NDT Advance Access originally published online on July 5, 2006
Nephrology Dialysis Transplantation 2006 21(10):2971-2974; doi:10.1093/ndt/gfl343
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A case of acute sodium chlorate self-poisoning successfully treated without conventional therapy
1Unit of Nephrology and Dialysis and 2Unit of Intensive Care, Ospedale S. Andrea, 13100 Vercelli, Italy
Correspondence and offprint requests to: Andrea Ranghino, MD, Unit of Nephrology and Dialysis, Ospedale S. Andrea, 13100 Vercelli, Italy. Email: andrearanghino{at}yahoo.com
Keywords: acute renal failure; haemodialysis; haemolysis; methaemoglobinaemia; sodium chlorate poisoning
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Introduction |
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Sodium chlorate is a non-selective herbicide, commonly used for vegetation control on roadsides, and as a defoliant and desiccant for cotton, corn, flax, etc. [1,2].
A single dose of 5–10 g/person of sodium chlorate can prove to be fatal in adults [2]. However, defining the lethal dose of the pesticide remains controversial, because in some instances patients survive massive doses [3,4].
Intoxication, usually by ingestion, by chlorate salts is characterized by methaemoglobinaemia (MetHb), haemolysis, disseminated intravascular coagulation and renal failure. The clinical features include nausea, vomiting and diarrhoea, cyanosis and dyspnoea [1,3,4].
Very little data are available regarding the pathophysiology as well as the therapy of sodium chlorate poisoning. Chlorate salts, which are known powerful oxidizing agents, can induce methaemoglobin that derives from oxidation of haemoglobin; methylene blue is unable to reduce it because of the denaturation of glucose-6-phosphate dehydrogenase induced by chlorate [5].
It has been reported that the haemolysis induced by chlorate is due to an increased erythrocyte membrane rigidity [6].
In 1981, Steffen and Seitz [4] showed that the disseminated intravascular coagulation as well as the renal failure may be regarded as a consequence of haemolysis because of the coagulating properties of the haemolysed erythrocyte ‘ghost cells’ and may be treated successfully with exchange transfusions, heparin and fresh plasma.
Nephrotoxicity of chlorate is mediated by methaemoglobinuria along with a vasoconstriction due to intravascular haemolysis that results in tubular damage [3–5]. In addition, it must be considered a direct toxic effect on the proximal tubule of chlorate itself [4]. Interestingly, sodium chlorate-dependent renal failure is characterized by the same histological lesions (fibrin deposition in afferent arterioles and glomerular capillaries) as those described in haemolytic uraemic syndrome [4]. In chlorate poisoning, haemodialysis (HD) is recommended not only as a renal replacement therapy (RRT) but also for removal of the toxic agent [4].
We report here a case of sodium chlorate poisoning in a patient who ingested the herbicide in an attempted suicide and was treated successfully with HD, fluid exchange, high oxygen flow rate and darbepoetin alfa. Exchange transfusion and fresh plasma were refused by the patient.
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Case |
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A 42-year-old male was admitted to our hospital because of abdominal pain, diarrhoea and arterial hypotension within 14 h after ingesting about 50 ml of an herbicide containing sodium chlorate, corresponding to a total dose of 27 g of sodium chlorate.
On arrival in the emergency department, the physical examination revealed cyanosed face and limbs, hypotension (blood pressure 100/60 mmHg, heart rate 80 bpm) and oliguria. He was alert and oriented and his neurological exam was normal. The abdomen was soft with normal bowel sounds. There were no peritoneal signs or hepatosplenomegaly. The body temperature was 36.5°C. His clinical history showed no surgical procedures and he had never smoked.
Initial laboratory evaluation disclosed the following: a serum creatinine of 1.27 mg/dl, haemoglobin 13.9 g/dl, platelets 246 x 103/µl, white blood cells (WBC) 23 600/µl with 22 767/µl granulocytes, bilirubin direct/total 0.5/2.8 mg/dl, lactic dehydrogenase (LDH) 800 U/l (normal 240–480 U/l), aptoglobin 0.66 g/l, glucose 182 mg/dl, potassium 5.2 mEq/l, sodium 139 mEq/l and calcium 8.2 mg/dl. Liver enzymes were within the normal limits.
An arterial blood gas performed with a fraction of inspired oxygen (FiO2) of 50% revealed a pH 7.37, pCO2 35 mmHg, pO2 106 mmHg, oxygen saturation (SpO2) 70%, bicarbonate 20.6 mEq/l and MetHb 48.9%.
The electrocardiogram and chest X-ray were normal.
Urine analysis showed: black urine, glucose 70 mg/dl, proteinuria 150 mg/dl and haemoglobin 1 mg/dl, erythrocytes [25–70 red blood cells (RBC/hpf)] and leucocytes (5–10 WBC/hpf) in the urinary sediment.
A renal ultrasound examination showed an increased echogenicity of the renal cortex. Initial treatment in the emergency department included oxygen, i.v. fluids and activated charcoal by nasogastric tube.
After 22 h, the patient was transferred to the intensive care unit (ICU), because of acute renal failure (serum creatinine 3.2 mg/dl) with anuria, worsening cyanosis and anaemia. Haemoglobin levels fell to 11 g/dl, LDH rose to 3583 U/l and the blood samples became brown (chocolate serum) suggesting haemolysis.
In intensive care, an infusion with sodium thiosulphate 1% 500 ml was initiated along with bicarbonate 1.4% 500 ml and i.v. bolus of furosemide (250 mg three times a day) plus furosemide infusion (10 mg/h).
The day after the intoxication the patient underwent the HD treatment for removing the toxin and because of the anuria which was unresponsive to loop diuretics.
HD was performed daily with an Integra dialysis machine (Hospal, Mirandola, Italy), using a bicarbonate-based dialysate and a low-flux polysulfone membrane (F8 HPS Fresenius Medical Care, Bad Homburg, Germany). The dialysate flow rate was 500 ml/min and the blood flow rate 250 ml/min. Mean ultrafiltration rate was 400 ml/h. The patient was dialysed for 4 h/day via a temporary catheter in the right internal jugular vein.
He underwent a total of 11 daily HDs that were then discontinued when the urinary output increased and definitively stopped at day 22 from intoxication.
During each HD session the ultrafiltrate volume (mean 1600 ml) was replaced with saline.
The patient's haemodynamic status remained stable during the dialysis treatments.
On the second day after admission, a disseminated intravascular coagulation ensued: platelets count 74 x 103/µl; antithrombin III: 65% (normal 80–125%); D-dimer: 18.8 µg/ml (normal < 0.5); prothrombin time: 1.81 International Normalized Ratio (INR). Thus, treatment with heparin was started. The patient refused exchange transfusion and fresh plasma for private reasons, although he was informed about the possible worsening of his disease without these therapies. Patient's consciousness was checked every day as well as his decision to refuse the therapy despite the associated risks. A neurological examination and a cardiac evaluation were performed daily to exclude ischaemia. In ICU, the patient was always alert and oriented, sometimes dysphoric, in spontaneous breathing with O2 high flow by facial mask with reservoir valve maintaining a SpO2 > 90%. A supranormal haemodynamic status was achieved by intravenous saline at the rate of 60 ml/kg/day for the first 4 days after intoxication and then tapered to 30 ml/kg/day along with a free oral water intake. Central venous pressure (CVP) was maintained between 10 and 12 mmHg.
Haematopoiesis was improved with darbepoetin alfa at the dose of 0.75 µg/kg once a week along with iron, folic acid and vitamin B12 supplementation. No symptoms and/or signs related to cerebral and/or cardiac ischaemia occurred.
On day 3 after intoxication, a chest X-ray showed a bilateral pleural effusion that disappeared on day 15. The lowest level of haemoglobin was 3.9 mg/dl on day 11. The patient was then transferred to the nephrology ward and discharged 24 days after the intoxication, when his serum creatinine and haemoglobin levels were 3.4 mg/dl and 9.4 g/dl, respectively.
Renal function returned to normal along with the haemoglobin levels, 2 months after intoxication.
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Discussion |
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We report here a patient with life-threatening acute sodium chlorate intoxication complicated by renal failure who was treated successfully without conventional therapy [4].
The very few cases of acute chlorate poisoning reported have been treated with exchange transfusion, HD, gastric lavage, bicarbonate infusion and fresh plasma [1,4].
Our patient had a severe degree of chlorate intoxication, based on the amount of herbicide ingested (27 g), high level of MetHb (48.9%), anuric renal failure and severity of haemolytic anaemia (haemoglobin 3.9 g/dl).
Treatment of MetHb with methylene blue was excluded since it is ineffective [5,7]. Consequently, the recommended treatment of MetHb induced by chlorate is exchange transfusion [7].
In our case, exhaustive information was given to the patient every day about his clinical state and the necessity of using transfusion of blood and its major components according to the rules of good practice [8]. He nonetheless refused blood transfusion, exchange transfusion and fresh plasma for private reasons, thus preventing the use of conventional therapy to correct the severe anaemia and disseminated intravascular coagulation.
After an ethical analysis of which treatment was to be undertaken, we decided to respect the patient's private reasons for refusing transfusion, reserving the possibility of changing our decision, should complications such as myocardial ischaemia or loss of consciousness occur.
Since there are no controlled studies but only anectodal case reports on sodium chlorate poisoning, according to our experience we propose an immediate therapy consisting of gastric lavage, activated charcoal by nasogastric tube, administration of i.v. sodium thiosulphate 1% 500 ml and bicarbonate 1.4% 500 ml. At the same time, we recommend a supportive therapy with administration of large amounts of i.v. fluids at the initial rate of 60 ml/kg/day associated with diuretics such as furosemide or mannitol.
In order to improve the imbalance between systemic oxygen delivery due to severe anaemia (haemoglobin 3.9 mg/dl on day 11 after intoxication) and tissue oxygen demand, we maintained a supranormal haemodynamic status (mean arterial pressure: 110 ± 3; mean CVP: 11 ± 2 mmHg) along with a supplemental oxygen using a facial mask (mean pO2: 110 ± 10 mmHg; arterial oxygen saturation: 99%) as is done in patients with septic shock [9–11].
A daily intermittent HD (D-IHD) with low-flux membrane was performed, starting the day after intoxication. Given the low molecular weight of sodium chlorate (MW: 106.4), we hypothesized that its removal by HD might be more efficient than convective treatments [12,13]. Moreover, data on intoxications with toxins with an MW between 32 and 167.01 (i.e. methanol, lithium and valproate), complicated by acute renal failure suggests that D-IHD is preferable to continuous RRT (CRRT), because it offers the advantage of a more rapid removal of the toxins [14–16].
On the other hand, CRRT such as high-flux continuous veno-venous haemodiafiltration (CVVHDF) would offer a sustained removal of the toxins, thus avoiding post-dialysis rebound [15,17]. In addition, CVVHDF or continuous veno-venous HD (CVVHD) should be considered in hypotensive and haemodynamically unstable patients who might not tolerate standard HD [14,15,18].
Nonetheless, HD performed with a cellulosic membrane or older ones [3] was able to remove active metabolites of sodium chlorate along with uraemic toxins and to correct fluid overload and electrolyte and acid–base abnormalities [4].
We hypothesize that a more biocompatible dialyser such as a polysulfone membrane as we used in our case might improve anaemia on the basis of its smaller inflammatory response compared with cellulosic membranes [19,20].
Giglio et al. [21] have demonstrated that in adult female Wistar rats, injection of human methaemoglobin induces a haemodynamically mediated acute renal failure and depressed plasma erythropoietin levels both in normoxic and in hypoxic conditions. Thus, we tried to improve haematopoiesis using darbepoetin alfa at the dose of 0.75 µg/kg i.v. once a week along with iron supplementation.
With reference to our case, we hypothesize that the conventional therapy implying blood transfusion to correct the anaemia can be considered as a ‘constant supply’ of blood cells, which are the main target of sodium chlorate. By excluding blood transfusion, this ‘vicious circle’ would be interrupted, leading to a quenching of the acute effect of sodium chlorate intoxication, i.e. haemolysis.
We conclude that the treatment described above may be considered a therapeutic option for patients suffering from chlorate poisoning and who refuse transfusions of whole blood or its components for private or religious reasons.
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Acknowledgements |
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We would like to thank Dr Teresa Rampino (Unit of Nephrology, Dialysis and Transplantation, IRCCS Policlinico San Matteo and University of Pavia, Italy) and Dr Sara Cabodi (Department of Biology, University of Torino, Italy) for reading the manuscript and providing very helpful suggestions.
Conflict of interest statement. None declared.
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References |
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Accepted in revised form: 17. 5.06
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