Lithium Toxicity
Summary
Lithium Carbonate (Priadel) is the most effective mood stabiliser for Bipolar Disorder, but it has an extremely Narrow Therapeutic Index (0.4 - 1.0 mmol/L). Toxicity can occur at levels >1.5 mmol/L and is life-threatening at >2.0 mmol/L. Toxicity arises in three forms: Acute (overdose in naive patient), Acute-on-Chronic (overdose in patient on lithium), and Chronic (accumulation due to renal failure/dehydration). Chronic toxicity is the most dangerous as lithium accumulates in tissues, causing severe neurotoxicity at relatively lower serum levels. Treatment relies on aggressive hydration (Saline) and, in severe cases, Haemodialysis. [1,2]
Key Facts
- Mechanism of Accumulation: Lithium is handled like Sodium by the kidney. It is filtered and reabsorbed in the Proximal Convoluted Tubule (PCT).
- The "DAN" Interactions:
- Diuretics (Thiazides > Loop): Hyponatraemia triggers compensatory Na+ (and Li+) reabsorption.
- ACE Inhibitors / ARBs: Reduce GFR.
- NSAIDs: Reduce GFR (constrict afferent arteriole).
- Dehydration: Vomiting, diarrhoea, or low salt diet causes avid Lithium retention.
- Charcoal: Activated Charcoal does NOT bind Lithium (it is a small charged ion). Do not use it.
Clinical Pearls
Tremor Types:
- Fine Tremor: Common side effect at therapeutic levels.
- Coarse Tremor: Sign of Toxicity. "If the cup spills, check the level."
The Silent Killer: Chronic toxicity presents insidiously. A patient may just seem "a bit confused" or "bumping into things" (ataxia). Diagnosis is often missed as "Dementia" or "Stroke".
Nephrogenic DI: Long term lithium makes the renal collecting duct resistant to ADH. Patients pass huge volumes of dilute urine (Polyuria) and get very thirsty (Polydipsia). This predisposes them to dehydration -> Toxicity cycle.
Risk Factors
- Renal Impairment: CKD, Elderly.
- Polypharmacy: The "DAN" drugs.
- Physical Illness: Gastroenteritis (fluid loss).
- Low Salt Diet: Body holds onto Li+ instead of Na+.
Pharmacokinetics
- Absorption: Rapid, complete. Peak 1-2h (or 4-5h for modified release).
- Distribution: No protein binding. Vd = 0.6-0.9 L/kg (Total Body Water). Enters CNS slowly but leaves slowly.
- Excretion: 95% Renal. Half life 24h (prolonged in elderly/OD).
Toxicity Mechanism
- CNS: Downregulates NMDA receptors -> Coma.
- Renal: Inhibits aquaporins (DI).
- Thyroid: Inhibits hormone release (Hypothyroidism).
By Severity
| Severity | Level (approx) | Features |
|---|---|---|
| Mild | 1.5 - 2.0 | Nausea, Diarrhoea, Coarse Tremor, Apathy, Weakness muscle twitching. |
| Moderate | 2.0 - 2.5 | Confusion, Ataxia, Dysarthria ("Drunk appearance"), Nystagmus, Hyperreflexia. |
| Severe | > 2.5 | Seizures, Coma, Renal Failure, Arrhythmia. |
By Type
- General: Dry mucous membranes (Dehydration)?
- Neurology:
- Gait: Ataxia (cerebellar).
- Eyes: Nystagmus.
- Tone: Rigidity / Clonus.
- Tremor: High amplitude, coarse.
Specific
- Serum Lithium Level:
- Ideally 12-hour post-dose trough. In OD, check on arrival.
- Repeat: Every 4-6 hours to check if rising (bezoar/delayed absorption) or falling.
- U&Es: Check Creatinine (Acute on Chronic Kidney Injury) and Sodium.
General
- ECG: Flattened/Inverted T waves. QT prolongation. Bradycardia.
- TFTs: Hypothyroidism?
- Blood Gas: Metabolic acidosis?
Management Algorithm
LITHIUM TOXICITY
(Clinical or Level >1.5)
↓
STOP LITHIUM & NEPHROTOXINS
(Stop NSAIDs/ACEi/Diuretics)
↓
HYDRATE (0.9% SALINE)
Goal: Urine Output >2ml/kg/hr
↓
MONITOR LEVELS Serially
↓
┌─────────────┴─────────────┐
IMPROVING DETERIORATING
(Levels dropping) or CRITERIA MET
↓ ↓
Continue Fluids HAEMODIALYSIS
Psych Review (The Gold Standard)
1. Decontamination
- Activated Charcoal: NO BENEFIT.
- Whole Bowel Irrigation (PEG): Consider only in massive acute overdose with sustained release preparations (requires expert advice).
2. Enhanced Elimination (Hydration)
- Fluid of Choice: 0.9% Sodium Chloride.
- Rationale: Sodium load reduces proximal tubular reabsorption of lithium.
- Rate: Aggressive (e.g. 1L stat then 200ml/hr) unless heart failure. Monitor fluid balance.
3. Haemodialysis
Consult Renal/ICU immediately if:
- Lithium >4.0 mmol/L (regardless of symptoms).
- Lithium >2.5 mmol/L AND severe symptoms (Seizures / Coma).
- Lithium >2.5 mmol/L AND Renal Failure (preventing clearance). Note: Levels often "rebound" 6-12 hours after dialysis as lithium moves from tissues back to blood. Repeat dialysis may be needed.
- SILENT Syndrome: Syndrome of Irreversible Lithium-Effected NeuroToxicity. Permanent cerebellar signs (ataxia/dysarthria) occurring despite removal of drug.
- Renal Failure: Permanent CKD.
- Serotonin Syndrome: If co-ingested with SSRIs.
- Acute: Good prognosis if hydration early.
- Chronic: Higher risk of permanent neuro sequelae (SILENT).
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| Lithium | TOXBASE | First line: Saline hydration. Dialysis limit lowered to 2.5 if chronic toxicity. |
| Bipolar | NICE CG185 | Monitor levels every 3 months. Monitor U&E/TFT every 6 months. |
Landmark Knowledge
1. The Sodium Link
- The kidney cannot distinguish Li+ from Na+.
- Low Na+ (diet/diuretics/dehydration) = Kidney greedily hangs onto Li+.
- High Na+ (saline drip) = Kidney dumps Li+.
What is Lithium Toxicity?
Lithium is a very effective medication, but the difference between the "right dose" and "too much" is tiny. Toxicity happens when levels build up in the blood.
How does it happen?
Usually, it's not because you took too many pills (though that can happen). It's because your kidneys slowed down clearing it.
- Dehydration: Vomiting, diarrhoea, or hot weather.
- Other Medicines: Ibuprofen (NSAIDs) or water tablets (diuretics) are the biggest culprits. Never take these without checking.
What are the signs?
- Early: Shaking hands (a coarse wobble, not a fine tremble), feeling sick, diarrhoea.
- Late: Confusion, walking like you are drunk, sleepiness.
Treatment
We give you lots of salty water via a drip to flush the lithium out through your kidneys. In extreme cases, we use a dialysis machine to filter your blood.
Primary Sources
- TOXBASE. Lithium Carbonate. toxbase.org.
- Waring WS. Management of lithium toxicity. Toxicol Rev. 2006;25:221-230. PMID: 17288494.
- Gitlin M. Lithium side effects and toxicity: prevalence and management strategies. Int J Bipolar Disord. 2016.
Common Exam Questions
- Prescribing: "Patient on Lithium needs painkiller for backache. What to avoid?"
- Answer: NSAIDs (Ibuprofen/Naproxen). Use Paracetamol.
- Psychiatry: "Monitoring frequency?"
- Answer: Levels every 3m. TFT/U&E every 6m.
- Emergency: "Patient OD'd on Lithium. Do you give Charcoal?"
- Answer: NO. It doesn't bind.
- Physiology: "Mechanism of polyuria?"
- Answer: Nephrogenic Diabetes Insipidus (Antagonism of ADH in collecting duct).
Viva Points
- Therapeutic Level: 0.4 - 1.0 mmol/L (sample taken 12 hours post dose).
- Ebstein's Anomaly: Teratogenic effect (tricuspid valve defect) if taken in first trimester.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.