Resources for Acute Stroke evaluation and treatment

This post is really just for me - so I can find a few certain documents without frantic Googling when the 3 hour clock is ticking...

AHA/ASA - Guidelines for the Early Management of Adults With Ischemic Stroke

 ACEP - Use of IV tPA for the Management of Acute Stroke in the ED

AHA/ASA Science Advisory - Expansion of the Time Window for Treatment of Acute Ischemic Stroke With Intravenous Tissue Plasminogen Activator (del Zoppo)

 

ECASS III Exclusion Criteria 

http://crashingpatient.com/medicine-surgery/095-stroke.htm  

Expansion of TPA window to 4.5 hours by AHA (Stroke 2009;40:) - ECASS III

• Age < 18 or > 80 years
• Onset of stroke > 4.5 hours before drug administration or symptom onset unknown
• Stroke symptoms present < 30 minutes or significantly improving before treatment
• Intracranial hemorrhage
• Severe stroke as defined by NIHSS > 25 or imaging (CT or MRI) displaying > 1/3 of middle cerebral artery territory involved
• Seizure at the onset of stroke
• --------
• Stroke or serious head trauma within the previous 3-months 
• Major surgery or severe trauma within 3-months
• Combination of previous stroke and diabetes mellitus
• --------
• SBP > 185 mm Hg or DBP > 110 mm Hg or IV treatment to reduce BP to these limits
• Glucose < 50 mg/dL or > 400 mg/dL
• Symptoms suggestive of subarachnoid hemorrhage even if CT normal
•  -------
• Heparin within the preceding 48 hours with PTT above normal limit
• Platelet count < 100,000 mm3
• Oral anticoagulation therapy (EVEN IF INR WNL)
• Other major disorders with an increased risk of bleeding

www.aaem.org/education/tpaedtool-AAEM.pdf

Transfusion triggers

Quick note today, just wanted to talk about the hemoglobin level at which we should consider transfusion.

There's a lot of bad data out there, much of it retrospective, heterogeneous populations, and so on. When I was a MICU resident, often the team would prefer to get the Hgb up above 10 to "help with the oxygen delivery." Marino, OTOH, in his The ICU Book, makes a persuasive case that the reduced viscosity in anemia facilitates oxygen delivery, and you mess with this compensatory mechanism (with pRBCs) at your peril. Incidently, Marino provides a review of some more recent transfusion-related papers from his website. Worth reading.

Let me review the single best, and most-oft cited, paper on this topic, which was done by Hêbert et al, published in the NEJM in 1999. The paper (pdf) can be downloaded free from NEJM, I think, but here's a copy.
Real interesting stuff.

They prospectively studied the effect of two different transfusion thresholds, either 7 g/dL (restrictive strategy) or 10 g/dL (liberal strategy), in ICU patients. The ICUs were mixed, both surgical and medical, and both community and academic. They excluded patients with, amongst other issues,  active hemorrhage or s/p cardiac surgery.
They found that 30-day mortality was the same in the two groups, but the hospitalization mortality was significantly lower in the restrictive-strategy group (22.3 percent vs. 28.1 percent, P=0.05).

Let me emphasize that a bit more:
28.1 - 22.3 = 5.8,  or an Absolute Rate Reduction of 5.8%
That gives us a Number Needed to Harm of a little over 17. In other words:

For every 17 patients that were transfused to stay above 10 g/dL, instead of above 7 g/dL, 1 died.

Closer look at the breakdown on adverse effects:

Hey, that's funny. Many folks feel that a chief reason to transfuse is to avoid exacerbating any cardiac ischemia. What they found here, however, was that bad cardiac events were more common with the liberal transfusion threshold!

Okay, that was in 1999 - what's changed since then? Not much. In fact, the evidence has become stronger with regard to the risks of transfusion, and the benefits of a restrictive strategy, across a spectrum of medical and surgical contexts.

Let me give the latest transfusion guidelines, published in 2009, written jointly by the Society for Critical Care Medicine,and the Eastern Association for Surgery on Trauma. This document is kinda unique, addressing both the medical and surgical perspectives regarding the literature. The salient recommendations are copied here. I just want to highlight a few of them:

1. Transfuse patients with active, ongoing hemorrhage. Be proactive!
2. If they're not bleeding out, don't transfuse until the Hgb drops below 7 g/dL.
3. At that point, only transfuse single units.

A. Recommendations Regarding Indications for RBC Transfusion in the General Critically Ill Patient 1.    RBC transfusion is indicated for patients with evidence of hemorrhagic shock. (Level 1)   2.    RBC transfusion may be indicated for patients with evidence of acute hemorrhage and hemodynamic instability or inadequate oxygen delivery. (Level 1)   3.    A “restrictive” strategy of RBC transfusion (transfuse when Hb < 7 g/dL) is as effective as a “liberal” transfusion strategy (transfusion when Hb < 10 g/dL) in critically ill patients with hemodynamically stable anemia, except possibly in patients with acute myocardial ischemia. (Level 1)   4.    The use of only Hb level as a “trigger” for transfusion should be avoided. Decision for RBC transfusion should be based on an individual patient's intravascular volume status, evidence of shock, duration and extent of anemia, and cardiopulmonary physiologic parameters. (Level 2)  5.    In the absence of acute hemorrhage RBC, transfusion should be given as single units. (Level 2)   6.    Consider transfusion if Hb < 7 g/dL in critically ill patients requiring mechanical ventilation (MV). There is no benefit of a “liberal” transfusion strategy (transfusion when Hb < 10 g/dL) in critically ill patients requiring MV. (Level 2)   7.    Consider transfusion if Hb < 7 g/dL in resuscitated critically ill trauma patients. There is no benefit of a “liberal” transfusion strategy (transfusion when Hb < 10 g/dL) in resuscitated critically ill trauma patients. (Level 2)   8.    Consider transfusion if Hb < 7 g/dL in critically ill patients with stable cardiac disease. There is no benefit of a “liberal” transfusion strategy (transfusion when Hb < 10 g/dL) in critically ill patients with stable cardiac disease. (Level 2)  9.    RBC transfusion should not be considered as an absolute method to improve tissue oxygen consumption in critically ill patients. (Level 2)  10.  RBC transfusion may be beneficial in patients with acute coronary syndromes (ACS) who are anemic (Hb ≤ 8 g/dL) on hospital admission. (Level 3)

...

Two "facts" about the diagnosis of ACS that you need to forget - Part I

Like the title says, I won't be discussing any new findings or developments in the recognition or diagnosis of ACS that you'll need to memorize, keep on your iPhone, or write on your hand. These are two "important facts" that are hammered into you during your training that are taking up valuable space in your brain, space that could be used for important stuff, like memorizing lines from The Simpsons.

The first thing you need to know is that asking crap about cardiac risk factors is a waste. Sure, it makes the chart look pretty and it gives the appearance of diligence. It also less-than-preferable when you are deep into presenting to an attending, having described in succinct but descriptive language the crushing pain the patient had, the sweating, the left arm heaviness, the relief with nitro, the concerning EKG findings... and all this becomes derailed when the attending asks about family history. "How can you possibly decide what to do with the patient," you are lectured, "if you don't know their risk factors!"

Don't fool yourself into believing that you are obtaining actionable intelligence, however. Knowing whether a patient smokes, takes Lipitor, or had a grampa that keeled over at 45 years of age should not be guiding your diagnostic reasoning.

Okay, so I can avoid sounding like some crazy heretic, let me start off the discussion with an appeal to authority. What do we find in the textbooks about this issue?

In the 2011 Tintinalli, we find that:

“All patients should also be questioned regarding the presence of cardiac risk factors, although these ‘risks’ are valid only for predicting the presence of coronary artery disease within a given population and are not predictive of the presence or absence of acute ischemia in an individual patient.”

Rosen's, as well, comments that:

“The presence of risk factors for a particular disease is primarily of value as an epidemiologic marker… In the ED, presence of risk factors in an individual patient without established disease has minimal or no effect on the clinical likelihood (pretest probability) of a specific disease process.”

Well, is this just the crazy, EM perspective? Nope, here's the American Heart Association in their 2007 NSTEMI guidelines, where they mention the use of risk factors in the initial history:

Even Lee Goldman, a cardiologist renowned for developing various eponymous criteria for determining cardiac risk, has not find the traditional risk factors to be useful, stating that "demographic and traditional risk factors (with the very notable exception of a history of MI or coronary disease) are of little importance in predicting the cause of acute chest pain.”

So, this isn't my wacky opinion, this is actually the conventional wisdom!

Now, perhaps you want some justification, a bit more meat in the argument. Let's check out the empirical evidence in two key studies. The first is the classic systematic review in JAMA, from their excellent Rational Clinical Exam series (results from these papers show up in the in-service!). Written by Panju et al., Is This Patient Having an MI? synthesizes a number of studies looking at the relative contribution of elements of the history, physical exam, and EKG.  There a few shortcomings in the methods, etc., but it is still one of the most oft-cited papers on the topic.
They find that:

Some of this was based on a nice study by Jayes in 1992. Multicenter, prospective collection of information of risk factors in adults being checked out for chest pain. Lotta patients, 1743 in fact. They ran the results through logistic regression and found:

Yeah, there seems to be a small bump in the RR for DM and family history, and barely for smoking. And only in men! These results are blown away by the RR for simply showing up with chest pain, in both men and women.

(Hey, wait a minute. Why is the risk of ACS higher in women with chest pain than for men? Aren't women supposed to present, like, all differently? I'll get to that "fact" in Part II.)

Well, that paper is a few years old now - anything newer out their? Why yes, in fact, there was an excellent single-center study done by Body et al. in Manchester, UK, in the ED. They prospectively obtained information on the standard risk factors (HTN, lipids, DM, smoking, and family history) on 804 adults coming in with "chest pain occurring within the past 24 h that the treating physician suspected to be cardiac in origin." Then they looked at who ruled in/out, and found that knowing the risk factors helped...

... not so much.

Of course, why did we ever expect that these classic risk factors would help us in the ED? This is epidemiological data, used in the office with the asymptomatic patient, to determine the risk of having an event in the next 10 years. Hey, if you're going to bust out your Framingham Risk calculator, knock yourself out, but realize you may be are answering a different question that the one you were aiming for.

You can also listen to this great podcast at ERCAST.

So, when it comes to the utility of cardiac risk factors in the ED, I'm actually not much of a heretic, and I'm not really espousing anything very controversial. I am going out on a bit of a limb, however, in Part II, where I deconstruct the "fact" that women with ACS present with significantly different symptoms and histories than men. Gonna have to show you some evidence there!

Anaphylactic reactions - 5 things.

I'm a little concerned that the treatment of anaphylaxis is not as well understood by EM folks as it should be. Now, in the acute management of ACS, you can be forgiven for not being familiar about the latest literature regarding the various antithrombotics, the merits of different DES, the proper initial dose of clopidogrel, etc. Too many trials, too much evidence.

But in anaphylaxis. there is hardly any evidence! It's possible to review the entirety of the best evidence in one pithy bog post, so let's get on with it.

First, get this paper. It's the best reference for current diagnosis and treatment of anaphylaxis out there.

Okay, 5 things:

1. Epinephrine is given IM (intramuscular), and in the lateral thigh. Not IM in the deltoid, not SQ in the buttocks. IM in the thigh, period.

The first time I ordered epi this way, the conversation with the nurse went something like this:
"Okay, let's give some epi. I want 0.5 mg IM in the thigh."
"No prob, I already drew it up." (Holds up syringe with 1/2 inch long needle on it)
"Uh, I don't think that'll make it to the muscle..."
"Well, it's only supposed to be SQ, right?"
"No, I want 0.5 mg epi, IM, in the thigh."
"Sure." (attaches longer needle, then rolls up patient's shirt sleeve, exposing the deltoid)
"Hold on a moment - I want that to go in the thigh, not the deltoid."
"You sure? We always do it this way."
"Yes, I want 0.5 mg epi IM in the thigh.
"Okay, you're the doc." (Turns around, eye rolling.)

Just in case you didn't catch it, epinephrine is given IM in the lateral thigh. Quiz later.

Okay, if this is the only thing you learned today, I'm happy. But let's look at the evidence for this, because it's beautiful. Some investigators decided to pay some healthy folks to get epi shots or saline injections. They were administered either IM or SQ, and in the area of either  the deltoid, or lateral thigh. They then measured the serum epi levels found in each of the possible combinations.

So elegant, I could cry. If they didn't give the epi IM in the thigh, the bump in serum epi was no different than placebo. Remember as well, these are healthy volunteers, without any cutaneous vasoconstriction.

2. The dose is 0.01 mg/kg, maxing out at 0.5 mg.  You can repeat this ever 5-15 minutes PRN.

3. The antihistamines and steroids are given only for the (putative) biphasic reaction, and have only a minor role in  acute management. A lot of folks think that this biphasic reaction doesn't even exist, and that "relapses" that occur in the following day or two just represent an incompletely treated MONOphasic reaction. In fact, if you look at this trial that involved giving bee stings to people who had had anaphylactic reactions to bee stings in the past, there is no mention of steroids or antihistamines.

I'm not even bothering to put in the Cochrane Collaboration analyses on the use of these adjunctive measures - both say "No evidence."

4. IV fluids.
They may not have as big a role in trauma these days, but when it comes to anaphylaxis, you want large-bore, proximal IVs, with 2 bags of saline hanging.  A patient in true anaphylactic shock not only has a distributive shock, they actually can lose up to 33% of their intravascular volume in the the initial few minutes. This is the time to break out the 14g catheters!

5.  Intravenous epinephrine
Here  we go - the patient's pressure is tanking, their thigh looks like a pincushion from all the IM epi you've given, and you have the 3rd and 4th liters of saline running in on pressure bags. Time for the IV epi! How do you do this without causing more problems than you already have? Try the 1-1-1 method, probably the best way to give enough, but not too much.

First, grab 1 mg of epinephrine - any concentration will do, the number work out with either the 1:10 or 1:1000 versions.

Next, put this in 1 liter NS.

You'll have a concentration of 1mcg/ml, and you want to start at 1 ml/minute, and titrate up quickly. In the protocol described in the bee sting study above, they would start off at 5 mcg/minute, but then it turns into the 1-1-5 rule. Just titrate up quickly.

Okay, a final word: Isn't epi dangerous? Well, yeah, if you give too much! There are a mess of case reports that show all manner of badness from epinephrine, but most of them appear to result from extraordinary doses.

For example, look at this case: a young adult was given what they describe as "low-dose" IV epi, and subsequently bumped her cardiac enzymes, despite a clean cath. However, what they call "low-dose" was actually 100µg IV, or 20 times the dose that the bee-sting protocol started with, and 100 times what we describe in this post!

Anyway, just remember that you want epinephrine, 0.01mg/kg, given IM, in the lateral thigh!

Tomorrow

Two "facts" about the evaluation of ACS that I will drone on about if you mention them to me. So let's get that out of the way.

Manifesto

I tend to forget things. Ok, things I read, I get it. When I find myself having to refer back to lectures I gave, or, heaven forfend, papers and chapters I've written, I realize I've got a problem.

This site is meant, really, only for me, to provide a running record of stuff I knew a lot about at one time, perhaps a cool article that I really liked, or maybe the outlines of a lecture I would love to present in  the future. But, in the end, it's just sort of my intellectual "Dear Diary."