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Osmolar Gaps: How does EtOH contribute to osmolar gaps? Can osmolar gaps be used to rule out toxic alcohols? Rob Hall PGY4 Lab Rounds Jan 15, 2004

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Why review? Osmolar gaps aren’t perfect thus why use? Routine measurement of toxic alcohols is impractical – Labor intensive – Long turn around time – Only measured in tertiary care centers Osmolar gaps thus likely have some role and we need to know the major limitations

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Osmolar Gap = Osmolality - Osmolarity Osmolality – Solute/kg of solvent – L ab measures Osmolarity – Solute/liter of solution – You calculate!

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Ddx of Osmolar Gap PProteins AAlcohols (EtOH, methanol, ethylene glycol, isopropanol, propylene glycol, diethylene glycol, triethylene glycol) SSugars (mannitol, glycerol, sorbital) CContrast dyes AAcidosis (ketoacidosis, lactic acidosis) LLipids AAcetone

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Osmolar Gaps Which formula is best?

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Osmolarity Formulas Other formulas…….

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Osmolarity Formulas Calgary – 1.86Na + BUN + glucose + 9 – Why 1.86: 93% is in Na+, Cl- (ionized form) and the remainder is in the NaCl (nonionized form) – Why +9 factor: intercept for multiple regression line – Thought to be the best formula: Dorwat. Clin Chemistry 1975. – NB: EtOH is not automatically added! Edmonton – 2Na + BUN + glucose – Serum is only 93% water: 1.86/0.93 = 2

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Case 1 Intoxicated male Na 140, BUN 5, Gluc 5, EtOH 75 Osmolality = 385 Osmolarity = 2(140)+5+5+75 = 365 Osm gap = 20 How does EtOH effect osmolar gaps?

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Ethanol and the Osmolar Gap Several studies have noted the increase in osmolar gap with rising EtOH in a NON 1:1 relationship Many different EtOH conversion factors have been developed… – Geller 1986: 1.20 – Galvan 1992: 1.14 – Synder 192:1.20 – Hoffman 1993:1.09 – Pappas 1985:1.12 – Britten 1972:1.74 – Glasser 1973: 1.1

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Ethanol and the Osmolar Gap Purssell. Ann Emerg Med 2001: 38: 653- 659. – Derived a formula to account for the relationship between ethanol and osmolar gap – Prospectively validated – Best formula = EtOH (mmol/L) X 1.25

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Explanation for EtOH X 1.25 Ethanol has a “non-ideal” osmotic behavior Ethanol has a non-ideal osmotic behavior because molecules form physiochemical bonds with other molecules resulting in an effect on osmolarity that is non-uniform

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Data from our own Lab! This data supports the 1.25 EtOH conversion

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Case 1 Osmolality = 385 Osmolarity = 2(140)+5+5+75 = 365 Osm gap = 20 How does EtOH effect osmolar gaps? EtOH X 1.25 = 94 Osmolality = 385 Osmolarity = 384 Osm gap = 1

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Case 2 35 yo male Took a swig of a mug that had antifreeze Na 140, BUN 5, Gluc 5, EtOH 25 Osmolality = 321 NO anion gap (HCO3 24) Osmolarity = 2Na + BUN + Gluc + EtOH X 1.25 = 321

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Case 2 Osmolar gap = 321 - 321 = 0 What is a normal osmolar gap?

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What is a “ Normal ” Osmolar Gap? Hard to define! Depends on……….. – Lab method of osmolality determination – Osmolarity formula used – Lab error of Na, BUN, Gluc, EtoH – EtOH conversion factors used There are few studies documenting what normal osmolar gaps are in the population

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What is a “ Normal ” Osmolar Gap? Traditional “Normal Osmolar Gap” is < 10 Case 2: osmolar gap = 0 Can osmolar gaps be used to rule out toxic alcohol ingestions? Is there a “cutoff” where toxic alcohols should be routinely measured?

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Normal Osmolar Gap: Hoffman. J Toxicol Clin Toxicol. 1993 2Na + BUN + Gluc + EtOH -8 -2 +4 +10 -14

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When should toxic alcohols be measured? AMA guidelines Calgary (1.86Na + BUN + Gluc + EtOH +9) – Osmolar gap > 10: measure methanol and ethylene glycol Edmonton (2Na + BUN + Gluc + EtOH) – Osmolar gap > 2: measure ethylene glycol – Osmolar gap > 5: measure methanol

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Can these cut offs r/o a significant toxic alcohol ingestion? Baseline -14 Osm gap 0 Methanol level of 14!!! -140

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Additional problems What is the normal distribution for the formula that we use in Calgary for osmolarity? What is the true effect of EtOH? What is a significant toxic alcohol level? – Nobody really knows! – Evidence for when to dialyze based on case series and case reports. – Are you willing to miss a methanol level of 5, 10, or 15 mmol/L?

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So what is the utility of the osmolar gap?

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Conclusions 1 EtOH has contributes more to osmolarity than expected: EtOH X 1.25 is likely the best conversion factor Which formula to use for osmolarity? – It doesn’t really matter, just be aware of suggested cut offs for toxic alcohol measurement and the inherent limitations of such cut offs

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Conclusions 2 Osmolar gaps are NOT 100% reliable to exclude treatable toxic alcohol ingestions Low suspicion ------ check osmolar gap High suspicion ------ low threshold to check toxic alcohol levels regardless of osmolar gap Remember: osmolar gaps are irrelevant when the patient has an AGMA from toxic metabolites

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REMINDER: how often to measure levels Dialysis of Methanol [Methanol] vs time to level < 6 mmol/L – 16012hrs – 10010hrs – 558hrs – 306hrs – 154hrs – 73hrs Ethanol therapy alone for Methanol – ADH is blocked by EtOH; excretion by pulmonary/renal – T1/2 increases A LOT – T ½ 30-70hrs – Don’t measure levels q 4hrs!

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