# Polyheme:  Ethicists want fake blood study stopped



## MMiz (Mar 5, 2006)

*Ethicists want fake blood study stopped*

CHICAGO, Illinois (AP) -- Imagine being in a car crash, lying unconscious and bleeding in an ambulance. With no blood on board, paramedics give you an experimental substitute, but even at the hospital, you get fake blood for several hours before doctors try the real thing.

Medical ethicists say a study that is doing just that on hundreds of trauma patients without their consent should be halted.

It's a renewed attack on research that began in 2004 after Northfield Laboratories got federal approval for its study of the blood substitute Polyheme.

Debate was reignited by a Wall Street Journal story last week that suggested the company tried to hide some crucial details about another blood substitute study back in 2000. The Journal reported that 10 heart surgery patients in that Polyheme experiment had heart attacks, while other patients given real blood did not.

*Read More!*


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## Jon (Mar 5, 2006)

I saw this and meant to post it.

"ER" on TV actually talked about some of the ethical dillemas in Season 4.


Long story short - Prehospitally, the study is a GREAT idea. In hospital, it becomes a slight gray area, BUT the case law backs it up for now.


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## Raf (Mar 5, 2006)

I'm a bit confused. So basically they want to use this Polyheme stuff to comfort the patients and possibly create some positive feeling within them to encourage healing? Or does this stuff actually have some physical therapeutic properties?


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## ffemt8978 (Mar 5, 2006)

Raf said:
			
		

> I'm a bit confused. So basically they want to use this Polyheme stuff to comfort the patients and possibly create some positive feeling within them to encourage healing? Or does this stuff actually have some physical therapeutic properties?



Actually, the purpose of Polyheme is to provide pre-hospital care providers with something that can actually help trauma patients in the field by providing an artificial source of hemoglobin that can carry oxygen to the bodies cells (the theraputic properties since with NS, all you do is thin out the concentration of RBC's during a major bleeding incident such as trauma)..  Being an artificial substance, you don't have to worry about disease transmission (as with real blood), it has a longer shelf life, and better storage capabilities than previous versions.  

I can understand the ethics question that is being posed, but I think you must first answer the question, "Is the Polyheme a direct cause of death in these patients?"  The answer is, we'll never know because we will never know if they would have survived without it.  How many of these patients would have never made it to the hospital in the first place without Polyheme?  How many of these patients would still be alive if they received real blood?

And the most important question is this: How do we balance the needs of the patient with the needs of legitimate medical research?  The needs of the patient are of obvious importance, but in some ways they must be balanced with the needs of research.  After all, that research may not only save lives in the future, it may actually save that patient.


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## Jon (Mar 6, 2006)

Polyheme SOUNDS good....

And, prehospitally, seems to be working. You do end up with an intresting ethical question of using fake blood or real blood once the option exists, but otherwise....


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## JJR512 (Mar 6, 2006)

Here's a twist on the ethical issue: Some religions, I believe Jehova's Witnesses is one if I'm not mistaken, do not allow blood transfusions. I believe they think that blood from another person put in their own body is a contamination or something to that effect. Anyway, I wonder if they would allow this stuff to be put in? Technically it's not blood, it's not from another person. And unless I'm mistaken, it's not putting something in their own body that's the problem, it's the fact that it comes from another body that's the problem, so this fake stuff should be no problem.


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## Jon (Mar 6, 2006)

I think that they DO permit it.... that was also an issue.


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## Raf (Mar 6, 2006)

If the polyheme is helping patients to some extent right now (at least lengthing their life span) I am sure this substance has more potential and can eventually save hundreds of lives. But unless we experiment with it and find out how to improve it, we will never be able to learn it's full capabilities.

I say we go for it and use it. What makes it any less unethical than using other drugs and life support to save people's lives? Is it just because it seems like we are trying to create something that God has created?


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## GaEMT (Mar 7, 2006)

I have seen this stuff in action and it is a promising product.    Check out  http://www.northfieldlabs.com/polyheme.html    There are some issues regarding storage of the product, but I would imagine the market place will offer solutions for this if approval is granted.


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## squid (Mar 8, 2006)

The ethical issue is one of informed consent, Raf.


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## Jon (Mar 9, 2006)

squid said:
			
		

> The ethical issue is one of informed consent, Raf.


BUT.... in the field, it is working better than saline... the issue becomes with the hospital continuing "fake blood" when there is real blood availible.


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## squid (Mar 9, 2006)

Did I misunderstand? I thought that was still an informed consent issue -- they weren't giving the patients a chance to decide to participate in the study or not.


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## squid (Mar 9, 2006)

Well, for heaven's sake, you can't edit messages.

So anyhow, the ethical issue is one of informed consent. It's not about using fake vs. real blood or about how well it works -- it's about not giving patients in the hospital the chance to agree to participate in a study. I was posting in response to Raf, who seemed to be asking what the problem was.


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## ffemt8978 (Mar 9, 2006)

squid said:
			
		

> Well, for heaven's sake, you can't edit messages.



You can edit your own posts, but you're limited to a 5 minute window to do so.  After that, only a mod/admin can edit posts.

The reason for this is that we had a problem before with a member going back and editing all of their posts to remove all content.  It caused some difficulty with thread continuity.  If you think the 5 minute limit is too short, feel free to post a poll in the Suggestions Forum and we'll see what the membership says.


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## squid (Mar 9, 2006)

No, no problem! It's just that I had an edit button but it wouldn't let me do it, which was frustrating.


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## Jon (Mar 10, 2006)

squid said:
			
		

> Well, for heaven's sake, you can't edit messages.
> 
> So anyhow, the ethical issue is one of informed consent. It's not about using fake vs. real blood or about how well it works -- it's about not giving patients in the hospital the chance to agree to participate in a study. I was posting in response to Raf, who seemed to be asking what the problem was.


The issue is "in hospital" use, where you would "deny" the patient real blood by enrolling them in the study for fake blood.   So yes, it is an issue of consent.


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## podmedic@mac.com (Mar 14, 2006)

GaEMT said:
			
		

> I have seen this stuff in action and it is a promising product.    Check out  http://www.northfieldlabs.com/polyheme.html    There are some issues regarding storage of the product, but I would imagine the market place will offer solutions for this if approval is granted.


I featured this recently on my podcast.  The main issue is one of informed consent and the withholding of real blood from patients for 12 hours once enrolled as an experimental subject.  The ethicists argue that the maintaining of the patient on polyheme once they have arrived at the ED is irresponsible and violates implied consent.

I have some links to both sides of the arguement and info on the nature of the studies in my shownotes here:

http://www.mediccast.com/blog/2006/03/07/episode-5-shownotes/


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## krj00 (Jun 14, 2006)

--------------------------------------------------------------------------------

Polyheme is part of a story in USA Today. Hank Williams Jr.'s daughter's rights were abused when a lifeflight crew unwittingly made her a guinea pig and infused her with that Polyheme stuff. 



http://www.usatoday.com/news/health/2006-06-13-traumas-trials_x.htm?POE=NEWISVA


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## gradygirl (Jun 14, 2006)

Wow, I had to write a research paper on PolyHeme for my college chem. class.

The use of PolyHeme is going to greatly advance the science of emergency medicine. As of yet (knock on wood), there have been no adverse reactions or other sort of physical harm done to any patients who have been given PolyHeme instead of whole blood. In fact, PolyHeme is the only human hemoglobin-based HBOC on the market. More or less, think of it as saline on steroids, a volume expander that carries oxygen. There is, more or less, nothing about the actual product itself that could cause any harm to a patient. It is completely sterile, has been chemically engineered so that the hemoglobin tetramers (the base units of hemoglobin) are are stabilized by polymerizing the tetramers into higher-order polymers, which prevent premature binding with NO (which causes mass vasoconstriction), as well as liver and kidney damage.

PolyHeme is incredible. It has a shelf life of four months. There is no need for cross typing, and so no chance of the body rejecting it. One extraordinary case of the use of PolyHeme was when a pt. experiencing massive hemorrhaging received 20 units of the HBOC in 20 minutes. 20 units of PolyHeme equates to more than 10 L of blood products. Also, as there are no blood products in PolyHeme, it can be used for pt.s that have a religious belief against receiving blood.

The only unethical aspect of the Phase III PolyHeme trials is the fact that the company, Northfield Labs, has not done an adequate job informing the communities in which the trials are being performed of their rights to refuse treatment with PolyHeme by wearing a special wrist band, one that, if seen by emergency personnel, will alert them to the unconscious patient's wishes to receive actual blood products.


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## Banana (Jun 14, 2006)

JJR512 said:
			
		

> Here's a twist on the ethical issue: Some religions, I believe Jehova's Witnesses is one if I'm not mistaken, do not allow blood transfusions. I believe they think that blood from another person put in their own body is a contamination or something to that effect. Anyway, I wonder if they would allow this stuff to be put in? Technically it's not blood, it's not from another person. And unless I'm mistaken, it's not putting something in their own body that's the problem, it's the fact that it comes from another body that's the problem, so this fake stuff should be no problem.



"Whole blood transfusions are rejected.[72] This is based on their understanding of the biblical admonition to "keep abstaining from blood" based on Acts 15:28, 29 (NWT). According to the conscience of the particular individual, they may accept derivatives of blood. In current medical practice, whole blood transfusions are very rare, and blood derivatives are used instead. Witnesses may accept a process called normovolemic hemodilution, a treatment that processes the individual's own blood in a closed loop that does not interrupt the circulation of blood, and delivers it immediately back into the person's body. Also left to conscience are procedures where a "quantity of blood is withdrawn in order to tag it or to mix it with medicine, whereupon it is put back into the patient."[73] Many members carry carefully prepared durable power of attorney outlining their medical wishes with respect to blood.
Jehovah’s Witnesses have been known to highlight the potential dangers of blood transfusions. Witness representatives have stated that plasma volume expanders are often times sufficient to take care of various medical emergency situations.[74][75]" - wikipedia

They might not reject it on the grounds of it being blood but they could decide that doing so is "going against Gods will" as if he wants to take their life, people shouldn't interfere.


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## Jon (Jun 14, 2006)

krj00 said:
			
		

> --------------------------------------------------------------------------------
> 
> Polyheme is part of a story in USA Today. Hank Williams Jr.'s daughter's rights were abused when a lifeflight crew unwittingly made her a guinea pig and infused her with that Polyheme stuff.
> 
> ...


I dissagree with how you put it.

From what it sounds like, her life was SAVED. The waived-consent trial is VERY important. Polyheme needs to work in trauma situations, and a waived-consent trial is the only real way to test it how it will be used.

When I saw how you put it, I thought this would be a bad article, but it is another well-written article by Bob Davis, Americas' EMS newspaper writer.

Jon


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## Jon (Jun 14, 2006)

MedicStudentJon said:
			
		

> I dissagree with how you put it.
> 
> From what it sounds like, her life was SAVED. The waived-consent trial is VERY important. Polyheme needs to work in trauma situations, and a waived-consent trial is the only real way to test it how it will be used.
> 
> ...


This has been discussed - it is each persons' choice, and there is a way to "opt out" of the study. BUT - the Jehovia's Wittnesses seem like the idea of Polyheme.


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## Guardian (Jun 14, 2006)

My two cents, where i work, we are participating in the polyheme trial.  Do i think it's a promising step forward in medicine? Yes.  Do I want polyheme used on me or my family in place of real blood during an emergency? No.


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## ffemt8978 (Jun 14, 2006)

Guardian said:
			
		

> My two cents, where i work, we are participating in the polyheme trial. Do i think it's a promising step forward in medicine? Yes. Do I want polyheme used on me or my family in place of real blood during an emergency? No.



Care to elaborate this a little more, especially why you wouldn't want it used on you or your family?


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## gradygirl (Jun 14, 2006)

Would I rather have blood products than an HBOC? Sure, absolutely. 

If I were an unconscious trauma pt. bleeding out in desperate need of blood volume who literally doesn't have the time to have blood cross typed and infused, would I care if I were given PolyHeme? Absolutely not.

Now, this is from a well informed person who is not having to worry about what I may or may not receive if I were to get into an accident and need blood. But, being a well informed person, I know that what is the most important thing in this whole PolyHeme debate is whether or not it will be passed by the FDA so we responders have one more tool by which we can try to stabilize our trauma pts. And, while I don't approve of the way Northfield is handling the testing, I will not say anything negative about PolyHeme until, god forbid, someone has a negative interaction with the product.


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## Guardian (Jun 14, 2006)

I'm not an expert on polyheme.........now that i've said that, I am not convinced polyheme works as well as real blood.  I'm concerned that i won't get real blood fast enough at hospital if i'm enrolled into polyheme trial.  Polyheme is a good step forward and I think it has great potential for pre-hospital use ("fake" blood better that saline) but when i arrive at the hospital, I want real blood and i want it fast!


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## gradygirl (Jun 14, 2006)

Alright, I am putting on the table the process through which a trial pt. goes.

In the trial areas, including somewhere between 25-30 Level 1 trauma centers across the U.S., 720 unconscious trauma pts. are to be enrolled into the trials. Ideally, the trial areas' residents should have been properly educated about the trial and given the option to opt-out of the trial by wearing a special bracelet indicating such wishes. *No conscious pts. are given PolyHeme in the trial.*

Treatment with PolyHeme begins on scene, is continued on the ambulance, and then is carried on in the hospital for up to 12 hours or 6 units while in the hospital.

This trial is being compared to the use of saline in the field and blood products in the hospital. AGAIN, treatment with PolyHeme is discontinued and blood products are used after 12 hours or 6 units. The trial endpoint measures the survival rate of trauma patients at 30 days.

This trial, again though violating a pt.'s right to choice, strictly adheres to the FDA's Title 21 Chapter 1 Section 50.24 Protection of Human Subjects guidelines.


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## Guardian (Jun 14, 2006)

discontinued after 12 hours, that's a long time when you're in shock


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## gradygirl (Jun 14, 2006)

That's what the PolyHeme treats. It's chemically engineered from real human hemoglobin to carry oxygen and replaces blood volume at the same time. Like I said in my first post, one pt. essentially bled out twice, but lived and was only given PolyHeme. As of yet, I don't know of any deaths related to PolyHeme use (or rather, a lack of blood product use). As soon as I hear of a 100% proven case that a pt. died because they received PolyHeme instead of blood products, I will promptly bight my tongue.

Also, PolyHeme has been in trials for a very, very long time. The fact that it has reached a Phase III FDA trial means that, if it does, indeed, pass, it could be available to the emergency medical system as early as 2007. No other HBOC has made it this far.

If the prior track record says anything about this product, it will be in use in a relatively short period of time.


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## Guardian (Jun 14, 2006)

tcert1987, it you had two pts in exactly the same condition (shock), and one was given polyheme while the other blood, which one do you think would have the better chance for survival?..........the truth is no one knows this, thats one of the questions phase 3 is trying to answer.  My point is this, i would rather be given the one that is sure to work, blood.


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## gradygirl (Jun 14, 2006)

I absolutely agree with you. As I said, I would much rather receive blood products than an experimental HBOC. My argument is just that PolyHeme is an incredible tool that we may be able to use in the future, but unfortunately, invasive human tests must be carried out to make sure that it's not going to kill anyone if it is passed. To be honest, I don't agree with Northfield that it must be used up to 12 hours after the accident, I think it should strictly be used in the field on an ambulance as a better volume expander than saline. I am simply trying to lay out the hard facts about what PolyHeme is and how the trial must work to deflate some of the misguided information posted.


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## gradygirl (Jun 14, 2006)

I am now getting off of my soap box.

*Steps down.*


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## Guardian (Jun 14, 2006)

I can't get off my soap box, it's just too high


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## krj00 (Jun 14, 2006)

This is why Northfield Labs AND the FDA  agreed to the 12 hours post arrival at hospital (via Special Protocol Agreement). In my opinion.

Polyheme may actually be better than blood.

http://www.bioethics.net/journal/j_articles.php?aid=998


Critics argue that, despite acknowledged limitations of banked blood, its general acceptance in resuscitation is prima facie evidence of its “satisfactory” nature.  Once blood is available, they profess, randomization should be reserved for consenting subjects.

Is the efficacy and safety of transfused blood “proven”?  Despite its widespread use and acceptance, the performance of banked blood has never been subjected to the level of scrutiny imposed on investigational new drugs.  Transfusions fail to improve oxygen consumption in critically ill patients (Fernades et al. 2001).  Attendant risks of transfusion reaction and transmission of infection are universally recognized.  Few accept transfusion absent life-threatening anemia. 

Is the transfusion of banked blood “satisfactory”?  Clearly, it is an effective means of immediate resuscitation in hemorrhagic shock, but at what price?  Clinical trials have demonstrated that transfusion increases the incidence of multiorgan failure (MOF) and increases mortality (Kao 2000; Johnson et al. 2001).  In particular, transfusion of six or more units within the first 12 hours is the primary risk factor for MOF, independent of injury severity (Moore, Moore and Sauaia 1997).  MOF is the leading cause of post-injury death, conferring a mortality of 35% and prolonging ICU stays an average of one month with mechanical ventilation and dialysis.  The adverse effect on outcomes is not limited to trauma victims, but is particularly pertinent to this population because of the pathophysiology of transfusion-related injury (Corwin et al. 2004; Herbert and Fergusson 2004; Napolitano 2004; Rao et al 2004).  Many thoughtful clinicians feel treatment that increases mortality and organ failure is unsatisfactory.

How could blood be bad?  It’s a universal natural product that serves us well.  Banked blood, however, is artificially preserved and gradually degrades with its 42-day storage, releasing from red cell membranes lipid mediators and cytokines.  These factors combine with traumatized tissue in a two-step priming of neutrophils and oxygen radical production, each of which is highly correlated with development of MOF (Moore, Moore and Sauaia 1997; Johnson et al. 2001).  Transfused units are necessarily the oldest in the blood bank with the highest concentration of toxins.  Furthermore, trauma patients requiring massive transfusions first receive unmatched blood.  Type-specific blood requires up to 20 additional minutes to deliver and fully cross-matched blood can require 45 minutes.  The risk of immunologic complications and medical error increases under the pressure of emergency delivery.  Blood’s failure to improve oxygen consumption in critically ill patients apparently stems from changes in red cell deformability with storage.  Such rheologic changes can produce red cell entrapment, microvascular obstruction and tissue ischemia (Fernandes et al. 2001; Berezina et al. 2002).  

By contrast, PolyHeme® has a long shelf life and is compatible with all blood types.  The risk of viral and bacterial transmission is extremely low.  Extensive pre-clinical and earlier clinical studies have shown very few adverse effects.  Deleterious vasoconstrictive effects that have plagued earlier blood substitutes are noticeably absent with this product


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## MMiz (Jun 14, 2006)

krj00,

What is your relationship with PolyHeme?  I've noticed that you've asked similar questions and prompted similar discussions on several discussion forums.


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## krj00 (Jun 15, 2006)

We've been seening one another for about six years or so. Nothing serious.


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## fm_emt (Jun 15, 2006)

The original link has expired. Blah. Stupid CNN.

Here's a new story about these kinds of trials & stuff:

http://www.usatoday.com/news/health/2006-06-13-traumas-trials_x.htm?POE=NEWISVA


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