Medical Policy:
Inhaled Nitric Oxide
Effective Date:
February 18, 2019
Issued Date:
February 18, 2019
Last Revision Date:
January 2019
Annual Review:
June 2018

Inhaled nitric oxide (INO) is a natural vasodilator and has been studied for the treatment of a variety of types of respiratory failure. Most commonly, it is used as an initial treatment for neonates with hypoxic respiratory failure to improve oxygenation and reduce the need for invasive extracorporeal membrane oxygenation (ECMO). It is also proposed as a treatment for premature infants, critically ill children and adults with respiratory failure, as well as in the postoperative management of children undergoing repair of congenital heart disease and individuals after lung transplantation to prevent or reduce reperfusion injury.

Policy Position

Inhaled nitric oxide may be considered medically necessary as a component of treatment of hypoxic respiratory failure in neonates born at more than 34 weeks of gestation.

Inhaled nitric oxide is considered experimental/investigational, and therefore non-covered, because the safety and/or effectiveness cannot be established by available published peer-reviewed literature, including, but not limited to ANY ONE of the following indications:

  • Treatment of premature neonates born at less than or equal to 34 weeks of gestation with hypoxic respiratory failure; or
  • Treatment of adults and children with acute hypoxemic respiratory failure; or
  • Postoperative use in adults and children with congenital heart disease; or
  • In lung transplantation, during and/or after graft reperfusion. 

Inhaled nitric oxide appears to be of greatest benefit to individuals for whom primary or secondary pulmonary hypertension is a component of hypoxic respiratory failure.

The benefit of INO appears limited in term or near-term infants whose hypoxic respiratory failure is due to diaphragmatic hernia.

The following criterion for hypoxic respiratory failure has been reported:

An oxygenation index (OI) of at least 25 on 2 measurements made at least 15 minutes apart. 

(The OI is calculated as the mean airway pressure times the fraction of inspired oxygen divided by the postductal partial pressure of arterial oxygen times 100. An OI of 25 is associated with a 50% risk of requiring ECMO or dying. An OI of 40 or more is often used as a criterion to initiate ECMO therapy.) 

Clinical input from specialty societies and academic medical centers indicates that:

  • Prolonged use (greater than 1-2 weeks) of INO has not been shown to improve outcomes. Use of INO beyond 2 weeks of treatment is therefore not recommended.
  • If ECMO is initiated in near-term or term neonates, INO should be discontinued because there is no benefit to combined treatment.















Place of Service: Inpatient

The policy position applies to all commercial lines of business


This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical or other circumstances may warrant individual consideration, based on review of applicable medical records, as well as other regulatory, contractual and/or legal requirements.

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