Serum lithium

Lithium carbonate is rapidly absorbed after oral administration. The most common adverse reactions include tremors, nausea, vomiting, thirst, and polyuria Toxic reactions may be seen when serum lithium levels are greater than 1.5 mEq/L (Table 32-1). Because some of these toxic reactions are potentially serious, lithium blood levels are usually obtained during therapy, and the dosage of lithium is adjusted according to the results. 

LITHIUM The dosage of lithium is individualized according to serum levels and clinical response to the drug. The desirable serum lithium levels are 0.6 to 1.2 mEq/L Blood samples are drawn immediately before die next dose of lithium (8-12 hours after the last dose) when lithium levels are relatively stable During die acute phase die nurse monitors serum lithium levels twice weekly or until die patient s manic phase is under control. During maintenance therapy, the serum lidiium levels are monitored every 2 to 4 months. 

Following initial assessment, including evaluation of potential suicidality, support systems, and need for inpatient versus outpatient treatment, MW was hospitalized briefly, then followed in the community on medication along with psychotherapy. She has abstained from illicit substances and has returned to her job. She has responded well to treatment with sustained-release lithium carbonate 900 mg once daily at bedtime with a snack. Steady-state 12-hour serum lithium concentrations have stabilized at 0.9 mEq/L (0.9 mmol/L). She now returns to clinic for routine followup. She has tolerated the lithium except for a mild tremor and a gain of 7 pounds (3.2 kg). She is willing to accept these side effects for now, but asks about how long she must take medication since she is now feeling well. 

If lithium toxicity is suspected, the patient should discontinue lithium and go immediately to the emergency room. Hemodialysis is generally required when serum lithium levels are above 4 mEq/L for patients on long-term treatment, or greater than 6 to 8 mEq/L after acute poisoning. 

Initially, serum lithium concentrations are checked once or twice weekly. After a desired serum concentration is achieved, levels should be drawn in 2 weeks, and if stable, they can be drawn every 3 to 6 months. 

Lithium, while not required for life, is used therapeutically in the form of lithium carbonate for the treatment of manic depression although its mechanism of action remains a mystery. Effective treatment requires attaining serum lithium concentrations of between 0.8 and 1.2 mmol/L. 

Lithium is used in the prophylaxis and treatment of mania and in the prophylaxis of bipolar disorders and recurrent depression. Lithium should be stopped 24 hours before major surgery but the normal dose can be continued for minor surgery, with careful monitoring of fluids and electrolytes. After major surgery, renal function is reduced and this may compromise clearance of lithium. Lithium is a drug with a narrow therapeutic index and it should be avoided if possible in patients with renal impairment. Renal function should be tested before initiating treatment. If lithium is given to patients with renal impairment, a reduced dose should be used and serum lithium concentrations should be monitored closely. 

A5. Amdisen, A., Serum lithium determinations for clinical use. Scand. J. Clin. Lab. Invest. 20, 104-108 (1967). 

L8. Levy, A. L., and Katz, E. M., A comparison of serum lithium determinations using flame photometry and atomic absorption spectrophotometry. Clin. Chem. 16, 840-842 (1970). 

Vll. Villeneuve, A., Dery, R., and Genest, P. H., A simple micromethod for serum lithium determination. Clin. Biochem. 4, 194-195 (1971). 

Toxicity is closely related to serum lithium levels and can occur at therapeutic doses. Facilities for serum lithium determinations are required to monitor therapy. 

Serum lithium levels Draw blood samples immediately prior to the next dose (8 to 12 hours after the previous dose) when lithium concentrations are relatively stable. Do not rely on serum levels alone. 

Acute mania Optimal patient response is usually established and maintained with 600 mg 3 times/day or 900 mg twice/day for the slow release form. Such doses normally produce an effective serum lithium level ranging between 1 and 1.5 mEq/L. 

III.a.4.3. Changes in renal blood flow. Blood flow through the kidney is partially controlled by the production of renal vasodilatory prostaglandins. If the synthesis of these prostaglandins is inhibited (e.g. by indomethacin), the renal excretion of lithium is reduced with a subsequent rise in serum levels. The mechanism underlying this interaction is not entirely clear, as serum lithium levels are unaffected by some potent prostaglandin synthetase inhibitors (e.g. aspirin). If an NSAID is prescribed for a patient taking lithium the serum levels should be closely monitored. 

Indications and Dosages Alert During acute phase, a therapeutic serum lithium concentration of 1-1.4 mEq/L is required. For long-term control, the desired level is 0.5-1.3 mEq/L. Monitor serum drug concentration and clinical response to determine proper dosage. 

Serum lithium concentrations drawn immediately prior to next dose (8-12 hr after previous dose), monitor biweekly until stable then q2-3mo therapeutic range 1.0-1.5 mEq/L (acute), 0.6-1.2 mEq/L (maintenance)... 

Reversible electrocardiographic (EKG) T-wave depression occurs frequently with therapeutic serum lithium concentrations. Arrhythmias have occurred rarely. The cardiac effects of lithium may result partly from displacement of potassium from intracellular myocardial sites by lithium, resulting in a slow, partial depletion of intracellular potassium (Kawata, 1979). 

CBC, BUN, creatinine (i.e., renal function), urinalysis, thyroid function tests EKG Serum lithium level (drawn 12 hours after dose) every 1-2 weeks until stable every 1—2 months during continuation phase Repeat thyroid function testast and urinalysis every 3-6 months... 

Geller, B. and Fetner, H.H. (1989a) Children s 24-hour serum lithium level after a single dose predicts initial dose and steady-state plasma level [letter]. / Clin Psychopharmacol 9 155. 

Cooper TB, Simpson GM The 24-hour serum lithium level as a prognosticator of dosage requirements a 2-year follow-up study. Am J Psychiatry 133 440-443, 1976... 

In a patient with a serum lithium level greater than 4.0 mEq/L or with serious manifestations of lithium toxicity, hemodialysis should be initiated. ... 

It has narrow therapeutic index and treatment requires facility for therapeutic monitoring of serum lithium levels. 

During pregnancy, serum lithium levels need to be carefully monitored. The 50% to 100% increase in glomerular filtration rate (GFR) that normally occurs in the third trimester will proportionally lower lithium levels due to its increased clearance. Thus, dosage may need to be increased to maintain a therapeutic range ( 341). Because the GFR and lithium clearance quickly return to normal after delivery, it may be wise to stop the drug shortly before delivery and restart a few days after delivery at a lower dose. In summary ... 

With normal renal function, all that may be necessary is watchful waiting, careful monitoring of the clinical status, and repeated serum lithium determinations. 

Lithium has a fairly narrow therapeutic range, i.e. the gap between minimum effective serum concentration (0.4 mmoFL-l) and that causing toxicity (1.2 mmoFL-l) is low. It is therefore important to monitor serum lithium regularly. Serum concentrations above 1.2 mmol L-l must be avoided. It should also be remembered that toxicity can occur in a few patients at concentrations below 1.2 mmol-L-l and that toxicity is always a clinical diagnosis. 

The management of toxicity requires monitoring of electrolytes, regular CNS observations, use of anticonvulsants should seizures occur, increased fluid intake to promote excretion (unless renal function is impaired) and cardiac monitoring. Haemodialysis should be considered if conservative measures are ineffective or serum lithium is above 3.0 mmol L-l. However, it may be of limited additional value as the volume of distribution of lithium is high. 

Clinicians rely on measurements of serum lithium concentrations for assessing both the dosage required for treatment of acute mania and for prophylactic maintenance. These measurements are customarily taken 10-12 hours after the last dose, so all data in the literature pertaining to these... 

An initial determination of serum lithium concentration should be obtained about 5 days after the start of treatment, at which time steady-state conditions should have been attained. If the clinical response suggests a change in dosage, simple arithmetic (new dose equals present dose times desired blood level divided by present blood level) should produce the desired level. The serum concentration attained with the adjusted dosage can be checked after another 5 days. Once the desired concentration has been achieved, levels can be measured at increasing intervals unless the schedule is influenced by intercurrent illness or the introduction of a new drug into the treatment program. 

Swartz. C M. "Serum Lithium During Treatment of Bipolar Disorder," N. Eng. J. Med., 1159 iApril 19, l990i. 

In four women serum lithium concentrations fell significantly within 3 days of starting calcitonin (23) because of increased renal clearance of lithium (23,24). Serum lithium concentrations should therefore be monitored in patients who start to take calcitonin. 

Serum lithium concentration should be monitored at the start of calcitonin therapy. 

After they had received 100 units of salmon calcitonin subcutaneously for 3 days, four patients had a 30% mean reduction in serum lithium concentration, which was attributed to reduced absorption and/or increased renal excretion (23). 

A 54-year old man, who had taken lithium for 15 years without problems, suddenly developed food and water aversion, hypercalcemia (2.75 mmol/1), and lithium toxicity, with a serum lithium concentration of 4.3 mmol/1 (677). He was confused, delirious, and irritable. Hemodialysis produced a marked improvement in laboratory tests, which became normal after 9 days. 

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