Publications

Verdant, Colin; Bruhn, Alejandro; Clausi, Carla; Su, Fuhong; Wang, Zhen; Backer, Daniel De; Vincent, Jean-Louis; Pries, Axel Author Information

In this large cohort of critically ill patients, underweight was independently associated with a higher hazard of 60-day in-hospital death and overweight with a lower hazard. None of the body mass index categories as independently associated with an increased hazard of infection during the ICU stay.

Measurement of nCD64 expression at ICU admission, especially when combined with CRP concentrations, is useful in diagnosing sepsis. Serial determinations of nCD64 could be used for monitoring purposes.

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

The final common pathway involved in the cardiovascular alterations of septic shock is incompletely defined. The opening of KATP channels is associated with vasorelaxation and alterations in cardiac contractility. This event may be triggered during septic shock by increased nitric oxide (NO) production, by a decreased intracellular content of ATP, or by a change in the transmembrane electrical potential. In the present study, we assessed the effects of glibenclamide, an agent that blocks the opening of KATP channels in vitro, on the contractile response of rat aortic rings to norepinephrine, and in vivo in anesthetized dogs, with or without exposure to Escherichia coli endotoxin. In vitro, glibenclamide decreased the contractile response to norepinephrine in the presence of endotoxin, provided that the endothelium was intact. In vivo, administration of 0.15 mg/kg increased systemic vascular resistance (SVR) in the absence of endotoxin only, and increased myocardial performance. A higher dose of 1 mg/kg increased SVR and decreased myocardial performance, both during endotoxic shock and in control conditions. Renal and mesenteric blood flows decreased, but the respective fractional flows were unchanged. Oxygen delivery decreased in both experimental conditions, but oxygen consumption decreased only in control conditions. The in vitro observations suggest that the opening of KATP channels is involved in the regulation of vascular tone during endotoxemia, via an endothelium-dependent mechanism. As different effects of glibenclamide were observed in vivo, the importance of the opening of KATP channels in endotoxic shock may be limited.

In this clinically relevant ovine model of septic shock, hypercapnia had similar effects to dobutamine on hemodynamic variables and lactic acidosis. Hypercapnia improved tissue oxygenation and reduced lung edema formation more than dobutamine administration.

O Ob bj je ec ct ti iv ve es s: : Acute renal failure (ARF) is a common complication following open heart surgery especially in infants. Effects of blood viscosity on renal function are well known, but have not been investigated in cardiopulmonary bypass (CPS) as yet.

Sepsis is the clinical syndrome derived from the host response to an infection and severe sepsis is the leading cause of death in critically ill patients. Several biomarkers have been tested for use in diagnosis and prognostication in patients with sepsis. Soluble urokinase-type plasminogen activator receptor (suPAR) levels are increased in various infectious diseases, in the blood and also in other tissues. However, the diagnostic value of suPAR in sepsis has not been well defined, especially compared to other more established biomarkers, such as C-reactive protein (CRP) and procalcitonin (PCT). On the other hand, suPAR levels have been shown to predict outcome in various kinds of bacteremia and recent data suggest they may have predictive value, similar to that of severity scores, in critically ill patients. This narrative review provides a descriptive overview of the clinical value of this biomarker in the diagnosis, prognosis and therapeutic guidance of sepsis.

Society of Critical Care Medicine; 27th Educational and Scientific Symposium; San Antonio, Texas, USA; February 4-8, 1998: Poster Hall: Thursday, February 5, 1998 5: 45-7: 15 pm; Friday, February 6, 1998 11: 40 am-1: 00 pm; Saturday, February 7, 1998 11: 40 am-1: 00 pm: Poster Presentations: Sepsis

ABSTRACT: INTRODUCTION: The aim of the study was to determine whether the degree of fluid responsiveness in critically ill septic patients is related to baseline mixed venous oxygen saturation (SvO2) levels. We also sought to define whether fluid responsiveness would be less likely in the presence of a high SvO2 (>70%). METHODS: This observational study was conducted in a 32-bed, university hospital medico-surgical intensive care unit (ICU). The hemodynamic response to a fluid challenge was evaluated in 65 critically ill patients with severe sepsis. Patients were divided into two groups (responders and non-responders) according to their cardiac index (CI) response to the challenge (>or < 10%). RESULTS: Of the 65 patients, 34 (52%) were fluid responders. Baseline SvO2, CI, heart rate (HR), and mean arterial pressure (MAP) were not statistically different between groups. The responders had lower pulmonary artery occlusion pressure (PAOP) and central venous pressure (CVP) at baseline than the non-responders. After the fluid challenge, there were no differences between the two groups in MAP, CVP, PAOP or HR. There was no correlation between changes in CI or stroke volume index (SVI) and baseline SvO2. ROC analysis showed that SvO2 was not a predictor of fluid responsiveness. CONCLUSIONS: The response of septic patients to a fluid challenge is independent of baseline SvO2. The presence of a high SvO2 does not necessarily exclude the need for further fluid administration.

Sepsis remains a major health problem in ICU patients worldwide and is associated with high mortality rates. However, there is wide variability in the sepsis rate and outcomes in ICU patients around the globe.