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.
OBJECTIVE
Different types of hydroxyethyl starch (HES) affect blood coagulation differently. We studied the effects of HES 130/0.4 on coagulation in major orthopaedic surgery in relation to the pharmacological parameter in vivo molecular weight.


METHODS
52 patients were randomly allocated to either HES 130/0.4 (6%, mean molecular weight 130 kDa, molar substitution 0.4) or HES 200/0.5 (6%, control) in a double-blind fashion. Colloidal volume requirements for intra- and postoperative haemodynamic stabilisation were compared. Safety analyses of this pharmacological study included a comparison of coagulation factor tests, in vivo molecular weight, and HES plasma concentrations.


RESULTS
The colloidal volumes given were similar at the end of surgery (1602 +/- 569 for HES 130/0.4 vs 1635 +/- 567mL for HES 200/0.5), 5h later (1958 +/- 467 vs 1962 +/- 398mL), and up to the first postoperative day (2035 +/- 446 vs 2000 +/- 424mL). HES in vivo molecular weight at the end of surgery was 88,707 +/- 13,938 versus 158,374 +/- 33,933Da (p < 0.001) and 5h later was 86,663 +/- 16,126 versus 136,299 +/- 26,208Da (p < 0.001). In parallel to the lower in vivo molecular weight, factor VIII and von Willebrand factor returned to almost normal in the HES 130/0.4 group up to 5h postoperatively, but not in the control group (p < 0.05). Residual HES plasma concentrations after 24h were low in the HES 130/0.4 group (1.0 mg/mL), but higher in the control group (2.6 mg/mL).


CONCLUSIONS
HES 130/0.4 and HES 200/0.5 were found to be similar with regard to volume efficacy. Sensitive coagulation parameters returned more rapidly to normal in the HES 130/0.4 group. Lower in vivo molecular weight and more rapid excretion of HES 130/0.4 are the likely explanations for the smaller influence on coagulation in this group.
Jungheinrich
Cornelius
C
Clinical Research, Fresenius Kabi, Bad Homburg, Germany. Cornelius.Jungheinrich@fresenius-kabi.com
Sauermann
Wilhelm
W
Bepperling
Frank
F
Vogt
Norbert H
NH
D000368:Aged; D001777:Blood Coagulation / Q000187:drug effects* / Q000502:physiology; D001810:Blood Volume / Q000187:drug effects* / Q000502:physiology; D016009:Chi-Square Distribution; D016001:Confidence Intervals; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000097:blood* / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D019637:Orthopedic Procedures / Q000379:methods*; D011446:Prospective Studies; D018709:Statistics, Nonparametric
C485123:HES 130-0.4; D006895:Hydroxyethyl Starch Derivatives