ModifiedCignaPolicy N/A

Inhaled Nitric Oxide (INO) Coverage Policy

Policy governing medical necessity and coverage of inhaled nitric oxide (INO) therapy for conditions related to reversible pulmonary vasoconstriction and pulmonary hypertension, and for vasoreactivity testing; applies to Cigna-administered health benefit plans and providers seeking coverage determinations.

Policy Summary

PayerCigna

PolicyInhaled Nitric Oxide (INO) Coverage Policy

Policy CodePolicy N/A

Change TypeRevisedmaterial changes to duration and neonatal hypoxic respiratory failure statements

Effective DateN/A

Next Review DateSep 15, 2025

Key ActionWhen requesting coverage, providers must document that the patient meets the policy's medically necessary indications and submit indication‑specific supporting evidence as required for prior authorization.

SourceLink

POLICY UPDATE CHANGES

Added policy statement for duration of treatment for inhaled nitric oxide.

Revised policy statement for hypoxic respiratory failure in term or near-term infants.

14 daysmax duration (days)

20 ppmrecommended dose

＞34 wkgestational age threshold

3CPT codes listed

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Coverage Criteria for Inhaled Nitric Oxide (iNO)

Medically Necessary Indications and Limits

INO therapy is considered medically necessary when ANY of the following indications are met; when met, treatment allowed up to 14 days or until oxygenation resolves.

Medically necessary indications: 1) Hypoxic respiratory failure in a term or near-term infant (born >34 weeks gestation) without congenital diaphragmatic hernia when there is failure, contraindication, or intolerance to conventional therapy (e.g., high concentrations of oxygen, hyperventilation, sedation). 2) Postoperative management of pulmonary hypertension following repair of congenital heart disease. 3) Postoperative management of pulmonary hypertensive crisis following pediatric heart or lung surgery. 4) Acute vasoreactivity testing during heart catheterization in individuals with pulmonary hypertension.maximum duration: 14 days; recommended starting dose 20 ppm

Use with ventilatory support and appropriate monitoring (PaO2/FiO2, oxygenation index, methemoglobin, NO2).

INO use in preterm infants and neonatal subgroups

Evidence and subgroup findings relevant to coverage decisions for INO in preterm infants (<34 weeks gestation):

Overall evidence: Multiple randomized trials, meta-analyses, and systematic reviews show inconsistent benefits of INO in preterm infants; routine early or prophylactic use in infants <34 weeks is not proven to improve survival or long-term neurodevelopmental outcomes and some trials reported higher rates of intracranial hemorrhage or no clear benefit on death/BPD endpoints.

Sources include Barrington Cochrane, Feng et al. 2024, Van Meurs and Hoehn meta-analyses.

Subgroup signals: Some analyses report subgroup signals (e.g., reduced BPD or composite death/BPD in African American infants in Askie et al.; in Feng et al. subgroup reductions in BPD for infants <3 days, birth weight >1000 g, INO dose ≥10 ppm, or duration >7 days). These findings are inconsistent and represent subgroup analyses rather than consistent trial-wide effects.

Sources: Feng 2024; Askie et al. 2018.

Harms and safety signals: Trials and reviews identified potential harms including higher rates of intracranial hemorrhage in some preterm studies and safety concerns; overall evidence does not support routine use in preterm infants <34 weeks.

Sources: Barrington Cochrane review, Van Meurs, Hoehn, and other trial reports.

INO use in ARDS (adult and pediatric) including COVID-19

Evidence summary for ARDS and COVID-19 associated ARDS:

Clinical findings: INO produces transient improvement in oxygenation (PaO2/FiO2 or OI) but randomized trials and systematic reviews do not show mortality benefit or increased ventilator-free days; some meta-analyses report an increased risk of acute kidney injury/renal failure in ARDS patients.

Sources: Di Fenza 2023 (COVID-19 trial), Wang et al. 2021 (AKI meta-analysis), Gebistorf et al. 2016 (Cochrane ARDS review).

COVID-19 specifics: Trials in COVID-19 ARDS showed short-term oxygenation improvements without mortality or ventilation-duration benefit; proposed antiviral effects remain theoretical and unproven.

Source: Di Fenza et al. 2023.

Coverage stance by indication

Coverage considerations by proposed indication based on randomized trial and systematic review evidence

ARDS / Acute Lung Injury: INO yields transient oxygenation improvement but does not reduce mortality or ventilator-free days; systematic reviews report increased renal failure risk; routine coverage for ARDS/ALI is not supported.

Gebistorf 2016; Adhikari/Angus trials; Wang 2021.

Bronchiolitis (infants): Randomized trials (pooled n=166) show no meaningful reduction in hospital length of stay and higher rate of treatment-related harms; evidence insufficient and use may be harmful.

Kuitunen & Renko 2024.

Perioperative / Cardiac Surgery / CPB oxygenator: Large pediatric RCT (n=1371) of NO into the CPB oxygenator showed no difference in ventilator-free days, ICU/hospital length of stay, or most secondary outcomes; routine perioperative use not supported.

Schlapbach et al. 2022.

Neonatal PPHN / Term and near-term infants

Covered when ALL of the following are met

Neonatal INO criteria: 1) Infant is term or near-term (≥34 weeks gestation). 2) Refractory hypoxemia defined as PaO2 <100 mm Hg on FiO2 1.0 and/or oxygenation index (OI) >25. 3) Failure, contraindication, or intolerance to conventional therapies (e.g., optimal ventilatory recruitment, surfactant where indicated, high FiO2, hyperventilation). 4) Administered in a center with appropriate neonatal critical care expertise and ECMO availability or with established transfer mechanisms. 5) INO dosing and monitoring consistent with product labeling and society recommendations (recommended starting dose 20 ppm; assess response within 30–60 minutes and wean to lowest effective dose).see node text

Based on AARC, AHA/ATS, EPPVDN recommendations and product labeling; maximum duration up to 14 days when criteria met.

Pediatric pulmonary hypertension / PH crises

Covered with criteria in intensive care setting

Pediatric PH INO use: 1) Acute pulmonary hypertensive crisis or acute right ventricular failure in children. 2) INO used as initial therapy alongside conventional postoperative or ICU care in mechanically ventilated patients to improve ventilation–perfusion matching and reduce risk of PH crisis. 3) Administration in an intensive care setting with continuous monitoring and availability of complementary therapies (e.g., inhaled prostacyclin, systemic vasopressors) and expertise in pediatric PH management.acute setting

AHA/ATS and EPPVDN guidance (Class I/II indications depending on context).

Vasoreactivity testing in adults/children with pulmonary arterial hypertension

Covered when ALL of the following are met

AVT using INO: 1) Performed for assessment of vasoreactivity in idiopathic pulmonary arterial hypertension or as indicated by treating specialists. 2) Use of a short-acting agent such as inhaled nitric oxide (INO), inhaled iloprost, or IV epoprostenol during right-heart catheterization. 3) Conducted at centers experienced in vasoreactivity testing with appropriate hemodynamic monitoring and interpretation capability.positive response = fall in mean PAP >10 mm Hg to <40 mm Hg with unchanged or increased cardiac output

Recommended by ESC/ERS and ACCP; Level of evidence C for vasoreactivity testing recommendations.

Other proposed indications (PE, LVAD/RV dysfunction, sickle cell VOC)

Not routinely covered / investigational due to insufficient evidence

Evidence summary: Randomized trials and systematic reviews have not demonstrated consistent clinical benefit of INO for acute pulmonary embolism, for improving RV geometry/function after LVAD, or for vaso-occlusive crises in sickle cell disease; available RCTs are small or show no effect on primary clinical endpoints. Thus, INO for these indications is considered investigational/ not routinely covered.evidence insufficient

Cochrane reviews and RCTs (Kline 2019; Kukucka 2011; Aboursheid/Gladwin reviews) report limited or negative findings.

iNO-associated procedure code medical necessity

Codes considered medically necessary when used in association with administration of inhaled nitric oxide and when applicable policy clinical criteria are met:

iNO-associated code coverage: Use of the listed CPT and ICD-10-PCS procedure codes is considered medically necessary when performed in association with administration of inhaled nitric oxide AND the clinical criteria in the applicable policy statements are met.

Confirm code applicability and that criteria in this policy are satisfied prior to billing.

Revised policy statements

See full policy for detailed medical necessity criteria; recent revisions affect duration and neonatal hypoxic respiratory failure statements.

Policy revisions include addition of a duration statement for INO treatment (maximum duration when criteria met) and revisions to the hypoxic respiratory failure criteria for term/near-term infants.

See full policy text and revision history for exact effective dates and wording.

INO (inhaled nitric oxide) is considered not medically necessary for any indication not explicitly listed as medically necessary above. Examples of conditions for which routine coverage is not supported include acute respiratory distress syndrome (ARDS), adult heart and/or lung transplantation, treatment in infants ≤34 weeks gestation, and congenital diaphragmatic hernia (CDH), based on insufficient evidence of safety and efficacy.

Routine or early use of INO in preterm infants and routine use of INO for ARDS (adult or pediatric) are not supported by the evidence summarized. Systematic reviews and randomized trials generally show only transient oxygenation benefits without reductions in mortality or ventilator‑free days, and some analyses report safety signals such as increased intracranial hemorrhage in preterm infants or renal dysfunction in ARDS.

Available randomized trials and systematic reviews do not support routine use of INO for ARDS/ALI, bronchiolitis, prevention or treatment of bronchopulmonary dysplasia/chronic lung disease (BPD/CLD) in preterm infants, interstitial lung disease (ILD), or routine perioperative cardiac indications. These indications lack consistent evidence of clinical benefit (survival, ventilator‑free days, long‑term function) and in some instances have demonstrated potential harms.

Per the GOLD guidance, INO is contraindicated in stable COPD because it can worsen gas exchange by altering hypoxic regulation of ventilation‑perfusion balance.

Deleted procedure or billing codes and codes that are not effective at the time the service is rendered may not be eligible for reimbursement. Confirm code validity and effective dates prior to billing.

No additional explicit exclusions beyond those summarized above are listed in the provided document extracts.

INO has not been proven beneficial for infants <34 weeks gestation, for congenital diaphragmatic hernia (CDH), or for certain preterm infants with PPHN. Early studies showed transient oxygenation improvement but no survival benefit and in some trials a higher rate of intracranial bleeding; therefore routine use in these neonatal subgroups is not supported.

Multiple high‑quality reviews and randomized trials conclude there is insufficient evidence to support routine INO for preterm infants under 34 weeks gestation and for routine treatment of ARDS in adults or children; reported effects are generally limited to short‑term oxygenation improvement without durable clinical benefit.

Across several indications, INO has not been shown to improve important clinical outcomes such as survival, ventilator‑free days, or long‑term functional outcomes. Systematic reviews and randomized trials commonly report only transient improvements in oxygenation and fail to demonstrate mortality or durable benefit.

Randomized trials and systematic reviews in sickle cell disease indicate INO is ineffective / not medically necessary for vaso‑occlusive crises or acute chest syndrome; trials did not show benefit for time to pain resolution, opioid use, or relevant clinical endpoints.

Evidence supporting INO for acute pulmonary embolism is limited and insufficient to support routine use. A randomized trial of inhaled NO for intermediate‑high‑risk PE did not meet its primary composite endpoint at 24 hours, and the broader literature is limited to small studies and case series.

The cited references and trial reports summarized in these extracts generally describe trials and systematic reviews that found no clear benefit for several proposed INO indications; the document extracts do not contain additional explicit 'not medically necessary' language beyond the summarized findings.

Codes, Dosing, and Gestational Thresholds

FDA-approved products/devicesmixed

INOmax	FDA-approved INO product example (INOmax ® )
Genosyl	FDA-approved INO product (Genosyl ® )
LungFit PH	FDA-approved nitric oxide generator/delivery system (LungFit ® PH)

Product identifiers / notesmixed

INOvent	Example delivery device (INOvent) referenced as an administration apparatus
Noxivent	FDA-approved therapeutic equivalent (Noxivent ® )
ULSPIRA	FDA-approved therapeutic equivalent (ULSPIRA™)

Considered Medically Necessary when used with INOCPTCovered

93463	Pharmacologic agent administration (eg, inhaled nitric oxide, intravenous infusion of nitroprusside, dobutamine, milrinone, or other agent) including assessing hemodynamic measurements before, during, after and repeat pharmacologic agent administration, when performed (List separately in addition to code for primary procedure).
94002	Ventilation assist and management, initiation of pressure or volume preset ventilators for assisted or controlled breathing; hospital inpatient/observation, initial day.
94003	Ventilation assist and management, initiation of pressure or volume preset ventilators for assisted or controlled breathing; hospital inpatient/observation, each subsequent day.

Considered Medically Necessary CPT Codes when used with iNOCPTCovered

93463	Pharmacologic agent administration (eg, inhaled nitric oxide, intravenous infusion of nitroprusside, dobutamine, milrinone, or other agent) including assessing hemodynamic measurements before, during, after and repeat pharmacologic agent administration, when performed (List separately in addition to code for primary procedure).
94002	Ventilation assist and management, initiation of pressure or volume preset ventilators for assisted or controlled breathing; hospital inpatient/observation, initial day.
94003	Ventilation assist and management, initiation of pressure or volume preset ventilators for assisted or controlled breathing; hospital inpatient/observation, each subsequent day.

Considered Medically Necessary ICD-10-PCS Procedure Codes when used with iNOmixedCovered

3E0F3SD	Introduction of Nitric Oxide Gas into Respiratory Tract, Percutaneous Approach.
3E0F7SD	Introduction of Nitric Oxide Gas into Respiratory Tract, Via Natural or Artificial Opening.
3E0F8SD	Introduction of Nitric Oxide Gas into Respiratory Tract, Via Natural or Artificial Opening Endoscopic.

INO dose — dosing limits and toxicity

Recommended starting dose20 ppm (initial recommended dose per FDA and society guidance)

Upper dosing guidanceDoses greater than 20 ppm are not recommended per FDA labeling

Toxicity thresholdToxicity is typically seen at doses ≥80 ppm (though toxicity has occurred at lower doses)

Gestational age — neonatal eligibility

Gestational age threshold for primary neonatal indication> 34 weeks gestation (term/near‑term) — required for primary neonatal hypoxic respiratory failure indication

FDA-approved indication age wording

Authorization, Documentation, and Billing Actions for Providers

Billing Rule

Claims Coding and Coverage Risk

Claims for services that are not accompanied by covered code(s) under the applicable Coverage Policy will be denied as not covered. When submitting requests for coverage or claims related to inhaled nitric oxide (INO), ensure the appropriate INO-associated CPT and procedure codes are billed only when the patient meets the policy criteria described in this Coverage Policy.

When billing, providers must use the most appropriate and effective codes as of the date of service; deleted or not-yet-effective codes may not be eligible for reimbursement.

Prior Authorization

Prior Authorization Required

Prior authorization is required for administration of inhaled nitric oxide when the service is for an indication that falls under policy coverage rules (e.g., neonatal hypoxic respiratory failure in term/near-term infants, postoperative pulmonary hypertension management, or acute vasoreactivity testing during right-heart catheterization). Requests for chronic or device-based INO therapies (for example, INOpulse®) or for perioperative delivery into a CPB oxygenator should also be submitted for prior authorization.

Background and Evidence Summary

Nitric oxide (NO) is an endogenous mediator that can be administered therapeutically as inhaled nitric oxide (INO). INO acts as a selective pulmonary vasodilator when delivered into ventilated lung regions, improving ventilation–perfusion matching and oxygenation. Clinical administration requires specialized delivery systems and monitoring for NO2 and methemoglobin per product labeling and guidance.

The policy references multiple randomized controlled trials and systematic reviews informing coverage decisions, including large meta‑analyses (e.g., Feng et al. 2024, k=17, n=4080) and Cochrane/systematic reviews (e.g., Gebistorf et al. 2016, k=14, n=1275). These trials provide both supporting and non‑supporting evidence across neonatal, ARDS, and other proposed indications and are summarized in the policy evidence sections.

Definitions and Key Terms

INO (Inhaled Nitric Oxide) — definition and delivery/monitoring requirements

DefinitionInhaled nitric oxide (INO) is a selective pulmonary vasodilator gas administered by inhalation to improve oxygenation in ventilated lung regions

Delivery system componentsA complete delivery system includes administration apparatus, NO gas analyzer, and NO2 gas analyzer (FDA description)

Monitoring requirementsContinuous in-line monitoring of NO, inspired NO2, and methemoglobin levels during administration is standard of care

Administration contextINO is administered in conjunction with ventilatory support and other appropriate therapies; FDA labeling recommends FDA‑approved delivery systems

PPHN (Persistent Pulmonary Hypertension of the Newborn) — definition and features

Definition of PPHN

Policy Revision History

2025-09-15annual_review_addedLatest

Added policy statement specifying a duration of treatment for inhaled nitric oxide.

2024-07-15annual_review_revised

Revised the policy statement for hypoxic respiratory failure in term or near-term infants.

Policy Summary

PayerCigna

PolicyInhaled Nitric Oxide (INO) Coverage Policy

Policy CodePolicy N/A

Change TypeRevisedmaterial changes to duration and neonatal hypoxic respiratory failure statements

Effective DateN/A

Next Review DateSep 15, 2025

SourceLink

On This Page

Chronic Lung Disease / BPD (preterm infants): Multiple RCTs including multicenter trials showed no reduction in BPD or death and no long-term neurodevelopmental benefit; routine prevention or treatment of BPD/CLD with INO is not supported.

Kinsella 2014; Mercier/EUNO; Durrmeyer; long-term follow-ups.

Interstitial Lung Disease (ILD): Phase III trial of INOpulse® in fibrotic ILD (n=145) showed no significant benefit in physical activity or secondary outcomes; evidence insufficient to support coverage for ILD.

Nathan et al. 2024.

Transplantation and LVAD: Small RCTs and reviews show inconsistent or no benefit of INO on graft function or postoperative outcomes; evidence insufficient for routine use to improve transplant or LVAD outcomes.

Botha 2007; Perrin 2006; Potapov 2011; Kukucka 2011.

Pulmonary Embolism (PE): A randomized trial (n≈76–78) did not meet the primary composite endpoint at 24 hours; secondary analyses suggested some echocardiographic improvement, but overall evidence is insufficient for routine use.

Kline et al. 2019; Bhat 2015 systematic review.

Term and near‑term neonates (>34 weeks gestation) with hypoxic respiratory failure associated with pulmonary hypertension

Society trial recommendationA trial of INO is recommended in newborns ≥34 wk gestation (per professional society guidance)

Neonatal initiation criteria — recommended trial parameters

PaO2/OI initiation thresholdsPaO2 < 100 mm Hg on FiO2 1.0 or oxygenation index (OI) > 25 — recommended criteria to consider a trial of INO

Gestational age for trialGestational age ≥34 weeks for neonatal INO trial per AARC/EPPVDN guidance

Response assessment timingAssess response to a short trial (30–60 minutes); discontinue if no improvement in PaO2 or OI

Provide clinical justification demonstrating the patient meets the applicable policy criteria.
Prior authorization is typically required for chronic outpatient INO delivery systems (e.g., INOpulse®) or investigational/off-label uses.

Documentation Required

Supporting Documentation for Neonatal Subgroup Requests

Provider requests that rely on neonatal subgroup evidence (for example, preterm infants or race-specific subgroup claims of benefit) must include indication- and subgroup-specific documentation demonstrating that the patient matches the subgroup characteristics and treatment parameters reported in the supporting literature.

Include gestational age at birth, postnatal age at treatment initiation, birth weight, race if cited as a subgroup effect modifier, INO dose, duration of therapy, timing relative to other interventions, and oxygenation metrics (PaO2, FIO2, oxygenation index).
If citing a subgroup (e.g., African American preterm infants or neonates meeting specific age/weight/dose/timing criteria), submit the trial/protocol details that justify the extrapolation to the individual patient.

Step Therapy

Sequencing with Conventional Therapy and Step Therapy Requirements

Documentation accompanying prior authorization requests and claims must demonstrate that conventional therapies were attempted and optimized prior to initiation of INO in indications where step-wise therapy is required. For neonates, document use of standard neonatal respiratory management strategies prior to INO.

Document trials and optimization of conventional therapies: supplemental oxygen, optimized ventilator strategy (including settings and PEEP), surfactant administration when indicated, CPAP or mechanical ventilation, sedation/paralysis if used, and other institution-specific rescue measures.
For neonatal hypoxic respiratory failure, include oxygenation metrics (PaO2, FIO2), oxygenation index (OI), and note whether criteria such as PaO2 <100 on FIO2 1.0 or OI >25 were met per society guidance.
For chronic lung disease (CLD)/bronchopulmonary dysplasia (BPD) prevention or treatment in preterm infants, document stepwise trials of standard neonatal respiratory therapies prior to INO (e.g., surfactant, noninvasive ventilation, invasive ventilation with optimized lung recruitment).

Documentation Required

Documentation for Neonatal INO Use and Diagnostic Testing

For neonatal INO use, and other inpatient short-course indications, document diagnostic testing and monitoring consistent with product labeling and society recommendations to support authorization and safe delivery.

Echocardiogram to evaluate for congenital heart disease and to assess pulmonary hypertension prior to or during INO therapy.
When used for pulmonary hypertension evaluation, include right-heart catheterization hemodynamics if performed, and detailed vasoreactivity testing notes when INO is used diagnostically.
Monitoring documentation: INO starting dose, titration/wean steps, methemoglobin measurements (approx. 8 and 24 hours after initiation and daily thereafter), NO2 alarm settings, and details of INO delivery system used (FDA-approved device).

Billing Rule

INO-associated CPT and Procedure Codes Require Policy Criteria

When billing CPT or ICD-10-PCS procedure codes associated with INO administration or related procedures, ensure submitted codes are supported by the clinical documentation and meet the policy criteria. Certain CPT codes are considered medically necessary only when used in association with INO and when the policy criteria are met.

Covered CPT codes (considered medically necessary when used in association with INO and policy criteria met): 93463 (pharmacologic agent administration with hemodynamic assessment), 94002 (ventilation assist and management, initiation, initial day), 94003 (ventilation assist and management, each subsequent day).
ICD-10-PCS / procedure codes for INO delivery (considered medically necessary when used in association with INO and policy criteria met): 3E0F3SD (Introduction of Nitric Oxide Gas into Respiratory Tract, Percutaneous Approach), 3E0F7SD (Introduction of Nitric Oxide Gas into Respiratory Tract, Via Natural or Artificial Opening), 3E0F8SD (Introduction of Nitric Oxide Gas into Respiratory Tract, Via Natural or Artificial Opening Endoscopic).
Verify that codes are active and not deleted at the time of service; deleted or inapplicable codes may lead to denial.

Documentation Required

Documentation to Support iNO-associated Procedures and Device-based Delivery

For perioperative or device-based INO delivery (for example, NO introduced into a cardiopulmonary bypass oxygenator) and for chronic outpatient devices (e.g., INOpulse®), include procedure- and device-specific documentation to support the request and to justify the selected codes.

Provide the operative report or CPB perfusion record noting NO delivery (dose, duration, and delivery method) when submitting codes for NO delivery into CPB oxygenator.
For INOpulse® or other ambulatory/chronically used INO systems, include the treatment protocol, duration, frequency, oxygenation and activity metrics, prior trials of conventional therapies, and documentation that device use follows a specified treatment protocol or clinical trial if applicable.
If using CPT 93463 or other monitoring/administration codes during catheterization, attach hemodynamic measurements before, during, and after INO administration and clearly indicate the pharmacologic agent administration was performed.

Denial Risk

Denial Risk for Off-label or Unproven Indications

Denial risk exists for off-label, unproven, or contraindicated uses of INO. Examples with frequent denial risk include routine use for ARDS (adult or pediatric), use in preterm infants <34 weeks gestational age without strong protocolized evidence, and other indications where evidence does not support improved mortality or safety.

INO has not demonstrated mortality benefit in ARDS and has been associated with an increased risk of renal failure in systematic reviews — routine ARDS use may be denied.
INO use in preterm infants <34 weeks gestation is not supported by consistent evidence and may be denied absent strong subgroup-specific justification and protocolized care.
Claims for codes not supported by documentation that meets policy criteria will be denied as not covered.

Sustained elevation of pulmonary vascular resistance in neonates causing severe hypoxemia due to extrapulmonary right‑to‑left shunting across PDA or PFO

Clinical featuresSevere hypoxemia in term/near‑term neonates often associated with conditions like meconium aspiration, RDS, pneumonia, sepsis, or pulmonary hypoplasia

Treatment goalMaximize oxygen transport; conventional therapies include high FiO2, hyperventilation, HFV, alkalinization, sedation; INO used when conventional therapy fails

ARDS — definition and clinical management context

Definition/contextARDS is acute onset pulmonary edema (not due to volume overload or LV failure) with impaired gas exchange requiring high FiO2, PEEP, and supportive care

INO clinical effect in ARDSINO produces transient improvements in oxygenation (PaO2/FiO2) but randomized trials and reviews do not show mortality benefit

Safety considerationsSystematic reviews have reported no mortality benefit and potential increased risk of renal failure; routine use in ARDS is not supported

BPD (bronchopulmonary dysplasia) — policy definition

Policy definition usedBPD defined as continuing need for supplemental inspired oxygen at 36 weeks postconceptional age

Clinical contextBPD/CLD arises from low birth weight, inflammation, mechanical and oxidative injury; INO proposed but evidence insufficient

Trial evidence summaryMultiple RCTs and trials (including multicenter EUNO and Kinsella) found no consistent reduction in BPD or death with INO in preterm infants

Chronic Lung Disease (CLD) / BPD — definition and policy reference

Definition referenceChronic Lung Disease (CLD)/BPD: continuing need for supplemental inspired oxygen at 36 weeks postconceptional age (Clark et al., 2000)

Proposed mechanismINO's anti‑inflammatory effects and improved V/Q matching proposed for CLD treatment, but evidence is insufficient

Policy stanceRoutine prevention or treatment of BPD/CLD with INO is not supported by available evidence

Positive acute vasoreactivity response — threshold for haemodynamic testing

Positive vasoreactivity response — hemodynamic thresholdA fall in mean pulmonary artery pressure (mPAP) >10 mm Hg to a mean <40 mm Hg with unchanged or increased cardiac output during challenge (eg, inhaled NO)

Context of useDefinition used for acute vasoreactivity testing in idiopathic PAH per ACCP/ESC/ERS guidance

Testing settingShould be performed at centers experienced in testing and interpretation

Administration of inhaled nitric oxide (iNO) — procedural definition and coding association

Procedural definitionAdministration of inhaled nitric oxide (iNO) is the procedural introduction of nitric oxide gas into the respiratory tract (percutaneous or via natural/artificial opening)

Associated procedure codesCPT codes 93463, 94002, 94003 and ICD‑10‑PCS codes 3E0F3SD, 3E0F7SD, 3E0F8SD are listed as medically necessary when provided in association with iNO and policy criteria are met

Documentation/monitoringProcedure should include monitoring and hemodynamic assessment as indicated; use FDA‑approved delivery systems per guidance

Persistent pulmonary hypertension of the newborn (PPHN) — literature and guideline references

PPHN — broader referencesPPHN: neonatal condition of elevated pulmonary vascular resistance causing right‑to‑left shunting and hypoxemia; discussed in multiple references and reviews (eg, Mandell, Kinsella, Abman)

Clinical implicationsINO improves oxygenation and can reduce need for ECMO in term/near‑term neonates with PPHN when conventional therapy fails

Society guidanceProfessional society statements (AAP, EPPVDN, AHA/ATS) provide diagnostic and management recommendations including INO use in PPHN