Low volume resuscitation – PEGged?

Really grateful to the correspondent who pointed me to interesting work being done on “cell impermeants” at Virginia Commonwealth University using the hydrogel PEG-20k.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4476060/

http://journals.lww.com/jtrauma/Abstract/publishahead/Low_Volume_Resuscitation_Using_Polyethylene.99474.aspx

I was previously unaware of the therapeutic potential for polyethylene glycol and remain uncertain about the “cell impermeant” rationale. Low volume hypertonic and/ or low volume hyperoncotic resuscitation have long had appeal but I am afraid the Michel-Weinbaum model predicts they will not have as much effect on circulating volume as we had hoped. Since my own experiences with septic shock and hypovolaemic shock swine in Glasgow in the 80’s I was impressed that death did not always occur at the haemodynamic nadir, rather the animal would often seem to be improving when death occurred. I therefore suspect outcomes can be improved with something like adenosine magnesium lidocaine https://www.ncbi.nlm.nih.gov/pubmed/23846412.

This is a thorny issue for the Military who need a morale-boosting low weight life preserver in the field with the troops. I can understand their dismay to be told that 250ml normal saline is probably just as effective as “RescueFlow” or any other unproven product. Rapid withdrawal of blood volume as used in these experiments is a wonderful way to bring about autotransfusion/ negative Jv/ reabsorption but as we know from Levick & Michel 2010 the initial reabsorption soon (maybe 20 minutes) gives way to no-absorption steady state equilibrium. This study therefore exploits the transience of acute reabsorption to put the ‘volume expansion’ capability in the best possible light. Real life trauma is associated with sympathetic overdrive, pain, tissue injury and haemorrhage rate proportional to intravascular pressure. Reabsorption as maximised in this study design just won’t happen. The study also raises the Colloid Delusion (anaemia disproportionate to resuscitative efficacy) and the Colloid Paradox (not all colloids exert oncotic force in the way we’d expect). I am not sure that PEG is unique when we consider lower molecular weight fractions of dextran or modified fluid gelatin should bring about similar ‘multiple osmotic gradients.’
Fig 2 suggests to me that the anti-hypotensive effect of PEG was down to an effect on systemic vascular resistance, plasma density or plasma viscosity, as cardiac output normalisation was delayed after blood pressure restoration. It is interesting that Starling and his Great War MRC colleagues understood that ‘colloids’ biophysical benefits might be more than just COP. Looks like we have some interesting conversations ahead!

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