Modified fluid gelatin 4% for perioperative volume replacement in pediatric patients (GPS): Results of a European prospective noninterventional multicenter study

Abstract

Introduction Modified fluid gelatin 4% is approved for use in children, but there is still a surprising lack of clinical studies including large numbers of pediatric patients. Therefore, we performed a European prospective noninterventional multicenter study to evaluate the use of a modified fluid gelatin 4% in saline (sal‐GEL) or an acetate‐containing balanced electrolyte solution (bal‐GEL) in children undergoing major pediatric surgery. Aims The primary aim was to assess the indications and dosing of modified fluid gelatin, and the secondary aim was to assess the safety and efficacy, focusing, in particular, on routinely collected clinical parameters. Methods Children aged up to 12 years with ASA risk scores of I‐III receiving sal‐GEL or bal‐GEL were followed perioperatively. Demographic data, surgical procedures performed, anesthesia, hemodynamic and laboratory data, adverse events, and adverse drug reactions were documented using a standardized case report form. Results 601 children that were investigated at 13 European pediatric centers from May 2015 to March 2020 (sal‐GEL 20.1%, bal‐GEL 79.9%; mean age 29.1 ± 38.6 (range 0–144) months; body weight 12.1 ± 10.5 (1.4–70) kg) were included in the analysis. The most frequent indications for GEL infusion were hemodynamic instability without bleeding (76.0%), crystalloids alone not being sufficient for hemodynamic stabilization (55.7%), replacement of preoperative deficit (26.0%), and significant bleeding (13.0%). Mean infused GEL volume was 13.0 ± 5.3 (2.4–37.5) ml kg−1. The total dose was affected by age, with higher doses in younger patients. After gelatin infusion, mean arterial pressure increased (mean change 8.5 ± 7.3 [95% CI: 8 to 9.1] mmHg), and the hemoglobin concentrations decreased significantly (mean change −1.1 ± 1.8 [95% CI: −1.2 to −0.9] g·dL−1). Acid–base parameters were more stable with bal‐GEL. No serious adverse drug reactions directly related to gelatin (i.e., anaphylactoid reaction, clotting disorders, and renal failure) were observed. Conclusion Moderate doses up to 20 ml kg−1 of modified fluid gelatin were infused most frequently to improve hemodynamic stability in children undergoing major pediatric surgery. The acid–base balance was more stable when gelatin in a balanced electrolyte solution was used instead of saline. No serious adverse drug reactions associated with gelatin were observed.

The impact of modified fluid gelatin 4% in a balanced electrolyte solution on plasma osmolality in children—A noninterventional observational study

“…11 This concept has been proven to be suitable for electrolyte solutions, but our study showed that it is probably not appropriate for gelatin-containing solutions for the TA B L E 2 Concentrations of osmotically active molecules and measured osmolality after in-vitro dilution of human blood with gelatin (GEL) or albumin (ALB) respectively, presented as mean ± SD Measuring the osmolality by freezing point depression is the gold standard, but, because of the observational study design of the GPS study, this was not possible in the in-vivo part. 5 Therefore, we calculated the osmolality using a modified version of Zander's formula, which showed excellent concordance with measured osmolality. 6 The results of our in-vitro experiment can be explained by simple dilution.…”

“…Measuring the osmolality by freezing point depression is the gold standard, but, because of the observational study design of the GPS study, this was not possible in the in‐vivo part 5 . Therefore, we calculated the osmolality using a modified version of Zander's formula, which showed excellent concordance with measured osmolality 6 .…”

“…This is a subgroup analysis of the European prospective noninterventional multicenter observational study evaluating the perioperative use of modified fluid gelatin in pediatrics (GPS), 5 which was approved by the local ethics committee of Hannover Medical School, Germany (Chairperson Prof. Dr. H. D. Troeger, No. 6866) on March 13, 2015, and registered in the database http://clinicaltrials.gov (ID: NCT02495285).…”

“…This is a subgroup analysis of the European prospective noninterventional multicenter observational study evaluating the perioperative use of modified fluid gelatin in pediatrics (GPS), 5…”