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Biomedical subjects

Jean-Louis Vincent

Publications and source records attributed to Jean-Louis Vincent.

At least 37 records · Page 2Linked to original sources
PubMed2006

The effects of dobutamine on microcirculatory alterations in patients with septic shock are independent of its systemic effects.

OBJECTIVE: To evaluate the effects of dobutamine on microcirculatory blood flow alterations in patients with septic shock. DESIGN: Prospective, open-label study. SETTING: A 31-bed, medico-surgical intensive care unit of a university hospital. PATIENTS: Twenty-two patients with septic shock. INTERVENTIONS: Intravenous administration of dobutamine (5 mug/kg.min) for 2 hrs (n = 22) followed by the addition of 10 M acetylcholine (topically applied, n = 10). MEASUREMENTS AND MAIN RESULTS: Complete hemodynamic measurements were obtained before and after dobutamine administration. In addition, the sublingual microcirculation was investigated with an orthogonal polarization spectral imaging technique before and after dobutamine administration and after topical application of acetylcholine. Dobutamine significantly improved capillary perfusion (from 48 +/- 15 to 67 +/- 11%, p = .001), but with large individual variation, whereas capillary density remained stable. The addition of topical acetylcholine completely restored capillary perfusion (98 +/- 1%, p = .001) and capillary density. The changes in capillary perfusion during dobutamine administration were not related to changes in cardiac index (p = .45) or arterial pressure (p = .29). Interestingly, the decrease in lactate levels was proportional to the improvement in capillary perfusion (y = 0.07 - 0.02x, r = .46, p = .005) but not to changes in cardiac index (p = .55). CONCLUSIONS: The administration of 5 mug/kg.min dobutamine can improve but not restore capillary perfusion in patients with septic shock. These changes are independent of changes in systemic hemodynamic variables.

Acetylcholine↗
PubMed2006

Does dopamine administration in shock influence outcome? Results of the Sepsis Occurrence in Acutely Ill Patients (SOAP) Study.

OBJECTIVE: The optimal adrenergic support in shock is controversial. We investigated whether dopamine administration influences the outcome from shock. DESIGN: Cohort, multiple-center, observational study. SETTING: One hundred and ninety-eight European intensive care units. PATIENTS: All adult patients admitted to a participating intensive care unit between May 1 and May 15, 2002. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were followed up until death, until hospital discharge, or for 60 days. Shock was defined as hemodynamic compromise necessitating the administration of vasopressor catecholamines. Of 3,147 patients, 1,058 (33.6%) had shock at any time; 462 (14.7%) had septic shock. The intensive care unit mortality rate for shock was 38.3% and 47.4% for septic shock. Of patients in shock, 375 (35.4%) received dopamine (dopamine group) and 683 (64.6%) never received dopamine. Age, gender, Simplified Acute Physiology Score II, and Sequential Organ Failure Assessment score were comparable between the two groups. The dopamine group had higher intensive care unit (42.9% vs. 35.7%, p=.02) and hospital (49.9% vs. 41.7%, p=.01) mortality rates. A Kaplan-Meier survival curve showed diminished 30 day-survival in the dopamine group (log rank=4.6, p=.032). In a multivariate analysis with intensive care unit outcome as the dependent factor, age, cancer, medical admissions, higher mean Sequential Organ Failure Assessment score, higher mean fluid balance, and dopamine administration were independent risk factors for intensive care unit mortality in patients with shock. CONCLUSIONS: This observational study suggests that dopamine administration may be associated with increased mortality rates in shock. There is a need for a prospective study comparing dopamine with other catecholamines in the management of circulatory shock.

Aged↗
PubMed2006

Transfusion in the intensive care unit.

OBJECTIVE: To summarize the incidences of anemia and blood transfusions in critically ill patients, assess their comparative risks and benefits, and briefly speculate on the possible effects of leukoreduction and blood storage on the need to reevaluate transfusion triggers. DESIGN: A review of the current literature was performed. RESULTS: Anemia is common in intensive care unit patients and is associated with increased mortality. Some 20-53% of intensive care unit patients will receive a blood transfusion during their stay, and these have also been associated with worse outcomes. Leukoreduction may limit some of the infectious and immunomodulatory risks associated with blood transfusion. CONCLUSIONS: Data on the risks and benefits of blood transfusion are conflicting, and with recent changes in blood transfusion practice, including the widespread introduction of leukoreduction, it is time to reevaluate our transfusion triggers.

Anemia↗
PubMed2006

Fluid challenge revisited.

OBJECTIVE: To discuss the rationale, technique, and clinical application of the fluid challenge. DATA SOURCE: Relevant literature from MEDLINE and authors' personal databases. STUDY SELECTION: Studies on fluid challenge in the acutely ill. DATA EXTRACTION: Based largely on clinical experience and assessment of the relevant published literature, we propose that the protocol should include four variables, namely 1) the type of fluid administered, 2) the rate of fluid administration, 3) the critical end points, and 4) the safety limits. CONCLUSIONS: A protocol for routine fluid challenge is proposed with defined rules and based on the patient's response to the volumes infused. The technique allows for prompt correction of fluid deficits yet minimizes the risks of fluid overload. LEARNING OBJECTIVES: On completion of this article, the reader should be able to: 1. Explain the signs of hypovolemia. 2. Describe how to administer a fluid challenge. 3. Use this information in a clinical setting.

Central Venous Pressure↗
PubMed2006

Pharmacokinetics and pharmacodynamics of once-weekly subcutaneous epoetin alfa in critically ill patients: results of a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To describe the erythropoietin pharmacokinetic profile after once-weekly epoetin alfa treatment in critically ill patients. Secondary objectives were to compare pharmacodynamic and safety profiles between active treatment and placebo in these patients. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Medical, surgical, or mixed medical/surgical intensive care units. PATIENTS: A total of 73 anemic critically ill adults with an expected stay of >3 days and a hematocrit value of <38%. INTERVENTIONS: Patients were randomized 2:1 to epoetin alfa, 40,000 IU, administered subcutaneously once weekly (n=48) or matching placebo (n=25) for up to 4 wks. MEASUREMENTS AND MAIN RESULTS: Serum erythropoietin concentration and hematologic variables (percentage reticulocytes [RETI], hemoglobin [Hb], and total red blood cell [RBC] counts) were measured, and area under the serum concentration-time curve from time 0 to the last blood sampling time at time t (t: 120, 144, or 168 hrs) postdose (AUC0-Tlast) for these three variables was determined. Mean serum erythropoietin concentrations in placebo patients were slightly higher than typical physiologic levels of erythropoietin in healthy subjects, although not appropriate for the degree of anemia in these patients. Overall, exposure of endogenous erythropoietin in the placebo group (in terms of AUC0-Tlast) was only about 20% of exposure to exogenous erythropoietin in the epoetin alfa group. Baseline hemoglobin levels were the same in both groups (9.9 g/dL). Mean change in hemoglobin level from baseline through day 29 was 1.9 g/dL and 1.6 g/dL in the epoetin alfa and placebo groups, respectively. Mean AUC(RETI)0-Tlast was higher with epoetin alfa than with placebo and was related to the AUC of erythropoietin. There were no apparent differences in AUC(Hb)0-Tlast and AUC(RBC)0-Tlast between epoetin alfa and placebo groups, which was most likely due to bleeding and transfusion events. Epoetin alfa was safe and well tolerated, with a rate of treatment-emergent complications similar to that seen with placebo. CONCLUSION: Epoetin alfa, once weekly, augmented the erythropoietic response in critically ill patients as indicated by the increased erythropoietin levels and larger AUC(RETI)0-Tlast in treated patients.

Adolescent↗
PubMed2006

Effects of drotrecogin alfa activated on microcirculatory alterations in patients with severe sepsis.

OBJECTIVE: Microvascular alterations may play an important role in the development of sepsis-induced organ dysfunction. Drotrecogin alfa activated (DAA) improves outcome in patients with severe sepsis, but its precise mechanism of action is not entirely defined. We investigated whether DAA can influence microcirculatory alterations in patients with severe sepsis. DESIGN: Prospective, nonrandomized study. SETTING: A 31-bed, medico-surgical intensive care unit of a university hospital. PATIENTS: Forty adult patients with severe sepsis who met the EU criteria for DAA administration. INTERVENTIONS: Twenty patients received the drug (DAA) and 20 had a contraindication to DAA administration (control). MEASUREMENTS AND MAIN RESULTS: An orthogonal polarization spectral imaging technique was used to visualize the sublingual microcirculation. In all patients, measurements were obtained at baseline, 4 hrs later, and then every 24 hrs for up to 7 days. In patients receiving DAA, measurements were also obtained just before and 4 hrs after the end of DAA infusion. The two groups were well matched for severity of disease, number of failing organs, and the degree of microvascular alterations at baseline. The proportion of perfused capillaries increased in the DAA treated patients already at 4 hrs (from 64% [51-80%] to 84% [71-88%], p < .01) but not in the control group (from 67% [59-76%] to 68% [61-71%], p = not significant). Microvascular perfusion decreased transiently at the end of DAA infusion. The improvement in microvascular blood flow was associated with a more rapid resolution of hyperlactatemia. CONCLUSIONS: DAA administration rapidly improves sepsis-induced microvascular alterations, whereas its cessation is associated with a transient deterioration.

Aged↗
PubMed2006

Beneficial effects of alkaline phosphatase in septic shock.

OBJECTIVE: Alkaline phosphatase may decrease the harmful effects of lipopolysaccharide by detoxifying lipid A. The aim of this study was to investigate whether administration of alkaline phosphatase is beneficial in a clinically relevant septic shock model. DESIGN: Interventional laboratory study. SETTING: University hospital animal research laboratory. SUBJECTS: Fourteen fasted, anesthetized, invasively monitored, mechanically ventilated, female sheep (27.6 +/- 3.9 kg). INTERVENTIONS: Each animal received 1.5 g/kg body weight of feces intraperitoneally to induce sepsis. Ringer's lactate and a 6% hydroxyethyl starch solution were infused throughout the experiment to prevent hypovolemia. Two hours after feces injection, animals were randomized to alkaline phosphatase (60 units/kg intravenous bolus followed by a continuous infusion of 20 units/kg/hr for a total of 15 hrs) or no alkaline phosphatase (control group). MEASUREMENTS AND MAIN RESULTS: All animals were studied until their spontaneous death or for a maximum of 30 hrs. Plasma alkaline phosphatase concentrations decreased in the control group but increased in the treatment group following alkaline phosphatase administration. In the treatment group, the Pao2/Fio2 ratio was higher (p < .05), blood interleukin-6 concentrations were lower (p < .05), and the survival time was longer (median time 23.8 vs. 17 .0 hrs, p < 0.05) than in the control group. There were no significant differences in systemic hemodynamics or diuresis. CONCLUSIONS: In this clinically relevant septic shock model, alkaline phosphatase administration improved gas exchange, decreased interleukin-6 concentrations, and prolonged survival time.

Alkaline Phosphatase↗
PubMed2006

Albumin administration improves organ function in critically ill hypoalbuminemic patients: A prospective, randomized, controlled, pilot study.

OBJECTIVE: To test the hypothesis that administration of albumin to correct hypoalbuminemia might have beneficial effects on organ function in a mixed population of critically ill patients. DESIGN: : Prospective, controlled, randomized study. SETTING: Thirty-one-bed, mixed medicosurgical department of intensive care. PATIENTS: All adult patients with a serum albumin concentration < or =30 g/L were assessed for eligibility. Principal exclusion criteria were expected length of stay <72 hrs, life expectancy <3 months or a do-not-resuscitate order, albumin administration in the preceding 24 hrs, or evidence of fluid overload. INTERVENTIONS: The 100 patients were randomized to receive 300 mL of 20% albumin solution on the first day, then 200 mL/day provided their serum albumin concentration was <31 g/dL (albumin group), or to receive no albumin (control group). MEASUREMENTS AND MAIN RESULTS: The primary outcome was the effect of albumin administration on organ function as assessed by a delta Sequential Organ Failure Assessment score from day 1 to day 7 (or the day of intensive care discharge or death, whichever came first). The two groups of 50 patients were comparable at baseline for age, gender, albumin concentration, and Acute Physiology and Chronic Health Evaluation II score. Albumin concentration did not change over time in the control group but increased consistently in the albumin group (p < .001). Organ function improved more in the albumin than in the control group (p = .026), mainly due to a difference in respiratory, cardiovascular, and central nervous system components of the Sequential Organ Failure Assessment score. Diuretic use was identical in both groups, but mean fluid gain was almost three times higher in the control group (1679 +/- 1156 vs. 658 +/- 1101 mL, p = .04). Median daily calorie intake was higher in the albumin than in the control group (1122 [935-1158] vs. 760 [571-1077] kcal, p = .05). CONCLUSIONS: Albumin administration may improve organ function in hypoalbuminemic critically ill patients. It results in a less positive fluid balance and a better tolerance to enteral feeding.

Adult↗
PubMed2006

Effects of dexamethasone on macrophage migration inhibitory factor production in sepsis.

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that plays a major role in the pathogenesis of sepsis. Some studies have indicated that glucocorticoids increase MIF production in physiological conditions. The goal of this study was to determine whether glucocorticoid treatment also upregulates MIF production in sepsis. Male NMRI mice (6-10 weeks old) underwent laparotomy, proximal ligation of the cecum, and double perforation with a 19-gauge needle (cecal ligation and puncture). Mice were randomly treated with saline (control) or dexamethasone at doses of 0.1, 1, or 10 mg/kg ip. At 6 or 18 h postoperatively, 10 mice per group were euthanized; and blood, peritoneal fluid, liver, lung, kidney, and heart tissue samples were retrieved. MIF, IL-6, TNF-alpha, and IL-10 were measured by enzyme-linked immunosorbent assay. Sepsis induced by cecal ligation and puncture produced a marked increase in MIF and cytokine levels in plasma and peritoneal fluid. Treatment with dexamethasone 10 mg/kg decreased MIF levels in plasma after 18 h, but there was no effect of dexamethasone on MIF production locally in the peritoneal cavity or in the liver, lungs, heart, or kidneys. We conclude that glucocorticoid treatment does not upregulate MIF production in sepsis.

Animals↗
PubMed2006

Prediction of postoperative complications after urgent laparotomy by intraperitoneal microdialysis: A pilot study.

OBJECTIVE: The aim of the present study was to investigate the role of intraperitoneal microdialysis (IPM) techniques in monitoring the evolution of postoperative critically ill patients requiring urgent laparotomy. SUMMARY BACKGROUND DATA: Postoperative intraabdominal sepsis is associated with an important degree of morbidity and mortality in acutely ill patients. Early diagnosis is critical to improve outcomes. METHODS: : The study included 25 consecutive patients admitted to the intensive care unit (ICU) after urgent laparotomy. Measurements of microdialysate fluid were performed through a microdialysis catheter, positioned intraperitoneally, during the first 5 postoperative days and lactate/pyruvate (L/P) ratios calculated. Patients were followed until hospital discharge. RESULTS: Ten patients had a complicated postoperative course, including 4 deaths (3 refractory shock, 1 mesenteric ischemia), 3 reinterventions (1 necrotic collection, 1 mesenteric ischemia, 1 biliary leak), 2 secondary peritonitis, and 1 intraabdominal collection. The IPM L/P ratio in these patients was already significantly higher during the first 24 postoperative hours compared with patients who had no complications (35 +/- 21 vs. 18 +/- 6, P < 0.01). An IPM L/P ratio above 22 on postoperative day 1 had a sensitivity of 0.64 and a specificity of 0.79 for complications. There were no significant differences between the two groups in pH, lactate, white blood cell count, or subcutaneous L/P ratio. No complication was associated with the technique. CONCLUSIONS: IPM is safe and reliable and provides valuable information after urgent laparotomy. Persistently high L/P values should raise the possibility of serious postoperative complications.

Adult↗
PubMed2006

How can the response to volume expansion in patients with spontaneous respiratory movements be predicted?

INTRODUCTION: The aim of the study was to evaluate the ability of different static and dynamic measurements of preload to predict fluid responsiveness in patients with spontaneous respiratory movements. METHODS: The subjects were 21 critically ill patients with spontaneous breathing movements receiving mechanical ventilation with pressure support mode (n = 9) or breathing through a face mask (n = 12), and who required a fluid challenge. Complete hemodynamic measurements, including pulmonary artery occluded pressure (PAOP), right atrial pressure (RAP), pulse pressure variation (DeltaPP) and inspiratory variation in RAP were obtained before and after fluid challenge. Fluid challenge consisted of boluses of either crystalloid or colloid until cardiac output reached a plateau. Receiver operating characteristics (ROC) curve analysis was used to evaluate the predictive value of the indices to the response to fluids, as defined by an increase in cardiac index of 15% or more. RESULTS: Cardiac index increased from 3.0 (2.3 to 3.5) to 3.5 (3.0 to 3.9) l minute-1 m-2 (medians and 25th and 75th centiles), p < 0.05. At baseline, DeltaPP varied between 0% and 49%. There were no significant differences in DeltaPP, PAOP, RAP and inspiratory variation in RAP between fluid responders and non-responders. Fluid responsiveness was predicted better with static indices (ROC curve area +/- SD: 0.73 +/- 0.13 for PAOP, p < 0.05 vs DeltaPP and 0.69 +/- 0.12 for RAP, p = 0.054 compared with DeltaPP) than with dynamic indices of preload (0.40 +/- 0.13 for DeltaPP and 0.53 +/- 0.13 for inspiratory changes in RAP, p not significant compared with DeltaPP). CONCLUSION: In patients with spontaneous respiratory movements, DeltaPP and inspiratory changes in RAP failed to predict the response to volume expansion.

Aged↗
PubMed2006

Recommendations on the use of recombinant activated factor VII as an adjunctive treatment for massive bleeding--a European perspective.

INTRODUCTION: Our aim was to develop consensus guidelines for use of recombinant activated factor VII (rFVIIa) in massive hemorrhage. METHODS: A guidelines committee derived the recommendations using clinical trial and case series data identified through searches of available databases. Guidelines were graded on a scale of A-E according to the strength of evidence available. Consensus was sought among the committee for each recommendation. RESULTS: A recommendation for use of rFVIIa in blunt trauma was made (grade B). rFVIIa might also be beneficial in post-partum hemorrhage (grade E), uncontrolled bleeding in surgical patients (grade E) and bleeding following cardiac surgery (grade D). rFVIIa could not be recommended for use: in penetrating trauma (grade B); prophylactically in elective surgery (grade A) or liver surgery (grade B); or in bleeding episodes in patients with Child-Pugh A cirrhosis (grade B). Efficacy of rFVIIa was considered uncertain in bleeding episodes in patients with Child-Pugh B and C cirrhosis (grade C). Monitoring of rFVIIa efficacy should be performed visually and by assessment of transfusion requirements (grade E), while thromboembolic adverse events are a cause for concern. rFVIIa should not be administered to patients considered unsalvageable by the treating medical team. CONCLUSIONS: There is a rationale for using rFVIIa to treat massive bleeding in certain indications; however, only adjunctively to the surgical control of bleeding once conventional therapies have failed. Lack of data from randomized, controlled clinical trials, and possible publication bias of the case series data, limits the strength of the recommendations that can be made.

Blood Substitutes↗
PubMed2006

Initial and delayed onset of acute respiratory failure: factors associated with development and outcome.

In a prospective observational study of 1038 adult admissions to a 31-bed medical/surgical intensive care unit (ICU), acute respiratory failure (ARF, defined as a Pao(2)/Fio(2) ratio 48 h after ICU admission) in 49 (16%). On admission, the cardiovascular sequential organ failure assessment (SOFA) score was higher in initial than in delayed onset ARF (1.1 +/- 1.5 vs 0.6 +/- 1.2, P < 0.05). High admission serum C-reactive protein concentrations (OR 1.08, 95% CI 1.04-1.12, P = 0.0001) and SOFA scores (OR 1.20, 95% CI 1.08-1.33, P = 0.0007) were the factors independently associated with initial ARF, and a low Glasgow coma scale (GCS) score (OR 1.13, 95% CI 1.04-1.21, P = 0.0018) was associated with delayed onset ARF. In initial ARF, a high SOFA score (OR 1.24, 95% CI 1.12-1.38, P = 0.0001) and a low GCS score (OR 0.89, 95% CI 0.83-0.96, P = 0.0013) on admission, and in delayed onset ARF, a low GCS score at 48 h (OR 0.67, 95% CI 0.54-0.84, P = 0.0011) were independently associated with death. The mortality rate was similar for initial and delayed onset ARF.

Adult↗
PubMed2006

Intensive care and emergency medicine: progress over the past 25 years.

Over the last quarter of a century, intensive care medicine has developed into an established hospital specialty with its own unique identity and characteristics. Significant advances have occurred, mostly in a succession of small steps rather than any dramatic leap, with many being linked to advances in health care across other disciplines. In addition, many changes have resulted from the scientific identification of the detrimental effects of certain traditional practices once thought to be therapeutic. Here, in an attempt to learn from the past and offer guidance for future progress, we detail some of the key changes in various aspects of intensive care medicine including respiratory, cardiovascular, metabolic, and nutritional care, as well as sepsis, polytrauma, organization, and management.

Cardiovascular Diseases↗
PubMed2006

Management of sepsis in the critically ill patient: key aspects.

Severe sepsis is a major cause of morbidity and mortality in the critically ill patient. Management involves identification and treatment of the underlying causative infection, with antimicrobial agents and surgery where necessary, haemodynamic resuscitation with fluids and vasoactive agents, steroids (for septic shock) and immunomodulation with drotrecogin-alpha (activated), where not contraindicated. Every effort must be made to identify sepsis early so as to optimise the patient's chances of a good outcome.

Adult↗
PubMed2006

Drotrecogin alfa (activated) in the treatment of severe sepsis.

Severe sepsis is a common and frequently fatal condition. Evidence showing a link between the coagulation system and the inflammatory response to sepsis led to the development of drotrecogin alfa (activated) as an agent in the treatment of severe sepsis. Recent studies have shown that the mode of action is actually more complex than initially thought. This recombinant form of the natural anticoagulant, activated protein C, has been demonstrated to reduce mortality in a large randomized controlled, Phase III study involving 1690 patients, even though the results of this and subsequent studies and the licensing of drotrecogin alfa (activated) have generated considerable debate. Administration of drotrecogin alfa (activated) is associated with an increased risk of bleeding and its use is contraindicated in patients with a high risk of bleeding or recent hemorrhagic events.

Animals↗