What is the initial dosing and administration protocol for inhaled nitric oxide (iNO) in adult patients?

Initiating Inhaled Nitric Oxide Therapy in Adults

The standard initial dose for inhaled nitric oxide (iNO) in adult patients is 20 parts per million (ppm), which has been shown to effectively decrease pulmonary vascular resistance and improve oxygenation in pulmonary hypertension. 1

Initial Dosing Protocol

1. Starting dose: 20 ppm

   • This dose has been demonstrated to acutely decrease pulmonary vascular resistance (PVR) and improve cardiac output in pulmonary hypertension 1
   • Provides rapid response in improving oxygenation compared to lower doses 2

2. Administration method:

   • Deliver through the inspiratory limb of the ventilator circuit
   • Ensure proper monitoring equipment is in place before initiation
   • Maintain continuous electrocardiographic monitoring during use 1

3. Monitoring parameters:

   • Pulmonary artery pressure (target: reduction from baseline)
   • Oxygenation (PaO₂/FiO₂ ratio)
   • Methemoglobin levels (keep <2%)
   • NO₂ levels (keep <2 ppm)
   • Continuous hemodynamic monitoring

Dose Titration

• Assess response after 30 minutes of initial administration 3, 4
• If inadequate response:
  • Consider increasing to maximum of 40 ppm
  • Note: Doses above 20 ppm may worsen oxygenation in some patients 3
• If adequate response:
  • Consider gradual downward titration to lowest effective dose (as low as 5 ppm)
  • Many patients respond well to doses between 5-10 ppm 3

Response Assessment Criteria

• Positive response defined as:
  • ≥20% increase in PaO₂/FiO₂ ratio 4
  • Reduction in mean pulmonary artery pressure 1
  • Improvement in cardiac output
  • No significant decrease in systemic blood pressure

Important Considerations

• Weaning protocol:

  • Gradual weaning is essential to prevent rebound pulmonary hypertension
  • Consider starting or restarting a phosphodiesterase inhibitor before weaning 1
  • Decrease by 5 ppm increments while monitoring for clinical deterioration

• Potential complications:

  • Rebound pulmonary hypertension upon abrupt discontinuation 1
  • Methemoglobinemia (especially at sustained high doses)
  • Formation of nitrogen dioxide (NO₂)
  • Tachyphylaxis with prolonged use

• Contraindications:

  • Left ventricular dysfunction with PCWP >18 mmHg
  • Methemoglobinemia
  • Severe bleeding risk (relative contraindication)

Clinical Pearls

• The maximum PaO₂/FiO₂ improvement often occurs at lower iNO concentrations than those required for minimal mean pulmonary artery pressure 3
• Approximately 69% of ARDS patients respond to iNO therapy; among responders, 64% respond at 1 ppm and 36% at 5 ppm 3
• For patients with severe hypoxemia, combining iNO with high-frequency oscillatory ventilation may provide additional benefit 4
• Maintain systemic vascular resistance (SVR) greater than pulmonary vascular resistance (PVR) to prevent right ventricular ischemia 1

By following this protocol for initiating inhaled nitric oxide therapy in adult patients, clinicians can effectively manage pulmonary hypertension while minimizing potential adverse effects.