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REVERSIBLE NEUROTOXICITY DUE TO EXCESSIVE USE OF ETHYL CHLORIDE

Open AccessPublished:December 17, 2022DOI:https://doi.org/10.1016/j.jemermed.2022.12.002

      Abstract

      Background

      Ethyl chloride is commercially available as a DVD/VCR cleaner, and can be found as a gasoline additive and topical anesthetic. There is an emerging trend of recreational huffing to enhance sexual relations. Neurotoxicity from repeated abuse is uncommon.

      Case Report

      A 36-year-old man with a history of intermittent ethyl chloride use for 15 years presented to the Emergency Department with an inability to walk for 4 days after frequent use for 1 week. The patient reported a rapid titration of inhalation from zero to eight cans of 4.6 oz ethyl chloride aerosol per day over a 1-week period. Initial vital signs were heart rate 88 beats/min, blood pressure 147/60 mm Hg, temperature 37.2°C (99°F), and respiratory rate 16 breaths/min. Physical examination was notable for slurred speech, ptosis, a wide-based and ataxic gait with short strides, inability to stand without support, loss of toe/finger proprioception, horizontal and vertical nystagmus, and dysmetria on coordination testing. Strength and sensation were preserved. His work-up included computed tomography and magnetic resonance imaging of the brain, cervical, thoracic, and lumbar spine that demonstrated no acute abnormalities. On hospital day 9, the patient was able to ambulate with mild difficulty.

      Discussion

      Toxicity from excessive ethyl chloride huffing has been rarely reported. The toxicity was characterized with cerebellar findings, no attributable laboratory abnormalities, and no radiographic abnormalities on computed tomography/magnetic resonance imaging. The neurotoxicity resolved with supportive care.
      Why Should an Emergency Physician Be Aware of This? This case of excessive huffing of ethyl chloride presenting with neurotoxicity and ataxia further characterizes a rare complication of ethyl chloride toxicity that is gaining popularity.

      Keywords

      INTRODUCTION

      Ethyl chloride is a colorless, volatile liquid that was previously used as a general anesthetic and is currently used as a topical anesthetic (
      Ethyl chloride.
      ). Ethyl chloride is also commercially available as a DVD/VCR head cleaner or topical anesthetic, and it is easy to purchase online. There is an emerging trend of recreational use for sexual enhancement within the men-who-have-sex-with-men (MSM) community, like the use of alkylated nitrites (“poppers”) (
      • Hall TM
      • Shoptaw S
      • Reback CJ.
      Sometimes poppers are not poppers: huffing as an emergent health concern among MSM substance users.
      ,
      • Curto Ramos J
      • Louzao Rojas II
      • Pastor Haro JM
      • et al.
      ,
      • Hager L
      • Kamp F
      • Proesbstl L
      • Behle N
      • Pogarell O
      • Koller G.
      Inhalant abuse of ethyl chloride spray: a case report.
      ).

      CASE REPORT

      A 36-year-old human immunodeficiency virus-negative, homosexual man with history of intermittent ethyl chloride huffing for 15 years presented to the Emergency Department (ED) with an inability to walk for 4 days after more frequent daily use for 1 week leading up to presentation. The patient reported a rapid titration of “ragging” from zero to eight 4.6-oz ethyl chloride aerosol cans per day over a 1-week period. The patient used the brands Maximum Impact® (Lake Worth, Florida) and Amsterdam® obtained from local adult entertainment stores (Fig. 1). He denied use of supplements or prescription medications. He recreationally used marijuana but denied other inhalant or drug use. He denied use of nitrous oxide. He ceased using ethyl chloride 3 days prior to presentation.
      Figure 1
      Figure 1Maximum Impact can of ethyl chloride.
      Photo Credit: G. Winkler.
      A similar episode of ataxia occurred 1 month prior after a similar episode of heavy ethyl chloride use, and symptoms resolved over 2 weeks. He reported a negative magnetic resonance imaging (MRI) scan of the brain during that evaluation, but the records were unobtainable. The patient was abstinent from ethyl chloride use from prior symptom resolution until this recent binge. Initial vital signs were heart rate 88 beats/min, blood pressure 147/60 mm Hg, temperature 37.2°C (99°F), and respiratory rate 16 breaths/min. Physical examination was notable for slurred speech, ptosis, a wide-based and ataxic gait with short strides, inability to stand without support, loss of toe/finger proprioception, horizontal and vertical nystagmus, bilateral finger-to-nose dysmetria, bilateral mild heel-to-shin dysmetria, and normal strength and sensation. Laboratory data were notable for serum bicarbonate of 20 mmol/L, creatinine 1.21 mg/dL, and alkaline phosphatase 35 U/L. Otherwise, laboratory data were normal; other pertinent labs are summarized in Table 1. Computed tomography of the brain and MRI of the brain, cervical, thoracic, and lumbar spine were performed to rule out other pathology such as demyelinating disease and demonstrated no acute abnormalities. Due to the lack of other etiologies being found and his history of ethyl chloride abuse previously with similar symptoms that improved with cessation, this diagnosis seemed the most likely. Further laboratory data were obtained to rule out other possible volatile hydrocarbons, vitamin deficiency, and nitrous oxide as the etiology of his presentation (Table 1). He initially had minimal improvement of his symptoms after admission; however, on symptom day 9 he dramatically improved and was able to ambulate with mild difficulty when using a cane. On 2-week follow-up after discharge, he reported minimal difficulty ambulating with a cane and denied any further ethyl chloride abuse. He had no other neurologic symptoms or complaints. Incidentally, the patient was observed walking normally at a local grocery store 221 days after discharge.
      Table 1Pertinent Labs During Hospitalization
      TestLaboratory ValueReference RangeDiagnostic Test for:
      Thiamine, whole blood134 nmol/L70–180 nmol/LAlcohol abuse
      Vitamin B12, plasma427 pg/mL232–1245 pg/mLNitrous oxide abuse (B12 deficiency)
      Homocysteine, total-blood9 umol/L0–14 umol/LNitrous oxide abuse (B12 deficiency)
      Methylmalonic acid, serum0.17 umol/L0.00–0.40 umol/LNitrous oxide abuse (B12 deficiency)
      Hippuric acid, urine1.6 g/LNormal for unexposed populations is ≤ 1.6 g/LToluene abuse
      Hippuric acid/creatinine ratio0.61 g/gNormal for unexposed populations is < 1.5 g/gToluene abuse
      Methylhippuric acid, urineNot detectedNot detected in nonexposed general populationXylene abuse
      Ethyl chloride (chloroethane, C2H5Cl) is a volatile aliphatic, halogenated hydrocarbon with a pungent ether-like smell. It is noted to be highly lipophilic and is rapidly absorbed by the lungs. Previously, it was used as a general anesthetic, but fell out of favor once safer anesthetics became available. Ethyl chloride is still used in modern medical practice as a topical anesthetic prior to orthopedic joint injections because evaporation from the skin produces a rapid cooling sensation (
      Ethyl chloride.
      ). It can also be used for analgesia after injury in Sports Medicine or prior to ear piercing.
      Ethyl chloride acts as a central nervous system depressant. Symptoms after exposure include lightheadedness, euphoria, elation, slurred speech, auditory and visual hallucinations, and confusion (
      Ethyl chloride.
      ). Cardiac dysrhythmias can occur with heavy ethyl chloride use as with other halogenated hydrocarbons. In recent years ethyl chloride has gained popularity as a sexual aide stimulant within the MSM community (
      • Hall TM
      • Shoptaw S
      • Reback CJ.
      Sometimes poppers are not poppers: huffing as an emergent health concern among MSM substance users.
      ,
      • Curto Ramos J
      • Louzao Rojas II
      • Pastor Haro JM
      • et al.
      ,
      • Hager L
      • Kamp F
      • Proesbstl L
      • Behle N
      • Pogarell O
      • Koller G.
      Inhalant abuse of ethyl chloride spray: a case report.
      ). Reportedly, the use is popular within the MSM community due to its anesthetic effect during sex (
      • Hager L
      • Kamp F
      • Proesbstl L
      • Behle N
      • Pogarell O
      • Koller G.
      Inhalant abuse of ethyl chloride spray: a case report.
      ). Ethyl chloride is “ragged,” unlike traditional poppers (alkylated nitrites) where the fumes are directly inhaled from the bottle. Ethyl chloride is commercially available in stores and online as DVD/VCR head cleaner and topical anesthetic. Common brand names include Maximum Impact, Amsterdam, Rush, and Jungle Juice (Fig. 1) (
      Ethyl chloride.
      ,
      • Hall TM
      • Shoptaw S
      • Reback CJ.
      Sometimes poppers are not poppers: huffing as an emergent health concern among MSM substance users.
      ). Ethyl chloride is eliminated unchanged through respiration and is hepatically metabolized by both the cytochrome P450 system and glutathione-S-transferase-dependent conjugation in rodents. Human metabolism and elimination is not well understood. Ethyl chloride can be measured by blood testing through gas chromatography/mass spectrometry, thus, ethyl testing is impractical, difficult, and not easily accessible (
      Ethyl chloride.
      ,
      • Pascali JP
      • Fais P
      • Viel G
      • Cecchetto G
      • Montisci M.
      Is old stuff back? A fatal case of ethyl chloride sniffing.
      ).
      Neurotoxicity and death from ethyl chloride use has been reported after heavy use, although the pathophysiology is poorly understood (
      Ethyl chloride.
      ,
      • Pascali JP
      • Fais P
      • Viel G
      • Cecchetto G
      • Montisci M.
      Is old stuff back? A fatal case of ethyl chloride sniffing.
      ,
      • Senussi MH
      • Chalise S.
      Acute reversible neurologic deficits due to ethyl chloride sniffing: a case report and review of literature.
      ,
      • Al-Ajmi AM
      • Morad MA
      • Cooper PE
      • et al.
      Reversible ethyl chloride neurotoxicity: a case report.
      ,
      • Kuthiah N
      • Er C.
      High” on muscle spray–ethyl chloride abuse.
      ,
      • Pothiawala S
      • Yong CK
      • Charles R.
      Inhaling muscle spray: a rising trend of abuse.
      ). Recreational use produces sexual stimulation, disinhibition, increased sexual arousal and pleasure, a euphoric rush, and feelings of drunkenness (
      Ethyl chloride.
      ,
      • Senussi MH
      • Chalise S.
      Acute reversible neurologic deficits due to ethyl chloride sniffing: a case report and review of literature.
      ). Further symptoms include central nervous system depression, respiratory depression, altered mental status, cardiac depression, cardiac dysrhythmias, and inability to walk or stand (
      Ethyl chloride.
      ,
      • Senussi MH
      • Chalise S.
      Acute reversible neurologic deficits due to ethyl chloride sniffing: a case report and review of literature.
      ,
      • Al-Ajmi AM
      • Morad MA
      • Cooper PE
      • et al.
      Reversible ethyl chloride neurotoxicity: a case report.
      ,
      • Kuthiah N
      • Er C.
      High” on muscle spray–ethyl chloride abuse.
      ,
      • Pothiawala S
      • Yong CK
      • Charles R.
      Inhaling muscle spray: a rising trend of abuse.
      ,
      • Hong IZ
      • Ponampalam R.
      Death related to ethyl chloride inhalation abuse: a case report.
      ,
      • Soult TA
      • Walker JS.
      Ethyl chloride intoxication.
      ,
      • Morad MA
      • Cooper PE
      • Hassino LH
      • Siddeiq MA.
      Reversible ethyl chloride neurotoxicity: a case report.
      ). Prolonged periods of toxicity exhibited by ataxia, unsteadiness, slurred speech, central nervous system depression, and abnormal gait have been reported (
      • Senussi MH
      • Chalise S.
      Acute reversible neurologic deficits due to ethyl chloride sniffing: a case report and review of literature.
      ,
      • Soult TA
      • Walker JS.
      Ethyl chloride intoxication.
      ,
      • Morad MA
      • Cooper PE
      • Hassino LH
      • Siddeiq MA.
      Reversible ethyl chloride neurotoxicity: a case report.
      ,
      • Demarest C
      • Torgovnick J
      • Sethi NK
      • et al.
      Acute reversible neurotoxicity associated with inhalation of ethyl chloride: a case report.
      ). The toxicity in this case is similar to prior reports and was characterized by cerebellar findings without attributable laboratory abnormalities or radiographic abnormalities on CT/MRI (
      • Senussi MH
      • Chalise S.
      Acute reversible neurologic deficits due to ethyl chloride sniffing: a case report and review of literature.
      ,
      • Kuthiah N
      • Er C.
      High” on muscle spray–ethyl chloride abuse.
      ,
      • Morad MA
      • Cooper PE
      • Hassino LH
      • Siddeiq MA.
      Reversible ethyl chloride neurotoxicity: a case report.
      ). The patient had a slow and prolonged recovery, most likely attributable to the significant central nervous system distribution and high lipophilicity. Treatment for ethyl chloride toxicity is supportive; there are no methods to enhance elimination or antidotes. Patients should be monitored for hypoxia, cardiac dysrhythmias, and electrolyte abnormalities. This patient's neurotoxicity was subacute and spontaneously resolved with supportive care. Interestingly, this case also represents an exposure, re-exposure for toxicity after repeated heavy abuse.

      WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?

      Ethyl chloride is widely available, easily obtained, and is used as a sexual enhancement drug and a drug of abuse (
      • Hall TM
      • Shoptaw S
      • Reback CJ.
      Sometimes poppers are not poppers: huffing as an emergent health concern among MSM substance users.
      ). Given the increasing use of this inhalant, clinicians should be aware that excessive inhalation of ethyl chloride may result in subacute, reversible neurotoxicity with normal imaging.

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