In this study, we compared the volume and hemodynamic effects of fluid challenges with crystalloid, 6% HES 130/0.4, and 5% Alb during surgical manipulation in patients undergoing major abdominal surgery. We found greater hemodilution, as well as a larger increase in COP and SVI, after fluid challenges with HES and Alb than with crystalloid.
The current study has two distinct features. First, all fluid challenges were rapid (finishing in less than 30 min). A meta-analysis by Toscani et al. revealed that fluid challenges that finished in less than 30 min resulted in a higher proportion of responders compared with fluid challenges that took longer than 30 min [20]. Aya et al. recently found that a 4 ml kg− 1 bolus over 5 min was adequate to reliably discriminate fluid responders from non-responders in post-cardiac surgical patients [21]. Furthermore, Miller et al. recommended a fluid challenge consisting of 5 consecutive injections of 50 ml by syringe push for goal-directed fluid management, which is the method adopted in the present study [5]. Collectively, our protocol corresponds well with recent studies and likely represents the contemporary standard of care for intraoperative goal-directed fluid management. Second, the volume effects of each study fluid were evaluated during actual surgical stress. Volume effects of administered fluids are considered context-sensitive [22] [23], and surgical manipulation and inflammatory response both increase vascular permeability, resulting in a significant fluid shift from the intravascular to the extravascular space [24] [25] [26]. Thus, the results of this study may be more clinically relevant than studies of healthy volunteers or surgical patients before or after surgery.
Increases in plasma volume were sustained for at least 30 min after fluid challenge with HES or Alb, but not with BRS. In patients undergoing major abdominal surgery, intravascular volume may be continuously lost to the interstitial space due to surgical stress and inflammation, as well as to the environment through evaporative loss. These findings suggest that, despite these fluid shifts, a significant proportion of administered HES or Alb remains intravascular, whereas a significant amount of administered BRS is lost from the vasculature after 30 min. There was a slight increase in COP 30 min after fluid challenge with HES or Alb; however, COP decreased 30 min after fluid challenge with BRS. Two clinical studies of healthy volunteers demonstrated slightly increased COP after colloid infusion [27] [28], and our data are basically in line with these previous reports. Therefore, we speculate that COP changes are at least partially due to the different volume effects of colloid and crystalloid.
Since fluid administration is generally guided by either subjective or objective hemodynamic parameters, the difference in volume effects between crystalloid and colloid in many clinical studies likely reflects differences in hemodynamic effects. Unfortunately, reports with detailed hemodynamic profiles after fluid challenges are rare. Aya et al. reported that cardiac output peaked 1 min after fluid challenge with 250 ml crystalloid in postoperative ICU patients and the effect was sustained for about 10 min after the completion of the fluid challenge [17]. Gandos et al. reported that the area under the curve of cardiac index was significantly higher after fluid challenges with HES or Alb than with crystalloid [13]. Our findings basically agree with these previous reports; however, they also provide interesting insights about the hemodynamic effects of fluid challenges. Fluid challenge with HES resulted in a higher peak SVI than fluid challenge with Alb; however, the area under the curve of SVI was not statistically different between fluid challenges with HES or Alb. Collectively, our data confirm that colloid, such as HES and Alb, generate larger hemodynamic effects than crystalloid. In addition, our data support the observed differences in volume effects between colloid and crystalloid [12] [29].
This study has several limitations. First, the context of each fluid challenge significantly affects data interpretation. We tried to minimize the influence of factors such as blood loss, changes in vascular compliance (epidural blockade and vasopressor use), and surgical manipulation. Nevertheless, such adjustments still remain subjective and cannot preclude the presence of confounding factors. The robust results found in this study suggest that the volume effects and subsequent hemodynamic effects of the study fluids are real. Second, COP was determined using a semipermeable filter with a cut-off value of 30 kDa. The renal excretion threshold is around 50 kDa [30]; therefore, molecules with a molecular weight between 30 and 50 kDa contribute to the COP value measured by the osmometer but are not osmotically active in vivo. Because this issue is particularly relevant to HES, this study may have overestimated the effect of HES on COP. Third, we did not fully account for the interaction between HES and BRS. Hahn et al. reported that the volume effect of acetate Ringer’s solution was modified by the preceding administration of HES [31]. Since all patients in the present study received both HES and BRS, the results may be affected by this interaction; however, we believe that the current protocol represents a realistic balance of crystalloid and colloid, which can maximize the benefits of goal-directed fluid management and prevent dose-dependent side effects of HES, especially in long cases. Fourth, this study included a significant number of elderly patients with multiple comorbidities, which may limit the generalizability of these results. Despite these limitations, the current study demonstrates a significant difference in the volume and hemodynamic effects of crystalloid and colloid during surgical manipulation under general anesthesia.
In conclusion, this study showed that the increase in plasma volume after rapid injection of crystalloid during major abdominal surgery was almost completely lost after 30 min. Conversely, rapid injection of both HES and Alb resulted in significantly greater increases in plasma volume and COP compared with BRS. Moreover, increases in plasma volume were accompanied by concomitant increases in stroke volume. These results correspond well with the results of other recent studies and confirm that colloid can reduce the total fluid input during goal-directed fluid management.