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Without evidence of benefit, an intervention should not be presumed to be beneficial or safe.

- Rogue Medic

Conspiracy Theory Week – Truthers, Anecdotalists, and Creationists, Oh My!

Sat, 15 Sep 2012 14:00:28 -0400 by
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Conspiracy theorists come in many flavors of self-deception, but they aren’t really that different from the typical true believer in anything else.

I have been writing about myths that we continue to use as standards of care, in spite of a lack of evidence. These are based on the same belief that are behind the myths being pushed by the 9/11 truthers.

The simplest argument against the truthers is that they blame the Bush administration. The same Bush administration that went to war with Iraq, but did not plant any weapons of mass destruction. Are we supposed to believe that thousands of people would murder thousands of Americans based on where they were when the planes hit, but we could not get a much smaller number of people to frame Saddam Hussein – a guy who is easy to hate.

Not just that, but the conspiracy is supposed to have been carried out in the first year of the first term of President Bush, while the absence of a conspiracy of weapons of mass destruction took place years later, after they had much more time to plan.
 

I know it because of Screwy Idea X.
 

Screwy Idea X may be true, may be partially true, may be completely false, or may be completely unrelated.
 

You have to prove that Screwy Idea X is false.
 

If Screwy Idea X is false, will it be easy to prove it is false? If it is not easy to prove that Screwy Idea X is false, does that mean that anecdote X is true?
 


Image credit.
 

The burden of proof should not be on the person who says, Screwy Idea X is ridiculous.
 

If you can’t prove that Screwy Idea X is false, that proves that Screwy Idea X is true.
 

Conspiracy theorists and denialists work on the same principle. There is never enough evidence to prove their idea is wrong.

As long as they can claim that there is a tiny possibility that they are right, that is their proof that they are right.

As long as they can claim that there is a tiny possibility that others are wrong, that is their proof that others are wrong.

Vaccines have saved millions of lives and are probably the safest medications we have, but what if your child has an extremely rare adverse reaction? No, autism is not caused by vaccines.

Alternative medicine is better than real medicine, because of _______. There are many problems with real medicine. I write about the problems – I don’t ignore the problems. Alternative medicine pushers ignore their problems and only criticize the problems of real medicine. Alternative medicine is pretending that an unknown treatment has been kept hidden by a conspiracy of Big Pharma and it really works. Except that the evidence consistently shows that alternative medicine does not perform any better than placebo. Alternative medicine is big business and the business is fraud.

We need to get rid of the prescription and over-the-counter medicines that don’t work. We do not need to add more medicines that don’t work.

Creationism is real and evolution is a lie because of conspiracy X. Even though plenty of religions do not see any conflict between their holy books and evolution. Individual preachers will claim that a literal interpretation is essential, but only when it supports what they preach. If the religious do not agree that 6 Day Creationism is real, and there is no evidence that 6 Day Creationism is real, then why should anyone believe that 6 Day Creationism is science?

We accept the crackpot idea because the true believer is charismatic.

Charisma can cover up a lot of flaws, even flaws as ridiculous as what I have already covered.
 

In medicine, we have our own true believers.

 

I know it because of Screwy Idea X.
 

Bleeding to get rid of bad humors.

Oxygen for myocradial infarction.

Antiarrhythmics for myocardial infarction.

Spinal immobilization for mechanism of injury.

Tourniquets mean amputations.

Ventilation for cardiac arrest.

Rotating tourniquets for CHF (because people with heart failure don’t mind a little amputation).

Furosemide (frusemide, brand name Lasix) moves fluid from the lungs to the kidneys.

Furosemide causes vasodilation.

If we give pain medicine, the patient will stop breathing.

Even though epinephrine causes heart failure, it is the best solution to a heart that has stopped.

Not just epinephrine for cardiac arrest – vasopressin, norepinephrine, phenylephrine, amiodarone, lidocaine, and magnesium.
 

The foundation of successful ACLS is high-quality CPR, and, for VF/pulseless VT, attempted defibrillation within minutes of collapse. For victims of witnessed VF arrest, early CPR and rapid defibrillation can significantly increase the chance for survival to hospital discharge.128,–,133 In comparison, other ACLS therapies such as some medications and advanced airways, although associated with an increased rate of ROSC, have not been shown to increase the rate of survival to hospital discharge.31,33,134,–,138 [1]

 

Maybe the 2015 ACLS Guidelines will be truly evidence-based and will NOT include any medications.
 

You have to prove that Screwy Idea X is false.

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Some of the treatments mentioned above have been eliminated, but there are many that continue to be used –

Sunday, I wrote about a doctor claiming that there is a screwy compelling idea that demonstrates that oxygen is good, regardless of the lack of evidence. He also claims that since there is not perfect proof that oxygen is harmful, that is PROOF that oxygen is good.
 

If it helps just one patient, that justifies killing other patients.
 

Monday, I wrote about a doctor claiming that there is a screwy compelling idea that demonstrates that spinal immobilization is good, regardless of the lack of evidence. He also claims that since there is not perfect proof that spinal immobilization is harmful, that is PROOF that spinal immobilization is good.
 

If it helps just one patient, that justifies disabling other patients.
 

Tuesday, I wrote about a bunch of doctors (the AHA – American Heart Association – and others) claiming that there is a screwy compelling idea that demonstrates that ventilation is good, regardless of the lack of evidence. They also claim that since there is not perfect proof that ventilation is harmful, that is PROOF that ventilation is good.
 

If it helps just one patient, that justifies preventing the resuscitation of other patients.
 

I didn’t write anything on Wednesday. I was working on something long for Thursday (even the title was long).

Thursday, I wrote about a bunch of doctors (including the AHA) claiming that there is a screwy compelling idea that demonstrates that tPA is good, regardless of the lack of quality of the evidence. They also claim that since there is not perfect proof that tPA is harmful, that is PROOF that tPA is good hours and hours later.
 

If it helps just one patient, that justifies causing bleeding in the brains of other patients.
 

Friday, I wrote about the way the standard of care is perceived. All of these people I mentioned are claiming that their pet treatments, about which they are very biased, should not be affected by any negative evidence and why the evidence in favor of their pet therapy is all that we should pay attention to.

Ignore the flaws of the positive research – assuming there is any positive research. Belief.

Only pay attention to the flaws of the negative research. Willful ignorance.

This is not the way to do what is best for our patients.
 

If it helps just one patient, that justifies all of the harm to the other patients.
 

Am I exaggerating?

No, I am just simplifying the excuses for the lack of evidence to support their belief.

If you can’t prove that Screwy Idea X is false, that proves that Screwy Idea X is true.

No.

This is just an example of a logical fallacy.

The argument from ignorance.[2]

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Footnotes:

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[1] Overview
2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Part 8: Adult Advanced Cardiovascular Life Support
Part 8.2: Management of Cardiac Arrest
Free Full Text from Circulation

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[2] Argument from ignorance
Wikipedia
Article

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Filed Under: 'Alternative' Medicine, 2010 AHA Guidelines, Creationism, Epinephrine, Ethics, Evidence, Heresy, Lasix, Mythology, Science, tPA

Is a clot-busting drug safe for 6 hours after stroke symptom onset – or only for an hour and a half? – Part I

Thu, 13 Sep 2012 08:00:25 -0400 by
ResearchBlogging.org
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The clot-buster tPA (tissue Plasminogen Activator) is given to stroke patients within 3 hours of onset of symptoms (some use 4 1/2 hours), based on a poorly done study. Some doctors are claiming that the benefits from tPA for stroke can be extended even to 6 hours.

Are the authors exhibiting stroke-like symptoms from sipping too much of their own Kool-Aid?

My first experience with a patient being given tPA for stroke was over a decade ago with a patient I brought to the hospital within about 45 minutes of symptom onset. The criteria for treatment were a negative CT (Computerized Tomography) scan for intracranial bleed, ruling out other bleeding risks, and a maximum of 3 hours from witnessed symptom onset.

The biggest delay was supposed to be the time it takes to get the CT scan. The neurologist was there, read the scan – all within an hour and a half of symptom onset, and then waited

and

waited

and

waited

and

– at 2 hours and 55 minutes from the onset of symptoms – the neurologist gave the order to begin treatment.

tPA is not an all-or-nothing drug. This isn’t a movie, where the hero can receive an antidote a few seconds before a poison would kill him, and he is unharmed. Damage is cumulative, and often permanent. The possible benefits decrease with time, while the side effects don’t have much reason to change with time. Damage to the brain does not magically go away.

If I want to take a hot shower, I want to run the water just long enough to get the water hot, but not so long that I run out of hot water. The amount of remaining hot water decreases the longer I wait. There is nothing wrong with cold showers, but if the goal is a hot shower, that is the wrong way to accomplish the goal.

With a stroke, the goal is appropriate treatment as quickly as possible, because the longer the ischemic part of the brain is ischemic, the worse the outcome. The benefit runs out over time.

The NINDS (National Institute of Neurological Disease and Stroke) trial, that led to the original rush to make tPA the standard of care, was the response to smaller studies that showed mixed results with use of tPA.

These results were enough to justify further investigation in the form of a larger, randomized, placebo-controlled trial.[1]

So, thousands of patients were enrolled in this huge stroke trial was begun. OK, there were 614 patients enrolled. Part 1 only looked at improvement 24 hours later. That may be the ROSC of stroke care – nice, but irrelevant if that is all we get. There were only 333 patients in the part that mattered – Part 2. Only 168 received the study drug in Part 2. But Part 2 was broken down into 0-90 minutes from symptom onset to treatment initiation and 91-180 minutes. There is no real controversy about using tPA within 90 minutes of symptom onset. The controversy is with treatment from 91 to 180 minutes (1 1/2 hours to 3 hours).

Only 82 patients received the study drug in Part 2 that time period. Maybe the Part 1 patients should be included, since their results are included by the authors, but that is still only 168 patients.

We need to be careful of drawing big conclusions from small numbers. These are small numbers representing a diverse patient population.

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The primary hypothesis for part 2 was that there would be a consistent and persuasive difference between the t-PA and placebo groups in terms of the proportion of patients who recovered with minimal or no deficit three months after treatment.[1]

The results reported suggest that this is what happened, but as more information has been released about the study, it has become apparent that the patients in the treatment group were much healthier than patients in the placebo group.
 


Picture credit.
 

Some people who want to get rich will trade on the futures market. How do you make a million dollars on the futures market? Start with two million dollars. Your two million dollars will soon become one million dollars.

The authors appear to have a similar philosophy. One way to make a drug look good is to compare it to a drug that is worse. In a placebo trial, that may not be possible, so the way to make an ineffective drug look good is to put the sicker patients in the placebo group. Even a dangerous drug will not look so bad by comparison.

Did the authors hide the difference in stroke severity intentionally? It doesn’t matter. The authors did not make it easy to get the relevant information.

tPA is a treatment that has become standard of care without good evidence.

The AHA (American Heart Association) has also been pushing this poorly studied treatment aggressively with mandatory content in their courses on treating heart problems.
 

The problems with the study have not gone unnoticed.

Dr. Jerome Hoffman wrote –

Another concern is that, in the 91-180 minute group, patients who received placebo were much sicker at baseline than those treated with tPA. Sicker patients tend to have worse outcomes, and these baseline differences may explain much of the apparent benefit that has been attributed to tPA. These problems make it unclear whether there was any benefit to the use of tPA. If so, it is almost certain that the time limit for benefit is far less than 180 minutes, and perhaps much closer to 90 minutes.[2]

 

Dr. Jeffrey Mann wrote –

In summary, the recommendations for the use of tPA in patients with acute ischemic stroke were based on an initial misinterpretation of the results of the NINDS trial and are, therefore, unwarranted.[3]

 

In defense of the lack of research, Dr. Patrick D. Lyden, one of the NINDS investigators, writes –

The limitations on this therapy—the only proven stroke treatment—are legendary: patients must be treated promptly after stroke onset, must have no contraindications to thrombolysis, and must be treated by a team skilled in preventing potential complications. Much has been made of these limitations, to the point of considerable nihilism among neurologists. Yet, results similar to the NINDS data are obtained in communities with active stroke teams dedicated to proper use of intravenous thrombolysis.[4]

 

Is the study just misunderstood?

Is tPA really a hooker with a heart of gold?

Results Seventy patients (1.8%) admitted with ischemic stroke received IV tPA. Of those, 11 patients (15.7%; 95% confidence interval [CI], 8.1%-26.4%) had a symptomatic ICH (of which 6 were fatal) and 50% (95% CI, 37.8%-62.2%) had deviations from national treatment guidelines. In-hospital mortality was significantly higher among patients treated with tPA (15.7%) compared with patients not receiving tPA (5.1%, P<.001) and compared with the model's prediction (7.9%; P<.006).[5]

 

Only half of the patients treated met the treatment criteria for tPA.

The in-hospital death rate was 5.1% without tPA.

The in-hospital death rate was 15.7% with tPA.

This is what Dr. Lyden is defending.

That paper was published before Dr. Lyden’s editorial

Dr. Lyden finishes with an absurd statement –

Perhaps we will find a way to treat patients later than 3 hours, and further studies are needed to push the outer limit of the time window, but within the 3-hour window, no further trials are needed; the drug works. The dictum primum no nocere still applies: we must do no harm, either by actively committing an act or by withholding a proven therapy through inaction.[4]

 

We have too many doctors defending too many poorly studied treatments.

Primum non nocere means first, do no harm.

Giving a poorly studied treatment, while claiming that it would be unethical to learn more about the treatment, is dangerous to the patient.

Giving a poorly studied treatment, while claiming that it would be unethical to learn more about the treatment, corrupts our ability to think rationally.

Giving a poorly studied treatment, while claiming that it would be unethical to learn more about the treatment, corrupts our ability to think ethically.

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IST-3[6] is an attempt to extend the treatment window for tPA to 6 hours. I will write about that later. This was just to set the stage and introduce some of the cast of characters.

When treating cardiac arrest, we try to minimize the amount of damage from reperfusion, but with stroke we only seem to be trying to minimize re-examination of a treatment that never should have become the standard of care.

Continued in Part II.

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Footnotes:

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[1] Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group.
[No authors listed]
N Engl J Med. 1995 Dec 14;333(24):1581-7.
PMID: 7477192 [PubMed – indexed for MEDLINE]

Free Full Text from NEJM.

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[2] Thrombolytic therapy for acute ischemic stroke – Tissue plasminogen activator for acute ischemic stroke: Is the CAEP Position Statement too negative?
Hoffman JR.
CJEM. 2001 Jul;3(3):183-5. No abstract available.
PMID: 17610781 [PubMed – in process]

Free Full Text from CJEM.

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[3] Truths about the NINDS study: setting the record straight.
Mann J.
West J Med. 2002 May;176(3):192-4. No abstract available.
PMID: 12016245 [PubMed – indexed for MEDLINE]

Free Full Text from PubMed Central.

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[4] Further randomized controlled trials of tPA within 3 hours are required-not!
Lyden PD.
Stroke. 2001 Nov;32(11):2709-10. No abstract available.
PMID: 11692041 [PubMed – indexed for MEDLINE]

Free Full Text from Stroke.

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[5] Use of tissue-type plasminogen activator for acute ischemic stroke: the Cleveland area experience.
Katzan IL, Furlan AJ, Lloyd LE, Frank JI, Harper DL, Hinchey JA, Hammel JP, Qu A, Sila CA.
JAMA. 2000 Mar 1;283(9):1151-8.
PMID: 10703777 [PubMed – indexed for MEDLINE]

Free Full Text from JAMA.

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[6] The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial.
IST-3 collaborative group, Sandercock P, Wardlaw JM, Lindley RI, Dennis M, Cohen G, Murray G, Innes K, Venables G, Czlonkowska A, Kobayashi A, Ricci S, Murray V, Berge E, Slot KB, Hankey GJ, Correia M, Peeters A, Matz K, Lyrer P, Gubitz G, Phillips SJ, Arauz A.
Lancet. 2012 Jun 23;379(9834):2352-63. Epub 2012 May 23. Erratum in: Lancet. 2012 Aug 25;380(9843):730.
PMID: 22632908 [PubMed – indexed for MEDLINE]

Free Full Text from PubMed Central.

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NINDS researchers (1995). Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. The New England journal of medicine, 333 (24), 1581-7 PMID: 7477192

Hoffman JR (2001). Thrombolytic therapy for acute ischemic stroke – Tissue plasminogen activator for acute ischemic stroke: Is the CAEP Position Statement too negative? CJEM, 3 (3), 183-5 PMID: 17610781

Mann J (2002). Truths about the NINDS study: setting the record straight. The Western journal of medicine, 176 (3), 192-4 PMID: 12016245

Lyden PD (2001). Further randomized controlled trials of tPA within 3 hours are required-not! Stroke; a journal of cerebral circulation, 32 (11), 2709-10 PMID: 11692041

Katzan IL, Furlan AJ, Lloyd LE, Frank JI, Harper DL, Hinchey JA, Hammel JP, Qu A, & Sila CA (2000). Use of tissue-type plasminogen activator for acute ischemic stroke: the Cleveland area experience. JAMA : the journal of the American Medical Association, 283 (9), 1151-8 PMID: 10703777

IST-3 collaborative group, Sandercock P, Wardlaw JM, Lindley RI, Dennis M, Cohen G, Murray G, Innes K, Venables G, Czlonkowska A, Kobayashi A, Ricci S, Murray V, Berge E, Slot KB, Hankey GJ, Correia M, Peeters A, Matz K, Lyrer P, Gubitz G, Phillips SJ, & Arauz A (2012). The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial. Lancet, 379 (9834), 2352-63 PMID: 22632908

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Filed Under: ACLS, Ethics, Evidence, Heresy, Mythology, Pharmacology, Research Blogging, tPA

Why are we making the heart work harder in heart failure?

Wed, 08 Aug 2012 08:00:28 -0400 by
ResearchBlogging.org
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Is the harm from furosemide (Lasix – frusemide in Commonwealth countries) anything new?

This study is looking at the effects of furosemide in patients with chronic CHF (Congestive Heart Failure), not acute exacerbations of CHF. This should have led to studies of the effects of furosemide on acute CHF. After all, in 1985 everyone seems to have been using furosemide for acute CHF.
 

Our clinical observation of what appeared to be acute worsening of symptoms after intravenous furosemide administration in some patients with severe heart failure led us to study the sequential hemodynamic and neurohumoral responses in a series of such patients.[1]

 

We have seen patients get worse. It is 1985. We are not the first to study this, but emergency medicine and EMS will not really cut back on the use of furosemide for acute CHF until after 2000 – more than a decade and a half.
 

All patients had clinical evidence of congestive heart failure for at least 6 months and were hospitalized for heart failure. No patient had frank pulmonary edema. The average ejection fraction, as measured by radionuclide angiography in 14 patients, was 22 ± 5% (SD).[1]

 

Each patient was on a sodium-restricted diet, and all had symptoms typical of New York Heart Association class III to IV.[1]

 

These were sick patients at baseline. It is not clear if these patients were already in the hospital for treatment of CHF or if they were recruited as outpatients. No patients had heart attacks within the previous 4 months.
 

Digitalis and diuretics were used chronically by all patients, but none had used vasodilator therapy for at least 72 hours before the study. Most patients were receiving chronic furosemide therapy, but the usual morning dose was withheld until the study (usually midmorning).[1]

 

Is IV (IntraVenous) furosemide worse than oral furosemide?

When treating acute CHF, do we really care?
 

Each patient then received an average dose of 1.3 ± 0.6 mg/kg body weight of furosemide given over 1 to 2 minutes.[1]

 

For a 70 kg patient, that would be 91 mg ± 42 mg (between 49 mg and 133 mg [between 0.7 mg/kg and 1.9 mg/kg]) over one to two minutes. Not a huge dose, but not a tiny dose, either.
 

Two patients became noticeably shorter of breath by 10 to 20 minutes after furosemide administration.[1]

 

If the patient is healthy enough for us to give them a drug that makes them sicker, are they surviving their illness or are they just surviving our abuse?
 


 

Immediately increased heart rate. How much worse would it become if the patient had acute pulmonary edema?
 


 
Immediately decreased stroke volume. How much worse would it become if the patient had acute pulmonary edema?

 

 

Immediately increased systemic vascular resistance. How much worse would it become if the patient had acute pulmonary edema?
 

If the heart rate gets worse, the stroke volume gets worse, and the systemic vascular resistance gets worse, then we expect the blood pressure to get worse. Is the blood pressure going to get worse by dropping or by increasing?
 


 

The most effective medical treatment for acute pulmonary edema is vasodilators – especially high-dose NTG (NiTroGlycerin – GTN GlycerylTriNitrate in Commonwealth countries).

Furosemide is doing exactly the opposite of what we want it to do.

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An increase in plasma arginine vasopressin levels after furosemide administration is also a new finding.[1]

 

This is not what we want.

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Activation of the sympathetic nervous system by intravenous furosemide treatment in patients with congestive heart failure is a new finding.[1]

 

This is not what we want.
 

The use of intravenous furosemide in patients with chronic congestive heart failure, although well established, can promote further clinical hemodynamic deterioration during the first 20 minutes.[1]

 

Traditional, but harmful.

In other words – Standard Of Care.
 

This deterioration may go largely unnoticed because such patients often are already dyspneic and show clinical improvement over the next hour.[1]

 

Maybe we need to pay more attention to what is going on with our patients, rather than paying attention to killer traditions.

We could get similar results with a bolus of epinephrine, but we usually wait until the patient is dead to do that.

Maybe the only reason we don’t give furosemide in cardiac arrest is that we are afraid that it might make the patient pee.
 

These patients were not having acute attacks of CHF before receiving furosemide.

These patients got a lot worse before they returned to their baseline.

Is there any reason to believe that the furosemide behaves any better when the CHF patient is already short of breath and his lungs are filling with fluid?

The furosemide is supposed to work on the kidneys, but acute CHF patients have poor circulation to the kidneys, so even that is not likely to do anything until after the patient is much better.
 

Other posts on furosemide (Lasix).

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Footnotes:

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[1] Acute vasoconstrictor response to intravenous furosemide in patients with chronic congestive heart failure. Activation of the neurohumoral axis.
Francis GS, Siegel RM, Goldsmith SR, Olivari MT, Levine TB, Cohn JN.
Ann Intern Med. 1985 Jul;103(1):1-6.
PMID: 2860833 [PubMed – indexed for MEDLINE]

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Francis GS, Siegel RM, Goldsmith SR, Olivari MT, Levine TB, & Cohn JN (1985). Acute vasoconstrictor response to intravenous furosemide in patients with chronic congestive heart failure. Activation of the neurohumoral axis. Annals of internal medicine, 103 (1), 1-6 PMID: 2860833

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Filed Under: Cardiology, Heresy, Lasix, Mythology, NTG, Pharmacology, Research Blogging, Risk Management, tPA

This is the Way to Bad Medicine – II

Thu, 02 Feb 2012 06:30:32 -0500 by
ResearchBlogging.org
 

A post at EM Literature of Note provides another example of bad research. Not just bad, but deadly.
 

The benefit of tPA in acute stroke is linked to the speed and degree of clot lysis and artery recanalization. 16 –18 [1]

 

Speed does appear to be most important. The debate about the efficacy of tPA (tissue-type plasminogen activator) for stroke is not that tPA will not be a good treatment when given within 90 minutes (1 1/2 hours). The debate is about the whether there is benefit when tPA is given between 90 minutes and 180 minutes (between 1 1/2 hours and 3 hours). The AHA (American Heart Association) quickly made it part of the guidelines to give tPA to as many patients with embolic stroke within 3 hours as possible. Some places have even expanded the fibrinolytic window to 270 minutes (4 1/2 hours).

If the AHA does the same with this proposed treatment, our stroke patients might be better off if we took them to hospitals NOT equipped to treat strokes.

Why?

Let’s look at the study –
 

Purpose
The primary purpose of this study was to assess the safety of combined Argatroban and tPA in ischemic stroke as measured by the incidence of significant intracerebral hemorrhage (ICH). The secondary objective was to evaluate drug activity by determining the speed and completeness of arterial recanalization and reocclusion.[1]

 

The primary purpose of this study is to determine safety.
 

Safety was defined as a rate of symptomatic ICH or Parenchymal Hematoma Type 2 intracranial hemorrhage not exceeding 10%. We hypothesized that a hemorrhage rate of 10% might be acceptable only in the setting of significant increases in arterial recanalization, which is highly associated with improved clinical outcomes. [1]

 

Highly associated with?

I love treatments that are highly associated with some surrogate endpoint, because that is what matters to the patient.

We achieved the surrogate endpoint. That surrogate endpoint is highly associated with improved outcome. Therefore, you’re cured. Don’t try to speak to thank us. Just trust us.

You are cured.

Your inability to speak is probably just a conversion disorder – and don’t try to get up. You are cured, but your inability to walk is probably just psychological. It’s all in your head.

Too much sarcasm? Am I being unfair? Keep reading.
 

All patients received intravenous tPA (0.9 mg/kg). There was no delay in starting intravenous tPA as a result of participation in this study. Informed consent and other qualifying activities for the study took place after the intravenous recombinant tPA bolus was given.[1]

 

This is good. There is no change that affects the initiation of the standard treatment.
 

(3) baseline NIHSS score 17 (modified to 15 after the first 15 patients) for right hemisphere and 22 (modified to 20) for left hemisphere strokes;[1]

 

Why modified?
 

The first 2 significant hemorrhages occurred with NIHSS scores of 15 and 21 (both right MCA strokes), prompting the data and safety monitoring board to reduce the upper limit of the NIHSS score to 15 (right hemisphere) and 20 (left hemisphere).[1]

 

The lower the NIHSS (National Institutes of Health Stroke Scale[2]) number, the less serious the stroke. Scores range from 0 to 42, with higher being worse, so these are not severe strokes. How much improvement is worth to each patient vs. the risk of worse neurological injury, or death, is difficult to state. Looking through the grading, very intoxicated might score around the 13 average for the patients in this trial. I would not classify that as mild.
 

A total of 32 serious adverse events occurred in 22 patients (see Table 3).[1]

 


 

I do not know why they calculated these as percentages of the serious adverse events, rather than according to patients treated.

If you develop a serious adverse event, you have a 21% chance of death.

They appear to be assuming that this ratio will persist across serious adverse events, which is not a reasonable conclusion. This is just a derivative of what I want to know. What I want to know is –

If I receive the treatment, what are my odds of death, disability, et cetera.

Their categorization of only 3 (out of 32) serious adverse events as Probably related to treatment and none as Definitely related to treatment suggests that they are not being objective. How do they explain this in the discussion? They don’t. Maybe they aren’t referring to the serious adverse events, but are referring to deaths. I don’t know and since they do not explain, I can only speculate.

We know that tPA increases the risk of bleeding. We expect that giving an anticoagulant (argatroban is a thrombin inhibitor) with tPA increases that risk of bleeding. We conclude that the bleeding in our patients is just a coincidence, because that’s the way we roll, Yo!

You had a thrombotic stroke, but now you have so much bleeding that your brain is squeezing out through any orifice possible. This is just one of the improbably large number of coincidences during this study.
 

On discharge, 76% of patients went either home or to acute rehabilitation, and 7 patients died (10.8%). Five of the 7 deaths resulted from large hemispheric infarction with herniation, whereas the other 2 died from respiratory failure. Six of the 7 deaths occurred after the family requested withdraw of care.[1]

 

Six of the 7 deaths occurred after the family requested withdraw of care.

I don’t know if they are just providing complete information or suggesting that the deaths are the fault of the families for not trying to keep their family members alive in nursing homes with zero quality of life.
 

long enough to prevent any reocclusion. 12 However, 3 of our 4 significant hemorrhages occurred 18 hours into the infusion. A 12- to 18-hour infusion might produce even safer and equally effective results.[1]

 

However, shortening the infusion to zero hours might produce even safer and equally effective results.
 

What does Dr. Radecki say about this trial?
 

Because NIHSS score predicts bleeding, we can compare to the NINDS trial TPA group, whose median NIHSS score of 14 compared with this trial’s median of 13. The NINDS trial showed a 10.8% rate of ICH and about 4% mortality at 7 days.[3]

 

3 dead patients would have been 4.6%.

There were 7 dead – 10.8%.

Is it safe?

I guess that depends on how much life insurance you have on the person being treated and how much you dislike them.
 

These rates of bleeding are of the same order of magnitude seen with intravenous recombinant tPA alone and therefore low enough to justify further evaluation in more patients to arrive at a more confident assessment of the true risks of bleeding.[1]

 

What is their point?

What if . . . ?

What if this really is beneficial? We wouldn’t want to miss out on this potentially useful, although potentially very dangerous, treatment.

They are ignoring the risks. The question, What if . . . ? can also be reversed –

What if the adverse events in this group are statistically much lower than what we should expect if we were to treat a large number of patients?
 

Do the authors understand the risks they are subjecting patients to?
 

Higher doses of Argatroban might also be safe and even more effective, but this will require careful evaluation.[1]

 

Maybe the patients had all of these bleeds because we gave too much of our study drug that causes bleeding, but we aren’t going to rule out the possibility that we did not give enough.

Is this really that much different from presuming that blood-letting is not working because of not taking enough blood?[4]
 

Further study of this treatment combination appears warranted.[1]

 

No.

 

I hope that no IRB (Institutional Review Board) is ever impaired enough to come to the conclusion that this should be expanded to harm more patients.

Earlier, I asked if I was using too much sarcasm, but now I think I may have been too subtle. What do you think.

–

Footnotes:

–

[1] The Argatroban and Tissue-Type Plasminogen Activator Stroke Study: Final Results of a Pilot Safety Study.
Barreto AD, Alexandrov AV, Lyden P, Lee J, Martin-Schild S, Shen L, Wu TC, Sisson A, Pandurengan R, Chen Z, Rahbar MH, Balucani C, Barlinn K, Sugg RM, Garami Z, Tsivgoulis G, Gonzales NR, Savitz SI, Mikulik R, Demchuk AM, Grotta JC.
Stroke. 2012 Jan 5. [Epub ahead of print]
PMID: 22223235 [PubMed – as supplied by publisher]

–

[2] NIH Stroke Scale
NINDS
PDF Download of Stroke Scale with explanations of scoring

–

[3] Helping TPA Help Patients Bleed
Wednesday, January 25, 2012
EM Literature of Note
Article

–

[4] Answer to What is this Dangerous Treatment and How Long Did it Take to Stop Using it
Wed, 01 Feb 2012
Rogue Medic
Article

–

Barreto, A., Alexandrov, A., Lyden, P., Lee, J., Martin-Schild, S., Shen, L., Wu, T., Sisson, A., Pandurengan, R., Chen, Z., Rahbar, M., Balucani, C., Barlinn, K., Sugg, R., Garami, Z., Tsivgoulis, G., Gonzales, N., Savitz, S., Mikulik, R., Demchuk, A., & Grotta, J. (2012). The Argatroban and Tissue-Type Plasminogen Activator Stroke Study: Final Results of a Pilot Safety Study Stroke DOI: 10.1161/STROKEAHA.111.625574

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Filed Under: Ethics, Heresy, Pharmacology, Research, Research Blogging, Science, tPA

Well deserved Recognition for an Excellent Medical Educator

Sat, 02 Jul 2011 06:30:22 -0400 by
–

Dr. Bryan Bledsoe is one of the people who has encouraged me to learn more about patient care and assessment, which is the most important part of patient care.

For an introduction to the writing of Dr. Bledsoe, the series about EMS myths is probably the best place to begin.

All of these are available as PDF downloads from Dr. Bledsoe’s website at this page.

Bledsoe BE. EMS Mythology Part 1: MAST.
Emergency Medical Services (EMS). 2003; 32(3):99-101

Bledsoe BE. EMS Mythology Part 2: tPA for Ischemic Stroke.
Emergency Medical Services (EMS). 2003; 32(4):

Bledsoe BE. EMS Mythology Part 3: Critical Incident Stress Management.
Emergency Medical Services (EMS). 2003; 32(5):77-80

Bledsoe BE. EMS Mythology Part 4: Lights and Sirens.
Emergency Medical Services (EMS). 2003; 32(6):72-73

Bledsoe BE. EMS Mythology Part 5: Steroids for Acute Spinal Cord Injury.
Emergency Medical Services (EMS). 2003; 32(7):92-95

Bledsoe BE. EMS Mythology Part 6: Helicopters.
Emergency Medical Services (EMS). 2003; 32(8):88-90

Bledsoe BE. EMS Mythology Part 7: System Status Management.
Emergency Medical Services (EMS). 2003; 32(9):158-159

Bledsoe BE. EMS Mythology Part 8: Public Utility Models.
Emergency Medical Services (EMS). 2003; 32(10):45-47

There are plenty of other articles available from Dr. Bledsoe’s website, but most of these are still being promoted as definitely helpful. Dr. Bledsoe demonstrates that they are often not helpful and that they can be dangerous.

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Filed Under: Critical Judgment, Education, Heresy, Mythology, tPA

Merit Badge Courses, Amiodarone, and tPA

Fri, 17 Sep 2010 11:57:40 -0400 by
At EP Monthly, there is an interesting article – Merit Badge Courses: Who Benefits?

This is the second part from me. First was the quality of the merit badge courses. This is the honesty of the evidence presented. I am not claiming that what the AHA (American Heart Association) does is dishonest.

I am claiming that the AHA does not do enough to demonstrate that they are objective.

Oh, but look at all of the conflict of interest documentation!

Very nice paperwork – paperwork that makes a bureaucrat wet at night, but that does nothing for the patients – at least nothing good.

Is this chain of survival broken?

Jan Shoenberger, MD writes –

The huge stroke chapter seems to cater to emergent tPA-based treatment of acute stroke despite the fact that scientific controversy continues regarding this issue. Lawsuits have been mounted against EPs both for giving tPA and for failing to give tPA. In 2009, the AHA accepted over $17 million from pharmaceutical companies and device manufacturers. This does little to reassure EPs that the standards are purely evidence based.

Since I write mainly for EMS, I am going to leave tPA alone, at least for now. However, . . .

Consider amiodarone.

Now amiodarone is off patent, but amiodarone was made the first line drug for everything arrhythmic when it was still an expensive drug only available from Wyeth. $1/mg and 300 mg/dose with 2 doses not being uncommon. Hundreds of thousands of cardiac arrests treated by EMS and emergency departments. A large percentage of them presenting with VF/pulseless VT (Ventricular Fibrillation/Pulseless Ventricular Tachycardia).

VF and pulseless VT are both treated with epinephrine, then $300 of amiodarone, then epinephrine, then $300 of amiodarone again as long as the patient does not have a pulse. What if the patient gets a pulse back (ROSC – Return Of Spontaneous Circulation) before the patient is given any amiodarone? Just in case, we give them a bunch of prophylactic amiodarone to prevent them from going back into VF/pulseless VT.

A lot of EMS agencies never switched from lidocaine to amiodarone. They said that they couldn’t afford to. Many did.

Why?

Guidelines are Gospel.

This is the Cinderella Gold Standard – at least until the midnight when the new guidelines are released and the spectacular new Gold Standard has its coronation.

But –

Antiarrhythmics
There is no evidence that any antiarrhythmic drug given routinely during human cardiac arrest increases survival to hospital discharge. Amiodarone, however, has been shown to increase short-term survival to hospital admission when compared with placebo or lidocaine.[1]

Let me repeat what the AHA states about amiodarone and survival to discharge –

no evidence

How much evidence?

no evidence

–

Ironically, at the time, I argued with the people who claimed that amiodarone only increased the number of patients dying in the hospital. My point was that there had not been enough research done to make the claim that amiodarone definitely does not improve survival, any more than the claim that amiodarone should be given to all VF/pulseless VT patients – yet.

There were studies underway and the only honest thing to do was to wait for the evidence before making any kind of definitive statement.

That was a decade ago.

Where are the results of those large enough to show a difference in outcome studies? I think that it is fair to conclude that there was nothing positive in the large enough to show a difference in outcome studies.

In other words amiodarone does only increase the number of patients dying in the hospital.

Where are the results of these survival studies we were told to wait for?

If the research had been positive, would Wyeth not advertise it?

I haven’t seen anything positive about amiodarone in cardiac arrest.

Nothing.

Amiodarone is just another over-hyped ineffective drug that has become a part of the standard of care nonsense that we use to harm patients.

–

If I wanted to practice alternative medicine I could make more and I wouldn’t even need to have any education. I could just claim to be anything I want – except a real doctor. I could use magic words like Quantum, Qi or other Q words.

No.

I have no desire to be a fraud. The AHA needs to stop imitating the alternative medicine frauds and start acting like a science-based medicine organization.

Epinephrine – no evidence of improved outcomes that matter.

Amiodarone – no evidence of improved outcomes that matter.

We need to stop abusing patients with the wishful thinking of alternative medicine.

The new AHA ACLS guidelines are coming out next month. what are the chances that they reflect reality, rather than wishful thinking?

Our patients deserve better.

–

Footnotes:

–

[1] Management of Cardiac Arrest
2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Part 7.2: Management of Cardiac Arrest
Medications for Arrest Rhythms
Free Full Text from the AHA

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Filed Under: 'Alternative' Medicine, Critical Judgment, Heresy, tPA

Ride-Along as an EMT Student

Tue, 25 Aug 2009 13:51:00 -0400 by

http://www.thehandover.wordpress.com/

When I was in EMT school, we had to ride along with EMS for 3 shifts. The school arranged for us to ride with the San Francisco Department of Public Health. This was before the take-over by the fire department.

Friday evening 1600-2400 shift. I arrive and meet the crew I will be riding with. they check out their gear and we head out on the road. One of the medics asks me if I know what AEIOU TIPS[1] stands for. Golly. A chance to impress them with my ability to repeat something we memorized, rather than understood.

A is for Alcohol. And E is for . . .

That’s all you need to know. Alcohol is all we do. All night. Every night.

I don’t mention that they appear to be a pretty sober pair of medics. One of them seems to be reading my mind, and states that they are referring to alcohol consumed by the patients. We won’t be getting drunk on duty.

Well, there was some devastation at the lack of iterest in my ability to fetch a mnemonic that we had been told would be so important. Another Charlie Brown moment.

That was only the beginning of the Skinner Box effect.[2] Something to addict even the most resistant to the appeal of anecdote – the rogue EMT student – which I most certainly was not. Not yet. By the end of the shift, with 2 codes, 2 traumas, and a few other patients, I was ready to go audition for NBC’s show Trauma.[3] Mayberry EMS was not going to cut it for me. This was EMS. This is the way we set students up to become the Barney Fifes of EMS. Stress the emergency at the expense of the medical service.

The shift turned out to be one that could have been written for TV. 2 cardiac arrests (1 regained pulses – AEIOU TIPS = A – chronic alcoholic homeless person). Not showing any signs of mental function, but he had a pulse. A SAVE. Hazel Motes couldn’t have been prouder.

2 critical trauma patients (both were pedestrians crossing the street together, when struck by the same truck – AEIOU TIPS = A – most alcohol involvement in auto/pedestrian incidents is on the part of the pedestrians.[4] Drunk pedestrians do a pretty poor job of looking both ways before playing in traffic. Looking both ways is a simple technique, that is very effective at preventing all kinds of auto/pedestrian incidents.

Looking both ways helps the pedestrian to avoid a bad driver. The driver with too much whatever to pay attention to the road: Too much confidence in his/her ability to handle alcohol/other drugs and a motor vehicle at the same time; Too much confidence in his/her ability to handle text messaging and a motor vehicle at the same time; Too much confidence in his/her ability to handle a cell phone and a motor vehicle at the same time; Too much confidence in his/her ability to just plain handle a motor vehicle; And too much motor vehicle.

Do racoons look both ways before playing in traffic?

No. Raccoons are road meat/street pizza/speed bumps/. . . .

Do skunks look both ways before playing in traffic?

No. Skunks are more aromatic road meat.

Do deer look both ways before playing in traffic?

No. Deer are also road meat, but they occasionaly take a driver/passenger/both
along with them. Road meat and front seat meat.

The most effective way to reduce auto/pedestrian injuries/fatalities is to not walk in front of moving motor vehicles. Green light? Look both ways. Maybe you have never run a red light, but others are not so well behaved, or even so observant. A bunch of people are crossing the street at the same time, so no need to look both ways? No, but you may have company in the ED, or in the morgue. Won’t that be a consolation?

Meanwhile back at the busy shift, we had an odd drug reaction. He stated that he had taken something to help him relax. It was not his. There was no more left. It was not in a marked pill bottle. His heart rate is on the fast side. His neck is on the side. His tongue is on the outside. I had no clue. We did not cover anything like this in EMT school. One of the medics called command and asked for permission to give diphenhydramine (Benadryl), but medical command was uncomfortable with the idea and just wanted the patient transported. We arrived at the hospital and they gave the patient benztropine (Cogentin), which does the same thing that the medics could have done a while earlier with the diphenhydramine. The patient was having a dystonic reaction.

Then we had a surprise for all of us. None of us had met this guy before, even though he would go to the hospital every day for chest pain or difficulty breathing. The local newspaper even wrote about him in good old politically correct San Francisco. They called him the Million Dollar Man. Over a 3 year period, with daily 911 calls and full work-ups in the hospitals, they calculated that he had cost the city over a million dollars in unreimbursed care. And that was just the cost to the city. 404 pounds (according to him) and he wanted to be carried. One of the neighbors pointed out that he has no problem walking every time he calls the ambulance, so our backs appreciated that. He also does not want to go to the closest hospital, because They were mean to me yesterday. By the time we arrived at the hospital, he had alienated another 3 people. The guy has at least one talent and it isn’t charm.

Since then, I have not had many shifts that were as eventful as that. That was my first time working on an ambulance.

Footnotes:

^ 1 AEIOU TIPS
This is a mnemonic to help remember the causes of a change in mental function.

I have repeated several of the words, since there are several ways to use this mnemonic. You may eliminate the ones that are duplicates, that do not help you remember. Endocrine, Insulin, OverDose, UnderDose, and Pharmacy overlap. Infection, Sepsis, and Temperature overlap, too – but they get you to think about similar things differently. That may be helpful.

A – Alcohol

E – Electrolytes and Encephalopathy and Endocrine

I – Infection and Insulin

O – OverDose and Oxygen

U – Uremia/UTI and Underdose (not taking medications that should be taken)

T – Temperature (Hypo/HyperThermia) and Toxidromes (OverDose) and Trauma

I – Infection and Insulin, again

P – Pharmacy and Psych and Porphyria

S – Sepsis and Space occupying lesion and Stroke and Subarachnoid Bleed and Seizure

^ 2 Superstition in the pigeon
The root of many superstitious beliefs, such as full moons being busy in the ED, black clouds, white clouds, causing bad things to happen by saying, Slow or Quiet, . . . . Skinner’s experiments demonstrated that we behave no better than birds, when dealing with intermittent reinforcement. So, it is perfectly appropriate to refer to superstitious people as bird brains. The scary thing is that some are doctors, nurses, medics, et cetera. These bird brains are responsible for making decisions that affect patients’ lives. And these bird brains vote.

We should end this through education, but as TOTWTYTR repeatedly states, You can’t cure stupid.
Wikipedia (part 10 in contents if the link does not take you directly to this part of the page, or click refresh).
Article

^ 3 Trauma – New NBC Drama To Ridicule EMS
Rogue Medic
Article

^ 4 Age, sex, and blood alcohol concentration of killed and injured pedestrians.
Holubowycz OT.
Accid Anal Prev. 1995 Jun;27(3):417-22.
PMID: 7639925 [PubMed – indexed for MEDLINE]

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Filed Under: Heresy, tPA Tagged With:

Overdose Treatment – One Perspective

Sat, 30 May 2009 17:44:39 -0400 by

Also posted over at Paramedicine 101. Go check out the rest of what is there.

Wandering a bit from the recent All Cardiac – All of the Time drift of Paramedicine 101, but not entirely, I must point out an excellent post on Heroin Overdoses by a blogger, who really is much more imaginative than that post title suggests – Too Old To Work, Too Young to Retire. He is just as direct as the title suggests.

Here is an example of education on junkie slang. It is both translated to everyday English and comes with an explanation of the most effective and most appropriate treatment.

commonly known as “nodding off” or being “on the nod”. The person is usually easily woken up by either a shake on their shoulder or speaking to them loudly. Despite what some in EMS think, this is NOT an overdose. Because it is the desired effect, I refer to this as “a dose”.

He describes the protocol that is in place where he works. His protocol uses respiratory depression as the criterion for treatment with naloxone (Narcan). Some of us have protocols that require treatment with naloxone for Altered Mental Status. I am not in favor of treating opioid overdoses under Altered Mental Status protocols, because this discourages the medic from delivering appropriate care. In stead, the medic ends up delivering vending machine care.

Enter minimal diagnostic criteria _____, remember to use only approved EMS terminology (the protocol vending machine does not recognize unapproved terminology), press Enter, and out pops a treatment. Eureka! No Fuss, No Muss, No Thought, No Possibility For Error. At least, this is the way that many seem to design protocols. Of course, the word diagnostic would not be in the list of approved terminology.

If we are designing a protocol with Foolproof in mind, aren’t we designing protocols to encourage the hiring of fools? How can we deny that we expect fools to use the protocols, if we are designing the protocols with fools in mind? We are designing protocols to prevent fools from doing too much damage, while using those protocols. Wouldn’t it be better to just keep the fools from being authorized to poison patients?

There is a great article by Dr. Bledsoe on the error of using a set treatment for every unconscious patient.[1]

TOTWTYTR points out the use of other diagnostic information in coming to the conclusion of heroin overdose. In addition to the respiratory depression, needle marks, pinpoint pupils, being in a shooting gallery, the presence of injection supplies, . . . are just some of the information that would lead a competent medic to use naloxone in treating this patient. Pennsylvania has a pretty good example of this in their protocols.[2]

With such a patient, my goal is not awake and alert, but breathing adequately. True, they will not have a GCS[3] of 15, but that is where the word competent becomes important. Were we called to the scene because a heroin user was sleeping (not awake), or because a heroin user could not go out and steal something to pay for more drugs (not alert enough to act as a lookout), or because a heroin user was not breathing adequately?

How awake do we want the patient to be?

How alert do we want the patient to be?

How much do we want to endanger EMS crews, just to have the vital signs part of the paperwork look pretty?

Is it possible that an HOD (Heroin OverDose) has a stroke at the same time? Gosh, injecting various impure and not exactly FDA approved solutions into the veins could result in something that should not be in the brain, ending up in the brain. And I am not referring to the heroin, but particles that do not become fully dissolved in the solution that is injected, or particles that precipitate out of solution at some point. These would not be described as good in the brain. What is baseline function of the addicted brain? Is it always GCS = 15? Can we identify signs of a stroke, even if the patient’s GCS ≠ 15? Yes. Why do we think we could not?

Reading TOTWTYTR’s blog is a good way to avoid the dumbing down of EMS. He does not only mention the shortcomings of EMS in this post, but points out the abuse of pulse oximetry in the hands of a nurse. Is he just looking for an opportunity to criticize nurses? No. He is pointing out that this is somebody who should not be a nurse – perhaps a Faux Nurse. No more representative of competent nurses than a Faux Paramedic (Medic X) would be representative of competent medics.

Anyway. Go read the whole thing. It is longer than his usual post (bad kettle), but it is very informative and entertaining.

Footnotes:

[1] No more coma cocktails. Using science to dispel myths & improve patient care.
Bledsoe BE.
JEMS. 2002 Nov;27(11):54-60.
PMID: 12483195 [PubMed – indexed for MEDLINE]
The Pubmed link is to the abstract. For the full article as a pdf, click below.
Free PDF

[2] Altered Level of Consciousness
Pennsylvania Adult Statewide ALS Protocol Nov. 2008
Note # 6
Pages 78/121 and 79/121 enter 78 in the page count window.
Page with link to the full text PDF of the protocols.

[3] Glasgow Coma Scale/Score
Wikipedia
Article

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Filed Under: Heresy, Paramedicine 101, Physician Oversight, tPA Tagged With: , , ,
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