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Lithium Overdose: The Tale of a Light Metal and its Skinny Therapeutic Index

Unfortunately, lithium has a well-known side effect profile from chronic use (renal toxicity, diabetes insipidus, thyroid dysfunction) and is potentially lethal at high serum concentrations. Lithium has a narrow therapeutic index, and because lithium is renally metabolized, kidney injury will increase blood serum levels. Acute lithium toxicity is an emergency, but because the lithium toxidrome can involve multiple organ systems including the CNS leading to altered mental status, it’s not always an obvious diagnosis. Rapid recognition of lithium toxicity, while difficult, is essential.

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  Lithium toxicity: A Battery of Problems

Clinical pearl: lithium levels do not always correlate with clinical symptoms. Serum lithium levels reflect only the extracellular lithium concentration, but it’s the intracellular concentration where Li exerts its effect.

Articles of Interest

Episode 130: Lithium toxicity

Whole bowel irrigation is an effective treatment for acute ingestion of sustained-release lithium. There is no role for whole bowel irrigation in chronic lithium toxicity.

Tox Pearls: Lithium Toxicity

Do you have a psychiatric patient with tremors, ataxia, or fasciculations? Think Lithium! No role for charcoal! In acute ingestion, whole bowel irrigation

“To dialyze or not to dialyze?” Emergency Department Management of Lithium Toxicity

The initial treatment for lithium toxicity is aggressive intravenous hydration. Whole bowel irrigation with polyethylene glycol is an option if there is concern for acute overdose. There is no role for activated charcoal as it does not absorb lithium ions. HD is effective in clearing lithium from serum. Peak renal clearance of lithium is typically 30-40mL/min, while HD can achieve 180mL/min of clearance.

A 54-year-old woman with chronic lithium toxicity

The most important component of management is isotonic intravenous fluid administration to improve the GFR and facilitate renal elimination. Failing this, extracorporeal treatment with hemodialysis is highly effective at removing lithium owing to its pharmacokinetic properties, including its small molecular weight and low volume of distribution.

A true dialytic urgency: lithium intoxication

It should be said that its diagnosis requires a high rate of suspicion because it presents various clinical manifestations such as neuropsychia-tric symptoms and even mental disorders of an organic type that can be complicated by an acute kidney injury requiring emergency dialysis therapy.

Chronic lithium toxicity

 Long-term lithium use increases the risk of nephrogenic diabetes insipidus, which causes loss of renal urine-concentrating ability and increased risk of lithium intoxication. Lithium should be discontinued in patients who develop diabetes insipidus and renal toxicity.

Early Aggressive Whole Bowel Irrigation to Prevent Severe Lithium Toxicity After Acute Overdose

In patients who present with early lithium poisoning, aggressive whole bowel irrigation offers a viable option to avoid short- and long-term neurologic manifestations of lithium toxicity. It is a non-invasive and effective method to prevent lithium absorption in patients who present within two to four hours of ingestion following ingestion of an extended-release formulation.

Hemodialysis Treatment for Patients with Lithium Poisoning

Lithium is not metabolized and is eliminated via the kidneys. Plasma lithium concentrations are sensitive to physiological factors that influence kidney function, for instance age, fluid status, hemodynamics and sodium balance. Therefore, drug interactions do not include biotransformation through enzyme systems such as cytochrome P450. On the other hand, the drug interactions occur through the direct effect of other medicines upon renal function and glomerular filtration rate.

Lithium intoxication

Levels don't always correlate well with clinical toxicity, because the danger from lithium poisoning is the lithium level in brain tissue (not in the blood).

Lithium: one drug, five complications

The case we report shows multiple lithium complications: pancytopenia, polyneuropathy, diabetes insipidus nephrogenic, seizure, and alopecia. Those complications are described for the first time together in our case report which illustrates how wide the spectrum of lithium-poisoning-related complications could be.

Mood Stabilizer Toxicities

First let's talk about lithium. In almost all medical texts, the tissue distribution of lithium is appropriately identified as being "complex." The easiest way I communicate that with patients, families, and medical learners is that in chronic therapy, lithium forms "stores" of drug in the body and intracellularly. Clinically that is relevant because after performing hemodialysis (HD) for lithium toxicity, you will reliably see an initial drop in lithium concentration followed by elevation approaching pre-dialysis levels if routine HD is performed.

POTD: Lithium Toxicity

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

REBEL Core Cast 93.0 – Lithium Toxicity

Lithium toxicity comes in a three flavors: acute, chronic and acute on chronic. Each form will have a different presentation as well as management. Lithium levels are often unreliable in terms of guiding management and must be taken in context with symptoms and time of ingestion (in acute overdose). IV fluids are a cornerstone of management as increasing intravascular volume and increasing renal elimination are critical. Hemodialysis is indicated for a lithium level > 5 mEq/L or a level > 4 mEq/L in a patient with renal failure. However, dialysis decisions should be made in conjunction with a toxicologist.

“Gotta Go Right Now”: Use of Whole Bowel Irrigation in the Treatment of Lithium Toxicity

The pneumonic “LIMPS” is a helpful reminder for some indications for use of whole bowel irrigation (lithium, iron, metals, packers/stuffers, sustained release drugs). The procedure entails placement of a nasogastric (NG) tube and initiation of polyethylene glycol (PEG) through the NG until clear rectal effluent is achieved. In adults, it is recommended to instill 1.5-2 L of PEG per hour (1 L/hr for pediatrics age 6-12, 0.5 L/hr for pediatrics <6 years).

Resources

A Case of Lithium Toxicity

In patients that cannot tolerate aggressive fluid hydration or those with severe toxicity, hemodialysis remains the best option for eliminating lithium. Unfortunately, there are no evidence-based guidelines for the initiation of dialysis in lithium toxicity.

BC Emergency Medicine Network

Activated charcoal is not recommended because it does not bind lithium. Whole bowel irrigation can be considered in large acute overdoses, particularly for extended release formulations. Lithium tablets can form bezoars, resulting in prolonged and fluctuating absorption. Initiation of whole bowel irrigation should be discussed with a toxicologist.

EMed

Acute toxicity usually occurs on background of chronic with altered metabolism eg dehydration

StatPearls

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. To determine the extent of lithium toxicity, one must determine the ingested amount, time of ingestion, whether there are co-ingestants, and if the ingestion was intentional or unintentional. It is worth noting that lithium toxicity signs do not often conform to the measured lithium level.