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Lessons of the month 3: Intravenous poppers abuse: case report, management and possible complications

Alexander Reisinger, Susanne Vogt, Anna Essl, Ines Rauch, Florian Bangerl, Philipp Eller and Gerald Hackl
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DOI: https://doi.org/10.7861/clinmed.2019-0469
Clin Med March 2020
Alexander Reisinger
AMedical University of Graz, Graz, Austria and Austrian Red Cross, Graz, Austria
Roles: critical care resident and research fellow
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  • For correspondence: alexander.reisinger@medunigraz.at
Susanne Vogt
BUniversity Medical Center, Freiburg, Germany
Roles: forensic toxicology scientist
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Anna Essl
CAustrian Red Cross, Graz, Austria
Roles: emergency medical technician (paramedic)
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Ines Rauch
DAustrian Red Cross, Graz, Austria
Roles: emergency medical technician
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Florian Bangerl
DAustrian Red Cross, Graz, Austria
Roles: emergency medical technician
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Philipp Eller
EMedical University of Graz, Graz, Austria
Roles: critical care consultant
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Gerald Hackl
FMedical University of Graz, Graz, Austria and Austrian Red Cross, Graz, Austria
Roles: critical care consultant
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ABSTRACT

Background Poppers are nitrite-containing liquids, which are inhaled for their aphrodisiac and hallucinogenic effects. Despite some cases of severe poisonings, poppers are often perceived as harmless by consumers. Inhalation and ingestion of poppers are well known, but, according to our literature review, intravenous abuse has not been reported before.

Case presentation A 34-year-old man injected poppers intravenously for recreational purposes. He then suffered from dyspnoea and general discomfort. Upon arrival of emergency medical services, the patient was dyspnoeic with blue-grey skin colour and oxygen saturation was 82% on ambient air. Non-invasive ventilation was necessary, and he was transferred to the intensive care unit. Toluidine blue was administered because of a methaemoglobinaemia of 40% and methaemoglobin levels dropped to 0.4%. He was discharged home after a 24-hour observation. We additionally analysed the contents of the poppers bottle: isopropyl nitrite, isopropanol and acetone were detected. Possible complications and the treatment regarding intravenous administration of poppers are discussed.

Conclusion We present the first published case of intravenous poppers abuse. Our patient suffered from methaemoglobinaemia and was rapidly discharged after treatment with toluidine blue. No specific treatment regarding the contents of the poppers bottle, apart from isopropyl nitrite, was necessary.

KEYWORDS:
  • Poppers
  • drug abuse
  • nitrites
  • methaemoglobinaemia

Background

Poppers are volatile inhalable liquids containing aromatic nitrites, which have euphoric and anal sphincter-relaxing effects. They became popular among men who have sex with men, frequently perceived as harmless by consumers and often sold stating other uses.1 The most commonly detected aromatic nitrites are amyl, butyl, isobutyl or isopropyl nitrite, but compositions vary.2,3 Intoxications caused by inhalation and oral ingestion have been reported comprehensively, but intravenous administration has not been described before.4,5

Case presentation

The emergency medical service was called regarding a 34-year-old man suffering from dyspnoea, general discomfort and palpitations. At his apartment, a dyspnoeic man with conspicuous blue-grey skin colour was encountered. The patient had fractionally self-administered 8 mL of poppers (‘boooster’; Fig 1) intravenously over 1.5 hours for recreational purposes. He then suffered from severe dyspnoea and headache. Peripherally measured oxygen saturation was 82% on ambient air, respiratory rate was 20 breaths per minute and blood pressure was 130/80 mmHg. Electrocardiography showed a sinus tachycardia of 140 beats minute with slight anterior ST depression. The patient was fully oriented without focal neurological deficits. He received 15 litres of oxygen via a non-rebreather mask, but non-invasive ventilation (positive end-expiratory pressure 5, assisted spontaneous breathing 8, fraction of inspired oxygen 1.0) was necessary. Oxygen saturation improved to 90% and he was transferred to the intensive care unit (ICU). Blood was obtained, which had a chocolate-brown colour. Blood gases showed a methaemoglobinaemia of 40% and an arterial oxygen saturation of 59%. Metabolic acidosis (base excess −2.6 mmol/L) and respiratory alkalosis (PaCO2 30 mmHg) were present. Lactate was 4.4 mmol/L and pH was 7.44. Laboratory analysis showed a leukocyte count of 13.0 × 109/L, a C-reactive protein value of 2.3 mg/L (normal range <10), a procalcitonin level of 0.03 ng/L (normal range 0.00–0.50), and normal kidney and liver function tests. Plasma osmolality and anion gap were within the normal range. Ethanol analysis and multidrug urine enzyme-immunoassay tests were negative. Echocardiography was unremarkable. The patient received a total of 240 mg (3 mg/kg) toluidine blue and methaemoglobin (Met-Hb) level dropped to 0.8% within 4 hours. No further respiratory support was necessary, and he was discharged after 24 hours of observation. To understand the implications of intravenous injection of this drug, we analysed the contents of the ‘boooster’ bottle via headspace gas chromatography with flame ionisation detection and detected isopropyl nitrite, isopropanol (isopropyl alcohol; 2-propanol) and acetone (Fig 2). However, therapeutic management would have not been changed by those results.

Fig 1.
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Fig 1.

Photograph of the front of the poppers bottle ‘boooster’. The content ‘isopropyl nitrite’ indicated on the bottle has been marked in red.

Fig 2.
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Fig 2.

Headspace gas chromatography with flame ionisation detection analysis of the ‘boooster’ contents. The left-most and highest peak is isopropyl nitrite, the middle peak is isopropanol and the right peak is acetone.

Discussion

Severe poppers intoxications usually occur because of exaggerated inhalation or ingestion of the fluid. Oral intake compared to inhalation is associated with increased systemic toxicity, including life-threatening methaemoglobinaemia.4 Additionally, local acid burns in the mouth and oesophagus with the risk of perforation can occur. In the intravenous abuse in our patient, haemodynamic instability was expected, but our patient was normotensive without any relevant arrhythmias. He had fractionally administered the substance and a bolus application might have far greater effects on the circulatory system. Usually, nitrites induce a decrease of blood pressure, but the short duration of action makes prolonged hypotensive periods unlikely.4,6 Phosphodiesterase-5-inhibitors have been reported to be commonly abused in combination with poppers. Concurrent use may result in life-threatening hypotension.7,8 Initially, pulmonary fat embolism was considered, but it is unlikely that the small amount would cause any relevant pulmonary artery obstruction as, in comparison, fat boluses of 1.5 mL/kg rarely cause embolism in lipid rescue therapy used for other intoxications.9 Brownish colour of the blood is a typical finding in methaemoglobinaemia.10 Physiologically, Met-Hb concentrations are about 1–2%. Responsible for the maintenance of these concentrations are erythrocyte cytochrome-b5 Met-Hb-reductase and nicotinamide-adenine-dinucleotide-phosphate (NADPH) Met-Hb-reductase. High Met-Hb concentrations result in generalised tissue hypoxia with consecutive hyperlactataemia. Severity of symptoms usually correlates with the Met-Hb concentration (Table 1).11 In this case, despite Met-Hb concentration of <50%, metabolic acidosis with elevated lactate levels and severe respiratory symptoms were present. Therapeutically, toluidine or methylene blue are used as antidotes. Thereby the Met-Hb reduction through the NADPH-Met-Hb-reductase pathway can be increased four to six-fold. Methylene blue should be given intravenously at a dose of 1–2 mg/kg over 3–5 minutes, and, if ineffective, repeated at 1 mg/kg within 30 minutes.12 If available, toluidine blue may be used instead of methylene blue as the effect onset and duration are similar, but a slightly better efficacy with fewer side effects has been reported.5,11,13 Hyperbaric oxygenation may be used as a treatment modality, particularly in patients who do not respond to therapeutic doses of methylene blue.12,14,15 Veno-arterial extracorporeal membrane oxygenation can be used in patients presenting with refractory cardio-circulatory shock, but it remains unclear whether it is possible to sufficiently load the erythrocytes with oxygen in the presence of methaemoglobinaemia.

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Table 1.

Clinical findings in patients with methaemoglobinaemia11

Regarding the findings from the content analysis, acetone is a common solvent used to decrease viscosity and increase vapor pressure. It is necessary in many pharmaceutical production processes but can also, when inhaled, cause central nervous effects. The fast-evaporating isopropanol is the hydrolysis product of isopropyl nitrite and often used in various disinfectants. The exact toxic doses are unknown but, when ingested, lethal doses of >100 mL and 3.4 mL/kg have been reported. Nevertheless, these doses are not well validated, and the cut-off regarding toxic intravenous doses is unknown.16–18 Clinically, isopropanol poisoning manifests with vomiting, diarrhoea, confusion, seizures and cardio-circulatory shock.16,19 Haemodialysis can be used to remove isopropanol. Ethanol or fomepizole are contraindicated as the degradation product (acetone) is less toxic then isopropanol itself.16,20 The amount injected by our patient is, in comparison, rather small and clinical presentation made a relevant isopropanol poisoning unlikely.

Conclusion

We present a case of intravenous injection of poppers, which led to methaemoglobinaemia and respiratory failure but did not affect haemodynamic stability. We suspect that intravenous bolus administration of poppers may lead to greater haemodynamic complications than the fractionated intravenous abuse observed in our case. The content analysis of the poppers bottle revealed isopropyl nitrite, isopropanol and acetone. Thereof, only the isopropyl nitrite required specific treatment.

Acknowledgements

We thank Stephan T Palm from Northeastern University, Boston, Massachusetts, for proofreading and spell-checking the manuscript and are very grateful for his time and input.

Ethical approval

Approval from the local ethics committee was obtained (ethics committee Graz, vote number 31-566 ex 18/19).

  • © Royal College of Physicians 2020. All rights reserved.

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Lessons of the month 3: Intravenous poppers abuse: case report, management and possible complications
Alexander Reisinger, Susanne Vogt, Anna Essl, Ines Rauch, Florian Bangerl, Philipp Eller, Gerald Hackl
Clinical Medicine Mar 2020, 20 (2) 221-223; DOI: 10.7861/clinmed.2019-0469

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Lessons of the month 3: Intravenous poppers abuse: case report, management and possible complications
Alexander Reisinger, Susanne Vogt, Anna Essl, Ines Rauch, Florian Bangerl, Philipp Eller, Gerald Hackl
Clinical Medicine Mar 2020, 20 (2) 221-223; DOI: 10.7861/clinmed.2019-0469
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