Low-Dose Nitric Oxide Therapy for Persistent Pulmonary Hypertension of the Newborn

Clark, Reese H.; Kueser, T J; Walker, M W; Southgate, W. Michael; Huckaby, Jeryl; Pérez, José A.; Roy, Beverly J; Keszler, Martin; Kinsella, John P.

doi:10.1056/nejm200002173420704

Cited by 662 publications

(363 citation statements)

References 30 publications

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“…Inhaled nitric oxide decreases the need for ECMO in patients with PPHN, 3,4,6,7 and following its approval for clinical use, the number of patients entered in the national registry of ECMO patients with a diagnosis of sepsis, idiopathic PPHN or meconium aspiration declined by about 50%. 16 In a randomized trial, improvement in oxygenation occurred more frequently in infants with PPHN treated with HFOV plus iNO as compared to infants treated with either HFOV or iNO alone.…”

Section: Discussionmentioning

confidence: 99%

“…2 Most often PPHN occurs in infants with meconium aspiration syndrome (34 to 51%), pneumonia/sepsis (20 to 23%), idiopathic PPHN (17 to 25%), congenital diaphragmatic hernia (10 to 15%) or respiratory distress syndrome (9 to 12%). 3,4 Prior to the introduction, in the late 1990s, of inhaled nitric oxide (iNO), therapies for PPHN included induced alkalosis, supplemental oxygen, mechanical ventilation and neuromuscular blockade; and patients who failed to respond to these measures were treated with extracorporeal membrane oxygenation (ECMO). 5 iNO has been shown to reduce the need for ECMO in term and near-term neonates with pulmonary hypertension.…”

Section: Introductionmentioning

confidence: 99%

“…5 iNO has been shown to reduce the need for ECMO in term and near-term neonates with pulmonary hypertension. 3,4,6,7 High-frequency ventilation (HFV) has been used with increasing frequency for PPHN, 8 and when combined with iNO results in an acute rise in arterial oxygen saturation, 9 and reduces the likelihood of ECMO treatment. 10 Studies of iNO delivered by HFV have, to date, utilized high-frequency oscillatory ventilation (HFOV).…”

Section: Introductionmentioning

confidence: 99%

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Neonatal pulmonary hypertension treated with inhaled nitric oxide and high-frequency ventilation

2008

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Term and near-term infants with pulmonary hypertension are frequently treated with inhaled nitric oxide. This therapy can be delivered with highfrequency ventilation, but there has been limited study of the relative effectiveness of high-frequency jet ventilation and high-frequency oscillatory ventilation.Objective: To compare short-term clinical outcomes of neonates with pulmonary hypertension treated with inhaled nitric oxide plus either high-frequency jet ventilation or high-frequency oscillatory ventilation.Study Design: Study infants met the following criteria: X35 weeks gestation, respiratory failure with pulmonary hypertension, no congenital malformations and treatment in the first week of life with inhaled nitric oxide plus either high-frequency jet ventilation (n ¼ 22) or high-frequency oscillatory ventilation (n ¼ 43). Data were collected from medical records. Result:The jet ventilation and oscillatory ventilation groups were similar in terms of gestational age, but the jet ventilation group had less severe respiratory illness (that is, lower oxygenation index) just prior to initiation of the combination of nitric oxide and high-frequency ventilation. The jet ventilation group spent more hours on inhaled nitric oxide (71.4 versus 40.8; P ¼ 0.004) but was less likely to require extracorporeal membrane oxygenation (2(9%) versus 19(44%); P ¼ 0.004). No difference was found in the ages at which oxygen and high-frequency ventilation were discontinued. Keywords: persistent pulmonary hypertension; inhaled nitric oxide; hypoxic respiratory failure; high-frequency ventilation; high-frequency oscillatory ventilation; high-frequency jet ventilation Introduction Persistent pulmonary hypertension of the newborn (PPHN) refers to a lack of normal cardiopulmonary adaptation following delivery, 1 including persistence of the elevated pulmonary vascular resistance that is characteristic of fetuses. 2 Most often PPHN occurs in infants with meconium aspiration syndrome (34 to 51%), pneumonia/sepsis (20 to 23%), idiopathic PPHN (17 to 25%), congenital diaphragmatic hernia (10 to 15%) or respiratory distress syndrome (9 to 12%). 3,4 Prior to the introduction, in the late 1990s, of inhaled nitric oxide (iNO), therapies for PPHN included induced alkalosis, supplemental oxygen, mechanical ventilation and neuromuscular blockade; and patients who failed to respond to these measures were treated with extracorporeal membrane oxygenation (ECMO). 5 iNO has been shown to reduce the need for ECMO in term and near-term neonates with pulmonary hypertension. 3,4,6,7 High-frequency ventilation (HFV) has been used with increasing frequency for PPHN, 8 and when combined with iNO results in an acute rise in arterial oxygen saturation, 9 and reduces the likelihood of ECMO treatment. 10 Studies of iNO delivered by HFV have, to date, utilized high-frequency oscillatory ventilation (HFOV). However, since patients treated with high-frequency jet ventilation (HFJV), as compared to conventional ventilation, require lower peak pressures to achieve t...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Neonatal pulmonary hypertension treated with inhaled nitric oxide and high-frequency ventilation

2008

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“…No differences were seen in length of hospital stay, days on ventilator, and chronic lung disease. The Clinical Inhaled Nitric Oxide research group (CINRGI) 10 enrolled infants with PPHN (n ¼ 186) and showed similar results, with a reduction in need for ECMO from 57 to 31% (P<0.001). The primary end point in the previous three trials was a reduction in need for ECMO since, during these trials, ECMO was considered a standard treatment for PPHN not responding to conventional treatments.…”

Section: Nitric Oxide In Term Infantsmentioning

confidence: 90%

“…The need for ECMO before availability of NO was 36 to 64% when the Oxygenation Index (OI) was 24 and 44, respectively. 10,11 Four randomized, placebo controlled clinical trials have been published in near term babies with hypoxemic respiratory failure. All of them were designed to show a reduction in death and/or the need for ECMO in these infants.…”

Section: Nitric Oxide In Term Infantsmentioning

confidence: 99%

Inhaled nitric oxide in term and preterm infants

Sekar

2006

J Perinatol

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Nitric oxide (NO) is a gas that has potent vasodilator properties. It can be administered via inhalation in situations where NO production is impaired and results in vasodilatation of the pulmonary capillaries. In term infants, the administration of inhaled NO, at a dose of 20 parts per million, may reduce the need for extracorporeal membrane oxygenation by reducing pulmonary vascular resistance and improving oxygenation. Inhaled NO is an approved therapy in term babies with severe hypoxemic respiratory failure. In premature infants, inhaled NO may increase bleeding time and decrease platelet aggregation resulting in an increased risk for intraventricular hemorrhage. Early administration of inhaled NO may also potentially decrease the risk for developing chronic lung disease in premature infants. However, since studies show conflicting results, inhaled NO should only be used in premature neonates following investigational review board approved protocols.

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Antidepressant Use Late in Pregnancy and Risk of Persistent Pulmonary Hypertension of the Newborn

Huybrechts

Bateman

Palmsten

et al. 2015

JAMA

223

125

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IMPORTANCEThe association between selective serotonin reuptake inhibitor (SSRI) antidepressant use during pregnancy and risk of persistent pulmonary hypertension of the newborn (PPHN) has been controversial since the US Food and Drug Administration issued a public health advisory in 2006. OBJECTIVE To examine the risk of PPHN associated with exposure to different antidepressant medication classes late in pregnancy. DESIGN AND SETTING Cohort study nested in the 2000-2010 Medicaid Analytic eXtract for 46 US states and Washington, DC. Last follow-up date was December 31, 2010.PARTICIPANTS A total of 3 789 330 pregnant women enrolled in Medicaid from 2 months or fewer after the date of last menstrual period through at least 1 month after delivery. The source cohort was restricted to women with a depression diagnosis and logistic regression analysis with propensity score adjustment applied to control for potential confounders.EXPOSURES FOR OBSERVATIONAL STUDIES SSRI and non-SSRI monotherapy use during the 90 days before delivery vs no use. MAIN OUTCOMES AND MEASURESRecorded diagnosis of PPHN during the first 30 days after delivery.RESULTS A total of 128 950 women (3.4%) filled at least 1 prescription for antidepressants late in pregnancy: 102 179 (2.7%) used an SSRI and 26 771 (0.7%) a non-SSRI. Overall, 7630 infants not exposed to antidepressants were diagnosed with PPHN (20.8; 95% CI, 20.4-21.3 per 10 000 births) compared with 322 infants exposed to SSRIs (31.5; 95% CI, 28.3-35.2 per 10 000 births), and 78 infants exposed to non-SSRIs (29.1; 95% CI, 23.3-36.4 per 10 000 births). Associations between antidepressant use and PPHN were attenuated with increasing levels of confounding adjustment. For SSRIs, odds ratios were 1.51 (95% CI, 1.35-1.69) unadjusted and 1.10 (95% CI, 0.94-1.29) after restricting to women with depression and adjusting for the high-dimensional propensity score. For non-SSRIs, the odds ratios were 1.40 (95% CI, 1.12-1.75) and 1.02 (95% CI, 0.77-1.35), respectively. Upon restriction of the outcome to primary PPHN, the adjusted odds ratio for SSRIs was 1.28 (95% CI, 1.01-1.64) and for non-SSRIs 1.14 (95% CI, 0.74-1.74). CONCLUSIONS AND RELEVANCEEvidence from this large study of publicly insured pregnant women may be consistent with a potential increased risk of PPHN associated with maternal use of SSRIs in late pregnancy. However, the absolute risk was small, and the risk increase appears more modest than suggested in previous studies.

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Low-Dose Nitric Oxide Therapy for Persistent Pulmonary Hypertension of the Newborn

Abstract: Inhaled nitric oxide reduces the extent to which extracorporeal membrane oxygenation is needed in neonates with hypoxemic respiratory failure and pulmonary hypertension.

Cited by 662 publications

References 30 publications

Neonatal pulmonary hypertension treated with inhaled nitric oxide and high-frequency ventilation

Neonatal pulmonary hypertension treated with inhaled nitric oxide and high-frequency ventilation

Inhaled nitric oxide in term and preterm infants

Antidepressant Use Late in Pregnancy and Risk of Persistent Pulmonary Hypertension of the Newborn

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