MN Arham
The Patient Mr X 53 years old Presented to OPD
  with
 Loose Stool from last 2 Days

 Nausea

 Loss of Energy

 Fatigu...
   Pulse 108 BP: 100/70 T: 36.6 R/R: 17/min
   Dehydrted
   CNS: Irritable, Confused, Mild tremor, Ataxia
   CVS: Tach...
   FBC normal
   Cusp normal
   LFT’s normal
   CRP 60
   Lithium level 3.17 mmol/L Ref: 0.50-1.20
   Lithium Toxicity
   Admit in ward
   I/V Fluids
   Stop the lithium
   Supportive care
   Lithium level repeated after 4 days is 0.68
...
•   Lithium is used in the treatment of depressive
    and bipolar affective disorders.
•   The CNS is the major organ sys...
•   The half-life of a single dose of lithium is from
      12-27 hours
  •   The half-life increases to approximately 36
...
•   Lithium is similar to sodium
•   In addition, lithium may inhibit the release of
    monoamines from nerve endings and...
•Acute poisoning - Voluntary or accidental ingestion in a
previously untreated patient

•Acute-on-chronic - Voluntary or a...
Drugs increase the lithium toxicity
•  nonsteroidal anti-inflammatory drugs [NSAIDs],
•  diuretics,
•  tetracyclines,
•  p...
Mild-to-moderate toxicity
• Generalized weakness
• Fine resting tremor
• Mild confusion
Moderate-to-severe toxicity
• Seve...
ACUTE             CHRONIC
GI (nausea, vomiting      42%                  20%
    & diarrhoea)
     CNS (seizures)     dela...
Mmol/L                    effects
         0.5    None

         1.0    Mild tremor

         1.5    Coarse tremor

      ...
•   Lithium toxicity is dose related
•   Lithium is minimally protein bound The
    therapeutic dose is 300-2700 mg/d with...
Tubular Lithium handling

                Li+           THIAZIDES




                      Li+


                        ...
   Loop diuretics may increase serum lithium
    levels and potentiate the risk of lithium
    toxicity.
   The exact me...
Tubular lithium handling:

Effect of Furosemide




                            Li+

                                  X  ...
   Measure serum lithium concentration
   Consider toxicology
   CUSP
   Imaging Studies
   Electrocardiogram
Prehospital Care
• Stabilize life-threatening conditions and initiate
  supportive therapy.
• Obtain IV access with isoton...
   Gastric decontamination
   Gastric lavage
   Activated charcoal
   Consider whole bowel irrigation.
   Role of sod...
•   Avoid onset of hypernatremia.
•   Hemodialysis
   In general, consider dialysis in patients with chronic
    toxicity...
•   Admit patients with significant signs or
    symptoms of toxicity.
•   Admit symptomatic patients, regardless of
    s...
 Accidental overdose
Asymptomatic patients and patients with serum
  lithium concentrations in the therapeutic range
  an...
 Truncal and gait ataxia
 Nystagmus

 Hypertonicity

 Short-term memory deficits

 Dementia (rare)

Prognosis
 Most ...
   Astruc B, Petit P, Abbar M. Overdose with sustained-release
    lithium preparations. Eur Psychiatry. Jun 1999;14(3):1...
Thanks
Lithium Toxicity
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Lithium Toxicity

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Lithium Toxicity

  1. 1. MN Arham
  2. 2. 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. On Lithium carbonate
  3. 3.  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. 4.  FBC normal  Cusp normal  LFT’s normal  CRP 60  Lithium level 3.17 mmol/L Ref: 0.50-1.20
  5. 5.  Lithium Toxicity
  6. 6.  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.
  7. 7. • 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,
  8. 8. • 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
  9. 9. • 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
  10. 10. •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 11
  11. 11. 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
  12. 12. 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 cardiovascular collapse
  13. 13. ACUTE CHRONIC GI (nausea, vomiting 42% 20% & diarrhoea) CNS (seizures) delayed Common > 2.mmol/L Renal Usualy non Universal signifiant ECG normal QT prolongation usual Thyroid none Hypothyroidism 20% Recovery Usual, rapid Disability 10% delayed Level correlation poor Good Hypertox. 2007 14
  14. 14. 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 15
  15. 15. • 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.
  16. 16. Tubular Lithium handling Li+ THIAZIDES Li+ LOOP AGENTS 17
  17. 17.  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.
  18. 18. Tubular lithium handling: Effect of Furosemide Li+ X Li+ 19
  19. 19.  Measure serum lithium concentration  Consider toxicology  CUSP  Imaging Studies  Electrocardiogram
  20. 20. 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.
  21. 21.  Gastric decontamination  Gastric lavage  Activated charcoal  Consider whole bowel irrigation.  Role of sodium polystyrene sulfonate (Kayexalate)  Hypokalemia.
  22. 22. • 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
  23. 23. • 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.
  24. 24.  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 overdose Obtain psychiatric clearance before discharge from the hospital
  25. 25.  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
  26. 26.  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
  27. 27. Thanks

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