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Lithium Poisoning: when is hemodialysis indicated?

Lithium Poisoning: when is hemodialysis indicated?. Kent R. Olson, MD Medical Director - SF Division California Poison Control System. Case. A 32 year old woman ingested 20 lithium carbonate 300 mg tablets in a suicide attempt She is drowsy and her speech is slurred Her serum Li = 6 mEq/L

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Lithium Poisoning: when is hemodialysis indicated?

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  1. Lithium Poisoning: when is hemodialysis indicated? Kent R. Olson, MD Medical Director - SF Division California Poison Control System

  2. Case • A 32 year old woman ingested 20 lithium carbonate 300 mg tablets in a suicide attempt • She is drowsy and her speech is slurred • Her serum Li = 6 mEq/L • Hemodialysis needed?

  3. Lithium • Alkali metal (like Na, K) • Widely used for bipolar disorder • Therapeutic range 0.6-1.2 mEq/L • Toxicity = mainly CNS • Tremor, slurred speech, muscle twitching • Confusion, delirium, seizures, coma • Recovery may take weeks • Toxicity may occur as a result of acute overdose or chronic use

  4. Pharmacokinetics • Completely absorbed orally • Volume of distribution approx 0.8 L/kg • Slow entry into CNS • Initial serum levels do NOT reflect brain levels • Eliminated entirely by the kidneys • Half-life 14-20 hours • Prolonged in patients with renal insufficiency • Promoting saline excretion hastens Li removal

  5. Li Case, continued • Na = 140 • K = 4.0 • Cl = 110 • HCO3 = 26 • BUN = 8 Cr = 1.0 • Glucose = 98 • EtOH = 0.16 gm% U Tox (+) benzo’s

  6. Enhanced drug elimination: • Who needs it? • Will it work? • What’s the best technique?

  7. Who needs it? • Critically ill despite supportive care • eg, phenobarbital OD w/ intractable shock • Known lethal dose or blood level • eg, salicylate; methanol / ethylene glycol • Usual route of elimination impaired • eg, lithium OD in oliguric patient • Risk of prolonged coma • eg, phenobarbital OD w/ level of 250

  8. Will it work? • Volume of distribution: • is the drug accessible? • how big a volume to clear? • Clearance (CL): • does the method efficiently cleanse the blood?

  9. Volume of distribution (Vd) • A calculated number - not real= amt. of drug / plasma conc.= mg/kg / mg/L = L/kg • Total body water = 0.7 L/kg or ~ 50 L • ECF = 0.25 L/kg or about 15 L in adult • Blood or plasma = 0.07 L/kg or ~ 5 L

  10. Large Vd: camphor antidepressants digoxin opioids phencyclidine phenothiazines Small Vd: alcohols lithium phenobarbital phenytoin salicylate valproic acid Vd for some common drugs

  11. “But they reported the CLEARANCE was really good - - - 200 mL/min . . .” • But Cl is expressed in mL/min . . . NOT mg/min or gm/hr or tons/day • Total drug elimination depends on drug concentration: mcg/mL x mL/min = mg/min

  12. Example: amitriptyline OD • 60 kg man ingests 100 x 25 mg Elavil tabs • Vd = 40 L/kg or 2400 L • Est. Cp = 2500 mg / 2400 L ~ 1 mcg/mL • Hemoperfusion with CL of 200 mL/min • Drug removal = 200 mL/min x 1 mcg/mL = 200 mcg/min or 0.2 mg/min or 0.5% per hour

  13. Two drugs with the same CL Dialysis CL Vd Fraction eliminated in 60 min of dialysis 200 mL/min 500 L 1% 200 mL/min 50 L 17% T½ = 0.693 Vd / CL

  14. Which method? • Urinary pH manipulation • Peritoneal dialysis • Hemodialysis • Hemoperfusion • Multiple dose activated charcoal • Continuous hemofiltration

  15. Urinary pH manipulation • Alkaline diuresis • traps weak acids in alkaline urine • useful for salicylates, phenobarbital, chlorpropamide • risk of fluid overload • Acid diuresis • traps weak bases • may enhance elimination of amphetamines • TOO RISKY - may worsen myoglobinuric RF

  16. Peritoneal dialysis • Theoretically useful if drug is: • water soluble • small (MW <500) • not highly protein bound • not so bad you don’t mind waiting . . . TOO SLOW • Rarely performed unless it’s the only available method

  17. Hemodialysis • Can be arteriovenous or veno-venous (double-lumen catheter) • Requires anticoagulation • Best if drug is: • water-soluble • small (MW <500) • not highly protein bound • Also good for correcting fluid & electrolyte abnormalities

  18. Hemodialysis, continued . . . • Newer machines have higher flow rates, better extraction ratios • Note: DON’T use the REDY system - these portable HD units have very limited volume dialysate which is recycled, and CL may be very poor

  19. Charcoal hemoperfusion • Uses same vascular access and dialysis pumps • Greater anticoagulation required • Saturation of charcoal limits duration • But, it is not dependent on drug size, water solubility or protein binding - as long as drug binds to charcoal • Can be used in series with dialysis

  20. Multiple dose oral charcoal - “gut dialysis” • Charcoal slurry along the entire intestinal tract • Large surface area for adsorption of drug diffusing across intestinal epithelium from capillaries • Useful if drug likes AC, small Vd, low protein binding • Clinical benefit unproven

  21. Continuous hemofiltration • Plasma moves across semipermeable membrane under hydrostatic pressure • No dialysate • Solutes follow the plasma water - size up to MW ~ 10,000-40,000 • CL lower than HD or HP, but it can be performed 24 hrs/day

  22. Salicylate poisoning • Indications for dialysis: • severe metabolic acidosis • serum level > 100 mg/dL (acute OD) • level > 60 mg/dL (elderly, chronic OD) • Note: • alkalinize serum and urine • dialysis preferred: can correct electrolyte and fluid abnormalities

  23. Methanol, Ethylene Glycol • Indications for dialysis: • elevated level > 50 mg/dL • severe acidosis • increased osmolal gap > 10-15 mmol/L • Notes: • HD only - not adsorbed to AC • give blocking drug (EtOH, 4-MP) - Note: need to increase dosing during dialysis

  24. Lithium case, cont . . . • The Poison Control Center was consulted about hemodialysis • The toxicologist advised: • IV saline at a rate of 150 cc/hr • Recheck serum Li in 4 hours

  25. Li case, cont . . . • After 4 hrs, the Li was 2.2 mEq/L • A 3rd level 4 hrs later was 1.1 • The patient gradually recovered from her alcohol and benzodiazepine intoxication

  26. What happened? “Two-compartment” Model

  27. Lithium

  28. Another Lithium Case • A 42 year old man brought from a board and care with mumbling, tremor, has a seizure in the ED • Chronic Li use, no other meds • BUN = 44 Cr = 2.6 Na = 148 • Li = 3.8 mEq/L • Repeat Li 4 hours later = 3.6 mEq/L

  29. Acute vs Chronic Li • Acute: • High level, drops rapidly • Absent symptoms • Chronic: • Often associated w/ renal insufficiency, DI • Occurs gradually • Symptoms more severe, even with lower levels (eg, 2 - 2.5 and above)

  30. Lithium and dialysis • Indications for dialysis: • serum level > 6?8?10? (acute OD) • level > 4 ? (chronic) • level 2.5-4 with severe Sx?

  31. Lithium and dialysis • Usual renal CL 25-35 mL/min • Hemodialysis adds 100-150 mL/min • But only for 3-4 hours at a time • Rebound between dialysis sessions • Not very good at removing intracellular Li

  32. CVVH (a.k.a. CRRT) • CVVH adds 20-35 mL/min • But can be provided continuously • Volume cleared ~ 50L/dayvs 36 L/day w/ 4 hours of HD • No rebound

  33. Lithium: summary • 2-compartment model • Early levels misleadingly high • By the way --- don’t use a green-top tube! • Acute vs chronic intoxication • Dialysis is not rapidly effective • Li is slow to leave intracellular compartment • IV fluids often the best bet

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