Date Published: April 29, 2019
Publisher: Public Library of Science
Author(s): Gernot Marx, Patrick Meybohm, Tobias Schuerholz, Gösta Lotz, Mandy Ledinko, Achim W. Schindler, Rolf Rossaint, Kai Zacharowski, Iratxe Puebla.
Balanced fluid replacement solutions can possibly reduce the risks for electrolyte imbalances, for acid-base imbalances, and thus for renal failure. To assess the intraoperative change of base excess (BE) and chloride in serum after treatment with either a balanced gelatine/electrolyte solution or a non-balanced gelatine/electrolyte solution, a prospective, controlled, randomized, double-blind, dual centre phase III study was conducted in two tertiary care university hospitals in Germany.
40 patients of both sexes, aged 18 to 90 years, who were scheduled to undergo elective abdominal surgery with assumed intraoperative volume requirement of at least 15 mL/kg body weight gelatine solution were included. Administration of study drug was performed intravenously according to patients need. The trigger for volume replacement was a central venous pressure (CVP) minus positive end-expiratory pressure (PEEP) <10 mmHg (CVP <10 mmHg). The crystalloid:colloid ratio was 1:1 intra- and postoperatively. The targets for volume replacement were a CVP between 10 and 14 mmHg minus PEEP after treatment with vasoactive agent and mean arterial pressure (MAP) > 65 mmHg.
The primary endpoints, intraoperative changes of base excess –2.59 ± 2.25 (median: –2.65) mmol/L (balanced group) and –4.79 ± 2.38 (median: –4.70) mmol/L (non-balanced group)) or serum chloride 2.4 ± 1.9 (median: 3.0) mmol/L and 5.2 ± 3.1 (median: 5.0) mmol/L were significantly different (p = 0.0117 and p = 0.0045, respectively). In both groups (each n = 20) the investigational product administration in terms of volume and infusion rate was comparable throughout the course of the study, i.e. before, during and after surgery.
Balanced gelatine solution 4% combined with a balanced electrolyte solution demonstrated significant smaller impact on blood gas analytic parameters in the primary endpoints BE and serum chloride when compared to a non-balanced gelatine solution 4% combined with NaCl 0.9%. No marked treatment differences were observed with respect to haemodynamics, coagulation and renal function.
ClinicalTrials.gov (NCT01515397) and clinicaltrialsregister.eu, EudraCT number 2010-018524-58.
During surgery volume therapy is one of the most important features. The assessment of intravascular volume is extremely difficult and challenging. While for the usual perioperative situation crystalloids are the option of choice, acute hypovolaemia or shock are indications for the use of colloids in order to minimise the duration of hypoperfusion and consecutive tissue hypoxia. Many studies investigating the value of advanced haemodynamic monitoring in high risk surgical patients demonstrated that using algorithm based colloid resuscitation in combination with inotropic support is associated with a significant reduction of cardiac events and morbidity in general.[1–2] In a retrospective analysis of more than 100,000 patients Khuri et al. demonstrated the importance of a single life-threatening complication on long-term survival after surgery.
This prospective, controlled, randomised, double-blind, dual centre study demonstrated safety using the balanced gelatine solution Gelaspan 4% combined with Sterofundin ISO perioperatively in surgical patients. In addition, significantly smaller influences on blood gas analytic parameters, in BE and chloride, in comparison with the unbalanced gelatine solution Gelafundin 4% combined with NaCl 0.9% could be shown. To our knowledge this is the first prospective randomized clinical study investigating the effect of a balanced colloid–here gelatin–and a balanced crystalloid vs. unbalanced solutions.
In conclusion, this study showed that a balanced gelatine solution compared with an unbalanced solution reduced acid-base-imbalances when used in the perioperative care of surgical patients in the OR and up to 12 hours postoperatively. Renal function and coagulation test remained similar with both solutions.