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

Screen Shot 2014-01-08 at 3.13.37 PM

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:

http://thesgem.com/2014/01/sgem61-blood-on-blood-transfusion-strategies-for-upper-gi-bleeds/

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

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