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Biomedical subjects

Jean-Charles Preiser

Publications and source records attributed to Jean-Charles Preiser.

At least 19 recordsLinked to original sources
PubMed2006

Diarrhoea in the critically ill.

PURPOSE OF REVIEW: The purpose of this review is to update the knowledge on diarrhoea, a common problem in critically ill patients. Epidemiological data will be discussed, with special emphasis on diarrhoea in tube-fed patients and during antibiotic therapy. The possible preventive and therapeutic measures will be presented. RECENT FINDINGS: The need for concise definitions of diarrhoea was recently re-emphasized. The use of pump-driven continuous instead of intermittent enteral feeding is less often associated with diarrhoea. The discontinuation of enteral feeding during diarrhoea is not justified. Clostridium difficile-associated diarrhoea is frequent during antibiotic therapy with quinolones and cephalosporins. Formulas enriched with water-soluble fibres are probably effective to prevent diarrhoea, and promising data on the modulation of gut microflora with probiotics and prebiotics were recently released. SUMMARY: Diarrhoea is common in critically ill patients, especially when sepsis and hypoalbuminaemia are present, and during enteral feeding and antibiotic therapy. The management of diarrhoea includes generous hydration, compensation for the loss of electrolytes, antidiarrheal oral medications, the continuation of enteral feeding, and metronidazole or glycopeptides in the case of moderate to severe C. difficile colitis. The place of enteral formulas enriched with water-soluble fibres, probiotics and prebiotics is not yet fully defined.

Anti-Bacterial Agents↗
PubMed2006

Glucose, insulin and myocardial ischaemia.

PURPOSE OF REVIEW: The importance of glucose metabolism and insulin therapy during myocardial ischaemia is increasingly being investigated. Insulin is used to achieve a tight glucose control or as part of glucose-insulin-potassium therapy. We have reviewed (1) the physiological and physiopathological consequences of hyperglycaemia focusing on potential machanisms of myocardial ischaemia, (2) the effects of insulin on vascular tone, on the release of free fatty acids, on inflammatory pathways, on the switch of energy source and on apoptosis, and (3) clinical data reporting the effects of intensive insulin therapy and glucose-insulin-potassium solutions during myocardial ischaemia and ischaemic heart failure. RECENT FINDINGS: In addition to its known toxic cellular effects, hyperglycaemia increases the activity of inducible nitric oxide synthase and promotes inflammation. Conversely insulin exerts anti-inflammatory and anti-apoptotic effects. Glucose-insulin-potassium solutions could improve survival after acute myocardial infarction or after surgery, according to recent meta-analyses, but confirmation of these data is eagerly awaited. SUMMARY: Hyperglycaemia is toxic, while insulin is beneficial during acute myocardial ischaemia. Some recent evidence confirms a substantial benefit of insulin administered either alone to achieve a tight glucose control or as a component of glucose-insulin-potassium therapy. Further research is needed to confirm that tendency and to define the threshold of tight glucose control.

Blood Glucose↗
PubMed2006

Biomarkers of oxidative stress in critically ill patients: what should be measured, when and how?

PURPOSE OF REVIEW: This review is dedicated to updating the knowledge on oxidative stress in critically ill patients with an intense inflammatory reaction, and to link it with recent findings supporting the possible involvement of oxidative injuries in systems and organs that frequently fail in the critically ill. RECENT FINDINGS: Some direct or indirect biomarkers of oxidative stress have been validated in critically ill patients, and further support the major role of oxidative stress in these conditions. SUMMARY: The assessment of oxidative stress, defined as the association between an increased production of oxygen-derived species and an exhaustion of the stores of antioxidants, requires a multimodal approach. Oxidative damage itself can be much better estimated by quantifying the oxidative byproducts of the lipids and proteins associated with an evaluation of the remaining stores of the corresponding functional antioxidants, or the activity of antioxidant enzymes, than by global tests of the total oxidative damage or the total antioxidant stores. Recent clinical data confirm an important role of increased oxidative stress in the acute dysfunctions of the respiratory, renal and cerebral systems.

Antioxidants↗
PubMed2006

Is it time for implementation of tight glycaemia control by intensive insulin therapy in every ICU?

The second study on tight glycaemia control by intensive insulin therapy (IIT) confirmed in medical intensive care unit patients the decrease in hospital mortality reported by the same team in the first IIT trial in surgical patients. However, methodological concerns, the high rate of hypoglycaemia in spite of the infusion of large doses of parenteral glucose and the frequent use of steroids presently preclude considering these results as recommendations in other intensive care units, but rather argue for the need for large-scale assessment of the IIT approach by multi-centre studies to confirm the efficacy and safety of this therapeutic modality.

Blood Glucose↗
PubMed2006

Combination therapy versus monotherapy: a randomised pilot study on the evolution of inflammatory parameters after ventilator associated pneumonia [ISRCTN31976779].

INTRODUCTION: Combination antibiotic therapy for ventilator associated pneumonia (VAP) is often used to broaden the spectrum of activity of empirical treatment. The relevance of such synergy is commonly supposed but poorly supported. The aim of the present study was to compare the clinical outcome and the course of biological variables in patients treated for a VAP, using a monotherapy with a beta-lactam versus a combination therapy. METHODS: Patients with VAP were prospectively randomised to receive either cefepime alone or cefepime in association with amikacin or levofloxacin. Clinical and inflammatory parameters were measured on the day of inclusion and thereafter. RESULTS: Seventy-four mechanically ventilated patients meeting clinical criteria for VAP were enrolled in the study. VAP was microbiologically confirmed in 59 patients (84%). Patients were randomised to receive cefepime (C group, 20 patients), cefepime with amikacin (C-A group, 19 patients) or cefepime with levofloxacin (C-L group, 20 patients). No significant difference was observed regarding the time course of temperature, leukocytosis or C-reactive protein level. There were no differences between length of stay in the intensive care unit after infection, nor in ventilator free days within 28 days after infection. No difference in mortality was observed. CONCLUSION: Antibiotic combination using a fourth generation cephalosporin with either an aminoside or a fluoroquinolone is not associated with a clinical or biological benefit when compared to cephalosporin monotherapy against common susceptible pathogens causing VAP.

Adult↗
PubMed2005

Pneumonia-induced sepsis and gut injury: effects of a poly-(ADP-ribose) polymerase inhibitor.

BACKGROUND: Pseudomonas aeruginosa is commonly associated with nosocomial pneumonia. Ileal mucosal injury may be induced by severe lung infection. During septic shock, peroxynitrite-mediated DNA strand-breaks activate the enzyme poly-(ADP)-ribose polymerase (PARP) resulting in cellular energetic suppression and cell dysfunction. The aim of this study was to determine whether gut injury could be demonstrated in sepsis induced by P. aeruginosa and the effects of a PARP inhibitor (PJ34) on the associated gut injury. MATERIALS AND METHODS: After baseline measurements, 20 rabbits were randomized into three groups: Sham (n = 5): transtracheally inoculated (TI) with 2 ml of phosphate buffer solution (PBS); P. aeruginosa + saline (n = 8), TI with 4 x 10(12) CFU/ml of P. aeruginosa in 2 ml/kg of PBS + i.v. saline; and P. aeruginosa + PJ34 (n = 7), TI with 4 x 10(12) CFU/ml of P. aeruginosa and i.v. treatment with PJ34. RESULTS: P. aeruginosa caused a hyperdynamic response with increased blood flow also in the superior mesenteric artery. No significant differences were found in luminal gut lactate concentrations or PCO(2)-gap between groups. Histological specimens showed moderate or diffuse alveolar infiltrate in the P. aeruginosa + saline group (6/8) and in the P. aeruginosa + PJ34 group (6/7). Gut wet-to-dry weight ratio was significantly higher in the P. aeruginosa + saline group than in Shams (7.5 +/- 0.8 versus 6.4 +/- 0.7, P < 0.05) and significantly lower in the P. aeruginosa + PJ34 group (6.1 + 0.5, P < 0.05 versus the other groups). Blood cultures were positive in 1/5 (Sham), 8/8 (P. aeruginosa + saline group) and 4/7 (P. aeruginosa + PJ34 group) (RR 0.57 CI 95% 0.30-1.08). CONCLUSIONS: Pharmacological inhibition of PARP reduces gut inflammation and may limit bacterial translocation.

Animals↗
PubMed2004

Tight blood glucose control: a recommendation applicable to any critically ill patient?

The issue of tight glucose control with intensive insulin therapy in critically ill patients remains controversial. Although compelling evidence supports this strategy in postoperative patients who have undergone cardiac surgery, the use of tight glucose control has been challenged in other situations, including in medical critically ill patients and in those who have undergone non-cardiac surgery. Similarly, the mechanisms that underlie the effects of high-dose insulin are not fully elucidated. These arguments emphasize the need to study the effects of tight glucose control in a large heterogeneous cohort of intensive care unit patients.

Blood Glucose↗
PubMed2004

A comparison among portal lactate, intramucosal sigmoid Ph, and deltaCO2 (PaCO2 - regional Pco2) as indices of complications in patients undergoing abdominal aortic aneurysm surgery.

Our aim in this observational, prospective, noncontrolled study was to detect, in 29 patients who underwent abdominal aortic aneurysm (AAA) surgery, correlations between the incidence of postoperative organ failure and intraoperative changes in arterial and portal blood lactate; changes in intramucosal sigmoid pH (pHi); differences between sigmoid Pco(2) and arterial Pco(2) (DeltaCO(2)); and hemoglobin (Hb). Hb, arterial blood lactate concentrations, pHi, and DeltaCO(2) (air tonometry) were recorded at the start of anesthesia (T0), before aorta clamping (T1), 30 minutes after clamping (T2), and at the end of surgery (T3). Portal venous lactate concentrations were recorded at T1 and T2. Patients were stratified into two groups: group A patients had no postoperative organ failure, and group B patients had one or more organ failures. As compared with group A (n = 16), group B patients (n = 13) had a lower pHi value at T2 and T3 and a higher DeltaCO(2) at T3. A pHi value of <7.15 was a predictor of organ failure, with a sensitivity of 92.3%, a specificity of 68.8%, and positive and negative predictive values of 70.6% and 91.7%, respectively, whereas a DeltaCO(2) value of >28 mm Hg predicted later organ failure with a sensitivity of 92.3%, a specificity of 62.5%, and positive and negative predictive values of 66.6% and 90.9%, respectively. Portal venous lactate concentrations were larger in group B at T2 (P < 0.001), and an increase >or=5 g/dL predicted later postoperative organ failure with a sensitivity of 92.3%, a specificity of 100%, and positive and negative predictive values of 100% and 94.1%, respectively. The comparison of the receiving operator characteristic curves to test the discrimination of each variable and the logistic regression analysis revealed that the increase in portal lactate was the best predictor for the development of postoperative organ failure. Hb concentration was significantly smaller in group B at T0 (13.8 +/- 1.0 g/dL versus 12.2 +/- 2.2 g/dL) and T2 (10.9 +/- 1.2 g/dL versus 9.1 +/- 1.9 g/dL). In conclusion, both pHi and DeltaCO(2) are reasonably sensitive prognostic indices of organ failures after AAA surgery, but they are less specific and accurate than portal venous lactate.

Aged↗
PubMed2003

Gut mucosal and plasma concentrations of glutamine: a comparison between two enriched enteral feeding solutions in critically ill patients.

BACKGROUND: Addition of glutamine to enteral nutrition formulas is consistently associated with a significant decrease in septic morbidity in critically ill patients, possibly related to the attenuation of gut dysfunction. This pilot study was undertaken to compare the effects of enteral administration of two glutamine-enriched formulas containing either additional free glutamine or glutamine-rich proteins, with a standard solution on plasma and mucosal concentrations of glutamine in patients admitted in the Department of Intensive Care. METHODS: Following randomization, glutamine concentration was determined in endoscopically sampled duodenal biopsies and plasma, before and after a 7-day period of continuous administration of the designated solution. RESULTS: The mucosal concentration of glutamine increased in the duodenal biopsies sampled from patients randomized to the solution containing the glutamine-rich proteins (from 3.6 +/- 2.2 to 6.7 +/- 5.2 micro-mol/g protein), but not from the others. There were no differences between the 3 groups in the plasma concentrations of glutamine, which remained stable over time. CONCLUSION: The source of supplemental glutamine can influence gut mucosal glutamine concentrations, suggesting differences in its availability or utilization.

Clinical Trial↗
PubMed2003

Gut mucosal damage during endotoxic shock is due to mechanisms other than gut ischemia.

Whether the gut alterations seen during sepsis are caused by microcirculatory hypoxia or disturbances in cellular metabolic pathways associated with mitochondrial respiration remains controversial. We hypothesized that hypoperfusion or hypoxia and local production of nitric oxide might play an important role in the development of gut mucosal injury during endotoxic shock and investigated their roles by using differing levels of fluid resuscitation and occlusion of the superior mesenteric artery (SMA). Anesthetized New Zealand rabbits were allocated to group I (sham, n = 8); group II [low-dose endotoxin (LPS, Escherichia coli-055:B5, 150 microg/kg)/fluid resuscitation (12 ml x kg(-1) x h(-1)); n = 8]; group III [high-dose LPS (1 mg/kg)/fluid resuscitation (12 ml x kg(-1) x h(-1)); n = 8]; group IV [high-dose LPS (1 mg/kg)/hypovolemia (4 ml x kg-1 x h(-1) fluids); n = 8]; and group V [SMA ligation/fluid resuscitation (12 ml x kg(-1) x h(-1)); n = 4]. Luminal gut lactate concentrations and PCO2 gap increased in groups IV and V (P < 0.05), reflecting alterations in gut perfusion. Interestingly, significant histological alterations were observed in all LPS groups but not in group V. Blood and luminal gut nitrate/nitrite concentrations increased only in group IV. The mechanism of gut injury in endotoxic shock seems unrelated to hypoxia and release of nitric oxide. Gut dysfunction may occur as a result of so-called "cytopathic hypoxia."

Animals↗
PubMed2003

Does aprotinin influence the inflammatory response to cardiopulmonary bypass in patients?

OBJECTIVES: Aprotinin has been shown to have anti-inflammatory properties, but its effects on the inflammatory reaction to cardiopulmonary bypass remain controversial. This prospective, randomized, double-blind study evaluated the influence of aprotinin on various blood markers of inflammation during and after cardiopulmonary bypass. METHODS: Sixty male patients underwent coronary artery bypass grafting. The patients were randomized into 3 groups: a placebo group, a second group receiving 2,000,000 KIU of aprotinin followed by an infusion of 500,000 KIU/h and 2,000,000 KIU in the pump prime, and a third group receiving half this dosage. Measurements of tumor necrosis factor, interleukin 6, interleukin 8, interleukin 10, endotoxin, histamine, complement factors, prekallikrein, and prostaglandin D(2) were obtained at baseline, 30 minutes after study drug loading, 10 minutes after the beginning of cardiopulmonary bypass, before the end of bypass, 4 hours after bypass, and on the first and second postoperative days. RESULTS: Aprotinin had no significant effect on any of these parameters. As expected, aprotinin reduced early blood loss in both treated groups. CONCLUSIONS: These results indicate that aprotinin at doses currently used to reduce blood loss has no significant influence on the systemic inflammatory response during moderate hypothermic cardiopulmonary bypass in human subjects, as assessed by the mediators measured in this study.

Aprotinin↗
PubMed2003

Monocyte CD40 expression in severe sepsis.

D40 is a cell surface protein belonging to the tumor necrosis factor (TNF) receptor family. Ligation of monocyte CD40 by the T cell-derived CD40 ligand can trigger the production of various mediators, the transcription and activation of enzymes, and the upregulation of costimulatory molecules involved in the pathogenesis of sepsis. To test the hypothesis that CD40 is expressed on the surface of monocytes during sepsis, we measured CD40 expression by flow cytometry on freshly sampled monocytes from 40 patients with severe sepsis, including 15 patients with bacteremia, and from eight healthy volunteers. Plasma concentrations of interleukin (IL) 6, IL-10, and IL-13 were also measured. We detected CD40 only on monocytes from patients with sepsis (mean 6.5 +/- 0.4 median channel fluorescence). There was an inverse correlation between peak CD40 expression and survival (P = 0.05), particularly in the patients with bacteremia (P = 0.019). In the bacteremic group, there was an inverse correlation between CD40 expression and bilirubin levels (r2 = 0.52, P = 0.004) and plasma IL-6 concentrations (r2 = 0.30, P = 0.04). Our results showed that upregulation of CD40 expression on peripheral blood monocytes is a protective phenomenon during severe sepsis. Monocyte deactivation reflected by low CD40 expression may represent impairment of immune function associated with severity of illness and poor outcome. Further studies on monocyte phenotype and function may help to assess the immune status of patients with sepsis and perhaps be useful to guide immunomodulatory strategy in the future.

Adult↗