Critically evaluate the role of nitric oxide in the management of the critically ill patient.

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College Answer

Nitric oxide has many potential benefits in the critically ill. In particular, selective delivery via the inhalational route allows local vasodilatation (potentially improving ventilation:perfusion matching, and reducing pulmonary arterial hypertension), as well as providing some immunomodulating effects (inhibiting neutrophil adhesion and platelet aggregation). Despite a number of prospective randomised trials (in acute lung injury and ARDS) demonstrating some short-term oxygenation benefits (up  to  72  hours), in  adult patients there have been  no improvements in  longer-term outcomes (such as weaning from ventilation or mortality). Similarly, physiological improvements in pulmonary hypertension in various clinical scenarios have been demonstrated (e.g. primary pulmonary hypertension, heart transplantation) but no longer-term benefits have been demonstrated. Use of NO requires complex equipment, including monitoring for NO and nitrogen dioxide concentrations. Administration of NO has not been without its own potential adverse effects: Methaemoglobinaemia, prolonged bleeding time, and reports of increased renal failure and nosocomial infections. (Adhikari N. JAMA 2004; 291:1629-31; Sokol J et al. Inhaled nitric oxide for acute hypoxemic respiratory failure in children and adults: A meta-analysis. Anesth Analg 2003;
97:989-98 & Sokol J et al. Inhaled nitric oxide for acute hypoxemic respiratory failure in children and adults (Cochrane Review). In: The Cochrane Library, Issue 1, 2004.)

Discussion

Nitric oxide is discussed elsewhere. It has fallen out of favour, but during 2004 it must have seemed like panacea. The pharmacology of nitric oxide is respectfully treated elsewhere.

Arguments for and against the use of nitric oxide:

  • NO is a potent pulmonary vasodilator
  • it improves ventilation-perfusion matching
  • it improves pulmonary pressures and oxygenation, but this effect is not sustained, nor is it associated with an improved outcome.
    • good Cochrane analysis demonstrated no benefit in mortality in ARDS
    • Oxygenation improves only for the first 24 hours of therapy.
  • It requires specialised equipment and its use is associated with complications eg. pulmonary haemorrhage, nitrogen dioxide toxicity and methaemoglobinaemia.
  • Thus, nitric oxide these days is seldom used.
  • In the manufacturers brochure, it is recommended for use only in the neonatal population.

Administration

  • via uniquely designed gas mixer
  • from its own tank
  • start at 5-10 ppm, go up to 160ppm as needed

Monitoring

  • Monitor PA pressures with PAC
  • monitor response with arterial oxygenation
  • regular CXR, watch for pulmonary haemorrhage
  • Monitor for toxicity, particularly methaemoglobin levels
  • Observe strict handling sfaeguards, including gas scavenging and ventilation precautions

References

References

Ikaria, the only company which produces this stuff in Australia, has an excellent product information pamphlet.