Lithium toxicity

(Redirected from Lithium overdose)


  • Mechanism of action is poorly understood.
  • Despite availability of newer drugs, Lithium remains most effective treatment for bipolar disorder, and it is 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
  • Lithium toxicity rarely fatal (only 11 deaths out of 6815 reported toxic exposures in 2012)[1]

Common Precipitants

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 symptoms predominate.


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

  • Symptoms are a mix of both acute and chronic - includes both GI and CNS effects


Occurs insidiously in patients on chronic lithium therapy. Toxicity is secondary to increased absorption or decreased elimination. CNS symptoms predominate.

Chronic lithium therapy is associated with nephrogenic diabetes insipidus, which → hypernatremia, fluid loss → ↑ lithium levels (can precipitate toxicity)

Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT)[4]

  • Persistent sequelae of lithium toxicity
  • Defined as neurologic dysfunction persisting > 2 months after cessation of lithium therapy
  • Exact mechanism unknown (possibly related to CNS demyelination).
  • Symptoms
  • Brainstem dysfunction
  • Dementia

Differential Diagnosis

Heavy metal toxicity


  • Lithium level
    • Therapeutic level = 0.6-1.2 meq/L
    • Serum level may be falsely elevated if placed in a green top tube due to the heparin lithium interaction
    • Serum levels do not predict CNS levels and only roughly correlate with clinical symptoms
  • Metabolic Panel
  • TSH
  • ECG
  • Acetaminophen and Salicylate Levels (possible coingestants)


GI decontamination

Fluid resuscitation

  • Average patient has Na/volume deficit; giving fluid helps reestablish normal renal Lithium excretion
  • Give 2L NS bolus, then start 200mL/hr or 2x maintenance rate


Most effective method of removal. Must follow serial lithium levels - levels will likely rise after HD due to redistribution from tissues; additional HD may be required. Indications:

  • Kidney function is impaired and the [Li+] >4.0 mEq/L (1D recommendation)[5]
  • Clinical deterioration
  • In the presence of a decreased level of consciousness, seizures, or life-threatening dysrhythmias irrespective of [Li+] (1D)[5]
  • [Li+].>5.0 mEq/L (2D suggestion)
  • If the expected time to obtain a [Li+]<1.0 mEq/L with optimal management is >36 h (2D suggestion)[5]
  • Baseline renal failure
  • Contraindication to aggressive fluid resuscitation (CHF, etc)
  • Make final decision after consulting toxicologist and/or nephrologist since it's a complex decision [6]


  • Consider discharge for patients who are asymptomatic after 4-6hr obs, 2 downtrending lithium levels, and no worsening of renal function
  • Admit all patients with Li level >1.5
  • Admit all patients with ingestion of sustained-release preparation (regardless of Li level)

See Also


  1. Mowry JB, Spyker DA, Cantilena LR Jr., Bailey JE, Ford M: 2012 annual report of the American association of poison control centers’ national poison data system (NPDS): 30th annual report. Clin Toxicol (Phila) 51: 949–1229, 2013
  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.
  4. Adityanjee, Munshi KR, Thampy A. The syndrome of irreversible lithium-effectuated neurotoxicity. Clin Neuropharmacol. 2005 Jan-Feb;28(1):38-49.
  5. 5.0 5.1 5.2 Extracorporeal Treatment for Lithium Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup. Decker BS et al. Clin J Am Soc Nephrol 2015 Jan 12 Extrip Recs
  6. Internet Book of Critical Care (IBCC) Lithium intoxication