THE GLYCOCALYX

This is a brief synopsis of the literature surrounding the glycocalyx and its role in resuscitation.  After some recent coverage of Marik’s opposition to the tenets of Early Goal Directed Therapy, I thought it would be useful to delve into some work covering the glycocalyx.  It is an interesting thing to think about in terms of the Starling principle which was engrained into us during our undergraduate and medical school careers.  The Starling model described transvascular exchange in terms of hydrostatic and oncotic pressure gradients.  At the arteriolar end of a capillary, the dominant hydrostatic pressure caused net fluid movement to filter into the interstitium.  Conversely, the venular end experienced a dominant colloid osmotic pressure causing net fluid movement back into the capillary.  (Note: colloid osmotic pressure is the same thing as oncotic pressure)

What is the endothelial glycocalyx layer (EGL)?

The endothelial glycocalyx layer (EGL) lines the lumen of vessels and consists of glycosaminoglycans and proteoglycans.  It interacts with the lumen contents and plays a role in the physiology of volume status regulation.  It can be thought of as a layer lining the lumen of the vessel, contributing to oncotic pressure and reacting to the environment around it.  The presence of specific glycoasminoglycans (heparan sulphate, chondroitin sulphate, and hyaluronic acid) and proteoglycans in the plasma can be taken as signs of damage to the EGL.  For example, rapid crystalloid infusion in volunteers resulted in elevated plasma levels of hyaluronic acid and may be indications of injury to the patient.

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Why is it relevant to resuscitation in the ED and ICU?

– Human studies have shown that the EGL is compromised in systemic inflammatory states like diabetes, trauma and sepsis.

– The EGL makes up a large volume of the intravascular space, excluding large molecules and affecting dilution studies of blood volume.  Therefore, protection of the EGL is an important therapeutic goal.  Patients in septic shock, for example, have been found to have increased plasma concentrations of GAGs, indicating damage to the EGL.

– Using traditional Starling principles, the filtration rate across the capillary is a product of opposing hydrostatic and opposing oncotic pressures.  However, the traditional Starling forces (hydrostatic pressure and colloid osmotic pressure of both capillary and interstitium) have recently been reevaluated and include the colloid osmotic pressure from the subglycocalyx layer.

– Taking into account the subglycocalyx colloid osmotic pressure, the physiology of fluid movement between intravascular and extravascular spaces isn’t as straightforward as an evaluation of the hydrostatic pressures (capillary and interstitial) and the colloid osmotic pressures (again, capillary and interstitial).

– The glycocalyx responds to shear stress, evidenced by its thicker presence in shear stress areas.

How will it affect our practice?

Recent debate amongst ED intensivists has focused on the role of the glycocalyx in our choice for resuscitation fluids.  While large trials such as SAFE have attempted to elucidate the ideal resuscitation fluid, there has been no definitive outcome.  The purpose of this short entry is to give us a chance to think about the complexities of the fluid movement in the setting of the glycocalyx.

In the recent past, crystalloids have been the fluid of choice for expanding intravascular volume in septic patients.  However, given the Starling forces at play in volume-depleted, hypoalbuminemic patients, the intuitive assumption is that colloids would be more useful.  You would think more protein in the blood increases the colloid osmotic pressure pulling fluid in from the interstitium.  The reality is unfortunately not so straightforward.  The glycocalyx is another variable added to the equation of fluid physiology.  It has a protein concentration gradient between that seen in the free-flowing plasma and the endothelial intercellular clefts.

The bottom line is that the investigation of the glycocalyx has been performed in hopes of uncovering the physiologic reasoning behind fluid movement between the vascular and interstitial systems.  The SAFE trial of 2004 looked at the difference of colloids and crystalloids but found no significant hemodynamic resuscitation differences between albumin and saline groups.  There’s been a surge of recent comments in the #FOAMed world regarding fluids and the glycocalyx, so keep a look out for other more detailed analyses and how it pertains to the ideal resuscitation fluid.

Here’s another great #FOAMed resource on the topic: http://thinkingcriticalcare.com/2013/12/10/the-glycocalyx-an-overview-for-the-clinician-foamed-foamcc/

References

Woodcock TE, Woodcock TM. Revised Starling equation and the glycocalyx model of transvascular fluid exchange: an improved paradigm for prescribing intravenous fluid therapy. Br J Anaesth 2012;108:384-94.

Myburgh JA, Mythen MG. Resuscitation fluids. N Engl J Med 2013;26;369(13):1243-51.

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3 thoughts on “THE GLYCOCALYX

  1. Much enjoyed this, very clear and excellent points. Glad to see many of us are focusing on the topic, even if there are no clear solutions right now. Reading your thoughts on albumin reminded me of a study that showed how slow infusion of albumin resulted in better volume expansion (3h vs the usual 1h) than a rapid infusion. Perhaps the glycocalyx has a role in that as well, and that a slow infusion results in less glycocalyx-fluid shift…

    thanks!

    Philippe

  2. Thanks for commenting Philippe. It’s great to hear your thoughts and we’re fans of your blog. I’ve taken a recent interest in studying the different resuscitation fluids we use in the hospital and their effects on different populations. Your comments on albumin are also great thought-provokers. I was speaking to another classmate of mine yesterday, and we realized that we knew very little about the science behind fluid choices. I was curious; the study you’re talking about…is it this one?

    Bark BP, Presson J, Grande PO. Importance of the infusion rate for the plasma expanding effect of 5% albumin, 6% HES 130/0.4, 4% gelatin, and 0.9% NaCl in the septic rat. Crit Care Med. 2013 Mar;41(3):857-66.

    – Clark

  3. By far essentially the most succinct and also up-to-date information I found about this topic matter. Certain pleased that I stumbled upon your write-up by opportunity. I will likely be signing up on your rss feed so as I’ll receive the newest posts. Enjoy everything right here.

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