Thallium, colourless and odourless as a salt (Thallium sulphate) has been popularized by Agatha Christie and has even been used as a poison. In 2012, the EXTRIP group issued guidance on the use of extracorporeal treatment (ECTR) of thallium poisoning (Ghannoum et al cJASN 2012). The group conducted a thorough literature search that included abstracts and conference proceedings, but found the quality of evidence was poor, with only case reports and case series identified. Information from 74 patients (11 of whom died) was included to form the final recommendations which are well worth reading in full. The salient points of their recommendations are summarized below.
Thallium is absorbed via all routes including skin contact, inhalation or ingestion, but toxic poisoning is mercifully rare with only around 20 reported cases per year in the United States. Toxicity may manifest clinically in a variety of ways, including abdominal pain, diarrhea or vomiting, alopecia, ascending peripheral neuropathy, somnolence, tremor or ataxia, altered mental state, reduced conscious levels/coma and may result in AKI and cardiac arrest. A high index of suspicion and a good history are required to make the diagnosis as laboratory measurement of serum thallium levels is not routinely available in many hospitals. Although urine thallium testing may confirm exposure, levels do not correlate well with serum levels.
Thallium has no natural function in the body, but is readily absorbed and widely distributed due to its ionic properties, which are similar to potassium. It causes cellular damage by disrupting enzymatic and electrochemical processes and causes direct intracellular mitochondrial injury. Largely eliminated unchanged in bile, feces and urine, due to its large volume of distribution, it is detectable in (and damaging to) pretty much all organs and tissues.
Theories of treatment
Treatment of toxicity involves removing source of exposure, supportive therapies and enhancing elimination. Reasonable early measures for enhancing elimination of ingested thallium salts include orogastric lavage and administration of activated charcoal. Forced potassium diuresis and traditional chelators are not advised due to the observation in some case reports of increased thallium redistribution and development neurological sequelae.
Thallium is not protein bound and is of very low molecular weight, thus it is theoretically cleared by ECTR. A large number of reports support the use of hemodialysis and hemoperfusion to aid elimination. Whilst both hemodialysis and hemoperfusion can achieve excellent plasma thallium clearance, the limiting factor of total body thallium elimination is its large volume distribution and slow intercompartmental transfer rates.
The consensus from the EXTRIP group was that although the quality of the available literature for management of thallium toxicity is poor, given the high morbidity and mortality from thallium toxicity (indeed mortality may occur with ingestion of quantities as low as 6mg/kg), the fact that thallium is dialyzable, and the relatively small and infrequent complications of ECTR, they recommend ECTR if:
- Thallium exposure is highly suspected on the basis of history or clinical features.
- Thallium concentration is >1.0 mg/L.
- Thallium concentration is between 0.4 and 1.0 mg/L.
The group acknowledge that routine testing may not be routinely available and therefore recommend consideration of early ECTR if patients demonstrate signs of severe thallium poisoning, noting that painful ascending neuropathy and alopecia seem to be particularly reliable clinical signs of severe toxicity. The group recommend ECTR even in cases where renal function is not impaired to enhance elimination, but acknowledge that in cases where thallium toxicity has resulted in severe AKI, ECTR would most likely be initiated anyway.
The EXTRIP group recommend initiation of ECTR as soon as possible after exposure to thallium (before the development of irreversible injury) and certainly within 24-48 hours due to it’s large volume distribution and the length of time required for elimination. They suggest continuing therapy until thallium levels are <0.1mg/L for a minimum of 72 hours. Again, given the limited availability of measuring serum thallium, improvements in clinical symptoms may also be used as an indicator for reviewing the need for ongoing ECTR with the understanding that some symptoms may be permanent.
Finally the group concluded that intermittent (daily) hemodialysis was the preferred method of ECTR, with hemoperfusion and hemofiltration valid alternatives in its absence. This is because of the superior speed with which small molecules (thallium in this case) can be cleared on hemodialysis and the fact that access is widely available in most centres. Peritoneal dialysis, plasma exchange and exchange transfusion were not considered acceptable alternatives.
Although the evidence available is of poor quality, the group has managed to put together a detailed, clinically relevant and genuinely useful consensus guideline to aid clinicians in the management of patients with thallium toxicity.
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About the author
Matthew Graham-Brown (BSc Hons, MBChB Hons, MRCP) is a Specialist Registrar in Renal Medicine at The John Walls Renal Unit, University Hospitals of Leicester and a Doctoral Research Fellow at the National Centre for Sport and Exercise Medicine, University of Loughborough. His research interests are in the development of novel cardiac and renal imaging techniques in patients with renal disease. His current research looks at the effects of a programme of intradialytic exercise on cardiac structure and function in dialysis patients, using cardiac MRI. He is the co-founder and editor of the renal medicine education website www.renalmed.co.uk (@RenalMed).