Tetrastarch 6% infusion 500ml bags

In a meta-analysis of cardiac surgery trials, we showed that hydroxyethyl starch increases postoperative blood loss, blood product transfusion and reoperation for bleeding [1]. Citing that meta-analysis, the US Food and Drug Administration determined excess bleeding to be a class effect of hydroxyethyl starch solutions and issued a safety warning [2]. Jacob and colleagues report a new meta-analysis suggesting lower perioperative blood loss with tetrastarch than albumin across three trials [3]. However, postoperative blood loss was in the opposite direction (Figure 1). By imputing key unreported data instead of contacting the trial investigators, Jacob and colleagues introduced major errors favoring tetrastarch; for example, inflating the blood loss difference in one trial by 2.3-fold. Furthermore, the other two trials were confounded by exposure of one group to both test fluids. The potential distortion is highlighted by a randomized trial in which coadministration of low-dose albumin with tetrastarch reduced blood loss by 21% (P < 0.05) versus tetrastarch alone [4]. Without confounding the blood loss differences would almost certainly have been larger, and any meta-analysis incorporating the confounded trials is likely to be biased in favor of tetrastarch. Figure 1 Partially corrected meta-analysis of postoperative blood loss in the three trials included by Jacob and colleagues comparing tetrastarch with albumin [ 3 ]. Upon request, individual patient postoperative blood loss data were supplied by Niemi and colleagues ... Their finding of lower blood loss with tetrastarch than pentastarch is attributable to publication bias, since an unpublished trial with higher blood loss and more frequent reoperation for bleeding after tetrastarch was omitted [1,5]. The omitted trial had been submitted to the US Food and Drug Administration in a New Drug Application by the same tetrastarch manufacturer who commissioned the new meta-analysis. That trial was included in two previous meta-analyses [1,5].

Abstract licence: CC BY 4.0

Purpose: To reassess the results of former meta-analyses focusing on the relationship between novel HES preparations (130/0.4 and 130/0.42) and acute kidney injury. Previous meta-analyses are based on studies referring to partially or fully unpublished data or data from abstracts only. Methods: The studies included in the former meta-analyses were scrutinized by the authors independently. We completed a critical analysis of the literature, including the strengths, weaknesses and modifiers of the studies when assessing products, formulations and outcomes. Results: Both the published large studies and meta-analyses show significant bias in the context of the deleterious effect of 6% 130/0.4-0.42 HES. Without (1) detailed hemodynamic data, (2) the exclusion of other nephrotoxic events and (3) a properly performed evaluation of the dose-effect relationship, the AKI-inducing property of 6% HES 130/0.4 or 0.42 should not be considered as evidence. The administration of HES is safe and effective if the recommended dose is respected. Conclusions: Our review suggests that there is questionable evidence for the deteriorating renal effect of these products. Further well-designed, randomized and controlled trials are needed. Additionally, conclusions formulated for resource-rich environments should not be extended to more resource-scarce environments without proper qualifiers provided.

Abstract licence: CC BY 4.0

AbstractObjectiveTo describe and compare prothrombin time (PT), activated partial thromboplastin time (aPTT), thromboelastography (TEG), HCT, and platelet count measurements in a hemorrhage/over‐resuscitation model.DesignRandomized crossover study.SettingUniversity teaching hospital.AnimalsSix cats.InterventionsAnesthetized cats underwent 3 treatments at 2‐month intervals. The treatments were as follows: NHR—no controlled hemorrhage and sham resuscitation; LRS—controlled hemorrhage and lactated Ringer's solution (LRS) for resuscitation; and Voluven—controlled hemorrhage and 6% tetrastarch 130/0.4 for resuscitation. The LRS and Voluven were administered at 60 and 20 mL/kg/h, respectively, for 120 minutes. Blood samples were drawn for PT, aPTT, TEG, HCT, and platelet count measurements at a healthy check (T − 7d), after controlled hemorrhage (T0), at 60 and 120 minutes of resuscitation (T60 and T120), and at 24 hours after completion of resuscitation (T24h). Data were analyzed using a general linear mixed model approach (significance was P < 0.05).Measurements and Main ResultsTotal median blood loss (controlled hemorrhage and blood sampling from T0 to T120) at T120 was 11.4, 31.0, and 30.8 mL/kg for NHR, LRS, and Voluven, respectively. PT and aPTT during LRS and Voluven were prolonged at T60 and T120 compared to NHR (P < 0.001). On TEG, the reaction time, kinetic time, and alpha‐angle were within reference intervals for cats at all time points in all treatments, while maximum amplitude was less than the reference interval (40 mm) at T0, T60, and T120 during Voluven and at T60 and T120 during LRS compared to NHR (both P < 0.001). The HCT and platelet count were significantly lower at T60 and T120 during LRS and Voluven compared to NHR (P < 0.001).ConclusionsHypocoagulopathy was observed during hemorrhage and liberal fluid resuscitation. Prolongation of PT and aPPT and decreased clot strength may have been caused by hemodilution and platelet loss.

Abstract licence: CC BY-NC-ND 4.0