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

- Rogue Medic

Prehospital cooling to improve successful targeted temperature management after cardiac arrest: A randomized controlled trial

ResearchBlogging.org
 
Also to be posted on ResearchBlogging.org when they relaunch the site.

This is a nice study, which unfortunately ran into problems with enrollment and funding. There are some things that I think should have been done differently.

The doses of chilled IV (IntraVenous) fluid were not weight-based, while the fluid in the human body is weight-based. If midazolam (Versed) was given, the dose was just a single dose of 5 mg, or 2 doses of 5 mg each. The effects of midazolam are much less weight-based, than fluid, but the appropriate way to administer midazolam is to titrate to effect. Even if administering 10 mg of midazolam produces the desired effect in 80%, or 90%, of patients, that can still leave a significant portion inadequately sedated. The goal of TTM (Targeted Temperature Management) may be defeated by the movement of an even mildly agitated patient.

Would another drug, such as ketamine, be more appropriate? How much does use of midazolam affect the use of pressors to counter the vasodilatory effects of midazolam? Unlike other sedatives, ketamine does not seem to produce vasodilation and/or depress cardiac activity. The midazolam was only mentioned in the description of the study interventions and only described as being given to prevent shivering, so the dose may be adequate, but there is only the one mention in the entire paper.

The fluid administration was shown to be different with a p value of <0.0001. The difference is only 170 ml (5 3/4 oz), so it is a distinction described as significant by p value, but it does not appear to be a significant difference in any way that would affect patients. The SD (Standard Deviation - how much variability exists in about 2/3 of patients) is the same as the amount of fluid given to the control group and 2 3/4 times the amount of the difference. In other words, there was a lot of overlap in the volumes administered to the patients in the two groups. While the p value of <0.0001 suggests confidence in the results being due to change only one time in 10,000, that is misleading.  

Total fluid infused was not documented for 98 (35%) patients who received Prehospital Cooling and 121 (40%) control patients.[1]

 


 

The raw data on the volumes is not included, nor is the shape of the graph of distribution of the volumes, but it looks as if 20%, or 30%, of the control group may have received more fluid that the intervention group – and then there are the more than 35% of patients without documentation of fluid volumes.

Since the amount of difference is small, it does not seem to matter, but the intervention group was forcing the chilled fluid into the patients with pressure bags, so why so little difference between the groups?

How long does it take to administer 170 ml of chilled IV fluid by pressure infusion? Does it take longer than it takes to get from the ambulance to the hospital stretcher?

That is just a statistical oddity that is not going to affect outcomes.

The next may be the true the significant finding of the study.
 

Patients in the prehospital cooling group were more likely to (ever) receive TTM in hospital [190 (68%) vs 170 (56%); RR 1.21, p = 0.003] than patients in the control group.[1]

 


 

TTM (Targeted Temperature Management) is the new term for therapeutic hypothermia, which has been shown to be effective.

If not, why not?
 

Across all studies that used conventional cooling methods rather than no cooling (three studies; 383 participants), we found a 30% survival benefit (RR 1.32, 95% CI 1.10 to 1.65). The quality of the evidence was moderate.[2]

 

With no difference in the rhythms of the control group and the intervention group, why the difference in the rate of TTM in the hospital?

Will this be similar to the case of waveform capnography? EMS ended up pressuring many/some EDs to begin to use EtCO2 on all intubated patients. This was a change from the previous, much too common, ED practice of complaining about and pulling at the EtCO2 tubing, because it was an unknown item that was in the way.

EMS should not need to encourage the ED to provide better care, especially about treatments/assessments that originated as in-hospital treatments/assessments. It should be the reverse.

There is an excellent review of TTM research at Life In The Fast Lane.[3]

Footnotes:

[1] Prehospital cooling to improve successful targeted temperature management after cardiac arrest: A randomized controlled trial.
Scales DC, Cheskes S, Verbeek PR, Pinto R, Austin D, Brooks SC, Dainty KN, Goncharenko K, Mamdani M, Thorpe KE, Morrison LJ; Strategies for Post-Arrest Care SPARC Network.
Resuscitation. 2017 Dec;121:187-194. doi: 10.1016/j.resuscitation.2017.10.002. Epub 2017 Oct 5.
PMID: 28988962

Free Full text Article from Resuscitation.

[2] Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation.
Arrich J, Holzer M, Havel C, Müllner M, Herkner H.
Cochrane Database Syst Rev. 2016 Feb 15;2:CD004128. doi: 10.1002/14651858.CD004128.pub4. Review.
PMID: 26878327

[3] Targeted temperature management (TTM) after cardiac arrest
Life In The Fast Lane
Chris Nickson
Reviewed and revised Aug 1, 2017 @ 7:07 pm
Article

Scales DC, Cheskes S, Verbeek PR, Pinto R, Austin D, Brooks SC, Dainty KN, Goncharenko K, Mamdani M, Thorpe KE, Morrison LJ, & Strategies for Post-Arrest Care SPARC Network (2017). Prehospital cooling to improve successful targeted temperature management after cardiac arrest: A randomized controlled trial Resuscitation, 121 (December), 187-194 : PMID: 28988962

Arrich J, Holzer M, Havel C, Müllner M, & Herkner H (2016). Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation Cochrane Database Syst Rev : PMID: 26878327

.

Does the parachute study prove that research doesn’t matter? Part III

Also to be posted on ResearchBlogging.org when they relaunch the site.
 

Continuing from Part II, which looked at the way the satirical parachute paper misrepresents EBM (Evidence-Based Medicine), but that is expected from satire. You could also provide a great defense of blood-letting as the best medicine using satire.

In the comments to Does the parachute study prove that research doesn’t matter? Part I is the following from Kevin –
 

After claiming to know what he is writing about, Kevin finishes with this –
 

As a reminder, there is not level 1 evidence that oxygen works during an acute heart attack either. That is because we do not withhold it from anyone to study it in randomized fashion due to ethical concerns and assumptions made from non-level 1 evidence.

 

What does Kevin mean by level 1?

There have been some studies of oxygen. It is unethical to not study the drug oxygen.
 

3D Isolated Oxygen Tank


Image credit.
 

For example, there was a study of One hundred percent oxygen in the treatment of acute myocardial infarction and severe angina pectoris in JAMA (Journal of the American Medical Association) way back in 1950.

If oxygen is so much better than room air for heart attack patients, the patients receiving 100% oxygen should have dramatically better outcomes than patients receiving room air by mask in this double-blinded study. The results were not statistically significant, but patients receiving 100% oxygen did not do as well as the patients receiving room air by mask.[1]

Hypoxic patients were treated with oxygen, rather than enrolled in the study, because the study looked at treating heart attack, rather than treating hypoxia. Whether we should treat hypoxia without symptoms is also a different question.

Kevin’s comment was written in September, which is ironically when the paper Oxygen Therapy in Suspected Acute Myocardial Infarction was published. We have stopped using blood-letting to treat patients, even though withholding blood-letting used to be considered just as unethical.
 

CONCLUSIONS: Routine use of supplemental oxygen in patients with suspected myocardial infarction who did not have hypoxemia was not found to reduce 1-year all-cause mortality.[2]

 

The evil scientists did not uphold dogma? Burn the heretics.

The acronym for the study reflects the addiction to continuing questionable treatments, which must not be questioned. DETO2X.

Have competent people condemned this research as unethical?

I have not looked at any of the other medical research blogs, but you should go ahead and read them (listen to the podcasts, watch the videos) and see what they write. Tell me if anyone condemns the research. Don’t quote Gwyneth Paltrow or Dr. Oz, but competent science bloggers.

The actual dogma was to give oxygen to heart attack patients, so is routine oxygen for heart attack just another case of harming patients with tradition?

What does Cochrane tell us?
 

Authors’ conclusions There is no evidence from randomised controlled trials to support the routine use of inhaled oxygen in people with AMI, and we cannot rule out a harmful effect. Given the uncertainty surrounding the effect of oxygen therapy on all-cause mortality and on other outcomes critical for clinical decision, well-conducted, high quality randomised controlled trials are urgently required to inform guidelines in order to give definitive recommendations about the routine use of oxygen in AMI.[3]

 

well-conducted, high quality randomised controlled trials are urgently required

The purpose of research is to learn what is effective and what is safe. We should only be using treatments that are both effective and safe outside of well-controlled trials.

We have been harming too many patients with treatments that should never have been used outside of well-controlled trials.

We need to stop trying to make treatments look better than they are.

We need to stop coming up with rationalizations for hurting patients.

We need higher standards.

 

I have also written about EBM and the parachute paper in these posts –

Does the parachute study prove that research doesn’t matter? Part I – Wed, 22 Aug 2012

Common Sense vs. Evidence – Thu, 28 Mar 2013

The Parachute Study as an Objection to Studying Ventilations in Cardiac Arrest – Mon, 08 Apr 2013

Do we know that these treatments do not help? – Mon, 15 Apr 2013

Why Ignoring Evidence Based Medicine Kills Patients – Fri, 28 Jun 2013

JAMA Opinion Article in Support of Anecdote-Based Medicine – Thu, 28 Nov 2013

Why US EMS will never get to sit at the adult table – The Appeal to Authority – Sun, 04 May 2014

Natural Alternatives to the EpiPen, Because We Believe in Parachutes – Wed, 23 Dec 2015

Does the parachute study prove that research doesn’t matter? Part II – Thu, 30 Nov 2017

Footnotes:

[1] One hundred percent oxygen in the treatment of acute myocardial infarction and severe angina pectoris.
RUSSEK HI, REGAN FD, NAEGELE CF.
J Am Med Assoc. 1950 Sep 30;144(5):373-5. No abstract available.
PMID: 14774103 [PubMed – indexed for MEDLINE]

[2] Oxygen Therapy in Suspected Acute Myocardial Infarction.
Hofmann R, James SK, Jernberg T, Lindahl B, Erlinge D, Witt N, Arefalk G, Frick M, Alfredsson J, Nilsson L, Ravn-Fischer A, Omerovic E, Kellerth T, Sparv D, Ekelund U, Linder R, Ekström M, Lauermann J, Haaga U, Pernow J, Östlund O, Herlitz J, Svensson L; DETO2X–SWEDEHEART Investigators.
N Engl J Med. 2017 Sep 28;377(13):1240-1249. doi: 10.1056/NEJMoa1706222. Epub 2017 Aug 28.
PMID: 28844200

[3] Oxygen therapy for acute myocardial infarction.
Cabello JB, Burls A, Emparanza JI, Bayliss SE, Quinn T.
Cochrane Database Syst Rev. 2016 Dec 19;12:CD007160. doi: 10.1002/14651858.CD007160.pub4. Review.
PMID: 27991651

.

Is placebo better than aggressive medical treatment for patients NOT having a heart attack?

Also to be posted on ResearchBlogging.org when they relaunch the site.
 

Is cardiac catheterization placebo better than aggressive medical treatment for patients not having a heart attack?

No.
 

The answer is not really different from before. This should not be surprising for anyone who pays attention to EBM (Evidence-Based Medicine). We should all pay attention to EBM, because it is the best way to find out what works.

Many routine treatments are not beneficial to patients, but are considered to be standards of care. We continue to give these treatments out of unreasonable optimism, a fear of litigation, or fear of criticism for not following orders. The difference between the banality of evil and the banality of incompetence does not appear to be significant in any way that matters.

PCI (Percutaneous Coronary Intervention) treatment does not add any benefit – unless you are having a heart attack.

The placebo group received sham PCI in addition to optimized medical treatment. this did not provide any benefit over actual PCI in addition to optimized medical treatment. The patients in the placebo group received all of the same medications that the patients in the PCI group received.

Why is this news today?

A recent article in The Lancet is encouraging snake oil salesmen and snake oil saleswomen to claim that it shows the miracle healing power of placebos, but this is not true.

Apparently, Big Placebo (the multi-billion dollar alternative medicine industry) is trying to use this to promote their scams (homeopathy, acupuncture, Reiki, naturopathy, prayer, . . . ).

Big Placebo seems to think that this study shows that placebo is better than medical treatment. A placebo is an inactive intervention that is undetectable when compared with the active treatment. The placebo group received the same aggressive medications that the treatment group received.
 

All patients were pretreated with dual antiplatelet therapy. In both groups, the duration of dual antiplatelet therapy was the same and continued until the fial (unblinding) visit. Coronary angiography was done via a radial or femoral arterial approach with auditory isolation achieved by placing over-the-ear headphones playing music on the patient throughout the procedure.[1]

 

What is new about this?

A much larger study a decade ago showed that aggressive medical therapy was as good as PCI and aggressive medical therapy. The difference is the use of sham PCI to create a placebo group for comparison, rather than using a No PCI group for comparison.
 

CONCLUSIONS:
As an initial management strategy in patients with stable coronary artery disease, PCI did not reduce the risk of death, myocardial infarction, or other major cardiovascular events when added to optimal medical therapy.
[2]

 

Compare that with the conclusion (interpretation) of the new paper.
 

INTERPRETATION:
In patients with medically treated angina and severe coronary stenosis, PCI did not increase exercise time by more than the effect of a placebo procedure. The efficacy of invasive procedures can be assessed with a placebo control, as is standard for pharmacotherapy.
[1]

 

The unfortunate outcome is that we will have fewer hospitals providing PCI, so patients with heart attacks (STEMI – ST segment Elevation Myocardial Infarctions) may have to wait longer for emergency PCI, which really does improve outcomes.
 

What other Standards Of Care are NOT supported by valid evidence?

Amiodarone is effective for cardiac arrest, whether unwitnessed, witnessed, or witnessed by EMS.

Kayexalate (Sodium Polystyrene) is a good treatment for hyperkalemia. Anything that causes diarrhea will lower your potassium level, but that does not make it a good treatment, unless you are in an austere environment (in other words – not in a real hospital).

Amiodarone is effective for VT (Ventricular Tachycardia).

Backboards are effective to protect against spinal injury while transporting patients.

Blood-letting is effective for anything except hemochromatosis (and some rare disorders).

More paramedics are better for the patient.

Prehospital intravenous lines save lives.

IV fluid saves lives in hemorrhagic shock.

Oxygen should be given to everyone having a heart attack.

The Golden Hour is important.

Driving fast saves lives. For only some rare conditions, it probably does – and that depends on traffic.

Flying people to the hospital saves lives. Again, for only some rare conditions, it probably does – and that depends on traffic and distance.

Tourniquets are dangerous. As with anything else, if used inappropriately, they are dangerous, but tourniquets save lives.

Prehospital intubation saves lives.

Ventilation in cardiac arrest improves outcomes (other than for respiratory causes of cardiac arrest, which are easy to identify).

Epinephrine improves outcomes in cardiac arrest. It does produce a pulse more often, but at what cost to the long-term survival of the patient and the patient’s brain? PARAMEDIC2 should help us to identify which patients benefit from epinephrine, since it is clear that many patients are harmed by epinephrine in cardiac arrest. If we limit treatment to patients reasonably expected to benefit from the treatment, we can improve long-term survival.

And there are many more.

Footnotes:

[1] Percutaneous coronary intervention in stable angina (ORBITA): a double-blind, randomised controlled trial.
Al-Lamee R, Thompson D, Dehbi HM, Sen S, Tang K, Davies J, Keeble T, Mielewczik M, Kaprielian R, Malik IS, Nijjer SS, Petraco R, Cook C, Ahmad Y, Howard J, Baker C, Sharp A, Gerber R, Talwar S, Assomull R, Mayet J, Wensel R, Collier D, Shun-Shin M, Thom SA, Davies JE, Francis DP; ORBITA investigators.
Lancet. 2017 Nov 1. pii: S0140-6736(17)32714-9. doi: 10.1016/S0140-6736(17)32714-9. [Epub ahead of print]
PMID: 29103656

[2] Optimal medical therapy with or without PCI for stable coronary disease.
Boden WE, O’Rourke RA, Teo KK, Hartigan PM, Maron DJ, Kostuk WJ, Knudtson M, Dada M, Casperson P, Harris CL, Chaitman BR, Shaw L, Gosselin G, Nawaz S, Title LM, Gau G, Blaustein AS, Booth DC, Bates ER, Spertus JA, Berman DS, Mancini GB, Weintraub WS; COURAGE Trial Research Group.
N Engl J Med. 2007 Apr 12;356(15):1503-16. Epub 2007 Mar 26.
PMID: 17387127

Free Full Text from N Engl J Med.

.

Have a Slow, Quiet Friday the Thirteenth

Also to be posted on ResearchBlogging.org when they relaunch the site.
 

 

Superstitious appears to be common among medical people, so this may be seen as offensive. If you doubt me, comment that it is slow or quiet and see how many respond negatively, while they do not receive any criticism for their superstition-based complaints. Rather, people will make excuses for coddling the superstitions of those who are entrusted with the lives of patients.

The evidence does not support their superstitions.

One study did appear to show that women die in motor vehicle collisions more often on Friday the 13th, but that appears to be due to a lack of understanding of statistics by many who cite the article.
 

An additional factor is anxiolytic medication, used by significantly more women than men in Finland (7), which has been reported to reduce attention span and worsen driving performance (8). . . . Why this phenomenon exists in women but not in men remains unknown, but perhaps the twice-as-high prevalence of neurotic disorders and anxiety symptoms in women (7) makes them more susceptible to superstition and worsening of driving performance.[1]

 

The author suspects that those people with conditions that could be diagnosed as neuroses or anxiety disorders may be disproportionately affected by superstition.

In other words, superstition is not an external force affecting you. You are doing it to yourself.

The sample size was national, but still small, and was not able to adjust for many possible confounding variables, so the study would need to be replicated using a much larger data base to be useful.

In other superstition news – the next apocalypse, in a long line of predicted apocalypses, is going to be this Sunday – the 15 of October, 2017, according to David Meade. Meade twice previously predicted that a magical planet would hit the Earth and kill us all. This time he claims that his calculations are accurate, because that was the problem with his previous calculations – inaccuracy, not that they were a superstition deserving of derision.

If you are superstitious, and feel that your neuroses/anxieties will cause you to harm others, or yourself, you may want to stay home today and Sunday – perhaps even until you are capable of grasping reality.

Of course, we would never base treatment on superstition in medicine.

Amiodarone is the go to antiarrhythmic drug for cardiac arrest and ventricular tachycardia, but there are much safer much more effective drugs available. We have our own prophets misrepresenting research results to make it seem that using amiodarone for these is a good idea. The research says these preachers are wrong. The next guidelines will probably promote the superstition and reject the science.[2],[3]

Ventilation during cardiac arrest has been shown to be a good idea only for patients who arrested for respiratory reasons. We do a great job of identifying these patients. We have our own prophets misrepresenting research results to make it seem that providing ventilations for these is a good idea. The research says these preachers are wrong. The next guidelines will probably promote the superstition and reject the science.[4]

Medicine is full of superstition and superstitious people.

Why?

Too many of us believe the lie that, I’ve seen it work.

I have also written about the superstition of Friday the 13th here –

Acute coronary syndrome on Friday the 13th: a case for re-organising services? – Fri, 13 Jan 2017

The Magical Nonsense of Friday the 13th – Fri, 13 May 2016

Happy Friday the 13th – New and Improved with Space Debris – Fri, 13 Nov 2015

Friday the 13th and full-moon – the ‘worst case scenario’ or only superstition? – Fri, 13 Jun 2014

Blue Moon 2012 – Except parts of Oceanea – Fri, 31 Aug 2012

2009’s Top Threat To Science In Medicine – Fri, 01 Jan 2010

T G I Friday the 13th – Fri, 13 Nov 2009

Happy Equinox! – Thu, 20 Mar 2008

Footnotes:

[1] Traffic deaths and superstition on Friday the 13th.
Näyhä S.
Am J Psychiatry. 2002 Dec;159(12):2110-1.
PMID: 12450968

Free Full Text from Am J Psychiatry.

[2] The PROCAMIO Trial – IV Procainamide vs IV Amiodarone for the Acute Treatment of Stable Wide Complex Tachycardia
Wed, 17 Aug 2016
Rogue Medic
Article

There are a dozen links to the research in the footnotes to that article. There are also links to other articles on the failure of amiodarone to live up to its hype.

[3] Dr. Kudenchuk is Misrepresenting ALPS as ‘Significant’
Tue, 12 Apr 2016
Rogue Medic
Article

[4] Cardiac Arrest Management is an EMT-Basic Skill – The Hands Only Evidence
Fri, 09 Dec 2011
Rogue Medic
Article

.

The Medical Journal of Australia is Scammed by Acupuncturists

ResearchBlogging.org
 

Acupuncture has been thoroughly studied in high quality studies. The result is that we know, yes we know, that acupuncture is just an elaborate placebo – a scam. A reputable journal is claiming that low quality evidence contradicts what we know and we should ignore the high quality evidence.[1]

So why did the Medical Journal of Australia fall for this? Are their reviewers incompetent, dishonest, or is there some other reason for misleading their readers with bad research?

What is acupuncture?

You stick special needles into magic qi spots on the patient’s body, in order to affect the body’s magic energy. Not mitochondrial energy. Not any real measurable energy, but some psychic powers, some Stephen King kind of energy.

Any competent/honest researcher would compare acupuncture with a valid placebo. What is a valid placebo? A valid placebo is one that the patient believes is the treatment being studied. If the treatment comes in a pill, you provide a pill that is indistinguishable from the pill, but without the active ingredient. If the treatment is to jab you with needles, you provide an experience that is indistinguishable from the needles, but without influencing any mechanism of action the proponents claim makes the needles work.
 


 

How do we get people to believe they are being stabbed with needles in magic qi spots, without actually stabbing them with needles in magic qi spots? Use toothpicks at spots that acupuncture specialists specify are definitely not magic qi spots.

Every study of acupuncture that has used a valid placebo has failed to show benefit over placebo.[2],[3],[4],[5],[6],[7],[8]

Does this study use a valid placebo?

No. This study uses jargon and misdirection to distract us from the only important part of this study.

This study is just propaganda.

It doesn’t matter where you put the needles.

It doesn’t matter if you use needles.

All that matters is that you believe in voodoo.

We already knew that acupuncture is merely fancy voodoo, with the needles going into the patient, rather than the doll. These researchers want us to ignore the high quality evidence and pretend that the man behind the curtain is as great and powerful as he initially claims to be.

Footnotes:

[1] Acupuncture for analgesia in the emergency department: a multicentre, randomised, equivalence and non-inferiority trial
Marc M Cohen, De Villiers Smit, Nick Andrianopoulos, Michael Ben-Meir, David McD Taylor, Shefton J Parker, Chalie C Xue and Peter A Cameron
Med J Aust 2017; 206 (11): 494-499. || doi: 10.5694/mja16.00771
Abstract from MJA

Free Full Text in PDF format from MJA

[2] A randomized trial comparing acupuncture, simulated acupuncture, and usual care for chronic low back pain.
Cherkin DC, Sherman KJ, Avins AL, Erro JH, Ichikawa L, Barlow WE, Delaney K, Hawkes R, Hamilton L, Pressman A, Khalsa PS, Deyo RA.
Arch Intern Med. 2009 May 11;169(9):858-66. doi: 10.1001/archinternmed.2009.65.
PMID: 19433697

Free Full Text from PubMed Central

[3] Acupuncture for treatment of persistent arm pain due to repetitive use: a randomized controlled clinical trial.
Goldman RH, Stason WB, Park SK, Kim R, Schnyer RN, Davis RB, Legedza AT, Kaptchuk TJ.
Clin J Pain. 2008 Mar-Apr;24(3):211-8.
PMID: 18287826 [PubMed – indexed for MEDLINE]

[4] Sham device v inert pill: randomised controlled trial of two placebo treatments.
Kaptchuk TJ, Stason WB, Davis RB, Legedza AR, Schnyer RN, Kerr CE, Stone DA, Nam BH, Kirsch I, Goldman RH.
BMJ. 2006 Feb 18;332(7538):391-7. Epub 2006 Feb 1.
PMID: 16452103 [PubMed – indexed for MEDLINE]

Free Full Text from PubMed Central.

[5] Another acupuncture study misinterpreted
Science Blogs – Respectful Insolence
Orac
May 13, 2009
Article

[6] Acupuncture in the ED
Steven Novella
Neurologica
Article

[7] Emergency acupuncture! (2017 edition)
Science Blogs – Respectful Insolence
Orac
June 20, 2017
Article

[8] On the pointlessness of acupuncture in the emergency room…or anywhere else
David Gorski
Science-Based Medicine
July 25, 2016
Article

Marc M Cohen, De Villiers Smit, Nick Andrianopoulos, Michael Ben-Meir, David McD Taylor, Shefton J Parker, Chalie C Xue, & Peter A Cameron (2017). Acupuncture for analgesia in the emergency department: a multicentre, randomised, equivalence and non-inferiority trial Medical Journal of Australia, 206 (11), 494-499 : doi: 10.5694/mja16.00771

Cherkin, D., Sherman, K., Avins, A., Erro, J., Ichikawa, L., Barlow, W., Delaney, K., Hawkes, R., Hamilton, L., Pressman, A., Khalsa, P., & Deyo, R. (2009). A Randomized Trial Comparing Acupuncture, Simulated Acupuncture, and Usual Care for Chronic Low Back Pain Archives of Internal Medicine, 169 (9) DOI: 10.1001/archinternmed.2009.65

Goldman, R., Stason, W., Park, S., Kim, R., Schnyer, R., Davis, R., Legedza, A., & Kaptchuk, T. (2008). Acupuncture for Treatment of Persistent Arm Pain Due to Repetitive Use The Clinical Journal of Pain, 24 (3), 211-218 DOI: 10.1097/AJP.0b013e31815ec20f

Kaptchuk TJ, Stason WB, Davis RB, Legedza AR, Schnyer RN, Kerr CE, Stone DA, Nam BH, Kirsch I, & Goldman RH (2006). Sham device v inert pill: randomised controlled trial of two placebo treatments bmj, 332 (7538), 391-397 : pmid: 16452103

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D10 in the Treatment of Prehospital Hypoglycemia: A 24 Month Observational Cohort Study

ResearchBlogging.org
 

Why treat hypoglycemia with 10% dextrose (D10), rather than the more expensive, potentially more harmful, and less available, but traditional treatment of 50% dextrose (D50)? Why not? The only benefit of 50% dextrose appears to be that it is what people are used to using, but aren’t we used to starting IVs (IntraVenous lines) and running fluids through the IVs?

We should be much more familiar with running in fluid, than in pushing boluses of syrup.

What happens when we have temporary shortages of 50% dextrose? Do we stop treating hypoglycemia? Are we supposed to panic, because we can no longer follow tradition? No. We give the more appropriate, and lower, dose of the much lower concentration of dextrose. We provide better care because of our need.
 

Despite the traditional use of D50, there is a minimal amount of data to support it as the standard of care.[1]

 

Is 10% dextrose the perfect treatment for hypoglycemia? No, but it does appear to be less likely to cause harm than the current overtreatment with 50% dextrose.
 

Seven patients had a drop in blood glucose after D10 administration, all of 10 mg/dL or less except for one patient with a drop of 19 mg/dL who had an insulin pump infusing that was not removed by EMS personnel during D10 infusion.[1]

 

Is that any different from what happens with 50% dextrose? If this is different from D50, how does the potential harm from giving too much dextrose to most hypoglycemic patients compare to the potential harm of giving a first that is too small to fewer than 1% of hypoglycemia patients?
 

There were no reported adverse events related to dextrose infusion. Six patients who received intravenous D10 were pronounced dead in the field during the period of study. On investigator review, all patients had altered level of arousal or were in cardiac arrest prior to arrival of EMS personnel and their deaths were deemed to be unrelated to dextrose administration.[1]

 

Dextrose does not reverse death, so there is no reason to expect a better outcome for dead patients with a higher concentration of a drug that does not reverse death. Go read the excellent review of the evidence on hypoglycemia, death, and the potential of dextrose to improve outcomes from death.[2]

But is 10% really better? We don’t have any good research, but is there any good reason to give all 25 grams of dextrose in a syringe of 50% dextrose if the patient wakes up before the full dose has been administered? Would we continue to give the entire syringe of morphine, or fentanyl, or most of the other drugs that we give, if our assessment shows that the patient no longer meets the protocol criteria for administration of the drug?
 


 

76% of patients received only 10 grams of dextrose, rather than the usual 25 grams. While it is not known if any of these patients required any further dextrose, or oral glucose, while in the hospital, they should have been awake enough to take any further dextrose orally, as they would the rest of the time.

23% of patients received only 20 grams of dextrose, rather than the usual 25 grams.

Fewer than 1% of hypoglycemia patients received a dose as large as we traditionally give.
 

We do not appear to be concerned with harm from administering more aggressive treatment than is justified by the evidence.

We do appear to be concerned about our anxiety of deviating from the traditional too much is not enough approach to hypoglycemia.

Footnotes:

[1] D10 in the Treatment of Prehospital Hypoglycemia: A 24 Month Observational Cohort Study.
Hern HG, Kiefer M, Louie D, Barger J, Alter HJ.
Prehosp Emerg Care. 2017 Jan-Feb;21(1):63-67. doi: 10.1080/10903127.2016.1189637. Epub 2016 Dec 5.
PMID: 27918858
 

Of the 1,323 patients administered D10 during the study period, the 452 patients excluded from the study cohort for the aforementioned reasons were similar demographically to the study cohort. The median initial blood glucose was the same at 37 mg/dL and the median age was also 66. There were slightly more women at 229 (51%) in the excluded group compared to the cohort.

 

[2] Using Dextrose in Cardiac Arrest
Wednesday, March 14, 2012
Mill Hill Ave Command
Dr. Brooks Walsh
Article

Hern, H., Kiefer, M., Louie, D., Barger, J., & Alter, H. (2016). D10 in the Treatment of Prehospital Hypoglycemia: A 24 Month Observational Cohort Study Prehospital Emergency Care, 21 (1), 63-67 DOI: 10.1080/10903127.2016.1189637

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Acute coronary syndrome on Friday the 13th: a case for re-organising services?

ResearchBlogging.orgAcute coronary syndrome on Friday the 13th - a case for re-organising services 1
 
There has been a bunch of research on the likelihood of bad things happening on Friday the 13th. These researchers thought that the big problem with all of the available research is that the populations studied have been too small. The authors took information on over 56,000 patients with acute coronary syndromes, broke them down into 217 day/date combinations (Friday the 1st, Saturday the 1st, . . . ,Wednesday the 31st, Thursday the 31st), and compared the outcomes of those 216 groups with their Friday the 13th group.

Cut to the conclusion –
 

Conclusion: On most days, there was no difference in the 13-year mortality rate for patients admitted with their first ACS from that for “unlucky” Friday the 13th. However, patients admitted on five day/number combinations were 20-30% more likely to survive at 13 years. These findings could be explained by subgroup analysis inflation of the type I error, although supernatural causes merit further investigation.[1]

 

No. Supernatural causes do not merit further investigation, at least, not based on anything in this paper.

The authors used Friday the 13th as their normal date for comparison with every other date, but the outcomes from Friday the 13th are not the true statistical mean. The outcomes on Friday the 13th were just chosen because of the superstition being investigated. Friday the 13th is so close to the statistical mean that this mistake is easy to make.
 

Surprisingly, however, we also identified five potentially “lucky” days on which mortality rates were significantly lower, by 20-30%.[1]

 

When analyzing 217 samples, it is not surprising that some of the data deviate from average by an amount that is expected to produce no more than one significant deviation out of every twenty comparisons. The authors had over 200 comparisons, so we should not have been surprised by up to 11 day/date combinations with p values of less than 0.05. There were only 5. Should anyone go looking for supernatural explanations for statistically normal outcomes?

While Friday the 13th was not the statistical mean, it was very close. Look at the five potentially “lucky” days and how close the ranges are to 1.00. If the range crosses (includes) 1.00, the results are not statistically significant according to the prospectively determined criteria of the authors. Crossing 1.00 is just another way of expressing P <0.05. Sunday the 1st and Monday the 29th each produced outcomes 29% worse than Friday the 13th. Saturday the 31st produced outcomes that were 36% worse. If we compared these with the actual statistical mean, Monday the 29th and Saturday the 31st become significantly “unlucky” using a p value of less than 0.05 and all of the significantly “lucky” days become insignificant.

As we should expect, the most extreme benefit and harm both fall on the 31st. Only 7/12 (58.3%) of months have 31 days, so these days have much smaller sample sizes. With smaller samples, the appearance of deviance is expected to be greater. The actual deviation is less important, because the sample size is smaller.

Friday the 13th is only slightly different from the statistical mean, using the data in this paper, which may be the largest examination of a possible Friday the 13th effect.

Once again, the biggest problem with Friday the 13th is that we end up listening to people promoting superstition.
 

I have also written about this kind of superstition here –

The Magical Nonsense of Friday the 13th – Fri, 13 May 2016

Happy Friday the 13th – New and Improved with Space Debris – Fri, 13 Nov 2015

Friday the 13th and full-moon – the ‘worst case scenario’ or only superstition? – Fri, 13 Jun 2014

Blue Moon 2012 – Except parts of Oceanea – Fri, 31 Aug 2012

2009’s Top Threat To Science In Medicine – Fri, 01 Jan 2010

T G I Friday the 13th – Fri, 13 Nov 2009

Happy Equinox! – Thu, 20 Mar 2008

Footnotes:

[1] Acute coronary syndrome on Friday the 13th: a case for re-organising services?
Protty MB, Jaafar M, Hannoodee S, Freeman P.
Med J Aust. 2016 Dec 12;205(11):523-525.
PMID: 27927150

Protty, M., Jaafar, M., Hannoodee, S., & Freeman, P. (2016). Acute coronary syndrome on Friday the 13th: a case for re-organising services? The Medical Journal of Australia, 205 (11), 523-525 DOI: 10.5694/mja16.00870

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The PROCAMIO Trial – IV Procainamide vs IV Amiodarone for the Acute Treatment of Stable Wide Complex Tachycardia

ResearchBlogging.org
 

This is a very interesting trial that may surprise the many outspoken amiodarone advocates, but it should not surprise anyone who pays attention to research.

ALPS showed that we should stop giving amiodarone for unwitnessed shockable cardiac arrest. The lead researcher is still trying to spin amiodarone for witnessed shockable cardiac arrest, even though the results do not show improvement in the one outcome that matters – leaving the hospital with a brain that still works.[1],[2],[3]

There is an excellent discussion of the study on the podcast by Dr. Salim Rezaie and Dr. Anand Swaminathan REBELCast: The PROCAMIO Trial – IV Procainamide vs IV Amiodarone for the Acute Treatment of Stable Wide Complex Tachycardia.

One problem with the study that they do not address on the podcast is that the patients in the study appear to have had time to watch Casablanca before treatment started. Here’s looking at you, while we’re waiting, kid. This is apparently unintentional one way of doing a placebo washout. If we wait long enough . . . .
 

Time from arrival to start of infusion was 87 ± 21 min for procainamide and 115 ± 36 min for amiodarone patients (P = 0.58).[4]

 

If nothing else, this demonstrates how little we need to worry about immediately pushing drugs for stable monomorphic VT (V Tach or Ventricular Tachycardia). Should we expect much from antiarrhythmic treatment?

Research shows that for stable monomorphic VT (V Tach or Ventricular Tachycardia) amiodarone is not very likely to be followed by an improvement. Only 29%[5] or only 25%[6] or only 15% within 20 minutes, but if we don’t mind waiting an hour it can be as much as 29%.[7] For those of you who are not good at math, that means amiodarone is about the same as doing nothing, only it comes in a syringe. Even though these poor outcomes ignore the side effects, they are the best evidence in favor of amiodarone, so what Kool-Aid are the advocates drinking?

Adenosine, yes adenosine the SVT (SupraVentricular Tachycardia) drug, appears to be more effective at treating ventricular tachycardia than amiodarone – and adenosine is faster and safer than amiodarone.[8]

What if the patient becomes unstable? First start an IV (IntraVenous) line. Then sedate the patient. Then apply defibrillator pads. After the patient is adequately sedated, then cardiovert. We do not need the pads on the patient first. If it takes a while to put the pads on, that is a problem with the ability of the doctors and nurses, not a medical problem.

It does not appear as if any patient received amiodarone or procainamide until after waiting in the ED (Emergency Department) for over an hour. Were some patients cardioverted in well under an hour? Probably. The important consideration is that the doctors and nurses be able to apply the defibrillator pads properly and quickly and deliver a synchronized cardioversion in less than a minute. If the patient has not yet been sedated, the cardioversion should be delayed until after the patient is adequately sedated, so the intervention that depends most on time is the sedation of the patient.
 

VT + Amiodarone Cardioversion
 

Is there a better treatment than amiodarone? Sedate the patient before the patient becomes unstable, then cardiovert. How do the MACEs (Major Adverse Cardiac Events) compare with sedation and cardioversion vs. antiarrhythmic treatment.
 

5.4 Proarrhythmia
Amiodarone may cause a worsening of existing arrhythmias or precipitate a new arrhythmia. Proarrhythmia, primarily torsade de pointes (TdP), has been associated with prolongation, by intravenous amiodarone, of the QTc interval to 500 ms or greater. Although QTc prolongation occurred frequently in patients receiving intravenous amiodarone, TdP or new-onset VF occurred infrequently (less than 2%). Monitor patients for QTc prolongation during infusion with amiodarone. Reserve the combination of amiodarone with other antiarrhythmic therapies that prolong the QTc to patients with life-threatening ventricular arrhythmias who are incompletely responsive to a single agent.
[9]

 

All antiarrhythmic drugs can cause arrhythmias. In the absence of information about a specific problem that is best addressed by a specific drug (amiodarone is the opposite of specific), we should avoid treatments that have such a high potential for harm.

Amiodarone doesn’t even do a good job of preventing arrhythmias.
 

Intravenous amiodarone did not prevent induction of sustained ventricular tachycardia in any of five patients inducible at baseline. Of six patients with non-sustained ventricular tachycardia, five had sustained ventricular tachycardia or fibrillation induced after amiodarone infusion.[10]

 

Is anything worse than amiodarone? Even epinephrine, yes epinephrine the inadequately tested cardiac arrest drug, has been followed by improved outcomes from V Tach after amiodarone failed.[11]
 

What is best for the patient?

Sedation, search for reversible causes, apply defibrillator pads, and be prepared to cardiovert.

Maybe sedation isn’t that important? This is by Dr. Peter Kowey, one of the top cardiologists in the world.
 

The man’s very first utterance was, “If it happens again, just let me die.”

As I discovered, the reason for this patient’s terror was that he had been cardioverted in an awake state. Ventricular tachycardia had been relatively slow, he had not lost consciousness, and the physicians, in the heat of the moment, had not administered adequate anesthesia. Although the 5 mg of intravenous diazepam had made him a bit drowsy, he felt the electric current on his chest and remembered the event clearly.

The patient’s mental state complicated the case considerably.[12]

 

How unimportant is sedation? How unimportant is consent?

For sedation, I would recommend ketamine, but etomidate was recommended in the podcast. Both work quickly and the most important obstacle to immediate treatment of a patient who suddenly deteriorates is the time to effect of sedation. Neither drug is expected to interfere with perfusion, which is the main excuse given for avoiding sedation for cardioversion.

This study is very small (not the fault of the authors), but it adds to the evidence that amiodarone is not a good first treatment for the patient.
 

Go listen to the podcast by Dr. Salim Rezaie and Dr. Anand Swaminathan REBELCast: The PROCAMIO Trial – IV Procainamide vs IV Amiodarone for the Acute Treatment of Stable Wide Complex Tachycardia

 

Over the years, I have written a bit about cardioversion and the importance of sedation –

Cardioversion – I’m not doing that, you do it! – Mon, 24 Mar 2008

Cardioversion – 2010 ACLS – Part I – Mon, 25 Oct 2010

Cardioversion – 2010 ACLS – Part II – Sun, 31 Oct 2010

Cardioversion – 2010 ACLS – Part III – Thu, 11 Nov 2010

On the relative wisdom of synchronized cardioversion without sedation – Part I – Thu, 11 Nov 2010

On the relative wisdom of synchronized cardioversion without sedation – Part II – Fri, 12 Nov 2010

Synchronized Cardioversion Without Sedation – Part II Scallywag’s Response – Sun, 14 Nov 2010

On the relative wisdom of synchronized cardioversion without sedation – Part III – Tue, 16 Nov 2010

On the relative wisdom of synchronized cardioversion without sedation – Part IV – Wed, 24 Nov 2010

Comments on Cardioversion – 2010 ACLS – Part II – Mon, 16 Apr 2012
 

I have also written a bit about amiodarone –

Merit Badge Courses, Amiodarone, and tPA – Fri, 17 Sep 2010

Amiodarone for Cardiac Arrest in the 2010 ACLS – Part I – Wed, 01 Dec 2010

Amiodarone for Cardiac Arrest in the 2010 ACLS – Part II – Fri, 03 Dec 2010

Is Nexterone the Next Amiodarone? – Sat, 04 Dec 2010

Amiodarone for Cardiac Arrest in the 2010 ACLS – Part III – Mon, 06 Dec 2010

Where are the Black Box Warnings on These Drugs – I – Mon, 05 Dec 2011

Where are the Black Box Warnings on These Drugs – II – Sun, 11 Dec 2011

Is Amiodarone the Best Drug for Stable Ventricular Tachycardia – Wed, 14 Dec 2011

V Tach Storm – Part I – Wed, 28 Dec 2011

V Tach Storm – Part II – Thu, 29 Dec 2011

Nifekalant versus lidocaine for in-hospital shock-resistant ventricular fibrillation or tachycardia – Wed, 04 Jan 2012

NIH launches trials to evaluate CPR and drugs after sudden cardiac arrest – Sun, 29 Jan 2012

What Will Be the Next Standard Of Care We Eliminate – Wed, 28 Mar 2012

Happy Adenosine Day – Tue, 12 Jun 2012

Too Much Medicine and Evidence-Based Guidelines – Part I – Tue, 26 Jun 2012

Too Much Medicine and Evidence-Based Guidelines – Part II – Tue, 03 Jul 2012

Ondansetron (Zofran) Warning for QT Prolongation – is Amiodarone next? – Part I – Mon, 02 Jul 2012

Ondansetron (Zofran) Warning for QT Prolongation – is Amiodarone next? – Part II – Thu, 05 Jul 2012

Wide variability in drug use in out-of-hospital cardiac arrest: A report from the resuscitation outcomes consortium – Part I – Mon, 17 Sep 2012

Wide variability in drug use in out-of-hospital cardiac arrest: A report from the resuscitation outcomes consortium – Part II – Tue, 18 Sep 2012

How do we measure the QT segment when there are prominent U waves? – Thu, 13 Dec 2012

Woman with Risks for Torsades de Pointes Dying within Hours of Leaving the Emergency Department – Wed, 02 Jan 2013

Examples of Ventricular Tachycardia Caused by Amiodarone – Part I – Tue, 28 May 2013

Publication Bias – The Lit Whisperers – Tue, 11 Jun 2013

Standards Of Care – Ventricular Tachycardia – Wed, 31 Jul 2013

Footnotes:

[1] Dr. Kudenchuk is Misrepresenting ALPS as ‘Significant’
Tue, 12 Apr 2016
Rogue Medic
Article

[2] Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest
Mon, 04 Apr 2016
Rogue Medic
Article

[3] Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest.
Kudenchuk PJ, Brown SP, Daya M, Rea T, Nichol G, Morrison LJ, Leroux B, Vaillancourt C, Wittwer L, Callaway CW, Christenson J, Egan D, Ornato JP, Weisfeldt ML, Stiell IG, Idris AH, Aufderheide TP, Dunford JV, Colella MR, Vilke GM, Brienza AM, Desvigne-Nickens P, Gray PC, Gray R, Seals N, Straight R, Dorian P; Resuscitation Outcomes Consortium Investigators.
N Engl J Med. 2016 May 5;374(18):1711-22. doi: 10.1056/NEJMoa1514204. Epub 2016 Apr 4.
PMID: 27043165

CONCLUSIONS
Overall, neither amiodarone nor lidocaine resulted in a significantly higher rate of survival or favorable neurologic outcome than the rate with placebo among patients with out-of-hospital cardiac arrest due to initial shock-refractory ventricular fibrillation or pulseless ventricular tachycardia.

[4] Randomized comparison of intravenous procainamide vs. intravenous amiodarone for the acute treatment of tolerated wide QRS tachycardia: the PROCAMIO study.
Ortiz M, Martín A, Arribas F, Coll-Vinent B, Del Arco C, Peinado R, Almendral J; PROCAMIO Study Investigators.
Eur Heart J. 2016 Jun 28. pii: ehw230. [Epub ahead of print]
PMID: 27354046

Free Full Text from European Heart Journal.

[5] Amiodarone or procainamide for the termination of sustained stable ventricular tachycardia: an historical multicenter comparison.
Marill KA, deSouza IS, Nishijima DK, Senecal EL, Setnik GS, Stair TO, Ruskin JN, Ellinor PT.
Acad Emerg Med. 2010 Mar;17(3):297-306.
PMID: 20370763 [PubMed – indexed for MEDLINE]

Free Full Text from Academic Emergency Medicine.

[6] Amiodarone is poorly effective for the acute termination of ventricular tachycardia.
Marill KA, deSouza IS, Nishijima DK, Stair TO, Setnik GS, Ruskin JN.
Ann Emerg Med. 2006 Mar;47(3):217-24. Epub 2005 Nov 21.
PMID: 16492484 [PubMed – indexed for MEDLINE]

[7] Intravenous amiodarone for the pharmacological termination of haemodynamically-tolerated sustained ventricular tachycardia: is bolus dose amiodarone an appropriate first-line treatment?
Tomlinson DR, Cherian P, Betts TR, Bashir Y.
Emerg Med J. 2008 Jan;25(1):15-8.
PMID: 18156531 [PubMed – indexed for MEDLINE]

[8] Adenosine for wide-complex tachycardia – diagnostic?
Thu, 23 Aug 2012
Rogue Medic
Article

[9] AMIODARONE HYDROCHLORIDE- amiodarone hydrochloride injection, solution
DailyMed
5 WARNINGS AND PRECAUTIONS
FDA Label

[10] Effects of intravenous amiodarone on ventricular refractoriness, intraventricular conduction, and ventricular tachycardia induction.
Kułakowski P, Karczmarewicz S, Karpiński G, Soszyńska M, Ceremuzyński L.
Europace. 2000 Jul;2(3):207-15.
PMID: 11227590 [PubMed – indexed for MEDLINE]

Free Full Text PDF + HTML from Europace

[11] Low doses of intravenous epinephrine for refractory sustained monomorphic ventricular tachycardia.
Bonny A, De Sisti A, Márquez MF, Megbemado R, Hidden-Lucet F, Fontaine G.
World J Cardiol. 2012 Oct 26;4(10):296-301. doi: 10.4330/wjc.v4.i10.296.
PMID: 23110246 [PubMed]

Free Full Text from PubMed Central.

[12] The calamity of cardioversion of conscious patients.
Kowey PR.
Am J Cardiol. 1988 May 1;61(13):1106-7. No abstract available.
PMID: 3364364

Kudenchuk PJ, Brown SP, Daya M, Rea T, Nichol G, Morrison LJ, Leroux B, Vaillancourt C, Wittwer L, Callaway CW, Christenson J, Egan D, Ornato JP, Weisfeldt ML, Stiell IG, Idris AH, Aufderheide TP, Dunford JV, Colella MR, Vilke GM, Brienza AM, Desvigne-Nickens P, Gray PC, Gray R, Seals N, Straight R, Dorian P, & Resuscitation Outcomes Consortium Investigators (2016). Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest. The New England journal of medicine, 374 (18), 1711-22 PMID: 27043165

Ortiz M, Martín A, Arribas F, Coll-Vinent B, Del Arco C, Peinado R, Almendral J, & PROCAMIO Study Investigators (2016). Randomized comparison of intravenous procainamide vs. intravenous amiodarone for the acute treatment of tolerated wide QRS tachycardia: the PROCAMIO study. European heart journal PMID: 27354046

Marill KA, deSouza IS, Nishijima DK, Senecal EL, Setnik GS, Stair TO, Ruskin JN, & Ellinor PT (2010). Amiodarone or procainamide for the termination of sustained stable ventricular tachycardia: an historical multicenter comparison. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, 17 (3), 297-306 PMID: 20370763

Marill KA, deSouza IS, Nishijima DK, Stair TO, Setnik GS, & Ruskin JN (2006). Amiodarone is poorly effective for the acute termination of ventricular tachycardia. Annals of emergency medicine, 47 (3), 217-24 PMID: 16492484

Tomlinson DR, Cherian P, Betts TR, & Bashir Y (2008). Intravenous amiodarone for the pharmacological termination of haemodynamically-tolerated sustained ventricular tachycardia: is bolus dose amiodarone an appropriate first-line treatment? Emergency medicine journal : EMJ, 25 (1), 15-8 PMID: 18156531

Kułakowski P, Karczmarewicz S, Karpiński G, Soszyńska M, & Ceremuzyński L (2000). Effects of intravenous amiodarone on ventricular refractoriness, intraventricular conduction, and ventricular tachycardia induction. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, 2 (3), 207-15 PMID: 11227590

Bonny A, De Sisti A, Márquez MF, Megbemado R, Hidden-Lucet F, & Fontaine G (2012). Low doses of intravenous epinephrine for refractory sustained monomorphic ventricular tachycardia. World journal of cardiology, 4 (10), 296-301 PMID: 23110246

Kowey PR (1988). The calamity of cardioversion of conscious patients. The American journal of cardiology, 61 (13), 1106-7 PMID: 3364364

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