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Lithium toxicity

Lithium is a monovalent cation (similar to sodium) with an unknown mechanism, is a very powerful, antimanic medication with a narrow therapeutic index.

Lithium is a monovalent cation (similar to sodium) with an unknown mechanism, is a very powerful, antimanic medication with a narrow therapeutic index.

History:

In the late 1800s, lithia water was first introduced as a mania and gout treatment . Afterward, lithium tablets with higher lithium concentration largely replaced lithia water. However, the higher lithium concentration found in the tablets was associated with tremors and weakness, and in 1898, lithium toxicity was first described. It is worth noting that lithium toxicity signs do not often conform to the measured lithium level. It was first approved by the U.S. Food and Drug Administration (FDA) as a mood-stabilizing medication for treatment of mania in the 1970s.


Aetiology

Lithium:

Monovalent cation (similar to sodium) with an unknown mechanism, is a very powerful, antimanic medication with a narrow therapeutic index.
  • Narrow therapeutic index: Effective dose range: 0.6–1.0 mmol/l, while in prolonged administration it may be toxic at 1.2 mmol/l or greater
    • Threshold for toxicity: 1.5 mmol/l

Risk factors:

  • Drugs altering renal function (NSAID, ACE inhibitors, thiazides)
  • Decreased circulating volume (great heat, sauna)
  • Infections (viral infections, gastroenteritis with diarrhea and vomiting)
  • Fever
  • Decreased oral intake of water
  • Renal insufficiency
  • Nephrogenic diabetes insipidus
  • Suicide attempt

Clinical features

Acute lithium intoxication:

Most often associated with gastrointestinal symptoms, cardiotoxic effects and late developing neurological signs. Lithium concentrations tend to fall rapidly soon after halting intake of lithium

Chronic lithium intoxication:

Manifest primarily as neurological symptoms, including confusion, myoclonus and seizures. Chronic toxicity faces lithium-saturated tissues
Clinical symptoms of different lithium intoxication patterns | Haussmann, R., Bauer, M., von Bonin, S., Grof, P., & Lewitzka, U. (2015). Treatment of lithium intoxication: facing the need for evidence. International journal of bipolar disorders, 3(1), 23. https://doi.org/10.1186/s40345-015-0040-2
  • Neurologic effects: Mostly reversible changes
    • Coarse tremor, hyperreflexia, nystagmus, and ataxia.
    • Varying consciousness levels (ranging from mild confusion to delirium)
  • Renal toxicity: Common in chronic lithium treatment
    • Impaired urinary concentrating ability
    • Nephrogenic diabetes insipidus (M/C cause of drug-induced NDI)
    • Sodium-losing nephritis
    • Nephrotic syndrome
  • Cardiovascular effects: Mild, non-specific and reversible
    • T wave flattening
    • Conduction defects: Sinus node dysfunction (M/C) > QT prolongation, intraventricular conduction defects, and U waves
  • Gastrointestinal effects: Typically occur within 1 hour of ingestion and are more common in the acute overdose setting
  • Endocrine effects:
    • Hypothyroidism (inhibition of thyroid hormone synthesis and subsequent release)
    • Hyperthyroidism (less commonly manifested, and can mask symptoms of lithium toxicity and boost its toxicity by prompting cellular unresponsiveness and altered renal tubular handling of lithium)

Management

Immediate management:

General approach to a lithium-intoxicated patient is similar to other poisonings, including airway management especially in cases of altered mental status, placing of a nasogastric tube and performing gastric lavage especially when patients present shortly after intoxication
  • Oral activated charcoal (cannot bind lithium ions)
  • IV hydration with isotonic saline: Dehydration, volume depletion regardless of the underlying origin is a common cause of chronic lithium intoxication. Lithium-induced diabetes insipidus and further volume loss by gastrointestinal decontamination measures need to be addressed as well
General treatment recommendations for lithium intoxication | Haussmann, R., Bauer, M., von Bonin, S., Grof, P., & Lewitzka, U. (2015). Treatment of lithium intoxication: facing the need for evidence. International journal of bipolar disorders, 3(1), 23. https://doi.org/10.1186/s40345-015-0040-2

Dialysis:

M/effective treatment, indicated in severe poisoning cases

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