Can somebody explain this to me (thrombolytic agents in stroke patients)

[Ezekiel20]

---

Members don't see this ad.

Dear all

I was reading my textbook on stroke, and saw this sentence which I could not understand clearly.

-------------------------------------------------------------------

Thrombosis and other revascularisation treatments

IV thrombolysis with urokinase, streptokinase or recombinant tPA increases the risk of haemorrhagic conversion of the cerebral infarct with potentially fatal results.

However, the risk may be offset by an improvement in overall outcome if thrombolysis is given within 6 hours of onset of an ischaemic stroke, in the absence of hypertension, when the CT does not show extensive low density.

-------------------------------------------------------------------

So basically they are saying that in patients who just suffered a cerebral infarct, using a thrombolytic agent may cause a secondary haemorrhagic stroke. But if patient does not have HT and if early enough in the disease progession, it may improve overall outcome. But what does it mean by 'when the CT does not show extensive low density'?

The next sentence is unrelated to the above, so I don't think I've taken out of context. If somebody could explain to me what the 'extensive low density on CT' means, it would be great.

FYI, this paragraph came from p1166 of Davidson's 'Principles and Practice of Medicine' 19th edition, a general medicine textbook very popular in UK and the Commonwealth (similar to Kumar and Clark's Clinical Medicine)

 

[lilmo]

We learned that before giving a thrombolytic agent to a stroke patient, you should take a CT to rule out intracranial bleeding. So perhaps, the low density being referred to is blood? Just a guess.

 

[Swimdoc]

I am a 4th year med student on a stroke team right now. We give tPA only for a confirmed ischemic stroke (embolic or thrombotic). If a patient had a hemorrhagic stroke (most likely due to HTN, or due to an aneurysm), then tPA would be contraindicated. Our cutoff is 3 hrs, not 6.

Thus, the need for a CT scan. You need to confirm there is no hemorrhage.

 

[Ezekiel20]

I am a 4th year med student on a stroke team right now. We give tPA only for a confirmed ischemic stroke (embolic or thrombotic). If a patient had a hemorrhagic stroke (most likely due to HTN, or due to an aneurysm), then tPA would be contraindicated. Our cutoff is 3 hrs, not 6.

Thus, the need for a CT scan. You need to confirm there is no hemorrhage.

Thanks to both of you for clearing this up - I think the sentence on CT was just badly worded.

Man I wish I was a 4th year med student.. 🙂

 

[.edu-MD]

We learned that before giving a thrombolytic agent to a stroke patient, you should take a CT to rule out intracranial bleeding. So perhaps, the low density being referred to is blood? Just a guess.

Actually, blood is high density on a CT scan.

 

[Hurricane]

Low density is infarcted tissue I believe. So perhaps they meant that the outcome is not improved if there are already changes visible on CT.

You give tPA to patients who woke up with a stroke, because you don't know if they are in the 3 hour window or not. So I'd suppose that those with more advanced strokes would have areas of low-density on CT.

 

[liveandlearn]

Low density is infarcted tissue I believe. So perhaps they meant that the outcome is not improved if there are already changes visible on CT.

Most patients who have had onset of ischemic stroke symptoms within 6 hours initially will have normal findings on CT scan. After 6-12 hours, sufficient edema is recruited into the stroke area to produce a regional hypodensity on CT scan. A large hypodense area present on CT scan within the first 3 hours of symptom onset should prompt careful requestioning regarding the time of stroke symptom onset.

Unfortunately, as many as 5% of patients with subarachnoid hemorrhages also have normal CT scans, making lumbar puncture imperative when subarachnoid hemorrhage is suspected. CT scans also may fail to demonstrate some parenchymal hemorrhages smaller than 1 cm.

So, what sort of presentation would make you get the LP in addition to the CT?

 

[THP]

So, what sort of presentation would make you get the LP in addition to the CT?

I don't know the answer but will guess: some sort of cranial nerve changes that might indicate herniation? If I recall, the posterior fossa isn't well visualized on CT.

 

[PickyBicky]

I don't know the answer but will guess: some sort of cranial nerve changes that might indicate herniation? If I recall, the posterior fossa isn't well visualized on CT.

Ouch....dude, no. Never, ever tap when there is evidence of increased ICP (eg, focal CN findings possibly 2o/o herniation, papiloedma, etc). It can give rise to a fatal uncal herniation with the pressure gradient you just established by sticking the needle in.

-PB

 

[Ezekiel20]

Thanks to all who replied.

This morning's lecture cleared this issue once and for all.

Haemorrhage appears less dense on CT - so thrombolytic therapy is indicated within 3-6 hours of the onset of stroke, given that haemorrhage was ruled out by CT

 

[Hurricane]

Thanks to all who replied.

This morning's lecture cleared this issue once and for all.

Haemorrhage appears less dense on CT - so thrombolytic therapy is indicated within 3-6 hours of the onset of stroke, given that haemorrhage was ruled out by CT

But recent blood is white on CT. I thought that less dense = dark. 😕

Unfortunately, as many as 5% of patients with subarachnoid hemorrhages also have normal CT scans, making lumbar puncture imperative when subarachnoid hemorrhage is suspected. CT scans also may fail to demonstrate some parenchymal hemorrhages smaller than 1 cm.

So, what sort of presentation would make you get the LP in addition to the CT?

Meningeal signs? Sudden onset of the classic "worst headache of my life"?

 

[THP]

Ouch....dude, no. Never, ever tap when there is evidence of increased ICP (eg, focal CN findings possibly 2o/o herniation, papiloedma, etc). It can give rise to a fatal uncal herniation with the pressure gradient you just established by sticking the needle in.

-PB

I knoww that dropping the pressure too quickly can cause a herniation but don't the taps have a barometer on them?

Also, is there ever a situation where an SAH doesn't cause increased ICP? Are we talking about a situation where the bleed is really small (not picked up on ct)?

Maybe the presentation he is looking for is a patient with past medical history that predisposes them to berry aneurysms and lack of risk factors for atherosclerosis.

 

[angel80]

Haemorrhage appears less dense on CT - so thrombolytic therapy is indicated within 3-6 hours of the onset of stroke, given that haemorrhage was ruled out by CT

Blood is hyperdense on a CT (ie. it's white) Hypodense is dark.

 

[liveandlearn]

But recent blood is white on CT. I thought that less dense = dark. 😕



Meningeal signs? Sudden onset of the classic "worst headache of my life"?

yup! and what are the names of the two physical exam meningeal signs? and what would you see on the LP?

 

[liveandlearn]

I knoww that dropping the pressure too quickly can cause a herniation but don't the taps have a barometer on them?

Also, is there ever a situation where an SAH doesn't cause increased ICP? Are we talking about a situation where the bleed is really small (not picked up on ct)?

Maybe the presentation he is looking for is a patient with past medical history that predisposes them to berry aneurysms and lack of risk factors for atherosclerosis.

Yes, there are situations that an SAH doesnt cause ICP. What you really dont want to LP is a brain absess.

 

[generalIM]

yup! and what are the names of the two physical exam meningeal signs? and what would you see on the LP?

Aren't eponyms fun:

Brudzinkski's sign - neck flexion causing hip flexion
Kernig's sign - with hips and knees flexed, extension of the knee causes pain and resistence to extension.

Depends on when you get the LP. Early you can try to figure it out by the presence of RBC (but you have to worry about iatrogenic cause from a traumatic tap, but often looking at RBCC of each tube helps separate the two), After 6-12 hours a LP should show xanthochromia because of hemolysis of the RBC cells from the SAH.

So what is the most common cause of death in patients with SAH (assuming patient is not one of the 30% die at when the aneurysm ruptures)?

 

[THP]

Aren't eponyms fun:

Brudzinkski's sign - neck flexion causing hip flexion
Kernig's sign - with hips and knees flexed, extension of the knee causes pain and resistence to extension.

Depends on when you get the LP. Early you can try to figure it out by the presence of RBC (but you have to worry about iatrogenic cause from a traumatic tap, but often looking at RBCC of each tube helps separate the two), After 6-12 hours a LP should show xanthochromia because of hemolysis of the RBC cells from the SAH.

So what is the most common cause of death in patients with SAH (assuming patient is not one of the 30% die at when the aneurysm ruptures)?

Out of curiosity, why would you have meningeal signs with an SAH, I thought they were caused by inflammation (usually of infectious origin)?

 

[cheech10]

Out of curiosity, why would you have meningeal signs with an SAH, I thought they were caused by inflammation (usually of infectious origin)?

It's irritation that causes the signs, and blood is very irritating to the meninges.

 

[Hurricane]

So what is the most common cause of death in patients with SAH (assuming patient is not one of the 30% die at when the aneurysm ruptures)?

The evil vasospasm Esp about 10 days out. Transcranial dopplers for all...

 

[jaydoc07]

I think there is still some confusion and a few things need cleared up.
1. Yes, CT is indicated prior to tPA to r/o intracranial hemorrhage, which acutely appears hyperdense on non-contrast CT (always get non-contrast in this instance)
2. The window for IV tPA is a confirmed 3 hours from the time of onset from an awake patient or a witness, or the last time the patient was seen awake and asymptomatic if sx are present upon awakening (thus people who wake up c symptoms don't automatically get tPA)
3. The 6 hour window people speak of is for interarterial tPA (assuming no contraindications which are the same for IV tPA like recent surgery, etc)
4. It would be really hard, i.e. impossible to hit a brain abcess with a lumbar punture
5. Where the heck did ruling out SAH enter the conversation? The presentation of stroke, be it hemorrhagic or ischemic is markedly different than SAH.

 

[liveandlearn]

4. It would be really hard, i.e. impossible to hit a brain abcess with a lumbar punture
QUOTE]

I love how you are trying to be cocky here but you might want to review the contraindications to LP before you start italicizing words you know nothing about. Research it and come back and post why you dont do an LP on a suspected brain abcess. If you dont reply by tommorow I'll tell you.

For future reference. don't "clarify" things for others if you dont know what you're talking about.

You are right though. one thing needs to be cleared up now that I have gone back over the thread. The reason it needs to be cleared up is because everyone was only thinking about hemm. stroke as a contraindication for tPA. The HYPO.... YES, HYPO... density on CT is edema that is recruited in an ischemic stroke usually AFTER 6 hours. SO, if there is a HYPOdensity then the stroke probably happend OVER 6 hours ago and tPA is contraindicated.

does that help 'clear things up'?

 

[jaydoc07]

For one, brain abcess is not a contraindication to LP. Spinal epidural abcess is, for obvious reasons. Thus, my sarcastic comment holds true.

Second, I understand that ischemic stroke will appear hypodense on CT. Notice how I was referring to hemorrhagic stroke and put the word acutely right in there as well. CT is not used to estimate the time of stroke onset, symptomatology is. CT is only used to confirm the stroke is not hemorrhagic in nature. Therefore, if symptoms have occurred within the time window and there is no evidence of hemorrhagic stroke (i.e. HYPERdense lesion), then you can proceed with tPA assuming there are no other contraindications.

I appreciate you attempt at being witty, but if anyone needs to go do some research it is you my friend.

 

[cheech10]

Let me spell it out for you jaydoc, since you seem to have missed the point:

brain abscess => increases ICP
so when you LP the guy => tonsillar herniation => really bad stuff for the patient and your future medical career. Ergo, don't LP the brain abscess.

 

[jaydoc07]

Brain abcess doesn't necessarily increase ICP, and if it does you can visualize it on CT. Thus, increased ICP is a contraindication for LP, not simply having a brain abcess.

 

[lilmo]

Brain abcess doesn't necessarily increase ICP, and if it does you can visualize it on CT. Thus, increased ICP is a contraindication for LP, not simply having a brain abcess.

hey jaydoc,

are you a jayhawk? (do you go to KU?)

 

[liveandlearn]

Brain abcess doesn't necessarily increase ICP, and if it does you can visualize it on CT. Thus, increased ICP is a contraindication for LP, not simply having a brain abcess.

~20% of brain abcess that get an LP die.

http://www.emedicine.com/EMERG/topic67.htm

there is a reference stating the "vast majority of LPs should be defered because of risk."

now, if there is a regional hypodensity on CT in a ischemic stroke then the stroke probably happened >6 hours ago. I dont know why you keep arguing with me, I wish you would look this stuff up.

 

[jaydoc07]

What do i have to look up?
First, I agree that a stroke over 6 hours will probably appear hypodense, but hypodensities secondary to ischemic stroke can appear well before 6 hours, even before 3 hours. Pts with EIC on CT given thrombolysis have no significant increased risk of hemorrhagic stroke, and overall outcomes are improved. There is a ton of literature that supports this.

So say it with me now.....a HYPOdense lesion is not a contraindication to thrombolysis. Why don't you go look this up.

Second, your reference says a vast majority should be referred due to risk of herniation from increased ICP...and just as I said before, increased ICP is the reason LP is contraindicated in brain abcess. You do realize that your emedicine reference sites its most recent source regarding management of brain abcess from a paper written in 1992.

Finally, no, I am not from KU. My name happens to be Jay, and I was not aware of their nickname until about 90 people brought it to my attention. I think I will be changing my handle now.

 

[liveandlearn]

you basically just repeated everything i have been saying

 

[jaydoc07]

Not really. For some odd reason you keep telling me to "look things up," when the inconsistencies are with the facts you present. What I said is not just the same thing you did.

 

[Poety]

What do i have to look up?
First, I agree that a stroke over 6 hours will probably appear hypodense, but hypodensities secondary to ischemic stroke can appear well before 6 hours, even before 3 hours. Pts with EIC on CT given thrombolysis have no significant increased risk of hemorrhagic stroke, and overall outcomes are improved. There is a ton of literature that supports this.

So say it with me now.....a HYPOdense lesion is not a contraindication to thrombolysis. Why don't you go look this up.

Second, your reference says a vast majority should be referred due to risk of herniation from increased ICP...and just as I said before, increased ICP is the reason LP is contraindicated in brain abcess. You do realize that your emedicine reference sites its most recent source regarding management of brain abcess from a paper written in 1992.

Finally, no, I am not from KU. My name happens to be Jay, and I was not aware of their nickname until about 90 people brought it to my attention. I think I will be changing my handle now.

I was under the impression that any mass effect (which an abscess would cause) is a contraindication to LP - this was from my neuro attending.

Re when do you do a tap: 24 yo obese female with a horrible HA w/or w/o papilledema- pseudotumor cerebri? tap and they feel 100% better

 

[liveandlearn]

Not really. For some odd reason you keep telling me to "look things up," when the inconsistencies are with the facts you present. What I said is not just the same thing you did.

good god you're stuborn. this is what I meant by "look it up."

http://www.ncbi.nlm.nih.gov/entrez/..._uids=15383482&query_hl=2&itool=pubmed_docsum

"Among the key recommendations in this chapter are the following: For patients with acute ischemic stroke (AIS), we recommend administration of i.v. tissue plasminogen activator (tPA), if treatment is initiated within 3 h of clearly defined symptom onset (Grade 1A). For patients with extensive and clearly identifiable hypodensity on CT, we recommend against thrombolytic therapy (Grade 1B)." (Albers et al., 2004)

jeez.. stop already

 

[jaydoc07]

http://www.ncbi.nlm.nih.gov/entrez/..._uids=16166579&query_hl=2&itool=pubmed_docsum