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Editor,—Peribulbar blockade is frequently used for anaesthesia in ophthalmic surgery. Owing to its short onset time and low incidence of cardiac and central nervous system toxicity, the local anaesthetic prilocaine is a popular choice for peribulbar blockade. Prilocaine is, however, the most potent methaemoglobin forming local anaesthetic. We report a case of prilocaine induced methaemoglobinaemia after peribulbar blockade for ophthalmic surgery.
A 27 year old Romanian woman presented with a detached retina requiring surgical repair. Her medical history was significant for insulin dependent diabetes mellitus complicated by chronic renal failure, anaemia, and diabetic retinopathy. Her daily medication included captopril 25 mg, verapamil 240 mg, isosorbide dinitrate 40 mg, and frusemide 40 mg. A mixture of prilocaine 80 mg, bupivacaine 30 mg, hyaluronidase, and naphazoline was used to perform a peribulbar anaesthesia. Vital signs at the beginning of the operation were normal, oxygen saturation (Spo 2) was 96% on room air. Sixty minutes after the peribulbar block was performed, the patient became tachypnoeic, somnolent, and the Spo 2decreased to 87% despite receiving 10 l/min of oxygen via facemask. There were no indications of myocardial ischaemia on the ECG and the breath sounds were clear. Arterial blood gas analysis demonstrated a Pao 2 236 mm Hg, Paco 232 mm Hg, pH 7.31, base excess of −5.1, Sao 298.4%, haemoglobin 5.3 g/dl, and methaemoglobin level of 11.2%. Surgery was interrupted, methylene blue (1.5 mg/kg) was administered, and the patient improved rapidly. She was discharged home without further incident a week later.
Oxygen normally binds reversibly to the sixth coordination position of haem iron in haemoglobin. Partial transfer of an electron from ferrous iron to oxygen leads to the formation of superoxo-ferrihaem (Fe3+O2−). Failure of the electron to transfer back to oxygen results in methaemoglobin (HbFe3+) formation.1 Methaemoglobin formation in vivo is normally limited by NADH dependent methaemoglobin reductase, which serves as an electron donor for methaemoglobin. NADPH dependent methaemoglobin reductase plays a minor part (approx 5% of methaemoglobin reduction) but transfers the electron taken from methylene blue to the methaemoglobin. When methaemoglobin formation exceeds >1% of total haemoglobin, tissue oxygen transport is compromised.2 Furthermore, the severity of tissue hypoxaemia may be underestimated by pulse oximetry which may constantly read 85% despite increasing methaemoglobin levels.3 4Thus, arterial blood-gas determinations are necessary in order to confirm the diagnosis of methaemoglobinaemia and to fully appreciate the degree of hypoxaemia.
Methaemoglobinaemia may be the result of primary or secondary (acquired) causes. Genetic conditions resulting in methaemoglobinaemia include mutagenic defects of haemoglobin and congenital reductase enzyme deficiency.5 Acquired methaemoglobinaemia may be caused by oxidant drugs that overwhelm the body's ability to limit methaemoglobin formation via enzymatic reduction. Local anaesthetics are the most common cause of perioperative methaemoglobinaemia.6 Prilocaine is the most potent methaemoglobin forming local anaesthetic. Methaemoglobin formation is dose dependent and correlates with the rate of systemic absorption. In general, doses less than 600 mg in adults are thought not to increase the patient's risk of methaemoglobinaemia.7 Despite this, the administration of only 80 mg in the present case resulted in methaemoglobinaemia. However, several predisposing factors may have contributed to the enhanced formation of methaemoglobin. Firstly, the risk of prilocaine induced methaemoglobinaemia in patients with renal failure may be increased as metabolic acidosis increases ionised prilocaine serum levels. Further, the unbound fraction of prilocaine may be elevated in renal failure as a result of decreased serum proteins.8Additionally, regular intake of isosorbide dinitrate which is also associated with methaemoglobin formation may have already predisposed this patient to the development of methaemoglobin formation.9 Finally, it is possible that our patient may also have suffered from an undiagnosed genetic predisposition to methaemoglobin formation. Although an abnormal haemoglobin pattern was ruled out by electrophoresis, we did not rule out a deficiency in methaemoglobin reducing enzymes such as NADH dependent methaemoglobin reductase. Thus, this patient had several underlying factors that may have predisposed her to prilocaine induced methaemoglobinaemia.
In conclusion, small concentrations of prilocaine can cause methaemoglobinaemia when used for peribulbar blockade in patients with reduced tolerance to oxidant drugs.
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