Ir Med J. 2009 Jun;102(6):184.

R Conway, P Browne, P O’Connell
Department of Rheumatology, Beaumont Hospital, Beaumont, Dublin 9

Abstract
Methaemoglobinaemia is a rare condition characterised by increased quantities of haemoglobin in which the iron of haem is oxidised to the ferric (Fe3+) form. Clinically the condition presents with cyanosis and low oxygen saturations on pulse oximetry but normal oxygen saturation on arterial blood gas analysis. Most cases are acquired and are frequently drug related. We present a case of methaemoglobinaemia which presented to our hospital.

Introduction
A 24 year old male presented to the Emergency Department having woken that morning and noticed that his face was blue. He felt generally unwell and was sweating. There were no other symptoms. This was the first occasion on which he had noted this facial discolouration. He had a history of cocaine abuse for the previous 5 years and had snorted 12 lines of cocaine over the preceding 2 days. His past history also included epilepsy, cocaine induced hallucinations, normochromic normocytic anaemia of unknown cause and mild asthma. His prescribed medications on admission were olanzapine and diazepam. He reported no drug allergies. He was unemployed, smoked 10 cigarettes a day for the past 8 years and drank 24 units of alcohol per week. He reported occasional marijuana use, but denied use of other illicit substances.

Case Report
Physical examination revealed O₂ saturation of 84% on pulse oximetry while receiving 100% O₂ via facemask. Vital signs were otherwise normal. He was centrally cyanosed. No other abnormalities were detected on examination. Laboratory investigation showed a normochromic normocytic anaemia of 11g/dl. Arterial blood gas measurements showed ph 7.39, pCO^₂ 5.82kPa, pO₂ 28.7kPa, HCO₃ 26mmol/L and O₂ saturation of 97%. Methaemoglobin levels measured on arterial blood were 28%. Otherwise, routine biochemistry and haematology, ECG and chest radiograph were normal. A diagnosis of cocaine induced methaemoglobinaemia was made. The patient was commenced on 10mls of 1% methylene blue in 1L 0.9% NaCl. Following two doses of methylene blue, his cyanosis resolved and peripheral O2 saturation returned to normal. Methaemoglobin levels at 24 hours were 2.1%. The patient made a full recovery and was reviewed by the addiction psychiatry team prior to discharge.

Discussion
Methaemoglobin is ineffective as an oxygen carrier and thus causes a varying degree of cyanosis. A “saturation gap” between oxygen saturation on pulse oximetry and arterial blood gas analysis is characteristic, as demonstrated in our case with a saturation of 84% on pulse oximetry versus 97% on blood gas measurement. This is due to the different mechanisms of measurement of O₂ saturation. When acute, symptoms of methaemoglobinaemia include fatigue, malaise, dyspnoea, headache and blue colour (or cyanosis). Treatment of acute acquired methaemoglobinaemia is with intravenous methylene blue. Methylene blue functions as a cofactor, accelerating the reduction of methaemoglobin via an NADPH-dependent pathway. Caution should be used with methylene blue in individuals of African or Mediterranean origin due to the risk of glucose-6-phosphate dehydrogenase deficiency, as methylene blue is both ineffective and associated with an increased risk of haemolysis in such individuals.
The condition may arise as a result of a genetic defect in red blood cell metabolism or haemoglobin structure when it is frequently asymptomatic. More commonly, it is acquired following exposure to various oxidant drugs or toxins. The list of drug causes of methaemoglobinaemia is long but certain drugs are more likely to cause it than others. These are dapsone, local anaesthetics, nitrites and antimalarial drugs. Local anaesthetics are classified into two groups depending on whether they have an ester or an amide linkage. Cocaine is an ester. Methaemoglobinaemia is not typically associated with cocaine use; it is however strongly associated with the use of local anaesthetics which have an amide linkage, including lignocaine, benzocaine and bupivacaine. Street market cocaine is frequently adulterated with various powdery fillers to increase its weight, these include baking soda; sugars, such as mannitol; and local anaesthetics, such as lignocaine. It is possible that our patient’s methaemoglobinaemia was caused by one or other such adulterant in the cocaine.

R Conway
Department of Rheumatology, Beaumont Hospital, Dublin 9
Email: [email protected]