Inhalant Abuse in the Military: An Unrecognized Threat

MILITARY MEDICINE, 172, 4:388, 2007 Inhalant Abuse in the Military: An Unrecognized Threat Guarantor: CPT Benjamin W. Lacy, MC USA Contributors: CPT Benjamin W. Lacy, MC USA; Thomas F. Ditzler, PhD FRIPH Although inhalant abuse represents the third most commonly abused class of drugs in the military, it is a frequently overlooked form of substance abuse in the active duty population. Inhalants lack of visibility is also evident in the civilian community. In both the civilian and military communities, the factors leading to underrecognition of inhalant abuse include high availability, low cost, lack of drug screening and drug treatment programs, and frequent misdiagnosis by clinicians. This review seeks to inform care providers about the prevalence, health risks, diagnosis, and treatment of inhalant abuse in the active duty population, and encourages clinicians to be more aggressive in the identification of this serious but underrecognized problem. Department of Psychiatry, Tripler Army Medical Center, 1 Jarrett White Road, Honolulu, HI 96859-5000. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Army, the Department of Defense, or the U.S. government. This manuscript was received for review in June 2006 and was accepted for publication in September 2006. Introduction nhalant abuse is defined as the intentional inhalation of I chemical vapors for the purpose of recreational intoxication. Nationally recognized substance abuse experts have described inhalant abuse as the Silent Epidemic, the forgotten drug abuse problem, and our least understood drug problem. 1 Inhalants are the only drug group in the Diagnostic and Statistical Manual of Mental Disorders that are defined by their route of administration. Typical sources include glues, paints, lacquers, correction fluid, and gases. The specific inhalation techniques are referred to variously as sniffing, snorting, huffing, and bagging. Sniffing refers to the inhalation of fumes directly from a substance or container. Snorting refers to placing the substance itself into the nasal passage. Huffing is performed on liquids and refers to breathing in fumes from a rag soaked with a volatile solvent. Bagging refers to inhalation of fumes after a substance has been placed into a paper or plastic bag. 2 Chronic abusers often make a progression from sniffing to bagging as a means of obtaining a higher concentration of chemical vapors. Inhalants are abused equally among males and females, although chronic abuse is more common in males. Rates of misuse are highest among Native Americans, Hispanics, and Caucasians and lowest among African Americans. Populations particularly at risk include those on reservations and in rural areas with a low socioeconomic background. 2,3 Similar demographics appear worldwide with inhalant abuse reaching epidemic proportions in some indigenous cultures and in emerging industrial nations in South America, Africa, and the Middle East. 1,4 U.S. health providers involved in military or humanitarian deployments overseas should be aware of developing countries with highly significant inhalant abuse problems, especially among street children. Inhalants are among the first drugs that young children abuse to get high, with an average first time use occurring at 16 years of age. 2 During the late 1990s, a national antidrug campaign aiming to increase public awareness of childhood inhalant abuse was initiated. Many practitioners and community-based prevention programs continue to focus on inhalant abuse as a gateway drug used mainly in early adolescence. A recent online search using key words inhalant abuse and army or military yielded numerous instructive web sites focused on prevention and recognition of inhalant abuse among young adolescent family members. However, very few results were found concerning community education or treatment programs for inhalant abuse in active duty or adult dependents. The exclusive focus on younger adolescents is contrary to evidence gathered by National Household Survey on Drug Abuse, which suggests the incidence of new use by 17-year olds was as great or greater than new use by 12-year olds. 5 Similar data exist in the Substance Abuse and Mental Health survey which showed 30% of the 1.2 million new users of inhalants were 18 years or older. 6 Survey data obtained through the 1998 and 2002 Department of Defense Survey of Health-Related Behaviors suggests that the prevalence of chronic inhalant abuse in the military population ranks equally with commonly tested drugs such as cocaine, opiates, and amphetamines. The success of drug-screening programs in reducing drug abuse in the military is substantial and well documented. 7 The past 30-day use of screened drugs such as marijuana, cocaine, and amphetamines is substantially lower in today s active duty military population than their civilian counterparts. However, past 30-day use of inhalants among military members is reported to be 0.8% and is roughly equal to corresponding civilian surveys (Fig. 1). 5,6,8 Due to a lack of randomized drug screening, inhalant abuse passes by undetected. Inhalants, like other forms of abused drugs, affect military readiness and negatively impact the health of service members. The following cases illustrate clinical characteristics and ensuing problems associated with inhalant abuse. Case 1 During week 2 of a field-training exercise, a 21-year-old Caucasian male Army E-3 was taken to the acute care clinic in the early evening after becoming confused, disoriented, and verbally combative toward his first sergeant. The soldier had a significant past medical history of frequent headaches resulting in missed work and several presentations to sick call while in garrison. On examination, the soldier appeared tired, was diaphoretic, disoriented to time and place, and responded to verbal commands in an uncoordinated manner. Screening laboratory tests, including urinary drug screen, electrolytes, and complete 388

Inhalant Abuse in the Military: An Unrecognized Threat 389 As the above cases illustrate, inhalants are inexpensive, readily available, and used repetitively to obtain a quick high. Inhalants represent a very broad range of commonly available substances that may be subdivided by type of substance, route of inhalation, chemical structure, or mechanism of action. In the review by Brouette and Anton, 10 inhalants are subclassified into volatile solvents of abuse (VSA), anesthetic gases, or shortacting vasodilators. This method of review is based on the differing epidemiology and mechanisms of action of each class. Fig. 1. Past 30-day drug use by percentage, civilian versus military. Sources: Substance Abuse and Mental Health Services Administration, Office of Applied Studies, National Survey on Drug Use and Health 2003, 2004 and Department of Defense Survey of Health-Related Behaviors 2002. blood count, were within normal limits. The patient was given intravenous fluids and within 1 hour of initial presentation became coherent with a full return of motor function. He was placed on bed rest for 24 hours and given presumptive diagnosis of dehydration and heat exhaustion, despite a core temperature of 98.8 F at the time of admission. Several weeks later, the soldier was taken to acute care clinic after missing formation. He was found asleep in his barracks room with several open cans of shoe polish nearby. He awakened to verbal and physical stimuli but once again appeared moderately sedated and confused. On physical examination, several fingers and nail beds appeared to be stained with black polish. The patient was further questioned by a physician in private and admitted to frequent use of inhalants such as shoe polish, room freshener, and deodorants to get high. Case 2 9 A staff sergeant driving on post failed to stop at a T intersection and accelerated his vehicle, crashing into on-post housing. The service member was pulled from the vehicle as the house and car caught fire, destroying the home. Witnesses testified that the service member appeared to be having a seizure and a silver-gray can was seen between the service member s legs at the time of the accident. A police search of the vehicle produced several cans of an aerosol cleaning agent. Two weeks later, the service member was again arrested when police were called due to suspicious activity in a restroom of the post library. Police heard moaning and a spraying sound coming from inside the locked stall. The service member emerged from the restroom stall confused and stumbling. An aerosol can was retrieved from the stall and the service member admitted to investigators and medical personnel that he had been inhaling it to get a quick high. The third incident occurred approximately 3 weeks later during a lunch break. When the service member did not return to work, a coworker was sent to the service member s house. The service member could be heard in the bathroom spraying aerosol. Due to safety concerns, military police and paramedics were called to the scene. The service member became belligerent and resisted arrest, biting one policeman s arm. Following the service member s arrest, the military police again retrieved aerosol cans from the home. Volatile Solvents Volatile solvents are by far the most commonly abused inhalants and are the larger focus of this review. They represent a wide variety of industrial and household products (Table I). 2 Due to high lipid solubility and uptake via the pulmonary circulation, VSAs have a quick onset of action within seconds to minutes and a duration of effect of approximately 1 to 2 hours. The short-lasting effects appeal to those abusing substances in school, military, or work environments where users may disappear for a relatively brief time, then return without obvious sign of intoxication. The particular mechanism by which inhalants cause intoxication is unclear, but VSAs are generally thought to act as central nervous system (CNS) depressants, causing potentiation of -aminobutyric acid (GABA) receptors, and negative interaction at glutamate receptors. 11 A second hypothesis is that VSAs act similarly to anesthetics which cause fluidization of neuronal membranes, leading to slowing of axonal ion transport systems. 2,12 Clinically, VSA intoxication resembles that of acute alcohol intoxication, including visual disturbances, poor motor coordination, disorientation, and slurred speech. TABLE I COMMONLY ABUSED VOLATILE SOLVENTS Volatile Substance Commercial Products Aliphatic hydrocarbons Propane Bottled fuel Butane Cigarette lighter fluid Gasoline Automotive fuel N-Hexane Glues, rubber cement Alkyl halides TCE Correction fluid, dry cleaning agents Trichloroethylene Dry cleaning agents, spot remover Trichlorofluoromethane Refrigerant, aerosol propellant (Freon 11) Aromatic hydrocarbons Benzene Resins, lacquers, varnishes, gas Toluene Adhesives, spray paint, glues, paint thinner Xylene Wood glues, lacquer thinner Nitrites Butyl/isobutyl nitrite Room air freshener Amyl nitrite ( poppers ) Vasodilators Ketones Acetone Nail polish remover Butanone Adhesives, general solvent MBK Various paints Table borrowed from Kurtzman et al. (Ref. 2).

390 Inhalant Abuse in the Military: An Unrecognized Threat Volatile Solvents: Acute Toxicity Intermittent or experimental inhalant users rarely present primarily for the treatment of inhalant abuse, but due to the toxic nature of many inhalants, patients may occasionally present for acute care. In the acute setting, mucous membrane irritation may lead to sneezing, coughing, excessive salivation, and conjunctival erythema. Higher doses result in an intoxicated, disoriented appearance marked by motor excitation, euphoria, and disinhibition. With further intoxication, patients display slurred speech, delusions, confusion, diplopia, ataxia, and visual hallucinations. High levels of intoxication may also result in decreased reflexes, nystagmus, severe CNS depression, seizures, and death. Specific signs of abuse include reports of hidden solvent containers or soaked rags, a characteristic odor on breath, a perioral huffer s rash, and paint or other stains on face, hands, and clothes. 13 Providers should entertain the diagnosis of inhalant intoxication and ask questions concerning inhalants when the above signs and symptoms are present in an adolescent or young adult. Inhalant intoxication has been associated with a high incidence of deaths. These fatalities are more commonly due to acute toxic effects of the drug but also may occur due to traumatic accidents associated with intoxication. 14 16 Lethal toxicity is generally secondary to the inhalants effect on the CNS, the respiratory system, and/or the cardiac system. Inhalants are irritating to the lungs and may lead to dyspnea, rales, and possibly, pulmonary distress. Asphyxiation also occurs due to partial or complete compromise of an airway by plastic bags or other modes of use. Most commonly, deaths associated with inhalants are due to cardiac toxicity described as sudden sniffing death syndrome. Patients are already in a hyperadrenergic state due to the psychological effects of intoxication and substance-associated hypoxia. VSAs chemically sensitize the myocardium further to catecholamines. This increased sensitization leads to increased risk of arrhythmia and subsequent sudden death. 16 Another less common form of cardiac death is associated with the rapid cooling of the larynx from aerosol propellants or spray paint. This cooling can cause sudden, reflex vagal inhibition leading to arrhythmias as well. 16 Volatile Solvents: Chronic Toxicity Patients present less frequently with medical illness due to the chronic effects of inhalants than with acute effects. Areas most frequently damaged with chronic use include the CNS, kidney, liver, heart, lung, and hematological system. The typical chronic inhalant user is more likely to display poor cognitive skills, antisocial traits, familial dysfunction, and polydrug use. 10,17 Due to common personality dysfunction and increased suicidal thinking, chronic abusers are as likely to present for psychiatric services as for medical concerns. Several inhalants have been studied and determined to cause specific neurological syndromes with prolonged use (Table II). Toluene, commonly found in glue, spray paint, and shoe polish, is the most frequently abused inhalant. 18 Long-term use results in cognitive dysfunction and subcortical dementia. Symptoms are characterized by poor attention, psychomotor dysfunction, insomnia, depression, irritability, and tremor. 10 Toluene has TABLE II INHALANTS KNOWN TO CAUSE SPECIFIC NEUROLOGICAL SYNDROMES WITH PROLONGED USE Solvent Toluene N-Hexane MBK TCE Methylene chloride NO Neurological Syndrome Cognitive dysfunction, cerebellar ataxia, optic neuropathy, sensorineural hearing loss Polyneuropathy (distal axonopathy) Polyneuropathy (distal axonopathy) Trigeminal neuropathy, other cranial nerve palsies None determined Polyneuropathy (resembling B 12 deficiency) also been associated with the development of multifocal CNS effects leading to ataxia, optic neuropathy, and/or sensorineural hearing loss. 19,20 A second class of volatile solvents also found in adhesives contains N-hexane and/or methyl butyl ketone (MBK). Chronic exposure to these compounds causes damage to the peripheral nervous system resulting in an axonal polyneuropathy characterized by decreased nerve conduction and a symmetric, progressive sensorimotor loss beginning in a stockingglove distribution. 21 24 A third class of commonly abused solvents, found in correction fluid and dry cleaning agents, includes trichloroethylene (TCE). Chronic TCE inhalation is associated with a slowly reversible trigeminal neuropathy that can be easily found on physical examination. 25 There are several other chemicals found in volatile solvents such as benzene (gasoline), Freon 11 (refrigerant), and dichloromethane (paint stripper) that have been associated with intoxication and acute medical problems. However, little is known of the deleterious neurological effects these compounds may cause with chronic use. Although the neurological system is most damaged with chronic solvent abuse, other organ systems may be affected as well. The cardiovascular and respiratory systems are most affected acutely and may lead to sudden death as described previously. Other organs affected by chronic use include the kidneys, liver, blood, and bone. A variety of renal disorders occur secondary to VSA, including toluene-associated renal tubular acidosis, urinary calculi, and glomerulonephritis. 25 Both chlorinated hydrocarbons and toluene have been shown to cause hepatoxicity. Chronic benzene use has been associated with disorders of bone marrow suppression and malignancies such as leukemia, lymphoma, and multiple myeloma. 26 29 Volatile Solvents: Tolerance and Withdrawal Unlike many other substances of abuse, there are few clinical studies dedicated to understanding mechanisms for tolerance, dependence, and withdrawal states in chronic inhalant abuse. Currently, inhalant tolerance and withdrawal states are not defined in the Diagnostic and Statistical Manual of Mental Disorders IV. There is debate over whether chemical dependence and withdrawal exist. Tolerance has been shown in several animal and human studies but has been difficult to quantify. 25 The reinforcing, addicting properties of inhalants in animal studies are supported by alterations in the dopamine neurons of the ventral tegmental area in a fashion similar to other drugs of abuse. 30 Several studies have shown clinical evidence of chronic users suffering withdrawal

Inhalant Abuse in the Military: An Unrecognized Threat symptoms such as insomnia, nausea, irritability, anxiety, tremor, and even delirium days after last use. 31 33 Nitrous Oxide (NO) NO, also known as laughing gas, is a nonsolvent inhalant that is chemically and physiologically separate from the volatile solvents described previously. NO was developed as an anesthetic and is still used as an induction agent due to its rapid onset and short half-life. NO abuse has been associated with adult, higher functioning individuals, and the educated middle class. Reports of abuse by dentists with access to NO are not uncommon. Nonmedical abusers tend to be younger and obtain NO through its use as a propellant in whipped cream ( whippets ). NO acts through the opiate system by binding directly to,, and receptors and mediates the release of -endorphins. 10,11 It also acts as an N-methyl-D-asparate antagonist likely leading to a calming, depressant effect and may be used in easing withdrawal of several drug classes such as alcohol and benzodiazepines. NO: Clinical Presentation NO abuse is more frequent among adults than adolescents. Intoxication is described as a dissociative experience with body tingling, numbness, dizziness, auditory hallucinations, stiffness, and warmth. 10 In the acute setting, abusers may present to the emergency room due to transient hypoxia or complaining of claustrophobia with associated nausea. Vasodilation and pooling of the blood in the lower extremities may lead to orthostatic hypotension and syncope. With chronic use, NO inactivates vitamin B 12 in the recycling of methionine and leads to a peripheral neuropathy similar to that of vitamin B 12 deficiency. 34,35 Patients present with memory impairment, numbness and weakness in limbs, loss of dexterity, and loss of balance. It is unknown whether chronic users of NO typically develop dependence or suffer a withdrawal syndrome. There has been animal data and at least one case report to suggest withdrawal occurs. 36 Nitrites Short-acting vasodilators such as nitrites can be found in aerosol propellants, some prescription medications, or purchased as a finished product from specialty retail stores. Nitrite abuse was much more common during the 1970s, especially among the homosexual community. 37 The prevalence of nitrite abuse among today s military members is likely very low. Like NO, the effects of nitrites are very short-acting. The onset of a high is within seconds of inhalation and disappears within 5 minutes. In addition to feelings of euphoria and depersonalization, nitrites cause vasodilatation and relaxation of smooth muscles. This leads to a floating sensation, increased skin perception, and heightened sexual arousal, to include prolonged orgasm. 37 Nitrites: Clinical Presentation Acute emergencies due to nitrites are usually secondary to severe drops in blood pressure and reflex tachycardia. 10 Nitrites have not been associated with long-term neurological sequelae. However, chronic nitrite abuse causes damage to the hematological and immune system. Inhalation leads to increased methemoglobin and is associated with hemolytic anemia 37 ). Nitrites have also been associated with the epidemiology of tumors and infectious diseases such as human immunodeficiency virus/ acquired immunodeficiency syndrome since the early 1980s. 38 Animal research has shown that nitrites may impair T cell function. 39 Among researchers, there is continued debate over whether the increased risk of diseases such as Kaposi sarcoma and acquired immunodeficiency syndrome is a confounder in epidemiology or a direct medical problem associated with nitrite abuse. Clinical Management 391 Data-based research on diagnosis and treatment of inhalant abuse is limited. 40 Although the profound psychosocial deterioration attendant to chronic abuse makes individual treatment highly problematic, the basic principles of effective substance abuse treatment still apply. 10,40 Treatment begins with a detailed history and physical examination. Family members, friends, and coworkers are important sources of information. The substance abuse history should include information about age of first use, pattern and frequency of use, assessment of tolerance and withdrawal, presence of other medical and psychiatric disorders, and an assessment of the patient s motivation for treatment. The medical review of systems and physical examination should focus more specifically on disease processes associated with the liver, kidneys, heart, and lungs. A detailed neurological examination is required, with particular attention to the sensorimotor and cognitive processes. The initial laboratory work-up should include screening electrolytes, blood urea nitrogen, creatinine, liver enzymes, and an electrocardiogram. 41 Because of the elevated risk of polydrug abuse, urine drug screening should be also performed. Laboratory tests for inhalants and their metabolites have been developed. One technique involves headspace gas chromatography of blood specimens; methods for detection of urinary metabolites have also been developed. 42 These assays have been used in research to detect inhalation exposure in individuals already suspected of abuse. 43 Currently, the U.S. military does not have a laboratory detection program for inhalants as it does for marijuana, cocaine, and amphetamines. The treatment of acute inhalation-related injury is generally supportive; no specific agents can reverse acute solvent intoxication. 44 Chronic abusers of inhalants may be at risk for significant withdrawal symptoms and prolonged cognitive dysfunction lasting weeks. Patients should be monitored as if being treated for alcohol withdrawal. Objective scales such as the Clinical Institute Withdrawal for Alcohol Scale may be helpful in determining the need for pharmacological intervention. Benzodiazepines are generally considered first-line treatment for significant withdrawal symptoms. 10,44 Atypical antipsychotics may be used to treat inhalantinduced psychiatric symptoms. In one case report, risperidone was shown to relieve both substance-induced psychosis and craving for inhalants. 45 Additional studies on the efficacy of benzodiazepines, antipsychotics, and other drugs such as naloxone and acamprosate are necessary to determine their possible role in the treatment of chronic inhalant use. The rate of recovery from inhalant abuse is generally slower than that for other substance use disorders such as alcohol dependence. Patients with heavy inhalant abuse histories may

392 Inhalant Abuse in the Military: An Unrecognized Threat benefit from a formal neuropsychological assessment using standardized psychometric tools. The assessment should be performed after a minimum of 2 to 6 weeks of documented abstinence. Due to the high degree of social dysfunction associated with inhalant abuse, treatment centers generally report poor response to treatment. Recommendations for improving outcomes include educating staff on neuropsychological effects of inhalants, allowing longer treatment stays, and combining intensive individual, family, and group therapies with active participation in community based support groups. 40 Conclusions Both logic and survey data would suggest that inhalant abuse represents a potentially serious threat to readiness. However, unlike other drugs of abuse in the military, inhalant abuse has historically received little in the way of prevention, detection, treatment, and legal accountability. Inhalant abuse often occurs sporadically and in groups of friends or associates. Due to the nonspecific symptoms of intoxication, inhalant abuse may be difficult for clinicians to detect. Perhaps in the future, appropriate laboratory assays may be added to the military s random and command referred drug-screening program. The discovery of one case by military health providers or command should act as an early warning and point toward the need for more aggressive education, prevention, and identification in the community. References 1. Epidemiology of inhalant abuse: an international perspective: proceedings of a meeting, July 21 22, 1993. NIDA Res Monogr 1995; 148: 1 306. 2. Kurtzman TL, Otsuka KN, Wahl RA: Inhalant abuse in adolescents. J Adolesc Health 2001; 28: 170 80. 3. Neumark YD, Delva J, Anthony JC: The epidemiology of adolescent inhalant drug involvement. Arch Pediatr Adolesc Med 1998; 152: 781 6. 4. 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