crystalloids

November 8, 2014

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! 

October 23, 2014

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

October 6, 2014

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

September 20, 2014

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

 

 

August 20, 2014

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

June 16, 2014

Another plea. Please stop embarassing us. #FOAMed, #FOAMcc.

Despite physiological rationale, common sense, and a JAMA article now almost 2 years old, I still sadly see most of my internal medicine colleagues still routinely reaching for (ab)normal saline.

Its embarrassing.

I genuinely feel bad recommending other fluids in consultations, or in the room of a crashing patient asking the nurse to stop the bolus of NS and change it at least to RL, because it is such a ‘basic’ intervention. Prior to the JAMA article, I mostly gave people the benefit of the doubt. Resuscitation isn’t everyone’s field of interest, nor is physiology, so I didn’t feel that necessarily everyone HAD to know this and ascribe to it. I do understand the 10 year time of knowledge translation, but that’s why #FOAMed exists, to try to cut that down.

So please, unless your goal is specifically chloride repletion, take a deep breath and release your grasp on habit and tradition, and embrace physiology (at least to some degree) and stop using NS as a volume expander whether in bolus or in infusion. RL or plasmalyte – although not physiological, at least not as biochemically disturbing as is 0.9% NaCl.

Having said that, let’s keep in mind that human fluid is colloid, whether it includes a cellular suspension (blood, lymph) or not (interstitial fluid), made of a varying mix of proteins, electrolytes, hormones and everything else we know – and some we don’t – floating around. There is no compartment that contains a crystalloid solution.

I’m quite aware that no meta-analysis has shown that colloids are superior, but it likely is just a matter of the right colloid. Resuscitating with crystalloids is kinda like throwing a bucketful of water at an empty bucket across the room. 70-80% spill, if you’re lucky. And the cleanup may be more costly than a few sweeps of the mop. This is evidence based (SOAP, VASST, etc..).

So a plea to all, spread the word. Its a simple switch. Boycott hyperchloremic acidosis at least.

For more details, here’s a link to my earlier post on NS: http://wp.me/p1avUV-5x

cheers

 

Philippe

January 29, 2014

CCUS 2014: Taking your Ultrasound Game to another level! Montreal may 9-11, 2014!

Registration is open!

For the 7th edition of our Annual Symposium, we’ve assembled a great cast of characters to bring your bedside ultrasound game to a whole new level! Whether you’re a novice or have some experience in bedside ultrasound, we’re sure you’ll find our program very interesting, as the perspective we have chosen to take is patient-based, with each lecture explaining how ultrasound findings are integrated into clinical decision-making.

First of all, it’s in Montreal, May 10th and 11th, 2014. If you’re from out of town, its an awesome city to visit, and if you’re a Montrealer, well, it’s an awesome conference at home!

Indeed, this isn’t “just” a “how-to” course – although that is what we’ll be covering in the workshops which will follow each lecture – but a “how to integrate ultrasound into your daily practice” course, so no matter what your level is, you’ll find something suited for you. The workshops will be divided into novice and experienced and with a low participant to faculty ratio, will ensure a great experience.

So what are we going to be talking about?

In the CC/ED/hospital scene:

–       the patient with chest pain, by Max Meineiri

–       the patient with CHF, by Mike Stone

–       the patient with renal failure, by Sara Sebbag

–       the patient with a swollenleg, by Michael Woo

–       what’s my patient’s volume status? By Ashraf Fayad

–       the patient with a decreased level of consciousness, by Robert Chen

–       the patient in shock, by JF Lanctot and Max Valois

–       the patient with abdominal pain, by Haney Mallemat

–       the patient with a bowel obstruction

–       the patient with broken bones: finding and freezing, by Catherine Nix

–       the patient with dyspnea, by Alberto Goffi and Edgar Hockmann (KEYNOTE)

–       the hemodynamically unstable patient: multi-modality assessment, by Andre Denault (KEYNOTE)

In the office scene:

–       the patient with a neck mass, by Sarah Sebbag

–       the patient with arthritis, by Alessandra Bruns

Here is the program:

CCUS 2014 Master Programme

Who made this up?  Our scientific committee is made up of Michael Woo, Catherine Nix, Edgar Hockmann, Alberto Goffi and Andre Denault, who is also the co-chair – with myself – of this year’s symposium.

For those of you part of the twitterverse and #FOAMed movement, you’ll get a chance to meet @criticalcarenow (Haney), @bedsidesono (Mike), @nobleultrasound (Vicki), @EGLS_JFandMax (JF and Max) and @ThinkingCC (yours truly)…and Matt (pulmccm.org) will be there to chronicle the event and bring the highlights to the #FOAMed world.

So who should come?  Anyone taking care of sick patients.  If you’re an ED doc, ICU doc, hospitalist, anaesthetist, surgeon, student or resident, this stuff is gold. Even if most of your practice is office-based, precise assessment of dyspnea, volume status and cardiac function is highly practical.

Additionally, there are several very interesting pre-congress courses taking place on May 9th, particularly the Echo-Guided Life Support course (JF Lanctot and Max Valois), a Bedside Ultrasound Course for Nurses, an Acute Care Procedures Course and a Symposium for Ultrasound Educators on how to set up training programs. All in all, a lot of great stuff.

For more details and registration, please go to www.ccusinstitute.org.  And yes, of course there are CME credits by the University of Montreal.

As I said a few months ago – well, tweeted, to be exact – if you’re an acute care MD and NOT using bedside point-of-care ultrasound, you’re stuck in the 20th century… rude, but true.

Hope to see you there!

Philippe Rola

President, CCUS Institute

January 28, 2014

Pleural effusion in the sick patient (Part 1of 3): Don’t miss it!!! #FOAMed, #FOAMcc

This, in my opinion, is an under-recognized problem when bedside ultrasound is NOT a routine part of examination of critically ill patients. I’m happy to say that as many of my colleagues have been picking up probes, it is somewhat less of an issue now, whereas a couple of years ago I’d often put in 4 or 5 pigtail catheters on day 1 of taking over the ICU.

The first and foremost reason for this is that the portable supine ICU CXR sucks at picking up the small to moderate to, yes, even the large pleural effusion.  Largely owing to the fact that many of our patients have some lung parenchymal abnormalities and to the recumbent position that causes a layering of the effusion, it is often difficult to properly assess the size of a pleural effusion.  Radiologists will usually report the presence of a probable effusion, but quantification is difficult, and physicians not performing routing bedside sonography will often realize the presence of a submassive effusion only on CT scan – after all it isn’t like you can turn and rotate your patient to percuss the shifting dullness, can you?  Not very practical.

So the following can often be seen:

pleural effusion

this is fairly large, or you might see:

pleural effusion and pneumonia

So the obvious and critical question is: when is it necessary to drain?

There are two elements to this question:

a) for diagnostic purposes: unless the diagnosis is clear (eg CHF, post-resuscitation “michelin man” patient, etc) a new effusion should be tapped.  Panapneumonic effusions, in particular, warrant ruling out empyema unless there is a compelling reason not to.  For diagnostic purposes a 22g needle usually does the trick unless you have frank pus – which generally shows up differently on ultrasound.

b) for therapeutic purposes: effusions are space occupying lesions which compress the lung and result in a variable degree of respiratory compromise, depending on chest wall and diaphragmatic compliance, as well as effusion volume.  The clinical effect is highly variable due to the above as well as the degree of parenchymal lung disease and the degree of PEEP.  In the ICU or ED, a simple way to think about it is that if your patient is in respiratory failure and has a large effusion, chances are that draining it will improve things.  It gets a little more controversial and complicated if you have a patient who is mildly dyspneic with a moderate sized effusion.

Here are a few clinical scenarios I like:

Mr. A is a 65 year old man with CHF, intubated, with large bilateral effusions. He has been aggressively diuresed to the point of his IVC being less than 5mm in diameter.  He has not been able to wean in the last 48 h.

Yes, I definitely drain this fellow. Been there and done that time and time again.  The pleural effusions are essentially the last to resolve (being the most “distal” to the circulation – vs the alveolar tissue itself) and hence can lag and cost a few more days or more of ventilation).

Mr. B is a 47 year old man with pneumonia, breathing spontaneously with a moderate (maybe 500ml) effusion. It appears free flowing and clear, he is afebrile with an improving white count, and mildly dyspneic.

Nah, I skip on this one.  If fever and WBC recur, I do a diagnostic tap to r/o empyema.

Mrs. C is intubated on PEEP 18 FiO2 85% for ARDS due to pancreatitis. She has some degree of intraabdominal hypertension (IAP 18) and has bilateral moderate pleural effusions, maybe 400-500ml.

Yup. She can physiologically benefit from decreased intra-thoracic pressure, both from the ventilatory and the intra-abdominal pressure standpoint (Remember the diaphragm is not a rigid structure so that IAP and ITP are very similar in most cases).

So is there any evidence for this?  Some. And that’s for part 2, coming within the next days. Part three will explain and show my procedure of choice for drainage.

Thanks!

love to hear what other guys’ practices are!   Apparently only about 15% of ICU guys “routinely” drain effusions.

Philippe

COMMENTS

Hi Philippe,
I am very happy to read your post tonight, bacause I am part of that 15% and luckily most of my colleagues are in the same group. I agree in particular when you say that pleural effusions are the last to resolve, being the most “distal” to the circulation. I often find patients, at a certain point during their ICU stay, be not only like a “michelin man” but also (and at the same time!) hypovolemic. I call this situation, when I try to explain it to residents, “empty in full” (maybe in english it doesn’t sound as good as in italian): we are trying with diuretics and some fluid restriction to manage those extravascular fluids that prevent weaning from mechanical ventilation, but often we get the only effect of causing renal failure rather than eliminating pleural effusions. In this case the only way is to drain.
Another important point is that bedside chest x-ray is absolutely useless when you have to discriminate between pleural effusion and parenchimal consolidation, both of them often coexisting in ICU patients.
In our routine we use 14-gauge single lumen CVCs, inserted with Seldinger technique and ultrasound assisted procedure, effective in 95% of the effusions and less invasive than a pleurocath (that we use most of the times for pneumothorax) or a real chest tube, which I keep for blood or traumatic pneumothorax.
Greetings from Italy,
Marco

 

Glad to hear it Marco!  I started with CVCs as well before we were able to find inexpensive pigtails – email me for info if you want I don’t want to “brand” these things!  They are actually really good because I found CVCs would often occlude. Patient comfort with either is so much more than chest tubes. 

Great point about the “michelin man” who is very “wet” but intravascularly dry, which we see commonly post acute phase of critical illness, especially when physicians are so keen to use crystalloids.

thanks for reading!

 

Philippe

January 22, 2014

Blood transfusion and serum S1P levels in Sepsis: a leaky proposition? (Protecting the Glycocalyx Part1) #FOAMed, #FOAMcc

So in my ongoing quest to reframe my resuscitation step-by-step, I’ve been following up on a number of leads regarding the glycocalyx, as previously stated, and John’s reference to this article in a previous comment I feel is highly relevant. So this is it:

Synergistic Effect of Anemia and Red Blood Cells Transfusion on Inflammation and Lung Injury,  Anping Dong, Manjula Sunkara, Manikandan Panchatcharam, Abdel Salous, Samy Selim, Andrew J.Morris, and Susan S. Smyth

Advances in Hematology, Volume 2012, Article ID 924042, 8 pages

http://www.hindawi.com/journals/ah/2012/924042/

S1P (sphingosine-1-phosphate) is a regulator of endothelial permeability and immune function.  Uh-oh, why had I not heard of it? Hmmm…I don’t think it was in Guyton’s or in Harrison’s…and there hasn’t been an RCT about it… Ok, that about explains it.

So here are some factoids about S1P:

–       serum levels correlate with HCT as RBCs serve as an S1P reservoir.

–       anemic patients’ S1P levels are NOT fully replenished by transfusion, especially the older the transfused blood is.

–       In fact, older RBCs may actually remove plasma S1P.

The study:

They basically took mice, and in the first group, bled them (by 20ml/kg) and looked at inflammatory markers, lung permeability and also S1P levels. That’s basically the control group, and they noted that hemorrhage significantly increased inflammatory markers (interesting in and of itself) . They then transfused these mice using wither fresh, S1P-loaded RBCs, or 14-day old RBCs, and, lo and behold, the fresh blood resulted in less inflammation, increased S1P, but most importantly, markedly decreased lung permeability. So clearly, S1P attenuates transfusion associated lung permeability.

In the next group, they injected the mice with LPS following hemorrhage, and found a synergistic effect of blood loss and LPS on inflammation and lung permeability, as could be imagined. Following the LPS, they were transfused with one of four strategies: fresh blood, old blood, fresh blood + S1P or old blood + S1P.  Well, lung permeability still increased in all groups, but least in the fresh blood + S1P, and the old blood + S1P a close second.

Note, interestingly enough, that saline alone (the “control”) also increased lung permeability, highlighting yet again that NS (and probably any crystalloid) is not innocuous…

So here we’re looking at the finer effects of transfusion, and why, against “common-sense” correcting a patient’s hemoglobin level does not seem to help in all situations.  We have understood the aging issue and loss of deformability, but it is time to take a finer look.  We are familiar – at least in concept – with transfusion-associated lung injury or TRALI, but the mechanism remains unclear.

Summary and Take-Home message:

S1P infusions in sepsis?  Maybe someday…

Yes, this is an animal study, and the results cannot be extrapolated directly to humans, but it is food for thought, as John had mentioned.  Certainly at least this should tell us to keep and ear/eye out for human work with S1P, but personally, it will make me even more comfortable in not transfusing my septic patients with hb’s in the low 70’s and maybe even high 60’s (try repeating the cbc, more often than not comes back a couple points higher and you can avoid transfusion), and for those who are a little more aggressive with transfusion, maybe this should make them think twice…

I’ll add what I can dig up on human S1P studies soon.

cheers!

Philippe

January 10, 2014

Transfusion and the Glycocalyx: John strikes again! #FOAMed, #FOAMcc

A great surprise this morning:  a comment from John. Yup, THE John. So taking a page out of Scott’s book, I thought it would be worth sharing with everyone as its own post, as opposed to just a comment. I think this is must-read material for everyone.

So without any further adue:

“I thought I might add some quirky ideas to your discussion.

We are now getting familiar with the concept of endothelial cells covered by a surface glycocalyx layer, that forms part of the barrier and mechano-sensing functions of the blood-tissue interface. We have discussed in some detail, the role of the glycocalyx in preserving endothelial integrity. I am gonna try and add a bit more spice into the whole transfusion drama.

In recent times, we have started talking a lot about a bioactive phospholipid called sphingosine-1-phosphate (S1P), as a crucial element in preserving vascular barrier integrity by ‘protecting’ the Glycolcalyx. (Most geeky papers on TRALI and other transfusion related complications do mention it).

Because albumin is one of the primary carriers of sphingosine-1-phosphate (S1P), it is possible that S1P, acting via S1P1 receptors, plays the primary role in stabilizing the endothelial glycocalyx. Infact, antagonism of S1P1 receptors have been shown to cause widespread shedding of the glycocalyx, as evidenced by increased serum concentrations of Heparan sulphate and Chondroitin sulphate. (This might probably be one of the mechanisms how albumin is glycocalyx friendly).

RBC transfusions are a double edged sword…..especially in situations of acute anemia as in post hemorrhagic situations ( major GI bleed or trauma.)….I totally agree with you in that the two are conceptually very similar.

Erythrocytes have been identified as an important buffer for sphingosine-1-phosphate . In mice, depletion of plasma S1P by genetic inactivation of S1P synthesizing enzymes (sphingosine kinases 1 and 2) elicits profound pulmonary vascular leak, which can be reversed by restoring circulating S1P via RBC transfusion.

In humans, hematocrit (Hct) predicts plasma S1P levels. There also seems to be a dynamic equlibrium between SIP levels of the plasma, and the circulating RBCs. It has been demonstrated that in anemic individuals, plasma S1P levels are not uniformly restored by RBC transfusion. Rather, the age of the RBC unit at the time of transfusion tended to negatively correlate with the ability of RBC transfusion to replenish plasma S1P. During storage, the S1P content of human RBC markedly declines, likely due to enzymatic degradation. Because erythrocytes serve as a buffer for circulating S1P, aged RBC with low S1P content may be incapable of restoring plasma S1P levels and may actually remove S1P from plasma, which in turn could contribute to increased endothelial permeability, capillary leak, and infiltration of inflammatory cells.

I hope this partly answers your question as to how the glycocalyx may be impacted by inappropriate and irresponsible transfusion triggers. I agree that these are all very novel ideas and as such, exist in the realm of experimental clinical physiology, but my gut tells me that the delicate Glycocalyx may hold the clue to a lot of answers to questions that have plagued us for a long long time!

Cheers,
John from India…”

So first of all, thank you very, very much for reading and taking the time to comment and enlighten us.

As John says, this is still in the realm of experimental physiology, but I think there are a lot of situations we are faced with, perhaps grey zone areas where we debate two potential therapeutic avenues, where we can use some of this data. We might debate giving that extra bit of fluid, or debate crystalloid vs albumin, or blood or no blood with an Hb of exactly 70, and I think we have to start weighing in some of this physiological data, even if it isn’t “evidence-based-by-RTC” to help guide these decisions.

The more I look into it the more it seems that our interventions – particularly fluid resuscitation, needs to be reassessed from the ground up both in nature, quantity and rate of infusion while measuring glycocalyx damage – e.g. biomarkers such as S1P, heparan or chondroitin sulfate, etc…

I’ve previously posted and podcasted about my general strategy for fluid resuscitation, and I am definitely in the process of revising it, still unsure what is best. I’d love to hear how John resuscitates his patients…

thanks!

Philippe

Other Comments:

Mystery John has an uncanny ability to describe complex physiology in the simplest way possible. I am very interested in digging more into his predictions of the possibility of aged erythrocytes removing S1P from circulating plasma.

Dr. John, if you’re out there, could you point us all to some of these studies you’ve mentioned? Any good S1P review papers you’d recommend to those, like me, who are S1P novices?

Thanks for your input! It was a pleasure.

Warm regards,

Derek

Thank you Derek, for the kind comments…. I think the concept of S1P is still in the process of evolving and assuming a definitive shape, so a good review might be hard to stumble across.

A good research article which cites some excellent references might be —

Synergistic Effect of Anemia and Red Blood Cells Transfusion on Inflammation and Lung Injury
— Anping Dong et al. (It is open access at http://dx.doi.org/10.1155/2012/924042).

Hope this helps……

John.

Here is the article:

924042

P