< Brief History
>
A 55-year-old
woman who has had bipolar disorder with regular medical
control with Depakine for 7 years presented with easy
fatigability, thirsty, urinary frequency, diuresis, and tremor
over bilateral hands one month earlier before admission. The
daily urine amount could reach 3 liters. Her family also noted
that her consciousness became drowsy gradually one week prior
to this admission. Two days before admission, she was found to
have incoherent speech, unsteady gait and weird behaviors such
as treating kitchen as restroom or going out without clothes.
Because of these strange behaviors, her family increased the
drug dosage because they thought the drug level was not
adequate. However, these weird symptoms became worse. She was
brought to our emergency service. At the emergency service,
she was in delirium status and the Glasgow coma scale was
E2M4V3. Her body temperature was 37.4 oC, blood pressure
144/84 mmHg, and pulse rate was 112
beat per minute. Upon physical examinations, skin turgor was
poor and oral mucosa was dry. There was no
focal neurologic deficit or other abnormal physical findings.
< Laboratory and Image Study
>
1. CBC/DC & coagulation profiles:
Day after admission |
WBC K/μL |
Hgb g/dL |
Hct % |
MCV fL |
Plt K/μL |
0 |
7.51 |
11.8 |
35.4 |
92.3 |
470 |
2nd |
7.33 |
11.3 |
34.0 |
92.2 |
461 |
5th |
7.22 |
11.1 |
33.9 |
92.2 |
458 |
2. Biochemistry
Day after admission
|
BUN mg/dl |
Cre mg/dl |
Na mmol/l |
K mmol/l |
GOT U/l |
T-Bil mg/dl |
Alb g/dL |
Li mmole/l
|
0 |
39.8 |
2.9 |
130 |
3.5 |
34 |
0.8 |
3.8 |
3.48 |
2nd |
39.7 |
2.8 |
132 |
3.7 |
|
|
|
3.34 |
3rd |
25 |
2.0 |
135 |
3.8 |
|
|
|
1.85 |
5th |
25.4 |
2.1 |
138 |
4.1 |
33 |
0.9 |
|
2.18
|
3. Urine analysis:
Day after admission
|
Appearance |
Sp. gr |
pH |
Protein mg/dL
|
Glu g/dL |
Ketones |
O.B |
Urobil EU/dL
|
Bil |
0 |
Y;C |
1.05 |
7.0 |
- |
- |
- |
- |
0.1 |
- |
3rd |
Y;C |
1.05 |
7.0 |
- |
- |
- |
- |
0.1 |
- |
Day after admission
|
Nitrite |
WBC |
RBC /HPF |
WBC /HPF |
EpithCell /HPF
|
Cast /LPF |
Crystal |
Bact |
0 |
- |
- |
0-1 |
0-1 |
0-3 |
- |
- |
- |
3rd |
- |
- |
0-1 |
0 |
3-5 |
- |
- |
- |
4. Artery blood gas: PH:7.36, PaCO2: 42.3, PO2: 95, HCO3-:
22.6
5. EKG: Normal sinus rhythm
6. CXR: Normal heart size and clear lung fields.
7. Renal echo:
Size |
R't 10.3 cm ; L't 10.9 cm |
Shape |
Bilaterally normal |
Cortical thinkness |
R't: 8 mm; L't: 9 mm (within normal limit) |
Central sinus |
No hydronephrosis |
Solid or cystic lesion |
Nil |
< Course and Treatment
>
Based on the history,
lithium (Li) intoxication was suspected. The patient was treated with
fluid replacement and the Li level was checked with
a level of 3.48 mmole/l. Besides, acute renal failure was
also noted. Because this patient already had CNS depression
and acute renal failure, hemodialysis was initiated
immediately. After emergent hemodialysis, her consciousness
improved gradually with decreases of Li levels. Because
a rebound of Li concentration after hemodialysis was not
uncommon, she was weaned from hemodialysis gradually after Li
levels was stablized. She was then transferred back to the local
hospital one week after admission. During the follow-up
period, her renal function returned to normal, and there
was no neurologic sequelae.
< Analysis
>
Lithium (Li)
is am important treatment for bipolar disorders, but this therapy is associated with many
side effects due to its narrow therapeutic range.
The side effects mainly involve the kidneys and central nervous
system (CNS). The therapeutic dose is 300-2700 mg/d with
desired serum levels of 0.7-1.2 mEq/L. Li is minimally
protein bound and its clearance is predominantly through the kidneys.
Li is freely filtered at a rate that is
dependent upon the glomerular filtration rate (GFR). Consequently, dosing must be adjusted
based on renal function. Individuals with chronic renal
insufficiency must be closely monitored if placed on
Li therapy. Most filtered Li is reabsorbed in the proximal
tubule and enhanced reabsorption of Li when patients are hyponatremic
and volume depleted. Toxicity does not necessarily correlate with
the measured Li level because toxicity is affected
by the nature and type of the poisoning. Acute poisoning is
due to voluntary or accidental ingestion in a previously
untreated patient; acute-on-chronic poisoning is due to voluntary
or accidental ingestion in a patient currently
using lithium; and chronic or therapeutic poisoning
is progressive lithium toxicity, generally in a
patient on lithium therapy.
The clinical symptoms of Li
intoxication are non-specific initially, and CNS symptoms
develop subsequently, such as nausea, vomiting, diarrhea,
weakness and fatigue, lethargy and confusion, tremor and
finally seizures. Measurement of serum Li concentration should
be performed if any degree of toxicity is suspected; however,
the suspicion of toxicity should be high in any patient with
known Li use because early toxic symptoms are very vague and
nonspecific. A second serum Li level measured 2 hours after
the first may disclose any trend and sustained-release Li
preparations may take several hours to reach peak
concentrations. Electrolyte disturbances, particularly
hyponatremia, may predispose an individual to Li toxicity. Li
toxicity is one of the few clinical entities that may be
associated with a decrease in the anion gap. Treatment for Li
intoxication is to enhance elimination by volume resuscitation
with normal saline or one-half isotonic sodium chloride
solution and hemodialysis. Continuous venovenous
hemodiafiltration also effectively removes Li and can prevent
post-dialysis rebound. In general, dialysis should be
considered in patients with chronic toxicity and serum lithium
concentrations higher than 4 mEq/L and in unstable chronic
patients with lithium levels higher than 2.5 mEq/L. However,
guidelines for hemodialysis are controversial in patients with
acute lithium intoxication and hemodialysis is generally
suggested in patients with higher serum lithium levels despite
relatively minor symptoms. Change in mental status assists in
determining need for dialysis.
Li may produce nephrogenic diabetes
(NDI), renal tubular acidosis, chronic interstitial nephritis
and even nephrotic syndrome. In our patient, she suffered from
Li-induced polyuria, but it improved gradually before we
tested the response to exogenous antidiuretic hormone (ADH).
Most patients with Li-induced polyuria are unresponsive to
exogenous ADH treatment as a result of abnormalities in the
medullary osmotic gradient or direct inhibition of the tubular
hydro-osmotic effects of ADH. Chronic administration of Li
diminishes the medullary and papillary osmolar gradients as a
result of depletion of urea without affecting sodium chloride
concentrations. However, Li-induced polyuria is largely due to
direct inhibition of the ADH-dependent aspects of water
conservation. Although Li-induced NDI usually improves after
Li withdrawal, some patients still have persistent
concentrating defect for several years. Amiloride rduces
urinary volume and enhances the concentrating ability of
patients with Li-induced NDI.
< Reference
>
- Harrison's principles of internal
medicine 15 edition
- Primer on Kidney Disease, 4th
edition
- Optimizing lithium treatment. J
Clin Psychiatry. 2000;61 Suppl 9:76-81
- eMedicine, Toxicity, Lithium, Last
Updated: June 13,
2006
|