ABSTRACT
Studies have shown that postoperative disseminated intravascular coagulopathy (DIC) occurs in some patients with cardiac disease, acute aortic dissection, and ruptured abdominal aortic aneurysm. The specific pathophysiology of DIC in these settings are related to low cardiac function, shock, infection and sepsis as well as activation of coagulation cascade in the aneurysm sac or dissected aorta. A soluble form of recombinant human thrombomodulin (rhsTM) was approved in 2008 for the treatment of DIC. This report describes the safety and efficacy of rhsTM for the treatment of DIC in patients with cardiovascular disease operated in our department. Between October 2010 and March 2012, 35 patients with postoperative DIC were treated with rhsTM. Diagnosis of DIC was based on the diagnostic criteria for DIC of the Japanese Association for Acute Medicine (JAAM). During the first 6 months of the study period, after a diagnosis of DIC was made, the patients were treated with gabexate mesilate and antithrombin III, and if patients showed no improvement with conventional treatment, they received rhsTM for 6 days. During the last 10 months of the study period, patients received rhsTM soon after a diagnosis of DIC was made. Twenty seven patients survived for 28 days after rhsTM treatment, and the mortality rate was 22.9% (8/35). Patients who survived showed improvement in acute phase DIC scores, FDP levels, D-Dimer, fibrinogen and platelet counts during rhsTM treatment, but no improvement was observed in patients who died. No serious adverse events were found up to 28 days after the start of rhsTM administration. In conclusion, this study showed no adverse events of rhsTM, and further studies are needed to confirm that rhsTM administration is an effective therapeutic modality in the management of DIC after cardiovascular surgery.
ABSTRACT
The purpose of this study was to investigate the pharmacokinetics of teicoplanin (TEIC) in patients undergoing open heart surgery. We also attemped to define the optimum TEIC therapy protocol for prevention of perioperative infection and for treatment of staphylococcal endocarditis such as that caused by methicillin-resistant <i>Staphylococcus aureus</i> (MRSA). Serum TEIC concentrations were measured in 14 patients divided into two groups of 7 patients each undergoing elective open heart surgery. Patients in group I received 400mg of TEIC and patients in group II received 800mg, both administered as a slow intravenous infusion over 20min immediately after induction of anesthesia. The peak serum level (mean±standard error) of TEIC was respectively 57±11 and 139±39μg/ml at 2min after administration and then the TEIC level decreased gradually to 26± 7 and 55±10μg/ml at 60min after administration. The serum level of TEIC decreased rapidly to 17±5 and 31±7μg/ml, respectively, at the start of extracorporeal circulation (ECC), and was 11±2 and 27±6μg/ml after 60min of ECC, 8±2 and 23±7μg/ml at 2min after the termination of ECC, 8±3 and 23±6μg/ml at 60min after the termination of ECC, and 7±2 and 22±5μg/ml on admission to ICU. No side effects were seen during the study, such as red neck syndrome, renal dysfunction, hearing disorders, or postoperative infection. Our results suggested that the optimum dose of TEIC for prevention of perioperative infection was around 400mg, providing levels in excess of the MIC for most pathogens that have been found to cause infection following open heart surgery, including MRSA. In addition, a dose of 800mg was needed to keep trough levels above 20μg/ml for treatment of staphylococcal endocarditis. It was also suggested that half of the initial dose should be administered on admission to ICU and also at the start of ECC if the operation is going to last longer than 7h on the basis of the concentration-time curve.
ABSTRACT
Recently several papers have been published on the use of vancomycin (VCM) to prevent perioperative infection during open-heart surgery, but there have been few papers from Japan. In this study, we evaluated the pharmacokinetics of VCM in the serum and right atrial tissues of eight patients (4 men and 4 women) who underwent open-heart surgery, to prevent perioperative infection. Preoperatively all patients had neither hearing disorder nor renal dysfunction. A total of 1, 000mg of VCM was given intravenously over 40-50 minutes before a skin incision. The serum levels of VCM were measured every 20 minutes during open-heart surgery with enzyme-immunoassay. VCM levels in the right atrial tissues were also assayed before the start of extracorporeal circulation (ECC). The peak serum levels of VCM were 55.3±10.1μg/ml and decreased gradually to 10μg/ml prior to the ECC. During the ECC, the serum levels of VCM remained between 7.6 and 9.9μg/ml, while VCM levels in the right atrial tissues were 18.9±6.9μg/ml (serum/tissue ratio: 0.34). Staphylococcal infection is generally inhibited by VCM levels of 2.0-6.5μg/ml. This study suggests that 1, 000mg of VCM given intravenously before a skin incision may be effective to prevent perioperative infection during open-heart surgery.
ABSTRACT
Under scheduled anticoagulation therapy, surgery for abdominal aortic aneurysm was performed in 4 patients who had undergone heart valve surgery and implantation of a mechanical prosthesis. Warfarin and antiplatelet agents were prescribed in all cases preoperatively. Antiplatelet agents were discontinued from seven to 10 days before operation. Warfarin was stopped from two to three days before operation and heparin (200IU/kg/day) was administered by continuous intravenous infusion to produce an activated clotting time of around 150 seconds. Bolus intravenous heparin of 3, 000 IU was added before aortic crossclamp. Oral anticoagulants were resumed from the beginning of oral intake, and heparin was stopped when the prothrombin time reached therapeutic levels (% PT=40%). In three patients perioperative courses were uneventful. Intraperitoneal hemorrhage occurred in one patient who simultaneously underwent cholecystectomy and aneurysmectomy with Y-grafting. He required blood transfusion and interruption of anticoagulation. Brain thromboembolism occurred in this patient 26 days after the operation. We believe that scheduled anticoagulation for the operation of abdominal aortic aneurysm is safe and useful in patients with prior prosthetic heart valve surgery. However, the coexistence of coagulopathy requires more intensive anticoagulation therapy.