Methaemoglobinaemia associated with the atypical use of sodium nitrite as a food additive

Clinical record

On 13 November 2019, a public health unit in Sydney, Australia was notified of two unrelated patients who presented on the previous day to different emergency departments (EDs) with methaemoglobinaemia.1 Both had sudden symptom onset after dining at the same restaurant, raising suspicion that these presentations were linked to contaminated food, and prompting investigation. Foodborne illness in two or more related cases is notifiable under the Public Health Act 2010 (NSW).2

Patient 1 was a 31‐year old woman who reported vision loss, headache, nausea and a presyncopal episode at the venue. Once home, she had shortness of breath; her friend noted blueish discolouration to her lips and fingers, and transported her to the ED. On initial assessment, her oxygen saturation was 81% (reference interval [RI], 95–100%) on room air. History, examination and preliminary investigations found no cardiac or respiratory cause for her presentation. A blood gas sample taken 2 hours after symptom onset showed a methaemoglobin level of 19.9% (RI, 0.4–1.2%) and a partial pressure of oxygen level of 173 mmHg (RI, 80–100 mmHg). Methylene blue (1 mg/kg) was administered for symptomatic methaemoglobinaemia, and her methaemoglobin level fell to 1.2% 4.5 hours after symptom onset.

Patient 2 was a 32‐year old woman brought to the ED by ambulance after collapsing at the venue. On arrival, she was confused, vomiting and cyanotic. Her oxygen saturation was 89% on 4 L oxygen; this was unchanged with increased oxygen. The remainder of her clinical examination and investigations were unremarkable. A blood gas sample taken 2 hours after symptom onset showed a methaemoglobin level of 28.3%, a partial pressure of oxygen level of 92 mmHg, and a lactate level of 2.2 mmol/L (RI, < 1.9 mmol/L). Methylene blue was administered, and her methaemoglobin level fell to 3.5% 4 hours after symptom onset.

Neither patient was found to have glucose‐6‐phosphate dehydrogenase deficiency, which can induce methaemoglobinaemia. Reviews of family and personal history of cyanosis and haematological disorders, and chemical or medication exposures identified no methaemoglobinaemia cause in either patient. Both reported symptom resolution shortly after methylene blue administration, but were admitted to hospital overnight for observation. Neither patient had methaemoglobinaemia recurrence, and both were discharged the following day.

Subsequent review by the NSW Poisons Information Centre found that both patients had ingested the same prawn dish at a restaurant, developing symptoms 15–30 minutes after consumption. Investigation commenced; the NSW Department of Primary Industries inspected the restaurant, identifying a container mislabelled “sodium nitrate” and invoices validating the purchase. Kitchen staff confirmed its use as a colour preservative for the prawns, and it was likely present in the dish consumed by the patients. Others who consumed the contaminated prawns were unable to be confirmed. The powder was analysed and confirmed as sodium nitrite; no leftover prawns were available for testing. Enforcement action was taken and the establishment was fined.

Discussion

Methaemoglobin forms when ferrous irons in haem oxidise to the ferric state. Ferric haems cannot bind oxygen and alter oxygen affinity for other haems, impairing oxygen delivery to tissues. Normal levels are regulated to < 3%, with clinically significant methaemoglobinaemia arising when regulation is disturbed. Clinical features include light‐headedness, dyspnoea and cyanosis. Methylene blue is recommended for patients with methaemoglobin levels > 20% and methaemoglobinaemia symptoms; one dose decreases methaemoglobin to non‐toxic levels in 10–60 minutes.3 Levels > 50% may lead to respiratory depression, coma, seizures and death.3 The half‐life of methaemoglobin is 60–120 minutes,4 indicating that both patients had significantly higher methaemoglobin levels at onset; initial blood gas samples were taken hours after exposure. Virtually all methaemoglobinaemia cases observed in clinical practice are acquired from toxin exposure. However, there are extremely rare genetic causes typically presenting in childhood, and the true incidence is unknown.3

Nitrite exposure is a common cause of acquired methaemoglobinaemia. Nitrates, having three oxygen atoms, are inert and only oxidise haemoglobin to methaemoglobin following reduction to nitrites by intestinal bacteria. Nitrites, having two oxygen atoms, can oxidise haemoglobin directly.5 This justifies the higher level of nitrates permitted in food preservation, and explains the clinically significant methaemoglobinaemia observed in these patients given that sodium nitrite, not nitrate, was used. In Australia, nitrate and nitrite use on commercial premises must comply with the Australia New Zealand Food Standards Code. This permits addition to select dairy and processed meat products, to a maximum level specific to the food type.6 Addition to prawns is a breach of this code. Previous methaemoglobinaemia clusters associated with unintentional sodium nitrite ingestion likewise reinforce need for its regulated usage.7

This cluster highlights the need for clinicians to consider foodborne exposures in patients with methaemoglobinaemia of unknown aetiology, and highlights the importance of early public health notification if a common food exposure is suspected. It similarly emphasises the significance of industry education regarding the dangers of incorrect food additive usage, and the need for regulatory action when public safety is compromised.