Tom Woodcock: The Revised Starling Principle and The Glycocalyx! #FOAMed, #FOAMcc

Screen Shot 2016-08-05 at 11.57.11 PM

So today, I had the chance of having a private tutorial with Dr. Thomas Woodcock (@thomaswoodcock) about the glycocalyx and the revised Starling principles.  For anyone interested in fluid resuscitation, this is an area you have to delve into. The basic principles we all learned (which are still being taught) are basically the physiological equivalent of the stick man we all started drawing as toddlers: overly simplified and far from an accurate representation of reality.

Now my first disclaimer is that I have been a colloid supporter for many years. My physiological logic for that had been to minimize the crystalloid spillover into inflamed/septic areas, particularly the lungs and abdomen, when those are the septic sources. However, I was likely misled by my education and lack of knowledge about the endothelium.

So I stumbled upon the whole glycocalyx thing a couple years ago, and this prompted me to try more enteral fluids – the only way fluids normally ever enter the vasculature – but little else. Aware that it’s there, but unsure what to do about it.

Now a year and a half ago, Andre Denault, my closest thing to a mentor, casually dropped the line to me about albumin not working. “Don’t use it. It doesn’t act the way we think it does.”  But it was a brief chat, and I didn’t get to pick his brain about it.  Just a few weeks ago, I discuss with Jon Emile (Kenny), and he’s coming to the same conclusion.  Damn. I’m finding it a bit harder to hang on to my albumin use, which is beginning to look a bit dogmatic and religious.

Here is Jon-Emile’s take on it – a must-read.

Here is Tom Woodcock’s site and article – another must-read.

And here is my discussion (in two parts) with Tom (to skip the silence, skip forward to about 30 seconds into each – sorry my editing skills are limited!)

 

Bottom line?

Probably stick to isotonic crystalloids, and some hypertonics.

 

Love to hear some thoughts!

Cheers

 

Philippe

 

 

The NYC Tracks with Jon-Emile: The Glycocalyx – The Next Frontier. #FOAMed, #FOAMcc

I was really psyched when Jon-Emile mentioned he would like to talk about the glycocalyx.  I first blogged about it here, basically when I stumbled on the extensive literature on this huge organ we have been completely ignoring in terms of physiology and therapeutics. It lines our entire endothelium, which is where most of our therapeutic interventions go, and we only heard of it in passing, possibly in histology class as med 1’s.   Hmmm.  Anyhow, here, Jon-Emile and I talk about it a little, discuss possible clinical implications, but more importantly Jon mentions the relatively new blog of Dr. Thomas Woodcock (@thomaswoodcock), http://www.fluidtherapy.org, who is one of the pioneer clinicians who have studied the glycocalyx, and who is now trying to bridge the bench to the bedside.

I’ve been fortunate enough to get in touch with him and we’re planning to record some discussions soon.

So, in my view, the glycocalyx is a formidable force we have been ignoring, and have been damaging often with our interventions. I’m hoping to see some developments allowing glycocalyx assessment outside of the labs in order to give us the tools to reassess every fluid in terms of the relative damage it does to what is essentially the gatekeeper between the blood and the tissues.

Love to hear some comments!

Here is the chat with Jon:

 

cheers

 

Philippe

Post-Arrest BP Study by Young et al (Resuscitation) – interesting & important, but not yet an N=1 answer! #FOAMed, #FOAMcc

Happy New Year to all!

So trying to catch up on some reading, here is an interesting paper I came across. Young et al did a retrospective study on post-arrest BP, in an attempt to answer the very pertinent and important question as to whether or not a higher MAP may confer better neurological recovery, which is a very sensical hypothesis. After all, a brain with potential swelling, both of tissue and endothelium, may “need” a higher BP. Some societies have advocated for a higher MAP than is usually targeted (i.e. 65) and in studies this has been anywhere from 60 to 100. In their particular institution (Vanderbilt) the protocol aimed for 80-90.

Here it is:

Young et al RESUS

So what did they find?

Basically, they were unable to demonstrate that a higher MAP – in this case defined as achieving 80 mmhm – improved anything, with a follow up to 3 months. There was also no increased mortality related to the use of vasopressors.

So, why might this be? Well, I think there are a couple of important principles to review, especially for the novices reading this.

1. Pressure does not equal flow. The relationship between pressure and flow is a complex one and depends on the interaction between the pump (CO) and the circuit resistance (SVR). Pressure rises when resistance is increased, output is increased, or both. If resistance is increased without increasing output – or by a disproportionate increase in resistance vs output, flow decreases. The effect of vasopressors such as norepinephrine is complex, with both vasoconstriction and increased cardiac output (both via beta stimulation and via increased venous return), and depends on volume status, alpha sensitivity and the recruitable cardiac reserve.

So…? This means that on the surface, a BP number tells you little about flow. The same MAP may represent a highly vasoconstrictor, low-flow state, or a normal flow state. Obviously, a certain minimum pressure is required, to drive the flow from artery down thru the capillaries, but what that number is is unclear. So when looking at any study using simply MAP without another assessment of flow, one cannot draw a conclusion that improving hemodynamics may not help the situation.  How does one assess this – in all likelihood  an integrated approach using ultrasound (volume status, cardiac function), tissue saturation (cerebral/somatic oximetry) and possibly other technologies, including simple physical exam looking at skin mottling.  This type of information could categorize patients into flow categories and make results much more interesting and applicable.

Note that this isn’t really criticism on the authors – it would be impossible to do this on a retrospective study, but simply food for thought for further studies to come.

2. The N=1 principle: remember that we are never treating hundreds of patients at once, and we do not have to decide what is best for most (which is what an RCT generally answers) but what is best for the one patient we are treating.  Hence, looking at any one patient and saying that the target BP should be 65 vs 80 based on this study is incorrect.  What we should be saying is that aiming for a higher MAP may not be necessary if we feel that the patient is well perfused at 65. How each of us figures that out will depend on individual skills and available technologies, but to simply aim for 65 without further thought and assessment is relinquishing your MD in favour of the printed word, essentially what any paper protocol could do.

In the next post I’ll discuss the use of tissue oximetry and how it can be used as part of a strategy to optimize vasopressor use and MAP targets.

 

Thanks and love to hear your opinions!

 

Oh, and don’t forget to register for CCUS 2015 at http://www.ccusinstitute.org, and for more info at http://wp.me/p1avUV-bh.  In those couple of days, Paul Marik, Scott Weingart (@emcrit), Josh Farkas (@pulmcrit), and a bunch of other totally amazing speakers will be talking about this stuff, and more!

Philippe

A Bedside Ultrasound Case & Poll: All Infiltrates are not created Equal: A Follow Up! #FOAMed #FOAMcc #FOAMus

Ok so so far, the votes show the following:

CHF 52%

PE 26%

Pneumonia 21%

So, as most of you had figured out, the fever and white count turned out to be fairly insignificant.  I started diuretics on him and stopped IV fluids (in truth, he spent a few hours still receiving IV NS at 100cc/hr as it sadly slipped by me – I know… NS to add insult to injury).  I also stopped antibiotics to the alarm of some, but keep in mind we have a lot of c.difficile in our institution, and I did not believe the had CHF AND a significant pneumonia (that would go against Occam’s razor…). He was not septic, and another discrepancy that led me away from the diagnosis of pneumonia is that a patient with significant bilateral infiltrates due to pneumonia is sick: toxic, dyspneic, fulfills Scott’s LLS score of 1 (Looks Like Shit – range 0 to 1).

Within a few hours and perhaps a negative balance of a liter or so, he feels much better. Here is his IVC at that point:

36 hours later, his CXR is clear and he is off O2.

Angiogram turns out normal – as anticipated – EKG only ever had some vague non-specific ST abnormalities. He likely had a viral cardiomyopathy – some ancillary tests still pending (HIV, etc), but is to be discharged soon.

For those who voted pneumonia, certainly initially it could not be ruled out, only the clinical evolution made it highly unlikely as a significant player.

For those who felt this represented pulmonary embolism, remember that the primary hemodynamic mechanism will be right heart failure, hence the RV would most likely be as large, and potentially larger depending on the severity of the embolism. Again, this cannot be ruled out by bedside ultrasound, it can only be ruled out as a main cause of respiratory failure. Also note that the chest xray is generally normal, or may show the peripheral wedge shaped infarct (Hampton’s hump). Bilateral infiltrates would not be the rule. But it’s always a good thing to keep it in mind!

Bottom Line?

I think this case illustrates well the limitations of physical examination, and although more commonly, pneumonias (especially in the elderly) get digressed because they “had crackles,” sometimes, patients we might not expect may have CHF.

From the moment one notes a large, plethoric IVC, one should anticipate downstream pathology of some kind (overzealous iatrogenic fluid overload being the exception), whether tamponade, pulmonary embolism, LV failure, pulmonary hypertension, but something.

Hence, in this case, bedside ultrasound proved invaluable. After all, he was recieving less-than-optimal therapy for CHF: fluids and antibiotics… This may be a case that would have proceeded to “ARDS”, and although I don’t doubt that at some point along the line, an echo would have been done, the delay may have had consequences. In our center, no one gets into the ICU without at the very least a cardiopulmonary bedside ultrasound. It is done routinely, not only for specific indications – the real indication is having a patient in front of you.

Please don’t forget, if this is up your alley, don’t miss CCUS 2015: Way Beyond EGDT and ACLS!!!  #CCUS2015

cheers!

Philippe

 

Jon Emile says:

Great case, great windows and images. I agree with your management totally. I do recall once, however, having a patient admitted for heart failure following a bedside TTE performed by a great resident, unfortunately [and in retrospect] the patient likely had a septic cardiomyopathy. The patient felt great with diuresis, but then his BP crashed as the sepsis took hold.

Recall the classic paper by Parrillo NEJM 1993 who looked at the left ventricle during the acute phase of septic shock and found LVEDV to LVESV values of 225 ml to 150 mL. The EF was in the low 30s. During the recovery phase, LVEDV to LVESV was 150 to 75 mL and EF of 50%. He noted that dilation of the left ventricle seemed to confer a mortality benefit, & that this may be a compensatory response to maintain stroke volume. This may be more striking in young patients as yours. When I first read your case a mycoplasma peri-myocarditis came to mind [I treated a case of this as a resident in the Manhattan VA]. The classic finding in this disease being bullous myringitis.

Thanks for the awesome echo videos!

 

Great point Jon!  Septic cardiomyopathy – which is very common – is definitely something to keep in mind. Indeed the LV dilation noted by Parillo would be a sensical adaptation to limited contractility. I remember seeing a particularly impressive case in a young woman with significant dilation and an EF in the 15-20% range, with incredibly rapid recovery to the 40’s and 50’s  by a day later. I’ve yet to see septic cardiomyopathy happen, however, in a patient who isn’t that sick, i.e. no pressors, no acidosis, etc…

Great point about mycoplasma, which was brought up by our ID consultant at first, but who also agreed he wasn’t that sick and agreed to stop once noting the CXR had cleared with diuresis.

 

Thanks for reading!

Limited EGDT in Zambia Study: Salt Water Drowning Syndrome… #FOAMed, #FOAMcc

So in this month’s issue of Critical Care Medicine, an interesting article was published, where investigators took a (necessarily) simplified version of EGDT to Zambia and applied it to septic patients. It turned out they had to stop it early due to an excessive number of cases of respiratory failure in the treatment group.  The difference was – you guessed it – they got “aggressive” volume resuscitation – up to 4l in the first 6 hours – guided by JVP assessment, and blood and dopamine if needed.

Simplified_Severe_Sepsis_Protocol___A_Randomized.1

The amounts received by 6, 24 and 72h were 2.9, 3.9 and 5.6 l for the treatment group vs 1.6, 3.0 and 4.3 l.

Now lets keep in mind that the patients, for the most part, did not have access to critical care, so the limited resources for ventilatory support made stopping the trial a bit early the only reasonable thing to do. Mortality in the treatment group was 64% and control 60%. High numbers, but this is explained in part by the prevalence of HIV (80%) and TB (37% of the HIV positive patients), so this data can’t necessarily be extrapolated to all populations, but to me, this is physiological support for the concept that aggressive fluid resuscitation – as I have stated in prior posts/podcasts – is most dangerous in those patients where the septic source – presumably “leaky” is ill-equipped to handle extra-physiological fluid.  In these patients, as Myburgh states in a sepsis talk, “noradrenaline is the fluid of choice,” and although perhaps a bit tongue in cheek, this certainly speaks to my beliefs of resuscitating to euvolemia rather than to the lack of volume responsiveness (http://intensivecarenetwork.com/myburgh-john-beta-blockers-and-sepsis/).

Additionally, these patients were not hypotensive, and lactate was not available – local limitations of medical system. Hence the definition of severe sepsis triggering aggressive fluid resuscitation was based  on SIRS type criteria, rather than some form of volume assessment.

 

Bottom line?

Be cautious in aggressive fluid administration in pulmonary sepsis. What, I really dislike when people say “be careful” or “be cautious,” because let’s face it, that doesn’t really mean anything, does it?  It doesn’t tell you what to actually do… We are frontline clinicians, so I’ll say to limit fluid resuscitation in pulmonary sepsis.  2 litres up front?  Probably ok so long as I have a varying, mid-size IVC (maybe 10-15mm – arbitrary and chronic pulmonary disease and hypertension have to be factored in) and a decent heart, but I don’t want to get to the point of no longer being fluid-responsive. Rather, go to pressors a bit earlier, perhaps, and no need for ongoing “maintenance” fluids at 100-150 cc’s an hour – remember that 80% of this wonderful therapy ends up where we don’t want it to.

 

cheers!

 

Philippe

PS for awesome talks by amazing speakers, don’t forget to register for CCUS 2015!!! For more info: http://wp.me/p1avUV-aU and register at http://www.ccusinstitute.org

Venous Hypertension: The Under-Appreciated Enemy…A Tale of Nephrologists, Neurosurgeons and Andre Denault…and a podcast. #FOAMed, #FOAMcc

So, some of you may have seen one of my earlier posts about the myth of low-flow renal failure in CHF (http://wp.me/p1avUV-2J), and be aware of my growing conviction that elevated venous pressures – too often sought after – are actually fairly nefarious.

So a couple of recent and very interesting pieces to add to the puzzle. First, I listened to an awesome podcast about

ICP by Wilson (http://intensivecarenetwork.com/wilson-monro-kellie-2-0/) which is an absolute MUST LISTEN to anyone in acute care.  One of those moments where all of a sudden someone shines a light in a dark corner you’d never really paid much attention to. Really, really cool and game-changing, at least certainly in the physiology model I play with in my head every time I deal with a patient who is genuinely sick.  In a nutshell, just to make sure everyone actually goes to listen to it, Wilson explains how you can get venous hypertension simply from increased cerebral blood flow… And we happen to be faced with one of the most common causes of increased CBF almost every day: hypoxia.  So when you are dealing with neurological injury (CVA/SAH/post-arrest), the danger of hypoxia (remember the concept of avoiding secondary injury of hypoxia, hypotension and hyperthermia?) lies not only in the obvious cellular lack of oxygen, but also that it is the most potent stimulus for increased CBF, and the main issue being that our venous system is simply not designed to accommodate that kind of traffic, resulting in venous hypertension without (yet) truly elevated ICP.

I’m also faced with the recurrent problem of having to be somewhat “rude” when not following suggestions from nephrology consultants in some of  my ICU patients, when they advise fluids or holding diuretics in patients with renal failure AND elevated venous pressures (as assessed by a large, non-varying IVC – in the absence of reversible causes such as tamponade, tension pneumo, etc…).  It isn’t their fault. They aren’t looking at the venous system (not bedside sonographers yet – “looks dry” on exam/gestalt is as much as you’ll get), and they don’t hold venous hypertension in high (or any) regard (yet, hopefully).

So I was totally psyched when, during a really cool conference (#BMBTL) organized by @EGLS_JFandMax, my highly esteemed colleague and friend Andre Denault (not yet on twitter…working on him) gave a talk – here is a segment:

And here is the article he is referring to:

Fluid+balance+and+acute+kidney+injury

So it isn’t like this is unknown, it simply isn’t at the forefront of our clinical mind-set, for the most part. Congestive renal failure and congestive cerebral failure are simply not things we routinely diagnose, though they MUST be just as as prevalent as congestive heart failure, which we all clearly believe in…

So just another angle to keep in mind, both when resuscitating and when managing patients with organ dysfunction of almost any sort…

 

Love to hear your thoughts!

…and if you like this kind of stuff, if you are an acute care doc, you’ll want to come to CCUS2015! http://wp.me/p1avUV-bG

Philippe

 

Jon-Emile Kenny (of the awesome heart-lung.org fame) says:

This is a great topic for review Philippe!

I have come across this problem, certainly on more than one occasion. I was first introduced to the idea of renal venous pressure and renal hemodynamics as a house-officer at Bellevue Hospital in New York. Dr. Jerome Lowenstein published work on this phenomenon as it pertained to ‘Minimal Change Syndrome.” He used to ‘wedge’ the renal vein and measure renal interstitial pressure in these patients and measured the response to diuresis. It was very enlightening and made me feel more comfortable given more diuretics in such patients. [Am J Med. 1981 Feb;70(2):227-33. Renal failure in minimal change nephrotic syndrome].

I am also glad that you bring up the cranial vault in this discussion, because I have often wondered if the encapsulated kidneys behave in a similar way. That is, as renal interstitial volume increases from edema, if there is some point on their compliance curve [like the cranium] where there is a very marked increase in renal interstitial pressure? I have found a few articles which loosely address this idea, but would be interested if anyone else knew of some. In such a situation, there would be a ‘vascular waterfall’ effect within the kidneys whereby the interstitial pressure supersedes the renal venous pressure [like West Zone II in the lungs]; then, renal blood flow would be driven by a gradient between MAP and renal interstitial pressure [not renal venous pressure]. I know of one paper that addresses this physiology in dogs, and finds the vascular ‘choke point’ to be in the renal venous system and not Bowman’s space.

What’s even more interesting, is that when renal interstitial pressure is elevated is that the kidney behaves in a sodium avid state [i.e. urine electrolytes will appear ‘pre-renal’] and this physiology has been known for at least a century!

Lancet. 1988 May 7;1(8593):1033-5. Raised venous pressure: a direct cause of renal sodium retention in oedema?

There is no good explanation as to why this occurs, but one I read is that the high renal interstitial pressure tends to collapse the afferent arteriole and the decrease in afferent arteriole trans-mural pressure which facilitates renin secretion [just like low blood pressure would]; but that would require a fairly high renal interstitial pressure unless the MAP was concomitantly low.

Again, what I must caution [and I’ve been personally wrong about this] is the reflex to give diuretics when seeing a ‘plump IVC’. When I was treating a woman with mild collagen-vascular-related pulmonary arterial hypertension, community-acquired pneumonia with a parapneumonic effusion and new acute renal failure, I assessed her IVC with ultrasound. It was plump an unvarying. I lobbied the nephrologist to try diruesis based on the aforementioned reasoning, but was very wrong. Her kidneys took a hit with lasix. What got her kidneys better was rehydration. In the end, what happened was her mild PAH raised her venous pressure and the hypoxemic vaso-constrction from her new pnuemonia only made that worse. Her right heart pressures, venous pressure and probably renal venous pressure were undoubtedly high. But I didn’t take into consideration her whole picture. She had a bad infection, had large insensible losses and had not been eating and drinking. She was hypovolemic, no doubt, despite her high right heart pressures. Fortunately, her pneumonia resolved and fluids brought her kidneys back to baseline.

Thanks again for another thought-provoking topic

 

dr.uthaler says:

hi, i am an anaesthesist / intensivist from austria. very interesting topic. at the esicm meeting last month in barcelona there was a very good session about hemodynamic monitoring focusing on the right heart and the venous system. the lectures about the guyton approach to fluid management were a big eye opener and certainly changed my approach to patients in the real life icu world. what i always do now is to correlate the cvp with the morphology of the right heart. lets say i have a cvp of 5 with a large right ventricle then i don’t hesitate to give diuretics. i really can’t understand how recent guidelines (surviving sepsis campaign) can still state a cvp of 10-12 as a target value ! new german s3 guidelines on fluid management at least advise not to use cvp for hemodynamic monitoring. guess who was against it? the german sepsis society, probably because they didn’t like to upset their friends from the surviving sepsis campaign group 🙂 let me send you a link to a very good article: Understanding venous return: Intensive Care Med. 2014 Oct;40(10):1564-6. doi: 10.1007/s00134-014-3379-4. Epub 2014 Jun 26. i went through some of the cited articles – awesome information! thanks for the interesting discussion and keep on posting !

Sounds like a good session!  I cannot understand why CVP remains in guidelines when there is clear, irrefutable evidence that it does not work to estimate either volume status or responsiveness.   As you say, other, more physiological information renders CVP irrelevant.  I have not used CVP in years. Thanks for the reference, will make sure to check it out!

thanks for reading!

Philippe

The ARISE Trial: Sealing the Deal. #FOAMed, #FOAMcc

So I’m putting this up cuz I had a few people ask me to, but in truth I don’t think I have anything really groundbreaking to say, nor do I feel the need to repeat what Scott (emcrit.org) and the Bottom Line crew (wessexics.com) have already broken down.

I would just caution the following, as I did a few months ago with PROGRESS, that not all usual care is of the same level (and I’m not talking about the community vs academic centre necessarily) and you all know your institutions, so its up to everyone to judge whether they are better off sticking to their current (likely EGDT-based) protocols or not.

Anyhow, here it is:

 

Don’t forget:  CCUS 2015 registration opens soon!

see http://www.ccusinstitute.org or http://wp.me/p1avUV-bh for more details, its gonna be awesome!

Fluid Responsiveness: Getting the right answer to the wrong question. #FOAMed, #FOAMcc, #FOAMus

Let me start with a clinical scenario: you have a 68 year old male in front of you who is intubated, has bilateral pleural effusions, pulmonary edema, a bit of ascites, significant peripheral edema, elevated CVP/JVP/large IVC, and a moderately depressed cardiac function.  What is the diagnosis?

If you said CHF, you might be right. If you said post-resuscitation state in a septic patient, you might equally be right. Hmmm….

So as any self-respecting FOAMite knows, there is an ongoing and endless debate about fluid responsiveness, how best to detect it, what exact percentage of some variation represents it – is it 9% or 13% – and everyone has the way they swear by.

Well, I think the entire premise behind this is essentially flawed.

The fact that this is the first question implies that the answer should radically change management (eg giving or not giving fluids “generously” – yes, the quotes imply facetiousness).  Basically, that you should stop giving fluids when your patient is no longer fluid-responsive. The implication is that fluids is a better, safer, healthier, more naturopathic, eco-friendly and politically correct therapy than any other option.

I think we should reflect on that a little.

If you put some faith into normal physiology, you have to acknowledge that the only situations in which our cardiopulmonary system finds itself nearly or no longer fluid responsive are pathological: CHF, renal failure, etc. None of those are healthy. None of those are a bridge to healing.

What do we do when we are hypovolemic?  We vasoconstrict, stop peeing, try to drink a bit (if at all possible) and slowly replete our intravascular space via the portal system. We might build up a little lactic acid (helps feed the heart and brain – yup, nothing toxic about it), but we get over it.  Of course, if we lose too much, the system fails and we head to meet our maker.

Now, having remembered that, why do we feel (and I say feel because the evidence isn’t there to back it up) like we have to get to pathological levels of intravascular venous pressure to fix the problem?  Especially when the problem at hand isn’t primarily hypovolemia, but mostly vasodilation, with possibly a relative hypovolemia in part related to increased venous capacitance.

The real question is: does my patient really, truly need a lot of fluid?

And here is the catch: just because someone is fluid responsive doesn’t mean that they need any, or that it is the best thing for them. Whoa… Heretic… I thought “aggressive fluid resuscitation is the cornerstone of resuscitation in sepsis.

I think that answer is relatively simple.

No matter which method you are using (mine is IVC ultrasound: -https://thinkingcriticalcare.com/2014/04/01/the-ivc-assessment-by-bedside-ultrasound-lets-apply-some-common-sense-foamed-foamcc/), if you are deciding based on a millimetre of diameter, or a couple of percentage points of variation whether or not to give liters of crystalloids to your patient, there is no truth to that in the individual patient. Trying to figure out the tiniest of differences to decide our therapeutic options is, in my opinion, a huge waste of time with no scientific basis in the one single patient you are treating.   It’s like haggling for a dollar on a hundred dollar item in a flea market: you’re missing the boat.

“85% of patients with a IVC/SVV/SPV/PLR of …. are volume responsive” or something of the sort does NOT apply to the one patient you have in front of you as a recommendation for fluids. You have to make a complete clinical picture of it – feel the belly, look at the inspiratory effort, examine the tissues for edema, etc.

Grey zone it. The best we can do is a gross categorization of truly hypovolemic (need a lot), full (please don’t give me any), and “normal” which may need maybe a little, but probably not “generous” amounts. You’ll end up generously feeding the interstitial space and making things worse – and later maybe saying “oh well, I guess he/she was just so sick…”

Even if my patient is fluid-tolerant, why to we want to push him into near-pathological states? Is it just the old adage of “You have to swell to get well?”  In the light of much of our literature, I’m not sure that old wives’ tale holds a lot of water.

Are vasopressors that bad?  Not according to what we know…

At least, avoid actually reaching the point of no longer being fluid responsive. You can’t tell me you think that CHF is actually a good thing, can you?

 

Love to hear your thoughts!

 

Philippe

PS, if you like to think out of the box and rather be on the cutting edge, make sure to mark your calendar for the coolest conference in Canada: #CCUS2015….http://wp.me/p1avUV-bh

 

 

COMMENTS

SQS Replies:

Philippe,
I think your logic is sound enough, but the moat that makes it currently unassailable is that you are working in an area with no or very little data. There is clearly a reasonably well developed and continuing to develop literature around the mortality effects of excess volume. There is an older literature that suggests that our vasopressors are actually having their effect on the more normally functioning arterioles and may shunt well oxygenated blood from the well functioning cells of a tissue and to the ones that are shocked and can’t use the oxygen, anyway. At this juncture, your guess is as good as mine, as to which of these is the greater evil. Ergo, your argument is as good as any.

One thing I will say is that the patients who concern us are those in whom endotoxin, blood loss, or other factors have resulted in a shock state wherein cells and even large parts of tissues have both inadequate oxygen supply and inadequate ability to use whatever oxygen is supplied them. Any tool we have to alter this pathological state is blunt. Blood pressure? CVP? IVC size and behavior? SVI? What do any of these say about how well we are doing at the tissue and cellular level? Even the interesting markers of lactate, ScvO2, CV CO2, etc. are blunt instruments. As is our bag of fluid and as are our vasopressors. And think about our end result – “hemodynamic stability”, “better mental functioning”, “good urine output”, “feeling better”, “walking around”, “able to go back to work”. Things that are important to us and to our patient, but barely even measurable. How blunt are they?

My own approach, which I suspect to be yours, too, is to recognize that the new onset shock patient is momentarily different from the chronic CHF patient/”chronic” shock patient you describe above. We know there is an oxygen deficit, and it behooves us to correctly that as quickly as we can. We believe, with some data to back us up, that rapid correction of that deficit, to the extent that we can, can prevent the ugly chronic state. I use the blunt measures of fluid responsiveness in the first hour or two of resuscitation to ensure that the CO component of oxygen delivery is not deficient, and then I stop giving fluid. Early in the course, I am prone to rechecking “volume responsiveness” in some hours, because I know that fluid is leaching out of the vascular space and the patient has not stabilized, yet. All the while, I am highly aware that I am hoping this makes a difference, not knowing that it does. I am aware that it is rather circular to check SVI or IVC, give fluid, see a change and say, “See? Volume responsive.” And all the while knowing that every patient has his or her own line, beyond which more fluid will not be helpful but harmful. And all the while knowing that I can’t see that line, nor measure it with any tool that currently exists.

I think perhaps that we are like Phoenicians, navigating our way across the ocean by the North Star and trying to keep land in sight. We do a pretty good job of getting where we’re going a lot of the time. But won’t it be nice when we come up with GPS? Or even the astrolabe?

SQS

 

Fantastic points!

I can’t agree more. I do check for fluid responsiveness, and I do believe in rapid intervention – just perhaps not quite a vigorous and generous as medical marketing would have us buy. There isn’t more data for that than for a somewhat more conservative approach, in my opinion. Even the rate of administration is rarely looked at, just the totals. There is good animal data showing that, for instance, a more rapid rate of albumin infusion results in greater leak and less intravascular albumin at 6, 12 and 24 hours.  Little reason to think it would be any different in humans.  There is also data showing that the oxygen deficit in sepsis is not as ubiquitous as we think.

Our understanding of the septic disease state is minimal at best, and our tools exceedingly blunt, as you point out.  

GPS or astrolabe would be amazing. I’ve had a few discussions with people working on cytochrome spectroscopy – a possibility to assess mitochondrial “happiness,” which could give us an oxygenation endpoint. Then we could have a trial that might end up showing which degree of mitochondrial oxygenation is optimal, if any.

I know I am playing a bit of a devil’s advocate and that, in strict numbers, I probably don’t give a lot less fluid or a lot slower than most, but I think it is important to keep our minds open to change rather than keep a clenched fist around the ideas we have. 

When we have two docs debating whether IVC, SVV, carotid flow time (I do like Vicki’s stuff a lot) or something else, I think we are mostly in the grey zone, and the good thing is that either way, we are dealing with two docs who are aware and conscientious and doing the rest of the right things. But keep in mind there are a lot of docs out there who are in the acute care front lines who believe that bicarb “buffers” lactate. And by buffers they understand “neutralizes.”

I just hope that when the GPS comes along, we don’t lose ten years of knowledge translation time because we are still clinging to (at that point) outdated ideas like the IVC ultrasound… 😉

cheers and thanks so much for contributing fantastic material!

Philippe

Marco says:

Philippe, I really feel like being on your same wavelength when I read your posts about fluid responsiveness. I think it’s obviously easy to agree that a bleeding hypovolemic patient is fluid responsive AND needs fluids, but the more accurately I think about the physiology of fluid resuscitation when a nurse is asking me “should we give him some fluids?” the more I realise that the “grey zone” is large and its upper limit is not easily detectable. Probably if you fill your patients to the point where they are no more fluid responsive, you are sure that no more fluid is needed, but you should be able to stop a bit earlier.
Blunt instruments and measures are an issue, and integration of the data is a possible solution (at least until a GPS comes along), but critical thinking is always a valuable resource.
The more I grow old the more I become minimalist in my approach to the “chronic acute ill” patient (90% of the patients on an ordinary day in my ICU). If a patient is in the grey zone, with a reasonably good hemodynamic stability, some vasopressor support, low dose diuretics and his urine output decreases, probably the decision of giving him fluids OR diuretics would be equally harmful. When a patient is in the grey zone and your instruments are not so accurate, it’s better to keep him safely in the grey zone. When you are in the mountains, you are caught in a snowstorm and cannot find your tracks, the safest decision is to stop and wait.. or follow your GPS 😉

Marco

thanks!

You hit the nail on the head with “integration is key.

Philippe

Fluids and Vasopressors in Sepsis, Wechter et al, CCM Journal: Anything Useful? #FOAMed, #FOAMcc

A couple of articles on fluid resuscitation worth mentioning. Not necessarily for their quality, but because they will be quoted and used, and critical appraisal of the content and conclusion is, without a doubt, necessary to us soldiers in the trenches.

The first one, Interaction between fluids and vasoactive agents on mortality in septic shock: a multi-center, observational study, from the october issue of the CCM Journal (2014) by Wechter et al, for the Cooperative Antimicrobial Therapy of Septic Shock Database Research Group, is a large scale effort do shed some light on one of the finer points of resuscitation, which is when to initiate vasopressors in relation to fluids in the face of ongoing shock/hypotension.

So they reviewed 2,849 patients in septic shock between 1989 and 2007, trying to note the patterns of fluid and vasopressor therapy which were associated with the best survival.  They found that survival was best when combining an early fluid loading, with pressors started somewhere in the 1-6 hour range.  I do invite you to read it for yourself, it is quite a complex analysis with a lot of permutations.

So…is it a good study?  Insofar as a retrospective study on a highly heterogeneous bunch of patients, I think so. But can I take the conclusion and generalize it to the patient I have in front of me with septic shock? I don’t think so. In all fairness, in the full text conclusion the authors concede that this study, rather than a clinical game-changer, is more of a hypothesis generator and should prompt further study. That, I think, is the fair conclusion.

In the abstract, however, the conclusion is that aggressive fluid therapy should be done, withholding vasopressors until after the first hour.  This is somewhat of a concern to me, since it isn’t uncommon for some to just read that part…

So why is this not generalizable?  First of all, I think that the very concept of generalizing is flawed.  We do not treat a hundred or a thousand patients at a time, and should not be seeking a therapeutic approach that works best for most, but for the one patient we are treating. Unfortunately, this is the inherent weakness of any large RCT and even more so in meta-analyses, unless the right subgroups have been drawn up in the study design.

Let me explain.

Patient A shows up with his septic peritonitis from his perforated cholecystitis. He’s a tough guy, been sick for days, obviously poor intake and finally crawls in. If you were to examine him properly, you’d have a hard time finding his tiny IVC, his heart would be hyperdynamic, his lungs would have clear A profiles, except maybe for a few B lines at the right base. You’d give him your version of EGDT, and he’d do pretty well. A lot better than if you loaded him with vasopressors early and worsened his perfusion. Score one for the guideline therapy.

Patient B shows up with his septic pneumonia, also a tough guy, but happens to be a diabetic with a past MI. He comes is pretty quick cuz he’s short of breath.  If you examine him properly, he has a big IVC, small pleural effusions, right basal consolidation and B lines in good quantity. He gets “EGDT” with an aggressive volume load and progressively goes into respiratory failure, which is ascribed to his severe pneumonia/ARDS, but more likely represents volume overload, as he was perhaps a little volume responsive, but not volume tolerant. An example of Paul Marik’s “salt water drowning.” (http://wp.me/p1avUV-aD) Additionally he goes into acute renal failure, ascribed to severe sepsis, but certainly not helped by the venous congestion (http://wp.me/p1avUV-2J). If he doesn’t make it, the thought process will likely be that he was just so sick, but that he got “gold standard” care. Or did he?

It may very well be that the studied group may include more Patient A types, and less B types, whose worse outcome will be hidden by the “saves” of the As. If you have a therapy that saves 15/100 but kills 5/100 you still come out 10/100 ahead… Great for those 15, not so much for the 5 outliers.

We, however, as physicians, need to apply the N=1 principle as we do not treat a hundred or a thousand patients at a time. I would not hesitate to be much more conservative in fluid resuscitating a B-type patient, regardless of the evidence.

Unfortunately, until trials include a huge number of important variables (an accurate measure of volume status, cardiac function, capillary leak, extravascular lung water, etc), it will be impossible to extrapolate results  to an individual patient.  These trials will, I suppose, eventually be done, but will be huge undertakings, and I do look forward to those results.

So, bottom line?

It’s as good a study of this type as could be done, but the inherent limitations make it of little clinical use, unless your current practice is really extreme on fluids or pressors. What it will hopefully be, however, is an onus to do the highly complex and integrative trials that need to be done to determine the right way to treat each patient we face.

 

thanks!

 

Philippe

 

COMMENTS:

Lawrence Lynn says:

Excellent post. This thoughtful quote should be read and understood by every sepsis trialists!!

“We do not treat a hundred or a thousand patients at a time, and should not be seeking a therapeutic approach that works best for most, but for the one patient we are treating.”

This single quote exposes the delay in progress caused by the ubiquitous oversimplification which defines present sepsis clinical trials. Bacteria (and viruses) generate “extended phenotypes” which are manifested in the host. These phenotypes combine with the phenotypic host response to produce the range of “dynamic relational hybrid phenotypes of bacterial and viral infection”. These hybrid phenotypes are also affected by the innoculum and/or the site of infection (vis-à-vis, your example of peritonitis).

Certainly Wechter et al and the Cooperative Antimicrobial Therapy of Septic Shock Database Research Group should be commended for beginning the process of moving toward the study of the dynamic relational patterns of complex rapidly evolving disease and treatment.

We are excited to see the beginning of the move of trialists toward the study of dynamic state of disease and treatment. However, before they can help us with meaningful results, trialists will need to study and define the range of “the dynamic relational phenotypes of severe infection” and then study the treatment actual phenotypes. This will not be easy as these organisms have had hundreds of thousands of years of evolution writing the complex genotypes which code for the extended of human infection. Sepsis trailists need to be encouraged by clinicians to rise to the task.

The clinicians must actively teach the trialists, (as you have in your post) that we expect trails which help to identity the therapeutic approach that works best in response to the dynamic hybrid phenotype “we are treating”.

The two linked articles below explain the present oversimplified state of the science of sepsis trails and why we clinicians must teach the trailists not to oversimplify and assure that they move quickly toward the study of the actual dynamic phenotypes of severe infection.

http://www.ncbi.nlm.nih.gov/pubmed/24834126

http://www.ncbi.nlm.nih.gov/pubmed/24383420

This is a paradigm shift so we, as clincians, must act to teach trailists this move is necessary. Otherwise we will continue to be left with hypotheses, which, while nice, are not useful at the bedside.

Lawrence Lynn

 

 

Revisiting our beliefs about Fluid Resuscitation: An N=1 Podcast. #FOAMed, #FOAMcc

So if you keep abreast of the fluid literature, you’ll note that more and more logical voices are bringing up very, very valid points against the powerful cultural backdrop of aggressive fluid resuscitation in various pathologies. Paul Marik’s recent publication, a great SMACC 2013 lecture by John Myburgh, not to mention several studies and analyses (VISEP, SOAP) illustrating consequences of overzealous fluid resuscitation. On the other side of the fence, you have the guidelines of various associations proclaiming loudly that fluids are “critically important” that there is a need to be “aggressive” and “generous.”  However, scratch a little beneath the surface and find…very little besides opinion and history. Zip. Nothing.

So my aim isn’t to make anyone stop giving fluids, but instead to treat fluids as any other therapy. Carefully given and assessed rather than in hyped-up frenzy.

I invite every physician reading or listening to, for a few minutes, put pre-concieved notions aside and approach the problem from a neutral and educated point of view, and come to your own conclusion, as unbiased as possible.

So here is my little podcast.

 

cheers

 

Philippe

 

ps just as I was uploading, checked my twitter and noted a great addition to the body of analysis by Josh Farkas, check it out:

http://www.pulmcrit.org/2014/08/the-myth-of-large-volume-resuscitation.html?m=1