What are the indications for inhaled nitric oxide (iNO) in adults?

Indications for Inhaled Nitric Oxide in Adults

Inhaled nitric oxide (iNO) in adults is primarily indicated as a rescue therapy for mechanically ventilated patients with severe ARDS and refractory hypoxemia despite optimizing ventilation, and for acute vasoreactivity testing in patients with idiopathic, heritable, or drug-induced pulmonary arterial hypertension. 1, 2

Primary Indications

1. Severe ARDS with Refractory Hypoxemia

• Strong indication: Use as rescue therapy in mechanically ventilated patients with COVID-19 or other causes of severe ARDS when hypoxemia persists despite:
  • Optimizing ventilation strategies
  • Use of prone positioning
  • Other rescue therapies 1
• Dosing:
  • Initial dose: 5-10 ppm
  • Maximum effective dose: 20 ppm (higher doses may worsen oxygenation) 3
• Expected benefits:
  • Improved ventilation-perfusion matching
  • Reduced pulmonary vascular resistance
  • Increased arterial oxygenation 3, 4

2. Pulmonary Arterial Hypertension (PAH) Assessment

• Vasoreactivity testing: Primarily for patients with:
  • Idiopathic PAH
  • Heritable PAH
  • Drug-induced PAH 2
• Not recommended for vasoreactivity testing in:
  • Other forms of PAH
  • PH groups 2,3,4, and 5 2
• Testing protocol:
  • Dose: 10-20 ppm
  • Duration: 5 minutes
  • Positive response: Reduction of mean PAP ≥10 mmHg to reach an absolute value ≤40 mmHg with unchanged or increased cardiac output 2

3. Acute Severe Pulmonary Hypertension with RV Dysfunction

• Indication: Acute severe pulmonary hypertension causing:
  • Right ventricular pressure overload
  • Right ventricular systolic dysfunction
  • Hemodynamic instability 1, 5
• Clinical context: Often in critically ill patients with hypoxemia and pulmonary hypertension 1
• Expected benefits:
  • Reduced pulmonary vascular resistance
  • Improved right ventricular function
  • Enhanced hemodynamic stability 5

Important Considerations

Monitoring and Administration

• Should only be administered in expert centers or ICU settings due to technical demands and potential complications 2
• Requires continuous monitoring of:
  • Arterial blood gases
  • Methemoglobin levels (especially with doses >5 ppm)
  • Hemodynamic parameters 4
• Risk of rebound pulmonary hypertension upon abrupt discontinuation 2

Dose-Response Relationship

• Pulmonary vasodilation occurs at lower doses (0.5-5 ppm) 4
• Optimal oxygenation improvement typically occurs at 5-20 ppm 3, 4
• Doses >20 ppm may worsen oxygenation and increase methemoglobin levels 3
• Individualized dose titration is necessary as response varies between patients 4

Limitations and Contraindications

• FDA approval is limited to neonates with hypoxic respiratory failure associated with pulmonary hypertension 6
• Use in adults is off-label but supported by clinical evidence and guidelines 1
• Not recommended for routine use in all mechanically ventilated COVID-19 patients with ARDS 1

Clinical Pearls

• Response to iNO should be assessed within 30-60 minutes of initiation
• Approximately 60-70% of ARDS patients respond to iNO with improved oxygenation 3
• Most responders show benefit at low doses (1-5 ppm) 3
• When weaning from iNO, gradual dose reduction is essential to prevent rebound pulmonary hypertension 2
• Consider alternative pulmonary vasodilators (e.g., epoprostenol) if iNO is unavailable 2

In summary, while iNO has specific indications in adult critical care, its use should be targeted to appropriate patient populations, administered at effective doses, and managed by experienced clinicians to maximize benefit while minimizing potential complications.