Transcript Osmolar Gaps

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
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 =
Osmolality - Osmolarity

Osmolality
– Solute/kg of solvent
–Lab measures

Osmolarity
– Solute/liter of solution
– You calculate!
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
Osmolar Gaps
Which formula is best?
Osmolarity Formulas

Other formulas…….
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
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?
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…
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–
–
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–
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Geller 1986:
Galvan 1992:
Synder 192:
Hoffman 1993:
Pappas 1985:
Britten 1972:
Glasser 1973:
1.20
1.14
1.20
1.09
1.12
1.74
1.1
Ethanol and the Osmolar Gap

Purssell. Ann Emerg Med 2001: 38: 653659.
– 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 1.25
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

Data from our own Lab!
O-Gap (absence of toxic Alc)
200
180
This data
supports
the 1.25
EtOH
conversion
O-GAP, mosmoL
160
140
120
100
80
60
40
20
0
0
50
100
Ethanol m m ol/L
150
200
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
Case 2





35 yo male
 Osmolarity = 2Na +
Took a swig of a mug BUN + Gluc + EtOH X
1.25 = 321
that had antifreeze
Na 140, BUN 5, Gluc
5, EtOH 25
Osmolality = 321
NO anion gap (HCO3
24)
Case 2

Osmolar gap = 321 - 321 = 0
 What is a normal osmolar gap?
What is a “Normal” Osmolar Gap?

Hard to define!
 Depends on………..
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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?
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?

Normal Osmolar Gap:
Hoffman. J Toxicol Clin Toxicol. 1993
2Na + BUN + Gluc + EtOH
-14
-8
-2
+4
+10
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
Can these cut offs r/o a significant
toxic alcohol ingestion?

-14
0
Baseline -14
 Osm gap 0
 Methanol
level of 14!!!
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?
So what is the utility of the
osmolar gap?
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
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
REMINDER: how often to
measure levels

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!

Dialysis of Methanol
 [Methanol] vs time to
level < 6 mmol/L
– 160
– 100
– 55
– 30
– 15
– 7
12hrs
10hrs
8hrs
6hrs
4hrs
3hrs