Mood stabilizer used to treat bipolar disorder and other psychiatric illnesses.
- Monovalent cation in group 1A of periodic table, situated directly above sodium and potassium. Similar size and charge allows lithium to compete for sodium and potassium receptors.
- Therapeutic mechanism poorly understood despite decades of use. Thought to modulate neurotransmitters and intracellular messenger systems.
- In toxicity, multiple systems are affected:
- GI irritation due to caustic injury: seen in acute toxicity, not chronic toxicity.
- Neurotoxicity: competition with sodium and potassium ions impairs normal cellular function.
- Cardiotoxicity: competition with sodium and potassium may lower intracellular potassium concentrations, impairing repolarization.
- Chronic toxicity can occur due to supra-therapeutic dosing, impaired elimination (renal dysfunction) or drug-drug interactions.
- Lithium is not metabolized and is eliminated solely by the kidneys. Any renal dysfunction predisposes patients to develop chronic toxicity.
- Lithium itself is nephrotoxic, and predisposes patients to chronic toxicity if renal function and dosing is not monitored closely.
- Patients taking NSAIDs, ACE inhibitors, diuretics or topiramate concomitantly with lithium are at increased risk of chronic lithium toxicity.
- Chronic therapeutic use can cause hypothyroidism, hyperparathyroidism, renal dysfunction and nephrogenic diabetes insipidus.
- Toxic dose not established, toxicity may occur with overdose or chronic therapeutic use.
- Therapeutic dose in adults is < 2400mg/day.
Signs and Symptoms
- Acute toxicity:
- GI distress predominates: nausea, vomiting, abdominal pain, diarrhea.
- Neurotoxicity: patients often initially present with high lithium level and few neurologic symptoms provided good renal function. As lithium redistributes from plasma into the central nervous system (CNS), patients can develop:
- Slurred speech.
- Severe cases can have seizures and coma – rare.
- Tremor is the most common neurologic symptom, but can also be seen with therapeutic use.
- Cardiotoxicity: generally mild, serious dysrhythmias are rare.
- Chronic toxicity
- Same neurotoxicity symptoms as acute toxicity.
- Unlike acute toxicity, neurological symptoms are often the presenting chief complaint; lithium has already distributed into CNS tissue in chronic toxicity.
- Neurotoxicity is often more severe in patients with chronic toxicity.
- Syndrome of irreversible lithium-effectuated neurotoxicity (SILENT)
- Persistent cerebellar and brainstem dysfunction, dementia and/or extrapyramidal signs >2 months after overdose or discontinuation of lithium therapy. Generally considered irreversible.
- Poorly understood. Patients with prolonged exposure to lithium and patients presenting with hyperpyrexia are thought to have higher risk of developing SILENT.
- Initial work-up: electrolytes, creatinine, glucose, serum lithium level, and extended electrolytes.
- Hypernatremia should prompt clinical concern for nephrogenic diabetes insipidus.
- Exam question – cause of decreased anion gap metabolic acidosis.
- Always check for co-ingestants in deliberate self-harm ingestions – ethanol level, acetaminophen level, ASA level, venous blood gas (VBG), lactate, serum osmolality and urea/blood urea nitrogen (to calculate osmolar gap).
- Serum lithium level
- Therapeutic: 1 mmol/L or less.
- Mild toxicity: 1.5-2.5 mmol/L.
- Moderate toxicity: 2.5-3.5 mmol/L.
- Severe toxicity: >3.5 mmol/L.
- Repeat q4-6h until levels are < 1mmol/L and do not rise over 12h.
- ECG: bradycardia, non-specific ST segment and T wave abnormalities, AV blockade.
- Check TSH and free T4 if clinical concern for hypothyroidism.
- Airway control if significant decreased level of consciousness.
- Aggressive fluid resuscitation for volume losses if GI injury present.
- Treat agitation and seizures with benzodiazepines.
- 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.
- Intravenous 0.9% normal saline at 1.5-2x maintenance.
- Fluid and sodium repletion promotes renal elimination of lithium. Lithium clearance increases with sodium loading. Target euvolemia and eunatremia.
- Insert Foley catheter and target urine output of 1.5-2cc/kg/h.
- Caution in patients at risk of volume overload (i.e. renal dysfunction, history of congestive heart failure).
- Caution in patients with hypernatremia/nephrogenic diabetes insipidus, discuss with toxicology/nephrology.
- Avoid diuretics and kayexalate.
- Initiation should be discussed with a toxicologist and nephrologist.
- HD recommended if:
- Severe neurologic symptoms (seizure, coma) or life-threatening cardiac dysrhythmia regardless of lithium level.
- Renal dysfunction (eGFR < 60) and lithium level > 4 mmol/L.
- HD suggested if:
- Normal renal function and lithium level > 5 mmol/L.
- Confusion present.
- Patient is unable to tolerate intravenous sodium repletion (ie. renal failure, congestive heart disease, liver failure).
- Expected time to obtain a lithium level <1.0 mmol/L with optimal management is >36 h.
- Rebound increase in lithium level after dialysis is common, as lithium redistributes out of tissue into serum. Check lithium level 6h post-dialysis.
- Serum lithium levels do not always correlate well with symptoms. Patients with chronic lithium toxicity can have significant tissue lithium stores with modest plasma lithium concentrations. Patients with signs of neurotoxicity should be considered for dialysis despite mild-moderate lithium levels.
- Thinking that diuresis beyond adequate urine production enhances lithium excretion – it does not. Use of diuretics can impair lithium excretion.
Quality Of Evidence?
We are highly confident that the true effect lies close to that of the estimate of the effect. There is a wide range of studies included in the analyses with no major limitations, there is little variation between studies, and the summary estimate has a narrow confidence interval.
We consider that the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. There are only a few studies and some have limitations but not major flaws, there are some variations between studies, or the confidence interval of the summary estimate is wide.
When the true effect may be substantially different from the estimate of the effect. The studies have major flaws, there is important variations between studies, of the confidence interval of the summary estimate is very wide.
Evidence on this topic is based on animal studies, case reports and case series.
The purpose of this document is to provide health care professionals with key facts and recommendations for the diagnosis and treatment of patients in the emergency department. This summary was produced by the BC Emergency Medicine Network and uses the best available knowledge at the time of publication. However, healthcare professionals should continue to use their own judgment and take into consideration context, resources and other relevant factors. The BC Emergency Medicine Network is not liable for any damages, claims, liabilities, costs or obligations arising from the use of this document including loss or damages arising from any claims made by a third party. The BC Emergency Medicine Network also assumes no responsibility or liability for changes made to this document without its consent.
Last Updated Jul 17, 2020
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