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  • Title: Evaluation of Variability in Inhaled Nitric Oxide Use and Pulmonary Hypertension in Patients With Congenital Diaphragmatic Hernia.
    Author: Putnam LR, Tsao K, Morini F, Lally PA, Miller CC, Lally KP, Harting MT, Congenital Diaphragmatic Hernia Study Group.
    Journal: JAMA Pediatr; 2016 Dec 01; 170(12):1188-1194. PubMed ID: 27723858.
    Abstract:
    IMPORTANCE: Inhaled nitric oxide (iNO) is an expensive, commonly used therapy among patients with congenital diaphragmatic hernia (CDH); however, data to support its ongoing use in this patient population are lacking. OBJECTIVE: To describe the spectrum of iNO use among patients with CDH and its association with pulmonary hypertension (pHTN) and mortality. DESIGN, SETTING, AND PARTICIPANTS: A review was conducted of prospectively collected patient data in the Congenital Diaphragmatic Hernia Study Group registry between January 1, 2007, and December 31, 2014, from 70 participating centers in 13 countries. A total of 3367 newborn infants diagnosed with CDH and entered into the registry were reviewed. On the basis of echocardiogram data, pHTN was defined as right ventricular systolic pressure greater than or equal to two-thirds of the systemic systolic pressure. Propensity score and regression analyses were performed. INTERVENTION: Use of iNO. MAIN OUTCOMES AND MEASURES: Variability in iNO use and its association with pHTN and mortality. These outcomes were formulated prior to data evaluation. RESULTS: Sixty-eight (97.1%) centers used iNO. Of 3367 patients with CDH (1366 [40.6%] females; median estimated gestational age, 38 weeks; range, 23-42 weeks), a total of 2047 (60.8%) received iNO; the mean percentage of those receiving iNO per center was 62.3% (range, 0%-100%). Median iNO dose and duration were 20 (range, 0.1-80) ppm and 8 (range, 0-100) days. Of the 2174 infants with pHTN, 1613 infants (74.2%) received iNO. Of the 943 infants without pHTN, 343 infants (36.4%) were treated with iNO. Based on propensity score analysis incorporating 10 clinically relevant variables, iNO use was significantly associated with increased mortality (average treatment effect on the treated: 0.15; 95% CI, 0.10-0.20). CONCLUSIONS AND RELEVANCE: Inhaled nitric oxide use is common but highly variable among centers, and 36% of patients without pHTN received iNO therapy. Based on data from 70 centers, iNO use in patients with CDH may be associated with increased mortality. Future efforts should be directed toward data-driven standardization of iNO use to ensure cost-effective practices.
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