In this episode, I’ll discuss 3 reasons to consider holding lithium in critically ill patients.
Chronic medications, especially neuro-active ones, are often resumed in the ICU as soon as critically ill patients can tolerate them. Lithium, however, has a particularly narrow therapeutic range and the potential for toxicity to develop while a patient is in the ICU is a very real possibility.
Several characteristics of ICU patients make the risk of toxicity more likely:
The kidneys treat lithium in the exact same manner as they do sodium. Sodium depletion leads to homeostatic mechanisms by the kidneys to retain sodium by increased reabsorption. This in turn enhances the reabsorption of lithium in the kidneys, impairs lithium excretion, and can lead to toxicity. Hyponatremia is a common finding in ICU patients with a 2016 study reporting the incidence of hyponatremia in critically ill patients is about 25%.
2. Fluid balance and management
ICU patients are frequently in need of loop diuretics to manage fluid balance. A 2015 study of over 7000 ICU patients found a 51% incidence of loop diuretic use. Unfortunately, loop diuretics are known to increase lithium concentration and have the potential to cause severe toxicity.
3. Kidney disease
A 2015 multi-center study found the incidence of acute renal failure in ICU patients to be 57%. In general, lithium is avoided in patients with significant renal disease due to the increased risk of toxicity.
Should lithium be resumed in a patient with a critical illness, there is a good chance they may develop hyponatremia, kidney injury, and/or a need for loop diuretic use. The trouble with this is that recognizing signs of lithium toxicity in ICU patients is difficult. The symptoms of ataxia, tremor, dystonia and hyperreflexia are difficult to assess in many ICU patients. Non-convulsive status epilepticus is similarly difficult to identify. If a seizure does occur, it may be attributed to numerous other causes. If multiple comorbidities are present the recognition of lithium toxicity becomes even more challenging.
Although there is no direct data to address the risk of mania recurrence in stable patients who suddenly stop lithium due to critical illness, there is reason to believe this is not a significant concern. Relevant lithium concentrations are intracellular, and it takes time to re-equilibrate these when lithium is stopped. The risk of manic episode recurrence with abrupt cessation of lithium is measured in months or years, a time that far surpasses the typical ICU length of stay. Put together these suggest that an acute manic episode is unlikely to occur if lithium is held while a patient is in the ICU.
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