Patients who present with an acute change in mental sta-tus along with generalized neurologic symptoms could

be experiencing any one of a number of medical or neurolog-ic conditions. The differential diagnosis is broad and includesstroke and other neurologic diseases, delirium, psychiatricillness, metabolic abnormalities, infectious diseases, ordrug effects. Drugs that are associated with changes inmental status and generalized neurologic symptoms in-clude anticholinergics, antiepileptics, antidepressants, an-tipsychotics, antiparkinsonians, anxiolytics, opiates, and ille-gal drugs of abuse. The pharmacist plays a key role in theidentification of drug-induced mental and neurologic disease.

Case Report

A 41-year-old African American male presented to the emergency de-partment with a mental status change. He stated that he “could not see

objects that were there.” He also complained of drowsiness, shakiness,and inability to walk due to weakness and impaired balance. He denied ahistory of alcohol or drug abuse. His past medical history was significantfor HIV infection diagnosed 4 years earlier. His CD4+ cell count uponadmission was 208 cells/mL. His home medications were zidovudine300 mg twice daily, lamivudine 150 mg twice daily, and nelfinavir 1250mg twice daily, all of which were continued upon admission.

Upon physical examination, the patient was drowsy but awake andoriented to person and place but not time; vital signs were normal andcranial nerves intact. He was markedly tremulous, dysarthric, weak, andataxic. Oxygen saturation on room air was 85%, and chest X-ray re-vealed a left lower lobe infiltrate. Vital signs were T 37 ˚C, HR 94beats/min, RR 18 breaths/min, and BP 145/74 mm Hg on admission. Anelectrocardiogram showed normal sinus rhythm. He remained afebrile,with normal vital signs, throughout the hospitalization. The white bloodcell (WBC) count was 8.5 × 103 cells/mm3 and remained within normallimits until discharge. The patient was treated empirically for possiblepneumonia with ceftriaxone 2 g daily, azithromycin 500 mg daily, andtrimethoprim/sulfamethoxazole 5 mg/kg every 6 hours intravenously. Inaddition, acyclovir was begun for possible herpes meningitis. Lorazepam1 mg every 8 hours was initiated for tremulousness, and this was contin-ued until hospital discharge.

A number of diagnostic tests were performed, none of which revealeda specific cause of the patient’s mental status change and neurologic

The Annals of Pharmacotherapy ■ 2005 January, Volume 39 ■ 169

Acute Inhalant-Induced Neurotoxicity with Delayed Recovery

Christopher K Finch and Bob L Lobo

www.theannals.com

Author information provided at the end of the text.

OBJECTIVE: To report a case of neurotoxicity and subsequent hospitalization due to abuse of an ethyl chloride inhalant.

CASE SUMMARY: A 41-year-old African American male presented to the emergency department due to mental status changes andan inability to walk. After the blood alcohol and urine drug screen returned negative, a family member revealed that the patientfrequently abused an inhalant containing the volatile solvent ethyl chloride.

DISCUSSION: Inhalant abuse is common and is facilitated by the widespread availability of volatile solvents that have legitimatecommercial or household uses. Most inhalants are central nervous system depressants and are highly lipophilic. Maximum Impact,which contains ethyl chloride, is sold in stores and is readily available over the Internet. While the product has a legitimate use as aVCR head cleaner, it is often illicitly marketed over the Internet as a means of getting a “rush” or “high” and for enhancing sexualpleasure. Neurologic symptoms have been reported after deliberate inhalational exposure to ethyl chloride, and 2 deaths have beenassociated with its use. An objective causality assessment using the Naranjo probability scale revealed a probable adverse drug event.

CONCLUSIONS: Inhalants should be included in the differential diagnosis of patients presenting with acute mental status changes andneurologic impairment that resolve over less than one week.

KEY WORDS: ethyl chloride, inhalant abuse, neurotoxicity.

Ann Pharmacother 2005;39:169-72.

Published Online, 8 Dec 2004, www.theannals.com, DOI 10.1345/aph.1E159

symptoms. Computed tomography and magnetic resonance imaging(both non-contrast) were interpreted as normal by a radiologist. Resultswere negative for rapid plasma reagin, pneumococcal antigen, and serumcryptococcal antigen. Urinalysis was normal (no bacteria or WBCs).Blood cultures remained negative for growth throughout the hospitaliza-tion. Lumbar puncture results were negative for cryptococcal antigenand VDRL; cerebral spinal fluid Gram stain and cultures were also nega-tive. Herpes simplex virus polymerase chain reaction was negative. Serumethyl alcohol and urine drug screen for opiates, cocaine, and benzodi-azepines were negative. No other toxicologic studies were performed.

On hospital day 2, the patient was still weak, markedly tremulous, andataxic, but denied experiencing any more hallucinations. On this day, afamily member indicated that the patient habitually inhaled the videohead cleaner product Maximum Impact. The patient then indicated that,approximately 2 years prior to admission, he began inhaling one canister(2 or 4 oz) of video head cleaner with 4 or 5 of his friends on an occa-sional basis, but denied other illicit substance use. However, over the lastfew months, his inhalant use increased and he was now inhaling the con-tents of 2 canisters alone over a 4- to 5-hour period up to several timeseach week. He had been inhaling the substance on the day of admission.He stated that weakness, shakiness, and difficulty walking sometimesoccur following heavy use and sometimes persist for several days.

On day 3 of hospitalization, the patient’s tremor, weakness, and ataxiawere improving, and by day 5, only a mild tremor (no weakness or ataxia)was noted. It is unknown whether the mild tremor eventually resolved. In-travenous antibiotics were discontinued on day 5, and the patient was dis-charged on his previous therapy and oral trimethoprim/sulfamethoxazole.

Discussion

Volatile solvents are present in a wide array of house-hold products and are used for such purposes as cleaning,degreasing, painting, and gluing. It is estimated that thereare >1000 products containing volatile solvents that are le-gal and readily obtained.1 These products typically containa halogenated hydrocarbon and may also contain smallamounts of other aliphatic, aromatic, or other fluorinated hy-drocarbons. Volatile solvents are intentionally concentratedand inhaled in order to produce a mind-altering effect. Be-cause these substances are commonly used householditems, their potential for abuse to achieve an intoxicatedstate may be underestimated.2

Inhalant abuse has become a significant health concernin the US and may be a stepping stone to future illicit druguse. Risk factors for abuse may be low socioeconomicclass, ethnicity, male gender, and delinquency. However,inhalant abuse seems to have also penetrated the middleclass youth.3 As with other types of substance abuse, pre-cise epidemiologic data are not available, but it is estimat-ed that there may be one million new users of inhalantseach year. The MTF (Monitoring the Future) study, whichhas been conducted under a series of research grants fromthe National Institute on Drug Abuse, monitors nationaltrends in substance use and abuse among adolescents andyoung adults.4 Data from the MTF study indicate that, in1997, 21% of eighth graders had abused an inhalant atsome point in their life. This rate had decreased to 15.8%of eighth graders in 2003—still a significant public healthconcern when the risks of inhalant abuse are taken intoconsideration.

Most abused inhalants are central nervous system de-pressants that slow nervous system conduction; however,an excitatory phase characterized by disinhibition can de-

velop prior to the depressant effects.5 Because these prod-ucts are highly lipophilic, inhalant distribution is very highto organs rich in lipids (eg, brain, liver, adrenal glands).Thus, inhalant intoxication resembles alcohol inebriation,but with a faster onset of action and shorter duration of ef-fect after use.3 Although uncommon, sudden sniffing deathsyndrome can occur with a single use or after chronic ad-ministration of an inhalant; therefore, these products arenever safe.5,6 Other causes of death have also been associ-ated with inhalant use: asphyxia (while using plastic bagscontaining the inhalant over the head), cardiac arrhythmiasand pump failure, violence, explosions, fires, and head in-jury from syncopal episodes.

Video head-cleaner products are readily available forpurchase at retail stores throughout the US. While theyhave a legitimate use, there are numerous Internet Websites and “head shops” that market these products as ameans of experiencing a euphoric “rush” and enhancingsexual pleasure. Many of the video head cleaners haveprovocative brand names such as Macho, Rush, JungleJuice Plus, Black-Jac, and Maximum Impact.

Maximum Impact, the product our patient was abusing,is a “premium grade video head cleaner” intended for useon all metallic and glass heads, including audio, video, anddata.7 It is available via the Internet through numerousprovocative sites from $7.50/$10.95 per 2/4.6-oz bottles,respectively.7 The primary ingredient is ethyl chloride orchloroethane; however, this volatile solvent has other syn-onyms.8 Ethyl chloride is a colorless gas with general anes-thetic properties in humans and animals. Its use as a gener-al anesthetic was abandoned after it was associated with atleast 71 deaths due to respiratory muscle paralysis and/orarrhythmias in the UK from 1945 to 1964. Only chloro-form has been blamed for more anesthetic deaths thanchloroethane.9 Currently, its major use is as a starting pointin the production of tetraethyl lead and as a refrigerant, sol-vent, and alkylating agent.8 It is also used in the medicalindustry as a topical anesthetic.

After inhalational exposure to ethyl chloride in humans,neurologic symptoms are frequently observed. Acutely,exposure has resulted in feelings of drunkenness, confu-sion, dizziness, hallucinations, lack of muscle coordina-tion, pronounced impairment of short-term memory, andunconsciousness.8,10,11 In one case report, cerebellar-relatedsymptoms, including ataxia, speech difficulties, and hallu-cinations, were reported in a 28-year-old female who in-haled ethyl chloride from her saturated shirt sleeve dailyfor 4 months.12 Her liver was also enlarged and tender. Theauthors were able to determine whether these effects re-flected substance intoxication or withdrawal. The majorityof these symptoms were also present in our patient at thetime of admission. Thus, it is possible that our patient’ssymptoms were related to ethylene chloride withdrawalrather than intoxication.

Two deaths have been attributed to inhalational expo-sure of ethyl chloride.13,14 The long-term chronic effects ofethyl chloride in humans are not known, although some

170 ■ The Annals of Pharmacotherapy ■ 2005 January, Volume 39 www.theannals.com

CK Finch and BL Lobo

animal studies suggest changes in the lungs, liver, and kid-neys due to chronic exposure.8 It has been reported that theminimum lethal concentration of ethyl chloride is 55 000ppm in rats and mice; however, the lethal concentration inhumans is not known.

The mechanism of chloroethane-induced neurotoxicityis unclear. Animal studies examining the histology of ner-vous tissue have not revealed specific pathology followinginhalational exposure. However, other volatile substances,such as toluene, have been associated with dissolution ofthe myelin sheath, resulting in damage to neurons and celldeath. Loss of neurons in the cerebellum, cerebrum, andperipheral nervous system has been postulated to explainthe symptoms of memory impairment, loss of coordina-tion, tremors, hallucinations, blurred vision, and weaknessthat are sometimes seen in people abusing volatile sub-stances. There is anecdotal evidence that some of thesepeople have wider cerebellar and cerebral sulci and ven-tricular systems.3,9

Conclusions

We believe that our patient’s mental status changes andacute neurologic symptoms were probably related to heavyabuse of a video head cleaner product containing ethylchloride. There are several published reports of this type ofreaction. The symptoms followed inhalant abuse. The re-action abated after cessation of use and, according to thepatient, was more severe with abuse of larger quantities ofthe substance. Although antiretroviral medications havebeen associated with central nervous system effects andperipheral neuropathy, this patient’s mental status changeand generalized neurologic symptoms resolved despitecontinuation of the antiretroviral medications. Althoughpneumonia may be associated with acute mental statuschanges, his generalized neurologic symptoms were notconsistent with pneumonia. Application of the Naranjoprobability scale indicated ethyl chloride as a probable ad-verse reaction.15 Clinicians should consider the possibilityof inhalant abuse in patients who present with confusion,hallucinations, ataxia, dysarthria, weakness, and tremorthat cannot be explained by drugs or medical causes.

Christopher K Finch PharmD BCPS, Critical Care Specialist,Methodist University Hospital, Memphis, TN; Assistant Professor,College of Pharmacy, University of Tennessee, MemphisBob L Lobo PharmD BCPS, Internal Medicine and NeuroscienceSpecialist, Methodist University Hospital; Associate Professor, Col-lege of Pharmacy, University of TennesseeReprints: Dr. Finch, Department of Pharmacy, Methodist Universi-ty Hospital, 1265 Union Ave., Memphis, TN 38104-3499, fax 901/726-8178, finchc@methodisthealth.org

References

1. National Inhalant Prevention Coalition. www.inhalants.org/index.htm(accessed 2004 Mar 19).

2. Inhalant abuse. Committee on Substance Abuse and Committee on Na-tive American Child Health. Pediatrics 1996;97:420-3.

3. Marelich GP. Volatile substance abuse. Clin Rev Allergy Immunol1997;15:271-89.

4. Monitoring the Future Study (Table 1). www.monitoringthefuture.org/data/03data.html#2003data-drugs (accessed 2004 Aug 26).

5. Meadows R, Verghese A. Medical complications of glue sniffing. SouthMed J 1996;89:455-62.

6. National Institute on Drug Abuse. www.drugabuse.gov/ResearchReports/Inhalants/Inhalants.html (accessed 2004 Mar 22).

7. XXX Action sex toys. www.xxx-action-sex-toys.com/SEX_TOY_Head_Cleaner_Maximum_Impact_Head_Cleaner_4_6_oz.shtml (accessed 2004Mar 19).

8. US Department of Health and Human Services. Hazardous substancesdata bank (HSDB, online database number-533 and CAS registry num-ber 75-00-3). Bethesda, MD: National Toxicology Information Pro-gram, National Library of Medicine, 2002. www.toxnet.nlm.nih.gov (ac-cessed 2004 Mar 19).

9. Lawson JM. Ethyl chloride. Br J Anaesth 1965;37:667-70.10. Agency for Toxic Substances and Disease Registry (ATSDR). Toxico-

logical profile for chloroethane. Atlanta: US Public Health Service, USDepartment of Health and Human Services, 1998. www.atsdr.cdc.gov/toxprofiles/tp105.html (accessed 2004 Mar 19).

11. Nordin C, Rosenqvist M, Hollstedt C. Sniffing of ethyl chloride—an un-common form of abuse with serious mental and neurological symptoms.Int J Addict 1988;23:623-7.

12. Hes JPH, Cohn DF, Streifler M. Ethyl chloride sniffing and cerebellardysfunction. Isr Ann Psychiatr Relat Discip 1979;17:122-5.

13. Broussard LA, Broussard AK, Pittman TS, Lirette DK. Death due to in-halation of ethyl chloride. J Forensic Sci 2000;45:223-5.

14. Yacoub I, Robinson CA, Simmons GT, Hall M. Death attributed to ethylchloride. J Anal Toxicol 1993;17:384-5.

15. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. Amethod for estimating the probability of adverse drug reactions. Clin Phar-macol Ther 1981;30:239-45.

EXTRACTO

OBJETIVO: Informar sobre un caso de neurotoxicidad y hospitalizacióndebido a abuso de inhalador de cloruro de etilo.

RESUMEN: Un hombre áfrico americano de 41 anos se presento aldepartamento de emergencia por cambios mentales e inhabilidad paracaminar. Luego de que el cernimiento de drogas en sangre y orinafueran negativos, un miembro de la familia revelo que el pacienteabusaba frecuentemente de un inhalador que contenía el solvente volátilcloruro de etilo.

DISCUSIÓN: El abuso de inhaladores es común y es facilitado por laaccesibilidad de solventes volátiles que tienen usos residenciales ocomerciales legítimos. La mayoría de estos inhaladores deprimen elsistema nervioso central y son altamente lipofílicos. Maximum Impact,que contiene cloruro de etilo, se vende en las tiendas y está accesiblefácilmente a través de la red cibernética. Aunque el producto tiene unuso legítimo, como limpiador de las cabezas de las video caseteras, semercadea ilícitamente a través de la red cibernética como un estimulantey para aumentar el pacer sexual. Se han reportado síntomas neurológicosluego de la exposición deliberada por inhalación a cloruro de etilo, y 2muertes se han asociado a su uso. Una evaluación objetiva de causalidadutilizando la escala de probabilidad de Naranjo reveló un efecto adversoprobable.

CONCLUSIONES: Hemos descrito un caso de neurotoxicidad inducida porcloruro de etilo con recuperación tardía. Los inhaladores deben serincluidos en el diagnostico diferencial de pacientes que se presentan concambios mentales agudos y otros síntomas neurológicos que resuelvenen menos de una semana.

Annette Pérez

RÉSUMÉ

OBJECTIF: Rapporter un cas de neurotoxicité suivi d’une hospitalisationdue à l’abus d’un inhalant au chlorure d’éthyle.

SOMMAIRE DU CAS: Un américain de 41 ans, d’origine africaine, s’estprésenté au département d’urgence suite à un changement de son étatmental et une incapacité à marcher. Après un dépistage négatif d’alcool

Inhalant-Induced Neurotoxicity with Delayed Recovery

The Annals of Pharmacotherapy ■ 2005 January, Volume 39 ■ 171www.theannals.com

dans le sang et l’urine, un membre de la famille a révélé l’abus fréquentdu patient pour un inhalant contenant le solvant volatile au chlorured’éthyle.

DISCUSSION: L’abus d’inhalant est commun et est facilité par la grandedisponibilité des solvants volatiles qui ont des usages commerciaux oudomestiques légitimes. La plupart des inhalants sont des dépressifs dusystème nerveux central et sont hautement lipophiles. Maximum Impact,qui contient du chlorure d’éthyle, est vendu dans les magasins et estaccessible via l’Internet. Bien que le produit ait un usage légitimecomme nettoyeur de têtes d’un VCR, il est fréquemment commercialiséde façon illicite via l’Internet comme moyen d’obtenir un rush ou unhigh et pour améliorer le plaisir sexuel. Des symptômes neurologiques

ont été rapportés après exposition à l’inhalation délibérée au chlorured’éthyle, et 2 décès ont été associés à son utilisation. Une évaluationobjective du lien de causalité à l’aide de l’échelle de probabilité deNaranjo révèle un effet adverse probable.

CONCLUSIONS: Nous décrivons un cas de neurotoxicité induit par lechlorure d’éthyle avec un rétablissement retardé. Les inhalants devraientêtre inclus dans le diagnostic différentiel des patients se présentant avecun changement rapide du statut mental et un désordre neurologique quise résorbent à l’intérieur d’une semaine.

Chantal Guévremont

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CK Finch and BL Lobo