Pharmacology | Rogue Medic

If you have a BVM (Bag Valve Mask resuscitator), you should not need naloxone. The problem is inadequate respiration, not inadequate naloxonation.

- Rogue Medic

Glucose before Thiamine for Wernicke Encephalopathy – A Literature Review

Tue, 24 Apr 2012 18:30:26 +0000 By Rogue Medic 3 Comments

I used to have protocols that insisted that thiamine (Vitamin B₁) be given before glucose.

Prolonged thiamine deﬁciency can lead to the development of Korsakoff syndrome, characterized by permanent mental impairment with confabulation and memory deﬁcits.^[1]

Maybe that explains how the requirement for thiamine before glucose came about – confabulation. Many of our traditional treatments are better explained by ~~narrative fallacy~~ confabulation, based on a persuasive hypothesis, than by any evidence of benefit to the patient.

in starvation, when glucose stores are depleted, the brain suffers most acutely as it relies almost entirely on glucose for energy and there is little thiamine available to act as cofactor for the conversion of any small amount of remaining glucose to ATP.^[1]

How should that affect patient care?

The prevailing teaching in medical school curricula and in medical textbooks is that if thiamine deﬁciency is suspected, thiamine supplementation should be given before administering glucose (10,11). The theory behind this is that if a thiamine-deﬁcient patient is given a glucose load, meager thiamine stores would rapidly be exhausted, glycolysis further limited, and Wernicke encephalopathy would promptly ensue (9,12–14). ^[1]

Reference 10 is the 6^th edition (2004) of the Emergency Medicine Manual by Tintinalli. Something that would be accepted as an authoritative reference by many people.

The 19 articles reviewed included expert opinion (n = 2), case reports (n = 13), and animal models (n = 4).^[1]

In other words – nothing.

They found an old expired expert opinion, some case reports that should generate some hypotheses for research, and some animal models that also should generate some hypotheses for further research, but nothing that should be the basis of treatment of humans.

The animal studies were rated the best overall, with outstanding quality,^[1]

Old McDonald would be thrilled.

Google and Google Scholar search identiﬁed 1 additional non-peer-reviewed report (Gussow, 2007) ^[1]

Gussow?

Incidentally, there is evidence that thiamine is taken up and utilized by cells significantly more slowly than is glucose, taking away even a theoretical justification for the thiamine-before-glucose canard.^[2]

Dr. Leon Gussow writes The Poison Review and has reviewed this paper.^[3] He provides a lot of useful information in his original paper from 5 years ago.^[2]

The most often cited source claiming a link between glucose loading and acute onset of Wernicke encephalopathy in thiamine-deﬁcient patients is a four-case series by Watson et al. from 1981 (9). However, as pointed out by Hack and Hoffman in 1998, none of these cases involved the acute administration of glucose (20).^[1]

The most often cited source – only four patients – and none of them received the treatment being referenced.

Do any of these people read the paper before citing it?

Do any of these people understand the difference between giving a treatment and not giving a treatment?

Maybe there are valid reasons for citing a paper that is completely irrelevant.

Maybe.

All other cases clearly showed deterioration in mental status after prolonged or massive (>2 L of 5%) glucose infusion, or showed evidence of Wernicke encephalopathy before glucose administration.^[1]

>2 L of 5% glucose is more than four 50 ml ampules of D50W (Dextrose 50% in Water). I have never given close to that much to any one patient.

So although the evidence does not support rapid deterioration after glucose administration, it likewise does not seem to support the lack of rapid deterioration.^[1]

Because we are in a largely evidence-free zone.

We can make all sorts of claims – as long as we do not expect to use any good evidence to support these claims.

Since we are not using evidence, we should ignore the following suggestion from the authors.

Patients with hypoglycemia should be restored to normoglycemia as quickly as possible (repeated dosing of dextrose 50% in adults until normoglycemia is achieved).^[1]

Where is there any evidence that 50% dextrose is any better than an infusion of 10% dextrose?

After demonstrating the lack of evidence supporting one tradition, they blithely encourage adherence to a different tradition. There is no good reason for us to be giving such hyperosmolar fluids peripherally. If we are going to use a peripheral line, we should be using a much more dilute form of dextrose. The total amount of dextrose administered will be significantly less. The risk of extravasation will be less. The cost will be less. The treatment time will not be different.

10% dextrose is a much better idea than 50% dextrose.

Both the median total dose of dextrose administered and post-treatment blood sugar level were significantly higher in the 50% group, and these subjects were more likely to have received the maximum permitted dose of 25 g (table 2).^[4]

Equal benefit with 10% dextrose, but less likelihood of harm.

We continue to use 50% dextrose because . . . ?

Image source.

Two of the subjects contacted by the researchers after treatment reported that before the study they had often had difficulty bringing their blood glucose back to their expected usual level after being treated by paramedics using 50% dextrose.^[4]

We need to question more of our traditional treatments.

Thanks to Christopher Watford of EMS 12 Lead and My Variables Only Have 6 Letters for bringing this to my attention.

Footnotes:

^[1] Glucose before Thiamine for Wernicke Encephalopathy: A Literature Review.
Schabelman E, Kuo D.
J Emerg Med. 2012 Apr;42(4):488-94. Epub 2011 Nov 21.
PMID: 22104258 [PubMed - in process]

^[2] Myths of Toxicology: Thiamine Before Dextrose
Gussow, Leon MD
Emergency Medicine News:
April 2007 – Volume 29 – Issue 4 – pp 3,11
doi: 10.1097/01.EEM.0000269582.88746.7d
Toxicology Rounds
Free Full Text from Emergency Medicine News

^[3] Myths and misconceptions of Wernicke’s encephalopathy: what every emergency physician should know.
Donnino MW, Vega J, Miller J, Walsh M.
Ann Emerg Med. 2007 Dec;50(6):715-21. Epub 2007 Aug 3. Review.
PMID: 17681641 [PubMed - indexed for MEDLINE]

Free Full Text in PDF format from ENA.org

^[4] Dextrose 10% or 50% in the treatment of hypoglycaemia out of hospital? A randomised controlled trial.
Moore C, Woollard M.
Emerg Med J. 2005 Jul;22(7):512-5.
PMID: 15983093 [PubMed - indexed for MEDLINE]

Free Full Text from PubMed Central

Schabelman, E., & Kuo, D. (2012). Glucose before Thiamine for Wernicke Encephalopathy: A Literature Review The Journal of Emergency Medicine, 42 (4), 488-494 DOI: 10.1016/j.jemermed.2011.05.076

Moore, C. (2005). Dextrose 10% or 50% in the treatment of hypoglycaemia out of hospital? A randomised controlled trial Emergency Medicine Journal, 22 (7), 512-515 DOI: 10.1136/emj.2004.020693

Filed Under: Heresy, Mythology, Pharmacology, Research Blogging

Preventing Medication Errors from Gathering of Eagles

Tue, 17 Apr 2012 13:45:55 +0000 By Rogue Medic 18 Comments

There are some interesting case studies in this presentation.^[1]

1. Rule out seizures, patient is waking up, then becomes combative, medication given IM (IntraMuscularly), combativeness continues, combativeness resolves, everything seems OK.

Later, the empty medication is found to be morphine, not midazolam (Versed).

There is a problem in giving the wrong medication. We need to be more careful about what we give.

Just because the packaging looks the same does not mean the contents are even remotely similar.

2. Rule out hypoglycemia, medication given IV (IntraVenously), but it was sodium bicarbonate, rather than D50W (50% dextrose), then D50W was given.

Similar appearance does not mean the drug is the same.

3. Rule out extrapyramidal reaction to psychiatric medications, medication given IV, the medication was 10 mg morphine, medical command was contacted, the appropriate 50 mg of diphenhydramine (Benadryl) was given.

Appearances can be deceiving.

We trust what we think we see, but our brains jump to conclusions on insufficient evidence. We need to find ways to prevent us from misleading ourselves.

It is interesting that morphine is the drug accidentally given in two of the three cases. It is expected that the morphine and midazolam would be stored together. The diphenhydramine might be stored with the controlled substances to make it easier to treat histamine release from morphine administration. There is plenty of time to get diphenhydramine after noticing a reaction to morphine. I do not know of any cases of anaphylactic reactions to morphine. Keeping the diphenhydramine with the morphine does not improve patient safety. If the controlled substances need to be opened each time that diphenhydramine is given, that is probably not going to please the DEA (Drug Enforcement Administration, the controlled substances oversight organization in the US).

The good news is that the sodium bicarbonate is probably only going to result in some hyperventilation to blow off the CO₂ (Carbon diOxide) produced by the breakdown of sodium bicarbonate.

The boxes do not look the same, but . . .

. . . the syringes do look alike (except for the identifying labels).

All the fear of giving too much morphine , but when 10 mg IV morphine is given to somebody who has no medical indication for morphine, there are no complications at all.

None.

10 mg morphine was harmless, but some doctors still worry about giving 2 mg without orders.

The medical education provided by some medical schools has some blatant gaps in the area of pain management and pharmacology.

Some medics still worry about giving 2 mg without orders.

The medical education provided by some paramedic schools also has some blatant gaps in the area of pain management and pharmacology.

Footnotes:

^[1] Preventing Medication Errors
Gathering of Eagles 2012
Page with links to presentations

Filed Under: Heresy, Morphine, Pharmacology

Comments on Cardioversion – 2010 ACLS – Part II

Mon, 16 Apr 2012 15:35:01 +0000 By Rogue Medic Leave a Comment

In response to Cardioversion – 2010 ACLS – Part II, there are some new comments. Chris from Sweden, had written -

What meds do you use in the hypotensive, but still conscious patient for sedation? Could ketamine and low dose of midazolam be of use here?

Gerardo Gastélum comments –

Not Ketamine for cardioversion. Ketamine rises heart rate and coronary O2 requirements.

Benzos like Midazolam or Diazepam + Opiates such as Fentanyl or Morphine can do the works. AHA also recomends etomidate, thiopental and propofol, but out of these I chose etomidate due to it´s cardiovascular stability.

I disagree.

There may be more of a desire to avoid sedatives that vasodilate and depress cardiac activity. This is one of the reasons that etomidate is recommended. I think that either effect is going to be short-term – if the cardioversion, or series of cardioversions, works.

Some people discourage sedation. One of the things that they do not appear to consider is the possibility of needing to cardiovert more than once.

I can get away with shocking her without sedation, justify it as saving her life, and sedate her afterward to deal with the side effects of such brutal treatment, but the idea of appropriate sedation prior to cardioversion almost scares me into an unstable tachycardia.

Fortunately, nobody here is recommending that we not sedate for cardioversion.

With comments on this topic, I tend to wonder, Has this been covered in an EMCrit podcast? What would Dr. Scott Weingart do? Maybe he can make up some EMCrit screensavers with the slogan WWWD? (What Would Weingart Do?). Dr. Weingart is trying to smooth the transition from treatment in the ED (Emergency Department) to treatment in the ICU (Intensive Care Unit) and possibly take over the world of emergency education.

I think the clever something to give is probably a low dose of etomidate, maybe 5 or 7 mg of etomidate. They’re not going to be fully unconscious, like when we gave the 10 or 15 mg, but it’ll take the edge off.

They’re getting no pain control whatsoever from that, so if you were really a smart guy, give a little etomidate with some ketamine, or even just ketamine alone.^[1]

Listen to the whole podcast – all 9 minutes of it. I just copied a few sentences, but this very short podcast covers a lot of material that is very important to understand before dealing with the unstable tachyarrhythmia patient.

Image credit.

In the second comment, Gerardo Gastélum provides a quote from the 2010 ACLS guidelines that is important for the understanding of the difference between unstable and just symptomatic.^[2]

Thank you for the great description from ACLS.

Footnotes:

^[1] EMCrit Podcast 20 – The Crashing Atrial Fibrillation Patient
by EMCRIT on FEBRUARY 12, 2010
Podcast page

^[2] Management of Symptomatic Bradycardia and Tachycardia
2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science
Part 8: Adult Advanced Cardiovascular Life Support
Part 8.3: Management of Symptomatic Bradycardia and Tachycardia
Free Full Text from Circulation

Unstable and symptomatic are terms typically used to describe the condition of patients with arrhythmias. Generally, unstable refers to a condition in which vital organ function is acutely impaired or cardiac arrest is ongoing or imminent. When an arrhythmia causes a patient to be unstable, immediate intervention is indicated. Symptomatic implies that an arrhythmia is causing symptoms, such as palpitations, lightheadedness, or dyspnea, but the patient is stable and not in imminent danger. In such cases more time is available to decide on the most appropriate intervention. In both unstable and symptomatic cases the provider must make an assessment as to whether it is the arrhythmia that is causing the patient to be unstable or symptomatic. For example, a patient in septic shock with sinus tachycardia of 140 beats per minute is unstable; however, the arrhythmia is a physiologic compensation rather than the cause of instability. Therefore, electric cardioversion will not improve this patient’s condition. Additionally, if a patient with respiratory failure and severe hypoxemia becomes hypotensive and develops a bradycardia, the bradycardia is not the primary cause of instability. Treating the bradycardia without treating the hypoxemia is unlikely to improve the patient’s condition. It is critically important to determine the cause of the patient’s instability in order to properly direct treatment. In general, sinus tachycardia is a response to other factors and, thus, it rarely (if ever) is the cause of instability in and of itself.

One of my earliest posts was a variation on the distinction between unstable and symptomatic –

Cardioversion – I’m not doing that, you do it!

Filed Under: 2010 AHA Guidelines, Cardioversion, EMCrit, Pharmacology, Sedation

Most Common Cause of Death in Anaphylaxis is Failure to Give Epinephrine

Thu, 12 Apr 2012 22:44:57 +0000 By Rogue Medic 2 Comments

The most common cause of death in anaphylaxis is failure to give epinephrine.

That is according to Dr. Corey Slovis, presenting at the 2012 Gathering of Eagles Conference.^[1]

This is shocking news. Where do we have any evidence of that?

Although five of the six children and adolescents had experienced definite allergic reactions to the incriminated food on previous occasions, none had had a near-fatal reaction.^[2]

No problem. There is no reason to expect that they will have a severe reaction this time, either.

Well, we can always use epinephrine to resuscitate them.

Near-fatal reactions were not that much better.

Three of the six children and adolescents appeared to be improving before the occurrence of terminal cardiorespiratory arrest.^[2]

With anaphylaxis, symptoms can mislead. Do not underestimate the condition of patients who have a history of anaphylaxis.

What did they have in common?

All the patients received epinephrine and appropriate medical care once they reached a hospital emergency room, but by then all were unresponsive and had had extended hypoxia and hypotension.^[2]

All the patients had asthma and were taking bronchodilator medications.^[2]

The asthma in all but one of the patients with nonfatal reactions appeared to be well controlled by medication, whereas two patients with fatal reactions and one with a nonfatal reaction had serious wheezing in the two weeks before the anaphylactic reaction.^[2]

All the patients had a history of serious anaphylactic reactions to food, and all but two had had such reactions to the food responsible for the fatal or near-fatal reaction.^[2]

A history of anaphylaxis is a good reason to give epinephrine to someone with minor, or moderate, symptoms. I will assume that nobody is withholding epinephrine from patients with severe symptoms.

Do we need to give an auto-injector, or an intramuscular injection?

No. We can approach this more gradually with a slow epinephrine drip –

1 mg in 1 liter starting at 1 ml per minute.

Corrected at 12:15 4/13/2012 from 1 mg in 1 ml starting at 1 ml per minute. It is 1 mg in 1,000 ml (1 liter) starting at 1 ml per minute. Thank you to Jeffrey R. Vaughn and Tony Heibel for pointing this out.

The starting dose epinephrine by IV infusion is 1-2 micrograms/minute.^[1]

If there is no protocol for this, calling medical command is always an option. Even though there may be systems that foolishly forbid medics from deviating from protocol with orders from medical command.

None of the patients were aware that the implicated allergen was in the food they ate, indicating that attempts at strict avoidance are often unsuccessful.^[2]

Even if the patient does not know of an exposure, there can still be a deadly exposure.

Too simple? Not simple enough? Just right?

Another explanation of how to treat anaphylaxis.^[3]

Read the PDF^[1] and listen to the recording from Free Emergency Medicine Talks and you should become comfortable with it.

Footnotes:

^[1] Using IV Epinephrine Expertly
Dr. Corey Slovis
2012 Gathering of Eagles
Presentation in PDF format

Care of the Wheezing Patient – Slovis, from Free Emergency Medicine Talks

^[2] Fatal and near-fatal anaphylactic reactions to food in children and adolescents.
Sampson HA, Mendelson L, Rosen JP.
N Engl J Med. 1992 Aug 6;327(6):380-4.
PMID: 1294076 [PubMed - indexed for MEDLINE]

Free Full Text from NEJM

^[3] Anaphylactic reactions – 5 things.
Sunday, September 4, 2011
Doc Cottle’s Desk
Article

Sampson, H., Mendelson, L., & Rosen, J. (1992). Fatal and Near-Fatal Anaphylactic Reactions to Food in Children and Adolescents New England Journal of Medicine, 327 (6), 380-384 DOI: 10.1056/NEJM199208063270603

Filed Under: Assessment, Epinephrine, Pharmacology, Research Blogging

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

Should We Start Using a Glucose-Insulin-Potassium Cocktail

Wed, 04 Apr 2012 14:40:18 +0000 By Rogue Medic 2 Comments

For two weeks straight, JAMA released EMS-related papers that received a lot of attention from the media. A clear, irrefutable trend.

OK, this paper is just an early release of a paper that is only available online.

Those unfamiliar with research have been making the usual exaggerated claims that come from wishful thinking and not considering the possible harm from rushing to adopt a treatment based on weak evidence.

Should we rush to make this a standard treatment, that will become a Standard Of Care through inertia and tradition?

No.

Ignore the media.

There are some other things to consider. This study is examined clearly and thoroughly by a couple of very trustworthy doctors on their blogs.^[1] ^[2]

For some different perspective, look at a graph of the numbers of patients involved and the tiny benefit –

Click on graphs to make them larger.

OK. We can ignore that the study was originally supposed to be large enough to produce statistically significant results – 15,450 people.

We can ignore that the resulting number of patients is only 6.7% of the original and that the error bars on the results are frequently much larger than the possible benefit of treatment.

Even looking at just the patients enrolled, the possible benefit loses significance after discharge.

Do we want a repeat of epinephrine?

Half a century of lack of survival benefit based on an unimportant surrogate endpoint. Is appeal to the Standard Of Care anything other than a logical fallacy?

We can provide a statistically significant benefit that disappears when you leave the hospital.

Even the authors do not make exaggerated claims.

Further studies are needed to assess the out-of-hospital use of GIK as therapy for patients with ACS.^[3]

Maybe we should listen to the authors encouragement to not read too much into this study. Studies of 20,000 earlier patients did not show benefit. Further study is needed, not further hype.

Go read -

The IMMEDIATE trial: Should EMS give Glucose-Insulin-Potassium?

and

Glucose-Insulin-Potassium For MI?

Footnotes:

^[1] The IMMEDIATE trial: Should EMS give Glucose-Insulin-Potassium?
Mill Hill Ave Command
Wednesday, March 28, 2012
Article

^[2] Glucose-Insulin-Potassium For MI?
EM Literature of Note
Friday, March 30, 2012
Article

^[3] Out-of-Hospital Administration of Intravenous Glucose-Insulin-Potassium in Patients With Suspected Acute Coronary Syndromes: The IMMEDIATE Randomized Controlled Trial.
Selker HP, Beshansky JR, Sheehan PR, Massaro JM, Griffith JL, D’Agostino RB, Ruthazer R, Atkins JM, Sayah AJ, Levy MK, Richards ME, Aufderheide TP, Braude DA, Pirrallo RG, Doyle DD, Frascone RJ, Kosiak DJ, Leaming JM, Van Gelder CM, Walter GP, Wayne MA, Woolard RH, Opie LH, Rackley CE, Apstein CS, Udelson JE.
JAMA. 2012 Mar 27. [Epub ahead of print]
PMID: 22452807 [PubMed - as supplied by publisher]

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Selker HP, Beshansky JR, Sheehan PR, Massaro JM, Griffith JL, D’Agostino RB, Ruthazer R, Atkins JM, Sayah AJ, Levy MK, Richards ME, Aufderheide TP, Braude DA, Pirrallo RG, Doyle DD, Frascone RJ, Kosiak DJ, Leaming JM, Van Gelder CM, Walter GP, Wayne MA, Woolard RH, Opie LH, Rackley CE, Apstein CS, & Udelson JE (2012). Out-of-Hospital Administration of Intravenous Glucose-Insulin-Potassium in Patients With Suspected Acute Coronary Syndromes: The IMMEDIATE Randomized Controlled Trial. JAMA : the journal of the American Medical Association PMID: 22452807

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