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Background: Over-aggressive intravenous fluid therapy with crystalloids has adverse effects in trauma patients. We assessed the role of large-volume (≥5l) administration of crystalloids within 24h of injury as an independent risk-factor for mortality, in-hospital complications, and prolonged mechanical ventilation., Methods: A retrospective cohort analysis of adult trauma patients admitted to a level 1-trauma center between December 2011 and December 2012. Patient demographics, clinical and laboratory values, and total resuscitation fluid administered within the first 24h of injury were obtained. Outcomes included mortality, in-hospital complications and ventilator-days. Multivariable logistic regression and Poisson regression analyses were performed to investigate any association between the administration of ≥5L crystalloids with the aforementioned outcomes while controlling for selected clinical variables., Results: A total of 970 patients were included in the analysis. 264 (27%) received ≥5L of crystalloids in the first 24h of injury. 118 (12%) had in-hospital complications and 337 (35%) required mechanical ventilation. The median age was 46 years (interquartile range (IQR) 27-65) years and 73% (n = 708) were males. The median injury severity score (ISS) was 17 (IQR 9-25). Overall mortality rate was 7% (n = 67). Multivariable logistic regression analysis showed several variables independently associated with mortality (p < 0.05), including resuscitation with ≥5L crystalloid in the first 24h (adjusted odds ratio (aOR) 2.55), older age (aOR 1.03), higher ISS (aOR 1.09), and lower temperature (aOR 0.68). The variables independently associated with in-hospital complications (p < 0.05) were older age, longer ICU stay, and platelet transfusion within 24h of the injury. Need for mechanical ventilation was more common in patients who received ≥5L crystalloids (RR 2.31) had higher ISS (RR 1.02), developed in-hospital complications (RR 1.91) and had lower presenting temperature (RR 0.87)., Conclusion: Large-volume crystalloid resuscitation is associated with increased mortality and longer time ventilated, but not with in-hospital complications such as pneumonia and sepsis. Based on this data, we recommend judicious use of crystalloids in the resuscitation of trauma patients.

Background: Preemptive treatment of trauma-associated coagulopathy involves transfusion of fresh frozen plasma (FFP) at 1:1 ratio with red blood cells (RBCs), but the optimal ratio remains controversial. In combat theaters, fresh whole blood (FWB) is also an option. The objective of this study was to determine the effect of FFP:RBC ratios 1:1, 1:2, 1:3 and FWB on coagulation during resuscitation., Materials and Methods: Thirty-six rats were randomized in the following six groups: Group 1: sham; Group 2: hemorrhage followed by sole lactated Ringer (LR) infusion; Group 3: FFP:RBC (1:1); Group 4: FFP:RBC (1:2); Group 5: FFP:RBC (1:3); Group 6: FWB transfusion. Another 25 animals were used for blood harvesting. Hemorrhage was induced by withdrawing 40% of total blood volume, mean arterial pressure (MAP) decreased to 45% of baseline, and laparotomy. Animals underwent LR infusion followed by blood product transfusion preset for each group. Blood samples were obtained at baseline and in the 105th minute for thromboelastometry and lactate., Results: Hemorrhage caused a significant decrease in MAP and increase in lactate (P < 0.05). MAP was persistently low in group 2 despite fluid infusion (P < 0.05), but not in the other groups after 20 min of resuscitation. Mean clot formation time, alpha angle, and maximum clot firmness decreased significantly (P < 0.05) in group 2 (LR) and group 5 (1:3) compared with other groups., Conclusions: FFP:RBC in a 1:2 ratio optimally harnessed hemostatic resuscitation and prudent use of blood products compared with 1:1 and 1:3 ratios and to FWB transfusion., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To investigate hemostatic effects of supplementary factor XIII and desmopressin (DDAVP) in resuscitation of uncontrolled bleeding., Methods: Fifty-four rabbits were randomized in nine groups: G1: Sham; G2: FXIII and normotensive resuscitation (NBP); G3: FXIII and permissive hypotension (PH) (MAP 60% baseline); G4: FXIII/DDAVP/NBP; G5: FXIII/DDAVP/PH; G6: NBP only; G7: FXIII no hemorrhage; G8: FXIII/DDAVP no hemorrhage; G9: PH only. Thromboelastometry and intra-abdominal blood loss were assessed. Scanning electron microscopy (EM) of the clots was performed., Results: Compared to Sham, only G8 (FXIII/DDAVP w/o hemorrhage) showed clotting time (CT) significantly lower (p<0.05). NBP alone (G6) resulted in significantly prolonged CT compared to G2, G3 and G5 (p<0.05). Similarly, median alpha angle was significantly larger in G3,4,5, and 9 compared to G6 (p<0.05). Area under the curve was significantly greater in G5 than G2. Intra-abdominal blood loss was lower in G5 and G9 compared to G2 and G6. FXIII/DDAVP and PH resulted in more robust fibrin mesh by EM., Conclusions: Normotensive resuscitation provokes more bleeding and worsens coagulation compared to pH, that is partially reversed by factor XIII and desmopressin. FXIII and DDAVP can synergistically improve coagulation. Permissive hypotension reduces bleeding regardless of those agents.

Background: Hemorrhage is a leading cause of death in trauma patients and coagulopathy is a significant contributor. Although the exact mechanisms of trauma-associated coagulopathy (TAC) are incompletely understood, hemostatic resuscitation strategies have been developed to treat TAC. Our study sought to identify which trauma patients develop TAC and the factors associated with its development, to describe the natural history of TAC, and to identify patients with TAC who may not require hemostatic resuscitation., Methods: Patients with early coagulopathy (International Normalized Ratio >1.3) who were admitted directly from the scene within 1 hour of injury were identified in our institutional trauma registry. We analyzed these data for the presence of TAC, predictors of early and delayed TAC, and evolution of TAC during the first 24 hours of admission., Results: Of 2,473 patients, 290 (12%) had early TAC (International Normalized Ratio >1.3) and 271 (11%) developed delayed TAC. Multivariate analysis identified female gender (odds ratio [OR] 1.25 [1.11-1.41]), lower pH (OR 0.08 [0.015-0.47]), lower hemoglobin (OR 0.96 [0.95-0.97]), lower temperature (OR 0.82 [0.70-0.95]), and blunt mechanism (OR 0.49 [0.33-0.71]) as factors significantly associated with development of early TAC. Progression of early TAC occurred in 64%, and these patients had more severe abdominal injury and received more emergency room crystalloid. Of patients with early TAC who did not receive fresh frozen plasma, only 49% developed worsening coagulopathy. Patients with isolated intracranial hemorrhage had higher rates of bleeding progression (75% vs. 20%, p < 0.005) in the presence of early TAC., Conclusions: TAC may appear in an early or delayed form and its presence and progression are associated with a number of identifiable factors. Although TAC commonly progresses, it also resolves spontaneously in many patients. Further research is required to identify which patients with TAC require hemostatic treatment, although those with intracranial hemorrhages seem to warrant aggressive therapy.

Clinically relevant animal models capable of simulating traumatic hemorrhagic shock are needed. We developed a hemorrhagic shock model with male New Zealand rabbits (2200-2800 g, 60-70 days old) that simulates the pre-hospital and acute care of a penetrating trauma victim in an urban scenario using current resuscitation strategies. A laparotomy was performed to reproduce tissue trauma and an aortic injury was created using a standardized single puncture to the left side of the infrarenal aorta to induce hemorrhagic shock similar to a penetrating mechanism. A 15-min interval was used to simulate the arrival of pre-hospital care. Fluid resuscitation was then applied using two regimens: normotensive resuscitation to achieve baseline mean arterial blood pressure (MAP, 10 animals) and hypotensive resuscitation at 60% of baseline MAP (10 animals). Another 10 animals were sham operated. The total time of the experiment was 85 min, reproducing scene, transport and emergency room times. Intra-abdominal blood loss was significantly greater in animals that underwent normotensive resuscitation compared to hypotensive resuscitation (17.1 ± 2.0 vs 8.0 ± 1.5 mL/kg). Antithrombin levels decreased significantly in normotensive resuscitated animals compared to baseline (102 ± 2.0 vs 59 ± 4.1%), sham (95 ± 2.8 vs 59 ± 4.1%), and hypotensive resuscitated animals (98 ± 7.8 vs 59 ± 4.1%). Evidence of re-bleeding was also noted in the normotensive resuscitation group. A hypotensive resuscitation regimen resulted in decreased blood loss in a clinically relevant small animal model capable of reproducing hemorrhagic shock caused by a penetrating mechanism.