Fluids in Sepsis: An EmCrit Webinar! #FOAMed, #FOAMcc

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So a few weeks ago Scott (@EmCrit) asked me to be part of a pretty cool webinar organized by the Greater New York Hospital Association about fluids in sepsis. The gang consisted of David Gaiesky, Emmanuel Rivers and moderated by Scott himself. And for some obscure reason, he asked me to be part of it – much to my honour (terror, also), naturally.  It was only afterwards that he told me it was to help stir the pot and be controversial, challenge the “old school” etc… He seemed to have overlooked that I am Canadian, and inherently and perhaps overly polite and considerate – at least live and in “person”!

We talk about a bunch of stuff around fluids, which, how much, how to assess, etc.

Anyhow, I hope I got a few ideas across, but it was really cool to hear that these gurus do use ultrasound – don’t necessarily strictly adhere to, for instance, EGDT, and also advocate that guidelines are guidelines and not necessarily gold standards.

Here is the link to the webinar for those interested:

 

https://t.co/dbL03Vuqlj

 

And here is the figure for the section where I refer to fluid responsiveness/tolerance:

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I further talk about this in a previous post here.

Scott and I also recorded a debrief which should be coming up in the next weeks on EmCrit – link to follow!

cheers!

 

Philippe

CCUS Institute Bedside Ultrasound Mini-Fellowships. #POCUS #CME

The personalized CCUS Institute’s Mini-Fellowships (CME-eligible) are focused on bedside ultrasound and designed to take clinicians with some degree of proficiency in basic ultrasound to a whole other level. The opportunity to follow a seasoned clinical ER/ICU sonographer and see actual cases, learn the clinical integration of ultrasound data into decision-making is a unique one, outside of a handful of residency programs whose faculty includes experienced bedside sonographers. Basic how-to courses are great, and certainly the first step for those clinicians adding ultrasound to their armamentarium, but what we have seen, sadly, is after initial enthusiasm, many don’t really pick up the probe because the confidence to “make the call” simply isn’t there. Yet.

In a sense, it’s almost as if, as medical students, we’d read Bates, practiced physical exam on each (more or less normal ) other, and were then set out to make diagnoses and treat without having residents and attendings around to confirm our findings a few times, until we got the hang of it. Hmm. That would be rough.

Some physicians are fortunate enough to practice in a center where there are a few “veterans” of bedside ultrasound and can gain some acumen that way, but others may be the ones spearheading their institution into the 21st century, and it is from the comments of several of those, attending the CCUS Symposium (2008-2014 – perhaps a return in 2017) asking for the possibility of shadowing some of us, that the Mini-Fellowships came to be.

Mini-Fellowship Structure

Montreal Mini-Fellowship: Participants shadow one of our instructors (ICU attending) during the regular working days and discuss the cases and ultrasound-relevant aspect of each case (more often than not the case in entirety), and are able to practice their ultrasound skills. The duration is flexible although we generally suggest a minimum of two or three days. Each day would usually be about 6-8 hours, some may be more.

Toronto Mini-Fellowship: Participants get a dedicated and highly experienced preceptor (Dr. Edgar Hockmann) who is not on clinical service but with access to the ICU patients, and will provide a structured and dynamic session adapted to the participant’s needs and abilities.

The case exposure will be mainly ICU as well as ER and ward patients. The focus will be on acute care issues. After two days, participants who had a basic ability in ultrasound should be fairly comfortable with assessing volume status, cardiac function, perform lung ultrasound, be able to identify and assess intrathoracic and intr-abdominal fluid collections, assess the kidneys, bladder and gall bladder, measure optic nerve sheath, assess carotid flow and some may have exposure to trans-cranial doppler. The focus may be shifted depending on a participant’s interest.

This takes place in Montreal, Quebec or Toronto, Ontario, Canada.

Participants will have the opportunity to work with handhelds, midrange and high-end ultrasound devices.

Space is limited as we can generally only accommodate 1-3 participants per month.

 

CME

So, great news, finally went thru the CME process and lo and behold, the Mini-Fellowships qualify for 25 Section 2 credits (regardless of the length) and 3 hours of Section 3 credits (per day of fellowship). For you americans:

Through an agreement between the Royal College of Physicians and Surgeons of Canada and the American Medical Association, physicians may convert Royal College MOC credits to AMA PRA Category 1 Credits™. 

Bonus!

Upcoming participants will also receive a copy of the forthcoming handbook:

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Requirements 

Please have basic experience in bedside ultrasound. We don’t want to teach you about depth and gain. We’re happy to fine tune your views but not to introduce you to the main cardiac views. It would just be wasting your clinical time. We’re here to show you how to assess pathology and integrate your findings into clinical decision-making. Take the basic group course to learn the views, or be self-taught from youtube/iphone and practicing on your patients. You don’t have to be great, but to get the most out of this experience it shouldn’t be your first time holding a probe.

Registration

email me at philipperola@gmail.com or reach out on twitter @ThinkingCC

Tuition

Montreal Mini-Fellowships: 575$ CAN / 475$ USD per day for 1 physician, 475$ CAN / 400$ USD per person per day for 2, and 400$ CAN / 350$ USD per person per day for 3 physicians (maximum)

Toronto Mini-Fellowships: 800$ per half day (4h).

100% refundable until you start. Even if you don’t show up. Really. We’re not in it for the business. We get to go home earlier if you don’t come.

Testimonials:

« I have had the chance to participate in a shadowing experience with Dr Rola at the Scarborough General Hospital ICU during two days in 2013. As a general internist and assistant program director, this experience really opened my eyes regarding the use of bedside ultrasound in general internal medicine and for IM residents. I think I would have benefited more of this experience if I had done more training previously, and I encourage future participants to do so. However, I came back from this experience with a very clear idea of the benefit of CUSE for my patients and for our residency training program. I really saw how ultrasound was used ‘in action’, in a much more realistic way than what is usually shown in CPD meetings. I also saw its limitations and the skills I needed to develop to generate good images (not something you can learn over the weekend!). Since then, I participated in formal trainings and licensing activities (more than 250 supervised US on acute care patients) and now practice bedside ultrasound autonomously. We now offer a bedside ultrasound training for our residents with the help of the emergency medicine department and an ultrasound-guided procedural simulation lab. Nothing in CPD has improved my practice and benefited the health of my patients as much as bedside ultrasound training. »

Alexandre Lafleur, MD, MSc (Ed.), FRCPC
Spécialiste en médecine interne
CHU de Québec – CHUL
alexandre.lafleur.1@ulaval.ca

“Thank you very much for the exposure and teaching offered via the CCUS “Mini-Fellowship.”  These few days allowed me to enormously improve my mastery of bedside ultrasound in clinical decision-making in critical care. I recommend the experience to clinicians already having experience in bedside ultrasound, but who feel they could benefit from the expertise of an instructor to attain a level beyond basic courses and available textbooks.”

Mathieu Brunet, MD, GP/ER/ICU, Magdalen Islands, Quebec, Canada

“The CCUS Mini Fellowship In House training is very essential in to experience the echo skills that we get from the courses,being supervised in ICU will offer the chance to be corrected and get real live practice/exposure by being at the bedside and learn what is priority in echo for the best of patient care. The in-house experience is very helpful, practical, I recommend this training to any physician involved in ER, ICU, CCU, Anesthesia and rapid response team.”

Joe Choufani, MD, Internal Medicine/Cardiology, St-Lawrence Health Association, NY

“Thanks for everything. I really appreciate you sharing your vast fund of knowledge with me.”

Sean Sue, MD, ER, Philadelphia

CME

So, great news, finally went thru the CME process and lo and behold, the Mini-Fellowships qualify for 25 Section 2 credits (regardless of the length) and 3 hours of Section 3 credits (per day of fellowship). For you americans:

Through an agreement between the Royal College of Physicians and Surgeons of Canada and the American Medical Association, physicians may convert Royal College MOC credits to AMA PRA Category 1 Credits™., #CME

NIRS-Assisted Resuscitation: Following the N=1 Principle. (Part 1) #FOAMed #FOAMcc #NIRS

So for anyone who has been reading any of my stuff, you know that I believe we best serve our patients by using the information in good evidence and blending it with bedside assessment (ultrasound being an integral part of physical examination) and physiology to come up with the best therapeutic approach to the one patient we are treating.  Contrast that to the blinded and naive belief that one protocol from one study is the best thing for all patients suffering from disease X.

So I am constantly looking for a way to fine tune resuscitation to the individual patient, given his/her particular cardiovascular function, volume tolerance (not just volume responsiveness), vasopressor tolerance (blue fingers probably mean blue livers and kidneys to some degree) and metabolic reactions.

One of my friends and mentors is Dr. Andre Denault. Absolutely incredible guy who is a complete triple threat of academia (internist/intensivist/anaesthetist massively published), experience and raw neuronal power. Throw in open-mindedness and humility (he actually once picked my brain about abdominal compartment syndrome pressure monitoring) and you have a lethal package. So after killing off the filed of intraoperative/critical care TEE (yes the leading textbook is his), he’s plunged into NIRS spectroscopy and is now dragging it from the OR to the ICU, and so in the last few years he’s put me on this trail with anecdotes and his (unpublished yet but coming) findings.

So a quick few words about NIRS (Near InfraRed Spectroscopy). The technology looks at hemoglobin saturation, and does so in a predominantly venous way. Hence this behaves similarly to a central or mixed venous gas, except at the local tissue level. A gross normal is >70% but this has to be interpreted in clinical context, along with the knowledge of simultaneous arterial saturation. Hence lower values (assuming normal arterial sats) will mean one of two things: increased demand or decreased supply. The demand issue is a clinical one. What we are looking for using this type of monitoring is decreased supply, e.g. cardiac output that is inadequate for current demands.

The information gleaned from our discussions was enough to make me get some loaner time with some devices, and that was enough to have a few clinical cases pique my interest.

Here is one:

In the ICU at Scarborough General in Toronto, I admit a lady with urosepsis on a stone-obstructed hydronephrosis. We get urology to slip in a double J, but she is still very norepinephrine-dependant. She isn’t intubated, lactate about 5 and on high doses of norepi to maintain MAP 60-65. Extremities are cold and mottled and there is mottling up to the thighs. She is awake and communicating. Over the next hour or so lactate rises to 5.5. I’m not liking this.

I put on the NIRS monitor with a cerebral lead and one on the thigh. They both read in the 50’s, somewhat suboptimal.

Bedside US reveals a good sized IVC with little variation. She’s well filled. Her LVEF is 50-60%, her RV is dynamic and with a normal RV/LV ratio. The hydronephrosis is improved on the affected side.

So I have a patient who’s adequately preloaded, without obstructive or systolic failure, who is on very high doses of norepinephrine with a rising lactate, despite source control and antibiotics. However, she doesn’t “look” that bad aside from the cold and blueish extremities…

So I decrease the norepinephrine. Systolic BP drops to 80…but…cerebral NIRS and tissue NIRS rise…now in the high 50’s. Patient remains awake and communicating. Drop norepinephrine some more. Systolic 75. Cerebral NIRS 62%, tissue 61%. Systolic 70. Cerebral 59%, tissue 57%. Back up to 75%. NIRS back up.  I finally settle on 75-80 systolic. NIRS settles in low 60’s. An hour later, lactate is 4, two hours later 2.5, then normalizes. Over that time span, the mottling gradually resolves and the urine output picks up. By the next morning she is off norepinephrine, and her BP sits around systolic 85-90 on its own. Turns out her usual BP is in the low 100’s.

I’m not sure how long – without the reassurance of improved tissue saturation – I would have been able to tolerate systolic BPs in the 70’s. Remember that lactate takes time to clear and urine takes time to make.

So this case reinforced my belief that not every patient’s needs are best met by an MAP of 65, and that targeting this may be harmful. It isn’t hard to imagine a scenario (which I may very well have pursued at a more junior stage) where further fluid resuscitation, coupled with insistence on a BP value may have resulted in iatrogenic fluid overload or Paul Marik’s “salt water drowning” (more commonly thought of as “ARDS”) and tissue ischemia/organ dysfunction (partly related to over-vasoconstriction) and who knows what outcome could have transpired… And very possibly, a bad outcome may have been blamed on severity of illness… Food for thought.

So one definitely possible use for NIRS is to find the “sweet spot” for the BP/vasopressor relationship.

More on NIRS in Part 2 in the next week or so.

Bedside Ultrasound-Assisted Procedure: Hepatic abcess drainage. #FOAMed, #FOAMcc

Hi,

Apologies for a long hiatus. Thought I’d share a case from last night. A 54 year old man had been admitted with e.coli sepsis complicated by portal vein thrombosis and multiple hepatic lesions a few weeks ago. A follow up scan by the hospitalist showed the following:

Yup, nasty. So our ICU Outreach service was called (we do all manners of procedures on the wards/er) and it happened to be me.

So 10pm I make my way with all the necessary gear (not much you can’t get done with ultrasound and caffeine!):

IMG_4242

Here is the clip:

So this is a synthesis of several US loops. The first ones simply show the lesion, which under US is clearly fluid – movement well seen with respiration/pulsation. Next you see the associated ascites and a quick peek at a subxiphoid view of the heart.

You then see the procedure itself, with a needle insertion (purposely jerky for visualization’s sake), and, following a 3 way stopcock connection, gradual drainage of the abcess.

IMG_4246

I chose to hand-drain it in this case to avoid possible blockage of the tube if simply left, since it was a small 8.5 french pigtail catheter (better for comfort). You can see that the access cavity was essentially obliterated. 400 ml or so drained:

IMG_4247

So technically this was very simple, however the one important teaching point is to pick an inferio-lateral approach, as an easier but more treacherous one – simple lateral – might result in going thru the pleural space because of the lateral costodiaphragmatic recess which extends quite inferiorly. So when picking the entry point, it is important to make sure it is below the diaphragmatic insertion. Otherwise the potential to seed the pleural space with abcess content is there. This would be sub-optimal.

The advantage of bedside ultrasound? Quick and easy drainage during the weekend when interventional radiology isn’t readily available.

cheers!

Philippe

The Great Septic Debate (Part 2): Resolution? #FOAMed, #FOAMcc

So, echoing my thoughts form the end of the debate, Steven adds:

Well, I didn’t expect to see my name in a headline, but I suppose it’s a hazard one should expect when they go spreading their arguments across the interwebs!

In truth, I don’t think that Dr. Lynn and I really think that much differently on these issues. We both desire for the science of sepsis to continue developing and to be better than it is. I, personally, would love to be a part of the clinical trials that use genome-based data to determine which treatment arm a patient belongs in. We both deplore any “old guard” attempting to prevent the onward march of discoveries that make our knowledge and abilities more complete. I am actually sorry that some young scientists feel intimidated and that there is anything less than civility and scientific curiosity in our community. Period.

Likewise, I would be shocked if Dr. Lynn did not at least use the observation of infection, SIRS, and organ dysfunction as physical markers of sepsis and warning signs that intervention is necessary. It will be true for a very long time that it is going to be an interaction between two human beings that initiates the diagnosis and treatment of sepsis. A physician will recognize a patient in distress by some means and start the process. For now, these findings are the best we have, and they should prompt us to intervene before the completely diagnostic test results are available. Even when we have the tricorder, something is going to trigger the doc to pull it out of a pocket and use it.

OK, so I have to admit that Dr. Lynn stung me a little with his characterization of TNF-alpha as a “biomarker”. I would rather say that TNF is one of the heavy hitters in the proteomics of sepsis, and I’ll bet that I can get him to concede that point! It stimulates receptors and causes other actions to take place, it’s synthesis and release are regulated and dysregulated; it’s more than just a marker! And I ABSOLUTELY agree that the failure of TNF-directed therapies stems from the fact that they were given both to patients who could benefit from them and patients who, with better characterization, we would have known had no chance of benefitting. The same goes for high dose corticosteroids, anti-endotoxin antibodies, IL-1 directed therapies, and coagulation based therapies. In fact, that’s what I’ve been teaching my trainees for years – if you can call bemoaning the fact that we can’t yet recognize and separate responders from non-responders teaching. We have a desperate need for understanding better, and the science MUST be encouraged. Again, period. Or full stop, for those of you who have that bent! That is, I think, Dr. Lynn’s argument in a nutshell.

I REALLY appreciate the interchange. It is healthy and necessary. The two of us are aiming at the same thing – fewer people dying from sepsis. I haven’t met Dr. Lynn (though I hope to), but I suspect that he spends more hours in his day formulating and doing the new science, while I spend more hours in my day pushing people who think that it isn’t sepsis until it’s shock and multiple organ failure to do something about it before it gets that far. Those are both important parts of the war, but in the end, it is the same war. And we are allies in it.

Steven Q Simpson

And, soon after, Lawrence reaches for that handshake:

I agree completely with Dr. Simpson. We all teach that a good history, physical, basic lab, and a high degree of vigilance for subtle signs of sepsis are pivotal. This includes the use of awareness campaigns which simplify sepsis to something easily understood and screening protocols to assure vigilance. These are great advances.

I also share Dr. Simpson’s concern about empowerment of naysayers who may use the promulgation of the imperfections of sepsis science as a reason not to move forward with early action based detection protocols.

Relevant TNF-alpga, I have to agree that it likely has a fundamental role in some phenotypes of sepsis including the sepsis-like syndrome generated in Ebola patients.

So Dr. Simpson and I probably agree on most sepsis related issues.

To explain a little further, many years ago our research team applied for an NIH grant to define the dynamic relational patterns of all the lab and vitals over time in infected patients. The reviewers did not seem to comprehend why we wanted to do that since a standard for a single unified phenotype of sepsis was already widely accepted. Yet had they realized the need for these types of complete data sets, the entire time time series matrix of vitals, lab, biomarkers, and treatment for each case would have been acquired in PROcess , ARISE, and Promise. This would have occurred if the entire field of scientists had not convinced themselves they already knew that “sepsis/septic shock ” comprised a unified phenotype, “an entity” “a single condition” “a thing or object” definable by a few static thresholds.

So this is why we say the young should call for reform ASAP of sepsis science (not sepsis awareness) and at the upcoming SCCM. Imagine a mult-center trial where these complete time matrices are generated and we define the phenotypes. We can define the phenotypic subtypes and then examine treatments in relation to these.

One might think of sepsis syndrome as analogous to the syndrome of CHF where there is systolic failure, diastolic failure, hypertensive failure, and valvular failure defined phenotypes of CHF.

Perhaps we might have sepsis with capillary membrane failure phenotype and/or, vascular muscle failure phenotype, coagulation control failure , neutrophilic control failure, TNF-alpha mediated immune control failure.

These are simply general gross simplistic considerations, Discussion points.

However the final conclusion of my original post is that, beginning at this SCCM, we must stop trying to explain away the anomalies caused by the past sepsis dogma and accept that these anomalies ARE counter instances. We must accept that we cannot rely on research which uses billing codes as data or by using retrospective controls at the same time the denominator balloons as a function of awareness.

Then we can finally assure that we do not fool ourselves because the world depends only on us. There is no back up. We must accept that we need a new surge of sepsis research ASAP, and…..in a new direction.

This, along with the effort and dedication of Dr. Simpson team, the Sepsis Alliance, and the SSC (now gathering the entire time series matrix of all the diagnostic and treatment data and not just thresholds) will produce an exciting future. If this happens, it would be great to be a young sepsis scientist in 2015.

So yes Dr. Simpson and I actually agree. We are simply fighting the war on sepsis from different fronts.

Most Respectfully
Lawrence Lynn

Thanks again Steven and Lawrence for what I think was both a really informative AND formative discussion.

Philippe

Venous Hypertension: The Under-Appreciated Enemy Part 2: Discussion with Jon-Emile

So I posted about this a few weeks ago, and the discussion it brought up with Jon-Emile (www.heart-lung.org) turned out to be way better than the original post, and I just wanted to make sure everyone interested got to see it, so here we go (part 1 is here, for those who didn’t come across it: http://wp.me/p1avUV-bJ):

Jon-Emile

 

Jon-Emile: 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

 

Me: Great points as usual Jon, and your last one brings up a bit of a concern I have always had. To play devil’s advocate, one could argue that it may have been resolution of the pneumonia and its metabolic sequelae and possibly other treatment that resulted in improvement of her renal failure, rather than the fluid, no? Did her hypoxia resolution decrease PAP back to normal – with IVC dynamics restoring – and relief of renal congestion, and improvement “despite” fluid?

To me, fluid administration must – at least transiently – increase CO to have any effect on the perfusion side. To do so, my understanding is that it has to go from right to left. Because of the pericardium and interdependence, if RAP exceeds LVEDP, we will start to impair LV preload, which sets up the vicious cycle of a shrinking LV and growing RV. If we can’s increase our RT heart output, obviously our LV CO headed to the kidneys can’t increase either. Hence the assumption would have to be that somehow this additional fluid can – by increasing RV preload (without increasing RV size and further impinging LV?) – help overcome elevated PAP and increase right to left flow. To me, hard to believe without a pericardiectomy (on a short time frame, naturally). Hence I struggle with understanding how a really plump IVC with little variation (if significant pleural pressure variation is occurring) can really still need fluid.

I’d really, really like to get your comments on this. I’ve had a number of conversations about this with people – some of them pretty bright – but none satisfying. Am hoping you can point out my flawed thinking.

 

Jon-Emile: Philippe, you ask very good questions. Your first point is quite valid. I think we have a bias of assigning meaning to a particular intervention because we think that particular intervention will work. For the patient I treated, we administered multiple drugs [oxygen, antibiotics, bronchodilators, we may have even given a dose of steroids] and yet I assign meaning to the fluids given. I think in all patients with complex hemodynamics that there are multiple co-varying interventions that all [hopefully] push the patient in the right direction – making it quite hard to grant significance to one in particular. Yet in the patient I treated, the timing with respect to creatinine change and urine output made it very hard to argue in favor of diuresis. We were checking her creatinine fairly regularly as she was in step-down and we were concerned about the trajectory of her illness. With lasix, her creatinine jumped abruptly on the following chemistry while with fluids, creatinine dropped and her urine output really picked up.

Which brings me to Ulrich’s point. It is well-taken and I hope to have a pulmccm post on this shortly. While the CVP does not have any correlation with volume status or volume responsiveness as you point out, the physiology of the CVP can help explain confusing echocardiographic findings.

All a plump, unvarying IVC with spontaneous inspiration means [if you believe the Guyton, or Magder approach] is that the IVC transmural pressure is remaining on the flat portion of its compliance curve during inspiration.

Click to access cc11824.pdf

In other words, the IVC is at such high volume [on the flat portion] that lowering its transmural pressure [lowering the CVP, raising the intra-abdominal pressure or both] does not cause it to shrink in volume.

The question then becomes why is the IVC in this state? And a great analysis to this question is to consider the determinants of great vein volume [which really is a question of great vein/right atrial pressure or the CVP – which is related to volume by compliance].

There are two primary processes which will raise great vein volume and these flow from the Guyton Diagram 1. excessive venous return 2. poor cardiac function or a combination thereof [its really just inflow versus outflow]. Volume status plays one part of venous return, so certainly, if someone is hugely fluid overloaded, their venous return will be enhanced and this will favour a high great vein volume and high great vein pressure, BUT this will be mediated by cardiac function because if the heart can eject the large venous return it is receiving, then the great vein pressure and volume won’t change or may be low. Conversely, if cardiac function is poor, a patient could have a low venous return [e.g. be hypovolemic or euvolemic] and still have a high great vein volume and pressure – simply, because the heart can’t expel from the thorax what little venous return it receives. Importantly, poor cardiac function can mean almost anything [valve dysfunction, tachycardia with arrhythmia, high afterload, poor contractility, etc.].

To me, the above is the true value of thinking about Guyton and the CVP, so when I approach a patient, I try to think about what their venous return curve looks like [by a clinical exam] and I use a TTE to actually see what their heart function looks like [and to me this is the true power of ICU TTE]. The above also explains why CVP simply cannot be a marker of volume status.

In the patient I was treating, her history and physical really suggested poor venous return [she was clearly with a pneumonia, hadn’t been eating and was euvolemic to dry on examination] yet her great vein volume was high on TTE which meant that her cardiac function was most likely poor [on the Guyton Diagram her low venous return curve would be intersecting a very low, flattened cardiac function curve such that shifts with intra-thoracic pressure would not change right heart pressure at all].

But why was her heart function poor? Why could her right heart not eject what little inflow it was receiving? It was probably a combination of things. The pneumonia probably increased right heart afterload which caused some TR, she was tachycardic so wasn’t getting optimal filling time, she was septic with perhaps some underlying cardiomyopathy, perhaps her diastolic blood pressure was lower than normal [she was an elderly lady with likely stiff arteries] and she wasn’t perfusing her right coronary artery well and was suffering from relative ishcemia] it’s certainly is a lot of hand-waving, but all taken together perhaps plausible.

The antibiotics improved her lung function as did the bronchodilators which lowered pulmonary vascular resistance which improved right heart forward flow, maybe the inhaled beta-agonists increased her contractility, maybe the oxygen also lowered her pulmonary vascular resistance, maybe the steroids sensitized her to catechols and this raised her blood pressure and coronary perfusion pressure which improved her right heart function, but also maybe the fluids? Empirically, and in retrospect, venodilating her with lasix probably really lowered her venous return and this crashed what little cardiac reserve she had. It was improving her venous return with fluids that helped.

Sorry if this post is getting too long …

In terms of ventricular interdependence [an excellent, under-appreciated point in the ICU] I think that you have to be very careful extrapolating whether or not this effect is present from an IVC examination. In a classic paper [that caused much consternation at the time] Pinsky found that right atrial pressure was completely uncoupled from right ventricular end-diastolic volume [why the CVP is a poor indicator of volume responsiveness]. Her is a recent review of that paper by Pinsky himself.

http://www.ncbi.nlm.nih.gov/pubmed/24760121

The take home is that while right atrial volume and pressure [and by corollary great vein volume and pressure] can be high, this may not translate to a right ventricle near its elastic limit. Pinsky offers no good explanation as to why this is, but postulates that it may have to do with the complex RV geometry and how this changes during diastole. So until there is a widely accepted means of assessing RV filling with TTE [like an Ea ratio] which could pick up a restricted filling pattern, this is really hard to call on echo. As you are aware, you could look for a flattened septum or D sign during diastole, but I’m not sure how well that sign predicts a patient’s response to a fluid challenge – it certainly screams caution.

This Pinsky paper also highlights a potential disconnect between the physiology proximal to the tricuspid valve and the physiology below it which is also part of my general reluctance to use IVC volume change as a marker of fluid responsiveness, just as I have total reluctance to use CVP [or its change with respiration] as a marker of fluid responsiveness.

Unfortunately, a lot of the time it comes down to ‘guess and check’ – give fluids or give lasix and see what happens. This is why I firmly believe that determining volume status and volume responsiveness are the hands-down hardest party of ICU medicine.

If you’re still reading, I hope this helps.

One more point. I don’t think I gave a full explanation to one of your questions. Please bear with me as this is exceptionally hard to explain with words [indeed why I made heart-lung.org].

The venous return and cardiac function curves are essentially inverse of each other [that is lowering right atrial pressure increases venous inflow but decreases cardiac outflow] so they approximate the letter X [venous return is the \ and cardiac function is the / & the point at which the two lines intersect make up the CVP and defines cardiac output].

If you consider the patient I described, If we assume her venous return is low [because she is venodilated from sepsis and hypovolemic from low PO] then the venous return curve [\] is shifted leftwards. If we assume her cardiac function is poor the cardiac function curve slope [/] is shifted down and to the right.

When she takes a breath in, the lowering of intrathoracic pressure pulls the cardiac function curve leftwards [lowers its pressure relative to venous return] while the increase in in abdominal pressure with diaphragm decent tends to temporarily increase venous return by decreasing abdominal venous capacitance. This effect shifts the venous return curve in a rightward manner.

If the patient’s venous return curve initially intersects the ascending portion of the cardiac function curve [i.e. she is truly volume responsive] BUT, the intersection is very near the plateau of the cardiac function curve [i.e. the portion of the cardiac function curve that will render the patient non-volume responsive and also favour unvarying respiratory change in right atrial pressure/volume with inspiration], THEN with inspiration it is possible to see the intersection of the two curves on the flat portion of the cardiac function curve [as the cardiac function curve is pulled leftwards and the venous return curve is pushed rightwards], even though she does have some cardiac preload reserve. This would be an example of impaired specificity of IVC volume change with spontaneous inspiratory effort as a predictor of volume unresponsiveness [i.e. a false positive for a plump IVC predicting the lack of fluid responsiveness].

I address this physiology in chapter 6 parts C and D and chapter 8 part F.

 

Me: Very, very interesting. I think this discussion, as many, show how medicine is not a “hard science” but remains a “pseudo-science”, inherent to the fact that we are blending physics, chemistry, biology and cannot really apply simple principles of flow and pressures when dealing with elastic, muscular systems lined with microscopic coating whose compliance and resistance change from moment to moment and thru effect of neural and hormonal influence. There are simply too many unmeasurable variables to come up with single guidelines and rules.

I think, as you say, that there remains a need for some degree of trial and error, that we are hopefully narrowing with the appropriate application of technology and proper data integration.

I’ll percolate all this and see how I can tweak my mental model!

Thanks a lot Jon-Emile!

Philippe

 

 

please visit Jon-Emile at http://www.heart-lung.org

Heart-Lung

 

 

cheers!

…and don’t forget to register for CCUS 2015 at http://www.ccusinstitute.org!!!

Philippe

A Bedside Ultrasound Case & Poll: All Infiltrates Are Not Created Equal. #FOAMed, #FOAMcc, #FOAMus

So I get an early morning call from a really good ER guy informing me of a likely ICU admission: a young guy (30’s) with a bilateral pneumonia and fever whom he suspected might get worse before he got better. He’s given him some fluids and started ceftriaxone and azithromycin. Sounds good to me. Sold. I tell him I’ll come take a look as soon as I roll into work (we do home call).

An hour or so later I head to the ED and see a him, in bed at 30 degrees or so with nasal prongs, maybe a little tachypneic but certainly not in severe distress and not particularly toxic. The nurse informs me that his temperature was apparently 40 degrees. The CXR (I’ll try to put it up soon) shows bilateral infiltrates, more predominant in the lower two thirds of the lung fields. WBC is 14, lactate 2.3.

So this guy had been short of breath for about 2 weeks, having some cough and localized left sided pain associated with movement, cough and pressure. The cough was non-productive.  As I was getting this history (yup, generally bedside ultrasound is simultaneous with history-taking for me), this is what I see:

(parasternal long axis)

(parasternal short axis)

(right lower costal margin)

(you can see this in most of the lung fields)

He has no past medical history or notable family history, drinks occasional wine, has not traveled of late and works as an electrician. He is active and played soccer – the last time a few weeks ago. He came to the ED for dyspnea, but had still been able to go up several flights of stairs, albeit with more dyspnea than he normally would have.

 

 

 

check back tomorrow and let’s see what happens!

 

cheers!

 

Philippe

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

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

 

 

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