Dissections & digitometers

hello. Hello. HELLO!!!!!

Hi there. Just wanted to let you know that I finally rediscoved a use for the digitometer.

No, seriously.

This was a historical matched case-control study from 2002-2014 of 111 aortic dissection patients at 2 Canadian tertiary are centers and one regional cardiac referral center (and 111 case controls) looking specifically at bilateral blood pressure differential as well as pulse deficits as a marker for acute aortic dissection in the ED.

Not surprisingly, combining the two (blood pressure differential and pulse deficit) increased sensitivity (from 21% to 77%), but greatly decreases specificity (99% to 56%) – which is not quite ideal when dealing with needle in the haystack diagnoses.

Now, I do not know if it was because it was documented retrospectively (“oh no, they have a dissection on imaging, I better check pulses!”), or pulled up as part of a macro as a default (“pulses equal and brisk bilaterally’), and I would not be at all surprised if this were the case, but regardless, 21% of dissections having a pulse deficit vs 0.9% of non-dissections is pretty darn good.

Like +LR of 23.4 good. And in line with other studies reporting 24% sensitivity and 92% specificity.

Dont believe that BP differential is not a specific sign? Talk to your triage nurses to see how many times they recheck a blood pressure on a hypertensive patient in triage on the other arm – verified by prior studies showing over 50% of ED patients have >10 mmHg differential, and 19% have >20 mmHg differentials.

So while pulse deficit may possibly be over-exaggerated because of retrospective / biased ED charting, still, the absence of a pulse should at be nudging providers to consider advanced imaging sooner rather than later.

Less transfusions, the better, platelet style.

Over 4 years, the Mayo clinic reviewed over 40,000 ICU patients, and sought to determine if prophylactic platelets for critically ill thrombocytopenics matter.

Of these 40,000 ICU patients, they excluded anyone who received RBCs within 24 hours prior to the PLT count that triggered transfusion “to minimize the risk of including those with active bleeding” … The primary outcome was essentially to determine if transfusing platelets led to more RBC transfusions, and, secondarily, all-cause mortality, ICU and hospital free days (among others). Seems backwards, but whatever.

So what falls out of this data?

For all comers, in a propensity matched cohort, one transfusion begets another – (46.3 % of those with platelet transfusions also had an RBC transfusion vs 10.4% of those without platelet transfusions who had an RBC transfusion). Interestingly, those transfused platelets had less ICU free days (22.7 vs 20.8), more hospital free days (15.8 vs 13). When you look specifically at the ~5000 patients with <50k platelet counts and compare those who were/were not transfused platelets, there was no change in ICU mortality, 30 day mortality, ICU-free days, or hospital free days. While this was underpowered to determine statistical significance for those with platelet counts <50k, it is not hard to imagine a larger study to suggest similar benefits of not transfusing these patients- particularly since this study saw fewer hospital free days and fewer ICU free stays (10.2 vs 7.8 days and 19.9 vs 18.3 days respectively) – favoring a more restrictive transfusion strategy (but again, not meeting statistical significance, perhaps due to so few patients with <50k PLT).

This is not the first study I have seen suggesting empiric transfusion or outright canceling of procedures based on platelet counts between 50k and 150k is essentially bunk, and that prophylactic platelet therapy is of little benefit, if not outright harmful. There is even a flicker of a signal that prophylactic platelet transfusions >20k may not be beneficial – but this has yet to be definitively shown true -yet.

I can not agree more with the last words to the authors, “Finally, it must be acknowledged that while clinical trajectories did not improve for the cohort as a whole after platelet transfusion, it is possible that certain subpopulations may indeed benefit from the intervention, though these subgroups have yet to be identified.”

Even Pharma is getting in on Vanco-PipTazo AKI

This was an entertaining 9 page meta-analysis espousing the therapeutic harm of vancomycin and pip-tazo in the form of acute kidney injury.  With a conflict of interest page that reads like a pharmaceutical mutual fund (The Medicines Company, Cubist, Pfizer, Merck, Forest/Allergan, Melinta), it’s no wonder that they infer increased mortality due to AKI, yet conveniently COMPLETELY ignore that the same papers they reference show no mortality difference – and if anything a trend towards mortality benefit for vanco-PipTazo.  Likewise, with dialysis rates <2%, the induced kidney injury is less likely to cause harm than a suboptimal drug that wont kill your bug.

They also fail to mention cefepime neurotoxicity.

There are other ways to go about this. Like, say, reviewing the damn cultures.

But in the end, since The Medicines Company and Melinta have new broad spectrum antibiotics on the market or on the way, it probably behooves them to run a slight smear campaign on current treatment regimens. Therefore, forgive me for considering the possibility that the authors intentions may not be pure.

FOAMed: embracing the skeptics, push dose edition.

Embrace the skeptics. Seek them out. They’re actually your greatest allies.  Even when they express concerns over FOAM’s beloved push-dose pressors.

This paper reviews three cases of push dose pressor usage at their institution over an unnamed time period.

1) A post-op patient (“with known blood loss”) with hypotension in transport (no BP or MAP measurements given), and rather than optimize the slurry of midazolam, fentanyl, hydromorphone the patient was currently receiving, push-dose phenylephrine was utilized.  Except that 50 mg rather than 50 mcg was given, and propofol was then given to treat the resultant hypertension.  Now, they also suggest fluid boluses and blood, but since it was in transport… I dont necessarily think push dose was wrong, and I’m not sure where they would have gotten blood from since they were in transit, but yes, the providers certainly could have used phenylephrine concomitantly with toning back on the sedation package.

Take on case one: Tough case. You’re in transport, so options are limited.  Good thought, room for improvement.

2) A post-laminectomy patient who was receiving a norepinephrine infusion developed Afib RVR and was treatment with diltiazem IV boluses followed by continuous infusion. The patient developed asymptomatic hypotension (again, no BP or MAP measurements given) and push dose phenylephrine was given.  Unfortunately 1000 mcg was given rather than 100mcg of phenylephrine.  All while norepinephrine was still at the bedside, waiting to be restarted & titrated.

Take on case two: Dont get ahead of yourself, you’ve likely got more time than you think. Do the basics well.  Slow is smooth and smooth is fast. 

3) A hypotensive patient with angioedema who had epinephrine doses of 100 mcg, 300 mcg, 500 mcg and 1mg all intravenously (!), rather than the intended 5-20mcg.  The authors mention that the patient did not get IM epinephrine.  Being in a situation that demands to push 4 rounds of IV epinephrine must be a sticky one; I’m sure tensions were running high in the resuscitation bay.

Take on case 3: This was probably a pants-crapping case to be involved in.  Things probably could be done in tandem (IM epi while prepping IV).  Again, slow is smooth and smooth is fast.  You also fight the way you train.  I’m sure this was a nerve-racking case to be involved in.

The authors readily admit that they cherry pick cases- and in an email to the author, these cases came from anesthesia, EM, and critical care providers – attendings, fellows, and residents.  Also, in their paper they state, “we feel the time taken to manipulate these concentrations to provide small doses of vasopressor actually take the same amount of time as admixing and initiating continuous infusion vasopressor. “

But… Could you do that in transport?  What about facilities where norepinephrine has to come from pharmacy?

I *partially* agree with the author’s call for a more thought out process, and I think that this can be a call for more appropriate training (mentally, simulations, etc) prior to implementation.  Using push-dose pressors without being able to pull up how to mix and give them is akin to saying “I heard it on a podcast” without digging into the data yourself.  Perhaps maybe premixed vials handy are not the worst idea, hey, maybe we can get a push dose pressors dispenser akin to a fast food restaurant straw dispenser!  I do not agree with completely giving up pushing the boundaries and settling for “par for the course” when there is potential to do better.  Joe Bellezzo managed to do everything wrong on his first ECMO cannulation, but it did not stop the group from refining their approach and pushing the envelop to improve the next patient’s care.

Procalcitonin: Holy Grail, or Holy Sh*t ?

Procalcitonin is marketed as, “a marker of broad routine use, both for differential diagnosis of bacterial infection as well as for antibiotic stewardship.”

But is it?  This study looks at 107 ICUs that had >25 sepsis cases in 2012, and had an ability to perform procalcitonin (PCT) levels on their septic patients, and essentially looked to compare the outcomes of those that had PCT ordered and those that did not.  All in all, there were about 17,000 septic patients without a PCT ordered, and about 3800 patients with a slightly lighter wallet and slightly more anemic after their admission than their comparators.

There was little difference in baseline characteristics – save for those having PCT ordered more likely hailing from the West (27.9% of PCT orders vs 12.7% of those not getting PCT ordered) and the opposite holding true for the South (55.3% without vs 49% with PCT).  PCT was slightly less ordered at teaching facilities (37.8% of septic patients without PCT orders vs 31.9% of those with a PCT ordered).  All other OR were <1.25.

There was no difference in length of stay and no differences in mortality.

There was an increase in days of antibiotic treatment for those in whom a PCT was ordered (relative risk increase 1.17), and with that an accompanying increase in Cdiff (OR 1.42) .  Of course, 1 PCT begets another (33% of the time, and about 3 days later).  Patients with serial PCT orders had higher rates of antibiotic use, higher Cdiff, and again, no mortality benefit.

Stop the madness.  Indiscriminately ordering tests that will not change management should not be done.  And they certainly should not be repeated.

Probing the dyspneic patient.

For undifferentiated dyspnea, how would you like to have an accurate diagnosis in 24 minutes?

I love this study.

Basically, for all dyspneic patients (not trauma related, and over age 18), 10 EP’s were given an H&P, vital signs, and an EKG, as well as access to a Chest X-Ray, Chest CT, cardiologist performed echo, and labs including an ABG.

These same 2,683 patients, in tandem, had point of care ultrasound testing (lung, IVC, echo). Here’s the catch – the ultrasonographers were only provided the H&P, vital signs, and EKG then asked to make a diagnosis. The treating provider was blinded to POCUS diagnosis.

These numbers for diagnostic accuracy of POCUS are astounding.

+LR for acute HF? 22 (-LR 0.12)

+LR for ACS? 105 !!!

+LR for pneumonia? 10.5 (-LR 0.13)

+LR for pleural effusion? 95 (-LR 0.23)

+LR for pericardial effusion? 325!!! (-LR 0.14)

+LR for COPD/asthma? 22 (-LR 0.14)

+LR for PE? 345!!!

+LR for pneumothorax? 4635!!! (-LR 0.12)

+LR for ARDS? 90

Yes, for certain things like pneumonia, the difference in p-values between tradition means and POCUS diagnosis was not significantly different, but what about volume status? I cant imagine blindly giving 30 cc/kg would benefit the patient with a plethoric IVC and pleural effusion. There is some elegance a play here.

Additionally, sure, ED diagnosis for ACS had a higher LR, but they also had a cardiologist performing and interpreting echos in the ED (a rather rare siting in a US ED I would imagine) – without much improvement in their -LR (0.53 vs 0.48). For PE, the -LR of POCUS was predictably mediocre if not outright bad (0.6), while the -LR for ED diagnosis of PE, with the benefit of chest CT, was -0.10.

Now look, I get that these EP’s were quite sono-savvy. They all had 2+ years of experience, over 80 hours of ultrasound lessons & training, with at least 150 lung and 150 ED echo’s under their belt. The diagnosis was made in 24 minutes with POCUS in comparison to 186 minutes for traditional means. And while most of us can not do a year+ ultrasound fellowship, and neither can we all be as savvy with the probe as these authors (or Matt, Mike, Jacob, Resa, Laleh, etc) – it does not mean we shouldnt try. You can still greatly increase your yield just by practicing. To boot, the cognitive offload you experience by saving yourself a few hours by (correctly!) knowing which direction you are heading with a patient is an immense boon to both your mental heath & your patients well being.

Who ya gonna call? #VancZosyn!

If there’s some strange cough in your resus room,

Who you gonna call? Vanc-ZoSyn!
If something’s fevered… and it don’t look good,
Who you gonna call? Vanc-ZoSyn!

I ain’t afraid of no Staph.
I ain’t afraid of no Strep.

If high lactates are running through your EMR,
Who you gonna call? Vanc-ZoSyn!

 

There’s been some FOAM rumblings about Vanc/ZoSyn causing AKI, but this was the first time it has been compared directly head to head with Vancomycin-Cefepime. This was a retrospective matched cohort study with 279 patients in each arm – one received combination therapy with vancomycin-cefepime (VC), the other received vancomycin-piptazobactam (VPT) for > 48 hours. Patients were excluded if their baseline serum creatinine was >1.2mg/dl or they were receiving RRT. Patients receiving VC were matched to patients receiving VPT based on severity of illness, ICU status, duration of combination therapy, vancomycin dose and number of concomitant nephrotoxins. The primary outcome was the incidence of RIFLE criteria-defined AKI, with a slew of secondary outcomes performed as well.

So, wait, what’s so special about RIFLE anyway? Glad you asked: In general, the worse the acute kidney injury, the higher the mortality.

Since this study shows an 11% AKI rate with VC and 29% AKI rate with VPT, maybe we can improve our mortality if we simply switch from zosyn to cefepime?

Except that this group reports mortality was actually worse in the VC group (though not statistically significant – 8.6% vs 5.7%). That’s right – the group with more AKI had less mortality. In other news, ICU stay was decreased (6 vs 8 days), which was statistically significant., and only ~1% of patients in both arms required long term hemodialysis.

While I was getting ready to click submit on this blog post, I found a second paper (published Nov 28, 2016) that looked at a matched cohort of 1633 VPT vs 578 VC patients, with essentially similar results – 21.4% AKI in VPT vs 12.5% VC.  This second paper found similar LoS, but also a similar trend in mortality-  6.9% for the VPT arm and 9.2 for VC.

So… I’m not certain what to make of this – but it seems more than fair to question whether drug induced AKI is a meaningful surrogate marker for sepsis mortality.  We need a long term look at mortality between VC vs VPT to see if VPT induced AKI follows the same trends. Maybe we’re trading a slight bump short term mortality for improved long term mortality with VC (or maybe not).  In the meantime, I think we need to pump the brakes on shouting about Vanc/Zosyn AKI until we sort this out a bit more.

Brady arrest? Go Full Bore.

Do you believe in full bore medicine?

(hat tip to SMACCdub for that line)

This paper puts those thoughts under the microscope a bit, and challenges us to think ahead and be prepared.

They looked at all OHCA from 2006 to 2012 with initial brady/asystolic arrests to determine if they may benefit from pre-hospital pacing, and to look at survival rates associated with various rhythms. Clear non-cardiac causes (trauma, drowning, respiratory, neurologic, suicide) were excluded.

7925 OHCA in the Netherlands

less non-cardiac (6681 patients)

less those without EKGs (~500 patients)

less ~3000 patients with VF/VT (now at 2643 patients)

less those with normo/tachycardia and those with pacers previously placed (~300 patients)

 

This leaves us with 2333 brady/asystolic (idioventricular, junctional, sinus brady, 3^rd degree with/without escape, asystole) patients – or, about 30% of their OHCA.

Unwitnessed arrest still protends a poor outcome, with survival about 0.5%. However, for witnessed arrests, they report 4% survival for idioventricular / junctional arrests and 6.8% for sinus brady arrests. This seems consistent with prior studies. However, for a study trying to determine whether or not pacing is beneficial, their pace rates were quite low. They paced 11 of 220 sinus brady patients and 41 of 452 idioventricular / junctional patients, with a delay of 30.1 and 16.5 minutes to pacing respectively – with an electrical capture rate of 55% and 70% to boot.  Esssentially, they can’t answer the question “Does pacing help” with such a care gap.

So, why is this? For sinus brady, maybe patients are hanging in the 40’s-50’s and felt to be quasi-stable. Maybe its the angst of floating a pacer. Perhaps the lengthy delay for sinus brady is giving atropine, then giving it again… and maybe again- akin to pressor-angst for sepsis (giving a 4^th, 5^th, and 6^th liter rather than starting pressors or a central line).  I imagine there is a mental barrier – whether it be not thinking about pacing or passing the buck (“I’ll let the ICU figure it out.”). The evolution of the ED-ICU model (and perhaps UPMC’s cardiac arrest unit) may be the best place to look at this type of “full bore” medicine and whether or not it would be beneficial.

But for now, there is a large gap in care. Bradycardic arrests represent about 10% of arrests, have a reasonable survival rate, and are (potentially) suboptimally managed – and you have the tools to potentially improve an outcome.  We can not say whether or not pacing is futile care for this condition.

Until then, go full bore. Your patients & their families deserve it until pacing is demonstrably shown to not be beneficial in bradycardic arrests.

Compazine… for infectious disease?

Today’s article’s (1, 2, 3 ) are a break from the usual trials that are typically discussed and a bit more “benchside medicine” than bedside medicine.  In fact, let’s look at this as an early request for one of the 12 trials of Christmas.

Phenothiazines have demonstrated in vitro (as well as some in vivo) activity for gram positive cocci, mycobacteria, amoeba (4; 5), and some gram negative rods.

It should be noted that Klebsiellae, pseudomonads and acenetobacters were highly resistant to almost all of these drugs.

The MIC for phenothiazines are usually not reached with conventionally used doses, but these compounds do enhance the activity of various antibiotics to which various bacteria are susceptible (including vancomycin), and even decrease the MIC of resistant organisms.

So where am I going with all of this? For starters, lets look at some common causes of meningitis, in no specific order:

Strep pneumo (gram positive); group B strep (gram positive); staph aureus (gram positive); Listeria (gram positive); Neisseria meningitidis (gram neg diplococci); H flu (gram neg)

All things phenothiazines are thought to have activity against.

You’re likely to be giving patients with potential meningitis something for pain (I hope?), so why not go with compazine?  Likewise, patients whom you may suspect bacteremia from a cellulitis, why not give compazine to, ummm, “counteract the nausea” associated with the opiates you gave for pain control?

I think this falls into the unlikely to harm, might help category, and is seemingly a ripe area for research.  Is this practice changing?  Nope, not at all.  Food for thought, but until compazine is proven unsafe in an infectious process, I will continue my love affair with compazine for headaches, nausea, and vomiting (regardless of suspected etiology).

1 in 10 EGLS saves a life.

Do current sepsis guidelines go far enough?

That was my first thought when I read today’s article. This single center ICU study looked at 220 patients divided into two categories- one category in which patients that were managed in adherence with the 2012 surviving sepsis guidelines – 20-49 ml / kg initial IV fluid bolus, continued fluid challenges until CVP of 8-12, with more given based on treating team. Noradrenaline until MAP of 65, and dobutamine for cvSO2 <70% in combination with either lactate >2 or urine output <0.5 ml / kg / hr). The other 110 patients had treatment guided by limited echo:

Treatment options looked like this:

1) IVC fluctuation <15% & normal LV function= give pressors only (discontinue IV fluid)

2) IVC fluctuation >15% & normal LV function = 20-40 ml /kg IV fluid given

3) IVC fluctuation >15% & mod/severe LV function = 10-20ml/kg IV fluid given AND initiate dobutamine 5ug/kg/min

4) IVC fluctuation <15% & mod/severe LV function = discontinue IV fluid and initiate dobutamine 5 ug/kg/min

 

These patients were pretty sick- all patients were mechanically ventilated and on noradrenaline. Limited echo was performed within 24 hours of presentation to ICU and within 36 hours of presentation to the ED (actual times were within 7-15 hours in the ICU, on average, 11 hours). Patient characteristics were pretty similar in terms of age, APACHE scores, and labs (similar ESRD/CHF percentage as well ~20% of both patient arms). Surprisingly, patients received a ridiculous amount of IV fluid from the ED – 68 (55-70) ml / kg in the echo group vs 65 (55-72) ml / kg in the standard of care arm. Yes, even with 20% of patients having ESRD / CHF – the least amount of IVF given was 55 ml / kg !

Results?

Despite all of this IV fluid given in the ED, 35% of patients still have >15% IVC collapse (!). 65% of patients had their fluid restricted, and 22% in the echo arm vs 12% in the standard of care were started on dobutamine. On Day 1 in the ICU, patients received less IVF in the echo arm (49 (33-74) ml / kg, vs 66 (42=100) ml / kg) – but still a significant amount if IVF.

28 day survival was 56% vs 66% in favor of the echo arm, with significantly less acute kidney injury (65% vs 88% for all AKI, and 19% vs 36% for stage 3 AKI).

So your NNT to save a life is 10, and 4 to reduce incidence of any AKI.

So, is this really an ED paper? Well, it depends on your area of practice. The local flavor of the authors is such that their local policy was to initiate dobutamine in the ICU and not in the ED. Are you boarding ICU players? Are your hospitalists ultrasono savvy? How involved are your intensivists in patient care while patients are awaiting an ICU bed? Are you okay with administering at least 40 ml /kg IV fluid and starting pressors on your septic shock patients? If the answer is no or “not really” to any of these questions, then the answer is yes.