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Lithium poisoning

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Myoclonia, ataxia,confusion. 2.5. 1. Hyperreflexia, dysarthria. 2.0. 1. Coarse ... Nystagmus, truncal ataxia, disoriented. SMA-7 normal except creatinine of 120 ... – PowerPoint PPT presentation

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Title: Lithium poisoning


1
Lithium poisoning
  • To dialyse or not to dialyse

Sophie Gosselin, md, FRCP September 2003
2
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

3
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

6
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
7
Lithium peak absorption
  • Immediate release
  • 2-6 h
  • Slow release
  • 6-24h

Poisindex. CPS 2003
8
Lithium toxicity
Hypertox. 2002
9
Symptoms with chronic toxicity
10
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.

11
Tubular lithium handling
Li
THIAZIDES
Li
LOOP AGENTS
12
Tubular lithium handlingEffect of furosemide
Li
X
Li
13
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

14
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.

15
Dialysis or not?
Poll of the assistance.
16
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

17
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.
18
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
19
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

20
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

21
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.

22
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
23
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

24
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.
25
Kerbush and al. Pharmacology and Toxicology 2002.
26
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
27
PCC perspective
Bailey and Mc Guigan. Therapeutic Drug Monitoring
2000.
28
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.
29
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
30
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..

31
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32
Creatinine clearance
  • Clearance Urine Li x Volume
  • Plasma Li x time
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