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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.