Hydroxyethyl starch

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European regulatory authorities removed marketing authorisation in 2018 on grounds risks outweighed benefits. Previously in 2013 it's only allowed indication had been reduced to hypovolaemic shock where crystalloids had failed to work[1]. As of 2018 still available but with restricted indications in USA and other countries

Hydroxyethyl starch (HES, HEAS) is usually used as a colloid solution volume expander. In late 2010 it was discovered that a major proponent of its use had distorted the literature through research fraud. It is likely that usage will decrease as the evidence base for benefit compared to cheaper alternatives does not exist[2][3]and this has been reinforced after removal of the likely fraudulent research[4]. Further studies will be necessary to determine place in therapy although this may be resisted as in some medical cultures use is very common[5]. The comparative studies in trauma are not reassuring with worse renal and mortality outcome data with 6% HES becoming available during 2011.[6] In 2012 130/0.4 hydroxyethyl starch was found to be inferior to Ringer's lactate in severe sepsis with higher mortality and greater likelihood of requiring renal-replacement therapy[7].

QuotationMarkLeft.png Researchers who show crystalloid to be superior always find crystalloid superior, whereas colloid supporters always favor colloids QuotationMarkRight.pngBoldt J[8]

QuotationMarkLeft.png In 2009 Dr. Joachim Boldt published a manuscript in Anesthesia & Analgesia comparing albumin and hydroxyethyl starch priming cardiopulmonary bypass. The study was retracted in December 2010 for lack of IRB approval. A subsequent investigation by Klinikum Ludwigshafen determined that the study was fabricated...The full list of 89 articles that for which LÄK could not verify IRB approval has been circulated QuotationMarkRight.png[9][10]

Side-effects

  • Pruritis - The incidence of this is likely to be formulation and total dose dependent. In most series seems to run at about 20% with intractable pruritus developing a few weeks after exposure and settling after a few months. The diagnosis can be proved by skin biopsy[11].
  • Renal failure - unclear at this time if association causative or associative but might almost double rate compared to alternatives[6]
  • Mortality - unclear at this time if association causative or associative but might almost double rate compared to alternatives[6]

Contraversy

As of 2018 some continue to interpret the evidence base as in equipoise for certain indications. Some relevant studies have yet to complete and the long term outcomes from the 2016 CHEST trial suggested equipose with normal saline ITU fluid resuscitation, although many have moved on to balanced salt resuscitation fluids. Further in the absence of a world wide ban and with evidence that partial regulation in Europe resulted in continued use outside the limited license of 2013 others are concerned that use could be diverted to post partum haemorrhage in countries without a complete ban. Evidence from the WOMAN trial is suggestive of this risk.

References

  1. PRAC recommends suspending marketing authorisations for infusion solutions containing hydroxyethyl starch EMEA 14 June 2013
  2. Dart AB, Mutter TC, Ruth CA, Taback SP. Hydroxyethyl starch (HES) versus other fluid therapies: effects on kidney function. Cochrane database of systematic reviews (Online). 2010; (1):CD007594.(Epub) (Link to article – subscription may be required.)
  3. Perel P, Roberts I. Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane database of systematic reviews (Online). 2011; 3:CD000567.(Epub) (Link to article – subscription may be required.)
  4. Bunn F, Trivedi D, Ashraf S. Colloid solutions for fluid resuscitation. Cochrane database of systematic reviews (Online). 2011; 3:CD001319.(Epub) (Link to article – subscription may be required.)
  5. Perner A, Haase N, Wetterslev J, Aneman A, Tenhunen J, Guttormsen AB, Klemenzson G, Pott F, Bødker KD, Bådstøløkken PM, Bendtsen A, Søe-Jensen P, Tousi H, Bestle M, Pawlowicz M, Winding R, Bülow HH, Kancir C, Steensen M, Nielsen J, Fogh B, Madsen KR, Larsen NH, Carlsson M, Wiis J, Petersen JA, Iversen S, Schøidt O, Leivdal S, Berezowicz P, Pettilä V, Ruokonen E, Klepstad P, Karlsson S, Kaukonen M, Rutanen J, Karason S, Kjældgaard AL, Holst LB, Wernerman J. Comparing the effect of hydroxyethyl starch 130/0.4 with balanced crystalloid solution on mortality and kidney failure in patients with severe sepsis (6S - Scandinavian Starch for Severe Sepsis/Septic Shock trial): Study protocol, design and rationale for a double-blinded, randomised clinical trial. Trials. 2011; 12(1):24.(Epub) (Link to article – subscription may be required.)
  6. a b c Lissauer ME, Chi A, Kramer ME, Scalea TM, Johnson SB. Association of 6% hetastarch resuscitation with adverse outcomes in critically ill trauma patients. American journal of surgery. 2011 May 18.(Epub ahead of print) (Link to article – subscription may be required.)
  7. Perner A, Haase N, Guttormsen AB, Tenhunen J, Klemenzson G, Aneman A, Madsen KR, Møller MH, Elkjær JM, Poulsen LM, Bendtsen A, Winding R, Steensen M, Berezowicz P, Søe-Jensen P, Bestle M, Strand K, Wiis J, White JO, Thornberg KJ, Quist L, Nielsen J, Andersen LH, Holst LB, Thormar K, Kjældgaard AL, Fabritius ML, Mondrup F, Pott FC, Møller TP, Winkel P, Wetterslev J. Hydroxyethyl Starch 130/0.4 versus Ringer's Acetate in Severe Sepsis. The New England journal of medicine. 2012 Jun 27.(Epub ahead of print) (Link to article – subscription may be required.)
  8. Boldt J. Pro: use of colloids in cardiac surgery. Journal of cardiothoracic and vascular anesthesia. 2007 Jun; 21(3):453-6.(Link to article – subscription may be required.)
  9. Shafer SL. Anesthesia & Analgesia 2011
  10. Editors-in-Chief Statement Regarding Published Clinical Trials Conducted without IRB Approval by Joachim Boldt. March 4, 2011
  11. Kamann S, Flaig MJ, Korting HC. Hydroxyethyl starch-induced itch: relevance of light microscopic analysis of semi-thin sections and electron microscopy. Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG. 2007 Mar; 5(3):204-8.(Link to article – subscription may be required.)
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