The changing pattern of inhaled nitric oxide use in the neonatal intensive care unit

Abstract

Objective: The purpose of this study was to evaluate the demographic characteristics and outcomes of neonates who were admitted to a neonatal intensive care unit and treated with inhaled nitric oxide (iNO) during the years 2000-08. The goal of studying this group of neonates was to evaluate how iNO use has evolved in infants and to estimate the frequency of off-label use of this drug in this population.Study Design: Retrospective review of the Pediatrix Clinical Data Warehouse de-identified data set. Pediatrix Medical Group provides intensive care services in 244 hospitals in 32 states and Puerto Rico. Nine (3.7%) centers provide extracorporeal membrane oxygenation.Result: There were 494 255 neonates in the data set; 4316 (0.9%) were treated with iNO. The use of iNO increased from 154 of 32 967 patients in 2000 to 921 of 75 911 patients in 2008; a 2.6-fold increase (0.47 to 1.23%). There were 155 872 infants <34 weeks estimated gestational age discharged between 1 January 2000 and 31 December 2008; 1656 (1.1%) were treated with iNO. Since approval in 2000, the reported use of iNO in neonates <34 weeks increased from 0.3 to 1.8% in 2008; a sixfold increase in the reported use of iNO. The biggest increase occurred in infants between 23 and 26 weeks' gestational age (0.8 to 6.6%). In contrast, the increase in iNO use among neonates born X34 weeks has only increased from 0.5 to 1%. Conclusion:The use of iNO has increased and the greatest increase has been the off-label use among preterm neonates. Journal of Perinatology (2010) In a meta-analysis of clinical studies involving term and late preterm neonates, Finer and Barrington 1 concluded that 'based on the evidence presently available, including the neurodevelopmental and general medical outcome information, near-term and term infants with hypoxic respiratory failure unresponsive to other therapy, excluding infants with diaphragmatic hernia, should have a trial of inhaled nitric oxide.' 1 The use of iNO in more premature (<34 weeks) infants has generally focused on two high-risk groups; those with severe acute respiratory distress 2,3 and those at high risk of developing bronchopulmonary dysplasia (BPD). [4][5][6] In a recent meta-analysis of the published clinical studies involving preterm infants, Barrington and Finer 7 concluded that 'y iNO should not be routinely used for preterm infants as a rescue therapy in cases of hypoxic respiratory failure. In contrast, the early routine use of iNO in ventilated preterm infants who are not severely ill, but nevertheless are at risk for serious brain injury or bronchopulmonary dysplasia, holds promise.' 7 The purpose of our study was to determine whether changes in practice are consistent with the suggestions of these two meta-analyses; more specifically, our goal was to evaluate how the off-label use of iNO has changed since its approval in late 1999.

Inhaled Nitric Oxide in Preterm Infants: A Systematic Review

“…One publication reported a sixfold increase in its use between 2000 and 2008 in a large multisite pediatric group. 34 The lack of standardized definitions, measurements, and reporting of outcomes in studies of preterm infants make direct comparisons between trials and synthesis of data from multiple trials difficult and likely contributed to the off-label use of iNO. Future research should address gaps in knowledge concerning iNO therapy for preterm infants by using standardized measurements and outcomes, which is particularly true for neurodevelopmental outcomes.…”

Guidelines for Rational and Cost-Effective Use of iNO Therapy in Term and Preterm Infants

“…In recent years, the use of iNO for “off-label” indications, such as for rescue treatment of preterm infants with severe respiratory failure, babies with severe chronic lung disease complicated by pulmonary hypertension and for prevention of bronchopulmonary dysplasia (BPD) has increased greatly. [12] Such off-label use is associated with potential exposure to unknown adverse effects not balanced by documentable benefit and incurs very high cost. The following guidelines summarize available evidence for the use of iNO in several distinct clinical conditions in which it has been used in recent years and formulates evidence-based recommendations for rational use of this therapy.…”

Inhaled nitric oxide improves systemic microcirculation in infants with hypoxemic respiratory failure

“…I nhaled nitric oxide (iNO) is used frequently as therapy in neonatal and pediatric intensive care, especially in neonates with pulmonary hypertension (1). Persistent pulmonary hypertension of the newborn (PPHN) describes the state in which pulmonary vascular resistance fails to decline after birth, resulting in a persistence of fetal circulation.…”