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

- Rogue Medic

$16M on EMS Stroke Trial? Dr. Rick Bukata Wants His Money Back!


 

FAST-MAG[1] actually has good methodology, so why is Dr. Rick Bukata so upset? Is this just USC vs. UCLA off the field/court?

Should the hypothesis being tested have received the Queen for a Decade treatment?

He wants his money back? Roughly 160 million tax payers in the US, so $0.10 per tax payer, but he makes more than the average schlub, so maybe as much as 50 cents for him. He can’t even buy enough caffeine to raise his blood pressure with that.
 

In a commentary regarding the IMAGES trial by Larry Goldstein of the Duke Center for Cerebrovascular Disease in the same issue of the Lancet in which the study was published, he noted that of more than 40 clinical trials of “neuroprotectants” involving over 11,000 patients, none has shown any evidence of benefit. Ten years later, the same is true.[2]

 

But look at the animal studies!

But look at the time being saved!

The authors actually like to repeat the term Golden Hour – as if that is new or valid.
 

So, if you are still a believer in the potential of magnesium, why not try and give magnesium in a pilot clinical study involving stroke patients in the ED? It would have been a relatively simple study to do. It could have been performed in selected EDs throughout the country and the answer would have been established in a fraction of eight years and at a very small fraction of $16 million.

Instead, the Fast-Mag investigators decide that giving magnesium in the field (probably about 10-20 minutes faster than could be given in the ED) would be a reasonable study.[2]

 

Gosh, when he brings reason into the argument, it just seems that the other side has none.

What could the money have been spent on?

Epinephrine vs. placebo in cardiac arrest? The number of lives affected is large and we are currently treating based on philosophy, not science.

IV (IntraVenous) bolus NTG (NiTroGlycerin – GTN GlycerylTriNitrate in Commonwealth countries) vs. SL (SubLingual) NTG for acute CHF (Congestive Heart Failure)? This affects even more patients than cardiac arrest and there is good evidence that IV bolus NTG dramatically improves outcomes, while SL NTG is not based on evidence.

Excited delirium treatment with various IM (IntraMuscular) medications to see what is safest and most effective and at what dose. A large trial would be necessary.

With no good reason to be optimistic about outcomes, why take this multimillion dollar long shot?

Maybe it has to do with tPA (tissue Plasminogen Activator) and the failure to get emergency physicians to accept the poor research on tPA – tPA showed harm, or no benefit, in 9 out of 11 studies.[3]

Ironically, if those studies used methodology similar to this study, that could be showed harm, or no benefit, in 11 out of 11 studies.

Dr. Jeffrey L. Saver, one of the authors, has a presentation on FAST-MAG that spends a lot of time on tPA, even prehospital tPA.

What does Dr. Sarver consider to be positive about FAST-MAG? Here are some of his slides.[4]
 


 

FAST-MAG means more tPA use.
 


 

FAST-MAG means doing a lot of things that have not been done before and expecting the outcome to be good.

This is the kind of person who starts turning all of the dials on a ventilator and then looks at the patient to see what the result is.

A reasonable approach to research is to limit variables, not brag about how much prudence has been abandoned.
 


 

FAST-MAG means time will be saved, but . . . .
 

Walter Koroshetz, MD, neurologist and deputy director of the National Institutes of Health’s (NIH’s) National Institute of Neurological Disorders and Stroke, sponsor of the FAST-MAG study, says that lessons can be learned from the trial.[5]

 

“The NIH have a new network to do more prehospital trials, but we need phase 2 studies first that demonstrate some biological effect before going into a large costly phase 3 trials.”[5]

 

This is a $16 million bet that time is the only factor that matters.

I hope these doctors do not drive the way they gamble.

What were the results?

The results were the same as all of the previous studies of magnesium – no improvement.

There is no Magnesium Golden Hour.
 

And, please, no – don’t even consider the idea of giving tPA in the field.[2]

 

Well, . . . .
 

Dr. Saver explained that tPA cannot be given at present in a prehospital setting because hemorrhagic stroke has to be ruled out with computed tomography (CT). The use of ambulances with a CT scanner on board has been studied in Germany and is now starting to be tested in the United States.[5]

 

Be very afraid.

On the other hand, the authors did not rush this treatment into EMS protocols, as we recently have in EMS in so many places with therapeutic hypothermia, based entirely on research done in the ED (Emergency Department). It works in the ED, but not in the ambulance. 😳

FAST-MAG was approved in 1999, several years after the EMS nifedipine (Procardia) for hypertensive crisis crisis. There was no study in the EMS setting of a treatment for the EMS setting. This involved treatment of the surrogate endpoint of blood pressure numbers, which makes for an easy win, such as a systolic drop of 250 -> 90 in ten minutes. 😳

We need a balance between rushing to add the new cool treatment (and the predictable removal of the treatment decades later) and the inappropriate rush to a large scale trial of something that has repeatedly failed smaller studies.
 

Go read Dr. Bukata’s full article.

Footnotes:

[1] Methodology of the Field Administration of Stroke Therapy – Magnesium (FAST-MAG) phase 3 trial: Part 2 – prehospital study methods.
Saver JL, Starkman S, Eckstein M, Stratton S, Pratt F, Hamilton S, Conwit R, Liebeskind DS, Sung G, Sanossian N; FAST-MAG Investigators and Coordinators.
Int J Stroke. 2014 Feb;9(2):220-5. doi: 10.1111/ijs.12242.
PMID: 24444117 [PubMed – in process]

Methodology of the Field Administration of Stroke Therapy – Magnesium (FAST-MAG) phase 3 trial: Part 1 – rationale and general methods.
Saver JL, Starkman S, Eckstein M, Stratton S, Pratt F, Hamilton S, Conwit R, Liebeskind DS, Sung G, Sanossian N; FAST-MAG Investigators and Coordinators.
Int J Stroke. 2014 Feb;9(2):215-9. doi: 10.1111/ijs.12243. Epub 2014 Jan 13.
PMID: 24444116 [PubMed – in process]

[2] $16M on EMS Stroke Trial? I Want My Money Back!
by Rick Bukata, MD
March 24, 2014
Emergency Physicians monthly
Article

[3] The Guideline, The Science, and The Gap
Wednesday, April 17, 2013
Dr. David Newman
Smart EM
Article

[4] Treat Stroke in the Field:
Lessons from the NIH FAST-MAG Trial

Jeffrey L. Saver, MD, Professor of Neurology
UCLA Stroke Center
2012
Presentation Slides in PDF Downoad format.

[5] FAST-MAG: No Benefit of Prehospital Magnesium in Stroke
Sue Hughes
February 14, 2014
Medscape
Article

.

Is 50 NTG Too Much for One Patient?


Image credit. Three different forms of nitroglycerin, intravenous, sublingual spray, and the nitroglycerin patch.
 

In the comments to Unreasonable Fear of Hypotension and High-Dose NTG – Part I is the following from Kasey Marshall on the patient I treated with over 50 NTG (NiTroGlycerin – GTN GlycerylTriNitrate in Commonwealth countries) for CHF/ADHF (Congestive Heart Failure/Acute Decompensated Heart Failure).
 

My question is how long did the study go on that one patient received over 50 NTG tablets and is still functioning.

 

That patient was not in the study.

That was a patient I was treating with over 50 NTG.

The patient’s systolic blood pressure (the top number) never dropped below 200 mmHg.

Where is the problem?
 

I didn’t think that an individual was supposed to receive more than 3 NTG tablets in 5 minutes intervals before professional medical assistance.

 

As used in this case, NTG is an off-label use of NTG, but there is good evidence that high-dose NTG is safe and effective for CHF/ADHF. There is better evidence for high-dose NTG to improve outcomes for CHF/ADHF patients than there is evidence that standard-dose NTG improves outcomes for patients with chest pain/heart attacks/ischemia.
 

INDICATIONS AND USAGE
Nitroglycerin is indicated for the acute relief of an attack or prophylaxis of angina pectoris due to coronary artery disease.
[1]

 

I am a paramedic.

I am professional medical assistance.

One reason for the maximum of 3 NTG is to encourage the patient to go to the hospital and not stay home taking NTG, which wears off quickly. Once at the hospital, the patient will often be receiving IV (IntraVenous) NTG.
 

Patients with ischemic discomfort should receive up to 3 doses of sublingual or aerosol nitroglycerin at 3- to 5-minute intervals until pain is relieved or low blood pressure limits its use (Class I, LOE B).[2]

 

By ischemic discomfort, they mean heart attack symptoms, not CHF patients, but they do not provide any evidence. They suggest that there is evidence by writing (Class I, LOE B), but there is not a single reference listed to support this.

There is no reference to doses for CHF treatment. Doses for CHF should be much higher than doses for heart attack.
 

I know the earlier NTG is administered, the better but I think that there should be a limit on how much can be can be administered to one patient in a 48 hour period before more serious medical attention should be sought.

 

I have not yet had a transport that came close to 48 hours, so I do not worry about that kind of time period.

Serious medical attention? Rein in my pathetic attempts at humor? 😳

We should give NTG to CHF patients until it is coming out of the patient’s ears, until the patient’s systolic blood pressure drops by 30%, or until the patient improves.

We should be giving IV boluses of 1 mg or 2 mg every three minutes with CPAP (Continuous Positive Airway Pressure), rather than interrupting CPAP to give SL (SubLingual) NTG or using NTG by an ineffective route (paste that is not absorbed through the skin, because circulation is shunted away from the skin).
 

Conclusion: In this single-center, retrospective, unadjusted analysis of primarily African-American patients with acute hypertensive heart failure, nitroglycerin administered by higher dose bolus without concurrent intravenous infusion was associated with a significant decrease in ICU admissions and hospital length of stay. Based on our findings, bolus higher dose nitroglycerin appears to be a viable option for the management of such patients.[3]

 

The IV bolus NTG was better than the IV drip NTG.
 

I know when my mom had a prescription for NTG she was only told to take two, NTG tablets and if a third was needed to call paramedics. And that it was needed two days in a row that she needed to stay in the hospital for observation.

 

I expect that the reason for staying in the hospital was the heart condition that resulted in her taking the NTG.

Two doses of NTG will wear off quickly and are not a reason for hospitalization.

EMS will probably be giving multiple-dose NTG every 3-5 minutes, often 10, 20, or 30 NTG to one patient for CHF/ADHF.
 

Administration of high-dose nitroglycerin is an effective treatment that has been shown to improve the respiratory symptoms associated with ADHF, and decrease the incidence of death due to myocardial infarction and mechanical ventilation, particularly when initiated early.4 – 6 [4]

 

MSN (Multiple Simultaneous Nitroglycerin) is safe and effective for CHF/ADHF.
 

CONCLUSION:
Hypotension was rare and self-limited in prehospital patients receiving MSN.
[4]

 

The scary side effect of high-dose NTG almost never happened, but when hypotension did occur, it went away without any need for treatment.

Footnotes:

[1] INDICATIONS AND USAGE
NITROGLYCERIN tablet
[Glenmark Generics Inc., USA]
DailyMed
FDA Label

[2] Nitroglycerin (or Glyceryl Trinitrate)
2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science
Part 10: Acute Coronary Syndromes
Initial General Therapy for ACS
Free Full Text from Circulation.

[3] Nitroglycerin for Treatment of Acute, Hypertensive Heart Failure: Bolus, Drip or Both?
Kwiatkowski GM, Saely S, Purakal J, Mahajan A, Levy PD/Detroit Receiving Hospital, Detroit, MI; Wayne State University School of Medicine, Detroit, MI
Annals of Emergency Medicine, Volume 60, issue 4 (October, 2012), p. S9.
ISSN: 0196-0644 DOI: 10.1016/j.annemergmed.2012.06.049
Abstract 22 Indexed with OhioLINK Journal Article Locator

[4] Prehospital High-dose Sublingual Nitroglycerin Rarely Causes Hypotension.
Clemency BM, Thompson JJ, Tundo GN, Lindstrom HA.
Prehosp Disaster Med. 2013 Aug 21:1-4. [Epub ahead of print]
PMID: 23962769 [PubMed – as supplied by publisher]

.

Unreasonable Fear of Hypotension and High-Dose NTG – Part II

ResearchBlogging.org
 

Continuing from Part I to look at the results of the study of high-dose SL (SubLingual) NTG (NiTroGlycerin – GTN GlycerylTriNitrate in Commonwealth countries) by EMS for CHF (Congestive Heart Failure) that Peter Canning wrote about.[1]
 

For CHF, more NTG does not produce more of a drop in blood pressure.
 

If you disagree, provide evidence.

I tend to get anecdotes, with excuses, rather than any kind of evidence.

Anecdotes are often indications that the person telling the anecdote does not understand and is trying to make up for that lack of understanding with bravado.
 


 

Therefore, we will continue to look at the evidence.
 


Click on images to make them larger.
 

You can see that some patients did have large drops in systolic blood pressure with only a double dose of NTG. To clarify, I highlighted the large drops in red below.
 


 

Only six large drops in systolic blood pressure.

Three systolic blood pressures dropped below 100 mmHg.

The expected happened with these dramatic drops in blood pressure and cases of hypotension –

Nobody had any bad outcomes.

The patients recovered without any intervention, such as fluid bolus, epinephrine, or whatever other placebo might be suggested.

Placebo?

A treatment that does not do anything more than doing nothing (benign neglect) is a placebo.

All these patients needed was a paramedic smart enough to use benign neglect.

Anecdotalists give a lot of treatments, because they mistakenly feel that that their intervention improve outcomes. Where is their evidence? In their overactive imaginations.

Those drops with double doses of NTG are scary. How bad was the outcome with triple doses of NTG?
 


 

Again, I highlighted the single big drop – only one – only dropped to about 130 mmHg systolic – in red below.

I added green to highlight the increases in systolic blood pressure after triple dose NTG. There were plenty of increases in systolic blood pressures after double dose NTG, but there were so many increases that it would have made the graph more difficult to read.
 


 

Multiple dose NTG every 5 minutes was clearly safe in this study.

Multiple dose anecdotes about Oh, no! What if . . . ? – continue to be wrong.

Forget the anecdotes.

There is plenty of evidence of safety.

Footnotes:

[1] Safety of High Dose Nitro in CHF
StreetWatch: Notes of a Paramedic
August 29, 2013
Peter Canning
Article

[2] Prehospital High-dose Sublingual Nitroglycerin Rarely Causes Hypotension.
Clemency BM, Thompson JJ, Tundo GN, Lindstrom HA.
Prehosp Disaster Med. 2013 Aug 21:1-4. [Epub ahead of print]
PMID: 23962769 [PubMed – as supplied by publisher]

Clemency BM, Thompson JJ, Tundo GN, & Lindstrom HA (2013). Prehospital High-dose Sublingual Nitroglycerin Rarely Causes Hypotension. Prehospital and disaster medicine, 1-4 PMID: 23962769

.

Comments on High-Dose NTG for CHF

 

There are a couple of important comments to Unreasonable Fear of Hypotension and High-Dose NTG – Part I. In one, Brooks Walsh writes –
 

50 NTG tabs for 1 patient? Holy cow, that sounds labor intensive!

 

This would have been labor intensive.
 


 

There are 52 NTG tabs in that picture. The study protocol mentioned tabs, but I was using NTG spray.

If I had been using tabs, the patient might have ended up being treated for thrush, or for a seizure, due to the white paste in his mouth, rather than CHF.

Even with all of the not expired, still potent, NTG spray, his systolic blood pressure never dropped below 200 mm/Hg.
 

Did you have to have another ALS unit intercept to re-supply you with more little brown bottles?

 

Medium-size red spray bottles.
 


 

The spray level did descent like a low MPG fuel gauge.
 

In the other comment, JJ Greulich writes –
 

We were just talking about this today in Medic class.

 

This is a topic that seems to require a lot more time than most others, but after seeing large doses dramatically improve outcomes without any significant side effects, the concept seems to be easier to grasp.
 

I was curious as to why it is alright to give NTG or another Nitrate every 3-5 minutes without worrying about the BP tanking, but didn’t have time to ask. Can you elaborate on this a little for me?

 

I do not worry about why. Failed treatments are often supported by claims that the mechanism is _________. Those are the failed treatments.

Similarly, misplaced endotracheal tubes are often accompanied by the words – I saw it go through the cords.

We have known since the 1970s that most CHF patients are not fluid overloaded, but people continue to claim that we need to remove the imaginary fluid overload with furosemide (Lasix). That’s a reasonable explanation, but it’s lousy medicine.

Expect explanations to be wrong.

High-dose NTG works. The improvement in outcomes is repeatable, predictable, and results in many fewer deaths and many fewer intubations.

Pathophysiology can be years behind research, because pathophysiology is derived from research, the conclusions of which may be extrapolated well beyond what is reasonable. Pathophysiology tends to lead us to believe that we know more than we do.

This can lead to excessive caution, which is dangerous, or to recklessness, which can be just as dangerous as excessive caution being too safe.

Based on research, we could probably save half of the patients who will die due to acute CHF, if we would only stop trying to be safe.

We are killing our patients with caution and congratulating ourselves on how careful we are.

CHF/ADHF (Congestive Heart Failure/Acute Decompensated Heart Failure) patients seem to be resistant to nitrates.

This may be similar to giving morphine to someone who has been taking regular doses of an opioid. To treat the patient’s pain, we need to give a much larger dose than would be needed for pain management for an opioid naive patient (no recent opioid use) with similar pain. The same is true for addicted patients, since tolerance is one part of what changes with addiction.

In-hospital treatment with nitrates can include nitrate holidays – temporary removal (holiday) of the nitrate to allow the tolerance to decrease.

The pathophysiology appears to be that high-dose NTG – especially when given as an IV Bolus – has much more of an effect on afterload (the resistance that the heart is pushing against and part of what is causing the failing heart to fail), than on anything else.

Large IV bolus doses of NTG to reduce afterload, even for hypotensive patients, may be the most beneficial drug treatment for acute CHF.
 

Go listen to the very first EMCrit podcast.
 

In under 10 minutes Dr. Weingart explains how to save the lives of crashing CHF patients.

.

Unreasonable Fear of Hypotension and High-Dose NTG – Part I

ResearchBlogging.org
 

Peter Canning writes about a study of high-dose SL (SubLingual) NTG (NiTroGlycerin – GTN GlycerylTriNitrate in Commonwealth countries) by EMS for CHF (Congestive Heart Failure).[1]

I have some problems with the study.
 


Click on images to make them larger.
 

This is just moderate-dose, not high-dose.

I have had protocols that allow for more aggressive dosing (every 3-5 minutes) going back to 2008.[2]
 


 

I have probably given more triple-dose NTG than was given to the entire intervention group. I have given over 50 SL NTG to just one patient, while they only managed to give a total of 87 tablets in 29 triple doses in the entire study.
 


 

It is good to provide more evidence that multiple dose NTG is safe, but we have had good evidence that prehospital high-dose IV NTG dramatically improves outcomes since the 1990s.

We need more prehospital aggressive IV (IntraVenous) NTG research.
 

Administration of high-dose nitroglycerin is an effective treatment that has been shown to improve the respiratory symptoms associated with ADHF, and decrease the incidence of death due to myocardial infarction and mechanical ventilation, particularly when initiated early.4 – 6 [3]

 

I agree with that.

However, EMS is the best earliest place to start IV NTG.
 

From 1984 through 1991, new guidelines for the use of intravenous nitrates, based on differential treatment according to blood pressure, were in use.

RESULTS:
Overall prehospital mortality rate for APE in all patients was 7.8% (50 of of 640 patients). Mortality after 1984 was significantly lower than before (5.3% versus 13%, P < .01). Nitrates were effective in reducing mortality, even in hypotensive patients. Multivariate analysis showed that outcome was significantly affected by two clinical features (dyspnea and low blood pressure), treatment with nitrates, and calendar period effects (before/after 1984).
[4]

 

Not just hypertensive patients, but also hypotensive patients benefited from EMS IV NTG!

Nitrates were effective in reducing mortality, even in hypotensive patients.

The CHF death rate dropped from 13% all the way down to 5.3%
 


 

Am I complaining that the current study is useless?

Not at all.

There is some excellent information that debunks much of the dogma against multiple-dose NTG.
 


Look at the cases of hypotension – systolic blood pressure less than 100 mm/Hg.

3 cases, but only in the double dose group.

All of the hypotension went away without any treatment.

Zero cases in the triple dose group and the quadruple dose patient did not become hypotensive.
 

For CHF, more NTG does not produce more of a drop in blood pressure.
 

Disagree?

Provide evidence, not anecdotes.

Part II will look at the evidence of safety from this study more closely.

Also see –

Nitroglycerin for Treatment of Acute, Hypertensive Heart Failure – Bolus, Drip or Both?
Wed, 17 Oct 2012

Is a half a bottle of nitro too much for a single dose?
Sun, 18 Nov 2012

NTG and the Hero Medic
Street Watch
November 7, 2012

Footnotes:

[1] Safety of High Dose Nitro in CHF
StreetWatch: Notes of a Paramedic
August 29, 2013
Peter Canning
Article

[2] Congestive Heart Failure
5002– ALS – Adult/Peds
2008, 2011, and 2013 Statewide ALS Protocol
Pennsylvania
Page with link to Full Text Download of Full Protocols in PDF format.

[3] Prehospital High-dose Sublingual Nitroglycerin Rarely Causes Hypotension.
Clemency BM, Thompson JJ, Tundo GN, Lindstrom HA.
Prehosp Disaster Med. 2013 Aug 21:1-4. [Epub ahead of print]
PMID: 23962769 [PubMed – as supplied by publisher]

[4] Intravenous nitrates in the prehospital management of acute pulmonary edema.
Bertini G, Giglioli C, Biggeri A, Margheri M, Simonetti I, Sica ML, Russo L, Gensini G.
Ann Emerg Med. 1997 Oct;30(4):493-9.
PMID: 9326864 [PubMed – indexed for MEDLINE]

Clemency BM, Thompson JJ, Tundo GN, & Lindstrom HA (2013). Prehospital High-dose Sublingual Nitroglycerin Rarely Causes Hypotension. Prehospital and disaster medicine, 1-4 PMID: 23962769

Bertini G, Giglioli C, Biggeri A, Margheri M, Simonetti I, Sica ML, Russo L, & Gensini G (1997). Intravenous nitrates in the prehospital management of acute pulmonary edema. Annals of emergency medicine, 30 (4), 493-9 PMID: 9326864

.

Dr. Nicholas DeRobertis, Improved Care for the Patients, Not for the Good Old Boys Club, Sudden Death at 60

 

One of my first medical directors was Dr. Nicholas DeRobertis. He tried to change the common practice of the local paramedics of dumping intoxicated, or otherwise undesirable patients, at Yonkers General Hospital regardless of which hospital was closest.

Sadly, this puerile EMS favoritism is still common in many places. He also tried to change other practices that are bad for patients and bad for EMS.
 


 

He was at St. Joseph’s on Sunday helping to implement a new electronic medical records system when he began to feel ill. He entered the emergency room he directed for many years – this time as a patient.

Friends said he suffered a heart attack. DeRobertis was later transferred to Montefiore Medical Center in the Bronx, where he died late Monday.
Dr. DeRobertis, and other attending physicians, would offer continuing education classes for free for EMS, but too often I was the only one attending. He had a lot of work to do to change EMS from the good old dangerous boys club to something that is focused on excellent patient care.
[1]

 

We had to call medical command for almost everything back then. I had one patient who was combative due to CHF (Congestive Heart Failure) and called for orders for aggressive NTG (NiTroGlycerin – GTN GlycerylTriNitrate in Commonwealth countries). The command doctor refused orders for NTG, with the excuse that “Prehospital nitro doesn’t work.” Even two decades ago, there was evidence that nitrates are the best medicine for CHF.

I talked with Dr. DeRobertis and he said that he would make sure that did not happen again. After talking with Dr. DeRobertis, I never encountered that problem again.

With Dr. DeRobertis it was clear that good patient care came first, not the doctors, not the nurses, not the most senior medics (often those who have been harming patients the longest), not even the protocol.

Back in the 1970s there was good evidence that furosemide (Lasix [frusemide in Commonwealth countries]) does not improve outcomes for CHF patients, but many of us still give furosemide to CHF patients.[2]

Back in the 1980s there was good evidence that aggressive treatment with nitrates (NTG, ISMN [IsoSorbide MonoNitrate], ISDN [IsoSorbide DiNitrate], . . . ) does improve outcomes for CHF patients, but many of us still only give small doses of nitrates to CHF patients.[3],[4],[5]

Dr. DeRobertis was making EMS evidence-based when even in-hospital emergency medical practice was still mostly traditional.

His death is is a great loss for his family, his patients, and all of the patients he affected through his recognition of the benefits treatment based on evidence, rather than tradition.

Footnotes:

[1] Dr. Nicholas DeRobertis, Westchester emergency medicine leader, dies
Jul. 2, 2013 11:01 AM
lohud.com
Jane Lerner
Article

[2] Blood volume prior to and following treatment of acute cardiogenic pulmonary edema.
Figueras J, Weil MH.
Circulation. 1978 Feb;57(2):349-55.
PMID: 618625 [PubMed – indexed for MEDLINE]

Free Full Text Download from Circulation in PDF format
 

The concept that acute heeart failure with pulmonary edema is associated with an increase in intravascular volume is therefore not supported. To the contrary, there is a reduction of blood volume during acute pulmonary edema.

This is just one of the studies from the 1970s showing the problems with furosemide.

[3] Comparison of nitroglycerin, morphine and furosemide in treatment of presumed pre-hospital pulmonary edema.
Hoffman JR, Reynolds S.
Chest. 1987 Oct;92(4):586-93.
PMID: 3115687 [PubMed – indexed for MEDLINE]

Free Full Text from Chest.

Group A patients were the only patients not to receive morphine sulfate, group B patients the only ones not to receive nitroglycerin, and group D patients the only ones not to receive furosemide. Group

Group A patients (No morphine [received NTG and furosemide]) had the best outcome. No intubations when eliminating morphine.

Group B patients (No NTG [received morphine and furosemide]) had the worst outcome. 31% intubated when eliminating NTG.

[4] [The use of injectable nitroglycerin (a bolus of 3 mg) in the treatment of cardiogenic pulmonary edema].
Bosc E, Bertinchant JP, Hertault J.
Ann Cardiol Angeiol (Paris). 1982 Oct-Nov;31(6):477-80. French. No abstract available.
PMID: 6818888 [PubMed – indexed for MEDLINE]
 
This is in French, but PMID: 7662071 (1995) describes the results –

Bosc et al4 administered one 3-mg intravenous trinitroglycerin bolus to patients with CPE. There was improvement in 71% of the 35 patients studied. Five patients (13%) became hypotensive to an SBP <90; however, each recovered after a few minutes.

[5] Emergency treatment of severe cardiogenic pulmonary edema with intravenous isosorbide-5-mononitrate.
Harf C, Welter R.
Am J Cardiol. 1988 Mar 25;61(9):22E-27E.
PMID: 3348137 [PubMed – indexed for MEDLINE]
 

These data indicate that i.v. IS-5-MN is effective and safe for the management of severe acute cardiogenic pulmonary edema.

.

The Art of Critical Thinking at The EMS Roundtable


 

Last night I called in to the EMS Roundtable because the topic was one of the most important in EMS – critical thinking.[1]
 

Critical thinking is the intellectually disciplined process of actively and skillfully conceptualizing, applying, analyzing, synthesizing, and/or evaluating information gathered from, or generated by, observation, experience, reflection, reasoning, or communication, as a guide to belief and action.[2]

 

More simply, in EMS critical thinking is how we make good decisions based on the limited information available in the emergency setting.

In EMS we definitely can be too safe.

Not applying a tourniquet, because What if the tourniquet causes a problem?

That is being too safe.

Not giving large doses of NTG to a hypertensive CHF patient, because What if the NTG causes the pressure to bottom?

That is being too safe.

Strapping someone to a backboard with straps and a collar, Just to be safe.

How is that not being too safe?

Where is there any evidence that spinal immobilization is safe?

Not sedating (or not adequately sedating) an excited delirium patient, because What if he stops hyperventilating?

That is being too safe.

These are some of the things that need to be considered when we engage in critical thinking.
 

Go listen to the podcast.
 

Show Notes:

Guest Dan Limmer: http://limmercreative.com

Live Call-in Tim Noonan: http://roguemedic.com

Chat Room:

Jim Hoffman: http://emsofficehours.com

Tom Bouthillet: http://EMS12Lead.com

 

Go listen to the podcast.
 

Footnotes:

[1] The Art of Critical Thinking
The EMS Roundtable
Wed, April 24, 2013 07:00 pm
Podcast page.

[2] Defining Critical Thinking
Criticalthinking.org
Web page

.

Is Nitroglycerin Bad for Severe Sepsis?

ResearchBlogging.org
 

Yesterday at The Paramedic’s Edge, this was the topic of reactive, reflexive, dogmatic, rejection discussion of a possible use of NTG (NiTroGlycerin – GTN GlycerylTriNitrate in Commonwealth countries).

NTG is a vasodilator and sepsis is a vasodialtion problem. There are other problems with sepsis, but vasodilation may be the primary problem.
 

Nitro for severe septic patients. What are your thoughts?[1]

 

Here is a sampling of some of the unfortunately typical responses.
 

The amateur lawyer who thinks that what we do should be guided by fear of law suits approach.
 

Oh to put them out of their misery?! Sounds like a lawsuit waiting to happen

 

The just drive fast, I don’t understand any of this medical mumbo jumbo appraoch.
 

We’re medics not doctors. Best thing we can do is a diesel infusion

 

The most common responses seemed to be of this kind.

The I only know one thing about nitro and that scares me approach.
 

True hemodynamic instability is a contraindication

 

Hmmmm let’s drop their pressure even more…that’s a thought? So my answer…HE’LL NO!!

 

We will probably end up using NTG in the treatment of cardiac arrest – the ultimate low blood pressure state, so how far fetched is using NTG for sepsis?[2],[3],[4],[5],[6],[7]

Why?

NTG can lower blood pressure, but it can also increase cardiac output.

To over-simplify things –

If the CO (Cardiac Output) increases by more than the the vasodilation would decrease the BP (Blood Pressure), the BP will actually be expected to increase.

CO = SV (Stroke Volume) x HR (Heart Rate).

CO MAP (Mean Arterial Pressure)/TPR (Total Peripheral Resistance).

BP = CO x TPR.

Are all cardiac outputs and vascular resistances the same? No, but we simplify things by making that assumption.
 


 

Jean-Charles Preiser and colleagues question the routine use of nitroglycerin because of the risk of hypotension and the possible induction of mitochondrial dysfunction.[8]

 

Many people question the use of NTG and worry about hypotension.
 

Although we observed a temporary drop in blood pressure, blood flow was maintained and, in fact, increased in our patients.[8]

 

We do worry obsess about things that are brief and insignificant (such as ROSC – Return Of Spontaneous Circulation – in treatment of cardiac arrest), while we ignore the things that are more important (such as living long enough to leave the hospital with a brain that works well enough to recognize family members).
 

Space constraints meant that we were not able to include specific haemodynamic results in our Research letter, but mean arterial pressure temporarily dropped by an average of 21 mm Hg (range 13—33 mm Hg) in the eight patients we investigated.[8]

 

A drop in MAP (Mean Arterial Pressure) of 21 mm/Hg is huge!
 

Mean arterial pressure returned to baseline level within 1 min in all patients with concomitant fluid infusion.[8]

 

Less than 1 minute?

Try using that as a pickup line.

I can rock your world for less than 1 minute.

How much alcohol is going to be required to make that sound significant?

We give adenosine to do what?

To completely stop the heart for usually less than one minute.

We cardiovert to do what?

To completely stop the heart for usually less than one minute.

A short-term worsening of vital signs for a long-term improvement in survival is an excellent trade-off.

Does NTG improve long-term survival?

That is not clear, but this does show that we need to abandon more dogma in our search for the best care of our patients.
 

The increase in microvascular blood flow as a result of this procedure confirms our clinical experience that resuscitation efforts should be aimed at optimising blood flow not blood pressure.[8]

 

NTG does improve blood flow.

Too many of us are afraid to use NTG, or afraid to use large doses of NTG, or afraid to use IV bolus NTG, or afraid to use large doses of IV bolus NTG out of too much concern for blood pressure and not enough concern for blood flow.

This quotes are from a response to a letter about research paper looking at NTG for sepsis. This paper is not something that should be summarily dismissed.[9]

The EMS drug of choice, dopamine, may be a bad idea for sepsis.[10],[11]

Think about that – For sepsis dopamine may make things worse and NTG may make things better.

Is it that simple? Maybe. Maybe not. Dopamine may make things better, but just not do as good a job as norepinephrine. Or all catecholamines may be harmful.

Dr. Mervyn Singer makes an excellent case that catecholamines are not helpful, or that they are at least tremendously overused. Go listen to his podcast.[12]

Footnotes:

[1] Nitro for severe septic patients. What are your thoughts?
The Paramedic’s Edge
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[2] High dose nitroglycerin treatment in a patient with cardiac arrest: a case report.
Guglin M, Postler G.
J Med Case Rep. 2009 Aug 10;3:8782. doi: 10.4076/1752-1947-3-8782.
PMID: 19830240 [PubMed]

Free Full Text from PubMed Central.
 

A possible explanation for the hemodynamic benefit of NTG in our patients is increased cardiac output produced by rapid vasodilatation in a heart operating at the extreme of the Frank-Starling curve. Vasodilators in heart failure with or without acute myocardial infarction have been proven to decrease left ventricular filling pressure and systemic vascular resistance while increasing cardiac index [7]. The more severe the failure, the more beneficial the effect of vasodilators [13].

[3] Sodium nitroprusside enhanced cardiopulmonary resuscitation improves survival with good neurological function in a porcine model of prolonged cardiac arrest.
Yannopoulos D, Matsuura T, Schultz J, Rudser K, Halperin HR, Lurie KG.
Crit Care Med. 2011 Jun;39(6):1269-74. doi: 10.1097/CCM.0b013e31820ed8a6.
PMID: 21358401 [PubMed – indexed for MEDLINE]

Free Full Text from acoep.org.

[4] Sodium nitroprusside-enhanced cardiopulmonary resuscitation improves resuscitation rates after prolonged untreated cardiac arrest in two porcine models.
Schultz JC, Segal N, Caldwell E, Kolbeck J, McKnite S, Lebedoff N, Zviman M, Aufderheide TP, Yannopoulos D.
Crit Care Med. 2011 Dec;39(12):2705-10. doi: 10.1097/CCM.0b013e31822668ba.
PMID: 21725236 [PubMed – indexed for MEDLINE]

Free Full Text from PubMed Central.

[5] Sodium nitroprusside enhanced cardiopulmonary resuscitation (SNPeCPR) improves vital organ perfusion pressures and carotid blood flow in a porcine model of cardiac arrest.
Schultz J, Segal N, Kolbeck J, McKnite S, Caldwell E, Yannopoulos D.
Resuscitation. 2012 Mar;83(3):374-7. doi: 10.1016/j.resuscitation.2011.07.038. Epub 2011 Aug 22.
PMID: 21864483 [PubMed – indexed for MEDLINE]

Free Full Text from PubMed Central.

[6] Sodium nitroprusside enhanced cardiopulmonary resuscitation prevents post-resuscitation left ventricular dysfunction and improves 24-hour survival and neurological function in a porcine model of prolonged untreated ventricular fibrillation.
Schultz J, Segal N, Kolbeck J, Caldwell E, Thorsgard M, McKnite S, Aufderheide TP, Lurie KG, Yannopoulos D.
Resuscitation. 2011 Dec;82 Suppl 2:S35-40. doi: 10.1016/S0300-9572(11)70149-6.
PMID: 22208176 [PubMed – indexed for MEDLINE]

[7] Controlled pauses at the initiation of sodium nitroprusside-enhanced cardiopulmonary resuscitation facilitate neurological and cardiac recovery after 15 mins of untreated ventricular fibrillation.
Yannopoulos D, Segal N, McKnite S, Aufderheide TP, Lurie KG.
Crit Care Med. 2012 May;40(5):1562-9. doi: 10.1097/CCM.0b013e31823e9f78.
PMID: 22430233 [PubMed – indexed for MEDLINE]

[8] Nitroglycerin for septic shock.
Preiser JC, De Backer D, Vincent JL.
Lancet. 2003 Mar 8;361(9360):880; author reply 880. No abstract available.
PMID: 12642079 [PubMed – indexed for MEDLINE]

Free Full Text from the Lancet.

[9] Nitroglycerin in septic shock after intravascular volume resuscitation.
Spronk PE, Ince C, Gardien MJ, Mathura KR, Oudemans-van Straaten HM, Zandstra DF.
Lancet. 2002 Nov 2;360(9343):1395-6.
PMID: 12423989 [PubMed – indexed for MEDLINE]

[10] Dopamine versus norepinephrine in the treatment of septic shock: a meta-analysis*.
De Backer D, Aldecoa C, Njimi H, Vincent JL.
Crit Care Med. 2012 Mar;40(3):725-30. doi: 10.1097/CCM.0b013e31823778ee.
PMID: 22036860 [PubMed – indexed for MEDLINE]

CONCLUSIONS:
In patients with septic shock, dopamine administration is associated with greater mortality and a higher incidence of arrhythmic events compared to norepinephrine administration.

[11] Norepinephrine or dopamine for septic shock: systematic review of randomized clinical trials.
Vasu TS, Cavallazzi R, Hirani A, Kaplan G, Leiby B, Marik PE.
J Intensive Care Med. 2012 May-Jun;27(3):172-8. doi: 10.1177/0885066610396312. Epub 2011 Mar 24. Review.
PMID: 21436167 [PubMed – indexed for MEDLINE]

CONCLUSIONS:
The analysis of the pooled studies that included a critically ill population with shock predominantly secondary to sepsis showed superiority of norepinephrine over dopamine for in-hospital or 28-day mortality.

[12] Catecholamines Should Be Banned
Mervyn Singer
2009-04-24-1545
6th Annual Critical Care Symposium
Manchester, UK
Page with link to free mp3 download from Free Emergency Medicine Talks.

Guglin, M., & Postler, G. (2009). High dose nitroglycerin treatment in a patient with cardiac arrest: a case report Journal of Medical Case Reports, 3 (1) DOI: 10.4076/1752-1947-3-8782

SPRONK, P., INCE, C., GARDIEN, M., MATHURA, K., & ZANDSTRA, D. (2003). Nitroglycerin for septic shock The Lancet, 361 (9360), 880-880 DOI: 10.1016/S0140-6736(03)12692-X

Spronk, P., Ince, C., Gardien, M., Mathura, K., Straaten, H., & Zandstra, D. (2002). Nitroglycerin in septic shock after intravascular volume resuscitation The Lancet, 360 (9343), 1395-1396 DOI: 10.1016/S0140-6736(02)11393-6

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