Bansal, Vikas

Abstract Patients hospitalized for pneumonia are at high risk for mortality. Effective therapies are therefore needed. Recent randomized clinical trials suggest that systemic steroids can reduce the length of hospital stays among patients hospitalized for pneumonia. Furthermore, preliminary findings from a feasibility study demonstrated that early treatment with a combination of an inhaled corticosteroid and a bronchodilator can improve oxygenation and reduce risk of respiratory failure in patients at risk of acute respiratory distress syndrome. Whether such a combination administered early is effective in reducing acute respiratory failure (ARF) among patients hospitalized with pneumonia is unknown. Here we describe the ARREST Pneumonia (Arrest Respiratory Failure due to Pneumonia) trial designed to address this question. ARREST Pneumonia is a two-arm, randomized, double-blinded, placebo-controlled trial designed to test the efficacy of a combination of an inhaled corticosteroid and a β-agonist compared with placebo for the prevention of ARF in hospitalized participants with severe pneumonia. The primary outcome is ARF within 7 days of randomization, defined as a composite endpoint of intubation and mechanical ventilation; need for high-flow nasal cannula oxygen therapy or noninvasive ventilation for >36 hours (each alone or combined); or death within 36 hours of being placed on respiratory support. The planned enrollment is 600 adult participants at 10 academic medical centers. In addition, we will measure selected plasma biomarkers to better understand mechanisms of action. The trial is funded by the U.S. National Heart Lung and Blood Institute. Clinical trial registered with www.clinicaltrials.gov (NCT 04193878).

Background: Little is known about hypoxemia surrounding endotracheal intubation in the critically ill. Thus, we sought to identify risk factors associated with peri-intubation hypoxemia and its effects’ on the critically ill. Methods: Data from a multicenter, prospective, cohort study enrolling 1,033 critically ill adults who underwent endotracheal intubation across 16 medical/surgical ICUs in the United States from July 2015-January 2017 were used to identify risk factors associated with peri-intubation hypoxemia and its effects on patient outcomes. We defined hypoxemia as any pulse oximetry ≤ 88% during and up to 30 minutes following endotracheal intubation. Results: In the full analysis (n = 1,033), 123 (11.9%) patients experienced the primary outcome. Five risk factors independently associated with our outcome were identified on multiple logistic regression: cardiac related reason for endotracheal intubation (OR 1.67, [95% CI 1.04, 2.69]); pre-intubation noninvasive ventilation (OR 1.66, [95% CI 1.09, 2.54]); emergency intubation (OR 1.65, [95% CI 1.06, 2.55]); moderate-severe difficult bag-mask ventilation (OR 2.68, [95% CI 1.72, 4.19]); and crystalloid administration within the preceding 24 hours (OR 1.24, [95% CI 1.07, 1.45]; per liter up to 4 liters). Higher baseline S p O 2 was found to be protective (OR 0.93, [95% CI 0.91, 0.96]; per percent up to 97%). Consistent results were seen in a separate analysis on only stable patients (n = 921, 93 [10.1%]) (those without baseline hypoxemia ≤ 88%). Peri-intubation hypoxemia was associated with in-hospital mortality (OR 2.40, [95% CI 1.33, 4.31]; stable patients: OR 2.67, [95% CI 1.38, 5.17]) but not ICU length of stay (point estimate 0.9 days, [95% CI −1.0, 2.8 days]; stable patients: point estimate 1.5 days, [95% CI −0.4, 3.4 days]) after adjusting for age, body mass index, illness severity, airway related reason for intubation (i.e., acute respiratory failure), and baseline S P O 2 . Conclusions: Patients with pre-existing noninvasive ventilation and volume loading who were intubated emergently in the setting of hemodynamic compromise with bag-mask ventilation described as moderate-severe were at increased risk for peri-intubation hypoxemia. Higher baseline oxygenation was found to be protective against peri-intubation hypoxemia. Peri-intubation hypoxemia was associated with in-hospital mortality but not ICU length of stay. Trial registration: Clinicaltrials.gov identifier: NCT02508948 and Registered Report Identifier: RR2-10.2196/11101.

Objectives: Use of observational data to inform the response and care of patients during a pandemic faces unique challenges. Design: The Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study COVID 2019 Registry Core data and research methodology team convened over virtual meetings throughout March to June 2020 to determine best practice goals for development of a pandemic disease registry to support rapid data collection and analysis. Setting: International, multi-center registry of hospitalized patients. Patients: None. Interventions: None. Measurements and Main Results: Large-scale observational data collection requires: 1) quality assurance and harmonization across many sites; 2) a transparent process for selecting from among many potential research questions; 3) the use of best practices in design of descriptive, predictive, and inferential studies; (4) innovative approaches to characterize random error in the setting of constantly updated data; (5) rapid peer-review and reporting; and (6) transitions from a focus on discovery to implementation. Herein, we describe the guiding principles to best practices and suggestions for innovations to study design and reporting within the coronavirus disease 2019 Viral Infection and Respiratory Illness Universal Study pandemic registry. Conclusions: Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study coronavirus disease 2019 registry sought to develop and implement prespecified best practices combined with grassroots efforts from clinical sites worldwide in order to develop clinically useful knowledge in response to a pandemic.

Objectives: The coronavirus disease 2019 pandemic has disproportionally strained intensive care services worldwide. Large areas of uncertainly regarding epidemiology, physiology, practice patterns, and resource demands for patients with coronavirus disease 2019 require rapid collection and dissemination of data. We describe the conception and implementation of an intensive care database rapidly developed and designed to meet data analytic needs in response to the coronavirus disease 2019 pandemic—the multicenter, international Society of Critical Care Medicine Discovery Network Viral Infection and Respiratory Illness Universal Study. Design: Prospective cohort study and disease registry. Setting: Multinational cohort of ICUs. Patients: Critically ill patients with a diagnosis of coronavirus disease 2019. Interventions: None. Measurements and Main Results: Within 2 weeks of conception of the Society of Critical Care Medicine Discovery Network Viral Infection and Respiratory Illness Universal Study, study leadership was convened, registry case report forms were designed, electronic data entry set up, and more than 250 centers had submitted the protocol for institutional review board approval, with more than 100 cases entered. Conclusions: The Society of Critical Care Medicine Discovery Network Viral Infection and Respiratory Illness Universal Study provides an example of a rapidly deployed, international, pandemic registry that seeks to provide near real-time analytics and information regarding intensive care treatments and outcomes for patients with coronavirus disease 2019.

Postobstructive pulmonary edema (POPE) also known as negative pressure pulmonary edema (NPPE) is an underdiagnosed entity in clinical practice and can lead to life-threatening hypoxemia. A 64-year-old male patient’s perioperative course was complicated by acute hypoxemic respiratory failure, after extubation following general anesthesia, following the excision of the right vocal cord papilloma. His chest X-ray showed features of pulmonary edema, EKG showed dynamic ST-T changes in the lateral leads, and echocardiography showed evidence of regional motion abnormalities. His coronaries were normal on the immediate angiogram. He was managed with lung protective mechanical ventilation strategy, diuretics, and fluid restriction. His respiratory status improved, and trachea was extubated after 10 hours of intensive care unit (ICU) stay. The case illustrates the various differentials of immediate postoperative flash pulmonary edema and ensuing appropriate management strategy.