Christine Gaarder

Definition and drivers of acute traumatic coagulopathy: clinical and experimental investigations

Summary.  Background: Acute traumatic coagulopathy (ATC) is an impairment of hemostasis that occurs early after injury and is associated with a 4‐fold higher mortality, increased transfusion requirements and organ failure. Objectives: The purpose of the present study was to develop a clinically relevant definition of ATC and understand the etiology of this endogenous coagulopathy. Patients/methods: We conducted a retrospective cohort study of trauma patients admitted to five international trauma centers and corroborated our findings in a novel rat model of ATC. Coagulation status on emergency department arrival was correlated with trauma and shock severity, mortality and transfusion requirements. 3646 complete records were available for analysis. Results: Patients arriving with a prothrombin time ratio (PTr) > 1.2 had significantly higher mortality and transfusion requirements than patients with a normal PTr (mortality: 22.7% vs. 7.0%; P < 0.001. Packed red blood cells: 3.5 vs. 1.2 units; P < 0.001. Fresh frozen plasma: 2.1 vs. 0.8 units; P < 0.001). The severity of ATC correlated strongly with the combined degree of injury and shock. The rat model controlled for exogenously induced coagulopathy and mirrored the clinical findings. Significant coagulopathy developed only in animals subjected to both trauma and hemorrhagic shock (PTr: 1.30. APTTr: 1.36; both P < 0.001 compared with sham controls). Conclusions: ATC develops endogenously in response to a combination of tissue damage and shock. It is associated with increased mortality and transfusion requirements in a dose‐dependent manner. When defined by standard clotting times, a PTr > 1.2 should be adopted as a clinically relevant definition of ATC.

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.

Reappraising the concept of massive transfusion in trauma

IntroductionThe massive-transfusion concept was introduced to recognize the dilutional complications resulting from large volumes of packed red blood cells (PRBCs). Definitions of massive transfusion vary and lack supporting clinical evidence. Damage-control resuscitation regimens of modern trauma care are targeted to the early correction of acute traumatic coagulopathy. The aim of this study was to identify a clinically relevant definition of trauma massive transfusion based on clinical outcomes. We also examined whether the concept was useful in that early prediction of massive transfusion requirements could allow early activation of blood bank protocols.MethodsDatasets on trauma admissions over a 1 or 2-year period were obtained from the trauma registries of five large trauma research networks. A fractional polynomial was used to model the transfusion-associated probability of death. A logistic regression model for the prediction of massive transfusion, defined as 10 or more units of red cell transfusions, was developed.ResultsIn total, 5,693 patient records were available for analysis. Mortality increased as transfusion requirements increased, but the model indicated no threshold effect. Mortality was 9% in patients who received none to five PRBC units, 22% in patients receiving six to nine PRBC units, and 42% in patients receiving 10 or more units. A logistic model for prediction of massive transfusion was developed and validated at multiple sites but achieved only moderate performance. The area under the receiver operating characteristic curve was 0.81, with specificity of only 50% at a sensitivity of 90% for the prediction of 10 or more PRBC units. Performance varied widely at different trauma centers, with specificity varying from 48% to 91%.ConclusionsNo threshold for definition exists at which a massive transfusion specifically results in worse outcomes. Even with a large sample size across multiple trauma datasets, it was not possible to develop a transportable and clinically useful prediction model based on available admission parameters. Massive transfusion as a concept in trauma has limited utility, and emphasis should be placed on identifying patients with massive hemorrhage and acute traumatic coagulopathy.

Prevalence, predictors and outcome of hypofibrinogenaemia in trauma: a multicentre observational study

IntroductionExsanguination due to trauma-induced coagulopathy is a continuing challenge in emergency trauma care. Fibrinogen is a crucial factor for haemostatic competence, and may be the factor that reaches critically low levels first. Early fibrinogen substitution is advocated by a number of authors. Little evidence exists regarding the indications for fibrinogen supplementation in the acute phase. This study aims to estimate the prevalence of hypofibrinogenaemia in a multi-center trauma population, and to explore how initial fibrinogen concentration relates to outcome. Also, factors contributing to low fibrinogen levels are identified.MethodsPatients arriving in hospital less than 180 minutes post-injury requiring full trauma team activation in four different centers were included in the study. Time from injury, patient demographics, injury severity scores (ISS) and 28 days outcome status were recorded. Initial blood samples for coagulation and blood gas were analyzed. Generalized additive regression, piecewise linear regression, and multiple linear regression models were used for data analyses.ResultsOut of 1,133 patients we identified a fibrinogen concentration ≤1.5g/L in 8.2%, and <2 g/L in 19.2%. A non-linear relationship between fibrinogen concentration and mortality was detected in the generalized additive and piecewise linear regression models. In the piecewise linear regression model we identified a breakpoint for optimal fibrinogen concentration at 2.29 g/L (95% confidence interval (CI): 1.93 to 2.64). Below this value the odds of death by 28 days was reduced by a factor of 0.08 (95% CI: 0.03 to 0.20) for every unit increase in fibrinogen concentration. Low age, male gender, lengthened time from injury, low base excess and high ISS were unique contributors to low fibrinogen concentrations on arrival.ConclusionsHypofibrinogenaemia is common in trauma and strongly associated with poor outcome. Below an estimated critical fibrinogen concentration value of 2.29 g/L a dramatic increase in mortality was detected. This finding indicates that the negative impact of low fibrinogen concentrations may have been previously underestimated. A number of clinically identifiable factors are associated with hypofibrinogenaemia. They should be considered in the management of massively bleeding patients. Interventional trials with fibrinogen substitution in high-risk patients need to be undertaken.

Scandinavian guidelines - "The massively bleeding patient"

c. gaarder, Trauma Unit, Ullevål University Hospital, Oslo, Norway p. a. naess, Trauma Unit, Ullevål University Hospital, Oslo, Norway e. Frischknecht christensen, Aarhus Trauma Centre, Aarhus University Hospital, Denmark p. hakala, Department of Anaesthesia and Intensive Care, Helsinki University Hospital, Finland l. handolin, Department of Orthopaedics and Traumatology, Helsinki University Hospital, Finland h. e. heier, Department of Immunology and Transfusion Medicine, Ullevål University Hospital, Oslo, Norway K. ivancev, Endovascular Centre, Malmö University Hospital, Malmö, Sweden p. Johansson, Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark a. leppäniemi, Department of Surgery, Meilahti Hospital, University of Helsinki, Helsinki, Finland F. lippert, Department of Anaesthesia and Intensive Care, Rigshospitalet, Copenhagen, Denmark h. m. lossius, Norwegian Air Ambulance, Drøbak, Norway h. Opdahl, Intensive Care Unit/NBC centre, Ullevål University Hospital, Oslo, Norway J. pillgram-larsen, Department of Cardiothoracic Surgery, Ullevål University Hospital, Oslo, Norway O. Røise, Orthopaedic Centre, Ullevål University Hospital, Oslo, Norway n. O. skaga, Department of Anaesthesia, Ullevål University Hospital, Oslo, Norway e. søreide, Department of Anaesthesia and Intensive Care, Stavanger University Hospital, Stavanger, Norway J. stensballe, Department of Anaesthesia, Rigshospitalet, Copenhagen, Denmark e. Tønnessen, Department of Anaesthesia and Intensive Care, Aarhus University Hospital, Aarhus, Denmark a. Töttermann, Department of Orthopaedics, Uppsala University Hospital, Uppsala, Sweden p. ́́ Ortenwall, Trauma Unit, Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden a. ́́ Ostlund, Department of Anaesthesia and Intensive care, Karolinska University Hospital, Stockholm, Sweden

Evaluation of TEG® and RoTEM® inter-changeability in trauma patients

BACKGROUND Massive haemorrhage is a leading cause of preventable deaths in trauma. Traumatic coagulopathy is frequently present early after trauma, and is associated with increased mortality. A number of recent trials suggest that viscoelastic haemostatic assays (VHA), such as thromboelastography and thromboelastometry, are useful tools in guiding transfusion. Treatment algorithms exist for the use of VHAs but are not validated in traumatic haemorrhage. In this study we examined the inter-changeability of two commonly used VHAs, TEG(®) and RoTEM(®). METHODS A total of 184 trauma patients over the age of 18, requiring full trauma team activation, were included at three different hospitals in three different countries (Copenhagen, Denmark, San Francisco, CA, USA and Oslo, Norway). Blood samples were drawn immediately upon arrival, and TEG(®) and RoTEM(®) analyzed simultaneously. Correlations were calculated using. Spearmans rank correlation coefficient. Agreement was evaluated by Bland-Altman plots and calculation of limits of agreement. RESULTS The mean ISS in the total population was 17, and the mortality was 16.5%. Mean base excess was -2.8 (SD: 4.2). The correlation coefficient for corresponding values for the two devices was 0.24 for the R-time vs CT in all centres combined. For the K-time vs CFT the correlation was 0.48, for the α-angleTEG vs α-angleRoTEM 0.44, and for MA vs MCF 0.76. Limits of agreement exceeded the preset clinically acceptable deviation of 10% for all variables in all centres except for MA/MCF in one centre (Copenhagen). Generally, correlation coefficients were lower and agreement poorer in the one centre (Oslo) where measurements were performed bedside by clinicians. CONCLUSION Inter-changeability between TEG(®) and RoTEM(®) is limited in the trauma setting. Agreement seems poorer when clinicians operate the devices. Development and validation of separate treatment algorithms for the two devices is required.

Ultrasound performed by radiologists-confirming the truth about FAST in trauma.

BACKGROUND For hemodynamically stable patients with suspected abdominal injuries, the diagnostic accuracy of computed tomographic scans remains unmatched. Focused assessment with sonography for trauma (FAST) is useful in trauma evaluation to identify intraabdominal fluid early in the unstable patient. In skilled hands, sensitivity is shown to be close to 100%. However, some recent studies have questioned its sensitivity in subgroups at risk of bleeding. In most studies, hemodynamic markers of instability have been limited to hypotension. The purpose of this study was to determine the sensitivity and specificity of initial FAST for detection of hemoperitoneum in the potentially unstable patient as judged by objective hemodynamic parameters available early during resuscitation. METHODS Prospective observational study at a major European trauma center. FAST was performed in trauma patients by the trauma team radiologist. The study population consisted of the subgroup deemed potentially unstable on arrival as defined by systolic blood pressure < or =90 mm Hg, pulse rate > or =120, or base deficit > or =8. Results were compared with one of the following reference standards: computed tomographic scan, diagnostic peritoneal lavage, exploratory laparotomy, or observation. RESULTS One hundred and four patients constituted the study group. There were 75 true-negative, 10 false-negative, 16 true-positive, and 3 false-positive FAST results. Sensitivity and specificity were 62% and 96%, positive and negative predictive values 84% and 89%, respectively, and overall accuracy was 88%. CONCLUSION A negative initial FAST in hemodynamically unstable patients, even in the hands of radiologists, cannot reliably exclude intraabdominal bleeding. These patients should undergo additional diagnostic tests to exclude intraperitoneal hemorrhage.

Refining the role of splenic angiographic embolization in high-grade splenic injuries.

BACKGROUND The justification and safety of splenic angiographic embolization (SAE) as an adjunct to nonoperative management (NOM) in high-grade splenic injuries are matters of controversy. At Oslo University Hospital-Ulleval, mandatory SAE was introduced in hemodynamically stable Organ Injury Scale (OIS) Grades 3 to 5 injuries in 2002. From October 2008, mandatory SAE was restricted to OIS Grade 4 injuries or higher. The aim of the present study was to evaluate clinical outcome in patients with high-grade splenic injuries and further define the role of SAE. METHODS All patients 17 years or older with splenic injury admitted from August 1, 2002, to July 31, 2010, were included. Patient charts, computed tomographic scans, and trauma registry data were reviewed. The OIS Grade 3 protocol was amended on October 1, 2008. RESULTS A total of 296 patients with splenic injuries (mean splenic OIS grade, 3.0) resulted in a 70% attempted NOM rate, with 96% success rate. NOM was attempted in 64 (70%) of 91 patients with Grades 4 and 5 injuries, with a 95% success rate. Comparing OIS Grade 3 injuries admitted before (n = 81) and after (n = 35) October 2008, we found similar admission physiology and Injury Severity Score (ISS). Despite the reduction in SAE rate (from 49% to 26%), the NOM rate remained unchanged, as did NOM failure rate (3% vs. 4%), rate of rebleeding, complications, and mortality. CONCLUSION A protocol with mandatory SAE in OIS Grades 4 and 5 injuries resulted in an overall 95% success rate among the 70% eligible for NOM. In OIS Grade 3 splenic injuries, mandatory SAE does not seem justified. LEVEL OF EVIDENCE Therapeutic study, level IV.

The twin terrorist attacks in Norway on July 22, 2011: The trauma center response

BACKGROUND The terrorist attacks in Norway on July 22, 2011, consisted of a bomb explosion in central Oslo, followed by a shooting spree in a youth camp. We describe the trauma center response, identifying possible success factors and suggesting improvements for institutional major incident plans. METHODS The in-hospital response is analyzed. Data on triage, patient flow, injuries, treatment, resources, and outcome were collected. RESULTS The explosion caused a total of 98 casualties and 8 died at scene. Ten patients were triaged to the trauma center, with the first patient arriving 18 minutes after the explosion and 7 patients within the next 19 minutes. The shooting caused 68 deaths at the scene and 61 injured. The trauma center received a total of 21 patients from the shooting incident. Surgical leadership was divided between emergency department triage with control of personnel and communication as well as control and supervision of treatment with retriage and optimal use of trauma surgical resources (dual command). Surge capacity was never exceeded in the emergency department, operating rooms, or intensive care units. Of the 31 patients treated at the trauma center, 20 had an Injury Severity Score of more than 15 and 25 required repeated operation, for a total of 125 operations during the first 4 weeks. One patient died, for a critical mortality of 5%. CONCLUSION A trauma center can handle many patients with severe injury, with low critical mortality when protected from a large number of walking wounded. Limited specific trauma surgical competence was managed by the adoption of a dual surgical command model. LEVEL OF EVIDENCE Therapeutic/care management study, level V.

Non‐operative management and immune function after splenic injury

There is still considerable controversy about the importance and method of preserving splenic function after trauma. Recognition of the immune function of the spleen and the risk of overwhelming postsplenectomy infection led to the development of spleen‐preserving surgery and non‐operative management. More recently angiographic embolization has been used to try to reduce failure of conservative management and preserve splenic function.