The Volume Effect and Safety of 6% Hydroxyethyl Starch 130/0.4 in Patients Undergoing Major Elective Surgery: An Uncontrolled, Open-Labeled, Multi-Center Study
Nobutada Morioka, Makoto Ozaki, Michiaki Yamakage, Hiroshi Morimatsu, Yasuyuki Suzuki, Frank Bepperling, Hideki Miyao, Akiyoshi Namiki, Kiyoshi Morita
Department of Anesthesia and Intensive Care Medicine, National Center for Child Health and Development, Tokyo, Japan;.
Department of Anesthesiology, Okayama University, Okayama, Japan;.
Department of Anesthesiology, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan;.
Department of Anesthesiology, Sapporo Medical University School of Medicine, Sapporo, Japan;.
Department of Anesthesiology, Tokyo Women’s Medical University, Tokyo, Japan;.
Fresenius Kabi Deutschland GmbH, Bad Homburg, Germany;.
Otaru City Hospitals, Otaru-shi, Japan..
DOI: 10.4236/ojanes.2013.37071   PDF    HTML     4,190 Downloads   7,393 Views   Citations


Purpose: The primary aim of this study was to investigate volume effect and safety of up to 50 mL/kg BW 6% hydroxyethyl starch (HES) 130/0.4 in adult and pediatric patients undergoing major elective surgery. The need to infuse human albumin may be reduced or avoided in Japan if these large doses 6% HES 130/0.4 can be infused. Methods: The study was an uncontrolled, open-labeled, multi-center trial. Fifteen adult and 5 pediatric patients undergoing major elective surgery received 6% HES 130/0.4 (Voluven®) with a maximum dose of 50 mL/kg from the start of surgery until 2 hours after the end of surgery according to a treatment algorithm. The primary efficacy endpoint was the volume effect of 6% HES 130/0.4 determined by the volume of saved albumin during the investigational period and the time course of hemodynamic stability in adult and pediatric patients. Safety parameters were fluid balance, hemodynamic and laboratory parameters ECG, local and systemic tolerance and adverse events. Results: Adult patients received a mean of 32.0 mL/kg of 6% HES 130/0.4. For 12 out of 15 adult patients an average amount of 1033.8 mL (18.6 mL/kg) albumin could be saved. The other 3 adult patients did not receive more than 1000 mL of HES 130/0.4. All pediatric patients received approximately 50 mL/kg of HES 130/0.4; for these patients an average amount of 39.9 mL/kg body weight albumin could be saved. The majority of adult patients, and all pediatric patients were hemodynamically stable at all 3 time points. The observed changes of the assessed laboratory parameters including hematological and coagulation parameters or in any other safety parameter determined did not reveal any safety concern related to the administration of 6% HES 130/0.4 up to doses of 50 mL/kg body weight. Conclusion: The study results indicate that 6% HES 130/0.4 has a reliable volume effect, could contribute to significant human albumin savings and was safe and well tolerated up to a maximum dose of 50 mL/kg body weight in adult and pediatric patients undergoing major elective surgery.

Share and Cite:

N. Morioka, M. Ozaki, M. Yamakage, H. Morimatsu, Y. Suzuki, F. Bepperling, H. Miyao, A. Namiki and K. Morita, "The Volume Effect and Safety of 6% Hydroxyethyl Starch 130/0.4 in Patients Undergoing Major Elective Surgery: An Uncontrolled, Open-Labeled, Multi-Center Study," Open Journal of Anesthesiology, Vol. 3 No. 7, 2013, pp. 326-337. doi: 10.4236/ojanes.2013.37071.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] M. C. Laxenaire, C. Charpentier and L. Feldman, “Anaphylactoid Reactions to Colloid Plasma Substitutes: Incidence, Risk Factors, Mechanisms. A French Multicenter Prospective Study,” Annales Francaises d’Anesthésie et de Réanimation, Vol. 13, No. 3, 1994, pp. 301-310. doi:10.1016/S0750-7658(94)80038-3
[2] J. Waitzinger, F. Bepperling, G. Pabst and J. Opitz, “Hydroxyethyl Starch (HES) [130/0.4], a New HES Specification: Pharmacokinetics and Safety after Multiple Infusions of 10% Solution in Healthy Volunteers,” Drugs in R & D, Vol. 4, No. 3, 2003, pp. 149-157. doi:10.2165/00126839-200304030-00002
[3] C. Jungheinrich, W. Sauermann, F. Bepperling and N. Vogt, “Volume Efficacy and Reduced Influence on Measures of Coagulation Using Hydroxyethyl Starch 130/0.4 (6%) with an Optimised in Vivo Molecular Weight in Orthopaedic Surgery: A Randomised, Double-Blind Study,” Drugs in R & D, Vol. 5, No. 1, 2004, pp. 1-9. doi:10.2165/00126839-200405010-00001
[4] P. Van Der Linden, M. James, M. Mythen and R. B. Weiskopf, “Safety of Modern Starches Used during Surgery,” Anesthesia & Analgesia, Vol. 116, No. 1, 2013, pp. 35-48.
[5] G. Godet, J. J. Lehot, G. Janvier, A. Steib, V. De Castro and P. Coriat, “Safety of HES 130/0.4 (Voluven®) in Patients with Preoperative Renal Dysfunction Undergoing Abdominal Aortic Surgery: A Prospective, Randomized, Controlled, Parallel-Group Multicentre Trial,” European Journal of Anaesthesiology, Vol. 25, No. 12, 2008, pp. 986-994. doi:10.1017/S026502150800447X
[6] B. E. Ickx, F. Bepperling, C. Melot, C. Schulman and P. J. Van Der Linden, “Plasma Substitution Effects of a New Hydroxyethyl Starch HES 130/0.4 Compared with HES 200/0.5 during and after Extended Acute Normovolemic Haemodilution,” British Journal of Anaesthesia, Vol. 91, No. 2, 2003, pp. 196-202. doi:10.1093/bja/aeg159
[7] T. Standl, H. Lochbuehler, C. Galli, A. Reich, G. Dietrich and H. Hagemann, “HES 130/0.4 (Voluven) or Human Albumin in Children Younger than 2 yr Undergoing NonCardiac Surgery. A Prospective, Randomized, Open Label, Multicentre Trial,” European Journal of Anaesthesiology, Vol. 25, No. 6, 2008, pp. 437-445. doi:10.1017/S0265021508003888
[8] C. Hanart, M. Khalife, A. De Villé, F. Otte, S. De Hert and P. Van der Linden, “Perioperative Volume Replacement in Children Undergoing Cardiac Surgery: Albumin versus Hydroxyethyl Starch 130/0.4,” Critical Care Medicine, Vol. 37, No. 2, 2009, pp. 696-701. doi:10.1097/CCM.0b013e3181958c81
[9] P. Van der Linden, A. De Villé, A. Hofer, M. Heschl and H. Gombotz, “Six Percent Hydroxyethyl Starch 130/0.4 (Voluven®) versus 5% Human Serum Albumin for Volume Replacement Therapy during Elective Open-Heart Surgery in Pediatric Patients,” Anesthesiology, 2013, Epub Ahead of Print.
[10] T. Gondos, Z. Marjanek, Z. Ulakcsai, Z. Szabó, L. Bogár, M. Károlyi, B. Gartner, K. Kiss, A. Havas and J. Futó, “Short-Term Effectiveness of Different Volume Replacement Therapies in Postoperative Hypovolaemic Patients,” European Journal of Anaesthesiology, Vol. 27, No. 9, 2010, pp. 794-800. doi:10.1097/EJA.0b013e32833b3504
[11] O. Langeron, M. Doelberg, A. Eng-Than, F. Bonnet, X. Capdevila and P. I. Coriat “Voluven, a Lower Substituted Novel Hydroxyethyl Starch (HES 130/0.4), Causes Fewer Effects on Coagulation in Major Orthopedic Surgery than HES 200/0.5,” Anesthesia & Analgesia, Vol. 92, No. 2, 2001, pp. 855-862. doi:10.1097/00000539-200104000-00011
[12] S. Gandhi, D. Warltier, R. Weiskopf, R. Koorn, D. Miller, R. E. Shangraw, D. S. Prough, D. Baus, F. Bepperling and D. C. Warltier, “Volume Replacement Therapy during Major Orthopedic Surgery Using Voluven® (Hydroxyethyl Starch 130/0.4) or Hetastarch,” Anesthesiology, Vol. 106, No. 6, 2007, pp. 1120-1127. doi:10.1097/01.anes.0000265422.07864.37
[13] N. H. Vogt, U. Bothner, G. Lerch, K. H. Lindner and M. Georgieff, “Large-Dose Administration of 6% Hydroxyethyl Starch 200/0.5 in Total Hip Arthroplasty: Plasma Homeostasis, Hemostasis, and Renal Function Compared to Use of 5% Human Albumin,” Anesthesia & Analgesia, Vol. 83, No. 2, 1996, pp. 262-268. doi:10.1213/00000539-199608000-00011
[14] P. Van der Linden and B. E. Ickx, “The Effects of Colloid Solutions on Hemostasis,” Canadian Journal of Anesthesia, Vol. 53, No. 6, 2006, pp. S30-S39. doi:10.1007/BF03022250
[15] S. A. Kozek-Langenecker, C. Jungheinrich, W. Sauermann and P. Van der Linden, “The Effects of Hydroxyethyl Starch 130/0.4 (6%) on Blood Loss and Use of Blood Products in Major Surgery: A Pooled Analysis of Randomized Clinical Trials,” Anesthesia & Analgesia, Vol. 107, No. 2, 2008, pp. 382-390. doi:10.1213/ane.0b013e31817e6eac
[16] M. F. James, W. L. Michell, I. A. Joubert, A. J. Nicol, P. H. Navsaria and R. S. Gillespie, “Resuscitation with Hydroxyethyl Starch Improves Renal Function and Lactate Clearance in Penetrating Trauma in a Randomized Controlled Study: The FIRST Trial (Fluids in Resuscitation of Severe Trauma),” British Journal of Anaesthesia, Vol. 107, No. 5, 2011, pp. 693-702. doi:10.1093/bja/aer229
[17] S. M. Kasper, P. Meinert, S. Kampe, C. Goerg, C. Geisen, U. Mehlhorn and C. Diefenbach, “Large-Dose Hydroxyethyl Starch 130/0.4 Does Not Increase Blood Loss and Transfusion Requirements in Coronary Artery Bypass Surgery Compared with Hydroxyethyl Starch 200/0.5 at Recommended Doses,” Anesthesiology, Vol. 99, No. 1, 2003, pp. 42-47. doi:10.1097/00000542-200307000-00010
[18] B. Ellger, J. Freyhoff, H. van Aken, M. Booke and M. A. Marcus, “High-Dose Volume Replacement Using HES 130/0.4 during Major Surgery: Impact on Coagulation and Incidence of Postoperative Itching,” Netherlands Tijdschrift Anesthesia, Vol. 19, No. 1, 2006, pp. 63-68.
[19] P. J. Van der Linden, S. G. De Hert, D. Deraedt, S. Cromheecke, K. De Decker, R. De Paep, I. Rodrigus, A. Daper and A. Trenchant, “Hydroxyethyl Starch 130/0.4 versus Modified Fluid Gelatin for Volume Expansion in Cardiac Surgery Patients: The Effects on Perioperative Bleeding and Transfusion Needs,” Anesthesia & Analgesia, Vol. 101, No. 3, 2005, pp. 629-634. doi:10.1213/01.ANE.0000175216.53374.27
[20] T. A. Neff, M. Doelberg, C. Jungheinrich, A. Sauerland, D. R. Spahn and R. Stocker, “Repetitive Large-Dose Infusion of the Novel Hydroxyethyl Starch 130/0.4 in Patients with Severe Head Injury,” Anesthesia & Analgesia, Vol. 96, No. 5, 2003, pp. 1453-1459. doi:10.1213/01.ANE.0000061582.09963.FD

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.