INHALED NITRIC OXIDE

Nitric Oxide, iNO

Reviewed by Dr David Knight
February 2001
Administration Newborn Drug Protocol Index Newborn Services Home Page

Nitric oxide (NO) is a gas that is given into the ventilator circuit. It is a potent vasodilator. When given into the ventilator circuit, it dilates the pulmonary vasculature. It is inactivated instantly in blood, by reacting with haemoglobin. Therefore it has no action on the systemic vasculature and therefore (theoretically) on systemic blood pressure.

Dose and Administration

  1. Start on 20ppm (approximately 200ml/min, and increase according to measurement on Nitric Oxide Monitor)
  2. Start on 0.2 litres per minute in 10 litres of 100% O2 = 17.4 ppm
  3. Reduce to 0.1 litres per minute: = 8.7 ppm
  4. Reduce according to response
  5. Doses above 20ppm are not indicated as generally a response is obtained prior to this.

Indications

  1. Persistent pulmonary hypertension of the newborn (proven on clinical grounds or by echocardiography)
  2. Severe respiratory failure

Contraindications and Precautions

  1. None in term infants.  This is now considered a recognised practice.
  2. Caution in preterm infants.  Benefit in preterm infants has not be proven by randomised studies.

Clinical Pharmacology

Nitric oxide is endothelial derived relaxing factor (EDRF). It is produced in the endothelium of blood vessels and diffuses out of the cells. It then enters vascular smooth muscle cells and activates guanalate cyclase which forms cyclic guanosine monophosphate (cGMP). This is a smooth muscle relaxer. cGMP is inactivated by cGMP phosphodiesterase. The half life of NO is 3-6 seconds.

NO is bound to haemoglobin and inactivated to nitosylhaemoglobins and methaemoglobin.

Possible Adverse Effects

  1. Combines with haemoglobin to form methaemoglobin. At clinically used doses high methaemoglobin levels have not been reported. In overdose, it may be fatal.  If methaemoglobinaemia occurs, check the ventilator circuit, particularly the delivery and measuring points of iNO.
  2. Is a toxic free radical and causes tissue damage. NO is used by macrophages to kill bacteria. It can theoretically damage the lung through lipid peroxidation. The precise importance of this has not been elucidated. Produces peroxynitrates which are toxic to tissue.
  3. NO converts to nitrogen dioxide NO2) spontaneously when mixed with oxygen. High concentration of NO in O2 lasts 6 seconds! At clinical doses (<20 ppm), the half-life is much longer. NO2 is very toxic.
  4. NO is an inhibitor of platelet function.  Caution when thrombocytopenia or bleeding problem.