Randomized, Placebo-controlled Trial of Inhaled Treprostinil for Patients at Risk for Acute Respiratory Distress Syndrome.

Rationale: Inhaled treprostinil may improve oxygenation and have additional antiinflammatory effects in early acute hypoxemic respiratory failure, potentially preventing or reducing the severity of acute respiratory distress syndrome (ARDS).Objectives: To determine whether administration of inhaled treprostinil to patients at risk for ARDS is feasible, safe, and efficacious.Methods: We performed a double-blind, placebo-controlled, single-center randomized pilot trial at a quaternary care academic medical center. Patients with acute hypoxemia due to pneumonia or signs of low-pressure pulmonary edema with a unilateral or bilateral infiltrate on chest imaging and a 4 L/min supplemental oxygen requirement not requiring positive pressure ventilation were evaluated. Randomized patients received study drug or placebo (2:1 ratio). Treatment was initiated at 6 breaths every 4 hours and titrated up to 12 breaths. Subjects were maintained on treatment for 7 days and then tapered off over a period of 4 days. Study drug was stopped if positive pressure ventilation was required (invasive or noninvasive).Results: Fourteen patients were enrolled over a period of 31 months. Baseline characteristics were not significantly different between treatment groups with respect to age, sex, race, Acute Physiologic Assessment and Chronic Health Evaluation score, lung injury prediction score, or baseline mean oxygen saturation as measured by pulse oximetry (SpO2):fraction of inspired oxygen (FiO2) ratio. Trends in daily baseline and 30-minute postdose SpO2:FiO2 ratio for all treatment points were not significantly different between placebo and treprostinil. Four patients required positive pressure ventilation in the treprostinil group versus one in the placebo group.Conclusions: Inhaled treprostinil administration is feasible in patients at risk for ARDS but was not associated with improvement in the SpO2:FiO2 ratio relative to placebo. Drug-associated adverse events were not severe nor unexpected based on the known adverse effect profile of inhaled treprostinil. The clinical benefit of this intervention is unclear at this time in the absence of larger studies.Clinical trial registered with Clinicaltrials.gov (NCT02370095).

A prognostic model for one-year mortality in patients requiring prolonged mechanical ventilation.

OBJECTIVE: A measure that identifies patients who are at high risk of mortality after prolonged ventilation will help physicians communicate prognoses to patients or surrogate decision makers. Our objective was to develop and validate a prognostic model for 1-yr mortality in patients ventilated for 21 days or more. DESIGN: The authors conducted a prospective cohort study. SETTING: The study took place at a university-based tertiary care hospital. PATIENTS: Three hundred consecutive medical, surgical, and trauma patients requiring mechanical ventilation for at least 21 days were prospectively enrolled. MEASUREMENTS AND MAIN RESULTS: Predictive variables were measured on day 21 of ventilation for the first 200 patients and entered into logistic regression models with 1-yr and 3-mo mortality as outcomes. Final models were validated using data from 100 subsequent patients. One-year mortality was 51% in the development set and 58% in the validation set. Independent predictors of mortality included requirement for vasopressors, hemodialysis, platelet count < or = 150 x 10(9)/L, and age > or = 50 yrs. Areas under the receiver operating characteristic curve for the development model and validation model were .82 (SE .03) and .82 (SE .05), respectively. The model had sensitivity of .42 (SE .12) and specificity of .99 (SE .01) for identifying patients who had > or = 90% risk of death at 1 yr. Observed mortality was highly consistent with both 3- and 12-mo predicted mortality. These four predictive variables can be used in a simple prognostic score that clearly identifies low-risk patients (no risk factors, 15% mortality) and high-risk patients (three or four risk factors, 97% mortality). CONCLUSIONS: Simple clinical variables measured on day 21 of mechanical ventilation can identify patients at highest and lowest risk of death from prolonged ventilation.