The drug of choice for recurrent bipolar illness management remains to be lithium. Lithium, a monovalent cation similar to sodium with an unknown mechanism, was first approved by the U.S. Food and Drug Administration (FDA) as a mood-stabilizing medication for treatment of mania in the 1970s. Lithium is a very powerful, antimanic medication with a narrow therapeutic index.
PharmacodynamicsLithium's physiologic role is unknown, and its mechanism is not well understood; however, some proposed mechanisms include:
Too much lithium can cause lithium toxicity. Factors increasing lithium concentration in the body include excessive intake and impaired excretion.
A study evaluated a group of patients treated with lithium between 1997 and 2013 and the recurrence of lithium intoxication along with changes in renal functionality was to be assessed. 96 patients out of 1340 experienced at least one episode of lithium levels ?1.5 mmol/L. a cohort of Seventy-seven participants had experienced 91 episodes, of whom 34% needed intensive care and 13% required haemodialysis with no deaths. Acute kidney injury occurred, but renal function at baseline was not different to renal function after the episode .
Excessive intake or impaired excretion can result in lithium accumulation.
Suicidal intent or accidental ingestion of excessive amount of lithium tablets result in acute or acute-on-chronic overdose settings . Moreover, excessive intake might arise from dose modifications for the patient chronically administering lithium .
Several factors might lead to impairment in lithium secretion. Sodium and volume depletion due to any conditions like vomiting, diarrhea, febrile illness, renal insufficiency, excessive exercise, water restriction, excessive sweating, low sodium diet, and congestive heart failure may enhance lithium reabsorption in the kidneys . Furthermore, drugs reducing glomerular filtration rate might inflict chronic toxicity.
In the late 1800s, lithia water was first introduced as a mania and gout treatment . Afterward, lithium tablets with higher lithium concentration largely replaced lithia water. However, the higher lithium concentration found in the tablets was associated with tremors and weakness, and in 1898 lithium toxicity was first described. To determine the extent of lithium toxicity, one must determine the ingested amount, time of ingestion, whether there are co-ingestants, and if the ingestion was intentional or unintentional. It is worth noting that lithium toxicity signs do not often conform to the measured lithium level.
Symptoms of intoxication include coarse tremor, hyperreflexia, nystagmus, and ataxia. Patients often show varying consciousness levels, ranging from mild confusion to delirium. Although the neurological symptoms are mostly reversible, some reports indicate that symptoms might persist for 12 months never resolve.
Renal toxicity is more common in patients on chronic lithium treatment. Toxicity includes impaired urinary concentrating ability, nephrogenic diabetes insipidus (the most common cause of drug-induced NDI), sodium-losing nephritis, nephrotic syndrome along with other manifestations is prescribed.
These are usually mild and non-specific. Almost all patients treated with lithium will develop T wave flattening. Sinus node dysfunction is the most common reported conduction defect followed by QT prolongation, intraventricular conduction defects, and U waves. These findings are reversible.
Symptoms typically occur within 1 hour of ingestion and are more common in the acute overdose setting .
Lithium administration leads to the inhibition of thyroid hormone synthesis and subsequent release, resulting in hypothyroidism. Hyperthyroidism is less commonly manifested, which can mask symptoms of lithium toxicity and boost its toxicity by prompting cellular unresponsiveness and altered renal tubular handling of lithium .
Initially, the studies should include cardiac monitoring, electrocardiogram, assessment of oxygenation and monitoring of urine output, serum electrolytes, calcium, renal function, glucose, serum lithium level, and thyroid-stimulating hormone . Moreover, both therapeutic lithium usage and intoxication can be accompanied by leukocytosis. Furthermore, interference by the carbonate anion after lithium carbonate acute ingestion in the calculation of anion gap might lead to a low anion gap.
Of note, lithium heparin is used as an anticoagulant in some specimen tubes which can falsely increase results of serum lithium .
Lithium toxicity signs are obvious and can be identified and managed easily; however, ignoring it can be fatal. Indeed, in some cases, lithium toxicity can lead to coma, brain damage, or even death. Moreover, lithium can induce serotonin syndrome, a potentially fatal and life-threatening condition. The use of serotonergic drugs or drugs inhibiting serotonin metabolism concomitantly with lithium will increase the risk of lithium precipitating serotonin syndrome.
Intoxication degree is of utmost importance for understanding lithium toxicity diagnosis and management.
The severity of lithium toxicity is often divided into the following three grades: mild, moderate, and severe.
During lithium treatment, the healthcare team including physicians and nurses should make sure serum levels are checked regularly to make sure of the treatment course. Lithium is classified as pregnancy category D which means that there is positive evidence of human fetal risk. Therefore, the nurses or clinician should educate the patient on a proper contraceptive method during treatment with lithium. If any signs of early toxicity appear, the patient should stop the medication and seek medical council. Extra care should be taken if any activity, illness, or medication might precipitate a profound loss of water and/or salt is taken in a patient administering lithium. [Leve V]
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