Lithium, Vomiting And Diarrhoea

Lithium is a small monovalent cation. It is primarily used as lithium carbonate in the treatment for bipolar affective disorder but its actual mechanism of action is not clearly understood. It is thought to modulate intracellular second messengers (such as inositol triphosphate) as well as affect neurotransmitter production and release.

Lithium carbonate is available as a standard release (250mg) or a slow-release (450mg) presentation.

Remember ADME:

• Absorption:
  • With standard release preparations, absorption is virtually complete within 6-8 hours with peak plasma levels occurring within 4 hours.
  • Slow release preparations reach peak levels up to 12 hours
• Distribution:
  • Total body water (Vd=0.7-0.9L/g) with slow entry into tissue compartments including the central nervous system.
  • No plasma protein binding.
• Metabolism:
  • None
• Excretion:
  • Almost entirely renally excreted (some sequestration in bone).
  • Excretion is dependent on creatinine clearance (about 20% equals lithium clearance) so is reduced in states such as hypovolemia, renal impairment and hyponatremia.
  • Elimination half-life is 24 hours

• Drugs: e.g. NSAIDs, ACE inhibitors, SSRIs, thiazide diuretics, topiramate
• Dehydration
• Hyponatremia
• Hyperthyroidism
• Renal impairment (acute or chronic)

Yes, it is relevant.

Lithium toxicity can present as two distinct entities, either:

• an acute poisoning (almost always a deliberate ingestion), or
• a chronic poisoning (usually where lithium excretion is altered by extraneous factors such as dehydration or renal impairment)

The context in which the patient presents determines how useful a lithium level is. In this case, the patient has acute lithium toxicity.

In acute ingestions, the plasma level allows confirmation of ingestion and allows monitoring of ongoing lithium excretion (important especially with regards to neurotoxicity caused by lithium), the latter also assisting in determining disposition.

In chronic poisoning, lithium levels help confirm the diagnosis but do not correlate well with the severity of toxicity (they do not reflect levels in tissue compartments well, most importantly in the central nervous system). As in acute poisoning, levels can also be used for monitoring in those receiving treatment.

Acute lithium toxicity mainly affects the GI tract as lithium (like other metal salts) is a direct irritant. It causes nausea, vomiting, abdominal pain and diarrhoea.

25 grams is the magic number for risk assessment

• Ingestions of less than 25 g are usually benign, causing the aforementioned symptoms.
• Ingestions greater than 25 g produce more severe GI symptoms but in rare cases can lead to the neurotoxicity seen in chronic lithium toxicity if clearance of lithium is impaired. Reduced ability to excrete lithium promotes entry of lithium into the central nervous system and can lead to subsequent neurotoxicity.

This patient has taken a large amount of lithium (much greater than 25 g) and has the classic GI symptoms of acute lithium ingestion. Of note, he has mild renal impairment, which, if it should worsen, could lead to neurotoxicity without appropriate supportive treatment.

The danger for this patient lies in the timing of treatment —  lithium clearance can become further impaired from the hypovolemia secondary to GI losses and consequently the risk of lithium neurotoxicity increases.

The patient’s alteration in heart rate may be related to lithium as it settled following treatment, but as he was not haemodynamically compromised it was of little further clinical relevance.

As lithium excretion is ultimately dependent on renal function, supportive therapy is paramount in both acute and chronic toxicity.

Resuscitation

• Patients should be managed in an appropriately equipped and staffed resuscitation area until potentially toxic coingestants are excluded.
• There are no immediate life threats in this patient.

Supportive care and monitoring

• Correction of water deficits and ongoing hydration with intravenous fluid to prevent renal impairment (e.g. normal saline). Monitor urine output, >1 ml/kg/hr is recommended
• Correction of sodium deficits is also important as this too can affect lithium clearance
• Avoidance and cessation of any drugs that impair lithium clearance
• Remember FASTHUGS IN BED Please as required

Investigations

• Screening paracetamol level, blood glucose and 12-lead ECG
• Lithium level
• Urea, electrolytes and creatinine

Decontamination

• Whole bowel irrigation has been advocated for overdose with sustained-release preparations, however there is no proven benefit compared to supportive therapy alone.
• As with other metals, activated charcoal does not adsorb lithium effectively and is not recommended.

Antidotes

• There are no antidotes for either acute or chronic lithium toxicity

Enhanced Elimination

• As lithium is not protein bound and has a small volume of distribution, it is potentially amenable to haemodialysis.
• In acute toxicity, haemodialysis is reserved for patients with established renal failure and those presenting with features of neurotoxicity.
• There is no lithium level cut-off for hemodialysis in acute lithium toxicity, unlike chronic lithium toxicity where hemodialysis is usually advised if serum lithium levels are >2.5mmol/L.

Disposition

• Patients with renal impairment or signs of neurotoxicity should be managed in an HDU/ICU environment until medically stable.
• Acutely poisoned patients without these concerning features can be admitted for observation and supportive care until resolution of GI symptoms, and may need ongoing monitoring of renal function and lithium levels (until <2.5 mmol/L and falling).

• Waring WS. Management of lithium toxicity. Toxicology Reviews 2006; 25(4):221-230. PMID: 17288494