Massive Transfusion Guidelines Research Articles

Physiopathology and treatment of critical bleeding: a literature review

Objectivesto develop the different factors involved in the physiopathology of trauma-induced coagulopathy, through a review of publications on the matter; as well as to assess the evidence available on the treatment of critical bleeding and the recommendations by clinical practice guidelines. Methodsa search has been conducted on the bibliography published about the physiopathology and treatment of critical bleeding in the PUBMED, BestPractice, UpToDate databases and the Cochrane Plus Library. The main key words used for this search were “early trauma induced coagulopathy”, “mechanisms of early trauma-induced coagulopathy”, “blood transfusion guidelines”, “massive transfusion guidelines” and “fibrinogen replacement therapy”. The most clinically relevant articles were selected for this review. Conclusionsthe physiopathology of the trauma-induced coagulopathy is a more complex matter and involves more factors than was initially assumed. The early treatment of the coa-gulopathy is critical for the initial management of the critical bleeding. However, the use of blood derivatives should be rational and based on homogeneous and high-quality scientific evidence.The main cornerstones for the treatment of critical bleeding are: fluid therapy, fibrinogen concentrate, prothrombin complex concentrate, plasma, erythrocyte or platelet concentrates, tranexamic acid, and calcium. Their administration should be assessed depending on the clinical condition of each patient.

Role of Fibrinogen in Trauma-Induced Coagulopathy.

Fibrinogen is the first coagulation factor to decrease after massive hemorrhage. European massive transfusion guidelines recommend early repletion of fibrinogen; however, this practice has not been widely adopted in the US. We hypothesize that hypofibrinogenemia is common at hospital arrival and is an integral component of trauma-induced coagulopathy. This study entailed review of a prospective observational database of adults meeting the highest-level activation criteria at an urban level 1 trauma center from 2014 through 2020. Resuscitation was initiated with 2:1 red blood cell (RBC) to fresh frozen plasma (FFP) ratios and continued subsequently with goal-directed thrombelastography. Hypofibrinogenemia was defined as fibrinogen below 150 mg/dL. Massive transfusion (MT) was defined as more than 10 units RBC or death after receiving at least 1 unit RBC over the first 6 hours of admission. Of 476 trauma activation patients, 70 (15%) were hypofibrinogenemic on admission, median age was 34 years, 78% were male, median New Injury Severity Score (NISS) was 25, and 72 patients died (15%). Admission fibrinogen level was an independent risk factor for MT (odds ratio [OR] 0.991, 95% CI 0.987-0.996]. After controlling for confounders, NISS (OR 1.034, 95% CI 1.017-1.052), systolic blood pressure (OR 0.991, 95% CI 0.983-0.998), thrombelastography angle (OR 0.925, 95% CI 0.896-0.954), and hyperfibrinolysis (OR 2.530, 95% CI 1.160-5.517) were associated with hypofibrinogenemia. Early cryoprecipitate administration resulted in the fastest correction of hypofibrinogenemia. Hypofibrinogenemia is common after severe injury and predicts MT. Cryoprecipitate transfusion results in the most expeditious correction. Earlier administration of cryoprecipitate should be considered in MT protocols.

How well does your massive transfusion protocol perform? A scoping review of quality indicators.

Management of patients with major haemorrhage often requires urgent administration of multiple blood products, commonly termed a massive transfusion (MT). Clinical practice in these scenarios is supported in part by evidence-based MT guidelines, which typically recommend use of an MT protocol (MTP). MTPs aim to provide practical and specific interpretation of MT guidelines for local institutional use, outlining tasks and pre-configuration of blood product packs to be transfused to provide efficient and evidence-based transfusion management. Institutions can support this aim by the measurement of MTP performance and patient outcomes through collection of quality indicators (QI). Many international guidelines now recommend the routine collection of a range of QIs relating to MT/MTP; however, there is significant variation in procedures and no benchmarks or minimal evidence to guide practice. We conducted a scoping review to document and evaluate reported QIs for MTP. We conducted a search of CENTRAL, MEDLINE and EMBASE for published studies from inception until May 14, 2020, that reported at least one MTP QI and use of an MTP or equivalent protocol. Included studies were evaluated using a QI classification system based on current MT QI guidelines and the Donabedian QI framework. We identified 107 eligible studies. Trauma patients were the most commonly evaluated group, and total blood products transfused and in-hospital mortality were the most commonly reported QIs. Reflecting the lack of international consensus and benchmarks, we found significant variability in the reporting of QIs, which often did not reflect guideline recommendations. Our review highlights the importance of establishing international consensus on prioritised QIs with quantifiable targets that are important to the process of MT.

Emergency Peripartum Hysterectomy

Uterine atony is a major cause of postpartum hemorrhage (PPH), an emergency event that remains one of the leading causes of maternal morbidity and mortality worldwide. This study reviews a case of severe atonic PPH after a primary cesarean, which resulted in an emergency peripartum hysterectomy. In the United States, prevalence studies have revealed a peripartum hysterectomy rate of almost 1 per 1,000 births. Multidisciplinary collaboration using effective communication is needed when responding to the severity of Stage 3 PPH. A 28-year-old woman, gravida 3 para 0, at 40.0-weeks gestation arrived at the labor and delivery unit in active labor. During labor, she received oxytocin augmentation and an epidural. Cervical dilation progressed slowly, with the patient remaining at 9.5 cm for 5 hr. On complete dilation, the patient pushed for 1.5 hr before the decision was made to proceed with a cesarean due to failure of the fetus to descend and maternal exhaustion. After the successful birth of a 4,042-g newborn by cesarean, persistent uterine atony developed. Interventions were then enacted, guided by the California Maternal Quality Care Collaborative Obstetric Emergency Management Plan. Additional staff arrived in operating room to provide support. Multidisciplinary teamwork was achieved through use of effective communication techniques, including situation–background–assessment–recommendation and closed-loop communication. Pharmacologic interventions included the use of oxytocin, misoprostol, methylergometrine maleate (×2), and carboprost tromethamine (×2). Procedural interventions by the physician included bimanual uterine massage, uterine packing, B-Lynch suture, and intrauterine balloon tamponade. Maternal hypotension and tachycardia developed, leading to the initiation of the massive transfusion guidelines. Despite interventions, severe uterine atony and brisk vaginal bleeding continued, resulting in a total quantitative blood loss of 4 L. The decision was made to proceed with an emergency peripartum hysterectomy. Postpartum emotional support was provided by a multidisciplinary team that included nursing, physician, chaplain, and social services. The mother and her newborn were discharged home on Postoperative Day 4. This case study demonstrates the success of quickly initiated PPH protocol interventions that are necessary to prevent maternal mortality and knowing the current literature on risk identification, management, and treatment of severe PPH.

Fluid Resuscitation and Massive Transfusion Protocol in Pediatric Trauma

Summary Trauma is the leading cause of morbidity and mortality in children due to the occurrence of hemorrhagic shock. Hemorrhagic shock and its consequences, anemia and hypovolemia, decrease oxygen delivery, due to which appropriate transfusion and volume resuscitation are critical. Guidelines for massive transfusion, in the pediatric trauma, have not been defined yet. Current data indicate that early identification of coagulopathy and its treatment with RBSs, plasma and platelets in a 1:1:1 unit ratio, and limited use of crystalloids may improve survival in pediatric trauma patients.

Update on the Massive Transfusion Guidelines on Hemorrhagic Shock: After the Wars

Over the past decade, crystalloid- and red blood cell-dominated massive resuscitation practices have largely been replaced with high-ratio transfusion of plasma, platelets, and red blood cells (RBCs) in massively bleeding trauma patients. Literature from military and civilian experiences with massive transfusion (MT) was reviewed, beginning with military transfusion practices at the onset of the wars in Afghanistan and Iraq and continuing through to present day. Early and balanced resuscitation (1:1:1 ratio of plasma, platelets, and RBCs) is superior to crystalloid- or red blood cell-driven resuscitation. Military research from Afghanistan and Iraq stimulated civilian investigations into ratio-based MT. 1:1:1 resuscitation carries the most benefit for massively bleeding trauma patients. Thrombelastography-guided MT can be used to supplement empiric 1:1:1 therapy in order to detect and address specific coagulopathies. Future directions in MT research presently include resuscitation with fresh whole blood and pre-hospital plasma-based resuscitation.

Tactical Study of Care Originating in the Out-of-Hospital Environment (TACSCOPE): Out-of-Hospital Application of Predictor Guidelines for Massive Transfusion and Survival

Analyze U.S. combat casualties from the Department of Defense Trauma Registry, focusing on out-of-hospital care. Compare current guidelines for predicting massive transfusion (MT) and 30-day survival, with two novel models using variables collectable in the out-of-hospital setting.

Evaluation of military trauma system practices related to damage-control resuscitation

The Joint Theater Trauma System (JTTS) was developed with the vision that every soldier, marine, sailor, and airman injured on the battlefield would have the optimal chance for survival and maximum potential for functional recovery. In this analysis, we hypothesized that information diffusion through the JTTS, via the dissemination of clinical practice guidelines and process improvements, would be associated with the acceptance of evidence-based practices and decreases in trauma practice variability. The current evaluation was designed as a single time-series quasi-experimental study as a preanalysis and postanalysis relative to the implementation of clinical practice guidelines and process improvement interventions. Data captured from patients admitted to hospital-level (Level III) military treatment facilities in Iraq and Afghanistan from 2003 to 2010 were retrospectively analyzed from the Joint Theater Trauma Registry (JTTR) to determine the potential impact of process improvement initiatives on clinical practice. The JTTS clinical practice guidelines for massive transfusion led to increased compliance with balanced component transfusion and decreased practice variability. During the course of the evaluation period, hypothermia on presentation decreased dramatically after the publication of the hypothermia prevention and management clinical practice guideline. Developed metrics demonstrate that evidence-based quality improvement initiatives disseminated through the JTTS were associated with improved clinical practice of resuscitation following battlefield injury. Therapeutic/care management study, level IV.

Acute coagulopathy and early deaths post major trauma

Introduction and aims Acute traumatic coagulopathy is observed in 10–25% of patients post major trauma and its management forms an integral part of haemostatic resuscitation. The identification and treatment of this coagulopathy is difficult and there is uncertainty regarding optimal therapeutic guidelines during the early phases of trauma resuscitation. This study aimed to examine the association between acute coagulopathy and early deaths post major trauma. Methods A retrospective review of data over a 5 year period was performed to determine the associations between variables considered to contribute to mortality for adult major trauma patients (Injury Severity Score (ISS) > 15) receiving blood transfusions as part of their initial resuscitation. Early death, defined as death in ED, or death in the operating theatre (OT), Intensive Care Unit (ICU) or wards within 24 h of admission was the primary end-point. Patients with non-survivable head injury on initial imaging were excluded. Univariate associations were calculated and multivariable logistic regression analysis was used to determine independent associations with mortality. Results There were 772 patients included in this study with a median ISS of 29 (19–41), with 91.7% blunt trauma. All-cause in-hospital mortality was 17.5%, while 77 (9.7%) patients died early. Increasing age (OR 1.04), a GCS of 3–8 (OR 5.05), and the presence of acute coagulopathy (OR 8.77) were significant independent variables associated with early death. Conclusions Acute traumatic coagulopathy, independent of injury severity, transfusion practice or other physiological markers for haemorrhage, was associated with early death in major trauma patients requiring a blood transfusion. Early recognition and management of coagulopathy, independent of massive transfusion guidelines, may improve outcome from trauma resuscitation. Further studies are required for the early recognition of acute traumatic coagulopathy to enable the development of an evidence base for management.

Massive transfusion and blood product use in the pediatric trauma patient

Hemorrhagic shock in the pediatric trauma patient is an uncommon but fundamental problem for the treating clinician. Current management of hemorrhagic shock involves initial resuscitation with crystalloid fluids followed by infusion of blood components as necessary. In management of the adult trauma patient, many institutions have implemented massive transfusion protocols to guide transfusion in situations requiring or anticipating the use of greater than 10 U of packed red blood cells. In the pediatric population, guidelines for massive transfusion are vague or nonexistent. Adult trauma transfusion protocols can be applied to children until a pediatric protocol is validated. Here, we attempt to identify certain principles of transfusion therapy specific to pediatric trauma and outline a sample pediatric massive transfusion protocol that may be used to guide resuscitation. Also, adjuncts to transfusion, such as colloid fluids, other plasma expanders or hemoglobin substitutes, and recombinant activated factor VII, are discussed.

Fresh frozen plasma (FFP) use during massive blood transfusion in trauma resuscitation

Introduction Recent retrospective studies have found high fresh frozen plasma (FFP) to packed red blood cell (PRBC) ratios during trauma resuscitation to be associated with improved mortality. Whilst this association may be related to a mortality bias present in these studies, there has been an overall tendency towards a 1:1 FFP:PRBC ratio in massive transfusion guidelines worldwide. The aim of this study was to retrospectively review the administration of FFP in patients undergoing massive transfusion during trauma resuscitation, to add to the evidence base for massive transfusion guidelines. Materials and methods Multi-trauma patients who were administered blood transfusions of 5 units or more of packed red blood cells (PRBCs) in the first 4 h were included in this study. Mortality was the primary endpoint with length of hospital stay, ICU hours and mechanically ventilated hours secondary endpoints. Results There were 331 patients included in this study with a median Injury Severity Score (ISS) of 36 (25–50) and a mortality of 29.9%. There was little change in the ratio of FFP:PRBC transfused per patient from 2005 to 2008. A low FFP:PRBC ratio in the first 4 h of resuscitation, older age, low initial GCS and coagulopathy on presentation were significant independent factors associated with mortality. When deaths in the first 24 h were excluded, the FFP:PRBC ratio had no association with mortality. Discussion This study has shown increased initial survival in association with higher FFP:PRBC ratios during massive transfusion in a population with a high proportion of blunt injuries. The association is difficult to interpret because of an inherent survival bias. The optimal ratio of FFP:PRBC during massive transfusion may be different to 1:1 and further prospective research is required. There is now an increasing need for well designed randomised controlled trials to determine the best FFP:PRBC ratio for the resuscitation of blunt multi-trauma patients.

Transfusion for trauma: civilian lessons from the battlefield?

Transfusion for trauma: civilian lessons from the battlefield?

Increased Plasma and Platelet to Red Blood Cell Ratios Improves Outcome in 466 Massively Transfused Civilian Trauma Patients

To determine the effect of blood component ratios in massive transfusion (MT), we hypothesized that increased use of plasma and platelet to red blood cell (RBC) ratios would result in decreased early hemorrhagic death and this benefit would be sustained over the ensuing hospitalization. Civilian guidelines for massive transfusion (MT > or =10 units of RBC in 24 hours) have typically recommend a 1:3 ratio of plasma:RBC, whereas optimal platelet:RBC ratios are unknown. Conversely, military data shows that a plasma:RBC ratio approaching 1:1 improves long term outcomes in MT combat casualties. There is little consensus on optimal platelet transfusions in either civilian or military practice. At present, the optimal combinations of plasma, platelet, and RBCs for MT in civilian patients is unclear. Records of 467 MT trauma patients transported from the scene to 16 level 1 trauma centers between July 2005 and June 2006 were reviewed. One patient who died within 30 minutes of admission was excluded. Based on high and low plasma and platelet to RBC ratios, 4 groups were analyzed. Among 466 MT patients, survival varied by center from 41% to 74%. Mean injury severity score varied by center from 22 to 40; the average of the center means was 33. The plasma:RBC ratio ranged from 0 to 2.89 (mean +/- SD: 0.56 +/- 0.35) and the platelets:RBC ratio ranged from 0 to 2.5 (0.55 +/- 0.50). Plasma and platelet to RBC ratios and injury severity score were predictors of death at 6 hours, 24 hours, and 30 days in multivariate logistic models. Thirty-day survival was increased in patients with high plasma:RBC ratio (> or =1:2) relative to those with low plasma:RBC ratio (<1:2) (low: 40.4% vs. high: 59.6%, P < 0.01). Similarly, 30-day survival was increased in patients with high platelet:RBC ratio (> or =1:2) relative to those with low platelet:RBC ratio (<1:2) (low: 40.1% vs. high: 59.9%, P < 0.01). The combination of high plasma and high platelet to RBC ratios were associated with decreased truncal hemorrhage, increased 6-hour, 24-hour, and 30-day survival, and increased intensive care unit, ventilator, and hospital-free days (P < 0.05), with no change in multiple organ failure deaths. Statistical modeling indicated that a clinical guideline with mean plasma:RBC ratio equal to 1:1 would encompass 98% of patients within the optimal 1:2 ratio. Current transfusion practices and survival rates of MT patients vary widely among trauma centers. Conventional MT guidelines may underestimate the optimal plasma and platelet to RBC ratios. Survival in civilian MT patients is associated with increased plasma and platelet ratios. Massive transfusion practice guidelines should aim for a 1:1:1 ratio of plasma:platelets:RBCs.

Massive blood transfusion and trauma resuscitation

To review the massive transfusion practice at a Level I adult Trauma Centre during initial trauma reception and resuscitation. All trauma patients presenting to The Alfred Emergency & Trauma Centre and receiving a transfusion of five units or more of packed red blood cells within 4h of presentation over a 26-month period were included in this study. Patient demographics, clinical characteristics, injuries, surgical management and volume of blood transfused were analysed with mortality as the primary endpoint. Initial clinical features and injuries predictive of massive transfusion were also analysed. There were 119 patients who received a transfusion of five units or more of packed red blood cells (PRBCs) within 4h of presentation. The median Injury Severity Score of this group of patients was 34.0 (IQR 26-48) and mortality was 27.7%. The median number of packed red blood cell transfused was 8.0 (IQR 6-14) in the 1st 4h. Initial clinical features and injuries independently associated with a larger volume of blood transfused were initial hypotension, fractures of the pelvis, kidney injuries, initial acidaemia, and thrombocytopaenia. The Injury Severity Score, initial coagulopathy measured by APTT and the presence of head injuries were the independent predictors of mortality. The volume of blood transfused during trauma resuscitation was not found to be an independent predictor of mortality. Prospective studies into transfusion practice and clinical features of patients during the trauma resuscitation phase requiring massive transfusion are needed to establish evidence-based guidelines for massive transfusion.

Minimizing dilutional coagulopathy in exsanguinating hemorrhage: a computer simulation.

Current massive transfusion guidelines are derived from washout equations that may not apply to bleeding trauma patients. Our aim was to analyze these guidelines using a computer simulation. A combined hemodilution and hemodynamic model of an exsanguinating patient was developed to calculate the changes in prothrombin time (PT), fibrinogen, and platelets with bleeding. The model was calibrated to data from 44 patients. Time intervals to subhemostatic values of each coagulation test were calculated for a range of replacement options. Prolongation of PT is the sentinel event of dilutional coagulopathy and occurs early in the operation. The key to preventing coagulopathy is plasma infusion before PT becomes subhemostatic. The optimal replacement ratios were 2:3 for plasma and 8:10 for platelets. Concurrent transfusion of plasma with blood is another effective strategy for minimizing coagulopathy. Existing protocols underestimate the dilution of clotting factors in severely bleeding patients. The model presents an innovative approach to optimizing component replacement in exsanguinating hemorrhage.