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Biomedical subjects

Jean-Louis Vincent

Publications and source records attributed to Jean-Louis Vincent.

At least 109 records · Page 6Linked to original sources
PubMed2004

Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock.

OBJECTIVE: To characterize the time course of microcirculatory alterations and their relation to outcome in patients with septic shock. DESIGN: Prospective, observational study. SETTING: Thirty-one-bed, medico-surgical intensive care unit in a university hospital. PATIENTS: Forty-nine patients with septic shock. INTERVENTIONS: The sublingual microcirculation was investigated with an orthogonal polarization spectral imaging device on the day of onset of septic shock (baseline) and each day until resolution of shock. MEASUREMENTS AND MAIN RESULTS: Five sequences of 20 secs each were recorded and analyzed off-line by a semiquantitative method. Data were analyzed with nonparametric tests and presented as median (25th-75th percentiles). Three patients died after the resolution of shock from unrelated causes and were excluded. Of the other 46 patients, 26 survived and 20 died: 13 due to unresolving shock and seven due to persistent multiple organ failure after resolution of shock. At the onset of shock, survivors and nonsurvivors had similar vascular density (5.6 [4.7-7.0] vs. 6.2 [5.4-7.0]/mL; p = nonsignificant) and percentage of perfused small vessels (65.0 [53.1-68.9] vs. 58.4 [47.5-69.1]%; p = nonsignificant). Small vessel perfusion improved over time in survivors (analysis of variance, p <.05 between survivors and nonsurvivors) but not in nonsurvivors. Despite similar hemodynamic and oxygenation profiles and use of vasopressors at the end of shock, patients dying after the resolution of shock in multiple organ failure had a lower percentage of perfused small vessels than survivors (57.4 [46.6-64.9] vs. 79.3 [67.2-83.2]%; p =.02). CONCLUSIONS: Microcirculatory alterations improve rapidly in septic shock survivors but not in patients dying with multiple organ failure, regardless of whether shock has resolved.

Aged↗
PubMed2004

Practice parameters for hemodynamic support of sepsis in adult patients: 2004 update.

OBJECTIVE: To provide the American College of Critical Care Medicine with updated guidelines for hemodynamic support of adult patients with sepsis. DATA SOURCE: Publications relevant to hemodynamic support of septic patients were obtained from the medical literature, supplemented by the expertise and experience of members of an international task force convened from the membership of the Society of Critical Care Medicine. STUDY SELECTION: Both human studies and relevant animal studies were considered. DATA SYNTHESIS: The experts articles reviewed the literature and classified the strength of evidence of human studies according to study design and scientific value. Recommendations were drafted and graded levels based on an evidence-based rating system described in the text. The recommendations were debated, and the task force chairman modified the document until <10% of the experts disagreed with the recommendations. CONCLUSIONS: An organized approach to the hemodynamic support of sepsis was formulated. The fundamental principle is that clinicians using hemodynamic therapies should define specific goals and end points, titrate therapies to those end points, and evaluate the results of their interventions on an ongoing basis by monitoring a combination of variables of global and regional perfusion. Using this approach, specific recommendations for fluid resuscitation, vasopressor therapy, and inotropic therapy of septic in adult patients were promulgated.

Adult↗
PubMed2004

Morbidity in hospitalized patients receiving human albumin: a meta-analysis of randomized, controlled trials.

OBJECTIVE: To determine the effect of albumin administration on morbidity in acutely ill hospitalized patients. DATA SOURCE: Computer searches of MEDLINE, EMBASE, and the Cochrane Library; hand searches of journals and Index Medicus; inquiries with investigators and fluid product suppliers; and examination of reference lists. No language or time period restrictions were adopted. STUDY SELECTION: Randomized, controlled trials comparing the administration of albumin with that of crystalloid, no albumin, or lower-dose albumin. DATA EXTRACTION: Two investigators independently extracted data. The primary endpoint for the meta-analysis was morbidity, defined as the incidence of complications, including death. Trial quality was evaluated by blinding, allocation concealment, presence of morbidity as a study endpoint, and individual patient crossover. DATA SYNTHESIS: Seventy-one trials were included in the categories of surgery or trauma, burns, hypoalbuminemia, high-risk neonates, ascites, and other indications. The 3,782 randomized patients in the included trials experienced a total of 3,287 complications, including 515 deaths and 2,772 cardiovascular, gastrointestinal, hepatic, infectious, renal, respiratory, and other complications. Albumin significantly reduced overall morbidity, with a risk ratio of 0.92 (confidence interval [CI], 0.86-0.98). Control group albumin dose significantly affected the incidence of complications (p = .002). In 32 trials with no albumin administered to the control group, the risk ratio was 0.77 (CI, 0.67-0.88) compared with 0.89 (CI, 0.80-1.00) in 20 trials with control patients receiving low-dose albumin and 1.07 (CI, 0.96-1.20) in 19 trials with moderate-dose control group albumin. CONCLUSIONS: Albumin reduces morbidity in acutely ill hospitalized patients. Concomitant administration of albumin in the control group can obscure the effects of albumin on clinical outcome in randomized trials.

Acute Disease↗
PubMed2004

Vasopressor and inotropic support in septic shock: an evidence-based review.

OBJECTIVE: In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for vasopressor and inotropic support in 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 to 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: The modified Delphi methodology used 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 to contrast adult and pediatric management are in the article by Parker et al. on p. S591. CONCLUSION: An arterial catheter should be placed as soon as possible in patients with septic shock. Vasopressors are indicated to maintain mean arterial pressure of <65 mm Hg, both during and following adequate fluid resuscitation. Norepinephrine or dopamine are the vasopressors of choice in the treatment of septic shock. Norepinephrine may be combined with dobutamine when cardiac output is being measured. Epinephrine, phenylephrine, and vasopressin are not recommended as first-line agents in the treatment of septic shock. Vasopressin may be considered for salvage therapy. Low-dose dopamine is not recommended for the purpose of renal protection. Dobutamine is recommended as the agent of choice to increase cardiac output but should not be used for the purpose of increasing cardiac output above physiologic levels.

Cardiotonic Agents↗
PubMed2004

Fluid resuscitation in severe sepsis and septic shock: an evidence-based review.

OBJECTIVE: In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for fluid resuscitation in 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: The modified Delphi methodology used 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 to contrast adult and pediatric management are in the article by Parker et al. on p. S591. CONCLUSION: Fluid resuscitation of severe sepsis may consist of natural or artificial colloids or crystalloids. Fluid challenge should be administered and repeated based on response (increase in blood pressure and urine output) and tolerance (evidence of intravascular volume overload).

Consensus Statements as Topic↗
PubMed2004

Sources of variability on the estimate of treatment effect in the PROWESS trial: implications for the design and conduct of future studies in severe sepsis.

OBJECTIVE: To elucidate sources of variability in the estimate of treatment effects in a successful phase 3 trial in severe sepsis and to assess their implications on the design of future clinical trials. DESIGN: Retrospective evaluation of prospectively defined subgroups from a large phase 3, placebo-controlled clinical trial (PROWESS). SETTING: The study involved 164 medical centers. PATIENTS: Patients were 1,690 patients with severe sepsis. INTERVENTIONS: Drotrecogin alfa (activated) (Xigris) 24 microg/kg/hr for 96 hrs, or placebo. MEASUREMENTS AND MAIN RESULTS: All prospectively defined subgroups were examined to identify treatment effects that potentially differed across subgroup strata (assessed by Breslow-Day p < .10). Potential interactions were identified for subgroups defined by a) presence vs. absence of a significant protocol violation (p = .07); b) original vs. amended protocol (p = .08); and c) Acute Physiology and Chronic Health Evaluation (APACHE) II quartile at baseline (p = .09). No treatment benefit was observed in patients having a protocol violation, regardless of type. There appeared to be less treatment effect in patients enrolled under the original vs. amended protocol. The risk ratio exceeded 1.0 for patients in the lowest APACHE II score quartile. A highly significant correlation was observed between the sequence of enrollment at a site, the frequency of protocol violations, and the observed treatment effect. As enrollment increased, frequency of protocol violations decreased (p < .0001) and the treatment effect improved. The correlation between the sequence of enrollment and improvement in treatment effect remained even after removal of patients with protocol violations. Removal of the first block of patients at each site from the analysis reduced the extent of interaction by protocol version and APACHE II score. CONCLUSIONS: A learning curve appeared to be present within the PROWESS trial such that the ability to demonstrate efficacy improved with increasing site experience. This potential learning curve may have implications for design of future trials. Investigational sites may need to require a minimum level of protocol-specific experience to appropriately implement a given trial. This experience should be an important consideration in designing trials and analysis plans. Diligence by coordinating centers, site investigators, study coordinators, and sponsors is necessary to ensure that the protocol is executed as designed such that a treatment benefit, if present, will be evident.

APACHE↗
PubMed2004

Use of low tidal volume in septic shock may decrease severity of subsequent acute lung injury.

Recent studies have indicated that protective lung strategies may improve outcomes in acute lung injury. We hypothesized that the use of a lower tidal volume early during septic shock may protect against the subsequent development of acute lung injury. Fourteen fasted, anesthetized, invasively monitored, mechanically ventilated, female sheep (26.4 +/- 4.5 kg) underwent cecal ligation and perforation to induce sepsis. Sheep were then randomized to ventilation with low (6 mL/kg) or high (12 mL/kg) tidal volumes. A positive end-expiratory pressure of 10 cm H(2)O was applied in each case. Ringer's lactate was titrated to maintain pulmonary artery occlusion pressure at baseline levels. No vasoactive agents or antibiotics were used. Survival time was longer in the low- than in the high-tidal-volume group (21.8 +/- 2.4 vs. 17.6 +/- 4.1 h, respectively, P < 0.05). The times to develop hypotension and anuria were longer in the low-tidal-volume group (18.1 +/- 3.1 vs. 12.0 +/- 2.8 h, P < 0.05, and 17.6 +/- 1.6 vs. 14.1 +/- 3.8 h, P < 0.05). Although the Pao2/Fio2 tended to be lower in the low- than in the high-tidal-volume group (P = 0.06), postmortem examination showed a lower lung tissue wet/dry ratio in the low- than in the high-tidal-volume group (7.1 +/- 0.5 vs. 9.1 +/- 0.7, P < 0.05). A low-tidal-volume ventilation strategy applied early during septic shock may be beneficial in terms of reducing the amount of lung edema and prolonging survival time.

Animals↗
PubMed2004

Association between the TNF-2 allele and a better survival in cardiogenic shock.

STUDY OBJECTIVES: Tumor necrosis factor (TNF)-alpha has been implicated in the pathophysiology of heart failure. We explored a possible association between TNF-alpha, interleukin (IL)-6, IL-10, transforming growth factor (TGF)-beta, and interferon (IFN)-gamma cytokine polymorphisms, their in vivo production, and mortality from cardiogenic shock. DESIGN: Prospective, observational study. SETTING: Thirty-one bed, university, medicosurgical department of intensive care. PATIENTS: Thirty-three adult patients with cardiogenic shock of recent (< 4 h) onset. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: TNF-alpha, IL-6, IL-10, TGF-beta1, and IFN-gamma plasma levels were measured by enzyme-linked immunosorbent assay. Polymorphisms of TNF-alpha within the promoter at position -308a-->g, IL-6 within the promoter at position -174c-->g, IL-10 within the promoter at position -1082a-->g/-819t-->c and -819t-->c/-592a-->c, TGF-beta1 at codon 10t-->c and codon 25c-->g, and IFN-gamma at intron 1 at position + 874t-->a were studied. The 33 patients had a mean (+/- SD) age of 64 +/- 17 years and a mean simplified acute physiology score II of 62.3 +/- 15.3. Twenty-three patients (70%) died in the ICU, including 21 of 26 patients (81%) in the TNF-1 group but only 2 of 7 patients (29%) in the TNF-2 group (p = 0.016). There were no significant differences in median plasma TNF-alpha levels between the TNF-1 and the TNF-2 groups, but TGF-beta1 levels were higher in the survivors than in the nonsurvivors (median, 866 pg/mL; range, 384 to 1,966 pg/mL; vs median, 454 pg/mL; range, 167 to 1,266 pg/mL, respectively; p = 0.02). There were no significant differences in TNF-2 polymorphism between the patients with cardiogenic shock and a group of healthy control subjects (7 of 33 patients vs 13 of 48 subjects, respectively; p = 0.61), but IFN-gamma polymorphism was less common in the cardiogenic shock group (p = 0.034). CONCLUSIONS: Patients with the TNF-2 allele have no greater risk of cardiogenic shock but a better survival rate when it develops. Different genetic factors appear to influence the risk of development of, and outcome from, cardiogenic shock.

Aged↗
PubMed2004

Septic shock of early or late onset: does it matter?

STUDY OBJECTIVES: To determine possible differences in morbidity and mortality between early and late onset of septic shock in ICU patients. DESIGN: Systematic data collection. SETTING: Thirty-one-bed, mixed, medicosurgical ICU in a university hospital. PATIENTS: All 65 patients who acquired septic shock after admission to the ICU between February 1999 and April 2000. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Forty-one of the 65 patients presented with septic shock within 24 h of admission to the ICU (early septic shock [ESS]); the other 21 patients acquired septic shock > 24 h after ICU admission (late septic shock [LSS]). Eleven patients had a second episode (7 patients in the ESS group, and 4 patients in the LSS group), and 1 patient in the LSS group had a third episode of septic shock. Patients with ESS had higher APACHE (acute physiology and chronic health evaluation) II (mean +/- SD, 26 +/- 6 vs 20 +/- 6; p = 0.002) and sequential organ failure assessment (SOFA) scores (11 +/- 3 vs 7 +/- 3, p < 0.001) on ICU admission, and a higher blood lactate concentration at the onset of shock (median 3.70 mEq/L; interquartile range, 2.6 to 6.6 mEq/L; vs median, 2.50 mEq/L [interquartile range, 1.8 to 4.0 mEq/L], p = 0.03) than patients with LSS. However, the duration of septic shock (median, 42 h [interquartile range, 21 to 97 h] vs median, 93 h [interquartile range, 32 to 241 h], p = 0.058) and the length of ICU stay after the onset of septic shock (median, 75 h; [interquartile range, 38 to 203 h] vs median, 321 h [interquartile range, 96 to 438 h], p = 0.018), was shorter in patients with ESS than patients with LSS. The ICU mortality rate was 63% (26 patients) in the ESS group, and 88% (21 patients) in the LSS group (p = 0.071). At the onset of the first episode of shock, patients with ESS had higher SOFA scores (11 +/- 3 vs 9 +/- 3, p = 0.045), lower pH (7.24 +/- 0.15 vs 7.33 +/- 0.12, p = 0.01), and were treated with higher doses of dopamine (median, 20 microg/kg/min [interquartile range, 14 to 20 microg/kg/min] vs median, 12 microg/kg/min [interquartile range, 8 to 20 microg/kg/min], p = 0.028) than patients with LSS. CONCLUSIONS: Septic shock is more severe when of early onset, as reflected by more severe organ dysfunction, greater lactic acidosis, and higher vasopressor requirements, yet the outcome is better, as reflected by a shorter duration of the shock episode, shorter ICU stay, and slightly lower mortality rates. These differences may influence clinical trials of therapeutic agents for sepsis, and should be taken into account when analyzing the results.

APACHE↗
PubMed2004

Evidence-based medicine in the ICU: important advances and limitations.

Evidence-based medicine (EBM) is an important strategy for assessing the vast amounts of published data and applying them appropriately to our patients. However, in intensive care medicine, there is a shortage of "gold standard" randomized controlled trial evidence to support (or not support) therapeutic decisions. In addition, even when well-conducted randomized trials have been performed, we are still left with unanswered questions. In the last 5 years, several clinical trials have yielded positive results with a number of interventions being shown to improve outcomes. Here, we will outline the limitations and advances of EBM in intensive care medicine, by discussing the key findings in the last few years from studies of therapeutic agents for ICU patients.

Adult↗
PubMed2004

Infection control in the intensive care unit.

Nosocomial infections are common in many hospital departments, but particularly so on the intensive care unit, where they affect some 20 to 30% of patients. While early diagnosis and appropriate treatment are, of course, important, perhaps the greatest challenge is in the application of techniques to limit the development of such infections. This review will briefly discuss some of the background pathophysiology and epidemiology of nosocomial infection, and then focus on general and infection-specific preventative strategies individually and as part of broader infection-control programs with infection surveillance.

Cross Infection↗
PubMed2004

[Roles of hydroxyethyl starch solution in resuscitation for shock induced by ischemia/reperfusion injury of the intestine].

OBJECTIVE: To compare the effects of high and low doses of 6% hydroxyethyl starch solution (HES) on resuscitation for shock induced by ischemia/reperfusion injury of the intestine in rabbits. METHODS: Thirty-two anesthetized rabbits were randomized into four groups of eight animals each. The animals in the control group received no fluid resuscitation, animals in group 2 received lactated Ringer's solution (LRS, 20 ml x kg(-1) x h(-1)), those in group 3 received LRS+HES (LRS 18 ml x kg(-1) x h(1)+HES 2 ml x kg(-1) x h(-1), low dosage of HES), and those in group 4 received HES only in high dosage of HES (20 ml x kg(-1) x h(-1)). All these rabbits underwent intestinal ischemia/reperfusion injury developed by occluding superior mesenteric artery (SMA) with a non-crushing vascular clamp for 60 minutes and then the clamp was loosened for 240 minutes. The fluid resuscitation began at the same time of reperfusion. Hemodynamic parameters including mean artery pressure, heart rate, aortic velocity (as cardiac output), and SMA blood flow were measured. Tissue oxygenation was assessed indirectly by measuring the tonometric parameters of the gut, including difference between partial pressure of carbon dioxide in intestinal intramucosal and partial pressure of carbon dioxide in arterial blood (Pt-aCO(2) gap), intestinal intramucosal pH (pHi), arterial blood lactate acid concentration and oxygen delivery. Mortality of the rabbits was counted at the end of the experiment. RESULTS: Hemodynamic parameters as measured in low and high doses of HES groups were significantly higher in values than LRS group (LRS) and control (all P<0.05). Low dose of HES was better in restoring hemodynamic parameters than high dose of HES (all P<0.05). Low dose of HES could greatly decrease lactate and Pt-aCO(2) gap, significantly improve pHi compared with other three groups (all P<0.05), but high dose of HES did not do so, and oral and nasal bleeding even death of some animals were seen. Low dose and high dose of HES significantly improved oxygen delivery while LRS did not (all P<0.05). CONCLUSION: Low dose of HES together with LRS is more effective than only high dose of HES or LRS in the resuscitation for shock induced by ischemia/reperfusion injury of the intestine in rabbits, resulting in better hemodynamic parameters and tissue oxygenation.

Animals↗
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↗