LITHIUM TOXICITY

MN Arham

Case

The Patient Mr X 53 years old Presented to OPD with

Loose Stool from last 2 Days Nausea Loss of Energy FatigueKnown patient of Bipolar Disorder and

under treatment by Psychiatry.On Lithium carbonate

Examination

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

Lab studies

FBC normal Cusp normal LFT’s normal CRP 60 Lithium level 3.17 mmol/L Ref: 0.50-1.20

Diagnosis

Lithium Toxicity

Management

Admit in ward I/V Fluids Stop the lithium Supportive care Lithium level repeated after 4 days is

0.68 mmol/L Discharged via Psychiatry after one week.

Back Ground & Pharmacokinetics

• Lithium is used in the treatment of depressive and bipolar affective disorders.

• The CNS is the major organ system affected, although the renal, GIT, endocrine, and CVS also may be involved.

• Lithium is available only for oral administration.

• Absorbed from the GI tract. • Peak levels occur 2-4 hours postingestion,

Pharmacokinetics

• The half-life of a single dose of lithium is from 12-27 hours

• The half-life increases to approximately 36 hours in elderly

• Additionally, half-life may be considerably longer with chronic lithium use.

• An estimated 10,000 toxic exposures occur per year. These data indicate a gradual increase over the past 10 years*.

* From USA

MOA

• Lithium is similar to sodium• In addition, lithium may inhibit the release of

monoamines from nerve endings and increase their uptake.

• The exact mode of action of lithium in affective disorders is unknown.

• Lithium has a narrow therapeutic ratio.• Blood concentration must be carefully monitored

to avoid toxicity. • Early signs of lithium toxicity are vomiting and

severe diarrhoea followed by tremor, ataxia, renal impairment and convulsions

Types of poisoning

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• Acute poisoning - Voluntary or accidental ingestion in a previously untreated patient

• Acute-on-chronic - Voluntary or accidental ingestion in a patient currently using lithium

• Chronic or therapeutic poisoning - Progressive lithium toxicity, generally in a patient on lithium therapy

Discussion

Drugs increase the lithium toxicity• nonsteroidal anti-inflammatory drugs [NSAIDs],• diuretics, • tetracyclines, • phenytoin,and • cyclosporine

Symptoms• Nausea and vomiting• Diarrhea• Weakness and fatigue• Lethargy and confusion• Tremor• Seizure

Clinical PictureMild-to-moderate toxicity• Generalized weakness• Fine resting tremor• Mild confusionModerate-to-severe toxicity• Severe tremor• Muscle fasciculations• Choreoathetosis• Hyperreflexia• Clonus• Opisthotonos• Stupor• Seizures• Coma• Signs of cardiovascular collapse

Lithium Toxicity Effects

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ACUTE CHRONIC

GI (nausea, vomiting & diarrhoea)

42% 20%

CNS (seizures) delayed Common > 2.mmol/L

Renal Usualy non signifiant

Universal

ECG normal QT prolongation usual

Thyroid none Hypothyroidism 20%

Recovery Usual, rapid Disability 10% delayed

Level correlation poor Good

Hypertox. 2007

Symptoms with chronic toxicity

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Mmol/L

effects

0.5 None

1.0 Mild tremor

1.5 Coarse tremor

2.0 Hyperreflexia, dysarthria

2.5 Myoclonia, ataxia,confusion

> 3.0 Delirium, coma, seizures

Hypertox 2007

Dosing

• Lithium toxicity is dose related• Lithium is minimally protein bound The

therapeutic dose is 300-2700 mg/d with desired serum levels of 0.7-1.2 mEq/L.

• Lithium clear via kidneys. • Most filtered lithium is reabsorbed in the PCT• Diuretics acting distally to the proximal tubule,

such as thiazides and spironolactone• Reabsorption of lithium is increased and toxicity

is more likely in patients who are hyponatremic or volume depleted, both of which are possible consequences of diuretic therapy.

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Tubular Lithium handling

Li+

Li+

THIAZIDES

LOOPAGENTS

Effects of Furosemide (an example)

Loop diuretics may increase serum lithium levels and potentiate the risk of lithium toxicity.

The exact mechanism is unknown but may be related to the sodium loss induced by loop diuresis, which produces a compensatory increase in proximal tubular reabsorption of sodium along with lithium.

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Li+

Li+X

Tubular lithium handling:

Effect of Furosemide

Investigation

Measure serum lithium concentration Consider toxicology CUSP Imaging Studies Electrocardiogram

Treatment

Prehospital Care• Stabilize life-threatening conditions and

initiate supportive therapy.• Obtain IV access with isotonic sodium

chloride solution.• Monitor cardiac function to assess rhythm

disturbances.• Obtain all pill bottles available to the patient.• Supportive therapy should take precedence.

Treatment (continued...)

Gastric decontamination Gastric lavage Activated charcoal Consider whole bowel irrigation. Role of sodium polystyrene sulfonate

(Kayexalate) Hypokalemia.

Treatment (continued...)

• Avoid onset of hypernatremia.• Hemodialysis In general, consider dialysis in patients with chronic

toxicity and serum lithium concentrations higher than 4mEq/L; also consider dialysis in unstable chronic patients with lithium levels higher than 2.5 mEq/L.

Guidelines for hemodialysis are more controversial in patients with acute lithium intoxication but generally refer to higher serum lithium levels despite relatively minor symptoms.

Change in mental status assists in determining need for dialysis

Further Inpatient Care

• Admit patients with significant signs or symptoms of toxicity.

• Admit symptomatic patients, regardless of serum lithium levels; admit patients with serum lithium levels higher than 2 mEq/L.

• Admit to an ICU patients with chronically elevated lithium levels higher than 4 mEq/L.

• Perform serial serum lithium determinations approximately 4 hours apart to confirm a declining trend.

Further Outpatient Care

Accidental overdose Asymptomatic patients and patients with

serum lithium concentrations in the therapeutic range and minor toxicity may be discharged with scheduled follow-up in 1-2 days.

Intentional overdoseObtain psychiatric clearance before

discharge from the hospital

Complications & Prognosis

Truncal and gait ataxia Nystagmus Hypertonicity Short-term memory deficits Dementia (rare)Prognosis Most cases of lithium toxicity result in a

favourable outcome; however, up to 10% of individuals with severe toxicity

References

Astruc B, Petit P, Abbar M. Overdose with sustained-release lithium preparations. Eur Psychiatry. Jun 1999;14(3):172-4.

Bailey B, McGuigan M. Comparison of patients hemodialyzed for lithium poisoning and those for whom dialysis was recommended by PCC but not done: what lesson can we learn?. Clin Nephrol. Nov 2000;54(5):388-92.

Chen KP, Shen WW, Lu ML. Implication of serum concentration monitoring in patients with lithium intoxication. Psychiatry Clin Neurosci. Feb 2004;58(1):25-29.

Eyer F, Pfab R, Felgenhauer N. Lithium poisoning: pharmacokinetics and clearance during different therapeutic measures. J Clin Psychopharmacol. Jun 2006;26(3):325-30.

Groleau G. Lithium toxicity. Emerg Med Clin North Am. May 1994;5. 12(2):511-31.

E-medicine Hypertox 2007 Tables

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