Treatment of a case of severe mercuric salt overdose with DMPS (dimercapo-1-propane sulphonate) and continuous haemofiltration

Pearl Pai1, Simon Thomas2, Nicholas Hoenich3, Russell Roberts1, Ivan House4 and Alison Brown1

1 Departments of Nephrology, and 2 Clinical Pharmacology, Freeman Hospital 3 Department of Nephrology, University of Newcastle, Newcastle-upon-Tyne, UK 4 Trace Elements Laboratory, Guy's Hospital, London, UK

Sir,

We present the clinical course of a man after deliberately taking inorganic mercury salt.

Case.

A 48-year-old man had deliberately taken approximately 10 ml of inorganic mercury salt. Vomiting and abdominal pain began within an hour of ingestion. At 6 h, haemoglobin (Hb) was 19.4 g/dl, white cell count (WCC) 16.6x109/l, platelets 259x109/l, serum potassium 4.8 mmol/l, urea 5.7 mmol/l, creatinine 126 µmol/l, bilirubin 46 µmol/l, alanine transaminase 39 IU/l, amylase 78 IU/l. This was followed over a 24-h period by onset of haematemesis, haemoptysis, hypovolaemic shock and oligoanuric renal failure. Serum creatinine rose to 329 µmol/l, urea 15 mmol/l, potassium unchanged, bilirubin 53 µmol/l, alanine transaminase 1149 IU/l, amylase 165 IU/l, Hb unchanged, WCC 41.1x109/l, platelets 218x109/l. Arterial blood gas analysis showed a pH of 7.29, PO2 13.2 kPa, pCO2 4.6 kPa, HCO3 16 mmol/l, base excess of -9. Haemodialysis (HD) was commenced.

Dimercaprol (150 mg), a chelating agent for mercury overdose was given intramuscularly 1 h before the first dialysis treatment. Twenty minutes after administration, the patient developed transient severe pain in the chest and abdomen, thought to be a reaction to dimercaprol. The patient underwent a 6-h HD session using a low-flux polysulphone membrane of 1.3 m2 surface area (F7, Fresenius Medical Care, Germany) at a blood flow rate of 200 ml/min and a dialysate flow rate of 500 ml/min. Samples of blood and dialysis fluid were taken at regular intervals for determination of whole-blood mercury concentration by cold vapour atomic absorption spectrometry.

In view of the possible reaction to dimercaprol, the patient was given intravenous DMPS (dimercapo-1-propane sulphonate) prior to the second HD treatment 10 h later. The dose used was 250 mg, 6-hourly for 7 days, then 8-hourly for 1 day, then 12-hourly for 8 days, then once a day for 7 days.

The initial blood mercury level was 5200 µg/l (normal <5 µg/l), which reduced to 3600 µg/l after the first HD treatment (Table 1Go). Daily HD lasting 4–7 h was carried out using the same type of dialyser, except for the fifth treatment session when a larger dialyser (F10, Fresenius) was used. It became clear that overall HD treatment had little effect on mercury removal, with dialysate mercury levels ranging from 0 to 75 µg/l. Treatment was changed to continuous venovenous haemofiltration (CVVH) with 6-hourly i.v. DMPS, followed by two sessions of (3 litres) plasma exchange (PE).


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Table 1. Whole blood mercury concentration during haemodialysis, continuous venovenous haemofiltration (CVVH), and plasma exchange

 
The patient underwent a total of 51 h of CVVH using a high-flux polysulphone membrane (Ultraflux AV 400, Fresenius) and a filtration rate of 1 l/h. A break in the treatment occurred after 32 h because of clotting of the filter. During this 32 h of treatment, 8735 µg of mercury were recovered from the ultrafiltrate and the patient's blood mercury level reduced from 5600 to 2300 µg/l. During the next 19 h of treatment, the blood mercury level fell further to 990 µg/l. Two sessions of PE were undertaken after the CVVH. The blood mercury level fell from 850 to 610 µg/l after the first session of PE. The plasma filtrate sample contained 5300 µg/l of mercury.

The patient began to pass urine on day 10. A final HD treatment was necessary on day 13 for hyperkalaemia and rising serum urea and creatinine. Normal serum creatinine was achieved by day 45. Gastrointestinal bleeding continued for a total of 4 weeks in spite of treatment with sulcrafate, proton pump inhibitor, tranexamic acid and aprotinin. The patient required a total of 58 units of blood transfusion.Comment. Inorganic mercury can induce an autoimmune glomerulonephritis, with an ingestion of 1–4 g of inorganic mercuric salt reported as lethal [1]. Mercuric ion binds to the sulphydryl group of proteins and causes necrosis to the mucosa of the gastrointestinal tract, leading to gastrointestinal bleeding. In the kidneys, rapid mercuric cation accumulation leads to necrosis of the proximal tubule and anuric renal failure, usually within 24 h.

The recommended emergency treatment is to reduce absorption by gastric lavage if presentation is within 1 h, and to enhance excretion by using chelating agents such as dimercaprol given via deep i.m. injection. Once given, it mobilizes the tissue-bound mercury to form a soluble complex that is then excreted in the urine. In an anuric patient, it must be used in conjunction with dialysis. DMPS, a water-soluble analogue of dimercaprol can be given i.v. or orally, and is increasingly used as an alternative to dimercaprol [2].

After the first HD treatment with dimercaprol, there was a 27% reduction of blood mercury concentration, but clearance of mercury by dialysis was <1 ml/min. In renal failure, mercury elimination occurs mainly via the biliary system. This was confirmed by bile sample obtained from our patient on day 4, containing 15 300 µg/l of mercury. The mercury reduction observed after the first HD may have been the consequence of such clearance or redistribution of mercury following dimercaprol. The rise in blood mercury level prior to the second HD may be the result of further mercury absorption from the gut, which can occur up to 6 days after acute mercuric salt poisoning.

In anuric patients, mercury elimination may be increased by extracorporeal elimination or by enhancing biliary excretion. In common with other reports, we failed to demonstrate any significant mercury clearance using DMPS and HD [3,4]. Manufacturer's specifications for the dialysers used indicate clearance of vitamin B12 (1355 daltons) of 98 and 112 ml/min respectively. The molecular size of DMPS–mercury complex is estimated to be the order of 600 daltons, consequently some diffusive and convective transport across the membrane would be expected. The poor removal of the DMPS–mercury complex across the membrane is attributed to the molecular volume of the complex, its shape, stearic hindrance, and charge.

CVVH involves principally convective mass transport and is more effective in removing large-molecular-weight substances than is HD. Removal is governed by sieving coefficient (S) of the membrane for the molecule expressed under continuous filtration conditions as S=ultrafiltration concentration/average of the inlet and outlet concentration. Using this relationship, the sieving coefficient for mercury was 0.08±0.03. In the presence of a filtration rate of 16.6 ml/min, this equated to a whole-blood clearance of 1.3 ml/min or 1.8 l/24 h. Plasma exchange has also been reported as effective in eliminating mercury, with reported clearances of 10–17 ml/min [3,5].

Our results confirm the ineffectiveness of HD in removing DMPS–mercury complex, which is more effectively removed by continuous therapy utilizing high-permeability membranes.

References

  1. Winek CL, Fochtman FW, Bricker JD, Wecht CH. Fatal mercuric chloride ingestion. Clin Toxicol1981; 18: 261–266[ISI][Medline]
  2. Schiele R von, Schaller KH, Weltle D. Mobilisation von Quecksilber-Speicherungen im Organismus mittels DMPS (Dimaval). Arbeitsmed Sozialmed Praventivmed1989; 24: 249–251[ISI]
  3. Yoshida M, Satoh H, Igarashi M, Akashi K, Yamamura Y, Yoshida K. Acute mercury poisoning by intentional ingestion of mercuric chloride. Tohoku J Exp Med1997; 182: 347–352[ISI][Medline]
  4. Toet AE, van Dijk A, Savelkoul TJF, Meulenbelt J. Mercury kinetics in a case of severe mercuric chloride poisoning treated with dimercapo-1-propane sulphonate (DMPS). Hum Exp Toxicol1994; 13: 11–16[ISI][Medline]
  5. Sauder Ph, Livardjani F, Jaeger A et al. Acute mercuric chloride intoxication. Effects of haemodialysis and plasma exchange on mercury kinetics. Clin Toxicol1988; 26: 189–197