If you have had your ear to the ground at all with podcasts, you may have seen and heard about the rise of the idea of using plasma as a resuscitation fluid of choice in a few different settings. The use of plasma in applications other than hemorrhage is not brand new to me, but I really caught interest in it after a few Prolonged Field Care podcasts back in September. I am finally getting around to putting my notes together, which is somewhat timely considering the announcement of FDA approval for freeze dried plasma. Could it be a game changer, maybe, probably.
Prehistoric Era
Like whole blood, the use of plasma for resuscitation is not a new or novel concept. Lyophilized plasma was the resuscitation fluid of choice next to blood through WWII and Korea. My ears always perk up a little bit when I hear Hawkeye asks for a unit of plasma during surgery on MASH. But… a little problem developed that outlawed the use of lyophilized plasma for decades, almost 40 years. There was a small, little, sort of problem with Hepatitis contamination of the pool supply and the subsequent infection of many recipients with Hep C. By the 70’s its use had been completely outlawed.1-3
Then came the age of the crystalloids. For the next 30 years, normal saline and lactated ringers would rule the resuscitation of countless patients in various forms of shock. Blood products also gained popularity during this phase sometime in the ~80s, but remained largely an in-hospital treatment. Single donor plasma, which was totally safe, soon found its place near the bottom of the algorithm for blood product administration. Crystalloid infusions prehospital and blood transfusions in-hospital would be the rhythm of resuscitation through the beginning of the Global War on Terrorism (GWOT).
The Old Testament
In the early 2000s, trauma-induced coagulopathy finds the spotlight in trauma resuscitation. Brohi et al discovered that a patient’s ability to form clots is deranged much sooner than previously thought.4 The lethal triad had been established for some time by this point, and we only supercharged the research and our understanding of it through the conflicts in Iraq and Afghanistan.4
For the last decade or so we have focused on giving bleeding patients back that which they lost, blood. PROPPR, PAMPer, and COMBAT all went a step further and revisited the place plasma had in the algorithm and thought that perhaps it should be given earlier.5-7 They show that it is not just beneficial in resuscitation but that it may have a more meaningful impact if given sooner in the resuscitation.5-7 Skeptics and proponents of these trials tend to hit on topics like positive, negative, and neutral as far as outcome results.8
I joined an air medical program at the time (2018ish) that carried 2 PRBC and 2 units of plasma on the aircraft, with PRBCs being prioritized over plasma. The reasoning was that the patients needed the PRBCs for their oxygen carrying capacity and that once we had replenished that, then it was appropriate to move to plasma. It was 2018, I was none the wiser and the science offered no clear consensus beyond, both are beneficial and your trauma patients likely need both.
I still had not been introduced to terms like endotheliopathy and glycocalyx (which would have turned my attention to plasma sooner). That would come a few years later after what could only be described as a MASSIVE mass transfusion case. You can check it out here:9 But what I learned was that those two physiologic factors were the one constant across all of our shock resuscitations from the beginning of time.
SHINE a Light on Plasma
There is one constant, across all types of shock: endotheliopathy. For the sake of brevity I will use the term SHock INduced Endotheliopathy or SHINE.
Inflammation, this is a normal response to damage and ischemia. But inflammation is a harbinger of this post resuscitation apocalypse when it becomes exaggerated and unregulated. Cytokines and inflammatory mediators destroy the vascular endothelium and the endothelial glycocalyx, which has a couple of untoward results.10-12 One is that the endothelial surface is exposed to substances that promote coagulation, resulting in clot formation in the microcirculation (inhibiting oxygen delivery distal to the clot). The other is that the vasculature loses integrity and begins to leak, leading to fluid loss. This also leaves the patient without the ability to quickly and adequately vasoconstrict to improve MAP and perfusion.
That damage leads to leakage or a leaky vascular system and eventually it inhibits the patient’s ability to vasoconstrict. But they aren’t just leaking plasma out into their tissue spaces. They’re also losing endogenous catecholamines and those are critical to maintaining perfusion.
The resulting septic shock-like state is a vasoplegic nightmare that often results in some combination of mechanical cardiac assist devices, vasopressors, inotropes, and death (in more cases than not).
The New Testament of Prehospital Plasma : Burns, Sepsis, TBI
Further Listening/Reading: Prolonged Field Care Podcast Episodes: 227, 242, 256
The literature on plasma usage, even prehospital plasma administration in hemorrhagic shock is rather supportive for its use. Some folks banter back and forth about how much and in what scheme (1:1:1 being the most prevalent). But what is not refuted is the positive effect plasma has on both repairing the endothelial glycocalyx and improving intravascular volume retention.
Hypoxia –> inflammation –> endothelial damage –> capillary leak & vasoplegia –> death
This same pathway is present in hemorrhagic shock, septic shock, burns, and although not exactly the same pathway, traumatic brain injury. These all share SHINE as a problem, and in each case, the worse the damage and the deeper in shock the patient gets, the worse the outcomes are.
Plasma, be it freeze dried or thawed donor product, corrects this problem. Not only that, if started early enough, it can change the trajectory of the patient’s clinical course. It is a colloid solution with a heavy dose of albumin present, which helps keep fluid in the intravascular space. At the same time it coats and repairs the glycocalyx and works to seal up the gaps in the endothelium to prevent capillary leakage. The patient wins.
Indication | Primary Resuscitation Target | Key Biological Action of Plasma | Primary Clinical Outcome |
Hemorrhage5-7,17 | Hemostasis & intravascular volume replacement | Replenishes clotting factors; seals glycocalyx | Reduced mortality |
TBI18-20 | Intracranial pressure & cerebral perfusion | Seals Blood-Brain Barrier; stops contusion expansion | Decreased secondary injury & lower mortality |
Sepsis21-23 | Microvascular patency & capillary integrity restoration | Blunts hyperpermeability | Reduced organ dysfunction |
Burns24-26 | Intravascular oncotic pressure & fluid creep | Restores GCX; stops extravasation | Decreased fluid creep & compartment syndromes. |
References
Kendrick JB, Simpson JB, Vincent AL, et al. Freeze-dried plasma: history and current status. J Spec Oper Med. 2016;16(2):16-24.
Murray CK, Holmes R, Pusateri AE. History of plasma use in the United States military. Transfusion. 2016;56(Suppl 2):S110-S127.
Pusateri AE, Given MB, Schreiber MA, et al. Dried plasma: state of the science and recent developments. Shock. 2018;49(4):365-377.
Brohi K, Singh J, Heron M, Coats T. Acute traumatic coagulopathy. J Trauma. 2003;54(6):1127-1130.
Holcomb JB, Tilley BC, Baraniuk S, et al. Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial. JAMA. 2015;313(5):471-482.
Sperry JL, Guyette FX, Brown JB, et al. Prehospital plasma during air medical transport in trauma patients at risk for hemorrhagic shock (PAMPer). N Engl J Med. 2018;379(4):315-326.
Moore HB, Moore EE, Chapman MP, et al. Plasma-first resuscitation to treat haemorrhagic shock during emergency ground transport in an urban area: a randomised trial (COMBAT). Lancet. 2018;392(10144):283-291.
Weingart S. EMCrit 230 – Prehospital plasma with Jason Sperry and the PAMPer trial vs. COMBAT. EMCrit Blog. Published August 20, 2018. Accessed August 26, 2026. https://emcrit.org/emcrit/pamper/
Air Medical Journal. Case study on massive transfusion and prehospital blood product administration. Air Med J. 2021;40(5):342-348.
Johansson PI, Stensballe J, Rasmussen LS, Ostrowski SR. A high admission syndecan-1 level, a marker of endothelial glycocalyx degradation, is associated with shock, early coagulopathy, and increased mortality in trauma patients. Ann Surg. 2011;254(2):194-200.
Ostrowski SR, Johansson PI. Endothelial glycocalyx degradation induces endogenous heparinization in patients with severe injury and early traumatic coagulopathy. J Trauma Acute Care Surg. 2012;73(1):60-66.
Chignalia AZ, Yetimyas F, Christiaans SC, et al. The glycocalyx and trauma: a review. Shock. 2016;45(4):338-348.
Dennis. Episode 256: Plasma for burns. Prolonged Field Care Podcast. Published November 27, 2025. Accessed August 26, 2026. https://prolongedfieldcare.org/
Dennis, Holcomb J. Episode 242: Plasma for TBI management. Prolonged Field Care Podcast. Published August 11, 2025. Accessed August 26, 2026. https://prolongedfieldcare.org/
Dennis, Alex. Episode 227: Burn resuscitation with Alex. Prolonged Field Care Podcast. Published April 28, 2025. Accessed August 26, 2026. https://prolongedfieldcare.org/2025/04/28/227-burn-resuscitation-with-alex/
Hartman JD, Antevy P. Bringing plasma to the prehospital setting: Dr. Peter Antevy on advancing emergency care. EMS World Podcast. Published August 19, 2026. Accessed August 26, 2026. https://emsworldpodcasts.podbean.com/
Guyette FX, Sperry JL, Peitzman AB, et al. Prehospital blood product and crystalloid resuscitation in the severely injured patient: a secondary analysis of the PAMPer trial. Ann Surg. 2020;273(2):358-364.
Gruen DS, Guyette FX, Brown JB, et al. Association of prehospital plasma transfusion with survival in patients with traumatic brain injury with and without shock: a secondary analysis of the PAMPer trial. JAMA Netw Open. 2020;3(10):e2016869.
Zhao Z, Wang M, Tian Y, et al. Fresh frozen plasma protects the blood-brain barrier and reduces edema formation after traumatic brain injury. J Trauma Acute Care Surg. 2018;84(4):618-625.
Haldrup M, Fog-Møller M, Schønemann-Blom M, et al. Resuscitation strategies in isolated traumatic brain injury: a systematic review on plasma vs crystalloids. Scand J Trauma Resusc Emerg Med. 2023;31(1):45.
Rimmer E, Houston BL, Kumar A, et al. The efficacy and safety of plasma transfusion in patients with sepsis: a systematic review and meta-analysis. Crit Care. 2018;22(1):331.
Long E, Babl FE, Duke T, Oakley E. Plasma resuscitation in septic shock: targeting microvascular endotheliopathy. Shock. 2021;55(2):162-171.
Hippensteel JA, Uchimido R, Tyler PD, et al. Intravenous fluid resuscitation is associated with septic endothelial glycocalyx degradation. Crit Care. 2019;23(1):259.
Rizzo JA, Rowan MP, Cancio LC. Plasma for burn resuscitation: the return to colloid. Surg Infect (Larchmt). 2021;22(1):54-61.
Cartotto R, Greenhalgh DG, Cancio LC. Burn state of the science: fluid resuscitation and the endotheliopathy of burn shock. J Burn Care Res. 2022;43(2):297-308.
O’Mara MS, Slater H, Goldfarb IW, Caushaj PF. A prospective, randomized evaluation of intra-abdominal pressure with crystalloid and colloid resuscitation in burn patients. J Trauma. 2005;58(5):1011-1018.
Editorial & AI Transparency Statement
This publication was researched and written by the author. Gemini AI was utilized solely for research assistance, literature synthesis organization, copyediting, and overall formatting. None of the clinical content, interpretations, data analyses, or conclusions were generated by AI.
