Centene inhaled nitric oxide Policy Update

Coverage Criteria for Inhaled Nitric Oxide (iNO)

Initial Therapy — Initiation of iNO

Initiation of iNO is medically necessary when meeting one of the following distinct indication groups:

Initial Indications: Any one of the following groups A–C

A. Neonatal hypoxic respiratory failure (≥34 weeks GA)

Evidence of pulmonary arterial hypertension (PAH): One of: (a) well-documented clinical evidence of pulmonary hypertension despite maximal respiratory support OR (b) echocardiogram suggestive of PAH
Additional neonatal requirements: Absence of unrepaired congenital diaphragmatic hernia (except as bridge to repair); failure of conventional therapies (mechanical ventilation, high O2 80–100%, high-frequency ventilation, induction of alkalosis, neuromuscular blockade and/or sedation); Oxygen Index (OI) > 25OI > 25
OI calculation required

B. Perioperative management in children and infants ≥34 weeks GA

Perioperative indications: One of: (a) congenital heart defect with iNO used post-cardiac bypass to treat PAH; (b) perioperative stabilization and management of hypoxia; (c) right ventricular heart failure; OR (d) pulmonary hypertensive crisis associated with heart or lung surgery (including immediately pre- or post-operatively for congenital diaphragmatic hernia)
Perioperative requirement: Initiation of alternative vasodilator therapy (e.g., sildenafil or others) during iNO administration with intent to wean or discontinue iNO (see continuation criteria)

C. COVID-19 severe ARDS rescue

COVID-19/ARDS rescue conditions: (1) Severe acute respiratory distress syndrome (ARDS) AND (2) Hypoxemia despite optimized ventilation and other rescue strategies
Panel recommends against routine use; reasonable as rescue

Perioperative Therapy — Perioperative management

Perioperative management in children and infants ≥34 weeks GA is medically necessary when BOTH of the following are met:

B. Perioperative management

Indication (one required): One of: (a) congenital heart defect with iNO for vasodilation used in response to cardiac bypass surgery to repair a congenital heart defect causing PAH; (b) perioperative stabilization and management of hypoxia; (c) right ventricular heart failure; OR (d) pulmonary hypertensive crisis associated with heart or lung surgery (including immediately pre- or post-operatively for congenital diaphragmatic hernia)
Right ventricular failure explicitly added as a sub-indication.
Therapeutic approach: Initiation of alternative vasodilator therapies (e.g., sildenafil or others) during iNO administration with the intent to wean or discontinue iNO per continuation criteria
See continuation criteria in section III.

COVID-19 / ARDS Rescue

C. COVID-19 diagnosis — iNO may be medically necessary when BOTH are met:

C. COVID-19 severe ARDS rescue

Clinical conditions: (1) Severe acute respiratory distress syndrome (ARDS) AND (2) Hypoxemia despite optimized ventilation and other rescue strategies
Use as rescue after other options have failed; taper quickly if no improvement

Continuation Therapy

Continuation of iNO is medically necessary when ALL of the following apply:

III. Continuation Therapy

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 a 20% decrease in OI)PaO2 ↑ ≥20 mmHg OR OI ↓ 20%
Trial up to 40 ppm, recommended 20 ppm
Weaning/stability criteria: A weaning protocol for iNO has been initiated after a 4–6 hour period of stability, indicated by inspired O2 requirement decreased/decreasing to 60–80% or OI < 10OI < 10 or FiO2 60–80%
Wean per specified intervals; if deterioration occurs, resume prior dose and reattempt slower wean

Coverage criteria and notable threshold/wording changes

Policy covers initiation and continuation of iNO when clinical criteria are met; document notes multiple revisions to neonatal and acute respiratory distress criteria.

Neonates and premature infants: Literature predominantly does not support iNO in premature infants <34 weeks gestational age; initiation requests for these infants may be reviewed case-by-case using criteria for premature newborns ≥34 weeks gestational agegestational_age < 34

Case-by-case review; see section I and revision notes

Oxygen Index threshold: Oxygen Index criterion under I.A.6 updated to 25OI >= 25

OI changed from >20 to 25 in consolidated revisions

Timing for continuation: Timing notation for criteria III updated from 48 hours to 72 hours

Inhaled nitric oxide (iNO) is not medically necessary for indications that lack established safety and effectiveness. Examples explicitly listed in the policy include: acute bronchiolitis, bronchopulmonary dysplasia (BPD), and congenital diaphragmatic hernia (CDH) except when used as a bridge to repair as noted under neonatal criteria. The policy also specifies iNO is not medically necessary for acute respiratory distress syndrome (except as noted elsewhere in this policy), acute lung injury, treatment of adults based solely on positive vaso-reactivity testing, routine use post‑operative in adult cardiac surgery, or for vaso‑occlusive crises in sickle cell disease. If no rapid improvement in oxygenation is observed during a trial, treatment should be tapered off.

Coverage of inhaled nitric oxide is governed by the member's benefit documents and applicable law. This clinical policy is a guide to medical necessity and does not supersede the terms, conditions, exclusions, and limitations of coverage documents (for example, EOC or certificate of coverage). State and federal requirements take precedence where applicable. The Health Plan retains the right to change, amend, or withdraw this clinical policy; providers must follow plan-level administrative policies and supply any requested supporting clinical information when prior authorization is required.

Any indication for inhaled nitric oxide that is not explicitly listed in the policy as medically necessary is considered not medically necessary due to insufficient evidence of safety and effectiveness. Providers requesting coverage for indications outside the stated medically necessary criteria should expect denial unless supportive evidence is provided and the request is otherwise consistent with the member's benefit contract.

The literature and the policy predominantly do not support initiation of iNO in premature infants born at 34 weeks gestational age. The policy permits case‑by‑case review: requests for initiation in infants <34 weeks may be considered individually using the criteria for premature newborns ≥34 weeks as a reference rather than being categorically denied. Providers should document rationale and clinical data when requesting such reviews.

Coding and Clinical Thresholds

Referenced CPT/HCPCS codesCPT

94799

Unlisted pulmonary service or procedure

ICD-10 (removed)ICD-10

removed

ICD-10 codes removed from document

Affected codes (unspecified)mixed

affected codes

Place-holder reference to codes affected by prior authorization (document references 'affected codes' in prior auth module)

inv-13: Oxygen Index threshold

Oxygen Index threshold> 25

Context for thresholdApplied to neonatal hypoxic respiratory failure (newborns ≥34 weeks GA) as initiation criterion

Calculation requirementOI calculation must be performed (mean airway pressure × FiO2 ×100 ÷ PaO2)

inv-14: Oxygen Index (OI)

Oxygen Index (OI) numeric value25

Policy noteOI criterion under I.A.6 updated from prior values to 25 in consolidated revisions

Provider Actions, Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for initiation of inhaled nitric oxide (iNO) therapy. Providers must submit requests for iNO initiation and continuation in accordance with the Health Plan's medical necessity review and prior authorization procedures before treatment is started whenever feasible.

Prior authorization required for initiation and continuation of iNO
Requests must follow plan-level prior authorization processes and medical necessity review

Denial Risk

Denial Risk from Benefit Exclusions

Coverage decisions are subject to the terms, conditions, exclusions and limitations of the member's benefit documents and to applicable state and federal requirements. A request for iNO may be denied if the service or indication is excluded by the member's benefit plan or conflicts with regulatory requirements.

Coverage subject to benefit document terms, exclusions, and limitations

Background and Rationale

Inhaled nitric oxide is a selective pulmonary vasodilator that improves oxygenation in 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 at two years. Evidence in preterm infants is inconclusive and may be associated with increased risk of intraventricular hemorrhage. In adults and patients with acute respiratory distress syndrome (ARDS), iNO produces transient improvements in oxygenation but has not demonstrated a mortality benefit and may worsen renal function; therefore guideline panels recommend limiting use in adults to rescue situations. In pediatric perioperative settings and pulmonary hypertensive crises, iNO may be reasonable for short‑term rescue or stabilization, with plans for early weaning to alternative vasodilator therapies as appropriate.

Definitions and Clinical Metrics

inv-24: Oxygen Index (OI) definition

Definition (formula)OI = (mean airway pressure in cm H2O × FiO2 × 100) ÷ PaO2 (mm Hg)

UnitsMean airway pressure in cm H2O; PaO2 in mm Hg; FiO2 as fraction

ApplicationRequired calculation for neonatal initiation criteria and for monitoring response/weaning

inv-25: Response to iNO

Response definitionAn increase in PaO2 of ≥20 mm Hg or a 20% decrease in Oxygen Index

Clinical useUsed to determine response during an initial up-to-40 ppm trial and to support continuation of iNO

Revision History and Policy Changes

2025-04-?consolidated_revisionsLatest

Merged prior revision entries (07/24 and 11/24) and finalized Oxygen Index threshold to 25 in I.A.6; moved I.A.7 to III.A.1 and removed certain continuation criteria entries.

2024-11-?terminology_update_and_threshold_change

Updated criteria IV language from 'adult respiratory distress' to 'acute respiratory distress' and recorded change of Oxygen Index under I.A.6 from >20 to 25 in consolidation notes.

2024-07-?correction_and_added_indication

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Therapeutic Utilization of Inhaled Nitric Oxide