Eur. surg. Res. 8: 497-503 (1976)

Intravascular Persistence of Hydroxyethyl Starch in Man J. C. Boon1, F. J esch, J. R ing and K. M essmer Institute for Surgical Research, Department of Surgery, University of Munich, Munich

Key Words. HES degradation • Dextran 60 • a-Amylase • Long-term study Abstract. In two groups, each consisting of five healthy volunteers, 7 ml blood/kg body weight were exchanged with equal amounts of hydroxyethyl starch (HES) and dextran 60 solutions, respectively. Dextran 60 plasma levels, determined by the anthrone method, were undetectable after 4 weeks. The elimination of HES from the blood, determined by an immunological technique and by the anthrone method, had a very protracted course. Two weeks after infusion the HES plasma concentrations were 9°/o of the initial value and after 17 weeks they were still above the l°/o level. The prolonged intravascular persistence of HES in its commercially available prepa­ ration, and the possibility of tissue accumulation after repeated HES infusions were considered undesirable. The hypothesis that HES infusion causes an augmentation of serum a-amylase concentrations in man was confirmed. This effect should be borne in mind when HES solutions are given to patients in whom the diagnosis of acute pancreatitis might be considered.

Although dextran has proved to be generally satisfactory as a plasma substitute, its application is not completely without risk of causing rare anaphylactoid reactions [10]. A newly developed colloid hydroxyethyl starch (HES), commercially available in various countries since 1973, seemed to be a very promising plasma substitute especially because of its expected compatibility with biological systems.

Received: August 26,1976; accepted: September 2, 1976.

Downloaded by: Leiden University Medisch Centrum 132.229.13.63 - 10/16/2018 5:34:31 PM

1 Present address: Dept, of General Surgery, Erasmus University, Rotterdam (The Netherlands).

498

Boon/J esch/R ing /M essmer

Recently, however, it was shown in a prospective clinical study that HES causes incompatibility reactions in man quite similar to the anaphy­ lactoid reactions seen with other colloids and with a comparable frequen­ cy [11]. Doubts have also risen concerning the effectiveness and com­ pleteness of the elimination of HES from the body. After infusion of equally high doses of HES and dextran 70 in rabbits, L indblad and F alk [6] found retention of HES in blood and liver even 1 year after infusion, a finding contrasting sharply with the complete and relatively fast excre­ tion of dextran 70 in the control group. This study was undertaken to investigate the intravascular persistence of HES and dextran 60 in man, over a period of 17 weeks. It was further­ more tested if the rise in a-amylase serum concentration found in dogs af­ ter infusion of HES [4], occurs in man too.

HES was obtained from Dr. Fresenius KG, Bad Homburg, FRG (Plasmasteril® produced under licence from Me Gaw Lab. Div., American Hospital Supply Corporation, Evanston, 111.) as a 6°/o solution in 0.9% saline solution in 500-ml bot­ tles in one lot, No. 57365. According to the manufacturer the mean molecular weight is 450,000 (ranging from 10,000 to 2,500,000). The degree of substitution is stated to be between 0.7 and 0.8. Dextran 60 (Macrodex®) with a mean molecular weight of 60,000 was obtained from Knoll AG, Chemische Fabriken, Ludwigshafen, FRG, as a 6%> solution in 0.9% saline solution in 500-ml bottles in two lots, No. 4810E5 and 4110F4. Ten healthy volunteers were randomly divided in two equally large groups and after bleeding 7 ml/kg body weight, they were given an isovolemic infusion of HES and dextran 60, respectively. In both groups blood samples were drawn for the de­ terminations of hematocrit, hemoglobin, serum a-amylase, serum albumin, plasma HES, and dextran concentrations, before and directly after bleeding, 2 min and 1, 3, 6, 24, and 48 h, and 1, 2, 4, 6, 10, and 17 weeks after termination of infusion. An aliquot of the blood anticoagulated with heparin-sodium powder (Vetren®) was used for the determination of the hematocrit and the hemoglobin concentration. The serum from the clotted centrifuged aliquot was used for the determination of albumin and a-amylase concentrations. 2 ml plasma were kept frozen at -70 °C un­ til HES and dextran determinations were made. The serum albumin concentrations were determined by radial immunodiffusion [7] on Partigen plates (Behringwerke, Marburg, FRG). The a-amylase serum con­ centrations were determined with the modified [4] phadebas-amylase test (Deutsche Pharmacia, Frankfurt, FRG). The plasma concentrations of both colloids were de­ termined by the anthrone method [3], HES concentrations were also measured by a single radial immunodiffusion technique, using a recently developed rabbit anti-HES serum [9].

Downloaded by: Leiden University Medisch Centrum 132.229.13.63 - 10/16/2018 5:34:31 PM

Methods and Materials

Table I. Alterations in hematocrit, hemoglobin, albumin, a-amylase, HES and dextran concentrations, in two groups of healthy volunteers (n = 5), before, during and after isovolemic exchange of 7 ml/kg blood with HES and dextran 60, respectively (mean ± SD) Control a.b.

a.i.

1h

3h

6h

24 h

48 h

1w

2w

4w

8w

10 w

17 w

47.4 4.4

41.7 2.1

44.4 3.4

44.3 3.5

42.1 4.5

43.2 3.2

42.1 5.1

43.8 5.4

44.4 4.9

44.9*1 7.8

47.0 5.3

45.1 5.3

15.75 1.82 4,180 156

14.17 1.37 3,360 282

14.76 14.61 1.76 1.61

-

-