Lithium toxicity

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  • Mechanism of action is poorly understood.
  • Despite availability of newer drugs, Lithium remains most effective tx for bipolar disorder, and it still in use
  • Lithium initially distributes in extracellular fluid, then gradually redistributes to other areas including the brain (takes up to 24 hours after absorption)
  • 95% renal excretion
    • NSAIDs, Diuretics, ACE-inhibitors → ↑ Lithium serum concentration by ↓ lithium excretion
  • Lithium toxicity rarely fatal (only 3 deaths in 2009)[1]


  • Overdose
  • Renal failure
  • Volume depletion
    • Diuretic use, vomiting, diarrhea, diaphoresis, decreased oral intake
  • Hyperthermia
  • Infection
  • CHF
  • Surgery
  • Cirrhosis

Clinical Features

Three recognized patterns of Lithium toxicity - "Acute", "Acute-on-chronic", and "Chronic".[2]


Occurs in patients not previously receiving lithium (i.e. with no current body stores)

Serum concentrations can fall rapidly as lithium redistributes to tissues, and serum level does not correlate with degree of toxicity.

  • GI - nausea, vomiting, diarrhea, abdominal pain
    • Earliest and most common symptoms
  • Cardiac effects - bradycardia, QT prolongation, T-wave flattening or inversion
    • Can also cause Brugada-like ECG pattern
  • CNS Depression - late finding (takes time for lithium to distribute to CNS)


Also called "Acute-on-therapeutic", occurs in patients currently taking lithium due to acute ingestion of supra-therapeutic doses.


Occurs insidiously in patients on chronic lithium therapy. Toxicity is 2/2 increased absorption or decreased elimination.

Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT)

  1. CNS
    1. Usually develops as GI symptoms are abating; more common in chronic toxicity
    2. Tremor
    3. Muscle weakness
    4. Ataxia
    5. Stupor
    6. Seizure
    7. Coma
  2. Cardiac
    1. Hypotension
    2. Conduction Abnormalities
    3. Ventricular dysrhythmias
    4. Prolonged QT, transient ST depression, TWI
  3. Endocrine
    1. Hyper/Hypothyroidism or hyperparathyroidism
    2. Hypothyroidism most common
  4. Renal
    1. Nephrogenic Diabetes Insipidus
      1. Can be seen mildly at therapeutic levels
      2. Causes polyuria and polydipsia


  • Lithium level
    • Therapeutic level = 0.6-1.2 meq/L
    • level may be falsely elevated if placed in a green top tube due to the heparin lithium interaction
  • Metabolic Panel
    • ↑ Na 2/2 nephrogenic diabetes insipidus
    • Evaluate renal function
  • TSH
  • ECG[3]
    • QT prolongation
    • T-wave flattening or inversion
  • Acetaminophen and Salicylate Levels (possible coingestants)


  1. GI decontamination
    1. Consider lavage for massive ingestions (>4gm) if can be performed w/in 1hr
    2. Activated charcoal is ineffective
  2. Fluid resuscitation
    1. Average pt has Na/volume deficit; giving fluid helps reestablish normal Li excretion
      1. Give 2L NS bolus; then give 200mL/hr
  3. Seizure
    1. Benzos are 1st line
    2. Phenobarbital is 2nd line
    3. Phenytoin is ineffective
  4. Dialysis
    1. Indications:
      1. Li level >4 (acute overdose)
      2. Li level >3.5 (chronic toxicity)
      3. Little change in Li level after 6hr IVF
      4. Sustained Li level >1.0 after 36hr
      5. Baseline renal failure
      6. Ingestion of sustained-release preparations
    2. Goal:
      1. Li level <1
        1. Must monitor for up to 8hr following dialysis to ensure levels stay <1


  • Consider discharge for pts asymptomatic after 4-6hr obs with 2 downtrending levels
  • Admit all pts w/ Li level >1.5
  • Admit all pts w/ ingestion of sustained-release preparation (regardless of Li level)

See Also


  1. Bronstein AC, et al: 2009 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS). Clin Toxicol (Phila) 2010; 48:979.
  2. Waring WS, Laing WJ, Good AM, Bateman DN. Pattern of lithium exposure predicts poisoning severity: evaluation of referrals to a regional poisons unit. QJM. 2007 May;100(5):271-6. Epub 2007 Apr 5.
  3. Canan F, Kaya A, Bulur S, Albayrak ES, Ordu S, Ataoglu A. Lithium intoxication related multiple temporary ecg changes: A case report. Cases Journal. 2008;1:156. doi:10.1186/1757-1626-1-156.
  • Tintinalli
  • Rosen's Chapter 160 - Lithium