Lithium Toxicity causes
=>Commonly used to treat Bipolar disorder
Toxicity can be:
=>Intentional-> acute toxicity
=>Mostly Unintentional(chronic tox):
* Intercurrent illness
* Drugs- NSAIDS, ACEI, Thiazide diuretics
* Dose changes(narrow therapeutic index)
* Decline in renal function
Clinical Side Effects of Lithium
- Fine tremor
- Downbeat nystagmus
- Nausea, headache
- Hypothyroidism
- Nephrogenic diabetes insipidus
- Hyperparathyroidism → hypercalcaemia
- Hyperlipidaemia
- Psoriasis / dermatitis
numerous neurological and endocrine effects
Pharmacology
- Drug: Lithium (Li₂CO₃)
- Class: Mood stabiliser
- Absorption: Oral, ~100% bioavailability
- Distribution
-Vd ~0.6–0.7 L/kg (≈ total body water)
-Slow CNS penetration (≥24 h) - Metabolism: None
- Elimination
- 100% renal- urine clearance dependent upon GFR.
- Handled like sodium
->↑ Na⁺ reabsorption → ↑ lithium reabsorption, hence excretion reduced in dehydration/ Na depleted states.
Mechanism of Toxicity
Li once ingested replaces Na and K ions–> Modulates the second messanger system (esp IP3)–>affects Neurotransmitter production and release- including Serotonin-> hence association with serotonin toxicity.
Acute vs Chronic toxicity
Why Acute vs Chronic toxicity matters
=>Acute overdose may have high serum levels early but delayed CNS toxicity ( due to slow BBB penetration).
=>Chronic toxicity: CNS burden is already high → patients can be very unwell at “modest” levels; dialysis thresholds are therefore often lower in practice, and expert opinion varies.
Acute Ingestion —
Additional Assessments
=>Ingested dose->
* <25 g ingestion, normal renal function:
-Usually benign
- May cause minor GI symptoms
- > 25 g ingestion:
- Neurotoxicity is rare & preventable with good supportive care
- Avoid dehydration
- Avoid sodium depletion
- Preserve renal function
->Any renal impairment, dehydration, or sodium depletion:
* ↑ lithium reabsorption→ ↑ Li levels
→↑ CNS redistribution → neurotoxicity
=>Late presentation with neurotoxicity:
* Treat as chronic lithium toxicity
=>Children:
* Rarely ingest toxic amounts
* No hospital assessment unless symptomatic
Chronic Ingestion
Additional Assessments
=>Chronic lithium users + acute overdose:
* Not at increased neurotoxicity risk
* Treat as acute ingestion, if renal function normal
=>Serum lithium level
* Correlates poorly with clinical toxicity
=>Suspect lithium toxicity in any patient on lithium with New neurological signs or symptoms
* High risk of permanent neurological sequelae
=>Endocrine effects of lithium:
* Nephrogenic diabetes insipidus
* Hypothyroidism
Invx
=>Screening (all toxicology patients)
* 12-lead ECG
* BSL
* Paracetamol level
=>Specific to lithium
* ECG->Usually minor ST/T wave changes
* EUC
-> Detect hyponatraemia
-> Hypercalcemia due to hyperparathyroidism
-> Monitor renal impairment
* Serum lithium levels
-> Confirm exposure
-> Trend levels to assess clearance
-> Levels >5 mmol/L may occur 4–8 h post ingestion
* Thyroid function tests
-> Lithium inhibits thyroid hormone release
-> Hypothyroidism may precipitate toxicity
Supportive Care (Cornerstone)
->Correct water and sodium deficits
* Maximises renal lithium excretion
* IV isotonic fluids
* Target urine output >1 mL/kg/hour in acute overdose
->Cease drugs impairing renal function or lithium clearance
* NSAIDs
* ACE inhibitors
* Thiazide diuretics
->Treat intercurrent illness (e.g. sepsis, dehydration)
Decontamination
- ❌ Activated charcoal ineffective
- Does not bind lithium
Enhanced Elimination
=>Haemodialysis
* Indications:
- Established renal impairment
- Clinical neurotoxicity
- Neurological dysfunction + Li⁺ >2.5 mmol/L
- May require prolonged or repeated sessions due to low redistribution from CNS
- Maintain concentration gradient
Forced diuresis-> Sufficient for most patients without neurotoxicity or renal failure
Antidote
None available
Disposition
=>Acute ingestion
->May be medically cleared if:
* No neurotoxicity
* Normal renal function
* Serum lithium <2.5 mmol/L and falling
=>Chronic toxicity
* Always admit
* Neurological recovery may take weeks
* Deficits may be incomplete or permanent
