Discussion about Lithium Toxicity

1. MN Arham

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.  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
 CRP 60
 Lithium level 3.17 mmol/L Ref: 0.50-1.20

5.  Lithium Toxicity

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.

8. • 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,

9. • 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

10. • 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

11. •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

12. 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

13. 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

14. 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

15. 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

16. • 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.

17. Tubular Lithium handling
Li+ THIAZIDES
Li+
LOOP
AGENTS
17

18.  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.

19. Tubular lithium handling:
Effect of Furosemide
Li+
X Li+
19

20.  Measure serum lithium concentration
 Consider toxicology
 CUSP
 Imaging Studies
 Electrocardiogram

21. 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.

22.  Gastric decontamination
 Gastric lavage
 Activated charcoal
 Consider whole bowel irrigation.
 Role of sodium polystyrene sulfonate
(Kayexalate)
 Hypokalemia.

23. • 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

24. • 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.

25.  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

26.  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

27.  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

28. Thanks