iNO is FDA approved for treatment of pulmonary hypertension in term and near-term (>34 week) infants.

Patient eligibility

• iNO therapy should be considered in infants with a PaO₂ < 80 mmHg despite 100% oxygen via the ventilator who have proven or suspected PPHN.

• Infants with cyanotic congenital heart disease and decreased pulmonary blood flow may also benefit from iNO and are candidates for treatment at the discretion of the attending cardiologist.

• Infants with congenital diaphragmatic hernia who are preoperative and have never achieved a PaO₂ > 100 mmHg are unlikely to benefit from iNO. iNO has been efficacious at times in infants with CDH who are post-op and in those rare infants who initially have high PaO₂ and then develop secondary reactive pulmonary hypertension.

• Infants who are already on iNO in transport from another institution should have it continued until ECMO is established.

• Insure adequate lung inflation prior to administration of exogenous NO. High frequency oscillatory ventilation has been demonstrated to augment iNO’s effect in this regard.

• An echocardiogram is recommended in infants with this degree of hypoxemia to exclude cyanotic congenital heart disease, but an Echo does not necessarily have to be obtained prior to initiating iNO in a deteriorating infant with a clinical diagnosis of PPHN.

Initiating iNO

• A baseline ABG should be obtained and recorded prior to iNO initiation.

• Inhaled NO is initiated at 20 ppm.

• Response is defined as an improvement in PaO₂ by 20 mmHg or a > 5% increase in SaO₂.

• Infants who fail to respond to iNO may have iNO discontinued. In the event the patient acutely deteriorates, ECMO should be readily available.

• iNO should be continued at ≥ 20 ppm until the patient has been able to wean to < 60% O₂

Weaning iNO

• A standing respiratory therapy protocol has been initiated to have RT automatically wean patients from iNO once the baby’s oxygen requirement has decreased to < 60%. The physician should be aware of this and either order a trial of weaning or specifically instruct RT not to wean.

• To wean, the iNO should be decreased to 3ppm and then to 1ppm and then turned off in q 1 hour intervals if the baby tolerates weaning.

• If the infant desaturates by 5% or more, the iNO dosage previously tolerated should be resumed.

• The respiratory therapist will attempt to wean the infant every 12 hours (0800 and 2000 hours) unless instructed differently by the physician’s orders.

• An infant with an O₂ requirement persistently >60% should have his/her response to iNO challenged and documented qod. If an infant needs iNO for > 6 days, consider an anatomic etiology of pulmonary hypertension, for ex. alveolar capillary dysplasia.

Toxicity

• Potential toxicity should be monitored by obtaining a methemoglobin level 4 hours after initiating iNO. A baseline methemoglobin level no longer needs to be obtained nor do methemoglobin levels need to be checked daily if the initial methemoglobin is within safe limits. Treatment should be modified if the methemoglobin level is > 3%.

• Increased toxicity without improved efficacy has been documented at iNO dosages of > 40 ppm.

Approved at Nursery Policy & Procedure Meeting 9/19/01.

References:

American Academy of Pediatrics. Use of Inhaled Nitric Oxide. Pediatrics 2000; 106: 344-5.

Finer NN, Barrington KJ. Nitric oxide for respiratory failure in infants born at or near term. Cochrane Database of Systematic Reviews, 2000; 2: CD000399.   http://www.nichd.nih.gov/cochraneneonatal/FINER/FINER.HTM

The Neonatal Inhaled Nitric Oxide Study Group. Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure. N Engl J Med 1997; 336: 597-604.

Clark RH, Kueser TJ, Walker MW, et al. Low-dose nitric oxide therapy for persistent pulmonary hypertension of the newborn. N Engl J Med 2000; 342: 469-74.

The Neonatal Inhaled Nitric Oxide Study Group. Inhaled nitric oxide and hypoxic respiratory failure in infants with congenital diaphragmatic hernia. Pediatrics 1997; 99: 838-45.

Davidson D, et al. Safety of withdrawing inhaled nitric oxide therapy in persistent pulmonary hypertension of the newborn. Pediatrics 1999; 104: 231-36.

Kinsella JP, Abman SH. Clinical approach to inhaled nitric oxide therapy in the newborn with hypoxemia. J Pediatr 2000; 136: 717-26.

Kinsella JP, Abman SH. High-frequency oscillatory ventilation augments the response to inhaled nitric oxide in persistent pulmonary hypertension of the newborn. Chest. 1998; 114: 100S.

Sokol GM, Fineberg NS, Wright LL, Ehrenkranz RA. Changes in arterial oxygen tension when weaning neonates from inhaled nitric oxide. Pediatric Pulmonology 2001; 32: 14-9.