Massive transfusions and severe hypocalcemia: An opportunity for monitoring and supplementation guidelines.

BACKGROUND: Massive transfusion protocols (MTPs) are associated with severe hypocalcemia, contributing to coagulopathy and mortality in severely injured patients. Severity of hypocalcemia following massive transfusion activation and appropriate treatment strategies remain undefined. STUDY DESIGN AND METHODS: This was a retrospective study of all MTP activations in adult trauma patients at a Level 1 trauma center between August 2016 and September 2017. Units of blood products transfused, ionized calcium levels, and amount of calcium supplementation administered were recorded. Primary outcomes were ionized calcium levels and the incidence of severe ionized hypocalcemia (iCa ≤1.0 mmol/L) in relation to the volume of blood products transfused. RESULTS: Seventy-one patients had an MTP activated during the study period. The median amount of packed red blood cells (PRBCs) transfused was 10 units (range 1-52). A total of 42 (59.1%) patients had periods of severe hypocalcemia. Patients receiving 13 or more units of PRBC had a greater prevalence of hypocalcemia with 83.3% having at least one measured ionized calcium ≤1.0 mmoL/L (p = .001). The number of ionized calcium levels checked and the amount of supplemental calcium given in patients who experienced hypocalcemia varied considerably. DISCUSSION: Severe hypocalcemia commonly occurs during MTP activations and correlates with the number of packed red blood cells transfused. Monitoring of ionized calcium and amount of calcium supplementation administered is widely variable. Standardized protocols for recognition and management of severe hypocalcemia during massive transfusions may improve outcomes.

Comparison of diagnostic imaging modalities for the evaluation of pancreatic duct injury in children: a multi-institutional analysis from the Pancreatic Trauma Study Group.

PURPOSE: Determining the integrity of the pancreatic duct is important in high-grade pancreatic trauma to guide decision making for operative vs non-operative management. Computed tomography (CT) is generally an inadequate study for this purpose, and magnetic resonance cholangiopancreatography (MRCP) is sometimes obtained to gain additional information regarding the duct. The purpose of this multi-institutional study was to directly compare the results from CT and MRCP for evaluating pancreatic duct disruption in children with these rare injuries. METHODS: Retrospective study of data obtained from eleven pediatric trauma centers from 2010 to 2015. Children up to age 18 with suspected blunt pancreatic duct injury who had both CT and MRCP within 1 week of injury were included. Imaging findings of both studies were directly compared and analyzed using descriptive statistics, Chi square, Wilcoxon rank-sum, and McNemar's tests. RESULTS: Data were collected for 21 patients (mean age 7.8 years). The duct was visualized more often on MRCP than CT (48 vs 5%, p < 0.05). Duct disruption was confirmed more often on MRCP than CT (24 vs 0%), suspected based on secondary findings equally (38 vs 38%), and more often indeterminate on CT (62 vs 38%). Overall, MRCP was not superior to CT for determining duct integrity (62 vs 38%, p = 0.28). CONCLUSIONS: In children with blunt pancreatic injury, MRCP is more useful than CT for identifying the pancreatic duct but may not be superior for confirmation of duct integrity. Endoscopic retrograde cholangiogram (ERCP) may be necessary to confirm duct disruption when considering pancreatic resection. LEVEL OF EVIDENCE: III.

Principal component analysis of a swine injury model identifies multiple phenotypes in trauma.

BACKGROUND: Trauma is the third leading cause of death in the United States and the primary cause of death for people between the ages of 1 year and 44 years. In addition to tissue damage, trauma may also activate an inflammatory state known as trauma-induced coagulopathy (TIC) that is associated with clotting malfunctions, acidemia, and end-organ dysfunction. Prior work has also demonstrated benefit to acknowledging the type and severity of endothelial injury, coagulation derangements, and systemic inflammation in the management of trauma patients. This study builds upon prior work by combining laboratory, metabolic, and clinical metrics into an analysis of trauma phenotypes, evolution of phenotypes over time after trauma, and significance of trauma phenotype on mortality. METHODS: Seventy 3-month-old female Yorkshire crossbred swine were randomized to injury and resuscitation groups. Principal component analysis (PCA) of longitudinal swine TEG data (Reaction time, Alpha-Angle, Maximum Amplitude, and Clot Lysis at 30 minutes), pH, lactate, and MAP was completed in R at baseline, 1 hour postinjury, 3 hours postinjury, 6 hours postinjury, and 12 hours postinjury. Subjects were compared by principal component factor scores to assess differences in survival, injury severity, and treatment group. RESULTS: Among injured animals, three phenotypes were observed at each time point. Five phenotypes were associated with differences in survival, and of these, four were associated with differences in injury severity. Phenotype alignment was not significantly different by treatment group. CONCLUSION: This application of PCA to a set of coagulation, hemodynamic, and organ perfusion variables has identified multiple evolving phenotypes after trauma. Some of these phenotypes may correlate with injury severity and may have implications for survival. Next steps include validating these findings over greater numbers of subjects and exploring other machine-learning techniques for phenotype identification. LEVEL OF EVIDENCE: Level IV, Therapeutic/Care Management.

FFP maintains normal coagulation while Kcentra induces a hypercoagulable state in a porcine model of pulmonary contusion and hemorrhagic shock.

BACKGROUND: Moderate injury can lead to a coagulopathy. Fresh frozen plasma (FFP) corrects coagulopathy by means of a balanced array of clotting factors. We sought to compare the late effects of FFP and a prothrombin complex concentrate (PCC) on the coagulopathy of trauma using a porcine model of pulmonary contusion (PC) and hemorrhagic shock (HS) designed to evaluate the organ protective effects of these treatments. METHODS: Female Yorkshire swine (40-50 kg) were randomized to receive PC + HS or control (instrumented and uninjured). A blunt PC was created using a captive bolt gun. To induce HS, a liver crush injury was performed. Eighty minutes after injury, swine were treated with 25 U·kg-1 PCC, 1 U FFP, or 50 mL lactated Ringer's vehicle in a blinded manner. Arterial blood samples were drawn every 6 hours. Swine were euthanized 48 hours postinjury. Data were analyzed by Pearson χ2, analysis of variance and Kruskal-Wallis tests with Tukey's or Mann-Whitney U tests for post hoc analysis. RESULTS: Twenty-seven swine received PC + HS, 3 groups of 9 per group received PCC, FFP, or vehicle. Nine were noninjured controls. When compared with control, PC + HS swine had significantly shortened R time at 6 hours, 36 hours, and 42 hours, decreased LY30 at 12 hours, shortened K time at 30 hours and reduced α angle at 42 hours. PC + HS swine showed significant differences between treatment groups in K and α angle at 3 hours, LY30 at 12 hours and 18 hours, and MA at 12 hours, 18 hours, and 30 hours. Post hoc analysis was significant for higher α angle in PCC versus vehicle at 3 hours, higher MA in vehicle versus PCC at 12 hours and 18 hours, and higher LY30 in PCC versus vehicle at 18 hours (p < 0.012) with no significant differences between FFP and vehicle. CONCLUSION: Severe injury with HS induced a coagulopathy in swine. While FFP maintained normal coagulation following injury, PCC induced more rapid initial clot propagation in injured animals.

Aggressive treatment of acute kidney injury and hyperkalemia improves survival in a combat relevant trauma model in swine.

INTRODUCTION: Our swine model of pulmonary contusion (PC) and hemorrhagic shock (HS) was initially complicated by renal failure, hyperkalemia, and premature death. To study the effects of novel therapies on organ failure, improved survival was necessary requiring the design of an aggressive treatment regimen. METHODS: Anesthetized swine sustained either PC or PC with grade V liver injury to induce HS (PC + HS). After injury, animals were resuscitated followed by either standard care (SC) with maintenance intravenous fluids (IVF) and treatment at potassium level of 6.0 mmol/L (n = 7; 3 PC, 4 PC + HS) or aggressive care (AC) with increased initial IVF, early and frequent potassium monitoring, and treatment at potassium level of 5.0 mmol/L (n = 15, 8 PC, 7 PC + HS). Hyperkalemia was treated with calcium, insulin, and glucose in both groups. RESULTS: Survival to 48 h was achieved in 13/15 (87%) in the AC group and 2/7 (29%) in the SC group (p = 0.014). Compared to SC, AC improved median survival (48 vs. 18 h, p = 0.008) and lowered potassium (5.0 vs. 7.5 mmol/L), creatinine (2.4 vs. 4.0 mg/dL), BUN (27.5 vs. 39.0 mg/dL), and lactate (0.97 vs. 3.57 mmol/L) at the last observed time-point prior to death. For PC + HS animals, survival to 48 h was achieved in 6/7 in the AC group and 0/4 in the SC group with an improved median survival in the AC group (48 vs. 18 h, p = 0.011) DISCUSSION: Aggressive and early hyperkalemia treatment prolongs survival while reducing kidney injury and potassium levels in a combat relevant injury model in swine.

Use of bilobed partial resuscitative endovascular balloon occlusion of the aorta is logistically superior in prolonged management of a highly lethal aortic injury.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a viable technique for management of noncompressible torso hemorrhage. The major limitation of the current unilobed fully occlusive REBOA catheters is below-the-balloon ischemia-reperfusion complications. We hypothesized that partial aortic occlusion with a novel bilobed partial (p)REBOA-PRO would result in the need for less intraaortic balloon adjustments to maintain a distal goal perfusion pressure as compared with currently available unilobed ER-REBOA. METHODS: Anesthetized (40-50 kg) swine randomized to control (no intervention), ER-REBOA, or pREBOA-PRO underwent supraceliac aortic injury. The REBOA groups underwent catheter placement into zone 1 with initial balloon inflation to full occlusion for 10 minutes followed by gradual deflation to achieve and subsequently maintain half of the baseline below-the-balloon mean arterial pressure (MAP). Physiologic data and blood samples were collected at baseline and then hourly. At 4 hours, the animals were euthanized, total blood loss and urine output were recorded, and tissue samples were collected. RESULTS: Baseline physiologic data and basic laboratories were similar between groups. Compared with control, interventions similarly prolonged survival from a median of 18 minutes to over 240 minutes with comparable mortality trends. Blood loss was similar between partial ER-REBOA (41%) and pREBOA-PRO (51%). Partial pREBOA-PRO required a significantly lower number of intraaortic balloon adjustments (10 ER-REBOA vs. 3 pREBOA-PRO, p < 0.05) to maintain the target below-the-balloon MAP. The partial ER-REBOA group developed significantly increased hypercapnia, fibrin clot formation on TEG, liver inflammation, and IL-10 expression compared with pREBOA-PRO. CONCLUSION: In this highly lethal aortic injury model, use of bilobed pREBOA-PRO for a 4-hour partial aortic occlusion was logistically superior to unilobed ER-REBOA. It required less intraaortic balloon adjustments to maintain target MAP and resulted in less inflammation.

The effect of hemorrhage control adjuncts on outcome in severe pelvic fracture: A multi-institutional study.

BACKGROUND: Hemodynamically unstable patients with severe pelvic fracture are a significant challenge to trauma surgeons and have high mortality. Significant variability across institutions in hemorrhage control adjuncts used to quell pelvic bleeding has been demonstrated. However, the effect of these methods on time to definitive bleeding control, type of resuscitation given, and outcomes remains unknown. We sought to elucidate those effects. METHODS: This was a multicenter retrospective review of severe pelvic fracture patients in shock between 2011 and 2016. Shock was defined as systolic blood pressure less than 90 mm Hg, heart rate greater than 120 beats per minute, or base deficit less than -5. Definitive bleeding control was defined as time to surgical control in the operating room or embolization by interventional radiology. Significance level was at p less than 0.05. RESULTS: A total of 279 severe pelvic fracture patients with shock on admission from 12 trauma centers were included. The cohort was primarily male (62%) with median (interquartile range) age of 40 years (28-54 years), Injury Severity Score of 38 (29-50), and Glasgow Coma Scale score of 13 (3-15). Overall mortality was 32%. The most common adjunct used was pelvic binder (50%) followed by no adjunct (30.5%); least common was resuscitative balloon occlusion of the aorta (REBOA) (2.5%). Preperitoneal packing alone and REBOA alone/with other adjunct(s) resulted in the fastest times to operating room/interventional radiology but also had the highest blood utilization and mortality rates. Resuscitative balloon occlusion of the aorta was most often used along with pelvic binder (6 of 13; 46%). CONCLUSION: Marked variation in management of severe pelvic fracture patients in shock indicates the need for a standardized approach to maximize outcomes and minimize transfusion requirements. The use of preperitoneal packing and/or REBOA yielded fastest times to definitive bleeding control. However, REBOA continues to be infrequently used. Future prospective analysis of this combination needs further validation in patients with severe pelvic hemorrhage. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Direct to operating room trauma resuscitation decreases mortality among severely injured children.

BACKGROUND: Expediting evaluation and intervention for severely injured patients has remained a mainstay of advanced trauma care. One technique, direct to operating room (DOR) resuscitation, for selective adult patients has demonstrated decreased mortality. We sought to investigate the application of this protocol in children. METHODS: All DOR pediatric patients from 2009 to 2016 at a pediatric Level I trauma center were identified. Direct to OR criteria included penetrating injury, chest injuries, amputations, significant blood loss, cardiopulmonary resuscitation, and surgeon discretion. Demographics, injury patterns, interventions, and outcomes were analyzed. Observed mortality was compared with expected mortality, calculated using Trauma Injury Severity Score methodology, with two-tailed t tests, and a p value less than 0.5 was considered significant. RESULTS: Of 2,956 total pediatric trauma activations, 82 (2.8%) patients (age range, 1 month to 17 years) received DOR resuscitation during the study period. The most common indications for DOR were penetrating injuries (62%) and chest injuries (32%). Forty-four percent had Injury Severity Score (ISS) greater than 15, 33% had Glasgow Coma Scale (GCS) score of 8 or less, and 9% were hypotensive. The most commonly injured body regions were external (66%), head (34%), chest (30%), and abdomen (27%). Sixty-seven (82%) patients required emergent procedural intervention, most commonly wound exploration/repair (35%), central venous access (22%), tube thoracostomy (19%), and laparotomy (18%). Predictors of intervention were ISS greater than 15 (odds ratio, 14; p = 0.013) and GCS < 9 (odds ratio = 8.5, p = 0.044). The survival rate to discharge for DOR patients was 84% compared with an expected survival of 79% (Trauma Injury Severity Score) (p = 0.4). The greatest improvement relative to expected mortality was seen in the subgroup with penetrating trauma (84.5% vs 74.4%; p = 0.002). CONCLUSION: A selective policy of resuscitating the most severely injured children in the OR can decrease mortality. Patients suffering penetrating trauma with the highest ISS, and diminished GCS scores have the greatest benefit. Trauma centers with appropriate resources should evaluate implementing similar policies. LEVEL OF EVIDENCE: Diagnostic tests or criteria, level II.

Proposed clinical pathway for nonoperative management of high-grade pediatric pancreatic injuries based on a multicenter analysis: A pediatric trauma society collaborative.

BACKGROUND: Guidelines for nonoperative management (NOM) of high-grade pancreatic injuries in children have not been established, and wide practice variability exists. The purpose of this study was to evaluate common clinical strategies across multiple pediatric trauma centers to develop a consensus-based standard clinical pathway. METHODS: A multicenter, retrospective review was conducted of children with high-grade (American Association of Surgeons for Trauma grade III-V) pancreatic injuries treated with NOM between 2010 and 2015. Data were collected on demographics, clinical management, and outcomes. RESULTS: Eighty-six patients were treated at 20 pediatric trauma centers. Median age was 9 years (range, 1-18 years). The majority (73%) of injuries were American Association of Surgeons for Trauma grade III, 24% were grade IV, and 3% were grade V. Median time from injury to presentation was 12 hours and median ISS was 16 (range, 4-66). All patients had computed tomography scan and serum pancreatic enzyme levels at presentation, but serial enzyme level monitoring was variable. Pancreatic enzyme levels did not correlate with injury grade or pseudocyst development. Parenteral nutrition was used in 68% and jejunal feeds in 31%. 3Endoscopic retrograde cholangiopancreatogram was obtained in 25%. An organized peripancreatic fluid collection present for at least 7 days after injury was identified in 59% (42 of 71). Initial management of these included: observation 64%, percutaneous drain 24%, and endoscopic drainage 10% and needle aspiration 2%. Clear liquids were started at a median of 6 days (IQR, 3-13 days) and regular diet at a median of 8 days (IQR 4-20 days). Median hospitalization length was 13 days (IQR, 7-24 days). Injury grade did not account for prolonged time to initiating oral diet or hospital length; indicating that the variability in these outcomes was largely due to different surgeon preferences. CONCLUSION: High-grade pancreatic injuries in children are rare and significant variability exists in NOM strategies, which may affect outcomes and effective resource utilization. A standard clinical pathway is proposed. LEVEL OF EVIDENCE: Therapeutic/care management, level V (case series).