Presentation on theme: "Rob Hall PGY4 Lab Rounds Jan 15, 2004"— Presentation transcript:
1Rob Hall PGY4 Lab Rounds Jan 15, 2004 Osmolar Gaps: How does EtOH contribute to osmolar gaps? Can osmolar gaps be used to rule out toxic alcohols?Rob Hall PGY4Lab RoundsJan 15, 2004
2Why review? Osmolar gaps aren’t perfect thus why use? Routine measurement of toxic alcohols is impracticalLabor intensiveLong turn around timeOnly measured in tertiary care centersOsmolar gaps thus likely have some role and we need to know the major limitations
3Osmolar Gap = Osmolality - Osmolarity Solute/kg of solventLab measuresOsmolaritySolute/liter of solutionYou calculate!
4Ddx of Osmolar Gap P Proteins A Alcohols (EtOH, methanol, ethylene glycol, isopropanol, propylene glycol, diethylene glycol, triethylene glycol)SSugars (mannitol, glycerol, sorbital)CContrast dyesAcidosis (ketoacidosis, lactic acidosis)LLipidsAcetone
7Osmolarity Formulas Calgary Edmonton 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 lineThought to be the best formula: Dorwat. Clin Chemistry 1975.NB: EtOH is not automatically added!Edmonton2Na + BUN + glucoseSerum is only 93% water: 1.86/0.93 = 2
8Case 1 Intoxicated male Na 140, BUN 5, Gluc 5, EtOH 75 Osmolality = 385Osmolarity = 2(140) = 365Osm gap = 20How does EtOH effect osmolar gaps?
9Ethanol and the Osmolar Gap Several studies have noted the increase in osmolar gap with rising EtOH in a NON 1:1 relationshipMany different EtOH conversion factors have been developed…Geller 1986:Galvan 1992:Synder 192: 1.20Hoffman 1993: 1.09Pappas 1985: 1.12Britten 1972: 1.74Glasser 1973: 1.1
10Ethanol and the Osmolar Gap Purssell. Ann Emerg Med 2001: 38:Derived a formula to account for the relationship between ethanol and osmolar gapProspectively validatedBest formula = EtOH (mmol/L) X 1.25
11Explanation 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
12Data from our own Lab!This data supports the 1.25 EtOH conversion
13Case 1 Osmolality = 385 Osmolarity = 2(140)+5+5+75 = 365 Osm gap = 20 How does EtOH effect osmolar gaps?EtOH X 1.25 = 94Osmolality = 385Osmolarity = 384Osm gap = 1
14Case 2 35 yo male Took a swig of a mug that had antifreeze Na 140, BUN 5, Gluc 5, EtOH 25Osmolality = 321NO anion gap (HCO3 24)Osmolarity = 2Na + BUN + Gluc + EtOH X 1.25 = 321
15Case 2Osmolar gap = = 0What is a normal osmolar gap?
16What is a “Normal” Osmolar Gap? Hard to define!Depends on………..Lab method of osmolality determinationOsmolarity formula usedLab error of Na, BUN, Gluc, EtoHEtOH conversion factors usedThere are few studies documenting what normal osmolar gaps are in the population
17What is a “Normal” Osmolar Gap? Traditional “Normal Osmolar Gap” is < 10Case 2: osmolar gap = 0Can osmolar gaps be used to rule out toxic alcohol ingestions?Is there a “cutoff” where toxic alcohols should be routinely measured?
18Normal Osmolar Gap: Hoffman. J Toxicol Clin Toxicol Normal Osmolar Gap: Hoffman. J Toxicol Clin Toxicol Na + BUN + Gluc + EtOH-14+10+4-8-2
19When should toxic alcohols be measured? AMA guidelines Calgary (1.86Na + BUN + Gluc + EtOH +9)Osmolar gap > 10: measure methanol and ethylene glycolEdmonton (2Na + BUN + Gluc + EtOH)Osmolar gap > 2: measure ethylene glycolOsmolar gap > 5: measure methanol
20Can these cut offs r/o a significant toxic alcohol ingestion? Baseline -14Osm gap 0Methanol level of 14!!!-14
21Additional problemsWhat 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?
23Conclusions 1EtOH has contributes more to osmolarity than expected: EtOH X 1.25 is likely the best conversion factorWhich 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
24Conclusions 2Osmolar gaps are NOT 100% reliable to exclude treatable toxic alcohol ingestionsLow suspicion check osmolar gapHigh suspicion low threshold to check toxic alcohol levels regardless of osmolar gapRemember: osmolar gaps are irrelevant when the patient has an AGMA from toxic metabolites
25REMINDER: how often to measure levels Dialysis of Methanol[Methanol] vs time to level < 6 mmol/L160 12hrs100 10hrs55 8hrs30 6hrs15 4hrs7 3hrsEthanol therapy alone for MethanolADH is blocked by EtOH; excretion by pulmonary/renalT1/2 increases A LOTT ½ 30-70hrsDon’t measure levels q 4hrs!