Difference between revisions of "Lithium toxicity"

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==Background==
 
==Background==
*Toxicity most often involves a drug-drug interaction or decreased renal excretion
+
*Mechanism of action is poorly understood.
*Lithium levels are only helpful for chronic toxicity
+
*Despite availability of newer drugs, [[Lithium]] remains most effective treatment for bipolar disorder, and it is still in use
*Pts die of respiratory failure or CV collapse
+
*Lithium initially distributes in extracellular fluid, then gradually redistributes to other areas including the brain (takes up to 24 hours after absorption)
 +
*95% renal excretion
 +
**[[NSAIDs]], [[diuretics]], [[ACE-inhibitors]] → ↑ Lithium serum concentration by ↓ lithium excretion
 +
*Lithium toxicity rarely fatal (only 11 deaths out of 6815 reported toxic exposures in 2012)<ref> Mowry JB, Spyker DA, Cantilena LR Jr., Bailey JE, Ford M: 2012 annual report of the American association of poison control centers’ national poison data system (NPDS): 30th annual report. Clin Toxicol (Phila) 51: 949–1229, 2013</ref>
  
==Precipitants==
+
===Common Precipitants===
#Overdose
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*[[Overdose]]
#Renal failure
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*[[Renal failure]]
#Volume depletion
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*Volume depletion
##Diuretic use, vomiting, diarrhea, diaphoresis, decreased oral intake
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**[[Diuretic]] use, [[vomiting]], [[diarrhea]], diaphoresis, decreased oral intake
#Hyperthermia
+
*[[Hyperthermia]]
#Infection
+
*Infection
#CHF
+
*[[CHF]]
#Surgery
+
*Surgery
#Cirrhosis
+
*[[Cirrhosis]]
  
 
==Clinical Features==
 
==Clinical Features==
#GI
+
''Three recognized patterns of Lithium toxicity - "Acute", "Acute-on-chronic", and "Chronic".<ref>Waring WS, Laing WJ, Good AM, Bateman DN. Pattern of lithium exposure predicts poisoning severity: evaluation of referrals to a regional poisons unit. QJM. 2007 May;100(5):271-6. Epub 2007 Apr 5.</ref>''
##Usually first to develop
 
##N/V
 
##Diarrhea
 
##Generalized abd pain
 
#CNS
 
##Usually develops as GI symptoms are abating; more common in chronic toxicity
 
##Tremor
 
##Muscle weakness
 
##Ataxia
 
##Stupor
 
##Seizure
 
##Coma
 
#Cardiac
 
##Hypotension
 
##Conduction Abnormalities
 
##Ventricular dysrhythmias
 
##Prolonged QT, transient ST depression, TWI
 
#Endocrine
 
##Hyper/Hypothyroidism or hyperparathyroidism
 
##Hypothyroidism most common
 
# Renal
 
##Nephrogenic Diabetes Insipidus
 
###Can be seen mildly at therapeutic levels
 
###Causes polyuria and polydipsia
 
  
==Diagnosis==
+
===Acute===
#Lithium level
+
Occurs in patients not previously receiving lithium (i.e. with no current body stores)
##Correlates better with chronic than acute toxicity
 
#Chemistry
 
##Low or negative ion gap
 
##Elevated osmolar gap
 
#TSH
 
#ECG
 
##QT prolongation
 
##Diffuse TWI
 
  
''level may be falsely elevated if placed in a green top tube due to the heparin lithium interaction''
+
Serum concentrations can fall rapidly as lithium redistributes to tissues, and serum level does not correlate with degree of toxicity. GI symptoms predominate.
  
==Treatment==
+
*GI - [[nausea/vomiting]], [[diarrhea]], [[abdominal pain]]
#GI decontamination
+
**Earliest and most common symptoms
##Consider lavage for massive ingestions (>4gm) if can be performed w/in 1hr
+
*Cardiac effects - [[bradycardia]], [[QT prolongation]], T-wave flattening or inversion<ref>Canan F, Kaya A, Bulur S, Albayrak ES, Ordu S, Ataoglu A. Lithium intoxication related multiple temporary ecg changes: A case report. Cases Journal. 2008;1:156. doi:10.1186/1757-1626-1-156.</ref>
##Activated charcoal is ineffective
+
**Can also cause [[Brugada]]-like ECG pattern
#Fluid resuscitation
+
*CNS Depression - late finding (takes time for lithium to distribute to CNS), indicates progression of toxicity
##Average pt has Na/volume deficit; giving fluid helps reestablish normal Li excretion
+
 
###Give 2L NS bolus; then give 200mL/hr
+
===Acute-on-Chronic===
#Seizure
+
Also called "Acute-on-therapeutic", occurs in patients currently taking lithium due to acute ingestion of supra-therapeutic doses.
##Benzos are 1st line
+
 
##Phenobarbital is 2nd line
+
*Symptoms are a mix of both acute and chronic - includes both GI and CNS effects
##Phenytoin is ineffective
+
 
#Dialysis
+
===Chronic===
##Indications:
+
Occurs insidiously in patients on chronic lithium therapy. Toxicity is secondary to increased absorption or decreased elimination. CNS symptoms predominate.
###Li level >4 (acute overdose)
+
 
###Li level >3.5 (chronic toxicity)
+
Chronic lithium therapy is associated with nephrogenic diabetes insipidus, which → hyponatremia, fluid loss → ↑ lithium levels (can precipitate toxicity)
###Little change in Li level after 6hr IVF
+
 
###Sustained Li level >1.0 after 36hr
+
*Neurotoxicity is major finding, and is generally more profound than that seen in acute toxicity
###Baseline renal failure
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**Mild symptoms include [[tremor]], drowsiness
###Ingestion of sustained-release preparations
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**Progressive symptoms include hyperreflexia, [[confusion]], [[ataxia]], [[seizures]], [[extrapyramidal symptoms]], [[coma]]
##Goal:
+
*[[Hypothyroidism]] (lithium inhibits thyroid hormone release)
###Li level <1
+
 
####Must monitor for up to 8hr following dialysis to ensure levels stay <1
+
===Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT)<ref>Adityanjee, Munshi KR, Thampy A. The syndrome of irreversible lithium-effectuated neurotoxicity. Clin Neuropharmacol. 2005 Jan-Feb;28(1):38-49.</ref>===
 +
*Persistent sequelae of lithium toxicity
 +
*Defined as neurologic dysfunction persisting > 2 months after cessation of lithium therapy
 +
*Exact mechanism unknown (possibly related to CNS demyelination).
 +
*Symptoms
 +
**Cerebellar dysfunction ([[dysarthria]], [[ataxia]], [[tremor]], gait instability)
 +
**Peripheral neuropathy
 +
**[[Extrapyramidal symptoms]]
 +
*Brainstem dysfunction
 +
*[[Dementia]]
 +
 
 +
==Differential Diagnosis==
 +
{{Heavy metals list}}
 +
 
 +
==Evaluation==
 +
*Lithium level
 +
**Therapeutic level = 0.6-1.2 meq/L
 +
**''Serum level may be falsely elevated if placed in a green top tube due to the heparin lithium interaction''
 +
**''Serum levels do not predict CNS levels and only roughly correlate with clinical symptoms''
 +
*Metabolic Panel
 +
*TSH
 +
*[[ECG]]
 +
*Acetaminophen and Salicylate Levels (possible coingestants)
 +
 
 +
==Management==
 +
===GI decontamination===
 +
*[[Whole bowel irrigation]] (only for extended release tablets)
 +
*[[Gastric lavage]] and [[activated charcoal]] not effective and potentially harmful
 +
===[[Fluid resuscitation]]===
 +
*Average patient has Na/volume deficit; giving fluid helps reestablish normal renal Lithium excretion
 +
*Give 2L NS bolus, then start 200mL/hr or 2x maintenance rate
 +
===[[Hemodialysis]]===
 +
''Most effective method of removal. Must follow serial lithium levels - levels will likely rise after HD due to redistribution from tissues; additional HD may be required.''
 +
'''Indications:'''
 +
*Kidney function is impaired and the [Li+] >4.0 mEq/L (1D recommendation)<ref name="extra">Extracorporeal Treatment for Lithium Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup. Decker BS et al. Clin J Am Soc Nephrol 2015 Jan 12 [http://www.extrip-workgroup.org/#!recommendations/cy1f Extrip Recs]</ref>
 +
*Clinical deterioration
 +
*In the presence of a decreased level of consciousness, seizures, or life-threatening dysrhythmias irrespective of [Li+] (1D)<ref name="extra"></ref>
 +
*[Li+].>5.0 mEq/L (2D suggestion)
 +
*If the expected time to obtain a [Li+]<1.0 mEq/L with optimal management is >36 h (2D suggestion)<ref name="extra"></ref>
 +
*Baseline renal failure
 +
*Contraindication to aggressive fluid resuscitation (CHF, etc)
 +
*Make final decision after consulting toxicologist and/or nephrologist since it's a complex decision <ref>Internet Book of Critical Care (IBCC) Lithium intoxication https://emcrit.org/ibcc/lithium/#dialysis</ref>
  
 
==Disposition==
 
==Disposition==
*Consider discharge for pts asymptomatic after 4-6hr obs with 2 downtrending levels
+
*Consider discharge for patients who are asymptomatic after 4-6hr obs, 2 downtrending lithium levels, and no worsening of renal function
*Admit all pts w/ Li level >1.5
+
*Admit all patients with Li level >1.5
*Admit all pts w/ ingestion of sustained-release preparation (regardless of Li level)
+
*Admit all patients with ingestion of sustained-release preparation (regardless of Li level)
  
 
==See Also==
 
==See Also==
 
*[[Toxicology (Main)]]
 
*[[Toxicology (Main)]]
 +
*[[Lithium]]
 +
*[[Heavy metals]]
  
==Source==
+
==References==
*Tintinalli
+
<references/>
  
[[Category:Tox]]
+
[[Category:Toxicology]]

Latest revision as of 06:43, 9 March 2021

Background

  • Mechanism of action is poorly understood.
  • Despite availability of newer drugs, Lithium remains most effective treatment for bipolar disorder, and it is still in use
  • Lithium initially distributes in extracellular fluid, then gradually redistributes to other areas including the brain (takes up to 24 hours after absorption)
  • 95% renal excretion
  • Lithium toxicity rarely fatal (only 11 deaths out of 6815 reported toxic exposures in 2012)[1]

Common Precipitants

Clinical Features

Three recognized patterns of Lithium toxicity - "Acute", "Acute-on-chronic", and "Chronic".[2]

Acute

Occurs in patients not previously receiving lithium (i.e. with no current body stores)

Serum concentrations can fall rapidly as lithium redistributes to tissues, and serum level does not correlate with degree of toxicity. GI symptoms predominate.

Acute-on-Chronic

Also called "Acute-on-therapeutic", occurs in patients currently taking lithium due to acute ingestion of supra-therapeutic doses.

  • Symptoms are a mix of both acute and chronic - includes both GI and CNS effects

Chronic

Occurs insidiously in patients on chronic lithium therapy. Toxicity is secondary to increased absorption or decreased elimination. CNS symptoms predominate.

Chronic lithium therapy is associated with nephrogenic diabetes insipidus, which → hyponatremia, fluid loss → ↑ lithium levels (can precipitate toxicity)

Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT)[4]

  • Persistent sequelae of lithium toxicity
  • Defined as neurologic dysfunction persisting > 2 months after cessation of lithium therapy
  • Exact mechanism unknown (possibly related to CNS demyelination).
  • Symptoms
  • Brainstem dysfunction
  • Dementia

Differential Diagnosis

Heavy metal toxicity

Evaluation

  • Lithium level
    • Therapeutic level = 0.6-1.2 meq/L
    • Serum level may be falsely elevated if placed in a green top tube due to the heparin lithium interaction
    • Serum levels do not predict CNS levels and only roughly correlate with clinical symptoms
  • Metabolic Panel
  • TSH
  • ECG
  • Acetaminophen and Salicylate Levels (possible coingestants)

Management

GI decontamination

Fluid resuscitation

  • Average patient has Na/volume deficit; giving fluid helps reestablish normal renal Lithium excretion
  • Give 2L NS bolus, then start 200mL/hr or 2x maintenance rate

Hemodialysis

Most effective method of removal. Must follow serial lithium levels - levels will likely rise after HD due to redistribution from tissues; additional HD may be required. Indications:

  • Kidney function is impaired and the [Li+] >4.0 mEq/L (1D recommendation)[5]
  • Clinical deterioration
  • In the presence of a decreased level of consciousness, seizures, or life-threatening dysrhythmias irrespective of [Li+] (1D)[5]
  • [Li+].>5.0 mEq/L (2D suggestion)
  • If the expected time to obtain a [Li+]<1.0 mEq/L with optimal management is >36 h (2D suggestion)[5]
  • Baseline renal failure
  • Contraindication to aggressive fluid resuscitation (CHF, etc)
  • Make final decision after consulting toxicologist and/or nephrologist since it's a complex decision [6]

Disposition

  • Consider discharge for patients who are asymptomatic after 4-6hr obs, 2 downtrending lithium levels, and no worsening of renal function
  • Admit all patients with Li level >1.5
  • Admit all patients with ingestion of sustained-release preparation (regardless of Li level)

See Also

References

  1. Mowry JB, Spyker DA, Cantilena LR Jr., Bailey JE, Ford M: 2012 annual report of the American association of poison control centers’ national poison data system (NPDS): 30th annual report. Clin Toxicol (Phila) 51: 949–1229, 2013
  2. Waring WS, Laing WJ, Good AM, Bateman DN. Pattern of lithium exposure predicts poisoning severity: evaluation of referrals to a regional poisons unit. QJM. 2007 May;100(5):271-6. Epub 2007 Apr 5.
  3. Canan F, Kaya A, Bulur S, Albayrak ES, Ordu S, Ataoglu A. Lithium intoxication related multiple temporary ecg changes: A case report. Cases Journal. 2008;1:156. doi:10.1186/1757-1626-1-156.
  4. Adityanjee, Munshi KR, Thampy A. The syndrome of irreversible lithium-effectuated neurotoxicity. Clin Neuropharmacol. 2005 Jan-Feb;28(1):38-49.
  5. 5.0 5.1 5.2 Extracorporeal Treatment for Lithium Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup. Decker BS et al. Clin J Am Soc Nephrol 2015 Jan 12 Extrip Recs
  6. Internet Book of Critical Care (IBCC) Lithium intoxication https://emcrit.org/ibcc/lithium/#dialysis