eMedicine Specialties > Neurology > Neurotoxicology

Inhalants

Author: Timothy Kaufman, MD, Staff Physician, Department of Emergency Medicine, Covenant Hospital, Saginaw Michigan
Coauthor(s): Edward C Jauch, MD, Faculty, Greater Cincinnati/Northern Kentucky Stroke Team, Associate Director of Research, Department of Emergency Medicine, Assistant Professor, University of Cincinnati College of Medicine; Rhonda S Cadena, MD, Staff Physician, Department of Emergency Medicine, University of Cincinnati College of Medicine
Contributor Information and Disclosures

Updated: Jul 9, 2007

Introduction

Background

Inhalants are volatile substances producing vapors that can be taken intentionally via the pulmonary route to produce a mind-altering "buzz" or high. Inhalants are dangerous and their use represents a vast abuse problem in the United States and abroad. At greatest risk of harm from these drugs are adolescents in their early teenage years. Although most inhalants are central nervous system (CNS) depressants, they do cause adverse medical effects on almost every organ system in the body. Both short- and long-term toxic effects occur. Short-term effects include diplopia, impaired memory, slurred speech, seizure, or even death from cardiac arrhythmias. Long-term chronic effects include permanent ataxias or sensorimotor peripheral neuropathies, blindness, cognitive impairment, and renal toxicity.

Historically, the use of inhaled volatile chemicals in religious ceremonies dates back to antiquity. Recreational use of inhalants in the United States increased in the 1950s and is now widespread amongst adolescents. Inhalants are frequently the first consciousness-altering substance abused by children. More than 1000 abusable products containing volatile chemicals are legal and readily obtained. These include solvents, aerosols, adhesives, fuels, dry-cleaning agents, tape-head cleaners, cigarette lighters, permanent markers, correction fluid, propellants used in whipped cream, deodorants, paints, and cooking sprays. These products are readily available, easy to purchase, not illegal to possess, easy to conceal, and can be found in every household or garage. They offer a quick-onset high of brief duration, lessening the chances of getting caught. Prosecution of offenders tends to be minimal, and few states have laws prohibiting inhalant abuse.

Although several categories of inhalants exist, the most commonly abused inhalants are the aliphatic hydrocarbons, alkyl halides, nitrites, and aromatic hydrocarbons.

• Aliphatic hydrocarbons are volatile fuels such as propane, butane (cigarette lighter fluid), and gasoline.
• Alkyl halides, 1,1,1-trichloroethane or trichloroethylene, are found in cleaning fluids, typewriter correction fluid, and compressed air for cleaning electronics.
• Nitrites, such as amyl nitrites found in room air fresheners, are used by some adolescents and homosexual men to enhance sexual activity.
• Aromatic hydrocarbons, such as toluene and xylene, are the most commonly used inhalants of abuse. This is because they cause an intense euphoric rush when inhaled. They are found in markers, adhesive cements, model glues, paint thinners, and spray paints, with the highest concentration found in gold and silver spray paint.

Terminology

"Sniffing" - Inhaling vapors from an open container

"Huffing" - Soaking a rag or sock with substance and placing it over the mouth and nose

"Bagging" - Spraying or pouring the substance into a paper or plastic bag and inhaling the vapors by placing the bag over the face or over the head

"Dusting" - Inhaling vapors directly from electronic equipment cleaning aerosols

Pathophysiology

Inhalants are highly lipid soluble; they easily cross both alveolar membranes in the lungs and then the blood-brain barrier to reach high concentrations in the brain. Inhalation avoids first-pass hepatic metabolism so the onset is fast. The onset of effect is seen in a few seconds to a few minutes, with peak plasma concentration 15-30 minutes after inhalation. The inhaled concentration depends on the mode of administration. Sniffing offers the lowest concentration, followed by huffing, with bagging offering the highest concentration. With a few exceptions, elimination occurs primarily through the lungs, with many inhaled compounds eliminated unchanged by exhalation. Some of the inhalants, including alkyl nitrites, aromatics, and methylene chloride, undergo significant hepatic metabolism that can produce damaging free nitrites and toxic carbon monoxide as byproducts.

The mechanism of inhalant's effects is not fully understood. Some authors propose the action is similar to the action of ethanol. They suggest the action is to stimulate the gamma-aminobutyric acid (GABA) and the glycine a1 receptors, as well as inhibit the N-methyl-D-aspartate (NMDA) receptor, leading to inhibition in the CNS. Other proposed mechanisms include fluidization or solubility changes of neuronal cell membranes. Pharmacologic properties of all inhalants vary, contributing to different gas potentials, solubility in the blood, and elimination, leading to slight differences in their actions, intoxicating effects, and abuse potential. More research is needed to better define these mechanisms of action.

Frequency

United States

Inhalant abuse is common among adolescents; more than 2 million children aged 12-17 years are reported to have used inhalants at least once in their lifetime and use continues to climb in the younger age groups. The most recent report by Monitoring the Future Study (MTF), a survey funded by the National Institute of Drug Abuse (NIDA), that monitors drug abuse in adolescents from grades 8-12, reported an increase in the annual base of inhalants from 2002-2005 in 8th graders (from 7.7-9.5%), while the annual abuse for 10th and 12th graders remained stable at 6% and 5% respectively.

In the United States, inhalant abuse usually precedes tobacco and alcohol experimentation. Although most teenagers outgrow inhalant use, many progress to "harder" drugs, including marijuana and cocaine.

Inhalant abuse is less common (though not rare) in adults. Those especially at risk are doctors, nurses, factory workers, dentists, shoemakers, hair stylists, painters, and dry-cleaning workers; all with ready access to chemicals or anesthetics. Besides the chemical high offered by these drugs, some adults seek an additional aphrodisiac effect reported to occur with some of these chemicals. Nitrite inhalant use, for example, is prevalent amongst homosexual males. In one survey, 69% of homosexual males sampled had experience with nitrite inhalants, though the AIDS crisis has likely decreased these numbers.

International

Across the globe, inhalant abuse is rampant among children in both developed areas and developing areas. Countries with particularly high abuse rates include Great Britain, Singapore, and Brazil.

Mortality/Morbidity

The debilitating and potentially lethal effects of inhalants can occur even with the first use. Although inhalant deaths are underreported in the United States, the 2005 report of the National Inhalant Prevention Coalition (NIPC) reports 100-125 deaths annually as a result of inhalant abuse.¹ Asphyxiation can result from the displacement of oxygen in the lungs by prolonged or repeated inhalations. Suffocation can occur if a plastic bag is placed over the head when inhaling the fumes and the user becomes unconscious. Death can also occur because of complications of the intoxication such as choking on aspirated gastric contents, fire-related injuries from inhalant combustion, or fatal injuries suffered as a result of high-risk behaviors.

A common cause of death in inhalant abusers is called sudden sniffing death syndrome (SSDS). Although the exact mechanism is unknown, the inhalant is believed to sensitize the myocardium to circulating catecholamines. This causes an exaggerated response to epinephrine released during a sudden alarm or increased physical activity, leading to a fatal arrhythmia. Death usually occurs while the user is running, attempting to flee, experiencing a particularly frightful hallucination, or during sexual activity. An in vitro study by Cruz et al, demonstrated that toluene inhibition of voltage-gated cardiac sodium channels may be the possible mechanism of increased sensitivity.²² The co-ingestion of a sympathomimetic agent, such as cocaine, may increase the risk of the fatal arrhythmia. Sudden sniffing death is particularly associated with the abuse of toluene, butyl nitrate, butane, propane, and chemicals in aerosols.

Inhalant abuse is associated with significant morbidity and mortality. Bowen and colleagues studied inhalant-related deaths in Virginia from 1987-1996 and documented the dangers of these drugs. In the 10-year study period, 39 deaths resulting from acute voluntary exposure were reported, an average of 4 deaths per year. These drugs have no social or geographic boundaries, but children abusing inhalants tend to be of lower socioeconomic class, male gender, suffering delinquency, and from broken families.

Race

Inhalant abuse rates are higher in white, Hispanic, and Native American children.

Sex

Abuse tends to be more prevalent in males, but over the past 2 decades, abuse has increased in females.

Age

The typical abusers of inhalants are aged 10-15 years, although use in children as young as 7 and 8 years has been reported. The average age of initial use of these chemicals was around 10 years in one study, which preceded the average initiation into cigarettes by 1.5 years and narcotics by almost 4 years. Experimentation typically occurs in late childhood and is short lived. Chronic abuse is usually seen in older adolescents, although it has also been reported as late as the fifth and sixth decades of life.

Clinical

History

In the emergency department setting, the acutely intoxicated patient most frequently arrives by ambulance, with the police, or with friends and family. In obtaining the history, ask prehospital personnel about empty chemical or spray containers found at the scene. Ask about rags, cloths, or strange smells about the patient. Also inquire about the possibility of co-ingestion, suggested by pill bottles found at the scene.

As inhalant abuse is typically a group activity, elicit a history from friends or family who were present. Discuss with parents changes in behavior or school performance, new groups of friends, or new types of social activities that might suggest use of these drugs. Strongly suspect inhalant abuse in the setting of sudden collapse during adolescent group activities. Occult trauma is common in these patients, as lost inhibition leads to dangerous activities during intoxication.

The clinical history can be broken down into acute intoxication, chronic inhalation use, and withdrawal syndrome.

• Acute intoxication - most symptoms resolve within 2 hours
• • In acute intoxication, neurologic, cardiac, and pulmonary symptoms predominate.
  • Acute neurologic symptoms resemble alcohol intoxication and include euphoria, slurred speech, ataxia, dizziness, diplopia, confusion, and CNS depression. Potential acute effects include headache, vertigo, auditory and visual hallucinations, seizures, stupor, and coma
  • Acute cardiac effects include heart palpitations and tachycardia.
  • Pulmonary symptoms are due to asphyxiation and direct lung damage, producing pneumonitis. In the history, inquire about dyspnea, wheezing, and coughing. Cyanosis of the extremities can develop secondary to methemoglobinemia associated with alkyl nitrite abuse and can produce skin discoloration and cyanosis.
• Chronic abuse
• • In chronic inhalant abuse, irreversible CNS complications can occur, including cerebral cortex atrophy, cerebellar degeneration, peripheral neuropathy, and neuropsychosis, leading to cognitive function decline, dementia, gait disturbances, and loss of coordination. Neurologic signs and symptoms to elicit include peripheral neuropathies (typically stocking-glove distribution), seizures, paresthesias, ataxia, weakness, confusion, memory loss, and delusions.
  • Long-term exposure can also lead to cranial nerve damage, causing optic neuropathy and blindness, tinnitus, and sensorineural hearing loss.
  • Chronic renal injury from inhalant use includes type I renal tubular acidosis, urinary calculi, and glomerulonephritis and typically produces flank pain, clouding of the urine, and decreased urine production with azotemia.
  • Toxic hepatitis and liver failure has also been seen in chronic users of chlorinated hydrocarbons by damage of toxic metabolites. The history may reveal symptoms of right upper quadrant abdominal pain, nausea, vomiting, low-grade fever, fatigue, or jaundice.
  • Rhabdomyolysis and severe muscle weakness, similar to Guillain-Barr é syndrome , has also been reported.
• Withdrawal symptoms
  
  
  • These symptoms include tremors, irritability, anxiety, insomnia, delirium, tingling sensations, seizures, and muscle cramps. If tolerance has developed, complaints of chills, headache, muscle cramps, and vague abdominal pain should be elicited.
  • These patients present with sleep disturbance, tremor, nausea, irritability, and abdominal pain. Withdrawal symptoms are worse during the period 2-5 days after inhalant cessation. Patients may present with symptoms similar to delirium tremens.

If the inhalant abuse patient is pregnant, special considerations need to be taken. Although well-controlled prospective data have not been collected, current information suggests adverse effects of maternal inhalant abuse on the fetus. Because of high lipophilicity, these solvents readily cross the placenta and cause fetal anomalies, including microcephaly, narrow bifrontal diameter, hypoplastic midface, and blunt fingertips. This syndrome closely resembles the physical findings of fetal alcohol syndrome. Increased rates of spontaneous abortion and fetal malformations have been reported, as have growth retardation and deficits in both speech and cognitive skills.

Physical

• Skin
• • Paint or stains on the face, hands, or clothing (see Media files 1-2)
  • "Huffer rash" - Erythematous "frost bite" eruption on the face and oral mucosa caused by severe drying and cracking of the skin and resultant bacterial infection
  • Thermal or chemical burns on the face or hands
  • Conjunctival injection
  • Jaundice (with chronic hepatic injury)
  • Cyanosis (with methemoglobinemia)
• Respiratory
• • Chemical odor in the breath
  • Wheezing, rhonchi, or rales
  • Oral or airway burns
  • Rhinitis
  • Respiratory distress with aspiration of gastric contents
• Neurologic/psychiatric
• • Slurred speech
  • Diplopia
  • Blurred vision
  • Nystagmus
  • Euphoria
  • Psychomotor retardation
  • Disorientation
  • Sense of invulnerability
  • Distortion of space and time
  • Auditory or visual hallucinations with paranoid ideations
  • Photophobia
  • Weakness
  • Impaired memory
  • Peripheral neuropathy (typically stocking-glove distribution)
  • Seizures
  • Agitated coma (unconsciousness with tremors, restlessness, and hyperreflexia)
• Cardiac
• • Arrhythmias, including premature ventricular contractions (PVCs) or supraventricular tachycardia (SVT)
  • Tachycardia or bradycardia
  • Hypotension
• Gastrointestinal tract
  
  
  • Nausea and vomiting
  • Diarrhea
  • Abdominal pain (suspect hepatic injury if the pain is in the right upper quadrant, especially in a chronic abuser)
  • Flank pain (suspect renal injury in chronic abusers)

Causes

The cause of inhalational injury is the use of inhalation agents. As described earlier, this use is affected by many factors such as age and socioeconomic status (see Frequency and Mortality/Morbidity).

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