It’s been a while since I took physiology. Oxygen simply diffuses across the cell walls and into somatic cells down it’s partial pressure concentration gradient right?
How would pure hemoglobin fair in plasma? Could direct hemoglobin injections into the blood stream be used to treat carbon monoxide poisoning? Combine it with pure oxygen breathing masks? Possibly used by EMT’s at fires?
I realize that this would probably kill a normal healthy person by lowering blood’s oxygen partial pressure. But it seems that extra hemoglobin in the plasma would compete for carbon monoxide in an afflicted patient leaving more hemoglobin available for oxygen.
Thinking further and assuming this would work I think the best place for injection would be the pulmonary artery, directly into the heart, somewhere along the right brachial veins or the jugular vein(these last 2 feed right back into the superior vena cava right?).
Would this require breathing pure oxygen for an extended amount of time until the kidneys filter out the hemoglobin in plasma?
Injecting hemoglobin in carbon monoxide victims would allow oxyhemoglobin to compete for carboxyhemoglobin. While it’s not a bad idea, I’m not sure it’s that practical, for several reasons.
Injecting something into the pulmonary artery is a big deal. It certainly can’t be done easily at an accident scene.
Hemoglobin would likely cause a “foreign body” reaction. When giving blood, quite a bit of testing of both blood group and “typing” has to be done to minimize the chance of donated blood causing more problems than it solves. This requires a lab, experienced personnel and quite a bit of time.
Hemoglobin concentration is just one factor in determining arterial oxygen pressure. Giving oxygen increases arterial oxygen available. Ambulances and EMTs are already equipped to give patients oxygen and have experience in handling it.
That being said, it is possible that hemoglobin could be used as an antidote for severe carbon monoxide poisoning. The idea isn’t bad.
Okay, I’ll play… what about increasing the oxygen carrying capacity by increasing the the hemacrit by transfusing packed cells and plasmaphoresis? Or what about an exchange transfusion? Why wouldn’t ECMO work? (for the uninitiated, that’s Extra Coporeal Membrane Oxygenation its similar to cardi-pulmonary bypass) It should.
My son died from carbon monoxide poisoning 4 years ago.
Okay, I’ll play… what about increasing the oxygen carrying capacity by increasing the the hemacrit by transfusing packed cells and plasmaphoresis? Or what about an exchange transfusion? Why wouldn’t ECMO work? (for the uninitiated, that’s Extra Coporeal Membrane Oxygenation its similar to cardi-pulmonary bypass) It should.
My son died from carbon monoxide poisoning 4 years ago.
If first responders could carry O neg , couldn’t it buy time until ECMO could be set up? Why aren’t we doing this? Or are we? I don’t work anymore…
Carbon monoxide is obviously a killer. The best remedies are avoidance, early suspicion of the diagnosis and to get oxygen on/intubation as quickly as possible. This isn’t always enough, as you know (particularly in suicide attempts/severe fires/co-morbidities). But, from the above link, it looks like “Type O” hemoglobin is still in the experimental stage. I don’t know a lot about ECMO, but in Canada paramedics don’t put people on cardiac bypass – lots of them don’t even intubate. I don’t see why exchange transfusion wouldn’t work, but again, tricky in the field.
Thank you, It was a suicide, and he was gone long before he was found, but his wife survived. ( yes, a suicide pact.) She ultimately did well, but had a long, hard road.
As I suggested, O neg could be given in the field, I know, it would be a bit dicey, driving the crit into the 50s. That would run the risk of sludgings and DIC, but I’d think the short term would be ok. The ECMO, or exchange could be set up at the hospital during transport.
I suppose the reason it isn’t done, is outcomes are so unpredictable, it would be adding risk when it all might resolve on its own. (shrug)
** Squink ** Thanks that link had alot of good information. Apparently alot of hemoglobin solutions already exist.
Dr Paprika
I would think that anything that reaches the either of the Vena Cavas quickly would do the trick. Doesn’t that vien which is always used for I.V. drips lead right back into Superior Vena Cava?
I don’t see why. Hemoglobin is extremely well evolutionarily conserved. I have a hard time seeing it cause an antigen response. The above link also provided examples were there was no immunogenicity due to ultra purified solutions lacking any membranes.
The article however mentions disassociated hemoglobin monomers reacting with NO and causing vaso-constriction(from lack of NO). But it says genetically modified crosslinked hemoglobin tetramers are Ok. I guess this says alot about needing to study blood chemistry.
I don’t see the problem here. I had meant for this to be combined with oxygen treatment. Increasing carrying capacity of carbon monoxide dilutes its saturation percent of hemoglobin, allowing oxygen to bind. However this also increases carrying capacity of oxygen which will in turn decrease arterial oxygen pressure. Oxygen treatment would raise this pressure back up.
I think the hemoglobin injection will allow oxygen treatment to more quickly outcompete carbon monoxide. I would think any amount of time saved from oxygen starvation is a good thing.
I would suppose that since people can only intake oxygen at a certain maximum rate there would be a point where oxygen carrying capacity is so great that it would be better to have a lower carrying capacity and greater arterial oxygen pressure.
Picunurse
i’m sorry to hear that =(
I think the type O blood is a great idea! But as you said it would suffer from promoting cloggage. Hemaglobin injections wouldn’t suffer from that.
I have a few more thoughts to run by you guys. I was thinking that since hemaglobin will bind CO, CO2 and O2 that an injection would soak up CO2 and screw with the carbonic acid equilibrium dropping PH. I think this would be solved with oxygen treatment by outcompeting CO2 for the hemoglobin and thus keeping the carbonic acid buffer/PH stable. I’m unsure of this though. How does oxygen treatment without a hemoglobin injection affect carbonic acid equilibrium?
I remember there being PH sensors in the blood which detected changes in carbonic acid concentration. I remember these sensors controlled the “I need to breathe” function of the brain. Would this be a problem with unconscious patients?
I could see a major problem with there being renal failure from this treatment. How large is hemoglobin and how big a particle will the glomerulus filter before it gets all clogged up?
Here is a more current study. While its very promising for trauma and big bloody surgeries, any other application is way down the road. Its still in early clinical trials, so figure another 5-7 years, before Dr. Welby gets to play with it. The trials are improving, but its still not perfect.
As I read one of the earlier trials, I realized that I, or rather, two of my patients participated in one arm of the study. It was a complete failure, but we collected usable data.
You aren’t in clinical medicine, are you? All veins lead to the same place. The IVC isn’t used in the field. The chances of the line placement itself causing a catastrophic event in the field are high. Its just not a controlled enough environment. Its one thing to have ants and grass in a perpheral line, but, not so good in the central circulation.
The HBOC should (once approved) be able to go through a big perpheral without a problem. The pulmonary artery is off limits to cannulization. Its on the other side of the river, and you with no boat.
The pulmonary artery pressure is an important parameter to follow when a patient is hemodynamicly unstable.
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The problem is that Oxygen is toxic. It causes barrow trauma, leading to ARDS (Acute Respriratory Distress Syndrome) a condition that is poorly survived.
Ventilation impacts pH not oxygenation.
Of course it would. It isn’t a true liquid. Its a volume expander, so would cause the same problems that O neg packed red cells would in the non-anemic patient.
The problem has nothing to do with clotting. The blood is still liquid, but its too thick.
Remember, Oxygen is toxic that’s why air has only 21% The lungs turn to cardboard in the face of 100% O2 for long periods of time. You have to regain equalibrium as fast as possible.
The barrow resceptors you’re talking about work as long as the person is alive. (that is, until you damage them with all that O2) They are a part of the system that will be damaged by prolonged use of 100% O2 Breathing is involuntary.
Renal failure would be an issue if your patient lived long enough, but blood pH has a very narrow tolerance, cells die at even a few minutes of 7.2 (arterial) Less than 7. 0 is incompatible with life. The heart is especially dependent. It will stop and NOT start again if pH isn’t managed immediately.
The sludging of the blood isn’t exactly a clotting problem. Banked blood is anticoagulated, in fact, you have to replace calcium with every 4 units, or it just leaks back out. Blood is, obviously, not all liquid, the body needs its volume to circulate at a minium rate, so to speak. If the hemocrit is above 50 it jus has a hard time getting through small vessels. There’s plenty of blood, but it can’t get to the end organs. So end organs fail, cells die, which drops the pH, which kills more cells… You get the picture. You might solve the carboxy-hemaglobin delemma, but you patient is dead anyway.
Hypotension is a sticky problem too when you can’t pump up the volume because all that heme is in the way.
So, for a problem that may have resolved without intervention, We now have a patient in cardiogenic shock. :eek: Which is rarely survivable.
I think the reason your wheels keep falling off, is you’re assuming a closed system. Humans are never static, when you change something everything else responds for better or worse.
Veins do return blood to the heart. With respect, you were the one who mentioned injecting into the pulmonary artery or directly into the heart, in your first post. Platelets may promote clotting, but that is probably not a major worry if the only problem is carbon monoxide overdose (more so if trauma and risk factors for pulmonary embolus).
I am not an expert in lab pathology. I would think hemoglobin causes a foreign body reaction. From the link above, I think this was likely a problem, and this irritation may play a role in the vasoconstriction – or perhaps it was neutralized by using appropriate bovine serum which is hypo-allergenic.
I’m sorry. I have a major problem with sounding antagonistic when I don’t mean to be. Again, i’m sorry and I duly appreciate your input.
With respect to injections. I was thinking in reverse order the quickest ways of getting the hemoglobin in an oxygenated form. From pulmonary artery back to peripheral veins a short distance from the Vena cavas.
Thanks, I realize now why it’s such a bad idea to inject an artery.
[insert kill bill animesque squirting image here]
No. I’m just a bored college student addicted to the dope.
Yea, I realize everything leads back to the same place. I guess i should have said right atrium. As I said earlier, I was thinking about things which would reach the lungs quickly.
Ok.
How would increased CO2 carrying capacity affect the Carbonic acid equilibrium? Ph? Would it be significant?
Are you referring to hemoglobin injections? I’m confused by this. Wouldn’t a hemoglobin injection have significantly less volume then RBCs of equal oxygen carrying capacity? It wouldn’t have the volume overhead of a cell.
Ok. I believe you, but I don’t understand why. I know Oxygen ion is extremely electronegative and reactive, but doesn’t O2 have negligible reactiveness?
Normal cardiac out put is depending on body surface area around 8 liters a minute. Normal blood volume is about 8 liters. It takes 30 minutes to hours to properly insert a pulmonary artery pressure monitor and fluid lines. It takes 30 seconds to a few minutes to insert a big perpheral IV. Now choose.
Hemoglobin is a solid its suspended in a liquid for delivery Packed red blood cells are solid suspended in plasma.
The volume is about the same. The part of the clinical trials I was briefly involved with, the HBOC was introduced directly into the lungs, in an attempt to oxygenate while holding open damaged alveloi. The volume was about the same as blood.
Oxygen is a corrosive It is the main factor in oxidation. It causes rust on iron. How much more reactive do you want?
hereand here are papers explaining oxygen toxicity.
You seem to forget the people are organic and fragile.
Are you pre-med? You remind me of some pre- clinical med students I knew in the dim past. They too had trouble remembering toat people are meat, not a chemistry lab.
I’ve enjoyed this. Any more questions?
I completely agree. I’m sorry I didn’t make that clearer earlier.
This is what confuses me. The point was to raise oxygen/carbon monoxide carrying capacity. I see no reason for the volume to be around the same size of oxygen carrying capacity equivalent RBC’s. A HBOC solution would have no cellular overhead taking up volume. One could simply concentrate the solution and let it dilute out in the blood.
I could see volume being an issue in transfusions during surgery where there is going to be blood loss and the volume is crucial for circulation.
Why the hell was it introduced directly into the lungs?!?!??!?! Wouldn’t the liquid INCREASE surface tension and causing an even faster collapse?
I believe Oxygen is corrossive to metals because metals have high electron density as well as a relatively free “Sea of electrons”. I do however see how oxygen radicals can form and overcome the antioxident defenses of the cell in high oxygen environments. My question now would be how long and how much exposure would it take before it becomes significant?
No. I’m not pre-med. I’m a biotechnology major emphasising in both animal and bacterial systems whom is simply curious.
I appreciate your input. But I assure you this is not the case and I think you are assuming alot by saying so. I am well aware that In vitro and In vivo systems are as different as night and day. I may lack experience, but the fragility of our existance isn’t lost to me.
I’m still wondering about the carbonic acid chemistry. Would increased CO2 carrying capacity significantly affect blood PH?
While this is hardly my specialty: as I recall, free myglobin (rhabdomyolysis) and hemoglobin (hemolysis) are distinctly toxic to the kidney, especially when it is vulnerable, and ischemia was the #1 physiological factor underlying vulnerabity, regardless of the nominative etiology. In fact, we were taught that ischemia was the primary shared physiological mechanism of almost all acute tubular necroses.
I note that the Hgb replacement therapies mentioned in the article were only approved for veterinary use, where standards are very different: the ‘patient’ is chattel whose commercial value limits the acceptable level of support and resources (i.e. few animals warrant $100K of veterinary care in an emergency, so cheaper options with fairly high risks become preferable to no options at all) In humans, such risks are often completely unacceptable, especially since we must consider functional sequelae for decades – far longer than most animals live.
I’m not contradicting, just asking. As I said this is not my expertise
Is ECMO often used in adults? I once had an interest in it. When I last investigated , it was still plagued by low replacement volume (I/O capacity of the catheter) and high vena caval by-flow, and heavily constrained by the risk of hemolytic damage. Most Boston Hospitals didn’t do it in-house, but sent ECMO candidates to Children’s. As a result it was used much less than it might have been. Is ECMO a standard therapy in your facility? Has it overcome its former limitations?
(I designed an “improved” high volume, low by-flow, low hemolysis ECMO catheter in medical school, but I could never get anyone interested enough to assist me with the materials selection and fabrication for animal studies. Since I only had limited time for the animal lab between my ward duties in third/fourth year, and didn’t plan on going into research (I’d had enough of that before med school), I only hoped to demonstrate its promise well enough for some specialist to take interest . I’m sad to say that, with age, I, too, tend to see its potential difficulties, rather than its promise. When did I become one of them?)
First and foremost, Harmonix I sincerely apologize if I sounded critical or condesending. I was trying for a little lite humor. I guess it didn’t come across as intended.
I knew I skipped something!
As the pCO2 increases the arterial pH rises significantly, if not corrected, quickly, death occurs… The implications of a low arterial pCO2 aren’t quite so dire, although, pronounced and prolonged alkylosis causes the CSF to decrease and can lead to brainstem herniation.
Correcting for acidemia can be tricky, giving NaHco3 was once standard, now we know, it has a rebound effect. Calcium can help stablize pH, but controlling ventilatory rate and quality, is the first line treatment.
Do read one or the other of the articles on O2 toxicity, They explain it much better than I can.
I concede on the volume issue
The liquid oxygenation study was in fact, a faint success in other hospitals. It was thought that healing of the damaged tissue would be helped by passive flow, with mechanical expansion of the alveoli. As I said, I took care of 2 children, I think, 3 and 9 years old. Both died, but we got some good data and they would have died sooner without . KP
You’re absolutely right, but you have to be alive for renal failure to be an issue.
The article I found was newer, form August of 04. It talked about being in the beginning of human clinical trials.Personally, I’ll be surprized to see any wide spread use in my lifetime. I’ve been hearing about it since the '70s
I know ECMO isn’t common in adults, mostly because it just isn’t that effective for the disease processes it was to address.
This thread has been mostly about speculation and brain storming in the face of Severe carbon monoxide poisoning.
It seems logical that it could bridge a bad CO victim. Just my thought.
ECMO has been the most successful for neonatal lung disease, But it is used as a bridge to heart transplant in older kids. I’ve also cared for post-op cardiac repairs that went south. Not all were successful, but more than without any intervention.
Its costly cumbersome and primitive, even a little barbaric, I’m sure it will be replaced with a more streamlined, safer version.
I haven’t gotten my hands dirty in about 4 (!) years. I keep in touch with some old friends, so I hear what’s new, but I’m not at the cutting edge any more.
yes, a suicide pact.) She ultimately did well, but had a long, hard road.
