Osmolar Gap

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  • Osmolar Gap

    1. 1. the osmolar gap Joel M. Topf, MD Nephrology pbfluids.com
    2. 2. • 65 yr old male • Clouded consciousness • History of mental illness http://www.cmaj.ca/cgi/content/full/176/7/921
    3. 3. 142 115 18.6 3.8 26 1.0 100 • Anion gap? • Osmolar gap? Osmolality 308
    4. 4. lithium level 6 mmol/L
    5. 5. 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
    6. 6. what do you do?
    7. 7. what do you do?
    8. 8. • lithium fell to 4.7 after 4 hours of dialysis
    9. 9. 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.
    10. 10. • 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
    11. 11. 3 categories of lithium toxicity Acute Acute-on-chronic Chronic
    12. 12. 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
    13. 13. 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
    14. 14. 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.   •
    15. 15. 143 109 14.6 100 Osmolality 324 Lithium 14.5 3.6 36 1.1
    16. 16. • Does lithium cause an osmolar gap? 143 109 14.6 100 Osmolality 324 Lithium 14.5 3.6 36 1.1
    17. 17. • 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
    18. 18. • 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
    19. 19. lactic acid • does it increase the osmolar gap • shouldn’t because it is anion
    20. 20. 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
    21. 21. • patient is agitated and bucking the vent • patient on pip/tazo, orazepam drip, TPN • Lactic acid 1.3
    22. 22. • patient is agitated and bucking the vent • patient on pip/tazo, orazepam drip, TPN • Lactic acid 1.3
    23. 23. • 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
    24. 24. • 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
    25. 25. • 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
    26. 26. • 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
    27. 27. propylene glycol • solvent for etomidate • nitroglycerin • phenytoin • digoxin • diazepam • hydralazine • lorazepam • TMP-SMX • phenobarbital
    28. 28. • 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
    29. 29. • 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
    30. 30. • found a high rate of developing eye sequelae in the initially unaffected (8/22) • 30% 6-year mortality found across all age groups
    31. 31. methanol • mortality increases from 8-36% to 50-80% when at the initiation of treatment the: • HCO < 10 3 • pH < 7.1
    32. 32. • formaldehyde has half life of 1-2 minutes • formic acid levels are proportional to pH • formic acid damages the optic disk independent of pH
    33. 33. methanol • visual changes • decreased acuity, photophobia • abdominal pain • pancreatitis • Neurologic changes • stupor, confusion, coma
    34. 34. putaminal necrosis • rigidity • tremor • masked faces • monotonous speech
    35. 35. 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.
    36. 36. • gi absorption is rapid and complete • little use of charcoal, emesis or gastric lavage
    37. 37. 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
    38. 38. fomepizol (Antizol) • molecular weight 82 • volume of distribution 0.6-1.0 • protein binding negligable
    39. 39. • 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
    40. 40. why is dialysis effective?
    41. 41. name the 3 factors that make a substance dialyzable
    42. 42. name the 3 factors that make a substance dialyzable • low volume of distibution
    43. 43. name the 3 factors that make a substance dialyzable • low volume of distibution • low protein binidng
    44. 44. name the 3 factors that make a substance dialyzable • low volume of distibution • low protein binidng • low molecular weight
    45. 45. intermittent hemodialysis continuous renal replacement therapy peritoneal dialysis
    46. 46. • 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
    47. 47. ethylene glycol • ratio of ethylene glycol to methanol intoxications: • 6:1 • 5,800 cases/year
    48. 48. woods lamp
    49. 49. woods lamp
    50. 50. • Glycolate causes most of the acidosis • oxalate + calcium causes tissue damage • kidney • hearty • brain • lung
    51. 51. • calcium oxalate deposition can also cause hypocalcemia • heart failure • hypotension
    52. 52. 3 phases of symptoms • symptoms in three stages • neurologic • confusion  focal neurologic defects • cardiopulmonary dysfunction • renal failure
    53. 53. 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
    54. 54. • can cause a false positive assay for lactic acidosis • thiamine and pyridoxime may shift ethylene glycol metabolsm to less toxic end- products
    55. 55. Diethylene Glycol Intoxication • break fluid • adulterant in alcoholic beverages
    56. 56. • acute kidney injury is common • hepatitis • pancreatitis • small changes in osmolal gap • molecular weight 106 • dialysis is effective
    57. 57. isopropyl alcohol • rubbing alcohol • no acidosis • dialysis for: • Coma • Hypotension • Isopropyl level over 200
    58. 58. • 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
    59. 59. 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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