Official Newsletter of the California Poison Control System
Volume 1, Number 6.
The medical use of lithium has evolved considerably since it was first used for gout and rheumatism in the 1800’s. It was also used as a salt substitute in patients with hypertension, and was at one point present in the soft drink 7-Up. In the 1970’s, the US FDA approved the use of lithium for the treatment of acute mania following studies in the 1950’s by Cade and Schou. Currently, lithium is used to treat a variety of disorders including cluster headaches, alcoholism, and Grave’s disease. Lithium is most commonly used, however, as the treatment of choice for recurrent bipolar disorder (manic-depressive illness).
1. What are the important pharmacokinetic characteristics of lithium?
2. What are the clinical signs and symptoms of lithium poisoning?
3. How well do serum lithium levels correlate with toxicity?
4. What are treatment options for lithium toxicity? What is the role for hemodialysis?
5. What can cause a falsely positive or elevated serum lithium level?
Each year approximately four to five thousand cases of lithium exposure are reported to poison control centers. About three quarters of these seek help at a health care facility. The American Association of Poison Control Centers (AAPCC) Toxic Exposures Surveillance System (TESS) reported 4954 cases of lithium exposure in 2002. Approximately one third of these were unintentional exposures. Moderate to severe intoxication was reported in 1527 cases and 15 patients died. Although the number of deaths is small, appropriate management is essential to avoid morbidity and prolonged hospitalization.
Initial treatment measures include appropriate airway management, assessment of vital signs, and continuous cardiac monitoring. In patients with altered mental status, check the fingerstick glucose and use dextrose and naloxone as appropriate. Treat hypothermia or hyperthermia appropriately. If seizures develop, treat initially with benzodiazepines, followed by barbiturates if needed.
Since activated charcoal binds very poorly to lithium, its use should be reserved for patients who are suspected of ingesting other substances. Consider gastric lavage for very recent ingestion (less than 1 hour), and whole bowel irrigation if very large amounts have been ingested or if a sustained release product was used. Although a few studies suggest that sodium polysterene sulfonate (Kayexelate) can bind ingested lithium, the magnitude of benefit was small and evidence of clinical efficacy is lacking. Intravenous fluid therapy is very important. Replace volume losses with isotonic saline boluses, followed by an infusion to maintain good urine output. Fluid replacement will help prevent the continued reabsorption of lithium by the kidney. However, there is no evidence that forced diuresis with very large volumes is any more effective, and it may lead to fluid and electrolyte disturbances.
Hemodialysis is an effective method for enhanced removal of lithium. Lithium has a small volume of distribution and minimal protein binding, and modern dialysis machines can achieve fairly high clearance rates for the ion. However, there is poor agreement about the selection of patients for dialysis, particularly the precise serum lithium levels at which to dialyze. As mentioned earlier, patients with very high levels after an acute overdose may remain asymptomatic, while patients with chronic intoxication may be seriously ill with only modest levels. In general, toxicologists agree that patients who have symptoms of severe toxicity, renal failure, or clinical deterioration should be dialyzed. During hemodialysis, serum lithium levels drop rapidly but symptoms often persist for hours or days, and serum levels often rebound as the drug re-equilibrates slowly from the intracellular space to the extracellular space. For this reason, repeated hemodialysis sessions are usually required. While hemodialysis may enhance the elimination of lithium there remains controversy in the available literature as to whether hemodialysis confers any short or long term benefits to the lithium poisoned patient.
Reports of successful lithium removal with use of continuous renal replacement therapy (CRRT, also known as continuous veno-venous hemofiltration or CVVH) do exist. Although CRRT does not achieve clearance rates as high as those with hemodialysis, it has the advantage of being easier to implement and requiring less specialized staff and facilities, and can be performed continuously 24 hours a day. To date, there are no controlled studies demonstrating an advantage of CRRT over hemodialysis.
All patients with symptoms of lithium intoxication not attributable to another cause should be admitted to a monitored setting. If symptoms are moderate or severe, they should be admitted to an intensive care unit. After an acute ingestion in asymptomatic patients, serial serum lithium levels should be obtained every 6 hours until there is a downward trend, serum levels are less than 1.5 mEq/L, and patients remain asymptomatic.
1. Lithium has a two compartment volume of distribution. It initially occupies a volume of distribution of 0.4 L/kg in the extracellular space but then gradually moves intracellularly and occupies a final volume of distribution of 0.9L/kg. Once it is inside the cell, lithium exerts its therapeutic and toxic effects.
2. Clinical signs of lithium toxicity include nausea, vomiting, diarrhea, tremor, dysarthria, nystagmus, ataxia, and slurred speech. Patients will also exhibit alterations in the level of consciousness, which may vary from confusion to agitation, delirium, and coma.
3. Serum lithium levels do not correlate well with systemic toxicity, particularly after an acute overdose.
4. Since charcoal is ineffective in binding lithium, treatment measures include whole bowel irrigation, volume replacement, and supportive care. Hemodialysis should be considered for patients who have renal insufficiency, clinical deterioration, or symptoms of severe toxicity.
5. Collecting blood in a green top tube which contains lithium heparin. Specimens should be collected in a plain red top tube. Consult the local laboratory for possible variations.
Consultation with a specialist in poison information or with a medical toxicologist can be obtained free of charge by calling the California Poison Control System at 1-800-411-8080.
This issue of CALL US... was written by Josef G. Thundiyil, MD
CALL US... is published by the California Poison Control System. Editorial Board: Executive Director, Stuart E. Heard, PharmD; CPCS Medical Directors Timothy E. Albertson, MD, Richard Clark, MD, Richard Geller, MD, Kent R. Olson, MD; CPCS Managing Directors Judith Alsop, PharmD, Thomas E. Kearney, PharmD, Anthony Manoguerra, PharmD. Managing Editor: Susan Kim, PharmD
The California Poison Control System is operated by the School of Pharmacy, University of California, San Francisco.
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