shock

April 13, 2014

An Update on Pulmonary Embolism: NEJM’s PIETHO Study…what’s the verdict? #FOAMed, #FOAMcc

As has been discussed in a previous post (http://wp.me/p1avUV-7T), patients with sub-massive PE (hypoxic, tachycardic, some troponin rise, etc…but no hypotension) remain in a grey zone, which is, to me , a dubious situation at best – their mortality can be up to 15%, morbidity likely more.  Everyone agrees the low-risk patients don’t need thrombolysis, and everyone pretty much agrees that the patient in shock needs it.  There is data out there suggesting that some patients clearly benefit from thrombolysis despite not being in shock, in good part relating to avoiding chronic pulmonary hypertension and its consequences.

The issue for many clinicians is that they have a “stable” patient in front of them, and they are considering giving them a drug that can potentially give them a bleed in the head and leave them dead or crippled. Many shy away from this. Part of this is cultural, because the same docs probably wouldn’t hesitate giving the drug to a lateral or posterior MI, which is not likely to kill you, or even leave you a cardiac cripple (just to be clear, I’m not advocating against thrombolysis in these cases, just trying to find a parallel), but since the AHA guidelines say to do it and everyone else does it, there’s no trepidation. It is the standard of care.  For most of us acute care clinicians who do not do outpatient medicine, if the patient survives and gets discharged home, chalk one up in the win column. But, as has become clear in recent years with the post-critical illness syndromes, morbidity can be just as important as mortality, especially in the younger patients. Kline et al (Chest, 2009) showed how almost 50% of “submassive PE” patients treated with anticoagulation alone had dyspnea or exercise intolerance at 6 months. They only had a 15% improvement in their pulmonary artery pressures (mean 45 mmhg).

What are the real risks? Pooling the data together gives a value around 2% with a spread between 0.8% and 8%, more or less. This represents each patient’s inherent risk of bleeding, as well as some of the inconsistencies with post-thrombolysis anticoagulation (safest to aim for 1.5-2 x PTT baseline in the first 48h).

The MOPETT trial which, as a #FOAMite you have certainly come across, showed that a half-dose of TPA was highly effective, and they felt it might be possible to go lower. The physiological beauty in that is that, unlike other sites we thrombolyse with full dose TPA, the lungs get 100% of the TPA (coronary artery gets maybe 5%, brain gets 15%).  Mind you, of course, the culprit clot/artery obviously doesn’t get 100%, but much, much more (if we figure that you need about 50% vascular area occlusion to cause RV dysfunction) TPA per “clot” than other pathologies. One can argue that anatomically, there is a greater clot burden than coronary or arterial thrombolysis, which may offset this somewhat. However, the date was quite clear in this trial that the therapy was effective, and the bleeding was none.

Ok, so let’s get to the PIETHO. 1000 patients, TPA+heparin vs heparin alone in normotensive but intermediate risk patients. So, first question is how was that risk defined?  Patients needed to have echocardiographic/CT signs of RV dysfunction AND a positive troponin. Interestingly enough, onset of symptoms was up to 15 days before randomization…not exactly early treatment, and unfortunately there is no information about the actual time to thrombolysis or subgrouping.  The results were as one could imagine. The combined endpoint of death or hemodynamic decompensation was 2.6% in the thrombolytic group vs 5.6% in the anticoagulation.  I’m not a fan of combined endpoints. Hemorrhagic stroke was 2.0% vs 0.2%. Their conclusion? Exercise caution. Hmmm…not much of a step forward. Basically tells us what we know. It helps the hemodynamics, but you can bleed. They do re-affirm that bleeding is more likely in the over-75.

 

What do we REALLY need to figure out? 

1. echographic risk stratification – at least into moderate and severe RV dysfunction.

2. longer term outcomes (hopefully PIETHO has a follow-up study in the pipeline, since they had good numbers).

3. a point-of-care study – time is of the essence, and may have an impact on dosage. IMHO thrombolysis should be done within a few hours of presentation at most.

4. further dosage data – 1/2? 1/3? 1/4? small boluses q1h until RV function improves?

I wish I could do it, but community hospitals don’t have the ideal setup, nor do I have a research team that can handle something of this scale. But surely someone can!

 

Bottom line?

It won’t change my practice. I will continue to offer thrombolysis in select cases, especially the younger patients, who obviously have a lower risk of bleeding, and stand to benefit the most, as pulmonary hypertension  can be crippling. I know I’d take the risk of bleeding when I see 50% dyspnea/exercise intolerance two years down the road…

Finally, bedside ultrasound to anyone with dyspnea/hypoxia should be a standard of care for every acute care physician. No ifs, ands or buts, no exception. Waiting for a CT angio or formal (read daytime hours) echocardiogram is, to me, unacceptable. If you, a friend or family member were in that ER bed, would you trust a physical examination and a CXR to rule out the need for an immediate intervention? I wouldn’t, not my own, and not even Dr. Bates’, Dr. DeGowin’s or Dr. Sapira’s, or all three combined.

cheers!

 

 

 

Kline JA, Steuerwald MT, Marchick MR, Hernandez-Nino J, Rose GA. Prospective evaluation of right ventricular function and functional status 6 months after acute submassive pulmonary embolism: frequency of persistent or subsequent elevation in estimated pulmonary artery pressure. Chest 2009;136:1202e1210.

Guy Meyer, M.D., Eric Vicaut, M.D., Thierry Danays, M.D., Giancarlo Agnelli, M.D., Cecilia Becattini, M.D., Jan Beyer-Westendorf, M.D., Erich Bluhmki, M.D., Ph.D., Helene Bouvaist, M.D., Benjamin Brenner, M.D., Francis Couturaud, M.D., Ph.D., Claudia Dellas, M.D., Klaus Empen, M.D., Ana Franca, M.D., Nazzareno Galiè, M.D., Annette Geibel, M.D., Samuel Z. Goldhaber, M.D., David Jimenez, M.D., Ph.D., Matija Kozak, M.D., Christian Kupatt, M.D., Nils Kucher, M.D., Irene M. Lang, M.D., Mareike Lankeit, M.D., Nicolas Meneveau, M.D., Ph.D., Gerard Pacouret, M.D., Massimiliano Palazzini, M.D., Antoniu Petris, M.D., Ph.D., Piotr Pruszczyk, M.D., Matteo Rugolotto, M.D., Aldo Salvi, M.D., Sebastian Schellong, M.D., Mustapha Sebbane, M.D., Bozena Sobkowicz, M.D., Branislav S. Stefanovic, M.D., Ph.D., Holger Thiele, M.D., Adam Torbicki, M.D., Franck Verschuren, M.D., Ph.D., and Stavros V. Konstantinides, M.D., for the PEITHO Investigators*, Fibrinolysis for Patients with Intermediate- Risk Pulmonary Embolism, N Engl J Med 2014;370:1402-11.

Mohsen Sharifi, MDa,b,*, Curt Bay, PhDb, Laura Skrocki, DOa, Farnoosh Rahimi, MDa, and Mahshid Mehdipour, DMDa,b, “MOPETT” Investigators, Moderate Pulmonary Embolism Treated With Thrombolysis (from the “MOPETT” Trial), Am J Cardiol 2012

March 7, 2014

Bedside Ultrasound and PEA: CPR or no CPR…? #FOAMed, #FOAMcc

The usefulness of bedside ultrasound in cardiac arrest is clear, giving the clinician instant information on the hemodynamic process resulting in arrest. My arrest sequence is generally done as follows:

Step 1: IVC assessment

Step 2: Subxiphoid cardiac views

Step 3: Lung views if pneumothorax suspected.

Step 4: remaining views if possible (eg abdominal views to find source of bleeding, etc…)

The important part (as per current recommendations) is to have minimal interference on chest compressions. The IVC view, albeit jumpy, can generally be obtained during CPR.  The subxiphoid view should be “prepared” during CPR, meaning that the sonographer warns the team member doing CPR not to stop compressions until he is told to do so (unless the team are already used to ultrasound in cardiac arrest), the probe positioned optimally, then instruction given to stop for five seconds while a look +/- loop is acquired. This should be enough to look for pericardial effusion, RV/LV ratio and LV contractility. In fact, experienced sonographers can usually get this while CPR is going on in many cases. Then CPR should be restarted. Hence for now, minimal interruptions in CPR (until the concept of “stutter CPR” really emerges!!!).

Here are a couple of views with active CPR:

In this case there is  a clear RV overload with a dynamic but underfilled LV.

From the information obtained in those 5 seconds, one should be able to consider the need for volume (hypovolemia), thrombolytics  (pulmonary embolism suspected) or drainage of fluid (tamponade) or air (pneumothorax). The possibility of an acute myocardial infarction must be considered as it is one of the most common causes but is difficult to confirm by ultrasound.

Pulseless Electrical Activity

This may be the most exciting area in which ultrasound will change management.  In the absence of ultrasound, all PEA is more or less alike: there is organized electrical activity, but no pulse. Physiologically however, the range of diagnoses is very wide, with on one end, a perfectly good heart that is empty (hypovolemic shock in extremis), and on the other, cardiac standstill despite electrical activity. An astute physician does not need a randomized clinical trial to know that the management and prognoses of those two extremes are very different. Without bedside ultrasound, however, these would appear identical: “PEA.”

 The heart rate cannot be relied on since it will largely depend on the phase (both would begin as tachycardic, then eventually bradycardic until asystole occurs).

Notwithstanding guidelines,  the information obtained should be considered strongly. If we start by looking at the first end of the spectrum, there would be no physiological rationale for performing chest compressions or an empty and hyperdynamic ventricle: rapid infusers and vasopressors (to recruit venous unstressed volume) should be used instead. At the other end, the heart in standstill definitely needs compressions. Of course, there is then the whole range of varying RV and LV pathologies, tamponade, etc, all of which need to be dealt with individually. It is really a huge grey zone…

CPR or no CPR?

A very important question is whether CPR should or should not be performed in certain cases of PEA.  Certainly ACLS protocol dictates so. However, ACLS has not yet truly integrated bedside ultrasound into management, only suggests in a very loose way – understandably since the protocols must be applied by all, and still only few use it regularly.

I have to credit Dr. Sue, an ER doc from Atlanta, who asked me the question about CPR in extreme hypotension, and I had to rewind in my mind the cases in which I had used physiological information to overrule the ACLS protocol in one direction or another and try to formulate an answer.

It is an excellent question and made me realize that there is no clear answer for two reasons:

One: PEA is not a diagnosis but a clinical syndrome. It relies on manual pulse check (unless the arrest occurs in a patient with an arterial line), hence the line between severe hypotension and true PEA is difficult to determine. Technically and physiologically speaking, if the LV contraction is sufficient to open the aortic valve, there is a “pulse.” Now how far along the arterial circuit this pulse travels is not known…unless it is monitored.

Two: The key question then becomes the following: at what level of endogenous blood pressure is the perfusion better than with “good” CPR?  We do not yet have that answer. The coronary perfusion pressure (diastolic pressure – wedge pressure) data often quotes a minimal range of 15-25 mmhg, which – if we arbitrarily choose a high-ish wedge – would suggest we need a diastolic pressure in the 40’s (also note that that data is imperfect). Hence the arterial line. Perhaps there could be a role for tissue saturation/near-infrared spectroscopy or other microvascular flow indices in the future…

Now what about the huge spectrum of cases in between?  Let us exclude the cases with immediately reversible causes such as tamponade and pneumothorax, where the initial management is clear, and instead focus on differing levels of RV and LV dysfunction resulting in the absence of a palpable pulse.

Predominant RV failure – although PE should be strongly suspected and thrombolysis considered, the question remains about management if you see a hyperdynamic but underfilled LV.  CPR would appear reasonable in an effort to try to get some RV to LA flow. Endotracheal milrinone, sometimes used in cardiac anasthesia, can be an option as it provides inotropy and pulmonary vasodilation.

Predominant LV or biventricular failure – if cardiac activity is present, it seems imperative to start an infusion of vasopressors, and traditionally, do CPR until there is a measurable blood pressure. I have used CPR with progressing bradycardic rhythms for a few seconds to circulate the epinephrine, with at least short-term success.

Here is a typical LV “PEA” from the subxiphoid view:

Ideally, an arterial line would be very useful in these patients, and may help to decide on an individual basis when CPR should be used. Remember that CPR on a beating heart will likely worsen cardiac output as asynchronicity and increased mean intrathoracic pressure will impair filling.

Additionally, the arterial line also allows us to notice small trends during resuscitation, such as seeing that a few seconds of CPR may help circulate a bolus of vasopressor and enable it to take effect – progressive BP increase, or that the BP may be trending downwards despite vasopressor infusion – CPR may be useful until enough vasopressor/inotropes have infused.

Bottom Line:

1. if possible, put in an arterial line

2. bedside ultrasound is mandatory if you don’t want to miss anything reversible

3. if you don’t have a palpable pulse and your diastolic pressure (arterial line) is less than 40, consider some CPR until vasopressors/inotropes have had effect.

4. if you are lucky enough to have ECMO (shout out to Joe and Zack at http://www.edecmo.org)  or other mechanical support, it would be the time to consider!

I think this is actually a really interesting area to develop, and I’d really, really like to hear what other sonographer-resuscitationists are doing, or what anyone else might think!

 

Philippe

 

Joe Bellezzo – yes, THE Joe, says:

Phil, I agree with all your points here. Great post! As you know, Shinar, Weingart and I recently published a rant on PEA (over at http://www.edecmo.org/13) and Weingart threw out two possible new monikers: PRE-M (Pulseless Rythm with Echocardiographic – Motion) and PRE-S (Pulseless Rythm with Echocardiographic – Standstill). I don’t disagree with any of those concepts but I think its simpler than that.

PRE-S (standstill) = asystole and you start compressions.
PRE-M (organized cardiac activity) = profound shock. In this setting I like the recent Littmann paper that gives a simplified approach (http://edecmo.org/wp-content/uploads/2014/08/A-Simplified-and-Structured-Teaching-Tool-for-the-Evaluation-and-Management-of-Pulseless-Electrical-Activity.pdf).

As you pointed out above, the real big question is at what point do you start compressions when you have cardiac motion? Your points above are spot on. The problem with compressions on a beating heart is that you don’t know what your end-point is. You lose the ability to do minute-minute diagnostics and doing any procedures with ongoing compressions is tough. And it seems to be a knee-jerk reaction for the RN or pharmacist to have an amp of epi ready to blast away at this point. NO!

I wait. I do stuff first. Step 1 is ECHO. If PRE-M (aka profound shock): EKG and arterial line NOW. Step 2: Stop, think and decide what you think is your top probable etiology of this profound shock and fix that. Step 3: reassess = repeat echo, EKG, and see what your art line pressures are doing. I try to do all that before I start compressions.

Example: “PEA” hits your door. Echo shows a wall motion abnormality and hypokinesis. EKG suggests ischemia but is not obvious STEMI. art line goes in simultaneously. I think this is MI. This heart does NOT NEED epi 1 mg! This is cardiogenic shock and I need to fix some stuff before I start pushing on the chest and blasting superhuman doses of epi! I usually start with a push dose epi (10-20 mics or so) while a pressor drip is prepped. Calcium bolus is given. I likely start dobutamine here (or milrenone if beta blocked). If that fixes your problem, then the pt goes to the cath lab. If it doesn’t, I cannulate and put the pt on VA-ECMO.

And what if I were wrong? what if this were a big PE? massive beta blocker OD? the protocol above is works in those cases too.

An aside, since you already placed a femoral venous line….and you popped in the Art line immediately, you have nice conduits to upsize to ECMO cannulas.

Great post Phil!

 

Thanks for sharing your approach!  As you know and clearly show, a sensical physiological approach is absolutely needed in a day and age when we can (bedside ultrasound) see what’s really going on, and we can (ECMO) give these patients a fighting chance!  See you at BMBTL in a couple of weeks!

Philippe

 

PS Joe (and Zack and Scott) will be talking about all this and more at CCUS 2015! http://www.ccusinstitute.org to register soon!

February 23, 2014

“Doc, I can breathe!” – Thrombolysis in PE…a case discussion. #FOAMed, #FOAMcc

So I was on call last weekend and got a call from one of the internists on the ward about a potential admission who may need dialysis.   She was a woman in her 60’s, diabetic, hypertensive with minimal baseline renal dysfunction, who had been admitted with a hepatic abscess due to biliary obstruction. This had been stented and a pigtail catheter had been inserted to drain the abscess.  However, over the last few days, her creatinine had risen to about 500 and she was becoming oliguric.  Her O2 requirements had also increased and she was now on 15 liters by nasal prongs. This had been ascribed to pleural effusion and possible pneumonia.

When I saw this lady, she was visibly dyspneic at 30 with a heart rate 115-120 and a systolic BP of about 105-110, saturating 90% on 50% face mask.

So on physical examination, she had a soft abdomen (the first thing I feel just before I put probe to skin), her skin was cool, and the CUSE revealed a large (>20mm) IVC with no respiratory variation (despite the effort).  I unfortunately forgot to hit the record clip button…and the parasternal long axis and apical 4 chamber are here:

Lung views showed “A” profiles except for the right base which had a small effusion and some consolidation/atelectasis and some B lines, but not very extensive.

So further assessment revealed she was not a smoker, previously quite active and easily able to go up and down several flights of stairs.  She had noted dyspnea about 3 days ago, without chest pain. There were no leg symptoms, and she had been on LMWH for dot prophylaxis.  The CXR was not very impressive – in a sense that there was not enough parenchymal disease to explain pulmonary hypertension.

This is PE until proven otherwise, and I would have been comfortable without further confirmation, but with the presence of some lung disease and an intrahepatic catheter, I preferred to have 100% confirmation before initiating thrombolysis.

After CT angiogram confirming bilateral and extensive embolism, I had a thorough discussion with her and her family and they all agreed to go ahead with TPA.  She was quite concerned with cardiorespiratory limitation, given that she was quite active. She was comfortable with a quoted risk of intracerebral bleeding below 2%. I used the MOPETT half-dose of 50mg.

Overnight, her HR slowed to about 100, and sats increased to 93-94%.

When I rounded on her in the morning, she said “Doc, I can breathe!” with a big grin. Her HR was 95-100, she was not on 3 litters by NPs, BP 115-120 systolic, and CUSE showed:

So we can see that even though the RV is still quite impaired, it has decreased in size and the LV is now filling better. This was about 12-13h post thrombolysis. She was able to sit up without dyspnea and mobilize to the chair. Her IVC, although it remained around 18-19 mm, had clear respiratory variation.

So…success? Who really knows. It is concievable that, with heparin alone, she might have improved similarly. It is possible. I’m not putting this up to formally support the concept of thrombolysis in “submassive” PE but more to contribute to the #FOAMed discussion regarding the “grey zone” of thrombolysis, since she was technically not in shock (eg SBP>90, lactate normal), but the degree of impairment of the RV to me and the clinical picture, 3 days post, was concerning enough to warrant thrombolysis, but importantly to stress the following:

Point 1: the importance of bedside ultrasound, especially in acute cases.  Without it, over a weekend, and with a patient in renal failure, how quickly would I have ordered a CT angio?  Not without some hesitation…

I won’t review the MOPETT trial, these guys did a much better job than I could hope to, so definitely listen to this if this topic is of any interest to you (and it should!!!):

http://emcrit.org/wee/mopett-trial/

http://ragepodcast.com/rage-session-two/

Great case debates in the RAGE podcast.

Keep in mind that morbidity, not mortality, is the main thing to focus on in sub-massive embolism and the MOPETT – even though I don’t really like the term, its quite vague – benefit in embolism with shock is quite clear.

Point 2: Equally interesting to me was the fact that the renal failure improved. In fact, overnight following thrombolysis, she had a urine output (without diuretic) over a litre, and over the next few days her creatinine normalized and renal replacement therapy was not needed.  Interesting, since she even got a good blast of toxic dye with the CT.  Some will feel that it is the improvement in CO that improved renal function, and this may be partly true, but in view of the lack of “systemic shock,” I think that venous decompression resolved the congestive renal failure, which I think was the main cause of her ARF. I posted about this topic a few months ago, so for more on this see:

https://thinkingcriticalcare.com/2013/09/25/chf-associated-renal-failure-low-flow-or-not/

so thanks for reading and love to hear anyone’s opinion!

PR

COMMENTS:

QUESTION. IF SOMEONE DOES NOT HAVE A PALPABLE PULSE BUT HAS CARDIAC ACTIVITY ON THE ECHO AND RATE IS 90 AND BP IS 50.  DO YOU CONSIDER THIS PEA AND INITIATE CPR?

SEAN

Great question!  There is a whole grey area in “PEA” and management is unclear. I don’t think there is a single answer to that, but physiologically and without further information about RV/LV, I would say your patient needs vasopressor/inotrope support, so I would probably give a small bolus of epi (maybe 100ug) and start an infusion. If I see little reaction (eg HR/BP doesn’t pick up in 30 seconds, I would probably give a short cycle of CPR to get the epi back to the heart.   Of course, hopefully there is a reversible cause (MI/PE), that can be addressed.

Thanks!

 

Philippe

January 10, 2014

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

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

So without any further adue:

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

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

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

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

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

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

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

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

Cheers,
John from India…”

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

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

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

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

thanks!

Philippe

Other Comments:

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

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

Thanks for your input! It was a pleasure.

Warm regards,

Derek

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

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

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

Hope this helps……

John.

Here is the article:

924042

P

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

October 18, 2013

CCUS 2013 Lectures – #FOAMed, #FOAMcc

This past may we had an amazing two day conference, the theme of which was challenging dogmatic practice and myths in acute care medicine.  Many of the lectures are now available to watch on our website at http://www.ccusinstitute.org/e-Store.asp?method=evideos#, you need to be a member to access – which is free, just register.

 

Lectures on bedside ultrasound, shock, ECMO in the ED, physiology and a lot of really, really good stuff.

 

We will be adding more in the next weeks!

 

Thanks!

 

PR

October 9, 2013

Bedside ultrasound clip quiz 1 – #FOAMed, #FOAMcc

62 year old with weight loss, tachycardia and progressive dyspnea…what do you see?

scroll below!

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

This was a case of pre-tamponade/tamponade.  Here is a view a few minutes later, with the guidewire in. This was a case of malignant pericardial effusion.

September 26, 2013

For students, residents, and anyone else: Key Articles! #FOAMed, #FOAMcc

For students or residents rotating though Santa Cabrini’s ICU, I will be attaching here a number of important articles – and adding to it frequently – which you should be familiar with and aware of. Please read them as we will undoubtedly be discussing these topics.

VISEP study

Fluid resuscitation in septic shock

Sepsis in European intensive care units_results of the SOAP study.

IVC ultrasound in CHF

Congestive RF in CHF – Mullens

Vasopressin review

SAFE study

Thanks,

Philippe Rola

September 25, 2013

Case Studies in Bedside Ultrasound

I’ll soon start putting up interesting bedside ultrasound loops and images (as soon as I can get this software figured out…), in the meantime, if anyone is interested, we have a casebook  which can be found on the CCUS website (http://www.ccusinstitute.org or an e-version on iTunes (https://itunes.apple.com/us/app/50-case-studies-in-bedside/id599201706?mt=8).

thanks!

September 25, 2013

CHF-associated Renal Failure: Low-Flow…or not??? #FOAMed, #FOAMcc

So here’s a common enough clinical scenario:  An elderly patient with CHF presents in exacerbation, requiring significant oxygen and eventual NIPPV. He is admitted to a critical care bed.  The next day, it’s noted that his creatinine has almost doubled. He remains on NIPPV. The intensivist is hesitant about how aggressively to pursue diuresis: he’s worried about worsening the “low-flow state” and the renal function.

I know I grew up hearing that as a resident, and never questioned it. On the surface, it makes plenty of sense. Someone with CHF has a “bad heart”, pre-renal failure is a definite entity, so why not?

So let’s examine those assumptions. First of all, not all patients who present with CHF actually have a bad ventricle, some may have valvular heart disease, hypertension with elevated filling pressures, etc… Secondly, few of our CHF patients are really in a severe “low-flow state”, since that would essentially be cardiogenic shock, a very different entity, even if along the same spectrum. More importantly, however, the renal autoregulation curve is actually broader that most of the rest of our tissues and organs. That makes it unlikely that, in someone normotensive (as most patients in CHF tend to be), worsening renal failure is attributable to a “low-flow state”.  The ARF attributable to a low-flow state – which we see often enough – is the organ failure resulting from shock: shock liver, shock kidneys, etc…

So…what could it be?  Let’s continue to apply basic physiological principles. What is the pathognomonic feature of CHF?

Congestion: pedal edema, ascites, effusions, anasarca, etc…

What if we had…congestive renal failure?

I have to credit a bright colleague of mine, Dr. Jason Fung (http://kidneylifescience.ca), for putting me on that track. As a bedside sonographer, what I could see in most of these patients is that their IVCs were still really full, and that most didn’t have other clinical signs of poor flow such as cool extremities and decreased mentation. And given that they were still in significant respiratory failure, I felt they needed diuresis. Also, the full IVCs suggest that these patients are on the flat part of the Starling curve (after all, that’s what the fluid retention causing CHF is trying to do!) and that they should not suffer a drastic drop in cardiac output with ongoing diuresis.

Well, Jason was the first to point out to me that the elevated IVC pressure (CVP) is directly downstream from the kidney! And directly by a couple of inches, the length of the renal veins! I have to say that was an embarrassing lightbulb moment, but a lightbulb moment nonetheless.

So let’s review renal blood supply and flow physiology. As is the case for any organ, the following applies:

Q = (P art – P ven) / R

where Q is renal blood flow (RBF), P art is MAP and P ven is CVP, and R is the renal vascular resistance.

Let’s keep that in mind.

Uniquely, the kidney has two set of arterioles which modulate the GFR and allow for the celebrated autoregulation curve. The resistance of each is controlled by the number of factors, hormones and drugs.

The reason P ven is CVP is that the renal vein drains directly into the IVC, which drains in turn into the RA, the pressure is the same. Now some of you may have read my rants against CVP in some of my posts (see https://thinkingcriticalcare.com/2013/09/18/96/), but that is in reference to its use as a marker of preload and volume responsiveness. When the answer one is seeking is the downstream venous pressure, barring some pathological venous obstruction, CVP is it.

Hence, the higher the CVP, the lower the RBF.

This makes complete sense, but how often has anyone heard this mentioned in the management of renal dysfunction in CHF patients?  As in the case for many things in medicine, we often forget (or are not taught to) link basic physiology (all that medical school stuff…) with clinical pathophysiology (…the “real” world).

Well, it turns out that fortunately, a bunch of smart people have been looking into this matter, and the best study in my opinion is by Mullens et al (JACC vol 53, n 7, 2009), which reveals a clear increase in prevalence of worsening renal failure with increasing CVP, but more interestingly, the lack of significant association between cardiac index and worsening renal failure, which is the “low-flow” traditional hypothesis.  The most clinically important finding in this study, however, is their finding that failing to reduce the CVP to below 8 resulted in a 51% incidence of renal failure (vs 18% for those patients who were reduced to a CVP < 8mmhg).

An excellent review for this was recently published by Gnanaraj et al (Kidney International 83, 384-391, mar 2013), which reveals a fairly strong association between an elevated CVP and renal dysfunction.

So it seems fair to conclude that congestive renal failure is an under-recognized clinical entity that is commonly untreated (or even improperly treated) due to unfounded and unphysiological concerns.

Now something our group will be focusing on is a study on the use of IVC sonography in the assessment of CHF-associated renal failure. We believe that IVC ultrasound will provide a better, simpler and less invasive method to assess renal congestion.

The use of IVC ultrasound in CHF would not be new:  Goonewardena et al (JACC Cardiovasc Imaging 2008; 1, 595-601, or imaging.onlinejacc.org/article.aspx?articleid=1109299) found that IVC size at discharge was the best predictor of readmission. In other words, if someone didn’t get your IVC down below 20 mm, you were much more likely to be readmitted.

As an ICU physician, I rarely discharge patients home.  But I do make sure I get IVCs into a normal range (below 15mm generally) before my CHF patients leave my unit, and, especially recently, I do make sure to continue diuresis when faced with a distended IVC with little variation and worsening renal failure.

This is certainly a topic that merits further study, but I think there is enough good evidence and physiological rationale to hang up those old beliefs in a dark closet and start treating congestive renal failure.

Please let me know what you think, what your practice experience is, and if you have anything else to add!

thank you,

Philippe Rola

www.ccusinstitute.org

www.thinkingcriticalcare.com