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  1. Alcohols are in many common household products. Ethanol is one of the most used and abused substances in the world. Methanol, ethylene glycol, and isopropyl alcohol are more toxic and can require ICU level of care.
    1. Ethanol accounts for nearly 100 000 deaths each year in the United States alone. Up to 40% of patients admitted to the hospital have alcohol use disorder and approximately half of these patients will experience alcohol withdrawal.
      1. Ethanol is metabolized in the liver, first by alcohol dehydrogenase and then by acetaldehyde dehydrogenase, yielding acetate. In acute intoxication, the effects of ethanol are exerted on γ-aminobutyric acid type A (GABAA) receptors by limiting glutamate activation of N-methyl-D- aspartate (NMDA) receptors. In chronic use, there is a downregulation of GABAA responses and upregulation of NMDA subtype glutamate receptors. In chronic ingestion, liver dysfunction and cirrhosis develop, leading to impaired hepatic function and portal hypertension. Wernicke (ophthalmoplegia, dementia, and ataxia)-Korsakoff (amnesia and aphasia, agnosia, or apraxia) syndrome can develop long term due to lack of thiamine.
      2. Acute intoxication typically presents with CNS depression and dehydration, though at higher blood alcohol concentrations, cardiopulmonary dysfunction or collapse can occur. Hypoglycemia is common in small children. Acute intoxication is generally treated with supportive care. Alcoholic ketoacidosis can develop secondary to decreased intake of proteins and carbohydrates during alcohol binges, along with other metabolic changes that favor the conversion to free fatty acids and ketogenesis.
      3. Alcohol withdrawal symptoms may occur following abrupt discontinuation in chronic users and can include tremors, irritability, and anxiety. Seizures and delirium tremens usually present 72 to 96 hours after the last drink. Withdrawal from chronic alcohol abuse can be lethal if not treated appropriately. Monitoring tools such as the Clinical Institute Withdrawal Assessment (CIWA) in patients who are awake or the Sedation Agitation Scale (SAS) in patients who are sedated or intubated have been developed to recognize and treat withdrawal. Benzodiazepines can lessen symptoms and prevent progression to severe symptoms via their effect on GABAA receptors. Phenobarbital is another treatment option that affects GABAA receptors as well but also acts as a direct GABA agonist and blocks glutamate activity at the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor. Clonidine and haloperidol are sometimes used as adjuncts. Propofol, dexmedetomidine, and ketamine may also be effective for patients with more severe symptoms.
    2. Methanol and ethylene glycol are both common solvents found in household and industrial materials. They can be ingested recreationally for their sedating and euphoric properties, unintentionally (eg, children drinking antifreeze), or intentionally (eg, attempts at self-harm). Common sources of exposure are antifreeze (ethylene glycol) and windshield wiper fluid (methanol). Methanol is also a potential by-product of ethanol distillation, such as in “moonshine.”
      1. Both methanol and ethylene glycol are readily absorbed through the GI tract. Methanol is initially metabolized by alcohol dehydrogenase into formaldehyde, which is further metabolized into formate. Ethylene glycol is also metabolized by alcohol dehydrogenase into glycolaldehyde which is then metabolized into glycolic, glyoxylic, and oxalic acids.
      2. Both methanol and ethylene glycol produce sedation, stupor, and gastrointestinal distress, akin to early ethanol intoxication. Later, methanol can lead to bright-visual-field or total blindness described as “snow-field blindness.” Formate, produced from methanol metabolism, is toxic to the mitochondria and interrupts oxidative phosphorylation. Neurons in the basal ganglia are most sensitive to these effects and may lead to lesions identifiable on CT or MRI. Oxalic acid from ethylene glycol metabolism can lead to acute kidney injury secondary to precipitation of calcium oxalate crystals in the kidneys. Ethylene glycol toxicity can also lead to cardiopulmonary compromise and failure.
      3. Diagnosis is typically based on a suspected or reported ingestion of either substance because toxic alcohol serum concentrations are not immediately available. An elevated osmolar gap is evident early after ingestion for both toxic alcohols; however, over time, this normalizes while the anion gap increases from metabolite accumulation. A serum ethanol concentration should also be obtained, as a level greater than 100 mg/dL nearly completely excludes toxicity from toxic alcohols as this ethanol concentration would inhibit metabolism to the toxic metabolites. Calcium oxalate crystals may be seen upon analysis of the urine. Neither methanol nor ethylene glycol poisoning directly leads to significant lactate generation. However, some analyzers mistake glycolic acid and/or glyoxylic acid from ethylene glycol as lactate, thereby reporting a falsely high lactate.
      4. Follow stabilization and initiation of supportive care, treatment of methanol and ethylene glycol toxicities typically involves the administration of fomepizole. Both fomepizole and ethanol act as competitive inhibitors of alcohol dehydrogenase, which significantly limits the breakdown of both ethylene glycol and methanol to their toxic metabolites (see dosing in Table 31.5). Fomepizole should typically be given for all suspected or confirmed methanol or ethylene glycol ingestions until confirmatory toxic alcohol concentrations can be obtained. Fomepizole should be continued until the toxic alcohol concentration is predicted or measured to be below 20 mg/dL. Hemodialysis is the definitive treatment for patients who are symptomatic with end-organ toxicity or persistent metabolic acidosis following ingestion of a toxic alcohol. For patients with blood pH less than 7.2, a bolus of sodium bicarbonate followed by an infusion may be considered.
    3. Isopropyl alcohol is a common household product and key component in antiseptic hand sanitizer. Unlike ethylene glycol and methanol, isopropyl alcohol is the toxic substance instead of metabolites. Isopropyl alcohol is metabolized by alcohol dehydrogenase into acetone. Symptoms include mild GI upset, hemorrhagic gastritis, hypotension, seizures, and coma. Unlike methanol/ethylene glycol poisoning, isopropyl alcohol causes an osmolar gap without metabolic acidosis. Treatment is generally supportive.
  2. Opioid overdoses, including both illegal and prescription opioids, are rapidly increasing. Over 100 000 people die worldwide every year from an opioid overdose, with a majority of those overdoses due to recreational use of synthetic opioids (eg, fentanyl).
    1. Many opioids are metabolized in the liver by CYP2D6 and CYP3A4, with some having active metabolites. Opioid overdoses present with somnolence, sedation, respiratory depression, and decreased central response to increasing Paco2. Constricted pupils are a classic finding that does not dissipate with chronic use. Always maintain a high index of suspicion for other coingestants, such as benzodiazepines, sleep aides, acetaminophen, or alcohol. Treatment of opioid overdose includes naloxone to reverse respiratory depression, though the dose selected depends on the patient’s history and current condition. Close monitoring is needed as the half-life of naloxone may be shorter than the opioid ingested (eg, methadone), in which case a naloxone infusion may be necessary. Watch for noncardiogenic pulmonary edema when treating with naloxone.
    2. Naloxone administration may precipitate acute withdrawal. Opioid withdrawal symptoms may also present while the patient is in the ICU. Withdrawal symptoms are the result of a reflexive increase in sympathetic outflow, resulting in tachycardia, hypertension, diaphoresis, nausea, vomiting, and abdominal pain. Effective treatments include reinstituting low-dose opioids, initiating methadone or buprenorphine, clonidine, and symptomatic treatment.
  3. Benzodiazepines are used frequently for anxiety, spasms, and sedation in both the inpatient and outpatient settings. Although this class of medications is generally safe, when combined with other substances that have sedative properties (eg, opioids, antidepressants, alcohol), their toxicity is additive.
    1. Benzodiazepines provide sedative hypnosis, anterograde amnesia, muscle relaxation, and anxiolysis through their actions on GABAA receptors. Within the class, there is significant variation between their onset, duration of action, metabolism, and excretion. Symptoms of benzodiazepine overdose are nondescript but include neurologic and respiratory depression. Downtitration or discontinuation of the agent is the primary treatment, aside from traditional supportive care. Flumazenil can be considered, but there is a potential for it to induce acute benzodiazepine withdrawal resulting in seizures. Because its half-life is short, observe the patient closely if long-acting benzodiazepines were ingested.
    2. Withdrawal from benzodiazepines occurs after chronic use. Symptoms include anxiety, irritability, sleep disturbances, hallucinations, vomiting, diarrhea, tachycardia, tachypnea, and seizures. Treatment typically consists of supportive care and a prolonged benzodiazepine taper or symptom-triggered management, similar to the treatment of alcohol withdrawal.