ACLS | Rogue Medic

Furosemide is good for filling the patient’s bladder, but the patient probably did not call for help filling his/her bladder.

- Rogue Medic

What should an epinephrine in cardiac arrest study look like?

Tue, 10 Apr 2012 08:00:34 +0000 By Rogue Medic 4 Comments

Since the Hagihara^[1] study was published, there is a lot more support for a study of epinephrine. One of the problems with studying epinephrine is the religious devotion that some have to maintaining the status quo.

How do we prevent paramedics from violating the study protocol?

I have been told of paramedics testing the study drug to see if it produces the cocaine-type of numbness to the tongue, since epinephrine produces effects similar to cocaine without the euphoria. If the study drug is not epinephrine, the syringe is broken, or replaced, or . . . .

How much epinephrine is needed on an ALS (Advanced Life Support) ambulance?

We generally carry a bunch of 1:10,000 epinephrine (1 mg in 10 ml) for cardiac arrest. Maybe 5 – 10 with a multi-dose 30 ml vial of 1:1,000 (1 mg in 1 ml) epinephrine for those prolonged arrests, so that 1 mg at a time can be drawn up and given to the patient.

We also carry some ampules of 1:1,000 epinephrine for IM (IntraMuscular), SC (SubCutaneous), or IV (IntraVenous) administration for anaphylaxis or asthma.

We can easily replace the 1:10,000 epinephrine and the multi-dose vial with just one study drug packet. After each code, a new packet would be placed in the ambulance’s drug bag/box. This would discourage the tendency to switch kits if the study drug is not epinephrine – not that there is any good reason for the medic to know what is being given.

For anaphylaxis/asthma, participating ambulances would be assigned only autoinjectors. This would decrease the availability of epinephrine available to violate protocol.

Supervisors would only carry study kits and autoinjectors.

Is it still possible to intentionally violate protocol? Yes, but anyone thinking that far ahead should be smart enough to realize that they are only harming patients by possibly requiring that the study be repeated. The maturity of the medics should be the best protection against protocol violation, but true believers can be immune to maturity.

What would the study kits include?

The RAMPART^[2], ^[3] study gives an excellent example of how to

Patients are not entered into the study unless they have reached the point in the algorithm where epinephrine would be given. When the kit is opened, the recording beginsand the first syringe of the study drug is given.

Monitors capable of recording the quality of CPR would also be used. The ROC (Resuscitation Outcomes Consortium) should already be using these, so it would not be an added expense.

What about patients who remain in a shockable rhythm after the syringes of study drug are all used? Transport them to the hospital. Let the hospital do whatever they want with these rare patients.

What if there is a problem with the study kit? Then the patient should not be receiving any medication and should be unblinded participants in the group not receiving epinephrine.

What about amiodarone/lidocaine? There is no good reason to give these derivative magic treatments until there is evidence that they work. This is to try to find out if the ~~primary magic treatment~~ epinephrine works, not to support the whole Chain of Magic.

Maybe the last part of that chain should not be there.

EMCrit Wee – Abandon Epinephrine?

Fri, 06 Apr 2012 08:00:11 +0000 By Rogue Medic 1 Comment

Dr. Weingart has a ~~mini~~ wee podcast about the recent epinephrine research and whether EMS should be using epinephrine. Maybe the EMCrit logo is too big for a wee podcast.

One of the EMCrit listeners, the medical director for a major EMS agency, wanted to know what Dr. Weingart thinks about removing epinephrine from their cardiac arrest protocols.

EMCrit Wee – Abandon Epinephrine?

While Dr. Weingart thinks that the evidence will show that epinephrine is beneficial in cardiac arrest . . .

Well, you’ll have to listen to the podcast, all five and a half minutes of it, to find out the rest of his thoughts on this topic.

He recommends reading what Dr. Radecki (EM Literature of Note) wrote about epinephrine here.

I think that there may be only isolated indications for epinephrine. I do not think that we will ever know what those legitimate indications are until after we do a large enough well designed randomized controlled trial to separate out any benefit in survival.

ROSC (Return Of Spontaneous Circulation) is not a valid endpoint after 50 years of routine use, but the only evidence we have in humans is ROSC. We would not settle for such flimsy evidence in treating cancer (unless using alternative medicine), so why is it acceptable in cardiac arrest?

While we have not yet reached double digits on studies showing harm from epinephrine, there still is not a single study showing improved survival with epinephrine in cardiac arrest.

Millions of cardiac arrest patients treated with epinephrine, but we still cannot find any valid evidence of improved survival.

Vladimir and Estragon would have stopped waiting long ago.

Expert recommendations must come with an expiration date.

No exceptions.

If the expert recommendation is not followed by appropriate research, then the expert recommendation should not be treated better than the patients.

I completely agree with Dr. Weingart’s recommended approach. We should also study nitrates in cardiac arrest.

Go listen to all 5 and a half minutes of the podcast.

Filed Under: ACLS, EMCrit, Epinephrine, Pharmacology, Research

Naloxone in cardiac arrest with suspected opioid overdoses

Thu, 05 Apr 2012 21:30:10 +0000 By Rogue Medic Leave a Comment

Peter Canning is doing a countdown of the 16 Most Significant EMS Treatment Changes in My 20 Years as a Paramedic. Number 15 is Narrower use of Narcan, which is important and an improvement in patient care. The topic did encourage me to write about this study on naloxone (Narcan) in cardiac arrest from suspected opioid overdose.

Can naloxone improve survival from cardiac arrest?

This is an interesting study that looks at some old charts to try to figure out if naloxone made any difference when it was given to cardiac arrest patients suspected of having an opioid overdose. Here is the interesting part of their hypothesis –

Naloxone has been demonstrated to reduce action potential upstroke in guinea pig, canine, rabbit, and sheep myocardium.^8,18,19 The inhibition of action potential upstroke is correlated with the inhibition of fast inward sodium currents. In addition, an effect on repolarizing potassium currents has been shown to suppress re-entrant rhythms by prolonging action potential duration and increasing the refractory period.23 Therefore, naloxone’s antiarrhythmic activity appears to be similar to both class I and III antiarrythmics.²³ ^[1]

Amiodarone also has a shotgun effect on the conduction system, just like the person who decides to change all of the settings on a ventilator without waiting to see what any of the effects might be.

Of course, relying on an antiarrhythmic effect is not likely to improve survival, but it is worth studying.

There is no evidence that any antiarrhythmic drug given routinely during human cardiac arrest increases survival to hospital discharge. Amiodarone, however, has been shown to increase short-term survival to hospital admission when compared with placebo or lidocaine.^[2]

The result is just more people dying in the hospital, but ROSC (Return Of Spontaneous Circulation – the short-term change that rarely lasts when obtained with drugs) is hard to ignore.

I have pointed out that the addition of naloxone to the ventilation and epinephrine we are already giving is not likely to add any benefit. With respiratory depression/rerspiratory arrest as the suspected cause of cardiac arrest, these patients are some of the minority who may benefit from ventilation and should be ventilated. When the potentially reversible cause is hypoxia/anoxia, ventilation is a part of the treatment.

Click on images to make them larger.

Not a lot of patients, but New Jersey protocols require medical command permission to give naloxone in cardiac arrest, so there is not a lot of dumping of drugs that “couldn’t hurt” and are coincidentally nearing their expiration date.

Changes in original rhythm noted immediately following naloxone administration, but before additional pharmacologic interventions, were deﬁned as immediate changes. Delayed changes were deﬁned as cardiac rhythm changes occurring after additional medications were administered but within a 10-min interval following initial naloxone dose. The primary outcome measure was change in cardiac activity from baseline based upon EKG rhythm. Secondary outcome measures examined included return of spontaneous circulation (ROSC), survival to hospital admission, and survival to hospital discharge.^[1]

If the primary endpoint is a change in rhythm, then it appears that the naloxone is being given as an antiarrhythmic, but it is difficult to measure any effect on anything else naloxone might affect.

Naloxone was never the first drug given, but it was occasionally the last prehospital drug given, because of ROSC.

What were the results?

The charts reviewed were from 01/01/2003 to 12/31/2007, so all of the asystole and PEA (Pulseless Electrical Activity) patients had atropine in the protocol. Only one patient started in VF (Ventricular Fibrillation).

Only one patient survived. A 36 year old female, found in asystole. She received epinephrine two times and atropine two times over a 13 minute period. She remained in asystole. Following medical command orders, she received 2 mg naloxone and converted to sinus tachycardia (130 bpm) within 2 min.

She survived to be discharged at 11 days. No information on neurological function is provided. She may have gone to a nursing home or she may be a brain surgeon. We do not know.

1 out of 36 is just 2.8%. Not very good, but these were patients presenting in asystole/PEA, so nothing good is really expected.

At the end of the paper, the authors switch to claiming that this use of naloxone is somehow reversing opioid-induced histamine release. As if we do not successfully treat histamine release much more successfully with epinephrine.^[3] Every patient received epinephrine at least one time in doses much larger than would be used for anaphylaxis prior to receiving naloxone. Anaphylaxis is the most extreme example of a histamine release effect.

If there is a positive effect from naloxone, that would be good to know. Unlike most other drugs used in cardiac arrest, naloxone does not appear to produce any significant harm to the heart or brain when used to treat cardiac arrest.

While we definitely do not want to just make this a part of the treatment algorithms without much better evidence, we should find out if there is any benefit. If naloxone has antiarrhythmic properties, is there any reason to limit the research to suspected opioid overdose? This might be difficult to study prospectively, although the other UMDNJ hospitals would seem to be ideal locations to look for suspected opioid overdose patients.

Footnotes:

^[1] Naloxone in cardiac arrest with suspected opioid overdoses.
Saybolt MD, Alter SM, Dos Santos F, Calello DP, Rynn KO, Nelson DA, Merlin MA.
Resuscitation. 2010 Jan;81(1):42-6. Epub 2009 Nov 13.
PMID: 19913979 [PubMed - indexed for MEDLINE]

^[2] Antiarrhythmics
2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science
Part 8: Adult Advanced Cardiovascular Life Support
Part 8.2: Management of Cardiac Arrest
Medications for Arrest Rhythms
Free Full Text from Circulation with link to PDF Download

^[3] What About IV Epinephrine for Patients Who Are Not Dead
Rogue Medic
Fri, 30 Mar 2012
Article

Saybolt, M., Alter, S., Dos Santos, F., Calello, D., Rynn, K., Nelson, D., & Merlin, M. (2010). Naloxone in cardiac arrest with suspected opioid overdoses Resuscitation, 81 (1), 42-46 DOI: 10.1016/j.resuscitation.2009.09.016

Filed Under: ACLS, Heresy, Naloxone, Pharmacology, Research Blogging

A Critic Reads My Mind, But Does He Read What I Write

Thu, 29 Mar 2012 08:00:58 +0000 By Rogue Medic 6 Comments

In response to What Will Be the Next Standard Of Care We Eliminate is this attempt at reason from SARmission –

@Roguemedic. After reading a number of your blogs I have come to the following conclusion. Your purpose in writing is not to make, those reading, better medics. Rather it is to create controversy, and try to make statements that you are not qualified to make.

You are entitled to your opinion, but you have not provided any evidence to support your opinion. You appear to be just trying to create controversy.

I present people with both my opinion and the evidence on which I base that opinion.

You have based your whole position on this epi debate on an OPINION paper.

How do you know what I have based my conclusions on? Please provide some evidence of your psychic ability.

I have been writing about epinephrine since long before the editorial by Dr. Callaway. I was also teaching about the problems with epinephrine before the AAEM Position statement and AAEM Working Group Report, but I was not writing a blog at that time.

Perhaps you are referring to the AAEM Position Paper, which includes a review of the literature and analysis by Amal Mattu, MD FAAEM, Carey Chisholm, MD FAAEM, and Jerome R. Hoffman, MA MD FAAEM.

I have written about epinephrine a lot –

2008

Epinephrine in Cardiac Arrest
Sun, 06 Apr 2008

Dead VT vs Not Quite Dead, Yet VT.
Tue, 08 Apr 2008

More on Epinephrine in Cardiac Arrest.
Sat, 19 Apr 2008

Narrative Fallacy I
Fri, 24 Oct 2008

2009

EMS Mythology Starter Kit
Tue, 10 Feb 2009

EMS Garage, CPR, Continuous Compressions, and Resuscitation – Jamie Davis comment
Tue, 21 Apr 2009

Why Can’t Medics Resuscitate? II
Tue, 14 Jul 2009

Narrative Fallacy II
Wed, 15 Jul 2009

C A S T and Narrative Fallacy comment from Shaggy
Wed, 22 Jul 2009

The Blame Game
Tue, 27 Oct 2009

Intravenous drug administration during out-of-hospital cardiac arrest: a randomized trial.
Thu, 24 Dec 2009

2010

EMS EdUCast – Journal Club 2: Episode 43
Thu, 28 Jan 2010

Correction on Intravenous drug administration during out-of-hospital cardiac arrest: a randomized trial.
Sun, 07 Mar 2010

How to Study Epinephrine in Cardiac Arrest
Fri, 30 Apr 2010

Current Drug Shortages
Fri, 30 Jul 2010

More on Drug Calculations
Mon, 02 Aug 2010

A Letter To Mom
Tue, 14 Sep 2010

Most Survive with Mystery Treatment for Cardiac Arrest – Comments from Christopher
Tue, 14 Sep 2010

More Drug Shortage Paranoia – Epinephrine
Wed, 06 Oct 2010

Ethics, Research, and IRBs – Part II
Tue, 26 Oct 2010

Ethics, Research, and IRBs – Part III
Fri, 29 Oct 2010

A Mistaken Bolus of Epinephrine Given to a Living Patient
Tue, 07 Dec 2010

2011

Changes to Pennsylvania Protocols – Post-Resuscitation Care – Part I
Wed, 20 Apr 2011

Rhythm Interpretation and Inattentional Blindness
Tue, 19 Jul 2011

Bogus Ethics and Epinephrine in Cardiac Arrest
Sat, 30 Jul 2011

A Couple of Comments on Bogus Ethics and Epinephrine in Cardiac Arrest – Part I
Sun, 31 Jul 2011

A Couple of Comments on Bogus Ethics and Epinephrine in Cardiac Arrest – Part II
Wed, 03 Aug 2011

A Couple of Comments on Bogus Ethics and Epinephrine in Cardiac Arrest – Part III
Mon, 08 Aug 2011

Cardiac Arrest Management is an EMT-Basic Skill
Wed, 07 Dec 2011

Does Epinephrine Improve Survival from Cardiac Arrest
Mon, 12 Dec 2011

Cardiac Arrest Management is an EMT-Basic Skill – The BLS Evidence – Comment from Windy City Medic
Sat, 17 Dec 2011

Where is the Evidence for Epinephrine in the 2010 ACLS Guidelines
Mon, 19 Dec 2011

The Danger of ROSC – Return Of Spontaneous Circulation
Tue, 20 Dec 2011

Why Does Epinephrine Cause Brain Damage During Resuscitation
Mon, 26 Dec 2011

2012

When Does Post-Resuscitation Care Begin
Wed, 18 Jan 2012

Why We Deceive Ourselves With Explanations
Sat, 04 Feb 2012

Killing Patients Just to Get a Temporary Pulse With Epinephrine
Wed, 21 Mar 2012

Dr. Ken Grauer on Killing Patients Just to Get a Temporary Pulse With Epinephrine – Part I
Thu, 22 Mar 2012

Dr. Ken Grauer on Killing Patients Just to Get a Temporary Pulse With Epinephrine – Part II
Fri, 23 Mar 2012

PROVE Epinephrine is Harmful
Mon, 26 Mar 2012

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

The Importance of Having ROSC
Sun, 01 Apr 2012

Before you start beating your drum, wait for the FACTS.

Facts?

The evidence that we are not waiting for before we give dangerous drugs to patients?

We should have been waiting for evidence that epinephrine works, or demanding that somebody find out with a large, randomized placebo controlled trial.

We have based treatment with epinephrine on only superficial facts.

Here is the research, look closely:

There isn’t anything there – just a black hole full of nothing.

Consider these statements by the AHA (American Heart Association) – the people who write the guidelines that guide cardiac arrest treatment in the US – about the research on epinephrine –

Deemphasis on Devices and Advanced Cardiovascular Life Support Drugs During Cardiac Arrest
At the time of the 2010 International Consensus Conference there were still insufficient data to demonstrate that any drugs or mechanical CPR devices improve long-term outcome after cardiac arrest.⁴⁵ Clearly further studies, adequately powered to detect clinically important outcome differences with these interventions, are needed.^[1]

The AHA calling for research a couple of years ago.

Why?

Lack of evidence of benefit from epinephrine.

To date no placebo-controlled trials have shown that administration of any vasopressor agent at any stage during management of VF, pulseless VT, PEA, or asystole increases the rate of neurologically intact survival to hospital discharge. There is evidence, however, that the use of vasopressor agents is associated with an increased rate of ROSC.^[2]

We have evidence of improved ROSC. I have never denied that.

I do not think that we should be harming patients just for ROSC.

There is no evidence that increasing ROSC with epinephrine improves any important outcome.

There are no RCTs that adequately compare epinephrine with placebo in treatment of and outcomes related to out-of-hospital cardiac arrest. A retrospective study²⁶⁷ compared epinephrine to no epinephrine for sustained VF and PEA/asystole and found improved ROSC with epinephrine but no difference in survival between the treatment groups. A meta-analysis and other studies have found improved ROSC, but none have demonstrated a survival benefit of high-dose epinephrine versus standard-dose epinephrine in cardiac arrest.^{135,268,–,272} ^[2]

No facts to justify routinely using epinephrine.

The causes of cardiac arrest are numerous; by far the most common in adults is ischemic cardiovascular disease.^4-6 The arrest is usually associated with the lethal arrhythmia of ventricular fibrillation triggered by an acutely ischemic or infarcted myocardium or by a primary electrical disturbance.^[3]

Are we supposed to be giving epinephrine to patients having heart attacks?

We are routinely giving epinephrine to patients who are likely to be having heart attacks.

There is very little high-level evidence for resuscitation therapies, and many traditional treatment recommendations such as the use of epinephrine/adrenaline, are based on animal studies and reluctance to change an existing treatment recommendation until it is proven ineffective or less effective than a novel therapy.^[4]

We don’t seem to need facts to use a treatment on a patient.

We do not seem to believe in the ethics of first, do no harm.

We seem to wait until there is so much evidence of harm that we cannot ignore the evidence any longer.

Then we get rid of the dangerous treatment.

Epinephrine is ordinarily administered with extreme caution to patients who have heart disease.^[5]

There is nothing cautious about the routine administration of 1 mg epinephrine every 3 to 5 minutes to everybody who is still dead when we reach that part of the algorithm.

Before you say it, I know that reading a blog is a choice. I choose to stop reading yours. Thank you for you time.

That suggests that this is not exactly your first time making controversial comments on a blog.

Is making controversial comments constructive when you do it, but destructive when others do it?

I present people with both my opinion and the evidence on which I base that opinion.

Footnotes:

^[1] Deemphasis on Devices and Advanced Cardiovascular Life Support Drugs During Cardiac Arrest
2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science
Part 1: Executive Summary
John M. Field, Co-Chair*; Mary Fran Hazinski, Co-Chair*; Michael R. Sayre; Leon Chameides; Stephen M. Schexnayder; Robin Hemphill; Ricardo A. Samson; John Kattwinkel; Robert A. Berg; Farhan Bhanji; Diana M. Cave; Edward C. Jauch; Peter J. Kudenchuk; Robert W. Neumar; Mary Ann Peberdy; Jeffrey M. Perlman; Elizabeth Sinz; Andrew H. Travers; Marc D. Berg; John E. Billi; Brian Eigel; Robert W. Hickey; Monica E. Kleinman; Mark S. Link; Laurie J. Morrison; Robert E. O’Connor; Michael Shuster; Clifton W. Callaway; Brett Cucchiara; Jeffrey D. Ferguson; Thomas D. Rea; Terry L. Vanden Hoek
New Developments in Resuscitation Science Since 2005
Free Full Text from Circulation with link to PDF Download

^[2] Vasopressors
2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science
Part 8: Adult Advanced Cardiovascular Life Support
Part 8.2: Management of Cardiac Arrest
Medications for Arrest Rhythms
Free Full Text from Circulation with link to PDF Download

^[3] Cardiac resuscitation.
Eisenberg MS, Mengert TJ.
N Engl J Med. 2001 Apr 26;344(17):1304-13. Review. No abstract available.
PMID: 11320390 [PubMed - indexed for MEDLINE]

Free Full Text with link to Free Full Text PDF Download

^[4] Controversial Topics from the 2005 International Consensus Conference on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations.
Nolan JP, Hazinski MF, Steen PA, Becker LB.
Resuscitation. 2005 Nov-Dec;67(2-3):175-9. No abstract available.
PMID: 16324986 [PubMed - indexed for MEDLINE]

Free Full Text from Circulation

^[5] EPIPEN (epinephrine) injection
EPIPEN JR (epinephrine) injection
[DEY]
DailyMed
FDA Label

Filed Under: ACLS, Epinephrine, Heresy, Mythology, Pharmacology, Research

What Will Be the Next Standard Of Care We Eliminate

Wed, 28 Mar 2012 08:00:46 +0000 By Rogue Medic 17 Comments

We have too many harmful Standards Of Care. Which will be the next to go?

Will it be Spinal Immobilization using a long spine board, straps, head blocks, and a cervical collar?

Will it be epinephrine in cardiac arrest?

Will it be amiodarone or lidocaine in cardiac arrest?

Will it be ventilations by EMS in cardiac arrest?

Will it be the idea that any treatment can become the Standard Of Care without any evidence of improvement in patient outcomes?

None of these have any evidence that they improve outcomes.

We have put ourselves in a difficult situation, where people claim that it would be unethical to find out if these treatments work. If medicine is about providing the best care to patients, then how can we use fashion to determine what is required patient care, even when all of the research shows that the Standard Of Care is harmful?

From the very beginning of the use of amiodarone in cardiac arrest, the idea of making amiodarone a Standard Of Care was rejected by emergency physicians.

AAEM Position Statement: Use of Amiodarone in Refractory Pulseless VT/VF
“It is the position of the American Academy of Emergency Medicine that the use of amiodarone in refractory pulseless ventricular tachycardia or ventricular fibrillation (VT/VF) should not be considered the current ‘standard of care’ for this condition. The Academy does not condemn non-research use of amiodarone given the absence of any proven beneficial alternatives, however, there is currently no reason to conclude that its use is mandatory or represents a ‘standard of care.’ Until ongoing or future research clarifies this issue, emergency physicians should use their own discretion regarding antiarrhythmic therapy in patients with cardiac arrest.”^[1]

Has anything changed?

Where is the survival research that was supposed to convince us that amiodarone did not just result in more people dying in the hospital?

They state this about High-Dose Epinephrine (HDE) –

Although it was assumed by some that a medication that is associated with improved ROSC and survival to hospital admission would also be associated with improved survival to hospital discharge and neurologic recovery, this was never the case with HDE. Subsequent studies confirmed that HDE in adult victims of cardiac arrest is not associated with an improvement in patient survival to hospital discharge or neurologic recovery (14-20). As a result, the use of high dosages of epinephrine is no longer recommended in the most recent Guidelines (5). =[1]

Does the AAEM consider the ACLS Guidelines to set the Standards Of Care?

Conclusion: This Working Group finds that the use of amiodarone in refractory pulseless VT/VF should not be considered “standard of care” for this condition. Indeed, it could be argued that amiodarone should only be used in cardiac arrest (if at all) in the context of further study protocols. Nevertheless, the Working Group believes it would be inappropriate to condemn non-research use of amiodarone, given the absence of any proven beneficial alternatives. On the other hand, there is certainly no reason to conclude that its use is mandatory, or represents a “standard of care.” Ongoing and future studies may clarify this issue, but until such time, emergency physicians should use their own discretion regarding antiarrhythmic therapy in patients with cardiac arrest.=[1]

Apparently not.

How long did it take to even start a study looking at survival from cardiac arrest with groups randomized to amiodarone, and placebo (with lidocaine thrown in as a crowd favorite in some areas)?

Why are we going to have results from this study?

Drug: amiodarone

300 mg will be given IV/IO push for reoccurrence of ventricular fibrillation or pulseless ventricular tachycardia after 1 or more shocks. A second dose of 150 mg will be given if VF/pulseless VT reoccurs after initial dose and a subsequent shock. The initial dose for patients estimated to be less than 100 pounds will be 150 mg, followed by a second dose of 150 mg if the VF/pulseless VT persists.
Other Name: PM 101, Nexterone^[2]

It is interesting that there is no mention of epinephrine. Based on the attitude of the investigators toward epinephrine, I don’t think they will be omitting that drug, but there is no mention of epinephrine, or any other pressor, in the study description.

Detailed Description:
The primary objective of the trial is to determine if survival to hospital discharge is improved with early therapeutic administration of a new Captisol-Enabled formulation of IV amiodarone (PM101) compared to placebo.

The corresponding null hypothesis is that survival to hospital discharge is identically distributed when out-of-hospital VF/VT arrest is treated with PM101 or placebo.

The secondary objectives of the trial are to determine if survival to hospital discharge is improved with early therapeutic administration of:

Lidocaine compared to placebo

PM101 compared to lidocaine The corresponding null hypotheses are that survival to hospital admission is identically distributed when out-of-hospital VF/VT arrest is treated with lidocaine as compared with placebo, and with PM101 as compared with lidocaine.^[2]

This study is expected to last 3 years and enroll 3,000 patients in three arms in an attempt to refute what people have been saying since the 1990s – Amiodarone just changes the location of death.

September 2015 is the estimated completion date, so this is unlikely to affect the next revision of ACLS (Advanced Cardiac Life Support) Guidelines.

Footnotes:

^[1] Position Statement on the Use of Amiodarone in Refractory Pulseless VT/VF
The AAEM Amiodarone for Refractory VT/VF Working Group is comprised of Amal Mattu, MD FAAEM, Carey Chisholm, MD FAAEM, and Jerome R. Hoffman, MA MD FAAEM.
American Academy of Emergency Medicine
Position Statements
May 5, 2001
Position Statement

^[2] Amiodarone, Lidocaine or Neither for Out-Of-Hospital Cardiac Arrest Due to Ventricular Fibrillation or Tachycardia (ALPS)
ClinicalTrials.Gov
Last Updated on September 21, 2011
ClinicalTrials.gov Identifier: NCT01401647
Trial data

Filed Under: ACLS, Heresy, Pharmacology, Research

Did Drugs Kill Whitney Houston

Mon, 13 Feb 2012 20:35:02 +0000 By Rogue Medic Leave a Comment

As with the death of Michael Jackson, this is not a call you want to be on, because everybody is going to be second-guessing everything that was done, but let’s assume that you are dispatched.

Law enforcement sources tell TMZ … multiple medicine bottles were found in the Beverly Hills hotel room where Whitney Houston died … but we’re told there were NOT a lot of pills at the scene.^[1]

there were NOT a lot of pills at the scene.

This suggests that a lot of pills were taken, but does not tell us over what time period?

How many pills should have been in the containers if the pills were taken as prescribed?

Among the pills … ibuprofen (painkiller), Xanax (anti-depressant), Midol (for menstrual cramps), amoxicillin (for treating bacterial infections) … and more.^[1]

Ibuprofen and Midol are sometimes the same thing, but Midol comes in so many different formulations, that you cannot tell without knowing the specific version.^[2] I did not know there were so many different drugs sold under essentially the same name. Besides, I use chocolate to keep my inner woman from PMSing.

The ones that catch my eye are – . . . Xanax … and more.

What is Xanax?

Xanax is the brand name for alprazolam, a benzodiazepine. Other benzodiazepines are drugs we commonly carry – diazepam (Valium), midazolam (Versed), and lorazepam (Ativan). Treatment of benzodiazepine overdose is supportive care (maintain oxygenation and ventilation, and maintain blood pressure). There is a competitive antagonist, flumazenil (Romazicon), but flumazenil does not bring benzodiazepine overdoses back from the dead any more than naloxone (Narcan) brings heroin overdoses back from the dead. The treatment for opioid overdose is also supportive care.

Absorption
Following oral administration, alprazolam is readily absorbed. Peak concentrations in the plasma occur in 1 to 2 hours following administration. Plasma levels are proportionate to the dose given; over the dose range of 0.5 to 3.0 mg, peak levels of 8.0 to 37 ng/mL were observed. Using a specific assay methodology, the mean plasma elimination half-life of alprazolam has been found to be about 11.2 hours (range: 6.3–26.9 hours) in healthy adults.^[3]

11+ hours can be a long time. Xanax XR (eXtended Release) does not appear to prolong the clearance of alprazolam, only the onset. What can affect the rate of elimination of alprazolam?

Metabolism/Elimination
Alprazolam is extensively metabolized in humans, primarily by cytochrome P450 3A4 (CYP3A4), to two major metabolites in the plasma: 4-hydroxyalprazolam and α-hydroxyalprazolam.^[3]

A lot of the technical drug information is not important, but the cytochrome P450 metabolism is important in the elimination of a lot of medications

CYP3A4 is a member of the cytochrome P450 superfamily of enzymes. . . . This enzyme is involved in the metabolism of approximately half the drugs that are used today, including acetaminophen, codeine, ciclosporin, diazepam, and erythromycin. . . . Most drugs undergo deactivation by CYP3A4, either directly or by facilitated excretion from the body. Also, many substances are bioactivated by CYP3A4 to form their active compounds, and many protoxins being toxicated into their toxic forms^[4]

Grapefruit juice can slow down metabolism by about half, so some consumer sites may recommend that people drink grapefruit juice to cut down on the cost of medications. This really is not a great idea, since it may affect other medications. It is something to discuss with a doctor, so that your doctor is aware of things that may interact with the medications you are taking, but doctors should do that anyway.

One interesting item that does not appear to be related to CYP3A4 metabolism. It makes me wonder about the effect flumazenil might have on smokers. There is no mention of smoking or cigarettes on the flumazenil label.^[5]

Cigarette Smoking
Alprazolam concentrations may be reduced by up to 50% in smokers compared to non-smokers.^[4]

We’re told some of the pills were old … some issued in 2011 … but some of the bottles were from 2012.^[1]

As long as a month and a half ago? Some people have milk and eggs that are that old, too. The medications should age much better than dairy products.

A prescription for alprazolam is often written as PRN (Pro Re Nata – Latin for according to the circumstances, or to be taken as needed). Alprazolam is an anti-anxiety drug that has addiction potential, just as with other GABA (GammaAminoButyric Acid) agonists (such as benzodiazepines and alcohol).

A PRN prescription that is more than a month old is not a problem. A prescription that is empty too soon is much more likely to be a problem. One problem with PRN prescriptions is that we usually do not know how quickly the patient has been taking them, so we do not know how many should be in the pill bottle. Some people do not want others to know that they are taking medication to manage anxiety (Tony Soprano), so their family may not even know they have a prescription for these medications.

In other words, with PRN medications, it is difficult to determine if too much has been taken

The acute oral LD50 in rats is 331–2171 mg/kg. Other experiments in animals have indicated that cardiopulmonary collapse can occur following massive intravenous doses of alprazolam (over 195 mg/kg; 975 times the maximum recommended daily human dose of 10 mg/day).^[3]

Prescriptions often come in a pill bottle that contains 100 pills of 0.5 mg, 1 mg, or 2 mg strengths. It is unlikely that a dose of even 200 mg would be enough by itself to kill a person.

General Treatment of Overdose
Overdosage reports with XANAX Tablets are limited. As in all cases of drug overdosage, respiration, pulse rate, and blood pressure should be monitored. General supportive measures should be employed, along with immediate gastric lavage. Intravenous fluids should be administered and an adequate airway maintained. If hypotension occurs, it may be combated by the use of vasopressors. Dialysis is of limited value. As with the management of intentional overdosing with any drug, it should be borne in mind that multiple agents may have been ingested.^[3]

With any potential overdose, always assume that other drugs/poisons have been taken.

We should use the Plus One Rule –

We should assume that there is at least one drug that we do not know about that the patient has taken. If we find out about more medication, wed still should assume that there is something that the patient has taken that we do not know about. The same rule applies to weapons. We should always assume that a violent/potentially violent patient has at least one weapon that we do not know about. Especially after they have been searched by police or prison personnel.

We should not expect antidotes to work the same way in dead patients as they do in living patients.^[6]

General supportive measures should be employed, along with immediate gastric lavage.

Lavage (pumping the stomach) is not something EMS should be doing. Inducing vomiting is a bad idea in a patient who may not be able to protect her airway – even with an endotracheal tube in place.

Intravenous fluids should be administered and an adequate airway maintained. If hypotension occurs, it may be combated by the use of vasopressors.

Always use fluids for hypotension before pressors, unless fluids are contraindicated, or unless a pressor is specifically indicated, even with acute CHF (Congestive Heart Failure).

Did drugs kill Whitney Houston?

I don’t know, but the drugs listed in this article probably did not kill her.

Footnotes:

^[1] Whitney Houston – Few Pills Recovered at Death Scene
TMZ
2/13/2012 7:45 AM PST by TMZ Staff
Article

^[2] Midol
Wikipedia
Article

As with cough and cold medicine, it is important to read the label to know what you are getting

The “Midol Complete” formulation consists of:

Acetaminophen 500 mg (Pain Reliever)
Caffeine 60 mg (Stimulant)
Pyrilamine Maleate 15 mg (Antihistamine)

The “Extended Relief” formulation consists of:

Naproxen Sodium 220 mg (NSAID, Pain Reliever/Fever Reducer)

The “Teen” formulation consists of:

Acetaminophen 500 mg (Pain Reliever)
Pamabrom 25 mg (Diuretic)

The “Liquid Gels” formulation consists of:

Ibuprofen 200 mg (Pain Reliever)

The “PM” formulation consists of:

Acetaminophen 500 mg (Pain Reliever)
Diphenhydramine citrate 38 mg (Sedative antihistamine)

^[3] XANAX (alprazolam) tablet
[Pharmacia and Upjohn Company]
DailyMed
NLM
FDA label

^[4] CYP3A4
Wikipedia
Article

Large list of drugs that affect CYO3A4 metabolism.

^[5] FLUMAZENIL injection, solution
[Baxter Healthcare Corporation]
DailyMed
NLM
FDA label

^[6] Dissecting the ACLS Guidelines on Cardiac Arrest from Toxic Ingestions
Rogue Medic
Tue, 01 Nov 2011
Article

Filed Under: ACLS, Heresy, Pharmacology

A Better Way to Locate the Closest AED

Thu, 09 Feb 2012 12:45:08 +0000 By Rogue Medic 1 Comment

In having to come up with games, or other methods of locating AED (Automated External Defibrillators), we are trying to solve a system design problem that might be as simple as an equipment design problem.

Maybe the answer is to put RFID (Radio Frequency IDentification) chips in each of the AEDs. Last night I was discussing this with Brandi Winemiller and she suggested that I write more about this.

RFID is usually short range, but the signal can be picked up at longer distances with the right equipment. Then it becomes a problem of where to place equipment to locate RFIDs or what type of mobile equipment to use and how to use it. RFID is easier to keep up to date than running the occasional contest.

Image credit.

If people willing to do CPR are encouraged in CPR courses to download an application that helps to locate the closest AED, that would bring the information to the target audience. The information might be from the AED itself, or from the mapping application, or both. Maybe RFID is the wrong technology, but it is certainly worth considering.

One application is AED4 US.

CPR only requires compressions (CPR/ACLS guidelines admit this is true for bystander CPR, but fear prevents the admission that the same is true for EMS and hospital personnel), so we could use a lot of the course time to teach AED use. Since teaching continuous compressions and AED use does not require a lot of time, we could shorten the courses significantly.

The video cannot be shown at the moment. Please try again later.

If the CPR course is shortened and simplified, then mobile CPR teaching might be a better way to bring the knowledge to the people who might use it. We need to get over our fascination with ventilation in cardiac arrest and the pit crew approach that is justified by the lack of understanding of the lack of benefit of ventilations.^[1]

CPR can be nice and simple and be even more effective than when we complicate things, but we continue to keep our resuscitation rates down just to satisfy the people who don’t understand.

CPR is not about the instructors.

CPR is not about the students.

CPR is about the patients.

Hands-Only CPR

1) Call 911

2) Push hard and fast

3) And use an AED

Resuscitation does not need to be more complicated than this.

Footnotes:

^[1] Vinnie Jones’ hard and fast Hands-only CPR
Rogue Medic
Wed, 11 Jan 2012
Article

Filed Under: ACLS, AED, Heresy

Would You Know Where to Find an AED If You Need One

Wed, 08 Feb 2012 17:00:49 +0000 By Rogue Medic 5 Comments

There is a contest in Philadelphia to map locations of all of the AEDs (Automated External Defibrillators) in the county –

$10,000 prize.

Who can map the most AEDs by March 13, 2012?

The MyHeartMap Challenge, which will run until Mar. 13, aims to draw awareness to automatic external defibrillators in the Philadelphia county. Through a scavenger hunt open to the public, the contest offers monetary prizes to groups that can locate the most defibrillators — machines that release electric shocks to the heart to restore normal heart rhythms after cardiac arrest.^[1]

Ooh! Ooh! I found one!

Image credit.

“This will be the first AED map in a U.S. city by the public that would be comprehensive for the public,” said Raina Merchant, co-director of MyHeartMap and an Emergency Medicine professor at the Medical School.^[1]

The medical school? In Philadelphia? There are Temple, Einstein, Jefferson, Drexel/Hahnemann, PCOM (Philadelphia College of Osteopathic Medicine), and HUP (Hospital of the University of Pennsylvania). As I explain to people, when I am criticizing the almost epidemic lack of understanding of medicine – You can’t swing a Philadelphia lawyer without hitting a medical school, so how do they get away with such ignorance? There is not just one medical school. The people at this medical school may not consider the other medical schools to be real medical schools, but that is nonsense. I searched for Dr. Merchant and found that she is at HUP.

“I ran up to a 50-year-old gentleman who had collapsed on the street and I assessed him, but he didn’t have a pulse,” he said. “A nurse helped me start CPR while I called for a defibrillator,” he added. But in spite of searching a big restaurant and CVS, they could not find an AED right away.^[1]

One clue would be to look in places that have a lot of people working there – large office buildings are some of the best places. Nursing homes should have AEDs, but do not expect them to let you use their AED.

“Starting at a local level, making the 911 services aware of where AEDs are is a good first step,” Merchant said.^[1]

No. In Pennsylvania all ambulances are required to carry an AED or a manual defibrillator. Why would EMS need to know where an AED is? Did I mention that all ambulances must have at least an AED.

Just because EMS shows up does not mean that EMS will be smart enough to actually provide appropriate treatment. With all of the time we spend training on CPR (CardioPulmonary Resuscitation), we should be able to remember to start compressions and to quickly deliver a shock, but my off-duty experiences with cardiac arrest suggest otherwise.

I dealt with some basic EMT, who insisted that delivering a shock on moist ground is deadly. He was wrong then. He is still wrong. We moved the patient to a backboard made of plastic, which should have satisfied the fool, but he appears to have been more interested in demonstrating that He was in charge, than in patient care. Then the patient was moved to the ambulance and He came up with some other excuse for not shocking the patient. It might have been – I’m not doing anything until the medic shows up! Any basic EMT who ever uses this excuse to not treat a patient should be fired on the spot. This clown was not fired. He was in charge.^[2]

Another off-duty cardiac arrest was almost as bad. The only difference is that the patient survived and had a good outcome, even though police and EMS did almost everything they could to avoid delivering a shock to the patient. I may tell about that another time.

I hope that my anecdotal experiences are just a couple of unusually bad cases. I hope that most patients receive better care. At about a year ago, Kelly Grayson and Too Old To Work, Too Young To Retire had a similar call, but they had a much more professional response from EMS in New Jersey.^[3]

Footnotes:

^[1] Med School scavenger hunt hopes to spread awareness about cardiac arrest
The Daily Pennsylvanian
By David Britto
January 31, 2012, 11:12 pm
Article

^[2] Off Duty CPR in the Middle of the Road
Rogue Medic
Mon, 24 Mar 2008
Article

^[3] Blogger Save!
A Day in the Life of an Ambulance Driver
Mon, 24 Mar 2008
Article