Top

Published in:

01-09-2007 | Experimental

Pharmacodynamics and organ storage of hydroxyethyl starch in acute hemodilution in pigs: Influence of molecular weightand degree of substitution

Authors: Christoph Eisenbach, Alexander H. Schönfeld, Norbert Vogt, Moritz N. Wente, Jens Encke, Wolfgang Stremmel, Eike Martin, Ernst Pfenninger, Markus A. Weigand

Published in: Intensive Care Medicine | Issue 9/2007

Abstract

Objective

To determine the differential influence of molecular weight and the degree of substitution of HES solutions on pharmacodynamics and pharmacokinetics including organ storage in a model of acute hemodilution in pigs.

Design

Prospective controlled randomized animal trial.

Interventions

After bleeding, 20 ml/kg, animals were substituted with 6% HES preparations (200/0.62, 200/0.5, and 100/0.5).

Measurements and results

We did not observe any significant differences in the ability to sufficiently achieve plasma volume expansion and restoration of macrocirculation, nor maintenance of indicators of microcirculation between the groups. Urine production was significantly higher in HES-treated animals and highest in animals substituted with HES 100/0.5. Plasma clearance was measured under steady-state conditions with significantly reduced clearance for the HES 200/0.62 group compared with HES 100/0.5 and HES 200/0.5 (6.6 vs. 13.2 and 13.9 ml/min; P ≤ 0.001), thus being dependent on the degree of substitution. Even after only 6 h, the amount of infused HES not detectable in either blood or urine was significantly higher in HES 200/0.62-treated animals (50.7% compared with HES 200/0.5 (28.8%), P = 0.020 and HES 100/0.5 (28.4%), P  = 0.018), with its proportion rising over time. Finally, we could demonstrate considerable amounts of all HES solutions being stored in liver, kidney, lung, spleen and lymph nodes.

Conclusions

All preparations analyzed sufficiently restored macro- and microcirculation; however, for all solutions relevant tissue storage of HES was observed after only 6 h.

Available only for authorised users

Lundberg JS, Perl TM, Wiblin T, Costigan MD, Dawson J, Nettleman MD, Wenzel RP (1998) Septic shock: an analysis of outcomes for patients with onset on hospital wards versus intensive care units. Crit Care Med 26:1020–1024PubMedCrossRef

Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M (2001) Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 345:1368–1377PubMedCrossRef

Grönwall A (1957) Dextran and its use in colloidal infusion solutions. Almquist and Wiksell, Uppsala, pp 10–21

Thompson WL (1980) Hydroxyethyl starch. Dev Biol Stand 48:259–266PubMed

Mishler JMT (1984) Synthetic plasma volume expanders: their pharmacology, safety and clinical efficacy. Clin Haematol 13:75–92PubMed

Treib J, Baron JF, Grauer MT, Strauss RG (1999) An international view of hydroxyethyl starches. Intensive Care Med 25:258–268PubMedCrossRef

Lenz K, Schimetta W, Polz W, Kroll W, Gruy-Kapral C, Magometschnigg D (2000) Intestinal elimination of hydroxyethyl starch? Intensive Care Med 26:733–739PubMedCrossRef

Hulse JD, Yacobi A (1983) Hetastarch: an overview of the colloid and its metabolism. Drug Intell Clin Pharm 17:334–341PubMed

Leuschner J, Opitz J, Winkler A, Scharpf R, Bepperling F (2003) Tissue storage of 14C-labelled hydroxyethyl starch (HES) 130/0.4 and HES 200/0.5 after repeated intravenous administration to rats. Drugs R D 4:331–338PubMedCrossRef

10.

Hankeln K, Radel C, Beez M, Laniewski P, Bohmert F (1989) Comparison of hydroxyethyl starch and lactated Ringer's solution on hemodynamics and oxygen transport of critically ill patients in prospective crossover studies. Crit Care Med 17:133–135PubMedCrossRef

11.

Haupt MT, Rackow EC (1982) Colloid osmotic pressure and fluid resuscitation with hetastarch, albumin, and saline solutions. Crit Care Med 10:159–162PubMedCrossRef

12.

Rackow EC, Falk JL, Fein IA, Siegel JS, Packman MI, Haupt MT, Kaufman BS, Putnam D (1983) Fluid resuscitation in circulatory shock: a comparison of the cardiorespiratory effects of albumin, hetastarch, and saline solutions in patients with hypovolemic and septic shock. Crit Care Med 11:839–850PubMedCrossRef

13.

Finfer S, Bellomo R, Boyce N, French J, Myburgh J, Norton R (2004) A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med 350:2247–2256PubMedCrossRef

14.

Boldt J, Muller M, Mentges D, Papsdorf M, Hempelmann G (1998) Volume therapy in the critically ill: Is there a difference? Intensive Care Med 24:28–36PubMedCrossRef

15.

Winkelmayer WC, Glynn RJ, Levin R, Avorn J (2003) Hydroxyethyl starch and change in renal function in patients undergoing coronary artery bypass graft surgery. Kidney Int 64:1046–1049PubMedCrossRef

16.

Schortgen F, Lacherade JC, Bruneel F, Cattaneo I, Hemery F, Lemaire F, Brochard L (2001) Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: a multicentre randomised study. Lancet 357:911–916PubMedCrossRef

17.

Cittanova ML, Leblanc I, Legendre C, Mouquet C, Riou B, Coriat P (1996) Effect of hydroxyethylstarch in brain-dead kidney donors on renal function in kidney-transplant recipients. Lancet 348:1620–1622PubMedCrossRef

18.

Gosling P, Rittoo D, Manji M, Mahmood A, Vohra R (2001) Hydroxyethylstarch as a risk factor for acute renal failure in severe sepsis. Lancet 358:581PubMedCrossRef

19.

Deman A, Peeters P, Sennesael J (1999) Hydroxyethyl starch does not impair immediate renal function in kidney transplant recipients: a retrospective, multicentre analysis. Nephrol Dial Transplant 14:1517–1520PubMedCrossRef

20.

Kumle B, Boldt J, Piper S, Schmidt C, Suttner S, Salopek S (1999) The influence of different intravascular volume replacement regimens on renal function in the elderly. Anesth Analg 89:1124–1130PubMedCrossRef

21.

Boldt J, Brenner T, Lehmann A, Lang J, Kumle B, Werling C (2003) Influence of two different volume replacement regimens on renal function in elderly patients undergoing cardiac surgery: comparison of a new starch preparation with gelatin. Intensive Care Med 29:763–769PubMed

22.

Appel W, Wirmer V, Sprengard D (1968) Quantitative micro determination of dextran. I. In body fluids. Z Klin Chem Klin Biochem 6:452–458PubMed

23.

Ahnefeld FW, Halmagyi M, Uberla K (1965) Studies for the evaluation of colloidal volume substitution. Anaesthesist 14:137–143PubMed

24.

Linko K, Makelainen A (1989) Cardiorespiratory function after replacement of blood loss with hydroxyethyl starch 120, dextran-70, and Ringer's acetate in pigs. Crit Care Med 17:1031–1035PubMedCrossRef

25.

Jungheinrich C, Neff TA (2005) Pharmacokinetics of hydroxyethyl starch. Clin Pharmacokinet 44:681–699PubMedCrossRef

26.

Kohler H, Zschiedrich H, Clasen R, Linfante A, Gamm H (1982) The effects of 500 ml 10% hydroxyethyl starch 200/0.5 and 10% dextran 40 on blood volume, colloid osmotic pressure and renal function in human volunteers. Anaesthesist 31:61–67PubMed

27.

Messmer K, Jesch F (1978) Blood volume replacement and hemodilution with hydroxyethyl starch. Infusionsther Klin Ernahr 5:169–177PubMed

28.

Neumann R, Worek FS, Blumel G, Zimmermann GJ, Fehm HL, Pfeiffer UJ (1989) Cortisol deficiency in metomidate anesthetized bacteremic pigs: results in circulatory failure - beneficial effect of cortisol substitution. Acta Anaesthesiol Scand 33:379–384PubMedCrossRef

29.

Weidler B, Bormann B von, Sommermeyer K, Lohmann E, Peil J, Hempelmann G (1991) Pharmacokinetic parameters as criteria for clinical use of hydroxyethyl starch preparations. Arzneimittelforschung 41:494–498PubMed

30.

Kalhorn TF, Yacobi A, Sum CY (1984) Biliary excretion of hydroxyethyl starch in man. Biomed Mass Spectrum 11:164–166CrossRef

31.

Thompson WL, Fukushima T, Rutherford RB, Walton RP (1970) Intravascular persistence, tissue storage, and excretion of hydroxyethyl starch. Surg Gynecol Obstet 131:965–972PubMed

32.

Dienes HP, Gerharz CD, Wagner R, Weber M, John HD (1986) Accumulation of hydroxyethyl starch (HES) in the liver of patients with renal failure and portal hypertension. J Hepatol 3:223–227PubMedCrossRef

33.

Parth E, Jurecka W, Szepfalusi Z, Schimetta W, Gebhart W, Scheiner O, Kraft D (1992) Histological and immunohistochemical investigations of hydroxyethyl-starch deposits in rat tissues. Eur Surg Res 24:13–21PubMed

34.

Jurecka W, Szepfalusi Z, Parth E, Schimetta W, Gebhart W, Scheiner O, Kraft D (1993) Hydroxyethylstarch deposits in human skin: a model for pruritus? Arch Dermatol Res 285:13–19PubMedCrossRef

35.

Sirtl C, Laubenthal H, Zumtobel V, Kraft D, Jurecka W (1999) Tissue deposits of hydroxyethyl starch (HES): dose-dependent and time-related. Br J Anaesth 82:510–515PubMed

36.

Reinhart K, Bloos F, Engel C, For the German Competence Network Sepsis (2006) Hydroxyethyl starch and ringer's lactate for fluid resuscitation in patients with severe sepsis: result from the VISEP study. Intensive Care Med 32:S213

Title: Pharmacodynamics and organ storage of hydroxyethyl starch in acute hemodilution in pigs: Influence of molecular weightand degree of substitution
Authors: Christoph Eisenbach
Alexander H. Schönfeld
Norbert Vogt
Moritz N. Wente
Jens Encke
Wolfgang Stremmel
Eike Martin
Ernst Pfenninger
Markus A. Weigand
Publication date: 01-09-2007
Publisher: Springer-Verlag
Published in: Intensive Care Medicine / Issue 9/2007
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-007-0716-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Pharmacodynamics and organ storage of hydroxyethyl starch in acute hemodilution in pigs: Influence of molecular weightand degree of substitution

Abstract

Objective

Design

Interventions

Measurements and results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objective

Design

Interventions

Measurements and results

Conclusions

Please log in to get access to this content

Other articles of this Issue 9/2007

Future trends in illness severity scores

Continuous renal replacement therapy: A worldwide practice survey

De-escalation therapy rates are significantly higher by bronchoalveolar lavage than by tracheal aspirate

Adenosine for salbutamol-induced supraventricular tachycardia

Traumatic pediatric brain injury and intracranial pressure monitoring: does it really improve outcome?

B-type natriuretic peptide as a marker for heart failure in patients with acute stroke