Lithium Toxicity

Symptoms:

• 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