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Biomedical subjects

Jean-Louis Vincent

Publications and source records attributed to Jean-Louis Vincent.

At least 163 records · Page 9Linked to original sources

Alterations of red blood cell shape and sialic acid membrane content in septic patients.

OBJECTIVE: To investigate the relationship between red blood cell (RBC) shape and modifications of RBC membrane protein content in critically ill patients with or without sepsis compared with healthy control volunteers. DESIGN: Prospective, observational in vitro study. SETTING: University-affiliated cell biology laboratory. SUBJECTS: Human erythrocytes from healthy volunteers and nonseptic and septic intensive care unit patients. INTERVENTIONS: Sialic acid membrane content was measured on isolated RBC membrane proteins by high-performance liquid chromatography. RBC shape, estimated by the spherical index (M2/M1) or by the moment and effect of osmolality on RBC shape, was studied by flow cytometry at 25 degrees C. Glycophorin A content was measured with antiglycophorin antibodies in flow cytometry. MEASUREMENTS AND MAIN RESULTS: Sialic acid content was lower in the septic than in the nonseptic patients (1.98 +/- 0.79, 2.20 +/- 0.39 microg/100 microg membrane protein, respectively; p =.01) and than in the volunteers (2.71 +/- 1.00 microg/100 microg membrane protein; p <.001). No significant difference was found in glycophorin A content between septic and nonseptic patients. RBCs from septic patients had a more spherical shape in isotonic solution than those of healthy volunteers, as assessed by a computed spherical index (M2/M1 ratio: 1.68 +/- 0.34 vs. 1.95 +/- 0.32; p =.001). Only the RBCs of septic patients failed to change their shape in hypo-osmolar solution (M2/M1 ratio: 1.68 +/- 0.34 in iso-osmolar, 1.56 +/- 0.28 in hypo-osmolar solution; p =.17). There was a significant correlation between the RBC shape evaluated by the spherical index or by the moment of the cytometric histogram and the sialic acid membrane content in all critically ill patients (septic and nonseptic patients) (r2 =.16, p =.01 for the moment, and r2 =.17, p =.01 for the spherical index, respectively). CONCLUSIONS: RBCs of septic patients are characterized by a more spherical shape, a decreased capacity of sphericity in hypo-osmolar solution, and a reduction in the sialic acid content of the RBC membrane. These modifications in RBC shape and membrane may contribute to the RBC rheologic abnormalities frequently described in sepsis.

Aged↗

Infection Probability Score (IPS): A method to help assess the probability of infection in critically ill patients.

OBJECTIVE: To develop a simple score to help assess the presence or absence of infection in critically ill patients using routinely available variables. DESIGN: Observational study of a prospective cohort of patients divided into a developmental set (n = 353) and a validation set (n = 140). SETTING: Department of intensive care at an academic tertiary care center. PATIENTS: Four hundred and ninety-three adult patients admitted to the intensive care unit for > or =24 hrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The presence of infection was defined using the Centers for Disease Control definitions. Body temperature, heart rate, respiratory rate, white blood cell count, and C-reactive protein concentrations were measured, and the Sequential Organ Failure Assessment score was calculated throughout the intensive care unit stay. Infection was documented in 92 of the 353 patients (26%) in the developmental set and in 41 of the 140 patients (29%) in the validation set. Univariate logistic regression was used to select significant predictors for infection. Each continuous predictor was transformed in a categorical variable using a robust locally weighted least square regression between infection and the continuous variable of interest. When more than two categories were created, the variable was separated into iso-weighted dummy variables. A multiple logistic regression model predicting infection was calculated with all the variables coded 1 or 0 allowing for relative scoring of the different predictors. The resulting Infection Probability Score consisted of six different variables and ranged from 0 to 26 points (0-2 for temperature, 0-12 for heart rate, 0-1 for respiratory rate, 0-3 for white blood cell count, 0-6 for C-reactive protein, 0-2 for Sequential Organ Failure Assessment score). The best predictors for infection were heart rate and C-reactive protein, whereas respiratory rate was found to have the poorest predictive value. The cutoff value for the Infection Probability Score was 14 points, with a positive predictive value of 53.6% and a negative predictive value of 89.5%. Model performance was very good (Hosmer-Lemeshow statistic, p =.918), and the areas under receiver operating characteristic curves were 0.820 for the developmental set and 0.873 for the validation set. CONCLUSIONS: The Infection Probability Score is a simple score that can help assess the probability of infection in critically ill patients. The variables used are simple, routinely available, and familiar to clinicians. Patients with a score <14 points have only a 10% risk of infection.

Adult↗

Hemoglobin solutions.

OBJECTIVE: To review current knowledge about cell-free hemoglobin solutions. DATA SOURCE: A computerized MEDLINE search was used to retrieve all studies concerning cell-free hemoglobin solutions from 1990 to 2003. The reference lists of all available review articles and primary studies were also reviewed to identify references not identified in the computerized search. STUDY SELECTION: All clinical and experimental studies involving cell-free hemoglobin solutions were included. DATA EXTRACTION: From the selected studies, information was obtained regarding the experimental model or the study population in which cell-free hemoglobin solutions were investigated, the type of cell-free hemoglobin solution used, their deleterious or beneficial effects, and their possible indications. DATA SYNTHESIS: In many studies, hemoglobin solutions were considered as efficient resuscitative agents and good alternatives to red blood cell transfusion, owing to their marked vasopressor effect, coupled with their capacity to improve the microcirculation and rapidly restore metabolic parameters. The main problems identified include excessive systemic vasoconstriction and oxidative damage. Initial enthusiasm in the development of hemoglobin solutions has been tempered recently by the negative results of a U.S. multicenter trial studying the early infusion of diaspirin cross-linked hemoglobin in trauma patients. Nevertheless, the properties of diaspirin cross-linked hemoglobin (and particularly the strong vasopressor effects) cannot be attributed to all hemoglobin solutions, and results of new clinical studies are eagerly awaited to evaluate the potential benefit of such solutions in the management of trauma patients. CONCLUSIONS: Today, we are aware of the effects of the first generation of blood substitutes. Further research is ongoing into newer solutions. One area of interest is the development of new molecular structures to decrease nitric oxide binding, thus minimizing any adverse events and maximizing potential benefits. Nevertheless, possible adverse effects need to be carefully evaluated before these agents can be widely administered.

Animals↗

Differential effects of a selective inhibitor of soluble guanylyl cyclase on global and regional hemodynamics during canine endotoxic shock.

Activation of soluble guanylyl cyclase (sGC) might occur early during septic shock and play a role in the regulation of vascular tone and the redistribution of blood flow. The aim of this study was to assess the effects of sGC inhibition with oxadiazoloquinoxalinone (ODQ) on global and regional hemodynamic parameters in a clinically relevant model of septic shock. Fifteen anesthetized adult mongrel dogs were equipped with femoral and pulmonary artery catheters and ultrasonic flow probes around the mesenteric, femoral and renal arteries. The animals were randomized to receive Escherichia coli endotoxin (2 mg/kg, i.v.) alone, endotoxin followed by ODQ (1 mg/kg i.v.), or ODQ alone. Endotoxin administration was followed by decreases in mean arterial pressure, cardiac index, mesenteric, renal and femoral blood flows (MBF, RBF and FBF), and increases in systemic and pulmonary vascular resistances. Fluid resuscitation restored cardiac index, systemic vascular resistance, pulmonary vascular resistance, MBF, RBF and FBF to pre-endotoxin levels. In the presence of endotoxin, ODQ administration increased MBF and prevented the restoration of FBF. Hence, selective inhibition of sGC may increase splanchnic blood flow in septic shock.

Animals↗

Hypoalbuminemia in acute illness: is there a rationale for intervention? A meta-analysis of cohort studies and controlled trials.

OBJECTIVE: To determine whether hypoalbuminemia is an independent risk factor for poor outcome in the acutely ill, and to assess the potential of exogenous albumin administration for improving outcomes in hypoalbuminemic patients. SUMMARY BACKGROUND DATA: Hypoalbuminemia is associated with poor outcomes in acutely ill patients, but whether this association is causal has remained unclear. Trials investigating albumin therapy to correct hypoalbuminemia have proven inconclusive. METHODS: A meta-analysis was conducted of 90 cohort studies with 291,433 total patients evaluating hypoalbuminemia as an outcome predictor by multivariate analysis and, separately, of nine prospective controlled trials with 535 total patients on correcting hypoalbuminemia. RESULTS: Hypoalbuminemia was a potent, dose-dependent independent predictor of poor outcome. Each 10-g/L decline in serum albumin concentration significantly raised the odds of mortality by 137%, morbidity by 89%, prolonged intensive care unit and hospital stay respectively by 28% and 71%, and increased resource utilization by 66%. The association between hypoalbuminemia and poor outcome appeared to be independent of both nutritional status and inflammation. Analysis of dose-dependency in controlled trials of albumin therapy suggested that complication rates may be reduced when the serum albumin level attained during albumin administration exceeds 30 g/L. CONCLUSIONS: Hypoalbuminemia is strongly associated with poor clinical outcomes. Further well-designed trials are needed to characterize the effects of albumin therapy in hypoalbuminemic patients. In the interim, there is no compelling basis to withhold albumin therapy if it is judged clinically appropriate.

Acute Disease↗

C-reactive protein levels correlate with mortality and organ failure in critically ill patients.

STUDY OBJECTIVES: C-reactive protein (CRP) is an acute-phase protein, the blood levels of which increase rapidly in response to infection, trauma, ischemia, burns, and other inflammatory conditions. Although used frequently in the ICU as a sepsis marker, the relation of CRP levels to organ damage is not well known. This study assessed the association between early serum CRP concentrations and the development of organ failure and mortality in ICU patients. DESIGN: A prospective cohort study. SETTING: A 31-bed ICU in a university hospital. PATIENTS: All 313 patients admitted to the ICU during the 4-month study period. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Patients with high CRP levels at ICU admission had more severe organ dysfunction (higher sequential organ failure assessment scores, days of renal extracorporeal support therapy), longer ICU stays, and higher mortality rates than patients with normal ICU admission CRP levels. CRP concentrations were correlated with the presence and number of organ failures. ICU admission serum CRP levels > 10 mg/dL were associated with a significantly higher incidence of respiratory (65% vs 28.8%, p < 0.05), renal (16.6% vs 3.6%, p < 0.05), and coagulation (6.4% vs 0.9%, p < 0.05) failures, and with higher mortality rates (36% vs 21%, p < 0.05) than CRP levels < 1 mg/dL. In patients with CRP concentrations > 10 mg/dL on ICU admission, a decrease in CRP level after 48 h was associated with a mortality rate of 15.4%, while an increased CRP level was associated with a mortality rate of 60.9% (relative risk, 0.25; 95% confidence interval, 0.07 to 0.91; p < 0.05). CONCLUSIONS: In a heterogeneous ICU population, elevated concentrations of serum CRP on ICU admission are correlated with an increased risk of organ failure and death. Moreover, persistently high CRP concentrations are associated with a poor outcome. Serial measurements may be helpful to identify those patients who require more aggressive interventions to prevent complications.

C-Reactive Protein↗

Do all nonsurvivors of cardiogenic shock die with a low cardiac index?

STUDY OBJECTIVES: To characterize the hemodynamic course of cardiogenic shock and to relate the cause of death to ongoing cardiac failure or multiple organ dysfunction. DESIGN: Retrospective study. SETTING: A 31-bed department of intensive care in a university hospital. PATIENTS: All patients admitted for cardiogenic shock from January 1999 to December 2000. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Charts were reviewed for demographic, clinical, hemodynamic, oxygen transport, inflammation, and organ dysfunction data. Of 62 patients with cardiogenic shock, 40 (65%) did not survive. Eight patients (20%) died from fatal arrhythmia, 14 patients (35%) died with low cardiac index (CI) [ie, < 2.2 L/min/m(2)], and 18 patients (45%) died with normalized CI (ie, > 2.2 L/min/m(2)) and a higher CI/oxygen extraction ratio. Of these 18 patients, 9 had evidence of infection. The patients with normalized CI were younger and stayed longer in the ICU than patients with low CI. CONCLUSION: A substantial number of patients with cardiogenic shock die with a normalized CI, suggesting a distributive defect, in the absence of obvious infection. These patients are younger and have a longer ICU course. The release of mediators may be secondary to gut hypoperfusion.

Aged↗

Infection/inflammation and hemostasis.

The association between coagulation and inflammation is a two-way process. Inflammation promotes coagulation, but key hemostatic proteins can promote inflammation. This two-way process creates a vicious cycle on a downward spiral to vascular injury, organ dysfunction, and death that are often the outcome of severe sepsis. Improved understanding of the basic mechanisms underlying the interaction between infection, inflammation, and coagulation has led to the development of several potential new agents for the treatment of severe sepsis. Among these agents, recombinant activated protein C has been shown to improve outcome, which is an exciting development in the search for effective treatments for patients with severe sepsis.

Antithrombins↗

Reducing mortality in sepsis: new directions.

Considerable progress has been made in the past few years in the development of therapeutic interventions that can reduce mortality in sepsis. However, encouraging physicians to put the results of new studies into practice is not always simple. A roundtable was thus convened to provide guidance for clinicians on the integration and implementation of new interventions into the intensive care unit (ICU). Five topics were selected that have been shown in randomized, controlled trials to reduce mortality: limiting the tidal volume in acute lung injury or acute respiratory distress syndrome, early goal-directed therapy, use of drotrecogin alfa (activated), use of moderate doses of steroids, and tight control of blood sugar. One of the principal investigators for each study was invited to participate in the roundtable. The discussions and questions that followed the presentation of data by each panel member enabled a consensus recommendation to be derived regarding when each intervention should be used. Each new intervention has a place in the management of patients with sepsis. Furthermore, and importantly, the therapies are not mutually exclusive; many patients will need a combination of several approaches--an "ICU package". The present article provides guidelines from experts in the field on optimal patient selection and timing for each intervention, and provides advice on how to integrate new therapies into ICU practice, including protocol development, so that mortality rates from this disease process can be reduced.

Animals↗

The Multiple Organ Dysfunction Score (MODS) versus the Sequential Organ Failure Assessment (SOFA) score in outcome prediction.

OBJECTIVE: To compare outcome prediction using the Multiple Organ Dysfunction Score (MODS) and the Sequential Organ Failure Assessment (SOFA), two of the systems most commonly used to evaluate organ dysfunction in the intensive care unit (ICU). DESIGN: Prospective, observational study. SETTING: Thirty-one-bed, university hospital ICU. PATIENTS AND PARTICIPANTS: Nine hundred forty-nine ICU patients. MEASUREMENTS AND RESULTS: The MODS and the SOFA score were calculated on admission and every 48 h until ICU discharge. The Acute Physiology and Chronic Health Evaluation (APACHE) II score was calculated on admission. Areas under receiver operating characteristic (AUROC) curves were used to compare initial, 48 h, 96 h, maximum and final scores. Of the 949 patients, 277 died (mortality rate 29.1%). Shock was observed in 329 patients (mortality rate 55.3%). There were no significant differences between the two scores in terms of mortality prediction. Outcome prediction of the APACHE II score was similar to the initial MODS and SOFA score in all patients, and slightly worse in patients with shock. Using the scores' cardiovascular components (CV), outcome prediction was better for the SOFA score at all time intervals (initial AUROC SOFA CV 0.750 vs MODS CV 0.694, p<0.01; 48 h AUROC SOFA CV 0.732 vs MODS CV 0.675, p<0.01; and final AUROC SOFA CV 0.781 vs MODS CV 0.674, p<0.01). The same tendency was observed in patients with shock. There were no significant differences in outcome prediction for the other five organ systems. CONCLUSIONS: MODS and SOFA are reliable outcome predictors. Cardiovascular dysfunction is better related to outcome with the SOFA score than with the MODS.

APACHE↗

The cuff leak test to predict failure of tracheal extubation for laryngeal edema.

OBJECTIVE: Laryngeal edema secondary to endotracheal intubation may require early re-intubation. Prior to extubation the absence of leak around an endotracheal tube may predict laryngeal edema after extubation. We evaluated the usefulness of a quantitative assessment of such a leak to identify the patients who will require early re-intubation for laryngeal edema. METHODS: This prospective study included 76 patients with endotracheal intubation for more than 12 h. The leak, in percent, was defined as the difference between expired tidal volume measured just before extubation, in volume-controlled mode, with the cuff inflated and then deflated. The best cut-off value to predict the need for re-intubation for significant laryngeal edema was determined and the patients were divided into two groups, according to this cut-off value. RESULTS: Eight of the 76 patients (11%) needed re-intubation for laryngeal edema. Patients requiring re-intubation had a smaller leak than the other patients [9 (3-18) vs 35 (13-53)%, p<0.01]. The best cut-off value for gas leak was 15.5%. The high leak group included 51 patients, of whom only two patients (3%) required re-intubation. The low leak group included 25 patients, among whom six patients (24%) required re-intubation ( p<0.01). The sensitivity of this test was 75%, the specificity 72.1%, the positive predictive value 25%, the negative predictive value 96.1% and the percent of correct classification 72.4%. CONCLUSIONS: A gas leak around the endotracheal tube greater than 15.5% can be used as a screening test to limit the risk of re-intubation for laryngeal edema.

Aged↗

Comparison of continuous thermodilution and bolus cardiac output measurements in septic shock.

OBJECTIVE: To compare continuous (CCO) and bolus (BCO) thermodilution cardiac output measurement techniques over a wide range of cardiac outputs and blood temperatures in a septic sheep model. DESIGN AND SETTING: Prospective experimental study in a university intensive care laboratory. SUBJECTS: Thirty-five anesthetized sheep. INTERVENTIONS: Pulmonary artery catheters allowing measurement of CCO and BCO were placed through the external jugular vein. Cecal ligation and perforation was performed to induce septic shock. In 14 sheep two femoral venous catheters were placed and connected to a hemofiltration system to alter blood temperature. MEASUREMENTS: CCO and BCO were measured every hour during the experiment. Three 10-ml bolus injections of iced normal saline were given through a closed injectate system and then averaged. The CCO readings were collected just before the BCO measurements. The relationship between CCO and BCO was assessed using Bland and Altman's method. RESULTS: In 465 paired data the temperature ranged between 34.0 degrees and 40.9 degrees C, CCO between 1.4 and 17.0 l/min, and BCO between 1.1 and 17.4 l/min. There was a highly significant correlation between CCO and BCO ( r=0.97). The bias (difference between CCO and BCO) was -0.19 l/min, the SD of the difference 0.45 l/min, and the limits of agreement -1.08/0.71 l/min. There were also highly significant correlations between CCO and BCO at the different temperatures (extreme values: 34.0-34.9 degrees C, r=0.90; 40.0-40.9 degrees C, r=0.98). CONCLUSIONS: Thermodilution measurements of CCO are reliable, when compared to BCO measurements, over a large range of cardiac outputs and blood temperatures.

Animals↗

Microvascular blood flow is altered in patients with sepsis.

Microvascular blood flow alterations are frequent in animal models of sepsis and may impair tissue oxygenation. We hypothesized that alterations of the microcirculation are present in patients with sepsis. We used an orthogonal polarization spectral imaging technique to investigate the sublingual microcirculation in 10 healthy volunteers, 16 patients before cardiac surgery, 10 acutely ill patients without sepsis (intensive care unit control subjects), and 50 patients with severe sepsis. The effects of topical application of acetylcholine (10(-2) M) were tested in 11 patients with sepsis. In each subject, five to seven sublingual areas were recorded and analyzed semiquantitatively. Data were analyzed with nonparametric tests and are presented as medians (25th-75th percentiles). No significant difference in microvascular blood flow was observed between healthy volunteers and patients before cardiac surgery or intensive care unit control subjects. The density of all vessels was significantly reduced in patients with severe sepsis (4.5 [4.2-5.2] versus 5.4 [5.4-6.3]/mm in volunteers, p < 0.01). The proportion of perfused small (< 20 microm) vessels was reduced in patients with sepsis (48 [33-61] versus 90 [89-92]% in volunteers, p < 0.001). These alterations were more severe in nonsurvivors. The topical application of acetylcholine totally reversed these alterations. In conclusion, microvascular blood flow alterations are frequent in patients with sepsis and are more severe in patients with a worse outcome.

Acetylcholine↗

Prone positioning in acute respiratory failure: survey of Belgian ICU nurses.

OBJECTIVE: To determine the frequency of use and attitudes towards prone positioning in patients with acute respiratory failure. DESIGN AND SETTING: Verbal questionnaire survey in all 79 intensive care units in French-speaking Belgium. METHODS: Of the 79 ICUs 29 performed prone-positioning, and 25 agreed to participate in the questionnaire. MEASUREMENTS AND RESULTS: Nurses at 9 of the 25 hospitals expressed reluctance to use prone positioning. The time schedules associated with prone positioning varied among the units surveyed, with no consensus. Units used two to six members of staff to turn a patient, with three most commonly being employed. Patients were most commonly positioned with both arms above the head and cushions under the chest, head, and legs, but there was considerable variation among units. The complications most commonly reported were facial edema and decubitus ulcers, with only three of the units reporting accidental extubation. Only two of the units had an established protocol for prone positioning although nurses from 14 of the units felt this would be useful. CONCLUSIONS: Prone positioning is approached with some reluctance by ICU staff. If the use of prone positioning in patients with acute respiratory distress syndrome is deemed worthwhile, discussion and development of departmental protocols may facilitate its use.

Attitude of Health Personnel↗

Clinical trials of immunomodulatory therapies in severe sepsis and septic shock.

Sepsis remains one of the leading causes of mortality in critically ill patients. Increased insight into the complexities of this disease process has resulted in the targeting of various aspects of the inflammatory response as offering potential therapeutic benefits. There have been encouraging results in the past few years. Some of the tested agents have been shown to improve mortality rates in large randomized controlled trials involving patients with severe sepsis. In this article, we discuss the positive and negative results of trials in this field; some of the possible reasons for the negative results are examined, and directions for the future are suggested.

Antitoxins↗