Jeffrey A Kline1, Michael A Puskarich2, Alan E Jones3, Ronald A Mastouri4, Cassandra L Hall5, Anthony Perkins6, Emily E Gundert7, Tim Lahm8. 1. Indiana University School of Medicine, Dept. of Emergency Medicine, USA. Electronic address: jefkline@iu.edu. 2. Department of Emergency Medicine, Hennepin County Medical Center, USA. 3. Department of Emergency Medicine, University of Mississippi Medical Center, USA. 4. Indiana University School of Medicine, Department of Medicine, Division of Cardiology, USA. 5. Indiana University School of Medicine, Dept. of Emergency Medicine, USA. 6. Indiana University Center for Health Innovation and Implementation Science, Indiana Clinical and Translational Sciences Institute, USA. 7. Department of Emergency Medicine, University of Texas Southwestern, USA. 8. Division of Pulmonary, Allergy, Critical Care, Occupational and Sleep Medicine, Indiana University School of Medicine, USA.
Abstract
OBJECTIVE: To test the hypothesis that adjunctive inhaled NO would improve RV function and viability in acute PE. METHODS: This was a randomized, placebo-controlled, double blind trial conducted at four academic hospitals. Eligible patients had acute PE without systemic arterial hypotension but had RV dysfunction and a treatment plan of standard anticoagulation. Subjects received either oxygen plus 50 parts per million nitrogen (placebo) or oxygen plus 50 ppm NO for 24 h. The primary composite endpoint required a normal RV on echocardiography and a plasma troponin T concentration <14 pg/mL. The secondary endpoint required a blood brain natriuretic peptide concentration <90 pg/mL and a Borg dyspnea score ≤ 2. The sample size of N = 76 tested if 30% more patients treated with NO would achieve the primary endpoint with 80% power and alpha = 5%. RESULTS: We randomized 78 patients and after two withdrawals, 38 were treated per protocol in each group. Patients were well matched for baseline conditions. At 24 h, 5/38 (13%) of patients treated with placebo and 9/38 (24%) of patients treated with NO reached the primary endpoint (P = 0.375). The secondary endpoint was reached in 34% with placebo and 13% of the NO (P = 0.11). In a pre-planned post-hoc analysis, we examined how many patients with RV hypokinesis or dilation at enrollment resolved these abnormalities; 29% more patients treated with NO resolved both abnormalities at 24 h (P = 0.010, Cochrane's Q test). CONCLUSIONS: In patients with severe submassive PE, inhaled nitric oxide failed to increase the proportion of patients with a normal troponin and echocardiogram but increased the probability of eliminating RV hypokinesis and dilation on echocardiography. CLINICAL TRIAL REGISTRATION: NCT01939301.
RCT Entities:
OBJECTIVE: To test the hypothesis that adjunctive inhaled NO would improve RV function and viability in acute PE. METHODS: This was a randomized, placebo-controlled, double blind trial conducted at four academic hospitals. Eligible patients had acute PE without systemic arterial hypotension but had RV dysfunction and a treatment plan of standard anticoagulation. Subjects received either oxygen plus 50 parts per million nitrogen (placebo) or oxygen plus 50 ppm NO for 24 h. The primary composite endpoint required a normal RV on echocardiography and a plasma troponin T concentration <14 pg/mL. The secondary endpoint required a blood brain natriuretic peptide concentration <90 pg/mL and a Borg dyspnea score ≤ 2. The sample size of N = 76 tested if 30% more patients treated with NO would achieve the primary endpoint with 80% power and alpha = 5%. RESULTS: We randomized 78 patients and after two withdrawals, 38 were treated per protocol in each group. Patients were well matched for baseline conditions. At 24 h, 5/38 (13%) of patients treated with placebo and 9/38 (24%) of patients treated with NO reached the primary endpoint (P = 0.375). The secondary endpoint was reached in 34% with placebo and 13% of the NO (P = 0.11). In a pre-planned post-hoc analysis, we examined how many patients with RV hypokinesis or dilation at enrollment resolved these abnormalities; 29% more patients treated with NO resolved both abnormalities at 24 h (P = 0.010, Cochrane's Q test). CONCLUSIONS: In patients with severe submassive PE, inhaled nitric oxide failed to increase the proportion of patients with a normal troponin and echocardiogram but increased the probability of eliminating RV hypokinesis and dilation on echocardiography. CLINICAL TRIAL REGISTRATION: NCT01939301.
Authors: Anthony J Weekes; Denise N Fraga; Vitaliy Belyshev; William Bost; Christopher A Gardner; Nathaniel S O'Connell Journal: Crit Care Date: 2022-06-04 Impact factor: 19.334
Authors: Jeffrey A Kline; Michael A Puskarich; Jonathan W Pike; John Zagorski; Nathan J Alves Journal: Nitric Oxide Date: 2020-01-12 Impact factor: 4.427