INTRODUCTION — "Lithia" water was first used in the late 1800s to treat mania and gout. Over time, and likely due to low lithium content, "Lithia" water was ultimately replaced by lithium tablets. With the higher concentrations in the tablets, lithium's association with tremors and weakness became apparent and in 1898 the first descriptions of lithium toxicity appeared [1]. About a half century later, the calming effects of lithium in 10 patients with mania were described [2]; the drug's more toxic effects were recognized when lithium chloride was used as a salt substitute in patients with heart failure in 1949 [3].

Lithium's toxic effects limited its clinical use until appropriate serum monitoring became more readily available. In the 1970s, Lithium carbonate was approved in the United States for the treatment of acute mania and bipolar disorder and it has been in use ever since. In 2018, there were 7055 cases of lithium intoxication reported to the American Association of Poison Control Centers [4-6].

This topic will review the diagnosis and management of acute and chronic lithium poisoning. The therapeutic use of lithium, major side effects of lithium therapy, and other aspects of the management of patients with acute poisoning are discussed separately. A summary table to facilitate emergent management of lithium poisoning is provided (table 1). (See "Bipolar mania and hypomania in adults: Choosing pharmacotherapy" and "Bipolar disorder in adults: Choosing maintenance treatment" and "Renal toxicity of lithium" and "Lithium and the thyroid" and "General approach to drug poisoning in adults".)

PHARMACOLOGY AND CELLULAR TOXICOLOGY — Lithium's exact mechanism of action is not clearly understood. It affects two intracellular signaling pathways, inositol monophosphate and glycogen synthase kinase-3 [7]. Lithium decreases intracellular inositol, which may be a mechanism for mood stabilization. Lithium also inhibits glycogen synthase kinase-3, a component of diverse signaling pathways involved in energy metabolism, neuroprotection, and neuroplasticity.

Lithium has a narrow therapeutic index; a large proportion of patients on chronic lithium therapy experience at least one episode of toxicity during treatment [8]. The highest intracellular lithium levels are found in the brain and the kidneys.

PHARMACOKINETICS — Gastrointestinal absorption of lithium is rapid after oral administration. Peak blood levels are reached in one to two hours following therapeutic ingestion of immediate release products, and four to six hours after therapeutic ingestion of sustained release products. Up to 12 hours or longer may be required before peak levels are reached in acute overdose [9,10].

Lithium is a small ion (74 Daltons) with no protein or tissue binding and is therefore amenable to hemodialysis. Lithium is freely distributed throughout total body water with a volume of distribution between 0.6 to 0.9 L/kg, although the volume may be smaller in older adults, who have less lean body mass and less total body water. Steady state serum levels are typically reached within five days at the usual oral dose of 1200 to 1800 mg/day. The half-life for lithium is approximately 18 hours in adults and 36 hours in older adults.

Lithium is excreted almost entirely by the kidneys and is handled in a manner similar to sodium. Lithium is freely filtered but over 60 percent is then reabsorbed by the proximal tubules.

Volume depletion or renal impairment from any cause increases lithium reabsorption. Examples of such conditions include gastrointestinal losses, acute decompensated heart failure, cirrhosis, and the administration of diuretics, nonsteroidal antiinflammatory drugs, or angiotensin converting enzyme inhibitors [11-14].

CLINICAL PRESENTATION

Types of poisoning and risk factors — Lithium poisoning may be acute, as occurs when a patient who is not on lithium therapy ingests a bottle of lithium tablets in a suicide attempt; acute-on-chronic, as occurs when a patient who is on lithium therapy also ingests a large number of lithium tablets all at once; or chronic, as occurs when a patient on a stable lithium regimen suffers a reduction in renal function secondary to dehydration, change in renal perfusion (eg, due to heart failure), or a new medication. The symptoms and signs of toxicity differ based upon the total body burden of lithium and the rate of onset of toxicity.

Older adult patients are especially at risk for lithium toxicity due to both a lower glomerular filtration rate and a reduced volume of distribution (secondary to reductions in lean body mass and total body water). Lithium toxicity can also occur with minor declines in renal function, as a result of nephrotoxic drug interactions, or from dehydration for any reason.

Acute and acute-on-chronic poisoning

History — With any acute ingestion, it is important to determine the formulation of the drug (eg, standard formulation or sustained release), the amount or dose ingested, the timing (eg, acute or chronic), and the intent (eg, intentional or not). Lithium can be prescribed as lithium carbonate or more commonly as a sustained release formulation (eg, Lithobid and Eskalith). Anticipated toxic effects of any lithium exposure dose will depend on renal function, hydration status, and whether the patient takes lithium chronically.

The "toxic dose" of lithium is not well defined. Death has been reported after acute ingestion of a "handful" of pills in a patient on chronic lithium therapy [15], while other patients have survived large ingestions of up to 84 grams. Any adult who ingests more than 2400 mg or child who ingests more than 30 mg/kg requires clinical and laboratory evaluation to assess toxicity.

With any lithium ingestion, it is important to ask about dehydration, medications, and coingestants. Any condition causing dehydration, such as vomiting or diarrhea, fever or heat-related illness, anorexia or infection, may contribute to lithium toxicity.

Medications that cause dehydration or renal impairment can precipitate lithium toxicity. Examples include diuretics, angiotensin converting enzyme (ACE) inhibitors, and nonsteroidal antiinflammatory drugs (NSAIDs) [12]. Therefore, it is important to inquire about any new medications or changes in the dose of long-standing medications.

Lithium poisoning often occurs in vulnerable populations, such as patients with mental illness and poor living conditions.

Clinical findings

●Gastrointestinal – Patients with acute lithium toxicity often develop and present with symptoms of nausea, vomiting, and diarrhea. If vomiting and diarrhea are severe, dehydration and compromised renal function can develop, impairing the ability to excrete lithium and exacerbating lithium toxicity.

●Cardiac – Although lithium toxicity can cause changes in the electrocardiogram (ECG), dangerous arrhythmias or other important clinical effects are rare [16,17]. Prolonged QTc intervals and bradycardia have been reported [17-19]. Lithium poisoning is not associated with elevations in cardiac biomarkers or left ventricular dysfunction.

●Neurologic – Neurologic findings develop late in acute lithium poisoning because time is required for the drug to be absorbed and to penetrate the central nervous system (CNS). Potential neurologic symptoms and signs include sluggishness, ataxia, confusion or agitation, and neuromuscular excitability, which can manifest as irregular coarse tremors, fasciculations, or myoclonic jerks. Severe lithium intoxication can lead to seizures, nonconvulsive status epilepticus, and encephalopathy.

Long-term neurologic sequelae — In some cases, neurologic complications persist despite lithium removal by hemodialysis. The syndrome of irreversible lithium effectuated neurotoxicity (SILENT) consists of prolonged neurologic and neuropsychiatric symptoms following lithium toxicity [20]. In typical cases of SILENT, neurologic toxicity develops along with an elevated lithium concentration, but symptoms persist despite successful removal of the drug.

Cerebellar dysfunction, extrapyramidal symptoms, brainstem dysfunction, and dementia can develop as part of SILENT [20,21]. Other neurologic sequelae may include nystagmus, choreoathetoid movements, myopathy, and blindness. A review of 90 published cases identified cerebellar dysfunction as the most common sequelae, and proposed that demyelination at multiple sites in the CNS may be the cause [20]. SILENT can continue for months and in rare cases effects persist for years [22].

Chronic toxicity

History and common presentations — Chronic lithium toxicity presents in a different manner than either acute or acute-on-chronic toxicity.

Long term lithium use may result in a concentrating deficit in the kidneys, such that a dilute urine is excreted. Normally, the resulting thirst and increased intake of free water compensate for these fluid losses. Thus, many patients on chronic lithium therapy have polyuria and polydipsia. However, when other toxic effects (eg, confusion), physical disability, or intercurrent illness prevent these patients from drinking free water, dehydration results and lithium toxicity ensues [23].

Chronic lithium toxicity can also develop solely from the effects of volume depletion, especially in warmer climates, or when concurrent medications, such as NSAIDs or ACE inhibitors, cause a decrease in renal excretion [12]. In such cases, the clinical manifestations of toxicity (eg, agitation, confusion, slurred speech) are often superimposed on complications from chronic use (eg, neuromuscular irritability, tremor).

Older adults generally suffer more severe chronic toxicity than younger adults despite being prescribed lower doses of lithium [24]. This is likely due to age-related declines in kidney function and other factors, such as drug interactions and concurrent infection or dehydration.

As with acute poisoning, it is important to inquire about the dose and formulation of lithium and the duration of therapy, as well as any recent illness associated with fluid loss (eg, vomiting, diarrhea, fever).

Clinical findings

●Neurologic – In contradistinction to patients with acute lithium poisoning, in whom neurologic signs develop late, patients on chronic lithium therapy develop toxicity gradually and often present with neurologic findings.

Potential neurologic symptoms and signs are identical to those seen with acute or acute-on-chronic poisoning and can include sluggishness, ataxia, confusion or agitation, and neuromuscular excitability, which can manifest as irregular coarse tremors, fasciculations, or myoclonic jerks. Severe toxicity can result in seizures, nonconvulsive status epilepticus, and encephalopathy.

According to a retrospective review involving 28 patients with lithium poisoning complicated by severe neurotoxicity, risk factors for developing neurotoxicity include age over 50 years, chronic lithium therapy (rather than acute overdose), development of nephrogenic diabetes insipidus, hyperthyroidism, and impaired renal function [25]. Patients with chronic toxicity are at risk for SILENT. (See 'Long-term neurologic sequelae' above.)

●Cardiac – Patients with chronic lithium toxicity may also manifest the cardiac findings noted above, with comparably benign outcomes. (See 'Acute and acute-on-chronic poisoning' above.)

●Renal – Patients on chronic lithium therapy are at risk for developing nephrogenic diabetes insipidus (NDI). Volume depletion can occur due to excessive urinary water loss, concomitant effects of other drugs, or hospitalization with lack of recognition of the increased fluid requirements. Such patients can develop hypernatremia. Lithium-induced NDI is discussed in detail separately. (See "Renal toxicity of lithium", section on 'Nephrogenic diabetes insipidus'.)

LABORATORY TESTING

General testing — The following laboratory studies should be performed in patients with lithium poisoning: serum lithium concentration, complete blood count, basic electrolytes (particularly serum sodium concentration), and BUN and creatinine. Of note, lithium alone elevates the white blood cell count in the absence of infection [26].

Acid base disorders do not typically occur as a result of lithium toxicity and if present should raise suspicion for other ingestions, such aspirin or toxic alcohols.

In the setting of intentional lithium ingestion, routine laboratory evaluation should be targeted at possible coingestants and should include the following:

●Fingerstick glucose, to rule out hypoglycemia as the cause of any alteration in mental status

●Acetaminophen and salicylate levels, to rule out these common coingestions

●Electrocardiogram, to rule out conduction system poisoning by drugs that affect the QRS or QTc intervals

●Pregnancy test in women of childbearing age

Serum lithium concentration

When to obtain measurements — Serum lithium concentrations are one tool in the assessment of the severity of an overdose and help to determine the need for hemodialysis. A concentration should be obtained in any patient with suspected toxicity. (See 'Extracorporeal removal' below.)

The recommended therapeutic concentration for lithium is between 0.8 and 1.2 mEq/L (0.8 and 1.2 mmol/L). (See "Bipolar disorder in adults and lithium: Pharmacology, administration, and management of adverse effects", section on 'Lithium dose and serum concentrations' and "Bipolar disorder in adults: Choosing maintenance treatment", section on 'Lithium'.)

Of note, lithium must be measured in a lithium free tube; some blood tubes are treated with lithiated heparin, which can cause falsely positive lithium levels [27].

A serum lithium concentration should be obtained when the patient presents to the emergency department. Early levels can be helpful to confirm exposure but may not represent peak serum concentrations in a patient who has ingested sustained release tablets. Thus, lithium concentrations are repeated every two to four hours initially to determine the adequacy of therapy (IV hydration or hemodialysis) and to confirm a trend of improvement. Once they approach the therapeutic range or are consistently trending downward in a patient who is improving clinically, serum lithium concentrations may be obtained less frequently (ie, every 6 to 12 hours) until symptoms resolve.

Correlation with clinical toxicity — Serum lithium concentrations often do not correlate with clinical signs of toxicity. Patients with acute ingestions may be relatively asymptomatic despite serum concentrations above 4 mEq/L (4 mmol/L) due to slow absorption into the central nervous system. In addition, reports exist of severe clinical toxicity despite therapeutic lithium concentrations [28-30]. Therefore, treatment should be based upon clinical manifestations and not solely upon drug levels.

Serum lithium concentrations correlate more closely with clinical signs in patients with chronic toxicity because drug distribution has reached a steady state [8]. Nevertheless, clinical manifestations are the primary basis for treatment.

In chronic poisoning, mild symptoms of toxicity, such as increased tremor, slurred speech, and mild lethargy, generally occur when the serum lithium concentration falls between 1.5 to 2.5 mEq/L (1.5 to 2.5 mmol/L).

Clinical findings of moderate severity, such as worsening lethargy, coarse tremors, and clonus, can be seen when lithium levels are between 2.5 to 3.5 mEq/L (2.5 to 3.5 mmol/L). Severe toxicity generally occurs when lithium levels exceed 3.5 mEq/L (3.5 mmol/L). (See 'Clinical presentation' above.)

Renal function — Lithium is associated with chronic but not acute renal toxicity. Serial creatinine and BUN concentrations should be obtained daily until the clinical manifestations of lithium toxicity have resolved. (See "Renal toxicity of lithium".)

Serum sodium — Nephrogenic diabetes insipidus (NDI) is a known complication of chronic lithium poisoning. In patients on chronic lithium therapy who are suspected of concomitant NDI, the serum sodium concentration should be followed closely, particularly in patients receiving IV hydration and those with altered mentation who may not drink in response to thirst.

In patients admitted with chronic lithium toxicity, measure the serum sodium concentration every 6 to 12 hours for the first 24 to 48 hours. Care must be taken to avoid hypernatremia from IV hydration in patients with inadequate free water intake. Lithium-induced NDI is discussed in detail separately. (See "Renal toxicity of lithium", section on 'Nephrogenic diabetes insipidus'.)

Thyroid function — Both hypothyroidism and hyperthyroidism, as well as calcium disturbances secondary to hyperparathyroidism, have been reported with lithium poisoning. Therefore, it is reasonable to obtain a thyrotropin (TSH) concentration in patients with suspected lithium poisoning. (See "Lithium and the thyroid" and "Renal toxicity of lithium", section on 'Hyperparathyroidism and hypercalcemia'.)

Electrocardiogram — Although lithium toxicity can cause changes in the electrocardiogram (ECG), dangerous arrhythmias or other important clinical effects are rare [16]. Flattened T waves, prolonged QTc intervals, and bradycardia have been reported [18,19].

DIAGNOSIS

Acute and acute-on-chronic poisoning — The diagnosis of acute or acute-on-chronic lithium poisoning is typically made on the basis of the history and suggestive examination findings, and confirmed by obtaining a serum lithium concentration. The history generally involves an acute overdose or a sudden decline in renal function (eg, from dehydration due to gastrointestinal illness) in a patient taking lithium, while the initial clinical presentation often involves gastrointestinal symptoms and signs (eg, vomiting, diarrhea). Neurologic findings, ranging from sluggishness to neuromuscular excitability (eg, tremor) to seizures, develop late. An elevated serum lithium concentration confirms the diagnosis, but may not correlate with the degree of toxicity. A single normal concentration does not rule out the diagnosis.

Chronic toxicity — The diagnosis of chronic lithium toxicity is typically made on a clinical basis and confirmed by obtaining a serum lithium concentration. Drug concentrations correlate more closely with clinical signs in patients with chronic toxicity. The presentation generally involves a patient on chronic lithium therapy who, due to toxic drug effects (eg, confusion), physical disability, or concurrent illness, does not drink enough free water, leading to gradual dehydration and reduced renal excretion of lithium. Alternatively, toxicity can develop solely from the effects of volume depletion, such as insensate losses in warmer climates, or from the renal effects of concurrent medications such as NSAIDs or ACE inhibitors. The initial symptoms and signs of chronic toxicity are often neurologic and encompass the same range of potential findings as in acute poisoning.

DIFFERENTIAL DIAGNOSIS — The differential diagnosis for a patient with presumptive lithium poisoning includes serotonin syndrome (SS) and neuroleptic malignant syndrome (NMS), particularly if the patient has a history of mental illness and is taking psychiatric medications. (See "Serotonin syndrome (serotonin toxicity)" and "Neuroleptic malignant syndrome".)

Both syndromes cause altered mentation and profound neuromuscular findings. Although an elevated temperature may be seen in either SS or NMS, fever can also precipitate lithium toxicity in a patient on chronic therapy. NMS is characterized by "lead pipe" rigidity. Patients with either SS or lithium toxicity may manifest clonus, but in SS this is most prominent in the lower extremities. Ultimately, a serum lithium concentration helps to confirm the diagnosis of lithium poisoning. (See 'Serum lithium concentration' above.)

Lithium toxicity may be confused with acute ethanol or benzodiazepine withdrawal. Signs and symptoms can include tachycardia, hypertension, hyperthermia, agitation, and possibly seizures and hallucinations. Neuromuscular findings are more prominent with lithium poisoning and less commonly seen with either ethanol or benzodiazepine withdrawal. (See "Management of moderate and severe alcohol withdrawal syndromes" and "Benzodiazepine poisoning and withdrawal".)

Other important diagnoses to consider in patients who present with alterations in mental status, neuromuscular excitability, or other neurologic findings include:

●Hypoglycemia

●Central nervous system infection (see "Clinical features and diagnosis of acute bacterial meningitis in adults")

●Head trauma (see "Management of acute moderate and severe traumatic brain injury")

●Stroke (see "Clinical diagnosis of stroke subtypes")

●Seizures and status epilepticus (table 2) (see "Evaluation and management of the first seizure in adults" and "Convulsive status epilepticus in adults: Classification, clinical features, and diagnosis")

●Drug intoxication (anticholinergic, phencyclidine, cocaine) (see "Anticholinergic poisoning" and "Phencyclidine (PCP) intoxication in adults" and "Cocaine: Acute intoxication")

●Myxedema coma or thyrotoxicosis (see "Lithium and the thyroid")

TREATMENT

ABCs and supportive care — The general approach to any poisoned patient begins with assessment and stabilization of the airway, breathing, and circulation. The treatment for lithium poisoning includes intravenous fluids to maintain the glomerular filtration rate and replace losses, gastrointestinal decontamination in selected circumstances, and, hemodialysis in cases of severe toxicity. A summary table to facilitate emergent management of lithium poisoning is provided (table 1). (See "General approach to drug poisoning in adults".)

Potential complications from lithium toxicity, including altered mental status and seizures, are treated with supportive care. Benzodiazepines are first line therapy for seizures. (See "Advanced cardiac life support (ACLS) in adults".)

Hydration — Restoration of sodium and water balance in hypovolemic patients with lithium toxicity is essential to maximize lithium clearance. Gastrointestinal losses from vomiting and diarrhea are replaced with isotonic (0.9 percent) saline.

In adults, IV hydration with isotonic saline is initiated at twice the maintenance rate for a total of approximately 2 to 3 liters, depending upon the patient's fluid status and cardiac function (if known). Quantifying urine output and measuring urine specific gravity can provide clues to the possibility of concomitant nephrogenic diabetes insipidus (NDI). (See "Maintenance and replacement fluid therapy in adults".)

In patients with lithium-induced NDI, the serum sodium concentration must be closely monitored. The combination of IV isotonic saline to restore euvolemia and hypotonic urinary losses can lead to hypernatremia in these patients, which can exacerbate the neurotoxicity of lithium poisoning. Early adjustments of saline therapy and the addition of free water can prevent hypernatremia in patients with NDI. Lithium-induced NDI is discussed in detail separately. (See "Renal toxicity of lithium", section on 'Nephrogenic diabetes insipidus'.)

Gastrointestinal decontamination — Oral activated charcoal (AC) does not prevent the absorption of charged particles such as lithium and has no role in the management of an isolated lithium ingestion [31-33].

Whole bowel irrigation with polyethylene glycol (PEG) solution can be effective in patients with large acute ingestions or ingestions of sustained release preparations of lithium [34-36]. There is no benefit from whole bowel irrigation in patients with chronic toxicity.

We suggest that whole bowel irrigation with PEG solution be given to awake asymptomatic patients who present within two to four hours after a presumed significant ingestion of sustained-release lithium (greater than 10 to 15 tablets). The dose is 500 mL to 2 L of PEG per hour via nasogastric tube until the rectal effluent is clear. Whole bowel irrigation is contraindicated in patients with altered mentation or lethargy.

Oral sodium polystyrene sulfonate (Kayexalate) has been shown to reduce lithium concentrations after a single dose or multiple doses in both humans and animals [37-40]. A retrospective study of 48 patients with chronic lithium toxicity describes significant reductions in the half-life of lithium among patients treated with polystyrene sulfonate as an adjunct to supportive care [40]. However, we do not recommend this treatment because of the impracticality of giving the large amounts of sodium polystyrene sulfonate required and the potential for hypokalemia [41].

Extracorporeal removal

Hemodialysis — Lithium is readily dialyzable due to its low molecular weight, negligible protein binding, and small volume of distribution. Therefore, hemodialysis is the treatment of choice for severe lithium toxicity.

The appropriate indications for the treatment of lithium poisoning with hemodialysis remain controversial. We recommend treatment with hemodialysis for lithium poisoning in the following settings regardless of the nature of the ingestion (ie, acute, acute-on-chronic, or chronic) [42-50]:

●Serum lithium concentration is greater than 5 mEq/L (5 mmol/L).

●Serum lithium concentration is greater than 4 mEq/L (4 mmol/L) in patients with renal impairment (creatine >2.0 mg/dL, or 150 mcmol/L)

●In the presence of decreased level of consciousness, seizure, or life-threatening complications, irrespective of the serum lithium concentration.

●Serum lithium concentration is greater than 2.5 mEq/L (2.5 mmol/L) and the patient manifests signs of significant lithium toxicity (eg, seizures, depressed mental status), has renal insufficiency or other conditions that limit lithium excretion, or suffers from an illness that would be exacerbated by aggressive IV fluid hydration (eg, decompensated heart failure) [51].

Many patients do not fall neatly into these categories, such as those with moderate to severe clinical signs but a lithium concentration below 2.5 mEq/L (2.5 mmol/L). In such cases, we recommend consultation with a medical toxicologist. (See 'Additional resources' below.)

Lithium clearance with hemodialysis ranges from 70 to 170 mL/min, compared to normal renal clearance of 10 to 40 mL/min (due to extensive reabsorption of lithium in the proximal tubules) and only 15 mL/min with peritoneal dialysis [52].

Lithium equilibrates slowly between the extracellular and intracellular fluids [53]. As a result, a rebound increase in serum lithium levels occurs after the cessation of hemodialysis, as intracellular lithium diffuses into the extracellular space. Continued gastrointestinal drug absorption may contribute to the rebound effect [54]. Therefore, it is generally recommended that a serum lithium concentration be measured six hours after hemodialysis to confirm that levels are decreasing.

Some experts recommend extending the duration of hemodialysis to minimize the rebound phenomenon and repeating dialysis as necessary until the serum lithium level remains below 1 mEq/L (1 mmol/L) for six to eight hours after treatment [31,52,55-57]. Nine hours of hemodialysis removes approximately 60 percent of the total lithium stores [41]. Some authors suggest that at least two sessions of hemodialysis are required for adequate treatment [13]. However, in most cases, unless serum lithium concentrations are extremely high, one session of hemodialysis is usually sufficient. We suggest obtaining consultation with a medical toxicologist or poison control center if additional hemodialysis treatment may be needed. (See 'Additional resources' below.)

Alternative methods — Experience with methods of extracorporeal removal other than conventional hemodialysis for the treatment of severe lithium toxicity is limited. Case reports suggest that lithium clearance is significantly lower with methods other than hemodialysis. However, alternative treatments minimize rebound elevations in lithium and may be useful in hemodynamically unstable patients who cannot tolerate hemodialysis [58], or when hemodialysis is not available [41].

Continuous renal replacement therapies are acceptable alternatives if intermittent hemodialysis is not available [59]. Continuous venovenous hemofiltration (CVVH) has been used successfully to treat an acute on chronic lithium poisoning. According to other reports, the combination of hemodialysis, followed by continuous venovenous hemofiltration with hemodialysis, provided safe and effective treatment for two children [60] and one adult who developed hypotension [57].

Disposition — Patients with symptoms of lithium toxicity are admitted to a monitored setting for observation, regardless of the serum lithium concentration. Patients with severe symptoms (eg, altered mental status, seizures) are admitted to an intensive care setting. Discharge is appropriate once patients are asymptomatic with a serum lithium concentration below 1.5 mEq/L (1.5 mmol/L). Psychiatric evaluation is recommended for any patient with an intentional ingestion.

ADDITIONAL RESOURCES — Regional poison control centers in the United States are available at all times for consultation on patients who are critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have clinical and/or medical toxicologists available for bedside consultation and/or inpatient care. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is available at the website in the following reference [61].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Treatment of acute poisoning caused by specific agents other than drugs of abuse".)

SUMMARY AND RECOMMENDATIONS

●Lithium poisoning may be acute, acute-on-chronic, or chronic. The symptoms and signs of toxicity differ based upon the total body burden of lithium and the rate of onset of toxicity. A summary table to facilitate emergent management of lithium poisoning is provided (table 1). (See 'Types of poisoning and risk factors' above.)

●Older adult patients are at higher risk for lithium toxicity due to both a lower glomerular filtration rate and a reduced volume of distribution (secondary to reductions in lean body mass and total body water). Lithium toxicity can also occur with minor declines in renal function (eg, from nephrotoxic medications) or from dehydration for any reason (eg, vomiting, diarrhea, fever).

●Patients with acute lithium toxicity often present with symptoms of nausea, vomiting, and diarrhea; neurologic findings develop late in acute poisoning. (See 'Acute and acute-on-chronic poisoning' above.)

●Patients with chronic lithium toxicity often present with neurologic symptoms and signs. Neurologic findings can include sluggishness, ataxia, confusion or agitation, and neuromuscular excitability. Severe poisoning can lead to seizures, nonconvulsive status epilepticus, and encephalopathy. (See 'Chronic toxicity' above.)

●The differential diagnosis for lithium poisoning includes serotonin syndrome and neuroleptic malignant syndrome. (See 'Differential diagnosis' above.)

●Serum lithium concentrations can be useful for determining the severity of an overdose or the need for hemodialysis and should be obtained in any patient with suspected toxicity. However, lithium concentrations often do not correlate with clinical signs of toxicity. The timing and frequency with which lithium concentrations should be measured, and other indicated laboratory tests (eg, serum sodium concentration, BUN and creatinine), are described in the text. (See 'Serum lithium concentration' above and 'Laboratory testing' above.)

●Restoration of sodium and water balance in hypovolemic patients with lithium toxicity is essential to maximize lithium clearance. Gastrointestinal losses are replaced with isotonic (0.9 percent) saline. (See 'Hydration' above.)

●Lithium is readily dialyzable due to its low molecular weight, negligible protein binding, and small volume of distribution. Therefore, hemodialysis is the treatment of choice for severe lithium toxicity. Indications for hemodialysis are described in the text. (See 'Extracorporeal removal' above.)