Altered Mental StatusJessica Hughes-Kisicki, M.D.Emergency Medicine Resident St. John Hospital and Medical Center Emergency Room visits following ingestion of alcohols occur commonly and can cause significant morbidity and mortality. The four types of alcohol include ethanol, isopropanol, methanol, and ethylene glycol. While ethanol represents the most commonly ingested alcohol, the other three types can cause serious toxicity when ingested and must be recognized and treated immediately and aggressively in clinical situations. Isopropanol, methanol, and ethylene glycol have relatively common clinical presentations, workup, and treatment strategies, with a few key elements distinguishing each. Ingestion of isopropanol, methanol, or ethylene glycol commonly occurs in the setting of accidents, suicide attempts, or as an ethanol substitute. All three are rapidly absorbed when ingested orally and metabolized mostly by alcohol dehydrogenase in the liver. Clinically, each may present with CNS and respiratory depression, hypotension, seizures, and early onset coma, among other signs and symptoms specific to each alcohol. Generally, when a patient arrives with altered mental status and suspected alcohol ingestion, initial measures should include intravenous access, accu-check measurement, and thiamine and naloxone administration to treat other possible causes of altered mental status. Supportive care is critical in the overall management of alcohol ingestions, including intubation and ventilation if needed. IV hydration should be given for hypotension, with vasopressors used as a second-line treatment. Gastric lavage and activated charcoal provide no benefit. Laboratory evaluation should include electrolytes, BUN, creatinine, CBC, glucose, acetone, serum osmolality, and lactate level. Tests such as a urine drug screen, salicylate, and acetaminophen levels should be obtained to check for co-ingestions. A toxic alcohol panel should be sent, however, the results are not available during the ED course, but can be used later to confirm ingestion. The major treatment goals in alcohol ingestion include supportive care, acidosis correction, antidote administration when applicable, and hemodialysis. Initiating these management approaches must occur immediately when history, clinical features, and lab values suggest isopropanol, methanol, or ethylene glycol ingestion. Outside of ethanol, the most commonly ingested alcohol is isopropanol, also known as isopropyl alcohol. This clear, volatile liquid has an aromatic odor and frequently comprises portions of products such as rubbing alcohol, industry solvents, disinfectants, skin and hair products, jewelry cleaners, detergents, paint thinner, and antifreeze. Excessive ingestion of isopropanol causes signs and symptoms similar to ethanol toxicity, but with twice the severity and lasting up to four times as long. Similar to methanol and ethylene glycol, isopropanol undergoes oxidation via alcohol dehydrogenase in the liver. It differs from the others due to the formation of a non-toxic metabolite, acetone. Clinically, patients commonly present with a fruity odor or smell of rubbing alcohol on their breath following intoxication; furthermore, they often complain of nausea, vomiting, and abdominal pain. In addition to CNS and respiratory depression, possible sequelae following ingestion include hypoglycemia, hepatic dysfunction, upper gastrointestinal hemorrhage, acute tubular necrosis, myoglobinuria, hemolytic anemia, rhabdomyolysis, and myopathy. Laboratory evaluation usually demonstrates an elevated osmolar gap; however, the hallmark laboratory findings with isopropanol intoxication include lack of an anion-gap metabolic acidosis and presence of ketonemia and ketonuria. These findings help differentiate this type of alcohol intoxication from methanol and ethylene glycol ingestion. As previously mentioned, management focuses mostly on supportive care, but can also involve additional measures like hemodialysis, which eliminates isopropanol and acetone. Dialysis should be initiated for hypotension refractory to IV fluids and vasopressors, for hemodynamic instability, or for peak isopropanol levels > 400mg/dL. Lastly, blood transfusions may play a role if hemorrhagic gastritis is present. Overall, patients who remain asymptomatic for 6-8 hours may be discharged, while symptomatic patients require admission. Another alcohol type encountered in the emergency room setting is methanol, known also as methyl alcohol, wood spirits, or wood alcohol. Products containing this alcohol type include contaminated whiskey, paint removers, varnishes, windshield washing fluid, wood distillation products, and antifreeze. Methanol is also a colorless, volatile liquid with a distinctive odor. Unlike the metabolism of isopropanol, alcohol dehydrogenase metabolizes methanol into two toxic metabolites, formaldehyde and formic acid. With folate as a cofactor, the formic acid can further break down into non-toxic metabolites. Unfortunately, folate deficiencies, as seen commonly in alcoholic patients, disrupt this metabolism and lead to the accumulation of the toxic metabolite. Also unlike isopropanol, clinical symptoms may not be present immediately due to the time required for toxic metabolite accumulation. Co-ingestion of ethanol can further delay symptom onset, as ethanol competes with methanol for metabolism by alcohol dehydrogenase. Clinically, apart from CNS and respiratory depression, other common symptoms of methanol poisoning include headache, vertigo, abdominal pain, nausea, and vomiting. One hallmark of methanol toxicity includes visual disturbances such as diplopia, blurred vision, decreased visual acuity, photophobia, constricted visual fields, the feeling of "looking into a snow field", or even blindness. On examination of the eye, there may be retinal edema, optic atrophy, or hyperemia of the optic disk. Laboratory evaluation shows a wide anion-gap metabolic acidosis and osmolar gap. Beyond supportive care, specific management in methanol toxicity involves a few additional measures, such as administration of sodium bicarbonate to maintain a normal pH and providing patients with the antidote fomepizole or ethanol. Fomepizole, the treatment of choice, or ethanol prevents metabolism of methanol to its toxic metabolites via competitive inhibition. Indications for treatment with these include a methanol level >20 mg/dL, ingestion of 0.4 mg/kg, or any history or symptoms suggestive of poisoning. If ethanol is used for treatment, the effective blood ethanol level is between 100-150 mg/dL. Lastly, hemodialysis functions to remove methanol and its metabolites from the blood if necessary. Indications for dialysis include any signs of visual or CNS dysfunction, peak methanol level >20 mg/dL, pH <7.15, or a history of ingestion of >30mL of methanol. Along with these measures, it is important to provide folate supplementation. Overall, hemodialysis and administration of fomepizole or ethanol should continue until the methanol blood level reaches zero and the acidosis completely resolves. All patients suspected of ingesting methanol should receive treatment and admitted for further care, even if they are asymptomatic. Patients with symptoms of methanol toxicity require admission to the intensive care unit for treatment. Finally, ethylene glycol is a colorless, odorless, sweet tasting fluid found in antifreeze, preservatives, glycerine substitute, lacquers, cosmetics, polishes, and detergents. Similar to methanol, its toxicity results from formation of two toxic metabolites, formaldehyde and formic acid. Unlike isopropanol and methanol, metabolism also forms oxalic acid, which can result in calcium oxalate crystalluria. On the other hand, ethylene glycol can also convert to non-toxic metabolites by pyridoxal phosphate or thiamine; however, deficiencies of these can shift the formation to the toxic metabolites. Clinically, there are three distinct phases of ethylene glycol toxicity. The first phase occurs 1-12 hours post-ingestion and causes CNS depression. Patients will appear inebriated with slurred speech and ataxia, and they may experience nystagmus and ophthalmoplegia, hallucinations, seizure, coma, and death. The second phase occurs during the 12-24 hours post-ingestion and results in cardiopulmonary instability. Patients may have myositis, tachycardia, hypertension, tachypnea, CHF, ARDS, cardiomegaly, and circulatory collapse. The last phase occurs during 24-72 hours following ingestion and results in nephrotoxicity secondary to the aldehyde metabolites and oxalic acid. During this phase, patients will experience flank pain and CVA tenderness, in addition to developing oliguric renal failure with acute tubular necrosis. Some additional abnormalities that may occur during ethylene glycol toxicity include leukocytosis, an elevated CPK causing generalized myalgias, and hypocalcemia secondary to precipitation of calcium oxalate. This hypocalcemia may lead to tetany and prolongation of the QT interval. Clinically, ethylene glycol toxicity should be considered if a patient presents inebriated with no ethanol scent, a wide anion-gap metabolic acidosis with an osmolar gap, and calcium oxalate crystalluria. The treatment for ethylene glycol ingestion parallels that used in methanol toxicity and includes supportive care, acidosis correction with sodium bicarbonate, fomepizole or ethanol administration, and hemodialysis. Use of fomepizole or ethanol is indicated for ethylene glycol levels >20 mg/dL or with suspicion of ingestion, especially when coupled with an anion-gap metabolic acidosis. Hemodialysis factors into the management of most patients suspected of ethylene glycol ingestion based on factors such as patient history, clinical presentation, laboratory workup, ethylene glycol levels >20mg/dL, signs of nephrotoxicity, and metabolic acidosis. It is also important to monitor for hypocalcemia and administer calcium gluconate if needed. Pyridoxine, thiamine, and magnesium should be supplemented daily as well. In general, patients presenting with signs or symptoms consistent with ethylene glycol toxicity or asymptomatic patients with a known history of ethylene glycol ingestion require admission to the intensive care unit for treatment.
Overall, isopropanol, methanol, or ethylene glycol ingestions occur less
frequently than ethanol ingestion, but can result in increased morbidity
and mortailty. These poisonings require prompt clinical recognition and
rapid, aggressive treatment in the emergency department, along with
likely admission to a medical floor or even intensive care setting in
certain situations. As a physician, it is important to remain vigilant
and suspect alcohol poisoning in a patient presenting with altered
mental status. # # # Posted:
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