Transcript 豐原醫院優點

急診雜誌討論會
• 題目: 鋰鹽中毒
• 來源: 1. Taiwan Medical Journal Vol.50 No.7
2. Up To Date
• 報告者: Stanley. Wang.
• 地點: 急診討論室. 署立台中醫院.
• 時間: 20110414
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Lithium---anti-manic agent
• Bipolar disorders: Oral: 900-2400 mg/day in 3-4
divided doses or 900-1800 mg/day in two divided doses
of extended release
• Note: Monitor serum concentrations and clinical
response (efficacy and toxicity) to determine proper
dose. ( 6th day prior to medication ).
• Do not confuse mEq (milliequivalent) with mg
(milligram). Note: 300 mg lithium carbonate or citrate
contain 8 mEq lithium. Dosage should be written in mg
(milligrams) to avoid confusion.
• Ligilin ( lethonate ) 300 mg/cap.
Therapeutic: 0.6 – 1.2 mEq/L.
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General consideration (1)
• Lithium poisoning may be acute, acute-on-chronic, or
chronic. The symptoms and signs of toxicity differ based
upon the total body burden of lithium and the rate of
onset of toxicity.
• Elderly patients are at higher risk for lithium toxicity
due to both a lower glomerular filtration rate and a
reduced volume of distribution (secondary to reductions
in lean body mass and total body water).
• Lithium toxicity can also occur with minor declines in
renal function (eg, from nephrotoxic medications) or
from dehydration for any reason (eg, vomiting, diarrhea,
fever).
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General consideration (2)
• Patients with acute lithium toxicity often present
with symptoms of nausea, vomiting, and diarrhea;
neurologic findings develop late in acute poisoning.
• Patients with chronic lithium toxicity often present
with neurologic symptoms and signs.
• Neurologic findings can include sluggishness, ataxia,
confusion or agitation, and neuromuscular
excitability.
• Severe poisoning can lead to seizures, nonconvulsive
status epilepticus, and encephalopathy.
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Complex partial status (nonconvulsive)
epilepticus
• Complex partial status (nonconvulsive)
epilepticus is characterized by continuous or
repeated episodes of focal motor, sensory, or
cognitive symptoms with impaired consciousness,
and should be considered in the differential
diagnosis of acute confusional states .
• Other symptoms, such as automatisms and
behavioral disturbances, may also occur.
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General consideration (3)
• The differential diagnosis for lithium poisoning
includes serotonin syndrome and neuroleptic
malignant syndrome.
• Serum lithium concentrations can be useful for
determining the severity of an overdose or the
need for hemodialysis and should be obtained
in any patient with suspected toxicity.
• However, lithium concentrations often do
not correlate with clinical signs of toxicity.
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General consideration (4)
• Restoration of sodium and water balance in
hypovolemic patients with lithium toxicity is
essential to maximize lithium clearance.
Gastrointestinal losses are replaced with
isotonic (0.9 percent) saline.
• Lithium is readily dialyzable due to its low
molecular weight, negligible protein binding,
and small volume of distribution. Therefore,
hemodialysis is the treatment of choice for
severe lithium toxicity.
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Case presentation
S: Vomiting & diarrhea with stool incontinence 8 hrs post
ingestion of 49 tablets of lithium this morning.
History of affective disorders.
O: TPR: 36.8 C/80/20, BP: 130/82 mmhg. Lab: Lithium
carbonate: 4.58 mEq/L, BUN/Cr: 8.0/1.1, Na/K:
142/2.4. EKG: Sinus bradycardia with QT prolong.
A: Lithium intoxication.
P: Emergent hemo-dialysis.
Patient discharged 6 days later
& regular FU at Psy. OPD.
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Lithium -- Mechanism
• Treat & prevent attack of manic-depressive disorders.
• Peak serum level: 30’-2 hrs post oral intake.
Complete absorption: 6 – 8 hrs.
Stable serum concentration: 5-6 days.
• Serum level best be checked 12 hrs post ingestion & 3-4 days later.
Be cautious in P’t with poor renal function. ( renal excretion )
• Prone to lithium intoxication: DM, Hypertension, Renal failure, Old
age, Low sodium diet, NSAIDs or Diuretics use .
• Side effect: Early: Thirsty, Increased urine output, G-I upset, Loose
stool, Tired, Hand tremor, Muscle twitching.
Maintenance dose: Hand tremor, BW gain, Thyroid
enlargement, edema, acne.
Single H.S dose to reduce side effect.
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Pharmacology & cellular Toxicology
• Lithium affects two intracellular signaling pathways,
inositol monophosphate and glycogen synthase kinase-3 .
• Lithium decreases intracellular inositol, which may be a
mechanism for mood stabilization. Lithium also inhibits
glycogen synthase kinase-3, a component of diverse
signaling pathways involved in energy metabolism,
neuroprotection, and neuroplasticity.
• Lithium has a narrow therapeutic index; a large
proportion of patients on chronic lithium therapy
experience at least one episode of toxicity during
treatment . ( 0.6 – 1.2 mEq/L )
• The highest intracellular lithium levels are found in the
brain and the kidneys.
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Inositol monophosphate
• Inositol play crucial roles in diverse cellular functions, such
as cell growth, apoptosis, cell migration, endocytosis, and
cell differentiation.
• Inositol is a substance produced by the human body and is
involved with fat and cell metabolism.
Adequate amounts of Inositol Monophosphate are claimed to
be potentially beneficial for:
• Diabetic nerve disorders
• Kidney failure.
• Low birth weight infants with respiratory distress syndrome
• Multiple sclerosis.
• Depression.
• Obsessive compulsive disorder.
• Panic disorders.
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Lithium intoxication – S/S
• Mild: Sleepy, Proximal muscle weakness, Impaired
memory, G-I: nausea, vomiting, diarrhea.
• Moderate: Neurotoxic: Delirium, Convulsion, Coma,
Incontinence, hyper- reflexia, Fasciculation,
Parkinson-like s/s : Ataxia. Un-coordination.
• Severe: Nephrotoxic: Nocturia, Distal tubular acidosis,
Impaired RFT.
Cardiotoxic: ST-T change, QT prolong, Flat T
Conduction delay, Hypotension.
• Acute intoxication– Less CNS depression.
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Long-term neurologic sequelae (1)
• In some cases, neurologic complications persist
despite lithium removal by hemodialysis.
• The syndrome of irreversible lithium
effectuated neurotoxicity (SILENT) consists of
prolonged neurologic and neuropsychiatric
symptoms following lithium toxicity . In typical
cases of SILENT, neurologic toxicity develops
along with an elevated lithium concentration,
but symptoms persist despite successful
removal of the drug.
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Long-term neurologic sequelae (2)
• Cerebellar dysfunction, extrapyramidal symptoms,
brainstem dysfunction, and dementia can develop as part
of SILENT (syndrome of irreversible lithium effectuated
neurotoxicity ) .
• Other neurologic sequelae may include nystagmus,
choreoathetoid movements, myopathy, and blindness.
• A review of 90 published cases identified cerebellar
dysfunction as the most common sequelae, and proposed
that demyelination at multiple sites in the CNS may be the
cause .
• SILENT can continue for months and in rare cases effects
persist for years.
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Lithium intoxication - Diagnosis
• History: Psychiatry ( Mania ) P’t with conscious
change + S/S of lithium intoxication.
• Serum level: Therapeutic: 0.6 – 1.2 mEq/L.
• Intoxication: Mild- Moderate: 1.5 – 2.5 mEq/L.
Severe: 2.5 – 3.0 mEq/L.
Lethal dose: 3.0 – 4.0 mEq/L.
• EKG, ABG, Biochemistry, BR.
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Lithium intoxication - Tx
• Hydration and electrolyte balance, beware of
hypernatremia.
• Gastric lavage if ingested within 1 hour.
Charcot is useless ( poor absroption ).
• Block proximal tubule re-absorption: Sod. Bicarbonate,
Diuretics, Amino-phylline.
• Moderate to severe intoxication with conscious change –
Hemo-dialysis: 10-12 hrs ( indication: Li level >4mEq/L )
Goal: Li level < 1 mEq/L 8 hrs later.
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Nephrogenic diabetes insipidus
• NDI is a known complication of chronic
lithium poisoning. In patients on chronic lithium
therapy who are suspected of concomitant NDI, the
serum sodium concentration should be followed closely,
particularly in patients receiving IV hydration and
those with altered mentation who may not drink in
response to thirst.
• In patients admitted with chronic lithium toxicity,
measure the serum sodium concentration every 6 to 12
hours for the first 24 to 48 hours. Care must be taken
to avoid hypernatremia from IV hydration in patients
with inadequate free water intake.
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H.D for lithium intoxication (1)
• Lithium is readily dialyzable due to its low molecular
weight, negligible protein binding, and small volume of
distribution. Therefore, hemodialysis is the treatment of
choice for severe lithium toxicity.
• The appropriate indications for the treatment of lithium
poisoning with hemodialysis remain controversial.
• We recommend treatment with hemodialysis for lithium
poisoning in the following settings regardless of the nature
of the ingestion (ie, acute, acute-on-chronic, or chronic) :
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H. D for lithium intoxication (2)
• The serum lithium concentration is > 4 mEq/L (4
mmol/L), regardless of the clinical status of the patient.
Lithium concentrations above 4 mEq/L represent a
large total body lithium burden and suggest a window
in which hemodialysis can remove substantial amounts
of toxin.
• The serum lithium concentration is > 2.5 mEq/L (2.5
mmol/L) and the patient manifests signs of significant
lithium toxicity (eg, seizures, depressed mental status),
has renal insufficiency or other conditions that limit
lithium excretion, or suffers from an illness that would
be exacerbated by aggressive IV fluid hydration (eg,
decompensated heart failure).
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H.D for lithium intoxication (3)
• Lithium clearance with hemodialysis ranges from 70 to 170
mL/min, compared to normal renal clearance of 10 to 40
mL/min (due to extensive reabsorption of lithium in the
proximal tubules), and only 15 mL/min with peritoneal
dialysis.
• Lithium equilibrates slowly between the extracellular and
intracellular fluids. As a result, a rebound increase in serum
lithium levels occurs after the cessation of hemodialysis, as
intracellular lithium diffuses into the extracellular space.
• Continued gastrointestinal drug absorption may contribute
to the rebound effect. Therefore, it is generally
recommended that a serum lithium concentration be
measured six hours after hemodialysis to confirm that levels
are decreasing.
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H.D for lithium intoxication (4)
• Some experts recommend extending the duration of
hemodialysis to minimize the rebound phenomenon and
repeating dialysis as necessary until the serum lithim level
remains < 1 mEq/L (1 mmol/L) for six to eight hours after
treatment .
• Nine hours of hemodialysis removes approximately 60 percent
of the total lithium stores . Some authors suggest that at least
two sessions of hemodialysis are required for adequate
treatment. However, in most cases, unless serum lithium
concentrations are extremely high, one session of hemodialysis
is usually sufficient.
• We suggest obtaining consultation with a medical toxicologist
or poison control center if additional hemodialysis treatment
may be needed.
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Lemat for H.D. , Chebic no charcot
• No Charcot: Corrosive agent, Hydrocarbon,
Ethanol ( Methanol ),
Boric acid, Metal ion, Cyanide.
• H.D: Lithium, Ethylene glycol, Methanol,
Aspirin, Theophylline.
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Thanks for Your Attention
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