Lithium poisoning

Abstract

Lithium salts are widely used for the treatment of bipolar affective disorders. Intentional lithium poisoning remains rare while unintentional lithium poisoning is more frequent due to lithium's narrow therapeutic index. Both may be associated with severe complications and fatalities. Lithium salts have a unique pharmacokinetic profile including complete bioavailability, low volume of distribution, lack of metabolism, and exclusive renal elimination [1] . Lithium toxicity is responsible for gastrointestinal (vomiting, diarrhea), neurological (decrease in consciousness, seizures) and cardiovascular (hypovolemic or vasoplegic shocks; cardiogenic shock remains unusual) complications. Some patients may develop persistent neurotoxicity including cognitive impairment and cerebellar dysfunction [2] . Routine investigations for acute poisoning should be considered, including an electrocardiogram (arrhythmia, QT prolongation) and serum electrolytes measurement (to assess kidney function and hydration state). An electroencephalogram should be considered in case of decrease in consciousness that may mask subclinical seizures. Finally, investigations include serial lithium concentrations (test tube without heparin sodium), whether the patient is symptomatic or not, to determine the pharmacokinetic phase (absorption, distribution, elimination). The measurement of red blood cell lithium concentrations is not of routine interest [2] . Clinical severity can be assessed by the Hansen and Amdisen classification, but its interest is limited in clinical practice. The pattern of poisoning has been suggested to be associated with severity. Three patterns of lithium poisoning have been described: acute lithium ingestion in a naive patient (acute), acute lithium ingestion in a chronically treated patient (acute-on-chronic) and accidental overdose (usually related to iatrogenic acute kidney dysfunction) in a chronically treated patient (chronic). However, despite controversies, all patterns can be responsible for severe complications. Other authors have suggested that sustained-release lithium formulations were associated with increased severity. However, those articles are only based on pharmacokinetic findings [3] . Lithium concentrations are not directly correlated with clinical severity; nevertheless, lithium concentration > 5 mmol/L seems to be almost constantly associated with serious poisoning [1] , [3] . Given the impossibility of predicting lithium poisoning toxicity, lithium poisoned patients, even asymptomatic, should be closely monitored in the intensive care unit. Other treatments include: parenteral hydration to restore kidney function (gastrointestinal disorders are usually responsible for severe dehydration) and gastrointestinal decontamination using polyethylene glycol (especially in case of a high amount of lithium ingested and/or sustained-release formulations) in the absence of contraindication [2] . Given lithium pharmacokinetic, hemodialysis would be the treatment of choice to enhance lithium elimination. However, hemodialysis indications remain controversial. To date, no data support the usefulness of hemodialysis to reverse clinical symptoms, avoid sequelae or prevent the onset of lithium toxicity. In the absence of validated prognostic criteria and given the invasiveness of hemodialysis, its requirment should be discussed case by case in the intensive care unit setting.