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

- Rogue Medic

How Bad is Epinephrine (Adrenaline) for Cardiac Arrest, According to the PARAMEDIC2 Study?

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

Do we have to stop using epinephrine (adrenaline in Commonwealth countries) for cardiac arrest?
 


 

PARAMEDIC2 (Prehospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug Administration in Cardiac Arrest) compared adrenaline (epinephrine) with placebo in a “randomized, double-blind trial involving 8014 patients with out-of-hospital cardiac arrest”.[1]

The results showed that 1 mg of epinephrine every 3 – 5 minutes is even worse than I expected, but a lot of the more literate doctors have not been using epinephrine that way. What does this research tell us about their various methods? The podcast REBEL Cast (Rational Evidence Based Evaluation of Literature in Emergency Medicine) has a discussion of this question in REBEL Cast Ep56 – PARAMEDIC-2: Time to Abandon Epinephrine in OHCA?.[2]

The current ACLS/ILCOR (Advanced Cardiac Life Support/International Liaison Committee on Resuscitation) advice on epinephrine does not state that epinephrine is a good idea, or even require that you give epinephrine to follow their protocol –
 

The major changes in the 2015 ACLS guidelines include recommendations about prognostication during CPR based on exhaled CO2 measurements, timing of epinephrine administration stratified by shockable or nonshockable rhythms, and the possibility of bundling treatment of steroids, vasopressin, and epinephrine for treatment of in-hospital arrests. In addition, the administration of vasopressin as the sole vasoactive drug during CPR has been removed from the algorithm.[3]

 

What was the ACLS/ILCOR advice in the 2010 guidelines?
 

The 2010 Guidelines stated that it is reasonable to consider administering a 1-mg dose of IV/IO epinephrine every 3 to 5 minutes during adult cardiac arrest.[4]

 

This is in a paragraph that links to the PICO (Population-Intervention-Comparator-Outcomes) question that has been an open question for over half a century – In cardiac arrest, is giving epinephrine better than not giving epinephrine?[5]

They only considered it reasonable, based on low quality evidence.

What was the ACLS/ILCOR advice in the 2015 guidelines?
 

Standard-dose epinephrine (1 mg every 3 to 5 minutes) may be reasonable for patients in cardiac arrest (Class IIb, LOE B-R).[6]

 

Again, ACLS/ILCOR only considered a dose of epinephrine to be reasonable. Again, this was based on low quality evidence. I am not criticizing the efforts of those who worked on the Jacobs study of adrenaline vs. placebo, because they were stopped by the willfully ignorant opponents of science.[7]

What about the method of attempting to titrate an infusion to the hemodynamic response, which Dr. Swaminathan and Dr. Rezaie alluded to?

There is a lot of anecdotal enthusiasm from doctors who use this method, but I do not know of any research that has been published comparing outcomes using this method with anything else. How do we know that the positive reports from doctors are anything other than confirmation bias? We don’t.

This year is the 200th anniversary of the publication of the very first horror novel – Frankenstein; or, The Modern Prometheus. The doctor in the novel used electricity to raise the dead (and the subjects were very dead). There were no chest compressions in the novel, but it is interesting that we have barely made progress from the fiction imagined by an 18 year old with no medical training, although she did have the opportunity to listen to many of the smartest people in England discuss science. Mary Godwin (later Mary Wollstonecraft Shelley by marriage) was 16 when she started writing the novel.[8]

We have barely made more progress at resuscitation than a teenager did 200 years ago in a novel. Most of our progress has been in finally admitting that the treatments we have been using have been producing more harm than benefit. Many of us are not even that honest about the harm we continue to cause.

We dramatically improved resuscitation in one giant leap – when we focused on high quality chest compressions and ignoring the medical theater of advanced life support.

There are two treatments that work during cardiac arrest – high quality chest compressions and rapid defibrillation.

Why haven’t we made more progress?

We have been too busty making excuses for remaining ignorant.

We need to stop being so proud of our ignorance.

We now know that amiodarone doesn’t work for cardiac arrest (and is more dangerous than beneficial for ventricular tachycardia – even adenosine appears to be better for VTach), atropine doesn’t work for cardiac arrest, calcium chloride doesn’t work for cardiac arrest (unless it is due to hyperkalemia/rhabdomyolysis), vasopressin doesn’t work for cardiac arrest, high dose epinephrine doesn’t work for cardiac arrest, standard dose epinephrine doesn’t work for cardiac arrest – in other words, we have tried all sorts of drugs, based on hunches and the weakest of evidence, but we still haven’t learned that there isn’t a magic resuscitation drug.

Should anyone be using any epinephrine to treat cardiac arrest outside of a well controlled study?

No.

Also –

A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest – Part I

Footnotes:

[1] A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest.
Perkins GD, Ji C, Deakin CD, Quinn T, Nolan JP, Scomparin C, Regan S, Long J, Slowther A, Pocock H, Black JJM, Moore F, Fothergill RT, Rees N, O’Shea L, Docherty M, Gunson I, Han K, Charlton K, Finn J, Petrou S, Stallard N, Gates S, Lall R; PARAMEDIC2 Collaborators.
N Engl J Med. 2018 Jul 18. doi: 10.1056/NEJMoa1806842. [Epub ahead of print]
PMID: 30021076

Free Full Text from NEJM

All supplementary material is also available at the end of the article at the NEJM site in PDF format –

Protocol

Supplementary Appendix

Disclosure Forms

There is also an editorial, which I have not yet read, by Clifton W. Callaway, M.D., Ph.D., and Michael W. Donnino, M.D. –

Testing Epinephrine for Out-of-Hospital Cardiac Arrest.
Callaway CW, Donnino MW.
N Engl J Med. 2018 Jul 18. doi: 10.1056/NEJMe1808255. [Epub ahead of print] No abstract available.
PMID: 30021078

Free Full Text from NEJM

[2] REBEL Cast Ep56 – PARAMEDIC-2: Time to Abandon Epinephrine in OHCA?
Anand Swaminathan, MD and Salim Rezaie, MD, FACEP
July 20, 2018
Episode 56 and show notes

[3] Introduction
Part 7: Adult Advanced Cardiovascular Life Support
2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Mark S. Link, Lauren C. Berkow, Peter J. Kudenchuk, Henry R. Halperin, Erik P. Hess, Vivek K. Moitra, Robert W. Neumar, Brian J. O’Neil, James H. Paxton, Scott M. Silvers, Roger D. White, Demetris Yannopoulos, Michael W. Donnino
Circulation. 2015;132:S444-S464, originally published October 14, 2015
https://doi.org/10.1161/CIR.0000000000000261
Introduction – scroll down to the last paragraph

[4] Vasopressors in Cardiac Arrest: Standard-Dose Epinephrine
Part 7: Adult Advanced Cardiovascular Life Support
2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Mark S. Link, Lauren C. Berkow, Peter J. Kudenchuk, Henry R. Halperin, Erik P. Hess, Vivek K. Moitra, Robert W. Neumar, Brian J. O’Neil, James H. Paxton, Scott M. Silvers, Roger D. White, Demetris Yannopoulos, Michael W. Donnino
Circulation. 2015;132:S444-S464, originally published October 14, 2015
https://doi.org/10.1161/CIR.0000000000000261
2010 epinephrine advice

[5] Epinephrine Versus Placebo
ILCOR Scientific Evidence Evaluation and Review
Epinephrine Versus Placebo

 

Among adults who are in cardiac arrest in any setting (P), does does the use of epinephrine (I), compared with compared with placebo or not using epinephrine (C), change Survival with Favorable neurological/functional outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year, Survival only at discharge, 30 days, 60 days, 180 days AND/OR 1 year, ROSC (O)?

 

[6] 2015 Recommendation—Updated
Part 7: Adult Advanced Cardiovascular Life Support
2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Mark S. Link, Lauren C. Berkow, Peter J. Kudenchuk, Henry R. Halperin, Erik P. Hess, Vivek K. Moitra, Robert W. Neumar, Brian J. O’Neil, James H. Paxton, Scott M. Silvers, Roger D. White, Demetris Yannopoulos, Michael W. Donnino
Circulation. 2015;132:S444-S464, originally published October 14, 2015
https://doi.org/10.1161/CIR.0000000000000261
2015 Recommendation—Updated

[7] Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial
Jacobs IG, Finn JC, Jelinek GA, Oxer HF, Thompson PL.
Resuscitation. 2011 Sep;82(9):1138-43. Epub 2011 Jul 2.
PMID: 21745533 [PubMed – in process]

Free Full Text PDF Download from reanimacion.net
 

This study was designed as a multicentre trial involving five ambulance services in Australia and New Zealand and was accordingly powered to detect clinically important treatment effects. Despite having obtained approvals for the study from Institutional Ethics Committees, Crown Law and Guardianship Boards, the concerns of being involved in a trial in which the unproven “standard of care” was being withheld prevented four of the five ambulance services from participating.

 

In addition adverse press reports questioning the ethics of conducting this trial, which subsequently led to the involvement of politicians, further heightened these concerns. Despite the clearly demonstrated existence of clinical equipoise for adrenaline in cardiac arrest it remained impossible to change the decision not to participate.

 

[8] Frankenstein
Wikipedia
Article

.

Should Basic EMTs Give Naloxone (Narcan)?

 
Should basic EMTs be giving naloxone (Narcan) when paramedics do not really understand the drug?

If a patient wakes up after naloxone, does that mean the patient had a drug overdose?

No – but most paramedics do not understand that.[1]

As of January 1, 2014, there will be even more people giving Narcan with little understanding of what they are doing.
 


Peter Thomson.
 

La Crosse firefighters soon could start carrying a life-saving drug for heroin users. The department is applying to be one of the state’s first groups of emergency medical technicians to administer Narcan, the antidote to an opiate overdose.[2]

 

Does naloxone save lives or just make it less work for first responders?

If the basic EMTs are not good at basic ventilation, will they be any better at drug administration?

Are drugs the cure for ventilation problems?
 

The department has witnessed a 53 percent jump in the number of potential drug overdoses since 2009, Chief Gregg Cleveland said.

In 2012, firefighters responded to 98 potential overdoses and 86 so far this year.[1]

 

A 53% increase?

98 last year.

86 so far this year (as of October).

10 months in, so an average of 8.6 per month = 103.2 for the whole year.

Going from 98 to 103 is not a 53% increase.

It isn’t even a 5.3% increase, but only 5.1%
 

Only 5% – not 53%.
 

Bad math.

Correction (13:00 12/28/2013) – the math is not based on the numbers in the article and I did not read the article correctly. The bad math is mine, not Chief Gregg Cleveland’s. Thank you to Christopher Jennison, Jordan L, and Parastocles for pointing out my error.

I apologize to Chief Gregg Cleveland for misrepresenting his statement as bad math, when it was my mistake.
 

Bad decisions.

What kind of time would be saved by having the fire department give naloxone?

What kind of bad outcomes would be prevented?

What kind of better outcomes would be expected?

What is the added cost of implementing this program?

What other programs would be deprived of this money?

Those are just some of the questions that should be asked.

The main question is –

If your fire department is doing such a bad job of managing BLS skills (BVM, positioning, painful stimulus, . . . ), why should we allow you to harm patients with ALS skills?

If your department is not harming patients, then where is the need?

Naloxone does not appear to be the answer to either problem.

Will naloxone cure the math problems of these drug pushing managers?

Footnotes:

[1] Acute heroin overdose.
Sporer KA.
Ann Intern Med. 1999 Apr 6;130(7):584-90. Review.
PMID: 10189329 [PubMed – indexed for MEDLINE]
 

Six of the 25 complete responders to naloxone (24%) ultimately were proven to have had false-positive responses, as they were not ultimately given a diagnosis of opiate overdose. In four of these patients, the acute episode of AMS was related to a seizure, whereas in two, it was due to head trauma; in none of these cases did the ultimate diagnosis include opiates or any other class of drug overdose (which might have responded directly to naloxone). Thus, what was apparently misinterpreted as a response to naloxone in these cases appears in retrospect to have been due to the natural lightening that occurs with time during the postictal period or after head trauma.

[2] Firefighters could be getting medication to save drug users
October 31, 2013 12:00 am
By Anne Jungen
ajungen@lacrossetribune.com
LaCrosse Tribune
Article

.

An EMS Giant is lost – Well-known educator Mike Smith dies at age 61

 


 

The EMS community lost one of its contemporaries early this morning. Mike Smith, chair of the Tacoma Community College EMS program and a well-known EMS speaker, died of an apparent heart attack.[1]

 

In EMS, we seem to die of things that as if they should be easily prevented. MVCs (Motor Vehicle Collisions) while not wearing a seat belt and heart attacks.

Why do I start writing about the death of Mike Smith by mentioning this? Because I think that is one thing he would want us to learn from his death at the ripe young age of 61.

We deal with death much more frequently than most other people, and yet we seem to be trying to get there faster than most other people.

Too many of us drink too much – and I do mean alcohol. Many of us drive while drunk and are able to get a free pass from the police, because we are the good guys. You didn’t kill anyone this time, so try harder next time. This is preventable.

Too many of us drive recklessly, even without the assistance of alcohol. The most common cause of LODD (Line Of Duty Death) is either heart attack or MVC, but how many of us regularly wear seat belts?

Mike Smith appears to have died of a heart attack.

What might Mike Smith use as lessons from this?

I barely knew him. I knew him well enough to say, Hi to him at EMS conferences.

I think that he would focus on preventing the pain that is inevitable from his death.
 

According to sources, Mike was transported by EMS from his home to a local hospital where he succumbed to a myocardial infarction.[1]

 

He might point out how painful this must have been for EMS, since he probably taught everyone who showed up.

He was a big guy, so maybe he had students press down on his chest in class to see that two inches is not going to do much on a big guy. But he would have been alive for that lesson.

How does EMS deal with the bad outcome, even if there was no way for EMS to change the outcome? This might be a class best taught by Shakespeare.
 

He is survived by his wife Sylvia and two grown children, as well as a new granddaughter.[1]

 

He might point out how much the patient would prefer to be around to see his children prosper and his grandchild grow up. How many things would he have told them, if he knew that he had so little time left?

Maybe the biggest lesson would be about taking better care of ourselves. We take care of other people, but we often do not take care of ourselves.
 

He was blunt and not afraid to share his thoughts and opinions with anyone. He was idealistic and filled with a zest for EMS and patient care. He loved people, and could be the best friend in the world or a formidable opponent if he thought you were unjust. Having grown up in Chicago, he would not back down from a fight when he was right.[2]

 

Are my comments too blunt?

Unlike his friend Jim Page, his death may not have been a tragedy of a lack of a defibrillator, but a tragedy of a big heart that did not beat long enough.

I have been trying to get rid of my EMS weight. I have lost about 20 pounds in the last five months, but I would like to lose another 30. Last night at work, I was the smallest person in the room at work, and I am not small.

I want to see my family grow old and become more successful. I want to make it beyond 61, 71, or even 81 – and with my brain still working. Exercise helps prevent stroke, too.[3]

It is painful for me to run, so I use a machine, then I walk for a while. I keep increasing the time. Eventually, I hope to be able to run, but even if I cannot, I can get good heart exercise from walking briskly. A few hours at about 140 beats per minute is over 75% of my calculated maximum heart rate and more than is recommended by the CDC (Centers for Disease Control and Prevention). This is prevention, the part that alternative medicine propagandists pretend that real doctors do not recommend.
 

10 minutes at a time is fine
We know 150 minutes each week sounds like a lot of time, but you don’t have to do it all at once. Not only is it best to spread your activity out during the week, but you can break it up into smaller chunks of time during the day. As long as you’re doing your activity at a moderate or vigorous effort for at least 10 minutes at a time.

Give it a try
Try going for a 10-minute brisk walk, 3 times a day, 5 days a week. This will give you a total of 150 minutes of moderate-intensity activity.[4]

 

It isn’t about me, or even Mike – it is about you and your family – even especially if you consider your family to be EMS – the people who would have to deal with treating you.

What is more important to you than your family, whoever your family may be?

 

Image replaced 17:10. Thank you to 9-ECHO-1. I had the wrong Mike Smith. I am not good at facial recognition and did not notice the differences. My apologies to everyone I upset with my error.

Footnotes:

[1] An EMS Giant is lost – Well-known educator Mike Smith dies at age 61
Art Hsieh
EMS1.com
Article

[2] Passing of an EMS Icon – Mike Smith, who died unexpectedly at age 61, was a well-known EMS educator and writer
A.J. Heightman, MPA, EMT-P
Letter by John Sinclair, Fire Chief, Emergency Manager, Kittitas Valley Fire Rescue, Ellensburg, WA
Monday, October 14, 2013
JEMS.com
Article

[3] Association of physical activity level and stroke outcomes in men and women: a meta-analysis.
Diep L, Kwagyan J, Kurantsin-Mills J, Weir R, Jayam-Trouth A.
J Womens Health (Larchmt). 2010 Oct;19(10):1815-22. doi: 10.1089/jwh.2009.1708. Review.
PMID: 20929415 [PubMed – indexed for MEDLINE]

Free Full Text from PubMed Central.
 

Although it is unclear how PA plays a protective role against stroke, results of this study suggest long-term benefits. Future research to examine the impact of PA on the pathophysiological mechanism of stroke will be desirable. Some studies37–41 have suggested that impact of PA on reducing the risk of stroke mortality could be explained by deceleration of the atherosclerotic process, amelioration of endothelial dysfunction, structural modification of the arteries, enhancement of myocardial electric stability, or attenuation of hypercoagulability.

 

[4] How much physical activity do adults need?
CDC (Centers for Disease Control and Prevention)
Physical Activity for Everyone
CDC page of recommendations.

.

Do Paralytics Improve Outcomes Following Resuscitation?

ResearchBlogging.org
 

This study will get some people excited because of an impressive p value for an odds ratio of improved cardiac arrest outcomes – 7.23 (1.56–33.38) p = 0.01.

NMBs (NeuroMuscular Blockers/Blockade) are paralytic drugs that are used to prevent movement by the patient. Does this study truly show that immediate use of NMBs improves neurologically intact survival from cardiac arrest?
 

Side effects of therapeutic hypothermia include an increased risk for arrhythmia, infection or bleeding, and shivering.6 [1]

 

NMBs could cause worse outcomes from therapeutic hypothermia use following ROSC (Return Of Spontaneous Circulation).
 

the American Heart Association (AHA) has recommended minimizing the use of NMB in post-CA patients or avoiding it altogether.11 [1]

 

Is this enough to get the AHA to change their minds?
 

We included patients who were 18 years of age or older who had suffered OHCA with sustained ROSC (defined as the presence of palpable pulses for >20 min) and who were comatose (not following commands) upon presentation to the NPARC hospital.[1]

 

That is an unusual definition of comatose. It would be interesting to know how many patients had a GCS (Glasgow Coma Score) of at least 8, but were not following commands. Many people are taught that a low GCS means that we should intubate. The mnemonic Less than 8 – intubate, is taught as if it is a substitute for a thorough assessment.

Maybe not following commands is the right metric to use for administration of NMBs, but we might want to describe this level of consciousness with a term other than coma. There is a lot of connotation associated with coma that might complicate decisions about treatment. If we use NMBs for patients with ROSC and a motor score of less than 6, will some people start to use a motor score of less than 6 for intubation with NMBs? RSI (Rapid Sequence Induction/Intubation) is the use of NMBs to facilitate intubation. A better question is How many of us will do this?, rather than Will any of us will do this?
 

Continuous neuromuscular blockade is associated with decreased mortality in post-cardiac arrest patients - Fig 1
 

Impressive.

So why am I suggesting caution?
 

Compared to those who did not receive sustained NMB, patients with 24-h NMB had shorter intervals from collapse-to-ROSC (13 min [IQR: 9–25] versus 22 min [IQR: 13–30]; p = 0.04) and higher baseline blood pH values (pH = 7.30 [IQR: 7.26–7.36] versus 7.22 [IQR: 7.12–7.31]; p = 0.04). There was a lower incidence of chronic obstructive pulmonary disease in patients with NMB compared to patients without NMB (0% versus 22%; p = 0.02).[1]

 

Time to ROSC demonstrates one of the problems with small numbers. The IQRs (InterQuartile Ranges) do not show that much difference, but the median times to ROSC are much farther apart. 22 minutes is in the middle of the 13-30 minute IQR for control patients, but 13 minutes is much quicker than the middle of the IQR for NMB patients.

Why does this matter?

The control patients appear to be evenly distributed around 22 minutes from collapse to ROSC, but the NMB patients had an uneven distribution that masks a tendency toward much quicker ROSC.
 

It is also odd that the group with the smaller numbers has a narrower IQR. Is this because of some uncontrolled variable in choosing which patients received early, sustained NMB treatment?
 

This is a post hoc analysis of data collected for a study with a different hypothesis, so the best that can be stated is that immediate NMB use (continued for 24 hours) is a promising treatment for further study.

Another big problem with this study is that it is so small. 18 patients received NMBs. The authors started the paper by mentioning that there are 400,000 cardiac arrests in the US each year. We need to demonstrate benefit on much more than 18 patients, regardless of p value, if we are going to start using this treatment outside of controlled trials.
 

There were 77 (69%) patients documented to have received NMB at any point within the first 24 h following ROSC. A portion of these patients (18/111, 16%) patients had NMB initiated immediately and sustained for a minimum duration of 24 h following return of circulation.[1]

 

This is not really a study comparing NMB use with absence of NMBs. This is a study comparing immediate NMB use that was continued for at least 24 hours against control group patients – most of whom received NMBs, but did not meet the full criteria for inclusion in the study group.

How different were the treatments? We do not know.

59 out of the 111 patients in the No NMB group received NMBs.

53% of the No NMB group did receive NMBs, just not for at least 24 hours and/or not immediately following ROSC. Correction – 15:20 7/08/2013.

59 out of 93 patients in the No NMB group received NMBs.

63% of the No NMB group did receive NMBs, just not for at least 24 hours and/or not immediately following ROSC.
 

The following is the main limitation pointed out by the authors.
 

An important limitation of this observational study is the uncertainty about why NMB was used in certain patients. It is possible that patients with more intact reflexes, shivering or spontaneous movement were more likely to receive NMB than patients with less vigorous neurological examinations. Thus, the possibility remains that patients without sustained NMB were less responsive (i.e., worse neurological status) and therefore did not clinically require continued therapy therefore creating selection bias. Finally, whether heavy sedation in the post-CA period would confer similar results is possible but has yet to be explored.[1]

 

Is a good physiologic explanation is leading them to minimize the weaknesses of this study? I don’t know, but they are not recommending anything other than more study, which is a reasonable conclusion for this study.

Unfortunately, the abstract presents a different conclusion – a conclusion that assumes too much.

I would discuss the physiology that is the basis for this study, but with no clear evidence of benefit and a lot of evidence that the data are misleading, there is no reason to spin tales about any possible mechanism(s).

The hypothesis is still essentially untested.

Footnotes:

[1] Continuous neuromuscular blockade is associated with decreased mortality in post-cardiac arrest patients.
Salciccioli JD, Cocchi MN, Rittenberger JC, Peberdy MA, Ornato JP, Abella BS, Gaieski DF, Clore J, Gautam S, Giberson T, Callaway CW, Donnino MW.
Resuscitation. 2013 Jun 21. doi:pii: S0300-9572(13)00331-6. 10.1016/j.resuscitation.2013.06.008. [Epub ahead of print]
PMID:23796602[PubMed – as supplied by publisher]
 

The National Post-Arrest Research Consortium (NPARC) is a clinical research network conducting research in post-cardiac arrest care. The network consists of four urban tertiary care teaching hospitals and was established to evaluate treatment strategies for individuals who are successfully resuscitated after out-of-hospital cardiac arrest. The current investigation is a post hoc analysis of a prospectively conducted NPARC trial evaluating mitochondrial injury in post-cardiac arrest patients (NIH 3UL1RR031990-02S1).

Salciccioli JD, Cocchi MN, Rittenberger JC, Peberdy MA, Ornato JP, Abella BS, Gaieski DF, Clore J, Gautam S, Giberson T, Callaway CW, & Donnino MW (2013). Continuous neuromuscular blockade is associated with decreased mortality in post-cardiac arrest patients. Resuscitation PMID: 23796602

.

Advanced Airway vs. BVM During CPR – Which is Worse?

ResearchBlogging.org
 

The authors wanted to find out what method is worst best for ventilating patients during out-of-hospital treatment of cardiac arrest.

Endotracheal tube?

Supraglottic airway (laryngeal mask airway, laryngeal tube, and esophageal-tracheal twin-lumen airway device)?

BVM (Bag Valve Mask)?

This assumes that ventilations provide some sort of benefit to the patient. There is no evidence to support this myth.

Their endpoint was neurological outcome at one month for all out-of-hospital cardiac arrest patients treated January 1, 2005, to December 31, 2010.
 

In addition, we postulated that both advanced airway techniques (endotracheal intubation or use of supraglottic airways) would be similarly associated with favorable neurological outcome after OHCA.[1]

 

Intubation training required more intubations in the operating room than is required in the US (zero to ? – 5 are typically given as the minimum requirement, but there is no standard accepted by all agencies), or in the UK.
 

Beginning in 2004, endotracheal intubation could be performed by specially trained emergency lifesaving technicians who had completed an additional 62 hours of training sessions and performed 30 supervised successful intubations in operating rooms.24 [1]

 

What were the results?
 

 
Click on images to make them larger.

Everything underlined in red is worse than BVM and statistically significant. The endotracheal tube numbers underlined in blue are only statistically significant until adjusted for confounding variables and only for ROSC (Return Of Spontaneous Circulation).

ROSC is important – if we do not mind causing long term harm in order to get this short term benefit. This is not a trade off that helps our patients.
 

A set of potential confounders was chosen a priori based on biological plausibility and a priori knowledge. These selected variables included age, sex, cause of cardiac arrest, first documented rhythm, witnessed status, type of bystander CPR, use of a public access automated external defibrillator, epinephrine administration, and time intervals from receipt of call to CPR by EMS and from receipt of call to hospital arrival.[1]

 

Not adjusting for confounders would be wrong.

There is one big confounder that I will get to at the end.

The supraglottic airways did even worse than the endotracheal tubes. There has been research in pigs showing that the inflation of the cuffs of supraglottic airways cause more interruption of carotid circulation than the cuffs of endotracheal tubes and that the cuffs of endotracheal tubes cause more interruption of carotid circulation than BVMs. BVMs have no cuffs to inflate to limit carotid circulation, which is the main source of blood flow to the brain.[2]

What else does not have a cuff?

A nonrebreather mask doesn’t have a cuff.

A nasal cannula doesn’t have a cuff.
 

 

Did failed tubes cause the study to be biased against intubation?
 

However, we defined advanced airway management as successful endotracheal intubation or supraglottic airway placement only. Thus, in our study, failed advanced airway management cases reverted to and were classified as bag-valve-mask ventilation cases. This would have biased our conclusions toward the null.[1]

 

The authors also calculated the results if all of the missing BVM patient data were negative and all of the missing supraglottic airway data were positive. The supraglottic airway data were associated with so much harm, that even this did not make the results look much less harmful for use of supraglottic airways.

Likewise, the authors calculated the results if all of the missing BVM patient data were negative and all of the missing endotracheal tube data were positive. The endotracheal tube data were also associated with so much harm, that even this did not make the results look much less harmful for endotracheal intubation.

Only 6.5% of the patients had endotracheal intubation, so this seems as if we could be dealing with small numbers producing statistical flukes. However, 6.5% of this huge sample is still 41,972. Therefore, this is not a case of statistical manipulation of small numbers with no clinical significance. There are more intubated patients in this study than there are total patients in most studies of airway management.
 

Assuming the validity of our study, a more secure airway, regardless of its technique, would be detrimental.[1]

 

Should we assume the validity of this study?
 

In addition, multiple studies arrived at similar conclusions despite differing populations, disease groups, and designs.7-10,12,13 [1]

 

There are two problems.

1.

There is no group with no ventilations. I realize that this was not within the control of the authors, but it would answer a more important question.

We are asking –

What is the best method of ventilation during cardiac arrest?

We have not yet answered –

Should we be ventilating during cardiac arrest?

We have not determined that any ventilation is beneficial during cardiac arrest, but we are spending our time choosing colors and arguing over which brand name is best.

2.

14 minutes to ROSC vs. 6 minutes to ROSC?

This is only mentioned tangentially and I am not satisfied with the explanation.

This presents a lot of different data. They all are similar – right up until the very last one.
 

 

This deserves some very specific description.

Unfortunately, the data probably do not include enough information to learn more about these differences.

The difference in time to ROSC is huge.

The IQRs (InterQuartile Ranges) show much more diversity than we should expect when everything else is so similar.

Could this explain the difference in outcomes?

The explanation of the authors (that their subgroup analyses account for this) seems to be unreasonably optimistic.

I want the authors to show that patients who have ROSC in 6 minutes should not be expected to have an outcome that is three times better than patients who take 2 13 times as long to achieve ROSC.

These numbers are large huge. 281,522 in one group and 367,837 in the other. How can such a heterogeneous variable be given so little attention?

If I tell someone that two groups of patients were resuscitated, but it took over twice as long to resuscitate one group as it took for the patients in another group, should I expect anyone to be surprised that the group resuscitated faster has outcomes that are three times better?

In cardiac arrest, as time increases bad outcomes can be expected to increase at an even greater rate.

There is not even much overlap in the IQRs of the times to ROSC. 8 – 20 minutes vs. 3 – 12. A 12 minute IQR with only 4 minutes of overlap.

Although everything else appears to be well matched, I do not see the subgroup analyses reconciling the differences in ROSC times.

I think that this could adequately explain the differences in outcomes. We do need prospective studies, but we should find out if there is any reason to be providing ventilations in cardiac arrest (except for those that are pediatric and/or respiratory in origin).

See also Advanced Airway Loses to BVM and read the comments.

Footnotes:

[1] Association of prehospital advanced airway management with neurologic outcome and survival in patients with out-of-hospital cardiac arrest.
Hasegawa K, Hiraide A, Chang Y, Brown DF.
JAMA. 2013 Jan 16;309(3):257-66. doi: 10.1001/jama.2012.187612.
PMID: 23321764 [PubMed – indexed for MEDLINE]

[2] Impairment of carotid artery blood flow by supraglottic airway use in a swine model of cardiac arrest.
Segal N, Yannopoulos D, Mahoney BD, Frascone RJ, Matsuura T, Cowles CG, McKnite SH, Chase DG.
Resuscitation. 2012 Aug;83(8):1025-30. doi: 10.1016/j.resuscitation.2012.03.025. Epub 2012 Mar 28.
PMID: 22465807 [PubMed – in process]
 

CONCLUSION:
The use of 3 different SGDs (Supraglottic airway devices) during CPR significantly decreased CBF (carotid blood flow ) in a porcine model of cardiac arrest. While the current study is limited to pigs, the findings suggest that further research on the effects of SGD use in humans and the effects on carotid artery blood flow is warranted.

Hasegawa K, Hiraide A, Chang Y, & Brown DF (2013). Association of prehospital advanced airway management with neurologic outcome and survival in patients with out-of-hospital cardiac arrest. JAMA : the journal of the American Medical Association, 309 (3), 257-66 PMID: 23321764

Segal, N., Yannopoulos, D., Mahoney, B., Frascone, R., Matsuura, T., Cowles, C., McKnite, S., & Chase, D. (2012). Impairment of carotid artery blood flow by supraglottic airway use in a swine model of cardiac arrest Resuscitation, 83 (8), 1025-1030 DOI: 10.1016/j.resuscitation.2012.03.025

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Is the Difference in Penetrating Trauma Mortality Truly Significant? Part I

ResearchBlogging.org
 

MV observed the following lack of distinction in scene time for penetrating trauma mortality, which I did not give the proper attention in EMS Time and Survival from Blunt and Penetrating Trauma. I will try to correct my mistake here.
 

I find it interesting (good) that they actually published those graphs. I’m not sure what you can really say based on the graphs, as the error bars are way too wide to make good conclusions. For instance, there is no real difference in death rate due to scene time on penetrating injuries that can be determined by this study based on Figure 5.

 

Here is Figure 5.
 

 

On multivariate regression of patients with penetrating trauma, we observed that a scene time greater than or equal to 20 minutes was associated with higher odds of mortality than scene time less than 10 minutes, with an odds ratio (OR) of 2.90 (95% confidence interval [CI] 1.09 to 7.74). Scene time of 10 to 19 minutes was not significantly associated with mortality (OR 1.19; 95% CI 0.66 to 2.16).[1]

 

I should have paid more attention to this, rather than just looking at the brief description of the 0-9 minute vs. the 10-19 minute scene time intervals, which are not graphed vs. mortality.

Clearly, this graph is not a graph of 0-9 minute, 10-19 minute, and 20-29 minute time periods, but there is no explanation of the numbers represented by the graph.

If we eliminate the blunt trauma part of the graph, the wide error bars on the penetrating trauma percent dying show a lot of overlap. The error bars cover as much as a 50% difference in survival in one time period, while the narrowest error bars cover over at least a 15% difference in survival.

Overlap on error bars is usually an indication that the results are not statistically significant, but it depends on the type of error bar. The text describes CIs (Confidence Intervals) when comparing the 0-9 minute vs. 10-19 minute scene time intervals. However, the graphs do not specify which type of error bar is used, so we do not know how the error bars should be interpreted.
 

Error bars are a graphical representation of the variability of data and are used on graphs to indicate the error, or uncertainty in a reported measurement. They give a general idea of how accurate a measurement is, or conversely, how far from the reported value the true (error free) value might be. Error bars often represent one standard deviation of uncertainty, one standard error, or a certain confidence interval (e.g., a 95% interval). These quantities are not the same and so the measure selected should be stated explicitly in the graph or supporting text.[2]

 

There should not be so much overlap if there is any significant difference. It appears that the only way there is a statistically significant difference is by covering a ten minute time period.
 

 
Click on images to make them larger.

The last time period (≈ 26 minute scene time) has error bars that overlap with all of the other time periods, including the ≈2 minute scene time. The ≈2 minute scene time is the only time period where the median is not within the error bars for the ≈ 26 minute scene time.

 

 

Even the shortest scene time (≈2 minute scene time) has wide enough error bars to include the medians from two other time periods (≈6 minute scene time and ≈10 minute scene time). These would all fall within the 0-9 minute scene time group and the larger group can have enough patients to narrow the error bars. Wide error bars are often an indication of small numbers. For an example of this, look at the graph that contains the blunt trauma patients – those error bars are much narrower than the error bars for the penetrating trauma patients. The study had 16,170 blunt trauma patients and only 2,997 penetrating trauma patients. That means 5.4 times as many blunt trauma patients.

Paradoxically, the much larger group of blunt trauma patients did not produce any statistically significant difference in outcomes based on scene times or transport times. with more penetrating trauma patients, would the statistical significance disappear?

We do not know.

The authors state that the choice of time periods was made before analysis of the data, so this does not appear to be an example of trying to find the right groups to make the data fit the hypothesis.
 

We categorized out-of-hospital times into 10-minute intervals a priori with the intent of choosing an interval that is operationally practical, clinically feasible, and politically acceptable.[1]

 

I would like to see what the graph of 0-9 minute, 10-19 minute, and 20-29 minutes would look like.

None of this suggests that the concept of the Golden Hour should survive.
 

It is crucial for medical researchers to critically examine concepts such as the golden hour that are widely accepted but are in fact not scientifically supported. We frequently strive to push ever higher the ceiling of medical knowledge, but we must also ensure that the knowledge base upon which we stand is solid.[3]

 

Ignorance may be bliss for some people, but we will not improve outcomes for our patients by promoting ignorance.

Footnotes:

[1] Emergency Medical Services Out-of-Hospital Scene and Transport Times and Their Association With Mortality in Trauma Patients Presenting to an Urban Level I Trauma Center.
McCoy CE, Menchine M, Sampson S, Anderson C, Kahn C.
Ann Emerg Med. 2013 Feb;61(2):167-74. doi: 10.1016/j.annemergmed.2012.08.026. Epub 2012 Nov 9.
PMID: 23142007 [PubMed – in process]

[2] Error bar
Wikipedia
Article

[3] The golden hour: scientific fact or medical “urban legend”?
Lerner EB, Moscati RM.
Acad Emerg Med. 2001 Jul;8(7):758-60. Review.
PMID: 11435197 [PubMed – indexed for MEDLINE]

Link to Free Full Text Download in PDF format from Academic Emergency Medicine

Lerner EB, & Moscati RM (2001). The golden hour: scientific fact or medical “urban legend”? Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, 8 (7), 758-60 PMID: 11435197

McCoy CE, Menchine M, Sampson S, Anderson C, & Kahn C (2013). Emergency Medical Services Out-of-Hospital Scene and Transport Times and Their Association With Mortality in Trauma Patients Presenting to an Urban Level I Trauma Center. Annals of emergency medicine, 61 (2), 167-74 PMID: 23142007

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Blue Moon 2012 – Except parts of Oceanea

ResearchBlogging.org

Tonight is a Blue Moon and a Friday the Dyslexic 13th Full Moon.

As conspiracy theorists say, That can’t be a coincidence!

Of course it can be a coincidence.

The next Blue Moon is in 2015, unless you are near the International Date Line, in which case the Blue Moon is not this month, but at the end of next month (and then in 2015).[1]
 


Click on images to make them larger.
 

Does anything special happen during a Blue Moon?

There is more light, but they are really only uncommon.

The full moon does not have an influence on our lives, except to annoy the superstitious, to provide more light, and to give me another reason to throw some light on the lunacy of full moon superstition.


Image credit.
 

“Have you university types ever looked at whether dog bites happen more around the full moon? It’s a well known fact that they do.”[2]

They could accept the old farmer’s tale or they could examine it. It appears that even though the farmer seems to be set in his belief, he is still open to evidence.

The influence of the full moon remains one of the more resilient popular explanations of a wide range of mostly traumatic or bizarre events. There is a pale reflection of this in epidemiology—recall bias—where those affected by a rare or severe disease are more inclined to associate unrelated non-disease exposures to the disease.[2]

This is a lighthearted look at the numbers of admissions for dog bites and whether there is any association with the full moon.
 

The beginning of the dates is the first full moon, although it is not marked. There is no peak at the beginning of the chart, so this was not done to mislead. It might be because there were so many days with very few dog bite admissions at that full moon.

Results
Altogether 1671 accident and emergency admissions for dog bites occurred during the study period (938 males, 733 females), representing an overall mean admission rate of 4.58 per day. Figure 1 shows 18 peak days (notionally >10 admissions/day), with the maximum peak centring on the New Year break (the highest peak (24) occurred on New Year’s Day 1998). Full moons coincided with none of these peaks.
[2]

There were 12 full moons, but none of the excessive dog bite days were at the time of any of the full moons.

None.

If there is any causal relationship between the full moon and serious dog bites, the occurrence of the peaks should be greater than predicted by chance.

By my calculation, there is just over a 64% chance of any of these 18 peak dog bite days and any of the full moons occurring together by chance in that one year period. A longer time period would be better for making this clear, but there does not appear to be any suggestion of any association between full moons and admissions for dog bites.

Overall, full moon days were associated with slightly lower mean admissions (4.6 compared with 4.8 per day).[2]

During the study, there were fewer serious dog bites during the full moon, than at other times.

As the plot of dog bite admissions and full moons clearly shows, more caution with dogs might be exercised over Christmas and especially at New Year—irrespective of the full moon.[2]

It may not be a good idea to try to make friends with strange dogs on those days.
 

Correction (8/21/2013 20:08) – Here is an article that shows I was wrong about the two full moons in a month definition of a full moon.

What’s a Blue Moon?
The trendy definition of “blue Moon” as the second full Moon in a month is a mistake.

Sky & Telescope
by Donald W. Olson, Richard Tresch Fienberg, and Roger Sinnott
July 27, 2006
Article
 

Footnotes:

[1] How often do two full moons happen in the same month?
EarthSky.org
Friday, August 31
Article

[2] Barking mad? another lunatic hypothesis bites the dust.
Chapman S, Morrell S.
BMJ. 2000 Dec 23-30;321(7276):1561-3.
PMID: 11124174 [PubMed – indexed for MEDLINE]

Free Full Text from BMJ

Chapman S, & Morrell S (2000). Barking mad? another lunatic hypothesis bites the dust. BMJ (Clinical research ed.), 321 (7276), 1561-3 PMID: 11124174

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Intramuscular Midazolam for Seizures – Part VI


ResearchBlogging.org
Also posted over at Paramedicine 101 (now at EMS Blogs) and at Research Blogging. Go check out the excellent material at these sites.

How aggressive should we be in treating seizure patients based on this large double-blind, randomized, noninferiority trial comparing IM (IntraMuscular) midazolam (Versed) with IV (IntraVenous) lorazepam (Ativan)?

Which seizure patients should be treated with benzodiazepines?

Most patients stop seizing without any treatment and benzodiazepines can cause respiratory depression, so we need to be careful.

 

You can’t be too careful!

 

Right?
 

status epilepticus . . . occurs in approximately 6% of visits to the emergency department for seizures. . . . Although the term “prolonged” was previously used to refer to seizures lasting 30 minutes or longer, this interval has been shortened to 5 to 10 minutes in recent studies. This change occurred for several reasons. First, almost all convulsive seizures in adults cease in less than 5 minutes without treatment; seizures lasting longer than this are more likely to be self-sustained and to require intervention.3,4 [1]

 

We used to be much more careful. We would wait half an hour before treating seizures out of a fear of making things worse. That fear caused us to make things worse by being too careful.

5 minutes seems to be the dividing line between seizures that will stop on their own and seizures that require treatment.
 

Second, the longer seizures persist, the harder they are to terminate pharmacologically.5 [1]

 

Being too careful resulted in higher doses of medication being given, because the dose that could have worked earlier in the seizure is no longer effective. The larger dose is also not effective. A different medication may also need to be added, even though it may not be effective, because we waited too long by being too careful!.

Delaying by more than 5 minutes increases the likelihood of not being able to stop the seizure with any medication. This is far worse than the potential side effects of giving a benzodiazepine to a patient who would otherwise have his seizure resolve spontaneously.
 

Third, outcome tends to correlate with seizure duration even after one controls for other factors. Mortality among patients who present in status epilepticus is 15 to 22%; among those who survive, functional ability will decline in 25% of cases.6 [1]

 

Benzodiazepine side effects should be easily managed, even by people with just advanced first aid training – protect the airway and make sure the patient is breathing. In the absence of adequate breathing, getting the patient to talk is most effective. If getting the patient to talk is unsuccessful, painful stimulus is indicated. If painful stimulus is unsuccessful, rescue breathing is indicated.
 

The effects of midazolam on the CNS are dependent on the dose administered, the route of administration, and the presence or absence of other medications. Onset time of sedative effects after IM administration in adults is 15 minutes, with peak sedation occurring 30 to 60 minutes following injection.[2]

 

Midazolam given IM is not metabolized as quickly as when given IV, but midazolam should still be metabolized more quickly than IV lorazepam (Ativan). Unfortunately, the label does not include information about the time to return to being alert following IM midazolam, so I can only make this apples and oranges comparison. When I have given midazolam IV, I have had to give more midazolam before arriving at the hospital (after I had given a total dose that was successful) or more sedation has had to be given the hospital (after I had given a total dose that was successful). I have never seen IV lorazepam metabolized that quickly. So midazolam is metabolized much more quickly IV, than lorazepam is metabolized IV. Unfortunately, I could not find more appropriate information to compare the metabolism of IM midazolam and IV lorazepam.
 

The intended effects of the recommended adult dose of ATIVAN Injection usually last 6 to 8 hours.[3]


Image credit.
 

This study does show that the patients receiving IM midazolam did not end up hospitalized as often, which may be due to more rapid metabolism of IM midazolam.
 

the proportion of subjects admitted was significantly lower (and the proportion discharged from the emergency department was significantly higher) in the intramuscular group than in the intravenous group (P=0.01).[4]

What is needed is a good study comparing buccal midazolam, IN (IntraNasal) midazolam, and IM midazolam to find out which works best. Perhaps a rectal diazepam group could be included to put another nail in that coffin, but rectal diazepam has the one thing going for it that no amount of evidence seems to be able to overcome – tradition. We need to stop killing our patients with tradition.
 

Multiple studies have shown that nasal or buccal midazolam stops seizures faster than rectal or intravenous diazepam13 and is absorbed faster than intramuscular midazolam.13 – 15 [1]

 

Buccal or IN midazolam stops seizures faster than IV or rectal diazepam, but is only absorbed faster than IM midazolam?

See also Part I, Part II, Part III, Part IV, Part V, and Images from Gathering of Eagles Presentation on RAMPART.

Footnotes:

Correction 01/15/2014 15:00 – I had the wrong paper listed as the source of the material in Footnote [1]. I listed the RAMPART study, but the source is the editorial that was published in the same issue. The correct source is below with the paper I originally cited below it. There is nothing wrong with the paper crossed out – only with my use of it as the source of the material I included above.
 

[1] Intramuscular versus intravenous benzodiazepines for prehospital treatment of status epilepticus.
Hirsch LJ.
N Engl J Med. 2012 Feb 16;366(7):659-60. doi: 10.1056/NEJMe1114206. No abstract available.
PMID: 22335744 [PubMed – indexed for MEDLINE]

Free Full Text PDF Download from the RAMPART Group.
 

Intramuscular versus intravenous therapy for prehospital status epilepticus.
Silbergleit R, Durkalski V, Lowenstein D, Conwit R, Pancioli A, Palesch Y, Barsan W; NETT Investigators.
N Engl J Med. 2012 Feb 16;366(7):591-600.
PMID: 22335736 [PubMed – in process]

Free Full Text from N Engl J Med.

[2] MIDAZOLAM HYDROCHLORIDE injection, solution
[Hospira, Inc.]

DailyMed
FDA Label

[3] ATIVAN (lorazepam) injection, solution
[Baxter Healthcare Corporation]

DailyMed
FDA Label

[4] Intramuscular versus intravenous therapy for prehospital status epilepticus.
Silbergleit R, Durkalski V, Lowenstein D, Conwit R, Pancioli A, Palesch Y, Barsan W; NETT Investigators.
N Engl J Med. 2012 Feb 16;366(7):591-600.
PMID: 22335736 [PubMed – in process]

Silbergleit, R., Durkalski, V., Lowenstein, D., Conwit, R., Pancioli, A., Palesch, Y., & Barsan, W. (2012). Intramuscular versus Intravenous Therapy for Prehospital Status Epilepticus New England Journal of Medicine, 366 (7), 591-600 DOI: 10.1056/NEJMoa1107494

Hirsch LJ (2012). Intramuscular versus intravenous benzodiazepines for prehospital treatment of status epilepticus. The New England journal of medicine, 366 (7), 659-60 PMID: 22335744

Hirsch LJ (2012). Intramuscular versus intravenous benzodiazepines for prehospital treatment of status epilepticus. The New England journal of medicine, 366 (7), 659-60 PMID: 22335744

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