Management of lithium toxicity

Abstract

Lithium salts have been used in the prophylaxis and treatment of depression and bipolar disorder for >50 years. Lithium has a narrow therapeutic range, and several well characterised adverse effects limit the potential usefulness of higher doses. Acute ingestion in lithium-naive patients is generally associated with only short-lived exposure to high concentrations, due to extensive distribution of lithium throughout the total body water compartment. Conversely, chronic toxicity and acute-on-therapeutic ingestion are associated with prolonged exposure to higher tissue concentrations and, therefore, greater toxicity. Lithium toxicity may be life threatening, or result in persistent cognitive and neurological impairment. Therefore, enhanced lithium clearance has been explored as a means of minimising exposure to high tissue concentrations. Although haemodialysis is highly effective in removing circulating lithium, serum concentrations often rebound so repeated or prolonged treatment may be required. Continuous arteriovenous haemodiafiltration and continuous venovenous haemodiafiltration increase lithium clearance, albeit to a lesser extent than haemodialysis, and are more widely accessible. Haemodiafiltration sustained for >16 hours allows effective removal of total body lithium, thereby avoiding rebound effects. Enhanced elimination should be considered in patients at greatest risk of severe poisoning: namely those with chronic or acute-on-therapeutic toxicity, those with clinically significant features, and those with chronic toxicity whose serum lithium concentration is >2.5 mmol/L. The choice between haemodialysis and continuous haemodiafiltration techniques will depend on local accessibility and urgency of enhancing lithium elimination. Further research is required to establish the potential benefits of assisted elimination on clinical outcome in patients with lithium poisoning.