Inhalation of volatile solvents can cause a brief euphoric intoxication. Symptoms include dizziness, drowsiness, slurred speech, unsteady gait, and irritability; delirium, hallucinations, seizures, asphyxia, arrhythmias, and cardiovascular collapse may occur. Diagnosis is with history and physical examination; monitor for complications with ECG. Treatment is with observation and sometimes benzodiazepines or esmolol. Chronic use can result in brain damage, lung damage, neuropathies, and liver damage.
Volatile solvents refers to liquids that rapidly vaporize at room temperature, generating "fumes." Examples include rubbing alcohol, paint thinner (methylene chloride), ether, chloroform, benzene, and glue. Toxicity from volatile solvents is commonly seen in workers and adolescents.
Workers may be exposed to volatile solvents depending on the nature of their job and the degree to which their work environment follows Occupational Health and Safety Association (OHSA) guidance or similar guidelines for ventilation, personal protective equipment, and exposure limits. Examples include industrial workers exposed to fumes from chemical solvents like ether and undertakers exposed to formaldehyde.
Adolescents typically ingest volatile solvents by placing a solvent-soaked rag in a bag or container that is held to the mouth and nose; the naturally volatilized vapors are then inhaled (huffing, sniffing). The central distinction between huffing and other methods, such as sniffing, insufflation ("snorting"), or inhalation, is that huffing involves rebreathing solvent from a closed bag. About 10% of adolescents in the United States intentionally inhale volatile solvents.
Street names for volatile solvents include Glue, Huff, and Laughing gas.
Nitrites, such as amyl, butyl, or isobutyl nitrite, are also a type of volatile solvent. Nitrites are often inhaled and are typically used by adults to enhance sexual pleasure. Nitrite-containing liquids may also be ingested with resultant symptoms.
Street names for nitrites include Poppers, Locker Room, and Rush.
Pathophysiology
Volatile solvents cause temporary central nervous system (CNS) stimulation followed by CNS depression. Some volatile solvents may contain methanol, like carburetor cleaning sprays.
Volatile solvents also excite the myocardium predisposing to tachydysrhythmias. The mechanism underlying this sensitization is not fully understood.
Toluene exposure causes distal renal tubular acidosis type 1 (RTA-1), which is characterized by a non-gap acidosis with elevated chloride and decreased potassium concentrations. The underlying mechanism is thought to be preventing proton back-diffusion in the distal collecting tubule.
Nitrates cause vasodilation by impairing nitric oxide synthesis.
Symptoms and Signs of Volatile Solvents
The acute effects of volatile anesthetics are neurological and cardiovascular.
Dizziness, drowsiness, slurred speech, and unsteady gait occur early. Impulsiveness, excitement, and irritability may occur. At higher exposures, illusions, hallucinations, and delusions develop. Users experience a euphoric, dreamy high, culminating in a short period of sleep. Delirium with confusion, psychomotor clumsiness, emotional lability, and impaired thinking develop. The intoxicated state may last from minutes to about 1 hour.
At recreational doses, nitrates also cause flushing from vasodilation and euphoria.
The acute signs of toxicity that require immediate intervention are asphyxia and cardiovascular collapse. Asphyxia may be due to depression of the central nervous system or failing to breathe in air with enough oxygen. In an enclosed space or container, volatile solvents and carbon dioxide will take up increasing portions of the air with each breath and exhalation. At higher doses, the 2 main toxicities are hypotension from profound vasodilation and methemoglobinemia. In those cases, 1 to 7 mg/kg of methylene blue is an effective antidote for both toxicities. The combination of nitrites with phosphodiesterase type II inhibitors can lead to profound hypotension.
Inhalant abuse during pregnancy can cause premature birth and fetal solvent syndrome, which has features like fetal alcohol syndrome.
Diagnosis of Volatile Solvent Use
History and physical examination
Sometimes urine testing
The definitive diagnosis of toxicity from a volatile solvent requires only a careful history and physical examination, identifying the agent and timing of symptoms with respect to the exposure. The clinical picture of a patient with syncope, a tachydysrhythmia, or seizures shortly after huffing, inhaling, or sniffing is sufficiently compelling.
Clinicians should identify the contents of the solvent whenever possible and discuss them with a medical toxicologist.
Some volatile solvent have unique toxicities. Methylene chloride (dichloromethane), a common ingredient in pain thinners, is metabolized to carbon monoxide beginning at about 12 hours after exposure. Methylene chloride is usually not metabolized into enough carbon monoxide to cause toxicity. Obtaining a carboxyhemoglobin concentration on every patient exposed to paint thinner is impractical. There is no consensus on which patients require testing. A reasonable approach is to test patients by co-oximetry 16 hours exposure if they show signs of encephalopathy or respiratory distress when they initially presented. These symptoms suggest a large exposure.
Detecting a carboxyhemoglobin saturation > 10% on co-oximetry should prompt the clinician to also evaluate for methanol toxicity by obtaining a methanol concentration. Methanol is another ingredient in many paint thinners. The metabolism of methanol leads to metabolic acidosis and retinal injury. The combination of methanol and carbon monoxide can be lethal without dialysis because they create a situation of acidemia and a reduced capacity for respiratory compensation. Many health care facilities cannot test for methanol in-house and rely on send-out tests and results are not available for days. If the COHb > 10% or there is unexplained metabolic acidosis, the clinician should obtain a methanol concentration. To estimate the methanol concentration if results will be delayed, the clinician should obtain an ethanol concentration, basic metabolic profile, and serum osmolarity to calculate the osmolar gap. The methanol concentration can be estimated by multiplying the osmolal gap by 32, the molecular weight of methanol in grams. Dialysis is needed for concentrations of methanol greater than 50 mg/dl (15.6 mmol/L) or for persistent acidosis or renal impairment. A medical toxicologist should be consulted in all but the simplest cases. .
Volatile solvents are not detected by routine drug screening tests. Some of them and their metabolites can be detected by gas chromatography of urine, or, less commonly, blood, at specialized laboratories. The metabolites of some volatile solvents can be detected in the urine. Urine tests confirm exposure but cannot be used to estimate the amount the patient was exposed to. For example, toluene is a metabolite of benzene. Detecting toluene in the urine suggests benzene exposure. Hippuric acid is a metabolite of toluene. Detecting hippuric acid in the urine suggests toluene exposure. . Hippuric acid is the main metabolite of toluene. Such testing may be helpful for forensic purposes or prompting a discussion about substance misuse. However, the relationship between these urinary concentrations and clinical presentation is not known. Positive results should be taken as illustrative of use but not definitive for a specific pattern of use.
Treatment of Volatile Solvent Use
Removing patient from the exposure
For seizures, benzodiazepines
For ventricular dysrhythmias, esmolol
Treatment of toxicity from volatile solvents is challenging and should involve consultation with a medical toxicologist when possible.
Preventing absorption
The first step is to remove the patient from the exposure, which is usually done by first responders.
Activated charcoal, whole bowel irrigation, and gastric lavage have no role in a exposure to substances in the gaseous state.
Enhancing excretion
No methods are known to enhance the excretion of volatile solvents. Due to their gaseous phase, they nearly instantly distribute to all body tissues.
Mitigating toxicity
To treat seizures, benzodiazepines should be used as for other xenobiotic-induced seizures.
A unique aspect of treatment is the use of esmolol to treat ventricular dysrhythmias after huffing volatile solvents, even when pulseless. Ventricular dysrhythmias ("sudden sniffing death") arise from volatile solvents because of myocardial sensitization. Beta-adrenergic agonists like norepinephrine or epinephrine worsen this state. Beta-adrenergic antagonists, like esmolol, improve it. Esmolol is preferred because it acts rapidly. There are no data on other beta-adrenergic antagonists or calcium channel blockers. If esmolol is not available, it is reasonable to try another cardioselective nodal blocking agent. There is no guidance on dosing for these alternate agents. Consult a medical toxicologist.
Chronic Use of Volatile Solvents
Complications
Repeated habitual use may irritate the skin around the mouth and nose, leading to "huffer's eczema", which is really a contact dermatitis. Complications of chronic use may result from effects of the solvent or of other ingredients such as lead in gasoline or methanol in paint thinner. Carbon tetrachloride may cause liver and kidney failure. Benzene may cause acute myeloid leukemia. Toluene may cause degeneration of central nervous system white matter ("solvent encephalopathy").
Chronic solvent encephalopathy refers to sensorimotor polyneuropathies and neurobehavioral deficits associated with habitual use. An MRI may show periventricular leukoencephalopathy, but this finding is neither sensitive nor specific. Unfortunately, these deficits may persist even after the patient stops using volatile solvents.
Tolerance and dependence
Tolerance and psychological dependence develop with repeated use. A withdrawal syndrome has not been described.
Misuse of solvents begins most often in adolescence. Most stop when they enter adulthood. Treatment of solvent-dependent adolescents is difficult. Relapse is frequent. The patient's primary clinician should identify the biopsychosocial triggers leading to use of these substances. Attempts to improve patients’ social skills and status in family, school, and society may help. For symptoms and treatment of poisoning with specific solvents, see table .
Key Points
Volatile solvents are inhaled (intentionally or accidentally) and cause brief euphoria.
Symptoms include dizziness, drowsiness, slurred speech, unsteady gait, and irritability; delirium, hallucinations, seizures, asphyxia, arrhythmias, and cardiovascular collapse may occur.
Patients using high doses may develop vasodilation or methemoglobinemia.
Diagnosis is with history and examination.
Treatment is usually observation, but benzodiazepines may be deeded for agitation. Agitation and seizures are treated with benzodiazepines and ventricular tachycardia with esmolol.
Chronic use may result in brain damage, lung damage, neuropathies, and liver damage.
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