Inhalant misuse in children and adolescents

INTRODUCTION — The epidemiology, clinical manifestations, toxic effects, and management of inhalant misuse will be reviewed here. Substances that are nasally insufflated (eg, snorted cocaine) or smoked (eg, tobacco, marijuana, cocaine, and opiates) are discussed separately.

●(See "Cocaine: Acute intoxication".)

●(See "Cannabis use and disorder: Epidemiology, pharmacology, comorbidities, and adverse effects".)

●(See "Cannabis use disorder: Clinical features, screening, diagnosis, and treatment".)

●(See "Opioid intoxication in children and adolescents".)

EPIDEMIOLOGY — In the United States, inhalant misuse is common with approximately 11 percent of high school students reporting having used inhalants in their lifetime [1]. An estimated 2 percent of United States adolescents (ages 12 to 17) have used an inhalant in the prior year [2]. Unlike nearly all other classes of drugs, their use is most common among younger adolescents with use peaking between seventh and ninth grade [3].

The incidence of inhalant misuse in children 12 to 18 years old has fluctuated over the past 25 years. Incidence of use tripled between 1983 and 1993 [4], peaking in 1995, and then showed a steady decline until 2002. The incidence stayed relatively unchanged but then decreased significantly starting in 2010 to 2013, coinciding with the phase-out of refrigerants that contain hydrochlorofluorocarbons by the United States Environmental Protection Agency [3,5,6]. In the past, Native American children and those residing in rural areas were at higher risk for inhalant misuse [7-11]. However, rates of misuse have fallen steadily in these groups and are now at levels comparable to the general population [2]. Education on prevention and treatment is thought to be responsible for this trend [12,13].

Similar to national survey data, adolescent exposures reported to United States poison control centers have declined from 73 cases per million in 1993 to 33, 26, and 5 cases per million in 2003, 2010, and 2021, respectively [6,10]. Among all age groups, there were 257 deaths out of 25,022 exposures between 2001 and 2021 [6]. Males comprised 73 percent of all cases reported to poison control centers. In the United Kingdom, deaths due to volatile substance misuse peaked in the early 1990s and subsequently have declined after education campaigns and laws prohibiting cigarette lighter refills went into effect [14].

Since 2000, recreational nitrous oxide (N₂O) use has increased [15]. In the United States, lifetime prevalence of N₂O use in individuals 12 years and older is between 4 and 5 percent [16,17]. A 2020 survey of 16 to 24 year olds in England and Wales found that nine percent had used N₂O in the prior year, which was second only to cannabis [18]. The terms "chroming" and "Whiptok" on social media refer to its misuse [19].

Numerous studies have demonstrated significant mental health and behavioral comorbidities among patients who misuse inhalants. They are more likely to have an episode of major depression [20,21], suicidality [22], conduct disorder [20], and are at an increased risk for future substance use disorders [23].

MECHANISM OF ACTION — Volatile hydrocarbons and nitrous oxide have a similar mechanism of action. Like ethanol and other inhalational anesthetic agents, they are highly lipid soluble. They are rapidly absorbed across the pulmonary bed into the bloodstream and are distributed throughout the body [24]. Neurons, which have high lipid content, are particularly susceptible to the solvent properties of these compounds [25,26].

These inhalants act as central nervous system (CNS) depressants. CNS depression is thought to be mediated by alteration of neuronal membrane function at glutamate or gamma amino butyric acid receptors [27-29].

These inhalants produce an effect within seconds that typically lasts 15 to 30 minutes. There have been rare cases of prolonged symptoms when large quantities have been inhaled [30]. Initial euphoria is followed by lethargy. Judgment and coordination are impaired [31]. Intoxication is maintained through repeated use. Symptoms of tolerance to the effects of inhalants and physiologic withdrawal have been described [32].

Nitrous oxide (N₂O) interferes with vitamin B12, folate, and methionine synthesis and metabolism. Vitamin B12 is an essential cofactor for methionine synthase. N₂O converts vitamin B12 from the active monovalent form to the inactive bivalent form, thereby causing an irreversible inhibition of methionine synthase. Methionine synthase is a ubiquitous cytosolic enzyme that plays a crucial role in the generation of methyl groups for the synthesis of DNA, RNA, tetrahydrofolate, methionine, and myelin, among other products. Inhibition of methionine synthase, which regenerates methionine from homocysteine, can increase homocysteine plasma concentrations [33]. N₂O can precipitate a functional vitamin B12 deficiency when used on a chronic basis or acutely in patients with marginal stores of vitamin B12 such as the elderly or malnourished [34].

Nitrites produce their pleasurable effects by intense vasodilation which produces a sensation of heat and warmth. Absorption is rapid across the pulmonary bed leading to onset of hypotension and reflex tachycardia within seconds of inhalation. Effects are brief, lasting less than five minutes. Nitrites are also used to enhance sexual pleasure by prolonging penile erection and promoting anal sphincter relaxation.

TECHNIQUES (SNIFFING, HUFFING, OR BAGGING) — In the United States, frequently misused inhalants include volatile substances (eg, glue, shoe polish, gasoline, paint thinners, lighter fluid, correction fluids, felt-tip markers), aerosols (eg, spray paint, computer and electronic duster sprays, deodorant and hair spray), gases (eg, nitrous oxide/"whippets", butane, propane), and nitrites ("poppers," room odorizers/"rush") [2,10]. Each of these substances may contain more than one toxic compound (table 1) [32].

Inhalants may be sniffed directly from a container or sprayed directly on to a heated surface to enhance vaporization ("sniffing") [35]. Volatile liquid substances also may be inhaled from a saturated cloth that is held under the nose or near the mouth ("huffing"), or from a bag that is placed over the mouth, nose, or head ("bagging"). The risk of asphyxia is increased with bagging because the partial pressure of hydrocarbon displaces oxygen in the alveoli. The possibility of a suicide attempt should be considered in an individual who "bags" inhalants, particularly when the bag is placed over the head [36]. The concentration of the inhaled substance increases from sniffing, to huffing, to bagging.

Nitrous oxide is misused most commonly as "whippets". These are small, cylindrical metal bulbs with a pierceable end that contains compressed nitrous oxide, which are meant for use as a propellant for whipped cream makers. When misused, the end is pierced with a "cracker" and the escaping gas is captured in a balloon and then inhaled. Nitrous oxide can also be sniffed from whipped cream canisters.

The desired effects of inhalant use include euphoria, lightheadedness, and a general state of intoxication similar to that produced by alcohol or marijuana. The effects usually last for only 15 to 30 minutes, but can be sustained by continuous or repeated use [37].

RECOGNITION OF INHALANT MISUSE — Inhalant misuse frequently goes undetected. Clues to inhalant misuse include chemical odors on the breath, skin, or clothes, and empty solvent containers or bags, rags, or gauze in the child's possession or trash [36]. "Glue-sniffer's rash" is an eczematoid dermatitis with erythema, inflammatory changes, and pruritus that occurs in the perioral area and extends to the midface. It is caused by the drying effects of hydrocarbons [38]. Symptoms and signs of inhalant use are listed in the table (table 2).

TOXICITY AND CLINICAL FINDINGS BY AGENT — Although the vast majority of children who misuse volatile inhalant substances do not seek or require medical attention, inhalant intoxication is potentially life-threatening. Death may result from asphyxia, suffocation, choking on vomitus, careless or dangerous behavior in potentially dangerous settings, and sudden sniffing death [39] seen with hydrocarbon use, especially halogenated hydrocarbons.

Hydrocarbons — Household products that are recreationally inhaled typically contain a mixture of hydrocarbons. They are categorized by structure: aliphatic, aromatic, and halogenated. (See "Acute hydrocarbon exposure: Clinical toxicity, evaluation, and diagnosis".)

Aliphatic compounds are straight-chain compounds and include butane, propane, kerosene, and mineral seal oil. Gasoline is a mixture of aliphatic hydrocarbons that also may contain other substances, such as xylene, toluene, benzene, naphthalene, or lead [24,40].

Aromatic hydrocarbons are cyclic compounds containing a benzene ring and are used as industrial solvents; benzene, toluene, and xylene are encountered most commonly. Toluene is found in a large number of household products including glues, adhesives, acrylic paints, paint thinners, and automotive products [24].

Halogenated hydrocarbons include fluorinated hydrocarbons (freons and propellants such as 1,2-difluoroethane) and chlorinated hydrocarbons (carbon tetrachloride, trichloroethylene, trichloroethane). They are used as solvents, degreasers, and spot removers, and in the dry cleaning industry. Freons are widely used as refrigerants, propellants, and in fire extinguishers [41-43].

The most important toxicities are cardiac and neurological, although hydrocarbons are toxic to essentially all body systems. Certain agents are more closely associated with a particular toxicity.

CNS effects — Acute CNS effects include slurred speech, ataxia, disorientation, headache, hallucinations, agitation, violent behavior, and seizures [4,44-47]. Generalized CNS depression may involve the respiratory centers of the brain, rarely causing respiratory arrest and death [48]. Toluene intoxication can cause temporary or progressive cerebellar dysfunction and cranial neuropathies [4,32].

The long-term CNS effects are equally worrisome and include neurocognitive impairment, cerebellar dysfunction, and peripheral neuropathy [36,47,49]. The neurologic findings may be related to loss of brain mass or abnormal perfusion. Computed tomography (CT) and magnetic resonance imaging (MRI) of inhalant users demonstrates loss of brain mass and degeneration of white matter (also called "toxic leukoencephalopathy"), respectively [50-53]. Single photon emission computed tomography (SPECT) in long-term inhalant users demonstrates abnormal perfusion [54].

Chronic inhalation of gasoline vapors can lead to persistent peripheral neuropathy and myopathy with myoglobinuria and creatine kinase elevation [55-58]. In addition, Parkinsonism can be caused by octane-enhancing additives [59], and lead poisoning with encephalopathy may occur if lead-containing gasoline is inhaled [60]. (See "Childhood lead poisoning: Clinical manifestations and diagnosis".)

Cardiovascular effects — Arrhythmias, myocarditis, or myocardial infarction may rarely occur with acute or chronic use [7,47,61]. Chronic heavy use of toluene has been reported to result in a statistically significant increase in QT dispersal, a marker for sudden death in a variety of clinical conditions [62].

"Sudden sniffing death" where a patient has cardiovascular collapse associated with inhalation of volatile compound has been reported with all classes of hydrocarbon, but is most commonly seen in children who inhale halogenated hydrocarbons [39,47,63]. Although a rare event, it is unpredictable and can occur in first time users. Commonly, it follows exertion or masturbation, both of which lead to increased catecholamine release [39,64]. It is thought to be due to sensitization of the myocardium to catecholamines that is possibly accentuated by hypoxia associated with inhalant misuse [32,38,39,48]. The cellular basis of this cardiac "sensitization" is uncertain but may relate to inhibition of sodium, calcium, and potassium channels, which results in an increase in QT duration and dispersion, and thus, susceptibility to catecholamine-induced delayed after-depolarizations and ventricular dysrhythmias [47,65]. In addition, sensitization of the myocardium to catecholamines may be explained by slowing of electrical conduction through membrane gap junctions due to dephosphorylation of connexin-43 by a combination of epinephrine and hydrocarbons [66].

Other effects

●Pulmonary effects – Hypoxia may result from displacement of oxygen in the alveoli, particularly with butane, isobutane, propane, and nitrous oxide [44], or suffocation when the patient huffs using a plastic bag. Pneumonitis with surfactant dysfunction, bronchospasm, or noncardiogenic or hemorrhagic pulmonary edema may occur [38,41,61,67]. Exposure to fluorocarbon may cause a reactive airway syndrome similar to asthma [68]. Pneumothorax may occur if gas is inhaled directly from a pressurized tank [36]. (See "Spontaneous pneumothorax in children".)

●Gastrointestinal effects – The gastrointestinal effects of inhalant use include nausea, vomiting, and abdominal cramps [44,61]. Anorexia and loss of weight may occur with chronic use [36]. Chlorinated solvents such as trichloroethylene and 1,1,1-trichloroethane are hepatotoxic [69].

●Renal effects – Volatile substance use may cause metabolic acidosis, urinary calculi, and glomerulonephritis [22,29,44,70]. Toluene, in particular, causes metabolic acidosis with profound potassium and phosphate wasting [47,71,72]. (See "Causes of hypokalemia in adults", section on 'Nonreabsorbable anions' and "The delta anion gap/delta HCO3 ratio in patients with a high anion gap metabolic acidosis", section on 'D-lactic acidosis and toluene inhalation'.)

●Hematologic effects – Inhalant misuse, particularly chronic exposure to benzene, may cause aplastic anemia and malignancy (eg, leukemia, lymphoma, multiple myeloma) [36,69,73-75]. (See "Acute myeloid leukemia: Pathogenesis", section on 'Chemical exposure'.)

Inhalation of methylene chloride (dichloromethane), which is metabolized to carbon monoxide, can result in a clinically important carbon monoxide exposure with elevated carboxyhemoglobin levels [76]. (See "Carbon monoxide poisoning", section on 'Epidemiology'.)

●Dermatologic effects – "Glue-sniffer's rash" is an eczematoid dermatitis with erythema, inflammatory changes, and pruritus that occurs in the perioral area and extends to the midface. It is caused by the drying effects of hydrocarbons [38,47]. Burns may occur when a flammable inhalant ignites.

●Musculoskeletal effects – Heavy toluene misuse is associated with generalized muscular weakness (often to the point of quadriparesis) and is typically accompanied by metabolic acidosis, profound hypokalemia, hypophosphatemia, rhabdomyolysis, and elevated creatine kinase. These metabolic abnormalities are caused primarily by the conversion of toluene to hippuric acid, with the subsequent rapid excretion of hippurate in the urine [77]. (See "The delta anion gap/delta HCO3 ratio in patients with a high anion gap metabolic acidosis", section on 'D-lactic acidosis and toluene inhalation'.)

●Pregnancy and postnatal effects – Inhalant use during pregnancy may increase the risk of spontaneous abortion, premature delivery, or fetal malformation [78-81]. Toluene, in particular, is associated with oral clefts, micrognathia, microcephaly, growth deficiency, and developmental delay [82]. Infants born to mothers who used inhalants during pregnancy may have symptoms of withdrawal [83].

●Miscellaneous – Trauma can result from falls, drowning, or motor vehicle accidents during the period of intoxication [84,85].

Nitrous oxide — Nitrous oxide (N₂O) is used as a propellant in canisters of whipped cream, as a power booster in automobiles and motorcycles, and as a sedative/amnestic agent for painful medical and dental procedures. It usually is inhaled from a balloon [31]. Neurologic, hematologic, and reproductive toxicity may result from exposure to N₂O.

●Neurologic effects – Neurologic toxicity is well documented in patients who misuse N₂O, and due to its effects on vitamin B12. Neurological findings include sensorimotor polyneuropathy [37,86-88], ataxia [34,87,89], and psychosis [89,90]. The clinical effects are commonly from a myelopathy involving the cervical spine similar to the subacute combined degeneration syndrome associated with pernicious anemia [91-95]. Neurotoxicity is potentially reversible with vitamin B12 (cyanocobalamin) supplementation and abstinence from N₂O [95].

●Hematologic effects – N₂O misuse or use as an anesthetic agent causes megaloblastic changes due to its interaction with vitamin B12 [96,97]. Macrocytic anemia occurs commonly in patients who chronically misuse [95,98].

Case reports have described N₂O misuse associated with venous thromboembolism (VTE), such as ischemic stroke, cerebral venous thrombosis, myocardial infarction, deep venous thrombosis (DVT), and pulmonary embolism (PE) [99-107]. N₂O inhibition of vitamin B12 and methionine synthase can result in increased plasma homocysteine concentrations, which has been associated with an increased risk of VTE in some studies. (See "Overview of homocysteine", section on 'Venous thromboembolism'.)

A single-center, retrospective study of patients with recreational N₂O misuse (326 patients) identified 17 patients with a VTE event [108]. The majority of events were DVT/PE but also included acute coronary syndrome, ischemic stroke, cerebral vein thrombosis, portal vein thrombosis, and femoral artery thrombosis. Most patients were young (median age 26 years, range 18 to 32, one patient was 53 years) and without VTE risk factors. In nine patients with VTE who had measured serum homocysteine concentrations, eight had elevated concentrations with a median concentration of 125 micromol/L and range of 22 to 253 micromol/L (normal homocysteine concentrations are 5 to 15 micromol/L; a concentration >100 micromol/L is considered severely elevated). In 104 patients with neurologic complaints and no VTE who had measured serum homocysteine concentrations, 94 had elevated concentrations with a median concentration of 99 micromol/L and range of 3 to 314 micromol/L. In this cohort, hyperhomocysteinemia was associated with N₂O misuse and may have been a contributing factor for VTE, although VTE did not occur in most patients with severe hyperhomocysteinemia.

●Reproductive effects – Given N₂O effects on vitamin B12 and methionine synthase, it is plausible to assume that N₂O may have reproductive health risks. Animal studies have demonstrated fetotoxicity with prolonged exposure to N₂O. Human studies are difficult to interpret given the number of confounding variables [29]. However, a study of occupationally exposed healthcare workers has demonstrated a dose-dependent correlation between N₂O exposure and DNA damage [109].

●Pulmonary effects – Pneumothorax may occur if gas is inhaled directly from a pressurized tank [36,110]. (See "Spontaneous pneumothorax in children".)

Nitrites — Alkyl nitrites (amyl, butyl, and isobutyl nitrites) have been misused for nearly 150 years [111]. Amyl nitrite is available by prescription for treatment of angina pectoris and as part of some commercially available kits for treatment of cyanide toxicity. It is available in a glass ampule encased in a woven absorbent covering. The ampule is broken or "popped" and the covering held close to the nose and inhaled. Butyl and isobutyl nitrites (also known as "Rush" and "Climax") are used as room deodorizers, particularly for locker rooms. They also are sold as "liquid incense." They were banned by the Anti-Drug Abuse Act of 1988, but are still available illegally, as are isopropyl and cyclohexyl nitrites [111]. They are typically sniffed directly from the container.

Inhalation of nitrite causes smooth muscle relaxation resulting in peripheral vasodilatation, flushing, and hypotension with reflex tachycardia. Dilation of cerebral blood vessels causes an increase in intracranial pressure (the "rush" reportedly experienced by users), headache, nausea, and syncope. Skin irritation, tracheobronchitis, and allergic reactions with wheezing and pruritus may occur [112,113].

Inhalation of nitrite may cause acute acquired methemoglobinemia, although this toxicity is much more common after oral ingestions [111,114] (see "Drug-induced hemolytic anemia", section on 'Methemoglobinemia'). Patients with acute acquired methemoglobinemia are symptomatic because the acute impairment of oxygen delivery to tissues does not allow sufficient time for compensatory mechanisms. Early symptoms include headache, fatigue, dyspnea, and lethargy. At higher methemoglobin levels (eg, greater than 70 percent), respiratory depression, altered consciousness, shock, seizures, and death may occur [24,111,115,116].

In addition, nitrite vapors are highly flammable, and serious burn injuries can occur if the substance comes into contact with a candle, cigarette, or other open flame.

ANCILLARY STUDIES — All patients with inhalant intoxication should have the following performed:

●Rapid blood glucose (all patients with altered mental status)

●Pulse oximetry

●Electrocardiogram and continuous cardiac monitoring for arrhythmias

●Urine screen for drugs of abuse

In addition, the following may be performed, especially in adolescents suspected of chronic misuse [25,117]:

●Complete blood count to evaluate for bone marrow suppression or macrocytic anemia (benzene, nitrous oxide misuse)

●Serum electrolytes to identify hypokalemia and metabolic acidosis (toluene misuse)

●Liver enzymes (AST [aspartate aminotransferase] and ALT [alanine aminotransferase]), blood urea nitrogen, and serum creatinine to detect liver or renal impairment (halogenated hydrocarbons)

●Vitamin B12, homocysteine, and methylmalonic acid (nitrous oxide misuse)

●Urine rapid dipstick and microscopic urinalysis to assess for renal tubular acidosis (chronic toluene use) or findings consistent with interstitial nephritis (halogenated hydrocarbons) (see "Overview and pathophysiology of renal tubular acidosis and the effect on potassium balance")

Methemoglobin levels should be obtained if nitrite misuse is suspected or if clinical features of methemoglobinemia are evident (eg, very dark or chocolate brown venous blood or cyanosis that does not resolve with supplemental oxygen). (See "Methemoglobinemia", section on 'Clinical presentation (acquired/toxic)'.)

A venous blood lead level is appropriate in patients in whom leaded gasoline misuse is suspected.

A chest radiograph should be obtained in patients with hypoxemia, rales, or respiratory distress. Abnormalities on chest radiograph may develop as late as 24 hours after exposure in symptomatic patients [38]. They include increased bronchovascular markings, bibasilar and perihilar infiltrates, and pneumatoceles [38].

In patients with signs or symptoms of peripheral neuropathy or myelopathy, especially with a history of nitrous oxide misuse, we obtain an MRI of the spine and nerve conduction studies [117]. In patients with chronic nitrous oxide misuse, a common MRI finding is T₂ hyperintensities in the posterior column of the cervical spinal cord [95,98,118]. Nerve conduction studies commonly show axonal degeneration with or without demyelination [92,94,95].

Although exposure to some hydrocarbons may be confirmed by detection of urinary metabolites (eg, trichloroethanol after chlorinated hydrocarbon exposure, hippuric acid after toluene exposure) or directly measured in the blood (eg, toluene), these laboratory studies are not rapidly available and do not change management priorities. Thus, they are not usually performed in patients with acute inhalant intoxication.

DIAGNOSIS — Inhalant misuse is a clinical diagnosis based on history or circumstance (eg, patient found unresponsive with toxic inhalant or inhalant apparatus nearby) and physical findings that distinguish inhalant misuse from other substances. (See 'Techniques (sniffing, huffing, or bagging)' above and 'Differential diagnosis' below.)

Specific inhaled agents are suggested by certain clinical findings as shown in the table (table 3).

The diagnosis of chronic nitrous oxide use is supported by increased serum concentrations of homocysteine and methylmalonic acid and decreased vitamin B12 (although the latter may be normal in one-third of patients with neurologic manifestations) [95,98,117,119]. The presence of T₂ hyperintensities on MRI of the spinal cord and axonal degeneration on nerve conduction studies also supports the diagnosis. (See 'Ancillary studies' above.)

Exposure to some hydrocarbons may be detected by urinary metabolites (eg, trichloroethanol after chlorinated hydrocarbon exposure, hippuric acid after toluene exposure) or directly measured in the blood (eg, toluene). Although not typically performed in patients with acute intoxication, such testing may be used to identify continued use during substance use disorder treatment.

DIFFERENTIAL DIAGNOSIS — Inhalant misuse causes a wide spectrum of physical findings. Patients with acute inhalant intoxication often have the characteristic sweet solvent odor of halogenated hydrocarbons or the "glue" odor of toluene detectable on the breath. Chronic users may also have the characteristic perioral skin rash (glue sniffer’s rash) (see 'Other effects' above). When the diagnosis is not clear based upon clinical findings, the clinician must consider other agents that can cause altered mental status and/or cardiac tachyarrhythmias as follows:

●Coma with respiratory depression – All patients with coma warrant measurement of a rapid blood glucose to exclude hypoglycemia. If not clinically apparent, acute inhalant intoxication can be difficult to distinguish from the many agents that can cause lethargy and coma (table 4). Opioids, ethanol, and sedative-hypnotics (eg, benzodiazepines or barbiturates) are key substances to consider. Opioid intoxication typically responds readily to naloxone administration. Ethanol can be detected by saliva, serum, and breath samples. Sedative-hypnotic agents are not typically associated with tachycardia or tachyarrhythmias which may arise from pulmonary hypoxia and catecholamine sensitization after inhalant use.

●Ventricular tachyarrhythmias – Many agents are associated with ventricular arrhythmias or prolongation of the QRS or QT intervals which predispose to such arrhythmias (table 5). Sympathomimetics such as cocaine and amphetamine and anticholinergic agents such as antihistamines, antipsychotics, and cyclic antidepressants can sometimes be distinguished from acute inhalant intoxication by the presence of characteristic toxidromes, ie, physical findings associated with poisoning by these agents (table 6). Electrolytes should be obtained rapidly to identify hyperkalemia or hypocalcemia.

MANAGEMENT — Management of acute inhalant intoxication is supportive. Maintenance of cardiorespiratory function and removal of the child from the source of the toxin (eg, bottle, rag or bag, or contaminated clothing) are of primary importance.

Supportive care — Supplemental 100 percent oxygen by a nonrebreather face mask is administered to treat hypoxia.

Coma with respiratory depression — Respiratory depression often responds transiently to tactile stimulation of the patient. However, clinicians should proceed with endotracheal intubation and mechanical ventilation if there is any doubt about the patient's ability to breathe adequately on their own or if pulmonary aspiration poses a significant risk.

Ventricular arrhythmias — Children with ventricular arrhythmias should receive countershock treatment according to international resuscitation guidelines (algorithm 1 and algorithm 2). (See "Technique of defibrillation and cardioversion in children (including automated external defibrillation)".)

If medication administration is necessary according to Pediatric Life Support Protocols (PALS), we suggest that patients who have ventricular arrhythmias after inhalant use receive amiodarone or lidocaine rather than epinephrine. Amiodarone has been successfully used to treat butane-induced ventricular fibrillation in one case [120]. Children who have inhaled halogenated hydrocarbons may develop ventricular arrhythmias in response to parenterally administered epinephrine or other catecholamines (eg, norepinephrine) because these treatments can theoretically precipitate or worsen arrhythmias in the irritable myocardium [61,75].

For patients who persist with ventricular arrhythmias after inhalant use despite the use of Pediatric Advanced Life Support protocols, administration of propranolol or esmolol is an option based upon case reports of reversal of arrhythmias in patients poisoned with trichloroethylene [121,122].

Hypokalemia — Chronic toluene inhalation can present with hypokalemia and weakness [123]. In one case series, parenteral potassium as well as sodium bicarbonate for pH <7.2 corrected serum and reversed electrolyte and muscle abnormalities within 24 to 36 hours. Patients with hypokalemia and muscle weakness caused by toluene misuse warrant careful administration of parenteral potassium while monitoring electrolytes, including calcium and phosphorus. Dextrose administration should be avoided as it can exacerbate hypokalemia. (See "Clinical manifestations and treatment of hypokalemia in adults", section on 'Intravenous therapy'.)

Antidotes — Specific antidotes may be necessary to treat methemoglobinemia caused by nitrite exposure, lead toxicity due to inhalation of leaded gasoline, or nitrous oxide (N₂O) neurotoxicity:

●Patients with methemoglobinemia who are symptomatic should be treated with high-dose oxygen and intravenous methylene blue. (See "Methemoglobinemia", section on 'Management (acquired/toxic)'.)

●Lead toxicity may require chelation therapy, depending on the results of lead levels obtained from whole blood. (See "Childhood lead poisoning: Management".)

●In a patient with neurotoxicity from N₂O misuse, we suggest treatment with vitamin B12 [119]. A reasonable approach is to administer 1000 mcg intramuscular (IM) or deep subcutaneous (SUBQ) daily for one to two weeks, then a 1000 mcg IM/SUBQ weekly or 2000 mcg orally daily until manifestations resolve [117]. N₂O misuse causes a functional vitamin B12 deficiency, but the benefit of vitamin B12 supplementation is not well studied, and evidence is limited to case reports and case series. Some experts also treat with methionine 1 g three times days for at least four to six weeks, but evidence is limited to even fewer case series [117,119,124-126].

Psychiatric care — Acutely, patients with findings of inhalant misuse should undergo screening for substance use disorder, depression, and suicidality [22]. (See "Substance use disorders: Clinical assessment" and "Screening for depression in adults".)

Long-term management includes referral for substance use disorder treatment and a formal period of detoxification if indicated [36]. Chronic complications of misuse may resolve if substance use is discontinued. Polydrug use and coexisting psychopathology are common occurrences, complicating substance use treatment. Residential treatment may improve outcome. Systematic data comparing different approaches to treatment are lacking [32].

Disposition — Patients with significant toxicity marked by central nervous system findings (eg, coma, seizures) or cardiac arrhythmias warrant hospital admission to a unit with pediatric critical care capability.

Children who receive treatment for methemoglobinemia or lead toxicity may also require admission depending on the degree of toxicity.

Children who express suicidal thoughts need urgent psychiatric evaluation for possible admission to a mental health facility.

Patients who are asymptomatic in the emergency department or have mild symptoms (eg, lethargy) that quickly resolve may be discharged home as long as appropriate mental health and primary care follow-up are assured.

PREVENTION — Pediatricians should maintain awareness of the clinical features and complications of inhalant misuse and promote education about the health hazards of inhalants to children, adolescents, parents, teachers, and vendors of volatile substances. Middle school and high school administrators should consider taking the following actions:

●Review purchases of school supplies and substitute water-based products for solvent-based products whenever possible. Explain that the school is looking for ways to reduce indoor air pollution. Describing solvent-based products as inhalants or drugs may arouse the curiosity of students.

●Closely monitor the use of solvent-based products and gases; in schools, such products should be checked out and in.

●Provide information to school faculty, staff, and nurses.

●Educate parents about the dangers of inhalant misuse.

●Review the appropriate use and consequences of misuse of solvents and gases whenever these products are used (eg, vocational programs, science, art).

●Develop a plan of action to treat students who use inhalants.

ADDITIONAL RESOURCES

Regional poison control centers — Regional poison control centers in the United States are available at all times for consultation on patients with known or suspected poisoning, and who may be critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have medical toxicologists available for bedside consultation. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is provided separately. (See "Society guideline links: Regional poison control centers".)

Society guideline links — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: General measures for acute poisoning treatment" and "Society guideline links: Treatment of acute poisoning caused by specific agents other than drugs of abuse" and "Society guideline links: Treatment of acute poisoning caused by recreational drug or alcohol use" and "Society guideline links: Poisoning prevention".)

SUMMARY AND RECOMMENDATIONS

●Mechanism of action – Volatile substances produce a rapid feeling of euphoria and inebriation because of their rapid absorption through the pulmonary vascular bed, their lipophilic properties that allow for quick distribution into the brain, and their effects on neuronal membrane function at glutamate or gamma amino butyric acid receptors. (See 'Mechanism of action' above.)

●Epidemiology – The most frequently used inhalants include glue, shoe polish, or toluene; gasoline or lighter fluid; nitrous oxide or "whippets"; and spray paints. Each of these substances may contain more than one toxic compound (table 1). Common routes of use involve sniffing, huffing, or bagging to concentrate the inhaled substance. (See 'Epidemiology' above and 'Techniques (sniffing, huffing, or bagging)' above.)

●Recognizing inhalant misuse – Inhalant misuse frequently goes undetected. Clues to inhalant misuse include chemical odors on the breath, skin, or clothes and empty solvent containers or bags, rags, or gauze in the child's possession or trash. Children may also display characteristic skin changes (eg, glue sniffer's rash) (table 2). (See 'Recognition of inhalant misuse' above.)

●Clinical features of toxicity – Although the vast majority of children who misuse volatile inhalant substances do not seek or require medical attention, inhalant intoxication is potentially life threatening. Cardiac arrhythmias and central nervous system dysfunction (inebriation, agitation, seizures) are the most concerning acute toxic effects of volatile inhalants, especially hydrocarbons. Death may result from asphyxia, suffocation, choking on vomitus, careless or dangerous behavior in potentially dangerous settings, and sudden sniffing death seen with hydrocarbon use. Additional findings or acute and chronic toxicity vary by agent, as presented in the table (table 3), and include the following (see 'Toxicity and clinical findings by agent' above):

•Methemoglobinemia (nitrites)

•Lead toxicity (leaded gasoline)

•Polyneuropathy, myelopathy, venous thromboembolism, and megaloblastic anemia (nitrous oxide)

•Muscle weakness, hypokalemia, and metabolic acidosis (toluene)

•Carbon monoxide poisoning (methylene chloride)

●Ancillary studies – Patients with altered mental status should undergo rapid measurement of blood glucose. Pulse oximetry and an electrocardiogram should be obtained. The following can be performed as indicated: urine screen for drugs of abuse, complete blood count, serum electrolytes, blood urea nitrogen, serum creatinine, liver transaminases, urinalysis, methemoglobin level, venous blood lead level, and chest radiograph. Patients with neurologic manifestations and chronic nitrous oxide use should have serum vitamin B12, homocysteine, and methylmalonic acid concentrations, MRI of spine, and nerve conduction studies. Exposure to some hydrocarbons (eg, toluene, trichloroethanol) may be confirmed with blood or urine metabolite assays; these laboratory studies are not rapidly available, do not change management priorities, and are not usually performed in patients with acute inhalant intoxication. (See 'Ancillary studies' above.)

●Management – Management of acute inhalant intoxication is primarily supportive (see 'Management' above):

•Respiratory depression or coma – Supplemental 100 percent oxygen by a nonrebreather face mask should be administered to treat hypoxia. Clinicians should proceed with endotracheal intubation and mechanical ventilation if there is any doubt about the patient's ability to breathe adequately or if pulmonary aspiration poses a significant risk. (See 'Coma with respiratory depression' above.)

•Ventricular arrhythmias – Children with ventricular arrhythmias should receive synchronized cardioversion or defibrillation according to international resuscitation guidelines (algorithm 1 and algorithm 2). (See 'Ventricular arrhythmias' above and "Technique of defibrillation and cardioversion in children (including automated external defibrillation)".)

In a patient with inhalant use who requires medication for ventricular arrhythmias according to Pediatric Life Support algorithms (algorithm 1 and algorithm 2), we suggest administration of amiodarone or lidocaine rather than epinephrine (Grade 2C). For a patient who persists with ventricular arrhythmias after inhalant use despite the use of Pediatric Advanced Life Support (PALS) protocols, administration of propranolol or esmolol may be beneficial. (See 'Ventricular arrhythmias' above.)

•Hypokalemia and muscle weakness – Patients with these caused by toluene misuse warrant careful administration of parenteral potassium while monitoring electrolytes, including calcium and phosphorus. Dextrose administration should be avoided. (See 'Hypokalemia' above and "Clinical manifestations and treatment of hypokalemia in adults", section on 'Intravenous therapy'.)

•Methemoglobinemia – Patients with methemoglobinemia (eg, from nitrite exposure) who are symptomatic should be treated with high-dose oxygen and intravenous methylene blue. (See 'Antidotes' above and "Methemoglobinemia", section on 'Management (acquired/toxic)'.)

•Lead toxicity – Patients with lead toxicity (eg, inhalation of leaded gasoline) may require chelation therapy depending on the results of lead levels obtained from whole blood. (See 'Antidotes' above and "Childhood lead poisoning: Management".)

•Neurotoxicity from nitrous oxide (N₂O) misuse – In a patient with neurotoxicity from N₂O misuse, we suggest treatment with vitamin B12 (Grade 2C). (See 'Antidotes' above.)

●Substance use disorder screening and treatment – Patients with findings of inhalation misuse should undergo screening for substance use disorder, depression, and suicidality. Long-term management includes referral for substance use disorder treatment and a formal period of detoxification, as needed. (See 'Psychiatric care' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Erin Endom, MD, who contributed to earlier versions of this topic review.