Osmolar Gaps: How does EtOH contribute to osmolar gaps? Can osmolar gaps be used to rule out toxic alcohols?

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Osmolar GapsHow 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 arent 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
• Lab measures

• Osmolarity
• Solute/liter of solution
• You calculate!

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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
A Acidosis (ketoacidosis, lactic acidosis)
L Lipids
A Acetone
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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)5575 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 11
  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)5575 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 lt 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 GapHoffman. J Toxicol Clin
Toxicol. 19932Na BUN Gluc EtOH
-14
10
4
-2
-8
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When should toxic alcohols be measured? AMA
guidelines

• Calgary (1.86Na BUN Gluc EtOH 9)
• Osmolar gap gt 10 measure methanol and ethylene
  glycol
• Edmonton (2Na BUN Gluc EtOH)
• Osmolar gap gt 2 measure ethylene glycol
• Osmolar gap gt 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!!!

-14
0
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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 doesnt 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 lt 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
• Dont measure levels q 4hrs!