Hetastarch Should be Avoided for Volume Expansion in Cardiac Surgery Patients
Blood conservation measures to reduce perioperative blood loss during cardiac surgery have been a subject of focus in recent years. This is due in part to the high cost of allogeneic blood transfusion, as well as the morbidity and mortality associated with transfusion.One such conservation measure is hemodilution with colloids such as human albumin (HA) or hydroxyethyl starch (HES). Hemodilution is an inevitable sine qua non condition of cardiopulmonary bypass (CPB) because of its circuit-priming requirements. On the other hand, correction of hypovolemia with intravenous (IV) fluids is one of the most frequent therapeutic interventions in cardiac surgery.
A variety of IV fluids currently are used for volume expansion in major surgery and in critically ill patients. Crystalloid solutions are inexpensive and widely available, while colloids have the theoretical advantage of a lower plasma clearance, and stronger and sustained colloid osmotic effect so that resuscitation fluid volume and overload consequences may be diminished. Avoidance of perioperative fluid overload and restrictive blood product utilization have been suggested as means to improve postoperative outcomes. Furthermore, it must be remembered that blood transfusion, surgical re-intervention, and perioperative renal dysfunction have been associated with decreased survival after cardiac surgery.
Despite US Food and Drug Administration (FDA) warnings, HES still is used for hemodilution in surgical patients, including those undergoing cardiac surgery. While many have argued that “modern” low-molecular-weight (130 kDa) and 0.4 to 0.42 substituted hetastarch is safe and as efficacious as tetrastarch and other colloids, many studies have presented convincing evidence to the contrary.
The use of HES in cardiac surgery has been reviewed by several authors in recent systematic reviews, meta-analyses, and clinical trials.2,3,5–7,12,15–18 In 2012, Navickis et al published a meta-analysis of randomized trials comparing the effect of HES to albumin on bleeding following CPB. The analysis included 18 trials and 970 patients. The primary endpoint was cumulative blood loss within the first 24 hours after surgery. Other outcomes such as fluid balance, hemodynamics, mechanical ventilator (MV) use, intensive care unit (ICU) stay, and mortality also were reviewed. HES was used for volume expansion, CPB priming, or both.
The meta-analysis sought to compare the outcomes between different molecular weight HES solutions and HA; however, the lack of a significant number of studies involving the use of HES 130 made the initial goal impossible. A comparison also was made between cases using HES with different molecular weights in the HES group. The meta-analysis concluded that HES increased postoperative bleeding by 33.3% when compared to HA (95% CI 18.2% - 48.3%; p < 0.001); however, transfusion requirements between the different HES groups (HES 450/0.7 and HES 200/0.5) did not differ significantly. Ventilator time and ICU stay did not differ significantly between groups. Acute kidney injury (AKI) is a feared complication after cardiac surgery. This outcome is difficult to evaluate in the current literature due to heterogeneity in the AKI criteria used between studies and the lack of universal adoption of RIFLE criteria (risk, injury, failure, loss of kidney function, and end-stage renal failure) and AKIN (Acute Kidney Injury Network) diagnostic tools. A systematic review and meta-analysis by Zarychanski et al in 2013 found a higher incidence of AKI when volume resuscitation was conducted with HES versus crystalloid, albumin, or gelatin in critically ill patients. Although this study did not specifically include cardiac surgery patients, the increased renal failure rate and increased need for renal replacement therapy (RRT) in the HES group were noteworthy. This review of the current literature indicated that HES use during cardiac surgery was associated with an increased incidence of coagulopathy, increased bleeding and transfusion requirements, increased need for surgical re-intervention, and increased rates of AKI and RRT. Furthermore, longer MV duration and ICU stay, as well as higher hospital costs, have been noted. These numerous adverse effects, along with the active FDA warnings should induce strong caution against the tendency to consider the newer low-molecular-weight (130 kDa) and 0.4-to-0.42 substituted hetastarch solutions as being unequivocally safe and efficacious when compared to tetrastarch, other colloids, and crystalloids. More conclusive studies are needed, particularly in the subspecialty of cardiac surgery. With the newer HES formulations, the authors believe that HES presently should be avoided for routine volume expansion in cardiac surgery patients.
