McIntyre LA, Fergusson D, Cook DJ, et al.Canadian Critical Care Trials Group. Fluid resuscitation in the management of early septic shock (FINESS): A randomized controlled feasibility trial

University of Ottawa Centre for Transfusion and Critical Care Research, Ottawa Hospital, Ottawa, Ontario, Canada.
Canadian Journal of Anaesthesia (Impact Factor: 2.53). 01/2009; 55(12):819-26. DOI: 10.1007/BF03034053
Source: PubMed


It is unknown whether fluid resuscitation with colloid or crystalloid in patients with severe sepsis or septic shock is associated with an improvement in clinical outcome. This randomized controlled trial determined the feasibility of conducting a large trial testing resuscitation with pentastarch vs normal saline in early septic shock, powered for a difference in mortality.
At three Canadian and one New Zealand academic centre, 40 patients with early septic shock defined by at least two systemic inflammatory response syndrome criteria, infectious source, and persistent hypotension after >or= 1 L of crystalloid fluid were recruited. Feasibility measures were patient recruitment, blinding of the study fluids, and acceptability of the goal directed algorithms. Boluses of blinded normal saline or pentastarch (500 mL - maximum 3 L or 28 mL x kg(-1)) were administered within goal directed care for the first 12 hr.
Of 161 patients screened, 121 were excluded and 40 patients were enrolled, for a recruitment rate of 0.75 patients/site/month. Only 57% of physicians and 54% of nurses correctly guessed the study fluid (P = 0.46 and P = 0.67, respectively). The goal directed algorithms were acceptable to 97% of physicians.
The ability to recruit patients in this pilot randomized controlled trial was below expectations. Blinding of study fluids was adequate, and resuscitation algorithms were acceptable to most physicians. Methods to improve recruitment are required to enhance the feasibility of conducting a multicentre fluid resuscitation trial in early septic shock.

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    • "It has to be highlighted, that most of the study protocols emphasised the exclusion of patients with pre-existing renal failure and/or RRT prior to randomisation. Under these conditions, good consistency between study protocol and baseline data was found in several studies [2,6,7,19,21]. However, we also found moderate implicit inconsistencies between study protocol specifications and published baseline data. "
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    ABSTRACT: Hydroxyethyl starch (HES) is a commonly used colloid in critically ill patients. However, its safety has been questioned in recent studies and meta-analyses. We re-evaluated prospective randomised controlled trials (RCT) from four meta-analyses published in 2013 which compared the effect of HES with crystalloids in critically ill patients, focusing on the adherence to 'presumably correct indication'. Regarding the definition of 'presumably correct indication', studies were checked for the following six criteria (max. six points): short time interval from shock to randomisation (< 6 h), restricted use for initial volume resuscitation, use of any consistent algorithm for haemodynamic stabilisation, reproducible indicators of hypovolaemia, maximum dose of HES, and exclusion of patients with pre-existing renal failure or renal replacement therapy. Duration of fluid administration ranged from 90 min up to a maximum of 90 days. Four studies considered follow-up until 90-day mortality, three studies 28-/30-day mortality, whereas four studies reported only early mortality. Included studies showed a large heterogeneity of the indication score ranging between 1 to 4 points with a median (25%; 75% quartile) of 4 (2; 4). The most important question, whether or not HES may be harmful when it is limited to immediate haemodynamic stabilisation, cannot be answered yet in the absence of any study sufficiently addressing this question. In order to overcome the limitations of most of the previous studies, we now suggest an algorithm emphasising the strict indication of HES. Additionally, we give a list of suggestions that should adequately be considered in any prospective RCT in the field of acute volume resuscitation in critically ill patients.
    Full-text · Article · Jul 2013 · Critical care (London, England)
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    • "Study name Odds ratio and CI Odds Lower Upper ratio limit limit Zetterström, Hedstrand 1981 Ginès et al. 1988 Hyperoncotic albumin Hyperoncotic colloid, Dead/N Control, Dead/N 0/15 1/15 2/52 2/53 Hyperoncotic HES London et al. 1989 Dehne et al. 1997 Pooled 22/245 36/244 2/50 1/44 4/10 3/15 Gentilini et al. 1999 Sort et al. 1999 Sola-Vera et al. 2003 1/63 0/63 14/63 26/63 1/37 1/35 Chen et al. 2009 4/15 6/15 Brunkhorst et al. 2008 McIntyre et al. 2008 107/262 93/275 9/21 6/19 0,31 0,012 8,28 1,02 0,14 7,52 0,52 0,28 0,95 1.79 0,16 20,5 2,67 0,45 16,0 3,05 0,12 76,3 0,41 0,19 0,88 0,94 0,057 15,7 0,55 0,12 2,55 1,35 0,95 1,92 1,62 0,44 5,95 1,41 1,01 1,96 Favors control Favors hyperoncotic colloid Pooled 122/343 103/353 Figure 3 "
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    ABSTRACT: It has been hypothesized that hyperoncotic colloids might contribute to acute kidney injury (AKI). However, the validity of this hypothesis remains unclear. A meta-analysis was conducted of randomized controlled trials evaluating AKI after infusion of hyperoncotic albumin and hydroxyethyl starch (HES) solutions. Mortality was a secondary endpoint. Eligible trials were sought by multiple methods, and the pooled odds ratios (OR) for AKI and death and 95% confidence intervals (CI) were computed under a random effects model. Eleven randomized trials with a total of 1220 patients were included: 7 evaluating hyperoncotic albumin and 4 hyperoncotic HES. Clinical indications were ascites, surgery, sepsis and spontaneous bacterial peritonitis. Hyperoncotic albumin decreased the odds of AKI by 76% (OR, 0.24; CI, 0.12-0.48; P < 0.0001), while hyperoncotic HES increased those odds by 92% (OR, 1.92; CI, 1.31-2.81; P = 0.0008). Parallel effects on mortality were observed, with hyperoncotic albumin reducing the odds of death by 48% (OR, 0.52; CI, 0.28-0.95; P = 0.035) and hyperoncotic HES raising those odds by 41% (OR, 1.41; CI, 1.01-1.96; P = 0.043). This meta-analysis does not support the hypothesis that hyperoncotic colloid solutions per se injure the kidney. Renal effects appear instead to be colloid-specific, with albumin displaying renoprotection and HES showing nephrotoxicity.
    Full-text · Article · Oct 2010 · Critical care (London, England)
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    ABSTRACT: Hydroxyethyl starch (HES) is a type of colloid fluid that is commonly used for volume resuscitation of patients admitted to the intensive care unit. Data regarding the renal consequences of HES are conflicting. To evaluate the effect of HES solutions on renal outcomes and mortality among critically ill patients requiring acute volume resuscitation. We searched electronic databases (MEDLINE, EMBASE, the Cochrane Central Registry of Controlled Trials and the SCOPUS database) from 1950 to 2008. Conference proceedings and grey literature sources were searched from 2002 to 2007. We included only randomized controlled trials of acute volume resuscitation of critically ill patients comparing HES fluid with an alternative resuscitation fluid. Two reviewers independently assessed trial eligibility, extracted data and evaluated trial quality. Random-effects models were used for all summary measures of effect. Twenty-two trials (n = 1865 patients) were included. Patients who received HES were more likely to have received renal replacement therapy (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.22-2.96, I(2) 9.5%, n = 749). There was no difference in overall mortality (OR 1.07, 95% CI 0.85-1.34, n = 1657). However, in trials that included patients with severe sepsis and septic shock, in high-quality and multicentre trials, and in trials with adequate allocation concealment, there was a trend toward increased risk of death in association with HES. Data regarding adverse events, including renal outcomes, were not reported in the majority of published randomized trials. Considerable clinical and methodologic heterogeneity existed among trials. The use of HES for acute volume resuscitation of critically ill patients, and in particular those with severe sepsis and septic shock, appeared to be associated with increased use of renal replacement therapy. Further randomized controlled trials evaluating clinically important end points are required to examine the efficacy and safety of HES fluids for critically ill patients.
    Preview · Article · Jan 2009 · Open Medicine
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