Lecture 6 Toxic Alcohol Poisoning Kent

TOXIC ALCOHOLS: MeOH and EG COMPARISON: METHANOL (MeOG) • Fuels, solvents SIMILARITIES • Both referred to as antifreeze • Windshield washer & gas line antifreeze • Potentially toxic if > 1 big mouthful • Lacquer thinner • Produce ↑ OG with delayed onset ↑ AG ETHYLENE GLYCOL (EG) • Radiator antifreeze • Present with early non-specific symptoms TOXIC DOSE • One mouthful  serious toxicity in adult • Both treated with bicarb, fomepizole and HD DIFFERENCES • End organ toxicity: MeOH eyes, EG kidney • Metabolism: MeOH much more slowly BOTTOM LINE: • Elimination during antidote: MeOH much slower • Why “toxic”? because they make you more than drunk …

o Ethylene glycol causes renal failure o Methanol causes blindness and brainstem infarcts ALCOHOLIC KETOACIDOSIS: o Metabolites cause metabolic acidosis • Chronic alcohol use, liver disease, binge drinking • Toxic/lethal dose is very small • Starvation (reduced food intake) • Similar at-risk group • Abd. pain, N/V, dehydration common +/- altered mental status • Diagnosis is critical !!! • Increased anion and osmole gap CAUSE: EXTENT OF PROBLEM IN BC: 1. Decreased oral intake • 30 – 40 hospital admissions/years  5 deaths/year 2. Depletion of glycogen stores • Variety of situations 3. Increased levels of NADH o Adults & adolescent: suicide, substance abuse, unintentional 4. Breakdown of fatty acids to acetyl CoA o Pediatric : unintentional 5. Conversion of acetyl CoA to acetoacetate & beta-hydroxybutyrate

CALCULATE “THE GAPS” KETONE TESTS: • Calculate anion gap (AG): Na – (Cl + HCO3) ROUTINE • Highly sensitive to acetoacetic acid o Normal = 8-12 (or lower) KETONE • Somewhat sensitive to acetone • Calculate osmole gap (OG): Om – [2*Na + urea + glucose + 1.25*ethanol] TESTS • Not sensitive to beta-hydroxybutyrate (BHB) o Normal < 10 WITH AKA • Routine ketones may result in low or normal • Need specific test for BHB TOXIC ALCOHOL POISONING: ALCOHOL POISONING VS. AKA COMPARISON: SIMILARITIES • Metabolic acidosis with ↑ AG, ↑ OG • Non-specific sx (GI, CNS, sick) • Similar at-risk patient group DIFFERENCES • OG with AKA is rarely > 20 – 30 • Serum EtOH usually low in AKA (post-binge) • AKA usually improves with supportive care

EARLY ADVANCED LATE o Toxic alcohol worsens

• EG < 4-6 h • Looks really sick • MeOH: visual sx • Beta-hydroxybutyrate elevated with AKA • MeOH < 10-12 h • Non-specific • EG: renal failure • • GI upset Brain Injury ISOPROPYL ALCOHOL (IPA): • Intoxication • CNS depression  IPA has twice the intoxicating effects of ethanol (maybe) • Ketosis, fruity breath odor

• Abdominal pain TREATMENT OF TOXIC ALCOHOL POISONING: • Hypotension and respiratory failure after large ingestions • MeOH or EG DIAGNOSIS: ADH INHIBITOR: Fomepizole or ethanol • Osmole gap elevated (both IPA & acetone are osmotically active) elimination t1/2 ↑↑ (EG to 18 h; MeOH to 48 h) • No anion gap, no acidosis

• Specific IPA levels – limited availability • Acid metabolites HEMODIALYSIS – enhances elimination, • Elevated SCr – acetone can interfere with some SCr assays (formate or glycolate) can correct acidosis

TREATMENT:

• Supportive care alone for most cases • Metabolic acidosis IV SODIUM BICARBONATE • For methanol: IV FOLIC ACID to enhance Hypotension – may require fluids and vasopressors formate metabolism • Respiratory depression – may require intubation and ventilation • Dialysis – almost never required TREATMENT GUIDELINES OF TOXIC ALCOHOL POISONING: • SODIUM BICARBONATE if pH < 7.25 TOXIC ALCOHOL POISONING VS. IPA COMPARISON: • ANTIDOTE: fomepizole or ethanol SIMILARITIES • Elevated OG (both IPA & acetone) o EG > 3, MeOH > 6 mmol/L OR • Non-specific symptoms (GI, CNS, sick) o OG > 10 and recent hx toxic alcohol ingestion OR • Similar at-risk patient group o Clinical suspicion and at least 2 of: • Elevated SCr (similar to EG) ▪ HCO3 < 20, OG > 10, AG > 16, pH < 7.3, oxylate crystals in urine DIFFERENCES • No AG or acidosis with IPA • HEMODIALYSIS: EG > 8, MeOH > 15, pH < 7.25, ↑ SCr, very sick • IPA usually improves with supportive care • FOLATE: for MeOH or if not sure • Elevated SCr (IPA is lab interference, o Leucovorin or folic acid 1 mg/kg (50 mg) q6hr EG is actual renal injury)