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 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 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 = 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: Clearance (CL):
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. Vd for some common drugs
Large Vd:
camphor
antidepressants
digoxin
opioids
phencyclidine
phenothiazines
Small Vd:
alcohols
lithium
phenobarbital
phenytoin
salicylate
valproic acid

11. mcg/mL x mL/min = mg/min
“But they reported the CLEARANCE was really good 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 L 1%
200 mL/min L %
T½ = 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

18. 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

19. 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

21. 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

22. 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

24. 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

25. Salicylate poisoning Indications for dialysis: Note:
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

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

27. 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

28. 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

29. What happened?
“Two-compartment”
Model

30. Lithium

31. 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 = Cr = Na = 148
Li = 3.8 mEq/L
Repeat Li 4 hours later = 3.6 mEq/L

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

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

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

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

37. Lithium: summary 2-compartment model Acute vs chronic intoxication
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