Randomised trials of 6 % tetrastarch (hydroxyethyl starch 130/0.4 or 0.42) for severe sepsis reporting mortality: systematic review and meta-analysis

Abstract

PurposeTo assess the impact of 6% tetrastarch (hydroxyethyl starch (HES) 130/0.4 and 130/0.42) in severe sepsis patients. The primary outcome measure was 90-day mortality. MethodsA structured literature search to identify prospective randomized controlled trials (RCT) in adult patients with severe sepsis receiving 6% tetrastarch (potato or waxy maize origin), as part of fluid resuscitation in comparison to other non-HES fluids after randomisation, in the critical care setting was undertaken. A systematic review and meta-analysis was performed. ResultsSix RCTs were included (n = 3033): three from 2012 (n = 2913) had a low risk of bias. Median tetrastarch exposure was 37.4 ml/kg (range 30 to 43). Ninety-day mortality was associated with tetrastarch exposure (relative risk (RR) 1.13; 95% confidence interval (CI) 1.02 to 1.25; p = 0.02) compared to crystalloid. The number needed to harm (NNH) was 28.8 (95% CI 14.6 to 942.5). Publication bias and statistical heterogeneity (I 2 = 0%) were not present. Tetrastarch exposure was also associated with renal replacement therapy (p = 0.01; NNH 15.7) and allogeneic transfusion support (p = 0.001; NNH 9.9). No difference between groups was observed for 28-day mortality, comparison with colloid as control, and for waxy maize derived tetrastarch, but power was lacking. Overall mortality was associated with tetrastarch exposure (RR 1.13; 95% CI 1.02 to 1.25; p = 0.02). ConclusionsIn our analysis, 6% tetrastarch as part of initial fluid resuscitation for severe sepsis was associated with harm, and as alternatives exist, in our view should be avoided.

Acute kidney injury in the perioperative period and in intensive care units (excluding renal replacement therapies)

“…(Grade 2+) STRONG agreement Rationale: Several randomized or observational studies and meta-analyses have examined the beneficial effect of a preferential administration of colloids compared to crystalloids [62][63][64][65][66][67][68][69][70][71][72][73]. In the ICU, the use of HES, regardless of its type, has been reported to be associated with an increase in mortality rate, AKI incidence and the need for RRT in several meta-analyses with a high level of proof [58][59][60][61][62][63][64][65][66][67][68][69][70][71]73]. A Cochrane meta-analysis simultaneously considering all colloids did not find any beneficial effect associated with the preferential use of colloids, regardless of nature, compared with crystalloids.…”

The Physiologic Perspective in Fluid Management in Vascular Anesthesiology

“…In addition, more recent meta-analysis showed an increased amount of acute kidney injury and a trend towards a higher mortality in patients with severe sepsis and septic shock treated with HES solutions compared to crystalloid solutions. [50][51][52][53] These findings led to an investigation of the European authorities concerning the risk of HES products and, as a first consequence, to a withdrawal of all starch products from the UK market. The Food and Drug Administration (FDA) recommended that HES should not be used in critically ill patients or in patients with pre-existing renal disease.…”

“Colloid twice daily” is not fluid resuscitation! Inappropriate inclusion of clinical trials in meta-analyses may distract from gaps in evidence

“…Dear Editor, We read with interest the recent systematic review investigating the impact of hydroxyethyl starch administration as part of initial fluid resuscitation for severe sepsis on mortality [1]. The authors claimed to have identified ''prospective randomised controlled trials (RCTs) in adult patients with severe sepsis receiving 6 % tetrastarch (of potato or waxy maize origin) as part of fluid resuscitation in comparison with other non-HES fluids after randomisation in the critical care setting''.…”

“…The authors claimed to have identified ''prospective randomised controlled trials (RCTs) in adult patients with severe sepsis receiving 6 % tetrastarch (of potato or waxy maize origin) as part of fluid resuscitation in comparison with other non-HES fluids after randomisation in the critical care setting''. They put emphasis on ''initial fluid resuscitation'', since in the concluding remarks they state that ''90-day mortality were significantly higher in severe sepsis patients receiving 6 % tetrastarch 130 kDa solutions as part of initial fluid resuscitation'' [1]. Bearing that in mind, we wonder why the authors included reference 41 in which patients were randomized to either 6 % HES 130/0.4, 250 ml every 6 h, or 20 % albumin, 100 ml every 12 h [2].…”

“…However, this analysis [1] does not seem to be an exceptional case of arbitrary terminology of sepsis-related fluid resuscitation, since other analyses have focused on a comparable clinical scenario and outcome. The paper by Dolecek et al in 2009 can be found in other systematic reviews as well [3,4], including a recent paper on ''fluid resuscitation'' in this journal [5].…”