Think You Understand Fluids–Cause I don’t have a grasp yet

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John (I think he wants to remain somewhat anonymous) is a clinically-retired, still actively teaching intensivist in India. He left the following comment on my Marik Response Post:

In the last 5 years or so, we have had a better understanding of capillary fluid dynamics, particularly in conjunction with an appreciation of the glycocalyx. We now know that the glycocalyx normally ‘traps’ about a litre and half of plasma water in it (due to its hydrophilic chemical composition!) and that normally in the capillaries, there is a central moving layer of plasma and a relatively immobile layer closer to the endothelium….the bit that is bound to the glycocalyx. This explains the differences in measured capillary and venous hematocrit values, and also why Crystalloid : Colloid equivalence is 1.3 : 1 rather than 4: 1 as previously thought.

We have also acquired a better understanding of the mechanisms of edema formation in critical illness and more importantly, the magical phenomenon of improved diuresis that we have all marvelled at, during the recovery phase.

In short, we have kinda debunked the original Starling theory of fluid dynamics in the capillary.

We now know that the colloid osmotic pressure in the intravascular space will only oppose the outward movement of water, and increasing the colloid osmotic pressure by synthetic colloids will not reverse the flow and draw fluid from the interstitial to the intravascular space. ( Multiple trials , starting with the SAFE trial have proved the futility of using synthetic colloids !) What they end up doing is, probably drawing water from the glycocalyx in the intravascular space itself and dehydrating and then disintegrating this vital layer. As a result you will find a transient improvement in blood pressures, but afterwards, a lot of this fluid will track into the extravascular space. Any hyperosmolar solution can do this including Soda Bicarb….we have all seen the very transient increase in blood pressure after bicarb which has always been incorrectly attributed to ‘reversal of acidosis’…bah!!

Extravasation of fluid from the capillaries is predominantly dependant on capillary hydrostatic pressure and not on decreased intravascular colloid osmotic pressure— because we have realised that interstitial and intravascular colloid osmotic pressures are very close to each other.

The way to prevent overloading and thus extravasation would be to minimise rapid increases in capillary hydrostatic pressure. How can we do that? – By small volume crystalloid boluses and early use of alpha1 agonists—the latter work by afferent arteriolar constriction and thus minimising huge increases in capillary hydrostaic pressures. This is where Marik’s argument takes a strong foothold.

Albumin is needed for the integrity of glycocalyx, — explaining why albumin is making a comeback into our fluid armamentarium.

The lymphatics have assumed a pivotal role in the normal mechanisms that prevent edema formation. We have realised that they are a very active conduit to return of interstitial fluid to the central circulation, and they they have contractile collecting ducts and passages that are calcium dependant. They are inhibited by the terrible twins ANP and BNP—therefore shutting down in active sepsis, where the twins tend to dominate. (This also partly explains the peripheral edema commonly seen with Ca channel blockers when they are used as antihypertensives). Once the sepsis resolves, ANP and BNP levels drop and the lymphatics recover their contractile elements. All the interstitial fluid can now be returned to the central circulation causing an improved diuresis.

In any case, fluids should only be used as any other drug should be— only if needed. We need to realise that fluid requirement and fluid responsiveness are two completely different things and focus on appropriate fluid balance rather than branding it as either restrictive or liberal.

What do you think? One question that I had is are we not doing the same thing with pressors if their true first action is to add to stressed venous volume?

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Comments

  1. Awesome summary of the really dynamic and weird state of fluid homeostasis.
    There is so much understanding we get from knowing how the glycocalyx works – seems to answer a lot of long held questions and matches with recent quality data on resuscitation.

    To use a metaphor – Resus without understanding the glycocalyx is like being a gastro doc who doesn’t get the intestinal brush border function.

    I think we will learn a lot about crit care down this path of research

  2. Erik Kistler says:

    Nice description of what might be happening in septic patients. I think that we really don’t understand what’s going on in sepsis, and what is happening during one condition and at one time point and in a particular organ may not be occurring elsewhere. So blindly we go on…
    Regarding the glycocalyx – it appears to be of some importance – how much is unclear. Caveoli also may play a role with regards to endothelial permeability and like the glycocalyx their importance is unclear to me. I still think Starling forces are at play and whether the reflection coefficient is due to the glycocalyx or something else doesn’t matter to me. What one sees physically, when looking at the microcirculation in sepsis, is a whole lot of capillaries that are not being perfused. However, it’s very difficult to point to a particular event, such as a microthrombus and say “aha! That’s what occluded this capillary.” The endothelium tends to be more robust than the surrounding parenchymal tissue (at least in the mesentery/bowel) and if one looks at it using vital stains it can be demonstrated that the endothelium remains viable longer; the cells detach from one another and tend to round up, ostensibly to wait for more favorable (energy rich?) conditions. This is akin to M Singer’s idea of “hibernation” of organs in sepsis; they often come back to life if the organism survives. At any rate, our thinking is that it is the flow through the tissues that is important – whether that means more oxygen or removal of bad stuff is unclear. And colloid might be beneficial, for example, by exerting shear stress on the endothelium thus releasing more NO. I think alpha-1 agents have a role in sepsis, particularly in ‘vasoplegic’ conditions where there is a global lack of vascular tone, but to use them to shut down the precapillaries is probably not optimal. Anyway, my two cents – it could be that nothing matters in sepsis except recognizing it, getting antibiotics on board (and source control) and then not screwing it up ?

  3. Grasp this…
    http://bja.oxfordjournals.org/content/108/3/384.full.pdf+html
    Colloids don’t work in low capillary pressure states because Jv is close to zero and delta pi (oncotic pressure gradient opposing filtration) will be increased even by crystalloid resuscitation, added colloid is unnecessary. Hyperoncotic solution boluses suck water out of the glycocalyx if it isn’t already flat as a pancake and should not be given to hypovolaemic patients. Now lets talk about the J-curve and the J-point.
    Declaration of interest… my son & I wrote it.

  4. Holy C^%#@%$#!!!!!!!

    Back to the drawing board…awesome!

    Always gotta be ready to re-examine your thinking!

    Great post, Scott!

  5. Fantastic article, Tom W……very nicely put indeed.

    Like I mentioned in our previous correspondence, the RSE&GM concept helps to very nicely put a lot of our clinical experiences in context. What people need to realise is that the cellular compartment, which is where life as we know happens, depends on extravasation of Oxygen and nutrients from the intravascular space into the interstitial space from where they get into the cellular compartment along electrochemical or physical gradients. In trying to chase an arbitrary MAP number, our desperate attempt to keep all the fluid in the intravascular space by perhaps synthetic colloids and other hyperoncotic stuff, will totally oppose this ‘normal extravascular shift’ which the system tries to preserve, even in states of low capillary hydrostatic pressure. (The concept of an osmotic pressure gradient building up in low pressure states, by movement of interstitial proteins back into the sub-glycocalyx cleft appears especially clever!) . It is this normal mechanism that we would upset, by jacking up intravascular colloid osmotic pressure with the use of hyperoncotic solutions…..

    The result would be that the mean arterial pressure would be excellent, but the cells would starve. Perhaps this accounts for some of the increased mortality associated with synthetic colloids, especially starches.( even excluding the impact of their chloride load)

    It is fascinating when we start to apply this concept of glycocalyx and RSE across clinical scenarios.. For instance, the use of mannitol and hypertonic saline in treating brain edema, For years, we had believed that mannitol works by ‘sucking up’ the edema fluid from the interstitum into the capillaries and then flushing it all out as a ‘brilliant diuresis’. Mannitol also has been attributed some hemo-rheological effects as well!! However,recently we have demonstrated from serial T2 weighted MRI studies, that the ICP starts decreasing even before the cerebral white matter water content starts dropping.

    It becomes clearer when we apply RSE and GM concept to the situation. The ICP depends on cerebral blood volume and CSF volume along with whatever pathological stuff that might find its way into the cranial cavity. The blood volume would depend on plasma volume as well as endothelial surface layer (glycocalx+water) volume. Any hypertonic solution can literally dessicate and flatten out the glycocalyx very quickly, as Tom W mentions.— the RBCs suddenly have more ‘space’ to roll through — this could well be the hemo-rheological effect that we had ascribed to mannitol. With the glycocalyx flattened, the total intracerebral blood volume drops, decreasing the ICP even before cerebral white matter water decreases.

    We have to give a lot of importance to the role of lymphatics in the whole fluid balance issue. They are no longer considered a slow moving passive system… In fact, through the course of a day, the entire plasma volume gets into the interstitial space ( this is normal….think about the poor cells!) and gets returned to the central circulation by the lympahtics several times over!. For edema to develop, all it takes is for capillary hydrostatic pressures to go up and lymphatics to slow down. The role of decreased intravascular colloid osmotic pressure has probably been over emphasized.

    This is turning out to be a good topic of discussion….. let’s keep it rolling!

  6. Great article, thanks Scott!

    Who says noradrenaline doesn’t clamp down on the lymphatic system as well? It does seem to make sense – to maintain any kind of prolonged fight/flight response we’d need to balance the increased intravascular pressure with lymphatic pressure so we don’t extravasate all our blood volume before the chase is over… Perhaps lymphatic pressure is the missing piece in the MAP puzzle. So then… antibiotics & noradrenalin as an empiric package for severe sepsis? Is anyone doing this?

  7. Dr James French says:

    I just had a stroke reading this.

  8. Positive pressure ventilation raises RAP, to some extent, and therefore MSFP (for a given cardiac output). How much does a change in MSFP impact upon capillary hydrostatic pressure? It may be insignificant but I can’t find anything about it.

Trackbacks

  1. […] EMCrit continues it’s mortgage on the ‘Ripper of the Week’ spot with Think You Understand Fluids–Cause I don’t have a grasp yet. The reason that this gets here is not because I love the glycocalyx (though I do — it is the […]

  2. […] New York Sepsis Collaborative, I started to dig a little…and whoa! And then of course, then now famous expose by John (Doe?) on EmCrit continued to convince me that this is definitely something I need to pay […]

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