Ethylene Glycol Poisoning

Ethylene Glycol Poisoning - Ethylene Glycol Poisoning...

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Unformatted text preview: Ethylene Glycol Poisoning Ethylene Trina Banerjee Questions to Answer How does ethylene glycol present How does the presentation differ from uremia How do you treat it? Outline Sources Pharmacology Metabolism Lab Findings Diagnosis Treatment Sources Antifreeze Brake fluids Industrial solvents Pharmacology Dihydric alcohol Odorless, colorless, water soluble, sweet tasting (“the sweet killer”) Molecular Weight 62 kDa Metabolism Absorption Excretion Absorption Absorption Readily absorbed from the GI tract Readily within 30-60 minutes Maximal blood concentration reached Maximal in 1-4 hours 1/2 life is 3-8 hours 1/2 Lethal dose is estimated as 1-1.5 Lethal mls/kg or 100mls Metabolism/Excretion Metabolism/Excretion Liver Liver Kidney Kidney Liver Liver Metabolizes 80% of what is absorbed Metabolizes Half life with liver metabolism is 3-8 Half hours Liver Continued Liver Broken down in the liver by alcohol Broken dehydrogenase to four compounds Glycoaldehyde which is metabolized Glycoaldehyde by aldehyde dehydrogenase to glycolic acid, which is metabolized to glycoxylic acid, which is metabolized to oxalic acid Liver Continued Liver The conversion of glycolic acid to The glycoxylic acid is the rate limiting step These metabolites are oxidative These phosphorylation toxins that cause CNS depression and cardio-pulmonary and renal failure Kidney Kidney The proximal tubule reabsorbs 80% of The what is filtered Half life with renal metabolism is 18Half 20 hours The remaining 20% is excreted The unchanged from the kidneys Clinical Presentation Clinical Neurologic: 30 minutes to 12 hours Neurologic: Cardiopulmonary: 12-36 Hours Cardiopulmonary: Renal: 24-72 Hours Renal: Neurologic Neurologic CNS manifestations: Somnolence, CNS Disorientation, agitation, confusion, ataxia (pt may appear drunk) – Pathophysiology: Initially a direct effect of ethylene glycol, which in low doses causes euphoria and in high doses causes CNS depression Cardiopulmonary Cardiopulmonary Deeper CNS Symptoms: Stupor, Deeper coma, nystagmus, ocular paresis, myoclonus and focal or universal seizures – Results from high dose of ethylene glycol – Results from calcium oxalate desposition in the brain Cardiopulmonary Cont. Cardiopulmonary Leukocytosis Leukocytosis Seizures Seizures – Direct effect of the calcium oxalate – May also result from hypocalcemia Heart failure Heart – Arrythmias result from hypocalcemia and acidosis Cardiopulmonary Cont. Cardiopulmonary Respiratory Distress Respiratory – As compensation for metabolic acidosis and from the hypoxia Tachycardia, HTN, Dyspnea, Tachycardia, Tachypnea, Kussmaul’s Respiration – As compensation for metabolic acidosis and from hypoxia Renal Renal Will get flank pain, renal tubular Will necrosis, hematuria, proteinuria, anuria or oliguria – Thought to result from calcium oxalate blocking the renal tubules – Calcium oxalate is internalized by the proximal tubule causing mitochondrial damage, and resulting in ATN Renal Continued Renal Calcium oxalate monohydrate crystals Calcium adhere to the proximal tubule membrane and are endocytosed within 30 minutes Once they enter the proximal cell, Once calcium oxalate can inhibit the electron transport chain Renal Continued Renal COM can also lead to the COM mitochondrial permeability transition (MPT) which increases the permeability of mitochondria – Molecules up to 1500 kDA can enter the mitochondria – Causes depolarization, inhibition of ox phos, and ATP depletion Cranial Nerve Cranial Abnormalities Occur with the ingestion of at least Occur 100 cc of ethylene glycol Occur 6-18 days after the ingestion of Occur ethylene glycol Postmortem studies attribute this to Postmortem inflammation around the nerve from oxalate microcrystal deposition Cranial Nerve Cranial Abnormalities Cont. Type of treatment is immaterial in Type terms of Full recovery may take a year Full Laboratory Findings Laboratory High osmolarity with osmolar gap High – Ethylene glycol and glycoaldehyde increase serum osmolarity – Occurs early on, may disappear later as ethylene glycol and glycoaldehyde are metabolized High anion gap metabolic High acidosis Partially because of glycolic acid Partially – Because the conversion of glycolic acid to glycoxilic acid is the rate limiting step, glycolic acid is able to build up High anion gap metabolic High acidosis Partially because lactic acidosis Partially – The first two steps in ethylene glycol metabolism cause the reduction of NAD to NADH. The elevated NADH to NAD ration causes the conversion of pyruvate to lactate Calcium oxalate crystals Calcium Appear in the urine 4-8 hours after Appear ingestion May appear as either an elongated May crystal (monohydrate) or octahedral like a pyramid Will deposit in almost every tissue of Will the body including the brain, heart, lungs, kidneys, and urine Further Metabolic Further Abnormalities Hypocalcemia: Hypocalcemia: – Caused by precipitation of oxalate Hyperkalemia: Hyperkalemia: – Caused by renal failure Diagnostic Tests Diagnostic Flourescin is added to antifreeze and Flourescin can be detected by Wood’s light, but is cleared within 4 hours of ingestion Serum ethylene glycol levels can Serum disappear after 5 days, whereas urine ethylene glycol levels persist for 17 days Treatment Treatment Inhibit Absorption Inhibit Correct Acidosis Correct Inhibition of Metabolism Inhibition Elimination of parent compound and Elimination the metabolites Inhibit Absorption Inhibit Gastric Treatment: Gastric – Gastric aspiration followed by lavage useful up to 1 hour after ingestion – Syrup of ipecac contraindicated because of aspiration – Activated charcoal: Not helpful Treatment of Acidosis Treatment Bicarb drip: Bicarb – Used to increase the bicarb, but also by increasing the urine pH will promote the excretion of glycolic acid and lactic acidosis Inhibition of Metabolism Inhibition Fomepizole (4-methylpyrazole) Fomepizole Ethanol Ethanol Thiamine Thiamine Pyridoxine Pyridoxine Fomepizole (4Fomepizole methylpyrazole) Mechanism of Action: Mechanism – Competitive inhibitor of alcohol dehydrogenase, alcohol dehydrogenase has 500-1000 times the affinity than for ethylene glycol Fomepizole (4Fomepizole methylpyrazole) Cont. Loading dose is 15mg/kg in 100 mls of Loading NS or D5W infused over 30 minutes Next 10mg/kg every 12 hours for two Next days Next 15mg/kg every 12 hours until the Next ethylene glycol level is less than 2 and pt. asymptomatic with a normal pH Fomepizole (4Fomepizole methylpyrazole) Cont. Dializable so administration interval Dializable should be reduced to 4 hours during dialysis Adverse effects are dizziness, Adverse headache, and nausea Ethanol Ethanol Mechanism of Action: Mechanism – Competitive inhibitor of alcohol dehydrogenase, alcohol dehydrogenase has 100 times the affinity than for ethylene glycol Ethanol Cont. Ethanol Dosing: Dosing: – Goal ethanol level of 10-12.5 mg/dl, which is enough to saturate the enzyme – Loading dos 0.6-0.7 g ethanol/kg, maintenance dose is 66 mg ethanol/kg/hr for nondrinkers and 154 mg/kg/hr for alcoholics – Goal is to use until the ethylene glycol level is <2 Ethanol Cont. Ethanol Frequent dose adjustments may be Frequent necessary, so the level should be checked every 1-2 hours Adverse effects are CNS depression, Adverse hepatotoxicity, and hypoglycemia Thiamine Thiamine Mechanism of Action: Mechanism – Prevents the formation of oxalic acid by facilitating the conversion of glycoxylic acid to alpha-Hydroxy Beta ketoadipic acid. Dose: Dose: – 100 mg IV q6 until ethylene glycol can no longer be measured in the serum Pyridoxine Pyridoxine Mechanism of Action: Mechanism – Prevents the oxalic acid by converting gylcoxylic acid to hippuric acid metabolites and glycine. Dose: Dose: – 50 mg IV q6 Adverse Reaction: Adverse – Can cause a toxic sensory neuropathy Elimination:Hemodialysis Elimination:Hemodialysis Mechanism of Action: Mechanism – Removes ethylene glycol and glycolate effectively Indications: Indications: – Ethylene glycol concentration>500mg/L or presence of severe metabolic acidosis, renal failure, severe electrolyte imbalance, or generally deteriorating ...
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