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Re: Measurement of methaemoglobin levels in babies

Nitric oxide (NO) is frequently used as a selective pulmonary vasodilator in neonates. Since its metabolite, methaemoglobin can potentially cause tissue hypoxia it is considered mandatory to measure methaemoglobin levels when using NO. In an attempt to review and rationalise our own practice of methaemoglobin measurement when using NO we undertook a search of current literature and conducted a postal survey of current practice.

38 questionnaires were sent to level II or III neonatal units in England, Scotland and Wales. Of the 32 (84%) returned, 24 were from centres using NO (63%). We asked about their timing for methaemoglobin levels and what level was considered to warrant intervention. Our replies found no standardised protocol for the timing of levels and no recognised ‘toxic’ level. The range of timings for levels was large varying from every 4 hours to every 24 hours after starting NO therapy. Most hospitals considered a methaemoglobin level of 4% needed a reduction in the dose of NO and that levels of 5 to 7% required the NO to be stopped. All centres agreed on the treatment of choice for toxic levels, ie, an infusion of methylene blue, but there was no agreement on what level required treating, quoted levels ranging from 5 to 15%. From the literature it would appear that neonates tolerate relatively high methaemoglobin levels well. Normal blood levels of methaemoglobin have been quoted as 0 to 1.9% for adults, 0 to 2.8% for term neonates and 0.08 to 4.7% for premature babies.[1] The higher level in neonates being due to their immature enzymatic system and the fact that fetal haemoglobin is more prone to oxidation. Furthermore, in a case where NO was inadvertently given in extremely high concentrations, a neonatal methaemoglobin level of 13.4% was measured with no clinical deterioration and no other intervention than stopping the NO therapy being required.[2]

Methaemoglobin has been shown to follow first order kinetics for both its formation and metabolism with a time constant of 39 to 91 minutes. Peak methaemoglobin levels occurred 3 to 5 hours after starting NO therapy after which steady state concentrations were achieved.[3] From this data it would seem appropriate to take a methaemoglobin levels 4 hours and 8 hours after starting NO and then daily unless the dose is increased, when levels should be re-measured at 4 and 8 hours after the change. Once the dose of NO is being decreased levels should no longer be necessary.

Our survey has highlighted a lack of agreement for the safe use of nitric oxide in neonates with regard to methaemoglbinaemia. The pharmacokinetic data quoted was from healthy adults inhaling NO and therefore may not be comparable to that of sick neonates. We therefore feel this is an area that warrants further research and would be grateful of other unit’s advice and experience in this area.

Dr RD Taylor*
Dr SA Calvert**
*Specialist Registrar anaesthetics
Frenchay Hospital
Bristol, UK
**Consultant Neonatologist
Neonatology Unit St George’s Health Care Trust
London SW17 OQT, UK

References
(1) Bowman WC, Rand MJ. Methaemoglobinaemia. In: Textbook of Pharmacology. Second edition. Blackwell Scientific publications.1984:21.45 – 48.

(2) Heal CA, Spencer SA. Methaemoglobinaemia with high dose nitric oxide administration. Acta Paediatr 1995;84:1318-19.