Nitric Oxide (NO)
Key Points
- Endogenous signaling molecule essential for vascular homeostasis
- Potent selective pulmonary vasodilator
- Primary therapeutic use in persistent pulmonary hypertension of newborn (PPHN)
- Critical role in treating hypoxemic respiratory failure
Chemical Properties
- Formula: NO
- Colorless gas at room temperature
- Short half-life (seconds)
- Rapidly converts to nitrite and nitrate in blood
Clinical Pharmacology
Mechanism of Action
- Diffuses into smooth muscle cells
- Activates soluble guanylate cyclase
- Increases cyclic GMP production
- Results in smooth muscle relaxation
- Selective effect on pulmonary vasculature when inhaled
Pharmacodynamics
- Onset: Within minutes of inhalation
- Duration: Effects cease within minutes of discontinuation
- No systemic vasodilation when properly administered
- Improves ventilation-perfusion matching
Therapeutic Applications
Primary Indications
- Persistent Pulmonary Hypertension of the Newborn (PPHN)
- Hypoxemic Respiratory Failure
- Post-cardiac surgery pulmonary hypertension
- Acute Respiratory Distress Syndrome (ARDS)
Specific Clinical Scenarios
- Meconium Aspiration Syndrome
- Congenital Diaphragmatic Hernia
- Primary Pulmonary Hypertension
- Bridge to ECMO therapy
- Post-operative management of congenital heart disease
Expected Outcomes
- Improved oxygenation (increased PaO2)
- Decreased pulmonary vascular resistance
- Reduced need for ECMO
- Decreased mortality in selected populations
Administration and Monitoring
Dosing Guidelines
- Starting dose: 5-20 ppm
- Maximum dose: 80 ppm
- Typical maintenance: 5-40 ppm
- Weaning: Gradual reduction by 5-10 ppm increments
Delivery Systems
- Specialized NO delivery devices
- Integration with mechanical ventilation
- Continuous flow systems
- Emergency backup systems
Monitoring Requirements
- Continuous NO and NO2 levels
- Methemoglobin levels q4-12h
- Continuous SpO2 monitoring
- Regular blood gases
- Pulmonary artery pressure when available
Clinical Considerations
Adverse Effects
- Methemoglobinemia
- NO2 toxicity
- Rebound pulmonary hypertension
- Platelet dysfunction (rare)
Contraindications
- Left ventricular dysfunction
- Bleeding diathesis
- Severe methemoglobinemia
Special Populations
- Premature infants: Increased risk of IVH
- Congenital heart disease: Careful evaluation needed
- Immunocompromised: Monitor for infection
Treatment Failure Criteria
- No response within 30-60 minutes
- Continued hypoxemia despite maximal therapy
- Worsening oxygenation index
- Need for ECMO evaluation
Further Reading
