Jan O. Jansen

Damage control resuscitation for patients with major trauma

#### Summary points Military conflict has always driven innovation and technical advances in medicine and surgery. Accepted concepts of trauma resuscitation and surgery have been challenged in the wars in Iraq and Afghanistan, and novel approaches have been developed to address the current complexity and severity of military trauma.1 A number of these new strategies have evolved into a single seamless approach that extends from the point of wounding to surgery, and on to critical care. Although the precise contribution of medical care is difficult to ascertain, better trauma management has almost certainly contributed to a remarkable reduction in the lethality of war wounds. Only 10% of United States servicemen wounded in Iraq and Afghanistan between 2003 and 2009 died, compared with 24% in the first Gulf War (1990-1991) and Vietnam War (1961-1973).w1 Initially derived from clinical experience, new concepts in caring for the injured have been refined with experiment and study and have been translated back to the battlefield in a dynamic process.2 Many of these advances are also relevant to trauma care in civilian practice. The aim of this article is to provide an overview of a new approach …

Association of cryoprecipitate and tranexamic acid with improved survival following wartime injury: findings from the MATTERs II Study

OBJECTIVE To quantify the impact of fibrinogen-containing cryoprecipitate in addition to the antifibrinolytic tranexamic acid on survival in combat injured. DESIGN Retrospective observational study comparing the mortality of 4 groups: tranexamic acid only, cryoprecipitate only, tranexamic acid and cryoprecipitate, and neither tranexamic acid nor cryoprecipitate. To balance comparisons, propensity scores were developed and added as covariates to logistic regression models predicting mortality. SETTING A Role 3 Combat Surgical Hospital in southern Afghanistan. PATIENTS A total of 1332 patients were identified from prospectively collected U.K. and U.S. trauma registries who required 1 U or more of packed red blood cells and composed the following groups: tranexamic acid (n = 148), cryoprecipitate (n = 168), tranexamic acid/cryoprecipitate (n = 258), and no tranexamic acid/cryoprecipitate (n = 758). MAIN OUTCOME MEASURE In-hospital mortality. RESULTS Injury severity scores were highest in the cryoprecipitate (mean [SD], 28.3 [15.7]) and tranexamic acid/cryoprecipitate (mean [SD], 26 [14.9]) groups compared with the tranexamic acid (mean [SD], 23.0 [19.2]) and no tranexamic acid/cryoprecipitate (mean [SD], 21.2 [18.5]) (P < .001) groups. Despite greater Injury Severity Scores and packed red blood cell requirements, mortality was lowest in the tranexamic acid/cryoprecipitate (11.6%) and tranexamic acid (18.2%) groups compared with the cryoprecipitate (21.4%) and no tranexamic acid/cryoprecipitate (23.6%) groups. Tranexamic acid and cryoprecipitate were independently associated with a similarly reduced mortality (odds ratio, 0.61; 95% CI, 0.42-0.89; P = .01 and odds ratio, 0.61; 95% CI, 0.40-0.94; P = .02, respectively). The combined tranexamic acid and cryoprecipitate effect vs. neither in a synergy model had an odds ratio of 0.34 (95% CI, 0.20-0.58; P < .001), reflecting nonsignificant interaction (P = .21). CONCLUSIONS Cryoprecipitate may independently add to the survival benefit of tranexamic acid in the seriously injured requiring transfusion. Additional study is necessary to define the role of fibrinogen in resuscitation from hemorrhagic shock.

A systematic review of the use of resuscitative endovascular balloon occlusion of the aorta in the management of hemorrhagic shock.

BACKGROUND Torso hemorrhage remains a leading cause of potentially preventable death within trauma, acute care, vascular, and obstetric practice. A proportion of patients exsanguinate before hemorrhage control. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an adjunct designed to sustain the circulation until definitive hemostasis. A systematic review was conducted to characterize the current clinical use of REBOA and its effect on hemodynamic profile and mortality. METHODS A systematic review (1946–2015) was conducted using EMBASE and MEDLINE. Original studies on human subjects, published in English language journals, were considered. Articles were included if they reported data on hemodynamic profile and mortality. RESULTS A total of 83 studies were identified; 41 met criteria for inclusion. Clinical settings included postpartum hemorrhage (5), upper gastrointestinal bleeding (3), pelvic surgery (8), trauma (15), and ruptured aortic aneurysm (10). Of the 857 patients, overall mortality was 423 (49.4%); shock was evident in 643 (75.0%). Pooled analysis demonstrated an increase in mean systolic pressure by 53 mm Hg (95% confidence interval, 44–61 mm Hg) following REBOA use. Data exhibited moderate heterogeneity with an I2 of 35.5. CONCLUSION REBOA has been used in a variety of clinical settings to successfully elevate central blood pressure in the setting of shock. Overall, the evidence base is weak with no clear reduction in hemorrhage-related mortality demonstrated. Formal, prospective study is warranted to clarify the role of this adjunct in torso hemorrhage. LEVEL OF EVIDENCE Systematic review, level IV.

Investigation of blunt abdominal trauma

#### Summary points Concealed haemorrhage is the second most common cause of death after trauma,1 and missed abdominal injuries are a frequent cause of morbidity and late mortality in patients who survive the early period after injury. Appropriate and expeditious investigation facilitates definitive management and minimises the risk of complications, so it is crucially important. #### Sources and selection criteria We searched the Medline database for reviews and clinical trials using the terms “blunt abdominal trauma”, “blunt abdominal injury”, “investigation”, “computed tomography”, “ultrasound”, “FAST”, and “diagnostic peritoneal lavage”. Search results were individually reviewed and manually cross referenced. We also searched the Cochrane Library and Clinical Evidence databases, reviewed guidelines from the American College of Radiology and the Royal College of Radiologists, and used references from our personal collections. The literature is dominated by non-randomised studies, and few systematic reviews and meta-analyses are available. Most of the evidence is level II-IV. Several high quality prospective and retrospective studies have shown non-operative management of solid organ injury to be safe and effective, and this strategy is now accepted into mainstream practice.2 3 4 In parallel, a paradigm shift has occurred in imaging algorithms, with greater emphasis being put on the detection of specific findings, rather than the mere detection of intraperitoneal fluid, which does not predict the need for intervention.5 The greater availability of computed tomography and ultrasound in emergency departments has contributed to changes in practice, but it has also created new controversies—diagnostic peritoneal lavage is now rarely performed, but the diagnosis of hollow …

Clotting Factor Deficiency in Early Trauma-Associated Coagulopathy

BACKGROUND Coagulopathic bleeding is a leading cause of in-hospital death after injury. A recently proposed transfusion strategy calls for early and aggressive frozen plasma transfusion to bleeding trauma patients, thus addressing trauma-associated coagulopathy (TAC) by transfusing clotting factors (CFs). This strategy may dramatically improve survival of bleeding trauma patients. However, other studies suggest that early TAC occurs by protein C activation and is independent of CF deficiency. This study investigated whether CF deficiency is associated with early TAC. METHODS This is a prospective observational cohort study of severely traumatized patients (Injury Severity Score ≥ 16) admitted shortly after injury, receiving minimal fluids and no prehospital blood. Blood was assayed for CF levels, thromboelastography, and routine coagulation tests. Critical CF deficiency was defined as ≤ 30% activity of any CF. RESULTS Of 110 patients, 22 (20%) had critical CF deficiency: critically low factor V level was evident in all these patients. International normalized ratio, activated prothrombin time, and, thromboelastography were abnormal in 32%, 36%, and 35%, respectively, of patients with any critically low CF. Patients with critical CF deficiency suffered more severe injuries, were more acidotic, received more blood transfusions, and showed a trend toward higher mortality (32% vs. 18%, p = 0.23). Computational modeling showed coagulopathic patients had pronounced delays and quantitative deficits in generating thrombin. CONCLUSIONS Twenty percent of all severely injured patients had critical CF deficiency on admission, particularly of factor V. The observed factor V deficit aligns with current understanding of the mechanisms underlying early TAC. Critical deficiency of factor V impairs thrombin generation and profoundly affects hemostasis.

Resuscitative endovascular balloon occlusion of the aorta: a gap analysis of severely injured UK Combat casualties

ABSTRACT The control of torso and junctional zone bleeding in combat casualties is particularly challenging because of its noncompressible nature. Resuscitative endovascular balloon occlusion of the aorta (REBOA) has demonstrated promise in translational large animal and early clinical series as an effective resuscitation and hemorrhage control adjunct. However, it is unknown what proportion of combat casualties has an injury pattern and clinical course that is amenable to REBOA deployment. The prospective UK Joint Theatre Trauma Registry was used to retrospectively identify all UK military personnel who has sustained a severe combat injury, defined as an Abbreviated Injury Scale of three or greater, in the course of 10 years. Patients were then divided into three groups based on Abbreviated Injury Scale injury pattern: no indications for REBOA, contraindications (mediastinal, cervical, and axillary hemorrhage), and indications (torso and pelvic hemorrhage). From a total of 1,317 patients, 925 (70.2%) had no indication, 148 (11.2%) had a contraindication, and 244 (18.5%) had an indication for REBOA. Within the group with indications for REBOA, there were 174 deaths: 79 at the point of wounding, 66 en route to hospital, and 29 in-hospital deaths. The median (interquartile range) time to death in patients dying en route was 75 (42–109) min, and the median prehospital time for casualties admitted to hospital was 61 (34–89) min. One-in-five severely injured UK combat casualties have a focus of hemorrhage in the abdomen or pelvic junctional region potentially amenable to REBOA deployment. The UK military should explore REBOA as a potential en route hemorrhage control and resuscitation adjunct.

Detecting critical illness outside the Icu: the role of track and trigger systems

Purpose of reviewCritical illness is often preceded by physiological deterioration. Track and trigger systems are intended to facilitate the timely recognition of patients with potential or established critical illness outside critical care areas. The aim of this article is to review the evidence for the use of such systems. Recent findingsExisting track and trigger systems have low sensitivity, low positive predictive values, and high specificity. They often fail to identify patients who need additional care and have not been shown to improve outcomes. The development of such systems must be based on robust methodological and statistical principles. At present, few track and trigger systems meet these standards. SummaryAlthough track and trigger systems, combined with appropriate response algorithms, have the potential to improve the recognition and management of critical illness, further work is required to validate their utility.

Injury pattern and mortality of noncompressible torso hemorrhage in UK combat casualties.

BACKGROUND Hemorrhage following traumatic injury is a leading cause of military and civilian mortality. Noncompressible torso hemorrhage (NCTH) has been identified as particularly lethal, especially in the prehospital setting. METHODS All patients sustaining NCTH between August 2002 and July 2012 were identified from the UK Joint Theatre Trauma Registry. NCTH was defined as injury to a named torso axial vessel, pulmonary injury, solid-organ injury (Grade 4 or greater injury to the liver, kidney, or spleen) or pelvic fracture with ring disruption. Patients with ongoing hemorrhage were identified using either a systolic blood pressure of less than 90 mm Hg or the need for immediate surgical hemorrhage control. Data on injury pattern and location as well as cause of death were analyzed using univariate and multivariate analyses. RESULTS During 10 years, 296 patients were identified with NCTH, with a mortality of 85.5%. The majority of deaths occurred before hospital admission (n = 222, 75.0%). Of patients admitted to hospital, survivors (n = 43, 14.5%) had a higher median systolic blood pressure (108 [43] vs. 89 [46], p = 0.123) and Glasgow Coma Scale (GCS) (14 [12] vs. 3 [0], p < 0.001) compared with in-hospital deaths (n = 31, 10.5%). Hemorrhage was the more common cause of death (60.1%), followed by central nervous system disruption (30.8%), total body disruption (5.1%), and multiple-organ failure (4.0%). On multivariate analysis, major arterial and pulmonary hilar injury are most lethal with odds ratio (95% confidence interval) of 16.44 (5.50–49.11) and 9.61 (1.06–87.00), respectively. CONCLUSION This study demonstrates that the majority of patients sustaining NCTH die before hospital admission, with exsanguination and central nervous system disruption contributing to the bulk cause of death. Major arterial and pulmonary hilar injuries are independent predictors of mortality. LEVEL OF EVIDENCE Epidemiologic study, level III.

Hypoperfusion in severely injured trauma patients is associated with reduced coagulation factor activity.

BACKGROUND Recent studies have shown that acute traumatic coagulopathy is associated with hypoperfusion, increased plasma levels of soluble thrombomodulin, and decreased levels of protein C but with no change in factor VII activity. These findings led to the hypothesis that acute traumatic coagulopathy is primarily due to systemic anticoagulation, by activated protein C, rather than decreases in serine protease activity. This study was designed to examine the effect of hypoperfusion secondary to traumatic injury on the activity of coagulation factors. METHODS Post hoc analysis of prospectively collected data on severely injured adult trauma patients presenting to a single trauma center within 120 minutes of injury. Venous blood was analyzed for activity of factors II, V, VII, VIII, IX, X, and XI. Base deficit from arterial blood samples was used as a marker of hypoperfusion. RESULTS Seventy-one patients were identified. The activity of factors II, V, VII, IX, X, and XI correlated negatively with base deficit, and after stratification into three groups, based on the severity of hypoperfusion, a statistically significant dose-related reduction in the activity of factors II, VII, IX, X, and XI was observed. Hypoperfusion is also associated with marked reductions in factor V activity levels, but these appear to be relatively independent of the degree of hypoperfusion. The activity of factor VIII did not correlate with base deficit. CONCLUSIONS Hypoperfusion in trauma patients is associated with a moderate, dose-dependent reduction in the activity of coagulation factors II, VII, IX, X, and XI, and a more marked reduction in factor V activity, which is relatively independent of the severity of shock. These findings suggest that the mechanisms underlying decreased factor V activity--which could be due to activated protein C mediated cleavage, thus providing a possible link between the proposed thrombomodulin/thrombin-APC pathway and the serine proteases of the coagulation cascade--and the reductions in factors II, VII, IX, X, and XI may differ. Preservation of coagulation factor activity in the majority of normally and moderately hypoperfused patients suggests that aggressive administration of plasma is probably only indicated in severely hypoperfused patients. Markers of hypoperfusion, such as base deficit, might be better and more readily available predictors of who require coagulation support than international normalized ratio or activated partial thromboplastin time.

Prehospital blood transfusion in the en route management of severe combat trauma: a matched cohort study.

BACKGROUND The value of prehospital blood transfusion (PHBTx) in the management of severe trauma has not been established. This study aimed to evaluate the effect of PHBTx on mortality in combat casualties. METHODS This is a retrospective cohort study of casualties admitted to the field hospital at Camp Bastion, Afghanistan, by the Medical Emergency Response Team from May 2006 to March 2011. Participants were divided into two consecutive cohorts by the introduction of PHBTx. Paired groups of patients were chosen by combining propensity score methodology with detailed matching of injury profile. Thus recipients of PHBTx were matched with nonrecipients who would have received it had it been available. RESULTS A total of 1,592 patients were identified. Of the 1,153 patients to whom PHBTx was potentially available, 310 received it (26.9%). The rate of severe injury (Injury Severity Score [ISS] > 15) rose from 28% before PHBTx was available to 43% thereafter (p < 0.001). Mortality in the latter group was higher (14% vs. 10%, p = 0.013) but not in the severely injured patients (32% vs. 28%, p = 0.343). Ninety-seven patients were paired. The mortality of matched patients who received PHBTx, compared with those with similar injury patterns who did not, was less than half (8.2% vs. 19.6%, p < 0.001). However, matched recipients had more prehospital interventions, reached hospital more quickly, and had lower heart rate at admission (all p < 0.05). Matched recipients received more red blood cells within 24 hours (median, 4 U; interquartile range [IQR], 2–10 U) than nonrecipients (median 0 U; IQR, 0–3.5 U) and more fresh frozen plasma (median, 2 U; IQR, 2–9 U vs. median, 0 U; IQR, 0–1 U) (both p < 0.001). CONCLUSION An aggressive approach to damage control resuscitation including the use of PHBTx was associated with a large improvement in mortality. However, because of confounders resulting from changes in practice, the isolated contribution of PHBTx cannot be determined from this study. LEVEL OF EVIDENCE Therapeutic study, level IV.