Coimbra response to devlin

The Journal of Emergency Medicine

boelastography (TEG). Using an electronic transducer and a filament suspended in a whole blood sample, TEG measures initiation of coagulation, propagation kinetics, fibrinplatelet interaction, clot strength, and fibrinolysis independent of sample temperature (7). This provides better identification of the deficient component of the coagulation cascade, potentially permitting more targeted therapy for coagulopathy reversal (8). In a prospective animal study using TEG, Martini et al. demonstrated that “hypothermia inhibited clotting times and clotting rates, whereas hemorrhage impaired clot strength. The combination of hypothermia with hemorrhage impaired all these clotting parameters” (6). Similar results have been reported in human studies (9). Further, TEG results are available to the emergency physician in a little over 30 min. This combination of accuracy and speed potentially makes TEG the ideal ED bedside test for trauma-associated coagulopathy. However, studies utilizing TEG to devise blood component-specific and goal-directed coagulopathy reversal are still needed (10). Obviously, we want to provide the best outcomes for the most patients. We should consider the potential harm from overuse of blood component therapy. U.S. Navy investigators have reported that in-theater blood transfusion is independently associated with infection and resource over-utilization (11). In addition to the acute adverse effects of transfusion listed by Dr. Fraga, longterm effects such as transfusion-associated microchimerism and potentially increased autoimmune disease risk have been identified in military populations after transfusion (12,13). We should strive to, first, do no harm and second, maximize the benefit for all our patients when resources are scarce. As in previous wars, the medical insights gained from Operations Iraqi Freedom and Enduring Freedom will go on to benefit generations of trauma patients. However, the dust has not settled regarding the potential benefits of current in-theater transfusion recommendations. We urge all emergency physicians to enter into a discussion with their surgical colleagues before implementing any militarily derived transfusion practices. John Joseph Devlin, MD Miguel A Gutierrez, MD Department of Emergency Medicine Naval Medical Canter Portsmouth Portsmouth, Virginia doi:10.1016/j.jemermed.2009.08.069 REFERENCES 1. Fraga GP, Bansai V, Coimbra R. Transfusion of blood products in trauma: an update. J Emerg Med 2010;39:253– 60.

343 2. Sperry JL, Ochoa JB, Gunn SR, et al. An FFP:PRBC transfusion ratio ⱖ 1:1.5 is associated with a lower risk of mortality after massive transfusion. J Trauma 2008;65:986 –93. 3. Scalea TM, Bochicchio KM, Lumpkins K, et al. Early aggressive use of fresh frozen plasma does not improve outcome in critically injured trauma patients. Ann Surg 2008;248:578 – 84. 4. Snyder CW, Weinberg JA, McGwin G, et al. The relationship of blood product to mortality: survival benefit or survival bias? J Trauma 2009;66:358 – 63. 5. Hess JR, Dutton RB, Holcomb JB, Scalea TM Giving plasma at a 1:1 ratio with red cells in resuscitation: who might benefit? Transfusion 2008;48:1763–5. 6. Martini WZ, Cortez DS, Dubick MA, Park MS, Holcomb JB. Thrombelastography is better than PT, aPTT, and activated clotting time in detecting clinically relevant clotting abnormalities after hypothermia, hemorrhagic shock and resuscitation in pigs. J Trauma 2008;65:535– 43. 7. Rugeri L, Levrat A, David JS, et al. Diagnosis of early coagulation abnormalities in trauma patients by rotation thrombelastography. J Thromb Haemost 2007;5:289 –95. 8. Jeger V, Zimmerman H, Exadaktylos AK. Can RapidTEG accelerate the search for coagulapathies in the patient with multiple injuries? J Trauma 2009;66:1253–7. 9. Dirkmann D, Hanke AA, Görlinger K, Peters J. Hypothermia and acidosis synergistically impair coagulation in human whole blood. Anesth Analg 2008;106:1627–32. 10. Wade CE, Dubick MA, Blackbourne LH, Holcomb JB. It is time to assess the utility of thromboelastography in the administration of blood products to the patient with traumatic injuries. J Trauma 2009;66:1258. 11. Dunne JR, Riddle MS, Danko J, Hayden R, Petersen K. Blood transfusion is associated with infection and increased resource utilization in combat casualties. Am Surg 2006;72:619 –26. 12. Dunne JR, Lee TH, Burns C, Cardo LJ, Curry K, Busch MP. Transfusion-associated microchimerism in combat casualties. J Trauma 2008;64(2 Suppl):S92– 8. 13. Utter GH, Lee TH, Rivers RM, et al. Microchimerism decades after transfusion among combat-injured US veterans from the Vietnam, Korean, and World War II conflicts. Transfusion 2008; 48:1609 –15.

e RESPONSE e To the Editor: We would like to thank Drs. Devlin and Gutierrez for their interest in our review article regarding massive blood transfusion in trauma (1). The authors pointed out that a number of scientific articles were not available at the time of our submission. We appreciate the opportunity to comment on important data recently published. The transfusion strategy for the severely hemorrhaging trauma patient cannot be universal. In this regard, trauma surgeons and emergency physicians must be able to differentiate between “hemorrhage requiring massive transfusion” and “hemorrhage that will likely need transfusion.” These scenarios have different physiologic consequences, in particular with regard to the patient’s coagulation profile. Unfortunately, studies that seem to challenge the benefit of a high packed red blood cells (PRBCs):fresh frozen plasma (FFP) ratio may not be

344

analyzing the appropriate patient population or patient variables, thus confusing the issue. As our colleagues have noted, Sperry et al. did not show a crude mortality difference in patients receiving an FFP:PRBC ratio ⱖ 1:1.5 when compared to those who received a ratio ⬍ 1:1.5. Importantly, and perhaps lost in the manuscript title, is the fact that patients receiving a higher FFP:PRBCs ratio were ultimately transfused 16.0 units of PRBCs compared to 22.0 units in the lower ratio group 24 h after injury. In addition, this analysis is a secondary analysis of a prospective study determining the genomic response after severe injury and hemorrhagic shock. Therefore, patients were not randomized and there was insufficient power to adequately study crude mortality. The study cohorts, however, were severely injured, with each group having a base deficit ⬎ 10.7 and an admission international normalized ratio ⬎ 1.75 (2). An aggressive PRBC-to-FFP strategy in these severely hemorrhaging patients may help prevent ongoing coagulopathy where an already baseline coagulopathy exists. In comparison, the Baltimore group showed exactly what should be avoided. It is no surprise that near-equal transfusion of PRBCs:FFP in the non-massively hemorrhaging patient does not improve outcomes. Their 250 patients receiving varying ratios of blood and FFP were not patients suffering from massive hemorrhage and therefore, the physiologic profile and coagulation status were quite different from the Sperry study. Blindly transfusing FFP should be avoided unless there is sufficient evidence that the patient is massively hemorrhaging and likely hypocoagulable (3). We disagree that “one of the difficulties with implementing early FFP involves predicting, at the time of emergency department presentation, who will go on to require massive transfusion.” We believe that this is not the critical issue when attempting to resuscitate a severely injured, massively hemorrhaging trauma patient. The real issue is that those individuals arrive at the trauma center already coagulopathic. The concept of initial trauma-induced coagulopathy in patients with acute severe hemorrhage being due to dilution of coagulation factors is wrong and outdated. Even if this theory was valid, aggressive infusion of plasma still offers the best chance for correction of coagulopathy. In this regard, Hirschberg et al., using a computerized model, showed that dilution of clotting factors in severely hemorrhaging patients is generally underestimated, and rapid infusion of plasma is useful in preventing the dilution of coagulation factors due to aggressive fluid resuscitation (4). Several studies have clearly documented that the development of early trauma-induced coagulopathy is accompanied by high mortality rates. Who develops early coagulopathy after injury? The answer is clear: severely injured patients (high injury se-

Letters to the Editor

verity scores) presenting with acute hemorrhage and shock. When do they develop coagulopathy? The answer is also clear: immediately after the injury. Most of those patients will be coagulopathic during transport and upon arrival to the trauma center (5–9). Waiting for laboratory tests before FFP infusion will certainly delay hemostasis. Finally, the group from the University of Alabama did show that the mortality benefit from a near 1:1 ratio in massively hemorrhaging patients might be secondary to statistical aberrancy when a time-dependent variant was included. They called it survival bias (10). However, it is important to note that 1:1 transfusion in their analysis was not done as part of an established protocol resuscitating with PRBCs and FFP evenly. Rather, the first unit of PRBC was given at a median time of 18 min, whereas the first unit of FFP was given at a median time of 93 min. An established massive transfusion protocol aggressively and evenly transfusing PRBCs, FFP, and platelets may ameliorate statistical discrepancies and show a mortality improvement. In fact, instead of a survival bias, by not having the state of readiness required to transfuse severely injured patients with early trauma-induced coagulopathy (immediate availability of thawed plasma), they might have described what others would call a death bias instead. Teixeira et al. showed that early and higher ratios of FFP:PRBCs decreased mortality in massively hemorrhaging patients. These patients were transfused with little lag time between PRBCs, FFP, and platelet therapies (11). The ideal ratio between PRBCs, FFP, and platelets is still under investigation. The current proposed strategy of “hemostatic resuscitation” or “damage control resuscitation,” part of which is a high PRBCs:FFP:platetet ratio, may be effective not only due to an “ideal” PRBCs:FFP ratio, but also due to the aggressiveness and readiness required to have thawed plasma immediately available for infusion concomitantly with PRBCs (12). In a recent publication, Zink et al. addressed the issue of PRBCs:FFP:platelet ratio in a multi-institutional fashion (13). To address the issue of “survival bias,” they excluded patients who died within 30 min from admission to the trauma center, as it was unlikely that any resuscitative strategy would change the final outcome. The following transfusion component ratios were studied: ⬎ 1:4, ⱖ 1:4 –1:1, and ⱖ 1:1. A marked decrease in 6-h and in-hospital mortality was observed (37.3%, 15.2%, and 2.0%, and 54.9%, 41.1%, 25.5%, respectively) from FFP:PRBC’s ratios as well as for platelet:PRBC’s ratios (22.8%, 19.0%, 3.2%, and 43.7%, 46.8%, and 27.4%, respectively). Drs. Devlin and Gutierrez discussed the potential harm from use of blood component therapy. We agree that blood transfusion has been independently associated

The Journal of Emergency Medicine

with infection and resource overutilization. It is possible that blood transfusion in retrospective studies using multivariate analysis was just a surrogate for severe injuries and prolonged shock, and therefore, the risk of infection was increased due to ischemia and reperfusion, and overwhelming inflammation. Zink et al. also examined in their study the potential harm of transfusion-induced lung dysfunction and Acute Respiratory Distress Syndrome (13). They found no difference in respiratory outcomes based on PRBCs:FFP ratios. Interestingly, respiratory outcomes improved with higher PRBCs:platelet ratios. Finally, Drs. Devlin and Gutierrez mentioned the issue of resource utilization. O’Keeffe et al. demonstrated that having a well-defined massive transfusion protocol decreased the overall blood product usage and cost (14). The Iraqi and Enduring Freedom conflicts have solidified the paradigm that not all transfusion strategies are equal. Despite the lack of randomized, prospective civilian trials (one is being launched soon), it is important to be cognizant that bleeding patients are also not equal. Rapid identification of the bleeding injured patient and immediate intervention to improve tissue perfusion and to correct the trauma-induced coagulopathy would certainly offer the best chance for survival. Gustavo Fraga, MD, PHD, FACS Vishal Bansal, MD Raul Coimbra, MD, PHD, FACS Division of Trauma, Surgical Critical Care, and Burns University of California San Diego School of Medicine San Diego, California doi:10.1016/j.jemermed.2010.03.001

REFERENCES 1. Fraga GP, Bansal V, Coimbra R. Transfusion of blood products in trauma: an update. J Emerg Med 2010;39:253– 60. 2. Sperry JL, Ochoa JB, Gunn SR, et al. An FF:PRBC transfusion ratio ⱖ1:1.5 is associated with a lower risk of mortality after massive transfusion. J Trauma 2008;65:986 –93. 3. Scalea TM, Bochicchio KM, Lumpkins K, et al. Early aggressive use of fresh frozen plasma does not improve outcomes in critically injured trauma patients. Ann Surg 2008;248:578 – 84. 4. Hirshberg A, Dugas M, Banez EI, et al. Minimizing dilutional coagulopathy in exsanguinating hemorrhage: a computer simulation. J Trauma 2003;54:454 – 63. 5. MacLeod JB, Lynn M, McKenney MG, et al. Early coagulopathy predicts mortality in trauma. J Trauma 2003;55:39 – 44. 6. Brohi K, Singh J, Heron M, et al. Acute traumatic coagulopathy. J Trauma 2003;54:1127–30. 7. Gonzalez EA, Moore FA, Holcomb JB, et al. Fresh frozen plasma should be given earlier to patients requiring massive transfusion. J Trauma 2007;62:112–9. 8. Duchesne JC, Islam TM, Stuke L, et al. Hemostatic resuscitation during surgery improves survival in patients with traumaticinduced coagulopathy. J Trauma 2009;67:33–9. 9. Niles SE, McLaughlin DF, Perkins JG, et al. Increased mortality

345

10.

11. 12. 13.

14.

associated with the early coagulopathy of trauma in combat casualties. J Trauma 2008;64:1459 – 63. Snyder CW, Weinberg JA, McGwin G, et al. The relationship of blood product to mortality: survival benefit or survival bias? J Trauma 2009;66:358 – 63. Teixeira PGR, Inaba K, Shulman I, et al. Impact of plasma transfusion in massively transfused trauma patients. J Trauma 2009;66: 693–7. Riskin DJ, Tsai TC, Riskin L, et al. Massive transfusion protocols: the role of aggressive resuscitation versus product ratio in mortality reduction. J Am Coll Surg 2009;209:198 –205. Zink KA, Sambasivan CH, Holcomb JB, et al. A high ratio of plasma and platelets to packed red blood cells in the first 6 hours of massive transfusion improves outcomes in a large multicenter study. Am J Surg 2009;197:565–70. O’Keeffe T, Refaai M, Tchorz K, et al. A massive transfusion protocolto decrease blood component use and costs. Arch Surg 2008;143:686 –91.

e ROCURONIUM VS. SUCCINYLCHOLINE REVISITED e To the Editor: I read with interest the review by Mallon et al. about the choice between rocuronium and succinylcholine for rapid sequence intubation (RSI) in the emergency department (ED) (1). I commend the authors on their review and assessment of the literature addressing this controversial topic. With respect to safety, succinylcholine has a long history of use in the ED and its track record cannot be impugned. On the other hand, succinylcholine has a number of absolute contraindications, some of which relate to pre-existing conditions that may not be known to providers at the time of intubation. Furthermore, cardiac arrest immediately after intubation is not a rare event, and this is often attributed to the circumstances that necessitated intubation in the first place; it is likely that succinylcholine-induced hyperkalemia as a cause or contributor in these cases would not be recognized. These concerns are theoretical and would not challenge the use of succinylcholine if an agent without contraindications were not available. With respect to efficacy, the data suggest that when both drugs are given at ideal doses, no clinically consequential difference in intubation conditions exists. Dr. Walls’ commentary after the review endorses this position. My primary concern is with the notion that “. . . the long duration of non-depolarizing drugs can be a problem if intubation is difficult because prolonged bag-valve-mask ventilation will be required,” an assertion that seems to be supported by the conclusion of the cited Cochrane review: “We found no statistical difference in intubation conditions when succinylcholine was compared to 1.2 mg/kg rocuronium; however, succinylcholine was clinically superior as it has a shorter duration of action.” The shorter duration of action of succinylcholine has been touted as an advantage for a number of reasons. The