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

- Rogue Medic

Anecdotes and the Appearance of Improvement

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

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

1. The patient had CHF.

2. I gave IV furosemide.

3. The patient produced urine.

4. The patient improved.
 

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

We can use logic to back up that conclusion.
 

1. CHF is fluid in the lungs.

2. CHF is too much fluid.

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

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

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

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

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

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

CHF = Pee or die!
 


Image credit.
 

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


 

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

 

The normal patients had 22% more total plasma volume.

The normal patients had 21% more total blood volume.

The need to remove fluids is based on what?

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

Hypothesis #2. IV Lasix almost immediately causes vasodilation.

No.

IV Lasix almost immediately causes vasoconstriction.

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


 

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

 

Lasix raises blood pressure in emergency treatment of CHF.
 

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

No.

IV Lasix does not improve outcomes for acute CHF patients.

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


 

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

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

Footnotes:

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

Free Full Text Download from Circulation in PDF format.

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

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

Free Full Text from Chest.

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

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

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

.

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

ResearchBlogging.org
 

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

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

50% dextrose has problems.
 

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

 

Furthermore, extravasation can cause necrosis.
 


Image credit.[2]
 

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

Is 10% dextrose practical?
 

Won’t giving less concentrated dextrose delay treatment?
 

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

 

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

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

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

 

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

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

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

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


 

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

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


 

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

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


 

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

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


 

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

Is this perfect?
 

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

 

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

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

Why are we still resisting switching to 10% dextrose?
 

Other articles on 10% dextrose.

Footnotes:

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

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

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

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

.

The Controversy of Admitting ‘We Do Not Know What Works’

ResearchBlogging.org

 

There are several news articles today criticizing a study because the patients might be deprived of a drug that has not been adequately studied in humans. This criticism is coming from journalists – the people who publicized the fraudulent vaccines research by Andrew Wakefield, who was trying to sell his competing vaccine and was being paid to produce negative research by lawyers suing the vaccine companies.[1]

The real controversy is that this untested drug became the standard of care with no evidence that it improves outcomes that matter.

Is it controversial to give a placebo, rather than a drug not yet adequately tested in humans?

No.

We are not informing patients that there is no evidence that the standard treatment is effective. We are not obtaining consent to give the unproven drug – epinephrine (Adrenaline in Commonwealth countries). How are the ethics different when we substitute a placebo for a mystery medicine?

What is less ethical than continuing the tradition of giving an inadequately studied drug to people who cannot consent to treatment?

Are we depriving patients of effective medicine or are we depriving them of witchcraft?

If you think that epinephrine is effective medicine at improving survival to discharge, provide the evidence and stop this study. The reason the study is being done is that evidence of benefit does not exist.
 

Click on image to make it larger.[2] The studies are in the footnotes.[3],[4],[5],[6],[7],[8],[9],[10]
 

Is Adrenaline beneficial in cardiac arrest?

Probably, but only for some patients and we do not know which patients benefit.

Is Adrenaline harmful in cardiac arrest?

Probably, but only for some patients and we do not know which patients are harmed.

What is the right dose of Adrenaline in cardiac arrest?

Pick a number – any number. We do not know the right dose.
 

 

Even the patients who only received the minimum dose – 1 mg – had worse outcomes.[11]

Wrong timing? Wrong dose? Wrong drug?

We do not know.
 

We have used this untested treatment for half a century and not bothered to find out if it works. A recent study shows that epinephrine produces worse outcomes when given by EMS later,[12] but that does not mean that the outcomes are good when epinephrine is given early. The study had no placebo group, so like a study comparing different doses of cyanide, just because one dose is not as bad as another dose, the results do not suggest that cyanide is beneficial.
 


 

This is comparing three different treatments HDE (High-Dose Epinephrine), SDE (Standard-Dose Epinephrine), and NE (NorEpinephrine). The lines for the HDE and NE are so close to each other, that you may not be able to see the gold line.[13] Other studies produce similar results.[3],[14],[15],[16],[17] Only one study showed better ROSC with standard dose epinephrine.[18]
 

Epinephrine does produce more ROSC (Return Of Spontaneous Circulation – at least a temporary pulse) than placebo, but high dose epinephrine produces even more ROSC than standard dose epinephrine, so why do we give the standard dose that only produces middling ROSC?

Is ROSC the goal? No.

For the guidelines (ACLS and ILCOR), ROSC is the basis for giving standard dose epinephrine, but it would make more sense to give high dose epinephrine if the goal is ROSC. More ROSC, but no more survivors leaving the hospital. If all we want is put the patient in a coma long enough to run up a big hospital bill, then the drugs are great.

If we want people to leave the hospital alive, then We Do Not Know What Works.
 

The guidelines are based on wishful thinking and rationalization. They are not based on improved survival. A lot of research is cited (hundreds of papers), but the research does not show improved survival with any drug(s).

Will the guidelines be revised to remove epinephrine? Maybe.
 

The exciting development is that these data create equipoise about the current standard of resuscitation care. The best available observational evidence indicates that epinephrine may be harmful to patients during cardiac arrest, and there are plausible biological reasons to support this observation. However, observational studies cannot establish causal relationships in the way that randomized trials can.[19]

 

Some cocktails have produced better results than epinephrine in tiny studies. It is too probably too early to tell if these are just statistical aberrations. I will write about them later.

Continued in Does a Placebo vs. Adrenaline Study Deprive Patients of Necessary Care According to the Resuscitation Guidelines?

Footnotes:

[1] “Piltdown medicine” and Andrew Wakefield’s MMR vaccine fraud
Science-Based Medicine
Posted by David Gorski
January 6, 2011
Article
 

In a mere decade and a half, several decades of progress in controlling this scourge had been unravelled like a thread hanging off a cheap dress, all thanks to Andrew Wakefield and scandal mongers in the British press.

[2] Vasopressors in cardiac arrest: a systematic review.
Larabee TM, Liu KY, Campbell JA, Little CM.
Resuscitation. 2012 Aug;83(8):932-9. Epub 2012 Mar 15.
PMID: 22425731 [PubMed - in process]
 

CONCLUSION: There are few studies that compare vasopressors to placebo in resuscitation from cardiac arrest. Epinephrine is associated with improvement in short term survival outcomes as compared to placebo, but no long-term survival benefit has been demonstrated. Vasopressin is equivalent for use as an initial vasopressor when compared to epinephrine during resuscitation from cardiac arrest. There is a short-term, but no long-term, survival benefit when using high dose vs. standard dose epinephrine during resuscitation from cardiac arrest. There are no alternative vasopressors that provide a long-term survival benefit when compared to epinephrine. There is limited data on the use of vasopressors in the pediatric population.

[3] High dose and standard dose adrenaline do not alter survival, compared with placebo, in cardiac arrest.
Woodhouse SP, Cox S, Boyd P, Case C, Weber M.
Resuscitation. 1995 Dec;30(3):243-9.
PMID: 8867714 [PubMed - indexed for MEDLINE]

[4] Adrenaline in out-of-hospital ventricular fibrillation. Does it make any difference?
Herlitz J, Ekström L, Wennerblom B, Axelsson A, Bång A, Holmberg S.
Resuscitation. 1995 Jun;29(3):195-201.
PMID: 7667549 [PubMed - indexed for MEDLINE]

[5] Survival outcomes with the introduction of intravenous epinephrine in the management of out-of-hospital cardiac arrest.
Ong ME, Tan EH, Ng FS, Panchalingham A, Lim SH, Manning PG, Ong VY, Lim SH, Yap S, Tham LP, Ng KS, Venkataraman A; Cardiac Arrest and Resuscitation Epidemiology Study Group.
Ann Emerg Med. 2007 Dec;50(6):635-42. Epub 2007 May 23.
PMID: 17509730 [PubMed - indexed for MEDLINE]

Free Full Text Download in PDF format from prdupl02.ynet.co.il

[6] Intravenous drug administration during out-of-hospital cardiac arrest: a randomized trial.
Olasveengen TM, Sunde K, Brunborg C, Thowsen J, Steen PA, Wik L.
JAMA. 2009 Nov 25;302(20):2222-9.
PMID: 19934423 [PubMed - indexed for MEDLINE]

Free Full Text from JAMA

[7] Outcome when adrenaline (epinephrine) was actually given vs. not given – post hoc analysis of a randomized clinical trial.
Olasveengen TM, Wik L, Sunde K, Steen PA.
Resuscitation. 2011 Nov 22. [Epub ahead of print]
PMID: 22115931 [PubMed - as supplied by publisher]

[8] 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 of In Press Uncorrected Proof from xa.yming.com
 

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.

 

[9] Prehospital epinephrine use and survival among patients with out-of-hospital cardiac arrest.
Hagihara A, Hasegawa M, Abe T, Nagata T, Wakata Y, Miyazaki S.
JAMA. 2012 Mar 21;307(11):1161-8. doi: 10.1001/jama.2012.294.
PMID: 22436956 [PubMed - indexed for MEDLINE]

Free Full Text from JAMA.

[10] Impact of early intravenous epinephrine administration on outcomes following out-of-hospital cardiac arrest.
Hayashi Y, Iwami T, Kitamura T, Nishiuchi T, Kajino K, Sakai T, Nishiyama C, Nitta M, Hiraide A, Kai T.
Circ J. 2012;76(7):1639-45. Epub 2012 Apr 5.
PMID: 22481099 [PubMed - indexed for MEDLINE]

Free Full Text from Circulation Japan.

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

Free Full Text from PubMed Central.

[12] Time to administration of epinephrine and outcome after in-hospital cardiac arrest with non-shockable rhythms: retrospective analysis of large in-hospital data registry.
Donnino MW, Salciccioli JD, Howell MD, Cocchi MN, Giberson B, Berg K, Gautam S, Callaway C; American Heart Association’s Get With The Guidelines-Resuscitation Investigators.
BMJ. 2014 May 20;348:g3028. doi: 10.1136/bmj.g3028.
PMID: 24846323 [PubMed - in process]

Free Full Text from BMJ.

[13] A randomized clinical trial of high-dose epinephrine and norepinephrine vs standard-dose epinephrine in prehospital cardiac arrest.
Callaham M, Madsen CD, Barton CW, Saunders CE, Pointer J.
JAMA. 1992 Nov 18;268(19):2667-72.
PMID: 1433686 [PubMed - indexed for MEDLINE]

[14] A comparison of standard-dose and high-dose epinephrine in cardiac arrest outside the hospital. The Multicenter High-Dose Epinephrine Study Group.
Brown CG, Martin DR, Pepe PE, Stueven H, Cummins RO, Gonzalez E, Jastremski M.
N Engl J Med. 1992 Oct 8;327(15):1051-5.
PMID: 1522841 [PubMed - indexed for MEDLINE]

Free Full Text from NEJM.

[15] Standard doses versus repeated high doses of epinephrine in cardiac arrest outside the hospital.
Choux C, Gueugniaud PY, Barbieux A, Pham E, Lae C, Dubien PY, Petit P.
Resuscitation. 1995 Feb;29(1):3-9.
PMID: 7784720 [PubMed - indexed for MEDLINE]

[16] A comparison of repeated high doses and repeated standard doses of epinephrine for cardiac arrest outside the hospital. European Epinephrine Study Group.
Gueugniaud PY, Mols P, Goldstein P, Pham E, Dubien PY, Deweerdt C, Vergnion M, Petit P, Carli P.
N Engl J Med. 1998 Nov 26;339(22):1595-601.
PMID: 9828247 [PubMed - indexed for MEDLINE]

Free Full Text from NEJM.

[17] High dose versus standard dose epinephrine in cardiac arrest – a meta-analysis.
Vandycke C, Martens P.
Resuscitation. 2000 Aug 1;45(3):161-6.
PMID: 10959014 [PubMed - indexed for MEDLINE]

[18] High-dose epinephrine in adult cardiac arrest.
Stiell IG, Hebert PC, Weitzman BN, Wells GA, Raman S, Stark RM, Higginson LA, Ahuja J, Dickinson GE.
N Engl J Med. 1992 Oct 8;327(15):1045-50.
PMID: 1522840 [PubMed - indexed for MEDLINE]

Free Full Text from NEJM.

[19] Questioning the use of epinephrine to treat cardiac arrest.
Callaway CW.
JAMA. 2012 Mar 21;307(11):1198-200. doi: 10.1001/jama.2012.313. No abstract available.
PMID: 22436961 [PubMed - indexed for MEDLINE]

Link to a free 6 1/2 minute recording of an interview with Dr. Callaway about this paper.

On the right side of the page, to the right of the First Page Preview, is a section with the title Multimedia Related by Topic. Below that is Author Interview. Below that is some information about the edition, . . . , and below that is an embedded recording of the interview. Press on the arrow to play. That has the recording of the interview with Dr. Callaway.

The interview with Dr. Callaway is definitely worth listening to.

Larabee TM, Liu KY, Campbell JA, & Little CM (2012). Vasopressors in cardiac arrest: a systematic review. Resuscitation, 83 (8), 932-9 PMID: 22425731

Woodhouse SP, Cox S, Boyd P, Case C, & Weber M (1995). High dose and standard dose adrenaline do not alter survival, compared with placebo, in cardiac arrest. Resuscitation, 30 (3), 243-9 PMID: 8867714

Herlitz J, Ekström L, Wennerblom B, Axelsson A, Bång A, & Holmberg S (1995). Adrenaline in out-of-hospital ventricular fibrillation. Does it make any difference? Resuscitation, 29 (3), 195-201 PMID: 7667549

Ong ME, Tan EH, Ng FS, Panchalingham A, Lim SH, Manning PG, Ong VY, Lim SH, Yap S, Tham LP, Ng KS, Venkataraman A, & Cardiac Arrest and Resuscitation Epidemiology Study Group (2007). Survival outcomes with the introduction of intravenous epinephrine in the management of out-of-hospital cardiac arrest. Annals of emergency medicine, 50 (6), 635-42 PMID: 17509730

Olasveengen, T., Sunde, K., Brunborg, C., Thowsen, J., Steen, P., & Wik, L. (2009). Intravenous Drug Administration During Out-of-Hospital Cardiac Arrest: A Randomized Trial JAMA: The Journal of the American Medical Association, 302 (20), 2222-2229 DOI: 10.1001/jama.2009.1729

Olasveengen TM, Wik L, Sunde K, & Steen PA (2011). Outcome when adrenaline (epinephrine) was actually given vs. not given – post hoc analysis of a randomized clinical trial. Resuscitation PMID: 22115931

Jacobs IG, Finn JC, Jelinek GA, Oxer HF, & Thompson PL (2011). Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial. Resuscitation, 82 (9), 1138-43 PMID: 21745533

Hagihara A, Hasegawa M, Abe T, Nagata T, Wakata Y, & Miyazaki S (2012). Prehospital epinephrine use and survival among patients with out-of-hospital cardiac arrest. JAMA : the journal of the American Medical Association, 307 (11), 1161-8 PMID: 22436956

Hayashi Y, Iwami T, Kitamura T, Nishiuchi T, Kajino K, Sakai T, Nishiyama C, Nitta M, Hiraide A, & Kai T (2012). Impact of early intravenous epinephrine administration on outcomes following out-of-hospital cardiac arrest. Circulation journal : official journal of the Japanese Circulation Society, 76 (7), 1639-45 PMID: 22481099

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

Donnino, M., Salciccioli, J., Howell, M., Cocchi, M., Giberson, B., Berg, K., Gautam, S., Callaway, C., & , . (2014). Time to administration of epinephrine and outcome after in-hospital cardiac arrest with non-shockable rhythms: retrospective analysis of large in-hospital data registry BMJ, 348 (may20 2) DOI: 10.1136/bmj.g3028

Callaham M, Madsen CD, Barton CW, Saunders CE, & Pointer J (1992). A randomized clinical trial of high-dose epinephrine and norepinephrine vs standard-dose epinephrine in prehospital cardiac arrest. JAMA : the journal of the American Medical Association, 268 (19), 2667-72 PMID: 1433686

Brown CG, Martin DR, Pepe PE, Stueven H, Cummins RO, Gonzalez E, & Jastremski M (1992). A comparison of standard-dose and high-dose epinephrine in cardiac arrest outside the hospital. The Multicenter High-Dose Epinephrine Study Group. The New England journal of medicine, 327 (15), 1051-5 PMID: 1522841

Choux C, Gueugniaud PY, Barbieux A, Pham E, Lae C, Dubien PY, & Petit P (1995). Standard doses versus repeated high doses of epinephrine in cardiac arrest outside the hospital. Resuscitation, 29 (1), 3-9 PMID: 7784720

Gueugniaud PY, Mols P, Goldstein P, Pham E, Dubien PY, Deweerdt C, Vergnion M, Petit P, & Carli P (1998). A comparison of repeated high doses and repeated standard doses of epinephrine for cardiac arrest outside the hospital. European Epinephrine Study Group. The New England journal of medicine, 339 (22), 1595-601 PMID: 9828247

Vandycke C, & Martens P (2000). High dose versus standard dose epinephrine in cardiac arrest – a meta-analysis. Resuscitation, 45 (3), 161-6 PMID: 10959014

Stiell IG, Hebert PC, Weitzman BN, Wells GA, Raman S, Stark RM, Higginson LA, Ahuja J, & Dickinson GE (1992). High-dose epinephrine in adult cardiac arrest. The New England journal of medicine, 327 (15), 1045-50 PMID: 1522840

Callaway, C. (2012). Questioning the Use of Epinephrine to Treat Cardiac Arrest JAMA: The Journal of the American Medical Association, 307 (11) DOI: 10.1001/jama.2012.313

.

What is the Best Way to Manage Cardiac Arrest According to the Evidence?

ResearchBlogging.org
 
There is an excellent review article by Dr. Bentley Bobrow and Dr. Gordon Ewy on the best management of sudden cardiac arrest from the bystander to the ICU (Intensive Care Unit).

They point out something that we tend to resist learning. Cardiac arrest that is not due to respiratory causes does not need respiratory treatment. A person who is unresponsive and gasping is exhibiting signs of cardiac arrest, not signs of respiratory problems.
 

Except in newborns, gasping or agonal breathing is a common sign of cardiac arrest, occurring in slightly more than 50% of patients with primary cardiac arrest.22-25 [1]

 

Gasping does not mean alive and well. Gasping means dead and having a good chance at resuscitation. Unresponsive and gasping means there is a need for compressions.
 

If adequate chest compressions are promptly initiated, the patient will continue to gasp.23 [1]

 


 

Of interest is that only a minority of individuals with noncardiac arrest received CO-CPR.35 In Arizona, the public was generally capable of recognizing respiratory arrest, where chest compressions and assisted ventilations were recommended.[1]

 


 

It probably has less to do with taking away the ventilation, than with making the compressions continuous and high quality, but ventilations do decrease blood return to the chest and increase the likelihood of vomiting (regardless of what has been eaten), so there are benefits from removing the ventilations.
 


 

Passive oxygen insufflation means just putting a mask over the patient’s mouth and nose and allowing oxygen to be delivered passively. The rise and fall of the chest, due to compressions, and diffusion will allow for all of the oxygenation the patient will need.

Standard CPR (Std CPR) means alternating compressions with two ventilations every 30 compressions. Standard CPR is clearly not what we want to do, unless we want to keep patients from being resuscitated.
 

The problem is that the vast majority of physicians have no idea what the survival rate of patients with OHCA is in their area. This needs to change if major progress is to be made.[1]

 

Many of us do not know the results of what we do, so it is not surprising that a lot of EMS treatment is mythological.

Medicine is a field that encourages superstition. Patients provide intermittent reinforcement, which may be the most effect means of creating superstitions. Intermittent reinforcement?[2]
 

The only way to know the effectiveness of your Emergency Medical System is to know the survival of patients with OHCA and a shockable rhythm. If it is less than 38%,they should be encouraged to institute CCR and reevaluate the results.[1]

 

Maybe you are already doing better than 38% walking out of the hospital, then you are probably already using continuous compressions and passive oxygen insufflation. If you are not, then you need to improve your patient care.

Footnotes:

[1] Cardiocerebral Resuscitation: An Approach to Improving Survival of Patients With Primary Cardiac Arrest.
Ewy GA, Bobrow BJ.
J Intensive Care Med. 2014 Jul 30. pii: 0885066614544450. [Epub ahead of print]
PMID: 25077491 [PubMed - as supplied by publisher]

[2] Intermittent reinforcements
Wikipedia
Article
 

Pigeons experimented on in a scientific study were more responsive to intermittent reinforcements, than positive reinforcements.[16] In other words, pigeons were more prone to act when they only sometimes could get what they wanted. This effect was such that behavioral responses were maximized when the reward rate was at 50% (in other words, when the uncertainty was maximized), and would gradually decline toward values on either side of 50%.[17] R.B Sparkman, a journalist specialized on what motivates human behavior, claims this is also true for humans, and may in part explain human tendencies such as gambling addiction.[18]

 

Ewy, G., & Bobrow, B. (2014). Cardiocerebral Resuscitation: An Approach to Improving Survival of Patients With Primary Cardiac Arrest Journal of Intensive Care Medicine DOI: 10.1177/0885066614544450

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Resuscitation characteristics and outcomes in suspected drug overdose-related out-of-hospital cardiac arrest

ResearchBlogging.org
 

This study is interesting for several reasons.

In a system that claims excellence, the most consistent way to identify the study group is by documentation of a protocol violation – but it is not intended as a study of protocol violations.

This may hint at some benefit from epinephrine (Adrenaline in Commonwealth countries), but that would require some study and we just don’t study epinephrine. We only make excuses for not studying epinephrine.

The atropine results suggest that the epinephrine data may be just due to small numbers, or that we may want to consider atropine for drug overdose cardiac arrest patients, or . . . .

The Sodium Bicarbonate (bicarb – NaHCO3) results suggest a flaw in EMS education (probably testing, too). If the patient is acidotic, this is one type of cardiac arrest where hyperventilation may be beneficial. Bicarb is the part of the drug that doesn’t do much, especially if the patient is dead. The sodium is what works, such as when the patient has taken too much of a sodium channel blocker, such as a tricyclic antidepressant or a class I antiarrhythmic. Acidosis is treated by hyperventilation. Use capnography.

Most important – antidotes probably don’t work as expected during cardiac arrest. Not even naloxone (Narcan).
 

Despite clear differences in the etiology of suspected OD [OverDose] and non-OD OHCA [Out of Hospital Cardiac Arrest], the International Liaison Committee on Resuscitation guidelines published in 2010 do not specify different treatments for suspected OD-OHCA patients during resuscitation,and state that there is no evidence promoting the intra-arrest administration of the opioid antagonist naloxone.8 [1]

 

What did they find in the study?

They may have located the highest concentration of heroin overdose in the country. 93% of OD-OHCA patients were treated with naloxone.
 

We relied on either naloxone administration or clear description of circumstantial evidence in the PCR [Patient Care Recod] to identify a suspected OD. Clear descriptions are also rare, and most (93%) of the cases were identified by naloxone administration. Naloxone during cardiac arrest is not part of any regional protocol, and all of these administrations are deviations from recommended practice. There may be other cases in which paramedics suspected OD, but did not deviate from protocol to administer naloxone. Therefore, it is impossible to be certain whether the actual number of OD cases is larger or smaller than the reported number. However, the use of naloxone as a proxy indicator of suspected OD has been supported in the literature.11 [1]

 

The EMS approach to naloxone still appears to be –
 


Image credits – 123
 

These results seem to show better response to the prehospital drugs in the OD-OHCA patients, but that ignores the ROSC (Return Of Spontaneous Circulation) rates.
 


Click on images to make them larger.
 

Why would OD-OHCA patients do better than non-OD-OHCA patients if they get a pulse back?

The average non-OD-OHCA patient is 20+ years older. These older patients may not be as capable of recovery nor as capable of tolerating the toxicity of the drugs they were treated with.

The change after ROSC is dramatic. Is that the important point of this study?

Are they doing anything special for OD patients in the hospital, or is it just a matter of That which does not kill me by anoxic brain damage, may allow me to recover twice as often as a typical cardiac arrest patient.
 

Do drugs (antidotes, antiarrhythmics, . . . ) work the same way in dead people as in living people?
 

Pharmacologic insults are just so massive and normal metabolism and physiology so deranged that no mere mortal can make a meaningful intervention. The seriously poisoned who maintain vital signs in the ED have the best, albeit never guaranteed, chance of rescue from a modicum of antidotes and intensive supportive care.[2]

 

We should understand that normal metabolism is irrelevant to cardiac arrest.

We should understand that we do not need to ventilate adult cardiac arrest patients, when the cause is cardiac. An absence of ventilation would not be appropriate in a living adult, but dead metabolism is not normal. If something as basic as oxygen changes, when the patient is dead, how much less do we understand the behavior of other drugs in dead patients?

Footnotes:

[1] Resuscitation characteristics and outcomes in suspected drug overdose-related out-of-hospital cardiac arrest.
Koller AC, Salcido DD, Callaway CW, Menegazzi JJ.
Resuscitation. 2014 Jun 26. pii: S0300-9572(14)00581-4. doi: 10.1016/j.resuscitation.2014.05.036. [Epub ahead of print]
PMID: 24973558 [PubMed - as supplied by publisher]

[2] Dissecting the ACLS Guidelines on Cardiac Arrest from Toxic Ingestions
Emergency Medicine News:
October 2011 – Volume 33 – Issue 10 – pp 16-18
doi: 10.1097/01.EEM.0000406945.05619.ca
InFocus
Roberts, James R. MD
Article

Roberts, J. (2011). InFocus: Dissecting the ACLS Guidelines on Cardiac Arrest from Toxic Ingestions Emergency Medicine News, 33 (10), 16-18 DOI: 10.1097/01.EEM.0000406945.05619.ca

Koller, A., Salcido, D., Callaway, C., & Menegazzi, J. (2014). Resuscitation characteristics and outcomes in suspected drug overdose-related out-of-hospital cardiac arrest Resuscitation DOI: 10.1016/j.resuscitation.2014.05.036

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Remote CPR Skills Testing Online – A Crazy Idea?

ResearchBlogging.org
 

On the MedicCast, Jamie Davis interviews Roy Shaw of SUMO about a method of remote CPR certification for health care providers.
 

The Single Use Manikin Option, or SUMO™, is an AHA-compliant way of getting certified in CPR completely online.[1]

 


BlendedCPR.com
 

It looks too simple, but how complicated should we make it?

One of the problems with EMS is that we do not maintain skills that we do not use frequently. We know that we lose our skills very quickly, but we only retrain every couple of years (or every year) for the skills considered most important. If we care about our patients’ outcomes, we need to do better.
 

Not only have varying rates of skill acquisition been documented after traditional American Heart Association (AHA) training classes, but also universally poor skill performance of varying providers 3 to 6 months after CPR training has been established.11,–,15 [2]

 

Supervised on-line mannequin practice may be the most practical way for us to increase the rate of providing hands-on practice. As cameras become cheaper and smaller, as cell phones become much more interactive, we may have a way to do the same for intubation. Is there any good reason for practicing intubation less than once a month?

We need to improve our intubation, but everyone seems to think that the problem is with other medics and they do not need any practice. When the research is done, the problems continue. We like to intubate. We assume we are good at it. We hate to practice. we really like to make excuses. Our patients are the ones who are harmed. Other than bad assessment, bad intubation is probably the most deadly skill we have.
 

Training sessions occurred at entry into the study (time 0: initial skill acquisition) and then 1, 3, and 6 months after study entry.[2]

 

Each training session was less than five minutes long (one minute of testing, then two minutes of training), so the interference with work would be minimal, while the benefit would be significant.
 

In this study, lower rates of retention were observed in the training group that did not use a live instructor (automated defibrillator feedback only) compared with the group that used an instructor without automated feedback (instructor-only training).[2]

 

They suggest that the participants relied on the feedback from the automated devices and may not have learned to assess their performance themselves. During testing, the lack of machine feedback may have put them at a disadvantage. If machine feedback can be provided at the time of initiating compressions, The machine feedback could help. currently, that does not seem likely, so the use of only machine feedback is not as good an option as feedback from an instructor or from an instructor and a machine.
 

Although the automated feedback provided was targeted to CPR psychomotor skill errors, these systems do not provide constructive positive feedback. Instructors have an advantage: they were able to comment not only on skills done incorrectly, but also praise good performance.[2]

 

How well would this work in EMS?

We could make this something that is done once a week, or even at the beginning of each shift, on a different skill each time. Intubation/Airway management is the weak spot of EMS, so we could use this to improve.

If are only retraining on intubation/airway management once a year, or once every other year, we obviously are not taking patient care seriously and are trusting our luck, rather than any skill.
 

Go listen to the podcast on the Single Use Manikin Option (SUMO™) and consider if that would be a better way of recertifying. Maybe it is one way of implementing brief low-dose, high-frequency booster training in addition to recertification.

Also check out the site –

BlendedCPR.com

Footnotes:

[1] SUMO Remote CPR Skills Testing Online and Episode 392
By podmedic
June 30, 2014
MedicCast
Podcast/videocast page

[2] Low-dose, high-frequency CPR training improves skill retention of in-hospital pediatric providers.
Sutton RM, Niles D, Meaney PA, Aplenc R, French B, Abella BS, Lengetti EL, Berg RA, Helfaer MA, Nadkarni V.
Pediatrics. 2011 Jul;128(1):e145-51. doi: 10.1542/peds.2010-2105. Epub 2011 Jun 6.
PMID: 21646262 [PubMed - indexed for MEDLINE]

Free Full Text from Pediatrics.

Sutton RM, Niles D, Meaney PA, Aplenc R, French B, Abella BS, Lengetti EL, Berg RA, Helfaer MA, Nadkarni V. (2011). Low-Dose, High-Frequency CPR Training Improves Skill Retention of In-Hospital Pediatric Providers PEDIATRICS, 128 (1) DOI: 10.1542/peds.2010-2105d

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Does Faster Epinephrine Administration Produce Better Outcomes from PEA-Asystole?

ResearchBlogging.org
 

If we are going to give epinephrine (Adrenaline in Commonwealth countries) to patients with rhythms that are not shockable (PEA [Pulseless Electrical Activity] or Asystole), it appears that patients receiving epinephrine earlier have better outcomes than patients who receive epinephrine later in the hospital in the less acute care settings.

Does this mean that patients who receive epinephrine have better outcomes than patients who do not receive epinephrine?

We remain willfully ignorant of the answer to that question.
 

Apart from cardiopulmonary resuscitation, no intervention has been shown to be efficacious in patients with non-shockable cardiac arrest.[1]

 

Would a placebo group have had better outcomes than the patients who received epinephrine the earliest? We have no way of knowing, because we discourage asking about what we take for granted.

 

We excluded patients with cardiac arrest in the emergency department, intensive care unit, or surgical or other specialty care or procedure areas,[1]

 


 

This does show an impressive association between giving epinephrine earlier and improved outcomes.

Does this mean that we should avoid giving epinephrine (a drug not yet adequately tested in humans) after a certain amount of time?

Does this mean that we should prioritize giving epinephrine (a drug not yet adequately tested in humans) before a certain amount of time?

Until we find out how harmful/beneficial epinephrine is compared to placebo, we do not know if we are helping with epinephrine, harming with epinephrine, or which patients we might be helping and which patients we might be harming. We have a half a century of I don’t know and I don’t care.
 

Despite a strong physiologic rationale and anecdotal reports of efficacy, there are no well controlled trials of epinephrine to assess endpoints such as improved survival and neurologically intact survival. A randomized trial failed to show efficacy for advanced cardiac life support drugs, and extrapolation to the potential lack of efficacy of epinephrine has been suggested; the dose, timing, and even use of epinephrine remains controversial.15-16 [1]

 

But some of the anecdotes are really good anecdotes!

Anecdote-based treatment is just ignorance-based treatment. We assume that we know what we are doing, but we are only imitating Skinner’s pigeons in our reaction to stimuli.
 


Download YouTube Video | YouTube to MP3: Vixy | Replay Media Catcher
 

We have fancier uniforms than the pigeons, but we are just as unaware of the source of our stimuli.
 

The data was prospectively obtained using specifically defined variables, but the study was a retrospective analysis of that data.
 

Because data were used primarily as the local site for quality improvement, sites were granted a waiver of informed consent under the common rule.[1]

 

Because of the way the data are entered, any errors are likely to be at time of entry and may not be capable of being detected at the time of analysis for research. The numbers are very large – 25,095 patients – so that should correct for idiosyncratic errors, but what about cultural errors?

 

In the sensitivity analyses with adjustment for delays in initiation of cardiopulmonary resuscitation, time to epinephrine administration remained independently associated with survival to hospital discharge after multivariable adjustments.[1]

 

In the context of our findings, future investigations should consider timing of epinephrine administration in design and interpretation.[1]

 

We should also consider that epinephrine, if it is beneficial, is probably only beneficial to some patients. We need to try to identify those patients. Our current method of give epinephrine to everybody and let the emergency department sort them out is not reasonable.

This study ran from 2000 to 2009, so the improvements due to the focus on chest compressions might only affect a tiny portion of patients.[2]

Does epinephrine administration – at any time – produce better outcomes from PEA-asystole?

We still have no idea.

Footnotes:

[1] Time to administration of epinephrine and outcome after in-hospital cardiac arrest with non-shockable rhythms: retrospective analysis of large in-hospital data registry.
Donnino MW, Salciccioli JD, Howell MD, Cocchi MN, Giberson B, Berg K, Gautam S, Callaway C; American Heart Association’s Get With The Guidelines-Resuscitation Investigators.
BMJ. 2014 May 20;348:g3028. doi: 10.1136/bmj.g3028.
PMID: 24846323 [PubMed - in process]

Free Full Text from BMJ.

[2] Delayed prehospital implementation of the 2005 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiac care.
Bigham BL, Koprowicz K, Aufderheide TP, Davis DP, Donn S, Powell J, Suffoletto B, Nafziger S, Stouffer J, Idris A, Morrison LJ; ROC Investigators.
Prehosp Emerg Care. 2010 Jul-Sep;14(3):355-60.
PMID: 20388032 [PubMed - indexed for MEDLINE]

Free Full Text from PubMed Central.

On December 13, 2005, the AHA published “Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care”

ROC EMS agencies required an average of 416 days to implement the 2005 AHA guidelines for OHCA. Small EMS agencies, BLS-only agencies, and nontransport agencies took longer than large agencies, agencies providing ALS care, and transport agencies, respectively, to implement the guidelines.

How relevant is that to implementation in the less acute care settings studied in these hospitalized patients?

Bigham BL, Koprowicz K, Aufderheide TP, Davis DP, Donn S, Powell J, Suffoletto B, Nafziger S, Stouffer J, Idris A, Morrison LJ, & ROC Investigators (2010). Delayed prehospital implementation of the 2005 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiac care. Prehospital emergency care : official journal of the National Association of EMS Physicians and the National Association of State EMS Directors, 14 (3), 355-60 PMID: 20388032

Donnino, M., Salciccioli, J., Howell, M., Cocchi, M., Giberson, B., Berg, K., Gautam, S., Callaway, C., & , . (2014). Time to administration of epinephrine and outcome after in-hospital cardiac arrest with non-shockable rhythms: retrospective analysis of large in-hospital data registry BMJ, 348 (may20 2) DOI: 10.1136/bmj.g3028

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Who Needs a 12 Lead ECG?

ResearchBlogging.org
 

Do we do too many 12 lead ECGs on patients who do not have chest pain?

This is something that some people worry about.

Save the electrodes!

Those poor little electrodes are being abused!

Are electrodes being abused?
 

Women and the elderly with STEMI are particularly likely to present with atypical chief complaints such as dyspnea and weakness. Such patients experience significant delays in door-to-ECG time and treatment and have increased morbidity and mortality compared with patients who present with chest pain.5,9-12 [1]

 

Tiredness/weakness is the second best predictor of STEMI (ST segment Elevation Myocardial Infarction).

After chest pain (pressure, tightness, heaviness, squeezing, et cetera), the best predictor of STEMI is dyspnea in akll age ranges, but dyspnea indicates 20% of STEMIs in patients over 80 years old.

Are we helping anyone by avoiding 12 lead ECG (ElectroCardioGram) assessment?
 

Presenting chief complaints among 6,464 patients with STEMI. Chest pain decreased in frequency with age, whereas a chief complaint of dyspnea, weakness, syncope, or altered mental status all increased in frequency with age.[1]

 


Click on images to make them larger.
 


 

The advantage of a logarithmic chart is that there is greater distinction among the smaller numbers (such as the other complaints that make up less than 5% in the image above). The disadvantage is that large changes are flattened. I modified the dyspnea line to show how it would look on a linear scale (from 5% to 20%). As you can see, the ability to predict STEMI increases dramatically with age – more dramatically than the logarithmic scale suggests.
 


 

How should we remember all of this?

The authors came up with a nice simple flow chart (below).

This is for the ED, but is there a good reason for EMS to ignore these STEMIs?
 


 

Even in the 18-49 year old patients, dyspnea is about as likely to predict a STEMI as weakness is likely to predict a STEMI in an 80+ year old patient.

Chest pain still indicates about 50% of STEMI patients over 80, but we will miss half of STEMIs in this population if we only do 12 leads on chest pain patients.

Can an 80+ year old patient have a good quality of life after a STEMI?

Absolutely.

Also see When should you get an ECG? at Mill Hill Ave Command.

Footnotes:

[1] Development and validation of a prioritization rule for obtaining an immediate 12-lead electrocardiogram in the emergency department to identify ST-elevation myocardial infarction.
Glickman SW, Shofer FS, Wu MC, Scholer MJ, Ndubuizu A, Peterson ED, Granger CB, Cairns CB, Glickman LT.
Am Heart J. 2012 Mar;163(3):372-82. doi: 10.1016/j.ahj.2011.10.021.
PMID: 22424007 [PubMed - indexed for MEDLINE]

Glickman SW, Shofer FS, Wu MC, Scholer MJ, Ndubuizu A, Peterson ED, Granger CB, Cairns CB, & Glickman LT (2012). Development and validation of a prioritization rule for obtaining an immediate 12-lead electrocardiogram in the emergency department to identify ST-elevation myocardial infarction. American heart journal, 163 (3), 372-82 PMID: 22424007

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