 12% did not recover. CONCLUSION: Severe NirAEs while uncommon, can be serious or even life-threatening if not diagnosed and treated early.

Single-Center Experience of Outcomes and Prescribing Patterns of IV Immunoglobulin Use in Critically Ill Patients.

Previous literature has not compared prescribing practices of IV immunoglobulin in medical ICU survivors and nonsurvivors. The objective of this study was to study IV immunoglobulin use in patients admitted to a medical ICU evaluating differences between hospital survivors and nonsurvivors in regards to level of evidence supporting use, prescribing patterns, and cost. DESIGN: Retrospective, observational study. SETTING: Single, academic medical center medical ICU. PATIENTS: Adults who received greater than or equal to 1 dose of IV immunoglobulin during their medical ICU admission from 2011 to 2018. INTERVENTIONS: Prescribing patterns, level of evidence supporting use, and cost. MEASUREMENTS AND MAIN RESULTS: A total of 389 patients received greater than or equal to 1 dose of IV immunoglobulin for 46 discrete indications and 36.5% of indications had low-quality data supporting use of IV immunoglobulin. The primary indication for IV immunoglobulin was hypogammaglobulinemia (35.5%) followed by antibody-mediated lung transplant rejection (15.4%). Nonsurvivors received lower median dosing (g/kg) and number of doses compared with survivors (0.4 g/kg [0.4-1 g/kg] vs 0.5 g/kg [0.4-1 g/kg] [p = 0.0003] and 1.0 [1-2] vs 2 [1-3] doses [p = 0.0001], respectively). Dosing was based on ideal body weight in 258 patients (66%). High-quality data supported IV immunoglobulin use in 15 patients (4%). The median cost per dose of IV immunoglobulin in nonsurvivors was $4,893 ($4,078-$8,155) versus $5,709 ($4,078-$10,602) in survivors (p = 0.04). CONCLUSIONS: IV immunoglobulin is prescribed for many indications in the medical ICU with low-quality evidence supporting its use and dosing regimens are variable. Hospital survivors received a higher dose and greater number of doses of IV immunoglobulin compared with nonsurvivors. National guidelines are needed to help inform IV immunoglobulin utilization and reduce healthcare costs.

Neuromuscular Blocking Agents for ARDS: A Systematic Review and Meta-Analysis.

BACKGROUND: Studies evaluating neuromuscular blocking agents (NMBAs) in the management of ARDS have produced inconsistent results in terms of their effect on mortality. The purpose of this systematic review and meta-analysis was to evaluate differences in mortality comparing subjects with ARDS who received NMBA to those who received placebo or usual care. METHODS: We searched Ovid, MEDLINE, Embase, CINAHL, Cochrane, Scopus, and Web of Science for randomized controlled trials evaluating administration of NMBAs in subjects with ARDS. RESULTS: We included 6 studies (N = 1,558 subjects) from 1,814 abstracts identified by our search strategy. The use of early, continuous-infusion NMBAs reduces the risk of short-term (ie, 21-28-d) mortality (relative risk 0.71 [95% CI 0.52-0.98], P = .030, I 2 = 60%) in subjects with ARDS but does not reduce the risk of long-term (ie, 90-d) mortality (relative risk 0.81 [95% CI 0.64-1.04], P = .10, I 2 = 54%). NMBAs decreased the risk of barotrauma (relative risk 0.55 [95% CI 0.35-0.85], P = .008, I 2 = 0%) and pneumothorax (relative risk 0.46 [95% CI 0.28-0.77], P = .003, I 2 = 0%) compared to control. CONCLUSIONS: In subjects with ARDS, early use of NMBAs improves oxygenation, reduces the incidence of ventilator-induced lung injury, and decreases 21-28-d mortality, but it does not improve 90-d mortality. NMBAs should be considered for select patients with moderate-to-severe ARDS for short durations.

Implementation of Protocolized Care in ARDS Improves Outcomes.

BACKGROUND: Treatments for ARDS that improve patient outcomes include use of lung-protective ventilation, prone ventilation, and conservative fluid management. Implementation of ARDS protocols via educational programs might improve adherence and outcomes. The objective of this study was to investigate the effects of an ARDS protocol implementation on outcomes and adherence with ARDS guidelines. METHODS: This was a single-center, interventional, comparative study before and after protocol implementation. Staff education for the ARDS protocol was implemented between June 2014 and May 2015. A retrospective cohort analysis was conducted during between January 2012 and May 2014 (pre-protocol) and between June 2015 and June 2017 (post-protocol). A total of 450 subjects with ARDS were included. After propensity score matching, 432 subjects were analyzed. Of those, 330 subjects were treated after protocol implementation. RESULTS: The median (interquartile range [IQR]) plateau pressure and tidal volume over the first 3 d decreased significantly after protocol implementation (30.5 [IQR 24.2-33] vs 25.5 [IQR 21.7-30], P = .01 and 7.65 vs 7.4 mL/kg predicted body weight, P = .032, respectively). The percentage of subjects with unsafe tidal volume (> 10 mL/kg predicted body weight) decreased (14.4% vs 5.8%, P = .02). The percentage of subjects with safe plateau pressure (≤ 30 cm H2O) increased (47.4% vs 76.5%, P < .001). PEEP deviation from the ARDSNet PEEP/[Formula: see text] table was significantly lower after the implementation. Mortality at 28 and 90 days improved after implementation (53.9% vs 41.8% and 61.8% vs 48.2%, respectively). Adjusted odds ratios for 28-d and 90-d mortality were 0.47 (95% CI 0.28-0.78) and 0.45 (95% CI 0.27-0.76), respectively. CONCLUSIONS: ARDS protocol implementation was associated with improved survival and rate of adherence.