Guidelines for Rational and Cost-Effective Use of iNO Therapy in Term and Preterm Infants (original) (raw)
Related papers
Inhaled Nitric Oxide for Respiratory Failure in Preterm Infants
Neonatology, 2012
no significant effect of iNO on mortality or BPD. Three studies with routine use of iNO in infants with pulmonary disease also demonstrated no significant reduction in death or BPD [typical RR 0.93 (95% CI 0.86-1.01)] although this small effect approached significance. Later treatment with iNO based on the risk of BPD (two trials) demonstrated no significant benefit for this outcome in analyses which are possible using summary data. There is no clear effect of iNO on the frequency of all grades of IVH or of severe IVH. Early rescue treatment was associated with a non-significant 20% increase in severe IVH. No effect on the incidence of neurodevelopmental impairment was found. Reviewers' Conclusions iNO as rescue therapy for the very ill preterm infant does not appear to be effective. Early routine use of iNO in preterm infants with respiratory disease does not affect serious brain injury or improve survival without BPD. Later use of iNO to prevent BPD might be effective, but requires further study. Barrington KJ, Finer N: Inhaled nitric oxide for respiratory failure in preterm infants. Cochrane Database of Systematic Reviews 2010, Issue 12. Art. No.: CD000509.
European Journal of Pediatrics, 1998
Inhaled nitric oxide (iNO) has been shown to improve oxygenation in severe persistent pulmonary hypertension of the newborn (PPHN). However, PPHN is often associated with various lung diseases. Thus, response to iNO may depend upon the aetiology of neonatal acute respiratory failure. A total of 150 (29 preterm and 121 term) newborns with PPHN were prospectively enrolled on the basis of oxygenation index (OI) higher than 30 and 40, respectively. NO dosage was stepwise increased (10±80 ppm) during conventional mechanical or high-frequency oscillatory ventilation while monitoring the oxygenation. Eective dosages ranged from 5 to 20 ppm in the responders, whereas iNO levels were unsuccessfully increased up to 80 ppm in the nonresponders. Within 30 min of iNO therapy, OI was signi®cantly reduced in either preterm neonates (51 21 vs 23 17, P < .0001) or term infants with idiopathic or acute respiratory distress syndrome (45 20 vs 20 17, P < .0001),`idiopathic' PPHN (39 14 vs 14 9, P < .0001), and sepsis (55 25 vs 26 20, P < .0001) provided there was no associated refractory shock. Improvement in oxygenation was less signi®cant and sustained (OI 41 16 vs 28 18, P < .001) in term neonates with meconium aspiration syndrome and much less (OI 58 25 vs 46 32, P < .01) in those with congenital diaphragmatic hernia. Only 21 of the 129 term newborns (16%) required extracorporeal membrane oxygenation (57% survival). Survival was signi®cantly associated with the magnitude in the reduction in OI at 30 min of iNO therapy, a gestational age ³34 weeks, and associated diagnosis other than congenital diaphragmatic hernia. Conclusion, iNO improves the oxygenation in most newborns with severe hypoxaemic respiratory failure including preterm neonates. However, response to iNO is disease-speci®c. Furthermore, iNO when combined with adequate alveolar recruitment and limited barotrauma using exogenous surfactant and HFOV may obviate the need for extracorporeal membrane oxygenation in many term infants.
Nitric oxide in respiratory failure in the newborn infant
Seminars in Perinatology, 1997
with improvements in oxygenation in near-term newborn infants with hypoxic respiratory failure and persistent pulmonary hypertension of the newborn (PPHN). Subsequently, at least eight prospective randomized controlled trials evaluating the use of INO in the near-term neonate with hypoxic respiratory failure have been presented or published. A meta-analysis of these trials has provided evidence that INO improves the PaO2 in the INO-treated infants by 52.8 mm Hg (weighted mean difference) compared with controls (95% CI, 38.2, 67.4), and significantly decreases the oxygenation index by 16.9 compared with controls (95% CI, -22.2, -11.6). The incidence of death or need for ECMO is significantly reduced by treatment with INO, relative risk 0.71 compared to control (95% CI, 0.57, 0.87), with the majority of the improvement observed in the reduction in the need for ECMO. A single study of infants with congenital diaphragmatic hernia (CDH) did not show a benefit for early INO therapy, with treated infants having a greater requirement for ECMO (P ---.043). At present, there are no long-term evaluations of infants who have received INO as part of these prospective trials. INO improves oxygenation and reduces the need for ECMO in the near-term hypoxic neonate, but further research is required to evaluate the ultimate safety and benefit of this therapy.
Early Use of Inhaled Nitric Oxide in Preterm Infants: Is there a Rationale for Selective Approach?
American journal of perinatology, 2016
Inhaled nitric oxide (iNO) is being increasingly used in preterm infants < 34 weeks with hypoxemic respiratory failure (HRF) and/or pulmonary hypertension (PH). Objective To evaluate the risk factors, survival characteristics, and lung histopathology in preterm infants with PH/HRF. Methods Retrospective chart review was conducted to determine characteristics of 93 preterm infants treated with iNO in the first 28 days and compared with 930 matched controls. Factors associated with survival with preterm HRF and smooth muscle actin from nine autopsies were evaluated. Results Preterm neonates treated with iNO had a higher incidence of preterm prolonged rupture of membrane (pPROM ≥ 18 hours), oligohydramnios and delivered by C-section. In infants treated with iNO, antenatal steroids (odds ratio [OR],3.7; confidence interval [CI], 1.2-11.3; p = 0.02), pPROM (OR, 1.001; CI, 1.0-1.004; p = 0.3), and oxygenation response to iNO (OR, 3.7; CI, 1.08-13.1; p = 0.037) were associated with surv...
Low-dose inhaled nitric oxide for neonates with pulmonary hypertension
Journal of Paediatrics and Child Health, 1996
Objective: Inhaled nitric oxide (iNO) has been shown to cause selective pulmonary vasodilatation and improve ventilationperfusion matching and may be an important therapeutic option for the treatment of persistent pulmonary hypertension of the newborn (PPHN). We report our experience on the use of iNO in neonates with severe PPHN. Methodology: Inhaled NO was administered to 10 infants with PPHN and persistent hypoxaemia (meconium aspiration syndrome, n = 9; pneumonia, n = 1) after failure of conventional therapy to improve oxygenation. With the exception of one infant, iNO was commenced at 10 ppm. Results: After 30 min exposure to iNO, the arterial oxygen tension (PaO,) rose from a median of 49 mmHg (6.5 kPa) [range 12-82mmHg (1.6-10.9 kPa)] to 75mmHg (10 kPa) [range 17-450mmHg (2.3-60 kPa)] (P = 0.005), while the median oxygenation index fell (pre-iNO of 37 vs post-iN0 20) (P = 0.005) and median systemic arterial pressure rose (pre-iNO 46.5 mmHg (6.2 kPa) [range 32-63 mmHg (4.3 to 8.4 kPa vs post-iN0 54.5 mmHg (7.3 kPa) [range 36-74 kPa]) P = 0.005). All infants subsequently continued to receive iNO with the duration of exposure to iNO ranging from 12 to 168 h (median duration 100 h). Three infants died despite showing an initial beneficial response to iNO. The mean duration of intubation for survivors was 11.9k2.6 days. Methaemoglobinaemia and toxic levels of nitrogen dioxide were not seen during iNO administration. Of the seven survivors, 12 month follow up in two infants and 4 month follow up in four infants showed age-appropriate neurodevelopmental skills, with one infant having very mild hearing loss. Conclusions: Inhaled NO reduces the oxygenation index by improving the PaO, and decreasing ventilation pressures, and appears to be clinically useful in severely hypoxaemic infants with PPHN refractory to conventional treatment.
A dose response study of inhaled nitric oxide in hypoxic respiratory failure in preterm infants
Early Human Development, 2006
Background: Inhaled nitric oxide (iNO) is used widely in newborn infants with hypoxic respiratory failure, despite the known and theoretical toxicity of iNO, and a relative lack of information about appropriate doses. Aim: To determine whether a dose-response relationship existed for iNO in preterm infants. Design: A four-period, four-dose, cross-over design was used with iNO given for 15 min in a randomised sequence in concentrations of 5, 10, 20 and 40 parts per million (ppm), with a minimum 5 min wash-out period. Data on ventilatory, blood gas and other physiological measurements were recorded before and at the end of each period. The relationship of clinical response with iNO dose and period was analysed using multivariate regression. Subjects: Infants with gestational age b34 weeks and b 28 days postnatal age with hypoxic respiratory failure were recruited. Outcome measure: A clinically significant dose-response was defined as a rise in the postductal arterial oxygen tension (PaO 2 ) of at least 3 kPa. Results: Thirteen infants were recruited. At trial entry, ten were b 3 days of age; 11 were being treated with high frequency oscillatory ventilation; median (inter-quartile range) gestational 0378-3782/$ -see front matter D (J. Ahluwalia). Early Human Development (2006) 82, 477 -483 a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m w w w . e l s e v i e r . c o m / l o c a t e / e a r l h u m d e v age 27 (25-29) weeks; birthweight 983 (765-1120) g; oxygenation index 27.1 (21.8-28.8). Six infants (46%) showed a clinically significant response. After adjusting for period and patient effect, no evidence for an overall dose effect was identified (likelihood ratio test, p = 0.34). Conclusion: No evidence of a dose-response relationship with iNO was found in this study of very preterm infants with respiratory failure. D
Clinical Therapeutics, 2010
Background: The use of inhaled nitric oxide (NO) has been studied for the treatment of hypoxic respiratory failure (HRF) in newborns who require mechanical ventilation. Although inhaled NO is typically used in patients with a greater severity of illness, the treatment response (eg, improvement in oxygenation) and the associated outcomes (eg, time on mechanical ventilation) may be affected by the timing of treatment and baseline severity of illness. Objectives: This analysis was conducted to assess the effects of inhaled NO on measures of oxygenation, efficacy of inhaled NO across a range of illness severity strata, and duration of mechanical ventilation. Methods: This was a retrospective pooled analysis of 3 pivotal clinical trials comparing inhaled NO (starting dose, 20 ppm) with control (100% oxygen or nitrogen gas) in term and late preterm (gestational age ≥34 weeks) infants with HRF who required mechanical ventilation. Data on partial pressure of arterial oxygen (PaO 2), inspired oxygen concentration, and mean airway pressure at 0 and 30 minutes after administration of inhaled NO were extracted from the case-report forms from the 3 clinical trials and used to calculate the oxygenation index (OI). The change in PaO 2 was assessed by baseline severity of illness, stratified based on the OI (≤15 = mild, >15 to ≤25 = moderate, >25 to ≤40 = severe, >40 = very severe). The duration of mechanical ventilation was compared between the inhaled NO and control groups. Results: Five hundred twenty-four patients were analyzed (260 inhaled NO, 264 control). The overall mean (SD) birth weight and gestational age of the patients were 3.4 (0.58) kg and 39.1 (1.96) weeks, respectively. After 30 minutes of treatment, there was a significant increase from baseline in PaO 2 with inhaled NO compared with control (54.91 vs 14.15 mm Hg, respectively; P < 0.001). The increases from baseline in PaO 2 at 30 minutes were statistically significant for inhaled NO compared with controls across all severity strata (mild: 62.39 vs-23.03 mm Hg, respectively [P = 0.003]; moderate: 52.93 vs 18.28 mm Hg [P = 0.004]; severe: 62.07 vs 13.95 mm Hg [P < 0.001]; very severe: 45.17 vs 18.66 mm Hg [P < 0.001]). On Kaplan-Meier analysis, the median duration of mechanical ventilation was 11 and 14 days in the inhaled NO and control groups, respectively (P = 0.003). Conclusions: This pooled analysis of data from 3 clinical trials in term and late preterm infants with HRF requiring mechanical ventilation found that inhaled NO at a starting dose of 20 ppm was associated with improved oxygenation acutely and a reduced median duration of mechanical ventilation. The improvements were significant across all severity-of-illness strata. (Clin Ther.
Lancet, 1999
Background. Inhaled nitric oxide improves oxygenation and lessens the need for extracorporealmembrane oxygenation in full-term neonates with hypoxaemic respiratory failure and persistent pulmonary hypertension, but potential adverse effects are intracranial haemorrhage and chronic lung disease. We investigated whether low-dose inhaled nitric oxide would improve survival in premature neonates with unresponsive severe hypoxaemic respiratory failure, and would not increase the frequency or severity of intracranial haemorrhage or chronic lung disease. Methods. We did a double-blind, randomised controlled trial in 12 perinatal centres that provide tertiary care. 80 premature neonates (gestational age ≤34 weeks) with severe hypoxaemic respiratory failure were randomly assigned inhaled nitric oxide (n=48) or no nitric oxide (n=32, controls). Our primary outcome was survival to discharge. Analysis was by intention to treat. We studied also the rate and severity of intracranial haemorrhage, pulmonary haemorrhage, duration of ventilation, and chronic lung disease at 36 weeks' postconceptional age. Findings. The two groups did not differ for baseline characteristics or severity of disease. Inhaled nitric oxide improved oxygenation after 60 min (p=0.03). Survival at discharge was 52% in the inhalednitric-oxide group and 47% in controls (p=0.65). Causes of death were mainly related to extreme prematurity and were similar in the two groups. The two groups did not differ for adverse events or outcomes (intracranial haemorrhage grade 2-4, 28% inhaled nitric oxide and 33% control; pulmonary haemorrhage 13% and 9%; chronic lung disease 60% and 80%). Interpretation. Low-dose inhaled nitric oxide improved oxygenation but did not improve survival in severely hypoxaemic premature neonates. Low-dose nitric oxide in the most critically ill premature neonates does not increase the risk of intracranial haemorrhage, and may decrease risk of chronic lung injury.