fluid resuscitation

January 8, 2014

“But doctor, he’s vomiting blood!!!” – The NEJM GI Bleed article by Villanueva: Yup, time to reassess transfusion in GI bleed! @FOAMed, @FOAMcc

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Last january a highly anticipated paper came out in the NEJM (http://www.nejm.org/doi/pdf/10.1056/NEJMoa1211801), which should be a game changer, given a few provisos.  Villanueva et al reported on their large (almost 1,000 patients) randomized study on liberal (<90 mg/dl) vs restrictive (<70 mg/dl) strategy.  Interestingly but no longer surprisingly, the patients in the restrictive strategy did better.

Hmmm…sound familiar?  By now everyone  accepts the TRICC trial threshold of 70 in ICU patients, but when it first came out, there were a fair bit of disbelievers and concerned health care workers.  At the time, they excluded GI bleeds and acute coronary syndromes, understandably,

So what do the numbers say?  First lets see if there was any difference in the actual treatment. Definitely. In the restrictive group, 51% of patients required transfusion, vs 86% in the liberal group.  Sizeable difference. Now in terms of outcomes:

a. rebleeding decreased: 10% vs 16%

b. 6 week survival was better: 95% vs 91%

c. less adverse events: 40% vs 48%

But you know what, even if we throw out all the above, the absence of any difference would result in the same conclusion: there is no advantage to a higher hemoglobin goal in GI bleed.

…except for this important proviso: in their institution, UGI endoscopy was performed within the first 6 hours.  Now I’m not necessarily suggesting that the results would have been any different with a real-life, “random” timing of endoscopy, but in the spirit of scientific rigour, it is important to note.

Now there are a few important points to make that are highly relevant in the whole transfusion issue.

Why is transfusion bad? For those who may not be aware, here are a couple of reasons why transfusion looks good on paper but not necessarily so good for the patients: (a) due to stored red cell loss of deformability, the capillary bed can suffer micro-occlusion, and (b) there seems to be some immune suppression related to receiving transfusion. And I don’t (yet) have a clue what it might do to the glycocalyx…

So this is the sort of situation (not uncommon even in other clinical scenarios) where the physicians and nurses breathe a sigh of relief when seeing a nice number on a paper or a screen following transfusion, but the patient’s microcirculation is actually worse off than it was.

How valid is a hemoglobin value in GI bleed?  The answer to this is why we have MD’s after our names, and hopefully live up to that. Let me give you a quick anecdote: sometime in the past year I was called on to help a sick patient in the OR, a young woman with some post-partum bleeding who remained unstable. So the anaesthetists are concerned, the OB’s are trying to fix things, and she’s pretty unstable. A quick CUSE (critical ultrasound examination) shows she has a tiny IVC (almost virtual) and a hyperdynamic LV/RV with a near-100% EFs.  They were concerned because they had already given her fluid, etc…might she have suffered an amniotic embolism? So we were reassured that her RV was fine but clearly she needed more fluid of some sort (SBP 60’s, HR 140’s).  Just at that moment a call comes thru and the OB resident declares with a smile “its ok, her hemoglobin is 105!” and for a split second, there seems to be a sense of relief in the room, which worries me even more. I remind the resident that if he bleeds fast enough, the very last drop of his blood will have a very similar hemoglobin to the one he had while quietly sipping coffee at starbucks… So although we tend to use hemoglobin as an answer to “how much blood does my patient have,” what it really says is what the concentration of red cells is in the blood that my patient has – hence a clinical assessment (preferably with ultrasound) is required to at least determine in our minds whether our patient is empty or full, and only then can a hemoglobin value be properly interpreted. I doubt I would treat the same was someone with only 2 liters of blood going around with a hemoglobin of 75 versus someone with 4 liters of that same blood going around.  In that exact moment their hemoglobins are the same, but in all likelihood, in the ensuing hours, the first will continue to drop as the intravascular volume seeks to replete itself from the interstitial space and from possible GI intake or IV fluids.  So consideration has to be given to what fluids the patient has been or is receiving.  This is why we have MDs. If it was just about using a number, the clerk could manage our patient off the computer census and consult GI. Yep, its the N=1 concept again.

GI bleed = Trauma?   Conceptually, GI bleed is not that different from trauma.  You have a breach in vascular integrity. What are the determinants of rate of bleeding? The size of the hole and the pressure gradient.  Our body will try to shrink the hole with a fibrin mesh and a platelet plug and some vasoconstriction, and hypotension will decrease the pressure gradient.  That’s why in major trauma we don’t want to “stay and play” but want to “scoop and run” to an OR while just maintaining life until someone can plug the hole surgically (just look up some of Karim Brohi’s great #FOAMed lectures), because all that medical resuscitation (big crystalloid boluses) will do is blow those fibrin meshes away and increase the pressure gradient!  So aggressive fluid resuscitation may not be the best idea in GI bleed either. And yes, I’ve used tranexamic acid in bad GI bleeders while waiting for intervention.

Philosophical rambling… 

I think most of us forget that phrase…what was it again? Primum…primum non nocere?  Oh yes, we all said it, know it, but do we really remember to apply it to everything we do, every day? And why not? Because, in our desire to help, we more often than not feel like we have to “do something.”  And in truth, so does staff, families and the patients themselves.

Conclusion:

So, how will this change my practice?  It will make me completely comfortable in allowing my hemodynamically stable and nearly euvolemic (IVC can be seen and LV/RV not just a tachycardic blur) GI bleeder to have a hemoglobin of 70. Will I insist on an endoscopy within 6 hours? Not necessarily, but I will be monitoring (as I usually do) for any deterioration to get on the phone and push a little or a lot.

What’s next…?   I’m thinking down the line we might just see small volume resuscitation (100 cc at a timewith a glycocalyx-friendly albumin), a bolus and infusion of tranexamic acid and a quick endoscopic intervention will be the way to go, while keeping a hemoglobin no greater than 70…cuz who knows, maybe 60 or 50 might be better…

love to hear what anyone has to say!

Philippe

Check out Ken and I discussing this on the SGEMs Podcast:

SGEM#61: Blood on Blood (Transfusion Strategies for Upper GI Bleeds)

January 2, 2014

CCUS 2014 – Ultrasound Enhanced Physical Examination: mark your calendars! #FOAMed, #FOAMcc

We’re in the final stretch of planning for this year’s conference, which will be totally awesome:

CCUS 2014 Master Programme

There are a couple of TBA lectures pending confirmation, as well as finalization of the pediatric side, but this should whet your appetites! Final one will be out by the end of the week!

Montreal (awesome spot to visit!) May 9th (pre-congress courses) 10th-11th (main symposium) filled with some really cool clinical lectures on how to integrate ultrasound in common and critical clinical scenarios.

The faculty is awesome:

Andre Denault, Haney Mallemat (@criticalcarenow), Vicki Noble (@nobleultrasound), Mike Stone (@bedsidesono), Edgar Hockmann, JF Lanctot and Maxime Valois (@EGLS_JFandMax), Robert Chen, Catherine Nix, Ashraf Fayad, Michael Woo and many more….

…and lots of intense workshops!

This isn’t just a “how to”, its a “how to really integrate in into daily practice.”  or maybe “how to take your game to a whole new level!”

Registration is open, and figure on the final programme to be out by the end of next week.

http://ccusinstitute.org/Symposium6.html

if you have any questions, feel free!

Hope to see you all there!

Philippe

January 1, 2014

The N=1 concept. #FOAMed, #FOAMcc

First of all, happy holidays to all and happy new year!

Following a few requests, I’m gonna put up a few words about the N=1 concept, as I think it comes up in every single therapeutic and diagnostic strategy.

We do not treat a thousand, a hundred or even ten patients at a time.  As clinicians, we deal with a single patient, with a certain pathology, and his own, unique physiological pattern of response to that pathology.

In a medical utopia, we would be able to have a precise biophysiological profile of our patient – probably including parameters that either don’t yet exist, or are on the verge of being found or invented.  We would know, for instance, the degree of glycocalyx damage, the nature of this damage, the degree of subsequent capillary leak, the specific inflammatory cytokine pattern, and thus be able to use a potential combination of agonists and antagonists to favor healing, and tailor fluid therapy to the “just right” amount, avoiding both under-resuscitation and tissue edema. This would be similar to antibiotic sensitivity testing. Who, in this century so far, would deliberately not order sensitivities, instead satisfying themselves with a positive result and happy with empiric therapy?

Just in terms of biological variability, it is impossible to believe that all patients would respond best to a single goal or therapy. How can an MAP of 65 be as good for a septic hypertensive patient as it is for a young septic woman who normally walks around with an SBP of 110? Not that I don’t use that number myself most of the time, but certainly food for thought, and something to keep in mind when treating either of those “types” of patients…

And the answer to the N=1 riddle isn’t just subgroup analysis. The questions have to be answered in prospective fashion, built into the study design. Not easy work, and especially since we don’t yet even know what the key variables/questions are… But personally, as mentioned in an earlier post, I do now suspect that the ubiquitous glycocalyx holds some of those answers.

Let’s look at the whole fluid debate through the N=1 lens: it makes no sense whatsoever to debate crystalloids versus colloids. This negates thinking and only encourages near-religious fervour amidst both camps. Rather, look at your patient. Is he truly dehydrated/volume depleted or just volume responsive on the basis of vasodilation. If we want to restore the ICF and the interstitium, then crystalloids are probably better, but if we want to restore effective circulatory volume, then some measure of colloid may help avoid excessive edema, though even this can be debated. Even more important is the composition of the resuscitation fluid. Much as we adjust our TPN, we should probably design our resuscitation fluids, rather than only using Ringer’s Lactate (I say only just to drive the point that NS should not be used as a resuscitation fluid, unless repleting chloride is specifically necessary).

Now this may sound like a rant against large trials, but it isn’t. Absolutely invaluable information can be derived from these, it is just a matter of thinking how that information can benefit the one patient you have in front of you. And this isn’t easy. You have to put together your history, physical exam, bedside ultrasound exam and labwork. You can’t just say  “sepsis? 2 litres,” or any other such recipe (aka protocols).

ok, enough for a january 1st!

 

Love to hear what anyone thinks!

 

Philippe

 

December 10, 2013

The Glycocalyx: an overview for the clinician. #FOAMed, #FOAMcc

Ok, so I’d had a couple of glimpses at articles in the past few years which referred to the glycocalyx, but, in truth, I tend to read most of the “bench” studies a little, well…quickly.  So basically, when I listened to Paul’s (Marik) recent lecture at Scott’s (Weingart, emcrit.org) New York Sepsis Collaborative, I started to dig a little…and whoa! And then of course, then now-famous expose by John (Doe?) on EmCrit continued to convince me that this is definitely something I need to pay attention to! Its not like there hasn’t already been a high level of scrutiny of the glycocalyx in the field of sepsis.  Google it. Its like a whole new world. It just hasn’t yet translated into an effective therapy, but nor has it seemed to spread into general awareness, and it seems like it’s high time it does, since it is the interface between the blood and the body – a “blood-body barrier” of sorts.

So here we go, a crash course on the glycocalyx for the clinician in the trenches…

The existence of an acellular layer lining the endothelium was described by Luft some 40 years ago (1), and in the last decade has come under scrutiny for its role in various pathophysiological states, which seems to be quite exhaustive. This has not yet translated into diagnostic or therapeutic interventions, but it seems its properties, or at least those we are currently aware of, should be kept in mind when we are faced with therapeutic choices given that some of these may have an effect on the glycocalyx.

Its existence was deduced due to the lower capillary hematocrit – meaning that the hematocrit in the capillaries, adjusted for the luminal volume, is lower than that of the large or medium vessels, implying an area where there are no red cells. This was confirmed by electron microscopy and found to be a gel-like epithelial lining which acts as an interface between the blood and the endothelial cells, of a thickness of about 0.5 um at the level of tha capillaries, and thicker in the larger vessels.

So what is it made of? Its is essentially a meshwork of glycoproteins and proteoglycans, anchored to the epithelial cells, in which many soluble molecules are enmeshed. It is important to note that there is a dynamic equilibrium between this layer and the adjacent flowing blood, which will affect the thickness and composition of the glycocalyx. The layer seems to be vulnerable to both enzymatic degradation as well as to shear forces, in variable degrees. Enzymatic removal of components seems to radically alter properties, pointing to a strong synergistic effect of the various components. It is a constantly shedding and regenerating structure.

glycocalyx em pic

EM view of the glycocalyx (reproduced with authors’ permission from Reitsma et al.)

glycocalix pic2

(reproduced with authors’ permission from Reitsma et al.)

Major components:

– Proteoglycans (protein core with chains of glycosaminoglycans) are the “backbone” of the glycocalyx, and consist of syndecans, glipicans, mimecan, perlecans and biglycans.

– Glycosaminoglycans (linear disaccharide polymers of a uronic acid and a hexosamine) are predominantly heparan sulfate (50-90%), then dermatan sulfate, chondroitin sulfate, keratan sulfate and hyaluronan (or hyaluronic acid).

– Glycoproteins are also part of the “backbone” structure and the main types are the endothelial cell adhesion molecules ( -cams, which are selectins, integrins and immunoglobulins) and components of the fibrin/coagulation system.  E- and P-selectins as well as others are involved in leukocyte-endothelial interaction and diapedesis, an important aspect of local inflammation.

– Soluble components are also embedded in the glycocalyx such as proteins and soluble proteoglycans and are important in preserving the charge of the layer and play critical roles in functionality.

Function of the glycocalyx (as far as we know…)

a. gatekeeper

It is a key determinant of vascular permeability. Partial enzymatic removal without damage to the endothelial cells themselves result in a radical change in permeability in aminal models. Charge, size and steric hindrance affect permeability. The glycocalyx has a highly net negative charge towards the bloodstream – neutralizing this induces an increase in cellular albumin uptake.

Weinbaum introduced a new model integrating the glycocalyx in the classical (but now outdated and disproven) Starling model of microvascular fluid exchange. The revised Starling principle stresses the importance of an intact glycocalyx.

Its role with cellular elements is interesting, as it contains key elements for interaction (-CAMs) but at the same time physically prevents direct interaction between cells (WBC, RBC, plt) and the endothelium. This clearly points to a pivotal role in controlling the interaction. Damage by various methods consistently shows increased neutrophil-endothelial interaction (often termed “leukocyte rolling”). It isn’t much of a stretch to see how the glycocalyx will thus be involved in the control of local inflammation.

b. mechanotransduction

The glycocalyx provides mechanical protection from shear stress to the endothelium.  Increased shear leads to upregulation of synthesis, and correspondingly, thicker glycocalyx is found in high shear areas.

c. microenvironment

Receptor binding, local growth and repair, and vasculoprotection. For instance, ATIII is bound to the glycocalyx (inhibits procoagulants), as well as superoxide dismutase, key in reducing oxidative stress and maintaining MO availability.

Clinical implications…

Now this is the real question.  I think that the first step is acknowledging the presence and importance of the glycocalyx, and trying to discern which of our interventions may have an impact.  It is quite clear that enzymes, cytokines and ischemia/reperfusion all damage the glycocalyx and result in increased cellular interaction and permeability. In a way this can explain the entire “SIRS” spectrum with diffuse damage resulting from an insult that may or may not be infectious in origin. Obviously, we know to avoid anything that might cause the above.

I think we can divide our interventions into two types:

a. those that inherently disrupt the glycocalyx –

b. those that secondarily disrupt it via another mediator – eg over-resuscitation and ANP/BNP (John’s “evil twins”) elevation causing breakdown.

Here are some interesting facts, in no particular order of importance:

a. in acute hyperglycemia and in type I diabetes, there is significant loss of glycocalyx volume.

Nieuwdorp M, van Haeften TW, Gouverneur MC, Mooij HL, van Lieshout MH, Levi M, Meijers JC, Holleman F, Hoekstra JB, Vink H, Kastelein JJ, Stroes ES (2006) Loss of endothelial glycocalyx during acute hyperglycemia coincides with endothelial dysfunction and coagulation activation in vivo. Diabetes 55:480–486.

Nieuwdorp M, Mooij HL, Kroon J, Atasever B, Spaan JA, Ince C, Holleman F, Diamant M, Heine RJ, Hoekstra JB, Kastelein JJ, Stroes ES, Vink H (2006) Endothelial glycocalyx damage coincides with microalbuminuria in type 1 diabetes. Diabetes 55:1127–1132

b. high fat/high cholesterol diet and high LDL levels disrupt the glycocalyx. The co-infusion of superoxide dysmutase and catalase with ox-LDL abolishes the glycocalyx shedding found with ox-LDL infusion only. (not exactly a big surprise, but certainly brings up a therapeutic possibility in acute coronary events, especially NSTEMIs…)

Vink H, Constantinescu AA, Spaan JA (2000) Oxidized lipoproteins degrade the endothelial surface layer: implications for platelet–endothelial cell adhesion. Circulation 101:1500–1502

van den Berg BM, Spaan JA, Rolf TM, Vink H (2006) Atherogenic region and diet diminish glycocalyx dimension and increase intima-to-media ratios at murine carotid artery bifurcation. Am J Physiol Heart Circ Physiol 290:H915–H920

c. hydrocortisone and antithrombin prevent TNF-a induced shedding of the glycocalyx. (we never really knew how steroids help in sepsis; ATIII trials failed, but were they designed with glycocalyx-sparing in mind…?)

Daniel Chappell MD, Klaus Hofmann-Kiefer, Matthias Jacob, Markus Rehm, Josef Briegel, Ulrich Welsch, Peter Conzen, Bernhard F. Becker TNF-α induced shedding of the endothelial glycocalyx is prevented by hydrocortisone and antithrombin Basic Research in Cardiology, January 2009, Volume 104, Issue 1, pp 78-89

 d. endotoxemia damages the pulmonary vascular endothelium and results in ALI (now the neutrophils can attach and activate inflammation…)

Eric P Schmidt, Yimu Yang, William J Janssen, Aneta Gandjeva, Mario J Perez, Lea Barthel, Rachel L Zemans, Joel C Bowman, Dan E Koyanagi, Zulma X Yunt, Lynelle P Smith, Sara S Cheng, Katherine H Overdier, Kathy R Thompson, Mark W Geraci, Ivor S Douglas, David B Pearse & Rubin M Tuder The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis, Nature Medicine 18,1217–1223 (2012)

e. sepsis and major abdominal surgery damage the glycocalyx (a good example of common pathway pathophysiology…)

Jochen Steppan, M.D., Stefan Hofer, M.D., Benjamin Funke, M.D., Thorsten Brenner, M.D., Michael Henrich, M.D., Ph.D., Eike Martin, M.D.,Jürgen Weitz, M.D., Ursula Hofmann, M.D., Markus A. Weigand, M.D.Sepsis and Major Abdominal Surgery Lead to Flaking of the Endothelial Glycocalix Journal of Surgical Research Volume 165, Issue 1 ,Pages 136-141, January 2011

f. molecules (eg Slit2N,  good old aPC) that enhance or preserve barrier function have shown some success in animal models. (the key might be to using a bunch of them at once, not one of them vs placebo)

N. R. London, W. Zhu, F. A. Bozza, M. C. Smith, D. M. Greif, L. K. Sorensen, L. Chen, Y. Kaminoh, A. C. Chan, S. F. Passi, C. W. Day, D. L. Barnard, G. A. Zimmerman, M. A. Krasnow, D. Y. Li, Targeting Robo4-dependent Slit signaling to survive the cytokine storm in sepsis and infl uenza. Sci. Transl. Med. 2, 23ra19 (2010).

…and this is just the tip of the iceberg. Seriously, google it…

Conclusion:

For now, it is difficult to make any hard recommendations, but it has certainly made me pause to regroup and re-strategize. I think the critical thing is to reframe our thinking and redesign our approach to be a glycocalyx-sparing therapy.

In sepsis therapy, so many molecules have failed, but little emphasis so far has been on targeting the glycocalyx, and in all likelihood, the key is not in finding the “magic bullet” but rather using multiple interventions to bolster it. One could think of this as the sepsis “chain-of-survival”, and now that we can see the complexity of the glycocalyx, it is easy to understand how no one therapy, even if it did do its job, would succeed in preventing the degradation of the other links in the chain, and fail.  In all likelihood, a successful strategy will probably involve the following:

1. fancy molecules to prevent glycocalyx damage.

2. fluid choices which are glycocalyx-friendly.

3. fluid in just the right amount (not by macro/volume-responsiveness but by micro/glycocalyx management).

4. rapid diagnosis/abx/source control, etc, all the good stuff we know about.

5. preventing hyperglycemia.

A trial like that would be a monumental undertaking. I can only hope someone does it.

My next step, as a guy in the bedside trenches and not at the bench, after gaining a modicum of understanding on the topic, will be to delve deeper into the effects of currently available fluids on the glycocalyx.  Look for a post on that in the next weeks.  As a starter, everyone should review Woodcock & Woodcock’s excellent clinical review.

And if anyone has any amazing information to share, please do!!! That’s what #FOAMed is for!!!

Suggested viewing/reading:

Woodcock and Woodcock, BJA 2012,  http://bja.oxfordjournals.org/content/early/2012/01/29/bja.aer515.full.pdf+html

Broken Barriers: A New Take on Sepsis Pathogenesis Neil M. Goldenberg,1* Benjamin E. Steinberg,1* Arthur S. Slutsky,2,3,4 Warren L. Lee2,4 Science Translational Medicine, 22 June 2011 Vol 3 Issue 88 88ps25

Click to access Science_Translational_Medicine_2011_Pathogenesis_of_Sepsis.pdf

a great article on understanding the glycocalyx in sepsis by a U of T gang!

emcrit:

http://emcrit.org/blogpost/best-fluids-comment-ever/

http://emcrit.org/podcasts/fluids-severe-sepsis/

http://emcrit.org/podcasts/paul-marik-fluids-sepsis/

all must-listen/watch material!

other refs.

Luft JH (1966) Fine structures of capillary and endocapillary layer as revealed by ruthenium red. Fed Proc 25:1773-1783

Reitsma et al, The endothelial glycocalyx: composition, functions, and visualization, Eur J Physiol (2007) 454:345–359

Zhang X, Adamson RH, Curry FR, Weinbaum S (2006) A 1-D model to explore the effects of tissue loading and tissue concentration gradients in the revised Starling principle. Am J Physiol Heart Circ Physiol 291:H2950–H2964

November 30, 2013

Bedside Ultrasound Clip Quiz #4 – #FOAMed, #FOAMcc

So you’ve been doing ACLS for a few minutes in the ED on an elderly male who collapsed at a bus stop and shocked out of VF on the scene by EMS, and when you do a 3 second pause to assess the heart, just after an epi got flushed, this is what you see in the subxiphoid view:

 

Is this a case of tamponade?

Scroll below!

 

 

 

 

 

 

 

 

Nope!  There’s no pericardial effusion, and the atria are huge!  What you do see is microbubbles from the flushed IV medication in the RA and RV, and severe LV dysfunction.   The severe LA dilation suggests at least a component of chronic overload (also supported by significant leg edema in this case). Note that you can have severe LV dysfunction (post-resuscitation myocardial dysfunction or PRMD) after cardiac arrest of ANY etiology and does not necessarily imply pre-existing LV dysfunction or predict eventual LV function.

 

 

 

 

November 27, 2013

A Paradigm shift: re-thinking sepsis, and maybe shock in general… #FOAMed, #FOAMcc

Thomas Kuhn, physicist and philosopher, in his groundbreaking and science changing text, The Structure of Scientific Revolutions, states that:

“Successive transition from one paradigm to another via revolution is the usual developmental pattern of a mature science.”

In other words, a science has growing pains and is bound to have a fair bit of debate and controversy, until a new paradigm becomes dominant.  I think that there is a current – in part prompted by the power of socio-professional media which has allowed minds to connect and knowledge to spread – that will see many of the things that are now “Standard of Care” out the door.

So first of all, the following are must-listens, the first a lecture by Paul Marik, whom I have had the chance to collaborate with in the last years and respect greatly, on knowledge, experience, and even more on his refusal to take anything for granted and being in a seemingly-constant quest for the improvement of medicine.

The second link is Scott Weingart’s take on it, which I think is equally awesome.

I think Paul is pushing the envelope in an essential way, and Scott does a fantastic job of seeing or putting it in perspective. Enjoy:

http://emcrit.org/podcasts/paul-marik-fluids-sepsis/

EMCrit 112 – A Response to the Marik Sepsis Fluids Lecture

My (very) humble opinion on this is a rather simple, almost philosophical one:  why are we seemingly obsessed with treating a predominantly vasodilatory pathology with large amounts of volume?  I’ve said this in previous posts and podcasts, but this, in my opinion, is largely cultural and dogmatic. “Levophed – Leave’em dead” is something I heard as a student and resident, and came to take for granted that I should give lots of fluid in hopes of avoiding pressors… But there’s no evidence at all to support this.  The common behavior of waiting until someone has clearly failed volume resuscitation before starting pressors befuddles me (think how long it takes to get two liters of fluid in most ERs…).  If I was in that bed, I’d much rather spend an hour a bit “hypertensive” (eg with a MAP above 70) than a bit hypotensive while awaiting final confirmation that I do, in fact, need pressors.

I strongly suspect that it’s just a matter of improving vascular tone, giving some volume (which may be that 3 liter mark), and ensuring that the microcirculation/glycocalyx is as undisturbed as possible. Now when I say it may be the 3 liters, I firmly believe this will not apply to everyone, and that it will be 1 liter in some, and 4 in others, and that a recipe approach will be better than nothing, but likely harm some.

I think that blind (eg no echo assessment) of shock is absurd, and for anyone to propose an algorithm that does not include point-of-care ultrasound is only acceptable if they are in the process of acquiring the skill with the intention of modifying their approach in the very near future.

The whole microcirculation/glycocalyx is absolutely fascinating stuff, and undoubtedly will come under scrutiny in the next few years, and it is definitely something I will focus on in upcoming posts & podcasts. Our resuscitation has been macro-focused, and certainly it is time to take a look at the little guys, who might turn out to have most of the answers. For instance, there is some remarkable data on HDAC inhibitors (common valproic acid) and their salutatory effects in a number of acute conditions such as hemorrhagic shock (Dr. Alam) which have nothing to do with macro-resuscitation, and everything to do with cell signaling and apoptosis. Hmmm…

please share your thoughts!

thanks

Philippe

November 18, 2013

Enough with the “Normal” Saline!!!!! #FOAMed, #FOAMcc

Enough with the “Normal” Saline!
So its been about a year since a JAMA article (http://jama.jamanetwork.com/article.aspx?articleid=1383234) finally showed that the downside of 0.9% saline isn’t just theoretical, but has some associated clinical morbidity (bad for the kidneys!).  Sadly enough, it still seems to be the routine fluid used for boluses. Whether the ER, hospitalist or intensivist, residents, students…it seems people are reluctant to let go.
Today, rounding in the ICU, I was changing an order for a bolus from another doc from NS to RL, and a nurse asked me why.  I gave her a capsule summary and she was in disbelief.  “Come on Phil, they wouldn’t call it normal saline if it wasn’t!”
I’m an internist by training, so naturally I grew up using NS, since that’s what all the attendings and residents used around me.  Ringer‘s was the stuff the surgeons used, so well, I guess it had to be wrong…no?
So forward to 2001 and John Kellum‘s lecture on acid-base I’ve previously mentioned, and my exploring Stewart’s Physicochemical Approach, and wait, I look at the back of a bag of NS, and find out, much to my dismay, that the stuff I’ve been using like holy water has a pH of 5.6.  And who have I been giving liters and liters of this stuff to?  Yup, mostly patients with acidosis. Hmmm. Interesting. So although I don’t necessarily advocate correcting metabolic acidosis for the sake of doing so (see my previous post on bicarb), I’m not a proponent of worsening acidosis either, even if by another mechanism.
I think there are a number of factors that have resulted in this situation.  For starters, there is the issue of false advertising – the “normal saline” monicker has been influencing subliminal thought for decades (think Malcolm Gladwell thin-slicing), making physicians feel they are giving and inherently “good” substance.  Then there’s the whole tribalism thing with the surgeons vs non-surgeons making all the non-surgeons polarize away from RL (not that RL is perfect, just a bit better, and certainly closer to “normal”). Finally, there’s this sad, sad factor that makes people, even (or maybe even more) smart people reluctant to accept that they have been doing something wrong (or, for those who are offended right now, not ideal) for a long time (I sure was) and prefer to fight it and rationalize it for a few more years until, eventually, the evidence becomes overwhelming or the changing of the guard has fully taken place.
I think what we should be hanging on to is not a drug or a fluid but rather what we learned in the first couple of years of med school: physiology.  Now mind you, at that point we (or most of us) didn’t have a clue how to use it for anything more that answering multiple choice questions, but at some point, we have to go back to it and realize that is what we should be basing our assessment of our therapeutic acts and decisions.
So…if I have a situation where I am low on chloride, I might want to use NS. But otherwise, let try to give something whose composition is a bit closer to our own than NS is.  So, for my students and residents, don’t let me see you prescribing boluses of NS.  If you really, really need to, wait until your next rotation please.
thanks!
Philippe
ps for a great review of the original aritcle, please see Matt’s on PulmCCM at :
Reply:  by Marco Vergano
Totally agree!
I have been struggling for years with the bad habit of some of my colleagues prescribing NS as the most harmless and physiologic replacement fluid. Here in Italy we don’t have such a clear separation between internists and surgeons about NS/RL choice: the bad habit of easily prescribing NS is ubiquitous.
Given the results you mentioned about the increased incidence of renal failure with NS, I am wondering if the ban on ALL starch solutions would have been necessary after the introduction of new balanced starch/electrolyte solutions.
What I really don’t like about RL is that it’s not only hypotonic, but also low in sodium. In our ICU we often have many ‘neuro’ patients (trauma or vascular) and sodium variations become a major issue. Also I prefer Ringer’s acetate over lactate on most of the patients who struggle to ‘manage’ their own lactate.
So my favorite solution remains our good old “Elettrolitica reidratante III” (very similar to Plasma-lyte).
November 14, 2013

Bedside Ultrasound: The Sluggish IVC – something to look for… #FOAMed, #FOAMcc

So take a look at this:

I’m sure most experienced bedside sonographers come across this all the time.  For those who are starting out, and until now have just been looking at size and variation, take a second to look at the flow.  You can actually see the flow stop and start, which tells you your cardiac output is bad.  It could be bad because of the RV, the LV, the pericardium, the tension pneumothorax, anything, but it’s bad.  So just in case you were only gonna look at the IVC, keep looking! You will find something abnormal downstream, perhaps that you can do something about (not fluids, though).

I have seen this disappear and clear up with – when possible – correction of the problem, back to the normally anechoic IVC we usually see.

thanks!

Philippe

ps note there is also a mirror artifact in the right lower portion of the field, making it look as though there are two beating hearts.

November 4, 2013

NEJM Circulatory Shock Review by Vincent & DeBacker: the sweet and the not-so sweet… #FOAMed, #FOAMcc

So if anyone hasn’t read it, here it is:

Click to access Circulatory%20Shock%20-%20NEJM%202013.pdf

I read the article by critical care icons Dr. Jean-Louis Vincent and Dr. De Backer with interest  as I am always keen to find out what the cutting edge is… So here is my take on their review.

The not-so-sweet:

The inclusion of CVP in the assessment. Ouch. No evidence whatsoever. Evidence for lack of correlation to fluid responsiveness… I wonder if they themselves were cringing a little about including it, particularly form the fact that they just put high vs low rather than commit to a value, which makes me think they realize it’s a bit of a trap. (It reminds me a bit of those night-time orders I still sometimes see which say if u/o < 30 cc/hr give a bolus if CVP under 12 or lasix if over 12.  So basically depending on whether that patient’s head is elevated, or if he’s turned on one side or the other, he may go from “needing fluids” to “needing diuretics”…).

The sweet:

First of all, they obviously did an elegant job on description of shock states, and particularly of highlighting the common-ness of mixed etiology shock.

I like that they admitted that the end-point for fluid resuscitation is “difficult to define.”  Any answer other than that would really speak to non-physiological thinking, as I’ve referred to in prior posts/podcasts.

Dopamine: good job on trying to take it off the shelf for shock. As far as I’m concerned, only useful when you’ve run out of norepinephrine, although there is the odd time when you have a septic AND bradycardic patient where it could come in handy…

Bringing some focus on the microcirculation: no recommendations, but that’s appropriate since there are none to be made yet, but this is where the money is in the future, as far as I’m concerned. Once we figure out how to manage the microcirculation (we do ok with the macro circulation) we might forge ahead. But good to point the finger in that direction.

The super-sweet!

I do (not surprisingly) really, really like the fact that they included ultrasound in their assessment protocol, and emphasizing that focused echocardiography should be done as soon as possible.  Very nice. Finally.

Hopefully, this pushes mainstream ED and critical care physicians to realize they need basic bedside ultrasound skills…

 

Overall, I think it is a good review, certainly worth the read for trainees. I would like to see focus on re-examining and questioning our approach, which could spur readers to embark on research with a different angle. For instance, why do we assume that we need to fill patients to the point of no longer being fluid responsive in order to avoid vasopressors? Is there any evidence for that? Not that I know of…

But, for having put an emphasis on point-of-care ultrasound, it gets a big round of applause from me!

 

Philippe

October 23, 2013

CCUS Annual Symposium 2014 – The Ultrasound-Assisted Physical Exam! stay tuned!

This year, we’re putting together a really, really interesting event.  Bedside ultrasound being a hot topic and at the brink of revolutionizing clinical examination and practice, we figured that this year, we’d go back to basics to some degree with a general ultrasound approach, but also a step further in looking at it from an integration perspective, meaning how to approach clinical problems with ultrasound as an added tool.

Talks will be clinical problem-based – e.g. the patient with dyspnea, the patient with renal failure, etc, essentially showing participants how to integrate their growing ultrasound skills into routine use.  There will be a ton of faculty led workshops to review all the basic ultrasound skills (lung, cardiac, abdominal, vascular) on live models and on advanced CAE simulators, both adult and pediatric.

Our faculty will be fantastic, including Andre Denault, Haney Mallemat (@criticalcarenow), JF and Max (@EGLS_JFandMax), Edgar Hockmann, Catherine Nix, Alberto Goffi, Massimiliano Meineri, Matt Hoffmann (www.pulmccm.org), Jeff Burzynski, Jason Fisher, Alyssa Abo and many more…

The two day core event will take place in Montreal, on may 10th and 11th, and, equally interesting will be a pre-congress set of courses on may 9th, including:

EGLS (echo-guided life support)

Focused TEE

Bedside ultrasound for nurses (vascular access, IVC volume status assessment)

Critical Care Procedures (drains, tracheostomy, central lines)

 

Registration is not yet open but will be in the next few weeks, so for anyone interested please visit http://www.ccusinstitute.org and join (it’s free!) and we’ll email you when its up and running.

Please forward/link this to all your forward-thinking colleagues~

thanks!

 

Philippe