Lithium

Background

Primarily used for uni / bipolar depression
Narrow therapeutic range (0.6 - 1.0 mmol/L 12 hours post dose).
There is no single toxic level - interpret the lithium concentration alongside symptoms, renal function and whether poisoning is acute, acute-on-chronic or chronic.

Readily absorbed in GI tract over 4 - 6 hours post overdose
Renal excretion
Elimination t_1/2 usually 24 hours, dependent upon renal function (up to 36 h in the elderly and 40 - 50 h in renal impairment).

Acute:

Overdose, not taking lithium
Usually only mild toxicity, even with markedly raised levels, as brain concentrations are relatively low. More severe features can develop after a delay of several hours, particularly if renal elimination is reduced

Acute-on-Chronic:

Overdose in a patient already taking regular Lithium.
Tissues are already saturated, so serious toxicity can follow even a modest overdose. Risk is greater with impaired renal function, dehydration or hyponatraemia

Chronic:

Most common presentation
Carries the greatest risk of neurotoxicity, even with serum concentrations close to the therapeutic range.
Precipitants:
- Dehydration
- Drugs reducing renal lithium clearance (thiazides, NSAIDs, ACE inhibitors, ARBs)
- Impaired renal function
- Dose too high

Serum lithium sampling schedule
Presentation	Lithium Measurements
Acute ingestion in someone not taking lithium regularly	At 6 hours after ingestion, repeat 4 - 6 hours later, then 6 - 12 hourly, guided by clinical features
Patient already taking lithium	Immediately, repeat 6 hours after the last dose, then 6 - 12 hourly, guided by clinical features

* Do not use lithium-heparin tubes for lithium samples.

Supportive management - A, B, C with correction fluid / electrolyte imbalance
Admit all patients who require assessment for a minimum of 24 hours after ingestion - features can be delayed and deterioration can occur after 6 hours, unlike our usual approach to acute ingestions
After 24 hours, asymptomatic patients with normal bloods and a lithium concentration < 1 mmol/L can be considered for discharge, with advice to return if symptoms develop
Avoid forced diuresis

Activated charcoal is ineffective - does not adsorb lithium
Whole bowel irrigation can be considered in severe cases of acute ingestion (refer to TOXBASE for further information) - continue until effluent runs clear.
Gastric lavage - no established benefit; can be considered in exceptional circumstances, only once the airway has been protected

Impaired renal fxn
Serum Li conc > 4 mmol/L in acute on chronic toxicity
Serum Li conc > 5 mmol/L in acute toxicity (for consideration of haemodialysis, even without symptoms).

Discuss all potential cases with both the National Poisons Information Centre ((01) 809 2566) and the renal team

Treatment of choice for severe poisoning, and may prevent irreversible neurotoxicity
Haemodiafiltration is an acceptable alternative if haemodialysis is not possible
Continue until new neurological and cardiac features have resolved, OR lithium remains stable at < 1 mmol/L
Monitor lithium levels regularly after stopping - rebound can occur and repeat sessions may be needed

Indications for haemodialysis (TOXBASE)
Strength of recommendation	Criteria
Strongly recommended	Severe neurological toxicity - including reduced consciousness, cerebellar signs or convulsions - or life-threatening dysrhythmias, regardless of concentration
Strongly recommended	Lithium > 4 mmol/L with impaired renal function, defined here as eGFR < 45 mL/min/1.73 m²
Consider	Lithium ≥ 5 mmol/L, even without symptoms
Consider	Lithium > 4 mmol/L in acute-on-chronic overdose
Consider	Lithium > 2.5 mmol/L in chronic poisoning