Showing papers by "Gernot Marx published in 2012"

Effect of Empirical Treatment With Moxifloxacin and Meropenem vs Meropenem on Sepsis-Related Organ Dysfunction in Patients With Severe Sepsis: A Randomized Trial

Abstract: Context Early appropriate antimicrobial therapy leads to lower mortality rates associated with severe sepsis. The role of empirical combination therapy comprising at least 2 antibiotics of different mechanisms remains controversial. Objective To compare the effect of moxifloxacin and meropenem with the effect of meropenem alone on sepsis-related organ dysfunction. Design, Setting, and Patients A randomized, open-label, parallel-group trial of 600 patients who fulfilled criteria for severe sepsis or septic shock (n = 298 for monotherapy and n = 302 for combination therapy). The trial was performed at 44 intensive care units in Germany from October 16, 2007, to March 23, 2010. The number of evaluable patients was 273 in the monotherapy group and 278 in the combination therapy group. Interventions Intravenous meropenem (1 g every 8 hours) and moxifloxacin (400 mg every 24 hours) or meropenem alone. The intervention was recommended for 7 days and up to a maximum of 14 days after randomization or until discharge from the intensive care unit or death, whichever occurred first. Main Outcome Measure Degree of organ failure (mean of daily total Sequential Organ Failure Assessment [SOFA] scores over 14 days; score range: 0-24 points with higher scores indicating worse organ failure); secondary outcome: 28-day and 90-day all-cause mortality. Survivors were followed up for 90 days. Results Among 551 evaluable patients, there was no statistically significant difference in mean SOFA score between the meropenem and moxifloxacin group (8.3 points; 95% CI, 7.8-8.8 points) and the meropenem alone group (7.9 points; 95% CI, 7.5-8.4 points) (P = .36). The rates for 28-day and 90-day mortality also were not statistically significantly different. By day 28, there were 66 deaths (23.9%; 95% CI, 19.0%-29.4%) in the combination therapy group compared with 59 deaths (21.9%; 95% CI, 17.1%-27.4%) in the monotherapy group (P = .58). By day 90, there were 96 deaths (35.3%; 95% CI, 29.6%-41.3%) in the combination therapy group compared with 84 deaths (32.1%; 95% CI, 26.5%-38.1%) in the monotherapy group (P = .43). Conclusion Among adult patients with severe sepsis, treatment with combined meropenem and moxifloxacin compared with meropenem alone did not result in less organ failure. Trial Registration clinicaltrials.gov Identifier: NCT00534287

Clinical validation of a new thermodilution system for the assessment of cardiac output and volumetric parameters

Abstract: Introduction Transpulmonary thermodilution is used to measure cardiac output (CO), global end-diastolic volume (GEDV) and extravascular lung water (EVLW). A system has been introduced (VolumeView/EV1000™ system, Edwards Lifesciences, Irvine CA, USA) that employs a novel algorithm for the mathematical analysis of the thermodilution curve. Our aim was to evaluate the agreement of this method with the established PiCCO™ method (Pulsion Medical Systems SE, Munich, Germany, clinicaltrials.gov identifier: NCT01405040)

Impact of stable PGI₂ analog iloprost on early graft viability after liver transplantation: a pilot study.

Abstract: Background: Ischemia/reperfusion injury after liver transplanta- tion (LT) may be associated with primary graft dysfunction (PDF) or non- function. Prostaglandins were demonstrated to be beneficial in reducing ischemic injury by improving microcirculation and protecting endothelial cells. The aim of this study was to analyze the effect of the continuously administered prostaglandin I2 analog iloprost on allograft function after LT. Methods: Eighty patients were prospectively randomized and assigned to two groups. Patients in the treatment group received iloprost for seven d after transplantation, and those in the control group did not. The primary end point was graft dysfunction. Results: The incidence of PDF was 20% (n = 8) in the control group and 5% (n = 2) in the treatment group, respectively (p = 0.087). Four patients in the control group underwent re-transplantation for initial non-function (INF). There was no evidence for INF in the treatment group. Iloprost was associated with improved allograft function. Clinical course and outcome were comparable. Conclusions: We suggest iloprost to be beneficial for early post-transplant liver function. If the rate of PDF can be significantly reduced with this treatment concept, it should be analyzed in a larger number of patients (ISRCTN95672167).

Impairment of renal function using hyperoncotic colloids in a two hit model of shock: a prospective randomized study

Abstract: One of the therapeutic essentials in severe sepsis and septic shock is an adequate fluid replacement to restore and maintain circulating plasma volume, improve organ perfusion and nutritive microcirculatory flow. The type of solution to be used as a fluid replacement remains under discussion. The aim of the study was to evaluate the effects of clinically used fluid replacement solutions on renal function and inflammatory response. A total of 23 anesthetized and ventilated female German Landrace pigs were investigated over 19 hours using a two-hit model that combined hemorrhagic and septic shock. The septic shock was induced using an Escherichia coli laden clot placed into the abdominal cavity. Infusions of 6% hydroxyethylstarch 130/0.42 in acetate (6% HES 130), 4% gelatin in acetate (4% gelatin) and 10% hydroxyethylstarch 200/0.5 in saline (10% HES200) compared to Ringer's acetate (RAc) were used for fluid replacement to maintain a central venous pressure of 12 mmHg. Ringer's acetate was also used in the sham-treated group (SHAM). At study end the cardiac output (10% HES200 143 ± 48 ml/kgBW; 6% HES130 171 ± 47 ml/kgBW; RAc 137 ± 32 ml/kgBW; 4% gelatin 160 ± 42 ml/kgBW), as well as mean arterial pressure did not differ between groups. N-acetyl-beta-D-glucosamidase was significantly higher in the hydroxyethylstarch 200 (157 ± 115 U/g creatinine; P < 0.05) group compared to hydroxyethylstarch 130 (24 ± 9 U/g creatinine), Ringer's acetate (2 ± 3 U/g creatinine) and SHAM (21 ± 15 U/g creatinine) at the study's end. Creatinine significantly increased by 87 ± 84 percent of baseline in the 10% HES200 group compared to RAc and 6% HES130. We demonstrated in the histology of the kidneys a significant increase in osmotic-nephrosis like lesions for 4% gelatin compared to RAc, 6% HES130 and SHAM. Urine output was lowest in the 10% HES200 and 4% gelatin group, however not significantly. Interleukin(IL)-6 levels were significantly elevated in the 10% HES200 group (3,845 ± 1,472 pg/ml) two hours after sepsis induction compared to all other groups (6% HES130 1,492 ± 604 pg/ml; RAc 874 ± 363 pg/ml; 4% gelatin 1,623 ± 1,242 pg/ml). Despite similar maintenance of macrocirculation 6% hydroxyethylstarch 130/0.42 and Ringer's acetate significantly preserve renal function and attenuate tubular damage better than 10% hydroxyethylstarch 200/0.5 in saline.

Comments on Reinhart et al.: consensus statement of the ESICM task force on colloid volume therapy in critically ill patients

Abstract: Dear Editor, We are grateful that a task force has addressed colloid volume therapy in critically ill patients [1]. This issue is currently the focus of considerable debate, and new data from ongoing trials can be expected in the new future. A task force is considered to be a group of specialists who have been appointed to work together on a temporary basis with the specific aim to provide an answer to a specific question. In this respect, the consensus statement of the European Society of Intensive Care Medicine’s task force on colloid volume replacement in critically ill patients immediately raises two questions: what is the basis on which the task force was selected? Which entity initiated this initiative? The methodology of the article does not provide any information on these points, and the reader is left with some degree of doubt on how the individual members of the “task force” were selected. Eight individuals (“the eight panel members”) apparently voted on each aspect of the statement. However, it seems highly questionable whether a small group of only eight individuals are capable of representing a true consensus of the various opinions among experts in the field in Europe—particularly when the group included two authors from the same department, representing 25 % of the votes. Our concern is not whether the statement is correct or incorrect, but rather whether the approach used to establish the consensus was the most suitable one and whether it was capable of representing the opinions of intensivists throughout Europe—particularly since current data on the topic are limited, and several trials currently in progress are likely to provide new data in the very near future. Was the methodology for drawing up guidelines on best medical practices—as recommended by the European Health Committee (Comite Europeen de la Sante, CDSP) and adopted by the Committee of Ministers of the Council of Europe in 2001 [2]—followed during the review process and publication of the statement? It is therefore very surprising that such an important statement was apparently accepted for publication by Intensive Care Medicine within 2 days of submission (as specified on p. 368). In the absence of any information on how the present recommendations were evaluated, the reader can only speculate on the peer review process regarding this consensus statement. Are these recommendations supported by the majority of European intensive care specialists or do they merely reflect the “expert opinion” of eight authors? Here, we suggest that these points need to be clarified. In future comparable cases, we would also recommend that such statements should be based on the input of representatives of all of the disciplines involved in critical care medicine (surgery, anesthesia, internal medicine, neurology, physiology, etc.). Such an approach, based on a comprehensible procedure, is currently being used in Germany to develop a guideline on intravascular volume therapy in adults, in accordance with the guidelines of the Working Group of Scientific Medical Specialist Societies (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF) [3].