Lithium

Introduction

Lithium poisoning is common and should be thought of as two distinct clinical entities.  

Acute lithium intoxication is typically well tolerated, providing the patient has normal renal function. This holds true even if the patient is currently on lithium (acute on therapeutic therapy).  

Chronic lithium poisoning is associated with considerable neurological morbidity and can require intensive management. Gastrointestinal side effects are less frequently seen.  

Toxicokinetics

Lithium is rapidly absorbed with peak concentrations achieved by 2-3h. Sustained release preparations are available and peak concentrations may be delayed up to 12 hours in overdose.

Lithium is not protein bound and its volume of distribution is roughly equivalent to TBW 

(~ 0.6L/kg). It distributes into cells is very slowly, with equilibrium with serum levels taking weeks.

Lithium is excreted unchanged in the urine. It is freely filtered and reabsorbed in the proximal convoluted tubule, following sodium. The Fractional Excretion of lithium is 25% of the GFR. The half-life of lithium at therapeutic doses is 8-12h, this maybe increased to 2-3 days with toxic concentrations

Risk Assessment

Clinical features of acute toxicity are predominantly gastrointestinal with nausea, vomiting, abdominal pain and diarrhoea. If renal function is maintained neurotoxicity should not manifest. The exception is very large overdoses (>1g/kg or 50g) where elevated concernations of lithium may persist for several days, allowing penetration in to the CNS. 

Clinical features of chronic toxicity are predominantly neurological and roughly correlate with the serum concentration of lithium. 

Lithium levels are helpful in diagnosing and guiding management of chronic poisoning. In acute ingestions levels help determine when the peak has occurred and when restarting of normal lithium treatment is appropriate.

Concentration (mmol/L)Observed effects
0.5None
1.0mild tremor
1.5Coarse tremor
2.0Hyperreflexia, dysarthria
2.5Myoclonic and other involuntary movements Ataxia and confusion
3.0Marked delirium, coma, seizures

Lithium levels and associated finding in chronic toxicity

Investigations:

  • Electrolytes
  • Renal function
  • Lithium level (normal range 0.4-0.8 mmol/L)
  • TFTs
  • ECG : QT prolongation, bradycardia 

Factors contributing to risk in chronic lithium toxicity:

  • Nephrogenic diabetes insipidus
  • Age > 50
  • Thyroid disease
  • Baseline renal impairment
  • Decreased fluid intake
  • Fluid loss with nausea, vomiting or diarrhoea
  • Hypercalcaemia leading to a diuresis
  • Drug interactions:
    • Thiazides 
    • NSAIDs 
    • Loop diuretics
    • ACEi

Management

Acute Toxicity

Acute toxicity is normally well tolerated. Management is focused on good supportive care with particular attention to hydration.  

Supplemental IV crystalloid, preferably 0.9% Sodium Chloride (due to higher sodium load), to account for losses is required until vomiting and diarrhoea settles.

WBI should be considered for very large overdoses (>50g) of slow release preparations. In cases where there is significant pre-existing renal impairment, dialysis may need to be considered, these patients should be discussed with a clinical toxicologist. 

Lithium levels should be taken 6 hours after ingestion and then every 6-12hours until the level is <1.5mmol/L.

Chronic Toxicity

The appropriate treatment of chronic lithium toxicity, particularly the use of dialysis, depends on the severity of the neurological toxicity evident and then presence of renal impairment.

Enhanced Elimination           

Indications for haemodialysis

  • Lithium > 2.5mmol/L and evidence of neurotoxicity
  • Seizures
  • Coma

Typically, haemodialysis is continued until the lithium level is consistently less than 1 mmol/L.  Due to redistribution, lithium levels can rebound following intermittent cessation of dialysis.

Supportive Measures

  • Stop lithium and any contributing agents (e.g. diuretics, NSAIDs)
  • Achieve euvolaemia
  • Identify and manage nephrogenic DI (Oral/IV fluids to match renal losses)
  • Thiamine supplementation
  • Treat hypo/hyperthyroidism

Disposition

Patients presenting with acute ingestions, symptomatic of gastrointestinal toxicity can be admitted to SSU under the toxicology team with attention to rehydration and maintaining euvolaemia.

Patients presenting with chronic lithium toxicity should be discussed with the toxicology team once the diagnosis is appreciated. These patients will typically require ward admissions as recovery is delayed (often weeks).

References

  1. Wikitoxwebsite – Lithium; http://www.wikitox.org/doku.php?id=wikitox:2.1.11.9.4_mood_stabilizers