Hydrocarbon Toxicity

The toxicity of hydrocarbons is directly related to their physical properties, specifically the viscosity, volatility, surface tension, and chemical activity of the side chains. The viscosity is a measure of resistance to flow and is measured in Saybolt Seconds Universal (SSU). Substances with a lower viscosity (SSU < 60, eg, turpentine, gasoline, naphtha) are associated with a higher chance of aspiration. The surface tension is a cohesive force created by van der Waals forces between molecules and is a measure of a liquid's ability to "creep." Like the viscosity, the surface tension is also inversely related to aspiration risk. The viscosity is the single most important chemical property associated with the aspiration risk. ^[3]

Volatility is the tendency for a liquid to change phases and become a gas. Hydrocarbons with a high volatility can vaporize and displace oxygen, which can lead to a transient state of hypoxia. Not surprisingly, the degree of volatility is directly related to the risk of aspiration. The amount of hydrocarbon ingested has not consistently been linked to the degree of aspiration and hence pulmonary toxicity.

The exact mechanism of action for the volatile substances on the whole is unknown. Two theories have been postulated for the mechanism of action of inhalants. One hypothesis is that the volatile solvents produce a generalized slowing of axonal ion-channel transport by altering the membranes, similar to anesthetic gasses. ^[4] The second theory suggests that potentiation of the gamma-aminobutyric acid (GABA) receptors occurs (GABA being a major inhibitory neurotransmitter in the brain); a cross-tolerance between 1,1,1-trichloroethane, toluene, ethanol, barbiturates, and benzodiazepines is noted. ^[5]

Toxicity from hydrocarbon exposure can be thought of as different syndromes, depending on which organ system is predominately involved. Organ systems that can be affected by hydrocarbons include the pulmonary, neurologic, cardiac, gastrointestinal, hepatic, renal, dermatologic, and hematologic systems. The pulmonary system is the most commonly involved system. ^[6]

Pulmonary

Pulmonary complications, especially aspiration, are the most frequently reported adverse effect of hydrocarbon exposure. While most aliphatic hydrocarbons have little GI absorption, aspiration frequently occurs, either initially or in a semidelayed fashion as the patient coughs or vomits, thereby resulting in pulmonary effects. Once aspirated, the hydrocarbons can create a severe pneumonitis.

Hydrocarbon pneumonitis results from a direct toxic affect by the hydrocarbon on the lung parenchyma. The type II pneumocytes are most affected, resulting in decreased surfactant production. This decrease in surfactant results in alveolar collapse, ventilation-perfusion mismatch, and hypoxemia. Hemorrhagic alveolitis can subsequently occur, which peaks 3 days after ingestion. ^[7] The end result of hydrocarbon aspiration is interstitial inflammation, intra-alveolar hemorrhage and edema, hyperemia, bronchial necrosis, and vascular necrosis. Rare pulmonary complications include the development of pneumothorax, pneumatocele, or bronchopleural fistula. ^[8]

Nervous system

Central nervous system (CNS) toxicity can result from several mechanisms, including direct injury to the brain or indirectly as a result of severe hypoxia or simple asphyxiation.

Many of the hydrocarbons that affect the CNS can directly make their way across the blood-brain barrier because certain hydrocarbons are highly lipophilic. In addition, for individuals who are huffing or bagging, the act of rebreathing can result in hypercarbia, which can contribute to a decreased level of arousal.

As solvent abuse becomes chronic, damage to the CNS becomes irreversible, with changes occurring in the cerebellar and cerebral white matter, including demyelination and gliosis. ^[9]  In addition, prolonged exposure to certain hydrocarbons (eg, n-hexane or methyl-n-butyl ketone [MnBK]) can result in peripheral neuropathy, blurred vision, sensory impairment, muscle atrophy, and parkinsonism. ^[10]

Cardiovascular

Exposure to hydrocarbons can result in cardiotoxicity. ^[11]  Most importantly, the myocardium becomes sensitized to the effects of catecholamines, which can predispose the patient to tachydysrhythmias, which can result in syncope or sudden death.

In addition, ventricular fibrillation, myocardial infarction, and multifocal premature ventricular contractions have been observed.

Gastrointestinal

Many of the hydrocarbons create a burning sensation because they are irritating to the GI mucosa. Vomiting has been reported in up to one third of all hydrocarbon exposures.

Hepatic  ^[12]

The chlorinated hydrocarbons, in particular carbon tetrachloride, are hepatotoxic. Usually, the hepatotoxicity results after the hydrocarbon undergoes phase I metabolism, thereby inducing free radical formation. These free radicals subsequently bond with hepatic macromolecules and ultimately cause lipid peroxidation. This metabolite creates a covalent bond with the hepatic macromolecules, thereby initiating lipid peroxidation.

The common histopathologic pattern is centrilobular (zone III) necrosis.

Liver function test results can be abnormal within 24 hours after ingestion, and clinically apparent jaundice can occur within 48-96 hours.

Methylene chloride, a hydrocarbon commonly found in paint remover, is metabolized via the P450 mixed function oxidase system in the liver to carbon monoxide (CO). Unlike with other cases of CO exposure, with methylene chloride, CO formation can continue for a prolonged period of time.

Renal

Chronic exposure to toluene, an aromatic hydrocarbon, can result in a distal renal tubular acidosis and present with an anion gap acidosis (see the Anion Gap calculator). A patient may have chronic exposure either via an occupational environment or by repeated recreational inhalation.

Hematologic

Prolonged exposure to certain aromatic hydrocarbons (especially benzene) can lead to an increased risk of aplastic anemia, multiple myeloma, and acute myelogenous leukemia. In addition, hemolysis has been reported following the acute ingestion of various types of hydrocarbons. ^[13]

Fetal

Many solvents, particularly toluene, are lipophilic and readily cross the placenta, resulting in characteristic fetal anomalies that include microcephaly, narrow bifrontal diameter, short palpebral fissures, hypoplastic midface, wide nasal bridge, abnormal palmar creases, and blunt fingertips. The syndrome of toluene embryopathy closely resembles the phenotypic features found in fetal alcohol syndrome. ^{[14, 15]}

A literature review by Kounlavong et al reported that fetal growth restriction and preterm delivery (< 37 weeks) were among the most frequent fetal outcomes linked to inhalant use by pregnant persons. Withdrawal symptoms, including jitteriness, trouble feeding, and dystonia, were found in affected neonates, with subsequent demonstration of developmental delays (such as cognitive and speech impairments) and postnatal growth restriction (including microcephaly). ^[16]

Hydrocarbon exposure can be divided into the four broad categories summarized below.

Nonintentional, nonoccupational exposure

Accidental ingestions are the most frequent type and commonly involve young children tasting a hydrocarbon. Typically, children do not drink large quantities, as hydrocarbons generally taste bad. Adults and older children occasionally consume a hydrocarbon if liquid is placed in an unlabeled can or bottle resulting in accidental ingestion.

Recreational exposure

Inhaling of hydrocarbons or other volatile solvents for the purpose of producing a transient state of euphoria is becoming more common. This pattern of use is most common in junior-high– and high-school–aged children.

Occupational exposure

This type of exposure is most often industrial, where a worker has either a dermal exposure to the liquid or an inhalational exposure to the vapors.

Intentional exposure

This type of exposure usually involves consuming a large amount of the hydrocarbon as an oral ingestion during a suicide attempt.

According to the 2022 Annual Report of the National Poison Data System (NPDS) from America’s Poison Centers, hydrocarbons ranked 12th in nonpharmaceutical substance exposures, with 27,701 hydrocarbon exposures for the year. This included 18,066 exposures in adults over age 20 years. Nineteen fatalities in which hydrocarbon exposure was involved were reported, including three in adolescents aged 13-19 years. ^[17]  (However, poison control data are widely known to be an underestimate of the true incidence because of underreporting.)

Inhalant abuse is common among adolescents. It is estimated that approximately 20% of students in middle school and high school have abused volatile substances. ^[18]

Pulmonary, renal, gastrointestinal (GI), cardiac, and even neurologic dysfunction usually resolves with abstinence. Prolonged abuse increases the risk that residual organ dysfunction, particularly neurologic sequelae, will persist.

Patients who abuse solvent-inhalants are frequently abusers of other drugs and alcohol.

Hypocalcemia is frequently encountered during fluid and electrolyte repletion and may be severe enough to precipitate tetany or seizures.

Many abusers perform poorly in school, are chronically unemployed as adults, and commit criminal acts; therefore, efforts at early recognition and provision of long-term care with frequent monitoring are justified.

With acute intoxication, deaths due to asphyxiation from a plastic bag over the head or from aspiration of stomach contents are not unusual. Also, trauma-related injury and motor vehicle accidents have been reported, resulting from disinhibition and disorientation following inhalation.

Although mild ingestions are usually devoid of complications, the morbidity and mortality associated with such poisoning are primarily related to pulmonary aspiration. Subsequent complications—most importantly, secondary bacterial infections—can worsen the clinical condition.