20B17: Exam Report

Describe the pharmacology of inhaled nitric oxide (NO).

24% of candidates passed this question.

Nitric Oxide (NO) is an inorganic colourless and odourless gas presented in cylinders containing 100/800 ppm of NO and nitrogen. Many candidates mentioned oxygen instead of nitrogen. The exposure of NO to oxygen is minimized to reduce formation of nitrogen dioxide and free radicals. Hence it is administered in inspiratory limb close to the endotracheal tube. Many candidates did not mention the contraindications/caution for NO use. Candidates generally did well in mentioning the impact on improving V/Q mismatch by promoting vasodilatation only in the ventilated alveoli and reducing RV afterload. Many candidates did not mention the extra cardio-respiratory effects. The expected adverse effects of NO were nitrogen dioxide related pulmonary toxicity, methemoglobinemia and rebound pulmonary hypertension on abrupt cessation. Pharmacokinetics of NO carried a significant proportion of marks. It was expected that the answers would involve mention of location of delivery of NO in inspiratory limb and reason behind it, the high lipid solubility and diffusion, the dose (5-20ppm), very short half-life of < 5 seconds and combination with oxyhemoglobin to produce methaemoglobin and nitrate. The main metabolite is nitrate which is excreted in urine.

F11iii / 20B17: Describe the pharmacology of inhaled nitric oxide (NO)


  • Inorganic, colourless gas used as a pulmonary vasodilator
  • Used to treat refractory hypoxaemia in ARDS and in the treatment of pulmonary hypertension


  • Stored in cylinders as a compressed gas with nitrogen
  • Brand name INOmax
  • Contains 99.92% nitrogen and 0.08% nitric oxide (800ppm)


  • NO activates sGC -> cGMP -> protein kinase G -> decreasing Ca
  • This causes vasodilation via inhibition of SM contraction
  • Given via inhaled route, distributed to well ventilated alveoli, crosses the capillaries of these alveoli and selectively vasodilates the blood vessels supplying these alveoli
  • This causes improved V/Q matching and improved oxygenation
  • It also results in pulmonary vasodilation and reduced PVR, reducing RV afterload
  • Also decreases angiogenesis and decreases platelet aggregation



  • Administered via inhalational route only
  • Administered via inspiratory limb of circuit close to ETT (to minimise exposure to O2 and formation of nitrogen dioxide and free radicals
  • Delivered at a desired concentration in ppm after dilution (usually 1-40ppm)


  • To well ventilated alveoli only
  • High lipid solubility
  • Hence easily diffused across capillary membrane


  • Inactivated by Hb (hence short half life of < 5 secs)
  • Reacts with heme and OxyHb to form nitrate and MetHb


  • 70% of NO excreted as nitrate in urine at rate approaching GFR
  • Cleared renally within 48h

Adverse Effects

  • MetHbaemia and reduced O2 carrying capacity
  • Systemic hypotension
    • Systemic vasodilation
    • LV depressant effect
  • Rebound pulmonary hypertension on abrupt cessation
  • Environmental contamination
  • Formation of toxic nitrogen dioxide when it reacts with O2 (pulmonary irritatant)
  • Thrombocytopenia


  • Existing MetHb
  • LV failure (may cause APO)
  • Left to right shunt (NO decreases PA pressure, increasing amount of blood shunted across septal defect)
  • Haemorrhage (may increase bleeding time)

Author: Craig Johnston