Hartmann C, Loconte M, Antonucci E, Holzhauser M, Hölle T, Katzsch D, Merz T, McCook O, Wachter U, Vogt JA, Hoffmann A, Wepler M, Gröger M, Matejovic M, Calzia E, Georgieff M, Asfar P, Radermacher P, Nussbaum BL
Crit Care Med. 2017 Dec;45(12):e1270-e1279
OBJECTIVES: Investigation of the effects of hyperoxia during resuscitation from hemorrhagic shock in swine with preexisting coronary artery disease.
DESIGN: Prospective, controlled, randomized trial.
SETTING: University animal research laboratory.
SUBJECTS: Nineteen hypercholesterolemic pigs with preexisting coronary artery disease.
INTERVENTIONS: Anesthetized, mechanically ventilated, and surgically instrumented pigs underwent 3 hours of hemorrhagic shock (removal of 30% of the calculated blood volume and subsequent titration of mean arterial blood pressure ≈40 mm Hg). Postshock resuscitation (48 hr) comprised retransfusion of shed blood, crystalloids (balanced electrolyte solution), and norepinephrine support. Pigs were randomly assigned to "control" (FIO2 0.3, adjusted for arterial oxygen saturation ≥ 90%) and "hyperoxia" (FIO2 1.0 for 24 hr) groups.
MEASUREMENTS AND MAIN RESULTS: Before, at the end of shock and every 12 hours of resuscitation, datasets comprising hemodynamics, calorimetry, blood gases, cytokines, and cardiac and renal function were recorded. Postmortem, organs were sampled for immunohistochemistry, western blotting, and mitochondrial high-resolution respirometry. Survival rates were 50% and 89% in the control and hyperoxia groups, respectively (p = 0.077). Apart from higher relaxation constant τ at 24 hours, hyperoxia did not affect cardiac function. However, troponin values were lower (2.2 [0.9-6.2] vs 6.9 [4.8-9.8] ng/mL; p < 0.05) at the end of the experiment. Furthermore, hyperoxia decreased cardiac 3-nitrotyrosine formation and increased inducible nitric oxide synthase expression. Plasma creatinine values were lower in the hyperoxia group during resuscitation coinciding with significantly improved renal mitochondrial respiratory capacity and lower 3-nitrotyrosine formation.
CONCLUSIONS: Hyperoxia during resuscitation from hemorrhagic shock in swine with preexisting coronary artery disease reduced renal dysfunction and cardiac injury, potentially resulting in improved survival, most likely due to increased mitochondrial respiratory capacity and decreased oxidative and nitrosative stress. Compared with our previous study, the present results suggest a higher benefit of hyperoxia in comorbid swine due to an increased susceptibility to hemorrhagic shock.
Herrera-Escobar JP(1), Rios-Diaz AJ, Zogg CK, Wolf LL, Harlow A, Schneider EB, Cooper Z, Ordonez CA, Salim A, Haider AH.
J Trauma Acute Care Surg. 2018 Jan;84(1):139-145
BACKGROUND: Severely injured trauma patients have higher in-hospital mortality at Level II versus Level I trauma centers (TCs). To better understand these differences, we sought to determine if there were any periods during which hemodynamically unstable trauma patients are at higher risk of death at Level II versus Level I TCs within the first 24 hours postadmission.
STUDY DESIGN: Trauma patients aged 18 years to 64 years, with Injury Severity Score of 15 or greater, systolic blood pressure less than 90 mm Hg at admission, and treated at Level II or Level I TCs, were identified using the 2007 to 2012 National Trauma Data Bank. Burn patients, transfers, and patients dead on arrival were excluded. Log-binomial regression models, adjusted for patient- and hospital-level confounders, were used to compare mortality at Level II versus Level I TCs over the first 24 hours postadmission.
RESULTS: Of 13,846 hemodynamically unstable patients, 4,212 (30.4%) were treated at 149 Level II TCs, and 9,634 (69.6%) at 116 Level I TCs. Within the first 24 hours, 3,059 (22.1%) patients died. In risk-adjusted models, mortality risk was significantly elevated at Level II versus Level I TCs during the 24 hours postadmission (relative risk, 1.08; 95% confidence interval, 1.01-1.16). Hourly mortality risk was significantly different between Level II and Level I TCs during 4 hours to 7 hours postadmission, with a maximal difference at 7 hours (relative risk, 1.70; 95% confidence interval, 1.23-2.36) and comparable mortality risk beyond 7 hours postadmission.
CONCLUSION: The 4-hour to 7-hour time window postadmission is critical for hemodynamically unstable trauma patients. Variations in available treatment modalities may account for higher relative mortality at Level II TCs during this time. Further investigation to elucidate specific risk factors for mortality during this period may lead to reductions in in-hospital mortality among hemodynamically unstable trauma patients.
Kalkwarf KJ, Cotton BA
Surg Clin North Am. 2017 Dec;97(6):1307-1321
ABSTRACT:Hemorrhage is the leading cause of preventable deaths in trauma patients. After presenting a brief history of hemorrhagic shock resuscitation, this article discusses damage control resuscitation and its adjuncts. Massively bleeding patients in hypovolemic shock should be treated with damage control resuscitation principles including limited crystalloid, whole blood or balance blood component transfusion to permissive hypotension, preventing hypothermia, and stopping bleeding as quickly as possible.
Malgras B, Prunet B, Lesaffre X, Boddaert G, Travers S, Cungi PJ, Hornez E, Barbier O, Lefort H, Beaume S, Bignand M, Cotte J, Esnault P, Daban JL, Bordes J, Meaudre E, Tourtier JP, Gaujoux S, Bonnet S
J Visc Surg. 2017 Dec;154 Suppl 1:S19-S29
ABSTRACT:The concept of damage control (DC) is based on a sequential therapeutic strategy that favors physiological restoration over anatomical repair in patients presenting acutely with hemorrhagic trauma. Initially described as damage control surgery (DCS) for war-wounded patients with abdominal penetrating hemorrhagic trauma, this concept is articulated in three steps: surgical control of lesions (hemostasis, sealing of intestinal spillage), physiological restoration, then surgery for definitive repair. This concept was quickly adapted for intensive care management under the name damage control resuscitation (DCR), which refers to the modalities of hospital resuscitation carried out in patients suffering from traumatic hemorrhagic shock within the context of DCS. It is based mainly on specific hemodynamic resuscitation targets associated with early and aggressive hemostasis aimed at prevention or correction of the lethal triad of hypothermia, acidosis and coagulation disorders. Concomitant integration of resuscitation and surgery from the moment of admission has led to the concept of an integrated DCR-DCS approach, which enables initiation of hemostatic resuscitation upon arrival of the injured person, improving the patient's physiological status during surgery without delaying surgery. This concept of DC is constantly evolving; it stresses management of the injured person as early as possible, in order to initiate hemorrhage control and hemostatic resuscitation as soon as possible, evolving into a concept of remote DCR (RDCR), and also extended to diagnostic and therapeutic radiological management under the name of radiological DC (DCRad). DCS is applied only to the most seriously traumatized patients, or in situations of massive influx of injured persons, as its universal application could lead to a significant and unnecessary excess-morbidity to injured patients who could and should undergo definitive treatment from the outset. DCS, when correctly applied, significantly improves the survival rate of war-wounded.
Moe DM, Lallemand MS, McClellan JM, Smith JP, Marko ST, Eckert MJ, Martin MJ.
J Trauma Acute Care Surg. 2017 Dec;83(6):1114-1123
BACKGROUND: Bleeding is a leading cause of preventable death after severe injury. Prothrombin complex concentrates (PCC) treat inborn coagulation disorders and reverse oral anticoagulants, but are proposed for use in "factor-based" resuscitation strategies. Few studies exist for this indication in acidosis, or that compare 3-factor PCC (3PCC) versus 4-factor PCC (4PCC) products. We aimed to assess and compare their safety and efficacy in a porcine model of severe hemorrhagic shock and coagulopathy.
METHODS: Twenty-five adult Yorkshire swine underwent 35% volume hemorrhage, ischemia-reperfusion injury, and protocolized crystalloid resuscitation. Seventeen animals were randomized at 4 hours after model creation to receive a 45-IU/kg dose of either 3PCC or 4PCC. An additional eight animals received autologous plasma transfusion before 4PCC to better characterize response to PCC. Individual factor levels were drawn at 4 hours and 6 hours.
RESULTS: The model created significant acidosis with mean pH of 7.21 and lactate of 9.6 mmol/L. After PCC, 66.7% of 3PCC animals and 25% of 4PCC animals (regardless of plasma administration) developed consumptive coagulopathy. The animals that developed consumptive coagulopathy had manifested the "lethal triad" with lower temperatures (36.3°C vs. 37.8°C), increased acidosis (pH, 7.14 vs. 7.27; base excess, -12.1 vs. -6.5 mEq/L), and worse coagulopathy (prothrombin time, 17.1 vs. 14.6 seconds; fibrinogen, 87.9 vs. 124.1 mg/dL) (all p < 0.05). In the absence of a consumptive coagulopathy, 3PCC and 4PCC improved individual clotting factors with transient improvement of prothrombin time, but there was significant depletion of fibrinogen and platelets with no lasting improvement of coagulopathy.
CONCLUSION: PCC failed to correct coagulopathy and was associated with fibrinogen and platelet depletion. Of greater concern, PCC administration resulted in consumptive coagulopathy in the more severely ill animals. The incidence of consumptive coagulopathy was markedly increased with 3PCC versus 4PCC, and these products should be used with caution in this setting.
Nugent WH, Cestero RF, Ward K, Jubin R, Abuchowski A, Song BK
Shock. 2017 Dec 15. doi: 10.1097/SHK.0000000000001082.
BACKGROUND: Hemorrhage and its complications are the leading cause of preventable death from trauma in young adults, especially in remote locations. To address this, deliverable, shelf-stable resuscitants that provide therapeutic benefits throughout the time course of hemorrhagic shock and the progressive ischemic injury it produces are needed. SANGUINATE is a novel bovine PEGylated carboxyhemoglobin-based oxygen carrier, which has desirable oxygen-carrying and oncotic properties as well as a CO moiety to maintain microvascular perfusion.
OBJECTIVES: To compare the crystalloid (Lactated Ringer's Solution; LRS), and the colloid (Hextend) standards of care with SANGUINATE in a post "golden hour" resuscitation model.
METHODS: Rats underwent a controlled, stepwise blood withdrawal (45% by volume), were maintained in untreated hemorrhagic shock state for > 60 min, resuscitated with a 20% bolus of one of the three test solutions, and observed till demise. Parameters of tissue oxygenation (PISFO2), arteriolar diameters, and mean arterial pressure (MAP) were collected.
RESULTS: SANGUINATE-treated animals survived significantly longer than those treated with Hextend and LRS. SANGUINATE also significantly increased tissue PISFO2 two hours after resuscitation, whereas LRS and Hextend did not. SANGUINATE also produced a significantly higher MAP, which was hypotensive compared to baseline, that endured until demise.
CONCLUSIONS: Resuscitation with SANGUINATE after PHS improves survival, MAP, and PISFO2 compared to standard of care plasma expanders. Since the pathologies of hemorrhagic shock and the associated systemic ischemia are progressive, preclinical studies of this nature are essential to determine efficacy of new resuscitants across the range of possible times to treatment.
Samuels JM, Moore HB, Moore EE.
Chirurgia (Bucur). 2017 Sept-Oct;112(5):514-523
Damage control surgery is a combination of temporizing surgical interventions to arrest hemorrhage and control infectious source, with goal directed resuscitation to restore normal physiology. The convention of damage control surgery largely arose following the discovery of the lethal triad of hypothermia, acidosis, and coagulopathy, with the goal of Damage Control Surgery (DCS) is to avoid the initiation of this "bloody vicious cycle" or to reverse its progression. While hypothermia and acidosis are generally corrected with resuscitation, coagulopathy remains a challenging aspect of DCS, and is exacerbated by excessive crystalloid administration. This chapter focuses on resuscitative principles in the four settings of trauma care: the prehospital setting, emergency department, operating room, and intensive care unit including historical perspectives, resuscitative methods, controversies, and future directions. Each setting provides unique challenges with specific goals of care.
Clavier B, Pouget T, Sailliol A
Transfusion. 2018 Feb;58(2):313-316
BACKGROUND: Life-threatening situations requiring blood transfusion under extreme conditions or in remote and austere locations, such as the battlefield or in traffic accidents, would benefit from reliable blood typing practices that are easily understood by a nonscientist or nonlaboratory technician and provide quick results.
STUDY DESIGN AND METHODS: A simplified protocol was developed for the lateral flow-based device MDmulticard ABO-D-Rh subgroups-K. Its performance was compared to a reference method (PK7300, Beckman Coulter) in native blood samples from donors. The method was tested on blood samples stressed in vitro as a model of hemorrhage cases (through hemodilution using physiologic serum) and dehydration (through hemoconcentration by removing an aliquot of plasma after centrifugation), respectively.
RESULTS: A total of 146 tests were performed on 52 samples; 126 in the hemodilution group (42 for each native, diluted 1/2, and diluted 1/4 samples) and 20 in the hemoconcentration group (10 for each native and 10% concentrated samples). Hematocrit in the tested samples ranged from 9.8% to 57.6% while hemoglobin levels ranged from 3.2 to 20.1 g/dL. The phenotype profile detected with the MDmulticard using the simplified protocol resulted in 22 A, seven B, 20 O, and three AB, of which nine were D- and five were Kell positive. No discrepancies were found with respect to the results obtained with the reference method.
CONCLUSION: The simplified protocol for MDmulticard use could be considered a reliable method for blood typing in extreme environment or emergency situations, worsened by red blood cell dilution or concentration.
Garrigue D, Godier A, Glacet A, Labreuche J, Kipnis E, Paris C, Duhamel A, Resch E, Bauters A, Machuron F, Renom P, Goldstein P, Tavernier B, Sailliol A, Susen S
J Thromb Haemost. 2018 Mar;16(3):481-489
ESSENTIALS: An immediate supply of plasma in case of trauma-induced coagulopathy is required. The Traucc trial compared French Lyophilised Plasma (FLyP) and Fresh Frozen Plasma (FFP). FLyP achieved higher fibrinogen concentrations compared with FFP. FLyP led to a more rapid coagulopathy improvement than FFP.SUMMARY:
BACKGROUND: Guidelines recommend beginning hemostatic resuscitation immediately in trauma patients. We aimed to investigate if French lyophilized plasma (FLyP) was more effective than fresh frozen plasma (FFP) for the initial management of trauma-induced coagulopathy.
METHODS: In an open-label, phase 3, randomized trial (NCT02750150), we enrolled adult trauma patients requiring an emergency pack of 4 plasma units within 6 h of injury. We randomly assigned patients to receive 4-FLyP units or 4-FFP units. The primary endpoint was fibrinogen concentration at 45 min after randomization. Secondary outcomes included time to transfusion, changes in hemostatic parameters at different time-points, blood product requirements and 30-day in-hospital mortality.
RESULTS: Forty-eight patients were randomized (FLyP, n = 24; FFP, n = 24). FLyP reduced the time from randomization to transfusion of first plasma unit compared with FFP (median[IQR],14[5-30] vs. 77[64-90] min). FLyP achieved a higher fibrinogen concentration 45 min after randomization compared with FFP (baseline-adjusted mean difference, 0.29 g L-1 ; 95% confidence interval [CI], 0.08-0.49) and a greater improvement in prothrombin time ratio, factor V and factor II. The between-group differences in coagulation parameters remained significant at 6 h. FLyP reduced fibrinogen concentrate requirements. Thirty-day in-hospital mortality rate was 22% with FLyP and 29% with FFP.
CONCLUSION: FLyP led to a more rapid, pronounced and extended increase in fibrinogen concentrations and coagulopathy improvement compared with FFP in the initial management of trauma patients. FLyP represents an attractive option for trauma management, especially when facing logistical issues such as combat casualties or mass casualties related to terror attacks or disasters.
Graham BC, Graham LJ, Rose CH, Winters JL
Am J Obstet Gynecol. 2018 Feb;218(2):219.e1-219.e4
ABSTRACT:The US Department of Defense recently made the decision to open direct ground combat roles to women. Blood product transfusion is an essential component of the US Military guidelines for tactical combat casualty care and damage control resuscitation, but blood transfusion carries with it the specific side effect of alloimmunization-a uniquely significant side effect for young women who may desire subsequent pregnancies. Presently to be considered are the changes that may need to be made to blood transfusion in the setting of battlefield medicine to optimally care for combat-injured women, as a majority of the existing data regarding the risks of transfusion in the trauma setting involve predominantly men. This article delves into the possibility of a new cohort of women at risk for hemolytic disease of the fetus and newborn, the need for women's health professionals to appropriately counsel women considering serving in direct ground combat roles about this specific risk, and the appropriate steps that should be considered to provide these women optimal medical care.
Heschl S, Andrew E, de Wit A, Bernard S, Kennedy M, Smith K; Study Investigators.
Emerg Med Australas. 2018 Apr;30(2):236-241.
OBJECTIVE: The optimal volume and type of intravenous fluid for the treatment of blood loss in the prehospital setting is controversial. The use of red cell concentrates (RCCs) may be associated with improved outcomes; however, the administration of blood products is limited to physicians in many jurisdictions. We sought to describe the characteristics of RCC transfusions in a paramedic-staffed helicopter emergency medical system in Victoria, Australia.
METHODS: We performed a retrospective analysis of all cases where paramedics consulted the responsible physician for approval of RCC transfusion between July 2011 and December 2015 in Victoria, Australia. Ambulance data was retrieved from electronic patient care records and hospital and outcome data was retrieved from a state-wide trauma registry.
RESULTS: A total of 180 primary missions was identified where paramedics requested approval for transfusion of RCCs during the study period. A total of 150 patients received prehospital RCCs, of which 136 had suffered trauma. The majority of these patients were male (66.7%) and were involved in a car accident (62.5%). Most (97.4%) patients had an Injury Severity Score ≥12. There were improvements in median systolic blood pressure (80 mmHg vs 94 mmHg, P < 0.001) and shock index (1.50 vs 1.23, P < 0.001) between time of consultation and arrival at hospital. Overall, mortality for trauma patients was 37.7%. There were no transfusion-related complications identified.
CONCLUSION: Prehospital transfusion of RCC by paramedics is feasible. Future studies should compare the outcomes of patients receiving prehospital RCCs with outcomes for patients in which RCCs are administered in hospital.
Holzmacher JL, Reynolds C, Patel M, Maluso P, Holland S, Gamsky N, Moore H, Acquista E, Carrick M, Amdur R, Hancock H, Metzler M, Dunn J, Sarani B
Brain Inj. 2018;32(3):325-330
INTRODUCTION: Platelet dysfunction following traumatic brain injury (TBI) is associated with worse outcomes. The efficacy of platelet transfusion to reverse antiplatelet medication (APM) remains unknown. Thrombelastography platelet mapping (TEG-PM) assesses platelet function. We hypothesize that platelet transfusion can reverse the effects of APM but does not improve outcomes following TBI.
METHODS: An observational study at six US trauma centres was performed. Adult patients on APM with CT evident TBI after blunt injury were enrolled. Demographics, brain CT and TEG-PM results before/after platelet transfusion, length of stay (LOS), and injury severity score (ISS) were abstracted.
RESULTS: Sixty six patients were enrolled (89% aspirin, 50% clopidogrel, 23% dual APM) with 23 patients undergoing platelet transfusion. Transfused patients had significantly higher ISS and admission CT scores. Platelet transfusion significantly reduced platelet inhibition due to aspirin (76.0 ± 30.2% to 52.7 ± 31.5%, p < 0.01), but had a non-significant impact on clopidogrel-associated inhibition (p = 0.07). Platelet transfusion was associated with longer length of stay (7.8 vs. 3.5 days, p < 0.01), but there were no differences in mortality.
CONCLUSION: Platelet transfusion significantly decreases platelet inhibition due to aspirin but is not associated with change in outcomes in patients on APM following TBI.
Hess JR, Ramos PJ, Sen NE, Cruz-Cody VG, Tuott EE, Louzon MJ, Bulger EM, Arbabi S, Pagano MB, Metcalf RA.
Transfusion. 2018 Feb;58(2):480-484.
BACKGROUND: Massive transfusion is a response to massive uncontrolled hemorrhage. To be effective, it must be timely and address the patient's needs for blood volume, oxygen transport, and hemostasis.
STUDY DESIGN AND METHODS: A review was performed on all activations of the massive transfusion protocol (MTP) in a hospital with large emergency medicine, trauma, and vascular surgery programs. Indications, transfused amounts, and outcomes were determined for each MTP event to determine appropriateness of MTP use. Results are presented as descriptive statistics, categorical associations, and simple linear trend relationships.
RESULTS: The MTP was activated 309 times in 2016. Of these episodes, 237 were for trauma, 29 for gastrointestinal bleeding, 16 for ruptured abdominal aortic aneurisms, and 25 for a variety of other causes. Trauma-related MTP activations had a mean injury severity score of 32. Blood use averaged 6.6 units of red blood cells (RBCs), 6.5 units of plasma, and 1.2 units of apheresis platelets. Fourteen activations ended without the administration of any blood products, and 45 (14%) did not meet the critical administration threshold of three components. Only 60 (19%) activations met the historic definition of massive with at least 10 units of RBCs administered. Mortality was 15% for the trauma-related activations.
CONCLUSIONS: Massive transfusion protocol activations were frequent and conducted with high fidelity to the 1:1:1 unit ratio standard. Making blood components available quickly was associated with low rates of total component usage and low mortality for trauma patients and was not associated with overuse.
Kyle T, Greaves I, Beynon A, Whittaker V, Brewer M, Smith J
Emerg Med J. 2018 Mar;35(3):176-179
BACKGROUND: Hypocalcaemia is a common metabolic derangement in critically ill patients. Blood transfusion can also contribute to depleted calcium levels. The aims of this study were to identify the incidence of hypocalcaemia in military trauma patients receiving blood products en route to a deployed hospital facility and to determine if intravenous calcium, given during the prehospital phase, has an effect on admission calcium levels.
METHODS: This was a retrospective review of patients transported by the UK Medical Emergency Response Team in Afghanistan between January 2010 and December 2014 who were treated with blood products in the prehospital setting. Total units of blood products administered, basic demographics, Injury Severity Score and trauma type were collected. Ionized serum calcium levels on admission to hospital were compared between those who received blood products without prehospital intravenous calcium supplemental therapy (non-treatment) and patients who were treated with 10 mL of intravenous calcium chloride (10%) concurrently with blood products (treatment).
RESULTS: The study included 297 patients; 237 did not receive calcium and 60 did. The incidence of hypocalcaemia in the non-treatment group was 70.0% (n=166) compared with 28.3% (n=17) in the treatment group. Serum calcium levels were significantly different between the groups (1.03 mmol/L vs 1.25 mmol/L, difference 0.22 mmol/L, 95% CI 0.15 to 0.27). In the non-treatment group, 26.6% (n=63) had calcium levels within the normal range compared with 41.7% (n=25) in those who received calcium. There was a dose response of calcium level to blood products with a significant decrease in calcium levels as the volume of blood products increased.
CONCLUSION: Trauma patients who received blood products were at high risk of hypocalcaemia. Aggressive management of these patients with intravenous calcium during transfusion may be required.
Leibowitz A, Brotfain E, Koyfman L, Klein M, Hess S, Zlotnik A, Boyko M
Eur J Trauma Emerg Surg. 2018 Jan 17. doi: 10.1007/s00068-018-0908-9.
INTRODUCTION: Treatment of combined traumatic brain injury and hemorrhagic shock, poses a particular challenge due to the possible conflicting consequences. While restoring diminished volume is the treatment goal for hypovolemia, maintaining adequate cerebral perfusion pressure and avoidance of secondary damage remains a treatment goal for the injured brain. Various treatment modalities have been proposed, but the optimal resuscitation fluid and goals have not yet been clearly defined. A growing body of evidence suggests that in hypovolemic shock, resuscitation with fresh whole blood (FWB) may be superior to component therapy without platelets (which are likely to be unavailable in the pre-hospital setting). Nevertheless, the effects of this approach have not been studied in the combined injury. Previously, in a rat model of combined injury we have found that mild resuscitation to MABP of 80 mmHg with FWB is superior to fluid resuscitation or aggressive resuscitation with FWB. In this study, we investigate the physiological and neurological outcomes in a rat model of combined traumatic brain injury (TBI) and hypovolemic shock, submitted to treatment with varying amounts of FWB, compared to similar resuscitation goals with fractionated blood products-red blood cells (RBCs) and plasma in a 1:1 ratio regimen.
MATERIALS AND METHODS: 40 male Lewis rats were divided into control and treatment groups. TBI was inflicted by a free-falling rod on the exposed cranium. Hypovolemia was induced by controlled hemorrhage of 30% blood volume. Treatment groups were treated either with fresh whole blood or with RBC + plasma in a 1:1 ratio, achieving a resuscitation goal of a mean arterial blood pressure (MAP) of 80 mmHg at 15 min. MAP was assessed at 60 min, and neurological outcomes and mortality in the subsequent 24 h.
RESULTS: At 60 min, hemodynamic parameters were improved compared to controls, but not significantly different between treatment groups. Survival rates at 48 h were 100% for both of the mildly resuscitated groups (MABP 80 mmHg) with FWB and RBC + plasma. The best neurological outcomes were found in the group mildly resuscitated with FWB and were better when compared to resuscitation with RBC + plasma to the same MABP goal (FWB: Neurological Severity Score (NSS) 6 ± 2, RBC + plasma: NSS 10 ± 2, p = 0.02).
CONCLUSIONS: In this study, we find that mild resuscitation with goals of restoring MAP to 80 mmHg (which is lower than baseline) with FWB, provided better hemodynamic stability and survival. However, the best neurological outcomes were found in the group resuscitated with FWB. Thus, we suggest that resuscitation with FWB is a feasible modality in the combined TBI + hypovolemic shock scenario, and may result in improved outcomes compared to platelet-free component blood products.
Maher P, Utarnachitt R, Louzon MJ, Gary R, Sen N, Hess JR
Air Med J. 2017 Sep - Oct;36(5):263-267
ABSTRACT:Over the past few decades, reports have described favorable results from transfusion of blood products in helicopter EMS (HEMS). Nevertheless, the initiation of a HEMS transfusion program requires consideration of many factors, some unique to each clinical site. This paper describes our experience developing a HEMS transfusion program in an urban non-hospital based HEMS program with a history of long transport times. When considering blood use away from the hospital, major consideration must be given to safe storage and monitoring of blood products both on the ground and while in flight. PRBCs have been shown to generally be resilient to helicopter transit and have a prolonged storage duration. Transfusion of other blood products, such as plasma, involves additional challenges but has been achieved by some HEMS sites. Flight protocols should be developed addressing when and how many blood products should be transported, potentially considering patient factors, scene factors, and the regional availability of blood products during interfacility transport. Quality assurance and documentation protocols must also be developed for blood product use in flight. In our center's experience, we have so far transfused a limited number of patients with generally good results. Patient outcomes are described as below.
Mclennan JV, Mackway-Jones KC, Smith JE
Injury. 2018 Feb;49(2):184-190
BACKGROUND: The predominant cause of preventable trauma death is bleeding, and many of these patients need resuscitation with massive blood transfusion. In resource-constrained environments, early recognition of such patients can improve planning and reduce wastage of blood products. No existing decision rule is sufficiently reliable to predict those patients requiring massive blood transfusion. This study aims to produce a decision rule for use on arrival at hospital for patients sustaining battlefield trauma.
METHODS: A retrospective database analysis was undertaken using the UK Joint Theatre Trauma Registry to provide a derivation and validation dataset. Regression analysis of potential predictive factors was performed. Predictive factors were analysed through multi-logistic regression analysis to build predictive models; sensitivity and specificity of these models was assessed, and the best fit models were analysed in the validation dataset.
RESULTS: A decision rule was produced using a combination of injury pattern, clinical observations and pre-hospital data. The proposed rule, using a score of 3 or greater, demonstrated a sensitivity of 82.7% and a specificity of 88.8% for prediction of massive blood transfusion, with an AUROC of 0.93 (95% CI 0.91-0.95).
CONCLUSIONS: We have produced a decision tool with improved accuracy compared to any previously described tools that can be used to predict blood transfusion requirements in the military deployed hospital environment.
McQuilten ZK, Crighton G, Brunskill S, Morison JK, Richter TH, Waters N, Murphy MF, Wood EM
Transfus Med Rev. 2018 Jan;32(1):6-15
ABSTRACT:Optimal dose, timing and ratio to red blood cells (RBC) of blood component therapy (fresh frozen plasma [FFP], platelets, cryoprecipitate or fibrinogen concentrate) to reduce morbidity and mortality in critically bleeding patients requiring massive transfusion is unknown. We performed a systematic review for randomized controlled trials (RCT) in MEDLINE, The Cochrane Library, Embase, CINAHL, PubMed the Transfusion Evidence Library and using multiple clinical trials registries to 21 February 2017. Sixteen RCTs were identified: six completed (five in adult trauma patients, one pediatric burn patients) and ten ongoing trials. Of the completed trials: three were feasibility trials, comparing a FFP, platelets and RBC ratio of 1:1:1 to laboratory-guided transfusion practice [n=69], early cryoprecipitate compared to standard practice [n=41], and early fibrinogen concentrate compared to placebo [n=45]; one trial compared the effect of FFP, platelets and RBC ratio of 1:1:1 with 1:1:2 on 24-hour and 30-day mortality [n=680]; one compared whole blood to blood component therapy on 24-hour blood use [n=107]; one compared a FFP to RBC ratio of 1:1 with 1:4 [n=16]. Data from two trials were pooled in a meta-analysis for 28-day mortality because the transfusion ratios achieved were similar. Results from these two trials suggest higher transfusion ratios were associated with transfusion of more FFP and platelets without evidence of significant difference with respect to mortality or morbidity. On the limited evidence available, there is insufficient basis to recommend a 1:1:1 over a 1:1:2 ratio or standard care for adult patients with critical bleeding requiring massive transfusion.
Nguyen C, Bordes J, Cungi PJ, Esnault P, Cardinale M, Mathais Q, Cotte J, Beaume S, Sailliol A, Prunet B, Meaudre E
J Trauma Acute Care Surg. 2018 Jan 12. doi: 10.1097/TA.0000000000001801.
BACKGROUND: Early transfusion of high ratio of fresh frozen plasma (FFP) and red blood cells (RBC) is associated with mortality reduction. However, time to reach high ratio is limited by the need to thaw the FFP. French lyophilized plasma (FLYP) used by French army and available in military teaching hospital does not need to be thawed and is immediately available. We hypothesize that the use of FLYP may reduce time to reach a plasma:RBC ratio of 1/1.
METHODS: A retrospective study performed in a Level 1 trauma center between January 2012 and December 2015. Severe trauma patients who received 2 units of RBC in the emergency room were included and assigned to two groups according to first plasma transfused: FLYP group and FFP group.
RESULTS: 43 severe trauma patients in the FLYP group and 29 in the FFP group, were included. The time until first plasma transfusion was shorter in the FLYP group than in the FFP group, respectively 15 min (10-25) vs. 95 min (70-145) (P < 0.0001). Time until a 1/1 ratio was shorter in FLYP group than if the FFP group. There were significantly fewer cases of massive transfusion in the FLYP group than in the FFP group with respectively 7% vs. 45% (P < 0.0001).
CONCLUSION: The use of FLYP provided significantly faster plasma transfusions than the use of FFP as well as a plasma and RBC ratio superior to 1:2 that was reached more rapidly in severe trauma patients. These results may explain the less frequent need for massive transfusion in the patients who received FLYP. These positive results should be confirmed by a prospective and randomized evaluation.
Parker ME, Khasawneh MA, Thiels CA, Berns KS, Stubbs JR, Jenkins DH, Zietlow SP, Zielinski MD
Air Med J. 2017 Nov - Dec;36(6):315-319
OBJECTIVE: Gastrointestinal (GI) bleeding is a common medical emergency with significant morbidity and mortality. Many patients are coagulopathic, which may perpetuate bleeding. Remote damage control resuscitation, including early correction of coagulopathy and anemia, may benefit exsanguinating patients with GI bleeding.
METHODS: We conducted a retrospective review of patients with acute GI bleeding who received packed red blood cells (pRBC) and/or plasma during transportation to our institution between 2010 and 2014. A comparison group of patients who were not transfused en route was selected, and demographics, outcomes, and response to resuscitation were compared.
RESULTS: A total of 112 patients with GI bleeding received pRBC (82%, n = 92 pRBC, mean 1.7 ± 0.9 units), plasma (62%, n = 69, mean 1.7 ± 0.8 units) or both (44%, n = 49) en-route. The comparison group comprised 49 patients transported by helicopter who were not transfused en-route. Demographics, crystalloid resuscitation, transfusion prior to transfer, rate of intervention, ICU days, length of stay, and mortality were similar between groups. Patients transfused en route had a significant increase in hemoglobin from 8.3 ± 2.2 to 8.9 ± 2.1 (P = .03) and decrease in INR from 2.0 ± 1.0 to 1.6 ± 1.4 (P = .01), whereas those not transfused en route experienced stable hemoglobin (8.7 ± 2.8 to 9.4 ± 2.5; P = .21) and INR values (1.9 ± 1.0 to 1.6 ± 1.4; P = .32). Both groups had a significant improvement in hemodynamic parameters with resuscitation.
CONCLUSION: Prehospital damage control resuscitation with pRBC and/or plasma resulted in the improvement of hemodynamic instability, coagulopathy and anemia in patients with acute GI bleeding. Almost all patients required additional inpatient interventions and/or transfusions, suggesting that pre-hospital transfusion is being utilized for appropriately selected patients.
Peters JH, Smulders PSH, Moors XRJ, Bouman SJM, Meijs CMEM, Hoogerwerf N, Edwards MJR
Eur J Emerg Med. 2017 Nov 17. doi: 10.1097/MEJ.0000000000000516.
INTRODUCTION: In the prehospital setting, crystalloid fluids are frequently used, but only erythrocytes are capable of transporting oxygen to tissues. The aim of this study was to establish the efficacy and safety of the prehospital use of uncross matched type O rhesus-negative packed red blood cells (URBC) by the Dutch physician-staffed helicopter emergency medical service. We hypothesized that prehospital URBC transfusions are safe and more effective with respect to survival than resuscitations with crystalloids.
METHODS: The effects of prehospital URBC transfusions were studied by comparing a cohort of patients (>18 years) who were treated with a combination of URBC and crystalloid fluids with a matched control group of patients who received crystalloid fluids alone.
RESULTS: Among 73 adults who received prehospital URBC transfusions, 50 (68%) patients were included. No transfusion reactions were observed. No effect of prehospital transfusion on 24-h or 30-day survival was found. Haemoglobin levels at presentation to the emergency department were higher in the URBC cohort. The two groups had similar cumulative erythrocyte requirements within the first 24 h.
CONCLUSION: Neither survival benefits nor a decreased incidence of shock on admission were observed after prehospital helicopter emergency medical service URBC transfusions. There were no prehospital transfusion reactions in this study; therefore, URBC transfusions were deemed to be safe. A prospective randomized study is warranted to evaluate the effect of early URBC transfusions and transfusions with preheated URBC on the survival of patients with severe prehospital haemorrhagic shock.
Sanders S, Tien H, Callum J, Nascimento B, Peng H, Funk C, Schmid J, Rizoli S, Rhind S, Beckett A
Mil Med. 2018 Jan 1;183(1-2):e45-e50
Introduction: Hemorrhage is the most common cause of death among Special Operations Force (SOF) soldiers. Bringing remote damage control resuscitation into the far-forward combat environment is logistically challenging, as it requires blood products that generally require a robust cold chain. Alternatively, lyophilized products such as fibrinogen concentrate, which does not require thawing or blood group compatibility testing before use, might be advantageous in damage control resuscitation in the battlefield. In this report, we review the evidence for the use of fibrinogen concentrate in the Canadian SOF environment.
Materials and Methods: The literature on the use of fibrinogen concentrate in the trauma setting was reviewed by Canadian Forces Services Working Group, in three separate meetings. Multiple stakeholders were consulted to obtain authoritative perspectives from subject matter experts on the use of fibrinogen concentrate in the Canadian SOF environment. We also conducted a comparison review of fibrinogen content, pathogen risk, shelf life, and methods required for use for fresh frozen plasma, cryoprecipitate, and fibrinogen concentrate relevant to their application in the far-forward combat environment.
Results: Indications and a protocol for the use of fibrinogen as an adjunct to fresh whole blood were formulated based on a literature review and clinical expert opinion. Alternative strategies and other lyophilized blood products were considered before selecting fibrinogen concentrate as the lyophilized blood product of choice. Fibrinogen concentrate is an ABO-universal blood product with an excellent safety profile. Training was conducted by subject matter experts within civilian trauma centers and at military training facilities. The clinical efficacy and safety were confirmed by monitoring the use of fibrinogen concentrate in deployed combat settings.
Conclusion: Fibrinogen concentrate is a useful adjunct to remote damage control resuscitation in the SOF environment. Fibrinogen concentrate was found to be robust for transport into the SOF environment and is widely accepted among SOF operators and medics.
Sheppard FR, Mitchell TA, Macko AR, Fryer DM, Schaub LJ, Ozuna KM, Glaser JJ
J Trauma Acute Care Surg. 2017 Dec 20
BACKGROUND: Hemorrhage is the leading cause of preventable death in traumatically injured civilian and military populations. Pre-hospital resuscitation largely relies on crystalloid and colloid intra-vascular expansion, as whole blood and component blood therapy are logistically arduous. In this experiment, we evaluated the bookends of Tactical Combat Casualty Care Guidelines recommendations of pre-hospital resuscitation with Hextend and whole blood in a controlled hemorrhagic shock model within non-human primates, as means of a multi-functional resuscitative fluid development.
METHODS: In the non-human primate, a poly-trauma model was utilized, consisting of a musculoskeletal injury (femur fracture), soft tissue injury (15cm laparotomy), and controlled hemorrhage to a mean arterial pressure of 20 mmHg, demarcating the beginning of the shock period. Animals were randomized to pre-hospital interventions of whole blood or Hextend at T=0 minutes, and at T=90 minutes definitive surgical interventions and balanced sanguineous damage control resuscitation could be implemented. All animals were euthanized at T=480 minutes. Data are expressed as mean±SEM; significance, p<0.05.
RESULTS: No significant differences in survival, 83% vs. 100%, p=0.3), tissue perfusion (EtCO2 & StO2) or endpoints of resuscitation (base deficit, lactate, pH) between Hextend and whole blood were identified. Secondly, whole blood compared to Hextend demonstrated significantly earlier normalization of clot formation time, maximal clot firmness, and α angle.
CONCLUSION: A future multi-functional resuscitative fluid including an asanguineous, oncotic, non-oxygen carrying component to facilitate intra-vascular volume expansion and a component with synthetic coagulation factors and fibrinogen to deter coagulopathy may show equivalence to whole blood.
STUDY TYPE: Translational animal model LEVEL OF EVIDENCE: N/A.
Vitalis V, Carfantan C, Montcriol A, Peyrefitte S, Luft A, Pouget T, Sailliol A, Ausset S, Meaudre E, Bordes J
Injury. 2017 Nov 23. pii: S0020-1383(17)30821-5.
INTRODUCTION: Haemorrage is the leading cause of death after combat related injuries and bleeding management is the cornerstone of management of these casualties. French armed forces are deployed in Barkhane operation in the Sahel-Saharan Strip who represents an immense area. Since this constraint implies evacuation times beyond doctrinal timelines, an institutional decision has been made to deploy blood products on the battlefield and transfuse casualties before role 2 admission if indicated. The purpose of this study was to evaluate the transfusion practices on battlefield during the first year following the implementation of this policy.
MATERIALS AND METHODS: Prospective collection of data about combat related casualties categorized alpha evacuated to a role 2. Battlefield transfusion was defined as any transfusion of blood product (red blood cells, plasma, whole blood) performed by role 1 or Medevac team before admission at a role 2. Patients' characteristics, battlefield transfusions' characteristics and complications were analysed.
RESULTS: During the one year study, a total of 29 alpha casualties were included during the period study. Twenty-eight could be analysed, 7/28 (25%) being transfused on battlefield, representing a total of 22 transfusion episodes. The most frequently blood product transfused was French lyophilized plasma (FLYP). Most of transfusion episodes occurred during medevac. Compared to non-battlefield transfused casualties, battlefield transfused casualties suffered more wounded anatomical regions (median number of 3 versus 2, p = 0.04), had a higher injury severity score (median ISS of 45 versus 25, p = 0,01) and were more often transfused at role 2, received more plasma units and whole blood units. There was no difference in evacuation time to role 2 between patients transfused on battlefield and non-transfused patients. There was no complication related to battlefield transfusions. Blood products transfusion onset on battlefield ranged from 75 min to 192 min after injury.
CONCLUSION: Battlefield transfusion for combat-related casualties is a logistical challenge. Our study showed that such a program is feasible even in an extended area as Sahel-Saharan Strip operation theatre and reduces time to first blood product transfusion for alpha casualties. FLYP is the first line blood product on the battlefield.
Wu X, Darlington DN, Montgomery RK, Liu B, Keesee JD, Scherer MR, Benov A, Chen J, Cap AP
Br J Haematol. 2017 Dec;179(5):802-810. doi: 10.1111/bjh.14999.
Abstract:
The in vitro haemostatic functions of fresh whole blood (FWB) are well preserved after cold storage. This study aimed to determine whether platelets derived from FWB and stored whole blood (SWB) contribute to clot formation in tissue injury after transfusion into coagulopathic rats with polytrauma/haemorrhage (T/H). The rats were resuscitated 1 h after trauma with FWB or SWB collected from green fluorescence protein (GFP) transgenic rats. After transfusion, a liver incision was made and the tissue was collected 10 min after injury to identify GFP+ platelets by immunohistochemistry. In comparison to FWB, platelet aggregation to adenosine diphosphate and protease-activated receptor-4 was reduced by 35% and 20%, and clotting time was shortened by 25% in SWB. After transfusion, SWB led to a significant increase in platelet activation as measured by an elevation of CD62P and phosphatidylserine expression. The platelets from SWB were in a higher activation state, and showed higher clearance rate and formation of platelet-leucocyte aggregates than those from FWB after transfusion. Platelets from both FWB and SWB were equivalently incorporated into the clot at the incisional site, as determined by co-localization of CD61 and GFP. This study suggests that SWB contributes to haemostatic function and is an effective alternative resource to treat trauma patients.
Yang J, Yin W, Zhang Y, Sun Y, Ma T, Gu S, Gao Y, Zhang X, Yuan J, Wang W
Transfusion. 2018 Mar:58(3):736-747.
BACKGROUND: Platelet (PLT) storage at cold temperatures (4°C) can reduce bacterial contamination and lower the risk of transfusion-related complications. We compared the effects of 22 and 4°C storage conditions for PLTs to further explore the efficiency of hemostasis in acute bleeding and extended PLT shelf life.
STUDY DESIGN AND METHODS: Manually prepared PLTs (PLT concentrates in plasma, not PLT additive solution) were stored at 4 and 22°C. The PLT counts, scanning electronic microscope observations, blood gas indices, biochemical indices, PLT aggregative function, and surface CD62P expression were monitored and compared between the groups.
RESULTS: There was no obvious change in PLT counts between Day 21 at 4°C and Day 5 at 22°C. PLTs stored at 4°C for 10 to 14 days were dramatically activated, had rough surfaces, and showed a significant degree of long pseudopodia formation. The pH of the PLTs on Day 5 was lower at 22°C than at 4°C, while the lactate dehydrogenase and lactic acid levels in the former group were significantly higher (p < 0.005). The maximum aggregation rates induced by collagen and arachidonic acid in the PLTs stored at 4°C for 5 days remained higher than 80%, while the rates induced by four inducers in the PLTs stored at 22°C were less than 5%. PLTs stored at 4°C for 10 to 14 days showed higher surface expression of PAC-1 and CD62P.
CONCLUSION: PLT counts, cellular morphologies, PLT membranes, cytoplasmic structures, aggregation rates, and hemostatic PLT function stored at 4°C for 10 to 14 days were better than those stored at 22°C for 5 days.
Yazer MH, Spinella PC
J Trauma Acute Care Surg. 2017 Dec 28. doi: 10.1097/TA.0000000000001790.
Abstract:
The AABB (formerly the American Association of Blood Banks) is an international authority on transfusion medicine and tissue banking. The Trauma, Hemostasis and Oxygenation Research (THOR) Network is an international multidisciplinary network of civilian and military providers ranging from first responders and medics to critical care physicians, and from basic scientists to clinical trialists. The THOR Network's vision is to improve outcomes from traumatic hemorrhagic shock by optimizing the acute phase of resuscitation. Its mission is to develop and implement best practices for prehospital care through to the completion of the acute phase of hemorrhagic shock resuscitation. Thus, there is significant overlap between the missions of these two groups. To this end, the joint THOR-AABB working party (WP) was created in the summer of 2016 with a view to improving patient outcomes by the establishment of a formal collaboration between these two groups. The WP has been engaged in many different endeavors, from successfully changing the AABB's standards for the administration of whole blood, to writing commentaries on the safety of uncrossmatched red blood cells and antibody titer methods and thresholds in potentially incompatible plasma products, to hosting a day-long symposium on blood product resuscitation of massively bleeding patients in conjunction with the AABB annual meeting. This review details the activities of the WP and indicates some future activities.
Younis M(1), Ray-Zack M(1), Haddad NN(1), Choudhry A(1), Hernandez MC(1), Wise K(1), Zielinski MD(2).
World J Surg. 2018 Feb 1. doi: 10.1007/s00268-018-4520-2.
BACKGROUND: Coagulopathy can delay or complicate surgical diseases that require emergent surgical treatment. Prothrombin complex concentrates (PCC) provide concentrated coagulation factors which may reverse coagulopathy more quickly than plasma (FFP) alone. We aimed to determine the time to operative intervention in coagulopathic emergency general surgery patients receiving either PCC or FFP. We hypothesize that PCC administration more rapidly normalizes coagulopathy and that the time to operation is diminished compared to FFP alone.
METHODS: Single institution retrospective review was performed for coagulopathic EGS patients during 2/1/2008 to 8/1/2016. Patients were divided into three groups (1) PCC alone (2) FFP alone and (3) PCC and FFP. The primary outcome was the duration from clinical decision to operate to the time of incision. Summary and univariate analyses were performed.
RESULTS: Coagulopathic EGS patients (n = 183) received the following blood products: PCC (n = 20, 11%), FFP alone (n = 119, 65%) and PCC/FFP (n = 44, 24%). The mean (± SD) patient age was 71 ± 13 years; 60% were male. The median (IQR) Charlson comorbidity index was similar in all three groups (PCC = 5(4-6), FFP = 5(4-7), PCC/FFP = 5(4-6), p = 0.33). The mean (± SD) dose of PCC administered was similar in the PCC/FFP group and the PCC alone group (2539 ± 1454 units vs. 3232 ± 1684, p = .09). The mean (±SD) time to incision in the PCC alone group was significantly lower than the FFP alone group (6.0 ± 3.6 vs. 8.8 ± 5.0 h, p = 0.01). The mean time to incision in the PCC + FFP group was also significantly lower than the FFP alone group (7.1 ± 3.6 vs. 8.8 ± 5.0, p = 0.03). The incidence of thromboembolic complications was similar in all three groups.
CONCLUSIONS: PCC, alone or in combination with FFP, reduced INR and time to surgery effectively and safely in coagulopathic EGS patients without an apparent increased risk of thromboembolic events, when compared to FFP use alone.
LEVEL OF EVIDENCE: IV single institutional retrospective review.
Ghodraty MR, Rokhtabnak F, Dehghan HR, Pournajafian A, Baghaee Vaji M, Koleini ZS, Porhomayon J, Nader ND
Surgery. 2017 Nov;162(5):1055-1062
BACKGROUND: The main objective of this study was to compare the effect of perioperative administration of crystalloid versus colloid solutions and its impact on reversal of ileus after resection with primary anastomosis of intestine. We hypothesized that inclusion of colloids will improve the return of intestinal motility.
METHODS: In a double-blinded clinical trial, 91 the American Society of Anesthesiologists I to III patients undergoing abdominal operation for resection with anastomosis of small or large intestine were randomized to receive either lactated Ringer solution crystalloid group or 6% hydroxyethyl starch colloid group to replace intraoperative fluid loss (blood loss + third space). The time to resume normal intestinal motility was the primary end point and the prevalence of composite postoperative complications was the secondary end point.
RESULTS: Average duration of ileus was 86.7 ± 23.6 hours in crystalloid group and it lasted 73.4 ± 20.8 hours in colloid group (P = .006). While there was no difference in the frequency of postoperative nausea and vomiting between the 2 groups (P = .3), the actual vomiting occurred less frequently in colloid group (P = .02). Serum concentrations of potassium ion decreased significantly in both groups, whereas the degree of potassium changes was more remarkable in colloid group compared with crystalloid group (P = .03). Postoperative ileus did not correlate with sex, age, and the duration of operation. Duration of hospital stay was similar between the 2 groups.
CONCLUSION: We concluded that administration of colloids as a part of perioperative fluid management improves intestinal motility and shortens the duration of ileus after gastrointestinal operations. This may improve the tolerance for enteral feeding and reduce ileus-related symptoms.
Naumann DN, Hancox JM, Raitt J, Smith IM, Crombie N, Doughty H, Perkins GD, Midwinter MJ; RESCUER Collaborators.
BMJ Open. 2018 Jan 23;8(1):e019627
OBJECTIVES: We investigated how often intravenous fluids have been delivered during physician-led prehospital treatment of patients with hypotensive trauma in the UK and which fluids were given. These data were used to estimate the potential national requirement for prehospital blood products (PHBP) if evidence from ongoing trials were to report clinical superiority.
SETTING: The Regional Exploration of Standard Care during Evacuation Resuscitation (RESCUER) retrospective observational study was a collaboration between 11 UK air ambulance services. Each was invited to provide up to 5 years of data and total number of taskings during the same period.
PARTICIPANTS: Patients with hypotensive trauma (systolic blood pressure <90 mm Hg or absent radial pulse) attended by a doctor.
PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the number of patients with hypotensive trauma given prehospital fluids. Secondary outcomes were types and volumes of fluids. These data were combined with published data to estimate potential national eligibility for PHBP.
RESULTS: Of 29 037 taskings, 729 (2.5%) were for patients with hypotensive trauma attended by a physician. Half were aged 21-50 years; 73.4% were male. A total of 537 out of 729 (73.7%) were given fluids. Five hundred and ten patients were given a single type of fluid; 27 received >1 type. The most common fluid was 0.9% saline, given to 486/537 (90.5%) of patients who received fluids, at a median volume of 750 (IQR 300-1500) mL. Three per cent of patients received PHBP. Estimated projections for patients eligible for PHBP at these 11 services and in the whole UK were 313 and 794 patients per year, respectively.
CONCLUSIONS: One in 40 air ambulance taskings were manned by physicians to retrieve patients with hypotensive trauma. The most common fluid delivered was 0.9% saline. If evidence justifies universal provision of PHBP, approximately 800 patients/year would be eligible in the UK, based on our data combined with others published. Prospective investigations are required to confirm or adjust these estimations.
Pati S, Peng Z, Wataha K, Miyazawa B, Potter DR, Kozar RA
PLoS One. 2018 Feb 2;13(2):e0192363
ABSTRACT:In severe trauma and hemorrhage the early and empiric use of fresh frozen plasma (FFP) is associated with decreased morbidity and mortality. However, utilization of FFP comes with the significant burden of shipping and storage of frozen blood products. Dried or lyophilized plasma (LP) can be stored at room temperature, transported easily, reconstituted rapidly with ready availability in remote and austere environments. We have previously demonstrated that FFP mitigates the endothelial injury that ensues after hemorrhagic shock (HS). In the current study, we sought to determine whether LP has similar properties to FFP in its ability to modulate endothelial dysfunction in vitro and in vivo. Single donor LP was compared to single donor FFP using the following measures of endothelial cell (EC) function in vitro: permeability and transendothelial monolayer resistance; adherens junction preservation; and leukocyte-EC adhesion. In vivo, using a model of murine HS, LP and FFP were compared in measures of HS- induced pulmonary vascular inflammation and edema. Both in vitro and in vivo in all measures of EC function, LP demonstrated similar effects to FFP. Both FFP and LP similarly reduced EC permeability, increased transendothelial resistance, decreased leukocyte-EC binding and persevered adherens junctions. In vivo, LP and FFP both comparably reduced pulmonary injury, inflammation and vascular leak. Both FFP and LP have similar potent protective effects on the vascular endothelium in vitro and in lung function in vivo following hemorrhagic shock. These data support the further development of LP as an effective plasma product for human use after trauma and hemorrhagic shock.
Roberts DA, Shaw AD
Best Pract Res Clin Anaesthesiol. 2017 Sep;31(3):345-352
Abstract
Volume resuscitation to correct hypotension in surgical and critically ill patients is a common practice. Available evidence suggests that iatrogenic volume overload is associated with worse outcomes in established acute kidney injury. Intraoperative arterial hypotension is associated with postoperative renal dysfunction, and prompt correction with fluid management protocols that combine inotrope infusions with volume therapy targeted to indices of volume responsiveness should be considered. From the perspective of renal function, the minimum amount of intravenous fluid required to maintain perfusion and oxygen delivery is desirable. Available evidence and expert opinion suggest that balanced crystalloid solutions are preferable to isotonic saline for volume resuscitation. Moreover, albumin has a similar safety profile as crystalloids. Hetastarch-containing colloids have a clear association with acute kidney injury.
Robinson BRH, Cohen MJ, Holcomb JB, Pritts TA, Gomaa D, Fox EE, Branson RD, Callcut RA, Cotton BA, Schreiber MA, Brasel KJ, Pittet JF, Inaba K, Kerby JD, Scalea TM, Wade CE, Bulger EM; PROPPR Study Group.
Shock. 2017 Nov 30
BACKGROUND: The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) study evaluated the effects of plasma and platelets on hemostasis and mortality after hemorrhage. The pulmonary consequences of resuscitation strategies that mimic whole blood, remain unknown.
METHODS: A secondary analysis of the PROPPR study was performed. Injured patients predicted to receive a massive transfusion were randomized to 1:1:1 vs. 1:1:2 plasma-platelet-RBC ratios at 12 Level I North American trauma centers. Patients with survival >24 hours, an ICU stay, and a recorded PaO2/FiO2 (P/F) ratio were included. ARDS was defined as a P/F ratio < 200, with bilateral pulmonary infiltrates, and adjudicated by investigators.
RESULTS: 454 patients were reviewed (230 received 1:1:1, 224 1:1:2). Age, sex, injury mechanism, and regional abbreviated injury scale (AIS) scores did not differ between cohorts. Tidal volume, PEEP, and lowest P/F ratio did not differ. No significant differences in ARDS rates (14.8 vs. 18.4%), ventilator-free (24 vs. 24) or ICU-free days (17.5 vs. 18), hospital length of stay (22 vs. 18 days), or 30-day mortality were found (28 vs. 28%). ARDS was associated with blunt injury (OR 3.61 [1.53-8.81] p < 0.01) and increasing chest AIS (OR 1.40 [1.15-1.71] p < 0.01). Each 500 mL of crystalloid infused during hours 0-6 was associated with a 9% increase in the rate of ARDS (OR 1.09 [1.04-1.14] p < 0.01). Blood given at 0-6 or 7-24 hours were not risk factors for lung injury.
CONCLUSION: Acute crystalloid exposure, but not blood products, is a potentially modifiable risk factor for the prevention of ARDS following hemorrhage.
Semler MW, Self WH, Wanderer JP, Ehrenfeld JM, Wang L, Byrne DW, Stollings JL, Kumar AB, Hughes CG, Hernandez A, Guillamondegui OD, May AK, Weavind L, Casey JD, Siew ED, Shaw AD, Bernard GR, Rice TW; SMART Investigators and the Pragmatic Critical Care Research Group.
N Engl J Med. 2018 Mar 1;378(9):829-839
BACKGROUND: Both balanced crystalloids and saline are used for intravenous fluid administration in critically ill adults, but it is not known which results in better clinical outcomes.
METHODS: In a pragmatic, cluster-randomized, multiple-crossover trial conducted in five intensive care units at an academic center, we assigned 15,802 adults to receive saline (0.9% sodium chloride) or balanced crystalloids (lactated Ringer's solution or Plasma-Lyte A) according to the randomization of the unit to which they were admitted. The primary outcome was a major adverse kidney event within 30 days - a composite of death from any cause, new renal-replacement therapy, or persistent renal dysfunction (defined as an elevation of the creatinine level to ≥200% of baseline) - all censored at hospital discharge or 30 days, whichever occurred first.
RESULTS: Among the 7942 patients in the balanced-crystalloids group, 1139 (14.3%) had a major adverse kidney event, as compared with 1211 of 7860 patients (15.4%) in the saline group (marginal odds ratio, 0.91; 95% confidence interval [CI], 0.84 to 0.99; conditional odds ratio, 0.90; 95% CI, 0.82 to 0.99; P=0.04). In-hospital mortality at 30 days was 10.3% in the balanced-crystalloids group and 11.1% in the saline group (P=0.06). The incidence of new renal-replacement therapy was 2.5% and 2.9%, respectively (P=0.08), and the incidence of persistent renal dysfunction was 6.4% and 6.6%, respectively (P=0.60).
CONCLUSIONS: Among critically ill adults, the use of balanced crystalloids for intravenous fluid administration resulted in a lower rate of the composite outcome of death from any cause, new renal-replacement therapy, or persistent renal dysfunction than the use of saline. (Funded by the Vanderbilt Institute for Clinical and Translational Research and others; SMART-MED and SMART-SURG ClinicalTrials.gov numbers, NCT02444988 and NCT02547779 .).
Tran A, Yates J, Lau A, Lampron J, Matar M
J Trauma Acute Care Surg. 2018 Jan 24. doi: 10.1097/TA.0000000000001816.
BACKGROUND: Aggressive fluid resuscitation in trauma promotes deleterious effects such as clot disruption, dilutional coagulopathy and hypothermia. Animal studies suggest that permissive hypotension maintains appropriate organ perfusion, reduces bleeding and improves mortality. This review assesses the efficacy and safety of permissive hypotension in adult trauma patients with hemorrhagic shock.
METHODS: We searched the MEDLINE and EMBASE databases from inception to May 2017 for randomized controlled trials comparing permissive hypotension vs. conventional resuscitation following traumatic injury. We included pre-operative and intraoperative resuscitation strategies. The primary outcome was 30-day or in-hospital mortality. Secondary outcomes included blood product utilization, estimated blood loss and in-hospital complications. Pooling was performed with a random-effects model.
RESULTS: We screened 722 abstracts, from which five randomized trials evaluating 1158 patients were included. Blood pressure targets in the intervention arms varied from systolic BP 50 - 70 mmHg or MAP ≥ 50 mmHg as compared to systolic BP 65 - 100 mmHg or MAP ≥ 65 in the control arms. Two studies evaluated only patients with penetrating injury while the remaining three additionally included blunt injuries. Four trials suggested a survival benefit for 30-day or in-hospital mortality with hypotensive resuscitation, although three studies were insufficiently powered to find statistical significance. Studies were of poor to moderate quality due to poor protocol reporting and lack of blinding. The pooled odds ratio was 0.70 (95% CI 0.53 to 0.92), suggesting a survival benefit for permissive hypotension. Those patients received fewer blood products and had lesser estimated blood loss.
CONCLUSION: Permissive hypotension may offer a survival benefit over conventional resuscitation for patients with hemorrhagic injury. It may additionally reduce blood loss and blood product utilization. However, the majority of studies were underpowered, thus reflecting a need for high quality, adequately powered trials.
LEVEL OF EVIDENCE: Systematic Review, Level II PROSPERO REGISTRATION: CRD42017070526.