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OBJECTIVE: To assess shock reversal and required fluid volumes in patients with septic shock. DESIGN: Prospective before and after study comparing three different treatment periods. SETTING: Fifty-bed single-center surgical intensive care unit. PATIENTS: Consecutive patients with severe sepsis. INTERVENTIONS: Fluid therapy directed at preset hemodynamic goals with hydroxyethyl starch (predominantly 6% hydroxyethyl starch 130/0.4) in the first period, 4% gelatin in the second period, and only crystalloids in the third period. MEASUREMENTS AND MAIN RESULTS: Main outcome was time to shock reversal (serum lactate <2.2 mmol/L and discontinuation of vasopressor use). Hemodynamic goals were mean arterial pressure >70 mm Hg; ScvO2 <70%; central venous pressure >8 mm Hg. Safety outcomes were acute kidney injury defined by Risk, Injury, Failure, Loss, and End-stage kidney disease criteria and new need for renal replacement therapy. Hemodynamic measures, serum lactate, and creatinine were comparable at baseline in all study periods (hydroxyethyl starch n = 360, gelatin n = 352, only crystalloids n = 334). Severity scores, hospital length of stay, and intensive care unit or hospital mortality did not differ significantly among groups. All groups showed similar time to shock reversal. More fluid was needed over the first 4 days in the crystalloid group (fluid ratios 1.4:1 [crystalloids to hydroxyethyl starch] and 1.1:1 [crystalloids to gelatin]). After day 5, fluid balance was more negative in the crystalloid group. Hydroxyethyl starch and gelatin were independent risk factors for acute kidney injury (odds ratio, 95% confidence interval 2.55, 1.76-3.69 and 1.85, 1.31-2.62, respectively). Patients receiving synthetic colloids received significantly more allogeneic blood products. CONCLUSIONS: Shock reversal was achieved equally fast with synthetic colloids or crystalloids. Use of colloids resulted in only marginally lower required volumes of resuscitation fluid. Both low molecular weight hydroxyethyl starch and gelatin may impair renal function. [ABSTRACT FROM AUTHOR]

Objectives: To determine clinical outcomes of synthetic colloids, tetrastarch, and gelatin, used before and after cardiac surgery., Design: Prospective observational cohort study., Setting: Fifty-bed cardiac ICU., Patients: Six thousand four hundred seventy-eight consecutive patients with cardiopulmonary bypass surgery., Interventions: Fluid therapy in the operating room and on the ICU directed at preset hemodynamic goals: 1) hydroxyethyl starch (predominantly 6% hydroxyethyl starch 130/0.4) in 2004-2006, n = 2,137; 2) 4% gelatin in 2006-2008, n = 2,324; and 3) only crystalloids in 2008-2010, n = 2,017., Measurements and Main Results: Renal replacement therapy was more common during periods when patients received synthetic colloids compared to only crystalloids. Risk of renal replacement therapy was greater after hydroxyethyl starch (odds ratio, 2.29; 95% CI, 1.47-3.60) and gelatin (odds ratio, 2.75; 95% CI, 1.84-4.16; both p < 0.001) compared to crystalloid. Propensity score stratification confirmed greater use of renal replacement therapy in the hydroxyethyl starch and gelatin periods compared to the crystalloid period (odds ratio, 1.46 [1.08, 1.97]; p = 0.013 and odds ratio, 1.72 [1.33, 2.24]; p < 0.001, respectively). Time to vasopressor cessation, normalization of serum lactate, and mean arterial pressure did not differ among groups. Total fluid requirement was 163 mL/kg in the hydroxyethyl starch period, 207 mL/kg in the gelatin period, and 224 mL/kg in the crystalloid period. Fluid intake was higher in the crystalloid group only during the first 20 hours., Conclusions: In cardiac surgery patients, fluid therapy with perioperative administration of synthetic colloids carries a high risk of renal replacement therapy and is not more effective than treating with only crystalloids.

Objectives: Hydroxyethyl starch 200 is associated with renal impairment in sepsis, but hydroxyethyl starch 130/0.4 and gelatin are considered to be less harmful. We hypothesized that fluid therapy with only crystalloids would decrease the incidence of acute kidney injury., Design: Prospective sequential comparison during intensive care unit stay., Setting: Surgical intensive care unit., Patients: Patients with severe sepsis., Interventions: Changes in standard fluid therapy, with predominantly 6% hydroxyethyl starch from January 2005 to June 2005, 4% gelatin from January 2006 to June 2006, and only crystalloids from September 2008 to June 2009., Measurements and Main Results: Acute kidney injury was defined by the presence of at least one RIFLE class; 118 patients received hydroxyethyl starch, 87 patients received gelatin, 141 patients received only crystalloids. Baseline serum creatinine values were similar. Patients received median cumulative doses of 46 (interquartile range, 18-92) mL/kg hydroxyethyl starch and 43 (interquartile range, 18-76) mL/kg gelatin. Total median fluid amounts were 649 (interquartile range, 275-1098) mL/kg in the hydroxyethyl starch group, 525 (237-868) mL/kg in the gelatin group, and 355 (173-911) mL/kg in the crystalloid group. The difference was statistically significant for hydroxyethyl starch after adjustment for multiple testing. Mean daily fluid intake and fluid balance were higher on days 0 and 1 in the crystalloid group. Acute kidney injury occurred in 70% of patients receiving hydroxyethyl starch (adjusted p = .002) and in 68% of patients receiving gelatin (adjusted p = .025) vs. 47% patients receiving crystalloids. Need for renal replacement therapy tended to be higher in the hydroxyethyl starch group (34%; adjusted p = .086) and in the gelatin group (34%; adjusted p = .162) in comparison to the crystalloid group (20%). Intensive care unit and hospital mortality were similar in each group (hydroxyethyl starch: 35% and 43%; gelatin: 26% and 31%; crystalloids: 30% and 37%)., Conclusion: Fluid resuscitation with only crystalloids was equally effective, resulted in a more positive fluid balance only on the first 2 days, and was associated with a lesser incidence of acute kidney injury.

Objectives: To review the literature on direct and indirect markers of endothelial activation and damage in patients with sepsis and systemic inflammation and to assess their clinical usefulness for diagnosis and outcome. Various markers derived from or activated by endothelial cells are described, such as adhesion molecules, thrombomodulin, von Willebrand factor, parameters of the coagulation system, and interleukin-6. Furthermore, the association of these markers with the severity of sepsis, systemic inflammation, and outcome is evaluated., Data Extraction and Synthesis: Published research and review articles related to these parameters, with special emphasis on clinical studies., Conclusions: Endothelial activation and damage occur early during sepsis and play a major role in the pathophysiology of systemic inflammation. Various markers of endothelial activation are increased during sepsis and systemic inflammation, and in most studies, the level of markers such as soluble intercellular adhesion molecule, vascular cell adhesion molecule, and E selectin correlate well with the severity of inflammation and the course of the disease. However, to date, it remains unclear whether adhesion molecules and coagulation parameters are superior in this respect to interleukin-6 and procalcitonin, as direct comparisons are lacking. In addition, it is evident that markers of endothelial activation and coagulation parameters lack specificity for infection-induced endothelial damage and organ dysfunction.