Evaluation of Unfractionated Heparin Dosing by Antifactor Xa During Targeted Temperature Management Post Cardiac Arrest.

Purpose: To evaluate unfractionated heparin (UFH) dosing guided by antifactor Xa levels during targeted temperature management (TTM) post-cardiac arrest. Methods: Single-center, retrospective, observational study between January 1, 2014 and September 1, 2020. Patients initiated on TTM post-cardiac arrest and UFH were evaluated for inclusion. Patients included were ≥18 years of age and received weight-based UFH for ≥6 hours with 2 antifactor Xa levels drawn at target temperature. Excluded patients had no available temperature readings, received extracorporeal membrane oxygenation (ECMO) or factor Xa inhibitor (within 72 hours), or had hypertriglyceridemia or hyperbilirubinemia. The primary endpoint was to evaluate the proportion of patients that achieved a therapeutic antifactor Xa level between 0.3 and 0.7 IU/mL at steady state during TTM. Secondary endpoints included average UFH dose and average time to therapeutic antifactor Xa level at steady state; percent of first and total antifactor Xa levels subtherapeutic, therapeutic, and supratherapeutic during TTM. Results: A total of 73 patients met inclusion criteria. Of these, 21 patients achieved steady-state therapeutic antifactor Xa levels during TTM. The average time and dose to steady-state therapeutic antifactor Xa levels were 8.1 ± 4.5 hours and 9.9 ± 3.2 units/kg/hour. Overall, 61.7% of first and 47.4% of all antifactor Xa levels were supratherapeutic during TTM. Three (4.1%) patients experienced a major bleeding event. Conclusions: Guideline recommended UFH dosing, 12 or 18 units/kg/hour, during TTM resulted in more supratherapeutic antifactor Xa levels. Reduction of UFH infusion dose to 10 units/kg/hour may be required during TTM to maintain therapeutic antifactor Xa levels.

Model for End-Stage Liver Disease-Lactate and Prediction of Inpatient Mortality in Patients With Chronic Liver Disease.

BACKGROUND AND AIMS: Compared to other chronic diseases, patients with chronic liver disease (CLD) have significantly higher inpatient mortality; accurate models to predict inpatient mortality are lacking. Serum lactate (LA) may be elevated in patients with CLD due to both tissue hypoperfusion as well as decreased LA clearance. We hypothesized that a parsimonious model consisting of Model for End-Stage Liver Disease (MELD) and LA at admission may predict inpatient mortality in patients with CLD. APPROACH AND RESULTS: We examined all patients with CLD in two large and diverse health care systems in Texas (North Texas [NTX] and Central Texas [CTX]) between 2010 and 2015. We developed (n = 3,588) and validated (n = 1,804) a model containing MELD and LA measured at the time of hospitalization. We further validated the model in a second cohort of 14 tertiary care hepatology centers that prospectively enrolled nonelective hospitalized patients with cirrhosis (n = 726). MELD-LA was an excellent predictor of inpatient mortality in development (concordance statistic [C-statistic] = 0.81, 95% confidence interval [CI] 0.79-0.82) and both validation cohorts (CTX cohort, C-statistic = 0.85, 95% CI 0.78-0.87; multicenter cohort C-statistic = 0.82, 95% CI 0.74-0.88). MELD-LA performed especially well in patients with specific cirrhosis diagnoses (C-statistic = 0.84, 95% CI 0.81-0.86) or sepsis (C-statistic = 0.80, 95% CI 0.78-0.82). For MELD score 25, inpatient mortality rates were 11.2% (LA = 1 mmol/L), 19.4% (LA = 3 mmol/L), 34.3% (LA = 5 mmol/L), and >50% (LA > 8 mmol/L). A linear increase (P < 0.01) was seen in MELD-LA and increasing number of organ failures. Overall, use of MELD-LA improved the risk prediction in 23.5% of patients compared to MELD alone. CONCLUSIONS: MELD-LA (bswh.md/meldla) is an early and objective predictor of inpatient mortality and may serve as a model for risk assessment and guide therapeutic options.

Role of B-Type Natriuretic Peptide in Predicting In-Hospital Outcomes in Acute Exacerbation of Chronic Obstructive Pulmonary Disease With Preserved Left Ventricular Function: A 5-Year Retrospective Analysis.

BACKGROUND: The role of B-type natriuretic peptide (BNP) is less understood in the risk stratification of patients with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD), especially in patients with normal left ventricular ejection fraction (LVEF). METHODS: This retrospective study from 2008 to 2012 evaluated all adult patients with AECOPD having BNP levels and available echocardiographic data demonstrating LVEF ≥40%. The patients were divided into groups 1, 2, and 3 with BNP ≤ 100, 101 to 500, and ≥501 pg/mL, respectively. A subgroup analysis was performed for patients without renal dysfunction. Outcomes included need for and duration of noninvasive ventilation (NIV) and mechanical ventilation (MV), NIV failure, reintubation at 48 hours, intensive care unit (ICU) and total length of stay (LOS), and in-hospital mortality. Two-tailed P < .05 was considered statistically significant. RESULTS: Of the total 1145 patients, 550 (48.0%) met our inclusion criteria (age 65.1 ± 12.2 years; 271 [49.3%] males). Groups 1, 2, and 3 had 214, 216, and 120 patients each, respectively, with higher comorbidities and worse biventricular function in higher categories. Higher BNP values were associated with higher MV use, NIV failure, MV duration, and ICU and total LOS. On multivariate analysis, BNP was an independent predictor of higher NIV and MV use, NIV failure, NIV and MV duration, and total LOS in groups 2 and 3 compared to group 1. B-type natriuretic peptide continued to demonstrate positive correlation with NIV and MV duration and ICU and total LOS independent of renal function in a subgroup analysis. CONCLUSION: Elevated admission BNP in patients with AECOPD and normal LVEF is associated with worse in-hospital outcomes and can be used to risk-stratify these patients.

Effect of Compliance With a Nurse-Led Intensive Care Unit Checklist on Clinical Outcomes in Mechanically and Nonmechanically Ventilated Patients.

BACKGROUND: Use of checklists brings about improvements in a variety of patient outcomes. Nevertheless, whether compliance with a nurse-led intensive care unit (ICU) checklist produces the same effect is currently unknown. METHODS: This is a retrospective analysis of data obtained during the implementation of a quality improvement project consisting of the utilization of a nurse-led ICU checklist. A consecutive series of checklists obtained from patients admitted in our ICU during 7 consecutive months were included. The ICU stay, hospital stay, and ventilator stay were compared between patients whose practitioners completed or did not complete the checklist. Variables were analyzed using Mann-Whitney U tests for continuous variables and Fisher exact tests for categorical variables. A 2-tailed P < .05 was considered statistically significant. RESULTS: One thousand checklists, corresponding to 346 eligible patients, were collected over 7 months. Mechanical ventilation was used in 203 (59%) patients. Completed checklists were observed for 37.6% (n = 130) of all patients and 38.9% (n = 79) of mechanically ventilated patients. After adjusting for age, Acute Physiology and Chronic Health Evaluation II (APACHE II), body mass index, reason for admission, and type of ICU, completion of the checklist was associated with a 20% increase in the number of days in the ICU compared with the group with incomplete lists. In mechanically ventilated patients, completion of the checklist was associated with a 31% increase in hospital length of stay, a 34% increase in the number of ICU days, and a 32% increase in mechanical ventilation days. CONCLUSION: Compliance with completion of a nurse-led ICU checklist was associated with prolonged ICU stay, hospital stay, and ventilator stay.

Fatal case of tension pneumothorax and subcutaneous emphysema after open surgical tracheostomy.

Tracheostomy tube placement remains one of the most commonly performed procedures in the intensive care unit. Its utilization permits ventilation in patients with severe compromise of the airway patency as well as facilitation of liberation of mechanical ventilation in patients with prolonged ventilatory needs. Despite its frequent use, the tracheostomy procedure, whether performed surgically or percutaneously, is not free of severe, and, in some cases devastating, complications. In fact, severe adverse events, such as pneumomediastinum, pneumothorax, hemorrhage, infections, and, occasionally, death, have been described. We report a case of a surgical tracheostomy complicated with fatal tension pneumothorax and subcutaneous emphysema secondary to an iatrogenic posterior tracheal wall laceration. This complication is barely seen in usual practice, and its recognition and aggressive therapy may avoid fatal outcomes.

Enhancing the awakening to family engagement bundle with music therapy.

Survivors of prolonged intensive care unit (ICU) admissions may present undesirable long-term outcomes. In particular, physical impairment and cognitive dysfunction have both been described in patients surviving episodes requiring mechanical ventilation and sedation. One of the strategies to prevent the aforementioned outcomes involves the implementation of a bundle composed by: (1) Spontaneous awakening trial; (2) Spontaneous breathing trial; (3) Choosing proper sedation strategies; (4) Delirium detection and management; (5) Early ICU mobility; and (6) Family engagement (ABCDEF bundle). The components of this bundle contribute in shortening length of stay on mechanical ventilation and reducing incidence of delirium. Since the first description of the ABCDEF bundle, other relevant therapeutic factors have been proposed, such as introducing music therapy. This mini-review describes the current evidence supporting the use of the ABCDEF bundle, as well as current knowledge on the implementation of music therapy.

Sepsis mortality and ICU length of stay after the implementation of an intensive care team in the emergency department.

Emergency department patient boarding is associated with hospital mortality and increased hospital length of stay. The objective of the present study is to describe the impact of deploying an Intensive Care team in the ED and its association with sepsis mortality and ICU length of stay. Patients admitted to ICU through the ED with an ICD-10 CM diagnosis of sepsis were included. Preintervention and postintervention phases included 4 and 15 months, respectively. Sepsis time zero, SEP-1 compliance, and lag time from time zero to antibiotic administration were compared. Outcomes of interest were mortality and ICU LOS. 1021 septic patients were included. Sixty-six percent fulfilled compliance with 3 h SEP-1 bundle. Lag time from time zero to antibiotic administration was 75 min. Multivariate analysis showed no association between ICU team in the ED and hospital mortality (Log OR 0.94, CI 0.67-1.34; p = 0.73). The ICU team in the ED was associated with prolonged ICU LOS (Log OR 1.21, CI 1.13-1.30; p < 0.01). Septic shock and ED boarding time were associated with prolonged ICU LOS. Compliance with SEP-1 bundle was associated with its reduction. Implementation of an ICU team in the ED for the treatment of septic patients during high volume hospitalizations is not associated with a reduction of mortality or ICU LOS.

Daily Oxygenation Support for Patients Hospitalized With SARS-CoV-2 in an Integrated Health System.

BACKGROUND: Many COVID-19 studies are constructed to report hospitalization outcomes, with few large multi-center population-based reports on the time course of intra-hospitalization characteristics, including daily oxygenation support requirements. Comprehensive epidemiologic profiles of oxygenation methods used by day and by week during hospitalization across all severities are important to illustrate the clinical and economic burden of COVID-19 hospitalizations. METHODS: This was a retrospective, multi-center observational cohort study of 15,361 consecutive hospitalizations of patients with COVID-19 at 25 adult acute care hospitals in Texas participating in the Society of Critical Care Medicine Discovery Viral Respiratory Illness Universal Study COVID-19 registry. RESULTS: At initial hospitalization, the majority required nasal cannula (44.0%), with an increasing proportion of invasive mechanical ventilation in the first week and particularly the weeks to follow. After 4 weeks of acute illness, 69.9% of adults hospitalized with COVID-19 required intermediate (eg, high-flow nasal cannula, noninvasive ventilation) or advanced respiratory support (ie, invasive mechanical ventilation), with similar proportions that extended to hospitalizations that lasted ≥ 6 weeks. CONCLUSIONS: Data representation of intra-hospital processes of care drawn from hospitals with varied size, teaching and trauma designations is important to presenting a balanced perspective of care delivery mechanisms employed, such as daily oxygen method utilization.

Environmental improvements brought by the legal interventions in the homes of poorly controlled inner-city adult asthmatic patients: a proof-of-concept study.

OBJECTIVES: Domestic contamination with mold, cockroaches, rodents, and dust worsens asthma severity. This violates warranty of habitability laws in most of the states, but patients often find it beyond their means to remedy their housing situation. We aimed to study the effect of a medical-legal collaborative intervention to force landlords into providing better living conditions for patients with poorly controlled asthma. METHODS: We retrospectively studied charts of adult patients aged 18 years or older with poorly controlled asthma (moderate or severe persistent) despite maximum medical therapy. Additionally, patients had self-reported domestic allergen exposures such as mold, cockroaches, mice or rats, and dust. The patients received legal assistance to improve their domestic environments, including fixing leaks, exterminating pests, or providing a different apartment. Post-intervention change in peak expiratory flow rate (PEFR), asthma severity class, medications, emergency department (ED) visits, hospitalizations, and requirement for systemic steroids for symptom control was assessed. RESULTS: Data were available for 12 patients (9-12 months pre-intervention and 6-12 months post-intervention). Analysis of paired data revealed that mean PEFR rose by 38.6 LPM (95% CI: 9.9-67.3; p = .014). The number of ED visits and hospital admissions declined from 22 ED visits and 11 admissions to 2 ED visits and 1 admission (91% reduction), respectively. Of the 11 patients requiring systemic steroids, only three required these post-intervention. All patients had reductions in the dose and/or number of medications. During post-intervention, 11 (91.7%) patients dropped ≥2 classes in asthma severity. CONCLUSIONS: Medical-legal collaboration is highly effective in improving the control of inner-city asthmatics by effecting improvements in the domestic environment.

The ICU follow-up clinic: a new paradigm for intensivists.

Over the last 15 years the management of patients admitted in the ICU has changed dramatically. A growing number of well designed randomized controlled studies have been published, resulting in improved medical care and reduction of short-term morbidity and mortality. Despite these important achievements, little attention has been placed on the long-term complications of subjects discharged from the ICU. This review will focus on the most common long-term outcomes post-ICU admission, and will emphasize the importance of developing ICU clinics to provide comprehensive care to ICU survivors. We also describe our experience regarding the organization, functioning, and limitations for the development of our post-ICU clinic.

Implementation of a medical intensive care team in the emergency department of a tertiary medical center in the USA.

OBJECTIVE: Critically ill patients boarding in the ED have higher mortality rates. Several strategies have been implemented to deliver care to boarding patients. Our institution opted for a strategy consisting on deploying an Intensive Care team in the ED. This article reports outcomes before-and-after implementation of that team. METHODS: On November 2020, a Medical Intensive Care Team was deployed in the ED. The team performed consultations for ICU patients boarding in the ED. A retrospective analysis of critically ill patients arriving to the ED before-and-after team implementation was performed. Outcome data were reviewed. Direct hospitalization costs per patient, and direct costs per department were assessed. Wilcoxon rank sum and Chisq-test were utilized to compare differences pre- and post-implementation. Multivariate analyses to model outcomes toward pre- and post-implementation and other variables were performed. RESULTS: 1,828 and 3,272 patients were included in the pre- and post-intervention groups. ICU LOS (days) pre- and post-intervention were 3 (1,6) and 3 (1,6), respectively (p = 0.41). ICU readmission rates were 6.7% pre-intervention and 7.4% post-intervention (p = 0.37). Total direct costs were US$ 19,928 (11,006, 37,815) and US$ 15,795 (9016, 28,993), respectively (p < 0.01). Multivariate analysis showed no association between team deployment and ICU LOS or readmission. However, there was association between its implementation and hospitalization cost reduction per patient of US$ 7,171. CONCLUSION: The implementation of a Medical Intensive Care team in the ED is not associated with a reduction of ICU LOS or ICU readmission. Nevertheless, its implementation is associated with a reduction of hospitalization costs.

Critically ill patients boarding in the emergency department and the association with intensive care unit length of stay and hospital mortality during the COVID-19 pandemic.

Boarding of critically ill patients in the emergency department (ED) has been associated with mortality and intensive care unit (ICU) length of stay (LOS). This study evaluated whether boarding time in the ED was associated with those outcomes. A retrospective analysis of patients admitted through the ED to the ICU was performed. Information on demographics, severity score, and diagnoses was collected. The continuous primary endpoint of ICU LOS was fitted by a log normal model on covariates, including ED LOS. A multivariate log normal model was also used to model covariates toward ICU LOS. The binary patient expiration status was modeled by univariate and multivariate logistic regressions to evaluate the association of mortality with covariates. ED LOS was not associated with ICU LOS (correlation with an estimate of -0.02 ± 0.06 [SE], P = 0.76). ED LOS was not associated with hospital mortality (estimate correlation of -0.07 ± 0.07 [SE], P = 0.33). Body mass index, APACHE IV score, mechanical ventilation, and diagnosis of COVID-19 were associated with LOS. Age, APACHE IV score, mechanical ventilation, sepsis, and COVID-19 were associated with mortality. In conclusion, ED LOS is not associated with ICU LOS or hospital mortality. These findings may be related to early therapeutic interventions applied in the ED.

Evaluation of aerosolized epoprostenol for hypoxemia in non-intubated patients with coronavirus disease 2019.

OBJECTIVES: Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) frequently present with a febrile illness that may progress to pneumonia and hypoxic respiratory failure. Aerosolized epoprostenol (aEPO) has been evaluated in patients with acute respiratory distress syndrome and refractory hypoxemia. A paucity of literature has assessed the impact of aEPO in patients with SARS-CoV-2 receiving oxygen support with high flow nasal cannula (HFNC). The objective of this study was to evaluate whether aEPO added to HFNC prevents intubation and/or prolong time to intubation compared to controls only treated with HFNC, guided by oxygen saturation goals. METHODS: This was a single-center, retrospective study of adult patients infected with coronavirus 2019 (COVID-19) and admitted to the medical intensive care unit. A total of 60 patients were included. Thirty patients were included in the treatment, and 30 in the control group, respectively. Among patients included in the treatment group, response to therapy was assessed. The need for mechanical ventilation and hospital mortality between responders vs. non-responders was evaluated. RESULTS: The primary outcome of mechanical ventilation was not statistically different between groups. Time from HFNC initiation to intubation was significantly prolonged in the treatment group compared to the control group (5.7 days vs. 2.3 days, P = 0.001). There was no statistically significant difference between groups in mortality or length of stay. Patients deemed responders to aEPO had a lower rate of mechanical ventilation (50% vs 88%, P = 0.025) and mortality (21% vs 63%, P = 0.024), compared with non-responders. CONCLUSION: The utilization of aEPO in COVID-19 patients treated with HFNC is not associated with a reduction in the rate of mechanical ventilation. Nevertheless, the application of this strategy may prolong the time to invasive mechanical ventilation, without affecting other clinical outcomes.

A 55-Year-Old Woman With Frequent Pulmonary Exacerbations and Endobronchial Lesions.

CASE PRESENTATION: A 55-year-old woman with COPD, heart failure with preserved ejection fraction (congestive heart failure), diabetes mellitus, and hypertension presented with baseline dyspnea at rest that had worsened over the last week. She reported associated runny nose, congestion, and cough productive of green sputum. She smoked six cigarettes per day and denied alcohol, drugs, or occupational exposure. She was admitted and initiated on treatment for acute exacerbation of COPD; however, her condition did not improve with steroid, ceftriaxone, and nebulized albuterol and budesonide treatments. She had been diagnosed with asthma and COPD without ever undergoing pulmonary function testing. She presented 11 times to the ED with six hospital admissions in the last 1.5 years for worsening dyspnea at rest, wheezing, and lower extremity edema deemed secondary to exacerbation of her COPD or congestive heart failure. She reported medication compliance, which included fluticasone-vilanterol, tiotropium bromide, and furosemide. She repeatedly demonstrated mild vascular congestion on imaging without hyperinflation, a normal to mildly elevated brain natriuretic peptide (<10 to 200 pg/mL), and dyspnea without hypoxia. She was treated normally for both COPD and congestive heart failure exacerbations simultaneously with methylprednisolone, albuterol, and furosemide with rapid improvement over the course of 1 to 2 days. No significant improvement was noted with steroid therapy, despite receiving them as an inpatient and outpatient. At the time of discharge, her symptoms would be at her baseline.

Echocardiography, 6-minute walk distance, and distance-saturation product as predictors of pulmonary arterial hypertension in idiopathic pulmonary fibrosis.

BACKGROUND: Pulmonary arterial hypertension (PAH) is frequently seen in patients with idiopathic pulmonary fibrosis (IPF). We sought to examine the performance of echocardiography, 6-min walk test (6MWT) distance, distance-saturation product (DSP), and pulse oximetry (SpO2) in detecting underlying PAH in IPF. METHODS: 626 lung transplanted patients from February 1990 to December 2007 were considered. Subjects with pre-transplant diagnosis of IPF were evaluated. Based on findings in pre-transplant right heart catheterization, the presence or absence of PAH was recorded. Right-ventricle systolic pressure, 6MWT distance, DSP, and lowest SpO2 during 6MWT were compared in PAH and non-PAH groups. Receiver operating characteristic curves for each variable to assess prediction of PAH were constructed. RESULTS: 131 patients were transplanted due to IPF. Of these 131 patients, 58 (44%) were eligible. PAH was diagnosed by right heart catheterization in 25 (43%) of 58 eligible patients. The mean pulmonary arterial pressure in PAH patients was 33 mm Hg, and 19 mm Hg in non-PAH patients (P = .001). 6MWT distance was 321 m in the PAH group, and 346 m in the non-PAH one (P = .38). DSP in PAH subjects was 272 meters% and 286 meters% in those with no PAH (P = .57). The lowest SpO2 in the PAH and non-PAH groups were 84% and 82%, respectively (P = .38). The diagnostic accuracy of the echocardiography exceeded that of the other variables (area under the curve 0.72). CONCLUSIONS: Right-ventricle systolic pressure measured by echocardiography, by 6MWT distance, by DSP, or by SpO2 performs poorly in detecting PAH in IPF. Measured by right heart catheterization, right-ventricle systolic pressure performs better to predict PAH in IPF.

Anemia post-lung transplantation: mechanisms and approach to diagnosis.

Anemia is a common complication in post-lung transplant recipients. Although its mechanism is often multifactorial, clinicians should investigate an eventual underlying explanation to provide the best care. Among the reasons for anemia in lung transplant recipients, blood loss should be thought within the first few days after surgery. Later on, immune-mediated mechanisms, microangiopathic hemolytic anemia and reduction in red blood cell production mediated by viruses, drugs and infiltrative disorders prevail. This article reviews the mechanisms of anemia in post-lung transplant patients and provides an algorithm towards its approach.

The acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a prevalent cause of acute respiratory failure with high rates of mortality, as well as short- and long-term complications, such as physical and cognitive impairment. Therefore, early recognition of this syndrome and application of well-demonstrated therapeutic interventions are essential to change the natural course of this entity and bring about positive clinical outcomes. In this article, we review updated concepts in ARDS. Specifically, we discuss the current definition of ARDS, its risk factors, and the evidence supporting ventilation management, adjunctive therapies, and interventions required in refractory hypoxemia.

Inhaled epoprostenol utilization pattern after implementation of an administration policy.

Epoprostenol, a pulmonary vasodilator, is used to reduce pulmonary artery pressure. Its inhaled administration results in ventilation and perfusion matching with oxygenation improvement. Epoprostenol is used as treatment for various conditions, particularly acute respiratory distress syndrome (ARDS) and pulmonary arterial hypertension. In 2018, Baylor University Medical Center implemented a policy for inhaled epoprostenol utilization aimed at standardizing clinical practice. This study analyzed epoprostenol utilization patterns in patients with ARDS after implementation of this administration policy. Drug responders and nonresponders were compared for clinical outcomes and physiologic changes before and after use, and policy compliance was evaluated. Of 79 eligible patients, 30 fulfilled inclusion criteria: 14 (47%) had ARDS and 16 (53%) had non-ARDS. In all patients with ARDS, epoprostenol was a second rescue agent after neuromuscular blockade, prone positioning, corticosteroids, and extracorporeal membrane oxygenation. Epoprostenol was associated with statistically significant improvement of oxygenation before and after utilization in patients with ARDS (ratio of arterial oxygen partial pressure to fractional inspired oxygen 70 vs 140, respectively; P = 0.04). Overall, 10 (71%) ARDS patients were epoprostenol responders; 9 (56%) were deemed responders among subjects with non-ARDS. Comparison of outcomes between responders and nonresponders showed no statistically significant variations. Policy compliance was obtained in 24 (80%) patients.

The dynamic treatment of SARS-CoV-2 disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or novel coronavirus disease 2019 (COVID-19) emerged from China in December 2019 and progressed to become a global pandemic. Our understanding of its pathophysiology and potential management was initially extrapolated from previous epidemics of coronaviruses like SARS and MERS. SARS-CoV-2 is asymptomatic or minimally symptomatic in more than 80% of patients and requires no additional management; however, the remaining patients progress to pneumonia and hypoxemia with ranging severity, including a smaller group that requires intensive care unit admission. To date, there are no approved treatments for SARS-CoV-2, and current management is focused on supplemental oxygen and supportive care. The antiviral medication remdesivir recently received emergency use authorization by the US Food and Drug Administration for patients with severe disease. Multiple clinical trials evaluating different treatment modalities such as antivirals, immunomodulators, convalescent plasma, and monoclonal antibodies, among others, are still ongoing. We believe that patients present with clinical phenotypes that correlate with the spectrum of disease. Each phenotype may benefit from one or multiple interventions. We discuss treatments under evaluation in clinical trials and their potential application based on clinical phenotype presentation.

Detection of upper airway obstruction with spirometry results and the flow-volume loop: a comparison of quantitative and visual inspection criteria.

BACKGROUND: There are important gaps in our understanding of the epidemiology and diagnosis of upper-airway obstruction. METHODS: We examined the diagnostic value of several criteria for predicting upper-airway obstruction, and we measured the frequency of detecting upper-airway obstruction via quantitative and visual assessment of flow-volume loops. We studied 4 quantitative and 3 visual criteria for their ability to detect upper-airway obstruction. The quantitative criteria were: ratio of forced expiratory volume in the first second (FEV(1)) to maximum expiratory flow (MEF) > 10 mL/L/min; ratio of the flow at the mid-point of the forced expiratory maneuver (MEF(50%)) to the flow at the mid-point of the forced inspiratory maneuver (MIF(50%)) < 0.3 or > 1; MIF(50%) < 100 L/min; and FEV(1)/FEV(0.5) > 1.5. The visual criteria were: presence of a plateau; biphasic shape; and oscillations. The accepted standard tests for diagnosing upper-airway obstruction were bronchoscopy, laryngoscopy, and chest or neck computed tomogram. We considered 979 consecutive flow-volume loops from the Cleveland Clinic's pulmonary function laboratory. We calculated the sensitivity, specificity, and positive and negative predictive values of the individual criteria and an aggregate criterion for predicting upper-airway obstruction. RESULTS: We excluded 504 flow-volume loops because the workups for those patients did not include any of the accepted standard tests for diagnosing upper-airway obstruction, so there were 475 eligible flow-volume loops (48.6% of the 979 loops considered). Thirty-six (7.5%) of the 475 workups that included an accepted standard test reported a cause of upper-airway obstruction. The aggregate sensitivity for detecting upper-airway obstruction was 69.4%. Receiver-operating-curve analysis found that the individual criteria had poor diagnostic performance (area under the curve < 0.522) but that a newly proposed aggregate criterion performed better (area under the curve 0.605). CONCLUSIONS: The prevalence of reported upper-airway obstruction was 7.5%. The quantitative criteria showed low sensitivity for detecting upper-airway obstruction but exceeded that of visual criteria. The aggregate criterion increased the sensitivity to 69.4%, which suggests the need for additional criteria to help predict upper-airway obstruction.