Severe pain + 2mg of Morphine = severe pain.

- 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

.

Safety of Intranasal Fentanyl in the Out-of-Hospital Setting – A Prospective Observational Study

ResearchBlogging.org
 
I have been very critical of plans to have first responders treat people they suspect of having a heroin (or other) opioid overdose with naloxone.

Would first responders be safer with fentanyl?

It is not really the same question, but it does highlight the differences and why I think fentanyl is safer. The patient will be seen by someone more likely to recognize when the treatment is inappropriate. This study looked at IN (IntraNasal) fentanyl given by basic EMTs prior to transport to the ED (Emergency Department).
 


Image credit.
 

Previous studies demonstrate adverse effects in 3.3% to 39% of patients treated with intranasal fentanyl,3, 4 and 5 providing an ambiguous safety profile.[1]

 

The concentration of fentanyl (Instanyl in this study) is different from what I have available. They use 500 µg/ml, while I only have fentanyl in a concentration of 50 µg/ml. Ten times the volume does make measurement easier, but ten times the volume may impair absorption.
 

The atomizer contains a single dose with a prefixed quantity of either 50 μg (500 μg/mL) or 100 μg (1,000 μg/mL) fentanyl and has a dose volume of 0.1 mL (lower than the 0.15 mL limit necessary to avoid pharyngeal runoff7). The Instanyl preparation contains fentanyl in no other recipients than purified water and a phosphate buffer to match the physiologic environment of the nasal cavity and to increase bioavailability.9 [1]

 

Patients were not limited to healthy trauma patients, so these results can be generalized to a variety of patients.
 

We administered 50 μg to patients younger than 18 years, older than 65 years, with chronic obstructive pulmonary disease, or who were considered generally weakened or malnourished by the attending paramedic/EMT. All others received 100 μg. In patients reporting insufficient analgesia, the initial dose could be repeated once or twice after 10 and 25 minutes, respectively.[1]

 


 

The smaller decrease in level of pain suggests that they were more cautious in administering fentanyl to the comorbid patients.

The time between doses did lead to some extended scene times (first dose at 0 minutes, second dose at least 10 minutes later, and the third dose at least 35 minutes after the first dose), but that is usually preferable to causing extreme pain by moving the patient with inadequate pain management, regardless of the proximity of the hospital.
 


 

What many people fail to realize, doctors included, is that the hospital may only be five minutes away after we are in the ambulance, but we need to manage the pain before we move toward the ambulance. When I call for orders to give more pain medicine than I can give on standing orders, medical command doctors sometimes ask how far away from the hospital we are. I respond that it depends on when the pain is managed. Unless there is some medical condition that requires us to move the patient more quickly, we should move the patient only when the patient feels the pain is managed.
 

How effective was the intranasal fentanyl at managing pain?
 

I would prefer to lower the level of pain by more than they did, but I am accustomed to giving IV (IntraVenous) fentanyl, so I am able to titrate it more accurately.
 


 

Patients received 1 (n=526), 2 (n=333), or 3 (n=44) doses of fentanyl, with a mean cumulative dose of 114 μg.[1]

 

Fewer than 5% of patients required more than two doses.

They did give a variety of total doses of fentanyl. The result seemed to be similar regardless of the total dose. This could indicate that fentanyl is just a placebo (unlikely) or that the EMTs did a good job of titrating the medicine to the response.
 


 
 

This was a safety study, so how safe was intranasal fentanyl?
 

The criterion for hypotension is a bit different from what I am accustomed to. Even using MAP (Mean Arterial Pressure), I have not considered patients to be hypotensive above a MAP of 60.
 

We calculated the mean arterial pressure (MAP) and defined hypotension as a MAP reduction greater than or equal to 10 mm Hg and an end MAP less than or equal to 70 mm Hg.14 [1]

 

How much respiratory depression and hypotension did they have?
 

We did not observe respiratory depression (respiratory rate less than 11 breaths/min), GCS score reduction to 14 in 5 patients was transient, and there was no use of naloxone or mask ventilation. Ten patients (1%) had measurable hypotension; however, none experienced syncope and only 1 experienced dizziness, suggesting that these events were of low clinical importance. Indeed, pain relief may be partially responsible for the decrease in MAP.[1]

 

Studies repeatedly show that fentanyl can be given safely to hypotensive patients and half of the hypotensive patients were no longer hypotensive after fentanyl was given in one prehospital trauma study.[2] This suggests that a fluid bolus may be less effective than fentanyl at getting rid of hypotension.
 

As pointed out by O’Donnell et al,20 out-of-hospital undertreatment of pain in pediatric patients may be due to safety concerns. Our study supports the safety of intranasal fentanyl in children.[1]

 

Fentanyl is even safe in children and safe in adults with comorbidities even when given by basic EMTs.

It seems that fentanyl is safe and much more effective than not treating the pain. Is IN fentanyl more effective than other pain medicines? We still do not know.

Footnotes:

[1] Safety of intranasal fentanyl in the out-of-hospital setting: a prospective observational study.
Karlsen AP, Pedersen DM, Trautner S, Dahl JB, Hansen MS.
Ann Emerg Med. 2014 Jun;63(6):699-703. doi: 10.1016/j.annemergmed.2013.10.025. Epub 2013 Nov 22.
PMID: 24268523 [PubMed – in process]

[2] Fentanyl in the out-of-hospital setting: variables associated with hypotension and hypoxemia.
Krauss WC, Shah S, Shah S, Thomas SH.
J Emerg Med. 2011 Feb;40(2):182-7. Epub 2009 Mar 27.
PMID: 19327928 [PubMed – in process]

Full Text PDF Download at medicalscg.

My review of this paper –

Fentanyl in the out-of-hospital setting: variables associated with hypotension and hypoxemia
Fri, 27 May 2011
Rogue Medic
Article

Krauss, W., Shah, S., Shah, S., & Thomas, S. (2011). Fentanyl in the Out-of-Hospital Setting: Variables Associated with Hypotension and Hypoxemia The Journal of Emergency Medicine, 40 (2), 182-187 DOI: 10.1016/j.jemermed.2009.02.009

Karlsen AP, Pedersen DM, Trautner S, Dahl JB, & Hansen MS (2014). Safety of intranasal fentanyl in the out-of-hospital setting: a prospective observational study. Annals of emergency medicine, 63 (6), 699-703 PMID: 24268523

.

Is First Responder Narcan the Same as First Responder AED?


Image credit.
 

Are these the same?

If one works, does the other work?
 


Image credit.
 

The idea that first responders can safely give naloxone (Narcan) is popular, but only based on things that we want to be true. Dr. Oz would love it.

It has been suggested that giving first responders naloxone is the same as giving them AEDs (Automated External Defibrillators).[1] AEDs are defibrillators that can deliver the same shock as a manual defibrillator, but AEDs do not require all of the education needed to become a paramedic, nurse, PA, NP, or doctor.

Unlike naloxone, AEDs are designed to do almost all of the assessment for the first responder. The AED is only supposed to be attached to a pulseless patient, so assessment for responsiveness and the presence of a pulse is expected by the first responder. Is naloxone assessment that simple?

When a patient actually has an opioid overdose, it can be that simple, but –

Not all patients who respond after naloxone, respond because of naloxone.

This is the concept that is difficult to explain to the advocates of first responder naloxone programs.

1. Some advocates deny that this happens, even though it is documented.

2. Some advocates claim that we already know all that we need to know about naloxone.

3. Some advocates also claim that we should not study this because we already know all that we need to know.

Since there is overlap among the groups, the failure to understand the problem of improper assessment, especially among paramedics, nurses, and doctors is a huge problem. If we do not understand naloxone, with all of our education in pharmacology, how can we expect first responders to understand naloxone without any education in pharmacology?

What kind of education can prevent mistakes? How do we know?

If we listen to those who don’t know, but claim that they know all that they need to know, we will be ignoring the possibility of unintended consequences and assuming that we are too smart to make mistakes. Is that reasonable?

Do AEDs save lives?
 

CONCLUSION:

Addition of AEDs to this EMS system did not improve survival from sudden cardiac death. The data do not support routinely equipping initial responders with AEDs as an isolated enhancement, and raise further doubt about such expenditures in similar EMS systems without first optimizing bystander CPR and EMS dispatching.[2]

 

The problem is not that AEDs do not work.

The problem is not that AEDs are not safe.

The problem is thinking that AEDs are a simple solution to a problem that is not as simple as some would like us to believe.
 

The concept of equipping as many emergency responders as possible with AEDs has been widely adopted,2 and 31 but it should not be blindly adopted without improving the EMS system at all levels. This decision should be individualized to each EMS system based on all of the variables in EMS response. As an isolated enhancement, it is doubtful that addition of AEDs will provide a measurable survival benefit.[2]

 

If first responder naloxone were limited to people found with needles in their arms, less thought would be required. As the presentation of overdose changes to prescription opioids, there is less clear evidence of overdose and more of a need for a good assessment and understanding of pharmacology.

First responder naloxone may save lives, when it is administered appropriately. We should study this before implementation. Discouraging us from studying the safety and efficacy of this type of use of naloxone is bad medicine.
 

Also see –

Is ‘Narcan by Everyone’ a Good Idea?

Should Basic EMTs Give Naloxone (Narcan)?

The Myth that Narcan Reverses Cardiac Arrest

To Narcan or not Narcan

What About Nebulized Naloxone (Narcan) – Part I

Footnotes:

[1] I’ve heard that PA is looking to follow down the “Narcan for everyone” route, in allowing PD and BLS folks to give intranasal naloxone. . . .
Facebook
Narcan post

[2] EMT defibrillation does not increase survival from sudden cardiac death in a two-tiered urban-suburban EMS system.
Sweeney TA, Runge JW, Gibbs MA, Raymond JM, Schafermeyer RW, Norton HJ, Boyle-Whitesel MJ.
Ann Emerg Med. 1998 Feb;31(2):234-40.
PMID: 9472187 [PubMed – indexed for MEDLINE]

.

Is ‘Narcan by Everyone’ a Good Idea?


Image credit.
 

My friend Jonathan Blatman asks the following question about naloxone (Narcan) on Facebook –
 

I’ve heard that PA (Pennsylvania) is looking to follow down the “Narcan for everyone” route, in allowing PD and BLS folks to give intranasal naloxone.[1]

 

The problem is not that basic EMTs, or first responders, or police are stupid people.

The problem is that all people are stupid people.

Doctors, nurses, and paramedics do not understand naloxone, so we need to improve the understanding of pharmacology among doctors, nurses, and paramedics, before we increase the ranks of ignorant people inappropriately administering the drug.

Naloxone itself is very safe.

A quack once challenged me to take 1,000 times the dose of any medicine I chose, while he would do the same with some natural product. I accepted and chose naloxone, with the condition that he first take 1,000 time the daily recommended dose of one of something he considered completely safe and natural – water.

The quack had it pointed out to him that this dose of all natural water would be deadly. The quack backed out. Whether naloxone’s standard dose is 0.4 mg (it should not be more than this) or the dose more popular in areas with frequent fentanyl overdoses (2.0 mg) does not matter. Naloxone has been demonstrated to be relatively safe at massive doses.
 

Adult Patients
In one small study, volunteers who received 24 mg/70 kg did not demonstrate toxicity.
In another study, 36 patients with acute stroke received a loading dose of 4 mg/kg (10 mg/m2/min) of naloxone hydrochloride injection followed immediately by 2 mg/kg/hr for 24 hours. Twenty-three patients experienced adverse events associated with naloxone use, and naloxone was discontinued in seven patients because of adverse effects. The most serious adverse events were: seizures (2 patients), severe hypertension (1), and hypotension and/or bradycardia (3).
[2]

 

400 mg (0.4 mg dose x 1,000) or 2,000 mg (2.0 mg x 1,000) would be higher than the doses tested in these patients, but would still be much safer than 1,000 times the recommended daily dose of water, even though water is safe and essential for life. It does not matter if there is fluoride in the water for it to be lethal, but we should fluoridate water, because only conspiracy theorists think that fluoride is dangerous in drinking water.
 


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

We engage in magical thinking about the drugs we give.

The problem is not with the drug. The problem is with the actions of the people giving the drug – us.

We still have a big push for giving fibrinolytics (tPA – tissue Plasminogen Activator) to patients with acute ischemic stroke, even though most of the improvement may be due to the transience of stroke symptoms in some stroke patients (TIS – Transient Ischemic Attack). Fibrinolytics do not appear to be beneficial for acute ischemic stroke and there is no reason to give them for a TIA.

There is weak beneficial evidence in only two out of eleven studies (only 18% of studies) – and increases in death in most studies of fibrinolytics for acute ischemic stroke.[3] The problem is not with the drug. The problem is with the actions of the people giving the drug. Most of the evidence shows death increased, but we ignore that.

Naloxone and tPA are both given based on a rush to treatment and a fear of not giving the standard of care – the Yuppie Nuremberg Defense.
 

Everyone’s got a mortgage to pay. [inner monologue] The Yuppie Nuremberg defense.[4]

 

Will this be a matter of providing naloxone, rather than providing ventilations?
 

An epidemic of naloxone-resistant heroin overdoses due to fentanyl adulteration has led to significant morbidity and mortality throughout the central and eastern United States. According to records of the Philadelphia County Medical Examiner’s office, at least 250 overdose deaths have been associated with fentanyl between April 1, 2006, and March 1, 2007.[5]

 

What about people who take more than one drug?

If the opioid is reversed, will there be problems?
 

All were initially lethargic and became agitated and combative after emergency medical service (EMS) personnel treated them with parenteral naloxone, which is routinely used for suspected heroin overdose to reverse the toxic effects of opioids (e.g., coma and respiratory depression). All patients received diazepam or lorazepam for sedation, and signs and symptoms resolved during the next 12-24 hours.[6]

 

Will we identify the patients who have other medical conditions that may respond after naloxone, but not because of naloxone, such as hypoglycemia, stroke, seizures, clonidine overdose, arrhythmia, head trauma, dehydration, syncope, et cetera?
 

Six of the 25 complete responders to naloxone (24%) ultimately were proven to have had false-positive responses, as they were not ultimately given a diagnosis of opiate overdose. In four of these patients, the acute episode of AMS was related to a seizure, whereas in two, it was due to head trauma; in none of these cases did the ultimate diagnosis include opiates or any other class of drug overdose (which might have responded directly to naloxone). Thus, what was apparently misinterpreted as a response to naloxone in these cases appears in retrospect to have been due to the natural lightening that occurs with time during the postictal period or after head trauma.[7]

 

The problem is not with the administration of naloxone, but with the faulty assumption that because a patient wakes up after naloxone, the patient woke up because of naloxone.

Doctors, nurses, and paramedics do not do a good job of identifying the difference currently. We need to educate them, rather than encourage others to replicate their mistakes.

Pharmacology is poorly understood by people with medical education.
 

The documented indication for nebulized naloxone administration was suspected opioid overdose in 70 patients (66.7%), altered mental status in 34 patients (32.3%), and respiratory depression in one patient (0.9%).[8]

 

The indication for naloxone is respiratory depression.

The treatment for respiratory depression is to supplement oxygen and/or ventilations. We have decided to give naloxone in stead.

Naloxone was used appropriately in fewer than 1% of patients.

How good bad will our naloxone by everyone education be?

Don’t wait with bated breath – someone my administer naloxone.
 

Also read –

Should Basic EMTs Give Naloxone (Narcan)?

The Myth that Narcan Reverses Cardiac Arrest

To Narcan or not Narcan

What About Nebulized Naloxone (Narcan) – Part I

Footnotes:

[1] I’ve heard that PA is looking to follow down the “Narcan for everyone” route, in allowing PD and BLS folks to give intranasal naloxone. . . .
Facebook
Narcan post

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

DailyMed
Adverse reactions
Overdosage
FDA Label

[3] The Guideline, The Science, and The Gap
Wednesday, April 17, 2013
Dr. David Newman
Smart EM
Article

[4] Thank You for Smoking
Movie, based on the book by Christopher Buckley
Wikiquote
Quote page

[5] Heroin: what’s in the mix?
Muller AA, Osterhoudt KC, Wingert W.
Ann Emerg Med. 2007 Sep;50(3):352-3.
PMID: 17709054 [PubMed – indexed for MEDLINE]

[6] Scopolamine Poisoning among Heroin Users — New York City, Newark, Philadelphia, and Baltimore, 1995 and 1996
MMWR (Morbidity and Mortality Weekly Report).
Vol 45, No 22;457;
Free Full Text from the Centers for Disease Control and prevention.

[7] The empiric use of naloxone in patients with altered mental status: a reappraisal.
Hoffman JR, Schriger DL, Luo JS.
Ann Emerg Med. 1991 Mar;20(3):246-52.
PMID: 1996818 [PubMed – indexed for MEDLINE]

[8] Can nebulized naloxone be used safely and effectively by emergency medical services for suspected opioid overdose?
Weber JM, Tataris KL, Hoffman JD, Aks SE, Mycyk MB.
Prehosp Emerg Care. 2012 Apr-Jun;16(2):289-92. doi: 10.3109/10903127.2011.640763. Epub 2011 Dec 22.
PMID: 22191727 [PubMed – indexed for MEDLINE]

.

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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The FDA Gives Us Recalls and Label Changes for EMS Week


Image credit.
 

The FDA (Food and Drug Administration) has been busy with recalls and label changes this past week for EMS week.
 

Labetalol Hydrochloride Injection, USP, 100 mg/20 mL (5 mg/mL) 20 mL Multidose Vial, NDC 0409-2267-20, Lot 36-225-DD, Expiration 12/01/2015.[1]

 

This is worse than the usual particulate matter. Since this is often used to lower the blood pressure of patients with bad things happening in the brain or the heart, a bit of particulate matter could be the coup de grâce.
 

The embedded particulate was identified as stainless steel and the floating particulate as iron oxide. To date, Hospira has not received reports of any adverse events associated with this issue for this lot. Hospira has attributed the embedded particulate to a supplier’s glass defect.[1]

 
 


Image at DailyMed.
 

Dobutamine is another medication with a recall that is given to some of our less stable patients.
 

In general, injected particulate matter may result acutely in local inflammation, phlebitis, and/or low level allergic response through mechanical disruption of tissue or immune response to the particulate. Small capillaries may become obstructed.[2]

 

Dobutamine is supposed to improve circulation through small capillaries. :oops:
 
 


 

Suppose you would like to ventilate a patient with a BVM (Bag Valve Mask) resuscitator (with the mask or connected to an endotracheal tube, a tracheostomy tube, and LMA, a King airway, . . . ). Some of them might not work properly.
 

voluntary medical device removal of a limited number of Ventlab™ Resuscitator Bags after becoming aware of complaints regarding a sticking duckbill valve that resulted in the resuscitation bags delivering no air through the patient valve, to the patient. The valves may stick due to incomplete curing during the manufacturing process. Resuscitation bags affected may not function properly and may result in a delay of treatment and life threatening health consequences that include hypoxia and hypoventilation.[3]

 

A sticking duckbill valve?

At 25 seconds of this video, there is a good view of the duckbill valve from the patient end.
 


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

There has been one report of injury requiring medical intervention due to the lack of a functional resuscitation bag and 31 reports of a delay in oxygenation due to the requirement to utilize a 2nd or 3rd device. The FDA has been notified of this voluntary action by Ventlab, LLC.[3]

 

If you are using injectable risperidone (Risperdal), watch out for anaphylaxis. It is rare, but it can make a bad situation worse and you probably were not injecting risperidone because the patient is being helpful.
 

6.8 Postmarketing Experience [for Risperdal Consta ]

  • added: Very rarely, cases of anaphylactic reaction after injection with RISPERDAL CONSTA have been reported during postmarketing experience in patients who have previously tolerated oral risperidone.[4]
  •  
     

    One of the new anticoagulants does not appear to increase the rate of stroke or heart attack (compared to warfarin [Coumadin]). Yay!

    But it does appear to increase the rate of GI bleed (GastroIntestinal bleed) (compared to warfarin [Coumadin]). Remember to pay attention to any signs of changes in bowel habits of signs of anemia in patients taking the newer anticoagulants.
     

    The new study included information from more than 134,000 Medicare patients, 65 years or older, and found that among new users of blood-thinning drugs, Pradaxa was associated with a lower risk of clot-related strokes, bleeding in the brain, and death, than warfarin. The study also found an increased risk of major gastrointestinal bleeding with use of Pradaxa as compared to warfarin. The MI risk was similar for the two drugs.[5]

     
     

    NTG (NiTroGlycerin – GTN GlycerylTriNitrate in Commonwealth countries) no longer has the following precaution –
     

    PRECAUTIONS
    Drug Interactions

    deleted: “Patients receiving antihypertensive…..concomitantly”
    [6]

     

    That was the good news.

    NTG is still discouraged if a patient is taking a PDE-5 (PhosphoDiEsterase-5) inhibitor.
     

    Footnotes:

    [1] Hospira Announces Voluntary Nationwide Recall Of One Lot Of Labetalol Hydrochloride Injection, USP, 100 MG/20 ML (5MG/ML), 20 ML, Multidose Vial, Due To Visible Particulates
    May 16, 2014
    Recalls, Market Withdrawals, & Safety Alerts
    FDA
    Recall

    [2] Hospira Announces Voluntary Nationwide Recall Of One Lot Of Dobutamine Injection, USP, 250 MG, 20 ML, Single-Dose Fliptop Vial, Due To Visible Particulates
    May 16, 2014
    Recalls, Market Withdrawals, & Safety Alerts
    FDA
    Recall

    [3] Ventlab, LLC. Issues a Nationwide Recall of Ventlab Resuscitator Bags Due to Possible Health Risk
    May 16, 2014
    Recalls, Market Withdrawals, & Safety Alerts
    FDA
    Recall

    [4] Risperdal (risperidone) tablets, oral solution, Risperdal M-Tab (risperidone) orally disintegrating tablets, and Risperdal Consta (risperidone) long-acting injection.
    Page Last Updated: 05/16/2014
    Safety information
    FDA
    Label change

    [5] Pradaxa (dabigatran): Drug Safety Communication – Lower Risk for Stroke and Death, but Higher Risk for GI Bleeding Compared to Warfarin
    [Posted 05/13/2014]
    Safety information
    FDA
    Label change

    [6] Nitrostat (nitroglycerin, USP) Sublingual Tablets
    Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)

    Page Last Updated: 05/16/2014
    Safety information
    FDA
    Label change

    .

    The Silver Lining of Epi – Organ Donation – Part 2

     

    Continuing from Part 1. In writing about why we should not get rid of epinephrine, Scott makes the following statement –
     

    Patients who receive epinephrine in cardiac arrests have worse outcomes.[1]

     

    Go read the full paragraph. I am not taking that out of context.

    Scott suggests that this is acceptable, because some of these patients will be brain dead and some of those brain dead patients will end up being organ donors.

    While it is true that some of those resuscitated from cardiac arrest following administration of epinephrine will end up being organ donors, should that affect our attempts to resuscitate the patient? Currently, the AHA (American Heart Association) does not encourage using treatments that may produce worse outcomes just for the purposes of increasing the number of organ donors.[2]
     

    Even hearts can be transplanted from cardiac arrest patients can produce good outcomes.[3]
     


     

    So far, so good.
     

    Maybe it is time to look at them from a different angle. We need to look at dealing with a cardiac arrest in stages. Stage one, of course, is to work as hard as we can to achieve ROSC. ROSC is an absolute: there is a pulse, or there is not a pulse.[1]

     

    How much harm do we do in order to get more ROSC (Return Of Spontaneous Circulation)?

    ROSC is binary, but there are many ways to obtain ROSC.

    The way we obtain ROSC seems to affect the survival of the patient and the brain function in those who do survive.
     

    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.[4]
     

    Compare that chart of HDE, SDE, and NE with this chart comparing Epinephrine and No Epinephrine.[5]
     


     

    More ROSC, but fewer survivors.[6]

    More organs, because of fewer survivors of cardiac arrest?

    Is this our goal?

    We could take the extreme utilitarian approach of Your organs can benefit far more people – if they are not in you.

    Scott wouldn’t advocate for that with any other patient, so why head that way with cardiac arrest?
     

    Patients who receive epinephrine in cardiac arrests have worse outcomes.[1]

     

    Is epinephrine the cause of the harm? We do not know and we are perversely not trying to find out.

    If giving epinephrine decreases survival from cardiac arrest, then giving epinephrine increases the pool of available organs at the expense of our original cardiac arrest patients. That is not the goal.

    Organ donation is important. Harming patients, in order to obtain more organs, is not the goal of organ donation.

    Footnotes:

    [1] The Silver Lining of Epi
    February 3, 2014
    EMS in the New Decade
    Scott
    Article

    [2] Organ Donation After Cardiac Arrest
    2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science
    Part 9: Post–Cardiac Arrest Care
    Free Full Text from AHA.

    [3] Cardiac arrest in the organ donor does not negatively influence recipient survival after heart transplantation.
    Ali AA, Lim E, Thanikachalam M, Sudarshan C, White P, Parameshwar J, Dhital K, Large SR.
    Eur J Cardiothorac Surg. 2007 May;31(5):929-33. Epub 2007 Mar 26.
    PMID: 17387020 [PubMed – indexed for MEDLINE]

    Free Full Text from Eur J Cardiothorac Surg.

    [4] 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]

    [5] 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.

    [6] Are We Killing People With ROSC?
    Wed, 05 Jun 2013
    Rogue Medic
    Article

    .