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Publication Bias – The Lit Whisperers

Tue, 11 Jun 2013 23:30:25 +0000 by Rogue Medic 1 Comment

The Lit Whisperers raise an important point about publication bias and the validity of published drug company studies that show benefit of treatments that still have patent exclusivity.^[1]

There are many problems with science. Science will never be perfect, but only people who do not understand science claim that it should be perfect.

One of the problems with science is publication bias. A paper that has a positive results about a brand name drug is twice as likely to be published than a paper with neutral results or with negative results.

The drug company has no incentive to publish a paper that does not make their drug look good. If you think that this is conspiracy talk, ask the drug companies for the results of the studies that have not been published.

Dr. Joe Lex states that we should take the published positive results for any drug and cut the claimed benefit in half, because the first published studies are often the most positive results that we will ever see.

Positive results may be seen as the best case scenario.

Look at the way that the antiarrhythmic amiodarone (Cordarone by Wyeth Pharmaceuticals Company, a subsidiary of Pfizer Inc.) became the ACLS (Advanced Cardiac Life Support) standard of care for VF/Pulseless VT (Ventricular Fibrillation/Pulseless Ventricular Tachycardia). One study showed that we had more ROSC (Return Of Spontaneous Circulation) with amiodarone than with lidocaine (Xylocaine by Astra Apotekarnes Kem Fab [SE], now AstraZeneca LP, originally patented in 1948 as a local anesthetic, but probably no longer patent protected as an antiarrhythmic at the time of the studies).

In the 2000 ACLS guidelines, we were told that we should treat every VF/Pulseless VT patient with amiodarone.

Why?

A single study compared ROSC among patients treated with 300 mg amiodarone or an equal volume of Polysorbate 80. Polysorbate 80 is a diluent in amiodarone that appears to cause bradycardia and hypotension, so it is not appropriate as a placebo.^[2]

Wow! That’s Effective!

There was a statistically significant difference in ROSC. 44 percent (108 of 246) of the amiodarone group and 34 percent (89 of 258) in the placebo group had ROSC for a p value of 0.03.

There was not a statistically significant difference in survival to discharge – 13.4 percent (33 of 246) of the amiodarone group and 13.2 percent (34 of 258) of the ~~Polysorbate 80~~ placebo group.

Yawn. That’s NOT Effective.

Of the 504 study patients, 67 (13 percent) were discharged alive from the hospital. Of the remaining 130 patients who were admitted to the hospital, 13 patients awakened, and 117 (90 percent) never regained consciousness.^[3]

Since the best outcome for 90% of these patients was a short-term coma, followed by death, was this result of a single study appropriate to change the standard of care?

More patients had ROSC, but none of them survived to discharge.

ROSC is the wrong goal.

The standard of care was changed based on this single study that did not show any improvement that mattered.

Wyeth stated that they were studying the effect of amiodarone on survival to discharge, but after becoming the standard of care, Wyeth had no reason to publish a study that did not show improved outcomes with

Brandon Oto mentions this 13 1/2 minute presentation by Dr. Ben Goldacre at Ted Talks, which is very good to watch.

Ben Goldacre: What doctors don’t know about the drugs they prescribe

A better, much more informative 1 1/2 hour presentation by Dr. Goldacre is available at CSPAN –

Go watch the discussion of Bad Pharma.

Listen to Dr. Joe Lex’s A Skeptic’s Guide to the Medical Literature.

Footnotes:

^[1] Publication Bias
June 5, 2013
by Brandon Oto
The Lit Whisperers
Article

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

The adverse hemodynamic effects of the IV formulation of amiodarone are attributed to vasoactive solvents (polysorbate 80 and benzyl alcohol).

^[3] Amiodarone for resuscitation after out-of-hospital cardiac arrest due to ventricular fibrillation.
Kudenchuk PJ, Cobb LA, Copass MK, Cummins RO, Doherty AM, Fahrenbruch CE, Hallstrom AP, Murray WA, Olsufka M, Walsh T.
N Engl J Med. 1999 Sep 16;341(12):871-8.
PMID: 10486418 [PubMed - indexed for MEDLINE]

Free Full Text from New England Journal of Medicine.

Kudenchuk, P., Cobb, L., Copass, M., Cummins, R., Doherty, A., Fahrenbruch, C., Hallstrom, A., Murray, W., Olsufka, M., & Walsh, T. (1999). Amiodarone for Resuscitation after Out-of-Hospital Cardiac Arrest Due to Ventricular Fibrillation New England Journal of Medicine, 341 (12), 871-878 DOI: 10.1056/NEJM199909163411203

Filed Under: Ethics, Evidence, Heresy, Research Blogging

Examples of Ventricular Tachycardia Caused by Amiodarone – Part I

Tue, 28 May 2013 09:30:50 +0000 by Rogue Medic Leave a Comment

How much worse could the patient get if we give amiodarone?

But amiodarone doesn’t cause V Tach (Ventricular Tachycardia). Amiodarone stops V Tach.

Right?

If amiodarone can cause V Tach, shouldn’t someone have told us?

Click on image to make it larger.

This is a wide complex tachycardia, which should be presumed to be V Tach. The diagnosis of the rhythm as V Tach is supported by the P-wave dissociation and by the history of a heart attack a couple of weeks before. 19 QRS complexes in 5 seconds (multiply by 12 to get the rate for 60 seconds) = 228.

According to ACLS (Advanced Cardiac Life Support) what drug would be indicated for the above rhythm?

For the old timers, let’s throw in a bit of information that is supposed to be important in deciding among the various antiarrhythmics –

Transthoracic echocardiography was performed, and the ejection fraction was 34% based on the modified Simpson method.^[1]

Does the ejection fraction matter in treating wide-complex tachycardia?

Note that amiodarone becomes the antiarrhythmic of choice (after failure of adenosine) if the patient’s cardiac function is impaired and the ejection fraction is <40% or there are signs of congestive heart failure.^[2]

That was only mentioned in the 2000 ACLS guidelines. The 2005 ACLS guidelines and the 2010 ACLS guidelines do not mention ejection fraction in the treatment of V Tach.

Do we have good evidence that amiodarone is effective for stable V Tach?

Amiodarone has not been studied specifically for the pharmacological termination of hemodynamically stable VT, but it is effective in treating hemodynamically unstable VT and VF.^{78 81 82 83 84 85 86 87 88 89 90 91} ^[2]

That was written in 2000 and the answer was NO.

Now we have evidence that amiodarone may be effective in about one out of four patients – if we are prepared to wait a half hour, or more. In other words, it is rare for amiodarone to work and rarer still for amiodarone to work before we can get the patient to the hospital.^[3],^[4],^[5]

We do have evidence that amiodarone may be a part of the long-term treatment of unstable V Tach. On the other hand, maybe not.

I do mean long-term treatment, even though these are unstable patients.

Twenty-seven (58.5%) of the 46 patients responded to intravenous amiodarone, and an additional 6 patients (13%) showed a late response to amiodarone (Fig. I). Fifteen of the 27 responders (33% of all patients) responded immediately (0 to 2 h), and 26 responded within 72 h . The other patient responded within 84 h (Fig. 2).^[6]

Up to 84 hours to take effect.

Not exactly an emergency drug.

I have worked some very long shifts. I have never worked an 84 hour shift.

If amiodarone can take 84 hours to work, and the patient is receiving a variety of other treatments during those 84 hours, is it really the amiodarone that is working?

Compared with 84 hours, a less than two hour time to response seems almost instantaneous, but it is not fast for EMS.

This patient was treated with oral amiodarone for sustained V Tach during his previous hospital admission for an acute anterior MI (Myocardial Infarction) treated with a stent in the LAD (Left Anterior Descending) coronary artery.

This time he was treated with IV (IntraVenous) amiodarone. The problems began on the first day of IV amiodarone treatment.

On the first day of hospitalization, the patients had 10 attacks of pulseless VT treated with successful DC shocks. Occasionally, VT attacks degenerated to ventricular fibrillation.^[1]

And continued –

On the second day of hospitalization, the patient had 14 pulseless VT attacks with successful DC shocks.^[1]

But the V Tach stopped after the amiodarone was stopped and antithyroid therapy was begun.

Thyroid gland toxicity is one of the most important adverse effects of amiodarone and is called amiodarone-induced thyrotoxicosis. Thyrotoxicosis may alter arrhythmia and lead to frequent ventricular tachycardia attacks.^[1]

All things are poison, and nothing is without poison; only the dose permits something not to be poisonous. – Paracelsus (1493-1541)

We do not seem to explain that well in EMS, or even in emergency medicine.

All antiarrhythmic agents have some degree of proarrhythmic effects.^[7]

Amiodarone is one of the most dangerous drugs we carry in EMS.

How much thought do we give to the problems we can cause for our patients with this drug?

How much do we understand about the problems we could be causing when we push medications, such as amiodarone?

Footnotes:

^[1] Therapy-resistant ventricular tachycardia caused by amiodarone-induced thyrotoxicosis: a case report of electrical storm.
Erdogan HI, Gul EE, Gok H, Nikus KC.
Am J Emerg Med. 2012 Nov;30(9):2092.e5-7. doi: 10.1016/j.ajem.2011.12.035. Epub 2012 Mar 3.
PMID: 22386340 [PubMed - indexed for MEDLINE]

^[2] Amiodarone
2000 ECC Guidelines
Part 6: Advanced Cardiovascular Life Support
Section 5: Pharmacology I: Agents for Arrhythmias
Arrhythmias and the Drugs Used to Treat Them
Hemodynamically Stable Wide-/Broad-Complex Tachycardias
Treatment of Wide-Complex Tachycardias
Free Full Text from Circulation.

^[3] Amiodarone is poorly effective for the acute termination of ventricular tachycardia.
Marill KA, deSouza IS, Nishijima DK, Stair TO, Setnik GS, Ruskin JN.
Ann Emerg Med. 2006 Mar;47(3):217-24. Epub 2005 Nov 21.
PMID: 16492484 [PubMed - indexed for MEDLINE]

^[4] Amiodarone or procainamide for the termination of sustained stable ventricular tachycardia: an historical multicenter comparison.
Marill KA, deSouza IS, Nishijima DK, Senecal EL, Setnik GS, Stair TO, Ruskin JN, Ellinor PT.
Acad Emerg Med. 2010 Mar;17(3):297-306. doi: 10.1111/j.1553-2712.2010.00680.x.
PMID: 20370763 [PubMed - indexed for MEDLINE]

Free Full Text from Academic Emergency Medicine.

^[5] Intravenous amiodarone for the pharmacological termination of haemodynamically-tolerated sustained ventricular tachycardia: is bolus dose amiodarone an appropriate first-line treatment?
Tomlinson DR, Cherian P, Betts TR, Bashir Y.
Emerg Med J. 2008 Jan;25(1):15-8.
PMID: 18156531 [PubMed - indexed for MEDLINE]

^[6] Use of intravenous amiodarone for emergency treatment of life-threatening ventricular arrhythmias.
Helmy I, Herre JM, Gee G, Sharkey H, Malone P, Sauve MJ, Griffin JC, Scheinman MM.
J Am Coll Cardiol. 1988 Oct;12(4):1015-22.
PMID: 3417974 [PubMed - indexed for MEDLINE]

Page with link to Free Full Text Download in PDF format from J Am Coll Cardiol.

This is footnote 84 from the second 2000 ACLS quote.

^[7] New Concerns From the International Guidelines 2000 Conference: Impaired Hearts and “Proarrhythmic Antiarrhythmics”
2000 ECC Guidelines
Part 6: Advanced Cardiovascular Life Support
Section 5: Pharmacology I: Agents for Arrhythmias
Arrhythmias and the Drugs Used to Treat Them
Hemodynamically Stable Wide-/Broad-Complex Tachycardias
Free Full Text from Circulation.

Erdogan, H., Gul, E., Gok, H., & Nikus, K. (2012). Therapy-resistant ventricular tachycardia caused by amiodarone-induced thyrotoxicosis: a case report of electrical storm The American Journal of Emergency Medicine, 30 (9), 209200000-2147483647 DOI: 10.1016/j.ajem.2011.12.035

Marill, K., deSouza, I., Nishijima, D., Stair, T., Setnik, G., & Ruskin, J. (2006). Amiodarone Is Poorly Effective for the Acute Termination of Ventricular Tachycardia Annals of Emergency Medicine, 47 (3), 217-224 DOI: 10.1016/j.annemergmed.2005.08.022

Marill, K., deSouza, I., Nishijima, D., Senecal, E., Setnik, G., Stair, T., Ruskin, J., & Ellinor, P. (2010). Amiodarone or Procainamide for the Termination of Sustained Stable Ventricular Tachycardia: An Historical Multicenter Comparison Academic Emergency Medicine, 17 (3), 297-306 DOI: 10.1111/j.1553-2712.2010.00680.x

Tomlinson, D., Cherian, P., Betts, T., & Bashir, Y. (2008). Intravenous amiodarone for the pharmacological termination of haemodynamically-tolerated sustained ventricular tachycardia: is bolus dose amiodarone an appropriate first-line treatment? Emergency Medicine Journal, 25 (1), 15-18 DOI: 10.1136/emj.2007.051086

Helmy, I., Herre, J., Gee, G., Sharkey, H., Malone, P., Sauve, M., Griffin, J., & Scheinman, M. (1988). Use of intravenous amiodarone for emergency treatment of life-threatening ventricular arrhythmias Journal of the American College of Cardiology, 12 (4), 1015-1022 DOI: 10.1016/0735-1097(88)90470-6

Filed Under: ACLS, Cardiology, Education, Heresy, Pharmacology, Research Blogging

Does experience matter – Part II

Wed, 08 May 2013 16:30:57 +0000 by Rogue Medic

In spite of the evidence to the contrary and a lack of rationality in the claim, we continue to be told that increasing the number of people with a title, such as paramedic, will result in better care.

Here is more evidence that dividing the skills among more people leads to less skilled care.

The authors begin by referring to other studies that demonstrate the high failure rate of doctors performing procedures on children.

How is that relevant to EMS? We have a low frequency of use of critical skills – and that is with our adult patients. With children, our absence of experience is even more of a problem. When we do use our infrequently used skills, we often use them inappropriately.^[1],^[2]

Emergency physicians must be competent in the performance of critical procedures associated with pediatric resuscitation. It has traditionally been assumed that the clinical practice of pediatric emergency medicine is sufficient for the acquisition and maintenance of these skills. If the relative low acuity of the pediatric emergency medicine patient population provides inadequate opportunity, there is a risk that procedural skills will not be acquired by trainees or maintained by faculty. An accurate description of the frequency with which faculty and trainees perform critical procedures in a pediatric ED would allow for more informed discussion and targeted interventions to reduce this risk.^[3]

We need similar examinations of what we do in EMS.

We hypothesized that even in a high-volume pediatric ED, the overall frequency of critical procedures would be very low and the exposure of individual providers to critical procedures negligible.^[3]

Would that be any different from a busy EMS system with a lot of paramedics?

From April 1, 2009, through March 31, 2010, 3,067 evaluations were performed on medical and trauma patients in the resuscitation bays. Two hundred sixty-one critical procedures were performed during 194 evaluations, representing 6.3% of all resuscitation bay evaluations and 0.22% (2.2/1,000) of all ED patient evaluations during the study period.^[3]

Click on images to make them larger.

That does not look bad.

147 intubations, 9 needle chest decompressions, and 6 synchronized cardioversions in a year.

Except – that is for the entire hospital.

When broken down by the doctor actually performing the procedure

Only 39% were able to try to perform any procedure during a year when there were 147 intubations, 9 needle chest decompressions, and 6 synchronized cardioversions.

Look at the range for all critical procedures combined –

0 to 6, with a median of 0.

The white clouds were most of the doctors. Zero critical procedures for the year.

The busiest of the black clouds^[4],^[5],^[6] were only averaging performing one critical procedure every two months.

How much experience do paramedics get when there are a lot of paramedics available to deprive them of experience?

Do we track this and post it for all to see?

What is the level of inexperience in an EMS system that has a paramedic in every seat of every piece of apparatus?

What kind of daily, or even weekly training is required to make up for this absence of experience?

Nearly two thirds of our faculty did not perform a single critical procedure during the 12-month study period.^[3]

Does experience matter – Part I

Footnotes:

^[1] Inadequate needle thoracostomy rate in the prehospital setting for presumed pneumothorax: an ultrasound study.
Blaivas M.
J Ultrasound Med. 2010 Sep;29(9):1285-9.
PMID: 20733183 [PubMed - in process]

Free Full Text from J Ultrasound Med.

^[2] Low quality is identified by inability to use critical thinking
Mon, 20 Aug 2012
Rogue Medic
Article

Click on the image to make it larger.

The chart is for all patients treated with needle decompression for suspected tension pneumothorax.

Many patients never had any kind of pneumothorax.

Did any patient have a tension pneumothorax?

We do not know.

^[3] The spectrum and frequency of critical procedures performed in a pediatric emergency department: implications of a provider-level view.
Mittiga MR, Geis GL, Kerrey BT, Rinderknecht AS.
Ann Emerg Med. 2013 Mar;61(3):263-70. doi: 10.1016/j.annemergmed.2012.06.021. Epub 2012 Jul 27.
PMID: 22841174 [PubMed - indexed for MEDLINE]

Free Full Text from Annals of Emergency Medicine.

^[4] Quantification and perception of on-call podiatric surgical resident workload.
Meyr AJ, Gonzalez O, Mayer A.
J Foot Ankle Surg. 2011 Sep-Oct;50(5):535-6. doi: 10.1053/j.jfas.2011.04.035. Epub 2011 Jun 11.
PMID: 21652228 [PubMed - indexed for MEDLINE]

The results of these data suggest that all residents shared a similar workload during the study period without a clinically significant “black cloud” or “white cloud.” However, a difference was found in the perception of which resident was a “black cloud” or “white cloud.”

^[5] Black clouds. Work load, sleep, and resident reputation.
Tanz RR, Charrow J.
Am J Dis Child. 1993 May;147(5):579-84.
PMID: 8488808 [PubMed - indexed for MEDLINE]

A reputation for difficult on-call experiences was strongly associated with few hours of sleep (r = -.77; 95% confidence interval, -0.49 to -0.91), but not with actual work load measured by the number of admissions, patients, deaths, or other variables. Sleep was the major predictor of reputation (multiple R2 = .567 using multiple linear regression analysis).

CONCLUSIONS:
Some residents did have a black cloud; they slept less, perceived that they worked harder than average, and had a reputation for having difficult on-call experiences. Residents with a black cloud function differently from their colleagues; for example, some may be inefficient, while others may create extra work for themselves. Residency program directors must recognize these functional differences to effectively evaluate and counsel house officers.

^[6] Fooled by Randomness: The Hidden Role of Chance in Life and in the Markets
(Google eBook)
Nassim Nicholas Taleb
Random House Digital, Inc.,
Oct 14, 2008
316 pages
Google Books

Believing in black clouds, or other personifications of random occurrences is being fooled by randomness. Dr. Taleb does a good job of describing these errors of judgment.

Mittiga, M., Geis, G., Kerrey, B., & Rinderknecht, A. (2013). The Spectrum and Frequency of Critical Procedures Performed in a Pediatric Emergency Department: Implications of a Provider-Level View Annals of Emergency Medicine, 61 (3), 263-270 DOI: 10.1016/j.annemergmed.2012.06.021

Blaivas M (2010). Inadequate needle thoracostomy rate in the prehospital setting for presumed pneumothorax: an ultrasound study. Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine, 29 (9), 1285-9 PMID: 20733183

Tanz RR, & Charrow J (1993). Black clouds. Work load, sleep, and resident reputation. American journal of diseases of children (1960), 147 (5), 579-84 PMID: 8488808

Meyr, A., Gonzalez, O., & Mayer, A. (2011). Quantification and Perception of On-call Podiatric Surgical Resident Workload The Journal of Foot and Ankle Surgery, 50 (5), 535-536 DOI: 10.1053/j.jfas.2011.04.035

Filed Under: Experience, Heresy, Research Blogging, Risk Management

Will IV Oxygen Save Lives?

Thu, 02 May 2013 16:30:43 +0000 by Rogue Medic

Image credit.

Intravenous oxygen delivery that works?

Maybe temporary oxygenation, but not yet.

Will this change the approach to CICV (Can’t Intubate, Can’t Ventilate) patients?

No, but it may change the approach to CICO (Can’t Intubate, Can’t Oxygenate) patients.

The distinction is important. If we can deliver oxygen without ventilation, we can avoid some of the problems of hypoxia, but we will still have to deal with the acidosis that results from the inability to eliminate CO₂ (Carbon DiOxide).

In the early 1900s, intravenous administration of oxygen gas was used in attempts to relieve refractory cyanosis (4–7). Most reported that spontaneously breathing, cyanotic animals exhibited signs of pulmonary embolism at infusion rates in excess of 0.2 to 1 ml/kg per minute and required frequent pauses in the infusion (4, 5); . . . None of these studies documented an increase in oxygen content in the blood as a result of the intervention.^[1]

Try walking up several flights of stairs while only breathing through your nose. You will become short of breath very quickly.

Unless you are in truly horrible shape, it is not a lack of oxygen that is causing you to become short of breath. It is the inability to remove CO₂ (Carbon DiOxide) that is the problem.

Most of us breathe because of a buildup of CO₂, not because of a lack of oxygen.

The reflexive response of some people might be to give the anti-acidosis drug NaHCO₃ (sodium bicarbonate). We will ignore the sodium, which at 5.8% in NaHCO₃ is over 6 times the concentration of the NSS (Normal Saline Solution – 0.9% sodium) we routinely give. The sodium in NaHCO₃ may be effective for treating sodium channel blocking drugs, such as antidepressnts, antiseizure medications, antiarrhythmics, and antivirals.^[2]

The sodium is not the real danger. The bicarbonate (HCO₃^-) is the problem. When binding with the excess hydrogen ions to neutralize metabolic acidosis, CO₂ is produced.

HCO₃^- + H⁺

Produces:

CO₂ + H₂O

a patient with complex airway anatomy and difficulty maintaining oxygenation using basic airway maneuvers could avert a hypoxemic crisis during a prolonged intubation attempt. To date, safe and effective intravascular delivery of oxygen gas has not been realized.^[1]

In the cute little bunnies used in the study (7 LOM [Lipidic Oxygen–containing Microparticles] and 6 Control), these were the results.

Click on images to make them larger.

Oxygen saturation remained between 40% and 60% with the LOM, but that was much better than the less than 20% for the controls. since the study animals received LOMs titrated to an arterial oxygen tension of greater than 30 mmHg, this is not a surprise. The controls just received fluid at a similar rate.

CO₂ more than doubled for both groups.

Providing oxygen does nothing to remove CO₂.

When CO₂ increases, the pH will decrease (acidosis will increase).

Sodium bicarbonate will not decrease the acidosis for these patients.

Sodium bicarbonate will increase the acidosis for these patients.

Sodium bicarbonate produces CO₂, which must be removed by ventilation. If we are giving LOM to patients we can adequately ventilate, maybe we do not understand what we are doing.

We should only give sodium bicarbonate to a patient who is well ventilated – unless we are trying to kill the patient.

In (F) and (G), data are means ±SEM. The blue lines end at 10.2 min because no animals treated as controls had spontaneous circulation after that time and received chest compression–only cardiopulmonary resuscitation (CPR) during the remainder of asphyxia. (H) Kaplan-Meier plot of animals experiencing cardiac arrest during asphyxia (left; P =0.0002, log-rank test), restoration of mechanical ventilation (shaded box), and subsequent recovery and observation (right).^[1]

None of the bunnies reported any near-death experiences.

Consider the time involved. Many in the media have been reporting this as a way to provide half an hour of apneic oxygenation. That is ridiculously optimistic. This will be something that might provide an extra 5-10 minutes to manage a hypoxic patient, if the patient has not already died due to the hypoxia.

5-10 minutes can be the difference between life and death.

Don’t believe me?

Hold your breath for 10 minutes. Just stop breathing and hold your breath.^[3]

Without LOMs, all of the bunnies were pulseless after a little more than 10 minutes, but at 15 minutes, when ventilation was resumed, almost all of the LOM bunnies still had pulses (6 out of 7).

LOMs are not just to make it possible to deliver a patient with a pulse to the hospital, so that we can say that They didn’t die in the ambulance.

That is not changing anything.

LOMs are to provide time for us to provide an airway – if this ever demonstrates safety and efficacy in humans.

Footnotes:

^[1] Oxygen gas-filled microparticles provide intravenous oxygen delivery.
Kheir JN, Scharp LA, Borden MA, Swanson EJ, Loxley A, Reese JH, Black KJ, Velazquez LA, Thomson LM, Walsh BK, Mullen KE, Graham DA, Lawlor MW, Brugnara C, Bell DC, McGowan FX Jr.
Sci Transl Med. 2012 Jun 27;4(140):140ra88. doi: 10.1126/scitranslmed.3003679.
PMID: 22745438 [PubMed - indexed for MEDLINE]

Free Full Text Download in PDF format from medlive.cn

At the end of the asphyxial period, mechanical ventilation was restored with 100% oxygen until return of pulsations (in animals receiving chest compressions) and then titrated downward to achieve arterial saturations of >92%. Animals achieving return of spontaneous circulation after relief of asphyxia were treated with standard intensive care management, including inotropic support (dopamine, 2 to 10 mg/kg per minute, intravenous infusion) to maintain MABP of at least 40 mmHg during the follow-up period. Hyperthermia was avoided by passive ambient cooling (goal, 34 to 35° C). Animals were sacrificed 90 min after the end of asphyxia for lab and histology sampling.

Everyone seems to be using therapeutic hypothermia and trying to avoid giving too much oxygen.

^[2] Management of sodium-channel blocker poisoning: the role of hypertonic sodium salts.
Di Grande A, Giuffrida C, Narbone G, Le Moli C, Nigro F, Di Mauro A, Pirrone G, Tabita V, Alongi B.
Eur Rev Med Pharmacol Sci. 2010 Jan;14(1):25-30. Review.
PMID: 20184086 [PubMed - indexed for MEDLINE]

Free Full Text in PDF format from EuropeanReview.org

As more substances having sodium-channel blocking properties become available, the incidence of this poisoning may be expected to increase, and clinician, particularly the emergency physician, should be familiar with this potential fatal condition.

A little evidence supports the treatment with hypertonic sodium salts, and current recommendations have not been based on randomized clinical trials.

^[3] Longest time breath held voluntarily (male)
Guinness World Records
Web page.

The longest time holding the breath underwater was 22 min 00 sec by Stig Severinsen (Denmark) at the London School of Diving in London, UK, on 3 May 2012.

Stig was allowed to hyperventilate with oxygen prior to the attempt, and did this for 19 minutes and 30 seconds.

Kheir, J., Scharp, L., Borden, M., Swanson, E., Loxley, A., Reese, J., Black, K., Velazquez, L., Thomson, L., Walsh, B., Mullen, K., Graham, D., Lawlor, M., Brugnara, C., Bell, D., & McGowan, F. (2012). Oxygen Gas-Filled Microparticles Provide Intravenous Oxygen Delivery Science Translational Medicine, 4 (140), 140-140 DOI: 10.1126/scitranslmed.3003679

Filed Under: Heresy, Intubation, Oxygen, Pharmacology, Research Blogging

Is Nitroglycerin Bad for Severe Sepsis?

Wed, 17 Apr 2013 16:30:12 +0000 by Rogue Medic

Yesterday at The Paramedic’s Edge, this was the topic of ~~reactive, reflexive, dogmatic, rejection~~ discussion of a possible use of NTG (NiTroGlycerin – GTN GlycerylTriNitrate in Commonwealth countries).

NTG is a vasodilator and sepsis is a vasodialtion problem. There are other problems with sepsis, but vasodilation may be the primary problem.

Nitro for severe septic patients. What are your thoughts?^[1]

Here is a sampling of some of the unfortunately typical responses.

The amateur lawyer who thinks that what we do should be guided by fear of law suits approach.

Oh to put them out of their misery?! Sounds like a lawsuit waiting to happen

The just drive fast, I don’t understand any of this medical mumbo jumbo appraoch.

We’re medics not doctors. Best thing we can do is a diesel infusion

The most common responses seemed to be of this kind.

The I only know one thing about nitro and that scares me approach.

True hemodynamic instability is a contraindication

Hmmmm let’s drop their pressure even more…that’s a thought? So my answer…HE’LL NO!!

We will probably end up using NTG in the treatment of cardiac arrest – the ultimate low blood pressure state, so how far fetched is using NTG for sepsis?^[2],^[3],^[4],^[5],^[6],^[7]

Why?

NTG can lower blood pressure, but it can also increase cardiac output.

To over-simplify things –

If the CO (Cardiac Output) increases by more than the the vasodilation would decrease the BP (Blood Pressure), the BP will actually be expected to increase.

CO = SV (Stroke Volume) x HR (Heart Rate).

CO ≈ MAP (Mean Arterial Pressure)/TPR (Total Peripheral Resistance).

BP = CO x TPR.

Are all cardiac outputs and vascular resistances the same? No, but we simplify things by making that assumption.

Jean-Charles Preiser and colleagues question the routine use of nitroglycerin because of the risk of hypotension and the possible induction of mitochondrial dysfunction.^[8]

Many people question the use of NTG and worry about hypotension.

Although we observed a temporary drop in blood pressure, blood flow was maintained and, in fact, increased in our patients.^[8]

We do ~~worry~~ obsess about things that are brief and insignificant (such as ROSC – Return Of Spontaneous Circulation – in treatment of cardiac arrest), while we ignore the things that are more important (such as living long enough to leave the hospital with a brain that works well enough to recognize family members).

Space constraints meant that we were not able to include specific haemodynamic results in our Research letter, but mean arterial pressure temporarily dropped by an average of 21 mm Hg (range 13—33 mm Hg) in the eight patients we investigated.^[8]

A drop in MAP (Mean Arterial Pressure) of 21 mm/Hg is huge!

Mean arterial pressure returned to baseline level within 1 min in all patients with concomitant fluid infusion.^[8]

Less than 1 minute?

Try using that as a pickup line.

I can rock your world for less than 1 minute.

How much alcohol is going to be required to make that sound significant?

We give adenosine to do what?

To completely stop the heart for usually less than one minute.

We cardiovert to do what?

To completely stop the heart for usually less than one minute.

A short-term worsening of vital signs for a long-term improvement in survival is an excellent trade-off.

Does NTG improve long-term survival?

that is not clear, but this does show that we need to abandon more dogma in our search for the best care of our patients.

The increase in microvascular blood flow as a result of this procedure confirms our clinical experience that resuscitation efforts should be aimed at optimising blood flow not blood pressure.^[8]

NTG does improve blood flow.

Too many of us are afraid to use NTG, or afraid to use large doses of NTG, or afraid to use IV bolus NTG, or afraid to use large doses of IV bolus NTG out of too much concern for blood pressure and not enough concern for blood flow.

This quotes are from a response to a letter about research paper looking at NTG for sepsis. This paper is not something that should be summarily dismissed.^[9]

The EMS drug of choice, dopamine, may be a bad idea for sepsis.^[10],^[11]

Think about that – For sepsis dopamine may make things worse and NTG may make things better.

Is it that simple? Maybe. Maybe not. Dopamine may make things better, but just not do as good a job as norepinephrine. Or all catecholamines may be harmful.

Dr. Mervyn singer makes an excellent case that catecholamines are not helpful, or that they are at least tremendously overused. Go listen to his podcast.^[12]

Footnotes:

^[1] Nitro for severe septic patients. What are your thoughts?
The Paramedic’s Edge
Facebook
Facebook discussion page

^[2] High dose nitroglycerin treatment in a patient with cardiac arrest: a case report.
Guglin M, Postler G.
J Med Case Rep. 2009 Aug 10;3:8782. doi: 10.4076/1752-1947-3-8782.
PMID: 19830240 [PubMed]

Free Full Text from PubMed Central.

A possible explanation for the hemodynamic benefit of NTG in our patients is increased cardiac output produced by rapid vasodilatation in a heart operating at the extreme of the Frank-Starling curve. Vasodilators in heart failure with or without acute myocardial infarction have been proven to decrease left ventricular filling pressure and systemic vascular resistance while increasing cardiac index [7]. The more severe the failure, the more beneficial the effect of vasodilators [13].

^[3] Sodium nitroprusside enhanced cardiopulmonary resuscitation improves survival with good neurological function in a porcine model of prolonged cardiac arrest.
Yannopoulos D, Matsuura T, Schultz J, Rudser K, Halperin HR, Lurie KG.
Crit Care Med. 2011 Jun;39(6):1269-74. doi: 10.1097/CCM.0b013e31820ed8a6.
PMID: 21358401 [PubMed - indexed for MEDLINE]

Free Full Text from acoep.org.

^[4] Sodium nitroprusside-enhanced cardiopulmonary resuscitation improves resuscitation rates after prolonged untreated cardiac arrest in two porcine models.
Schultz JC, Segal N, Caldwell E, Kolbeck J, McKnite S, Lebedoff N, Zviman M, Aufderheide TP, Yannopoulos D.
Crit Care Med. 2011 Dec;39(12):2705-10. doi: 10.1097/CCM.0b013e31822668ba.
PMID: 21725236 [PubMed - indexed for MEDLINE]

Free Full Text from PubMed Central.

^[5] Sodium nitroprusside enhanced cardiopulmonary resuscitation (SNPeCPR) improves vital organ perfusion pressures and carotid blood flow in a porcine model of cardiac arrest.
Schultz J, Segal N, Kolbeck J, McKnite S, Caldwell E, Yannopoulos D.
Resuscitation. 2012 Mar;83(3):374-7. doi: 10.1016/j.resuscitation.2011.07.038. Epub 2011 Aug 22.
PMID: 21864483 [PubMed - indexed for MEDLINE]

Free Full Text from PubMed Central.

^[6] Sodium nitroprusside enhanced cardiopulmonary resuscitation prevents post-resuscitation left ventricular dysfunction and improves 24-hour survival and neurological function in a porcine model of prolonged untreated ventricular fibrillation.
Schultz J, Segal N, Kolbeck J, Caldwell E, Thorsgard M, McKnite S, Aufderheide TP, Lurie KG, Yannopoulos D.
Resuscitation. 2011 Dec;82 Suppl 2:S35-40. doi: 10.1016/S0300-9572(11)70149-6.
PMID: 22208176 [PubMed - indexed for MEDLINE]

^[7] Controlled pauses at the initiation of sodium nitroprusside-enhanced cardiopulmonary resuscitation facilitate neurological and cardiac recovery after 15 mins of untreated ventricular fibrillation.
Yannopoulos D, Segal N, McKnite S, Aufderheide TP, Lurie KG.
Crit Care Med. 2012 May;40(5):1562-9. doi: 10.1097/CCM.0b013e31823e9f78.
PMID: 22430233 [PubMed - indexed for MEDLINE]

^[8] Nitroglycerin for septic shock.
Preiser JC, De Backer D, Vincent JL.
Lancet. 2003 Mar 8;361(9360):880; author reply 880. No abstract available.
PMID: 12642079 [PubMed - indexed for MEDLINE]

Free Full Text from the Lancet.

^[9] Nitroglycerin in septic shock after intravascular volume resuscitation.
Spronk PE, Ince C, Gardien MJ, Mathura KR, Oudemans-van Straaten HM, Zandstra DF.
Lancet. 2002 Nov 2;360(9343):1395-6.
PMID: 12423989 [PubMed - indexed for MEDLINE]

^[10] Dopamine versus norepinephrine in the treatment of septic shock: a meta-analysis*.
De Backer D, Aldecoa C, Njimi H, Vincent JL.
Crit Care Med. 2012 Mar;40(3):725-30. doi: 10.1097/CCM.0b013e31823778ee.
PMID: 22036860 [PubMed - indexed for MEDLINE]

CONCLUSIONS:
In patients with septic shock, dopamine administration is associated with greater mortality and a higher incidence of arrhythmic events compared to norepinephrine administration.

^[11] Norepinephrine or dopamine for septic shock: systematic review of randomized clinical trials.
Vasu TS, Cavallazzi R, Hirani A, Kaplan G, Leiby B, Marik PE.
J Intensive Care Med. 2012 May-Jun;27(3):172-8. doi: 10.1177/0885066610396312. Epub 2011 Mar 24. Review.
PMID: 21436167 [PubMed - indexed for MEDLINE]

CONCLUSIONS:
The analysis of the pooled studies that included a critically ill population with shock predominantly secondary to sepsis showed superiority of norepinephrine over dopamine for in-hospital or 28-day mortality.

^[12] Catecholamines Should Be Banned
Mervyn Singer
2009-04-24-1545
6th Annual Critical Care Symposium
Manchester, UK
Page with link to free mp3 download from Free Emergency Medicine Talks.

Guglin, M., & Postler, G. (2009). High dose nitroglycerin treatment in a patient with cardiac arrest: a case report Journal of Medical Case Reports, 3 (1) DOI: 10.4076/1752-1947-3-8782

SPRONK, P., INCE, C., GARDIEN, M., MATHURA, K., & ZANDSTRA, D. (2003). Nitroglycerin for septic shock The Lancet, 361 (9360), 880-880 DOI: 10.1016/S0140-6736(03)12692-X

Spronk, P., Ince, C., Gardien, M., Mathura, K., Straaten, H., & Zandstra, D. (2002). Nitroglycerin in septic shock after intravascular volume resuscitation The Lancet, 360 (9343), 1395-1396 DOI: 10.1016/S0140-6736(02)11393-6

Filed Under: Heresy, Mythology, NTG, Research Blogging

Does the Goal of a Pulse Lead to Bad Resuscitation Decisions

Tue, 26 Mar 2013 10:30:47 +0000 by Rogue Medic

First, this is a paper that was just added to the Articles In Press for Resuscitation with the editing not yet completed. Do not fault the authors for the lack of polish. The paper does address some interesting aspects of resuscitation.

ROSC (Return Of Spontaneous Circulation) is the goal for many people.

ROSC is a red herring.

Those of us who think ROSC is important do not seem to understand how much long-term damage we can do in our attempts to get ROSC, or to get ROSC quickly.

This study helps to point out some of the inconsistencies with our ROSC fetish.

Here is a table of the results from the study comparing early epinephrine (≤10 minutes) with late epinephrine (>10 minutes).

Click on images to make them larger.

Everything highlighted in blue is favoring early epinephrine and statistically significant.

Overall, things look good for early epinephrine, but VF/VT (Ventricular Fibrillation/Ventricular Tachycardia) is most responsive to resuscitation, yet the results for VF/VT never reach statistical significance. VF/VT may also be most associated with an early response

There is only a trend toward better ROSC for VF/VT, but as with the NINDS study of tPA for ischemic stroke, the healthiest patients are in the intervention group, so they are expected to have better outcomes.

With asystole there are survivors with late epinephrine, but no survivors with early epinephrine. What should we make of that? It is far from statistically significant, but there is not even a trend toward more ROSC with early epinephrine.

PEA (Pulseless Electrical Activity) has not just a trend toward more ROSC with early epinephrine, the results are statistically significant.

One of the reasons may be that PEA is sometimes due to assessment problems. We used to call it EMD (Electro-Mechanical Dissociation) because many of us assumed that if no pulse could be palpated, there was no cardiac output. These were termed pseudo-EMD, since imaging could show that there is heart motion, even though there is no palpable pulse.

I have had a handful of patients who were awake and alert, but did not have any palpable pulses. Clearly, EMD is not a description of reality.

How many of these patients are responding to being shaken up, rather than to the mechanical effects of chest compressions in the circulation? We do not know.

Early Epi may increase blood pressure to allow palpation of a pulse in cases with presumed PEA, but who are actually cases of “pseudo-PEA” which have some cardiac output but not enough to be identified clinically.^[1]

Modified portion of EMS 12 Lead image.

Then there are the expected confounders in this kind of study. Faster response times would be expected to result in earlier epinephrine and less deterioration of the rhythm to asystole.

The faster response times occur in fewer patients, so there should be a much wider confidence interval/standard deviation. That is not the case, because there is an upper limit on the numbers that can be included. The numbers include response time, time to patient contact, time to establish access, and time to epinephrine. All of those have to be less that 11 minutes combined.

Bystander CPR is much more common with early epinephrine. This may be related the higher incidence of arrest in public, but the bystander CPR rate is about twice as high as the rate of arrest in public.

With early epinephrine we have a decrease from the odds of ROSC to the odds of survival.

With witnessed arrest, bystander CPR, and VF/VT the opposite is true.

With VF/VT the difference is dramatic.

Is this an indication of the effect of epinephrine on survival that we have seen in other studies?

Clearly more work is needed to understand the importance of the timing of epi administration and its impact on outcomes from OHCA.^[1]

OHCA is Out of Hospital Cardiac Arrest.

Clearly more work is needed to understand the ~~importance of the timing~~ effects of epi administration and its impact on outcomes from OHCA.

Why should we assume that it is the timing and not the drug?

Maybe the problem is using such a drug that is so dangerous to the heart to treat heart problems.

Samuel Hahnemann would love this use of epinephrine, just at a much lower dose.

Footnotes:

^[1] Rapid Epinephrine Administration Improves Early Outcomes in Out-of-Hospital Cardiac Arrest.
Koscik C, Pinawin A, McGovern H, Allen D, Media D, Ferguson T, Hopkins W, Sawyer K, Boura J, Swor R.
Resuscitation. 2013 Mar 21. doi:pii: S0300-9572(13)00175-5. 10.1016/j.resuscitation.2013.03.023. [Epub ahead of print]
PMID: 23523823 [PubMed - as supplied by publisher]

Koscik, C., Pinawin, A., McGovern, H., Allen, D., Media, D., Ferguson, T., Hopkins, W., Sawyer, K., Boura, J., & Swor, R. (2013). Rapid Epinephrine Administration Improves Early Outcomes in Out-of-Hospital Cardiac Arrest Resuscitation DOI: 10.1016/j.resuscitation.2013.03.023

Filed Under: ACLS, Epinephrine, Heresy, Research Blogging

Equipoise and Ethics and IRBs, Oh My!

Fri, 22 Mar 2013 10:00:49 +0000 by Rogue Medic

In the comments to what I wrote yesterday about seizures and a study comparing lorazepam (Ativan), diazepam (Valium), and placebo,^[1] Brooks Walsh had the following comment –

Although I’ve read the study before, I am only wondering now how the IRB for Alldredge 2001 thought there was “equipoise” between placebo and benzos.

Equipoise?

Not just he race horse mentioned in one of the songs from Guys and Dolls, or a mouse being a raced in Stalag 17. Maybe I should have written this with Nathan Detroit being stranded on Gilligan’s Island, or I could try that for something on ketamine.

In short, clinical equipoise means that there is genuine uncertainty in the expert medical community over whether a treatment will be beneficial.^[2]

In many cases, there is equipoise, but we are too biased to realize how little we know about the treatments we are using. Epinephrine in cardiac arrest, ventilations in cardiac arrest, and prehospital use of backboards and EMS collars are a few examples of this kind of bias.

We have been using the treatments for so long that we can’t imagine that we have been doing something useless, or even worse, something harmful.

Download Video from YouTube | Convert YouTube to MP3

Our knowledge of the effects of the treatments we use may not be any better than what we see in the video of the the knowledge of the horses that the characters are betting on. Selective memory and wishful thinking are the basis for our choices.

The diazepam vs. lorazepam vs. placebo study is a bit of a different situation. EMS was still largely doing what medical directors felt could safely be moved from the ED (Emergency Department) to the EMS setting, but we did not know if any of it worked as used by EMS. We also worried that the respiratory depression would be common and cause more problems than the potential benefits of stopping the seizures.

The doses were small.

With the doses we used, I felt that the seizures were more likely to stop on their own, rather than because of the small doses of diazepam that I could give – up to 5 mg at a time.

A lot of people (including emergency physicians) do not seem to realize that most seizures are self-limiting. EMS is not treating aggressively for these seizures, which would go away even if treated with homeopathy (or any other placebo treatment).

We are treating all of the patients who might have status epilepticus because the outcome for those who do have status epilepticus is so bad when they are not treated aggressively.

There do not appear to have been any studies that compared EMS administered benzodiazepines with EMS not administering benzodiazepines. There are only two studies that I found published before this study was published, but both were published years after this study began.^[3],^[4]

Here is what the authors wrote about the state of the evidence before they began the study.

Several randomized trials of drug treatment for status epilepticus in hospitalized patients have been conducted.^1,3,4 However, patients with seizures and status epilepticus are commonly encountered outside of the hospital by emergency-medical-services personnel. Traditionally, these patients have been transported quickly to emergency departments for treatment. In recent years, many emergency-medical-services systems have implemented protocols that allow the intravenous administration of benzodiazepines (principally diazepam) by paramedics. However, the risks and benefits of treatment with benzodiazepines outside of the hospital have not been studied. Potential benefits include the prevention of systemic and neurologic sequelae of prolonged convulsive seizures. Potential risks include respiratory depression and cardiovascular compromise associated with benzodiazepines and misdiagnosis leading to inappropriate treatment.² ^[5]

It is easy to forget how much things have changed in a couple of decades.

This study began to enroll patients January 4, 1994, so the planning of the study began over twenty years ago.

Because of the emergency nature of status epilepticus and the unconscious state of the patient, enrollment took place under a waiver of informed consent pursuant to federal regulations. The rationale for the waiver was that diazepam, lorazepam, or no benzodiazepines were used by various emergency-medical-services systems for the management of status epilepticus at the time of the study and that insufficient data were available to determine the optimal out-of-hospital treatment for this condition.^[5]

In other words, we doid not know what was best.

In another word – equipoise.

The average time from patient contact to arrival in the ED was only 15 minutes.

Click on images to make them larger.

The outcomes showed that waiting until the patient is in the ED to treat the seizure is not a good idea.

Before this study, that was just an opinion.

After the study, it had been demonstrated objectively.

Some people have similar criticism about a lot of other treatments that have never been demonstrated to improve outcomes.

A year ago yesterday, the Hagihara study^[6] comparing cardiac arrest outcomes with and without epinephrine was published in JAMA.

In the editorial accompanying that paper, Dr. Clifton Callaway wrote the following about the state of equipoise of epinephrine in cardiac arrest.

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.^[7]

Similarly –

The best available observational evidence indicates that ~~epinephrine~~ ventilation may be harmful to patients during cardiac arrest, and there are plausible biological reasons to support this observation.

or –

The best available observational evidence indicates that ~~epinephrine~~ use of backboards and EMS collars may be harmful to patients ~~during cardiac arrest~~ with unstable injuries of the spine, and there are plausible biological reasons to support this observation.

When we base our treatments on hunches, or expert opinions, we will eventually have to go back and find out if they work.

Or, as a quote attributed to John Wooden puts it –

If You Don’t Have Time to Do It Right, When Will You Have Time to Do It Over?

We expect that our experts will have gotten combinations of treatments just right on the first try, or the second try, or even on the third try, even though there is no good reason to expect this.

Experts have a history of repeated failure and eventual success, not a history of continual success.

An expert is a man who has made all the mistakes which can be made in a very narrow field. – Niels Bohr.

Image credit.

Is it safe to bet on the opinions of experts?

That depends on what they are expressing opinions on, how accurate they have been with previous opinions, and the quality of the information on which they base their opinions.

In this case, the odds are against the experts.

Maybe we think that because an expert has made all of the known mistakes in a field, the expert cannot make any more mistakes in the same field.

We continue to think that ROSC (Return Of Spontaneous Circulation) is the most important factor in resuscitation, but we have proven that to be false.

Norepinephrine and high-dose epinephrine produced more ROSC than standard-dose epinephrine.

If ROSC were the most important factor in resuscitation, we would use these treatments, rather than standard-dose epinephrine.

We do not.

Norepinephrine and high-dose epinephrine produce more brain damage than standard-dose epinephrine.^[8]

We know that epinephrine produces brain damage, but we foolishly believe that the doses we use are not toxic.

We need to demonstrate the safety and efficacy of epinephrine in cardiac arrest.

We need to demonstrate the safety and efficacy of ventilations in cardiac arrest.

We need to demonstrate the safety and efficacy of backboards and EMS collars for injuries to the spine.

The stakes are too high to keep playing a hunch – whether Paul Revere, Valentine, Epitaph, epinephrine, ventilation, or backboards and EMS collars.

Look at how we rejected making high-dose epinephrine routine –

A meta-analysis and other studies have found improved ROSC, but none have demonstrated a survival benefit of high-dose epinephrine versus standard-dose epinephrine in cardiac arrest.^{135,268,–,272} ^[8]

What do we do with the same, or worse, results when the comparison is between epinephrine and not drug?

There are no RCTs that adequately compare epinephrine with placebo in treatment of and outcomes related to out-of-hospital cardiac arrest. A retrospective study²⁶⁷ compared epinephrine to no epinephrine for sustained VF and PEA/asystole and found improved ROSC with epinephrine but no difference in survival between the treatment groups.^[8]

We have to do something.

We rejected high-dose epinephrine, which had improved ROSC, but no improved survival.

We embrace standard-dose epinephrine, which has improved ROSC, but no improved survival.

We might as well be playing the ponies.

It is reasonable to consider administering a 1 mg dose of IV/IO epinephrine every 3 to 5 minutes during adult cardiac arrest (Class IIb, LOE A).^[8]

LOE A?

LOE is Level Of Evidence. A is the highest ranking of evidence.

That means that the AHA (American Heart Association) is confident that they have excellent evidence, but that the evidence is not enough to give anything more than their weakest recommendation for use.

This Class IIb recommendation remains unaffected, even though the studies published continue to be neutral or negative.

Epinephrine equipoise is nothing new. what is new is that it is being acknowledged.

Footnotes:

^[1] Giving New Meaning to Carpe Diem
Thu, 21 Mar 2013
Rogue Medic
Article

^[2] Clinical equipoise
Wikipedia
Article

^[3] Pediatric emergency medicine practice patterns: a comparison of pediatric and general emergency physicians.
Schweich PJ, Smith KM, Dowd MD, Walkley EI.
Pediatr Emerg Care. 1998 Apr;14(2):89-94.
PMID: 9583386 [PubMed - indexed for MEDLINE]

^[4] Prehospital management of the seizure patient.
Nicholl JS.
Emerg Med Serv. 1999 May;28(5):71-5; quiz 77.
PMID: 10537415 [PubMed - indexed for MEDLINE]

Free Full Text Download in Word format from angelfire.com.

^[5] 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.

^[6] 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.

^[7] 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.

This is definitely worth listening to.

^[8] Epinephrine
2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science
Part 8: Adult Advanced Cardiovascular Life Support
Part 8.2: Management of Cardiac Arrest
Medications for Arrest Rhythms
Free Full Text from Circulation.

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

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

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) DOI: 10.1001/jama.2012.294

Filed Under: Ethics, Heresy, Pharmacology, Probability, Research Blogging

Japanese man dies after 25 hospitals reject him

Sun, 10 Mar 2013 22:00:08 +0000 by Rogue Medic

In January, in Japan, 25 hospitals refused to permit an ambulance to transport a man who was pronounced dead when he finally arrived at a hospital.

Were the patients already in the ED (Emergency Department) less stable than this patient?

Was this patient going to be the straw that breaks the camel’s back and result in the deaths of other patients already in the ED?

What kind of evidence do we have to justify diversion?

Paramedics rushed to his house but were told in turn by all 25 hospitals in the area that they could not accept the man because they did not have enough doctors or any free beds, a local city official said, adding some institutions were contacted more than once.^[1]

We do not know if he would still be alive if he had been transported to the first ED, or to the second, or to the third, . . . . We do not even know the cause of death. However, this is a good way to introduce the topic of diversion.

Diversion is not just a problem in Japan, but also in the US and other countries. It has become more convenient for many people to go to the ED than to wait to see a primary care physician. Until that problem is fixed (assuming that it ever is fixed), is diversion appropriate?

There have been a couple of studies in San Diego of what happens when diversion is minimized, or eliminated.

Even though volume went up, diversion dropped to almost zero.

Click on images to make them larger.

The authors acknowledge that the main limitation of this study was the short time frame of the analysis, comparing one week to another.^[2]

In a longer study, diversion decreased and the need for transfers between hospitals dropped. There did not appear to be any negative consequences of minimizing diversion.

In summary, a community-wide effort to improve getting patients to requested EDs and decreasing ambulance diversion hours can be successful in a large community with an urban, suburban, rural, and remote population distribution. The success of such a process had the additional effect of decreasing the need for ED interfacility transfers for payer request reasons.^[3]

In this month’s Annals of Emergency Medicine is a study looking at what happened when Massachusetts banned diversion.

Figure 1. Changes in ED length of stay by hospital among A, admitted patients and B, discharged patients. C, Changes in ambulance turnaround time by hospital. D, Changes in total hospital volume before and after a ban on ambulance diversion by hospital.^[4]

It seems that the benefits of diversion are just another medical myth.

Research has led to the consensus that crowding is largely due to output factors, particularly the practice of boarding admitted patients in the ED^2,7-10 because of lack of inpatient capacity. Ambulance diversion, in contrast, is an input factor, which has little effect on ED crowding.⁴ ^[2]

Very few of the patients coming in to the ED are arriving by ambulance.

On July 3, 2008, the department released a policy directive ending the practice of ambulance diversion in the state, except in cases of internal hospital disaster.¹⁷ The policy took effect on January 1, 2009, allowing hospitals 6 months to prepare for the changes necessary for its implementation. This policy represented the first statewide ambulance diversion ban in the United States.^[2]

A lot of the bad things were supposed to occur when diversion was banned.

None of them happened.

Preliminary reports from hospitals suggest that the end of ambulance diversion has been a relative success because of operational changes made at individual hospitals in anticipation of the ban.^24,28 Early reports from Boston Emergency Medical Services (EMS) suggest that there has not been an increase in ambulance turnaround time as feared, although this has not been formally studied.²⁹ ^[2]

At the Gathering of Eagles conference, this was one of the topics.

-It negatively impacts EMS operations and could jeopardize our ability to respond to the next critical patient.

-It often results in patients being transported to ED’s other than where their MD’s or medical records are.

-It negatively impacts patient satisfaction and provider morale.

-It does little if anything to reduce ED overcrowding.^[5]

In places that use diversion, when all of the hospitals are on divert, the dispatch center is supposed to notify the hospitals that dispatch will be making destination decisions until things improve. I have not seen any explanation for why that was not the case in Japan.

Diversion does not appear to provide any real benefit to anyone, except that it is consistent with the superstitions of many people, and medical people are as superstitious as gamblers.

Footnotes:

^[1] Saitama man dies after hospitals reject him 36 times
Japan Today
Mar. 06, 2013 – 02:31PM JST
Article

^[2] The effects of minimizing ambulance diversion hours on emergency departments.
Khaleghi M, Loh A, Vroman D, Chan TC, Vilke GM.
J Emerg Med. 2007 Aug;33(2):155-9. Epub 2007 Jun 18.
PMID: 17692767 [PubMed - indexed for MEDLINE]

^[3] Community trial to decrease ambulance diversion hours: the San Diego county patient destination trial.
Vilke GM, Castillo EM, Metz MA, Ray LU, Murrin PA, Lev R, Chan TC.
Ann Emerg Med. 2004 Oct;44(4):295-303.
PMID: 15459611 [PubMed - indexed for MEDLINE]

^[4] The effect of an ambulance diversion ban on emergency department length of stay and ambulance turnaround time.
Burke LG, Joyce N, Baker WE, Biddinger PD, Dyer KS, Friedman FD, Imperato J, King A, Maciejko TM, Pearlmutter MD, Sayah A, Zane RD, Epstein SK.
Ann Emerg Med. 2013 Mar;61(3):303-311.e1. doi: 10.1016/j.annemergmed.2012.09.009. Epub 2013 Jan 24.
PMID: 23352752 [PubMed - in process]

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^[5] Taking a Turn For The First: Taking Aim at Diversion Practices
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Khaleghi, M., Loh, A., Vroman, D., Chan, T., & Vilke, G. (2007). The Effects of Minimizing Ambulance Diversion Hours on Emergency Departments The Journal of Emergency Medicine, 33 (2), 155-159 DOI: 10.1016/j.jemermed.2007.02.014

Vilke, G., Castillo, E., Metz, M., Upledger Ray, L., Murrin, P., Lev, R., & Chan, T. (2004). Community trial to decrease ambulance diversion hours: The San Diego county patient destination trial Annals of Emergency Medicine, 44 (4), 295-303 DOI: 10.1016/j.annemergmed.2004.05.002

Burke, L., Joyce, N., Baker, W., Biddinger, P., Dyer, K., Friedman, F., Imperato, J., King, A., Maciejko, T., Pearlmutter, M., Sayah, A., Zane, R., & Epstein, S. (2013). The Effect of an Ambulance Diversion Ban on Emergency Department Length of Stay and Ambulance Turnaround Time Annals of Emergency Medicine, 61 (3), 303-3110 DOI: 10.1016/j.annemergmed.2012.09.009

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