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Nitric Oxide. 2019 Mar 1;84:60-68. doi: 10.1016/j.niox.2019.01.006. Epub 2019 Jan 8.

Inhaled nitric oxide to treat intermediate risk pulmonary embolism: A multicenter randomized controlled trial.

Author information

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.

KEYWORDS:

Brain natriuretic peptide; Echocardiography; Heart failure; Nitric oxide; Pulmonary embolism; Pulmonary hypertension; Randomized trial; Troponin

PMID:
30633959
DOI:
10.1016/j.niox.2019.01.006

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