Osmolar Gaps:Osmolar Gaps:How does EtOH contribute to osmolar gaps?How does EtOH contribute to osmolar gaps?

Can osmolar gaps be used to rule out toxic alcohols?Can osmolar gaps be used to rule out toxic alcohols?

Rob Hall PGY4

Lab Rounds

Jan 15, 2004

Why review?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

Osmolar Gap = Osmolar Gap = Osmolality - OsmolarityOsmolality - Osmolarity

Osmolality– Solute/kg of solvent

–Lab measures

Osmolarity– Solute/liter of solution– You calculate!

Ddx of Osmolar GapDdx of Osmolar GapP 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

Osmolar GapsOsmolar Gaps

Which formula is best?

Osmolarity FormulasOsmolarity Formulas

Other formulas…….

Osmolarity FormulasOsmolarity 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

Case 1Case 1

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

Ethanol and the Osmolar GapEthanol 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

Ethanol and the Osmolar GapEthanol 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

Explanation for EtOH X 1.25Explanation for EtOH X 1.25

Ethanol has a “non-ideal” osmotic behaviorEthanol has a non-ideal osmotic behavior

because molecules form physiochemical bonds with other molecules resulting in an effect on osmolarity that is non-uniform

Data from our own Lab!Data from our own Lab!O-Gap (absence of toxic Alc)

0

20

40

60

80

100

120

140

160

180

200

0 50 100 150 200

Ethanol mmol/L

O-G

AP

, mo

smo

L

This data supports the 1.25 EtOH conversion

Case 1Case 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

Case 2Case 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

Case 2Case 2

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

What is a “Normal” Osmolar Gap?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

What is a “Normal” Osmolar Gap?What is a “Normal” Osmolar Gap?

Traditional “Normal Osmolar Gap” is < 10 Case 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?

Normal Osmolar Gap:Normal Osmolar Gap:Hoffman. J Toxicol Clin Toxicol. 1993Hoffman. J Toxicol Clin Toxicol. 1993

2Na + BUN + Gluc + EtOH2Na + BUN + Gluc + EtOH

-8 -2 +4 +10-14

When should toxic alcohols be When should toxic alcohols be measured? AMA guidelinesmeasured? 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

Can these cut offs r/o a significant Can these cut offs r/o a significant toxic alcohol ingestion?toxic alcohol ingestion?

Baseline -14 Osm gap 0 Methanol

level of 14!!!

-14 0

Additional problemsAdditional 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?

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

Conclusions 1Conclusions 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

Conclusions 2Conclusions 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

REMINDER: REMINDER: how often to how often to measure levels 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!