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.
Etiology
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.
Manifestations:
Neurological:
Coarse tremor
Hyperreflexia
Nystagmus
Ataxia
Altered mental status
Seizures/non-convulsive status epilepticus
Renal:
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
Gastrointestinal
Nausea/vomiting
Diarrhea
Ileus
**this can worsen toxicity due to increased renal reabsorption of sodium and lithium
Endocrine
Hypothyroidism (inhibition of hormone synthesis)
Also worsens lithium toxicity
Evaluation:
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
Treatment
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.
References:
https://emcrit.org/wp-content/uploads/2016/09/Lithium-Toxicity.pdf
https://www.ncbi.nlm.nih.gov/books/NBK499992/
https://www.uptodate.com/contents/lithium-poisoning