Discriminating Acute Respiratory Distress Syndrome from other forms of respiratory failure via iterative machine learning

Acute Respiratory Distress Syndrome (ARDS) is associated with high morbidity and mortality. Identification of ARDS enables lung protective strategies, quality improvement interventions, and clinical trial enrolment, but remains challenging particularly in the first 24 h of mechanical ventilation. To address this we built an algorithm capable of discriminating ARDS from other similarly presenting disorders immediately following mechanical ventilation. Specifically, a clinical team examined medical records from 1263 ICU-admitted, mechanically ventilated patients, retrospectively assigning each patient a diagnosis of "ARDS” or "non-ARDS” (e.g., pulmonary edema). Exploiting data readily available in the clinical setting, including patient demographics, laboratory test results from before the initiation of mechanical ventilation, and features extracted by natural language processing of radiology reports, we applied an iterative pre-processing and machine learning framework. The resulting model successfully discriminated ARDS from non-ARDS causes of respiratory failure (AUC = 0.85) among patients meeting Berlin criteria for severe hypoxia. This analysis also highlighted novel patient variables that were informative for identifying ARDS in ICU settings.

Randomized Open Investigation Determining Steroid Dose in Severe COVID-19: The ROIDS-Dose Clinical Trial.

Introduction Treatment with dexamethasone reduces mortality in patients with coronavirus disease 2019 (COVID-19) pneumonia requiring supplemental oxygen, but the optimal dose has not been determined. Objective To determine whether weight-based dexamethasone of 0.2 mg/kg is superior to 6 mg daily in reducing 28-day mortality in patients with COVID-19 and hypoxemia. Materials and methods A multicenter, open-label, randomized clinical trial was conducted between March 2021 and December 2021 at seven hospitals within Northwell Health. A total of 142 patients with confirmed COVID-19 and hypoxemia were included. Participants were randomized in a 1:1 ratio to dexamethasone 0.2 mg/kg intravenously daily (n = 70) or 6 mg daily (n = 72) for up to 10 days. Results There was no statistically significant difference in the primary outcome of 28-day all-cause mortality with deaths in 12 of 70 patients (17.14%) in the intervention group and 15 of 72 patients (20.83%) in the control group (p = 0.58). There were no statistically significant differences among the secondary outcomes. Conclusion In patients with COVID-19 and hypoxemia, the use of weight-based dexamethasone dosing was not superior to dexamethasone 6 mg in reducing all-cause mortality at 28 days. Clinical trial registration This study was registered under ClinicalTrials.gov (identifier: NCT04834375).

Pneumothorax in COVID-19 Acute Respiratory Distress Syndrome: Case Series.

Objective The study aims to describe the clinical characteristics and outcomes of patients with COVID-19 related acute respiratory distress syndrome (ARDS) who developed pneumothorax. Design and setting A retrospective chart review was performed of the electronic medical record. Patients were included if they were identified as having confirmed COVID-19 as well as pneumothorax from March 16, 2020 to May 31, 2020. Patients' demographic and clinical characteristics, mechanical ventilator parameters, lung compliance measurements and outcomes during hospitalization were collected. This case series was conducted in intensive care units at two large tertiary care centers within the Northwell Health System, located in New York State. Patients A total of 75 patients were identified who were predominantly male (73.3%) with an average age of 62.8 years. Thirty (40%) were Hispanic, 20 (26.7%) were White, 16 (21.3%) were Asian, and nine (12%) were Black. Common comorbid conditions were hypertension (52%), diabetes mellitus (26.7%), hyperlipidemia (32.0%), and chronic pulmonary disease (8, 10.7%). Measurements and main results Most of the patients were diagnosed with pneumothorax while on mechanical ventilation (92%) despite overall adherence with lung-protective ventilation strategies. Average tidal volume was 6.66 mL/kg) of ideal body weight. The average positive end-expiratory pressure (PEEP) was 10.83 (cm) H2O. Lung compliance was poor, with average peak and plateau pressures of 41.9 cm H2O and 35.2 cm H2O, respectively. Inpatient mortality was high in these patients (76%). Conservative management with initial observation had a success rate (73.3%) with similar mortality and shorter length of stay (LOS) on average. Significant factors in the conservatively managed group included lack of tension physiology, the smaller size of pneumothorax, lack of underlying diabetes, presence of pneumomediastinum, and not being on mechanical ventilation during diagnosis. Conclusion Despite overall adherence to best practice ventilator management in ARDS, we observed a large number of pneumothoraces during the COVID-19 pandemic. Conservative management may be appropriate if there are no clinical signs or symptoms of tension physiology and pneumothorax size is small.

Physiologic Response to Angiotensin II Treatment for Coronavirus Disease 2019-Induced Vasodilatory Shock: A Retrospective Matched Cohort Study.

OBJECTIVES: To assess the early physiologic response to angiotensin-II treatment in patients with coronavirus disease 2019-induced respiratory failure and distributive shock. DESIGN: Retrospective consecutive-sample cohort study. SETTING: Three medical ICUs in New York during the coronavirus disease 2019 outbreak. PATIENTS: All patients were admitted to the ICU with respiratory failure and were receiving norepinephrine for distributive shock. INTERVENTIONS: The treatment groups were patients who received greater than or equal to 1 hour of angiotensin-II treatment. Time-zero was the time of angiotensin-II initiation. Controls were identified using a 2:1 hierarchical process that matched for 1) date and unit of admission; 2) specific organ support modalities; 3) age; 4) chronic lung, cardiovascular, and kidney disease; and 5) sex. Time-zero in the control group was 21 hours post vasopressor initiation, the mean duration of vasopressor therapy prior to angiotensin-II initiation in the treated group. MEASUREMENTS AND MAIN RESULTS: Main outcomes were trajectories of vasopressor requirements (in norepinephrine-equivalent dose) and mean arterial pressure. Additionally assessed trajectories were respiratory (Pao2/Fio2, Paco2), metabolic (pH, creatinine), and coagulation (d-dimer) dysfunction indices after time-zero. We also recorded adverse events and clinical outcomes. Trajectories were analyzed using mixed-effects models for immediate (first 6 hr), early (48 hr), and sustained (7 d) responses. Twenty-nine patients (n = 10 treated, n = 19 control) were identified. Despite matching, angiotensin-II-treated patients had markedly greater vasopressor requirements (mean: 0.489 vs 0.097 µg/kg/min), oxygenation impairment, and acidosis at time-zero. Nonetheless, angiotensin-II treatment was associated with an immediate and sustained reduction in norepinephrine-equivalent dose (6 hr model: ß = -0.036 µg/kg/min/hr; 95% CI: -0.054 to -0.018 µg/kg/min/hr, p interaction=0.0002) (7 d model: ß = -0.04 µg/kg/min/d, 95% CI: -0.05 to -0.03 µg/kg/min/d; p interaction = 0.0002). Compared with controls, angiotensin-II-treated patients had significantly faster improvement in mean arterial pressure, hypercapnia, acidosis, baseline-corrected creatinine, and d-dimer. Three thrombotic events occurred, all in control patients. CONCLUSIONS: Angiotensin-II treatment for coronavirus disease 2019-induced distributive shock was associated with rapid improvement in multiple physiologic indices. Angiotensin-II in coronavirus disease 2019-induced shock warrants further study.

“Ambulatory Management of Moderate to High Risk COVID-19 Patients: The Coronavirus Related Outpatient Work Navigators (CROWN) Protocol”

During the height of the novel 2019 coronavirus disease (COVID-19) pandemic in New York City, area hospitals were filled to 150% capacity, and there was a significant fear among the public of going to the hospital. Many hospitalized patients were treated with therapies that could be administered in a home setting under proper monitoring. We designed the CROWN Program, a Home-Care based ambulatory protocol to evaluate, monitor, and treat moderate to high risk COVID-19 patients in their homes, with escalation to hospital care when necessary. Patients were evaluated with telehealth visits with a Pulmonologist, and a Home-Care protocol, including RN visit, pulse-oximetry, and oxygen, lab-work, intravenous fluids, medication if needed patient data, comorbidities, and symptoms were collected. Labs, including COVID-19 PCR, D Dimer, CRP, Ferritin, Procalcitonin, CBC, and metabolic panel were measured, as were homecare, home oxygen, and intravenous fluids orders, radiographic studies and initiation of an anticoagulant. Emergency Department visits and need for hospital admission during the study period were recorded. A total of 182 patients were enrolled between the start date of April 27th and June 1st, and fell into two categories: not-admitted (101) and post-discharge (81). Two patients were referred for hospital admission, seven were treated and released from the ED, and one was referred to home hospice. There were no unexpected admissions or deaths. The CROWN program has demonstrated the feasibility and apparent safety of a specialized, Home-Care based protocol for the ambulatory management of moderate to high risk COVID-19 patients.

Association of anticoagulation dose and survival in hospitalized COVID-19 patients: A retrospective propensity score-weighted analysis.

BACKGROUND: Hypercoagulability may contribute to COVID-19 pathogenicity. The role of anticoagulation (AC) at therapeutic (tAC) or prophylactic doses (pAC) is unclear. OBJECTIVES: We evaluated the impact on survival of different AC doses in COVID-19 patients. METHODS: Retrospective, multi-center cohort study of consecutive COVID-19 patients hospitalized between March 13 and May 5, 2020. RESULTS: A total of 3480 patients were included (mean age, 64.5 years [17.0]; 51.5% female; 52.1% black and 40.6% white). 18.5% (n = 642) required intensive care unit (ICU) stay. 60.9% received pAC (n = 2121), 28.7% received ≥3 days of tAC (n = 998), and 10.4% (n = 361) received no AC. Propensity score (PS) weighted Kaplan-Meier plot demonstrated different 25-day survival probability in the tAC and pAC groups (57.5% vs 50.7%). In a PS-weighted multivariate proportional hazards model, AC was associated with reduced risk of death at prophylactic (hazard ratio [HR] 0.35 [95% confidence interval {CI} 0.22-0.54]) and therapeutic doses (HR 0.14 [95% CI 0.05-0.23]) compared to no AC. Major bleeding occurred more frequently in tAC patients (81 [8.1%]) compared to no AC (20 [5.5%]) or pAC (46 [2.2%]) subjects. CONCLUSIONS: Higher doses of AC were associated with lower mortality in hospitalized COVID-19 patients. Prospective evaluation of efficacy and risk of AC in COVID-19 is warranted.

General and Intensive Care Outcomes for Hospitalized Patients With Solid Organ Transplants With COVID-19.

PURPOSE: COVID-19 has been associated with a dysregulated inflammatory response. Patients who have received solid-organ transplants are more susceptible to infections in general due to the use of immunosuppressants. We investigated factors associated with mechanical ventilation and outcomes in solid-organ transplant recipients with COVID-19. MATERIALS AND METHODS: We conducted a retrospective cohort study of all solid-organ transplant recipients admitted with a diagnosis of COVID-19 in our 23-hospital health system over a 1-month period. Descriptive statistics were used to describe hospital course and laboratory results and bivariate comparisons were performed on variables to determine differences. RESULTS: Twenty-two patients with solid-organ transplants and COVID-19 were identified. Eight patients were admitted to the ICU, of which 7 were intubated. Admission values of CRP (p = 0.045) and N/L ratio (p = 0.047) were associated with the need for mechanical ventilation. Seven patients (32%) died during admission, including 86% (n = 6) of patients who received mechanical ventilation. CONCLUSIONS: In solid-organ transplant recipients with COVID-19, initial CRP and N/L ratio were associated with need for mechanical ventilation.

Therapeutic Anticoagulation Delays Death in COVID-19 Patients: Cross-Sectional Analysis of a Prospective Cohort.

A hypercoagulable state has been described in coronavirus disease 2019 (COVID-19) patients. Others have reported a survival advantage with prophylactic anticoagulation (pAC) and therapeutic anticoagulation (tAC), but these retrospective analyses have important limitations such as confounding by indication. We studied the impact of tAC and pAC compared with no anticoagulation (AC) on time to death in COVID-19. We performed a cross-sectional analysis of 127 deceased COVID-19 patients and compared time to death in those who received tAC ( n = 67), pAC ( n = 47), and no AC ( n = 13). Median time to death was longer with higher doses of AC (11 days for tAC, 8 days for pAC, and 4 days for no AC, p < 0.001). In multivariate analysis, AC was associated with longer time to death, both at prophylactic (hazard ratio [HR] = 0.29; 95% confidence interval [CI]: 0.15 to 0.58; p < 0.001) and therapeutic doses (HR = 0.15; 95% CI: 0.07 to 0.32; p < 0.001) compared with no AC. Bleeding rates were similar among tAC and remaining patients (19 vs. 18%; p = 0.877). In deceased COVID-19 patients, AC was associated with a delay in death in a dose-dependent manner. Randomized trials are required to prospectively investigate the benefit and safety of higher doses of AC in this population.

Pulmonary Embolism in Patients Hospitalized With COVID-19 (From a New York Health System).

Pulmonary embolisms (PEs) in coronavirus disease 2019 (COVID-19) have increasingly been reported in observational studies. However, limited information describing their clinical characteristics and outcomes exists. Our study aims to describe clinical features and risk stratification strategies of hospitalized COVID-19 patients with PE. We retrospectively analyzed 101 hospitalized patients with COVID-19 infection and acute PE. Clinical outcomes measured were intensive care unit admission, mechanical ventilation, bleeding and transfusion events, acute kidney injury (AKI) and mortality. Pulmonary severity index (PESI) scores were used for risk stratification. The most common comorbidities were hypertension (50%), obesity (27%) and hyperlipidemia (32%) among this cohort. Baseline D-dimer abnormalities (4,647.0 ± 8,281.8) were noted on admission with a 3-fold increase at the time of PE diagnosis (13,288.4 ± 14,917.9; p <0.05). Five (5%) patients required systemic thrombolysis and 12 (12%) patients experienced moderate to severe bleeding. Thirty-one (31%) patients developed AKI and 1 (1%) patient required renal replacement therapy. Twenty-three (23%) patients were admitted to intensive care unit, of which 20 (20%) patients received mechanical ventilation. The mortality rate was 20%. Most patients (65%) had Intermediate to high risk PESI scores (>85), which portended a worse prognosis with higher mortality rate and length of stay. In conclusion, this study provides characteristics and early outcomes for hospitalized patients with COVID-19 and acute pulmonary embolism. PESI scores were utilized for risk stratifying clinical outcomes. Our results should serve to alert the medical community to heighted vigilance of this VTE complication associated with COVID-19 infection.

Critical Care Transesophageal Echocardiography in Patients during the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic has placed an extraordinary strain on healthcare systems across North America. Defining the optimal approach for managing a critically ill COVID-19 patient is rapidly changing. Goal-directed transesophageal echocardiography (TEE) is frequently used by physicians caring for intubated critically ill patients as a reliable imaging modality that is well suited to answer questions at bedside. METHODS: A multidisciplinary (intensive care, critical care cardiology, and emergency medicine) group of experts in point-of-care echocardiography and TEE from the United States and Canada convened to review the available evidence, share experiences, and produce a consensus statement aiming to provide clinicians with a framework to maximize the safety of patients and healthcare providers when considering focused point-of-care TEE in critically ill patients during the COVID-19 pandemic. RESULTS: Although transthoracic echocardiography can provide the information needed in most patients, there are specific scenarios in which TEE represents the modality of choice. TEE provides acute care clinicians with a goal-directed framework to guide clinical care and represents an ideal modality to evaluate hemodynamic instability during prone ventilation, perform serial evaluations of the lungs, support cardiac arrest resuscitation, and guide veno-venous ECMO cannulation. To aid other clinicians in performing TEE during the COVID-19 pandemic, we describe a set of principles and practical aspects for performing examinations with a focus on the logistics, personnel, and equipment required before, during, and after an examination. CONCLUSIONS: In the right clinical scenario, TEE is a tool that can provide the information needed to deliver the best and safest possible care for the critically ill patients.

Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area.

Importance: There is limited information describing the presenting characteristics and outcomes of US patients requiring hospitalization for coronavirus disease 2019 (COVID-19). Objective: To describe the clinical characteristics and outcomes of patients with COVID-19 hospitalized in a US health care system. Design, Setting, and Participants: Case series of patients with COVID-19 admitted to 12 hospitals in New York City, Long Island, and Westchester County, New York, within the Northwell Health system. The study included all sequentially hospitalized patients between March 1, 2020, and April 4, 2020, inclusive of these dates. Exposures: Confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by positive result on polymerase chain reaction testing of a nasopharyngeal sample among patients requiring admission. Main Outcomes and Measures: Clinical outcomes during hospitalization, such as invasive mechanical ventilation, kidney replacement therapy, and death. Demographics, baseline comorbidities, presenting vital signs, and test results were also collected. Results: A total of 5700 patients were included (median age, 63 years [interquartile range {IQR}, 52-75; range, 0-107 years]; 39.7% female). The most common comorbidities were hypertension (3026; 56.6%), obesity (1737; 41.7%), and diabetes (1808; 33.8%). At triage, 30.7% of patients were febrile, 17.3% had a respiratory rate greater than 24 breaths/min, and 27.8% received supplemental oxygen. The rate of respiratory virus co-infection was 2.1%. Outcomes were assessed for 2634 patients who were discharged or had died at the study end point. During hospitalization, 373 patients (14.2%) (median age, 68 years [IQR, 56-78]; 33.5% female) were treated in the intensive care unit care, 320 (12.2%) received invasive mechanical ventilation, 81 (3.2%) were treated with kidney replacement therapy, and 553 (21%) died. As of April 4, 2020, for patients requiring mechanical ventilation (n = 1151, 20.2%), 38 (3.3%) were discharged alive, 282 (24.5%) died, and 831 (72.2%) remained in hospital. The median postdischarge follow-up time was 4.4 days (IQR, 2.2-9.3). A total of 45 patients (2.2%) were readmitted during the study period. The median time to readmission was 3 days (IQR, 1.0-4.5) for readmitted patients. Among the 3066 patients who remained hospitalized at the final study follow-up date (median age, 65 years [IQR, 54-75]), the median follow-up at time of censoring was 4.5 days (IQR, 2.4-8.1). Conclusions and Relevance: This case series provides characteristics and early outcomes of sequentially hospitalized patients with confirmed COVID-19 in the New York City area.