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1.  Perioperative goal-directed hemodynamic therapy based on radial arterial pulse pressure variation and continuous cardiac index trending reduces postoperative complications after major abdominal surgery: a multi-center, prospective, randomized study 
Critical Care  2013;17(5):R191.
Several single-center studies and meta-analyses have shown that perioperative goal-directed therapy may significantly improve outcomes in general surgical patients. We hypothesized that using a treatment algorithm based on pulse pressure variation, cardiac index trending by radial artery pulse contour analysis, and mean arterial pressure in a study group (SG), would result in reduced complications, reduced length of hospital stay and quicker return of bowel movement postoperatively in abdominal surgical patients, when compared to a control group (CG).
160 patients undergoing elective major abdominal surgery were randomized to the SG (79 patients) or to the CG (81 patients). In the SG hemodynamic therapy was guided by pulse pressure variation, cardiac index trending and mean arterial pressure. In the CG hemodynamic therapy was performed at the discretion of the treating anesthesiologist. Outcome data were recorded up to 28 days postoperatively.
The total number of complications was significantly lower in the SG (72 vs. 52 complications, p = 0.038). In particular, infection complications were significantly reduced (SG: 13 vs. CG: 26 complications, p = 0.023). There were no significant differences between the two groups for return of bowel movement (SG: 3 vs. CG: 2 days postoperatively, p = 0.316), duration of post anesthesia care unit stay (SG: 180 vs. CG: 180 minutes, p = 0.516) or length of hospital stay (SG: 11 vs. CG: 10 days, p = 0.929).
This multi-center study demonstrates that hemodynamic goal-directed therapy using pulse pressure variation, cardiac index trending and mean arterial pressure as the key parameters leads to a decrease in postoperative complications in patients undergoing major abdominal surgery.
Trial registration, NCT01401283.
PMCID: PMC4057030  PMID: 24010849
2.  Detection of “Candidatus Neoehrlichia mikurensis” in Two Patients with Severe Febrile Illnesses: Evidence for a European Sequence Variant▿  
Journal of Clinical Microbiology  2010;48(7):2630-2635.
Recently, a new genus of Anaplasmataceae termed “Candidatus Neoehrlichia” was discovered in ticks and rodents. Here, we report on two patients who suffered from febrile bacteremia due to “Candidatus Neoehrlichia mikurensis” associated with thrombotic or hemorrhagic events. 16S rRNA and groEL gene sequencing provided evidence of three groups of sequence variants.
PMCID: PMC2897504  PMID: 20519481
3.  Resuscitation of hemorrhagic shock with normal saline versus lactated Ringer's: effects on oxygenation, extravascular lung water, and hemodynamics 
Critical Care  2009;13(2):128.
Which type of fluid to use in the resuscitation from hemorrhagic shock, within and between crystalloids or colloids, is still a matter of debate. In this context, with respect to organ dysfunction, early detection of lung injury is widely considered of particular clinical importance. For these purposes, the transpulmonary thermodilution technique that enables one to assess extravascular lung water as a marker of pulmonary edema is applied in the clinical setting. In this issue of Critical Care, Phillips and colleagues describe that early resuscitation of hemorrhagic shock in pigs with two different crystalloid solutions – normal saline or Ringer's lactate – had little impact on oxygenation when the resuscitation volume was <250 ml/kg. Ringer's lactate had more favorable effects than normal saline, however, on extravascular lung water, pH, and blood pressure but not on oxygenation. Although several pathophysiological aspects remain unanswered, these data are interesting in so far as they indicate that clinically applied amounts of crystalloids per se do not negatively influence pulmonary function, while with larger amounts the type of fluid has different effects on the extent of fluid extravasation in the lungs.
PMCID: PMC2689467  PMID: 19435471
4.  Diagnosis of Bacteremia in Whole-Blood Samples by Use of a Commercial Universal 16S rRNA Gene-Based PCR and Sequence Analysis▿  
Journal of Clinical Microbiology  2009;47(9):2759-2765.
In a prospective, multicenter study of 342 blood samples from 187 patients with systemic inflammatory response syndrome, sepsis, or neutropenic fever, a new commercial PCR test (SepsiTest; Molzym) was evaluated for rapid diagnosis of bacteremia. The test comprises a universal PCR from the 16S rRNA gene, with subsequent identification of bacteria from positive samples by sequence analysis of amplicons. Compared to blood culture (BC), the diagnostic sensitivity and specificity of the PCR were 87.0 and 85.8%, respectively. Considering the 34 BC-positive patients, 28 were also PCR positive in at least one of the samples, resulting in a patient-related sensitivity of 82.4%. The concordance of PCR and BC for both positive and negative samples was (47 + 247)/342, i.e., 86.0%. In total, 31 patients were PCR/sequencing positive and BC negative, in whom the PCR result was judged as possible or probable to true bacteremia in 25. In conclusion, the PCR approach facilitates the detection of bacteremia in blood samples within a few hours. Despite the indispensability of BC diagnostics, the rapid detection of bacteria by SepsiTest appears to be a valuable tool, allowing earlier pathogen-adapted antimicrobial therapy in critically ill patients.
PMCID: PMC2738079  PMID: 19571030
5.  Population Pharmacokinetics and Pharmacodynamics of Continuous versus Short-Term Infusion of Imipenem-Cilastatin in Critically Ill Patients in a Randomized, Controlled Trial▿  
Beta-lactams are regularly administered in intermittent short-term infusions. The percentage of the dosing interval during which free drug concentrations exceed the MIC (fT>MIC) is the measure of drug exposure that best correlates with clinical outcome for beta-lactams. Therefore, administration by continuous infusion has gained increasing interest recently. We studied 20 critically ill patients with nosocomial pneumonia and investigated whether continuous infusion with a reduced total dose, compared to the standard regimen of intermittent short-term infusion, results in a superior probability of target attainment as assessed by the fT>MIC value of imipenem. In this prospective, randomized, controlled clinical study, patients received either a loading dose of 1 g/1 g imipenem and cilastatin (as a short-term infusion) at time zero, followed by 2 g/2 g imipenem-cilastatin per 24 h as a continuous infusion for 3 days (n = 10), or 1 g/1 g imipenem-cilastatin three times per day as a short-term infusion for 3 days (total daily dose, 3 g/3 g; n = 10). Imipenem concentrations in plasma were determined by using a validated liquid chromatography-tandem mass spectrometry assay. A two-compartment open model was employed for population pharmacokinetic modeling. We simulated 10,000 intensive-care-unit patients via Monte Carlo simulations for pharmacodynamic evaluation using the target 40% fT>MIC. The probability of target attainment by MIC for intermittent infusion was robust (>90%) up to MICs of 1 to 2 mg/liter. The corresponding value for continuous infusion was 2 to 4 mg/liter. Although all 20 patients had an fT>MIC of 100%, 3 patients died. Patient survival was best described by employing a sepsis-related organ failure assessment score as a covariate in a logistic regression analysis. Larger clinical trials are warranted for evaluation of continuous infusions at a reduced dose of imipenem for critically ill patients.
PMCID: PMC2043189  PMID: 17620371
6.  Clinical review: Influence of vasoactive and other therapies on intestinal and hepatic circulations in patients with septic shock 
Critical Care  2003;8(3):170-179.
The organs of the hepatosplanchnic system are considered to play a key role in the development of multiorgan failure during septic shock. Impaired oxygenation of the intestinal mucosa can lead to disruption of the intestinal barrier, which may promote a vicious cycle of inflammatory response, increased oxygen demand and inadequate oxygen supply. Standard septic shock therapy includes supportive treatment such as fluid resuscitation, administration of vasopressors (adrenergic and nonadrenergic drugs), and respiratory and renal support. These therapies may have beneficial or detrimental effects not only on systemic haemodynamics but also on splanchnic haemodynamics, at both the macrocirculatory and microcirculatory levels. This clinical review focuses on the splanchnic haemodynamic and metabolic effects of standard therapies used in patients with septic shock, as well as on the recently described nonconventional therapies such as vasopressin, prostacyclin and N-acetyl cysteine.
PMCID: PMC468887  PMID: 15153235
adrenergic drugs; nonconventional treatments; septic shock; splanchnic circulation; supportive treatment

Results 1-6 (6)