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Biomedical subjects

Jean-Louis Vincent

Publications and source records attributed to Jean-Louis Vincent.

At least 91 records · Page 5Linked to original sources
PubMed2004

Relationship between CRP and hypofibrinolysis: Is this a possible mechanism to explain the association between CRP and outcome in critically ill patients?

BACKGROUND-: Endothelial cell dysfunction may be implicated in the development of multiple organ failure (MOF) by a number of mechanisms. Among these, altered fibrinolysis promotes fibrin deposition, which may create microvascular alterations during inflammation. Elevated concentrations of C-reactive protein (CRP), especially when these persist over time, are correlated with an increased risk of MOF and death. CRP may inhibit fibrinolysis by inducing plasminogen activator inhibitor-1 (PAI-1) release from human aortic endothelial cells. Moreover, the administration of recombinant CRP in volunteers may increase circulating PAI-1 levels.In this study, we tested the hypothesis that CRP is associated with hypofibrinolysis in intensive care patients with and without sepsis. METHODS-: We studied the association of inflammation and abnormal fibrinolysis in intensive care unit (ICU) patients with (n = 11) and without (n = 21) sepsis. The inflammatory response was assessed by serum concentration of C-reactive protein (CRP), a marker of the acute phase reaction, which increase rapidly in the inflammatory response, and the plasma fibrinolytic capacity was evaluated by the Euglobulin Clot Lysis Time (ECLT), determined by a new semi-automatic method. RESULTS-: ECLT was significantly higher in septic than non-septic patients (1104 +/- 439 vs 665 +/- 275 min; p = 0.002) and was significantly correlated with CRP concentration (R2 = 0.45; p < 0.001). In a multivariate analysis, CRP was the strongest predictor of ECLT (R2 = 0.51, F = 25.6, p < 0.001). In addition, the overall ICU length of stay was significantly correlated with CRP (R2 = 0.264, p = 0.003) and ECLT (R2 = 0.259, p = 0.003). CONCLUSION-: In critically ill patients a significant correlation thus exists between plasma fibrinolytic capacity and serum CRP levels. Our data were obtained in the first 24 hours of ICU admission or of sepsis, thus, the relation between CRP and hypofibrinolysis appeared very quickly. This finding is compatible with a link between inflammation and abnormal fibrinolysis, and may explain the negative prognostic value of CRP in critically ill patients.

Journal Article↗
PubMed2004

Diagnostic and prognostic implications of endotoxemia in critical illness: results of the MEDIC study.

A novel assay for endotoxin, based on the ability of antigen-antibody complexes to prime neutrophils for an augmented respiratory burst response, was studied in a cohort study of 857 patients admitted to an intensive-care unit (ICU). On the day of ICU admission, 57.2% of patients had either intermediate (>or=0.40 endotoxin activity [EA] units) or high (>or=0.60 units) EA levels. Gram-negative infection was present in 1.4% of patients with low EA levels, 4.9% with intermediate levels, and 6.9% with high levels; EA had a sensitivity of 85.3% and a specificity of 44.0% for the diagnosis of gram-negative infection. Rates of severe sepsis were 4.9%, 9.2%, and 13.2%, and ICU mortality was 10.9%, 13.2%, and 16.8% for patients with low, intermediate, and high EA levels, respectively. Stepwise logistic regression analysis showed that elevated Acute Physiology and Chronic Health Evaluation II score, gram-negative infection, and emergency admission status were independent predictors of EA.

APACHE↗
PubMed2004

Ethics roundtable debate: child with severe brain damage and an underlying brain tumour.

A young person presents with a highly malignant brain tumour with hemiparesis and limited prognosis after resection. She then suffers an iatrogenic cardiac and respiratory arrest that results in profound anoxic encephalopathy. A difference in opinion between the treatment team and the parent is based on a question of futile therapy. Opinions from five intensivists from around the world explore the differences in ethical and legal issues. A Physician-ethicist comments on the various approaches.

Brain Neoplasms↗
PubMed2004

Role of iron in anaemic critically ill patients: it's time to investigate!

Anaemia is a common problem in critically ill patients admitted to intensive care units. Many factors can be involved in its development, including rapid alterations of iron metabolism. Maintenance of iron homeostasis is a prerequisite for many essential biological processes and a central element for the development of erythroid precursors and mature red blood cells. With the inflammatory process, iron distribution is disturbed, with decreased serum iron levels and increased iron stores. Little information is available on the precise role of alterations of iron metabolism in the development of iron anaemia in critically ill patients.

Anemia↗
PubMed2004

Coagulation in sepsis.

Coagulation abnormalities, ranging from a simple fall in platelet count to full-blown disseminated intravascular coagulation, are a common occurrence in critically ill patients and have been associated with increased mortality. In sepsis, activation of the extrinsic coagulation pathway by tissue factor induces increased coagulation, and simultaneous depression of the inhibitory mechanisms of coagulation, and suppression of the fibrinolytic system results in a procoagulant state that may lead to the formation of microvascular thrombi disturbing organ microcirculation and promoting the development of organ dysfunction. Many inflammatory mediators are involved in the activation of coagulation, but many coagulation proteins are themselves actively involved in the inflammatory process. In this article, we explore the complex relationship between inflammation and coagulation and how improved understanding of this interaction has led to the development of new therapeutic agents for patients with severe sepsis.

Animals↗
PubMed2004

Analysis of terminal events in 109 successive deaths in a Belgian intensive care unit.

OBJECTIVE: To determine the incidence of end-of-life decisions in intensive care unit (ICU) patients. DESIGN AND SETTING: Prospective data collection and questionnaire in a 31-bed medicosurgical ICU in a university hospital. PATIENTS AND PARTICIPANTS: All 109 ICU patients who died during a 3-month period (April-June 2001). Members of the ICU team were also invited to complete a questionnaire regarding the circumstances of each patient's death. Cardiopulmonary resuscitation was performed in 21 of the patients; other mechanisms leading to death were brain death (n=19), refractory shock (n=17), and refractory hypoxemia (n=2). The decision was taken in the remaining 50 patients to withdraw (n=43) or withhold (n=7) therapy. Questionnaires were completed for 68 patients, by physician and nurse in 40 cases, physician only in 20 cases, and nurse only in 8 cases. Questionnaires were obtained for 34 of 50 patients for whom a decision was made to limit therapy. RESULTS: Respondents generally felt that the decision was timely (n=28, 82%), 5 (15%) felt the decision was too late, and one (3%) that the decision was made too soon, before the family could be informed. CONCLUSIONS: Therapeutic limitations are frequent in patients dying in the ICU, with withdrawing more common than withholding life support. Generally members of the ICU staff were satisfied with the end-of-life decisions made.

Attitude of Health Personnel↗
PubMed2004

Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock.

OBJECTIVE: To develop management guidelines for severe sepsis and septic shock that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis. DESIGN: The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. The modified Delphi methodology used for grading recommendations built upon a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along 5 levels to create recommendation grades from A-E, with A being the highest grade. Pediatric considerations were provided to contrast adult and pediatric management. PARTICIPANTS: Participants included 44 critical care and infectious disease experts representing 11 international organizations. RESULTS: A total of 46 recommendations plus pediatric management considerations. CONCLUSIONS: Evidence-based recommendations can be made regarding many aspects of the acute management of sepsis and septic shock that will hopefully translate into improved outcomes for the critically ill patient. The impact of these guidelines will be formally tested and guidelines updated annually, and even more rapidly when some important new knowledge becomes available.

Adult↗
PubMed2004

Ethical principles in end-of-life decisions in different European countries.

The majority of ICU deaths are preceded by a decision to limit treatment in some way. Decisions to withhold or withdraw treatment vary considerably depending on many factors including local practice, cultural and religious background, family and peer pressure. Here we will discuss the current situation across Europe, based on the findings from three large international studies.

Attitude to Death↗
PubMed2004

Can the experienced ICU physician predict ICU length of stay and outcome better than less experienced colleagues?

OBJECTIVE: To assess the ability of physicians with varying degrees of experience to predict the length of stay and outcome of intensive care unit (ICU) patients. DESIGN: Prospective, interview-based study. SETTING: A 31-bed mixed medical-surgical ICU. PATIENTS: A total of 223 consecutive patients (excluding those admitted for routine post-operative surveillance) admitted to the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Physicians immediately responsible for each patient, and others fully aware of the case, were interviewed separately during the first 12 h of ICU admission to determine their assessment of the patient's likely duration of stay on the ICU and the probable outcome. Degree of predictive accuracy was assessed using the Kappa statistic with kappa < or =0.2 poor, 0.21-0.4 fair, 0.41-0.60 moderate, 0.61-0.8 good, and 0.81-1.0 very good. Physicians were graded according to their degree of experience as junior (less than 1 year ICU experience), medium (critical care fellow), and senior (staff physician with supervising functions). For lengths of stay less than 5 days, senior physicians were better predictors than less experienced doctors. For outcome prediction, physicians were generally moderately good at predicting death, with senior physicians tending to be more accurate than their less experienced colleagues (senior kappa 0.68, medium kappa 0.52, junior kappa 0.43). CONCLUSIONS: Prediction of length of ICU stay was poor amongst all physicians in patients with a length of stay greater than 5 days. Experienced physicians were better predictors of ICU lengths of stay less than 5 days and, in contrast to some reports, of ICU outcome than their more inexperienced counterparts.

Adolescent↗
PubMed2004

Effects of fluid challenge on gastric mucosal PCO2 in septic patients.

OBJECTIVE: To determine the effects of fluid challenge on systemic hemodynamic variables and gastric intramucosal partial pressure of carbon dioxide (PCO(2)) in septic patients. DESIGN: Short-term interventional study. SETTING: Medical-surgical intensive care unit in a university hospital. PATIENTS: Twenty-four adult patients with severe sepsis or septic shock requiring volume replacement. All patients were studied within 24 h of onset of severe sepsis or septic shock. INTERVENTIONS: Five hundred milliliters of a 6% hydroxyethyl starch (HES) solution were administered in 30 min. MEASUREMENTS AND RESULTS: Complete hemodynamic data, blood samples, and gastric mucosal PCO(2) (automatic gas capnometry) determinations were obtained at baseline and 15 min after the end of fluid infusion. After fluid challenge, cardiac index (CI) increased from 3.8 (range 2.9-4.2) to 4.2 (range 3.1-4.9) l/min m(-2) ( p<0.05). The PCO(2) gap decreased from 9.8 (range 6.9-26.0) to 8.5 (range 6.6-17.4) mm Hg ( p<0.05), but important individual variations were observed. We failed to observe significant relationships between changes in CI and in PCO(2) gap, or between indices of preload (pulmonary artery occluded pressure, right atrial pressure, and pulse pressure variations) and changes in PCO(2) gap. In addition, changes in PCO(2) gap and in (v-a) CO(2) were not related; however, changes in PCO(2) gap were related to baseline PCO(2) gap ( p=0.003), PEEP ( p=0.02), and cumulative doses of vasopressors ( p=0.02). CONCLUSIONS: The effects of fluid challenge on gastric mucosal PCO(2) are variable and related to baseline PCO(2) gap rather than to systemic variables. In general, rapid volume infusion decreases PCO(2) gap, but this effect is more pronounced in patients with presumably impaired mucosal perfusion.

Adult↗
PubMed2004

Effect of patient sex on intensive care unit survival.

BACKGROUND: Human observations have shown different mortality rates between men and women with various pathological conditions, but this issue has not been widely studied in a heterogeneous population of critically ill patients. METHODS: Retrospective analysis of all patients admitted to a mixed medical-surgical, 31-bed intensive care unit (ICU) during 2 different years (1983 and 1995) to evaluate possible differences in mortality between male and female patients and between medical and surgical admissions and variations in these differences over time. RESULTS: From a total of 4420 admissions (1587 women, 2833 men), women showed a higher mortality, with an odds ratio (OR) of 1.18 (95% confidence interval [CI], 1.02-1.38). This pattern was the same for the 2 periods, and all patient data were therefore analyzed together. After age stratification, the differences were significant for female patients older than 50 years (OR, 1.33; 95% CI, 1.12-1.58) but not in the younger age group. The subgroup of medical admissions had a higher mortality (24.4% vs 7.4%, P<.001) and a higher female proportion (37.9% vs 34.2%, P =.01) than surgical admissions. In multivariate analysis, female sex remained an important predictor of mortality (OR, 1.54; 95% CI, 1.25-1.89). Women had a higher mortality than men in the subgroup of cardiovascular diseases. The highest mortality in female patients was present in the first days after admission and decreased over time, showing a covariance of time and sex. CONCLUSIONS: In a mixed medical-surgical ICU, older women have a higher mortality rate than men. This difference is not apparent for patients staying longer in the ICU.

Age Factors↗
PubMed2004

Microvascular alterations in patients with acute severe heart failure and cardiogenic shock.

BACKGROUND: Microvascular blood flow alterations may impair tissue oxygenation and may participate in the development of multiple organ failure in patients with severe heart failure. We hypothesized that microvascular blood flow alterations are present in patients with severe heart failure and cardiogenic shock. METHODS: We used an orthogonal polarization spectral imaging technique to investigate the sublingual microcirculation in 40 patients with acute severe heart failure, including 31 patients with cardiogenic shock, and in a control group of 15 patients who were examined the day before cardiac surgery. The effects of topical application of acetylcholine (10-2M) were also tested in 5 patients with cardiogenic shock. Five sublingual areas were recorded, allocated a random number, and later analyzed semiquantitatively. Data were analyzed with non-parametric tests and presented as medians (percentiles 25-75). RESULTS: The density of all the vessels was similar in the 3 groups. The proportion of perfused small (<20 microm) vessels was lower in patients with cardiac failure and cardiogenic shock than in control patients (63% [46%-65%] and 49% [38%-64%] vs 92% [90%-93%], P <.001). The perfusion of large vessels was preserved in all groups. The proportion of perfused vessels was higher in patients who survived than in patients who did not survive in all vessels (90% [84%-93%] vs 81% [74%-87%], P <.05) and in small vessels (64% [49%-68%] vs 43% [37%-62%], P <.05). The topical application of acetylcholine totally reversed these alterations CONCLUSIONS: Microvascular blood flow alterations are frequently observed in patients with severe heart failure and are more severe in patients who do not survive.

Acetylcholine↗
PubMed2004

Drowning: a review of epidemiology, pathophysiology, treatment and prevention.

Although often preventable, drowning remains a leading cause of accidental death, especially in children. New definitions classify drowning as the process of experiencing respiratory impairment from submersion or immersion in a liquid. The key pathophysiological feature in drowning is hypoxia. Accurate neurological prognosis cannot be predicted from the initial clinical presentation, laboratory, radiological, or electrophysiological examinations. Prompt and aggressive resuscitation attempts are crucial for optimal survival. This article reviews the epidemiology, pathophysiology, treatment, and prevention of drowning.

Drowning↗
PubMed2004

The hepatosplanchnic contribution to hyperlactatemia in endotoxic shock: effects of tissue ischemia.

We investigated the role of the hepatosplanchnic region in the hyperlactatemia observed during endotoxic shock. The study included 18 dogs anesthetized with pentobarbital and mechanically ventilated. After baseline measurements, including gut lactate production (GLP), liver lactate uptake (LLU), liver lactate extraction (LLE), and hepatosplanchnic lactate production (HSLP), each dog received 2 mg/kg of E. coli endotoxin. After a second set of measurements, cardiac tamponade was induced in 12 dogs (EDTX + Tamp) by repeated injections of normal saline into the pericardial sac to progressively reduce cardiac output and hepatic blood flow. The six remaining dogs served as septic controls (EDTX). From a net lactate consumer before endotoxin infusion, the gut became a lactate producer after the endotoxin infusion, with GLP increasing from -11.4 +/- 27.0 to 32.9 +/- 38.2 x 10(-3) mEq/min (P < 0.05). LLU increased from 48.1 +/- 26.2 to 86.6 +/- 45.2 x 10(-3) mEq/min (P < 0.05), so that LLE and HSLP did not change. In the EDTX + Tamp group, LLE became negative, and HSLP became positive only when hepatic oxygen delivery reached its critical value during cardiac tamponade. In the EDTX group, LLE remained positive and HSLP negative. In endotoxic shock, GLP is increased, but the liver can metabolize this additional load of lactate, so that the hepatosplanchnic area is not a major source of lactate unless the liver becomes profoundly hypoxic.

Animals↗
PubMed2004

Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock.

OBJECTIVE: In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for severe sepsis and septic shock that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis. DESIGN: The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. METHODS: We used a modified Delphi methodology for grading recommendations, built on a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade. Pediatric considerations were provided to contrast adult and pediatric management. RESULTS: Key recommendations, listed by category and not by hierarchy, include early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition; appropriate diagnostic studies to ascertain causative organisms before starting antibiotics; early administration of broad-spectrum antibiotic therapy; reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate; a usual 7-10 days of antibiotic therapy guided by clinical response; source control with attention to the method that balances risks and benefits; equivalence of crystalloid and colloid resuscitation; aggressive fluid challenge to restore mean circulating filling pressure; vasopressor preference for norepinephrine and dopamine; cautious use of vasopressin pending further studies; avoiding low-dose dopamine administration for renal protection; consideration of dobutamine inotropic therapy in some clinical situations; avoidance of supranormal oxygen delivery as a goal of therapy; stress-dose steroid therapy for septic shock; use of recombinant activated protein C in patients with severe sepsis and high risk for death; with resolution of tissue hypoperfusion and in the absence of coronary artery disease or acute hemorrhage, targeting a hemoglobin of 7-9 g/dL; appropriate use of fresh frozen plasma and platelets; a low tidal volume and limitation of inspiratory plateau pressure strategy for acute lung injury and acute respiratory distress syndrome; application of a minimal amount of positive end-expiratory pressure in acute lung injury/acute respiratory distress syndrome; a semirecumbent bed position unless contraindicated; protocols for weaning and sedation/analgesia, using either intermittent bolus sedation or continuous infusion sedation with daily interruptions/lightening; avoidance of neuromuscular blockers, if at all possible; maintenance of blood glucose <150 mg/dL after initial stabilization; equivalence of continuous veno-veno hemofiltration and intermittent hemodialysis; lack of utility of bicarbonate use for pH > or =7.15; use of deep vein thrombosis/stress ulcer prophylaxis; and consideration of limitation of support where appropriate. Pediatric considerations included a more likely need for intubation due to low functional residual capacity; more difficult intravenous access; fluid resuscitation based on weight with 40-60 mL/kg or higher needed; decreased cardiac output and increased systemic vascular resistance as the most common hemodynamic profile; greater use of physical examination therapeutic end points; unsettled issue of high-dose steroids for therapy of septic shock; and greater risk of hypoglycemia with aggressive glucose control. CONCLUSION: Evidence-based recommendations can be made regarding many aspects of the acute management of sepsis and septic shock that are hoped to translate into improved outcomes for the critically ill patient. The impact of these guidelines will be formally tested and guidelines updated annually and even more rapidly as some important new knowledge becomes as available.

Adult↗
PubMed2004

Endpoints in sepsis trials: more than just 28-day mortality?

To determine whether an intervention, either therapeutic or diagnostic, is effective, it needs to be assessed according to a predefined endpoint (or outcome measure), the choice of which will vary according to the aims of the study in question and the anticipated effects of the intervention being tested. Studies can have one of several functions (which are not always mutually exclusive), including providing evidence of biological efficacy, determining a clinically important benefit, and achieving regulatory approval. In trials of therapeutic efficacy in sepsis, mortality rates are a good endpoint because death is common and mortality rates are an unambiguous measure: patients either survive or they do not. However, the time at which mortality should be recorded is less clear cut, and this single endpoint provides no information regarding the biological activity or disease modification effects of the agent under investigation. In this article, we will briefly discuss some of the potential alternative endpoints that could be used in the assessment of antisepsis agents.

Clinical Trials as Topic↗
PubMed2004

Neutrophil elastase inhibition in acute lung injury: results of the STRIVE study.

OBJECTIVE: Neutrophil elastase is believed to be an important mediator of acute lung injury. Sivelestat (ONO-5046, Elaspol) is a small molecular weight inhibitor of neutrophil elastase. The primary objectives of this study were to determine whether sivelestat would reduce 28-day all-cause mortality or increase the number of ventilator-free days (days alive and free from mechanical ventilation from day 1 to day 28) compared with placebo in mechanically ventilated patients with acute lung injury. DESIGN: Multiple-center, double-blind, placebo-controlled trial administering a continuous infusion of sivelestat at a dose of 0.16 mg.kg(-1)hr(-1). SETTING: One hundred and five institutions in the United States, Canada, Belgium, Spain, Australia, and New Zealand. PATIENTS: A total of 492 mechanically ventilated patients with acute lung injury. INTERVENTIONS: Patients were randomized in a 1:1 fashion to sivelestat or placebo. Study drug was administered as a continuous infusion for the duration of mechanical ventilation plus 24 hrs for a maximum of 14 days. All patients were managed using low tidal volume mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: The study was stopped prematurely at the recommendation of an external Data and Safety Monitoring Board, which noted a negative trend in long-term mortality rate. Final analysis revealed no effect of sivelestat on the primary end points of ventilator-free days (day 1-day 28) or 28-day all-cause mortality. There were 64 deaths in each treatment group within the 28-day study period, and the mean number of ventilator-free days was 11.4 and 11.9 in the sivelestat and placebo treatment groups, respectively (p =.536). There was no evidence of effect on measures of pulmonary function, including Pao2/Fio2, static lung compliance, and time to meeting weaning criteria. There was no difference in adverse events or serious adverse events between treatment groups. A comparison of the Kaplan-Meier 180-day survival curves showed no difference between treatment groups (p =.102), but there was an increase in 180-day all-cause mortality in the sivelestat treatment group compared with the placebo group (p =.006). CONCLUSIONS: Intravenous sivelestat had no effect on 28-day all-cause mortality or ventilator-free days in a heterogeneous acute lung injury patient population managed with low tidal volume mechanical ventilation.

Australia↗