Hydroxyethyl starch: Difference between revisions

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[[File:100 2512 (2).JPG|thumb|upright|left|A hydroxyethyl starch solution ready for intravenous infusion.]]
 
[[File:100 2512 (2).JPG|thumb|upright|left|A hydroxyethyl starch solution ready for intravenous infusion.]]
 
During 2010/11 a large number of research papers associated with a single author were retracted for ethical reasons and this may have an impact on clinical guidelines referring to HES preparations prepared before this date.<ref>[http://www.oxfordjournals.org/our_journals/jac/eic%20joint%20statement%20on%20retractions%204mar2011.pdf Editors-in-Chief Statement Regarding Published Clinical Trials Conducted without IRB Approval by Joachim Boldt. March 4, 2011]</ref>
 
During 2010/11 a large number of research papers associated with a single author were retracted for ethical reasons and this may have an impact on clinical guidelines referring to HES preparations prepared before this date.<ref>[http://www.oxfordjournals.org/our_journals/jac/eic%20joint%20statement%20on%20retractions%204mar2011.pdf Editors-in-Chief Statement Regarding Published Clinical Trials Conducted without IRB Approval by Joachim Boldt. March 4, 2011]</ref>
  +
Wiki Joachim Boldt ,Check details
 
This Person has also been the Most visible speaker pro HES and has written the largest number of positive Reviews pro HES,but at a low scientific Level.
 
This Person has also been the Most visible speaker pro HES and has written the largest number of positive Reviews pro HES,but at a low scientific Level.
 
Hartog C et al. Systematic analysis of HES Reviews: Proliferation of low Quality Reviews overwhelms Results of well Performed metaanalysis , Intensive Care Medicine 2012,38,pages 1258-71
 
Hartog C et al. Systematic analysis of HES Reviews: Proliferation of low Quality Reviews overwhelms Results of well Performed metaanalysis , Intensive Care Medicine 2012,38,pages 1258-71

Revision as of 14:18, 17 February 2013

[1] [2]

Hydroxyethyl starch
Hydroxyethylstärke.svg
Clinical data
Routes of
administration
Intravenous
ATC code
Pharmacokinetic data
Biological half-life 1.4 hrs
Excretion Renal
Identifiers
CAS Number
ChemSpider
UNII
ECHA InfoCard 100.120.749
Chemical and physical data
Molar mass 130 - 200 kDa (typical)
3D model (JSmol)
  (verify)

Hydroxyethyl starch (HES/HAES) is a nonionic starch derivative. It is one of the most frequently used volume expander under the trade names Hespan by B. Braun Medical Inc. and Voluven or Volulyte by Fresenius Kabi. HES is a general term and can be sub-classified according to average molecular weight, molar substitution, concentration, C2/C6 ratio and Maximum Daily Dose.[3] Distinguishing which preparation is used for treatment is key to understanding the potential for adverse effects.

Medical uses

An intravenous solution of hydroxyethyl starch is used to prevent shock following severe blood loss caused by trauma, surgery, or some other problem. It increases the blood volume, allowing red blood cells to continue to deliver oxygen to the body.

A hydroxyethyl starch solution ready for intravenous infusion.

During 2010/11 a large number of research papers associated with a single author were retracted for ethical reasons and this may have an impact on clinical guidelines referring to HES preparations prepared before this date.[4] Wiki Joachim Boldt ,Check details This Person has also been the Most visible speaker pro HES and has written the largest number of positive Reviews pro HES,but at a low scientific Level. Hartog C et al. Systematic analysis of HES Reviews: Proliferation of low Quality Reviews overwhelms Results of well Performed metaanalysis , Intensive Care Medicine 2012,38,pages 1258-71

Adverse effects

Anaphylactoid reactions: hypersensitivity, mild influenza-like symptoms, bradycardia, tachycardia, bronchospasm and non-cardiogenic pulmonary edema. Decrease in hematocrit and disturbances in coagulation. One liter of 6% solution (Hespan) reduces factor VIII level by 50% and will prolong aPTT.[5]

HES derivatives have been demonstrated to have increased rates of acute renal failure and need for renal replacement therapy and to decrease long-term survival when used alone in cases of severe sepsis compared with Ringer lactate solution (Brunkhorst 2008).[6] This study specifically used 10% HES with 0.45-0.55 substitution grade and molecular weight of 200 kDa (Hemohes). It also used a regimen without any crystalloids and was criticized for its study design.[7] The effects were tested recently on HES 130kDa/0.4 in patient with severe sepsis, and showed increased rates of renal failure and increased mortality when compared to LR (see NEJM "Hydroxyethyl Starch 130/0.42 versus Ringer's Acetate in Severe Sepsis" By Perner et Al.) It has been recommended that, since medium-MW HES solutions may be associated with harm, these solutions should not be used routinely for patients with septic shock.[8]

Contraindications

  • This product should not be used in people who are hypersensitive or allergic to hydroxyethyl starch.
  • Patients with kidney failure not related to low blood volume and patients on dialysis should avoid this product in high doses which are used for volume expansion.
  • Use of hydroxyethyl starch with normal saline in its preparation is contraindicated in people with severe increases in blood levels of sodium or chloride.
  • Patients with intracranial bleeds should not use this product.

Pharmacokinetics

Different types of hydroxyethyl starches are typically described by their average molecular weight, typically around 130 to 200 kDa (bearing in mind that there will be a range of different-sized molecules in any given solution); and their degree of molar substitution (what proportion of the glucose units on the starch molecule have been replaced by hydroxyethyl units), typically around 0.35 to 0.5. A solution of hydroxyethyl starch may further be described by its concentration in % (i.e. grams per 100ml). So for example, one commercially available hydroxyethyl starch (Voluven) is described as 6% HES 130 / 0.4.

The elimination depends on molar substitution degree. Molecules smaller than the renal threshold (60–70 kDa) are readily excreted in the urine while the larger ones are metabolized by plasma α–amylase before the degradation products are renally excreted.

Recent Safety Concerns

High molecular weight HES has been linked to coagulopathy, pruritus, as well as nephrotoxicity, acute renal failure and mortality.[9][10] On the other hand, low molecular weight HES seems not to demonstrate such adverse effects.[3] However, some suggest that low molecular weight HES poses significant safety concerns. They posit that studies concluding otherwise are not reliable for a number of reasons including “unsuitable comparators, too short observation periods, low cumulative dose and low-risk patients.” (Hartog & Reinhart, 2009, p 1340).[9] Recent results of 6S trial seem to confirm these concerns (see below).

In June 2012 6S paper was published in the New England Journal of Medicine raising concerns regarding the use of hydroxyethyl starch in sepsis - specifically, resuscitation with hydroxyethyl starch (as opposed to Ringer's acetate) resulted in an increased risk of death or end stage renal failure.[11] This study used Tetraspan (HES 130/0.42) of the pharmaceutical company B.Braun but the original version of the publication contained the product specification HES 130/0.4.[11] The pharmaceutical company, Fresenius Kabi, that makes a similar product but with the specification HES 130/0.4 is threatening to bring legal action against the author, Anders Perner, as they wanted the misleading use of their product specification to be corrected.[12] The academic community has raised concerns regarding this sort of behavior by a corporation although Fresenius Kabi did not doubt the results of the study.[12] The Chest study compared Hes130/0.40 with Saline in 7000 patients. The study was performed in patients,that were less Sick than in 6s.However,,the increase in Mortality was similar to 6s.There has also been a signifikant increase in dialysis Rate Overall. The increase in creatinin Confirmed the pathophysiological rationale. Furthermore,the patients needed more blood Products ,had Sig. More liverfailure and itching. The study has been Published in the NEJM Oct 2012 As a consequence the European Regulatory Agency ,EMA,has started an Official Procedure to Assess the Safety of all HES Products.(Nov 2012). The FDA in Sept 2012 conducted a Public Workshop addressing Safety concerns of HES,which according to the Majority of participants should be Adressed by Regulators.[13] The surviving Sepsis Campaign Decided to Ban HES from Treatment in Sepsis patients. ( Dellinger CCM 2013,Feb issue)

See also

References

  1. ^ Myburgh J (2012). NewEngland Journal of Medicine. 367 (20): 1901–1911. doi:10.1056 Check |doi= value (help) http://en.wikipedia.org/w/index.php?title=Hydroxyethyl_starch&action=edit. Retrieved 2/15/2013.  Check date values in: |access-date= (help); Missing or empty |title= (help)
  2. ^ FDA. "Public Workshop Risks and Benefits of HES solutions". Retrieved 2/15/2013.  Check date values in: |access-date= (help)
  3. ^ a b Westphal, M., James, M., Kozek-Langenecker, S., Stocker, R., Guidet, B., & Van Aken, H. (2009). Hydroxyethyl starches: different products--different effects. [Review] [140 refs]. Anesthesiology, 111(1), 187–202.
  4. ^ Editors-in-Chief Statement Regarding Published Clinical Trials Conducted without IRB Approval by Joachim Boldt. March 4, 2011
  5. ^ Miller: Anesthesia, 6th ed, p 1787
  6. ^ Brunkhorst FM; Engel C; Bloos F; et al. (2008). "Intensive insulin therapy and pentastarch resuscitation in severe sepsis". N. Engl. J. Med. 358 (2): 125–39. PMID 18184958. doi:10.1056/NEJMoa070716.  Unknown parameter |month= ignored (help); Unknown parameter |author-separator= ignored (help)
  7. ^ Zander R, Boldt J, Engelmann L, Mertzlufft F, Sirtl C, Stuttmann R (2007). "[The design of the VISEP trial. Critical appraisal]". Anaesthesist (in German). 56 (1): 71–7. PMID 17192828. doi:10.1007/s00101-006-1122-4.  Unknown parameter |month= ignored (help)
  8. ^ James Downar, Stephen E Lapinsky. Pro/con debate: Should synthetic colloids be used in patients with septic shock? Critical Care 2009, 13:203 (29 January 2009)
  9. ^ a b Hartog, C., & Reinhart, K. (2009). CONTRA: Hydroxyethyl starch solutions are unsafe in critically ill patients. Intensive Care Medicine, 35(8), 1337–42. doi:http://dx.doi.org.mutex.gmu.edu/10.1007/s00134-009-1521-5
  10. ^ Perner, A., Haase, N., Wetterslev, J., Åneman, A., Tenhunen, J., Guttormsen, A. B., Klemenzson, G., et al. (2011). 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, 12, 24. doi:10.1186/1745-6215-12-24
  11. ^ a b Perner, A (2012 Jul 12). "Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis.". The New England Journal of Medicine. 367 (2): 124–34. PMID 22738085.  Unknown parameter |coauthors= ignored (|author= suggested) (help); Check date values in: |date= (help)
  12. ^ a b Wojcik, Jeppe (July 24, 2012). "Pharma giant threatens Danish scientist". ScienceNordic. Retrieved 13 August 2012. 
  13. ^ 1

External links