Episode 106: Hydroxyethyl Starches with Marius Fassbinder

In this 106th episode I welcome Dr. Marius Fassbinder to the show to discuss the use of hydroxyethyl starches.

References:

1. Woodcock, T. E. & Woodcock, T. M. Revised Starling equation and the glycocalyx model of transvascular fluid exchange: an

improved paradigm for prescribing intravenous fluid therapy. British Journal of Anaesthesia 108, 384–394 (2012).

2. Westphal, M. et al. Hydroxyethyl starches: different products–different effects. Anesthesiology 111, 187–202 (2009).

3. Brunkhorst, F. M. et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N. Engl. J. Med. 358, 125–139

(2008).

4. Perner, A. et al. Hydroxyethyl Starch 130/0.42 versus Ringer’s Acetate in Severe Sepsis. N. Engl. J. Med. 367, 124–134 (2012).

6. Myburgh, J. A. et al. Hydroxyethyl Starch or Saline for Fluid Resuscitation in Intensive Care. N. Engl. J. Med. 367, 1901–1911

(2012).

7. Annane, D. et al. Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients presenting with

hypovolemic shock: the CRISTAL randomized trial. JAMA 310, 1809–1817 (2013).

8. Joosten, A. et al. Crystalloid versus Colloid for Intraoperative Goal-directed Fluid Therapy Using a Closed-loop System: A

Randomized, Double-blinded, Controlled Trial in Major Abdominal Surgery. Anesthesiology 128, 55–66 (2018).

9. Gillies, M. A. et al. Incidence of postoperative death and acute kidney injury associated with 6% hydroxyethyl starch use: systematic review and meta-analysis. British Journal of Anaesthesia 112, 25–34 (2014).

8 Replies to “Episode 106: Hydroxyethyl Starches with Marius Fassbinder”

  1. I don’t agree that there is good evidence that normal saline “causes” renal failure. If the comments refer to SALT-ED and SMART, then I would say that they have serious issues in terms of randomization and likelihood of bias. On the other hand, I think the SPLIT trial was well done, blinded and randomized, and did not show harm.

    I agree 100% that fluids should be treated as a drug. The wrong drug, or too much of the right drug, will be toxic in specific situations. Every crystalloid comes with its own caveats and I’ve become concerned with trends in medicine to make certain things “preferred” (or undesirable) for all scenarios (e.g. not using Nitrous Oxide, or using PlasmaLyte for everyone in every situation).

    1. Hi Peter,

      I absolutely agree that we need to be careful with trying to make things all or nothing. Specific patients and specific situations may need different approaches. And I also agree that “cause” is a strong word. That said, I almost never use normal saline anymore and while there isn’t necessarily overwhelming evidence against it, there’s enough out there to keep me using PL or LR. While these aren’t perfect, they’re probably better and almost definitely not worse.

    2. Dr. Fassbinder wanted to add this comment about the SPLIT trial:
      They used less than 2L of NS on average. The deleterious effects of NS are explained by hyperchloremia. If you give a 70kg patient 2l of NS, and you assume their starting chloride level is normal (which it was), you don’t reach hyperchloremic levels. So the SPLIT was maybe good in showing that small amounts of NS are ok, but the design didn’t allow you to show the deleterious effects based on the physiology.

      1. Thank you very much for the reply.

        I agree with Dr. Fassbinder’s comment regarding the dose of NS used in the SPLIT trial. This was actually kind of my point…. It’s not the drug, but the dose that makes something “toxic”. In my opinion, the same caveats should apply to all crystalloids. For example, we know that high doses of acetate (contained in Plasma Lyte) causes hemodynamic instability.

        The right drug at the right dose for the right condition. I feel that the trend to vilify NS regardless of how much or when is counterproductive. It is still the preferred fluid in TBI and, I would argue, renal failure (although I feel HCO3- is ideal in this scenario, but a bit of a pain).

        The other question I would ask is… do we know that hyperchloremia/NGMA is bad? Other than some evidence for renal vasoconstriction, I’m not aware of any good evidence for real outcomes, but I am keen to be swayed if some references are readily available?

        1. Hi Peter,

          I agree there isn’t amazing evidence against normal saline, but I think there is pretty good evidence. While there may be some issues with SALTED and SMART, I wouldn’t throw them out completely. And while it certainly doesn’t carry a ton of weight, there is a fair amount of animal study evidence as well. Check out Josh Farkas’ Pulmcrit post called “Nine reasons to quit using normal saline for resuscitation.” I think he does a nice job of making a case against using NS. You can find it at https://emcrit.org/pulmcrit/smart/

  2. Thank you for this very interesting discussion.

    In my previous pre anesthesiology days I worked in the US military out in the field. Dealing with Hypovemic shock 2/2 blood loss for an extended period of time out in the middle of no where was not uncommon at all for my work. Further carrying several liters of crystaloid in a bag that I needed to keep small for tactical maneuverability as well as limiting weight would not be ideal. Likewise, carrying blood products was often not feasible in this setting at that time (things have changed somewhat in this area depending on the circumstances). As a result Hetastarch was a ideal fluid to pack due to benefits of volume expansion as well as its smaller volume and relative ease to be packed in a rucksack (backpack).

    I have often wondered if I had done the right thing in the past with my extensive hetastarch usage in light of some of the complications noted in this episode. I still wonder this considering many of these warriors I cared for definitely eventually dealt with both coagulopathy as well as likely infectious processes. However, considering the circumstances this fluid choice may be the best suited choice for these scenarios and this episode reinforced this notion for me.

    Perhaps future studies in prehospital hypovolemic patient resuscitation with synthetic colloids then transitioned in hospital setting.

    1. Thanks for sharing that Jon! We often think mostly about in hospital care but, as you point out, there are other areans where the needs are different.

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