Lithium Poisoning: when is hemodialysis indicated?

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Lithium Poisoning when is hemodialysis indicated?

• Kent R. Olson, MD
• Medical Director - SF Division
• California Poison Control System

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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?

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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

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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

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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 () benzos

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Enhanced drug elimination

• Who needs it?
• Will it work?
• Whats the best technique?

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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

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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?

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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

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Vd for some common drugs

• Large Vd
• camphor
• antidepressants
• digoxin
• opioids
• phencyclidine
• phenothiazines

• Small Vd
• alcohols
• lithium
• phenobarbital
• phenytoin
• salicylate
• valproic acid

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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

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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

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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
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Which method?

• Urinary pH manipulation
• Peritoneal dialysis
• Hemodialysis
• Hemoperfusion
• Multiple dose activated charcoal
• Continuous hemofiltration

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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

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Peritoneal dialysis

• Theoretically useful if drug is
• water soluble
• small (MW lt500)
• not highly protein bound
• not so bad you dont mind waiting . . . TOO SLOW
• Rarely performed unless its the only available
  method

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Hemodialysis

• Can be arteriovenous or veno-venous (double-lumen
  catheter)
• Requires anticoagulation
• Best if drug is
• water-soluble
• small (MW lt500)
• not highly protein bound
• Also good for correcting fluid electrolyte
  abnormalities

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Hemodialysis, continued . . .

• Newer machines have higher flow rates, better
  extraction ratios
• Note DONT use the REDY system - these portable
  HD units have very limited volume dialysate which
  is recycled, and CL may be very poor

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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

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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

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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

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Salicylate poisoning

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

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Methanol, Ethylene Glycol

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

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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

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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

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What happened?
Two-compartment Model
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Lithium
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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

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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)

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Lithium and dialysis

• Indications for dialysis
• serum level gt 6? 8? 10? (acute OD)
• level gt 4 ? (chronic)
• level 2.5-4 with severe Sx?

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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

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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

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Lithium summary

• 2-compartment model
• Early levels misleadingly high
• By the way --- dont 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