A 39 year old industrial worker with no former medical history suddenly complained of nausea, dizziness, respiratory tract irritation, and dyspnea during sweeping several kilograms of a powder that had escaped from a barrel containing methylene bis(thiocyanate) (MBT). The worker was not wearing any personal protective equipment. Profound cyanosis developed, and the patient was admitted in our hospital, where mechanical ventilation with 100% oxygen was initiated. 4-dimethylaminophenol (4-DMAP; 250 mg) followed by sodium-thiosulfate (6000 mg) were immediately administered intravenously for treatment of assumed cyanide intoxication. Arterial blood gas examination by co-oxymeter performed a few minutes later revealed the following arterial-blood gas values: pH 7.39, partial pressure of carbon dioxide 37 mmHg, partial pressure of oxygen 381 mmHg, oxygen saturation 63%, methemoglobin level of 51%, oxyhemoglobin level of 48%, carboxyhemoglobin level 0.4%. The i.v. administration of tolonium chloride (toluidine blue, 300 mg, repeated once within 30 minutes) lowered the methemoglobin level to 12% within one hour. The patient was transferred to the medical ICU. In the meantime information on MBT toxicity was requested from several German Intoxication centers. Given the lack of a specific antidot, the experts at these centers recommended treatment with hemodialysis for toxin elimination in addition to general supportive care and monitoring of renal, hepatic and pulmonary function. Only very limited data, however, provided the rationale for these measures, and most information was obtained from anecdotal reports of intoxication with methyl-isocyanate, a chemical analogue of MBT (the accidental release of a methyl-isocyanate cloud (composed of phosgene and isocyanate) was implicated in the Bhopal, India, disaster in 1984) [
4,
5]. Laboratory and pulsoxymetric evaluation were markedly impeded by the bluish discoloration of skin and serum samples after toluidine blue administration. Daily hemodialysis treatment was started. On the second day a slight increase in renal retention parameters and transaminases was observed, together with massive hemolysis (hemoglobin decrease from 14.5 to 8.8 g/dl, LDH > 6000 U/l, haptoglobin < 0.3 g/l) and an increase of methemoglobin from 13 to 34%, all attributed to MBT toxicity. A total of seven units of packed red cells were administered. In the following days, anuric acute renal failure and adult respiratory distress syndrome developed, making the initiation of continuous veno-venous hemofiltration and adoption of a more aggressive ventilation strategy necessary. Hemolysis recovered spontaneously, but the further course of intensive care treatment was complicated by progressive hepatic failure with prominent hyperbilirubinemia and increasing liver function impairment (TBIL 16.5 mg/dl, DBIL 13.0 mg/dl, ALAT 50 U/l, ASAT 49 U/l, CHE 2820 U/l, prothrombine time 51%, INR 1.83, aPTT 34.9 sec, fibrinogen 2.03 g/l, AT III 81%). Extrahepatic cholestasis was excluded by ultrasonographic examination, and no clinical or laboratory signs of sepsis could be found. Three sessions of treatment with MARS (MARS monitor, Teraklin AG, Rostock, Germany) were performed on days 17, 18, and 22 after hospital admission in combination with ordinary hemodialysis (F8 HPS hemofilter, dialysate flow 800 ml/min, Fresenius 4008H, Fresenius Medical Care AG, Bad Homburg, Germany) using albumin dialysate and blood flow rates of approximately 150–180 ml/min for 7 to 8 hours each session. Anticoagulation with unfractionated heparin was monitored by activated clotting time (target range: 160–180 seconds). After the first procedure the bilirubin level decreased by 46%. The final bilirubin level after the third MARS session was 6.0 mg/dl. Liver function and the general condition then recovered, and the patient could be extubated 2 days after the third liver dialysis treatment. Due to persisting anuric renal failure, a permanent dialysis catheter for chronic hemodialysis treatment was implanted. The patient was discharged on a peripheral ward on day 36 after hospital admission. Renal function slowly recovered over the next days, and the patient could finally be withdrawn from hemodialysis program on day 44 of his hospital stay. The further course was complicated by a severe peripheral neuropathy that was characterised electrophysiologically by a predominantly axonal damage pattern. Differential diagnosis included critical-illness neuropathy and MBT-mediated neurotoxicity. The patient was transferred to a rehabilitation centre. Final blood chemistry at our hospital included following results: creatinine 1.42 mg/dl, urea 62 mg/dl, TBIL 2.7 mg/dl, ALAT 125 U/l, ASAT 59 U/l, CHE 3667 U/l, hemoglobine 9.1 g/dl, LDH 175 U/l, and prothrombine time 99 % (Table
1).
Table 1
Selected Blood Chemistry Before and After Treatment with MARS Albumin Liver Dialysis
TBIL (mg/dl) | 0.6 | 16.5 | 8.9 | 5.9 | 2.7 |
DBIL (mg/dl) | n.a. | 13.0 | n.a. | 3.1 | n.a. |
ALAT (U/l) | 23 | 50 | n.a. | 79 | 125 |
ASAT (U/l) | 17 | 49 | n.a. | 34 | 59 |
Prothrombine time (%); [INR] | 90 [0.98] | 68 [1.51]* | 64 [1.56] | 95 [0.97] | 99 [0.96] |
CHE (U/l) | 5577 | 2820 | 2237 | 2766 | 3667 |
Creatinine (mg/dl) | 1.04 | 5.70 | 2.78 | 3.48 | 1.42 |