Inefficiency of early prophylactic hemodialysis in cis-platinum overdose.

Abstract

Department of Internal Medecine and Intensive Care Unit, Hopital A. B6cl~re, F-92140 Clamart, France 2 Biochemistry and Enzymology Unit, Institut Gustave Roussy, F-94805 Villejuif, France 3 Department of Hematology, Hopital A. B6cl6re, F-92140 Ctamart, France Sir, Platinum complexes can induce nephrotoxicity, as other heavy metals do [4]. Following a cisplatin (CDDP) over- dose (200 mg/m 2 or 6.4 mg/kg in 8 h), we performed he- modialysis 4 h after the end of the CDDP infusion, with the aim of limiting nephrotoxicity and bone marrow de- pression [1]. The patient, a 41-year-old nurse suffering from stage III [6] primary ovarian carcinoma, was transferred to our Intensive Care Unit (ICU) for CDDP overdose adminis- tered on day 5 of the first course of polychemotherapy. On day 1 she had received doxorubicin (25 mg/m 2) and tenip- oside (35 mg/m2)i On days 2-4 the treatment consisted in cyclophosphamide (200 mg/m 2) and 5-fluorouracil (350 mg/m2). On day 5 (19. 10. 84) a 100-mg/m 2 CDDP in- fusion was started. During the next 5 h 1000 ml 5% dex- trose was administered. Six hours after the beginning of this CDDP infusion the patient inadvertently received a new dose of CDDP (100 rag/m2). The onset of nausea, vomiting, and diarrhea 1 h after the end of this second dose led to discovery of the error. Thus, i.v. treatment with 25% mannitol and 5% dextrose was immediately initiated, and the patient was transferred to the ICU. She com- plained of nausea, thirst, a metallic taste in her mouth, and headache. Four hours after the end of the second CDDP dose hemodiatysis was initiated. Despite this treatment, which was associated with osmotic polyuria (mannitol), acute renal failure (ARF), metabolic acidosis, and febrile bone marrow aplasia (Table 1) occurred 5 days after CDDP toxification. The patient was treated with three ses- sions of hemodialysis, amikacin, cefotaxin, and platelet transfusions. On 4. 11. 1984, ARF and pancytopenia had resolved; the patient was discharged from the ICU in good condition. Two months later, during the second course of chemotherapy (CDDP: 50 mg/m2), asymptomatic myelo- suppression was observed without ARF. Since platinum nephrotoxicity is dose-dependent [4], and in view of the high risks of ARF [1] and bone marrow aplasia [1] and of the biphasic plasma clearance of CDDP [4, 5], we decided to perform 'early prophylactic' hemodi- alysis. A further reason for this treatment was the poor prognosis of patients suffering from multiple organ system failure [2]. The inability of hemodialysis to prevent ARF in our patient is clearly explained by its failure to remove CDDP (Table 1). The kinetics demonstrate that CDDP plasma clearance is biphasic: there is a rapid initial phase (half-life: 45 min) followed by a slow decay period with a half-life of 65 h. This second phase is due to the high bind- ing (65%-90%) of CDDP to plasma proteins [4, 5]. Despite the fact the plasma protein binding increases with time, the Table 1. Partial laboratory data and plasma platinum concentrations 18. 10. 84 * 19. 10. 84 21.10. 84 24. 10. 84 4. 11.84 Hours after second 8 dose of CDDP 4 After HD a BUN (mmol/l) 1.9 2.3 3 21.5 41.75 5.2 Creatinine (lxmol/1) 72 100 172 390 108 Carbon dioxide (mmol/l) 23 23 20 25 9 26 Hb (g/100 ml) 13.3 13.3 11.5 9.9 9.6 WBC X 109/1 7.2 8.9 7.6 0.4 7.8 Platelets X 109/1 242 278 170 45 143 Total platinum (ugPt/ml) [3] 4.21 4.08 1.91 * Cisplatin overdose HD, hemodialysis