The Abuse of Volatile Substances

Chemical Dependency

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The Abuse of Volatile Substances

Michael J. McHugh, MD*

The use of volatile substances to alter consciousness has been practiced since ancient times. The Pythoness of Delphi drew her power of divination from a naturally occurring carbon dioxide vent in the rocks. Inhalation of the gas resulted in a trancelike state during which prophecies were made. When the flow of gas ceased, sacred laurel leaves scorched in a bowl were used as the carbon dioxide source. 8 The use of nitrous oxide, chloroform, and ether were genuinely fashionable in nineteenth century society. The twentieth century has witnessed one inhalent fad after another. A partial listing of abused volatile substances would include items as diverse as model airplane glue, paint thinners, fuels, shoe polishes, vegetable nonstick frying sprays, fire extinguishing agents, antiperspirants, and coronary artery dilators. The appeal of these substances is difficult to appreciate by a nonuser. Some of the substances used are judged to be toxic enough to warrant strict statutes limiting exposure of workers to them. Cohen has outlined some typical reasons for use of these agents 8 : 1. Rapid onset of effect. The "high" induced by solvents begins within a few minutes of inhalation. The agents used are noteworthy for their lipid solubility. They are rapidly absorbed across the alveolar membrane and distributed throughout the body. They traverse the blood-brain barrier easily and, because of their lipophilic nature, tend to accumulate in brain tissue. 2o. 25 The "high" produced is much faster than that produced by alcohol.' 2. Quality and pattern of the 'high." Most users of volatile substances report decreased inhibitions and a "floaty euphoria.'" The user is frequently giddy and lightheaded.25 Misperceptions and illusions are common. Inebriation induced by alcohol or marijuana use is usually described as similar but not identical.' 3. Low cost. Many solvent inhalers are from low-income families. These substances may not be the users' first choice in inebriant, but they are frequently the most economical.' 4. Easy availability. Many of the volatile substances are available in homes in which alcohol cannot be found. Nearly every garage or household has a small supply *Assistant Director, Pediatric and Surgical Intensive Care Unit, The Cleveland Clinic Foundation, Cleveland, Ohio

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of paint thinner, cleaners, or gasoline. These materials are also easily available in supermarkets, hardware stores, and drug stores. 5. Convenient packaging. Many of these substances are sold in very small containers that can be hidden with ease. This is particularly important to those who wish to "get high" during the school day. 6. The legal question. In contrast to alcohol and the controlled substances, purchase and possession of these substances is not illegal in most jurisdictions.

PREVALENCE OF USE Inhalants are frequently the first consciousness-altering substances used by children. 8 Adolescents tend to abandon the use of inhaled agents after a year or two, sometimes moving on to other substances. 25 In the report by Stevens et al. on inhalant use among junior and senior high school students in New York State, students in the lower grade levels were more likely to have used solvents recently that were those in the upper grades. Use of solvents tended to decrease with increasing age. There was a strong and consistent inverse relationship between the grade point average of the student and the likelihood of solvent use. There was likewise a correlation between lack of family cohesiveness and solvent use. 29 The use of inhaled substances appears to have remained relatively constant over the last few years. In a survey of drug use by high school seniors from 1975 to 1982, lO to 13 per cent of each senior class reported using inhalants at least once. Use of amyl and butyl nitrites, which was not surveyed until 1979, also held steady at lO to 11 per cent. A maximum of 0.1 per cent of the senior classes reported daily use of these substances. Daily users were defined as those persons using the substances 20 or more times in the month prior to the survey. These rates of use are approximately equivalent to the rates reported for lysergic acid diethylamide (LSD) and phencyclidine (PCP).22 By comparison, 6 to lO per cent of high school seniors in the same survey reported themselves as daily users of marihuana and 5 to 6 per cent of the seniors reported themselves as daily users of alcohol. The prevalence of inhalant abuse varies markedly from one population to another. Boeckx et al. reported on two isolated Canadian Indian reservations in which nearly 100 per cent of the children had sniffed gasoline at least once. 5 Coulehan et aI., in a study of Navajo adolescents, reported that 11.4 per cent of their junior and senior high school students had sniffed gasoline at least once, and 7.5 per cent reported regular use. TECHNIQUES OF USE As a general rule, inhalant use is a group activity.8. 25 Most commonly, the agent is placed in a plastic or paper bag and the fumes inhaled. Another preferred method of administration is to soak a rag or handkerchief with the agent and to inhale through the cloth, using the nose and the mouth ("huffing").2 Liquids, such as industrial solvents, frequently are inhaled

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Table 1. Commonly Abused Volatile Substances ALIPHATIC AND AROMATIC HYDROCARBONS

Hexane Gasoline Benzene Toluene Xylene HALOGENATED HYDROCARBONS

Trichloroethane Trichloroethylene Halothane Freons TrichloroHuoromethane (Fluorocarbon 11) DichlorodiHuoromethane (Fluorocarbon 114) DichlorotetraHuoromethane (Fluorocarbon 12) ALIPHATIC NITRITES ("SNAPPERS" OR "POPPERS")

Amyl nitrite n-Butyl Nitrite Isobutyl nitrite NITROUS OXIDE

directly from a container. 2, 25 Aerosolized products may be sprayed into a bag or passed through a cloth to separate the particular contents from the gas. 25. 33 Less commonly, the substances may be inhaled over a heated pan to increase vaporization. 23

CLINICAL SYMPTOMS The actual pharmacology of most of these agents presently is unknown. 33 The changes in consciousness are analogous to the levels induced by progressive anesthesia. The first stage is characterized by excitation. The subjective effects are those of euphoria and exhilaration. Sneezing, coughing, and salivation are common. Nausea and vomiting frequently occur during this first stage. As the inhalation progresses, eNS depression becomes more evident. The patient becomes confused and disoriented. There is a generalized loss of inhibitions, which frequently leads to impulsive behavior and subsequent trauma. Many users experience a sense of invulnerability.33 Nearly all of the commonly used agents are able to induce these first two levels of changes. As inhalation continues, eNS depression becomes more marked, with a further reduction in coordination. The user becomes ataxic, and reflexes are depressed. A fourth and final stage of eNS depression is reached when stupor develops. Seizures or cardiorespiratory arrest may occur during this final phase. 20, 33

SPECIFIC INHALANTS Toluene

Toluene (methylbenzene) is a colorless liquid used extensively as a solvent. Most commonly, it is used in glues and adhesives, acrylic paint

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preparations, paint thinners, and automotive products. It has gained widespread use as a replacement for the solvent benzene, which causes bone marrow depression. Many clinical syndromes have been ascribed to both acute and chronic toluene abuse. Acutely, neurologic symptoms predominate. King et al. reported on 19 children aged 8 to 14 years admitted with acute encephalopathy following toluene intoxication. 17 Seven patients had a history of euphoria or hallucinations. Four patients presented with coma, three with ataxia, and three with convulsions. Thirteen of the children had complete resolution of their symptoms. One child showed persistent cerebellar signs 1 year after his presentation. Five cases were lost to follow up. Cronk et al. reported a case of respiratory arrest following an acute toluene inhalation. 11 Four different patterns of symptoms have been described in chronic toluene abusers. Streicher et al. described three different patterns in 25 adult abusers: muscle weakness, gastrointestinal complaints, and neuropsychiatric disorders. The muscle weakness experienced by nine patients was severe. It generally spared the respiratory and central musculature and was accompanied by normal reflexes. In four of the nine patients, the weakness was manifested as a quadriparesis. Six of these patients had evidence of rhabdomyolysis with creatine phosphokinase (CPK) levels greater than two times normal. As a group, they had strikingly low levels of serum potassium and phosphorus. The degree of hypokalemia and hypophosphatemia was probably responsible for the significant muscle weakness. Six patients presented with complaints of abdominal pain, nausea, vomiting, and hematemesis. Ten patients were admitted with neuropsychiatric problems. Two of the ten had paresthesias or peripheral neuropathy and three had cerebellar ataxia. Mental status changes tended to resolve over a period of hospitalization of up to 8 days. The peripheral neuropathy and cerebellar abnormalities tended to persist. 3O Persistent cerebellar ataxia,fi permanent encephalopathy,l8 and optic neuropathy1fi have been described by other authors. The fourth syndrome seen with chronic toluene abuse is that of distal renal tubular acidosis. First reported by Taher et al. 31 and subsequently by others. 13. 32 it is noteworthy for high anion gaps, hyperchloremia, hypokalemia, and hypophosphatemia. Azotemia is common and usually resolves with abstinence. Toluene-induced renal tubular acidosis was implicated as a cause of urinary calculi in the patient of Kroeger et al. 19 Sixteen to twenty per cent of inhaled toluene is eliminated by the lungs unchanged. 23 Approximately 80 per cent of the inhaled dose is oxidized to benzoic acid, then conjugated with glycine. It is eliminated in the urine as hippuric acid. Measurement of urinary excretion of hippuric acid is used as an indicator of the degree of toluene exposure. Blood toluene levels also may be measured. Blood concentrations of toluene may be biphasic. An initial peak is followed by a drop in blood level, which reflects the binding of the substance by the fatty tissues of the body. Following the termination of exposure, a second peak may appear as the toluene is slowly released from the lipid-containing tissues. 17

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Gasoline The composition of gasoline varies from brand to brand. This variability is a reflection of the origin of the petroleum from which the gasoline is derived, the molecular modifications made during refining, and the subsequent additives. Gasoline is primarily a mixture of C C C 12 aliphatic hydrocarbons. 14 The saturated hydrocarbons from C 4 to C s have strong narcotic properties. 24 With sufficient exposure, nausea, ataxia, and loss of consciousness may be induced. Appreciable amounts of other substances such as xylene, toluene, benzene, paraffins, and naphthenes are present. 14 These substances may contribute to the inebriation. Gasoline is rapidly absorbed from the lungs, and the desired onset of symptoms is noted within 3 to 5 minutes. 24 Fifteen to twenty breaths of the vapor is sufficient to inebriate for 5 to 6 hours. An inhaled concentration of 1 per cent produces dizziness and drunkenness in about 5 minutes. 12 The major acute and chronic toxicities of gasoline sniffing are neurologic. Ataxia, tremor, myoclonus, and encephalopathy have been reported in chronic users. 5 . 9, 15, 26 Forty-nine of Seshia's fifty patients presented nonencephalopathic after a minimum 6 months history of gasoline sniffing. Forty-six of the fifty had abnormal neurologic signs at the time of the first assessment. The most commonly noted abnormal findings included abnormally brisk reflexes, postural and intention tremors, and ataxic gaits. 26 Coulehan et al. reported on 23 Navajo adolescents who were hospitalized 47 times for presumed lead intoxication secondary to gasoline sniffing. Of the 23 children, 15 presented with encephalopathy. In 14 of these admissions, tremor, ataxia, and chorea were also present. 9 Organic lead poisoning from the breakdown of tetraethyl lead, an antiknock agent, is believed to be responsible for the neurologic changes induced by chronic gasoline abuse. Encephalopathic patients invariably have elevated blood lead levels, and neurologic improvement is the rule with standard lead chelation therapy. 5, 9, 15,26 Blood lead levels appear to be the best indicators of acute tetraethyl lead poisoning. 9 Free erythrocyte protoporphyrin may be used to screen for more chronic exposures. Because of the social nature of gasoline sniffing, it may be useful to screen siblings and close friends of identified patients by one of the assays. 9 Halogenated Hydrocarbons Certain halogenated hydrocarbons are used as solvents, degreasers, and spot removers; among the most popular are trichloroethane and trichloroethylene. A group of halogenated hydrocarbons that was used extensively in the past as intoxicants was the freons. Freons were widely employed as aerosol propellants and were among the most commonly abused inhalants in the 1960s. Their use as a propellant in most products was discontinued in this country after 1968. Halogenated hydrocarbons produce a significant depression of the cardiovascular system. One mechanism of cardiovascular toxicity involves the sensitization of the heart to circulating catecholamines, which increases the possibility of ventricular tachycardia and fibrillation. Bass, in his study of 110 "sniffing" deaths, drew attention to a common theme of sudden

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activity or stress immediately preceding death in several halogenated hydrocarbon inhalations. 3 Trichloroethane and fluorinated hydrocarbons were the most commonly implicated inhalants. Another potential cardiovascular toxicity is that of decreased myocardial contractility, which results in decreased cardiac output, decreased coronary blood flow, and adrenal release of catecholamines. 1 The increased levels of circulating catecholamines are able to induce arrhythmias in the previously sensitized heart. Nitrous Oxide Nitrous oxide is another widely available potential inhalant. It is used commercially as a propellant for whipping cream and as a power booster for automobiles and motorcycles. As mvcr. as 3.5 liters of nitrous oxide may be obtained from readily available whipped cream dispensers.21 Like the other inhalants, nitrous oxide frequently prodvces a "floating" sensation and euphoria. Visual hallucinations also may occur. Heavy exposures may produce coma, respiratory depr~ssion, and seizures.213 Hypoxic brain damage is a real possibility when this agent is inhaled without supplemental oxygen. Nitrites The alkyl nitrites (amyl, n-butyl, and isobutyl) have become very popular recently as orgasm enhancers. They are widely available and sold in "head shops" under various trademarks as room deodorants and "liquid incense. "27 Amyl nitrite is widely available as an industrial cyanide antidote. The nitrites are potent smooth muscle relaxants. The giddiness, dizziness, and syncope induced by these agents is thought to represent a spectrum of cerebral ischemia caused by vasodilation. The perceived enhancement of the orgasmic experience is also believed to be the result of vasodilation of penile blood vessels. 4 The major toxicities of nitrite inhalation result primarily from vasodilation and the formation of methemoglobin. The vasodilation may cause orthostatic syncope. The induced methemoglobinemia may be sufficient to cause tissue hypoxia. Cyanosis is seen with methemoglobin levels greater than 10 per cent. In extreme cases (methemoglobin levels greater than 50 per cent), metabolic acidosis, lethargy, myocardial ischemia, coma, and convulsions may be seen. Methemoglobin levels greater than 70 per cent of circulating hemoglobin may produce cardiovascular collapse and death from asphyxia. 4 A simple bedside assessment of degree of methemoglobinemia may be performed by plqcing a drop of the patient's blood on a filter paper. If methemoglobin greater than 10 per cent is present, the patient's blood will appear brown when compared to that of a control subject. 20 If there is evidence of metabolic acidosis, altered mental status, or if the methemoglobin concentration is over 40 per cent, the patient should be treated immediately with oxygen and intravenous methylene blue. The usual dose of methylene blue is 1 to 2 mg per kg administered over several minutes. Repeat doses may be administered to reduce the methemoglobin concentrations to safe levels.

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SUMMARY Volatile substances have been used to alter consciousness since ancient times. Societal trends have brought forth one inhalant fad after another. It would be reasonable to expect this pattern to change as certain of the inhalants come under greater control or become less available (e.g., leaded gasoline). Experimentation with these agents among younger adolescents probably will continue, and for this reason, pediatric practitioners should be aware of the use of these agents and their potential toxicities.

REFERENCES 1. Aviado OM: Pharmacology of abused inhalants. In Sharp CW, Carroll LT (eds): Voluntary Inhalation of Industrial Solvents. Washington, DC, U.S. Government Printing Office, 1978 2. Barnes GE: Solvent abuse: A review. Int J Addict 14:1-26, 1979 3. Bass M: Sudden sniffing death. JAMA 212:2075--2079, 1970 4. Benowitz NL: Nitrites and nitrates. In Haddad LM, Winchester JF (eds): Clinical Management of Poisoning and Drug Overdose. Philadelphia, WB Saunders, 1983 5. Boeckx RL, Post! B, Coodin FJ: Gasoline sniffing and tetraethyllead poisoning in children. Pediatrics 60:140-145, 1977 6. Boor JW, Hurtig HI: Persistent cerebellar ataxia after exposure to toluene. Ann Neurol 2:440-442, 1977 7. Chenoweth MB: Abuse of inhalation anesthetic drugs. In Sharp CW, Brehm ML (eds): Review of Inhalants: Euphoria to Dysfunction (NIDA Monograph 15). Washington, DC, U.S. Government Printing Office, 1977 8. Cohen S: Inhalent abuse: An overview of the problem. In Sharp CW, Brehm ML (eds): Review of Inhalants: Euphoria to Dysfunction (NIDA Monograph 15). Washington, DC, U.S. Government Printing Office, 1977 9. Coulehan JL, Hirsch W, Brillman J et al: Gasoline sniffing and lead toxicity in Navajo adolescents. Pediatrics 71:113--117, 1983 10. Crites 1. Schuckit MA: Solvent misuse in adolescents at a community alcohol center. J Clin Psychiatry 40:39-43, 1979 11. Cronk SL, Barkley DE, Farrell MF: Respiratory arrest after solvent abuse. Br Med J 290:897--898, 1985 12. Drinker P, Yaglov CP, Warren MF: The threshold toxicity of gasoline vapor. J Ind Hyg Toxicol 25:225--232, 1943 13. Fischman CM, Oster JR: Toxic effects of toluene. JAM A 241:1713--1715, 1979 14. Fortenberry JD: Gasoline sniffing. Am J Med 79:740-744, 1985 15. Hansen KS, Sharp FR: Gasoline sniffing, lead poisoning, and myoclonus. JAMA 240: 1375--1376, 1978 16. Keane JR: Toluene optic neuropathy. Ann Neurol 4:390, 1978 17. King MD, Day RE, Oliver JS et al: Solvent encephalopathy. Br Med J 283:663-665, 1981 18. Knox JW, Nelson JR: Permanent encephalopathy from toluene inhalation. N Engl J Med 275:1494-1496, 1966 19. Kroeger RM, Moore RJ, Lehman TH et al: Recurrent urinary calculi associated with toluene sniffing. J Urol 123:89--91, 1980 20. Kulberg A: Substance abuse: Clinical identification and management. Pediatr Clin North Am 33:325--361, 1986 21. Murray MJ, Murray WJ: Nitrous oxide availability. J Clin Pharmacol 20:202-205, 1980 22. National Institute on Drug Abuse: Student drug use attitudes and beliefs: National trends, 1975--1982. DHHS Publications No. (ADM) 83-1260. Washington, DC, U.S. Government Printing Office, 1982 23. Pagnotto LD, Lieberman LM: Urinary hippuric acid excretion as an index of toluene exposure. Am Ind Hyg Assoc J 27:129--134, 1967

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24. Poklis A, Burkett CD: Gasoline sniffing: A review. Clin Toxicalll:35-41, 1977 25. Schukit MA: Drug and Alcohol Abuse, Ed 2. New York, Plenum Press, 1983 26. Seshia SS, Rajani KR, Boeckx RL et al: The neurologic manifestations of chronic inhalation of leaded gasoline. Dev Med Child Neurol 20:323-334, 1978 27. Sharp CW, Stillman RC: Blush not with nitrites. Ann Intern Med 92:700--701, 1985 28. Steen PA, Michenfelder JD: Neurotoxicity of anesthetics. Anesthesiology 50:437-453, 1979 29. Stephens RC, Diamond SC, Speilman CR et al: Sniffing from Suffolk to Syracuse: A report of youthful solvent use in New York State. In Sharp CW, Carroll LT (eds): Voluntary Inhalation ofIndustriai Solvents. Washington, DC, U.S. Government Printing Office, 1978 30. Streicher HZ, Gabow PA, Moss AH et al: Syndromes of toluene sniffing in adults. Ann Intern Med 94:758-762, 1981 31. Taher SM, Anderson RJ, McCartney Ret aI: Renal tubular acidosis with toluene "sniffing." N Engl J Med 290:765-768, 1974 32. Voigts A, Kaufman CEo Acidosis and other metabolic abnormalities associated with paint sniffing. South Med J 76:443-447, 1983 33. Wyse DG: Deliberate inhalation of volatile hydrocarbons: A review. Can Med Assoc J 108:71-74, 1973 Pediatric and Surgical Intensive Care Unit The Cleveland Clinic Foundation 9500 Euclid Avenue Cleveland, Ohio 44106