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

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)
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

.

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

.

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

.

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

.

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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Anecdotes and the Appearance of Improvement

ResearchBlogging.org
 
We like to give treatments that produce results that we can see and logically attribute to the treatments we gave.

We like to give IV (IntaVenous) furosemide (Lasix – frusemide in Commonwealth countries) for CHF (Congestive Heart Failure).
 

1. The patient had CHF.

2. I gave IV furosemide.

3. The patient produced urine.

4. The patient improved.
 

Anecdotes like this can lead us to the conclusion that the furosemide produced the improvement, even if we have been giving many other treatments along with the Lasix.

We can use logic to back up that conclusion.
 

1. CHF is fluid in the lungs.

2. CHF is too much fluid.

3. Getting rid of the fluid gets rid of the problem.

4. The patient improved, so the logic must be sound.
 

But is the logic sound? Is the conclusion justified or are we seeing what we want to see?

The way we find out is by studying patients with similar enough presentations that they are treated the same way, except that not all patients are given Lasix.

When we study the results of furosemide on CHF, we see that the things we have been told about IV Lasix are not true.
 

Hypothesis #1. Acute CHF patients are overloaded with fluid. We have to remove the fluid to save them.

CHF = Pee or die!
 


Image credit.
 

This hypothesis was tested – all the way back in 1978, but the myth continues.
 


 

The concept that acute heeart failure with pulmonary edema is associated with an increase in intravascular volume is therefore not supported. To the contrary, there is a reduction of blood volume during acute pulmonary edema.[1]

 

The normal patients had 22% more total plasma volume.

The normal patients had 21% more total blood volume.

The need to remove fluids is based on what?

It is interesting that this study was of patients treated with oxygen, morphine, and furosemide. Only oxygen is still important in the acute treatment of CHF/ADHF.
 

Hypothesis #2. IV Lasix almost immediately causes vasodilation.

No.

IV Lasix almost immediately causes vasoconstriction.

This hypothesis was tested – in 1985, but this myth also continues.
 


 

The use of intravenous furosemide in patients with chronic congestive heart failure, although well established, can promote further clinical hemodynamic deterioration during the first 20 minutes.[2]

 

Lasix raises blood pressure in emergency treatment of CHF.
 

Hypothesis #3. IV Lasix improves outcomes for acute CHF patients.

No.

IV Lasix does not improve outcomes for acute CHF patients.

This hypothesis was also tested a long time ago (in 1987), and at other times, but the myth persists longer than the patients treated with Lasix.[3]
 


 

If we can eliminate a treatment and the outcomes of patients do not get worse, where is the benefit from the treatment?

Why expose the patient to the side effects of a treatment, if the patient is not expected to benefit from the treatment?

Footnotes:

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

Free Full Text Download from Circulation in PDF format.

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

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

Free Full Text from Chest.

Figueras J, & Weil MH (1978). Blood volume prior to and following treatment of acute cardiogenic pulmonary edema. Circulation, 57 (2), 349-55 PMID: 618625

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

Hoffman JR, & Reynolds S (1987). Comparison of nitroglycerin, morphine and furosemide in treatment of presumed pre-hospital pulmonary edema. Chest, 92 (4), 586-93 PMID: 3115687

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Dextrose 10% in the Treatment of Out-of-Hospital Hypoglycemia

ResearchBlogging.org
 

Is 50% dextrose as good as 10% dextrose for treating symptomatic hypoglycemia?

If the patient is disoriented, but becomes oriented before the full dose of dextrose is given, is it appropriate to continue to treat the patient as if the patient were still disoriented? If your protocols require you to keep giving dextrose, do the same protocols require you to keep giving opioids after the pain is relieved? Is there really any difference?

50% dextrose has problems.
 

Animal models have demonstrated the toxic effect of glucose infusions in the settings of cardiac arrest and stroke.2 Experimental data suggests that hyperglycemia is neurotoxic to patients in the setting of acute illness.1,3 [1]

 

Furthermore, extravasation can cause necrosis.
 


Image credit.[2]
 

I expect juries to look at this kind of image and say, Somebody has to take one for the 50% dextrose team. We can’t expect EMS to change.

Is 10% dextrose practical?
 

Won’t giving less concentrated dextrose delay treatment?
 

The median initial field blood glucose was 38 mg/dL (IQR = 28 mg/dL – 47 mg/dL), with subsequent blood glucose median of 98 mg/dL (IQR = 70 mg/dL – 135 mg/dL). Elapsed time after D10 administration before recheck was not uniform, with a median time to recheck of eight minutes (IQR = 5 minutes – 12 minutes).[1]

 

If that is going to slow your system down, is it because you are transporting patients before they wake up?

Did anyone require more than 10 grams of 10% dextrose, as opposed to 25 grams of 50% dextrose?
 

Of 164 patients, 29 (18%) received an additional dose of intravenous D10 solution in the field due to persistent or recurrent hypoglycemia, and one patient required a third dose.[1]

 

18% received a second dose, which is 20 grams of dextrose and still less than the total dose of 25 grams of dextrose given according to EMS protocols that still use 50% dextrose.

Only one patient, out of 164 patients, required a third dose. That is 30 grams of dextrose.

Only one patient, out of 164 patients, received as much as we would give according to the typical EMS protocol, which should be a thing of the past. If we are routinely giving too much to our patients, is that a good thing? Why?
 

Maybe the blood sugars were not that low to begin with.
 


 

The average was 38 mg/dL, which is not high.
 

Maybe the change in blood sugar was small after just 10 grams of dextrose, rather than 25 grams.
 


 

The average (mean) change was 67 mg/dL, which is enough to get a patient with a blood sugar of 3 up to 70.
 

Maybe the blood sugar was not high enough after just 10 grams of dextrose, rather than 25 grams.
 


 

The average (mean) repeat blood sugar was 106 mg/dL, which is more than enough.
 

Maybe it took a long time to treat patients this way.
 


 

The average (mean) time was 9 minutes, which is not a lot of time.
 

Is this perfect?
 

Three patients had a drop in blood glucose after D10 administration: one patient had a drop of 1 mg/dL; one patient had a drop of 10 mg/dL; and one patient had a drop of 19 mg/dL.[1]

 

All patients, even the three with initial drops in blood sugar (one had an insulin pump still pumping while being treated) had normal blood sugars at the end of EMS contact.

10% dextrose is cheaper, just as fast, probably less likely to cause hyperglycemia, probably less likely to cause rebound hypoglycemia, probably less likely to cause problems with extravasation, less of a problem with drug shortages, . . . .

Why are we still resisting switching to 10% dextrose?
 

Other articles on 10% dextrose.

Footnotes:

[1] Dextrose 10% in the treatment of out-of-hospital hypoglycemia.
Kiefer MV, Gene Hern H, Alter HJ, Barger JB.
Prehosp Disaster Med. 2014 Apr;29(2):190-4. doi: 10.1017/S1049023X14000284. Epub 2014 Apr 15.
PMID: 24735872 [PubMed – indexed for MEDLINE]

[2] Images in emergency medicine. Dextrose extravasation causing skin necrosis.
Levy SB, Rosh AJ.
Ann Emerg Med. 2006 Sep;48(3):236, 239. Epub 2006 Feb 17. No abstract available.
PMID: 16934641 [PubMed – indexed for MEDLINE]

Kiefer MV, Gene Hern H, Alter HJ, & Barger JB (2014). Dextrose 10% in the treatment of out-of-hospital hypoglycemia. Prehospital and disaster medicine, 29 (2), 190-4 PMID: 24735872

Levy SB, & Rosh AJ (2006). Images in emergency medicine. Dextrose extravasation causing skin necrosis. Annals of emergency medicine, 48 (3) PMID: 16934641

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