Lung Injury Prediction Model in Bone Marrow Transplantation: A Multicenter Cohort Study.

Rationale: Pulmonary complications contribute significantly to nonrelapse mortality following hematopoietic stem cell transplantation (HCT). Identifying patients at high risk can help enroll such patients into clinical studies to better understand, prevent, and treat posttransplantation respiratory failure syndromes. Objectives: To develop and validate a prediction model to identify those at increased risk of acute respiratory failure after HCT. Methods: Patients underwent HCT between January 1, 2019, and December 31, 2021, at one of three institutions. Those treated in Rochester, MN, formed the derivation cohort, and those treated in Scottsdale, AZ, or Jacksonville, FL, formed the validation cohort. The primary outcome was the development of acute respiratory distress syndrome (ARDS), with secondary outcomes including the need for invasive mechanical ventilation (IMV) and/or noninvasive ventilation (NIV). Predictors were based on prior case-control studies. Measurements and Main Results: Of 2,450 patients undergoing stem cell transplantation, there were 1,718 hospitalizations (888 patients) in the training cohort and 1,005 hospitalizations (470 patients) in the test cohort. A 22-point model was developed, with 11 points from prehospital predictors and 11 points from posttransplantation or early (<24-h) in-hospital predictors. The model performed well in predicting ARDS (C-statistic, 0.905; 95% confidence interval [CI], 0.870-0.941) and the need for IMV and/or NIV (C-statistic, 0.863; 95% CI, 0.828-0.898). The test cohort differed markedly in demographic, medical, and hematologic characteristics. The model also performed well in this setting in predicting ARDS (C-statistic, 0.841; 95% CI, 0.782-0.900) and the need for IMV and/or NIV (C-statistic, 0.872; 95% CI, 0.831-0.914). Conclusions: A novel prediction model incorporating data elements from the pretransplantation, posttransplantation, and early in-hospital domains can reliably predict the development of post-HCT acute respiratory failure.

Safety, feasibility, and impact on the gut microbiome of kefir administration in critically ill adults.

BACKGROUND: Dysbiosis of the gut microbiome is frequent in the intensive care unit (ICU), potentially leading to a heightened risk of nosocomial infections. Enhancing the gut microbiome has been proposed as a strategic approach to mitigate potential adverse outcomes. While prior research on select probiotic supplements has not successfully shown to improve gut microbial diversity, fermented foods offer a promising alternative. In this open-label phase I safety and feasibility study, we examined the safety and feasibility of kefir as an initial step towards utilizing fermented foods to mitigate gut dysbiosis in critically ill patients. METHODS: We administered kefir in escalating doses (60 mL, followed by 120 mL after 12 h, then 240 mL daily) to 54 critically ill patients with an intact gastrointestinal tract. To evaluate kefir's safety, we monitored for gastrointestinal symptoms. Feasibility was determined by whether patients received a minimum of 75% of their assigned kefir doses. To assess changes in the gut microbiome composition following kefir administration, we collected two stool samples from 13 patients: one within 72 h of admission to the ICU and another at least 72 h after the first stool sample. RESULTS: After administering kefir, none of the 54 critically ill patients exhibited signs of kefir-related bacteremia. No side effects like bloating, vomiting, or aspiration were noted, except for diarrhea in two patients concurrently on laxatives. Out of the 393 kefir doses prescribed for all participants, 359 (91%) were successfully administered. We were able to collect an initial stool sample from 29 (54%) patients and a follow-up sample from 13 (24%) patients. Analysis of the 26 paired samples revealed no increase in gut microbial α-diversity between the two timepoints. However, there was a significant improvement in the Gut Microbiome Wellness Index (GMWI) by the second timepoint (P = 0.034, one-sided Wilcoxon signed-rank test); this finding supports our hypothesis that kefir administration can improve gut health in critically ill patients. Additionally, the known microbial species in kefir were found to exhibit varying levels of engraftment in patients' guts. CONCLUSIONS: Providing kefir to critically ill individuals is safe and feasible. Our findings warrant a larger evaluation of kefir's safety, tolerability, and impact on gut microbiome dysbiosis in patients admitted to the ICU. TRIAL REGISTRATION: NCT05416814; trial registered on June 13, 2022.

Safety and Efficacy of Reduced-Dose Versus Full-Dose Alteplase for Acute Pulmonary Embolism: A Multicenter Observational Comparative Effectiveness Study.

OBJECTIVES: Systemic thrombolysis improves outcomes in patients with pulmonary embolism (PE) but is associated with the risk of hemorrhage. The data on efficacy and safety of reduced-dose alteplase are limited. The study objective was to compare the characteristics, outcomes, and complications of patients with PE treated with full- or reduced-dose alteplase regimens. DESIGN: Multicenter retrospective observational study. SETTING: Tertiary care hospital and 15 community and academic centers of a large healthcare system. PATIENTS: Hospitalized patients with PE treated with systemic alteplase. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Pre- and post-alteplase hemodynamic and respiratory variables, patient outcomes, and complications were compared. Propensity score (PS) weighting was used to adjust for imbalances of baseline characteristics between reduced- and full-dose patients. Separate analyses were performed using the unweighted and weighted cohorts. Ninety-eight patients were treated with full-dose (100 mg) and 186 with reduced-dose (50 mg) regimens. Following alteplase, significant improvements in shock index, blood pressure, heart rate, respiratory rate, and supplemental oxygen requirements were observed in both groups. Hemorrhagic complications were lower with the reduced-dose compared with the full-dose regimen (13% vs. 24.5%, p = 0.014), and most were minor. Major extracranial hemorrhage occurred in 1.1% versus 6.1%, respectively ( p = 0.022). Complications were associated with supratherapeutic levels of heparin anticoagulation in 37.5% of cases and invasive procedures in 31.3% of cases. The differences in complications persisted after PS weighting (15.4% vs. 24.7%, p = 0.12 and 1.3% vs. 7.1%, p = 0.067), but did not reach statistical significance. There were no significant differences in mortality, discharge destination, ICU or hospital length of stay, or readmission after PS weighting. CONCLUSIONS: In a retrospective, PS-weighted observational study, when compared with the full-dose, reduced-dose alteplase results in similar outcomes but fewer hemorrhagic complications. Avoidance of excessive levels of anticoagulation or invasive procedures should be considered to further reduce complications.

Temporal trends in critical care utilization and outcomes in allogeneic hematopoietic stem cell transplant recipients.

Historically, the prognosis of allogeneic hematopoietic stem cell transplant (allo-HCT) recipients who require intensive care unit (ICU) admission has been poor. We aimed to describe the epidemiological trends of ICU utilization and outcomes in allo-HCT patients. We conducted a retrospective cohort study including adults (≥ 18) undergoing allo-HCT between 01/01/2005 and 31/12/2020 at Mayo Clinic, Rochester. Temporal trends in outcomes were assessed by robust linear regression modelling. Risk factors for hospital mortality were chosen a priori and assessed with multivariable logistic regression modelling. Of 1,249 subjects, there were 486 ICU admissions among 287 individuals. Although older patients underwent allo-HCT (1.64 [95% CI: 1.11 to 2.45] years per year; P = 0.025), there was no change in ICU utilization over time (P = 0.91). The ICU and hospital mortality rates were 19.2% (55/287) and 28.2% (81/287), respectively. There was a decline in ICU mortality (-0.38% [95% CI: -0.70 to -0.06%] per year; P = 0.035). The 1-year post-HCT mortality for those requiring ICU admission was 56.1% (161/287), with no significant difference over time, versus 15.8% (141/891, 71 missing) among those who did not. The frequency and duration of invasive mechanical ventilation (IMV) declined. In multivariable analyses, higher serum lactate, higher sequential organ failure assessment (SOFA) scores, acute respiratory distress (ARDS), and need for IMV were associated with greater odds of hospital mortality. Over time, rates of ICU utilization have remained stable, despite increasing patient age. Several trends suggest improvement in outcomes, notably lower ICU mortality and frequency of IMV. However, long-term survival remains unchanged. Further work is needed to improve long-term outcomes in this population.

Diagnostic delay in pulmonary blastomycosis: a case series reflecting a referral center experience.

PURPOSE: The diagnosis of pulmonary blastomycosis is usually delayed because of its non-specific presentation. We aimed to assess the extent of diagnostic delay in hospitalized patients and detect the step in the diagnostic process that requires the most improvement. METHODS: Adult patients diagnosed with pulmonary blastomycosis during a hospital admission between January 2010 through November 2021 were eligible for inclusion. Patients who did not have pulmonary involvement and who were diagnosed before admission were excluded. Demographics and comorbid conditions, specifics of disease presentation, and interventions were evaluated. The timing of the diagnosis, antifungal treatment, and patient outcomes were noted. Descriptive analytical tests were performed. RESULTS: A total of 43 patients were diagnosed with pulmonary blastomycosis during their admissions. The median age was 47 years, with 13 (30%) females. Of all patients, 29 (67%) had isolated pulmonary infection, while 14 (33%) had disseminated disease, affecting mostly skin and musculoskeletal system. The median duration between the initial symptoms and health care encounters was 4 days, and the time to hospital admission was 9 days. The median duration from the initial symptoms to the diagnosis was 20 days. Forty patients (93%) were treated with empirical antibacterials before a definitive diagnosis was made. In addition, corticosteroid treatment was empirically administered to 15 patients (35%) before the diagnosis, with indications such as suspicion of inflammatory processes or symptom relief. In 38 patients (88%), the first performed fungal diagnostic test was positive. Nineteen patients (44%) required admission to the intensive care unit, and 11 patients (26%) died during their hospital stay. CONCLUSION: There was a delay in diagnosis of patients with pulmonary blastomycosis, largely attributable to the lack of consideration of the etiological agent. Novel approaches to assist providers in recognizing the illness earlier and trigger evaluation are needed.

Developing DELPHI expert consensus rules for a digital twin model of acute stroke care in the neuro critical care unit.

INTRODUCTION: Digital twins, a form of artificial intelligence, are virtual representations of the physical world. In the past 20 years, digital twins have been utilized to track wind turbines' operations, monitor spacecraft's status, and even create a model of the Earth for climate research. While digital twins hold much promise for the neurocritical care unit, the question remains on how to best establish the rules that govern these models. This model will expand on our group's existing digital twin model for the treatment of sepsis. METHODS: The authors of this project collaborated to create a Direct Acyclic Graph (DAG) and an initial series of 20 DELPHI statements, each with six accompanying sub-statements that captured the pathophysiology surrounding the management of acute ischemic strokes in the practice of Neurocritical Care (NCC). Agreement from a panel of 18 experts in the field of NCC was collected through a 7-point Likert scale with consensus defined a-priori by ≥ 80% selection of a 6 ("agree") or 7 ("strongly agree"). The endpoint of the study was defined as the completion of three separate rounds of DELPHI consensus. DELPHI statements that had met consensus would not be included in subsequent rounds of DELPHI consensus. The authors refined DELPHI statements that did not reach consensus with the guidance of de-identified expert comments for subsequent rounds of DELPHI. All DELPHI statements that reached consensus by the end of three rounds of DELPHI consensus would go on to be used to inform the construction of the digital twin model. RESULTS: After the completion of three rounds of DELPHI, 93 (77.5%) statements reached consensus, 11 (9.2%) statements were excluded, and 16 (13.3%) statements did not reach a consensus of the original 120 DELPHI statements. CONCLUSION: This descriptive study demonstrates the use of the DELPHI process to generate consensus among experts and establish a set of rules for the development of a digital twin model for use in the neurologic ICU. Compared to associative models of AI, which develop rules based on finding associations in datasets, digital twin AI created by the DELPHI process are easily interpretable models based on a current understanding of underlying physiology.

Characteristics and Outcomes of Critically Ill Patients With Pulmonary Hypertension Who Undergo Endotracheal Intubation and Mechanical Ventilation.

Background: Patients with pulmonary hypertension (PH) who undergo endotracheal intubation have an increased risk of adverse outcomes, but little is known regarding prognostic factors and there is limited evidence to guide management. We sought to define characteristics, prognostic factors, and outcomes of critically ill patients with PH who underwent intubation. Study Design: We performed a single-center retrospective cohort study of critically ill patients with group 1, 3 or 4 PH who underwent intubation. Results: Eighty-one patients were included. Patients had a median age of 56 years (interquartile range 44-65) and were predominantly female (n = 53, 65%) and Caucasian (n = 71, 88%). Forty-five (56%) had group 1 PH while 25 (31%) had group 3 PH and 11 (14%) had group 4 PH. Patients were admitted to the hospital for right ventricular failure (n = 21, 25.6%), sepsis (n = 18, 22.2%), and respiratory failure (n = 19, 23.1%). Hypoxemic respiratory failure (n = 54, 66.7%) was the most common indication for intubation. In-hospital mortality was 30.9% and 1-year mortality was 48.2%. All patients (11 of 11, 100%) intubated electively for intensive care unit procedures survived to hospital discharge while only 1 of 6 (16.7%) intubated in the setting of a cardiac arrest survived. After adjusting for right ventricular systolic pressure, pre-intubation PaO2 (odds ratio [OR] = 0.99, 95% confidence interval [CI] 0.97-1.00, P = .02) and postintubation PaO2 (OR = 0.97 per 1mm Hg, 95% CI 0.95 to 0.99, P = .003), pH (OR = 0.49 per 0.1 increase, 95% CI 0.29 to 0.80, P = .005) and PaCO2 (OR = 1.08 per 1mm Hg, 95% CI 1.02 to 1.14, P = .005) were significantly associated with in-hospital mortality. Results were similar when we excluded patients intubated electively or in the setting of cardiac arrest. Conclusions: Intubation in critically ill patients with PH is associated with significant in-hospital mortality and nearly 50% 1-year mortality. Potentially modifiable factors, such as peri-intubation gas exchange, are associated with an increased risk of death while other demographic and hemodynamic variables are not.

Biomarker-Concordant Steroid Administration in Severe Coronavirus Disease-2019.

BACKGROUND: Although corticosteroids have become the standard of care for patients with coronavirus disease-2019 (COVID-19) on supplemental oxygen, there is growing evidence of differential treatment response. This study aimed to evaluate if there was an association between biomarker-concordant corticosteroid treatment and COVID-19 outcomes. METHODS: This registry-based cohort study included adult COVID-19 hospitalized patients between January 2020 and December 2021 from 109 institutions. Patients with available C-reactive protein (CRP) levels within 48 h of admission were evaluated. Those on steroids before admission, stayed in the hospital for <48 h, or were not on oxygen support were excluded. Corticosteroid treatment was biomarker-concordant if given with high baseline CRP ≥150 mg/L or withheld with low CRP (<150 mg/L) and vice-versa was considered discordant (low CRP with steroids, high CRP without steroids). Hospital mortality was the primary outcome. Sensitivity analyses were conducted using varying CRP level thresholds. The model interaction was tested to determine steroid effectiveness with increasing CRP levels. RESULTS: Corticosteroid treatment was biomarker-concordant in 1778 (49%) patients and discordant in 1835 (51%). The concordant group consisted of higher-risk patients than the discordant group. After adjusting for covariates, the odds of in-hospital mortality were significantly lower in the concordant group than the discordant (odds ratio [95% confidence interval (C.I.)] = 0.71 [0.51, 0.98]). Similarly, adjusted mortality difference was significant at the CRP thresholds of 100 and 200 mg/L (odds ratio [95% C.I.] = 0.70 [0.52, 0.95] and 0.57 [0.38, 0.85], respectively), and concordant steroid use was associated with lower need for invasive ventilation for 200 mg/L threshold (odds ratio [95% C.I.] = 0.52 [0.30, 0.91]). In contrast, no outcome benefit was observed at CRP threshold of 50. When the model interaction was tested, steroids were more effective at reducing mortality as CRP levels increased. CONCLUSION: Biomarker-concordant corticosteroid treatment was associated with lower odds of in-hospital mortality in severe COVID-19.

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.

Coronavirus Disease 2019 in Pediatric Oncology Patients: A Matched-Cohort Analysis of the SCCM Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 Registry.

BACKGROUND: There is a paucity of multicenter data describing the impact of coronavirus disease 2019 (COVID-19) on hospitalized pediatric oncology patients. Using a large, multicenter, Society of Critical Care Medicine (SCCM) Discovery Viral Infection and Respiratory Illness University Study (VIRUS) database, we aimed at assessing outcomes of COVID-19 infection in this population. METHOD: This is a matched-cohort study involving children below 18 years of age hospitalized with COVID-19 between March 2020 and January 2021. Using the VIRUS; COVID-19 Registry database, children with oncologic diseases were compared with propensity score matched (age groups, sex, race, and ethnicity) cohort of children without oncologic diseases for the prevalence of Multisystem Inflammatory Syndrome in Children (MIS-C), intensive care unit (ICU) admission, interventions, hospital, and ICU length of stay. RESULTS: The number of children in the case and control groups was 45 and 180, respectively. ICU admission rate was similar in both groups ([47.7 vs 51.7%], P =0.63). The proportion of children requiring noninvasive and invasive mechanical ventilation, and its duration were similar between groups, same as hospital mortality. Interestingly, MIS-C was significantly lower in the oncology group compared with the control (2.4 vs 24.6%; P =0.0002). CONCLUSIONS: In this study using a multicenter VIRUS database, ICU admission rate, interventions, and outcomes of COVID-19 were similar in children with the oncologic disease compared with control patients. The incidence of MIS-C is lower in oncologic patients.

Association of Blood Pressure Variability with Delirium in Patients with Critical Illness.

BACKGROUND: The objective was to examine the association of blood pressure variability (BPV) during the first 24 h after intensive care unit admission with the likelihood of delirium and depressed alertness without delirium ("depressed alertness"). METHODS: This retrospective, observational, cohort study included all consecutive adult patients admitted to an intensive care unit at Mayo Clinic, Rochester, Minnesota, from July 1, 2004, through October 31, 2015. The primary outcomes were delirium and delirium-free days, and the secondary outcomes included depressed alertness and depressed alertness-free days. Logistic regression was performed to determine the association of BPV with delirium and depressed alertness. Proportional odds regression was used to assess the association of BPV with delirium-free days and depressed alertness-free days. RESULTS: Among 66,549 intensive care unit admissions, delirium was documented in 20.2% and depressed alertness was documented in 24.4%. Preserved cognition was documented in 55.4% of intensive care unit admissions. Increased systolic and diastolic BPV was associated with an increased odds of delirium and depressed alertness. The magnitude of the association per 5-mm Hg increase in systolic average real variability (the average of absolute value of changes between consecutive systolic blood pressure readings) was greater for delirium (odds ratio 1.34; 95% confidence interval 1.29-1.40; P < 0.001) than for depressed alertness (odds ratio 1.06; 95% confidence interval 1.02-1.10; P = 0.004). Increased systolic and diastolic BPV was associated with fewer delirium-free days but not with depressed alertness-free days. CONCLUSIONS: BPV in the first 24 h after intensive care unit admission is associated with an increased likelihood of delirium and fewer delirium-free days.

Association of hypothyroidism with outcomes in hospitalized adults with COVID-19: Results from the International SCCM Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is associated with high rates of morbidity and mortality. Primary hypothyroidism is a common comorbid condition, but little is known about its association with COVID-19 severity and outcomes. This study aims to identify the frequency of hypothyroidism in hospitalized patients with COVID-19 as well as describe the differences in outcomes between patients with and without pre-existing hypothyroidism using an observational, multinational registry. METHODS: In an observational cohort study we enrolled patients 18 years or older, with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection between March 2020 and February 2021. The primary outcomes were (1) the disease severity defined as per the World Health Organization Scale for Clinical Improvement, which is an ordinal outcome corresponding with the highest severity level recorded during a patient's index COVID-19 hospitalization, (2) in-hospital mortality and (3) hospital-free days. Secondary outcomes were the rate of intensive care unit (ICU) admission and ICU mortality. RESULTS: Among the 20,366 adult patients included in the study, pre-existing hypothyroidism was identified in 1616 (7.9%). The median age for the Hypothyroidism group was 70 (interquartile range: 59-80) years, and 65% were female and 67% were White. The most common comorbidities were hypertension (68%), diabetes (42%), dyslipidemia (37%) and obesity (28%). After adjusting for age, body mass index, sex, admission date in the quarter year since March 2020, race, smoking history and other comorbid conditions (coronary artery disease, hypertension, diabetes and dyslipidemia), pre-existing hypothyroidism was not associated with higher odds of severe disease using the World Health Organization disease severity index (odds ratio [OR]: 1.02; 95% confidence interval [CI]: 0.92, 1.13; p = .69), in-hospital mortality (OR: 1.03; 95% CI: 0.92, 1.15; p = .58) or differences in hospital-free days (estimated difference 0.01 days; 95% CI: -0.45, 0.47; p = .97). Pre-existing hypothyroidism was not associated with ICU admission or ICU mortality in unadjusted as well as in adjusted analysis. CONCLUSIONS: In an international registry, hypothyroidism was identified in around 1 of every 12 adult hospitalized patients with COVID-19. Pre-existing hypothyroidism in hospitalized patients with COVID-19 was not associated with higher disease severity or increased risk of mortality or ICU admissions. However, more research on the possible effects of COVID-19 on the thyroid gland and its function is needed in the future.

Plasma, platelet and red blood cell transfusion ratios for life-threatening non-traumatic haemorrhage in medical and post-surgical patients: An observational study.

BACKGROUND AND OBJECTIVES: Despite the broad utilization of component-based transfusion strategies that aim to reconstitute whole blood during acute traumatic haemorrhage, data for haemorrhage occurring outside of trauma and surgery are limited. METHODS: This is an observational cohort study of adults experiencing critical non-traumatic, non-intraoperative haemorrhage during hospitalization at an academic medical centre from 2011 to 2015. The primary goal was to evaluate differences in plasma and platelet to red blood cell (RBC) transfusion ratios across patient demographic, clinical and laboratory characteristics. Secondarily, associations between transfusion ratios and clinical outcomes were assessed. RESULTS: Seven hundred nine patients were included: 498 (70.2%) medical and 211 (29.8%) post surgical. The gastrointestinal tract (36.7%) was the most common site of bleeding. Most patients received RBCs without plasma (35.5%) or platelets (54.2%). Among those receiving plasma, 82.3% received a plasma to RBC ratio < 1:1 at 24 h. For platelets, the most common ratio was 1-2:1 (52.9%). Transfusion ratios were generally consistent across comorbid disease severity, admission type and anatomic sites of bleeding. Higher plasma utilization was observed in the emergency department, while greater platelet utilization occurred in intensive care units. Higher transfusion ratios were observed in those with greater laboratory haemostatic abnormalities prior to the haemorrhagic event. Clinical outcome differences were limited, though greater platelet utilization in the first 24 h was associated with higher mortality and fewer hospital-free days. CONCLUSIONS: Transfusion ratios for critical non-traumatic haemorrhage were primarily related to laboratory abnormalities preceding the haemorrhagic event and practice environments. Clinical outcome differences across ratios were limited.

Early, biomarker-guided steroid dosing in COVID-19 Pneumonia: a pilot randomized controlled trial.

ClinicalTrials.gov identifier (NCT number): NCT03852537 , Registered February 25, 2019.

Early Post-Hospitalization Hemoglobin Recovery and Clinical Outcomes in Survivors of Critical Illness: A Population-Based Cohort Study.

Anemia is common during critical illness, is associated with adverse clinical outcomes, and often persists after hospitalization. The goal of this investigation is to assess the relationships between post-hospitalization hemoglobin recovery and clinical outcomes after survival of critical illness. This is a population-based observational study of adults (≥18 years) surviving hospitalization for critical illness between January 1, 2010 and December 31, 2016 in Olmsted County, Minnesota, United States with hemoglobin concentrations and clinical outcomes assessed through one-year post-hospitalization. Multi-state proportional hazards models were utilized to assess the relationships between 1-month post-hospitalization hemoglobin recovery and hospital readmission or death through one-year after discharge. Among 6460 patients that survived hospitalization for critical illness during the study period, 2736 (42%) were alive, not hospitalized, and had available hemoglobin concentrations assessed at 1-month post-index hospitalization. Median (interquartile range) age was 69 (56, 80) years with 54% of male gender. Overall, 86% of patients had anemia at the time of hospital discharge, with median discharge hemoglobin concentrations of 10.2 (9.1, 11.6) g/dL. In adjusted analyses, each 1 g/dL increase in 1-month hemoglobin recovery was associated with decreased instantaneous hazard for hospital readmission (HR 0.87 [95% CI 0.84-0.90]; p < 0.001) and lower mortality (HR 0.82 [95% CI 0.75-0.89]; p < 0.001) through one-year post-hospitalization. The results were consistent in multiple pre-defined sensitivity analyses. Impaired early post-hospitalization hemoglobin recovery is associated with inferior clinical outcomes in the first year of survival after critical illness. Additional investigations are warranted to evaluate these relationships.

Trends in Therapy and Outcomes Associated With Respiratory Failure in Patients Admitted to the Cardiac Intensive Care Unit.

PURPOSE: To describe the epidemiology, outcomes, and temporal trends of respiratory failure in the cardiac intensive care unit (CICU). MATERIALS AND METHODS: Retrospective cohort analysis of 2,986 unique Mayo Clinic CICU patients from 2007 to 2018 with respiratory failure. Temporal trends were analyzed, along with hospital and 1-year mortality. Multivariable logistic regression was used to determine adjusted hospital mortality trends. RESULTS: The prevalence of respiratory failure in the CICU increased from 15% to 38% during the study period (P < 0.001 for trend). Among patients with respiratory failure, the utilization of invasive ventilation decreased and noninvasive ventilation modalities increased over time. Hospital mortality and 1-year mortality were 24% and 54%, respectively, with variation according to the type of respiratory support (highest among patients receiving invasive ventilation alone: 35% and 46%, respectively). Hospital mortality was highest among patients with concomitant cardiac arrest and/or shock (52% for patients with both). Hospital mortality decreased in the overall population from 35% to 25% (P < 0.001 for trend), but was unchanged among patients receiving positive-pressure ventilation. CONCLUSIONS: The prevalence of respiratory failure in CICU more than doubled during the last decade. The use of noninvasive respiratory support increased, while overall mortality declined over time. Cardiac arrest and shock accounted for the majority of deaths. Further research is needed to optimize the outcomes of high-risk CICU patients with respiratory failure.

Implementation and evaluation of sepsis surveillance and decision support in medical ICU and emergency department.

OBJECTIVE: To improve the timely diagnosis and treatment of sepsis many institutions implemented automated sepsis alerts. Poor specificity, time delays, and a lack of actionable information lead to limited adoption by bedside clinicians and no change in practice or clinical outcomes. We aimed to compare sepsis care compliance before and after a multi-year implementation of a sepsis surveillance coupled with decision support in a tertiary care center. DESIGN: Single center before and after study. SETTING: Large academic Medical Intensive Care Unit (MICU) and Emergency Department (ED). POPULATION: Patients 18 years of age or older admitted to *** Hospital MICU and ED from 09/4/2011 to 05/01/2018 with severe sepsis or septic shock. INTERVENTIONS: Electronic medical record-based sepsis surveillance system augmented by clinical decision support and completion feedback. MEASUREMENTS AND MAIN RESULTS: There were 1950 patients admitted to the MICU with the diagnosis of severe sepsis or septic shock during the study period. The baseline characteristics were similar before (N = 854) and after (N = 1096) implementation of sepsis surveillance. The performance of the alert was modest with a sensitivity of 79.9%, specificity of 76.9%, positive predictive value (PPV) 27.9%, and negative predictive value (NPV) 97.2%. There were 3424 unique alerts and 1131 confirmed sepsis patients after the sniffer implementation. During the study period average care bundle compliance was higher; however after taking into account improvements in compliance leading up to the intervention, there was no association between intervention and improved care bundle compliance (Odds ratio: 1.16; 95% CI: 0.71 to 1.89; p-value 0.554). Similarly, the intervention was not associated with improvement in hospital mortality (Odds ratio: 1.55; 95% CI: 0.95 to 2.52; p-value: 0.078). CONCLUSIONS: A sepsis surveillance system incorporating decision support or completion feedback was not associated with improved sepsis care and patient outcomes.

SARS-CoV-2 infection increases risk of acute kidney injury in a bimodal age distribution.

BACKGROUND: Hospitalized patients with SARS-CoV2 develop acute kidney injury (AKI) frequently, yet gaps remain in understanding why adults seem to have higher rates compared to children. Our objectives were to evaluate the epidemiology of SARS-CoV2-related AKI across the age spectrum and determine if known risk factors such as illness severity contribute to its pattern. METHODS: Secondary analysis of ongoing prospective international cohort registry. AKI was defined by KDIGO-creatinine only criteria. Log-linear, logistic and generalized estimating equations assessed odds ratios (OR), risk differences (RD), and 95% confidence intervals (CIs) for AKI and mortality adjusting for sex, pre-existing comorbidities, race/ethnicity, illness severity, and clustering within centers. Sensitivity analyses assessed different baseline creatinine estimators. RESULTS: Overall, among 6874 hospitalized patients, 39.6% (n = 2719) developed AKI. There was a bimodal distribution of AKI by age with peaks in older age (≥60 years) and middle childhood (5-15 years), which persisted despite controlling for illness severity, pre-existing comorbidities, or different baseline creatinine estimators. For example, the adjusted OR of developing AKI among hospitalized patients with SARS-CoV2 was 2.74 (95% CI 1.66-4.56) for 10-15-year-olds compared to 30-35-year-olds and similarly was 2.31 (95% CI 1.71-3.12) for 70-75-year-olds, while adjusted OR dropped to 1.39 (95% CI 0.97-2.00) for 40-45-year-olds compared to 30-35-year-olds. CONCLUSIONS: SARS-CoV2-related AKI is common with a bimodal age distribution that is not fully explained by known risk factors or confounders. As the pandemic turns to disproportionately impacting younger individuals, this deserves further investigation as the presence of AKI and SARS-CoV2 infection increases hospital mortality risk.

Incidence and Predictive Factors Associated with Beta-Lactam Neurotoxicity in the Critically Ill: A Retrospective Cohort Study.

BACKGROUND: Beta-lactam neurotoxicity is a relatively uncommon yet clinically significant adverse effect in critically ill patients. This study sought to define the incidence of neurotoxicity, derive a prediction model for beta-lactam neurotoxicity, and then validate the model in an independent cohort of critically ill adults. METHODS: This retrospective cohort study evaluated critically ill patients treated with ≥ 48 h of cefepime, piperacillin/tazobactam, or meropenem. Two separate cohorts were created: a derivation cohort and a validation cohort. Patients were screened for beta-lactam neurotoxicity by using search terms and diagnosis codes, followed by clinical adjudication using a standardized adverse event scoring tool. Multivariable regression models and least absolute shrinkage and selection operator were used to identify surrogates for neurotoxicity and develop a multivariable prediction model. RESULTS: The overall incidence of beta-lactam neurotoxicity was 2.6% (n/N = 34/1323) in the derivation cohort and 2.1% in the validation cohort (n/N = 16/767). The final multivariable neurotoxicity assessment tool included weight, Charlson comorbidity score, age, and estimated creatinine clearance as predictors of neurotoxicity. Incidence of neurotoxicity reached 4% in those with a body mass index more than 30 kg/m2. Use of the candidate variables in the neurotoxicity assessment tool suggested that a score more than 35 would identify a patient at high risk for neurotoxicity with 75% sensitivity and 54% specificity. CONCLUSIONS: In this single center cohort of critically ill patients, beta-lactam neurotoxicity was demonstrated less frequently than previously reported. We identified obesity as a novel risk factor for the development of neurotoxicity. The prediction model needs to be further refined before it can be used in clinical practice as a tool to avoid drug-related harm.

A novel multimodal needs assessment to inform the longitudinal education program for an international interprofessional critical care team.

BACKGROUND: The current global pandemic has caused unprecedented strain on critical care resources, creating an urgency for global critical care education programs. Learning needs assessment is a core element of designing effective, targeted educational interventions. In theory, multimodal methods are preferred to assess both perceived and unperceived learning needs in diverse, interprofessional groups, but a robust design has rarely been reported. Little is known about the best approach to determine the learning needs of international critical care professionals. METHOD: We conducted multimodal learning needs assessment in a pilot group of critical care professionals in China using combined quantitative and qualitative methods. The assessments consisted of three phases: 1) Twenty statements describing essential entrustable professional activities (EPAs) were generated by a panel of critical care education experts using a Delphi method. 2) Eleven Chinese critical care professionals participating in a planned education program were asked to rank-order the statements according to their perceived learning priority using Q methodology. By-person factor analysis was used to study the typology of the opinions, and post-ranking focus group interviews were employed to qualitatively explore participants' reasoning of their rankings. 3) To identify additional unperceived learning needs, daily practice habits were audited using information from medical and nursing records for 3 months. RESULTS: Factor analysis of the rank-ordered statements revealed three learning need patterns with consensual and divergent opinions. All participants expressed significant interest in further education on organ support and disease management, moderate interest in quality improvement topics, and relatively low interest in communication skills. Interest in learning procedure/resuscitation skills varied. The chart audit revealed suboptimal adherence to several evidence-based practices and under-perceived practice gaps in patient-centered communication, daily assessment of antimicrobial therapy discontinuation, spontaneous breathing trial, and device discontinuation. CONCLUSIONS: We described an effective mixed-methods assessment to determine the learning needs of an international, interprofessional critical care team. The Q survey and focus group interviews prioritized and categorized perceived learning needs. The chart audit identified additional practice gaps that were not identified by the learners. Multimodal methods can be employed in cross-cultural scenarios to customize and better target medical education curricula.