question about myocardial ischemia

[jolu]

Can someone explain to me how tissue plasminogen activator (tPA) is useful in dissolving clots in coronary arteries and why it is important to use it only iwthin a short period (about 4 hours) after the onset of myocardial ischemia (heart attack)??

thanks a lot!!

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[southerndoc]

TPA activates plasminogen, converting it to plasmin. Plasmin dissolves fibrin clots. So TPA dissolves the clot.

TPA can be given within 6 hours (3 hours for a stroke), but it's usually not too effective around the end of the time frames. The main reason it's not given any later is that (1) the muscle has most likely suffered irreversible injury, and more importantly (2) the risks outweigh the benefits.

Thrombolytics have significant side effects, the most notable of which is increased incidence of intracranial hemorrhage. This is more common than one would think. A retrospective review that I did a few months ago revealed a 1.7% ICH rate for MI patients receiving thrombolytics. 1 in 50 is a significant number.

 

[defiant]

Although tpA is typically utilized...don't forget to recognize other requirements to manage an MI.....

Aside from tpa - streptokinase may be an alternative thrombolytic still used by some clinicians.

Adjunct to thrombolytic therapy, pain management - through vasodililation of coronory arteries with Nitroglycerin IV...3 mcg/min start and titrate to effect

And even after the initial bolus, and two stage tpa regimen, a Heparin bolus, followed by a continuous heparin IV per protocol is required to maintain therapeutic PT, PTT & INR.

Regards,
Brad
CCRN, MS1

 

[womansurg]

Acute MI is usually, not always, a thrombotic event. Arteries which are critically narrowed by calcific plaque develop a thrombotic plug which then totally occludes the lumen. No blood flow equals injured cardiac muscle equals MI.

Thrombolytic therapy dissolves the small clot, re-establishing flow. After several hours of no flow however, the cardiac muscle is IRREVERSIBLY injured. Re-establishing flow is no longer helpful and also increases risks of bleeding, as the damaged/dead myocardium is now more likely to bleed.

Same principles with thrombolysis and stroke, where they talk about conversion of a cerebral infarction (no blood flow = dead brain) to a hemorrhagic stroke (intracranial bleeding at the site of the injured tissue).

 

[Surfer75]

use TNK instead of tPA here where I'm at in Canada... TNK's one nice thing about it is that it's administered as a single bolus...

 

[southerndoc]

Originally posted by Surfer75
use TNK instead of tPA here where I'm at in Canada... TNK's one nice thing about it is that it's administered as a single bolus...

Are we sacrificing patient safety for our own convenience? Seriously, the side effect profile is higher with tenecteplase when compared to alteplase. It seems all we gain from TNK-tPA is an easier time for the nurses to administer.

 

[Skip Intro]

Originally posted by Geek Medic
Are we sacrificing patient safety for our own convenience? Seriously, the side effect profile is higher with tenecteplase when compared to alteplase. It seems all we gain from TNK-tPA is an easier time for the nurses to administer.

Well, not to get too much into a U.S. vs. Canada debate... but, Canada medicine is formulary medicine. tPA, as you probably know, is about $2000 (U.S.) a dose. It may just be that TNK is more cost effective (although I don't know that to specifically be true) and the formulary board in the province that Surfer75 is from may use it for that reason alone (i.e., the added cost of tPA doesn't warrant it's use therapeutically when compared to TNK).

 

[MustafaMond]

TNK-ase is what is used in the VA hospital ICU. I have seen both streptokinase, and tPA used in community hospital settings. Im not sure how much the side effect profile is affected w/ TNK-ase.

They use a lot of anti-platelet drugs too, nowadays. Integrilin, Plavix, etc.

 

[droliver]

There was a big review of this last year in NJOM which concluded that the cath lab when available was superior to thrombolytics for AMI

 

[MustafaMond]

Originally posted by droliver
There was a big review of this last year in NJOM which concluded that the cath lab when available was superior to thrombolytics for AMI

I havent heard of NOJM before (NEJM?) , but JAMA published a study by Aversano et. al. which implied PTCA in a good setting was superior to Thrombolysis.

The problem, as you know, is availibility of PTCA at community hospitals.

http://jama.ama-assn.org/issues/v288n18/ffull/jlt1113-2.html

 

[southerndoc]

Originally posted by Skip Intro
Well, not to get too much into a U.S. vs. Canada debate... but, Canada medicine is formulary medicine. tPA, as you probably know, is about $2000 (U.S.) a dose. It may just be that TNK is more cost effective (although I don't know that to specifically be true) and the formulary board in the province that Surfer75 is from may use it for that reason alone (i.e., the added cost of tPA doesn't warrant it's use therapeutically when compared to TNK).

There are 3 forms of tPA available. The prices (last I checked) were:

Activase (alteplase) - standard tPA: $1800
Retevase (reteplase) - double bolus tPA: $3000
TNK-tPA (tenecteplase) - single bolus tPA: $3800

We were investigating it for possible use on an ambulance. That's how I know the prices. It's been a while since I checked, so there may have been some drastic changes. Heaven forbid if there is a sudden shortage of one of the above. It seems like every other drug is coming up short on a bimonthly basis now.

 

[southerndoc]

Oops, I forgot that alteplase and tenecteplase are Genentech products. Reteplase is made by another company... Centocor maybe?

There is a newer thrombolytic that's about to go before the FDA for approval. I don't know what could be different. Maybe instead of giving the bolus over 2 minutes you give it over 5 seconds. Bolusing TPA like it's adenosine. I just don't see the benefit of that.

 

[Skip Intro]

Originally posted by Geek Medic
There are 3 forms of tPA available. The prices (last I checked) were:

Activase (alteplase) - standard tPA: $1800
Retevase (reteplase) - double bolus tPA: $3000
TNK-tPA (tenecteplase) - single bolus tPA: $3800

We were investigating it for possible use on an ambulance. That's how I know the prices. It's been a while since I checked, so there may have been some drastic changes. Heaven forbid if there is a sudden shortage of one of the above. It seems like every other drug is coming up short on a bimonthly basis now.

Good info, Geek Medic. Thanks for pointing it out.

Interesting that you're considering using it on the meat wagon. Is there some specific advantage of TNK over tPA (i.e., it doesn't lyse older clots, etc.)? It seems kind of dangerous, no offense intended, to let paramedics use this in the field. What if the patient has a CVA, you open a healing GI bleed, etc.? Seems like the protocol would have to be fairly strict, you probably wouldn't get standing orders, and many ER docs would be unlikely to authorize over the radio anyway.

Just curious.

 

[southerndoc]

Actually there are quite a few ambulance services that carry thrombolytics now. Most have transitioned to Retavase, but some are using Tenecteplase now.

There are some studies that show benefits to pre-hospital thrombolysis, but most have not reached statistical significance for long-term mortality improvement.

Contrary to what most people think, TIMI-19 did not investigate the benefit of pre-hospital thrombolytics on mortality. Their published results concentrated on patients receiving thrombolytics quicker if treated in the field than if treated in the ED.

You do raise a valid point about CVA's. There is a significant risk of that when given thrombolytics. In addition, there is a major risk of significant bleeding if the ambulance is ever involved in an accident, which is a significant risk itself when the ambulance is driving emergently.

It appears that patients who do NOT receive thrombolytics in the field and who are transported directly to a hospital with cardiac catheterization abilities, and who undergo PTCA within 3 hours of onset of symptoms, fare better than those that receive thrombolytics in the field. Hence the possibility of the ACS recommending the designation of "cardiac centers" much like there are trauma centers in existance today.

Only time will tell how this thrombolytic v. PTCA thing will resolve.

 

[Surfer75]

Originally posted by Geek Medic
Are we sacrificing patient safety for our own convenience? Seriously, the side effect profile is higher with tenecteplase when compared to alteplase. It seems all we gain from TNK-tPA is an easier time for the nurses to administer.

Sure you read ASSENT-II?

FINDINGS: Covariate-adjusted 30-day mortality rates were almost identical for the two groups--6.18% for tenecteplase and 6.15% for alteplase. The 95% one-sided upper boundaries of the absolute and relative differences in 30-day mortality were 0.61% and 10.00%, respectively, which met the prespecified criteria of equivalence (1% absolute or 14% relative difference in 30-day mortality, whichever difference proved smaller). Rates of intracranial haemorrhage were similar (0.93% for tenecteplase and 0.94% for alteplase), but fewer non-cerebral bleeding complications (26.43 vs 28.95%, p=0.0003) and less need for blood transfusion (4.25 vs 5.49%, p=0.0002) were seen with tenecteplase. The rate of death or non-fatal stroke at 30 days was 7.11% with tenecteplase and 7.04% with alteplase (relative risk 1.01 [95% CI 0.91-1.13]). INTERPRETATION: Tenecteplase and alteplase were equivalent for 30-day mortality. The ease of administration of tenecteplase may facilitate more rapid treatment in and out of hospital.

 

[MustafaMond]

Good post, surfer.

As to the question about EMTs delivering thrombolytics...I dont see why not. The choice to use these drugs is PURELY algorythmic. You either do, or you dont, depending upon the EKG/time-frame/and Chest Pain.

EMTs do a lot more clinical problem solving than it would take to decide upon thrombolysis...

Yes, a CVA could occur, (1% chance)

I ask you what the chance of a pneumothorax afer a central line is...whats the chance of snapping someones neck while moving them after a massive MVA..whats the chance of a Chest Tube leaking and getting tension pneumo..whats the chance of someone reacting badly to Lidocaine, or going into CHF from an IV bag.

They should be given the tPA, because time is so crucial an issue in the administration of this drug.

 

[southerndoc]

I will see if I can get ahold of the data we used to make our decision with. It will be at least 2 weeks (I'm doing an away rotation right now).

 

[Skip Intro]

Originally posted by MustafaMond
I ask you what the chance of a pneumothorax afer a central line is...whats the chance of snapping someones neck while moving them after a massive MVA..whats the chance of a Chest Tube leaking and getting tension pneumo..whats the chance of someone reacting badly to Lidocaine, or going into CHF from an IV bag.

I don't think you're putting a fine enough point on it, Mustafa. In all of these examples, there is a clear correlation to immediate treatment equaling better prognosis - benefit/risk ratio is clearly in treatment's favor (i.e., you can't leave the victim in the car, non-treatment of a tension pneumo results in rapid death, etc.) Myocardial tissue can be hypoperfused for four to six hours and still recover. Likewise, so many people report chest pains (that turn out to be MI) way too late anyway and thrombolytics don't do them any good. Besides, you can't do CK-MB and troponin levels in the field, and many ER docs won't give thrombolytics until they have a clear cut diagnosis.

Also, I remember a study that was quoted (and I'm trying to find it) where they showed doing 12-leads in the field was an abyssmal failure in one EMS (I think it was Seattle's) system. Distinguishing between an old infarct and a fresh one can be tricky, even for cardiologists, sometimes.

And, what about the legal liablility? What happens if you exsanguinate someone in the field because you gave them thrombolytics when what they really had a GI ulcer with equivocal ECG findings... all when the hospital was only 20 minutes away anyway?

I think those are the real issues here. Of course, we all want the best, fastest, and most effective treatment for all patients. No one is arguing that.