Inhalant Use Disorder

Definition and Epidemiology

Definition

Inhalant use disorder (IUD) is the chronic (> 12 months), problematic pattern of inhalant use causing significant distress. 

• Inhalants are typically volatile hydrocarbons that are in a gaseous state at room temperature. 
• As with other substance use disorders, those with IUDs develop:
  • Physical tolerance Tolerance Pharmacokinetics and Pharmacodynamics
  • Impairment in their daily functioning

Epidemiology

• Among the most easily and widely available substances for misuse, especially in younger populations 
• Lifetime prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency: 11% of high school students in the United States report use at some point.
• Approximately same use among men and women
• 20% of emergency department encounters secondary to inhalant use disorder occur in those < 18 years of age. 
• Mental health comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus: major depression, suicidality, conduct disorder Conduct Disorder Conduct disorder (CD) is a pediatric mental disorder characterized by a recurrent behavior in which patients do not comply with social norms and rules or the basic rights of others. Examples include violence, destruction, theft, lying, and serious breaking of rules present over ≥ 1 year. Conduct Disorder, abuse of other drugs

Pharmacology

Types of inhalants

There are 4 commonly used types of inhalants with slightly different effects and side effects.

• Volatile solvents:
  • Found in common household items such as glue and adhesives, paint thinners, gasoline, and marker tips
  • Most often used substance in young adolescents 
  • Very toxic to the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy, bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis, and kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy
• Aerosols Aerosols Colloids with a gaseous dispersing phase and either liquid (fog) or solid (smoke) dispersed phase; used in fumigation or in inhalation therapy; may contain propellant agents. Coxiella/Q Fever: contained in hair spray, cooking spray, spray paint
• Gases: ether, halothane Halothane A nonflammable, halogenated, hydrocarbon anesthetic that provides relatively rapid induction with little or no excitement. Analgesia may not be adequate. Nitrous oxide is often given concomitantly. Because halothane may not produce sufficient muscle relaxation, supplemental neuromuscular blocking agents may be required. Inhaled Anesthetics, nitrous oxide Nitrous oxide Nitrogen oxide (N2O). A colorless, odorless gas that is used as an anesthetic and analgesic. High concentrations cause a narcotic effect and may replace oxygen, causing death by asphyxia. Inhaled Anesthetics (also known as whippets) 
• Organic nitrates Nitrates Nitrates are a class of medications that cause systemic vasodilation (veins > arteries) by smooth muscle relaxation. Nitrates are primarily indicated for the treatment of angina, where preferential venodilation causes pooling of blood, decreased preload, and ultimately decreased myocardial O2 demand. Nitrates:
  • Include amyl nitrate, isobutyl nitrate
  • Used as anal sexual intercourse enhancers because they relax smooth muscle
  • Cause dizziness Dizziness An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. Lateral Medullary Syndrome (Wallenberg Syndrome), tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children, hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension, flushing
  • Associated with vitamin B deficiency Vitamin B Deficiency A condition due to deficiency in any member of the vitamin B complex. These B vitamins are water-soluble and must be obtained from the diet because they are easily lost in the urine. Unlike the lipid-soluble vitamins, they cannot be stored in the body fat. Water-soluble Vitamins and their Deficiencies → might lead to polyneuropathy Polyneuropathy Polyneuropathy is any disease process affecting the function of or causing damage to multiple nerves of the peripheral nervous system. There are numerous etiologies of polyneuropathy, most of which are systemic and the most common of which is diabetic neuropathy. Polyneuropathy
  • Might lead to methemoglobinemia Methemoglobinemia Methemoglobinemia is a condition characterized by elevated levels of methemoglobin in the blood. Methemoglobin is the oxidized form of hemoglobin, where the heme iron has been converted from the usual ferrous (Fe2+) to the ferric (Fe3+) form. The Fe3+ form of iron cannot bind O2, and, thus, leads to tissue hypoxia. Methemoglobinemia
  • Lipoid pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia and death from aspiration of liquid form

Pathophysiology

• Volatile hydrocarbons and nitric oxide Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from arginine by nitric oxide synthase. Nitric oxide is one of the endothelium-dependent relaxing factors released by the vascular endothelium and mediates vasodilation. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic gmp. Pulmonary Hypertension Drugs are highly lipid-soluble → rapidly absorbed across the pulmonary capillary bed into the bloodstream → distributed throughout the body
• Onset is rapid and duration is relatively short. 
• Neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology (high lipid content) are highly affected by inhalants.
• CNS depression by alteration of neuronal membrane function at glutamate Glutamate Derivatives of glutamic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Synthesis of Nonessential Amino Acids or GABA GABA The most common inhibitory neurotransmitter in the central nervous system. Receptors and Neurotransmitters of the CNS receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors
• Concentration of inhalant substances increase when they are taken with alcohol → both substances metabolized by the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy

Clinical Presentation and Diagnosis

Inhalant intoxication

• CNS:
  • Tremor Tremor Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of parkinson disease. Myotonic Dystrophies
  • Muscle weakness
  • Hyporeflexia Hyporeflexia Duchenne Muscular Dystrophy
  • Ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia
  • Dilated pupils
  • Slurred speech Slurred Speech Cerebellar Disorders
  • Euphoria Euphoria An exaggerated feeling of physical and emotional well-being not consonant with apparent stimuli or events; usually of psychologic origin, but also seen in organic brain disease and toxic states. Hepatic Encephalopathy
  • Apathy Apathy Lack of emotion or emotional expression; a disorder of motivation that persists over time. Wernicke Encephalopathy and Korsakoff Syndrome 
  • Aggression Aggression Behavior which may be manifested by destructive and attacking action which is verbal or physical, by covert attitudes of hostility or by obstructionism. Oppositional Defiant Disorder
  • Perceptual disturbances, paranoia
  • Lethargy Lethargy A general state of sluggishness, listless, or uninterested, with being tired, and having difficulty concentrating and doing simple tasks. It may be related to depression or drug addiction. Hyponatremia, clouding of consciousness
  • Coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma
  • Dizziness Dizziness An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. Lateral Medullary Syndrome (Wallenberg Syndrome)
  • Headaches
  • Nystagmus Nystagmus Involuntary movements of the eye that are divided into two types, jerk and pendular. Jerk nystagmus has a slow phase in one direction followed by a corrective fast phase in the opposite direction, and is usually caused by central or peripheral vestibular dysfunction. Pendular nystagmus features oscillations that are of equal velocity in both directions and this condition is often associated with visual loss early in life. Albinism
  • Lacrimation
  • Respiratory depression 
• Cardiovascular:
  • Cardiac arrhythmias
• GI:
  • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics
  • Vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
• Dermatologic:
  • Nasal crusting
  • Rash Rash Rocky Mountain Spotted Fever ( dermatitis Dermatitis Any inflammation of the skin. Atopic Dermatitis (Eczema))

Inhalant withdrawal

A withdrawal syndrome does not usually occur. However, the following symptoms may appear:

• Craving and irritability
• Sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep disturbance
• Increased sweating
• Muscle aches
• Anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder
• Depression
• Hallucinations Hallucinations Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders. Schizophrenia

Management

Acute intoxication

• Supportive care: monitor airway Airway ABCDE Assessment, breathing, and circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment
• Identify solvent: Some substances (e.g., leaded gasoline) may require specific treatment, such as chelation.
• Avoid use of hypnotics during acute intoxication and use antipsychotics in cases of acute agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus.

Withdrawal

• Supportive care
• Psychotherapy Psychotherapy Psychotherapy is interpersonal treatment based on the understanding of psychological principles and mechanisms of mental disease. The treatment approach is often individualized, depending on the psychiatric condition(s) or circumstance. Psychotherapy as well as group therapy Group therapy A form of therapy in which two or more patients participate under the guidance of one or more psychotherapists for the purpose of treating emotional disturbances, social maladjustments, and psychotic states. Psychotherapy

Long-term management

• Hyperbaric chambers
• May take up to 28 weeks to get substance out of the system
• No proven treatment available for cognitive impairments caused by inhalants 
• Psychologic counseling
• Community prevention and treatment programs

Complications

CNS

• Neurocognitive impairment
• Cerebellar dysfunction
• Parkinsonism Parkinsonism West Nile Virus
• Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
• Peripheral neuropathy Neuropathy Leprosy

Cardiovascular

• Myocarditis Myocarditis Myocarditis is an inflammatory disease of the myocardium, which may occur alone or in association with a systemic process. There are numerous etiologies of myocarditis, but all lead to inflammation and myocyte injury, most often leading to signs and symptoms of heart failure. Myocarditis
• MI MI MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction

Renal

• Metabolic acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis
• Urinary calculi
• Glomerulonephritis

Other

• Myopathy Myopathy Dermatomyositis
• Aplastic anemia Aplastic Anemia Aplastic anemia (AA) is a rare, life-threatening condition characterized by pancytopenia and hypocellularity of the bone marrow (in the absence of any abnormal cells) reflecting damage to hematopoietic stem cells. Aplastic anemia can be acquired or inherited, however, most cases of AA are acquired and caused by autoimmune damage to hematopoietic stem cells. Aplastic Anemia
• Malignancy Malignancy Hemothorax
• Hepatotoxicity Hepatotoxicity Acetaminophen

Differential Diagnosis

• Methemoglobinemia Methemoglobinemia Methemoglobinemia is a condition characterized by elevated levels of methemoglobin in the blood. Methemoglobin is the oxidized form of hemoglobin, where the heme iron has been converted from the usual ferrous (Fe2+) to the ferric (Fe3+) form. The Fe3+ form of iron cannot bind O2, and, thus, leads to tissue hypoxia. Methemoglobinemia: Nitrites can oxidize iron Iron A metallic element with atomic symbol fe, atomic number 26, and atomic weight 55. 85. It is an essential constituent of hemoglobins; cytochromes; and iron-binding proteins. It plays a role in cellular redox reactions and in the transport of oxygen. Trace Elements, converting it into a state of lower affinity to oxygen and higher affinity to cyanide Cyanide Inorganic salts of hydrogen cyanide containing the -cn radical. The concept also includes isocyanides. It is distinguished from nitriles, which denotes organic compounds containing the -cn radical. Cyanide Poisoning, leading to tissue hypoxia Hypoxia Sub-optimal oxygen levels in the ambient air of living organisms. Ischemic Cell Damage. Nitrites may be absorbed through dietary intake, polluted high-altitude water sources, and local anesthetics Anesthetics Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. Anesthesiology: History and Basic Concepts. Treatment involves the administration of methylene blue and vitamin C Vitamin C A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. Water-soluble Vitamins and their Deficiencies. History of inhalant usage as well as persisting hypoxemia Hypoxemia Neonatal Respiratory Distress Syndrome after oxygen supplementation distinguish this diagnosis from inhalant use disorder. 
• Cannabis use disorder Cannabis use disorder Cannabis use disorder (CUD) is characterized by the pathologic consumption of cannabis, which is the most commonly used illicit substance worldwide. While cannabis has some beneficial medical uses, it also has the potential to cause intoxication characterized by psychosis or cognitive impairment, especially in chronic use. Cannabis Use Disorder: Cannabis (marijuana) is the most commonly used illicit substance worldwide. Intoxication symptoms include euphoria Euphoria An exaggerated feeling of physical and emotional well-being not consonant with apparent stimuli or events; usually of psychologic origin, but also seen in organic brain disease and toxic states. Hepatic Encephalopathy, laughter, lethargy Lethargy A general state of sluggishness, listless, or uninterested, with being tired, and having difficulty concentrating and doing simple tasks. It may be related to depression or drug addiction. Hyponatremia, conjunctival injection, and increased appetite. Withdrawal symptoms include irritability, anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder, insomnia Insomnia Insomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking. Insomnia, and decreased appetite. Cannabis is popular in a similar demographic as for inhalants. Careful history taking of the substance ingested and urine testing can help in distinguishing inhalant ingestion from cannabis use.
  Alcohol use disorder Alcohol use disorder Alcohol is one of the most commonly used addictive substances in the world. Alcohol use disorder (AUD) is defined as pathologic consumption of alcohol leading to impaired daily functioning. Acute alcohol intoxication presents with impairment in speech and motor functions and can be managed in most cases with supportive care. Alcohol Use Disorder: level of alcohol consumption exceeding the sociocultural standard. Marked by a mental and physical addiction Addiction Substance use disorders are a significant cause of morbidity and mortality, especially among adolescents and young adults. A substance-related and addictive disorder is the continued use of a substance despite harmful consequences; these include significant impairment to one’s health or relationships or failure to fulfill major responsibilities at work, school, or home because of substance use. Substance-Related and Addictive Disorders with an irresistible desire for the substance and development of tolerance Tolerance Pharmacokinetics and Pharmacodynamics with a consecutive increase of dosage Dosage Dosage Calculation and withdrawal symptoms during abstinence. While intoxication with alcohol and inhalants may present very similarly, careful history taking and alcohol breath testing can help in distinguishing one from the other.