Even the ordinarily calloused news media in Philadelphia was particularly shocked by the recent death of a 10-year-old boy in our area. This child was found in his suburban family garage, apparently the sudden death victim of intentional gasoline sniffing. Several news accounts focused on the young age of the victim, and the radio reporter that interviewed this author was incredulous when it was explained that, in fact, the intentional abuse of commonly available household volatile substances was a serious and growing problem among pre-adolescent children as well as high school students. Inhalants (also frequently referred to as volatile substances) are probably unique in that younger teens and preteens have higher rates of abuse for these substances than do older adolescents. In 1993, more US 8th graders (19.4%) than 12th graders (17.4%) reported some use of inhalants.1
The American experience with solvent abuse was first reported in the early 1950s, beginning in California and then spreading to the Midwest and reaching the East Coast by the mid-1960s.2 Of course, human experience with substance abuse by inhalation in order to alter or "expand" consciousness dates back to antiquity. It is reported that the Pythoness of Delphi achieved her powers of divination by inhaling carbon dioxide fumes from a vent in the naturally occurring rock formation or from the heating of sacred laurel leaves.3
During the 19th century, chloroform and ether parties were fashionable. In the early years of recognized solvent abuse in the United States, the potential complications of "glue-sniffing" were felt to be relatively few.4 However, by 1970, Bass reported on 110 deaths due to the abuse of inhalants that had occurred between 1962 and 1969.2 Inhalant abuse has since been reported from Canada and the United Kingdom, as well as a number of underdeveloped countries.5 A recent epidemiologic study from the United Kingdom found a significant rise in volatile substance abuse deaths between 1981 and 1990.6
A vast number of common household volatiles are abused, including solvents, aerosols, adhesives, fuel gases, spot removers and dry cleaning agents, and typewriter correction fluid (Table 1). The popularity of volatile substances as agents of abuse for young teens is understandable. These compounds are readily available at home and easily purchased at the drug store, supermarket, hardware, or paint supply store. They are not illegal and are relatively inexpensive. Their packaging allows easy transport and concealment. The "high" achieved by inhalation of these agents is deemed pleasurable and occurs very rapidly via the rich pulmonary capillary bed and subsequent rapid passage across the blood-brain barrier. The duration is relatively brief, 15 to 45 minutes, and the child or teen may return to home or school without as much obvious impairment as might be the case with alcohol or other orally ingested euphoriants. All these factors contribute to the observation that volatiles are frequently the first abused substance experienced by youth.
The typical volatile substance abuser is male, 10 to 15 years of age, although regular use has been reported as early as 7 to 8 years of age, and girls are increasingly involved. They tend to be of lower socioeconomic status, with poor school performance and high measures of family dysfunction. Particular high-risk demographic groups have been identified for volatile substance abuse in the United States, including Hispanics who are recent immigrants from Latin American countries and Native Americans on reservations.3,5,7 Volatile substance abusers usually inhale the intoxicant during a group activity with peers and tend to give up the practice after a short period of experimentation. Frequent use is unusual, with 73% of adolescent users reporting use of inhalants once or twice during the prior 12 months.
In some users, abuse may become regular or chronic, although this appears less likely than with other popular drugs. Only 1.5% of adolescent inhalant abusers report more than 40 uses per year, in contrast to 6.4% and 20% of marijuana and alcohol users, respectively. Most inhalant abusers seem to "outgrow" this phase of substance abuse, although some move on to other drugs. Between 1975 and 1982, 10% to 13% of high school seniors reported having used inhalants at least once.9 In 1990, despite the emphasis on anti-drug educational campaigns of the prior decade, 18.5% of seniors reported such use.5
The most recent data for 1993, as noted above, demonstrate an even more alarming increase in substance abuse among younger students. Unfortunately, even infrequent or one-time use of inhalants may be associated with catastrophic events. In 1994, the American Association of Poison Control Centers reported 19 deaths due to intentional substance abuse in US 13 to 19 year olds. Of these, 16 were associated with volatiles, including 9 exposures to butane, 3 to air fresheners, and 1 each to disc brake cleaner, gasoline, leather protector, and propane.10 The practicing pediatrician may well be called on to manage the acute or chronic consequences of these toxic exposures.
Pattern of Usage
Inhalation may be achieved by several techniques, variously referred to as "sniffing," "huffing," or "bagging."3 Sniffing implies inhaling vapors directly from an open container, or from a surface to which the volatile has been applied (such as a heated pan, used to enhance vaporization). Huffing suggests inhaling vapors from a piece of volatile-soaked cloth held over or next to the mouth and nose. Bagging refers to the application of the volatile (especially semisolid substances, such as model airplane glue) into a paper or plastic bag, which is then held over the mouth and nose. In addition, aerosol abusers may spray the substance directly into their mouth or filter it through a piece of cloth to avoid particulate matter or paint. Novice users tend to start with sniffing and then progress through huffing to bagging, as this affords a progressively higher substance concentration.
Classification of Volatile Substances
The compounds commonly abused are gaseous or highly volatile at room temperature, possess psychoactive effects, and are relatively free of irritant effects (Table 1). Several are considered sweet or pleasant in odor. They derive primarily from several related but distinct classes of hydrocarbon compounds or derivatives.8 These include aliphatics, alkyl halides, alkyl nitrites, aromatics, ethers, ketones, and nitrous oxide.5,8
Aliphatics (alkanes, paraffins) are typically an open 1-to 16-carbon chain. These include butane and propane, which are widely available as liquid fuel gases, such as butane in cigarette lighters and propane in tanks intended for barbecue grills. Also in this group are the common fuel/solvent mixtures of several C-5 to C- 16 compounds, eg, naphtha, gasoline, mineral spirits, and kerosene.
Chemical Classification of Commonly Abused Volatile Substances*
Abused halides are typically one or two-carbon compounds with bromine, chlorine, or fluorine sub' stitutions. They include carbon tetrachloride, chloroform, methylene chloride, trichloroethane, trichloroethylene, perchloroethylene, and freon. These are commonly available as paint additives, paint strippers or thinners, degreasers, spot removers, typewriter correction fluids, refrigerants, fire extinguishants, and aerosol propellants.
Nitrites include amyl nitrite, and butyl or isobutyi nitrite, which are available in room deodorizers, and are also sold in "head shops," marketed as aphrodisiacs. The most commonly abused aromatic hydrocarbons are benzene, toluene, and xylene. These are frequent constituents of glues and adhesives, acrylic paints, lacquers and varnishes, and shoe polish. Ethers and ketones may be found in solvents, nail polish remover (acetone), and adhesives (methylethylketone). Finally, although not a hydrocarbon per se, nitrous oxide is also widely available in food product propellants, eg, whipped cream, and is similarly abused.
The relevant pharmacokinetics of these agents may be generalized for the group as a whole, with a few notable annotations.8 High lipid solubility and rapid absorption via the pulmonary route, which circumvents first pass metabolism in the liver (eg, is equivalent to intravenous dosing), results in rapid entry to the brain. Clinical effects are usually apparent within seconds to minutes. Most of these highly lipophilic agents have a high volume of distribution (largely partitioned in the intracellular space of lipidrich organs). Elimination for most of these substances is primarily via the lungs. Three exceptions of note are the alkyl nitrites, aromatice (particularly benzene), and methylene chloride that undergo significant hepatic metabolism, producing free nitrites, reactive intermediates, and carbon monoxide, respectively, all of which may be of additional toxicologic importance.
The acute intoxicated state is similar for most of the volatile substances and is further discussed below. Several of the more commonly abused agents have a propensity for causing particular organ system pathology. These effects are reviewed by system. The toxicities of the more important substances are tabulated in Table 2.
All of the volatiles share the acute effect of central nervous system (CNS) depression.8 Much as the case for ethanol, the early stages of "anesthesia" produced results primarily in cortical inhibition with resultant euphoric and hyperactive effects. As the dose increases, severe narcosis may ensue. These effects o the volatiles are believed to be related more to a generalized alteration of neuronal membrane function than to specific neurotransmitter or receptor mediation, as has been the traditional view of alcohol and general anesthetic agents. Recent work on these latter drugs has suggested that some of their effects may in fact be mediated by CNS gamma amino butyric acid or glutamate receptors, and this may prove to be true as well for several of the abused volatiles.11
Chronic neurologic effects are of considerable concern in habitual abusers. Central nervous system toxicity in children has been particularly observed in chronic gasoline and toluene abuse. Gasoline sniffing has been a significant health concern in native American Indians in the southwest United States and Canada. This gasoline toxicity has been complicated by the presence of organic (tetraethyl) lead, which is believed to be the major etiology of the observed encephalopathy.3,12 Toluene sniffing also has been reported to cause severe encephalopathy in children.13 It may present With coma, ataxia, and seizures as well as euphoria and/or hallucinations. In several cases, prolonged or permanent sequelae have been described. Chronic hexane exposure from sniffing hexane-containing glues is the classic cause of sensorimotor peripheral neuropathy with a stocking-glove distribution; neuropathy also has been reported with chronic naptha fume inhalation.14
Summary of Unique Clinical Effects of Major Volatile Substances of Abuse
The volatiles have potentially lethal effects on the heart and peripheral vasculature. Several agents, particularly the aliphatics and halogenated hydrocarbons, are associated with the "sudden sniffing death" syndrome, believed to the result of ventricular fibrillation due to sensitization of the myocardium to endogenous catecholamines. This syndrome was described with detailed anecdotal reports by Bass in his 1970 review of 110 such cases.2 Most of the victims were adolescents who became agitated during a sniffing exposure, jumped up, ran a short distance, and then collapsed. Post-mortem findings were generally unrevealing. The majority of these deaths were associated with fluorocarbon aerosols, but several were due to gasoline, benzene, toluene, and trichloroethane use. Subsequent reports in the 1990s have extended this syndrome to abuse of butane and propane.14 A recent case report details the successful resuscitation of a 1 5 -year-old boy from protracted ventricular fibrillation after freon abuse.15 This patient may well represent a "save" with modern bystander cardiopulmonary resuscitation, rapid emergency medical service response, and expert ACLS protocols initiated in the emergency department. Such a patient undoubtedly would have been one of Bass' sudden deaths in the 1960s.
Animal studies have found that halogenated hydrocarbons produce arrhythmias in association with infused epinephrine and that the propensity to such "sensitization" relates primarily to the ratio of the volatile's partial pressure/vapor pressure, rather than molecular weight, structure, degree of halogenation, or saturation.16 Hydrocarbons also may cause decreased myocardial contractility and peripheral vasodilatation, with initial mild hypotension and reflex tachycardia at low doses. At higher doses, bradycardia and decreased cardiac output are observed.17 It is likely that asphyxia and perhaps coronary ischemia secondary to systemic hypotension may contribute to clinical episodes of volatile - induced arrhythmias.15
The act of bagging may result in asphyxia, as the partial pressure of the volatile displaces oxygen to a critical level.8 Some volatiles abo cause direct pulmonary irritation with a chemical pneumonitis. Central nervous system depression associated with high doses may lead to primary respiratory arrest or depress airway protective reflexes, such that aspiration might further compromise airway and breathing.
Hepatic, Renal, and Bone Marrow
The halogenated hydrocarbons, particularly trichloroethylene and toluene have been associated with severe centrilobular necrosis. Toluene has been classically associated with distal renal tubular acidosis, although other renal pathology, including acute tubular necrosis and chronic renal failure also have been described.8,11 Toluene-associated renal tubular acidosis is accompanied by profound hypokalemia, hypophosphatemia, hyperchloremia, and normal anion gap. It may be complicated by renal failure and urinary lithiasis. Bone marrow damage, including aplastic anemia and leukemia, have been associated with chronic benzene toxicity. The chronic abuse of nitrous oxide has been associated with a pernicious anemia-type syndrome, including anemia, leukopenia, sensorimotor neuropathy and posterior/lateral column spinal cord disease. These effects are mediated by nitrous oxide inactivation of vitamin B12.8
Chronic toluene abuse during pregnancy has been associated with an embryopathy similar to fetal alcohol syndrome.18 Affected infants were noted to exhibit intrauterine growth retardation, microcephaly, craniofacial abnormalities, and developmental delay.
Typical acute effects are comparable for all the volatiles and similar to those of alcohol inebriation, with euphoria and hyperactivity initially.3,8 Mucous membrane irritation may manifest as sneezing, coughing, salivation, and conjunctival erythema. Some patients may experience nausea and vomiting.
Respiratory symptoms include dyspnea and wheezing or rales may be noted. With low-dose exposure, recovery is usually rapid, and most symptoms resolve within 30 minutes to 2 hours. As dose increases, patients may develop slurred speech, diplopia, ataxia, disorientation, and visual hallucinations. A sense of invulnerability may occur that leads to impulsive and dangerous acts resulting in severe or fatal trauma. The high flammability of the volatiles may predispose to accidental burns. With further CNS depression, coma, seizures, and respiratory arrest may occur. As noted, at any stage the sudden onset of agitation and physical activity may be complicated by sudden ventricular arrhythmia and death.
As expected with the multiple-organ system toxicity outlined above, chronic volatile substance abusers may present with numerous patterns of multisystem dysfunction, even in the absence of acute intoxication.5,8 Evidence of chronic neuropsychiatrie or encephalopathic changes may predominate. Such patients may present with confusion, delusions, hallucinations, paranoia, psychomotor retardation, paresthesias, ataxia, extremity weakness, and visual disturbances. There may be evidence of subacute or chronic hepatic and renal disease, with gastrointestinal symptoms, abdominal or flank pain and tenderness, fatigue, myalgias, fever, or dark urine. Skin findings might include jaundice with hepatic disease, cyanosis from nitrite-induced methemoglobinemia, or an erythematous, papular eruption ("huffer's rash") about the mouth and nose. Psychologic dependence appears to occur for some sniffers. Both tolerance and withdrawal, characterized by chills, headache, abdominal pain, and muscle cramps that may progress to delirium tremens have been reported, although the latter is uncommon and in some patients may represent concommitant addiction to other classes of drugs.11
Most acutely intoxicated abusers of volatiles do not seek medical attention, and it is likely that only the exceptional case that has suffered a significant complication will arrive to the emergency department. The management of such a patient includes careful assessment and stabilization of the "ABCs." Airway control and ventilatory support must be provided as necessary. Since the catastrophic consequences are usually cardiac, respiratory, or neurologic, initial interventions in the more stable patient should include establishment of intravenous access and cardiorespiratory monitoring.8,15 As these exposures occur via inhalation, traditional gastrointestinal decontamination interventions would not be helpful unless a concomitant ingestion was suspected. Supportive care for arrhythmias, hypotension, bronchospasm, or seizures should follow usual ACLS guidelines, with a few caveats. The potential for cardiac sensitization makes the use of catecholamine pressors or bronchodilators less desirable than in the otherwise comparable patient. To the extent possible, hypotension should be managed with positioning and fluid support. Wheezing may respond to steroids and oxygen. Cautious use of nebulized beta-agonists may be considered if these measures fail to improve significant respiratory distress or hypoxia (which probably themselves increase endogenous catecholamines).
An effort should be made as soon as feasible to obtain an exact history of exposure. Often, friends or relatives who found the patient or brought the patient to the hospital are able to ascertain the circumstances surrounding the exposure. Evidence of paint or other suspicious chemicals on the patient's skin or clothing, odors on breath or clothing, or empty containers at the scene may provide useful clues. The description of a previously healthy teenager who suddenly collapses while engaged in a group activity or party with friends should at least raise the suspicion of acute volatile substance abuse. A careful physical examination should focus on vital signs and evidence of cardiorespiratory, neurologic, and abdominal findings. Most acutely ill patients will warrant an arterial blood gas, complete blood cell count, comprehensive chemistry panel, serum and urine toxicologic screen, urinalysis, electrocardiogram, and chest radiograph. For selected volatile agents, additional laboratory testing and specific antidotal therapy may be indicated.3,8
Methylene chloride exposure can be associated with clinically significant carbon monoxide poisoning. Such patients require specific carboxyhemoglobin determinations by spectrophotometry. Elevated levels are managed with 100% oxygen by nonrebreather mask in the alert, ventilating patient or via endotracheal tube in the critically ill. Patients who were obtunded or comatose may benefit from hyperbaric oxygen therapy. The duration of such methylene chloride- induced carbon monoxide toxicity is prolonged relative to the more common inhalational exposures to carbon monoxide, and patients may require monitoring and treatment for 12 to 24 hours.
Alkyl nitrite abuse may result in significant methemoglobinemia. Patients with levels greater than 30% to 40%, or who are symptomatic, should be treated with methylene blue, 1 to 2 mg/kg IV over 5 minutes. This dose may be repeated in 30 to 60 minutes as necessary. Repeated doses should not exceed 7 mg/kg, since large doses of methylene blue can have a paradoxical oxidant, pro-methemoglinemic effect.
Acute poisoning due to carbon tetrachloride may cause acute hepatic necrosis, and some experimental support exists for the use of N-acetylcysteine, charcoal hemoperfusion, and hyperbaric oxygen therapy as adjunctive treaments.8 Fortunately, exposures to this substance are rare in the United States today; no cases were reported in the 1994 American Association of Poison Control Centers' report.10 Consultation with a regional poison center certainly would be indicated in the rare event of such an occurence. Chronic gasoline sniffing was formerly associated with organic lead poisoning, and a history of such exposure might warrant blood lead testing, although most gasoline sold in the United States today is unleaded.
Most adolescent patients who reach medical care for the acute effects of volatile substance abuse would probably benefit from hospitalization for a period of medical observation and initiation of appropriate social work and psychologic interventions. Patients and their families need to be educated about the potentially life-threatening consequences of this "phase" of drug experimentation.
The intentional abuse of volatile inhalants is an alarming and growing manifestation of substance abuse among American youth today. Although often a transient phase of drug experimentation, it may lead to habitual usage or to experience with other pyschoactive agents. The medical consequences of acute intoxication include severe and potentially fatal multiorgan system effects, including sudden death from cardiac arrhythmia. Chronic use may be associated with both visceral and encephalopathy sequelae. Pediatricians should be aware of this ominous threat to their patients, particularly younger teens or even préadolescents.
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14. Tenenbein M, De Groot W, Rajani KR. Peripheral neuropathy following Intentional inhalation of naptha fumes. CMAJ. 1984;131:1077-1079.
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Chemical Classification of Commonly Abused Volatile Substances*
Summary of Unique Clinical Effects of Major Volatile Substances of Abuse