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Relevance of non-albumin colloids in intensive care medicine

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Current guidelines on initial haemodynamic stabilization in shock states suggest infusion of either natural or artificial colloids or crystalloids. However, as the volume of distribution is much larger for crystalloids than for colloids, resuscitation with crystalloids alone requires more fluid and results in more oedema, and may thus be inferior to combination therapy with colloids. This chapter describes the currently available synthetic colloid solutions [i.e. dextran, gelatin and hydroxyethyl starch (HES)] in detail, and critically discusses their specific effects including potential adverse effects. Literature was selected from medical databases (including Medline and the Cochrane library), as well as references extracted from the available publications. Dextrans appear to have the most unfavourable risk/benefit ratio among the currently available synthetic colloids due to their relevant anaphylactoid potential, risk of renal failure and, particularly, their major impact on haemostasis. The effects of gelatin on kidney function are currently unclear, but potential disadvantages of gelatin include a high anaphylactoid potential and a limited volume effect compared with dextrans and HESs. Modern HES preparations have the lowest risk of anaphylactic reactions among the synthetic colloids. Older HES preparations (hetastarch, hexastarch and pentastarch) have repeatedly been reported to impair renal function and hemostasis, especially when the dose limit provided by the manufacturer is exceeded, but no such effects have been reported to date for modern tetrastarches compared with gelatin and albumin. However, no large-scale clinical studies have investigated the impact of tetrastarches on the incidence of renal failure in critically ill patients. When considering the efficacy and risk/benefit profile of synthetic colloids, modern tetrastarches appear to be most suitable for intensive care medicine, given their high volume effect, low anaphylactic potential and predictable pharmacokinetics. However, the impact of tetrastarch solutions on mortality and renal function in septic patients has not been fully determined, and further comparison with crystalloids in prospective, randomized studies is required. Such studies are currently ongoing and their results should be awaited before drawing final conclusions on the HES preparations.

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Pharmacology of different synthetic colloids

The development of synthetic colloids was markedly driven during times of war to facilitate transport of wounded soldiers to medical centres, where blood transfusions were available. Gum arabic, a natural colloid from the Acacia senegalis tree based on polysaccharides, was the first synthetic compound to be tested successfully as a plasma substitute in bled dogs in 1906. It was used clinically during World War I, as reported by the physiologist William M. Bayliss17, but use ceased in 1937 when

Structure and pharmacokinetics

Dextrans are neutral, high-molecular-weight glucopolysaccharides based on glucose monomers (Fig. 2). The polysaccharides are derived from extracellular, enzymatic synthesis from sucrose by the bacteria Leuconostoc mesenteroides or dextranicum, which catalyse the α-1,6-glycosidic linkage of glucose monomers. The first dextran (dextran 75) was introduced to the market for blood volume replacement by Grönwall and Ingelman from Sweden in 194422, and approval by the US Food and Drug Administration

Structure and pharmacokinetics

Gelatin products are derived from bovine collagen and prepared as polydispersive solutions by multiple chemical modifications. Denaturation (Fig. 4) and hydrolysation of the natural collagen produce polypeptide fractions that are cross-linked by distinct additives (e.g. glyoxal, succinate anhydride, diisocyanate). Commercially available gelatin preparations contain either oxypolygelatin, polygelin (urea cross-linked polymerized polypeptides, Fig. 5) or gelatin polysuccinate. Succinylation

Structure and pharmacokinetics

HES has been synthesized for industrial purposes since 1934. However, it was as late as 1957 that Wiedersheim (who labelled it as ‘oxyethylstarch’) used it as an experimental plasma substitute.36 Thereafter, HES was used extensively to treat wounded soldiers during the Vietnam War (1959–1975). The raw material for the production of HES is amylopectin, a highly branched polymer of glucose, derived from either waxy-maize or potato starch (Fig. 7). This multibranched structure makes it the first

Anaphylactoid reactions following synthetic colloids

Although frequently discussed in the literature, severe, life-threatening anaphylactic/anaphylactoid reactions in response to either of the three synthetic colloids are very rare with the use of modern preparations.55, 56 Within all three types of synthetic colloid, optimization of the particular preparations has been associated with a marked reduction in anaphylactic reactions during the last decades. A French prospective multicentre study published in 1994 observed an overall frequency of

Effects of synthetic colloids on renal function

The impact of synthetic colloids on renal function is one of the most frequently studied and discussed topics in the colloid literature of the 21st Century.57, *58, *59, 60, *61 The increase in intravascular volume and the decrease in plasma viscosity associated with modern synthetic colloids usually improve renal perfusion in hypovolaemic patients. However, since all synthetic colloids are mainly eliminated via the kidney, impaired renal function may contribute to colloid accumulation. As

Comparative randomized clinical studies of different synthetic colloids

To date, no randomized controlled trial has demonstrated a survival benefit associated with the infusion of colloids compared with crystalloids alone.76 In addition, a meta-analysis revealed no significant differences in outcome between either albumin and synthetic colloids or different types of synthetic colloid.16, *77

However, previous meta-analyses have not distinguished between the particular subtypes among dextrans, gelatin and HES.*76, *77 Therefore, the following paragraphs will

Conclusions

Among the currently available synthetic colloids, dextrans appear to have the worst risk/benefit ratio due to their relevant anaphylactoid potential, risk of renal failure and, particularly, the major influence on haemostasis. The effects of gelatin on kidney function are currently unclear, but the disadvantages of gelatin include its high anaphylactoid potential and the limited volume effect compared with dextrans and HESs. Modern HES preparations have the lowest risk of anaphylactic reactions

References (109)

  • C. Legendre et al.

    Hydroxyethylstarch and osmotic-nephrosis-like lesions in kidney transplantation

    Lancet

    (1993)
  • Y. Sakr et al.

    Effects of hydroxyethyl starch administration on renal function in critically ill patients

    British Journal of Anaesthesia

    (2007)
  • J. Boldt et al.

    Comparison of the effects of gelatin and a modern hydroxyethyl starch solution on renal function and inflammatory response in elderly cardiac surgery patients

    British Journal of Anaesthesia

    (2008)
  • R. Beyer et al.

    Use of modified fluid gelatin and hydroxyethyl starch for colloidal volume replacement in major orthopaedic surgery

    British Journal of Anaesthesia

    (1997)
  • J. Verheij et al.

    Effect of fluid loading with saline or colloids on pulmonary permeability, oedema and lung injury score after cardiac and major vascular surgery

    British Journal of Anaesthesia

    (2006)
  • G. Haisch et al.

    Influence of a new hydroxyethylstarch preparation (HES 130/0.4) on coagulation in cardiac surgical patients

    Journal of Cardiothoracic and Vascular Anesthesia

    (2001)
  • J. Boldt et al.

    Effects of a new modified, balanced hydroxyethyl starch preparation (Hextend) on measures of coagulation

    British Journal of Anaesthesia

    (2002)
  • J.C. Schadt et al.

    Hemodynamic and neurohumoral responses to acute hypovolemia in conscious mammals

    The American Journal of Physiology

    (1991)
  • J.L. Vincent et al.

    Fluid challenge revisited

    Critical Care Medicine

    (2006)
  • F. Hinder et al.

    Early multiple organ failure after recurrent endotoxemia in the presence of vasoconstrictor-masked hypovolemia

    Critical Care Medicine

    (2003)
  • A.M. Moller et al.

    Perioperative risk factors in elective pneumonectomy: the impact of excess fluid balance

    European Journal of Anaesthesiology

    (2002)
  • R.S. Simmons et al.

    Fluid balance and the adult respiratory distress syndrome

    The American Review of Respiratory Disease

    (1987)
  • M. Rehm et al.

    Changes in blood volume and hematocrit during acute preoperative volume loading with 5% albumin or 6% hetastarch solutions in patients before radical hysterectomy

    Anesthesiology

    (2001)
  • M. Rehm et al.

    Endothelial glycocalyx as an additional barrier determining extravasation of 6% hydroxyethyl starch or 5% albumin solutions in the coronary vascular bed

    Anesthesiology

    (2004)
  • K. Lang et al.

    Colloids versus crystalloids and tissue oxygen tension in patients undergoing major abdominal surgery

    Anesthesia and Analgesia

    (2001)
  • J. Boldt et al.

    Influence of different volume replacement strategies on inflammation and endothelial activation in the elderly undergoing major abdominal surgery

    Intensive Care Medicine

    (2004)
  • B. Chalidis et al.

    Safety and efficacy of albumin administration in trauma

    Expert Opinion on Drug Safety

    (2007)
  • F. Wong

    Drug insight: the role of albumin in the management of chronic liver disease

    Nature Clinical Practice. Gastroenterology & Hepatology

    (2007)
  • A. Liberati et al.

    Human albumin solution for resuscitation and volume expansion in critically ill patients

    Internal and Emergency Medicine

    (2006)
  • C.M. Mendez et al.

    Albumin therapy in clinical practice

    Nutrition in Clinical Practice

    (2005)
  • P. Alderson et al.

    Human albumin solution for resuscitation and volume expansion in critically ill patients

    Cochrane Database of Systematic Reviews (Online)

    (2004)
  • W.M. Bayliss

    Intravenous injection in wound shock

    British Medical Journal

    (1918)
  • Y.M. Le Gal

    A review of the history of blood replacement from the 17th to the 20th centuries

    Review of Surgery

    (1975)
  • J.J. Hogan

    The intravenous use of colloidal (gelatin) solutions in shock

    The Journal of the American Medical Association

    (1915)
  • G. Hecht et al.

    Periston, ein neuer Blutflüssigkeitsersatz

    MMW, Münchener Medizinische Wochenschrift

    (1943)
  • H. Wesse et al.

    Pharmacology of periston N

    Deutsche Medizinische Wochenschrift (1946)

    (1951)
  • A. Grönwall et al.

    Untersuchungen über Dextran und sein Verhalten bei parenteraler Zufuhr. I. Chemische und physikalisch-chemische Untersuchungen über Dextran

    Acta Physiologica Scandinavica

    (1944)
  • K. Aktories

    General and specific pharmacology and toxicology

    (2006)
  • L.J. Koekenberg

    Experimental use of macrodex as a prophylaxis against post-operative thrombo-embolism

    Bulletin de la Société Internationale de Chirurgie

    (1962)
  • U.F. Gruber

    Prevention of fatal postoperative pulmonary embolism by heparin dihydroergotamine or dextran 70

    The British Journal of Surgery

    (1982)
  • U.F. Gruber et al.

    Incidences of fatal postoperative pulmonary embolism after prophylaxis with dextran 70 and low-dose heparin: an international multicentre study

    British Medical Journal

    (1980)
  • M.K. Hohl et al.

    Prevention of postoperative thromboembolism by dextran 70 or low-dose heparin

    Obstetrics and Gynecology

    (1980)
  • M. Kamler et al.

    Extracorporal-circulation-induced leukocyte/endothelial cell interaction is inhibited by dextran

    Clinical Hemorheology and Microcirculation

    (2004)
  • K.G. Ljungstrom

    The antithrombotic efficacy of dextran

    Acta Chirurgica Scandinavica. Supplementum

    (1988)
  • A.W. Bronwell et al.

    Evaluation of blood loss from a standardized wound after dextran

    Surgical Forum

    (1955)
  • K. Kruger et al.

    Infusion incidents with dextran

    Acta Anaesthesiologica

    (1988)
  • F. Schortgen et al.

    The risk associated with hyperoncotic colloids in patients with shock

    Intensive Care Medicine

    (2008)
  • G. Godwin

    Dextrans and compatibility testing

    Transfusion

    (1987)
  • F. Schortgen et al.

    Preferred plasma volume expanders for critically ill patients: results of an international survey

    Intensive Care Medicine

    (2004)
  • S.F. Hussain et al.

    Acute renal failure after infusion of gelatins

    British Medical Journal

    (1989)

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