ModifiedCentenePolicy CP.MP.87

Therapeutic Utilization of Inhaled Nitric Oxide

Medical necessity criteria and utilization guidance for initiation and continuation of inhaled nitric oxide therapy for newborns, children, and select cases (including COVID-19/ARDS), for Centene-affiliated health plans.

Policy Summary

PayerCentene

PolicyTherapeutic Utilization of Inhaled Nitric Oxide

Policy CodePolicy CP.MP.87

Change TypeUpdated clinical criteria and thresholds (OI changed to 25added COVID-19/ARDS and right ventricular failure)

Effective Date

Next Review Date

Key ActionSubmit initiation and continuation requests with documentation of gestational age, OI calculation, response to up-to-40 ppm trial (response = PaO2 ↑≥20 mm Hg or 20% OI decrease), and follow prior authorization requirements; extended use >72 hours requires secondary medical director review.

SourceLink

POLICY UPDATE CHANGES

Under I.A.6. changed oxygen index (OI) >20 to 25.

Added iNO as medically necessary for COVID-19, severe ARDS, and hypoxemia despite optimized ventilation and other rescue strategies.

Added indication I.B.1.a.3) right ventricular failure.

Updated oxygen index thresholds in criteria I.A.6 several times, including change from >20 to 25, and notation from 48 hours to 72 hours in criteria III.

Removed criterion stating iNO must be administered via endotracheal tube or tracheostomy (I.A.).

Condensed statement that medical literature predominantly does not support iNO in premature infants <34 weeks GA but allows case-by-case review referencing criteria for ≥34 weeks.

OI > 25OI threshold (neonates)

Policy Summary

PayerCentene

PolicyTherapeutic Utilization of Inhaled Nitric Oxide

Policy CodePolicy CP.MP.87

Change TypeUpdated clinical criteria and thresholds (OI changed to 25added COVID-19/ARDS and right ventricular failure)

Effective Date

Next Review Date

SourceLink

On This Page

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Coverage Criteria for Inhaled Nitric Oxide (iNO)

Initial Therapy

Initiation of iNO therapy is medically necessary when meeting ONE of the following groups:

I.A Hypoxic respiratory failure in newborns >=34 weeks GA

Evidence of PAH: Evidence of pulmonary arterial hypertension (PAH), demonstrated by either: (a) well-documented clinical evidence of pulmonary hypertension despite maximal respiratory support; or (b) echocardiogram suggestive of PAH.
Absence of unrepaired CDH: Absence of unrepaired congenital diaphragmatic hernia (CDH), except when used as a bridge to surgical repair of CDH.
Failed conventional therapies: Conventional therapies (mechanical ventilation, administration of high concentrations of oxygen 80–100%, high-frequency ventilation, induction of alkalosis, neuromuscular blockade, and/or sedation) have failed.
OI threshold: Oxygen index (OI) > 25.OI > 25
OI = mean airway pressure × FiO2 × 100 / PaO2.

I.B Perioperative management in children and infants >=34 weeks GA

Perioperative indications: One of the following indications: (a) congenital heart defect with one of: (1) iNO for vasodilation after cardiac bypass for congenital heart defect causing PAH; (2) perioperative stabilization/management of hypoxia; or (3) right ventricular heart failure; OR (b) pulmonary hypertensive crisis associated with heart or lung surgery (including immediately pre- or post-operatively for CDH).
Alternative vasodilator initiation: Initiation of alternative vasodilator therapies (e.g., sildenafil or others) during iNO administration with intent to wean or discontinue iNO.
See continuation criteria for wean details.

I.C COVID-19 diagnosis

Severe ARDS: Severe acute respiratory distress syndrome (ARDS).
Refractory hypoxemia: Hypoxemia despite optimized ventilation and other rescue strategies.

Continuation Therapy

Continuation of iNO therapy is medically necessary when ALL of the following are met (and prior approval criteria have been met):

Continuation

Response to trial: Response seen with administration of up to 40 ppm trial of iNO with a recommended dose of 20 ppm (response defined as PaO2 increase ≥20 mm Hg or 20% decrease in OI).up_to_40_ppm_trial; recommended 20 ppm
Response definition per policy.
Weaning initiated after stability: A weaning protocol for the iNO has been initiated after a 4–6 hour period of stability, indicated by inspired oxygen decreased to 60–80% or OI < 10.OI < 10 or FiO2 60–80%
Weaning steps described in policy (dose reductions at 4–6 hour intervals).

ref':

Not Medically Necessary

Not medically necessary: iNO is not medically necessary for indications including but not limited to acute bronchiolitis, bronchopulmonary dysplasia (BPD); congenital diaphragmatic hernia (CDH) except as bridge to repair; acute respiratory distress syndrome (except as noted above); acute lung injury; treatment in adults with positive vaso-reactivity testing; post-operative cardiac surgery in adults; or vaso-occlusive crises in sickle cell disease because safety and effectiveness have not been established.

Key criteria statements and edits

Policy-level coverage stance and notable criteria modifications as documented in revision log

Neonatal prematurity guidance: While the medical literature predominantly does not support the use of iNO in premature infants <34 weeks gestational age at birth, requests for initiation of iNO therapy in these infants may be reviewed on a case-by-case basis with consideration of the criteria for premature newborns ≥34 weeks gestational age at birth in section I.gestational_age < 34 weeks -> case_by_case

Condensed statement per revision log.

Oxygen index threshold: Criteria I.A.6 oxygen index (OI) threshold updated to 25.OI > 25

Revision history shows changes from >20 to 25 in recent updates.

Indications addition: Added indication: right ventricular failure included under perioperative congenital heart defect indications (I.B.1.a.3).

Inhaled nitric oxide (iNO) is not medically necessary for the majority of the listed non‑approved indications. This includes, but is not limited to, acute bronchiolitis, bronchopulmonary dysplasia (BPD), congenital diaphragmatic hernia (CDH) except when used as a bridge to surgical repair, most cases of acute respiratory distress syndrome (ARDS) (except where specifically noted in the policy), acute lung injury, use for adults with positive vasoreactivity testing, post‑operative cardiac surgery in adults, and vaso‑occlusive crises in sickle cell disease. These indications are considered not medically necessary because safety and effectiveness have not been established.

Specific ICD‑10 diagnosis codes previously listed in the policy have been removed from this document. The revision log documents removal of those ICD‑10 codes and indicates that lists of diagnosis codes are no longer included in the policy text.

Requests for iNO for indications identified as not medically necessary in this policy will be denied. The list of not medically necessary indications mirrors the policy statement and includes conditions for which the literature does not support established safety or effectiveness such as acute bronchiolitis, BPD, most CDH (except bridge to repair), most ARDS, acute lung injury, adult vasoreactivity testing, adult post‑operative cardiac surgery, and sickle cell vaso‑occlusive crises.

The policy clarifies that the medical literature predominantly does not support routine use of iNO in premature infants born at <34 weeks gestational age. However, the policy allows that requests for initiation of iNO in these infants may be reviewed on a case‑by‑case basis, with consideration of the criteria that apply to premature newborns ≥ 34 weeks GA as described in section I.

Coding and Clinical Thresholds

CPT / Procedure codes referencedCPT

94799

Unlisted pulmonary service or procedure

No codes in this sectionmixed

No codes listed

Oxygen Index (OI) threshold

OI threshold for initiationOxygen index (OI) > 25

Context in criteriaUsed in Initial Therapy I.A.4 for hypoxic respiratory failure in newborns ≥34 weeks GA

Policy revision noteRevision log documents change of OI threshold to 25 in merged 2024-2025 updates

Oxygen Index — reference value

Numeric OI value referenced25

Use in policy textOI value applied to criteria I.A.6 (oxygen index threshold updated to 25)

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for initiation and continuation of inhaled nitric oxide (iNO) therapy. Requests for initiation, including for premature infants <34 weeks gestational age, will be reviewed using the policy's medical necessity criteria; initiation in infants <34 weeks GA may be considered on a case-by-case basis referencing the criteria for newborns ≥34 weeks GA. Extended administration of iNO beyond 72 hours requires secondary review by a medical director.

Applies to initiation and continuation requests for iNO
Premature infants <34 weeks GA: case-by-case review referencing section I criteria
Extended iNO >72 hours: secondary medical director review

Prior Authorization

Perioperative Vasodilator Transition

For perioperative management in infants and children ≥34 weeks gestational age, when iNO is used for perioperative stabilization, vasodilation after cardiac bypass, right ventricular failure, or pulmonary hypertensive crisis associated with surgery, providers should initiate alternative vasodilator therapies (e.g., sildenafil or others) during iNO administration with the intent to wean or discontinue iNO per continuation and weaning criteria.

Background

Inhaled nitric oxide is a selective pulmonary vasodilator that can improve oxygenation in many term and near‑term neonates with hypoxic respiratory failure and has been shown to reduce the need for extracorporeal membrane oxygenation (ECMO) without increasing adverse neurodevelopmental outcomes. The policy background therefore supports iNO use in defined neonatal populations while noting limited or transient benefit and potential harms in preterm infants and most adult ARDS/ALI settings; this underlies the policy's selective, criteria‑based coverage approach.

Definitions and Clinical Metrics

Oxygen Index (OI) definition

FormulaOI = mean airway pressure (cm H2O) × FiO2 × 100 / PaO2 (mm Hg)

Parameters definedMean airway pressure (cm H2O), fraction of inspired oxygen (FiO2), partial pressure of arterial oxygen (PaO2 in mm Hg)

Policy referenceOI calculation specified in Initial Therapy I.A.4 and in documentation requirements

iNO response definition

Positive response criteriaPositive response defined as PaO2 increase ≥20 mm Hg or 20% decrease in OI

Timing of responseA positive response generally occurs in less than 30 minutes during an up-to-40 ppm trial

Note

Coverage Limitations and Conflicts

Coverage decisions are subject to the Health Plan's terms, conditions, exclusions and limitations of coverage documents. This clinical policy is a guide to medical necessity used to aid coverage determinations but does not guarantee payment. Providers must follow applicable benefit plan documents and administrative policies; state Medicaid or Medicare rules supersede when applicable.

Coverage subject to evidence of coverage / contract terms, exclusions, and limitations
State Medicaid provisions take precedence over this policy where conflicts exist
Medicare NCDs/LCDs and Coverage Articles should be reviewed for Medicare enrollees

Documentation Required

Required Clinical Documentation

Providers must document medical necessity consistent with the Health Plan's clinical guidance. Documentation should include gestational age, evidence of pulmonary arterial hypertension or indication, failure of conventional therapies, oxygenation indices (e.g., OI), response to iNO trials, details of perioperative management and any concurrent vasodilator therapy, and justification for extended administration if applicable.

Include gestational age and indication (e.g., PAH, perioperative reason)
Document failed conventional strategies and OI or PaO2 metrics
For extended iNO >72 hours, include rationale and plan; be prepared for secondary review