Mid-Level Providers

Mid-Level Providers

Who they are, what they do, and why they’re changing emergency medicine

How to make sense of the puzzle and improve your practice.

When Patients Lie

When Patients Lie

How to Spot Deception, What You Can Do, and Why it Matters

Accusing anyone of lying is serious business, but when that person is your patient, the stakes are even higher. 

Raves and Saves

Raves and Saves

Advanced Emergency Management at Mass Gatherings

EM is crucial at drug-fueled electronic dance festivals, like this month’s Electric Zoo in New York.  

Transfusion Confusion

Transfusion Confusion

Knowing the Real Risks of Blood Transfusion

This routine procedure bears real risks and should be handled accordingly.

The ABCs (and T) of Rural EM

The ABCs (and T) of Rural EM

Situational Awareness is Key

When you’re practicing in the middle of nowhere, planning out a timely patient transfer can be as critical as securing…

DNR Means Do Not Treat . . . and Other End-of-Life Care Myths

DNR Means Do Not Treat . . . and Other End-of-Life Care Myths

Debunking 5 Fallacies

Improve your EOL care and communicate more effectively.

Through the Looking Glass

Through the Looking Glass

Three Novel Use Cases for Google Glass in the ED

How might augmented reality change your practice?

Augmented ED

Augmented ED

The future of emergency medicine?

EPs in Rhode island overcome hurdles to trial Glass for telemedicine and consider other applications.

All About Metoclopramide (Reglan)

All About Metoclopramide (Reglan)

Know the risks

Reglan should be used with caution if patients have Parkinson’s disease or are on antipsychotics.

Physicians Won't Be Silenced

Physicians Won't Be Silenced

ACEP's Gag Order Rejected

EPM readers speak out against ACEP’s new ruling prohibiting incoming leaders from answering questions from non-ACEP publications.

Changemaker

Changemaker

How One EP Transformed Mental Health Admissions in Virginia

Debra Perina combined her experience as a coroner with her time leading an ED to challenge the establishment.

Get the Gear Off

Get the Gear Off

Removing the Helmet and Pads is Crucial to Treating Spinal Injuries from Football

Up to 25% of c-spine injuries from football collisions may be exacerbated by the poor removal of helmet and pads.

The War on Death

The War on Death

by Greg Henry, MD

The guns and butter debate is really over, I guess.

How Do I Know if I'm Being Paid Fairly?

How Do I Know if I'm Being Paid Fairly?

Trust is key

I get paid based on my productivity, but I don't trust that my company is paying me accurately.

The Stethoscope of the Future

The Stethoscope of the Future

Bedside Ultrasound

The applications of bedside ultrasound have gone well beyond scanning the gallbladder . . . to the lungs?

The Medical Malpractice Rundown: A State-by-State Report Card

The Medical Malpractice Rundown: A State-by-State Report Card

When it comes to medical liability laws and culture, where you live matters.

Find out how your state stacks up against the other 49.

Oxygen is a Drug— Act Accordingly

Oxygen is a Drug— Act Accordingly

Understanding the dangers of indiscriminate oxygenation in the ED setting

As with many things in medicine, dogma seems to overpower the evidence in this arena. 

Gag Order

Gag Order

New ruling prohibits would-be ACEP leaders from answering questions from non-ACEP publications.

Greg Henry seldom fails to deliver on a promise. But this time, it looks like it’s out of his control.

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Over the past few years, the emergency department treatment of septic patients has dramatically changed.  Much of this is due to the implementation of early goal directed therapy which emphasizes aggressive fluid resuscitation, early antibiotic initiation, vasopressors, and transfusion as needed.  Another innovation in the treatment of sepsis was the development of Xigris (recombinant human activated protein C or drotrecogin alfa) by Eli Lilly. This medication was approved with much controversy by the FDA in 2001 based on a single phase 3 randomized control study known as the PROWESS study, which showed overall survival benefits at 28 days with Xigris (Phase 3 studies compare the newer treatment or regimen with the pre-existing standard for treatment while phase 1 and 2 trials focus on the safety, kinetics, and dosages of the new treatment). The medication was approved in septic patients with minimum APACHE  II scores of  25 or  2 sepsis induced organ dysfunction.  There was, however, some controversy regarding the methodology of the study. Because of this, sales of Xigris did not meet expectations despite its approval. As a result  Eli Lilly hired a public relations firm to develop a marketing strategy to improve sales.

In recent years there has been a drive to put evidence-based intervention into “bundles” which are used to develop a protocol for physicians to follow. While this practice has a measureable effect on patient outcomes, it may have some harmful effects as well. One such effect is that some pharmaceutical companies may use these guidelines to promote their own products. Another effect of bundles is that they make it very easy to develop pay-for-performance packages in which compensation is dependent on compliance with the entire bundle.  In the authors’ opinion, Eli Lilly took advantage of such protocols to promote their drug Xigris in the sepsis protocol.

The marketing strategy consisted of “3 prongs” or phases.  The first phase involved establishing a Surviving Sepsis Campaign to raise physicians and the medical media’s awareness of sepsis. Second, Eli Lilly heightened the demand for Xigris by spreading the word that it was being rationed because of its high cost and physicians were being forced to decide who would receive it, and in turn, survive. The company provided a $1.8 million grant to establish the Values, Ethics, and Rationing in Critical Care (VERICC) task force to address the ethics behind rationing a potentially life threatening drug such as Xigris.  Eli Lilly also helped to fund the international panel of critical experts which gathered to develop the guidelines for management of sepsis which were published in Critical Care Medicine in 2004.  Lastly the Surviving Sepsis campaign was established to promote treatment of sepsis.  Lilly provided more than 90% of the funding for the first 2 phases of the campaign.

Even though many proponents will argue that despite their funding, Lilly did not influence the establishment of the sepsis guidelines, the fact that these recommendations are largely based on randomized controlled trials, automatically tends to favor newer treatments, such as Xigris, which need such trials for approval. Frequently already established practices such as antibiotics and fluid, are ranked less highly in such guidelines because they lack randomized controlled studies as established standards of care.
           
Furthermore, the original PROWESS study, also demonstrated an increased risk in bleeding (approximately 3.5% of patients) with Xigris which again manifest in the ADDRESS and RESOLVE studies. In the ENHANCE trial the risk was found to be even greater.  These results, however, were not included in the Surviving Sepsis Campaign Guidelines. In fact, the efficacy of rhAPC has not been prospectively shown even though the FDA had asked for further testing when Xigris was approved. While the PROWESS study showed a significant overall survival benefit at 28 days, the FDA only approved it for patients with APACHE scores greater than 25 even though the efficacy of Xigris has not been demonstrated in a prospective trial consisting of these patients.
 
In their final marketing phase, Eli Lily established the “Implementing the Surviving Sepsis Campaign” program in 2004 in order to create performance bundles based on  recommendations from the campaign guidelines. One branch of this bundle included a recommendation of Xigris even though the results of the ADDRESS and RESOLVE studies were not mentioned. These bundles are now being implemented internationally by the Society for Critical Care Medicine with funding from Eli Lilly.  It should be mentioned that the Infectious Diseases Society of America has declined to endorse the guidelines.

In conclusion , practice guidelines can be helpful in standardization of practices across diverse international health care settings improving patient outcomes.  To minimize bias and ulterior motives, pharmaceutical industry involvement in guideline development must be closely scrutinized.
 

 

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