Lithium Toxicity

Symptoms:
(Neurological findings appear late in acute ingestion, but are common presenting complaints in chronic toxicity.)
  • Nausea
  • Vomiting
  • Diarrhea
  • QTc prolongation (rare)
  • Lethargy
  • Ataxia
  • Confusion
  • Tremors, fasciculations, or myoclonic jerks
  • Seizures
  • Encephalopathy
  • Nephrogenic Diabetese Insipidus (in chronic toxicity)
Testing:
  • Lithium level
    • Therapeutic  lithium level is 0.8 – 1.2 mEq/L  (mmol/L)
    • 1.5-2.5 mEq/L (mmol/L) – mild symptoms, chronic toxicity, tremor, slurred speech,  lethargy
    • 2.5-3.5 mEq/L (mmol/L) – moderate symptoms, worsening lethargy, tremors,  clonus
    • > 3.5 mEq/L (mmol/L) – severe toxicity
    • Repeat levels every 2-4 hours until trend proven
    • Serum lithium levels correlate more closely with symptoms in chronic toxicity due to steady state level in CNS
    • Repeat lithium level 6 hours post dialysis as lithium equilibrates, or in sustained release ingestion.
  • Complete blood count
  • Serum electrolytes / metabolic profile
  • ECG
  • Glucose
  • Pregnancy test
  • Acetaminophen level
  • Salicylate level
  • Alcohol level
  • TSH level (hypo and hyperthyroidism have been reported)
Treatment:
  • Oral activated charcoal does not work (Lithium is a charged particle)
  • Whole bowel irrigation can be considered in acute large volume sustained release lithium ingestion, if patient is awake and asymptomatic.
  • IV hydration and sodium replacement
  • Dialysis
    • Lithium level > 5 mEq/L (mmol/L).
    • Lithium level > 4 mEq/L (mmol/L) AND creatinine >2.0 mg/dL
    • Lithium level > 2.5 mEq/L (mmol/L) AND severe toxicity with inability to receive large volume IV fluids (ie. CHF)
    • Decreased level of consciousness, seizure, encephalopathy, severe dysrhythmia, regardless of level
Causes:
  • Dehydration resulting in kidney injury and reduced excretion
  • Intentional or accidental overdose
  • Medications
    • diuretics
    • angiotensin converting enzyme (ACE) inhibitors
    • nonsteroidal antiinflammatory drugs (NSAIDs)
Pharmacology:
  • GI absorption is rapid with peak levels in 1-2 hours  for immediate release preparations, up to 6 hours for sustained release.
  • Lithium is a small ion with no protein binding
  • Steady state reached in 5 days for therapeutic use.
  • Half life is 18 hours in adults, up to 36 hours in the elderly.
  • Excretion is renal.
  • Re-absorption can occur in the kidneys in response to volume depletion.
  • Highest tissue levels are found in the brain and kidneys.
Notes:
  • Chronic toxicity can occur from dehydration or alteration in excretion due to kidney injury. Elderly patients are especially susceptible.
  • Acid base disorders are not common in lithium toxicity and should prompt testing for salicylate and alcohol ingestion
  • Lithium can elevate WBC levels.
References:
  1. Mcknight RF, Adida M, Budge K, Stockton S, Goodwin GM, Geddes JR. Lithium toxicity profile: a systematic review and meta-analysis. Lancet. 2012;379(9817):721-8. PubMed
  2. Clendeninn NJ, Pond SM, Kaysen G, et al. Potential pitfalls in the evaluation of the usefulness of hemodialysis for the removal of lithium. J Toxicol Clin Toxicol 1982; 19:341. PubMed
  3. Lee D, et al. Lithium Toxicity. Medscape 2018; accessed August 2018. Medscape
  4. Perrone J., et al: Lithium Poisoning. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2018. Accessed 08/18

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