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?

• 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



• Does lithium cause an anion gap?

143

3.6

109

36

14.6



• Does lithium cause an anion gap?

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

143

3.6

109

36

14.6


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



• Lactic acid 1.3

138

3.8

100

18

24

1.2

Osm 303 Lactic Acid 1.2

141



• Lactic acid 1.3

138

3.8

100

18

24

1.2


141138

3.8

98

16

28

1.2

Osm 312 Lactic Acid 4

166



• Lactic acid 1.3

138

3.8

100

18

24

1.2


141138

3.8

98

16

28

1.2


166

136

3.8

94

15

22

1.3


154



• Lactic acid 1.3

138

3.8

100

18

24

1.2


141138

3.8

98

16

28

1.2


166

136

3.8

94

15

22

1.3


154135

3.8

95

16

24

0.9


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


• low volume of distibution



• low protein binidng



• 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

• 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.

Osmolar Gap

Health & Medicine

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