UnitedHealthcare inhaled nitric oxide Coverage Update

Coverage Criteria for Inhaled Nitric Oxide (iNO)

Initial therapy for term/near-term infants with hypoxic respiratory failure or PPHN

Covered when ALL of the following are met

Term/near-term infant criteria: Infant is term or near-term (≥ 34 weeks gestation) and within the infancy age groupgestational age >= 34 weeks; infancy = birth through 1 year

Reference: policy definition and coverage rationale

Clinical condition: Presence of hypoxic respiratory failure or echocardiographic evidence of persistent pulmonary hypertension of the newborn (PPHN)

Absence of contraindicating condition: Absence of congenital diaphragmatic hernia (CDH)

Infants with CDH are evaluated separately and generally considered unproven/not medically necessary

Failure of conventional therapy: Failure of conventional treatments (e.g., mechanical ventilation) prior to initiation of iNO

Policy indicates iNO after failure of conventional treatments; AHA/ATS guidance cites OI > 25 as a trigger

Postoperative bridge therapy

Covered as bridge therapy when ALL of the following are met

Postoperative pulmonary hypertension: Postoperative management of pulmonary hypertension associated with heart or lung surgery in infants during the acute recovery phase

iNO is a clinically accepted option as bridge therapy during acute postoperative recovery; AHA/ATS recommends iNO as initial therapy for postoperative PH crises

Acute treatment of PPHN in term/near-term neonates

Covered when ALL of the following are met (per FDA and guideline-aligned indications and supporting evidence):

Gestational age and diagnosis: Patient is a term or near-term neonate (> 34 weeks gestation) with hypoxic respiratory failure and clinical or echocardiographic evidence of pulmonary hypertension (PPHN)>34 weeks gestation

Matches FDA indication for INOmax and EPPVDN guidance

Severity criteria: Either PaO2 < 100 mm Hg on 100% oxygen OR oxygenation index > 25 (or equivalent severe hypoxemia) indicating need for pulmonary vasodilator therapyPaO2 <100 mm Hg OR OI >25

EPPVDN and AHA/ATS recommend these thresholds for initiating iNO

Regulatory alignment: Use consistent with FDA-cleared indication for INOmax in term/near-term neonates with hypoxic respiratory failure associated with pulmonary hypertension

Not routinely supported

Not routinely covered / not supported by evidence when ANY of the following apply:

Preterm routine or prophylactic use: Preterm infants (< 34 weeks gestation) receiving iNO for routine prophylaxis, prevention of bronchopulmonary dysplasia (BPD), or as early rescue therapy without confirmed pulmonary hypertension<34 weeks gestation

Multiple RCTs, systematic reviews, and guideline statements do not support routine benefit and advise against routine use

Use in CDH without clear indication: Use of iNO for newborns with congenital diaphragmatic hernia (CDH) when benefit is not establishedCDH diagnosis

Observational and trial data show inconsistent mortality/ECMO benefit and potential harm in subgroups; routine use not supported

Conditional/individualized use

May be considered when ALL of the following are met:

Preterm infant with confirmed pulmonary hypertension: Preterm infants (< 34 weeks gestation) with respiratory failure and echocardiographically confirmed pulmonary hypertension may be considered for individualized iNO use after other therapies have failedechocardiographic confirmation of PH

EPPVDN and select guidance note iNO may be considered in preterm infants with confirmed PH on a case-by-case basis; evidence is limited

Postoperative PH crisis or right-heart failure: Infants/children experiencing postoperative pulmonary hypertensive crises or right heart failure where iNO is used as initial therapy to stabilize and bridge recoverypostoperative PH crisis

AHA/ATS recommends iNO (and/or inhaled prostacyclin) as initial therapy for postoperative PH crises (Class I/LOE B); use should be individualized

Use of inhaled nitric oxide (iNO) for newborns with congenital diaphragmatic hernia (CDH) and for preterm newborns born before 34 weeks gestation is considered unproven and may be denied. The policy states that iNO is proven and medically necessary only for term or near-term infants (≥ 34 weeks gestation

Inhaled nitric oxide (iNO) treatment for individuals outside the defined Infancy age group (the period from birth through the first year of life) is considered experimental or investigational because there are no FDA‑approved indications for older children or adults in the policy. The Coverage Rationale explicitly states iNO therapy outside of infancy lacks FDA‑approved indications and is therefore investigational.

The FDA-cleared product INOmax is indicated for treatment of term and near-term neonates (> 34 weeks) with hypoxic respiratory failure associated with clinical or echocardiographic evidence of pulmonary hypertension; importantly, INOmax is not approved for use in preterm infants (≤ 34 weeks). National guidance (NICE NG124) similarly advises: do not routinely use inhaled nitric oxide for preterm babies who need respiratory support for RDS unless there are other indications such as pulmonary hypoplasia or pulmonary hypertension, and notes such use is off‑label in infants <34 weeks.

The policy references multiple systematic reviews, randomized trials, and guideline documents as the evidence base for its coverage positions. The cited references include randomized clinical trials and meta-analyses (for example, Barrington et al., Hasan et al., and the NEWNO trial), as well as guideline statements such as NICE NG124; the referenced chunks supply evidence summaries but do not themselves contain explicit additional coverage language beyond what is summarized in this policy.

iNO is stated as not medically necessary for preterm newborns born before 34 weeks gestation for the treatment of respiratory distress or for prevention/treatment of bronchopulmonary dysplasia (BPD). Systematic reviews, meta-analyses, and randomized trials cited in the policy fail to show consistent benefit in this population and identify potential harms (for example, increased risk of severe intraventricular hemorrhage or necrotizing enterocolitis), supporting the policy’s not‑medically‑necessary determination for routine use in preterm infants <34 weeks.

Routine, prophylactic, or early‑rescue use of iNO in preterm infants to prevent bronchopulmonary dysplasia (BPD) or to improve survival is not supported by the evidence cited. Long‑term follow-up of randomized trials and Cochrane meta-analyses did not demonstrate sustained benefits for prevention of BPD or improved survival, and several analyses raised concerns about possible harms; therefore routine or prophylactic use in preterm infants is not recommended by the policy.

Coding and Clinical Thresholds

Applicable CPT Codes (reference)CPT

94799

Unlisted pulmonary service or procedure.

Oxygenation Index

ThresholdOxygenation Index (OI) > 25

ContextReferenced by AHA/ATS guideline for initiating iNO to reduce need for ECMO in term and near-term infants with PPHN or hypoxemic respiratory failure

Equivalent criteria notedPaO2 < 100 mm Hg on 100% oxygen OR OI > 25 used by EPPVDN as severity threshold for iNO

iNO Initial Concentration

Initial concentration20 ppm

Population studiedTerm and near-term infants with hypoxic respiratory failure (excluding diaphragmatic hernia in primary analysis)

Provider Actions, Authorization, and Documentation

Prior Authorization
Prior Authorization for Off‑Label / Younger Gestational Ages
Prior authorization is required for use of inhaled nitric oxide (iNO) when the indication is outside the FDA-labeled population (e.g., preterm infants ≤34 weeks gestation) or otherwise considered off‑label. Providers should obtain prior authorization before initiating therapy for younger gestational ages or other non‑labeled uses to document medical necessity and reduce coverage risk.
Prior authorization required for off‑label use (including preterm infants ≤34 weeks).
Prior authorization does not guarantee coverage; benefit terms govern final determination.

Denial Risk
FDA Labeling and Coverage Risk
INOmax is FDA‑approved for treatment of term and near‑term neonates (>34 weeks gestation) with hypoxic respiratory failure and clinical/echocardiographic evidence of pulmonary hypertension. INOmax is not approved for preterm infants (≤34 weeks). Off‑label use in populations not included in FDA labeling may increase the risk of denial; document clinical rationale and prior authorization decisions carefully.

Background and Rationale

Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator that relaxes pulmonary vascular smooth muscle to reduce pulmonary vascular resistance and improve ventilation‑perfusion matching. In the neonatal setting, iNO is used to improve oxygenation in hypoxic respiratory failure and to treat persistent pulmonary hypertension of the newborn (PPHN); when used appropriately in term or near‑term infants it can reduce the need for extracorporeal membrane oxygenation (ECMO). iNO therapy increases methemoglobin levels and has been associated in observational data with potential long‑term risks, which should be weighed against expected short‑term benefits.

Definitions

Infancy

DefinitionInfancy = the period from birth through the first year of life.

CitationBarfield 2016 (policy definition)

Scope noteAge group used in coverage criteria for neonatal and infant iNO indications

INOmax

ProductINOmax (nitric oxide gas)

FDA indicationTreatment of term and near-term (> 34 weeks) neonates with hypoxic respiratory failure associated with clinical or echocardiographic evidence of pulmonary hypertension.

Regulatory notes

Revision History

2025-11-01revisionLatest

Updated Description of Services, Clinical Evidence, and References sections; archived previous policy version CS173KS.01.

OpenPayer

Inhaled Nitric Oxide Therapy (for Kansas Only)