Date Published: October 18, 2017
Publisher: Public Library of Science
Author(s): Mona Momeni, Lompoli Nkoy Ena, Michel Van Dyck, Amine Matta, David Kahn, Dominique Thiry, André Grégoire, Christine Watremez, Shree Ram Singh.
The safety of hydroxyethyl starches (HES) is still under debate. No studies have compared different dosing regimens of HES in cardiac surgery. We analyzed whether the incidence of Acute Kidney Injury (AKI) differed taking into account a weight-adjusted cumulative dose of HES 6% 130/0.4 for perioperative fluid therapy. This retrospective cohort study included all adult patients undergoing elective or emergency cardiac surgery with or without cardiopulmonary bypass. Exclusion criteria were patients on renal replacement therapy (RRT), cardiac trauma surgery, heart transplantation, patients with ventricular assist devices, subjects who required a surgical revision for bleeding and those whose medical records were incomplete. Primary endpoint was AKI following the creatinine based RIFLE classification. Secondary endpoints were 30-day mortality and RRT. Patients were divided into 2 groups whether they had received a cumulative HES dose of < 30 mL/kg (Low HES) or ≥ 30 mL/kg (High HES) during the intra- and postoperative period. A total of 1501 patients were analyzed with 983 patients in the Low HES and 518 subjects in the High HES group. 185 (18.8%) patients in the Low HES and 119 (23.0%) patients in the High HES group developed AKI (P = 0.06). In multivariable regression analysis the dose of HES administered per weight was not associated with AKI. After case-control matching 217 patients were analyzed in each group. AKI occurred in 39 (18.0%) patients in the Low HES and 50 (23.0%) patients in the High HES group (P = 0.19). In conditional regression analysis performed on the matched groups a lower weight-adjusted dose of HES was significantly associated with a reduced incidence of AKI [(Odds Ratio (95% CI) = 0.825 (0.727–0.936); P = 0.003]. In the absence of any safety study the cumulative dose of modern HES in cardiac surgery should be kept less than 30 mL/kg.
Fluid resuscitation with hydroxyethyl starch (HES) has been associated with an increased risk of renal—replacement therapy (RRT) [1, 2] and/or mortality in critically ill patients admitted to the intensive care unit (ICU) . These trials showing harmful effects of HES have mainly evaluated a non-surgical population [1–3]. The VISEP study  and the 6S trial  compared HES and crystalloids in ICU patients with severe sepsis. In the CHEST trial HES was compared with crystalloids in a heterogeneous group of patients treated in the ICU . In their trial 42,5% of patients in the HES group and 42,9% of patients in the saline group were surgical cases. However, the pathophysiology of renal failure in a non-surgical population differs from patients undergoing surgery [4, 5].
This was a retrospective cohort study. The review of the patients’ medical records was approved on October the 27th 2014 by «La Commission d’Ethique Hospitalo-Facultaire de l’UCL» in Brussels, Belgium (2014, 505).
During the study period 1826 patients underwent a cardiac surgery. In total the data of 1501 patients were reviewed as 63 patients had not received any HES solution and 262 patients did not meet the inclusion criteria. 983 subjects had received a low dose of HES and 518 patients were in the High HES group. Fig 1 shows the flowchart of the study.
This retrospective analysis of 1501 patients who underwent cardiac surgery evaluated whether the incidence of in-hospital AKI based on the creatinine criterion of RIFLE classification was different between patients who had received a cumulative HES dose of < 30 mL/kg compared with patients who had received a dose of ≥ 30 mL/kg during the intraoperative period and their postoperative stay in the ICU. After matching there was no significant difference in the incidence of AKI between both groups. However, in multivariable analysis conducted on the matched population, a lower administered volume of HES per kg of weight was significantly associated with a reduced incidence of AKI (Odds Ratio; 95% CI: 0.825; 0.727 to 0.936; P = 0.003). Furthermore, a subanalysis of the groups showed that patients who had received a cumulative HES dose of ≥ 50 mL/kg showed a higher incidence of AKI compared with patients receiving a cumulative HES dose of < 30 mL/kg and a HES dose of 30–50 mL/kg. This retrospective study in cardiac surgery compared the incidence of in-hospital AKI in function of the cumulative dose of HES 6% 130/ 0.4 administered for intra- and postoperative fluid resuscitation. After matching and in multivariable analysis, a cumulative volume of ≥ 30 mL/kg HES was significantly associated with an increased odds ratio of AKI. In the setting of the perioperative care of cardiac surgical patients fluid resuscitation with modern HES should be weight-adjusted and given at a maximum dose less than 30 mL/kg. Source: http://doi.org/10.1371/journal.pone.0186403