POTD: Lithium Toxicity (Toxicology Thursday)

Lithium has been used to treat patients with bipolar disorder since the 1870s and is still widely used today, but has a very narrow therapeutic index! Toxicity can due to acute deliberate ingestions (18%) or, more commonly, chronic ingestions.

There are three categories of toxicity:

Acute: due to ingestion in a lithium naive patient, generally, an ingestion of > 7.5mg/kg of elemental lithium or 40 mg/kg of lithium carbonate. Prognosis tends to be better in acute poisoning because there is not sufficient time for distribution, which decreases the risk of neurotoxicity.

Acute-on-Chronic: an acute ingestion in a patient chronically on lithium

Chronic poisoning: occurs when chronic ingestion exceeds elimination. Highest risk of neurotoxicity because there is sufficient time to accumulate. Also the half life of lithium in chronic toxicity is prolonged due to underlying renal impairment.


Toxicity from chronic ingestions occur from impaired excretion due to:

  • Reduced GFR (NSAIDs, ACE inhibitors)

  • Increased renal tubular reabsorption (thiazides, spironolactone)

  • Calcium channel blockers (unknown mechanism)

 Renal processing is similar to that of sodium – meaning if the kidneys find any reason to retain sodium, it will also retain lithium! A major example is dehydration.

Serum lithium levels may be high, but the patient may be asymptomatic because effects only occur when moved intracellularly.




  • Coarse tremor

  • Hyperreflexia

  • Nystagmus

  • Ataxia

  • Altered mental status

  • Seizures/non-convulsive status epilepticus


  • Nephrogenic diabetes insipidus

  • Sodium losing nephritis

  • Nephrotic syndrome

Cardiovascular (usually mild)

  • Wandering atrial pacemaker

  • Sinus bradycardia

  • ST-segment elevation

  • Prolonged QT syndrome

  • T-wave flattening


  • Nausea/vomiting

  • Diarrhea

  • Ileus

**this can worsen toxicity due to increased renal reabsorption of sodium and lithium


  • Hypothyroidism (inhibition of hormone synthesis)

    • Also worsens lithium toxicity


Labs including TFTs, renal function, calcium, serum lithium level, EKG, cardiac monitoring. Make sure the tube was not treated with lithiated heparin. Remember, the serum level does not reflect the intracellular level, so a patient may be asymptomatic with high levels and normal levels do not exclude toxicity!!

However, generally:

  • Mild intoxication (1.5-2.5 mEq/L): nausea/vomiting, lethargy, tremor

  • Moderate intoxication (2.5-3.5 mEq/L): confusion, agitation, delirium, tachycardia, hypertonia

  • Severe intoxication (> 3.5 mEq/L): coma, seizures, hyperthermia, hypotension 


Symptomatic treatment (e.g. benzos for seizures, magnesium for torsades).

IVF – the goal is to preserve GFR so that lithium does not get reabsorbed!

Activated charcoal does not work, but you may consider gastric lavage or whole-bowel irrigation for acute ingestions.

Hemodialysis for severe toxicity or renal failure

Patient should be admitted to a monitored setting. Admit to ICU for severe symptoms!! If patients are asymptomatic with a lithium level < 1.5 mEq/L, they may be discharged.