Lithium Poisoning

Abstract

Lithium is a commonly prescribed treatment for bipolar affective disorder. However, treatment is complicated by lithium's narrow therapeutic index and the influence of kidney function, both of which increase the risk of toxicity. Therefore, careful attention to dosing, monitoring, and titration is required. The cause of lithium poisoning influences treatment and 3 patterns are described: acute, acute-on-chronic, and chronic. Chronic poisoning is the most common etiology, is usually unintentional, and results from lithium intake exceeding elimination. This is most commonly due to impaired kidney function caused by volume depletion from lithium-induced nephrogenic diabetes insipidus or intercurrent illnesses and is also drug-induced. Lithium poisoning can affect multiple organs; however, the primary site of toxicity is the central nervous system and clinical manifestations vary from asymptomatic supratherapeutic drug concentrations to clinical toxicity such as confusion, ataxia, or seizures. Lithium poisoning has a low mortality rate; however, chronic lithium poisoning can require a prolonged hospital length of stay from impaired mobility and cognition and associated nosocomial complications. Persistent neurological deficits, in particular cerebellar, are described and the incidence and risk factors for its development are poorly understood, but it appears to be uncommon in uncomplicated acute poisoning. Lithium is readily dialyzable, and rationale support extracorporeal treatments to reduce the risk or the duration of toxicity in high-risk exposures. There is disagreement in the literature regarding factors that define patients most likely to benefit from treatments that enhance lithium elimination, including specific plasma lithium concentration thresholds. In the case of extracorporeal treatments, there are observational data in its favor, without evidence from randomized controlled trials (none have been performed), which may lead to conservative practices and potentially unnecessary interventions in some circumstances. More data are required to define the risk-benefit of extracorporeal treatments and their use (modality, duration) in the management of lithium poisoning.

Do not treat the numbers: lithium toxicity

“…We feel that in elderly patients, especially those taking medications known to increase lithium levels (nonsteroidal anti-inflammatory drugs, ACE inhibitors, angiotensin receptor blockers, thiazides, spironolactone, diltiazem and verapamil),2 and those with risk factors for chronic kidney disease, lithium levels in the lower therapeutic range should be targeted.…”

“…Severe lithium toxicity can cause seizures, coma and permanent neurological effects such as dementia 5. Neurological side effects are the most common in chronic toxicity, as it takes time for lithium to distribute into the central nervous system 2. The risk of chronic lithium toxicity is increased during times of sodium or volume depletion 9…”

“…A recent review highlights the physiological basis behind which lithium more readily causes neurotoxicity in chronic users 2. With chronic lithium use, lithium distributes to a steady-state concentration in the brain and serum, and it is noted that there can be interindividual variation between the relative concentrations 2.…”

“…With chronic lithium use, lithium distributes to a steady-state concentration in the brain and serum, and it is noted that there can be interindividual variation between the relative concentrations 2. In patients taking chronically high doses, lithium will accumulate at a level in CNS tissue that induces toxicity.…”

“…However, lithium’s narrow therapeutic range (0.6–1.0 mmol/L) requires monitoring to prevent toxicity 1. The clinical manifestations of lithium toxicity are manifold, involve multiple systems and can be classed as acute, acute-on-chronic, or chronic 2. There has been much debate surrounding the long-term effects of lithium on renal function.…”