Introduction

Lithium is one of the most common drugs used for the treatment of mood disorders. Due to its narrow therapeutic index, lithium can have toxic effects on multiple organ systems.¹ The usual therapeutic level is between 0.6 and 1.5 mEq/L, and severe toxicity occurs at levels >2.5 mEq/L.² Life-threatening severe symptoms, which are associated with serum levels above 3.5 mEq/L, are coma, convulsions, respiratory failure, deteriorating mental status, or renal failure. Hemodialysis should be performed if these symptoms occur.² Although hemodialysis treatment is effective in lithium removal, it is not tolerated as well as continuous venovenous hemodiafiltration (CVVHDF) in hemodynamically unstable patients.³ We report a case of a patient with severe life-threatening symptoms, who was treated for severe lithium intoxication with CVVHDF therapy.

Case Report

A 37-year-old male patient was found unconscious on the road and transferred by the emergency team to our hospital’s emergency department. Empty boxes of 300 mg lithium tablets had been discovered near the patient. The patient presented with central cyanosis and a Glasgow Coma Scale (GCS) value of 4. He was orotracheally intubated by the emergency team and transferred to the ICU. The unconscious patient was mechanically ventilated. In the first examination, the heart rate was 98 beats/min, the arterial blood pressure was 68/35 mmHg, and the oxygen saturation was 96%. The ECG was in normal sinus rhythm. The patient’s cranial computed tomography was normal. The patient’s relatives reported that the patient had bipolar affective disorder, that he had been using lithium for 2 years, and that he hallucinated that committing suicide was necessary to enable him to donate his organs. Gastric lavage and laxatives were added to the treatment regimen. Following urinary catheterization, no urine was observed. Fluid resuscitation was performed and fluid management was arranged due to central venous pressure (CVP) control values. A norepinephrine infusion was started to address the resistant hypotension at a dose of 0.5 mcg/kg/min. The first serum lithium level recorded was 3.9 mEq/L, the blood urea nitrogen (BUN) level was 86 mg/dl, and the creatinine level was 2.4 mg/dl; all other laboratory parameters were normal. In spite of the appropriate fluid therapy was performed, the urine output was below 0.5 ml/kg/hr in the first 3 hours after his acceptance to the ICU. CVVHDF therapy was commenced for lithium removal by the end of the 3rd hour. Subsequent serum lithium levels were: 3.1 mEq/L at the 6th hour, 2.5 mEq/L at the 12th hour, 1.8 mEq/L at the 18th hour, and 1.2 mEq/L at the 24th hour of CVVHDF therapy. During this time, the need for norepinephrine infusion decreased and eventually ceased. At the 28th hour of CVVHDF therapy, the patient regained consciousness, and extubation was performed. CVVHDF therapy was stopped at the 30th hour when the serum lithium level was 1.1 mEq/L. During CVVHDF therapy, the urine output, the BUN and creatinine serum levels returned to normal. The hemodynamically stable patient’s GCS value was 15 on the third day. His organ functions, serum lithium level and laboratory parameters were normal. At the end of the 3rd day, the patient was transferred to the psychiatry clinic. During his stay at the clinic, his daily controlled serum lithium levels were normal.

Discussion

There are three types of lithium intoxication: acute intoxication, acute intoxication in chronic accumulation, and chronic intoxication .² Clinical effects of lithium toxicity are based on the type of intoxication. The rate of lithium equilibration between intracellular and extracellular compartments is slow.⁴ Due to the pharmokinetic profile of lithium, a large amount of lithium remains in the intracellular compartment in chronic or acute-on-chronic intoxication. During treatment, redistribution of this amount of lithium prolongs the time to the elimination half-life of lithium.⁴ In these types of lithium intoxication, severe life-threatening symptoms can occur more frequently and can be maintained for a longer period. Intoxication also resolves more slowly than with the acute type.⁴ Serum concentrations above 3–4 mEq/L are associated with life-threatening severe symptoms and require hemodialysis.²

Hemodialysis is more effective than continuous renal replacement therapies (CRRT) for lithium removal. Redistribution of lithium from the intracellular to the extracellular compartments causes the lithium level to rebound after hemodialysis. Therefore, repeated hemodialysis sessions are required. CRRT eliminates the lithium more slowly than hemodialysis, but completely removes the lithium from the intracellular compartments, and lithium levels do not rebound.^3,5 CVVHDF sustained for >16 hours provides effective removal of total body lithium.⁶ Leblanc et al. reported that high-performance continuous arteriovenous and venovenous hemodiafiltration therapies are effective alternatives to intermittent hemodialysis for the treatment of lithium intoxication.⁷

Meyer et al. reported two cases with chronic and acute-on-chronic lithium intoxication in pediatric patients who were successfully treated with hemodialysis followed by continuous venovenous hemofiltration with dialysis.⁴ In addition, Bailey et al. compared intermittent hemodialysis, prolonged intermittent renal replacement therapy (PIRRT), and continuous renal replacement hemofiltration for lithium intoxication. They reported that PIRRT is superior to the other therapies.⁸ However, in both of these case reports, the patients did not have hemodynamic instability.

Our patient had acute-on-chronic intoxication. His serum lithium level was 3.9 mEq/L, and he presented with coma, acute renal failure, respiratory failure, and hemodynamic instability. Due to his hemodynamic instability, CVVHDF therapy, in addition to support treatment, was performed instead of hemodialysis for lithium removal. Although his clinical situation was life-threatening, the rapid commencement (3rd hour) and the appropriate duration (30 hours) of CVVHDF therapy completely removed the lithium and resulted in the return of all organ functions. In conclusion, the CVVHDF technique is a safe and effective treatment for life-threatening lithium intoxication in hemodynamically unstable patients who may not tolerate hemodialysis.