ModifiedmhnPolicy CP.MP.87

Therapeutic Utilization of Inhaled Nitric Oxide

Defines medical necessity, initiation, and continuation criteria for inhaled nitric oxide therapy for neonates, infants, children, and adults (including COVID-19/ARDS rescue use) for members of Centene-affiliated health plans.

Policy Summary

Payermhn

PolicyTherapeutic Utilization of Inhaled Nitric Oxide

Policy CodePolicy CP.MP.87

Change TypeMaterial revisions to criteria, thresholds, and indications

Effective Date

Next Review Date

Key ActionObtain prior authorization and document that initiation criteria are met (e.g., OI threshold, failed conventional therapies, evidence of pulmonary hypertension) before starting iNO.

SourceLink

POLICY UPDATE CHANGES

Updated oxygen index (OI) criterion in neonatal hypoxic respiratory failure from ≥25 to >20 and later reconciled back to >25 in a subsequent merge.

Added indication I.B.1.a.3) right ventricular failure as an additional perioperative indication.

Clarified continuation criteria requiring prior meeting of initial approval criteria and defined response to a trial of up to 40 ppm iNO.

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

Oxygen index threshold in section I.A.6. was changed multiple times (reported changes between >20, 25, and back to 25).

Criteria wording and timing notation were updated (48 hours changed to 72 hours in criteria III).

Removed the explicit administration route criterion 'iNO will be administered via endotracheal tube or tracheostomy' (I.A. removed).

Terminology in criteria IV. was updated from 'adult respiratory distress' to 'acute respiratory distress.'

OI > 25OI threshold

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Coverage Criteria for Inhaled Nitric Oxide (iNO)

Initial Therapy — Neonatal hypoxic respiratory failure

Covered when ALL of the following are met (initial neonatal hypoxic respiratory failure indication):

Neonatal hypoxic respiratory failure (≥ 34 weeks GA): 1) Evidence of pulmonary arterial hypertension (either clear clinical evidence despite maximal respiratory support or echocardiogram suggestive of PAH); 2) Absence of unrepaired congenital diaphragmatic hernia (except when used as a bridge to surgical repair); 3) Failure of conventional therapies (mechanical ventilation, administration of high concentrations of oxygen 80–100%, high-frequency ventilation, induction of alkalosis, neuromuscular blockade and/or sedation); 4) Oxygen index (OI) > 25.OI > 25

OI = (mean airway pressure [cm H2O] × FiO2 × 100) / PaO2.

Perioperative / Postoperative indications

Covered when ALL of the following are met (perioperative management in infants/children ≥34 weeks GA):

Perioperative management: 1) One of the following indications: (a) congenital heart defect and one of: i) iNO used in response to cardiac bypass surgery to treat PAH; ii) perioperative stabilization and management of hypoxia; iii) right ventricular heart failure; (b) pulmonary hypertensive crisis associated with heart or lung surgery (including immediately pre- or post-operatively for congenital diaphragmatic hernia). 2) Initiation of alternative vasodilator therapies (e.g., sildenafil or others) during iNO administration with intent to wean or discontinue iNO (see continuation criteria).

Perioperative indication limited to infants/children ≥ 34 weeks GA; see continuation criteria for response and weaning guidance.

COVID-19 / Severe ARDS (Rescue)

Covered when ALL of the following are met (COVID-19 / ARDS rescue use):

COVID-19 severe ARDS rescue therapy: 1) Diagnosis of COVID-19 with severe acute respiratory distress syndrome (ARDS); 2) Hypoxemia despite optimized ventilation and other rescue strategies (for example, prone ventilation, recruitment maneuvers, and other recommended supportive measures);

iNO may be used as an inhaled pulmonary vasodilator rescue therapy; if no rapid improvement in oxygenation is observed, treatment should be tapered off promptly.

Continuation Therapy

Continuation Therapy — covered when ALL of the following are met:

Continuation after initial approval: Member/enrollee previously met initial approval criteria AND one of the following: (1) Response to an administration trial of up to 40 ppm iNO with recommended dose of 20 ppm (response defined as PaO2 increase ≥ 20 mmHg or a 20% decrease in OI); (2) A weaning protocol for iNO has been initiated after a four-to-six-hour period of stability, indicated by inspired oxygen requirement decreased/decreasing to 60–80% or OI < 10.OI < 10 for wean initiation

Extended administration beyond 72 hours requires secondary review by a medical director; weaning steps and monitoring described in policy.

Summary of materially revised coverage criteria

Policy criteria were revised; notable content changes include:

OI threshold and section moves: Oxygen index (OI) threshold in neonatal criteria was changed multiple times between >20 and 25 in revision history; final reconciliation references OI = 25 in merged entries.OI = 25 (final in revision log)

See revision history entries for dated changes.

New indication added: Right ventricular failure was added as an additional perioperative indication (I.B.1.a.3).n/a

Material addition documented in revision log.

Timing update: Notation in continuation criteria (section III) was updated from 48 hours to 72 hours for extended administration review timing.72 hours

Inhaled nitric oxide (iNO) is not medically necessary for indications other than those specifically listed as covered in this policy. Examples of excluded indications include acute bronchiolitis, bronchopulmonary dysplasia (BPD), congenital diaphragmatic hernia (CDH) except as a bridge to surgical repair, acute respiratory distress syndrome when not meeting the rescue criteria described herein, acute lung injury, use for vaso-reactivity testing in adults, routine post-operative cardiac surgery in adults, and treatment of vaso-occlusive crises in sickle cell disease, because safety and effectiveness for these uses have not been established.

Coverage of inhaled nitric oxide is subject to the member’s benefit terms and the Health Plan’s exclusions, limitations, and conditions of coverage. State Medicaid provisions and other applicable legal or regulatory requirements take precedence when they conflict with this clinical policy. Providers should follow plan procedures for prior authorization and benefit determination.

Any use of inhaled nitric oxide that does not meet the specific covered criteria outlined in this policy is considered not medically necessary and is not eligible for coverage under the terms described.

The medical literature predominantly does not support routine use of inhaled nitric oxide in premature infants born at 34 weeks gestational age. Requests for initiation of iNO in these premature infants may be reviewed on a case-by-case basis, with consideration given to the criteria for premature newborns ≥ 34 weeks gestational age described elsewhere in this policy.

Coding and Clinical Thresholds

CPT referencedCPT

94799

Unlisted pulmonary service or procedure

Oxygen Index (OI) policy threshold

Neonatal OI threshold (current policy)> 25

OI usage contextRequired for hypoxic respiratory failure in newborns ≥34 weeks GA as part of initial therapy criteria

OI calculation noteOI is computed as (mean airway pressure × FiO2 × 100) / PaO2

Documented revisions to Oxygen Index (OI)

Revision history summaryRevision log documents changes to the OI threshold between ≥25, >20, and reconciled back to 25 in merged entries

Specific entriesMay 2024 entry noted change from ≥25 to >20; later merged 11/24 and 07/24 entries changed OI >20 back to 25 (04/25 merge)

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for initiation of inhaled nitric oxide (iNO) therapy. Requests will be reviewed against the Health Plan's medical necessity criteria; initiation is considered medically necessary only when documented criteria are met.

Obtain prior authorization before initiating iNO for members/enrollees.
Coverage determinations are subject to the member's benefit terms, exclusions, and limitations.

Documentation Required

Documentation and Applicability

Documentation must demonstrate clinical indications and applicability to the Health Plan policy and any state or federal requirements. Providers should include objective evidence to support medical necessity.

Document gestational age at birth (in weeks) when applicable.
Provide evidence of pulmonary hypertension (e.g., echocardiogram report, clinical notes describing persistent pulmonary hypertension).

Background and Clinical Context

Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator used to improve oxygenation by reducing pulmonary vascular resistance. It is most often considered in term and near-term neonates with hypoxic respiratory failure and pulmonary hypertension, where randomized trials have shown a reduction in the need for extracorporeal membrane oxygenation (ECMO) without increasing neurodevelopmental abnormalities at two years. In clinical practice, iNO is used as an initial therapy for neonates with evidence of pulmonary arterial hypertension unresponsive to maximal conventional support, as a perioperative agent for infants/children with specific cardiac or pulmonary surgical indications, and as a rescue inhaled pulmonary vasodilator in severe acute respiratory distress (including selected COVID-19 cases) when other optimized ventilation and rescue strategies have failed. Response to a monitored trial (commonly a recommended starting dose of 20 ppm with assessment up to 40 ppm) is defined by improvement in oxygenation (increase in PaO2 ≥ 20 mmHg or a 20% decrease in Oxygen Index) and guides continuation or weaning decisions.

Definitions and Clinical Metrics

Oxygen Index (OI) — definition & formula

DefinitionOxygen Index (OI) quantifies severity of hypoxemic respiratory failure

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

Clinical useUsed in neonatal criteria to determine need for iNO when OI threshold exceeded

iNO clinical response definition

iNO response — primary definitionIncrease in PaO2 ≥ 20 mmHg OR a 20% decrease in OI following a trial of iNO up to 40 ppm

Recommended starting doseRecommended dose commonly 20 ppm; trial may escalate up to 40 ppm to assess response

Revision History and Policy Changes

2024-07material_addition

Added right ventricular failure as an additional perioperative indication (I.B.1.a.3) and removed criterion I.A. requiring administration via endotracheal tube or tracheostomy; oxygen index in I.A.6. was reported updated from ≥25 to >20 in the May/July log entries.

2024-11terminology_update

Updated wording in criteria IV from 'adult respiratory distress' to 'acute respiratory distress' (Approval Date = 11/24).

2025-04threshold_reconciliation_and_reorg

Policy Summary

Payermhn

PolicyTherapeutic Utilization of Inhaled Nitric Oxide

Policy CodePolicy CP.MP.87

Change TypeMaterial revisions to criteria, thresholds, and indications

Effective Date

Next Review Date

Key ActionObtain prior authorization and document that initiation criteria are met (e.g., OI threshold, failed conventional therapies, evidence of pulmonary hypertension) before starting iNO.

SourceLink

On This Page

Note

Required Prior/Concomitant Therapies

Prior to initiation of iNO, conventional and/or concomitant therapies should have been attempted and documented unless contraindicated or the situation is emergent.

Conventional respiratory support: mechanical ventilation and optimization of ventilator settings.
High fraction of inspired oxygen (FiO2), typically 80–100% prior to initiating iNO.
High-frequency oscillatory ventilation (HFOV) when clinically indicated.
Induction of alkalosis when used as a strategy to improve oxygenation.
Use of neuromuscular blockade and/or sedation as appropriate to clinical status.
For perioperative use: initiation of alternative vasodilator therapy (e.g., sildenafil) during iNO with intent to wean or discontinue, per policy continuation criteria.

Denial Risk

Denial Risk and Coverage Limits

Use of iNO for indications listed as not medically necessary in this policy is a denial trigger. Coverage decisions are additionally subject to the member's coverage documents and applicable law.

Denials may be issued if requested use does not meet the medical necessity criteria (e.g., indications such as acute bronchiolitis, BPD, most cases of CDH, ARDS outside specified criteria, sickle cell vaso-occlusive crisis).
Coverage is subject to Health Plan-level administrative policies, state/federal requirements, and benefit-specific terms, conditions, exclusions and limitations.