Risk factors for prilocaine-induced methaemoglobinaemia following peripheral regional anaesthesia

The local anaesthetic prilocaine has a low systemic toxicity mainly because of a high absorption in the lung and a large volume of distribution and thus is associated with a lower risk of neurological or cardiac side-effects. However, the major disadvantage is the formation of methaemoglobin by its metabolite o-toluidine. This prospective observational study was performed to identify factors that are associated with increased prilocaine-induced methaemoglobinaemia.

One Hundred and sixty two patients undergoing major knee surgery under general anaesthesia combined with peripheral nerve blocks (femoral nerve block, combined femoral/sciatic nerve block or lumbar plexus block) received a single bolus injection of 300 or 400 mg prilocaine about 30 min before surgery via a catheter. The proper placement was verified using nerve stimulation via a stimulating catheter. Three hours after prilocaine injection, venous blood samples were drawn and methaemoglobin levels were measured by standard photometric technique. Data was subjected to a stepwise multiple regression analysis.

The mean methaemoglobin for all patients was 2.7% (range: 0.9-15.4%). A higher dose of prilocaine and younger age were the most important predictive factors for higher methaemoglobin formation. Female sex and to a lesser extent the use of high-concentration/low-volume prilocaine also increased methaemoglobin levels. These four factors of the model explain 36% of the total variance. Other investigated factors, including the patient's height, weight, body mass index, the site of catheter insertion, the anaesthetist's judgement concerning the difficulty of catheter placement, duration of catheter placement or an inadvertent puncture of a venous or arterial vessel, had no significant impact on the concentration of methaemoglobin.

The use of prilocaine for regional block is safe, since the older patients who might be more susceptible to suffer from clinical symptoms of methaemoglobinaemia usually form less methaemoglobin. However, since prediction of high methaemoglobin levels is difficult, anaesthesiologists performing regional blocks in patients who might be jeopardized by a decreased oxygen transport capacity should avoid high doses of prilocaine.