Toxic Alcohols Pathophysiology of methanol and ethylene glycol overdose Clinical presentation of methanol and ethylene glycol overdose Management of methanol and ethylene glycol overdose Antidote and hemodialysis in toxic alcohol Zohair Al Aseri MD,FRCPC EM & CCM

METHANOL Perspective Certain products found in the home Antifreeze; Windshield washer fluid; Carburetor fluid; Glass cleaners Thinners Adhesives Zohair Al Aseri MD,FRCPC EM & CCM

METHANOL Perspective Treatment delay is associated with increased morbidity, making early recognition of clinical and laboratory clues crucial. Zohair Al Aseri MD,FRCPC EM & CCM

Pharmacology and Metabolism Principles of Disease Pharmacology and Metabolism Methanol is absorbed rapidly from the gastrointestinal tract, and blood levels peak 30 to 60 minutes after ingestion. Inhalational abuse of methanol is a recent trend that can result in toxic serum levels. Zohair Al Aseri MD,FRCPC EM & CCM

Pharmacology and Metabolism Principles of Disease Pharmacology and Metabolism A prolonged half-life of 24 to 30 hours results, Small amounts of ingested methanol may be exceptionally toxic. The smallest lethal dose reported is 15 mL of 40% methanol Zohair Al Aseri MD,FRCPC EM & CCM

Pharmacology and Metabolism Principles of Disease Pharmacology and Metabolism Methanol is oxidized by alcohol dehydrogenase (ADH) to formaldehyde, which is rapidly converted by aldehyde dehydrogenase to formic acid. Zohair Al Aseri MD,FRCPC EM & CCM

Pharmacology and Metabolism Principles of Disease Pharmacology and Metabolism Formic acid is the primary toxicant and accounts for much of the anion gap metabolic acidosis and ocular toxicity peculiar to methanol ingestion. Zohair Al Aseri MD,FRCPC EM & CCM

Metabolism of methanol Zohair Al Aseri MD,FRCPC EM & CCM

Pathophysiology Diagnosis should be considered in patients with altered mental status, visual complaints, or metabolic acidosis Symptoms are primarily neurologic, gastrointestinal, or ocular in nature. Zohair Al Aseri MD,FRCPC EM & CCM

Clinical Features Prognosis correlate with the degree of acidosis time to presentation initiation of treatment within 8 hours of exposure. coma, seizures pH less than 7.0. Zohair Al Aseri MD,FRCPC EM & CCM

Diagnostic Strategies A severe anion gap metabolic acidosis Because the onset of acidosis may be delayed 12 to 24 hours, the presence of a normal anion gap does not rule out methanol exposure. anion gap is due primarily to the presence of formic acid, with a variable contribution from lactic acid Zohair Al Aseri MD,FRCPC EM & CCM

serum toxic alcohol level is necessary Diagnostic Strategies High osmol gap. serum toxic alcohol level is necessary Zohair Al Aseri MD,FRCPC EM & CCM

Differential Considerations Ethylene glycol and methanol may cause a “double gap” (i.e., an osmol gap in addition to the anion gap). Zohair Al Aseri MD,FRCPC EM & CCM

Most ethylene glycol poisonings occur with antifreeze. Perspective Ethylene glycol is a viscous, colorless, odorless, slightly sweet-tasting liquid. Most ethylene glycol poisonings occur with antifreeze. Zohair Al Aseri MD,FRCPC EM & CCM

Pathophysiology 2.3%of a dose of ethylene glycol ultimately is converted to oxalic acid Anion gap metabolic acidosis caused mainly by glycolic acid Zohair Al Aseri MD,FRCPC EM & CCM

Clinical Features The clinical syndrome with ethylene glycol ingestionis divided into four stages: acute neurologic stage cardiopulmonary stage renal stage delayed neurologic sequelae stage Patients may die in any stage Zohair Al Aseri MD,FRCPC EM & CCM

Diagnostic Strategies serum electrolytes, calcium, BUN, creatinine, serum glucose, serum osmolality, blood ethanol level, ABG, ethylene glycol level Electrocardiogram urinalysis. crystalluria is considered the hallmark of ethylene glycol ingestion, its absence does not rule out the diagnosis because less than half of patients have this finding. Zohair Al Aseri MD,FRCPC EM & CCM

Diagnostic Strategies Freshly voided urine can be examined for fluorescence with a Wood's lamp. Sodium fluoresceinis added to antifreeze to aid in the detection of radiator leaks. Urinary fluorescence may be seen 6 hours after ingestion of fluorescein-containing antifreeze. The lack of fluorescence does not rule out ethylene glycol ingestion Zohair Al Aseri MD,FRCPC EM & CCM

Management Methanol and ethylene glycol ingestions are treated essentially the same Resuscitation and stabilization are paramount. For any significant history of exposure, treatment should be initiated pending a confirmatory toxic alcohol blood level. Zohair Al Aseri MD,FRCPC EM & CCM

Management Intubate early Gastric emptying has not been shown to alter clinical course or outcome and may be associated with complications Activated charcoal is not useful. Intubate early Zohair Al Aseri MD,FRCPC EM & CCM

Management 3 ttt goals for methanol or ethylene glycol toxicity: (1) correction of metabolic acidosis with bicarbonate (2) ADH enzyme blockade, which inhibits the metabolism of methanol and ethylene glycol to toxic metabolites (3) removal of the parent alcohol and its metabolites by hemodialysis. Zohair Al Aseri MD,FRCPC EM & CCM

Management Depending on the severity of the patient's acidosis, IV bicarbonate can be administered With ethylene glycol, the potential for worsened hypocalcemia sodium with bicarbonate should be considered. Zohair Al Aseri MD,FRCPC EM & CCM

Management Metabolism of the parent compounds by the enzyme ADH must be blocked by either ethanol or fomepizole (Antizol). Zohair Al Aseri MD,FRCPC EM & CCM

Management Ethanol may be given orally or intravenously. Potential side effects of IV administration include CNS depression Respiratory depression Hypotension Vomiting Hypoglycemia Thrombophlebitis Oral ethanol loading may be associated with gastritis. Zohair Al Aseri MD,FRCPC EM & CCM

Dosing changes are required during hemodialysis. Management Fomepizole Blocks the metabolism of methanol and ethylene glycol Fomepizoleis a pregnancy category C drug Dosing changes are required during hemodialysis. Zohair Al Aseri MD,FRCPC EM & CCM

Management Hemodialysis Indications metabolic acidosis renal compromise visual symptoms (methanol) deterioration despite intensive supportive care electrolyte imbalances unresponsive to conventional therapy. Zohair Al Aseri MD,FRCPC EM & CCM

Management Ethanol or Fomepizole Hemodialysis 50 mg of leucovorin (folinic acid) should be given for methanol toxicity In ethylene glycol cofactors thiamine and pyridoxine empirical administration is reasonable IV calcium for symptomatic hypocalcemia Magnesium is a cofactor along with thiamine for the detoxification of glycolic acid and should be replaced in patients who are deficient. If hemodiyalsis is not available, the patient should be givenan ADH inhibitor and transferred to a setting where dialysis is available. Zohair Al Aseri MD,FRCPC EM & CCM