Starches for fluid therapy: Is it time for a re-appraisal, or has the horse left the barn?

Abstract

In 1994, the Canadian Blood Services (CBS) introduced the synthetic colloid, Pentaspan TM (10% pentastarch in 0.9% sodium chloride injection, 200/0.45), A a hydroxyethyl starch (HES) solution, as an alternative to the humanderived colloid, albumin, for distribution in Canada. Despite attempts to introduce other HES solutions (e.g., Hespan TM and Hextend TM ), Pentaspan remained the only HES solution that CBS supplied at no charge to Canadian hospitals. Circumstances changed in late 2007 when Voluven TM (6% tetrastarch in 0.9% sodium chloride injection, 130/0.40) B was purchased by the CBS for distribution in Canada. On April 1, 2012, CBS transferred the cost and responsibility for the distribution of HES solutions to individual hospitals, and at the same time, Volulyte Ò (6% tetrastarch in an isotonic electrolyte injection, 130/0.40), C a HES solution in a balanced salt carrier, was introduced into clinical practice. Since HES solutions are drugs (drug identification number 02278057), it could be argued that they should have been reviewed by the hospitals' Pharmacy and Therapeutics Committees before they were added to the hospital formulary. In most cases, however, the responsibility within hospitals came under the material services department, which is the same department that handles the distribution of the crystalloids. As a result, the evaluation of the HES solutions for therapeutic efficacy and safety was largely bypassed at the hospital level, and by most accounts, their use went unchecked at the hospital level.The recent publications of large randomized trials comparing HES solutions with crystalloids in critically ill patients 1-4 has renewed the discussion over the use of HES solutions. This is evident by the number of recent reviews and editorials (count one more) on this topic. In our opinion, the missing issue in this discussion and debate over the use of HES in fluid resuscitation is the consideration that these colloids are in essence drugs with specific indications, contraindications, and toxicity. We understand how they are synthesized; we know their average molecular weight, their degree of substitution, their metabolism and kinetics, but unlike how we manage most drugs, we seem to overlook these properties when comparing HES solutions with other intravenous fluids. This oversight likely relates to the lack of evidence used to develop fluid therapy protocols in general. If fluid therapy or fluid resuscitation was appropriately considered as a therapeutic intervention requiring assessment and reassessment of its efficacy, then we would likely have been more careful in our consideration of the HES solutions.Hydroxyethyl starch solutions are ''indicated for the treatment of hypovolemia when plasma volume expansion is required'', 2 but this basic principle may not have been adequately addressed in clinical trials. In the following two