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Lithium Toxicity

  • Author: David C Lee, MD; Chief Editor: Asim Tarabar, MD  more...
 
Updated: Feb 02, 2015
 

Background

Lithium has been used in medicine since the 1870s. Lithium was initially used to treat depression, gout, and neutropenia, and for cluster headache prophylaxis, but it fell out of favor because of its side effects. The US Food and Drug Administration (FDA) banned the use of lithium in the 1940s because of fatalities but lifted the ban in 1970.

Presently, lithium is commonly used as maintenance treatment of bipolar disorder. Lithium poisoning occurs frequently, since it is used in a population at high risk for overdose. Furthermore, lithium has a relatively narrow therapeutic index that predisposes patients on lithium maintenance treatment to poisoning with relatively minor changes in medications or health status.

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Pathophysiology

The central nervous system (CNS) is the major organ system affected, although the renal, gastrointestinal (GI), endocrine, and cardiovascular (CV) systems also may be involved.

Lithium is available only for oral administration. It is almost completely absorbed from the GI tract. Peak levels occur 2-4 hours postingestion, although absorption can be much slower in massive overdose or with ingestion of sustained-release preparations.

Lithium dosing

Lithium is minimally protein bound (< 10%) and has an apparent volume of distribution of 0.6-1 L/kg. The therapeutic dose is 300-2700 mg/d with desired serum levels of 0.6-1.2 mEq/L.

Lithium clearance is predominantly through the kidneys. Because it is minimally protein bound, lithium is freely filtered at a rate that is dependent upon the glomerular filtration rate (GFR). Consequently, dosing must be adjusted based on renal function. Individuals with chronic renal insufficiency must be closely monitored if placed on lithium therapy.

Most filtered lithium is reabsorbed in the proximal tubule; thus, drugs known to inhibit proximal tubular reabsorption, such as carbonic anhydrase inhibitors and aminophylline, may increase excretion. Diuretics acting distally to the proximal tubule, such as thiazides and spironolactone, do not directly affect the fractional excretion of lithium (although they may affect serum lithium levels indirectly through their effects on volume status). Reabsorption of lithium is increased and toxicity is more likely in patients who are hyponatremic or volume depleted, both of which are possible consequences of diuretic therapy.

Lithium half-life

The plasma elimination half-life of a single dose of lithium is from 12-27 hours (varies with age). The half-life increases to approximately 36 hours in elderly persons (secondary to decreased GFR). Additionally, half-life may be considerably longer with chronic lithium use.

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Epidemiology

Frequency

United States

In 2013, the American Association of Poison Control Centers’ National Poison Data System reported 6610 case mentions and 3488 single exposures to lithium.[1] The figures are similar to those reported in the preceding 5 years.[2]

Mortality/Morbidity

In the 3488 single exposures to lithium reported to the American Association of Poison Control Centers’ National Poison Data System in 2013, outcomes were moderate in 1180 cases and major in 153 cases, with five deaths.[1] Lethal outcomes in lithium toxicity are generally secondary to severe CNS effects with subsequent cardiovascular collapse. Renal, gastrointestinal, and endocrine morbidity may also occur.

Race

No predilection exists.

Age

In 2013, of the 3488 single exposures to lithium reported to the American Association of Poison Control Centers’ National Poison Data System, 2722 (78%) were in patients aged 20 years or older; 391 (11%) were in patients 13 to 19 years old, and 138 (4%) were in children younger than 6 years.[1]

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Contributor Information and Disclosures
Author

David C Lee, MD Research Director, Department of Emergency Medicine, Associate Professor, North Shore University Hospital and New York University Medical School

David C Lee, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Amit Gupta, MD Department of Emergency Medicine, Staten Island University Hospital

Amit Gupta, MD is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.

Specialty Editor Board

John T VanDeVoort, PharmD Regional Director of Pharmacy, Sacred Heart and St Joseph's Hospitals

John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists

Disclosure: Nothing to disclose.

John G Benitez, MD, MPH Associate Professor, Department of Medicine, Medical Toxicology, Vanderbilt University Medical Center; Managing Director, Tennessee Poison Center

John G Benitez, MD, MPH is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Medical Toxicology, American College of Preventive Medicine, Undersea and Hyperbaric Medical Society, Wilderness Medical Society, American College of Occupational and Environmental Medicine

Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Disclosure: Nothing to disclose.

Additional Contributors

Mark S Slabinski, MD, FACEP, FAAEM Vice President, EMP Medical Group

Mark S Slabinski, MD, FACEP, FAAEM is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, Ohio State Medical Association

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, James G Linakis, PhD, MD, to the development and writing of this article.

References
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