There are plenty who … claim to be competent at intubation even though their last intubation was months ago on the third attempt and if the patient had not already been dead – that would have finished the patient off …

- Rogue Medic

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

.

Acupuncture vs intravenous morphine in the management of acute pain in the ED

ResearchBlogging.org
 

What does elaborate placebo mean?

An elaborate placebo is a placebo that does better than a pill, or injection, apparently because the patient has more invested in the belief the placebo will work. An injection of a placebo (saline solution) may be more effective than a pill of real pain medicine because of the ceremony involved in giving the placebo through IV (IntraVenous) access. A placebo that is more expensive tends to have more of an effect than a less expensive placebo.[1],[2]

Acupuncture requires a lot of investment on the part of the patient. A more elaborate placebo might be fire walking. I don’t know of any research on fire walking as a treatment for pain, but I would not be surprised if it is extremely effective.
 

fire walking 1
Image credit. Do not try at home.
 

We know that acupuncture is just a placebo because research shows that sham (fake/placebo) acupuncture works just as well as real acupuncture. Sham acupuncture generally means using toothpicks (rather than needles), not penetrating the skin, but always using locations that are not qi points.[3],[4],[5]

If the essence of acupuncture is the magic of the qi points, but the same effect is produced when staying away from the qi points, the qi points aren’t doing anything.

This study did not use a sham acupuncture group. We have no reason to expect real acupuncture to provide more pain relief than sham acupuncture, so how should we use this information?

Should we have people providing fake acupuncture in the ED (Emergency Department)?

If so, how should we do this?

Since it is not the acupuncture, but the patient’s reaction to the ceremony of the placebo that appears to be providing the pain relief, how many different ways might we vary the treatment to improve the placebo effect?

Should we set up a fire walking pit?

What are the ethical concerns of using placebo medicine, when the placebo appears to provide similar, but safer, relief than real medicine?

What are the ethical concerns of using deception to treat patients?
 

Acupuncture versus intravenous morphine in the management of acute pain in the emergency department 1 with caption
 

Overall, 89 patients (29.3%) experienced minor adverse effects: 85 (56.6%) in morphine group and 4 (2.6%) in acupuncture group; the difference was signi ficant between the 2 groups (Table 3). The most frequent adverse effect was dizziness in the morphine group (42%) and needle breakage in the acupuncture group (2%). No major adverse effect was recorded during the study protocol. (See Table 4.)[6]

 

If we ignore the problems with this study and with the problem of lying to patients to make them feel better, can we expect research journals to look more like alternative medicine magazines with article titles like –

How to lie to patients, so that . . . .

What is the best scam to relieve pain?

How much integrity do we sacrifice?

Since the ED does not appear to be the source of the increase in opioid addiction, should we sacrifice any integrity in pursuit of placebo treatments?

We have an epidemic of opioid addiction because of excessive prescriptions for long-term pain.

The answer is not to try to create an epidemic of magical thinking.
 

This paper was also covered by –

Emergency Medicine Literature of Note

NEJM Journal Watch Emergency Medicine

Life in the Fast Lane

Science-Based Medicine

And thank you to Dr. Ryan Radecki of Emergency Medicine Literature of Note for providing me with a copy of the paper.

Footnotes:

[1] Placebo effect of medication cost in Parkinson disease: a randomized double-blind study.
Espay AJ, Norris MM, Eliassen JC, Dwivedi A, Smith MS, Banks C, Allendorfer JB, Lang AE, Fleck DE, Linke MJ, Szaflarski JP.
Neurology. 2015 Feb 24;84(8):794-802. doi: 10.1212/WNL.0000000000001282. Epub 2015 Jan 28.
PMID: 25632091

Free Full Text from PubMed Central

[2] Commercial features of placebo and therapeutic efficacy.
Waber RL, Shiv B, Carmon Z, Ariely D.
JAMA. 2008 Mar 5;299(9):1016-7. doi: 10.1001/jama.299.9.1016. No abstract available.
PMID: 18319411

Free Full Text in PDF format from Duke.edu

[3] Acupuncture for Menopausal Hot Flashes: A Randomized Trial.
Ee C, Xue C, Chondros P, Myers SP, French SD, Teede H, Pirotta M.
Ann Intern Med. 2016 Feb 2;164(3):146-54. doi: 10.7326/M15-1380. Epub 2016 Jan 19.
PMID: 26784863

Free Full Text in PDF format from carolinashealthcare.org

[4] 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

[5] 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]

[6] Acupuncture vs intravenous morphine in the management of acute pain in the ED.
Grissa MH, Baccouche H, Boubaker H, Beltaief K, Bzeouich N, Fredj N, Msolli MA, Boukef R, Bouida W, Nouira S.
Am J Emerg Med. 2016 Jul 20. pii: S0735-6757(16)30422-3. doi: 10.1016/j.ajem.2016.07.028. [Epub ahead of print]
PMID: 27475042

ClinicalTrials.gov page for this study.

Grissa, M., Baccouche, H., Boubaker, H., Beltaief, K., Bzeouich, N., Fredj, N., Msolli, M., Boukef, R., Bouida, W., & Nouira, S. (2016). Acupuncture vs intravenous morphine in the management of acute pain in the ED The American Journal of Emergency Medicine DOI: 10.1016/j.ajem.2016.07.028

Espay, A., Norris, M., Eliassen, J., Dwivedi, A., Smith, M., Banks, C., Allendorfer, J., Lang, A., Fleck, D., Linke, M., & Szaflarski, J. (2015). Placebo effect of medication cost in Parkinson disease: A randomized double-blind study Neurology, 84 (8), 794-802 DOI: 10.1212/WNL.0000000000001282

Waber RL, Shiv B, Carmon Z, Ariely D. (2008). Commercial Features of Placebo and Therapeutic Efficacy JAMA, 299 (9) DOI: 10.1001/jama.299.9.1016

Ee, C., Xue, C., Chondros, P., Myers, S., French, S., Teede, H., & Pirotta, M. (2016). Acupuncture for Menopausal Hot Flashes Annals of Internal Medicine, 164 (3) DOI: 10.7326/M15-1380

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

.

Dr. Kudenchuk is Misrepresenting ALPS as ‘Significant’

ResearchBlogging.org
 

The results of ALPS (Amiodarone, Lidocaine, Placebo Study) are clear. There is no statistically significant difference in cardiac arrest outcomes with amiodarone or lidocaine, when compared with placebo.
 

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.[1]

 

This study was very well done, but it was not designed to provide valid information about the effects of amiodarone or lidocaine on witnessed arrests or on EMS Witnessed arrests. Maybe the authors were overconfident.

In resuscitation research, we have abundant evidence that overconfidence is much more common than improvements in outcomes. There is no study that has shown an improvement in neurologically intact survival to discharge with any drug. Leaving the hospital with a working brain is the result that matters most to patients. We give drugs because we have too much confidence in the drugs and we are treating our confidence, not because we are doing anything to benefit the patients.
 

I WANT TO BE DECEIVED version of Domenichino, Virgin and Unicorn 1 copy
 

In ALPS there was a subgroup that might have reached statistical significance, but the researchers never determined what would be statistically significant when setting up the study, so these results are merely post hoc data mining (fitting the numbers to allow for a positive spin).

This is the Texas sharpshooter fallacy. The Texas sharpshooter shoots at the side of a barn, then draws targets around the bullet holes so that the the bullet holes are in the bull’s eyes.
 


 

The Texas sharpshooter didn’t shoot at any target, but he went back later and made it look like he hit the center of the target, because he drew the target around the bullet holes. Science requires that we state our hypotheses ahead of time, so that scientists are kept honest. Science requires that we calculate statistical significance ahead of time, especially for secondary outcomes/subgroup analysis, which may mean decreasing the p value to less than 0.03, or to less than 0.01, or even lower to reach statistical significance, so that scientists are kept honest. You are not permitted to bet on the outcome of a horse race that is already in progress for the same reason.

Why do we need to keep scientists honest? Because, as Dr. Peter Kudenchuk unintentionally demonstrates, scientists are just as biased as everyone else. Scientists need to follow the rules of science to minimize the influence of prejudices, such as overconfidence. When scientists do not follow these rules, they are just as easily fooled as everyone else and they may use that self-delusion, and their reputation, to fool others. Dr. Oz makes a fortune telling people what they want to hear about treatments that do not work.

I don’t claim that Dr. Kudenchuk, or even Dr. Oz, is deliberately fooling others, only that they have fooled themselves and are trying to convince others that their prejudices are accurate representations of reality. Here is what Dr. Kudenchuk has been telling people –
 

Researchers have confirmed that certain heart rhythm medications, when given by paramedics to patients with out-of-hospital cardiac arrest who had failed electrical shock treatment, improved likelihood of patients surviving transport to the hospital.[2]

 

The researchers have not confirmed any such thing.

If Dr. Kudenchuk wants to study whether amiodarone or lidocaine or both improve outcomes for witnessed cardiac arrest patients, or for EMS witnessed cardiac arrest patients, he needs to set up a study with all of the criteria for a positive result specified before the start of the study, because this study did not. The study explicitly states this, so Dr. Kudenchuk should be able to just read the study and see that he is wrong. Here is another statement that contradicts the information that was published.
 

Two groups of patients were pre-specified by the study as likely to respond differently to treatment: those with a witnessed cardiac arrest and those with an unwitnessed arrest. When it was originally designed, the study predicted that because patients with witnessed cardiac arrest are recognized and treated sooner, they would more likely be responsive to effective treatments than unwitnessed arrests. When first discovered, patients with an unwitnessed arrest are more likely to have already sustained irreversible organ damage resulting from a longer “down time” and less likely to respond to any treatment. This is precisely what was seen in the study – a statistically significant 5% improvement in survival to hospital discharge in witnessed arrests, and no effect from the drugs in unwitnessed arrests.[3]

 

Why does the published version of the paper contradict Dr. Kudenchuk? One of our biases is to remember things differently from the way things really happened. This is why eyewitness testimony is so often wrong. Here is what the published paper states about the witnessed arrest results.
 

We observed an interaction of treatment with the witnessed status of out-of-hospital cardiac arrest, which is often taken as a surrogate for early recognition of cardiac arrest, a short interval between the patient’s collapse from cardiac arrest and the initiation of treatment, and a greater likelihood of therapeutic responsiveness. Though prespecified, this subgroup analysis was performed in the context of an insignificant difference for the overall analysis, and the P value for heterogeneity in this subgroup analysis was not adjusted for the number of subgroup comparisons. Nonetheless, the suggestion that survival was improved by drug treatment in patients with witnessed out-of-hospital cardiac arrest, without evidence of harm in those with unwitnessed arrest, merits thoughtful consideration.[1]

 

The authors did not adjust the p value, so the authors do not claim that the witnessed cardiac arrest results are statistically significant. They only state that these results merit thoughtful consideration. In other words, if we want to claim this hypothesis is true, we need to set up a study to actually examine this hypothesis.

One earlier study (also by ROC – the Resuscitation Outcomes Consortium) even has similar results.[4],[5] These results are also not statistically significant, but suggest that with larger numbers the results might be significant. So why did the authors set up such a small study? Overconfidence and an apparent lack of familiarity with their own research.
 


 

The Seattle phenomenon (they claim that their resuscitation rate is the highest in America) seems to be due to excellent bystander CPR rates (apparently the highest in America), but that is only good enough for them to be experts on improving bystander CPR rates. The rest is probably due to defibrillation and chest compressions, which are the only prehospital interventions demonstrated to improve neurologically intact survival.

Why does a bystander CPR specialist focus on drugs? Overconfidence and an apparent lack of understanding of the resuscitation research. Dr. Kudenchuk preaches like Timothy Leary about the benefits of drugs and with just as little evidence. We should give appropriate credit for Dr. Kudenchuk’s work on CPR, but we should not mistake that for a thorough understanding of the resuscitation research, even the research with his name attached.
 

A new podcast reviews ALPS. Dominick Walenczak does not notice the mistakes of Dr. Kudenchuk, but he is not one of the researchers, so that is easy to overlook. The rest of the podcast is excellent. Listen to it here.
 

Episode 8: Conquering the ALPS (Study)
CritMedic – Critical Care Paramedicine Podcast
Dominick Walenczak
April 7, 2016
Podcast page
 

Footnotes:

[1] 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 Apr 4. [Epub ahead of print]
PMID: 27043165

Free Full Text from NEJM

[2] Antiarrhythmic drugs found beneficial when used by EMS treating cardiac arrest
Press release
For Immediate Release:April 4, 2016
NHLBI (National Heart Lung and Blood Institute)
Press release

[3] Dr. Kudenchuk: Study reveals exciting news about cardiac arrest treatment
Lindsay Bosslet
18 hours ago
Public Health Insider
Article

[4] Wide variability in drug use in out-of-hospital cardiac arrest: A report from the resuscitation outcomes consortium.
Glover BM, Brown SP, Morrison L, Davis D, Kudenchuk PJ, Van Ottingham L, Vaillancourt C, Cheskes S, Atkins DL, Dorian P; Resuscitation Outcomes Consortium Investigators.
Resuscitation. 2012 Nov;83(11):1324-30. doi: 10.1016/j.resuscitation.2012.07.008. Epub 2012 Jul 31.
PMID: 22858552 [PubMed – indexed for MEDLINE]

Free Full Text from PubMed Central.

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

 
Kudenchuk, P., Brown, S., Daya, M., Rea, T., Nichol, G., Morrison, L., Leroux, B., Vaillancourt, C., Wittwer, L., Callaway, C., Christenson, J., Egan, D., Ornato, J., Weisfeldt, M., Stiell, I., Idris, A., Aufderheide, T., Dunford, J., Colella, M., Vilke, G., Brienza, A., Desvigne-Nickens, P., Gray, P., Gray, R., Seals, N., Straight, R., & Dorian, P. (2016). Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest New England Journal of Medicine DOI: 10.1056/NEJMoa1514204

 

Glover BM, Brown SP, Morrison L, Davis D, Kudenchuk PJ, Van Ottingham L, Vaillancourt C, Cheskes S, Atkins DL, Dorian P, & the Resuscitation Outcomes Consortium Investigators (2012). Wide variability in drug use in out-of-hospital cardiac arrest: A report from the resuscitation outcomes consortium. Resuscitation PMID: 22858552

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Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest

ResearchBlogging.org
 

I wrote about the start of the ALPS (Amiodarone, Lidocaine, Placebo Study) in 2012[1] and the results are now in.
 

In this randomized, double-blind, placebo-controlled, prehospital trial, we found that treatment with amiodarone or lidocaine did not result in a significantly higher rate of survival to hospital discharge or favorable neurologic outcome at discharge than the rate with placebo after out-of-hospital cardiac arrest caused by shock-refractory initial ventricular fibrillation or pulseless ventricular tachycardia. There were also no significant differences in these outcomes between amiodarone and lidocaine.[2]

 

The primary endpoint is that amiodarone does not improve survival to discharge and neither does lidocaine. However, the results are a bit more complicated than just throw out the drugs.

Two subgroups did have better outcomes, but as the authors appropriately point out, subgroup analysis requires a higher level of significance, because you are essentially getting extra shots at the goal for every subgroup. The more subgroups we have, the more likely that one of them will reach the p value of <0.05.  

We observed an interaction of treatment with the witnessed status of out-of-hospital cardiac arrest, which is often taken as a surrogate for early recognition of cardiac arrest, a short interval between the patient’s collapse from cardiac arrest and the initiation of treatment, and a greater likelihood of therapeutic responsiveness. Though prespecified, this subgroup analysis was performed in the context of an insignificant difference for the overall analysis, and the P value for heterogeneity in this subgroup analysis was not adjusted for the number of subgroup comparisons. Nonetheless, the suggestion that survival was improved by drug treatment in patients with witnessed out-of-hospital cardiac arrest, without evidence of harm in those with unwitnessed arrest, merits thoughtful consideration.[2]

 

Another important point is that the possibility of an effect was probably overestimated by the researchers. A much larger study would be needed to show this smaller effect.
 

Finally, the point estimates of the survival rates in the placebo group and the amiodarone group differed less than anticipated when the trial was designed, which suggests that the trial may have been underpowered. If amiodarone has a true treatment effect of 3 percentage points, approximately 9000 patients across the three trial groups would be needed to establish this difference in outcome with 90% power. Though seemingly small, a confirmed overall difference of 3 percentage points in survival with drug therapy would mean that 1800 additional lives could be saved each year in North America alone after out-of-hospital cardiac arrest.[2]

 

How could the top doctors in the field be so far off in their estimate?

We dramatically overestimate the good we do and we dramatically underestimate the harm we do. We are unreasonably optimistic.
 

Monty Hall problem vs medicine 1
Image credit.
 

We still do not have any evidence that anything other than compressions and defibrillation improve outcomes for adult patients with cardiac arrest, but we insist on using these treatments, because we believe in magic pills.

Should we consider giving amiodarone or lidocaine to only witnessed cardiac arrest patients or only EMS-witnessed cardiac arrest? Yes, but that is really just limiting the use of these drugs to those who have some weak evidence of benefit.

We are already giving too many treatments to too many patients, based on too little evidence.

That is assuming that we have any valid evidence at all. Medical ethics appears to be only for other people, because we don’t care enough to find out if our treatments work. We just make excuses for the harm we cause to our patients.

Footnotes:

[1] What Will Be the Next Standard Of Care We Eliminate
Wed, 28 Mar 2012
Rogue Medic
Article

[2] Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest
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 Apr 4. [Epub ahead of print]
PMID: 27043165

Free Full Text from NEJM

 
Kudenchuk, P., Brown, S., Daya, M., Rea, T., Nichol, G., Morrison, L., Leroux, B., Vaillancourt, C., Wittwer, L., Callaway, C., Christenson, J., Egan, D., Ornato, J., Weisfeldt, M., Stiell, I., Idris, A., Aufderheide, T., Dunford, J., Colella, M., Vilke, G., Brienza, A., Desvigne-Nickens, P., Gray, P., Gray, R., Seals, N., Straight, R., & Dorian, P. (2016). Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest New England Journal of Medicine DOI: 10.1056/NEJMoa1514204

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The RAD-57 – Still Unsafe?

ResearchBlogging.org
 

Brandon Oto of EMS Basics and Degrees of Clarity organized The First EMS What-if-We’re-Wrong-a-Thon. I did not participate, because I was taking a break from blogging at the time. Brandon is doing it again, so I decided to look for something I wrote that I have been wrong about to contribute. I thought about Masimo. I had been very critical of Dr. Michael O’Reilly (then Executive Vice President of Masimo Corporation) for being an advocate of bad science. He has since been hired away by Apple.[1] He should be less dangerous with a telephone than he was with the RAD-57. At the time, he wrote –
 

Masimo stands by its products’ performance and knows that when SpCO-enabled devices are used according to their directions for use, they provide accurate SpCO measurements that provide significant clinical utility, helping clinicians detect carbon monoxide poisoning in patients otherwise not suspected of having it and rule out carbon monoxide poisoning in patients with suspected carbon monoxide poisoning.[2]

 

The problem is that there is no evidence that the RAD-57 is safe or effective at ruling out carbon monoxide poisoning in anyone.

There is evidence that the RAD-57 will fail, if used to try to rule out carbon monoxide poisoning. One study showed that the RAD-57 will miss half of the people with elevated carbon monoxide levels.
 

The RAD device correctly identified 11 of 23 patients with laboratory values greater than or equal to 15% carboxyhemoglobin (sensitivity 48%; 95% CI 27% to 69%).[3]

 

What if I was wrong?

Is there any evidence that the RAD-57 is able to rule out covert, but life threatening carbon monoxide poisoning?[4]
 


 
 

Was I wrong?

While there have been several studies of the RAD-57, I could not find any evidence that the RAD-57 is safe or effective at ruling out carbon monoxide poisoning.

There does not appear to be any research on the use of the RAD-57 to screen firefighters to rule out carbon monoxide poisoning, even though advertising shows using the RAD-57 to screen firefighters.

Was I wrong? No. That is why this is not a part of The First EMS What-if-We’re-Wrong-a-Thon.

However, I did find some interesting carbon monoxide poisoning papers –

One shows that we may be causing harm by aggressively providing oxygen. This is not enough of a reason to stop providing oxygen, but if this hypothesis is supported by further research, we will need to change treatment.
 

While CO’s affinity for hemoglobin remains undisputed, new research suggests that its role in nitric oxide release, reactive oxygen species formation, and its direct action on ion channels is much more significant. In the course of understanding the multifaceted character of this simple molecule it becomes apparent that current oxygen based therapies meant to displace CO from hemoglobin may be insufficient and possibly harmful.[5]

 

Another shows that the addition of catalytic converters seems to have dramatically decreased the car exhaust suicide rate and the level of carbon monoxide in survivors of these suicide attempts.
 

RESULTS:
Since 1985, the CDR for suicidal motor vehicle-related CO poisoning has decreased in parallel with CO emissions (R2 = 0.985). Non-fatal motor vehicle-related intentional CO poisoning cases decreased 63% over 33 years (p = 0.0017). COHb levels decreased 35% in these patients (p < 0.0001).
[6]

 

CO is Carbon monOxide.
CDR is Crude Death Rate.
COHb is CarbOxyHemoglobin.

There are still some papers that show that we do not understand what the RAD-57 can’t do –
 

The fact that all the Paramedic Rescue Squads were equipped with medical triage sets and were able to conduct non-invasive measurements of carboxyhemoglobin made it possible to introduce effective procedures in the cases of suspected carbon monoxide poisoning and abandon costly and complicated organisational procedures when they proved to be unnecessary.[1]

 

No. The Magic 8 Ball did not indicate a problem, but that does not mean that it is safe to rule out carbon monoxide poisoning with a Magic 8 Ball. The Magic 8 Ball RAD-57 is not accurate enough to rule out carbon monoxide poisoning.

The RAD-57 is only appropriate for sending more people to the hospital. While the extra cost of these false positives is a problem and will cause people to mock Masimo, this may save some lives or just prevent more serious consequences of carbon monoxide poisoning.

If you use the RAD-57 to determine that someone does not need to go to the hospital, get a lot of very good insurance, because eventually one of those patients will have a heart attack, or a stroke, or die and carbon monoxide will be part of the reason for the bad outcome. Your advice will have contributed.

If you send a firefighter back into a fire because you think you have ruled out carbon monoxide poisoning, eventually you will be the cause of death or disability of firefighters. Don’t do it.
 

CONCLUSIONS:
While the Rad-57 pulse oximeter functioned within the manufacturer’s specifications, clinicians using the Rad-57 should expect some SpCO readings to be significantly higher or lower than COHb measurements, and should not use SpCO to direct triage or patient management. An elevated S(pCO) could broaden the diagnosis of CO poisoning in patients with non-specific symptoms. However, a negative SpCO level in patients suspected of having CO poisoning should never rule out CO poisoning, and should always be confirmed by COHb.
[7]

 

Highlighting in bold is mine.

SpCO is Masimo’s registered trademark for their noninvasive indirect measurement of carbon monoxide using the RAD-57.

Was I wrong? I will find something else to write about, because there is even more evidence that the RAD-57 should not be used to try to rule out carbon monoxide poisoning now than when I originally criticized Masimo.
 

Also read the article by Dr. Brooks Walsh on the RAD-57 and screening for carbon monoxide poisoning in fire fighters – Checking firefighters for carbon monoxide – recent studies, persistent concerns.
 

Here is the rest of what I have written about the Dr. O’Reilly, Masimo, and the RAD-57

The RAD-57 Pulse Co-Oximeter – Does It Work – Part I
Fri, 12 Nov 2010

The RAD-57 Pulse Co-Oximeter – Does It Work – Part II
Wed, 17 Nov 2010

How Not to Respond to Negative Research
Fri, 26 Nov 2010

How Not to Respond to Negative Research – Addendum
Fri, 26 Nov 2010

How TO Respond to Negative Research
Sun, 05 Dec 2010

Bad Advice on Masimo’s RAD-57 – Part I
Fri, 18 Feb 2011

Bad Advice on Masimo’s RAD-57 – Part II
Mon, 21 Feb 2011

Bad Advice on Masimo’s RAD-57 – Part III
Thu, 24 Feb 2011

Bad Advice on Masimo’s RAD-57 – Part IV
Mon, 28 Feb 2011

Performance of the RAD-57 With a Lower Limit – Better?
Wed, 18 May 2011

Accuracy of Noninvasive Multiwave Pulse Oximetry Compared With Carboxyhemoglobin From Blood Gas Analysis in Unselected Emergency Department Patients
Tue, 21 Feb 2012

Mass sociogenic illness initially reported as carbon monoxide poisoning
Wed, 22 Feb 2012

Psychic vs. RAD-57
Thu, 23 Feb 2012

Footnotes:

[1] Apple makes yet another medical field hire for unknown project
By AppleInsider Staff
Thursday, January 30, 2014, 04:04 pm PT (07:04 pm ET)
AppleInsider
Article

[2] Performance of the Rad-57 pulse co-oximeter compared with standard laboratory carboxyhemoglobin measurement.
O’Reilly M.
Ann Emerg Med. 2010 Oct;56(4):442-4; author reply 444-5. No abstract available.
PMID: 20868919 [PubMed – indexed for MEDLINE]

Free Full Text of letter and author reply from Ann Emerg Med.

[3] Performance of the RAD-57 pulse CO-oximeter compared with standard laboratory carboxyhemoglobin measurement.
Touger M, Birnbaum A, Wang J, Chou K, Pearson D, Bijur P.
Ann Emerg Med. 2010 Oct;56(4):382-8. Epub 2010 Jun 3.
PMID: 20605259 [PubMed – indexed for MEDLINE]

Free Full Text Article from Ann Emerg Med.

[4] Accuracy of Noninvasive Multiwave Pulse Oximetry Compared With Carboxyhemoglobin From Blood Gas Analysis in Unselected Emergency Department Patients
Rogue Medic
Tue, 21 Feb 2012
Article

[5] A modern literature review of carbon monoxide poisoning theories, therapies, and potential targets for therapy advancement.
Roderique JD, Josef CS, Feldman MJ, Spiess BD.
Toxicology. 2015 Aug 6;334:45-58. doi: 10.1016/j.tox.2015.05.004. Epub 2015 May 18. Review.
PMID: 25997893

[6] Suicidal carbon monoxide poisoning has decreased with controls on automobile emissions.
Hampson NB, Holm JR.
Undersea Hyperb Med. 2015 Mar-Apr;42(2):159-64.
PMID: 26094291

[7] False positive rate of carbon monoxide saturation by pulse oximetry of emergency department patients.
Weaver LK, Churchill SK, Deru K, Cooney D.
Respir Care. 2013 Feb;58(2):232-40. doi: 10.4187/respcare.01744.
PMID: 22782305

Free Full Text from Respir Care.

Weaver, L., Churchill, S., Deru, K., & Cooney, D. (2012). False Positive Rate of Carbon Monoxide Saturation by Pulse Oximetry of Emergency Department Patients Respiratory Care DOI: 10.4187/respcare.01744

Hampson NB, & Holm JR (2015). Suicidal carbon monoxide poisoning has decreased with controls on automobile emissions. Undersea & hyperbaric medicine : journal of the Undersea and Hyperbaric Medical Society, Inc, 42 (2), 159-64 PMID: 26094291

Roderique, J., Josef, C., Feldman, M., & Spiess, B. (2015). A modern literature review of carbon monoxide poisoning theories, therapies, and potential targets for therapy advancement. Toxicology, 334, 45-58 DOI: 10.1016/j.tox.2015.05.004

Touger, M., Birnbaum, A., Wang, J., Chou, K., Pearson, D., & Bijur, P. (2010). Performance of the RAD-57 Pulse Co-Oximeter Compared With Standard Laboratory Carboxyhemoglobin Measurement Annals of Emergency Medicine, 56 (4), 382-388 DOI: 10.1016/j.annemergmed.2010.03.041

O’Reilly, M. (2010). Performance of the Rad-57 Pulse Co-Oximeter Compared With Standard Laboratory Carboxyhemoglobin Measurement Annals of Emergency Medicine, 56 (4), 442-444 DOI: 10.1016/j.annemergmed.2010.08.016

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Why is progress so slow in resuscitation research?

ResearchBlogging.org
 

Why is progress so slow in resuscitation research? A lot of money and time went in to finding out which type of blood-letting ventilation works best – ignoring the absence of valid evidence that ventilation is better than no ventilation. Why not gamble with our patients?

In response to The Fatal Flaw in Trial of Continuous or Interrupted Chest Compressions during CPR,[1],[2] Kenny commented that –
 

there are many things in your blog that are not correct.[1]

 

I asked for specifics and received the following from Anonymous (maybe Kenny and maybe not) –
 

That the study design ASSUMES we don’t want to know if ventilation is useful or not.[1]

 

Ventilation study implied facepalm
 

Assumes is not many things, but the comments may be from different people and there may be so many things, that Kenny is still documenting all of the examples. Perhaps the following is more specific wording that will satisfy defenders of the study –

    The study design strongly suggests that

        in the attempted resuscitation of adult patients

            with cardiac causes of cardiac arrest

                which is almost all cardiac arrest patients

                    active ventilation does not need evidence,

                        but selecting the favorite flavor of ventilation

                            does need expensive high quality evidence

                                just in case someone ever produces valid evidence

                                    that these patients are not harmed by ventilations

                                        and that these patients receive some benefit from ventilations.
 

That is a lot to assume believe without appropriate evidence.

Based on the available evidence, what are the odds that ventilations are not harmful and are beneficial?
 

Does anyone have any good argument to give ventilations as much as a 50% chance?
 

What about a 40% chance that ventilations will survive a valid study?

How about a 30% chance?

20%?

Is there any justifiable reason to be so optimistic?

If there isn’t any justifiable reason to be optimistic, then we are only making assumptions when we take shortcuts to eliminate the essential research in order to study something that is traditional, rather than based on valid evidence.
 

Do the authors understand that there isn’t valid evidence of any benefit/lack of harm from active ventilations?

Do the authors care that there is not valid evidence of any benefit/lack of harm from active ventilations?

If I have overlooked a third possibility, somebody should let me know. If there is valid evidence, somebody should provide it.

Footnotes:

[1] The Fatal Flaw in Trial of Continuous or Interrupted Chest Compressions during CPR
Wed, 25 Nov 2015 10:15:20
by Rogue Medic
Article

[2] Trial of Continuous or Interrupted Chest Compressions during CPR.
Nichol G, Leroux B, Wang H, Callaway CW, Sopko G, Weisfeldt M, Stiell I, Morrison LJ, Aufderheide TP, Cheskes S, Christenson J, Kudenchuk P, Vaillancourt C, Rea TD, Idris AH, Colella R, Isaacs M, Straight R, Stephens S, Richardson J, Condle J, Schmicker RH, Egan D, May S, Ornato JP; ROC Investigators.
N Engl J Med. 2015 Nov 9. [Epub ahead of print]
PMID: 26550795

Free Full Text from NEJM.

Nichol, G., Leroux, B., Wang, H., Callaway, C., Sopko, G., Weisfeldt, M., Stiell, I., Morrison, L., Aufderheide, T., Cheskes, S., Christenson, J., Kudenchuk, P., Vaillancourt, C., Rea, T., Idris, A., Colella, R., Isaacs, M., Straight, R., Stephens, S., Richardson, J., Condle, J., Schmicker, R., Egan, D., May, S., & Ornato, J. (2015). Trial of Continuous or Interrupted Chest Compressions during CPR New England Journal of Medicine DOI: 10.1056/NEJMoa1509139

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The Fatal Flaw in Trial of Continuous or Interrupted Chest Compressions during CPR

ResearchBlogging.org
 

Trial of Continuous or Interrupted Chest Compressions during CPR — NEJM
 

In conclusion, among patients with out-of-hospital cardiac arrest in whom CPR was performed by EMS providers, a strategy of continuous chest compressions with positive-pressure ventilation did not result in significantly higher rates of survival or favorable neurologic status than the rates with a strategy of chest compressions interrupted for ventilation.[1]

 

This is not a study that has a valid control group to determine if there is any benefit from ventilation. There is no group that does not receive ventilations, so it is like a study of one type of blood-letting vs. another type of blood-letting with the researchers taking for granted that blood-letting does improve outcomes. That is not a problem if blood-letting actually improves outcomes.

Should we take it for granted that blood-letting improves outcomes and that the only hypothesis worth studying is which brand to choose?

Should we assume that ventilations are too sacred to ever be doubted?

Should we assume that there are better arguments for ventilations than for blood-letting? That is not true.
 

If we ignore this fatal flaw, the study is very well done. I really like the study design. It is an excellent example of how to study two different versions of an intervention after that intervention has been demonstrated to improve outcomes, but ventilations have never been demonstrated to improve outcomes in adult patients with cardiac causes of cardiac arrest.

Should we have assumed that blood-letting was too sacred to ever be doubted?
 

We do know that outcomes for seizure patients improve when EMS gives benzodiazepines, because some people cared enough to find out.[2]

Assuming that a treatment is too important to study is like building on a foundation in a swamp.
 


 

We still do not know if there is any benefit from including ventilations, because the study design assumes that we don’t want to know.

There is no good reason to believe that ventilations improve outcomes for adult patients with cardiac causes of cardiac arrest. This study has not done anything to change that.

Our patients deserve better. Why aren’t we finding out what improves outcomes?

Footnotes:

[1] Trial of Continuous or Interrupted Chest Compressions during CPR.
Nichol G, Leroux B, Wang H, Callaway CW, Sopko G, Weisfeldt M, Stiell I, Morrison LJ, Aufderheide TP, Cheskes S, Christenson J, Kudenchuk P, Vaillancourt C, Rea TD, Idris AH, Colella R, Isaacs M, Straight R, Stephens S, Richardson J, Condle J, Schmicker RH, Egan D, May S, Ornato JP; ROC Investigators.
N Engl J Med. 2015 Nov 9. [Epub ahead of print]
PMID: 26550795

Free Full Text from NEJM.

[2] A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus.
Alldredge BK, Gelb AM, Isaacs SM, Corry MD, Allen F, Ulrich S, Gottwald MD, O’Neil N, Neuhaus JM, Segal MR, Lowenstein DH.
N Engl J Med. 2001 Aug 30;345(9):631-7. Erratum in: N Engl J Med 2001 Dec 20;345(25):1860.
PMID: 11547716 [PubMed – indexed for MEDLINE]

Free Full Text from N Engl J Med. with link to PDF Download.

Nichol, G., Leroux, B., Wang, H., Callaway, C., Sopko, G., Weisfeldt, M., Stiell, I., Morrison, L., Aufderheide, T., Cheskes, S., Christenson, J., Kudenchuk, P., Vaillancourt, C., Rea, T., Idris, A., Colella, R., Isaacs, M., Straight, R., Stephens, S., Richardson, J., Condle, J., Schmicker, R., Egan, D., May, S., & Ornato, J. (2015). Trial of Continuous or Interrupted Chest Compressions during CPR New England Journal of Medicine DOI: 10.1056/NEJMoa1509139

Alldredge BK,, Gelb AM,, Isaacs SM,, Corry MD,, Allen F,, Ulrich S,, Gottwald MD,, O’Neil N,, Neuhaus JM,, Segal MR,, & Lowenstein DH. (2001). A Comparison of Lorazepam, Diazepam, and Placebo for the Treatment of Out-of-Hospital Status Epilepticus New England Journal of Medicine, 345 (25), 1860-1860 DOI: 10.1056/NEJM200112203452521

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How Bad is the Evidence for the New 2015 ACLS Guidelines?

ResearchBlogging.org
 
    The new ACLS guidelines are out. How bad is the evidence?

    The short answer – The Advanced Cardiac Life Support guidelines could be worse.

How does the American Heart Association determine that a recommendation is not beneficial?
 

Class III: No Benefit, is a moderate recommendation, generally reserved for therapies or tests that have been shown in high-level studies (generally LOE A or B) to provide no benefit when tested against a placebo or control.[1]

 

The tobacco enema has been used successfully as a treatment for cardiac arrest, so the evidence of lack of benefit is poor.[2] Clearly, the Advanced Cardiac Life Support guidelines cannot claim that the tobacco enema is Class III. Successfully? The treatment was used and a dead person was no longer dead. In other words, just as successfully as most of the ACLS treatments.
 

From Eisenberg, MS. Life in the balance: emergency medicine and the quest to reverse sudden death. 1997; Oxford University Press. [betterworldbooks][3]

 

This is one way to make excuses for justify doing something just because of ideology. In the absence of good evidence of benefit, we should not harm our patients to protect our ideology. We used to do this with blood-letting, which was defended even after there was clear evidence of harm. That is just the best known example, but this dishonesty continues and continues to be defended.

Why don’t we hold anyone accountable, when we have the evidence that our treatments are harmful? Because we all seem to go along to get along.

The 2015 ACLS guidelines are not all bad, but they clearly do not encourage withholding harmful treatments until we have obvious evidence of harm. Should we assume that a treatment works just because the explanation appeals to some experts as much as the explanation for blood-letting appealed to the experts when that was in vogue?

This is not medicine. This is a fashion show. Our patients are the ones harmed.
 

Footnotes:

[1] 2015 AHA Classes of Recommendation
2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Part 2: Evidence Evaluation and Management of Conflicts of Interest
Development of the 2015 Guidelines Update
Circulation.
2015; 132: S368-S382
Free Full Text from Circulation.

[2] Tobacco smoke enemas
Ghislaine Lawrence
Volume 359, No. 9315, p1442,
20 April 2002
Lancet
Abstract with link to Full Text PDF download.

[3] Ever tried smoking?
by Chris Nickson
Life in the Fast Lane
Article

Morrison LJ, Gent LM, Lang E, Nunnally ME, Parker MJ, Callaway CW, Nadkarni VM, Fernandez AR, Billi JE, Egan JR, Griffin RE, Shuster M, & Hazinski MF (2015). Part 2: Evidence Evaluation and Management of Conflicts of Interest: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation, 132 (18 Suppl 2) PMID: 26472990
 

Lawrence, G. (2002). Tobacco smoke enemas The Lancet, 359 (9315) DOI: 10.1016/S0140-6736(02)08339-3

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