Lithium is a small cation and acts similar like sodium. Lithium is almost completely absorbed after oral administration [5]. Like potassium, intracellular concentrations are higher than extracellular concentrations. It distributes widely in total body water and accumulates in the kidney, bones, thyroid and certain areas of the brain [6,7].

Lithium does not bind to serum proteins and is excreted unchanged by the glomerulus for 89-98% [8]. Just like sodium, lithium is reabsorbed for 70-80% by the proximal tubule and by the thick ascending limb of the loop of Henle [4]. Volume depletion and diuretics will increase proximal tubule reabsorption of sodium and lithium and therefore cause toxic lithium concentrations in the blood [4]. Normally, the half-life of lithium is 12-27 hours. However, it can be up to 58 hours in older patients, patients with renal dysfunctions or chronic lithium users [4]. Three types of lithium intoxication are distinguished: acute poisoning (in a lithium-naive patient), acute-on-chronic and chronic poisoning (in a patient already on a daily dose of lithium). Symptoms are mostly gastro-intestinal (nausea, vomiting) and neurological (tremors, confusion, agitation). Severe symptoms like coma, seizures, hypotension and arrhythmias have been described. Due to slow diffusion of lithium into the central nervous system (up to 24 hours) gastro-intestinal symptoms usually precede neurological symptoms in acute poisoning. The neurological symptoms can occur at lower lithium levels in acute-on-chronic or chronic poisoning, because of the already increased lithium level in the central nervous system [9]. Symptoms can even occur at normal or slightly increased lithium levels, especially in chronic poisoning. For supportive measures stopping the lithium, whole bowel irrigation (activated charcoal is not useful) and volume resuscitation (in case of volume depletion due to gastro-intestinal or renal losses) are suggested.

Hemodialysis (HD) or continuous renal replacement therapy (CRRT)) has long been recommended for severe lithium intoxication.

Hemodialysis uses the concentration gradient between the blood and a dialysate in counter-current flow over a semi-permeable membrane to excrete waste products and toxins via diffusion. CRRT uses hydrostatic pressure over a filter to achieve the same effect via convection.

Due to its low molecular weight, predominant renal excretion, absence of metabolism, good solubility in water and lack of binding to plasma proteins, hemodialysis is an effective way of reducing lithium levels. Lithium clearance up to 106.9 ml/min can be reached via hemodialysis (with a reduction of 1 mEq/L per 4 hours of hemodialysis) [10], compared to 10.6 ml/min via endogenous renal clearance and 43.1 ml/min via CRRT [4]. A rebound effect of distribution from the tissues to the plasma can occur.

In the literature diverse indications for hemodialysis have been described, ranging from criteria purely based on symptoms, blood levels and a combination of both. Evidence-based consensus recommendations of the Extracorporeal Treatments in Poisoning (EXTRIP) Workgroup recommended hemodialysis with a) impaired kidney function and a lithium level > 4.0 mEq/L, b) the presence of a decreased level of consciousness, seizures or life-threatening dysrhythmias and suggested hemodialysis in case of c) a lithium level > 5.0 mEq/L, d) significant confusion, e) or the expected time to reduce lithium level < 1 mEq/L is > 36 hours [4]. Later retrospective analyses suggested that the EXTRIP criteria are too broad and created narrower criteria (a lithium level > 5.2 or a creatinine level > 200 µmol/L) [11] or created different criteria for chronic toxicity and acute-on-chronic poisoning [12].

Earlier case reports have described both cerebral seizures as a complication of hemodialysis for lithium intoxication and progressive encephalopathy and unresponsiveness after starting peritoneal dialysis for lithium intoxication [13,14]. Gradual onset of encephalopathy during hospital admission after stopping lithium has been described as well [5]. A clear pathophysiological cause of the seizures has not been described. An analogy to the neurological symptoms of osmotic demyelination in too rapid correction of chronic hyponatremia has been made, with high lithium levels leading to intraneuronal hyponatremia and thus the lithium removal to correction of this unmeasurable intraneuronal hyponatremia [15].

Our patient presumably suffered a grand mal seizure after starting hemodialysis for an acute-on-chronic lithium intoxication.

Although the literature is scarce and there is no clear physiological mechanism, after this literature study we think that in this case hyperhydration should have been given and hemodialysis should only be considered after failure of hyperhydration or with severe life-threatening neurological symptoms.

Conflict of interest: No conflict of interest for all involved authors to disclose.
All authors have provided equal input for this article.
Funding: None
Ethical approval: An informed consent form was signed by the patient