The pharmacokinetics of piperacillin-tazobactam were investigated in eight anuric intensive care patients treated by continuous venovenous hemodialysis (CVVHD). The elimination half-life of piperacillin was 4.3 ؎ 1.2 h, and that of tazobactam was 5.6 ؎ 1.3 h. The contribution of CVVHD to the overall elimination was relevant (>25%) for both drugs.Piperacillin-tazobactam is a ␤-lactam-␤-lactamase inhibitor combination with a broad spectrum of antibacterial activity against gram-positive as well as gram-negative pathogens. It is frequently used for the empirical treatment of infection in intensive care patients (2, 15). The aim of this investigation was to determine the pharmacokinetics of piperacillin-tazobactam in critically ill patients with acute anuric renal failure treated by continuous venovenous hemodialysis (CVVHD).Eight critically ill patients were included in the investigation (Table 1). Inclusion criteria were an age of Ͼ18 years, acute renal failure treated by CVVHD, anuria (Ͻ100 ml of urine/day), and treatment with piperacillin-tazobactam. Patients with severe liver failure or cholestasis were excluded. The protocol of the study was approved by the local ethical committee, and informed consent was obtained from a first-degree relative. CVVHD was performed with an AN69 hollow-fiber dialyzer (Multiflow 60; Hospal, Nuremberg, Germany) under the following conditions: a blood flow rate of 150 ml/min, a dialysate flow rate of 1.5 liters/h, and an ultrafiltrate flow rate of 80 to 200 ml/h. Doses of piperacillin-tazobactam (4.5 g of Tazobac; Wyeth-Lederle) and dosing schedules were chosen empirically by the attending physicians (Table 2). Piperacillin-tazobactam was administered intravenously over 15 min. Corresponding predialyzer blood samples and dialyzer-outlet dialysate samples were taken before drug administration, at 10 and 30 min after infusion, and at 1, 2, 4,6,8,12,20, 22, and 24 h after infusion. Sampling was performed in the first dosage interval after the dialyzer membrane was changed. Blood samples were centrifuged immediately after they were taken, and plasma and dialysate samples were frozen at Ϫ80°C until analysis. The concentrations of piperacillin and tazobactam were determined by reversed-phase high-performance liquid chromatography with UV detection, with modification of the methods reported previously (13, 16). Plasma specimens were deproteinated, and dialysate was used without pretreatment. The presence of piperacillin was determined from the water layer extracted with dichloromethane; tazobactam samples were derivatized with 1,2,3-triazole and injected without extraction. The chromatographic conditions for piperacillin were as follows: a guarded Nucleosil C 18 100-5/250 ϫ 4 column, an eluent of methanol-KH 2 PO 4 (1:1, vol/vol; 67 mM; pH 3), ambient temperature, a flow rate of 0.5 ml/min, a of 214 nm, and a retention time of ϳ20 min. The chromatographic conditions for tazobactam were as follows: a Superspher C 18 100-5/250 ϫ 4 column; an eluent of acetonitrile-Na 2 HPO 4 (1:3, vol/vol; ...

IntroductionNeutrophil granulocytes are the first defense line in bacterial infections. However, granulocytes are also responsible for severe local tissue impairment. In order to use donor granulocytes, but at the same time to avoid local side effects, we developed an extracorporeal immune support system. This first-in-man study investigated whether an extracorporeal plasma treatment with a granulocyte bioreactor is tolerable in patients with septic shock. A further intention was to find suitable efficacy end-points for subsequent controlled trials.MethodsThe trial was conducted as a prospective uncontrolled clinical phase I/II study with 28-day follow-up at three university hospital intensive care units. Ten consecutive patients (five men, five women, mean age 60.3 ± 13.9 standard deviation (SD) years) with septic shock with mean ICU entrance scores of Acute Physiology and Chronic Health Evaluation (APACHE) II of 29.9 ± 7.2 and of Simplified Acute Physiology Score (SAPS) II of 66.2 ± 19.5 were treated twice within 72 hours for a mean of 342 ± 64 minutes/treatment with an extracorporeal bioreactor containing 1.41 ± 0.43 × 10E10 granulocytes from healthy donors. On average, 9.8 ± 2.3 liters separated plasma were treated by the therapeutic donor cells. Patients were followed up for 28 days.ResultsTolerance and technical safety during treatment, single organ functions pre/post treatment, and hospital survival were monitored. The extracorporeal treatments were well tolerated. During the treatments, the bacterial endotoxin concentration showed significant reduction. Furthermore, noradrenaline dosage could be significantly reduced while mean arterial pressure was stable. Also, C-reactive protein, procalcitonin, and human leukocyte antigen DR (HLA-DR) showed significant improvement. Four patients died in the hospital on days 6, 9, 18 and 40. Six patients could be discharged.ConclusionsThe extracorporeal treatment with donor granulocytes appeared to be well tolerated and showed promising efficacy results, encouraging further studies.Trial registrationClinicalTrials.gov Identifier: NCT00818597

A highly conservative approach avoiding open necrosectomy in NP results in significantly lower mortality than previous serial FNA and consecutive indication for surgery in case of proven infection. Open surgery in NP should be reserved for concomitant intra-abdominal complications.

Purpose. Granulocyte transfusions have been used to treat immune cell dysfunction in sepsis. A granulocyte bioreactor for the extracorporeal treatment of sepsis was tested in a prospective clinical study focusing on the dosage of norepinephrine in patients and influence on dynamic and cell based liver tests during extracorporeal therapies. Methods and Patients. Ten patients with severe sepsis were treated twice within 72 h with the system containing granulocytes from healthy donors. Survival, physiologic parameters, extended hemodynamic measurement, and the indocyanine green plasma disappearance rate (PDR) were monitored. Plasma of patients before and after extracorporeal treatments were tested with a cell based biosensor for analysis of hepatotoxicity. Results. The observed mortality rate was 50% during stay in hospital. During the treatments, the norepinephrine-dosage could be significantly reduced while mean arterial pressure was stable. In the cell based analysis of hepatotoxicity, the viability and function of sensor-cells increased significantly during extracorporeal treatment in all patients and the PDR-values increased significantly between day 1 and day 7 only in survivors. Conclusion. The extracorporeal treatment with donor granulocytes showed promising effects on dosage of norepinephrine in patients, liver cell function, and viability in a cell based biosensor. Further studies with this approach are encouraged.

IntroductionThe management of a patient suffering from blunt abdominal trauma (BAT) remains a challenge for the emergency physician. Within the last few years, the standard therapy for hemodynamically stable patients with BAT has transitioned to a non-operative approach. The purpose of this study is to evaluate the outcome of patients with BAT and to determine the reasons for failure of non-operative management (NOM).Materials and methodsAnalysis of 176 consecutive patients treated for BAT was conducted in a German level 1 trauma center from 2004 to 2011. Abdominal injuries were classified according to the American Association for the Surgery of Trauma (AAST). Patients included were demonstrated to have objective abdominal trauma with either free fluid on focused assessment with sonography for trauma (FAST) or computed tomography (CT), or proven organ injury.ResultsPatients, 142 of 176 (80.7%), with BAT were initially managed non-operatively, with a success rate of 90%. The rates of NOM success were higher among those with less severe injuries; 100% with Abbreviated Injury Scale (AIS) of 1. In total, 125 patients (71.0%) were managed non-operatively, and 51 (29.0%) required surgical intervention. NOM failure occurred in 9.2% of the patients, the most common reason being initially undiagnosed intestinal perforation (46.2%). Positive correlation was identified (r = 0.512; p < 0.001) between the ISS (injury severity score) and the NACA (National Advisory Committee of Aeronautics) score. The delay in operation in NOM failure was 6 h in patients with underlying hepatic or splenic rupture and 34 h with intestinal perforation. The overall mortality of 5.1% was attributed especially to old age (p = 0.016), high severity of injury (p < 0.001), and greater need for blood transfusion (p < 0.001).ConclusionNOM was successful for the vast majority of blunt abdominal trauma patients, especially those with less severe injuries. NOM failure and operative delay were most commonly due to occult hollow viscus injury (HVI), the detection of which was achieved by close clinical observation and abdominal ultrasound in conjunction with monitoring for rising markers of infection and by multidetector computed tomography (MDCT) if additionally indicated. Based on this concept, the delay in operation in patients with NOM failure was short. This study underscores the feasibility and benefit of NOM in BAT.