Canadian Journal of Anesthesia, Vol 14, 1-10, Copyright © 1967 by Canadian Anesthesiologists' Society

The Significance of Methaemoglobinaemia Induced by Prilocaine (Citanest)

¹ Department of Anaesthesia, University of Western Ontario, London, Ontario
² University of Western Ontario

1. With the dose of 600 mg. recommended by the manufacturer given in a single injection, the methaemoglobin content will usually not rise above 1 gm. per cent and cyanosis will be mild or absent. However, since the causative metabolite is part of the breakdown process of prilocaine, methaemoglobin will be formed with any dosage of prilocaine, no matter how small.

2. With continuous techniques using repeated injections there is a cumulative effect, and even if the dosage of each single injection is small, the methaemoglobin level may rise to values above the level of cyanosis. To avoid this it is recommended that dosages not exceed 600 mg. during a 12-hour period. Although with prolonged continuous use a plateau is reached and this plateau is related to the increments of prilocaine injected, there are wide individual variations, and dangerously high levels may occur.

3. Methaemoglobin interferes with the oxygen transport. While normal indi-viduals have a remarkable tolerance to a reduction in functioning haemoglobin, this does not apply to situations where the oxygen transport is already critical. Particularly with severe anaemia, in cardiac failure, with coronary, cerebral or peripheral arterial insufficiency, and in patients in shock, even a moderate reduction in oxygen-carrying capacity may cause serious complications.

4. The placenta represents a critical situation for oxygen transport, and since prilocaine produces methaemoglobin in mother and infant, the oxygen-carrying capacity of maternal as well as foetal blood is reduced. The shift of the oxyhaemoglobin dissociation curve would further aggravate this situation. We concur with the opinion of Scott¹ that prilocaine should not be used for continuous epidural analgesia in obstetrics.

5. It is well known that the recognition of cyanosis depends on lighting and on the astuteness of the observer. Cyanosis is usually seen with methaemoglobin concentrations of about 1.5 gm. per cent; subtle changes in colour may be observed with as little as 0.8 gm. per cent. This cyanosis is a less serious condition than that produced by hypoxia, where 5 gm. per cent of reduced haemoglobin must be present for clinical recognition. The magnitude of the hazard introduced by the frequent use of an agent likely to produce a more harmless form of cyanosis is not known; however, the standard of safety in modern anaesthesia is so high that we cannot afford to err in distinguishing between these two states of cyanosis. In practice, we believe, the methaemoglobin formation is as much of a limiting factor for the permissible dosage of prilocaine as the central nervous system toxicity may be for the use of lidocaine or other local anaesthetic agents.

Note:

Presented at the Annual Meeting of the Canadian Anaesthetists' Society at Banff, June 6 to 10, 1966.