CurrentKaiser PermanentePolicy N/A

Inhaled_Nitric_Oxide

Clinical review criteria describing when inhaled nitric oxide (iNO) is considered medically necessary or not for neonates, pre-term newborns, pediatric and adult patients, including indications (PPHN, CDH, ARDS), exclusions, typical dosing/duration guidance, safety concerns, and applicable coding note.

Policy Summary

PayerKaiser Permanente

PolicyInhaled_Nitric_Oxide

Policy CodePolicy N/A

Change TypeClarified (revision history through 03/03/2026; no material change)

Effective Date

Next Review Date

Key ActionDocument gestational age (>34 weeks for covered PPHN indication) and that conventional therapies have failed or are expected to fail before initiating iNO for PPHN.

SourceLink

POLICY UPDATE CHANGES

Revision history entries listed through 03/03/2026; no explicit material policy change was identified.

1Covered Primary Indication (PPHN term/near-term neonates)

2Not Covered Indications (pre-term ≤34 weeks, ARDS adults/children)

20 ppmTypical Initial Dose

<=3 ppmNO2 Safety Threshold

This policy addresses inhaled nitric oxide (iNO), a selective pulmonary vasodilator used primarily for neonates with persistent pulmonary hypertension of the newborn (PPHN). The primary covered indication is treatment of PPHN in term or near-term neonates born at >34 weeks gestation when conventional therapies have failed or are expected to fail and the neonate does not have congenital diaphragmatic hernia (CDH). Key not-covered indications include use in pre-term newborns (≤34 weeks) and use for acute respiratory distress syndrome/acute lung injury (ARDS/ALI) in adults and children, which do not meet Kaiser Permanente Medical Technology Assessment Criteria. Typical initial dosing is 20 ppm with usual courses normally less than 5 days (may be longer on a case-by-case basis); important safety thresholds include maintaining nitrogen dioxide (NO2 ≤ 3 ppm) and monitoring methemoglobin to avoid levels associated with symptoms (methemoglobin > 10% is unsafe).

Key thresholds and dosing

Recommended initial dose20 ppm

Typical durationnormally less than 5 days; may be up to 14 days

NO2 safety<= 3 ppm (maintain below 3 ppm)

Methemoglobinemia threshold>10% (associated with cyanosis and symptoms)

Typical Initial Dose (20 ppm)Recommended starting concentration for iNO therapy

Medical Necessity Criteria

Treatment of pulmonary hypertension (PPHN) in term or near-term neonates (>34 weeks)

Covered when ALL of the following are met:

ALL of the following

Neonate is born at or near term (>34 weeks).
Neonate does not have congenital diaphragmatic hernia (CDH).
Conventional therapies (high concentrations of oxygen, hyperventilation, high-frequency ventilation, induction of alkalosis, neuromuscular blockade, sedation) have failed or are expected to fail.

Treatment of Congenital Diaphragmatic Hernia (CDH)

Covered in specific stabilization/ECMO transition scenarios:

ONE of

iNO is required to stabilize a patient during transition to ECMO (usually required for a few hours before).
iNO is required during transition off of ECMO when pulmonary arterial pressures are high (this can be a period ranging from hours to several days).

Provider Actions / Operational Requirements

Documentation Required

Confirm gestational age and prior conventional therapy

Document the neonate's gestational age (>34 weeks for covered PPHN) and that conventional therapies have failed or are expected to fail before initiating iNO for PPHN.

Prior Authorization

Pre-authorization check

Verify authorization requirements prior to service using the Pre-authorization Code Check.

Use the Pre-authorization Code Check to verify specific codes and the member's plan type.

Documentation Required

Monitor NO2 and Methemoglobin levels

Maintain nitrogen dioxide (NO2) concentrations at or below 3 ppm and monitor methemoglobin levels during iNO therapy.

Avoid methemoglobin levels >10% (associated with cyanosis and symptoms).

Denial Risk

Coverage denial for pre-term and ARDS indications

Claims for iNO for pre-term newborns (≤34 weeks) and for ARDS/ALI in adults and children may be denied because these uses do not meet Kaiser Permanente Medical Technology Assessment Criteria.

Policy assessment: insufficient evidence for preterm neonates and no demonstrated survival benefit (and potential renal harm) for ARDS/ALI.

Background and Evidence

The FDA approved iNO (INOmax®) in 1999 for use as a vasodilator in conjunction with ventilatory support for term and near-term (>34 weeks) neonates with hypoxic respiratory failure and clinical or echocardiographic evidence of pulmonary hypertension. Evidence supports benefit in reducing the need for extracorporeal membrane oxygenation (ECMO) for PPHN. Potential harms described in the literature and labeling include formation of nitrogen dioxide (NO2) when NO mixes with oxygen (with dose-related toxicity and a recommendation to maintain NO2 below 3 ppm), dose-dependent methemoglobinemia (with levels > 10% associated with symptoms), increased bleeding risk, and reports of renal impairment particularly noted in ARDS studies; these safety considerations require monitoring of NO2 and methemoglobin during therapy.

Evidence	Summary
PPHN evidence	Cochrane review and randomized trials support use in term/near-term neonates; meets Kaiser Permanente Medical Technology Assessment Criteria.
Preterm evidence	Meta-analyses and RCTs do not demonstrate safety/long-term benefit; does not meet Assessment Criteria.
ARDS evidence	Meta-analyses show no survival benefit and potential harm (including increased renal impairment); does not meet Assessment Criteria.

Definitions

Near-term/Term neonate>34 weeks gestation

Pre-term newborn≤34 weeks gestation

iNOInhaled Nitric Oxide, selective pulmonary vasodilator delivered via ventilator/delivery system

Revision History

03/03/2026revisionLatest

Revision history entry dated 03/03/2026; revision entries listed through this date and noted as non-material. Revision detail: Revision history entries listed through 03/03/2026; document includes prior revision dates but states criteria content (coverage positions) as presented.

03/04/2025revision

Revision history entry dated 03/04/2025; revision entries are non-material. Revision detail: Revision history entries listed through 03/03/2026; document includes prior revision dates but states criteria content (coverage positions) as presented.

03/12/2024revision

Revision history entry dated 03/12/2024; revision entries are non-material. Revision detail: Revision history entries listed through 03/03/2026; document includes prior revision dates but states criteria content (coverage positions) as presented.

12/09/2023revision

Revision history entry dated 12/09/2023; revision entries are non-material. Revision detail: Revision history entries listed through 03/03/2026; document includes prior revision dates but states criteria content (coverage positions) as presented.

12/06/2022revision

Revision history entry dated 12/06/2022; revision entries are non-material. Revision detail: Revision history entries listed through 03/03/2026; document includes prior revision dates but states criteria content (coverage positions) as presented.

12/07/2021revision

Revision history entry dated 12/07/2021; revision entries are non-material. Revision detail: Revision history entries listed through 03/03/2026; document includes prior revision dates but states criteria content (coverage positions) as presented.

12/01/2020revision

Revision history entry dated 12/01/2020; revision entries are non-material. Revision detail: Revision history entries listed through 03/03/2026; document includes prior revision dates but states criteria content (coverage positions) as presented.

09/04/2012creation

Original document date 09/04/2012 listed in revision history; revision entries are non-material. Revision detail: Revision history entries listed through 03/03/2026; document includes prior revision dates but states criteria content (coverage positions) as presented.