Journal of CASE REPORT Accident and Emergency J Accid Emerg Med: first published as 10.1136/emj.12.2.138 on 1 June 1995. Downloaded from Medicine 1995 Extreme methaemoglobinaemia secondary to 12,138-142 recreational use of amyl nitrite R.J. EDWARDS & J. UJMA Department of Emergency Medicine, Westmead Hospital, Westmead, New South Wales, Australia INTRODUCTION CASE REPORT Haemoglobin is continuously oxidized from the A 44-year-old man was brought by ambulance to ferrous (Fe2+) to the ferric (Fe3+) form and reduced St Vincent's Hospital Emergency Department at back again. The ferric (Fe3+) form, termed 23.37 hours. The patient had been found in the methaemoglobin (MetHb), is incapable of steam room of a bathhouse, unconscious, blue and transporting oxygen. In the normal physiological lying in a pool of vomitus. There was an empty state the concentration of methaemoglobin is less bottle of amyl (isobutyl) nitrite next to him, and than 1 %. Figure 1 illustrates the physiological workers at the establishment stated that he had reactions responsible for the reduction of MetHb 'consumed' large amounts of amyl nitrite. back to Hb. It is reported that MetHb levels of 10- On arrival of the paramedics, the patient was 25% produce cyanosis, 35-40% produce mild hypoventilating, hypotensive, unresponsive to pain symptoms (e.g. dyspnoea), levels of 60% produce and had poor skin colour. There was no response lethargy and coma and levels of 70% or more are to 2 mg of naloxone, administered intravenously. lethal.23 A case of extreme, life-threatening The patient was intubated endotracheally by the methaemoglobinaemia due to the recreational use paramedics, given 100% oxygen, ventilated of amyl (isobutyl) nitrite is presented. No case has manually and transported to hospital. been found in the literature where the MetHb level On arrival at the Emergency Department his skin was so high. was noted to be a deep charcoal grey colour, Key words: amyl nitrate, methaemoglobinaemia, despite the fact that he was receiving 100% oxygen http://emj.bmj.com/ methylene blue and having good air entry into both lungfields on Fig. 1. Mechanisms for reduction Major pathway (handles 95% of metHb. under physiological conditions) of methaemoglobin. MB, on September 28, 2021 by guest. Protected copyright. NADH MetHb. methylene blue; MW, methylene white; *Embden-Meyerhoff NADH* + MetHB. * NAD+ + Hb. reductase pathway is the major source of NADH in red blood cells; **hexose mono-phosphate shunt is the major source of NADPH. G6PD is required for its production. Pathway activated by methylene blue 20 Correspondence: Rob J. Edwards, NADPH MetHb. reductase Staff Specialist, Department of NADPH**. + MB MW + NADPH + Emergency Medicine, Westmead Hospital, CNR Hawkesbury Road & Darcy Street, Westmead, Hb MetHb NSW 2145, Australia © 1995 Blackwell Science Ltd R.J. Edwards et al. auscultation. His systolic blood pressure was 70 therapy unit to the ward. mmHg, and his pulse was 60 beats min-'. He was It was decided to keep the patient in hospital J Accid Emerg Med: first published as 10.1136/emj.12.2.138 on 1 June 1995. Downloaded from unresponsive to pain, and his pupils were and monitor him for haemolytic anaemia. However, constricted, equal and fixed. the patient discharged himself, against medical Arterial and venous samples were drawn for advice, on day 5. There was no evidence of arterial blood gas (ABG) analysis, MetHb, full blood anaemia at this time, and he showed no evidence count (FBC), and determination of electrolytes, of any residual neurological deficit on clinical urea and creatinine levels. testing. Total creatinine phosphokinase (CPK) However, 12 min after arrival the patient suffered levels 12 and 36 h after admission were 385 and a bradycardic arrest, requiring cardio-pulmonary 681 U L-', respectively (<130 U L-'). The MB resuscitation and 2 mg adrenaline, administered fractions at these times were 24 and 25U L-1, intravenously. He regained a cardiac output after respectively (<15 U L-1). A repeat ECG before 30 s. The patient's MetHb level was 94% (n< 1.5%) discharge was normal. Clinically, the patient had and he was given 80 mg (c.1 mg kg-1) of made a complete, uncomplicated recovery. Further tetramethylthionine (methylene blue) intravenously follow-up was performed by the patient's local over a period of 10 min. Twenty minutes after medical officer. The patient refused counselling administration of the methylene blue, the patient's from the drug and alcohol service. colour had improved slightly and there was a return We note that the patient presented again to our of spontaneous respiration, but he remained Emergency Department 6 months later with chest unresponsive to pain. pain after injecting cocaine intravenously. ECG on Further physical examination revealed a core this occasion was normal, and he was discharged temperature of 32.5° C (per rectum). There were for follow-up with his local medical officer. no focal neurological signs, and the systolic blood pressure remained low (70 mmHg). The abdomen DISCUSSION was soft and not distended. There was no sign of trauma, and no other abnormality was found. Although rare, it is important to diagnose The results of initial investigations were as methaemoglobinaemia when it presents because follows (ranges in parenthesis): ABG (FiO2=1) pH it is potentially fatal and yet readily treated. A clue 7.17, (7.35-7.45); Po2, unable to be measured due to the diagnosis is the appearance of chocolate to technical problems; Pco2, 39 mmHg (32-45); brown blood upon venesection or arterial HCO3,14 mmol L-1 (24-31); and base excess (B.E.) sampling.14'14 The diagnosis can be confirmed by -14 (-3-+3). Chest radiograph was normal. A 12- spectrophotometric analysis of the patient's blood, http://emj.bmj.com/ lead electrocardiograph showed sinus rhythm, rate giving a MetHb level expressed as a percentage 98 beats min-1 with ST elevation (concave down) of the total Hb level. The blood should be analysed in leads V1-V6. Hb was 13.1 g dL-1 (13.0-18.0), very soon after being drawn, as the MetHb level in WCC was 9.7 x 109 L-1 (4.0-11.0), and platelet count the sample will decrease with time.36 was 211 x 109 (150-400). Blood alcohol level was 0.15%. Aetiology on September 28, 2021 by guest. Protected copyright. A repeat MetHb measurement gave a value of 26%. The patient was given another 100 mg of Table 1 lists the agents that most commonly cause methylene blue at this time. A further 50 mL of 8.4% acquired methaemoglobinaemia. It has been sodium bicarbonate were administered for a reported that ingestion of nitrites is not dangerous persisting metabolic acidosis (pH, 7.05; Pco2, 46; because they are degraded in the GIT.41 However, Po2, could not be measured; HCO3, 13; B.E., -19). there are many case reports of severe, sometimes By 06.00 hours, the patient's colour was pink. A fatal, methaemoglobinaemia resulting from repeat MetHb level was 1.6% at 09.30 hours. At ingestion of isobutyl nitrite.3'6'9'20 this time the patient was opening his eyes to of speech and obeying commands. He continued to Management acquired methaemoglobinaemia improve and was extubated at 18.00 hours. He was After ensuring and protecting the airway, providing confused initially, but his sensorium had cleared appropriate respiratory and cardiovascular support by the next morning. He remembered no details and decontamination (e.g., removing soiled from the night of his overdose. Thirty-six hours after clothing or decontaminating oxidants in the gut), 139 admission he was transferred from the intensive tetramethylthionine (methylene blue, MB) should © 1995 Blackwell Science Ltd, Journal of Accident and Emergency Medicine 12, 138-142 Extreme Table 1. Agents most commonly implicated in acquired methaemoglobinaemia methaemoglo- J Accid Emerg Med: first published as 10.1136/emj.12.2.138 on 1 June 1995. Downloaded from Nitrates, nitrites binaemia Isobutyl (amyl) nitrite 3.5.6.16.19.20 secondary to Glyceryl trinitrate (sublingual, i.v.)21-24 recreational use of Food/water contaminants2830 amyl nitrite Local anaesthetics Topical 7.17.18.25.27.29 Intravenous8 Benzocaine, prilocaine and lignocaine most commonly Aniline dyes Industrial411 Domestic products Antimicrobial agents Sulfonamides Dapsone (high dose)31.32 Quinones33 be used early on if it is indicated. Figure 1 shows above enzymes, or there is failure of an adequate its mechanism of action. dose of MB (up to 7 mg kg-1) to reduce the MetHb Accepted indications for MB are a MetHb level level and produce a clinical improvement, 3436 then of >30-40%, or a situation where the patient is alternative or additional treatment with an symptomatic or anaemic, regardless of the MetHb exchange transfusion should be considered. Apart level.24 The clinician must be careful to treat each from the above situations, MB should not be case individually according to the clinical indicators withheld if the indications for its use and reuse are of severity (e.g., level of consciousness, dyspnoea, present. This is because the methaemoglobin- myocardial ischaemia), as some patients have producing effects of MB in vivo are small,10'11 and died1'16 or have been severely symptomatic17 with are dominated by the methaemoglobin-reducing MetHb levels under 35%, while other patients have effects. Table 2 lists the reasons why acquired recovered with levels above 80%.1418 The initial methaemoglobinaemia may fail to respond to MB. http://emj.bmj.com/ dose is 1- 2 mg kgh-1 body weight, administered Methylene blue, especially at doses of 7 mg kg-', intravenously over 5 min.249 Significant clinical may cause a sensation of dyspnoea, pressure on improvement and a substantial reduction in the the chest, restlessness, excitation, apprehension, MetHb level usually occur within 30-60 min.