Severe Electrolyte Disturbances After Hyperthermic Intraperitoneal Chemotherapy: Oxaliplatin Versus Mitomycin C

ArticleinAnnals of Surgical Oncology 18(1):174-80 · January 2011with22 Reads
DOI: 10.1245/s10434-010-1210-1 · Source: PubMed
Oxaliplatin (OX) is increasingly used for hyperthermic intraperitoneal chemotherapy (HIPC) for patients with peritoneal metastases. Our aim was to review electrolyte disturbances and complications after HIPC with oxaliplatin (OX) versus mitomycin C (MMC). We included patients enrolled in single-institution prospective clinical trials who underwent cytoreductive surgery and HIPC with MMC or OX. We reviewed patient demographics, pathology, perioperative course, HIPC administration, and postoperative electrolyte disturbances. Measured postoperative sodium values were corrected for systemic hyperglycemia using the formula: (measured Na(+)) × [(glucose - 100/100) × 1.6]. From January 2002 to April 2009 we performed 80 HIPC procedures. A total of 60 patients (75%) received MMC (dose range 12.5-50 mg/m(2)) carried in lactated ringers solution. There were 20 patients (25%) who received OX (dose range 300 × 400 mg/m(2)) carried in 5% dextrose solution. For patients receiving HIPC with OX, electrolyte disturbances were the most common complication. Compared with MMC, patients receiving OX had significant 24-h postoperative uncorrected hyponatremia (P < 0.001), corrected hyponatremia (P < 0.001), hyperglycemia (P < 0.001), and metabolic acidosis (P < 0.001). In the OX group, corrected (mean 130.5) and uncorrected (mean 127.4) sodium levels were significantly lower than preoperatively (mean 139.9, P < 0.001). The overall nonelectrolyte complication rate was 56.2%. (MMC n = 33, 55.0%; OX n = 12, 60%); the 30-day mortality rate was 0% in both groups. Compared with MMC, HIPC with OX was associated with significant but predictable electrolyte disturbances; however, these electrolyte disturbances were not associated with higher overall complication rates. Close monitoring with early correction is imperative to maximize perioperative care. Further studies are needed to provide mechanistic insight.
    • "Most drugs for intraperitoneal perfusion are administered in chloride-containing solutions. Because of its degradation in sodium-based solutions [38], oxaliplatin is preferably dissolved in dextrose 5%, which may cause pronounced electrolyte disturbances, including hyperglycaemia [39,40]. As this degradation is limited, and does not affect in vitro cytotoxicity , further research is warranted to investigate whether oxaliplatin for HIPEC can be dissolved in other solutions with similar clinical efficacy and safety. "
    [Show abstract] [Hide abstract] ABSTRACT: Several studies have shown the potential benefit of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer patients. At present the most effective chemotherapeutic regime in HIPEC for gastric cancer is unknown. The aim of this review was to provide a comprehensive overview of chemotherapeutic agents used for HIPEC in gastric cancer. A literature search was conducted using the PubMed database to identify studies on chemotherapy used for HIPEC in gastric cancer patients. The chemotherapeutic regime of choice in HIPEC for gastric cancer has yet to be determined. The wide variety in studies and study parameters, such as chemotherapeutic agents, dosage, patient characteristics, temperature of perfusate, duration of perfusion, carrier solutions, intraperitoneal pressure and open or closed perfusion techniques, warrant more experimental and clinical studies to determine the optimal treatment schedule. A combination of drugs probably results in a more effective treatment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Full-text · Article · Apr 2015
    • "The use of large intraperitoneal volumes of 5% dextrose is associated with serious hyperglycemias and electrolyte disturbances, resulting in significant postoperative morbidity and mortality (Ceelen et al., 2008; De Somer et al., 2008; Rueth et al., 2011). These metabolic disturbances have not been observed in patients treated with mitomycin C, in which more physiological chloride-containing carrier solutions have been used (Rueth et al., 2011). It is surmised that the chloride ions in these solutions could potentially limit oxaliplatin stability and therefore its oncolytic capacity during CRS–HIPEC. "
    [Show abstract] [Hide abstract] ABSTRACT: Purpose: Oxaliplatin is increasingly becoming the chemotherapeutic drug of choice for the treatment of peritoneal malignancies using cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Oxaliplatin is unstable in chloride-containing media, resulting in the use of 5% dextrose as the carrier solution in these procedures. Exposure of the peritoneum to 5% dextrose during perfusion times varying from 30 min to 90 min is associated with serious hyperglycemias and electrolyte disturbances. This can result in significant postoperative morbidity and mortality. In order to find out whether safer, chloride-containing carrier solutions can be used, we report the results of in-vitro analysis of oxaliplatin stability in both chloride-containing and choride-deficient carrier solutions and discuss the implications for oxaliplatin-based CRS-HIPEC procedures. Methods: 5 mg of oxaliplatin was added to 50 mL of various carrier solutions at 42 °C: 5% dextrose, 0.9% sodium chloride, Ringer lactate, Dianeal(®) PD4 glucose 1.36% solution for peritoneal dialysis and 0.14 M sterile phosphate buffer pH 7.4. Samples were collected at standardized intervals and oxaliplatin concentration was determined using a stability indicating high-performance liquid chromatographic method, coupled to an UV detector (HPLC-UV); oxaliplatin degradation products were identified using HPLC-mass spectometry. Results: In 5% dextrose, oxaliplatin concentration remained stable over a 2-hour period. Increasing chloride concentrations were associated with increasing degradation rates; however, this degradation was limited to <10% degradation after 30 min (the standard peritoneal perfusion time in most clinical CRS-HIPEC protocols) and <20% degradation after 120 min at 42 °C. In addition, oxaliplatin degradation was associated with the formation of its active drug form [Pt(dach)Cl2]. Conclusions: The use of chloride-containing carrier solutions for oxaliplatin does not relevantly affect its concentrations under the tested in-vitro conditions. Chloride seems to promote formation of the active cytotoxic drug form of oxaliplatin and therefore could enhance its cytotoxic effect. These data show that more physiological, chloride-containing carrier solutions can be used safely and effectively as a medium for oxaliplatin in CRS-HIPEC procedures.
    Article · Dec 2014
    • "In contrast to the severe electrolyte disturbances seen with oxaliplatin in D5W, we found that the electrolyte changes associated with HIPEC using mitomycin C in NS—mild decreases in bicarbonate, BUN, and glucose— to be by comparison, lesser in severity and magnitude than those found with oxaliplatin in D5W. Our finding of a decrease in serum glucose after HIPEC with mitomycin C in NS is in contrast to the increase reported else- where [5]. This study characterizes the changes in electrolyte values that are associated with the intraoperative administration of HIPEC. "
    [Show abstract] [Hide abstract] ABSTRACT: The administration of hyperthermic intraperitoneal chemotherapy (HIPEC) is often associated with significant intraoperative electrolyte changes. We retrospectively examined the pre-HIPEC and post-HIPEC intraoperative basic metabolic panel (BMP) values of the 20 patients who underwent HIPEC at our institution between December 2009 and January 2012. For the five patients who underwent HIPEC with oxaliplatin in 5% dextrose in water (D5W), there were statistically significant changes between the pre-and post-HIPEC values of sodium (135 to 124 mmol/L), chloride (105 to 94 mmol/L), glucose (143 to 388 mg/dl) and sodium corrected for hyperglycemia (135 to 127 mmol/L). For the 14 patients who received HIPEC with mitomycin C in normal saline (NS), there were statistically significant changes in bicarbonate (24 to 21 meQ/L), blood urea nitrogen (BUN) (10 to 9 mg/dl) and glucose (158 to 134 mg/dl). The BMP changes for the one patient who received doxorubicin/cisplatin in peritoneal dialysate are reported separately.
    Full-text · Article · Jan 2014
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