Lithium poisoning

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Lithium poisoning

• To dialyse or not to dialyse

Sophie Gosselin, md, FRCP September 2003
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Objectives for today

• Brief review of lithium poisoning
• Anyone can read Rosen and Goldfrank
• Clinical correlation between serum levels and
  toxicity
• Lithium elimination with renal physiology
• Show off a great slide I borrowed from someone
  else.
• Current controversy with overall usefullness of
  dialysis.
• Have Martin Laliberté in the room to answer
  questions I cant answer

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Case

• 37 years old female
• Bipolar
• Had a prescription for lithium
• Found confused by sister
• Told her she ingested her months worth of meds.
• Questions?

4
Case

• A
• B
• C
• D
• Coingestants?
• Time of ingestion?
• Other medical disease?

5
Types of poisoning

• Acute toxicity
• Acute on chronic
• Chronic

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Lithium

• Monovalent cation
• Rapid GI absorption
• No protein binding
• Small Vd ( 0.66-0.8 L/ kg)
• 80 tubular reabsorption.
• 20 renally excreted
• T 1/2 18 hours average
• Toxicity increased by dehydration- wait for great
  slide on this later.
• Unit mEq/L mmol/L (charge 1)

Poisindex. CPS 2003
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Lithium peak absorption

• Immediate release
• 2-6 h
• Slow release
• 6-24h

Poisindex. CPS 2003
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Lithium toxicity
Hypertox. 2002
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Symptoms with chronic toxicity
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Decontamination

• Sodium polystyrene sulfonate
• 13 published studies- human case reports
• Acute versus chronic dosing???
• Time of ingestion versus time of treatment????
• Electrolytic complications
• Theoretically good, practically ???
• Bentonite
• Ponampalam R, Otten EJ. In vitro adsorption of
  lithium by bentonite. Singapore Med J. 2002
  Feb43(2)086-9.
• Polyethylene glycol
• Smith SW, Ling LJ, Halstenson CE Whole-bowel
  irrigation as a treatment for acute lithium
  overdose. Ann Emerg Med. 1991 May20(5)536-9.

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Tubular lithium handling
Li
THIAZIDES
Li
LOOP AGENTS
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Tubular lithium handlingEffect of furosemide
Li
X
Li
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Li and loop diuretics

• Furosemide increases lithium clearance
• in single doses / healthy volunteers
• In real world
• lithium
• furosemide / ECFV contraction
• comorbidity (LV dysfunction, kidney disease)
• Li toxicity

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Back to our case

• In ressuscitation area
• No activated charcoal given
• BP 110/80, HR 115, RR 24,
• Nystagmus, truncal ataxia, disoriented.
• SMA-7 normal except creatinine of 120
• ASA, APAP, Et-OH negative.
• Normal anion gap
• Initial serum level Li 3.0
• What would be your next intervention.

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Dialysis or not?
Poll of the assistance.
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Pub Med search

• Lithium poisoning and dialysis
• 84 articles
• Minus
• foreign languages
• Mild increase in lithiemia for psychiatry
  medication management
• 13 winner articles.
• References, Poisindex, toxin, various PCC
  guidelines

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Pharmacokinetics of lithium overdose

• One case study over 12 days
• Calculation of CSF, serum, urine and dialysate
  concentration of lithium
• Urinary excretion of lithium not affected by
  hemodialysis but dependant of renal function
• Lack of parallelism of serum and CSF
  concentration slow equilibrium between
  compartements
• Rebound peaks after HD
• Hemodialysis effective in decreasing cellular
  pool of lithium

Jaeger and al. Toxicokinetics of lithium
intoxication treated by hemodialysis Clin Tox
1985.
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When to dialyse?

• kinetics of 14 patients all with HD
• Levels 1.4-9.6mmol/L
• Pre HD
• Serum t ½ 23 h
• total clearance 26 mL/min
• With HD
• serum t ½ 3.6-5.7h
• clearance 63-110 ml/min
• Dependant on type of poisoning,renal impairment
• No rigid indication for HD
• Decision should be based of first 12h data

Jaeger and al. Clinical Toxicology 1993
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Hemodialysis and lithium levels

• 1978. Hansen and Amdisen
• HD if Li level cannot be less 1mmol/l in 30h
• 1979. Thomsen and Schou
• HD if Li higher 4 mmol/l of cardiovascular sx
• 1988. Amdisen
• All CNs symptomatic WITH increasing levels
• 1987. Dyson
• Only those with renal failure, rising or very
  high levels
• 1985- 1993 Jaeger
• Severe intoxication (coma, seizxure,)
• Deterioration of status despite treatment
• Acute on chronic or chronic poisoning

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Hemodialysis and lithium levels -2

• Most studies were done with chronic poisoning.
• Not based on population PCC study
• Physicians tend to react to high lithium levels
  rather than symptoms or decrease lithium
  excreation

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Rebound lithium levels

• HD associated with rebound levels
• CVVHD
• Continous
• Can be done in ICU at bedside.
• Case reports.
• Nephro Dial Transplant 2001, 161301
• Am J Kidney Disease September 2000
• Am J. Kidney Disease. May 2001.
• Clinical Toxicology 2001.

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1.Beckmann U, Oakley PW, Dawson AH, Byth PL.
Efficacy of continuous venovenous hemodialysis in
the treatment of severe lithium toxicity. J
Toxicol Clin Toxicol. 200139(4)393-7. 2
Meyer RJ, Flynn JT, Brophy PD, Smoyer WE, Kershaw
DB, Custer JR, Bunchman TE. Hemodialysis followed
by continuous hemofiltration for treatment of
lithium intoxication in children.Am J Kidney
Dis. 2001 May37(5)1044-7. 3 van Bommel EF,
Kalmeijer MD, Ponssen HH., Treatment of
life-threatening lithium toxicity with
high-volume continuous venovenous
hemofiltration.Am J Nephrol. 2000
Sep-Oct20(5)408-11. 4 Menghini VV, Albright
RC Jr. Treatment of lithium intoxication with
continuous venovenous hemodiafiltration.Am J
Kidney Dis. 2000 Sep36(3)E21. 5 Leblanc M,
Raymond M, Bonnardeaux A, Isenring P, Pichette V,
Geadah D, Quimet D, Ethier J, Cardinal J.
Lithium poisoning treated by high-performance
continuous arteriovenous and venovenous
hemodiafiltration.Am J Kidney Dis. 1996
Mar27(3)365-72.
CVVHD and lithium- Pubmed results
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CVVHD and lithium- Pubmed results

• All studies showed efficacious
• Better tolerated than HD
• Lithium clearance rate
• Normal kidneys 25-35 mL/min
• renal dysfunction 5-15 mL/min
• HD 50-105 mL/min
• CCVHD 25-35 mL/min (high dialysate flow rates)
• Alternative if unable to tolerate hemodialysis
• Adjunct to hemodialysis

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Bayesian approach- value of HD

• Case report
• Intentionnal overdose
• With co-ingestants
• Ingestion 40h prior to lithium sample
• Level 5.89
• Creatinine baseline 90. Now 515

Kerbush and al. harmacology and Toxicology 2002.
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Kerbush and al. Pharmacology and Toxicology 2002.
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What happens if dialysis not done??

• 205 lithium overdoses ,110 levels over 1.4
• 12 acute OD no HD recommended.
• 174 acute chronic OD
• 9 HD recommended
• Done in 6
• 19 chronic poisoning
• 9 recommendation of HD
• Done in 2
• One had HD when not recommended
• One didnt have HD and died.
• No difference observed
• Dialysis should be only for the more severe cases.

Bailey and Mc Guigan. Clinical Nephrology 2000
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PCC perspective
Bailey and Mc Guigan. Therapeutic Drug Monitoring
2000.
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PCC perspective

• 50-70 of patient with acute OD had
  co-ingestants.
• Difficult to assess severity of Sx due only to
  Li.
• Acute on chronic can be either chronic or acute
  depending on compliance.
• Similar toxicity at much lower lever with chronic
  poisoning than acute on chronic overdose
• Hansen and Amdisen not usefull clinical tool.
• Morbidity and mortality do not correlate with
  lithium levels.

Bailey and Mc Guigan. Therapeutic Drug Monitoring
2000.
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Morbidity of lithium

• Retrospective review of 97 cases of Li poisoning
• 28 cases had severe neurotoxicity
• All were chronic intoxication
• No neurotoxicity after acute or acute on chronic
  poisoning
• Peak serum concentration higher 2.3 vs 1.6 mmol/L
  
• Logistic regression showed 3 independant factors
• Nephrogenic DI
• Age over 50 yrs
• Thyroid disease
• Baseline creatinine clearance below normal

Oakley, Whyte and al. Australian and NZ Journal
of Psychiatry. 2001
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Conclusions

• Lithium is a complex intoxication
• Existence of acute-on-chronic type?
• Neurotoxicity occurs with chronic poisoning
• CVVHD works but not as much as HD
• HD should be reserved for the most severe cases.
• TREAT THE PATIENT NOT THE LEVEL..

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Creatinine clearance

• Clearance Urine Li x Volume
• Plasma Li x time