Osmolar Gap

the osmolar gap Joel M. Topf, MD Nephrology pbﬂuids.com

• 65 yr old male • Clouded consciousness • History of mental illness http://www.cmaj.ca/cgi/content/full/176/7/921

142 115 18.6 3.8 26 1.0 100 • Anion gap? • Osmolar gap? Osmolality 308

lithium level 6 mmol/L

12 hours later 143 109 14.6 3.6 36 1.1 100 • urine output 2.4 liters over 6 hours Osmolality 324 Lithium 14.5

what do you do?

• lithium fell to 4.7 after 4 hours of dialysis

Peak levels occur 2-4 hours post-ingestion, 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? • Li CO = 74 2 3 • 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. •

143 109 14.6 100 Osmolality 324 Lithium 14.5 3.6 36 1.1

• Does lithium cause an osmolar gap? 143 109 14.6 100 Osmolality 324 Lithium 14.5 3.6 36 1.1

• Does lithium cause an osmolar gap? • Does lithium cause an anion gap? 143 109 14.6 100 Osmolality 324 Lithium 14.5 3.6 36 1.1

• Does lithium cause an osmolar gap? • Does lithium cause an anion gap? • What is lithium’s contribution to the osmolar gap? 143 109 14.6 100 Osmolality 324 Lithium 14.5 3.6 36 1.1

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 1.3 138 100 24 141 3.8 18 1.2 Osm 303 Lactic Acid 1.2

• patient is agitated and bucking the vent • patient on pip/tazo, orazepam drip, TPN • Lactic acid 1.3 138 100 24 138 98 28 141 166 3.8 18 1.2 3.8 16 1.2 Osm 303 Lactic Acid 1.2 Osm 312 Lactic Acid 4

• patient is agitated and bucking the vent • patient on pip/tazo, orazepam drip, TPN • Lactic acid 1.3 138 100 24 138 98 28 141 166 3.8 18 1.2 3.8 16 1.2 Osm 303 Lactic Acid 1.2 Osm 312 Lactic Acid 4 136 94 22 154 3.8 15 1.3 Osm 325 Lactic Acid 5

• patient is agitated and bucking the vent • patient on pip/tazo, orazepam drip, TPN • Lactic acid 1.3 138 100 24 138 98 28 141 166 3.8 18 1.2 3.8 16 1.2 Osm 303 Lactic Acid 1.2 Osm 312 Lactic Acid 4 136 94 22 135 95 24 154 123 3.8 15 1.3 3.8 16 0.9 Osm 325 Lactic Acid 5 Osm 335 Lactic Acid 5

propylene glycol • solvent for etomidate • nitroglycerin • phenytoin • digoxin • diazepam • hydralazine • lorazepam • TMP-SMX • phenobarbital

• 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: • HCO < 10 3 • 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 • HCO < 20 3 • 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

• 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 • HCO < 20 3 • 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.

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Osmolar Gap

by Joel Topf on Aug 20, 2009

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