Effect of 6% hydroxyethyl starch 130/0.4 on kidney and haemostatic function in cardiac surgical patients: a randomised controlled trial

Abstract

Summary Whether third‐generation hydroxyethyl starch solutions provoke kidney injury or haemostatic abnormalities in patients having cardiac surgery remains unclear. We tested the hypotheses that intra‐operative administration of a third‐generation starch does not worsen postoperative kidney function or haemostasis in cardiac surgical patients compared with human albumin 5%. This triple‐blind, non‐inferiority, clinical trial randomly allocated patients aged 40–85 who underwent elective aortic valve replacement, with or without coronary artery bypass grafting, to plasma volume replacement with 6% starch 130/0.4 vs. 5% human albumin. Our primary outcome was postoperative urinary neutrophil gelatinase‐associated lipocalin concentrations, a sensitive and early marker of postoperative kidney injury. Secondarily, we evaluated urinary interleukin‐18; acute kidney injury using creatinine RIFLE criteria, coagulation measures, platelet count and function. Non‐inferiority (delta 15%) was assessed with correction for multiple comparisons. We enrolled 141 patients (69 starch, 72 albumin) as planned. Results of the primary analysis demonstrated that postoperative urine neutrophil gelatinase‐associated lipocalin (median (IQR [range])) was slightly lower with hydroxyethyl starch (5 (1–68 [0–996]) ng.ml−1) vs. albumin (5 (2–74 [0–1604]) ng.ml−1), although not non‐inferior [ratio of geometric means (95%CI) 0.91 (0.57, 1.44); p = 0.15] due to higher than expected variability. Urine interleukin‐18 concentrations were reduced, but interleukin‐18 and kidney injury were again not non‐inferior. Of 11 individual coagulation measures, platelet count and function, nine were non‐inferior to albumin. Two remaining measures, thromboelastographic R value and arachidonic acid‐induced platelet aggregation, were clinically similar but with wide confidence intervals. Starch administration during cardiac surgery produced similar observed effects on postoperative kidney function, coagulation, platelet count and platelet function compared with albumin, though greater than expected variability and wide confidence intervals precluded the conclusion of non‐inferiority. Long‐term mortality and kidney function appeared similar between starch and albumin.

WITHDRAWN: Hydroxyethyl Starch 130/0.42 Effect’s on Renal Function in Patients After Cardiac Surgery: A Retrospective Cohort Analysis

“…Besides the theoretical framework, our favourable results are also supported by a previously reported retrospective exploratory analysis and a prospective randomised controlled trial [44,45]. In this study, the administration of HES was non-inferior to fluid resuscitation with albumin with regard to adverse kidney outcomes determined by biomarkers (urinary neutrophil gelatinaseassociated lipocalin and interleukin-18) as well as the 'Risk Injury Failure Loss End stage renal disease' (RIFLE) criteria [45]. Moreover, an earlier major prospective study concerning fluid management in intensive care even reported a lower mortality rate in patients when fluid resuscitation was achieved by the use of colloids (including HES) [13].…”

“…a long intravascular half-life), HES appears to be another treatment option to achieve fast volume resuscitation with a low risk of fluid overload [15,17,42,43]. Besides the theoretical framework, our favourable results are also supported by a previously reported retrospective exploratory analysis and a prospective randomised controlled trial [44,45]. In this study, the administration of HES was non-inferior to fluid resuscitation with albumin with regard to adverse kidney outcomes determined by biomarkers (urinary neutrophil gelatinaseassociated lipocalin and interleukin-18) as well as the 'Risk Injury Failure Loss End stage renal disease' (RIFLE) criteria [45].…”

“…To summarize the existing and conflicting evidence, different independent studies could not detect an increased risk for adverse outcomes after postoperative administration of HES in cardiac surgery patients without septic shock [13,18,[44][45][46][47]. These findings underline the hypothesis that patient populations and settings need to be taken in account when evaluating adverse renal outcomes after HES administration rather than extrapolating data from one population and setting to another.…”

Substanzen zur Flüssigkeitstherapie und Outcome – ein Update

“…Diese gründen aber z. T. auf älteren Daten, die nur bedingt auf die heutige Zeit übertragen werden können [55]. Verschiedene aktuelle, aber kleine klinische Studien zeigen keine klaren Vorteile einer Therapie mit Albumin 5 % hinsichtlich allgemeiner Morbidität und Organfunktion im Vergleich mit HES bei großen abdominalchirurgischen [56], urologischen [57] oder herzchirurgischen [58] Eingriffen. Im Gegensatz fand sich in einer großen, retrospektiven Kohortenstudie eine signifikant reduzierte Krankenhaussterblichkeit, aber kein Einfluss auf die Inzidenz von Nierenfunktionsstörungen bei mittels Albumin 5 % behandelten herzchirurgischen Patienten [59].…”

Effect of Goal-Directed Crystalloid versus Colloid Administration on Perioperative Hemostasis in Partial Hepatectomy: A Randomized, Controlled Trial

“…However, in spite of a lively scientific debate over the last two decades, the perioperative use of synthetic colloids remains a controversial issue [3][4][5][6][7]. Following two studies published in 2012 [8,9], the European Medicine Agency (EMA) and the US Food and Drug Administration (FDA) issued warnings that hydroxyethyl starch (HES) should no longer be used in critically ill patients due to a possible rise in kidney injury and mortality associated with the administration of HES [10,11].…”