Lithium toxicity can be acute or chronic in nature. Acute lithium toxicity primarily affects the gastrointestinal system followed by the central nervous system. The various signs and symptoms of acute as well as chronic lithium toxicity have been described below:

Acute lithium toxicity

• Diarrhea
• Nausea accompanied by vomiting
• Dizziness
• Abdominal pain
• Ataxia 
• Tremors 
• Slurred speech
• Muscle twitches
• Nystagmus 

Chronic lithium toxicity

• Hand tremors
• Coma
• Slurred speech
• Increased reflexes
• Kidney disorders
• Memory problems
• Psychosis

• Fatigue

  The Patient Mr X 53 years old Presented to OPD with  Loose Stool from last 2 Days  Nausea  Loss of Energy  Fatigue Known patient of Bipolar Disorder and under treatment by Psychiatry. [slideshare.net]

  Neurological side-effects of lithium can be mild, in the form of tremor, headache [1] and fatigue only or they can be severe, in the form of muscle fasciculations, weakness, ataxia, slurred speech and extrapyramidal syndrome. [neurologyindia.com]

  Early signs of lithium toxicity include nausea, fatigue, vomiting, diarrhea and muscular weakness. Contact your doctor if you experience these symptoms. Lithium is a simple salt and is similar to table salt. [livestrong.com]

  Physical exam reveals an uncomfortable, fatigued male who has diffuse muscle soreness. Urinalysis shows 3+ blood without red blood cells. What is the most important next test to direct the acute management of this patient? A. [foamcast.org]

• Fever

  Tell your doctor if you have been sweating excessively, or if you are sick with fever, vomiting, or diarrhea. Avoid becoming overheated or dehydrated during exercise and in hot weather. [drugs.com]

  People taking lithium should contact a health care provider without delay if they experience unresolved diarrhea, sudden changes in weight, muscular tremors or lack of coordination, fever, or any noticeable changes in their urinary volume. [dmentdcinema.com]

  Excessive sweating, fever, weight reduction and low salt diets may increase lithium levels. Methyldopa, L dopa, and diuretics may also increase lithium concentration. Blood should be drawn 12 hours after the last dose. [clinlabnavigator.com]

  In light of Mak's slight fever and mental confusion, doctors also performed a lumbar puncture to obtain cerebrospinal fluid to test for infection of the central nervous system. [scmp.com]

  Haug Browse recently published Learning/CME Learning/CME View all learning/CME CME Case 3-2019: A 70-Year-Old Woman with Fever, Headache, and Progressive Encephalopathy Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura Randomized [nejm.org]

• Rigor

  Chronic toxicity slowly and gradually harms the system causing irreversible damages that do not get corrected even with rigorous treatment regime. Elderly patients with lithium toxicity has a worse prognosis. [symptoma.com]

  In this instance, more rigorous evaluation and sober judgment prevailed. Initial safety reports were found to be grossly overestimated. [nature.com]

• Vomiting

  Acute Lithium Toxicity Acute lithium toxicity manifests itself as nausea, vomiting and diarrhea. This means that every patient on lithium who has vomiting and diarrhea should have their lithium stopped immediately! [jailmedicine.com]

  We are reporting a patient who was on lithium for bipolar disorder and was admitted with a history of sudden collapse following vomiting, and sinus bradycardia with ST-T changes. [ncbi.nlm.nih.gov]

  Clinical signs of lithium toxicity include nausea, vomiting, diarrhea, tremor, dysarthria, nystagmus, ataxia, and slurred speech. [calpoison.org]

  As with acute ingestion of many other metals, gastrointestinal manifestations (nausea, vomiting, diarrhea) predominate at first. [journals.lww.com]

• Nausea

  After 3 hours of observation, nausea and tremor were resolved, and she was subsequently transferred to a psychiatric hospital for further care. [ncbi.nlm.nih.gov]

  As with acute ingestion of many other metals, gastrointestinal manifestations (nausea, vomiting, diarrhea) predominate at first. [journals.lww.com]

  The Patient Mr X 53 years old Presented to OPD with  Loose Stool from last 2 Days  Nausea  Loss of Energy  Fatigue Known patient of Bipolar Disorder and under treatment by Psychiatry. [slideshare.net]

• Diarrhea

  Acute Lithium Toxicity Acute lithium toxicity manifests itself as nausea, vomiting and diarrhea. This means that every patient on lithium who has vomiting and diarrhea should have their lithium stopped immediately! [jailmedicine.com]

  There was no notation regarding the complaints of diarrhea for which he saw the patient five days earlier, nor did he note that her symptoms had improved or resolved. [lubinandmeyer.com]

  The patient was a 64-year-old woman who was admitted for muscle weakness in the lower extremities, diarrhea, and palpitations. She had bipolar disorder and was being treated with lithium carbonate, which she discontinued one week before admission. [ncbi.nlm.nih.gov]

  You have nausea, vomiting, abdominal pain, or diarrhea. You are shaky. Your muscles feel weak. You have questions or concerns about your condition or care. Care Agreement You have the right to help plan your care. [drugs.com]

  Clinical signs of lithium toxicity include nausea, vomiting, diarrhea, tremor, dysarthria, nystagmus, ataxia, and slurred speech. [calpoison.org]

• Abdominal Pain

  You have nausea, vomiting, abdominal pain, or diarrhea. You are shaky. Your muscles feel weak. You have questions or concerns about your condition or care. Care Agreement You have the right to help plan your care. [drugs.com]

  Symptoms: Preliminary signs of acute lithium toxicity include nausea, diarrhea, vomiting, abdominal pain and seizures. [symptoma.com]

  Haug Browse recently published Learning/CME Learning/CME View all learning/CME CME Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis Case 4-2019: An 18-Year-Old Man with Abdominal Pain and Hematochezia Bridging the Gap Challenge Yourself [nejm.org]

  It causes nausea, vomiting, abdominal pain and diarrhoea. 25 grams is the magic number for risk assessment Ingestions of less than 25 g are usually benign, causing the aforementioned symptoms. [lifeinthefastlane.com]

  Common side-effects These can usually be reduced or eliminated by lowering the lithium dose or changing the dosage schedule: Abdominal pain. Nausea. Metallic taste in the mouth (usually wears off). Fine tremor. [patient.info]

• Hypotension

  Hemodialysis could not be undertaken because of persistent hypotension. He remained comatose for the next three days but no seizure occurred after that. On Day 3 he succumbed to his illness. [neurologyindia.com]

  The patient required a norepinephrine infusion for hypotension. Emergent hemodialysis was initiated to remove lithium and to treat the monomorphic ventricular tachycardia, which was felt to be secondary to lithium toxicity. [ncbi.nlm.nih.gov]

  […] psychomotor retardation, slow mental functioning, slurred speech, startled response, restlessness, agitation, confusion, hallucinations, poor memory, worsening of organic brain syndrome, stupor, coma, epileptiform seizures CV: bradycardia, ECG changes, hypotension [medical-dictionary.thefreedictionary.com]

  […] photophobia lethargy moderate intoxication (serum lithium 2.5-3.5 mmol/l) agitation fascicular twitching confusion nausea, vomiting, diarrhoea cerebellar signs severe toxicity (>3.5 mmol/l) seizures, coma cardiovascular instability sinus bradycardia hypotension [aic.cuhk.edu.hk]

  The next day she was noted to have persistent severe dehydration with metabolic derangement and hypotension, as well as acute renal failure, a known consequence and sign of lithium toxicity. The patient died on May 13, 2002. [lubinandmeyer.com]

• Muscle Twitch

  There may be tremors in the hand, muscle twitches, slurring of speech, eye movements that are uncontrollable, alterations in the level of consciousness and even coma. [medicalfoxx.com]

  The various signs and symptoms of acute as well as chronic lithium toxicity have been described below: Acute lithium toxicity Diarrhea Nausea accompanied by vomiting Dizziness Abdominal pain Ataxia Tremors Slurred speech Muscle twitches Nystagmus Chronic [symptoma.com]

  twitches Seizures Slurred speech Uncontrollable eye movement Heart problems may occur in rare cases. [medlineplus.gov]

  twitching such as pronounced jerking of arms or legs Blurred vision Marked dizziness Difficulty walking Slurred speech Irregular heartbeat Swelling of the feet or lower legs Even if your lithium levels are not toxic, serious side effects such as the [bipolar-lives.com]

• Tinnitus

  Acute Lithium Toxicity Blurred vision Tinnitus Dizziness Nausea/vomiting Diarrhea Poor motor coordination Muscle aches Tremors/Seizure Coma Chronic Lithium Toxicity Any of the acute toxicity symptoms Slurred speech Memory problems Frequent urination Electrolyte [blogs.psychcentral.com]

  Concurrent use of calcium channel blocking agents with lithium may increase the risk of neurotoxicity in the form of ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus. Caution is recommended. [rxlist.com]

  Concurrent use of calcium channel blocking agents with lithium may increase the risk of neurotoxicity in the form of ataxia, tremors, nausea, vomiting, diarrhea and/or tinnitus. Caution is recommended. [healthyplace.com]

  […] worsening of organic brain syndrome, stupor, coma, epileptiform seizures CV: bradycardia, ECG changes, hypotension, sinus node dysfunction with severe bradycardia and syncope, arrhythmias, peripheral circulatory collapse EENT: blurred vision, nystagmus, tinnitus [medical-dictionary.thefreedictionary.com]

• Tremor

  Immediate discontinuation of lithium resulted in slow reduction of serum lithium levels and gradual resolution of tremor but his delirium persisted for 2 weeks. [ncbi.nlm.nih.gov]

  Neurol India 2008;56:484-5 Sir, Lithium toxicity is known for its diverse clinical manifestations ranging from mild tremor to severe coma and death. We report two cases of lithium toxicity. [neurologyindia.com]

  Mild-to-moderate toxicity • Generalized weakness • Fine resting tremor • Mild confusion Moderate-to-severe toxicity • Severe tremor • Muscle fasciculations • Choreoathetosis • Hyperreflexia • Clonus • Opisthotonos • Stupor • Seizures • Coma • Signs of [slideshare.net]

• Seizure

  Lithium decreases seizure threshold leading to isolated seizure (Case 1) or it may lead to status epilepticus (Case 2). Our Case 2 had status epilepticus leading to aspiration pneumonitis, hypotension and death. [neurologyindia.com]

  Any patient with significant neurologic symptoms such as seizure should be dialyzed, as should patients with extremely high lithium levels. [pharmacyjoe.com]

  Seizures can be controlled with benzodiazepines, phenobarbital, or propofol. GI decontamination Gastric lavage may be attempted if the patient presents within one hour of ingestion. [emedicine.medscape.com]

  Mild-to-moderate toxicity • Generalized weakness • Fine resting tremor • Mild confusion Moderate-to-severe toxicity • Severe tremor • Muscle fasciculations • Choreoathetosis • Hyperreflexia • Clonus • Opisthotonos • Stupor • Seizures • Coma • Signs of [slideshare.net]

• Ataxia

  Injury to the cerebellum commonly results in clumsiness or uncoordinated movement, which is referred to as ataxia. The severity of ataxia varies according to the extent of the lesion. [ncbi.nlm.nih.gov]

  On Day 15 she was discharged with mild gait ataxia which persisted for approximately three months. [neurologyindia.com]

   Pulse 108 BP: 100/70 T: 36.6 R/R: 17/min  Dehydrted  CNS: Irritable, Confused, Mild tremor, Ataxia  CVS: Tachycardia Noramal heart sounds  Resp: Normal  GIT: Soft non tender B/S present no viceromegaly 4.  FBC normal  Cusp normal  LFT’s normal [slideshare.net]

• Confusion

  In two patients the presentation mimicked mania, but the third presented with a more typical toxic confusion state. Improvement in all cases paralleled the drop in serum lithium levels. [ncbi.nlm.nih.gov]

   Pulse 108 BP: 100/70 T: 36.6 R/R: 17/min  Dehydrted  CNS: Irritable, Confused, Mild tremor, Ataxia  CVS: Tachycardia Noramal heart sounds  Resp: Normal  GIT: Soft non tender B/S present no viceromegaly 4.  FBC normal  Cusp normal  LFT’s normal [slideshare.net]

• Slurred Speech

  […] lithium toxicity Hand tremors Coma Slurred speech Increased reflexes Kidney disorders Memory problems Psychosis Blood and urine analysis should reveal elevated levels of lithium. [symptoma.com]

  Slurred speech, jerking muscles. In any case - in never hurts to have those levels checked! Good luck! [mdjunction.com]

  Symptoms that can occur include: Increased reflexes Slurred speech Uncontrolled shaking (tremors) In severe cases of chronic toxicity, there may also be nervous system and kidney problems, such as: Kidney failure Memory problems Movement disorders Problems [medlineplus.gov]

Blood and urine analysis should reveal elevated levels of lithium. The sample should be sent in lithium free tubes as false elevated levels of lithium have been reported in the past due to collection of sample in tubes containing lithium. Renal function tests should be done to assess the functioning of kidneys and its ability to filter off the lithium from the body. Initial electrocardiographic examination of patients with lithium toxicity may show signs of increased QT intervals and T wave inversion [7]. Imaging studies such as CT scan of the head will be required to rule out other associated secondary conditions.

• EEG Normal

  The elevated serum lithium level decreased before EEG normalization, which was associated with disappearance of all neurotoxic symptoms. [ncbi.nlm.nih.gov]

• Hyponatremia

  The disorder was related to the rapid correction of pregnancy-related hyponatremia, as a consequence of lithium-induced diabetes insipidus. [ncbi.nlm.nih.gov]

  The serum sodium level is maintained as well because hyponatremia is associated with reduced excretion of lithium. If these measures are not successful in lowering serum level of lithium, hemodialysis may be initiated in the patient [1, 2, 3, 4, 5]. [medicalfoxx.com]

  So with hyponatremia, more Li is reabsorbed causing higher Li levels and lithium toxicity. This goes for anything that causes lower na levels. [forums.studentdoctor.net]

  She was admitted with severe hyponatremia, hyperkalemia, and volume depletion. Her lithium level was noted to be 6.8 mEq/L, a critically high value. Lithium levels between 0.6 and 1.2 mEq/L are considered to be within the normal, non-toxic range. [lubinandmeyer.com]

• Sinus Arrest

  Initially, fluid therapy was started, but she lost consciousness and had a cardiac arrest for 2 minutes due to prolonged sinus arrest. Chest compression and manual artificial ventilation were performed, and body surface pacing was started. [ncbi.nlm.nih.gov]

The primary goal of the treatment would be to stabilize the patient’s condition and make immediate arrangement to remove any pills before they are absorbed by the gastrointestinal system. This is done through gastric lavage and is the treatment of choice only when the toxicity has occurred due to swallowing of large number of pills containing lithium. Dialysis will be required to remove out excess of lithium from the body [8]. Recent researches have determined that sodium polystyrene sulfonate as a cation exchanger has successfully removed lithium from both human and animal subjects making it a promising cure [9]. Intestinal irrigation and forced diuresis may also be implored to reduce absorption of lithium in the system during toxicity [10]. Medications are given to effectively manage the symptoms.

Individuals who receive prompt medical help and do not present with symptoms of deteriorated functioning of the nervous system often have a good prognosis. Those, who have taken larger doses of lithium and present with disorders of the nervous system, may suffer from debilitating symptoms for the rest of the life [5]. If dialysis is carried out immediately, other symptoms may resolve; but symptoms of nervous system may stay on for remaining part of their life. In chronic toxicity, diagnosis sometimes is delayed which can give rise to development of secondary complications. Chronic toxicity slowly and gradually harms the system causing irreversible damages that do not get corrected even with rigorous treatment regime. Elderly patients with lithium toxicity has a worse prognosis [6].

Complications

In severe cases, lithium toxicity may call for development of the following complications:

• Heart diseases characterized by first degree heart block, bradycardia and dysrhythmias
• Convulsions
• Coma
• Permanent damage to the central nervous system
• Cerebellar symptoms
• Psychosis
• Kidney failure

Accidental or intentional consumption of excess lithium is the major cause of toxicity. Individuals may tend to take extra dosage for several days together or may intentionally take a large dose together. Such an activity can lead to life threatening complications if prompt treatment is not initiated. Patients with other medications that causes the lithium to accumulate in the serum has been implicated as major source of lithium toxicity [2]. As per the guidelines given by FDA, consumption of more than 1.2 mEq/L of lithium can lead to its toxicity.

It has been estimated that cases of lithium toxicity occurs in about 10,000 individuals per year. Statistical data also point towards the fact that, about 2000 individuals in the US suffer from moderate to severe mortality due to lithium toxicity. An estimated 10% population below the age of 19 years is known to be affected by lithium toxicity.

With lithium toxicity, the organs affected are the central nervous system, followed by the renal system [3], gastrointestinal and the endocrine system. Patients with renal diseases should be closely monitored for lithium dosages because the drug is filtered from the body through the kidneys. Serum levels at 15mg/L may cause some confusion and speech impairment, while levels beyond 20mg/L may have risks for death [4]. The half-life of lithium is known to be 12 to 27 hours; however for the elderly population, the half-life increases to 32 hours.

The best way to prevent lithium toxicity if it was not intentional is to watch the dosage schedule before ingesting any pills. It is also recommended that patients with bipolar disorder should not be tempted to take any extra dose without the doctor’s consent. If symptoms of bipolar disorder tend to get worse then individuals are advised to seek medical help and not take any extra medications without consulting the doctor.

Ingestion of excess amount of lithium either accidentally or intentionally can lead to lithium toxicity. Lithium is a soft metal that is used for treating bipolar disorder. In the past this metal was meant for treating depression, gout and cluster headache. However, the use of this drug was discontinued due to its various side effects. Later on, the drug was found to have calming effects which proved to be beneficial for patients with bipolar disorder [1]. When an individual consumes more than the recommended dosage of lithium either together or slowly over a period of several days then lithium toxicity sets in.

Definition: Lithium toxicity is defined as ingestion of over 1.2mEq/L of lithium. The toxicity can either be intended or accidental. Intended toxicity occurs when individuals knowingly consume large doses of lithium to harm themselves. Accidental toxicity occurs as a result of consumption of more than prescribed dosage of medications.

Cause: Consumption of more than the recommended doses of lithium causes its toxicity. Lithium is prescribed for treatment of bipolar disorder. Patients can accidentally consume more doses and end up developing toxicity. Or certain individuals may deliberately ingest large doses of lithium causing toxicity.

Symptoms: Preliminary signs of acute lithium toxicity include nausea, diarrhea, vomiting, abdominal pain and seizures. In more severe cases, patients may experience kidney failure, coma, mood disorders, and damage to the central nervous system, tremors, increased reflexes and slurred speech.

Diagnosis: Diagnosis of the condition begins with a blood and urine test to determine the levels of lithium ingested. The blood sample needs to be collected in lithium free tubes to avoid false results. In addition, CT scan of the brain would also be required to rule out other disease conditions. Renal functions tests should be done to assess the kidney functioning. 

Treatment: Preliminary gastric lavage may be carried out to eliminate the excess lithium pills before they are absorbed into the system. Following this, if the kidneys are affected dialysis may be required to aid the organ in eliminating the lithium from the body. In addition, medications would also be administered to stabilize the condition of patients.

1. Freeman MP, Freeman SA. Lithium: clinical considerations in internal medicine. Am J Med. Jun 2006; 119(6):478-81.
2. Eyer F, Pfab R, Felgenhauer N, et al. Lithium poisoning: pharmacokinetics and clearance during different therapeutic measures. J Clin Psychopharmacol. Jun 2006; 26(3):325-30.
3. Gitlin M. Lithium and the kidney: an updated review. Drug Saf. Mar 1999; 20(3):231-43.
4. Aral H, Vecchio-Sadus A. Toxicity of lithium to humans and the environment--a literature review. Ecotoxicol Environ Saf. Jul 2008; 70(3):349-56.
5. Chen KP, Shen WW, Lu ML. Implication of serum concentration monitoring in patients with lithium intoxication. Psychiatry Clin Neurosci. Feb 2004; 58(1):25-9.
6. Burkhart, K. Lithium. In: Rosen's Emergency Medicine: Concepts and Clinical Practice. Sixth Edition. Mosby Elsevier; 2006:2442-2444.
7. Hsu CH, Liu PY, Chen JH, Yeh TL, Tsai HY, Lin LJ. Electrocardiographic abnormalities as predictors for over-range lithium levels. Cardiology. 2005; 103(2):101-6.
8. Menghini VV, Albright RC Jr. Treatment of lithium intoxication with continuous venovenous hemodiafiltration. Am J Kidney Dis. Sep 2000; 36(3):E21.
9. Ghannoum M, Lavergne V, Yue CS, Ayoub P, Perreault MM, Roy L. Successful treatment of lithium toxicity with sodium polystyrene sulfonate: a retrospective cohort study. Clin Toxicol (Phila). Jan 2010; 48(1):34-41.
10. Scharman EJ. Methods used to decrease lithium absorption or enhance elimination. J Toxicol Clin Toxicol. 1997; 35(6):601-8.