What are the indications for inhaled nitric oxide (iNO) in an adult on a ventilator?

Indications for Inhaled Nitric Oxide in Adults on Mechanical Ventilation

Inhaled nitric oxide (iNO) should only be used as a rescue therapy in mechanically ventilated adults with severe ARDS and refractory hypoxemia despite optimization of ventilation strategies and other rescue therapies. 1

Primary Indications

Inhaled nitric oxide is not recommended for routine use in mechanically ventilated patients. The specific indications for its use are:

1. Severe ARDS with refractory hypoxemia - When all the following have been attempted:

   • Optimization of lung-protective ventilation (tidal volumes 4-8 ml/kg PBW, plateau pressure <30 cm H₂O) 1
   • Higher PEEP strategy (>10 cm H₂O) 1
   • Prone positioning for 12-16 hours 1
   • Conservative fluid management 1
   • Neuromuscular blockade as needed 1
   • Recruitment maneuvers (if appropriate) 1

2. Pulmonary hypertension with right ventricular dysfunction - When associated with severe hypoxemia that hasn't responded to conventional therapies 2, 3

Dosing Considerations

• Starting dose: 5 ppm is appropriate for most patients 2, 4
• Dose range: 1-20 ppm for improving oxygenation 2
• Dose titration:
  • Increase in 5 ppm increments based on oxygenation response
  • Maximum dose should not exceed 20 ppm as higher doses may worsen oxygenation 2
  • Response should be assessed within 30 minutes of each dose adjustment 2, 5

Response Assessment

A positive response to iNO is defined as:

• ≥20% increase in PaO₂/FiO₂ ratio 5
• Reduction in mean pulmonary artery pressure (if measured) 2, 3

Important Considerations and Caveats

• Temporary therapy: iNO should be considered a temporary bridge to improvement, not a long-term solution
• Response variability: Approximately 60-70% of ARDS patients respond to iNO therapy 2
• Methemoglobinemia risk: Monitor methemoglobin levels, especially at doses >5 ppm 4
• Weaning protocol:
  • If no improvement in oxygenation is observed within 30-60 minutes, iNO should be discontinued 1
  • For responders, gradual weaning should occur once oxygenation has stabilized
  • Abrupt discontinuation should be avoided due to risk of rebound hypoxemia

Algorithm for iNO Implementation

1. Confirm severe ARDS: PaO₂/FiO₂ <100 despite optimal ventilator management
2. Ensure optimization of conventional therapies:
   • Lung-protective ventilation strategy
   • Prone positioning (if not contraindicated)
   • Appropriate PEEP
   • Neuromuscular blockade if needed
3. Initiate iNO at 5 ppm
4. Assess response after 30 minutes:
   • If PaO₂/FiO₂ increases by ≥20%, continue therapy
   • If inadequate response, titrate up to 10 ppm, then 20 ppm maximum
   • If no response at 20 ppm, discontinue therapy
5. For responders, maintain lowest effective dose
6. Consider alternative strategies if iNO fails (e.g., ECMO evaluation) 1

Contraindications

• Left ventricular dysfunction (relative contraindication)
• Methemoglobinemia
• Bleeding disorders or thrombocytopenia (relative contraindication)

Remember that while iNO can temporarily improve oxygenation in select patients with severe ARDS, it has not been shown to reduce mortality and should be used judiciously as a rescue therapy when conventional strategies have failed.