Toxic neonatal methaemoglobinaemia after prilocaine administration for circumcision

I.S. Arda, N. Özbek*, E. Akpek⁺ and E. Ersoy
Baskent University Faculty of Medicine, Department of Paediatric Surgery, *Paediatric Haematology Unit, ⁺Department of Anaesthesiology, Ankara, Turkey

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Case report

A 5-day-old boy, weighing 3.4 kg, was circumcised at an outpatient clinic using the standard surgical technique. Prilocaine was administered subcutaneously (5 mg/kg) around the radix of the penis; there were no complications. He developed per-oral cyanosis 2 h after the circumcision and then general cyanosis; a physical examination showed no other abnormality. His haemoglobin level was 150 g/L, haematocrit 46%, white blood cell count 7600/mm3, arterial pH 7.40, paO₂ 94.2 mmHg, and paCO₂ 26 mmHg. A chest X-ray was normal and electrophoresis showed a methaemoglobin level of 32.6%. Methylene blue (1 mg/kg in 1% saline) was infused intravenously when the cyanosis had not cleared after the application of nasal oxygen. The patient became symptom-free in an hour and methaemoglobin levels returned to normal in 8 h.

Comment

Methaemoglobin is one of the major side-effects of prilocaine use and occurs more frequently in newborns [1]. The increased susceptibility of infants to prilocaine during the first week of life is related to high levels of fetal haemoglobin, which is oxidized more readily to the ferric state than is haemoglobin A, and the transient deficiency of cytochrome C5 reductase enzyme activity that persists for the first 3–4 months of life [2]. Cyanosis appears within 6 h after the administration of prilocaine but may occur earlier in neonates when methaemoglobin levels are > 15 g/100 mL, whereas recognizable cyanosis does not occur until the concentration is > 35 g/100 mL. Nasal oxygen is applied in the treatment of mild methaemoglobinaemia and patients with methaemoglobin levels of > 15–20% of total haemoglobin are treated with methylene blue (1 mg/kg) in 1% normal saline. A rapid decrease occurs within 2 h. As prilocaine hydrochloride may cause methaemoglobinaemia, particularly in newborns, such patients should be followed for at least 6 h. A topical anaesthetic, e.g. a eutectic mixture of local anaesthetic, can be a reliable alternative.

References

1. Tse S, Barrington K. Methemoglobinemia associated with prilocaine use in neonatal circumcision. Am J Perinatol 1995; 12: 331 [PubMed]
2. Nilsson A, Engberg G, Henneberg S, Danielson K, De Verdier CH. Inverse relationship between age-dependent erythrocyte activity of methaemoglobin reductase and prilocaine-induced methaemoglobinaemia during infancy. Br J Anaesth 1990;64: 72–6 [Abstract]
3. Taddio A, Ohlsson A, Einarson TR, Stevens B, Koren G. A systematic review of lidocaine-prilocaine cream (EMLA) in the treatment of acute pain in neonates. Pediatrics 1998; 101: E1

Authors

I.S. Arda, Paediatric Surgeon.
N. Özbek, Paediatric Haematologist.
E. Akpek, Anaesthesiologist.
E. Ersoy, Resident, Surgery.