There are plenty who … claim to be competent at intubation even though their last intubation was months ago on the third attempt and if the patient had not already been dead – that would have finished the patient off …

- Rogue Medic

The RAD-57 – Still Unsafe?

ResearchBlogging.org
 

Brandon Oto of EMS Basics and Degrees of Clarity organized The First EMS What-if-We’re-Wrong-a-Thon. I did not participate, because I was taking a break from blogging at the time. Brandon is doing it again, so I decided to look for something I wrote that I have been wrong about to contribute. I thought about Masimo. I had been very critical of Dr. Michael O’Reilly (then Executive Vice President of Masimo Corporation) for being an advocate of bad science. He has since been hired away by Apple.[1] He should be less dangerous with a telephone than he was with the RAD-57. At the time, he wrote –
 

Masimo stands by its products’ performance and knows that when SpCO-enabled devices are used according to their directions for use, they provide accurate SpCO measurements that provide significant clinical utility, helping clinicians detect carbon monoxide poisoning in patients otherwise not suspected of having it and rule out carbon monoxide poisoning in patients with suspected carbon monoxide poisoning.[2]

 

The problem is that there is no evidence that the RAD-57 is safe or effective at ruling out carbon monoxide poisoning in anyone.

There is evidence that the RAD-57 will fail, if used to try to rule out carbon monoxide poisoning. One study showed that the RAD-57 will miss half of the people with elevated carbon monoxide levels.
 

The RAD device correctly identified 11 of 23 patients with laboratory values greater than or equal to 15% carboxyhemoglobin (sensitivity 48%; 95% CI 27% to 69%).[3]

 

What if I was wrong?

Is there any evidence that the RAD-57 is able to rule out covert, but life threatening carbon monoxide poisoning?[4]
 


 
 

Was I wrong?

While there have been several studies of the RAD-57, I could not find any evidence that the RAD-57 is safe or effective at ruling out carbon monoxide poisoning.

There does not appear to be any research on the use of the RAD-57 to screen firefighters to rule out carbon monoxide poisoning, even though advertising shows using the RAD-57 to screen firefighters.

Was I wrong? No. That is why this is not a part of The First EMS What-if-We’re-Wrong-a-Thon.

However, I did find some interesting carbon monoxide poisoning papers –

One shows that we may be causing harm by aggressively providing oxygen. This is not enough of a reason to stop providing oxygen, but if this hypothesis is supported by further research, we will need to change treatment.
 

While CO’s affinity for hemoglobin remains undisputed, new research suggests that its role in nitric oxide release, reactive oxygen species formation, and its direct action on ion channels is much more significant. In the course of understanding the multifaceted character of this simple molecule it becomes apparent that current oxygen based therapies meant to displace CO from hemoglobin may be insufficient and possibly harmful.[5]

 

Another shows that the addition of catalytic converters seems to have dramatically decreased the car exhaust suicide rate and the level of carbon monoxide in survivors of these suicide attempts.
 

RESULTS:
Since 1985, the CDR for suicidal motor vehicle-related CO poisoning has decreased in parallel with CO emissions (R2 = 0.985). Non-fatal motor vehicle-related intentional CO poisoning cases decreased 63% over 33 years (p = 0.0017). COHb levels decreased 35% in these patients (p < 0.0001).
[6]

 

CO is Carbon monOxide.
CDR is Crude Death Rate.
COHb is CarbOxyHemoglobin.

There are still some papers that show that we do not understand what the RAD-57 can’t do –
 

The fact that all the Paramedic Rescue Squads were equipped with medical triage sets and were able to conduct non-invasive measurements of carboxyhemoglobin made it possible to introduce effective procedures in the cases of suspected carbon monoxide poisoning and abandon costly and complicated organisational procedures when they proved to be unnecessary.[1]

 

No. The Magic 8 Ball did not indicate a problem, but that does not mean that it is safe to rule out carbon monoxide poisoning with a Magic 8 Ball. The Magic 8 Ball RAD-57 is not accurate enough to rule out carbon monoxide poisoning.

The RAD-57 is only appropriate for sending more people to the hospital. While the extra cost of these false positives is a problem and will cause people to mock Masimo, this may save some lives or just prevent more serious consequences of carbon monoxide poisoning.

If you use the RAD-57 to determine that someone does not need to go to the hospital, get a lot of very good insurance, because eventually one of those patients will have a heart attack, or a stroke, or die and carbon monoxide will be part of the reason for the bad outcome. Your advice will have contributed.

If you send a firefighter back into a fire because you think you have ruled out carbon monoxide poisoning, eventually you will be the cause of death or disability of firefighters. Don’t do it.
 

CONCLUSIONS:
While the Rad-57 pulse oximeter functioned within the manufacturer’s specifications, clinicians using the Rad-57 should expect some SpCO readings to be significantly higher or lower than COHb measurements, and should not use SpCO to direct triage or patient management. An elevated S(pCO) could broaden the diagnosis of CO poisoning in patients with non-specific symptoms. However, a negative SpCO level in patients suspected of having CO poisoning should never rule out CO poisoning, and should always be confirmed by COHb.
[7]

 

Highlighting in bold is mine.

SpCO is Masimo’s registered trademark for their noninvasive indirect measurement of carbon monoxide using the RAD-57.

Was I wrong? I will find something else to write about, because there is even more evidence that the RAD-57 should not be used to try to rule out carbon monoxide poisoning now than when I originally criticized Masimo.
 

Also read the article by Dr. Brooks Walsh on the RAD-57 and screening for carbon monoxide poisoning in fire fighters – Checking firefighters for carbon monoxide – recent studies, persistent concerns.
 

Here is the rest of what I have written about the Dr. O’Reilly, Masimo, and the RAD-57

The RAD-57 Pulse Co-Oximeter – Does It Work – Part I
Fri, 12 Nov 2010

The RAD-57 Pulse Co-Oximeter – Does It Work – Part II
Wed, 17 Nov 2010

How Not to Respond to Negative Research
Fri, 26 Nov 2010

How Not to Respond to Negative Research – Addendum
Fri, 26 Nov 2010

How TO Respond to Negative Research
Sun, 05 Dec 2010

Bad Advice on Masimo’s RAD-57 – Part I
Fri, 18 Feb 2011

Bad Advice on Masimo’s RAD-57 – Part II
Mon, 21 Feb 2011

Bad Advice on Masimo’s RAD-57 – Part III
Thu, 24 Feb 2011

Bad Advice on Masimo’s RAD-57 – Part IV
Mon, 28 Feb 2011

Performance of the RAD-57 With a Lower Limit – Better?
Wed, 18 May 2011

Accuracy of Noninvasive Multiwave Pulse Oximetry Compared With Carboxyhemoglobin From Blood Gas Analysis in Unselected Emergency Department Patients
Tue, 21 Feb 2012

Mass sociogenic illness initially reported as carbon monoxide poisoning
Wed, 22 Feb 2012

Psychic vs. RAD-57
Thu, 23 Feb 2012

Footnotes:

[1] Apple makes yet another medical field hire for unknown project
By AppleInsider Staff
Thursday, January 30, 2014, 04:04 pm PT (07:04 pm ET)
AppleInsider
Article

[2] Performance of the Rad-57 pulse co-oximeter compared with standard laboratory carboxyhemoglobin measurement.
O’Reilly M.
Ann Emerg Med. 2010 Oct;56(4):442-4; author reply 444-5. No abstract available.
PMID: 20868919 [PubMed – indexed for MEDLINE]

Free Full Text of letter and author reply from Ann Emerg Med.

[3] Performance of the RAD-57 pulse CO-oximeter compared with standard laboratory carboxyhemoglobin measurement.
Touger M, Birnbaum A, Wang J, Chou K, Pearson D, Bijur P.
Ann Emerg Med. 2010 Oct;56(4):382-8. Epub 2010 Jun 3.
PMID: 20605259 [PubMed – indexed for MEDLINE]

Free Full Text Article from Ann Emerg Med.

[4] Accuracy of Noninvasive Multiwave Pulse Oximetry Compared With Carboxyhemoglobin From Blood Gas Analysis in Unselected Emergency Department Patients
Rogue Medic
Tue, 21 Feb 2012
Article

[5] A modern literature review of carbon monoxide poisoning theories, therapies, and potential targets for therapy advancement.
Roderique JD, Josef CS, Feldman MJ, Spiess BD.
Toxicology. 2015 Aug 6;334:45-58. doi: 10.1016/j.tox.2015.05.004. Epub 2015 May 18. Review.
PMID: 25997893

[6] Suicidal carbon monoxide poisoning has decreased with controls on automobile emissions.
Hampson NB, Holm JR.
Undersea Hyperb Med. 2015 Mar-Apr;42(2):159-64.
PMID: 26094291

[7] False positive rate of carbon monoxide saturation by pulse oximetry of emergency department patients.
Weaver LK, Churchill SK, Deru K, Cooney D.
Respir Care. 2013 Feb;58(2):232-40. doi: 10.4187/respcare.01744.
PMID: 22782305

Free Full Text from Respir Care.

Weaver, L., Churchill, S., Deru, K., & Cooney, D. (2012). False Positive Rate of Carbon Monoxide Saturation by Pulse Oximetry of Emergency Department Patients Respiratory Care DOI: 10.4187/respcare.01744

Hampson NB, & Holm JR (2015). Suicidal carbon monoxide poisoning has decreased with controls on automobile emissions. Undersea & hyperbaric medicine : journal of the Undersea and Hyperbaric Medical Society, Inc, 42 (2), 159-64 PMID: 26094291

Roderique, J., Josef, C., Feldman, M., & Spiess, B. (2015). A modern literature review of carbon monoxide poisoning theories, therapies, and potential targets for therapy advancement. Toxicology, 334, 45-58 DOI: 10.1016/j.tox.2015.05.004

Touger, M., Birnbaum, A., Wang, J., Chou, K., Pearson, D., & Bijur, P. (2010). Performance of the RAD-57 Pulse Co-Oximeter Compared With Standard Laboratory Carboxyhemoglobin Measurement Annals of Emergency Medicine, 56 (4), 382-388 DOI: 10.1016/j.annemergmed.2010.03.041

O’Reilly, M. (2010). Performance of the Rad-57 Pulse Co-Oximeter Compared With Standard Laboratory Carboxyhemoglobin Measurement Annals of Emergency Medicine, 56 (4), 442-444 DOI: 10.1016/j.annemergmed.2010.08.016

.

Why is progress so slow in resuscitation research?

ResearchBlogging.org
 

Why is progress so slow in resuscitation research? A lot of money and time went in to finding out which type of blood-letting ventilation works best – ignoring the absence of valid evidence that ventilation is better than no ventilation. Why not gamble with our patients?

In response to The Fatal Flaw in Trial of Continuous or Interrupted Chest Compressions during CPR,[1],[2] Kenny commented that –
 

there are many things in your blog that are not correct.[1]

 

I asked for specifics and received the following from Anonymous (maybe Kenny and maybe not) –
 

That the study design ASSUMES we don’t want to know if ventilation is useful or not.[1]

 

Ventilation study implied facepalm
 

Assumes is not many things, but the comments may be from different people and there may be so many things, that Kenny is still documenting all of the examples. Perhaps the following is more specific wording that will satisfy defenders of the study –

    The study design strongly suggests that

        in the attempted resuscitation of adult patients

            with cardiac causes of cardiac arrest

                which is almost all cardiac arrest patients

                    active ventilation does not need evidence,

                        but selecting the favorite flavor of ventilation

                            does need expensive high quality evidence

                                just in case someone ever produces valid evidence

                                    that these patients are not harmed by ventilations

                                        and that these patients receive some benefit from ventilations.
 

That is a lot to assume believe without appropriate evidence.

Based on the available evidence, what are the odds that ventilations are not harmful and are beneficial?
 

Does anyone have any good argument to give ventilations as much as a 50% chance?
 

What about a 40% chance that ventilations will survive a valid study?

How about a 30% chance?

20%?

Is there any justifiable reason to be so optimistic?

If there isn’t any justifiable reason to be optimistic, then we are only making assumptions when we take shortcuts to eliminate the essential research in order to study something that is traditional, rather than based on valid evidence.
 

Do the authors understand that there isn’t valid evidence of any benefit/lack of harm from active ventilations?

Do the authors care that there is not valid evidence of any benefit/lack of harm from active ventilations?

If I have overlooked a third possibility, somebody should let me know. If there is valid evidence, somebody should provide it.

Footnotes:

[1] The Fatal Flaw in Trial of Continuous or Interrupted Chest Compressions during CPR
Wed, 25 Nov 2015 10:15:20
by Rogue Medic
Article

[2] Trial of Continuous or Interrupted Chest Compressions during CPR.
Nichol G, Leroux B, Wang H, Callaway CW, Sopko G, Weisfeldt M, Stiell I, Morrison LJ, Aufderheide TP, Cheskes S, Christenson J, Kudenchuk P, Vaillancourt C, Rea TD, Idris AH, Colella R, Isaacs M, Straight R, Stephens S, Richardson J, Condle J, Schmicker RH, Egan D, May S, Ornato JP; ROC Investigators.
N Engl J Med. 2015 Nov 9. [Epub ahead of print]
PMID: 26550795

Free Full Text from NEJM.

Nichol, G., Leroux, B., Wang, H., Callaway, C., Sopko, G., Weisfeldt, M., Stiell, I., Morrison, L., Aufderheide, T., Cheskes, S., Christenson, J., Kudenchuk, P., Vaillancourt, C., Rea, T., Idris, A., Colella, R., Isaacs, M., Straight, R., Stephens, S., Richardson, J., Condle, J., Schmicker, R., Egan, D., May, S., & Ornato, J. (2015). Trial of Continuous or Interrupted Chest Compressions during CPR New England Journal of Medicine DOI: 10.1056/NEJMoa1509139

.

The Fatal Flaw in Trial of Continuous or Interrupted Chest Compressions during CPR

ResearchBlogging.org
 

Trial of Continuous or Interrupted Chest Compressions during CPR — NEJM
 

In conclusion, among patients with out-of-hospital cardiac arrest in whom CPR was performed by EMS providers, a strategy of continuous chest compressions with positive-pressure ventilation did not result in significantly higher rates of survival or favorable neurologic status than the rates with a strategy of chest compressions interrupted for ventilation.[1]

 

This is not a study that has a valid control group to determine if there is any benefit from ventilation. There is no group that does not receive ventilations, so it is like a study of one type of blood-letting vs. another type of blood-letting with the researchers taking for granted that blood-letting does improve outcomes. That is not a problem if blood-letting actually improves outcomes.

Should we take it for granted that blood-letting improves outcomes and that the only hypothesis worth studying is which brand to choose?

Should we assume that ventilations are too sacred to ever be doubted?

Should we assume that there are better arguments for ventilations than for blood-letting? That is not true.
 

If we ignore this fatal flaw, the study is very well done. I really like the study design. It is an excellent example of how to study two different versions of an intervention after that intervention has been demonstrated to improve outcomes, but ventilations have never been demonstrated to improve outcomes in adult patients with cardiac causes of cardiac arrest.

Should we have assumed that blood-letting was too sacred to ever be doubted?
 

We do know that outcomes for seizure patients improve when EMS gives benzodiazepines, because some people cared enough to find out.[2]

Assuming that a treatment is too important to study is like building on a foundation in a swamp.
 


 

We still do not know if there is any benefit from including ventilations, because the study design assumes that we don’t want to know.

There is no good reason to believe that ventilations improve outcomes for adult patients with cardiac causes of cardiac arrest. This study has not done anything to change that.

Our patients deserve better. Why aren’t we finding out what improves outcomes?

Footnotes:

[1] Trial of Continuous or Interrupted Chest Compressions during CPR.
Nichol G, Leroux B, Wang H, Callaway CW, Sopko G, Weisfeldt M, Stiell I, Morrison LJ, Aufderheide TP, Cheskes S, Christenson J, Kudenchuk P, Vaillancourt C, Rea TD, Idris AH, Colella R, Isaacs M, Straight R, Stephens S, Richardson J, Condle J, Schmicker RH, Egan D, May S, Ornato JP; ROC Investigators.
N Engl J Med. 2015 Nov 9. [Epub ahead of print]
PMID: 26550795

Free Full Text from NEJM.

[2] A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus.
Alldredge BK, Gelb AM, Isaacs SM, Corry MD, Allen F, Ulrich S, Gottwald MD, O’Neil N, Neuhaus JM, Segal MR, Lowenstein DH.
N Engl J Med. 2001 Aug 30;345(9):631-7. Erratum in: N Engl J Med 2001 Dec 20;345(25):1860.
PMID: 11547716 [PubMed – indexed for MEDLINE]

Free Full Text from N Engl J Med. with link to PDF Download.

Nichol, G., Leroux, B., Wang, H., Callaway, C., Sopko, G., Weisfeldt, M., Stiell, I., Morrison, L., Aufderheide, T., Cheskes, S., Christenson, J., Kudenchuk, P., Vaillancourt, C., Rea, T., Idris, A., Colella, R., Isaacs, M., Straight, R., Stephens, S., Richardson, J., Condle, J., Schmicker, R., Egan, D., May, S., & Ornato, J. (2015). Trial of Continuous or Interrupted Chest Compressions during CPR New England Journal of Medicine DOI: 10.1056/NEJMoa1509139

Alldredge BK,, Gelb AM,, Isaacs SM,, Corry MD,, Allen F,, Ulrich S,, Gottwald MD,, O’Neil N,, Neuhaus JM,, Segal MR,, & Lowenstein DH. (2001). A Comparison of Lorazepam, Diazepam, and Placebo for the Treatment of Out-of-Hospital Status Epilepticus New England Journal of Medicine, 345 (25), 1860-1860 DOI: 10.1056/NEJM200112203452521

.

How Bad is the Evidence for the New 2015 ACLS Guidelines?

ResearchBlogging.org
 
    The new ACLS guidelines are out. How bad is the evidence?

    The short answer – The Advanced Cardiac Life Support guidelines could be worse.

How does the American Heart Association determine that a recommendation is not beneficial?
 

Class III: No Benefit, is a moderate recommendation, generally reserved for therapies or tests that have been shown in high-level studies (generally LOE A or B) to provide no benefit when tested against a placebo or control.[1]

 

The tobacco enema has been used successfully as a treatment for cardiac arrest, so the evidence of lack of benefit is poor.[2] Clearly, the Advanced Cardiac Life Support guidelines cannot claim that the tobacco enema is Class III. Successfully? The treatment was used and a dead person was no longer dead. In other words, just as successfully as most of the ACLS treatments.
 

From Eisenberg, MS. Life in the balance: emergency medicine and the quest to reverse sudden death. 1997; Oxford University Press. [betterworldbooks][3]

 

This is one way to make excuses for justify doing something just because of ideology. In the absence of good evidence of benefit, we should not harm our patients to protect our ideology. We used to do this with blood-letting, which was defended even after there was clear evidence of harm. That is just the best known example, but this dishonesty continues and continues to be defended.

Why don’t we hold anyone accountable, when we have the evidence that our treatments are harmful? Because we all seem to go along to get along.

The 2015 ACLS guidelines are not all bad, but they clearly do not encourage withholding harmful treatments until we have obvious evidence of harm. Should we assume that a treatment works just because the explanation appeals to some experts as much as the explanation for blood-letting appealed to the experts when that was in vogue?

This is not medicine. This is a fashion show. Our patients are the ones harmed.
 

Footnotes:

[1] 2015 AHA Classes of Recommendation
2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Part 2: Evidence Evaluation and Management of Conflicts of Interest
Development of the 2015 Guidelines Update
Circulation.
2015; 132: S368-S382
Free Full Text from Circulation.

[2] Tobacco smoke enemas
Ghislaine Lawrence
Volume 359, No. 9315, p1442,
20 April 2002
Lancet
Abstract with link to Full Text PDF download.

[3] Ever tried smoking?
by Chris Nickson
Life in the Fast Lane
Article

Morrison LJ, Gent LM, Lang E, Nunnally ME, Parker MJ, Callaway CW, Nadkarni VM, Fernandez AR, Billi JE, Egan JR, Griffin RE, Shuster M, & Hazinski MF (2015). Part 2: Evidence Evaluation and Management of Conflicts of Interest: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation, 132 (18 Suppl 2) PMID: 26472990
 

Lawrence, G. (2002). Tobacco smoke enemas The Lancet, 359 (9315) DOI: 10.1016/S0140-6736(02)08339-3

.

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

.