ABSTRACT
BACKGROUND: Minimal invasive extracorporeal circulation (MiECC) reduces the impact of cardiopulmonary bypass during cardiac surgery on inflammation and hemostasis. Pulsatile perfusion may enhance organ perfusion and help to prevent renal and neuronal damage. The present study investigated the impact of pulsatile MiECC in low-risk coronary artery bypass grafting (CABG) patients. METHODS: CABG patients were prospectively randomized for non-pulsatile (np: n=19) and pulsatile (p: n=21) MiECC. Blood and urine samples were collected at several time points until 72 h post-operative and analyzed for biochemical markers of fibrinolytic capacity, renal damage, and neuronal damage. RESULTS: Although intraoperative tissue plasminogen activator (tPA) levels tended to be higher in the p group, none of the fibrinolysis markers including plasminogen activator inhibitor (PAI-1) and the PAI-1/tPA ratio were significantly affected by pulsation. Hemolysis and markers of renal and neuronal damage were comparable between groups. Intraoperative urinary excretion [np: 400 mL (355 to 680) vs. p: 530 mL (360 to 900)] and cumulative 24 h volume intake [np: 7,090 mL (5,492 to 7,544) vs. p: 7,155 mL (6,682 to 8,710)] were increased by pulsation whereas blood losses up to 12 h post-operative [np: 365 mL (270 to 515) vs. p: 310 mL (225 to 470)] and up to 24 h post-operative [np: 760 mL (555 to 870) vs. p: 520 mL (460 to 670)] were attenuated. CONCLUSIONS: The present study did not find evidence for a beneficial effect of pulsation on markers of fibrinolysis, renal damage, and neuronal damage. However, pulsatile perfusion increased intraoperative urinary secretion and reduced post-operative blood losses.
ABSTRACT
BACKGROUND: Several studies have demonstrated the efficacy of systemic oxaliplatin (Oxa) in combination with 5-fluorouracil (5-FU) and folinic acid (FA) for the treatment of colorectal liver metastases (CRLM). However, nothing is presently known about the pharmacokinetics of Oxa administered via the hepatic artery and only very little about the feasibility and toxicity of Oxa used for hepatic artery infusion (HAI). PATIENTS AND METHODS: We designed a phase II trial using Oxa in combination with 5-FU/FA and mitomycin C (MMC) for HAI treatment of patients with isolated non-resectable CRLM. Oxa (130 mg/m2) was delivered on day (d) 1 as a 120-min infusion followed by FA (140 mg/m2) for 10 min and 5-FU (480 mg/m2) for 120 min from d1 to d5 and MMC (7 mg/m2) for 30 min on d5 every 35 days. For Oxa pharmacokinetics, peripheral venous blood was collected before, during and after arterial infusion. Oxaliplatin was determined by liquid chromatography with post-column derivatization in blood ultra filtrate. RESULTS: A total of 33 HAI cycles were administered to 5 patients with tolerable toxicity, which mainly consisted of grade I and II nausea, vomiting, leucopenia, thrombopenia and abdominal pain. During 4 cycles nausea/vomiting III degree occurred, during 3 cycles diarrhoea and abdominal pain III degree. No neurotoxicity > or = II degree and no catheter occlusion was observed. Staging showed 4 PR and 1 PD. Pharmacokinetic analysis revealed an AUC value of 85.3 micrograms x min/ml after HAI. Recalculating these values with the previously reported AUC value for systemic administration (161 micrograms x min/ml) revealed a liver extraction ratio of 0.47 for Oxa. CONCLUSION: We conclude from our results that Oxa in combination with 5-FU/FA and MMC may be a feasible protocol for HAI treatment without major toxicity, especially avoiding higher grade neurotoxicity. This is probably attributable to the low systemic bioavailability of Oxa.
