Osmolar Gap

the osmolar gap

Joel M. Topf, MDNephrologypbfluids.com

• 65 yr old male

• Clouded consciousness

• History of mental illness

http://www.cmaj.ca/cgi/content/full/176/7/921

• Anion gap?

• Osmolar gap?

142

3.8

115

26

18.6

1.0

Osmolality 308

100

lithium level 6 mmol/L

12 hours later

• urine output 2.4 liters over 6 hours

143

3.6

109

36

14.6

1.1

Osmolality 324

Lithium 14.5

100

what do you do?

what do you do?

• lithium fell to 4.7 after 4 hours of dialysis

Peak levels occur 2-4 hours pos t - i nges t i on , although absorption can be m u c h s l o w e r in massive overdose or with ingestion of sustained-release preparations.

• therapeutic dose is 300-2700 mg/d

• Molecular weight of lithium carbonate?

• Li2CO3 = 74

• Volume of distribution of 0.6-1 l/kg

• Desired levels 0.6-1.2 mEq/L

• Half-life is from 12-27 hours after a single dose

• 36 hours in elderly persons

• Half-life grows with chronic use

3 categories of lithium toxicity

Acute

Acute-on-chronic

Chronic

Acute• No tissue body burden

• Symptoms are predominately GI

• nausea, vomiting, cramping, diarrhea. 

• Progression can involve neuromuscular signs

• tremulousness, dystonia, hyperreflexia, and ataxia 

• Cardiac dysrhythmias have been reported but rarely occur. 

• The most common ECG finding is T-wave flattening

Acute-on-chronic

• Take lithium regularly and have sudden ingestion

• May display both GI and neurologic symptoms,

• Serum levels can be difficult to interpret

• Treated according to clinical manifestations

Chronic

• Large body burden of lithium

• Due to newly impaired renal excretion possibly via hypovolemia

• Primarily neurologic. 

• Mental status is often altered

• From coma to seizures

• Syndrome of Irreversible Lithium-Effectuated NeuroToxicity (SILENT) such as cognitive impairment, sensorimotor peripheral neuropathy, and cerebellar dysfunction.  

•

143

3.6

109

36

14.6

1.1Osmolality 324 Lithium 14.5100

• Does lithium cause an osmolar gap?

143

3.6

109

36

14.6

1.1Osmolality 324 Lithium 14.5100

• Does lithium cause an osmolar gap?

• Does lithium cause an anion gap?

143

3.6

109

36

14.6

1.1Osmolality 324 Lithium 14.5100

• Does lithium cause an osmolar gap?

• Does lithium cause an anion gap?

• What is lithium’s contribution to the osmolar gap?

143

3.6

109

36

14.6

1.1Osmolality 324 Lithium 14.5100

lactic acid

• does it increase the osmolar gap

• shouldn’t because it is anion

sick patient

• 58 year old white male

• history of COPD

• automobile accident with blunt trauma to chest

• intubated on the vent

• day 6 in the ICU, increasing oxygen demand

• patient is agitated and bucking the vent

• patient on pip/tazo, orazepam drip, TPN

• Lactic acid 1.3

• patient is agitated and bucking the vent

• patient on pip/tazo, orazepam drip, TPN

• Lactic acid 1.3

• patient is agitated and bucking the vent

• patient on pip/tazo, orazepam drip, TPN

• Lactic acid 1.3

138

3.8

100

18

24

1.2

Osm 303 Lactic Acid 1.2

141

• patient is agitated and bucking the vent

• patient on pip/tazo, orazepam drip, TPN

• Lactic acid 1.3

138

3.8

100

18

24

1.2

Osm 303 Lactic Acid 1.2

141138

3.8

98

16

28

1.2

Osm 312 Lactic Acid 4

166

• patient is agitated and bucking the vent

• patient on pip/tazo, orazepam drip, TPN

• Lactic acid 1.3

138

3.8

100

18

24

1.2

Osm 303 Lactic Acid 1.2

141138

3.8

98

16

28

1.2

Osm 312 Lactic Acid 4

166

136

3.8

94

15

22

1.3

Osm 325 Lactic Acid 5

154

• patient is agitated and bucking the vent

• patient on pip/tazo, orazepam drip, TPN

• Lactic acid 1.3

138

3.8

100

18

24

1.2

Osm 303 Lactic Acid 1.2

141138

3.8

98

16

28

1.2

Osm 312 Lactic Acid 4

166

136

3.8

94

15

22

1.3

Osm 325 Lactic Acid 5

154135

3.8

95

16

24

0.9

Osm 335 Lactic Acid 5

123

propylene glycol

• solvent for etomidate

• phenytoin

• diazepam

• lorazepam

• phenobarbital

• nitroglycerin

• digoxin

• hydralazine

• TMP-SMX

• icu patients

• especially with liver/ kidney dysfunction

• metabolism generates D-lactic and or L-lactic acid

• typically mild 2-6

• increase serum osmolality maybe only indication of toxicity

• Contamination of spirits with 50-100% methanol

• 154 ingestions

• 43 died without making it to the hospital

• 111 admissions with confirmed methanol intoxication

• 25 died

• 66 survived, no sequelae

• 20 survived, + sequelae

http://www.biomedcentral.com/1472-6904/9/5

• found a high rate of developing eye sequelae in the initially unaffected (8/22)

• 30% 6-year mortality found across all age groups

methanol

• mortality increases from 8-36% to 50-80% when at the initiation of treatment the:

• HCO3 < 10

• pH < 7.1

• formaldehyde has half life of 1-2 minutes

• formic acid levels are proportional to pH

• formic acid damages the optic disk independent of pH

methanol

• visual changes

• decreased acuity, photophobia

• abdominal pain

• pancreatitis

• Neurologic changes

• stupor, confusion, coma

putaminal necrosis

• rigidity

• tremor

• masked faces

• monotonous speech

T2-weighted MRI of the brain: bilateral, symmetric hyperintense putaminal lesions, suggesting hemorrhagic necrosis (arrows). Direct toxicity of formic acid (an end product of methanol metabolism), ischemic injury, and acidosis are postulated mechanisms of putaminal injury.

• gi absorption is rapid and complete

• little use of charcoal, emesis or gastric lavage

indications for ADH inhibition

• Methanol level > 20 mg/dL

• history of ingestion and osmolal gap > 10

• strong suspicion with two of the following

• pH <7.3

• HCO3 < 20

• osmolal gap > 20

fomepizol (Antizol)

• molecular weight 82

• volume of distribution 0.6-1.0

• protein binding negligable

• ethanol has 10-20x the affinity of alcohol dehydrogenase than other alcohols

• at 100 mg/dL it completely inhibits alcohol dehydrogenase

• fomepazole has 500-1000x the affinity of ADH than ethanol

why is dialysis effective?

name the 3 factors that make a substance dialyzable

name the 3 factors that make a substance dialyzable

• low volume of distibution

name the 3 factors that make a substance dialyzable

• low volume of distibution

• low protein binidng

name the 3 factors that make a substance dialyzable

• low volume of distibution

• low protein binidng

• low molecular weight

intermittent hemodialysis

continuous renal replacement therapy

peritoneal dialysis

• folic acid promotes metabolism of formate to CO2 and water

• thiamine promotes conversion of glyoxylate to glycine and glycolic acid to alpha-hydroxy-beta-ketoadipate

ethylene glycol

• ratio of ethylene glycol to methanol intoxications:

• 6:1

• 5,800 cases/year

woods lamp

woods lamp

• Glycolate causes most of the acidosis

• oxalate + calcium causes tissue damage

• kidney

• hearty

• brain

• lung

• calcium oxalate deposition can also cause hypocalcemia

• heart failure

• hypotension

3 phases of symptoms

• symptoms in three stages

• neurologic

• confusion focal neurologic defects

• cardiopulmonary dysfunction

• renal failure

indications for ADH inhibition

• Ethylene glycol level > 20 mg/dL

• history of ingestion and osmolal gap > 10

• strong suspicion with two of the following

• pH <7.3

• HCO3 < 20

• osmolal gap > 10

• oxalate crystals

• can cause a false positive assay for lactic acidosis

• thiamine and pyridoxime may shift ethylene glycol metabolsm to less toxic end-products

Diethylene Glycol Intoxication

• break fluid

• adulterant in alcoholic beverages

• acute kidney injury is common

• hepatitis

• pancreatitis

• small changes in osmolal gap

• molecular weight 106

• dialysis is effective

isopropyl alcohol

• rubbing alcohol

• no acidosis

• dialysis for:

• Coma

• Hypotension

• Isopropyl level over 200

• 131 patients

• 20 exposed to ethylene glycol or methanol

• Using a cut-off of 10 mmol/kg

• sensitivity of 0.85

• specificity of 0.50

• cut-off of 20

• sensitivity 0.76

• specificity of 0.61

osmolar gap, normal anion gap

• mannitol

• causes acute renal failure from osmotic damage of proximal tubule cells

• increased risk of acute renal failure when the osmolar gap is over 55.