Lithium - Chemical Poisons

Lithium

·              Lithium is strictly speaking not a heavy metal. It actually belongs to the same group of elements as sodium and potas- sium. However, convention demands that it be classed with the metals.

·              Lithium chloride was once used as a substitute for table salt in hypertensive patients. Numerous reports of toxicity led to its abandonment. Today lithium salts are mainly used for the treatment of manic depressive psychosis (or bipolar disorder), treatment of alcoholism, amelioration of neutropenia induced by chemotherapy, and prevention of cluster headaches. The usual dosage recommended varies from 600 to 900 mg/day initially, and later reduced to an optimal maintenance dose (which produces a blood level of 0.7 to 1 mEq/L).

·              Lithium is also used industrially in nuclear reactors as a coolant, alkaline storage batteries, and alloys.

Clinical Features

Adverse effects—

·              Common side effects of lithium (which unfortunately has a very narrow toxic therapeutic index), include thirst, polyuria, tremor, acne, hypothyroidism, dysar- thria, ataxia, alopecia, and exacerbation of psoriasis.

·              In about 10% of patients, nephrogenic diabetes insip- idus can occur.

·              GI effects are usually mild and reversible. 10 to 20% of patients experience diarrhoea, vomiting, abdominal pain, nausea, and anorexia in the early stages of treat- ment. Dehydration is a common finding in patients with chronic lithium intoxication.

·              Other effects include exophthalmos, restlessness, and anxiety.

·              A parkinsonian syndrome characterised by tremor, fasciculations and cogwheel rigidity may occur with or without other signs of toxicity.

·              Hypercalcaemia with cardiac rhythm disturbances has been reported as a side effect of lithium treatment.

·              Neutrophilia is a reported side effect of treatment with lithium, and significant leukocytosis may develop with lithium toxicity.

·              There is evidence to indicate that lithium is teratogenic and may cause cardiac malformations.

·              Toxicity has also been noted in newborn babies breastfed by lithium-ingesting mothers, manifesting as hypotonicity, lethargy, and cyanosis (floppy babysyndrome).

Lithium overdose is characterised by the following:

·              CNS—Weakness, fatigue, tremor, confusion, ataxia,choreoathetosis, myoclonus, opisthotonus, blurred vision with nystagmus, dysarthria, seizures, and coma. A disorder similar to neuroleptic malignant syndrome (NMS) or serotonin syndrome has been associated with lithium therapy and toxicity.

·              CVS—Arrhythmias with prolonged QT interval, andflattened, inverted T waves.

·              Blood—Leukocytosis, aplastic anaemia.

·              Renal—Polyuria, polydipsia (nephrogenic diabetesinsipidus).

·              Endocrine—Goitre, myxoedema.

·              Dermal—Dermatitis, localised oedema, ulcers.

·              GIT—Vomiting, diarrhoea.

·              RS—Acute respiratory distress syndrome.

Diagnosis

·      Determine serum electrolytes (especially sodium) and lithium concentration. Correct any sodium deficiency.

·      Monitoring— Serum levels should be monitored regularlyduring treatment of intoxication. After termination of drug the plasma level drops by 1/2 every 2 to 3 days.

·      Anion Gap—Because lithium may be an unmeasured cation,an elevated level may result in a decreased or absent anion gap.

·      Lithium Induced Renal Disease—Serum B2 microglobulinhas been found to be a more sensitive indicator than serum creatinine for monitoring glomerular filtration rates in patients on chronic lithium therapy.

·      Toxicity—

o     Therapeutic Levels: 0.6 to 1.2 mEq/L

o     Mild-Moderate Symptoms: 1.5 to 2.5 mEq/L

o     Potentially Lethal: 3 to 4 mEq/L.

·      Thyroid—Periodic monitoring of thyroid function mayhelp detect preexisting hypothyroidism or lithium-induced hypothyroidism.

·      Urinalysis—Perform urinalysis and determine serum creati-nine to rule out impaired renal function.

·      ECG—The predominant change during intoxication isslowing of the dominant rhythm. These changes may persist for several days.

·      Magnetic Resonance Imaging—Brain and tissue lithiumlevels can be quantified using Li-7 magnetic resonance imaging.

·      EEG—Should be performed on all patients who presentwith altered sensorium, to assist in diagnosis of seizure activity.

·      Lithium is easily measured by atomic spectrophotometry, ion selective electrode, or by emission photometery.

Treatment

·              Activated charcoal does not adsorb lithium very well and must not be administered.

·      Whole bowel irrigation with polythelene glycol electrolyte lavage solution at a rate of 2 L/hr for 5 hours has been shown to be very useful in the early stages.

·      Haemodialysis: The indications for haemodialysis in lithium intoxication are inexact; some authors recommend haemodialysis for any patient with a level above 3.5 mEq/L. Other authors recommend haemodialysis for all patients with more than prodromal symptoms and slightly increased 12-hour serum lithium concentration. Lithium clearance during haemodialysis is approximately 100–120 ml/min, thus four hours of haemodialysis is equivalent to 24-hour clearance of 16–20 ml/min. Renal lithium clearance is 20 to 30% of creatinine clearance, thus those with renal impair-ment (calculated creatinine clearance less than 60 ml/min) are generally candidates for haemodialysis. Once begun, haemodialysis should be carried out as long as necessary to reduce the serum lithium concentration to less than 1 mEq/L after redistribution.

·      Continuous arteriovenous haemodiafiltration (CAVH), if available, is more efficacious than haemodialysis.

·      Administration of sodium polystyrene sulfonate can help reduce absorption of lithium.

a.  Dose—

Adults: 60 ml of suspension (15 gm resin) given orally four times a day; 120 to 200 ml of suspen-sion (30 to 50 gm resin) given rectally as retention enema following a cleansing enema.

Children and Infants: Dose is based on exchange ratio of about 1 mEq of potassium per 1 gram of resin or approximately 1 gram/kg/dose every 6 hours orally, or every 2 to 6 hours rectally.

·              Supportive measures: artificial ventilation, anticonvulsants, and correction of hypotension, dehydration, and hypovol-aemia.