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Jean-Louis Vincent

Publications and source records attributed to Jean-Louis Vincent.

180 records · Page 10Linked to original sources
PubMed2002

New management strategies in ARDS. Immunomodulation.

Acute respiratory distress syndrome is a common condition among the critically ill and is associated with high morbidity and mortality [table: see text] rates. Improved understanding of the underlying inflammatory pathogenetics has encouraged the search for strategies that, by modifying this immune response, can improve outcome for this group of patients. Some agents are obviously anti-inflammatory. Others have been used primarily for other purposes; their immune effects are incidental, but no less important. Although immunomodulatory strategies have been discussed for many years, they now are beginning to show positive results, as in the study using activated protein C. Most patients with ARDS die with ARDS, rather than from ARDS. The approach to treatment must not be lung-limited but must take into account the systemic effects of the inflammatory response. The complex nature of the syndrome makes it likely that no single agent will provide the long-desired cure. Rather, it is probable that an individual patient will require a combination of several agents or different agents at different times during the disease process (Table 1). Mortality rates from ARDS already are beginning to fall with improved nutritional and ventilatory support. Positive results from trials using immunomodulatory agents are being reported, and soon such agents will form part of the routine management of patients with ARDS, further improving the outlook for these patients.

Adjuvants, Immunologic↗
PubMed2002

Barbiturate coma for intracranial hypertension: clinical observations.

PURPOSE: To determine the neurologic outcome of patients with intracranial hypertension treated with barbiturate-induced coma. MATERIALS AND METHODS: The records of 49 patients who were admitted to a 31-bed medicosurgical intensive care unit over a 5-year period in whom a barbiturate coma was induced to control intracranial hypertension were analyzed retrospectively. Analysis included assessment of the response to barbiturate coma and evaluation of the long-term neurologic outcome according to the Glasgow Outcome Scale (GOS). RESULTS: Intracranial hypertension was caused by head trauma in 28 patients and subarachnoid hemorrhage in 21 patients. Eight of the head trauma patients and 5 of the patients with subarachnoid hemorrhage survived their hospital stay. The survivors were younger than the nonsurvivors, and had a good neurologic status after 1 year (except for 2 patients who died 1 and 3 months after discharge, respectively). There was no significant difference in the Glasgow Coma Score (GCS) on admission between the survivors and the nonsurvivors. The long-term outcome at 1 year was markedly better in the patients who had experienced a subarachnoid hemorrhage than in the trauma patients.

Adolescent↗
PubMed2002

Management of septic shock.

Severe sepsis is a common disease process affecting some 2-11% of hospital admissions in the US. Severe sepsis and septic shock are associated with considerable morbidity and mortality, and account for a large part of intensive care unit costs. Until recently, the management of septic shock relied on the treatment of underlying infection with antimicrobial agents and surgical removal of any infectious source, and individual support of failing organs. However, in the last few years we have seen huge strides being made in our understanding of the pathophysiology of the sepsis response, and in our ability to manipulate that response. In the last couple of years these advances have come to fruition with the development of a drug, drotrecogin alfa, which specifically reduces mortality from this all too often fatal disease. While intensive early resuscitation remains the cornerstone of management, new approaches are beginning to form part of sepsis management protocols and will lead to improved outcomes for patients with this disease process.

Adjuvants, Immunologic↗
PubMed2002

Randomized, controlled clinical trials in sepsis: has methodological quality improved over time?

OBJECTIVE: To systematically evaluate the methodological quality of randomized clinical trials and to determine whether randomized clinical trials of sepsis improved in methodological quality over time. DATA SOURCES: Computerized MEDLINE search of articles published in any language from 1966 to 1998 combined with a manual search of bibliographies of published articles and communication with known experts in the field. STUDY SELECTION: All randomized clinical trials of sepsis, severe sepsis, and septic shock performed in adults and published as full articles. DATA EXTRACTION: Abstracts of all retrieved records were reviewed and the inclusion criteria were applied. All selected articles were classified into (a) trials designed to detect differences in mortality as the primary end point, or (b) trials focusing on surrogate outcome measures (i.e., physiological or biochemical parameters). All retrieved trials were then graded for methodological quality using an objective grading scheme developed specifically for this study. The data selection and extraction process was carried out independently by two of the authors; any disagreement was resolved by discussion. DATA SYNTHESIS: Seventy-four randomized clinical trials involving septic patients qualified for inclusion in this study (40 reporting mortality outcomes, 34 reporting other surrogate outcomes). Trials reporting mortality as the primary outcome had significantly higher quality scores compared with trials reporting surrogate outcome measures (29.6 +/- 1.0 vs. 24.3 +/- 0.8, p =.0006). From 1976 to 1998, trial methodology improved significantly over time (an average of 0.36 points per year, p =.021). Mortality outcome trials improved an average of 0.58 points per year (p =.0011) whereas surrogate outcome trials did not demonstrate an improvement in methodological quality over time (p =.249). CONCLUSION: The methodological limitations identified in this article can help to target further improvement in trial design to enhance the validity of findings from future randomized clinical trials of sepsis.

Adult↗
PubMed2002

Platelet function in sepsis.

OBJECTIVE: To evaluate platelet function in sepsis. DATA SOURCES: The MEDLINE database and bibliographies of selected articles. DATA SYNTHESIS: The common occurrence of thrombocytopenia in critically ill patients has been recognized for many years and is known to be associated with an increased mortality rate. Platelet function can be divided into four areas: activation, adhesion, aggregation, and secretion. Studies have found that activated platelets secrete key components of the coagulation and inflammatory cascades and are involved in the regulation of vascular tone. However, studies on platelet function in sepsis have been scarce, and their data are often conflicting. In sepsis, aggregation of circulating platelets seems to be reduced, yet platelet receptors are present in normal amounts. CONCLUSIONS: Platelets play a complex role in sepsis; they are able to modulate not only their own function but also that of cells around them. Further study is needed to better define the precise mechanisms and effects of platelet activation in sepsis and to determine the benefits and risks of inhibiting platelet function.

Animals↗
PubMed2002

Multicenter clinical research in adult critical care.

OBJECTIVE: To describe the development, organization, and operation of several collaborative groups conducting investigator-initiated multicenter clinical research in adult critical care. DESIGN: To review the process by which investigator-initiated critical care clinical research groups were created using examples from Europe, Australia, the United States, and Canada. Various models of group structure and function are discussed, highlighting complementary approaches to protocol development, multicenter study management, and project funding. DATA SOURCES: Published peer review research and unpublished terms of reference documents on the structure and function of these groups. DATA SYNTHESIS: The overall goal of clinical critical care research groups engaged in multicenter studies is to improve patient outcomes through conducting large, rigorous investigations. Research programs we reviewed included the following: a) multicenter epidemiologic studies and surveys; b) technology evaluations of mechanical ventilation; c) investigations focused on three priority fields (acute lung injury, infection, and acute brain injury); d) a series of randomized trials of treatments for one syndrome (acute respiratory distress syndrome); and e) diverse methodologies addressing several clinical problems. The structure and function of these research groups differ according to their historical development, research culture, and enabling resources. Specific protocols emerge from clinical questions generated by investigators or from collectively prioritized research agendas. Project funding includes government support, peer-review grants, intensive care foundations, industry, local hospital funds, and hybrid models. Infrastructure for study management varies widely. CONCLUSIONS: Several national and international groups have engaged in investigator-initiated multicenter critical care research. The development, organization, and operational methods of these groups illustrate several collaborative models for clinical investigations in the intensive care unit. Common characteristics of these groups are a cohesive spirit, a sense of mission to achieve shared research goals, and acknowledgment that such an organization is much more than the sum of its parts.

Adult↗
PubMed2002

Use of albumin in the intensive care unit.

Recent publications have renewed interest in albumin use in the ICU. Meta-analyses have been published that demonstrate the safety of albumin administration and even potential benefits. Hypoalbuminemia, which has long been considered a marker of disease, has been causally linked to the development of complications. Finally, advances have been made in our knowledge of the unique and potentially beneficial properties of albumin.

Albumins↗
PubMed2002

The epidemiology of acute respiratory failure in critically ill patients(*).

STUDY OBJECTIVES: To describe the risk factors for the development of and mortality resulting from acute respiratory failure (ARF) in a large patient population. DESIGN: A substudy of a prospective, multicenter, observational cohort study, which was designed to validate the sequential organ failure assessment score. SETTING: Forty ICUs in 16 countries. PATIENTS: All critically ill patients who were admitted to one of the participating ICUs during a 1-month period were observed until the end of their hospital course. MEASUREMENTS AND RESULTS: Of the 1,449 patients who were enrolled into the study, 458 (32%) were admitted to an ICU with ARF, as defined by a PaO(2)/fraction of inspired oxygen ratio of < 200 mm Hg and the need for respiratory support. Patients who presented with ARF were older than the other patients (63 vs 57 years, respectively; p < 0.001) and more commonly had an infection (47% vs 20%, respectively; p < 0.001). The length of ICU stay was longer (6 vs 4 days, respectively; p < 0.001) and the ICU mortality rate was more than double (34% vs 16%, respectively; p < 0.001) in ARF patients compared to non-ARF patients. Of the 991 patients who were admitted to an ICU without ARF, 352 (35%) developed ARF later during the ICU stay. The independent risk factors for the development of ARF were infection developing in the ICU (odds ratio [OR], 7.59; 95% confidence interval [CI], 5.08 to 11.33) or present on ICU admission (OR, 2.3; 95% CI, 1.68 to 3.16), the presence of neurologic failure on ICU admission (OR, 2.73; 95% CI, 1.90 to 3.91), and older age (OR, 1.70; 95% CI, 1.30 to 2.22). Of all 810 patients with ARF, 253 (31%) died. The independent risk factors for death were multiple organ failure following ICU admission, history of hematologic malignancy, chronic renal failure or liver cirrhosis, the presence of circulatory shock on ICU admission, the presence of infection, and older age. CONCLUSIONS: The present study stresses that ARF is common in the ICU (56% of all patients) and that a number of extrapulmonary factors are related to the risk of development of ARF and to mortality rate in these patients.

Acute Disease↗
PubMed2002

Drotrecogin alfa: a new approach 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 sepsis. This recombinant form of the natural protein, activated protein C (Xigris, Eli Lilly Co.), has been shown to significantly reduce mortality in a large randomised, controlled Phase III study involving 1690 patients. The exact mode of action of drotrecogin alfa (activated) remains uncertain, although it clearly combines anticoagulant and anti-inflammatory properties. Although associated with an increased risk of bleeding, this is usually procedure-related rather than spontaneous. Although costly, this is a drug that effectively reduces mortality rates in patients with severe sepsis.

Anti-Infective Agents↗
PubMed2002

Response of tumour necrosis factor-alpha to delayed in vitro monocyte stimulation in patients with septic shock is related to outcome.

We hypothesized that cytokine production following delayed in vitro cell stimulation (to reproduce physiological cellular status at baseline) may be related to outcome in patients with septic shock. A total of 20 patients were included in a prospective clinical study, conducted in a medico-surgical intensive care unit in a university hospital. Blood samples were obtained at the onset of septic shock; these were treated to retain the cells, but to wash out autologous plasma (containing potential inflammatory stimuli such as cytokines, bacterial products and drugs) and replace it with foetal calf serum. Each treated sample was divided into two sets of four aliquots, to be stimulated either immediately or after an overnight period of resting incubation at 37 degrees C. The rest period was to allow recovery from potentially reversible endogenous or pharmacologically induced alterations in cellular response, in order to reproduce a near physiological state at baseline. In vitro cellular challenges used low-dose (0.2 ng/ml) or high-dose (1 ng/ml) CD14-dependent lipopolysaccharide and CD14-independent pokeweed mitogen to induce the production of tumour necrosis factor-alpha (TNF-alpha), and interleukins-1 beta and -10. Levels of TNF-alpha, interleukin-1 beta and interleukin-10 were significantly higher (P<0.05) when cell stimulation was delayed for 16 h, indicating a functional down-regulation of cells during septic shock. Moreover, TNF-alpha responses obtained with high-dose lipopolysaccharide were significantly greater in cells from patients who subsequently survived septic shock (n=13; median value 1392 pg/ml; range 592-2048 pg/ml) than in cells from non-survivors (n=7; median value 708 pg/ml; range 520-1344 pg/ml). These observations support the existence of individual differences in the inflammatory response that could influence patient outcome following septic shock.

Aged↗
PubMed2002

Brain function in the vegetative state.

Positron emission tomography (PET) techniques represent a useful tool to better understand the residual brain function in vegetative state patients. It has been shown that overall cerebral metabolic rates for glucose are massively reduced in this condition. However, the recovery of consciousness from vegetative state is not always associated with substantial changes in global metabolism. This finding led us to hypothesize that some vegetative patients are unconscious not just because of a global loss of neuronal function, but rather due to an altered activity in some critical brain regions and to the abolished functional connections between them. We used voxel-based Statistical Parametric Mapping (SPM) approaches to characterize the functional neuroanatomy of the vegetative state. The most dysfunctional brain regions were bilateral frontal and parieto-temporal associative cortices. Despite the metabolic impairment, external stimulation still induced a significant neuronal activation (i.e., change in blood flow) in vegetative patients as shown by both auditory click stimuli and noxious somatosensory stimuli. However, this activation was limited to primary cortices and dissociated from higher-order associative cortices, thought to be necessary for conscious perception. Finally, we demonstrated that vegetative patients have impaired functional connections between distant cortical areas and between the thalami and the cortex and, more importantly, that recovery of consciousness is paralleled by a restoration of this cortico-thalamo-cortical interaction.

Cerebral Cortex↗
PubMed1999

Antibiotic policy: a tool for controlling resistance of hospital pathogens.

Multiresistant Gram-negative bacilli, including strains of Klebsiella pneumoniae, Enterobacter spp, Acinetobacter baumannii and Pseudomonas aeruginosa, resistant to broad spectrum beta-lactams, aminoglycosides and fluoroquinolones, are recovered at increasing frequency from patients suffering from nosocomial infections, particularly from those receiving intensive care. The emergence and spread of resistant pathogens to endemic and epidemic levels has frequently been related in time and place to the intensive use of antibiotics to which these microorganisms have developed resistance, notably third generation cephalosporins and fluoroquinolones. Recent investigations have indicated that the prevalence of resistance can be reduced by scheduled changes of empiric treatment regimens, involving discontinuation of intensively prescribed drugs and substitution with newly introduced antibiotics of another class to which the prevalent resistant strains remain susceptible. Among these drugs, penicillins---beta-lactamase inhibitor combinations, 'fourth generation' cephalosporins and, where little used previously, fluoroquinolones, have been introduced successfully in high risk units where ceftazidime-resistant strains of K.pneumoniae, Enterobacter and Citrobacter spp or glycopeptide-resistant enterococci had become highly prevalent. However, these studies do not demonstrate a direct causal relationship between changes in prescribing practices and ecological improvements, because their observational design cannot be controlled. In most studies, several important factors influencing the dynamics of resistance were not monitored and the relative contribution of decreased emergence versus control of cross-transmission to the improved susceptibility rates is not clear. We propose that additional long-term studies are required to better track the ecological impact and to determine the optimal modalities of programmed changes of antibiotic prescribing as an antibiotic resistance prevention or control strategy.

Journal Article↗