1. Rob 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 PGY4
Lab Rounds
Jan 15, 2004

2. 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

3. Osmolar Gap = Osmolality - Osmolarity
Solute/kg of solvent
Lab measures
Osmolarity
Solute/liter of solution
You calculate!

4. Ddx of Osmolar Gap P Proteins A
Alcohols (EtOH, methanol, ethylene glycol, isopropanol, propylene glycol, diethylene glycol, triethylene glycol) S
Sugars (mannitol, glycerol, sorbital) C
Contrast dyes
Acidosis (ketoacidosis, lactic acidosis) L
Lipids
Acetone

5. Osmolar Gaps
Which formula is best?

6. Osmolarity Formulas
Other formulas…….

7. Osmolarity 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 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

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

9. 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:
Galvan 1992:
Synder 192: 1.20
Hoffman 1993: 1.09
Pappas 1985: 1.12
Britten 1972: 1.74
Glasser 1973: 1.1

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

11. 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

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

13. 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

14. 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

15. Case 2
Osmolar gap = = 0
What is a normal osmolar gap?

16. 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

17. 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?

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

19. 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

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

21. 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?

22. So what is the utility of the osmolar gap?

23. 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

24. 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

25. REMINDER: how often to measure levels
Dialysis of Methanol
[Methanol] vs time to level < 6 mmol/L
160 12hrs
100 10hrs
55 8hrs
30 6hrs
15 4hrs
7 3hrs
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!