Blood transfusion through LR

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Precedex

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Does anyone think this is a problem? I certainly was taught that and most residents/CRNAs at my joint hang NS if they anticipate giving blood. From what little evidence I could find it doesn't seem to be an issue provided you keep things flowing fairly briskly. Obviously the issue being calcium chelating citrate leading to clot formation in the IV tubing.

Thanks for sharing your thoughts/experiences on this.

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I had one attending during residency that would routinely just grab a bag at random. So not infrequently the blood was diluted with LR. I only saw a problem once when the filter became blocked, probably from chelation because it was only the second unit.

So I would say the risk is out there, but I wouldn't call it common.

If NS is readily available, I use it. I've only used LR once as an attending to dilute the blood.
 
I wouldn't use LR to dilute PRBC's, and I wouldn't run it concurrently with LR, but if you're just plugging your blood tubing into a line that has LR in it, no problem.
 
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Does anyone think this is a problem? I certainly was taught that and most residents/CRNAs at my joint hang NS if they anticipate giving blood. From what little evidence I could find it doesn't seem to be an issue provided you keep things flowing fairly briskly. Obviously the issue being calcium chelating citrate leading to clot formation in the IV tubing.

Thanks for sharing your thoughts/experiences on this.

Correct me if I am wrong but the mechanism isnt the calcium citrate its the free calcium leading to activation of the extrinsic pathway leading to clot.
 
Correct me if I am wrong but the mechanism isnt the calcium citrate its the free calcium leading to activation of the extrinsic pathway leading to clot.

Yes it is the free calcium that precipitates clot formation. That's why the blood has the citrate : to bind free calcium and prevent clotting. At some point, at least in theory, that chelating capability may be exceeded which allows the free calcium to do what you said.
 
Correct me if I am wrong but the mechanism isnt the calcium citrate its the free calcium leading to activation of the extrinsic pathway leading to clot.

citrate chelates calcium in prbc bags. there is usually excess citrate, which can contribute to hypocalcemia in humans. theoretically, added calcium can interact with the minute volume of platelets and clotting factors that could be present in rbc bags. ive mixed blood with LR/NS and plasmalyte and have never noticed an issue.

i dilute my rbc bags in non massive-transfusion settings...i feel like transfusing hemoconcentrated red blood cells in a patient who is probably volume depleted doesnt make sense. id rather have 5L circulating volume with a hematocrit of 30% than 3L/50%
 
citrate chelates calcium in prbc bags. there is usually excess citrate, which can contribute to hypocalcemia in humans. theoretically, added calcium can interact with the minute volume of platelets and clotting factors that could be present in rbc bags. ive mixed blood with LR/NS and plasmalyte and have never noticed an issue.

i dilute my rbc bags in non massive-transfusion settings...i feel like transfusing hemoconcentrated red blood cells in a patient who is probably volume depleted doesnt make sense. id rather have 5L circulating volume with a hematocrit of 30% than 3L/50%

I know that calcium activates clotting in prbc's. Once the chelating ability of the citrate has been exhausted. The way it was phrased by the op the calcium citrate causes clotting. Also, what should be discussed too is osmotic fragility of rbc reconstituted in lr, ns, albumin, once rbc,s are lysed the intracellular contents of rbcs would definetly lead to clotting millers chapter on tranafusion medicine deals with this issue.
 
Another side note question... Does anyone know if hand pumping platelets (as opposed to allowing them to drip) is contraindicated?

I had an attending once yell at me for hand pumping platelets stating that it destroys the platelets. I haven't found any mention of this in my anesthesia texts.
 
Does anyone think this is a problem? I certainly was taught that and most residents/CRNAs at my joint hang NS if they anticipate giving blood. From what little evidence I could find it doesn't seem to be an issue provided you keep things flowing fairly briskly. Obviously the issue being calcium chelating citrate leading to clot formation in the IV tubing.

Thanks for sharing your thoughts/experiences on this.

Done many times. No issues. I don't dilute the PRBC. What's the point in it going faster if it last longer? Give the rbcs and chase them with LR if you need more volume.
 
Another side note question... Does anyone know if hand pumping platelets (as opposed to allowing them to drip) is contraindicated?

I had an attending once yell at me for hand pumping platelets stating that it destroys the platelets. I haven't found any mention of this in my anesthesia texts.

True. Leave them platelets alone.
 
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According to the American Association of Blood Banks Technical Manual:

1) No medication or solutions other than 0.9% sodium chloride should be administered simultaneously with blood components through the same tubing. This goes for all blood components, including plasma, platelets, and cryoprecipitate. Many adverse events can occur if this is ignored, including clotting due to reversal of citrate by excessive calcium as well as osmotic lysis of red cells, resulting in a hemolytic transfusion reaction.

2) AABB Standards allow exceptions to the above restriction when a) the drug or solution has been approved by the FDA for use with blood administration, or b) there is documentation to show that the addition is safe and does not adversely affect the blood or component. Before any clinician makes this decision independantly, I strongly urge that your blood bank medical director be consulted before trying anything.

I would not recommend hand pumping platelets. Platelets are activated by shear force, which is increased by hand pumping. Platelets need to be handled gently to ensure they will be ready to act at sites of injury, not triggered before then.

TL-DR version: The only thing safe to co-infuse or mix with blood products is normal saline. If you have any questions about transfusion practice, consult your blood bank medical director.
 
Does anyone think this is a problem? I certainly was taught that and most residents/CRNAs at my joint hang NS if they anticipate giving blood. From what little evidence I could find it doesn't seem to be an issue provided you keep things flowing fairly briskly. Obviously the issue being calcium chelating citrate leading to clot formation in the IV tubing.

Thanks for sharing your thoughts/experiences on this.

I do all the time (give LR with PRBCs). I've only killed 7 patients so far.

I always mix the PRBCS with some fluid (usually LR).
 
According to the American Association of Blood Banks Technical Manual:

1) No medication or solutions other than 0.9% sodium chloride should be administered simultaneously with blood components through the same tubing. This goes for all blood components, including plasma, platelets, and cryoprecipitate. Many adverse events can occur if this is ignored, including clotting due to reversal of citrate by excessive calcium as well as osmotic lysis of red cells, resulting in a hemolytic transfusion reaction.

2) AABB Standards allow exceptions to the above restriction when a) the drug or solution has been approved by the FDA for use with blood administration, or b) there is documentation to show that the addition is safe and does not adversely affect the blood or component. Before any clinician makes this decision independantly, I strongly urge that your blood bank medical director be consulted before trying anything.

I would not recommend hand pumping platelets. Platelets are activated by shear force, which is increased by hand pumping. Platelets need to be handled gently to ensure they will be ready to act at sites of injury, not triggered before then.

TL-DR version: The only thing safe to co-infuse or mix with blood products is normal saline. If you have any questions about transfusion practice, consult your blood bank medical director.

Uh....

If you listen to them, you give 1 unit of blood over 4 hours.

Good luck with that.
 
I think the concern with LR & blood came from when they were still using CPDA, which had much more citrate in it than the AS-3 or AS-5 used currently
 
According to the American Association of Blood Banks Technical Manual:...

TL-DR version: The only thing safe to co-infuse or mix with blood products is normal saline. If you have any questions about transfusion practice, consult your blood bank medical director.

Oh come on. As an attending PHYSICIAN in transfusion medicine, can't you bring more to the plate than the AABB guidelines?



How about something like this.

(For those of you who don't want to read the whole thing, the evidence suggests that LR and PRBCs are compatible as long as the ratio of LR to PRBCs does not exceed 1:1. A safety margin of 1:2 is probably a good idea)


In 1975, Ryden and Oberman published the first data on the Compatibility of Common Intravenous Solutions with CPD Blood. Working with CPD preserved whole blood, they demonstrated grossly visible clot formation in vitro in samples of LR and whole blood at a citrate: calcium ratio of 4:1 or lower when incubated for 5 minutes. Largely based on these findings, AABB incorporated the prohibition against the combination of LR and blood components when they developed their guidelines.

Then, in 1991, Cull and Lally looked at the Compatibility of (CPD preserved) packed erythrocytes and Ringer's lactate solution.. They examined a variety of ratios of CPD PRBCs: LR from 5:1 to 1:20. Clotting was observed in the 1:1 dilution, but not in the 2:1 or 5:1 dilutions at up to two hours. Units of PRBCs diluted with LR and passed through a 170 micron filter were compared to PRBCs similarly diluted with NS. No difference in flow rate was found.

In 1998, Lorenzo et al advised that blood bank guidelines be revised to allow the use of LR in the rapid transfusion of PRBCs when they assessed infusion time, filter weight, and clot formation after admixing whole blood and PRBCs with NS, LR, and LR with increasing concentrations of added calcium chloride from 1g to 5g. They found no differences except for the presence of visible clot in the LR + 5g calcium chloride mixture.

In 2009, Albert et al found that Ringer's lactate is compatible with the rapid infusion of AS-3 preserved packed red blood cells. when they used ELISA to compare prothrombin activation fragment 1 + 2 (the breakdown products of thrombin generation) levels in units of PRBCs similarly diluted in NS and LR then run through filters and fluid warmers (to simulate intraoperative transfusion practices) and found the levels of F1+2 to be sub-physiologic.

Then last year, Levac et al demonstrated that Ringer's lactate is compatible with saline-adenine-glucose-mannitol preserved packed red blood cells for rapid transfusion.. "Samples from 12 units of SAGM-PRBC were diluted from 0-97.5% with RL and normal saline (NS), incubated for 30 min, and passed through 40 μm filters." F1+2 levels were measured via ELISA. 8 samples were diluted with LR and incubated for 30 to 240 min and analyzed in a similar manner. At 120 minutes and up, some clotting was observed, but there was no clotting at 60 minutes. They concluded that LR/ PRBC co-administration is safe as long as cells are administered over 60 minutes or less.

Many adverse events can occur if this is ignored, including... osmotic lysis of red cells, resulting in a hemolytic transfusion reaction.

Though generally resulting in benign hemoglobinemia and hemoglobinuria, there are case reports of serious sequelae from acute non-immune hemolytic transfusion reaction (pseudo-hemolytic transfusion reaction) including renal failure and hypotension. However, lysis of cells was never the concern with LR. It is an accurate concern if red blood cells are diluted/ co-administered in hypotonic solutions like D5W which should never be done.


To my knowledge, there are no papers refuting the safety of PRBC/LR co-administration with modern anticoagulant techniques. If you know of any, please share.

I am not aware of any study of the effect of LR other factors, although platelet activation might occur. That would be an interesting thing to look at.

Personally, I still make a good-faith effort to dilute/ transfuse with NS because the guidelines exist and have not been update to reflect the data (the number one problem with guidelines IMHO). However, I don't go out of my way if there is LR hanging and I need to give products rapidly. I do always run platelets through their own line so the latter is essentially a null issue to me.

- pod
 
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Your stated ratio in summary seems to fly against the Cull and Lally study you provided. This is likely just a typo but for clarification I'm assuming it should read PRBC:LR OF 1:1 with a safety margin of 2:1. Correct? It makes more sense to me that a higher ration of RBCs to LR means more citrate and less calcium to be chelated by that citrate. Where at 2:1 LR😛RBC you would have more calcium and likely overwhelm the citrate.
 
POD,

Nice post. Good info. I have not seen any problems using 1:1 ratio of LR to blood with a few units. I've never given more than a few units with LR as I usually switch to NS.
 
Your stated ratio in summary seems to fly against the Cull and Lally study you provided. This is likely just a typo but for clarification I'm assuming it should read PRBC:LR OF 1:1 with a safety margin of 2:1. Correct? It makes more sense to me that a higher ration of RBCs to LR means more citrate and less calcium to be chelated by that citrate. Where at 2:1 LR😛RBC you would have more calcium and likely overwhelm the citrate.


You are correct. It was a typo. I corrected it. I usually will leave typos in place, but thought it was important to correct this one.

Typing on the iPhone today.

-pod
 
This stuff was popular in the early 90s. I have given 30 bottles to one patient during a case in the 1990s.

You're probably thinking of Plasmanate (5% albumin in NS) which is in a bottle. Plasmalyte is an isotonic balanced salt solution and comes in bags. It's essentially all I use now, but thought it was expensive ($40 a liter). Anyone know the cost?
 
You're probably thinking of Plasmanate (5% albumin in NS) which is in a bottle. Plasmalyte is an isotonic balanced salt solution and comes in bags. It's essentially all I use now, but thought it was expensive ($40 a liter). Anyone know the cost?

Yes, you are correct. $40 for a bag of fluid? Really?
 
PlasmaLyte is a family of balanced crystalloid solutions with multiple different formulations available worldwide according to regional clinical practices and preferences. It closely mimics human plasma in its content of electrolytes, osmolality, and pH. These solutions also have additional buffer capacity and contain anions such as acetate, gluconate, and even lactate that are converted to bicarbonate, CO2, and water. The advantages of PlasmaLyte include volume and electrolyte deficit correction while addressing acidosis. It shares the same problems as most other crystalloid fluids (fluid overload, edema with weight gain, lung edema, and worsening of the intracranial pressure). A unique concern is that most formulations contain magnesium, which may affect peripheral vascular resistance, heart rate, and worsen organ ischemia. There are few studies on its use in trauma or hypovolemic shock. There is no evidence that PlasmaLyte is superior to other crystalloids for the prehospital management of traumatic hypovolemia.
 
OBJECTIVE:
Intravenous infusion of crystalloid solutions is a cornerstone of the treatment of hemorrhagic shock. However, crystalloid solutions can have variable metabolic acid-base effects, perpetuating or even aggravating shock-induced metabolic acidosis. The aim of this study was to compare, in a controlled volume–driven porcine model of hemorrhagic shock, the effects of three different crystalloid solutions on the hemodynamics and acid-base balance.

METHODS:
Controlled hemorrhagic shock (40% of the total blood volume was removed) was induced in 18 animals, which were then treated with normal saline (0.9% NaCl), Lactated Ringer's Solution or Plasma-Lyte pH 7.4, in a blinded fashion (n
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6 for each group). Using a predefined protocol, the animals received three times the volume of blood removed.

RESULTS:
The three different crystalloid infusions were equally capable of reversing the hemorrhage-induced low cardiac output and anuria. The Lactated Ringer's Solution and Plasma-Lyte pH 7.4 infusions resulted in an increased standard base excess and a decreased serum chloride level, whereas treatment with normal saline resulted in a decreased standard base excess and an increased serum chloride level. The Plasma-Lyte pH 7.4 infusions did not change the level of the unmeasured anions.

CONCLUSION:
Although the three tested crystalloid solutions were equally able to attenuate the hemodynamic and tissue perfusion disturbances, only the normal saline induced hyperchloremia and metabolic acidosis.

Keywords: Acidosis, Crystalloid Solution, Hyperchloremia, Hemorrhagic Shock, Strong Ion Difference
 
If I recall correctly it is about $1.75 for PlasmaLyte when bought in bulk on contract and about $0.75 for NS or LR.

I see PlasmaLyte online for $85 per case of 14 ($6.07 per liter) and NS for ~$2.00 per liter so probably in the 2-3x more expensive range.

Of course this is the cost. I have no idea what the patient charge is.

- pod
 
If I recall correctly it is about $1.75 for PlasmaLyte when bought in bulk on contract and about $0.75 for NS or LR.

I see PlasmaLyte online for $85 per case of 14 ($6.07 per liter) and NS for ~$2.00 per liter so probably in the 2-3x more expensive range.

Of course this is the cost. I have no idea what the patient charge is.

- pod


I could not find any evidence for the superiority of Plasmalyte over LR except for Liver transplant patients.
 
If I recall correctly it is about $1.75 for PlasmaLyte when bought in bulk on contract and about $0.75 for NS or LR.

I see PlasmaLyte online for $85 per case of 14 ($6.07 per liter) and NS for ~$2.00 per liter so probably in the 2-3x more expensive range.

Of course this is the cost. I have no idea what the patient charge is.

- pod

That makes more sense. In residency we only used Plasmalyte for liver transplants so maybe the volume wasn't enough.

I could not find any evidence for the superiority of Plasmalyte over LR except for Liver transplant patients.

Residency: NS/LR didn't matter. I would alternate the fluids to avoid the lab changes. Fellowship: LR but never gave a whole lot of crystalloid.
Practice: Plasmalyte. I don't think there's a big difference between any of them. NS does produce more lab abnormalities that aren't clinically significant or have any mortality impact other than make people worry (hyperchloremic metabolic acidosis). I do chuckle when people snatch the Plasmalyte down and put NS up instead for an ESRD patient.
 
I could not find any evidence for the superiority of Plasmalyte over LR except for Liver transplant patients.

i have been waiting for the evidence for the last few years - maybe i'll have to do (or encourage a resident to do) the retrospectostudy... but the change in osmolality alone.. makes sense to me not to rescuscitate c a hypotonic fluid

we have to steal PL from the perfusionists' stash at my institution; about $5/L compared to about $1/L for LR or NS.

did an elective AAA the other day - most of the volume was NS mostly as a function of what was in the room - postop to the ICU volume replete with a non-gap base def of -6 - explained to the nurse and R3 to be sure not to treat that hyperchloremic metabolic acidosis with volume (all other measures pointed to eu/hypervolemia), and to assess all fronts for preload estimation. as i was turning to leave heard the icu resident tell the nurse "i don't believe in all those anesthesia theories - give him a cuppla liters normal saline - let's get rid of that base def". turned back around and mentioned to her to review fundamentals of abg analysis and mentioned the incident to my buddy her attending... likely won't have much effect but i always take the NS out of the OR now so as not to confuse surgical residents in the ICU..
 
I could not find any evidence for the superiority of Plasmalyte over LR except for Liver transplant patients.

Agreed. If I had strong evidence I would insist on changing my current practice. I do believe that minimizing the amount of NS that I give to my off-pump patients does decrease the frequency of tremendous base deficits that we frequently see. This can, of course, be accomplished with LR.

- pod
 
I like it for a couple of reasons.
1. You can mix it with blood.

2. Doesn't have the chloride load of NS, so no non-gap acidosis with resuscitation

3. For neuro and neuro/trauma its isotonic, so unlike LR don't have to worry dropping sodium, and if you're giving a lot you don't have to worry about #2

The way I see it you get the best of LR and NS in one fluid.
 
Oh come on. As an attending PHYSICIAN in transfusion medicine, can't you bring more to the plate than the AABB guidelines?



How about something like this.

(For those of you who don't want to read the whole thing, the evidence suggests that LR and PRBCs are compatible as long as the ratio of LR to PRBCs does not exceed 1:1. A safety margin of 1:2 is probably a good idea)


In 1975, Ryden and Oberman published the first data on the Compatibility of Common Intravenous Solutions with CPD Blood. Working with CPD preserved whole blood, they demonstrated grossly visible clot formation in vitro in samples of LR and whole blood at a citrate: calcium ratio of 4:1 or lower when incubated for 5 minutes. Largely based on these findings, AABB incorporated the prohibition against the combination of LR and blood components when they developed their guidelines.

Then, in 1991, Cull and Lally looked at the Compatibility of (CPD preserved) packed erythrocytes and Ringer's lactate solution.. They examined a variety of ratios of CPD PRBCs: LR from 5:1 to 1:20. Clotting was observed in the 1:1 dilution, but not in the 2:1 or 5:1 dilutions at up to two hours. Units of PRBCs diluted with LR and passed through a 170 micron filter were compared to PRBCs similarly diluted with NS. No difference in flow rate was found.

In 1998, Lorenzo et al advised that blood bank guidelines be revised to allow the use of LR in the rapid transfusion of PRBCs when they assessed infusion time, filter weight, and clot formation after admixing whole blood and PRBCs with NS, LR, and LR with increasing concentrations of added calcium chloride from 1g to 5g. They found no differences except for the presence of visible clot in the LR + 5g calcium chloride mixture.

In 2009, Albert et al found that Ringer's lactate is compatible with the rapid infusion of AS-3 preserved packed red blood cells. when they used ELISA to compare prothrombin activation fragment 1 + 2 (the breakdown products of thrombin generation) levels in units of PRBCs similarly diluted in NS and LR then run through filters and fluid warmers (to simulate intraoperative transfusion practices) and found the levels of F1+2 to be sub-physiologic.

Then last year, Levac et al demonstrated that Ringer's lactate is compatible with saline-adenine-glucose-mannitol preserved packed red blood cells for rapid transfusion.. "Samples from 12 units of SAGM-PRBC were diluted from 0-97.5% with RL and normal saline (NS), incubated for 30 min, and passed through 40 μm filters." F1+2 levels were measured via ELISA. 8 samples were diluted with LR and incubated for 30 to 240 min and analyzed in a similar manner. At 120 minutes and up, some clotting was observed, but there was no clotting at 60 minutes. They concluded that LR/ PRBC co-administration is safe as long as cells are administered over 60 minutes or less.



Though generally resulting in benign hemoglobinemia and hemoglobinuria, there are case reports of serious sequelae from acute non-immune hemolytic transfusion reaction (pseudo-hemolytic transfusion reaction) including renal failure and hypotension. However, lysis of cells was never the concern with LR. It is an accurate concern if red blood cells are diluted/ co-administered in hypotonic solutions like D5W which should never be done.


To my knowledge, there are no papers refuting the safety of PRBC/LR co-administration with modern anticoagulant techniques. If you know of any, please share.

I am not aware of any study of the effect of LR other factors, although platelet activation might occur. That would be an interesting thing to look at.

Personally, I still make a good-faith effort to dilute/ transfuse with NS because the guidelines exist and have not been update to reflect the data (the number one problem with guidelines IMHO). However, I don't go out of my way if there is LR hanging and I need to give products rapidly. I do always run platelets through their own line so the latter is essentially a null issue to me.

- pod

Thanks. Great post.
 
250cc 5% albumin and 50cc 25% albumin cost $35 at my institution

I have given 1000s of units through LR without one problem.
I do not dilute my blood with any crystalloid anymore. I pressurize it through the large bore IV and it gets in just fine.

I let the platelets go in by gravity, which though the IVs I have is pretty fast.

If you expect blood loss put in big IVs. If you are unsure if there will be blood loss make sure you have a plan where you are going to place your large bore IVs if you need one emergently. If you don't think you will be able to get one during the case, put it in ahead of time. I never regretted putting in an IV that was too big.
 
Another side note question... Does anyone know if hand pumping platelets (as opposed to allowing them to drip) is contraindicated?

I had an attending once yell at me for hand pumping platelets stating that it destroys the platelets. I haven't found any mention of this in my anesthesia texts.
aside from trauma/massive transfusion events, couldn't the same be said for pressurizing PRBCs? seems the literature states that increased pressure (one study cited 150-300 torr) increases hemolysis, thereby decreasing oxygen carrying capacity, increasing concentration of cellular contents, etc... granted, this was a 1982 study (A&A 1982 Calkins 776-80).
perhaps in the grand scheme of things, not as 'relevant' as platelets, but still..
 
Does anyone think this is a problem? I certainly was taught that and most residents/CRNAs at my joint hang NS if they anticipate giving blood. From what little evidence I could find it doesn't seem to be an issue provided you keep things flowing fairly briskly. Obviously the issue being calcium chelating citrate leading to clot formation in the IV tubing.

Thanks for sharing your thoughts/experiences on this.

Dogma.

Got a liter of LR hanging and you need to give blood?

Hang the prbcs, shoot some LR in there to dilute it a little so it flows better,

and keep rolling.


More important than LR vs NS for hanging blood is to

use a new orange filter thinghy for each prbc.
 
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