Causes and associations with mortality in patients with pelvic ring injuries with haemorrhagic shock.

BACKGROUND: High energy pelvic ring injuries are associated with significant morbidity and mortality and can be accompanied by haemorrhagic shock following associated vascular injury. This study evaluated the causes and predictors of mortality in haemodynamically unstable pelvic fractures. METHODS: This retrospective observational study at a Major Trauma Centre reviewed 938 consecutive adult patients (≥ 18yrs) with pelvic ring injuries between December 2014 and November 2018. Patients with features of haemorrhagic shock were included, defined as: arrival Systolic BP < 90 mmHg, Base Deficit ≥ 6.0 mmol/l, or transfusion of ≥ 4 units of packed red blood cells within 24 h. RESULTS: Of the 102 patients included, all sustained injuries from high energy trauma, and 47.1% underwent a haemorrhage control intervention (Resuscitative Endovascular Balloon Occlusion of the Aorta-REBOA, Interventional Radiology-IR, or Laparotomy). These were more often required following vertical shear injuries (OR 10.7, p = 0.036). Overall, 33 patients (32.4%) died; 16 due to a head injury, and only 2 directly from acute pelvic exsanguination (6.1%). Multivariable logistic regression demonstrated that increasing age, Injury Severity Score, Abbreviated Injury Scale (AIS) Head ≥ 3 and open pelvic fracture were all independent predictors of mortality, and IR was associated with reduced mortality. Lateral Compression III (LC3) injuries were associated with mortality due to multiple organ dysfunction syndrome (MODS). CONCLUSION: Haemodynamically unstable patients with pelvic ring injuries have a high mortality rate, but death is usually attributed to other injuries or later complications, and not from acute exsanguination. This reflects improvements in resuscitative care, transfusion protocols, and haemorrhage control techniques.

Impact of resuscitative endovascular balloon occlusion of the aorta (REBOA) in traumatic abdominal and pelvic exsanguination: a systematic review and meta-analysis.

PURPOSE: Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) represents a minimally invasive technique of aortic occlusion (AO). It has been demonstrated to be safe and effective with appropriate training in traumatic hemorrhage with hemodynamic instability; however, its indications are still debated. The aim of this systematic review and meta-analysis is to assess the impact of REBOA on mortality in torso trauma patient with severe non-compressible hemorrhage compared to other temporizing hemostatic techniques. STUDY DESIGN: The primary outcome is represented by 24-h, and in-hospital mortality. Secondary outcomes are post-procedural hemodynamic improvement (systolic blood pressure-SBP), mean injury severity score (ISS) differences, treatment-related morbidity, transfusional requirements and identification of prognostic factors. RESULTS: A significant survival benefit at 24 h (RR 0.46; 95% CI 0.27-0.79; I2: 55%; p = 0.005) was highlighted in patients undergoing REBOA. Regarding in-hospital mortality (RR 0.99; 95% CI 0.75-1.32; I2: 73%; p = 0.98) no differences in risk of death were noticed. A hemodynamic improvement-although not significant-was highlighted, with 55.8 mmHg post-AO SBP mean difference between REBOA and control groups. A significantly lower mean number of packed Red Blood Cells (pRBCs) was noticed for REBOA patients (mean difference: - 3.02; 95% CI - 5.79 to - 0.25; p = 0.033). Nevertheless, an increased risk of post-procedural complications (RR 1.66; 95% CI 0.39-7.14; p = 0.496) was noticed in the REBOA group. CONCLUSIONS: REBOA may represent a valid tool in the initial treatment of multiple sites subdiaphragmatic hemorrhage with refractory hemodynamic instability. However, due to several important limitations of the present study, our findings should be interpreted with caution. LEVEL OF EVIDENCE: Level III according to ELIS (SR/MA with up to two negative criteria).

Development of a Selective Aortic Arch Perfusion System in a Porcine Model of Exsanguination Cardiac Arrest.

Hemorrhage constitutes the majority of potentially preventable deaths from trauma. There is growing interest in endovascular resuscitation techniques such as selective aortic arch perfusion (SAAP) for patients in cardiac arrest. This involves active perfusion of the coronary circulation via a thoracic aortic balloon catheter and is approaching clinical application. However, the technique is complex and requires refinement in animal models before human use can be considered. This paper describes a large animal model of exsanguination cardiac arrest treated with a bespoke SAAP system. Swine were anesthetized, instrumented and a splenectomy was performed before a controlled, logarithmic exsanguination was initiated. Animals were heparinized and the shed blood collected in a reservoir. Once cardiac arrest was observed, the blood was pumped through an extra-corporeal circuit into an oxygenator and then delivered through a 10 Fr balloon catheter placed in the thoracic aorta. This resulted in the return of a spontaneous circulation (ROSC) as demonstrated by ECG and aortic root pressure waveform. This model and accompanying SAAP system allow for standardized and reproducible recovery from exsanguination cardiac arrest.

Selective aortic arch perfusion with fresh whole blood or HBOC-201 reverses hemorrhage-induced traumatic cardiac arrest in a lethal model of noncompressible torso hemorrhage.

BACKGROUND: Hemorrhage-induced traumatic cardiac arrest (HiTCA) has a dismal survival rate. Previous studies demonstrated selective aortic arch perfusion (SAAP) with fresh whole blood (FWB) improved the rate of return of spontaneous circulation (ROSC) after HiTCA, compared with resuscitative endovascular balloon occlusion of the aorta and cardiopulmonary resuscitation (CPR). Hemoglobin-based oxygen carriers, such as hemoglobin-based oxygen carrier (HBOC)-201, may alleviate the logistical constraints of using FWB in a prehospital setting. It is unknown whether SAAP with HBOC-201 is equivalent in efficacy to FWB, whether conversion from SAAP to extracorporeal life support (ECLS) is feasible, and whether physiologic derangement post-SAAP therapy is reversible. METHODS: Twenty-six swine (79 ± 4 kg) were anesthetized and underwent HiTCA which was induced via liver injury and controlled hemorrhage. Following arrest, swine were randomly allocated to resuscitation using SAAP with FWB (n = 12) or HBOC-201 (n = 14). After SAAP was initiated, animals were monitored for a 20-minute prehospital period prior to a 40-minute damage control surgery and resuscitation phase, followed by 260 minutes of critical care. Primary outcomes included rate of ROSC, survival, conversion to ECLS, and correction of physiology. RESULTS: Baseline physiologic measurements were similar between groups. ROSC was achieved in 100% of the FWB animals and 86% of the HBOC-201 animals (p = 0.483). Survival (t = 320 minutes) was 92% (11/12) in the FWB group and 67% (8/12) in the HBOC-201 group (p = 0.120). Conversion to ECLS was successful in 100% of both groups. Lactate peaked at 80 minutes in both groups, and significantly improved by the end of the experiment in the HBOC-201 group (p = 0.001) but not in the FWB group (p = 0.104). There was no significant difference in peak or end lactate between groups. CONCLUSION: Selective aortic arch perfusion is effective in eliciting ROSC after HiTCA in a swine model, using either FWB or HBOC-201. Transition from SAAP to ECLS after definitive hemorrhage control is feasible, resulting in high overall survival and improvement in lactic acidosis over the study period.

Safety of direct true lumen cannulation after venous exsanguination: a study in a surviving porcine model†.

OBJECTIVES: Type A aortic dissection requires immediate surgery. Traditional cannulation methods such as the central aortic cannulation with the Seldinger technique and axillary cannulation are primary choices. Yet in the presence of tamponade or severe cardiogenic shock, these can be too time-consuming to complete. Direct true lumen cannulation after venous exsanguination not only avoids this issue but also leads to transient global ischaemia. We studied the safety of direct true lumen cannulation from the aspect of global ischaemia in a surviving porcine model. METHODS: Twelve pigs were randomized to either control or intervention groups (6 + 6). The intervention group underwent simulated direct true lumen cannulation by exsanguination and circulatory arrest for 5 min at 35°C before cardiopulmonary bypass (CPB). Both groups underwent CPB cooling to 25°C followed by a 25-min arrest period and subsequent warming to 36°C. Neuron-specific enolase levels were measured at 6 time-points from blood samples. Near-infrared spectroscopy was used to determine brain oxygenation. The neurological recovery was evaluated daily during a 7-day follow-up, and the brain was harvested for a histopathological analysis after euthanization. RESULTS: All pigs recovered their normal neurological behaviour. The neurobehavioural total score on postoperative day 2 reached borderline statistical significance, thus favouring the intervention group [(9 (8.75-9) vs 6.5 (5.5-9), P = 0.06]. Near-infrared spectroscopy values and neuron-specific enolase levels slightly favoured the control group during the cooling period, but the difference was not clinically significant. The histopathological analysis showed no difference between the groups. CONCLUSIONS: A 5-min period of normothermic global ischaemia before CPB does not impair the neurological outcome following hypothermic circulatory arrest in a surviving porcine model.

A systematic review and meta-analysis of the use of resuscitative endovascular balloon occlusion of the aorta in the management of major exsanguination.

BACKGROUND: Circulatory collapse is a leading cause of mortality among traumatic major exsanguination and in ruptured aortic aneurysm patients. Approximately 40% of patients die before hemorrhage control is achieved. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an adjunct designed to sustain the circulation until definitive surgical or endovascular repair. A systematic review was conducted for the current clinical use of REBOA in patients with hemodynamic instability and to discuss its potential role in improving prehospital and in-hospital outcome. METHODS: Systematic review and meta-analysis (1900-2017) using MEDLINE, Cochrane, EMBASE, Web of Science and Central and Emcare using the keywords "aortic balloon occlusion", "aortic balloon tamponade", "REBOA", and "Resuscitative Endovascular Balloon Occlusion" in combination with hemorrhage control, hemorrhage, resuscitation, shock, ruptured abdominal or thoracic aorta, endovascular repair, and open repair. Original published studies on human subjects were considered. RESULTS: A total of 490 studies were identified; 89 met criteria for inclusion. Of the 1436 patients, overall reported mortality was 49.2% (613/1246) with significant differences (p < 0.001) between clinical indications. Hemodynamic shock was evident in 79.3%, values between clinical indications showed significant difference (p < 0.001). REBOA was favored as treatment in trauma patients in terms of mortality. Pooled analysis demonstrated an increase in mean systolic pressure by almost 50 mmHg following REBOA use. CONCLUSION: REBOA has been used in trauma patients and ruptured aortic aneurysm patients with improvement of hemodynamic parameters and outcomes for several decades. Formal, prospective study is warranted to clarify the role of this adjunct in all hemodynamic unstable patients.

Development of the emergency preservation and resuscitation for cardiac arrest from trauma clinical trial.

BACKGROUND: Patients who suffer a cardiac arrest from trauma rarely survive, even with aggressive resuscitation attempts, including an emergency department thoracotomy. Emergency Preservation and Resuscitation (EPR) was developed to utilize hypothermia to buy time to obtain hemostasis before irreversible organ damage occurs. Large animal studies have demonstrated that cooling to tympanic membrane temperature 10°C during exsanguination cardiac arrest can allow up to 2 hours of circulatory arrest and repair of simulated injuries with normal neurologic recovery. STUDY DESIGN: The Emergency Preservation and Resuscitation for Cardiac Arrest from Trauma trial has been developed to test the feasibility and safety of initiating EPR. Select surgeons will be trained in the EPR technique. If a trained surgeon is available, the subject will undergo EPR. If not, the subject will be followed as a control subject. For this feasibility study, 10 EPR and 10 control subjects will be enrolled. STUDY PARTICIPANTS: Study participants will be those with penetrating trauma who remain pulseless despite an emergency department thoracotomy. INTERVENTIONS: Emergency Preservation and Resuscitation will be initiated via an intra-aortic flush of a large volume of ice-cold saline solution. Following surgical hemostasis, delayed resuscitation will be accomplished with cardiopulmonary bypass. OUTCOME MEASURES: The primary outcome will be survival to hospital discharge without significant neurologic deficits. Secondary outcomes include long-term survival and functional outcome. IMPLICATIONS: Once data from these 20 subjects are reviewed, revisions to the inclusion criteria and/or the EPR technique may then be tested in a second set of EPR and control subjects.

1: 1 Transfusion strategies are right for the wrong reasons.

BACKGROUND: Early assessment of clot function identifies coagulopathies after injury. Abnormalities include a hypercoagulable state from excess thrombin generation, as well as an acquired coagulopathy. Efforts to address coagulopathy have resulted in earlier, aggressive use of plasma emphasizing 1:1 resuscitation. The purpose of this study was to describe coagulopathies in varying hemorrhagic profiles from a cohort of injured patients. METHODS: All injured patients who received at least one unit of packed red blood cells (PRBC) in the first 24 hours of admission from September 2013 to May 2015 were eligible for inclusion. Group-Based Trajectory Modeling, using volume of transfusion over time, was used to identify specific hemorrhagic phenotypes. The thromboelastography profile of each subgroup was characterized and group features were compared. RESULTS: Four hemorrhagic profiles were identified among 330 patients-minimal (MIN, group 1); patients with large PRBC requirements later in the hospital course (LH, group 2); massive PRBC usage (MH, group 3), and PRBC transfusion limited to shortly after injury (EH, group 4). All groups had an R-time shorter than the normal range (3.2-3.5, p = NS). Patients in group 3 had longer K-times (1.8 vs. 1.2-1.3, p < 0.05), significantly flatter α-angles (66.7 vs. 70.4-72.8, p < 0.05), and significantly weaker clot strength (MA 54.6 vs. 62.3-63.6, p < 0.05). Group 3 had greater physiologic derangements at admission and worse overall outcomes. CONCLUSION: Hemorrhagic profiles suggest a rapid onset of clot formation in all subgroups but significantly suppressed thrombin burst and diminished clot strength in the most injured. Patients are both hypercoagulable, with early and precipitous clot formation, and also have a demonstrable hypocoagulability. The exact cause of traumatic hypocoagulability is likely multifactorial. Goal-directed resuscitation, as early as institution of the massive transfusion protocol, may be more effective in resuscitating the most coagulopathic patients. LEVEL OF EVIDENCE: Prognostic study, level III.

Diet-induced obesity prevents the development of acute traumatic coagulopathy.

BACKGROUND: Obesity and hemorrhagic shock following trauma are predictors of mortality but have conflicting effects on coagulation. Following hemorrhage, tissue injury and hypoperfusion lead to acute traumatic coagulopathy (ATC), producing a hypocoagulable state. Inversely, obesity promotes clotting and impairs fibrinolysis to yield a hypercoagulable state. High rates of venous thromboembolism, organ failure, and early mortality may be caused by hypercoagulability in obese patients. We hypothesize that obesity prevents the development of ATC following injury-induced hemorrhagic shock. METHODS: Male Sprague-Dawley rats (250-275 g) were fed a high-fat diet (32%kcal from fat) for 4 weeks to 6 weeks and diverged into obesity-resistant (OR, n = 9) and obesity-prone (OP, n = 9) groups. Age-matched control (CON) rats were fed normal diet (10% kcal from fat, n = 9). Anesthetized rats were subjected to an uncontrolled hemorrhage by a Grade V splenic injury to a mean arterial pressure (MAP) of 40 mm Hg. Hypotension (MAP, 30-40 mm Hg) was maintained for 30 minutes to induce shock. MAP, heart rate, lactate, base excess, cytokines, blood loss, and thrombelastography (TEG) parameters were measured before and after hemorrhagic shock. RESULTS: At baseline, OP rats exhibited a shorter time to 20-mm clot (K), and higher rate of clot formation (α angle), clot strength (maximal amplitude), and coagulation index, compared with the CON rats (p < 0.05), indicating enhanced coagulation. Physiologic parameters following shock were similar between groups. In the CON and OR rats, shock prolonged the time to clot initiation (R) and K and decreased α angle and coagulation index (all p < 0.05 vs. baseline). In contrast, shock had no effect on these TEG parameters in the OP rats. Maximal amplitude was the only TEG parameter affected by shock in the OP rats, which was decreased in all groups. CONCLUSION: Obesity prevents the development of ATC following hemorrhage shock. Complications associated with obesity following hemorrhagic shock may be attributed to the preserved hypercoagulable state.

Hemostatic resuscitation is neither hemostatic nor resuscitative in trauma hemorrhage.

BACKGROUND: Trauma hemorrhage continues to carry a high mortality rate despite changes in modern practice. Traditional approaches to the massively bleeding patient have been shown to result in persistent coagulopathy, bleeding, and poor outcomes. Hemostatic (or damage control) resuscitation developed from the discovery of acute traumatic coagulopathy and increased recognition of the negative consequences of dilutional coagulopathy. These strategies concentrate on early delivery of coagulation therapy combined with permissive hypotension. The efficacy of hemostatic resuscitation in correcting coagulopathy and restoring tissue perfusion during acute hemorrhage has not been studied. METHODS: This is a prospective cohort study of ROTEM and lactate measurements taken from trauma patients recruited to the multicenter Activation of Coagulation and Inflammation in Trauma (ACIT) study. A blood sample is taken on arrival and during the acute bleeding phase after administration of every 4 U of packed red blood cells (PRBCs), up to 12 U. The quantity of blood products administered within each interval is recorded. RESULTS: Of the 106 study patients receiving at least 4 U of PRBC, 27 received 8 U to 11 U of PRBC and 31 received more than 12 U of PRBC. Average admission lactate was 6.2 mEq/L. Patients with high lactate (≥5 mEq/L) on admission did not clear lactate until hemorrhage control was achieved, and no further PRBC units were required. On admission, 43% of the patients were coagulopathic (clot amplitude at 5 minutes ≤ 35 mm). This increased to 49% by PRBC 4; 62% by PRBC 8 and 68% at PRBC 12. The average fresh frozen plasma/PRBC ratio between intervals was 0.5 for 0 U to 4 U of PRBC, 0.9 for 5 U to 8 U of PRBC, 0.7 for 9 U to 12 U of PRBC. There was no improvement in any ROTEM parameter during ongoing bleeding. CONCLUSION: While hemostatic resuscitation offers several advantages over historical strategies, it still does not achieve correction of hypoperfusion or coagulopathy during the acute phase of trauma hemorrhage. Significant opportunities still exist to improve management and improve outcomes for bleeding trauma patients. LEVEL OF EVIDENCE: Epidemiologic study, level III.

Targeted resuscitation improves coagulation and outcome.

BACKGROUND: Acute trauma coagulopathy in seriously injured casualties may be initiated by tissue hypoperfusion. A targeted (or novel hybrid [NH]) resuscitation strategy was developed to overcome poor tissue oxygen delivery associated with prolonged hypotension. METHODS: Under the Animals (Scientific Procedures) Act 1986, terminally anesthetized large white pigs were divided into four groups (n = 6). Groups 1 and 2 received blast injury and 3 and 4 no blast (sham). All were given a controlled hemorrhage (35% blood volume) and an uncompressed grade IV liver injury. Five minutes later, all were resuscitated with 0.9% saline to a systolic arterial pressure (SAP) of 80 mm Hg. After 60 minutes, the NH groups (1 and 3) were resuscitated to a SAP (110 mm Hg), whereas hypotensive groups (2 and 4) continued with SAP 80 mm Hg for up to 8 hours from onset of resuscitation. RESULTS: Mean survival time was shorter in group 2 (258 minutes) compared with groups 1, 3, and 4 (452 minutes, 448 minutes, and 369 minutes). By the end of the study, hypotension was associated with a significantly greater prothrombin time (1.73 ± 0.10 and 1.87 ± 0.15 times presurgery, groups 2 and 4) compared with NH (1.44 ± 0.09 and 1.36 ± 0.06, groups 1 and 3, p = 0.001). Blast versus sham had no significant effect on prothrombin time (p = 0.56). Peak levels of interleukin 6 were significantly lower in NH groups. Arterial base excess was significantly lower with hypotension (-18.4 mmol/L ± 2.7 mmol/L and -12.1 mmol/L ± 3.2 mmol/L) versus NH (-3.7 mmol/L ± 2.8 mmol/L and -1.8 mmol/L ± 1.8 mmol/L, p = 0.0001). Hematocrit was not significantly different between groups (p = 0.16). CONCLUSION: Targeted resuscitation (NH) attenuates the development of acute trauma coagulopathy and systemic inflammation with improved tissue perfusion and reduced metabolic acidosis in a model of complex injury. This emphasizes the challenge of choosing a resuscitation strategy for trauma patients where the needs of tissue perfusion must be balanced against the risk of rebleeding during resuscitation.

Transfusion-related acute lung injury in a rat model of trauma-hemorrhage.

BACKGROUND: Major trauma often causes hemorrhage and predisposes to transfusion-related acute lung injury (TRALI). TRALI is a leading cause of transfusion-related deaths; however, its pathophysiology is uncertain. In the existing two-event models of TRALI, infection (lipopolysaccharide injection) is followed by the infusion of aged blood products. Our objective was to develop a trauma-relevant two-event model of TRALI by examining the effect of aged packed red blood cells (PRBC) on lung injury in rats with trauma-hemorrhage. METHODS: Male Lewis rats were used. Rat PRBC were prepared similar to human PRBC. Recipients were implanted with femoral arterial and venous catheters (isoflurane anesthesia) and then subjected to 30% controlled arterial hemorrhage after 16-hour recovery. After a 60-minute shock period, rats were resuscitated with crystalloid and PRBC (0-35 days old; 3:1 ratio) and followed for up to 6 hours. Lung edema was evaluated by Evans blue dye (EBD), protein, and cytokine-induced neutrophil chemoattractant-1 (CINC-1) accumulation in bronchoalveolar lavage fluid, and arterial blood gases were measured (iSTAT). RESULTS: CINC-1 levels increased over time in our PRBC stored for over 21 days. Transfusion survival was reduced, and Evans blue dye, protein, and CINC-1 accumulation in bronchoalveolar lavage fluid were increased in rats transfused with 28-day-old and 35-day-old PRBC compared with the 0-day group. Arterial PO2 and O2 saturation were decreased in rats transfused with 28-day-old and 35-day-old PRBC. However, pH and PCO2 were not different between groups. CONCLUSIONS: These results suggest that transfusion of 28-day-old and 35-day-old PRBC reliably promotes lung edema in a rat model of catheter surgery and hemorrhage. We propose that this model can be used as a trauma-relevant two-event model of TRALI.