Evaluation of Variability in Inhaled Nitric Oxide Use and Pulmonary Hypertension in Patients With Congenital Diaphragmatic Hernia

Abstract

for the Congenital Diaphragmatic Hernia Study Group 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 PARTICIPANTSA 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 RELEVANCEInhaled 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.

PBX transcription factors drive pulmonary vascular adaptation to birth

“…We found that the right ventricle of Pbx1/2-CKO mice was hypertrophied by P10 compared with that observed in control mice, while the left ventricle was similar in thickness at that stage ( Figure 2J). Patients with CDH often have constricted pulmonary vessels that do not relax normally after birth (8)(9)(10)(11)40). We hypothesized that in the Pbx-mutant model of CDH, deletion of Pbx1/2 might impair the normal VSM relaxation process.…”

“…Infants with CDH and PH do not respond consistently to treatment with pulmonary vasodilating medications (8)(9)(10)(11)40). Identifying the basis of this variation has been a major challenge in CDH treatment.…”

“…The severity of these defects is highly variable among patients. Furthermore, the PH that frequently leads to lethality in patients with CDH is often not responsive to available medications (8)(9)(10)(11).…”

Challenge of determining true outcome of congenital diaphragmatic hernia

“…Echocardiography was carried out in 85% of patients, although the timing of the examination and findings are not presented. Treatment of pulmonary hypertension (mostly inhaled nitric oxide) was employed in 36% of the cohort and in only 48% antenatally diagnosed CDH which is less than the International CDH Study group registry data 2. Extracorporeal membrane oxygenation (ECMO) was only used in 4% which is also significantly lower than the registry 3.…”

Treatment Strategies for Congenital Diaphragmatic Hernia: Change Sometimes Comes Bearing Gifts

“…Most probably, physicians’ motivation to normalize physiology prevails when faced with a hypoxic ventilated CDH baby. As this treatment is hugely expensive and potentially harmful (35), further studies should aim to evaluate its efficacy and standardize its application in order to optimize patient outcomes and ensure cost-effective practices.…”