Perflourocarbon Based Oxygen therapy

[emsbrian]

Well thought I would spawn a new thread about oxygen therapy, as appose to using oxygen as a a drug, using drugs for oxygen. The future of trauma, we have now, the first and truly only medicine designed to treat trauma. (okay a little over dramatic but I got high hopes on this one)

The future is here. A milky white substance will soon hang in the mini-fridge (next to the sodas) on our ambulances. (forgive me my science journal is at home on the toilet so namesake will come later) Artificial bloods are improving. While they will still not replace whole blood for its ablitity to carry waste products and other biological agents it is 50 TIMES better at carrying oxygen. This new artificial blood is also so small that that one single 50x loaded molecule can squeeze 6 side by side through a single RBC capillary. Whats this mean to us? Not only does it last longer on the truck then blood, but it carries oxygen so much better, through such smaller parts that it can bypass injured sites, including Spinal, Brain and cardiac injuries. Mouse studies have shown a 90% decrease in traumatic is chemic tissue damage with its use.

How does this apply to Oxygen discussion? The whole point is getting more oxygen to the patient by giving him more to absorb, but the underlying problem is the transport system. By giving this new form of artificial blood were looking at making super blood, we both increase oxygen carrying ability and the delivery of it. In theory a near complete blockage of a coronary artery would allow MORE oxygen through with this drug in a persons system, then if it was fully open?!?! Imagine the possibilities of this new line.

Perfluorocarbon based

* Oxygent, by Alliance Pharmaceutical. Status: U.S. phase II trials, European phase III trials

Oxygent is a solution used as an intravascular oxygen carrier to temporarily augment oxygen delivery to tissues and is currently being developed by Alliance Pharmaceutical Corp. Right now, the goal of the development of Oxygent is simply to reduce the need for donor blood during surgery, but this product clearly has the potential for additional future uses. Perfluorocarbons surrounded by a surfactant called lecithin and suspended in a water based solution give Oxygent its oxygen carrying capacity. The Oxygent particles are removed from the bloodstream within 48 hours by the body's normal clearance procedure for particles in the blood. Namely, the lecithin is digested intracellularly and the PFC's are exhaled through the lungs. The fact that this blood substitute is completely man-made gives it certain distinct advantages over blood substitutes that rely on modified hemoglobin, such as unlimited manufacturing capabilities, ability to be heat-sterilized, and the PFCs’ efficient oxygen delivery. Oxygent has done well in most clinical trials, but recently ran into some trouble, with participants in a cardiac surgery study slightly more likely to suffer a stroke if treated with Oxygent rather than the standard care.

* Oxycyte, by Synthetic Blood International. Status: U.S. phase II trials

* PHER-02, by Sanguine Corp. Status: In research

* Perftoran (Russian). Status: approved for Russian clinical trials in 1996

[EmergencyMedicalTigger]

I saw in an article where Oxygent has a 2 year shelf life if refrigerated. Can it be kept unrefrigerated just resulting in a shorter shelf life?

I voted for Polyheme, because there are services who run without mini-fridges. I think it would appeal to those services, so they wouldn't have to make changes to store it on their trucks.

Although Oxygent seems like it might have fewer negatives overall. We will probably see both in the future being used in prehospital care.

[Ridryder 911]

I believe oxygen carrying type fluids will be used but probably not within the next 5 -10 years. I heard aboutPolyheme or its counterpart about 12 years ago and it is still being investigated. The last I heard they are pulling some of those products from studies to increasing AMI's, I believe of last week. AS well as ethical questions of patients not being asked or informed that they will be given susbsitute. (kinda hard to do on an arrest, but one has to) So we still have a long way to go.

Oxygent may be under trial studies but who knows when and if this will ever be released as well the costs and containment may never make to the field level. Heck, most EMS still don't even carry Cordorone (antiarrhythmic) and Zofran (antiemetic) due to costs. So I would not hold my breath on it. It would be nice .. but that does not always make it available.

R/r 911

[tniuqs]

The last I heard they are pulling some of those products from studies to increasing AMI's, I believe of last week.

R/r 911

Yuppers was just pulled in Britian the "blood substitute products" have gone under very serious review, as of late that said I have used Pentaspan myself and had good success (anicdotally)

Agreed it will be a long time before we see perflurocarbons on the rigs.

[dzmohr]

I believe oxygen carrying type fluids will be used but probably not within the next 5 -10 years. I heard aboutPolyheme or its counterpart about 12 years ago and it is still being investigated. The last I heard they are pulling some of those products from studies to increasing AMI's, I believe of last week. AS well as ethical questions of patients not being asked or informed that they will be given susbsitute. (kinda hard to do on an arrest, but one has to) So we still have a long way to go.

Oxygent may be under trial studies but who knows when and if this will ever be released as well the costs and containment may never make to the field level. Heck, most EMS still don't even carry Cordorone (antiarrhythmic) and Zofran (antiemetic) due to costs. So I would not hold my breath on it. It would be nice .. but that does not always make it available.

R/r 911

Sure was cool to watch a predecessor fluid in " The Abyss" though( think they were using florurosol(sp?) , with the rat breathing the stuff submerged in it! Once they get it perfected there will be some amazing uses! ( by that way, that was NOT a stunt, I have watched it done ... the feeling was they will eventually be able to do an 80% exchange transfusion of the stuff without ill effect.

Needless to say the blood industry ( a multi BILLION dollar industry) is NOT impressed or in favor, not enough profit in it yet! Like so many drugs it is not that expensive to make but

the R&D costs and regulatory kickbacks -- I mean costs...are thru the roof. But give them time, they will find a way, then the stuff will be readily available and well used.

Sorry, don't have proof about any of the above except the rat breathing it, just feeling a little cynical tonight.

[emsbrian]

PFC can be used to breath, yest they carry so much oxygen that we can handle them in there lungs, As we speak there are patients with it in liquid form in there lungs to enhance oxygen carrying while on vents (research from what I understand, it was a WHILE back that I was reading about that) But yes the whole abyss thing was sweet, and may be possible. I cant remember much about the article except that the patients had some problem, they flooded there lungs with PFC and had them on vents (this was before my medic times)

Talking about that 80% transfusion, thats a LONG way off. The problem is not oxygen transport, but everything else. Obviously (and we all know this but gotta say it) There is more then RBS's in blood. An major PFC transfusion would have no problem transporting oxygen, but there would be no clotting agents, no WBC's ph balance ablity would change, and etc. etc. etc. I personally see PFC's as a oxygen carrying drug, the only reason it would be in a transfusion form would be the fact that it would also normally need to be give with a volume expander.

The day I have to breathe liquid is the day I stop diving.

[tniuqs]

I cant remember much about the article except that the patients had some problem, they flooded there lungs with PFC and had them on vents (this was before my medic times)

Yesseree, the PFC have been used in ventilation patients in ICUs for a while, not as routine but in studies and to the best of my recall first trialed in neonatals with (Hyaline Membrane Disease) and in ARDS (Adult Respiratory Distress Syndrome) the 2 types were Hi meniscus vs Low meniscus or fluid levels @ the Carina vs a set point in the ETT. The ICU I worked in was on the considered list for research grant in that area but alas we didn't get funding to do it. Could it be that my request for a 45 gallon drum of the stuff was too excessive :roll: as all the lit studies and trials were really promising. A couple of passing comments:

1- The present day Ventilators are not designed to move volumes of fluid (in and out) as the "out" part becomes a very serious complication human pulmonary mechanics in expiration are passive. Hence just emptying the lungs themselves sure would screw up I:E ratios to be sure, a totally different way of looking at Ventilating! the WOB would be beyond belief in the spontaneously breathing, patient I would postulate.

2- The PFC do an excellent job at removing the normal sputum production as it "floats" to the top of the PFCs...oh, but the CXRAYS look like a snow storm.... totally whited out, making that diagnostic method a dead loss, MRIs are really costly on a "good morning before rounds type of picture."

3- Using this stuff in a prehospital setting, oh man, I would not want to be setting up the protocols on that nightmare yikes, so don't call me...K!

Talking about that 80% transfusion, thats a LONG way off. The problem is not oxygen transport, but everything else. Obviously (and we all know this but gotta say it) There is more then RBS's in blood. An major PFC transfusion would have no problem transporting oxygen, but there would be no clotting agents, no WBC's ph balance ablity would change, and etc. etc. etc. I personally see PFC's as a oxygen carrying drug, the only reason it would be in a transfusion form would be the fact that it would also normally need to be give with a volume expander.

Very true I would think, what's wrong with whole blood in the first place maybe look at means of preserving it in a new light? Dump the citrates (changes PH and affects stored Calcium) try a new one...hey what about Vitamin C...half in ernest half in jest. :? Present day volume expanders are a good stopgap I believe, and after the comparison studies of treatment of blood loss, the Viet Nam vs the Falklands experiences have really changed how we look at this "field treatment" and normal human physiology to compensate, acidosis can be a preservative adaptation (proven at the cellular level at least) "STOP THE BLEEDING FIRST" does anyone out there pack out Abdo wounds the old way, control the bleed by Tamponading from the inside just a thought there?

So to go one step further why not in induce Hypothermia in the back of the gut wagon it works for cardiac surgery....and ice is cheap stuff.....ok of topic more coffee.

The day I have to breathe liquid is the day I stop diving.

Thats odd that you say that because PFCs first came from US navel tests for very deep sea diving, the panic period is short lasted... :shock:

I have heard :shock:

[bravofoxtrot]

For the chemistry majors out there, 10 points for answering these two questions:

- What kind of stroke (ischemic vs haemorrhagic) was probably seen?

- What would be the reason for this (simple question- simple answer)?

It might be useful in trauma but only up to a point for this reason.

[VentMedic]

In regards to PFC or liquid ventilation;

More than 470 adult, pediatric and neonatal patients have undergone PLV with Alliance's liquid ventilation agent, LiquiVent®, a pharmaceutical-grade PFC. Under normal conditions, LiquiVent can dissolve and carry approximately 20 times more O2 and three times more CO2 than saline, according to the company.

Liquid ventilation is delivered by one of two techniques. Total liquid ventilation (TLV) fills the lungs with PFC to a volume equivalent to the functional residual capacity, approximately 30 mL/kg, according to the University of Michigan information. An experimental "liquid ventilator" then generates tidal breathing with PFC. Optimal CO2 clearance occurs when TLV is performed at a rate of four to five breaths/minute. Researchers consider TLV the extreme end of the LV spectrum and have never tried it in humans.

The other technique is partial liquid ventilation (PLV), in which the clinician performs gas ventilation of the PFC-filled lungs using a standard ventilator. This was considered a breakthrough when introduced in 1991.

While TLV, theoretically, may hold more promise in certain lung disorders, PLV has the edge in practicality.

With TLV, its level of complexity would probably relegate it only to tertiary care centers. The advantage to partial is that it utilizes a ventilator technology every hospital not only already owns but can make work. Secondly, TLV's regulatory pathway has now doubled in complexity. You need FDA regulatory approval not only for the drug but the machines. That's a nightmare squared.

Ongoing Trials

More than 470 adult, pediatric and neonatal patients have undergone PLV with Alliance's liquid ventilation agent, LiquiVent®, a pharmaceutical-grade PFC. Under normal conditions, LiquiVent can dissolve and carry approximately 20 times more O2 and three times more CO2 than saline, according to the company.

http://www.allp.com/LiquiVent/lv.htm

http://www.allp.com/LiquiVent/LV_SUMM.HTM

The above data compiled from various Respiratory Therapy Sources.

My own experience with liquid ventilation was on neonates. Our adult ICU was also doing the trial on ARDs pts. Very good outcomes in both areas with neonatal leading.