a)  What does the cylinder pictured above contain?
b)  What   parameters   are   monitored   during   administration   of  the  cylinder’s contents?

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College Answer

a)  Nitric oxide 800ppm and Nitrogen


b)  PO2 pulmonary artery pressure, methaemoglobin and nitrogen dioxide

Discussion

The marvels and wonder of nitric oxide are discussed elsewhere.

The following adverse effects have been reported with its use:

  • Methemoglobinaemia, as abundantly discussed already
  • Hypotension (maybe some of it does leak into the systemic circulation, or maybe this the effect of depressed LV function
  • Rebound hypoxia after abrupt withdrawal
  • Thrombocytopenia (in as many as 10% of patients)
  • Increased susceptibility to pulmonary infections probably due to NO2 formation and associated lung injury

The college recommend some monitoring:

  • PO2 and presumably by extension SpO2, which seems like something standard for a hypoxic patient
  • Methaemoglobin levels, which are measured by all good ABG machines - and frequent ABGs appear inevitable in any situation in which nitric oxide therapy is seriously considered
  • PA pressure, which implies a PA catheter. This cannot be viewed as a mandatory step in the modern era, but most studies of nitric oxide come from a time when most ICU patients would have had a PA catheter.
  • Nitrogen dioxide levels, which seems problematic. The measurement of NO2 in air by the colorimetric Saltzman method (1960) using a commercially available badge device is possible at 1ppm resolution, but this is usually something done to monitor air pollution. Electrochemical or chemoluminiscent analysers for expired gas do exist (Fox, 2009), but their availability is limited.   In the lung its activity is local and mainly due to its tendency to cause oxidative stress (it produces nitric and nitrous acids upon contact with water), which makes measurement of blood NO2 levels some combination of difficult and pointless.

There are some official (1997) UK guidelines for the use of nitric oxide, which recommend:

  • Monitor for a 20 % rise in PaO2 as a test of a dose response (20% rise is a minimum response)
  • Monitor NO and NO2 concentration in expired gas using an electrochemical analyser (maximum NO2 concentration should be no more than 8ppm over an 8 hr period)
  • Monitor methaemoglobin levels at 1hr, 6 hrs and thereafter daily or with dose increases

References

References

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

Barker, Steven J., and John J. Badal. "The measurement of dyshemoglobins and total hemoglobin by pulse oximetry." Current Opinion in Anesthesiology21.6 (2008): 805-810.

Afshari, Arash, et al. "Inhaled nitric oxide for acute respiratory distress syndrome (ARDS) and acute lung injury in children and adults." Cochrane Database Syst Rev 7 (2010).

Cuthbertson, B. H., et al. "UK guidelines for the use of inhaled nitric oxide therapy in adult ICUs." Intensive care medicine23.12 (1997): 1212-1218.

Saltzman, BERNARD E. "Colorimetric microdetermination of nitrogen dioxide in the atmosphere." Anal. Chem 3 (1960): 135-136.

Fox, Terry. "Inspired and Expired Gas Monitoring." Respiratory Disease and its Management. Springer London, 2009. 121-126.