JC: The metabolic and biochemical characteristics of packed red cell transfusions.

In the UK it’s now standard practice in hypovolaemic/bleeding trauma to use packed red cells as the first line resuscitation fluid. That’s what we keep in the fridge in the emergency department resus room of most hospitals and trauma centres, and in many if not most cases the first IV fluids the patient receives will be in the form of O-ve packed red blood cells. Following this and the activation of a major haemorrhage protocol we hope to catch up to a 1:1:1 ration of RBCs:FFP:Platelets​1​, but initially it’s likely to be packed red cells.

Some services are now stocking FFP in the resus room (or in the prehospital environment) and there even a movement towards the use of whole blood​2​ as we have discussed before on the St Emlyn’s site, but for the majority of units in the UK, packed RBCs will be in first. In major trauma it’s likely that several units (4 or more) will be rapidly transfused into the patient and I suspect that you, like me have probably done this many times.

So stop for a second and ask yourself what’s actually in a bag of packed red blood cells and in particular what the metabolic implications of the contents are. Can you? I’m not sure I could either until I followed a recent twitter chat around the use of blood in prehospital care. Dr Nick Crombie, who leads the RePHILL trial (more of this later) tweeted the following which made me stop and think.

That was part of a debate about the use of interventions in prehospital care that are yet to be proven/replicated and I think in specific reference to the PAMPER trial which showed a benefit to the early use of FFP in major trauma patients​3​ (Ed – we’ve covered that on the blog here​4​).

Most of us don’t like normal saline in trauma for many reasons that I won’t expand on here beyond saying that it as supra-normal sodium and chloride levels, and interestingly a pH of 5.5 (gosh). What about blood though? We give enough of it so perhaps we should think about it’s metabolic profile.

A quick search of PubMed was a little disappointing as I did not find a huge amount of data out there, but there is this paper from 2001​5​.

What type of paper is this?

It’s an experimental study. It’s not a patient focused study, rather a descriptive experimental study of the characteristics of packed red blood cells.

What did they do?

Very simply the authors took blood samples from pre-transfusion bags of packed RBCs and ran them through a blood gas analyser. They looked in some detail about whether the age of the blood made a difference to these values.

What are the headline results?

Across all units the results are really interesting. I’ve summarised them below.

Storage (days)6.7
pH6.79
pCO279mmHg
Bicarbonate11.1mmol/l
Base Excess29.2mmol/l
Potassium20.5 mmol/l
Sodium126mmol/l
Glucose24.1mmol/l
Lactic Acid9.4mmol/l
Haemaglobin18.7g/dl
Haematocrit57%

These are remarkable values if we are trying to manage the metabolic insult that our patients suffer as a result of trauma. Packed cell transfusions have the potential to alter the acid-base balance of our patients and to produce an additional metabolic burden on the patient.

The authors also looked at the effect of age on these values. In their study much of the blood was pretty fresh (hence the average of about a week). In the UK colleagues suggest an expiry date of 35 days and so the values in practice could be much worse than those in the table above (see full paper for details). As an example, at 5 days the potassium estimate was 28mmol/l

https://twitter.com/danieltgaskin/status/1163085522471936001

Sadly, the concerns don’t end there. transfused cells have depleted levels of 2,3 DPG and therefore lack the ability to release oxygen to the tissues in the way that fresh, whole blood does​6​. Not only that but low pH reduces the binding of oxygen to haemaglobin​7​. So it’s double whammy of red cells taking up less O2 in an acidic environment, and then being less able to release because of low levels of 2,3,DPG. It also takes a significant amount of time to replace the 2,3 DPG​8​ which means that the red cells that we think we are transfusing are just not going to perform in the same way that we expect the patient’s own red cells to do​9​.

via Wikipedia https://en.wikipedia.org/wiki/Oxygen%E2%80%93hemoglobin_dissociation_curve

We also know that calcium is removed from packed RBC packs and that we need to replace calcium as part of major haemorrhage protocols​10​. We rarely get on top of the hypocalcaemia in trauma as rapidly as we think we do, despite knowing that hypocalcaemia is bad for the heart. Citrate is the anticoagulant used in blood products and it binds calcium and magnesium. This can result in myocardial depression and/or coagulopathy.

I could go on and on about the problems of managing the replacement of blood loss, but can’t finish without reminding us of the effects on coagulation. Packed cells do not clot and although we aim for 1:1:1 resuscitation we rarely achieve it in the early stages of resuscitation. Stored red cells also adversely affect coagulation pathways independently of calcium replacement​11,12​.

What does this mean in practice?

It’s important that we understand the characteristics and potential implications of the fluids that we give to patients. It’s clear that packed red blood cells are not physiologically normal with respect to normal acid base/electrolyte/lactate values. What is less clear to me (Ed – please add comments below on this if you’re an expert in these matters) is how these metabolic abnormalities are adjusted and mitigated physiologically. Clearly this happens else our patients would rapidly die of hyperkalaemia (and more), but how is less clear to me.

You mentioned RePHILL….

The RePHILL trial is a UK trial looking at the early (prehospital use of blood and plasma in major trauma patients. It’s recruiting now and should report in the next year or so. That trial may well lead us to a better understanding of the early use and metabolic impact of early blood products in trauma. You can read more about the trial here.

The bottom line.

All intravenous fluids have the potential for benefit and for harm. As clinicians we should understand what they contain and how that might affect our patients. Packed red cells are not whole blood and they too have the potential for harm. As prescribers we should know what they contain and how they might influence our patients.

We should also be mindful that when we call some fluids, ones that were previously the mainstay of treatment in trauma as ‘poisonous’ or ‘dangerous’ for our patients then we must understand that the current strategy of packed red cells as first resuscitation fluid may not be the panacea that some think it to be (Ed – I’ve used fluids such as Gelofusine, Saline, Haemaccel in my career). So the next person who tells you that Saline is rubbish because it’s acidotic, does not carry oxygen, contains poisonous ions and stuffs up coagulation, do remember that the bag of packed red cells shares many of the same characteristics.

So what do I do tomorrow with my bleeding trauma patient you might ask? Ideally I would give fresh whole blood. If you don’t have that and you’re giving packed red cells be aware and actively manage the coagulation, temperature, calcium, potassium and everything else that may result from massive transfusion.

Finally, I’m really looking forward to the results of several trials in this area such as Cryostat, RePHILL and more, pRBCs are probably not going to be the only solution for our trauma patients.

vb

S

References

  1. 1.
    Carden R. Getting the Balance Right. St Emlyn’s. http://www.stemlynsblog.org/jc-getting-balance-right-proppr-trial/. Published 2013. Accessed 2019.
  2. 2.
    Qasim Z. Whole Blood in Trauma. St Emlyn’s. Whole Blood in Trauma. Published 2018. Accessed 2019.
  3. 3.
    Sperry JL, Guyette FX, Brown JB, et al. Prehospital Plasma during Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock. N Engl J Med. July 2018:315-326. doi:10.1056/nejmoa1802345
  4. 4.
    Carley S. Top 10 trauma patients. St Emlyn’s. http://www.stemlynsblog.org/top-10-trauma-papers-2018-2019-for-traumauk-conference-st-emlyns/. Published 2019. Accessed 2019.
  5. 5.
    Sümpelmann R, Schürholz T, Thorns E, Hausdörfer J. Acid-base, electrolyte and metabolite concentrations in packed red blood cells for major transfusion in infants. Paediatr Anaesth. 2001;11(2):169-173. https://www.ncbi.nlm.nih.gov/pubmed/11240874.
  6. 6.
    MacDonald R. Red cell 2,3-diphosphoglycerate and oxygen affinity. Anaesthesia. 1977;32(6):544-553. https://www.ncbi.nlm.nih.gov/pubmed/327846.
  7. 7.
    Wikipedia W. Bohr Effect. Wikipedia. https://en.wikipedia.org/wiki/Bohr_effect. Published 2019. Accessed 2019.
  8. 8.
    Stan A, Zsigmond E. The restoration in vivo of 2,3-diphosphoglycerate (2,3-DPG) in stored red cells, after transfusion. The levels of red cells 2,3-DPG. Rom J Intern Med. 2009;47(2):173-177. https://www.ncbi.nlm.nih.gov/pubmed/20067168.
  9. 9.
    Yaojin Li, Yanlian Xiong, Ruofeng Wang, Fuzhou Tang, Xiang Wang. Blood banking-induced alteration of red blood cell oxygen release ability. Blood Transfusion. 2015. doi:10.2450/2015.0055-15
  10. 10.
    Lyon RM, de Sausmarez E, et al. Pre-hospital transfusion of packed red blood cells in 147 patients from a UK helicopter emergency medical service. Scand J Trauma Resusc Emerg Med. February 2017. doi:10.1186/s13049-017-0356-2
  11. 11.
    Aucar JA, Isaak E, Anthony D. The effect of red blood cell age on coagulation. The American Journal of Surgery. December 2009:900-904. doi:10.1016/j.amjsurg.2009.05.034
  12. 12.
    Aucar JA, Sheth M. The storage lesion of packed red blood cells affects coagulation. Surgery. October 2012:697-703. doi:10.1016/j.surg.2012.07.011

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Posted by Simon Carley

Professor Simon Carley MB ChB, PGDip, DipIMC (RCS Ed), FRCS (Ed)(1998), FHEA, FAcadMed, FRCEM, MPhil, MD, PhD is Creator, Webmaster, owner and Editor in Chief of the St Emlyn’s blog and podcast. He is Professor of Emergency Medicine at Manchester Metropolitan University and a Consultant in adult and paediatric Emergency Medicine at Manchester Foundation Trust. He is co-founder of BestBets, St.Emlyns and the MSc in emergency medicine at Manchester Metropolitan University. He is an Education Associate with the General Medical Council and is an Associate Editor for the Emergency Medicine Journal. His research interests include diagnostics, MedEd, Major incidents & Evidence based Emergency Medicine. He is verified on twitter as @EMManchester

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