Michel Teuben

Mortality patterns in patients with multiple trauma: a systematic review of autopsy studies

Purpose A high percentage (50%-60%) of trauma patients die due to their injuries prior to arrival at the hospital. Studies on preclinical mortality including post-mortem examinations are rare. In this review, we summarized the literature focusing on clinical and preclinical mortality and studies included post-mortem examinations. Methods A literature search was conducted using PubMed/Medline database for relevant medical literature in English or German language published within the last four decades (1980–2015). The following MeSH search terms were used in different combinations: “multiple trauma”, “epidemiology”, “mortality “, “cause of death”, and “autopsy”. References from available studies were searched as well. Results Marked differences in demographic parameters and injury severity between studies were identified. Moreover, the incidence of penetrating injuries has shown a wide range (between 4% and 38%). Both unimodal and bimodal concepts of trauma mortality have been favored. Studies have shown a wide variation in time intervals used to analyze the distribution of death. Thus, it is difficult to say which distribution is correct. Conclusions We have identified variable results indicating bimodal or unimodal death distribution. Further more stundardized studies in this field are needed. We would like to encourage investigators to choose the inclusion criteria more critically and to consider factors affecting the pattern of mortality.

Characterization of blunt chest trauma in a long-term porcine model of severe multiple trauma

Chest trauma has a significant relevance on outcome after severe trauma. Clinically, impaired lung function typically occurs within 72 hours after trauma. However, the underlying pathophysiological mechanisms are still not fully elucidated. Therefore, we aimed to establish an experimental long-term model to investigate physiological, morphologic and inflammatory changes, after severe trauma. Male pigs (sus scrofa) sustained severe trauma (including unilateral chest trauma, femur fracture, liver laceration and hemorrhagic shock). Additionally, non-injured animals served as sham controls. Chest trauma resulted in severe lung damage on both CT and histological analyses. Furthermore, severe inflammation with a systemic increase of IL-6 (p = 0.0305) and a local increase of IL-8 in BAL (p = 0.0009) was observed. The pO2/FiO2 ratio in trauma animals decreased over the observation period (p < 0.0001) but not in the sham group (p = 0.2967). Electrical Impedance Tomography (EIT) revealed differences between the traumatized and healthy lung (p < 0.0001). In conclusion, a clinically relevant, long-term model of blunt chest trauma with concomitant injuries has been developed. This reproducible model allows to examine local and systemic consequences of trauma and is valid for investigation of potential diagnostic or therapeutic options. In this context, EIT might represent a radiation-free method for bedside diagnostics.

Analysis of skeletal muscle microcirculation in a porcine polytrauma model with haemorrhagic shock: LOCAL MICROCIRCULATION IN A PORCINE POLYTRAUMA MODEL

Polytraumatised patients with haemorrhagic shock are prone to develop systemic complications, such as SIRS (systemic inflammatory response syndrome), ARDS (acute respiratory distress syndrome) and MOF (multiple organ failure). The pathomechanism of severe complications following trauma is multifactorial, and it is believed that microcirculatory dysfunction plays an important role. The aim of this study was to determine the changes in the microcirculation in musculature over time during shock and subsequent resuscitation in a porcine model of haemorrhagic shock and polytrauma. Twelve pigs (German Landrace) underwent femur fracture, liver laceration, blunt chest trauma, and haemorrhagic shock under standard anaesthesia and intensive care monitoring. Microcirculation data were measured from the vastus lateralis muscle using a combined white light spectrometry and laser spectroscopy system every 15 min during the shock and resuscitation period, and at 24, 48, and 72 h. Oxygen delivery and oxygen consumption were calculated and compared to baseline. The relative haemoglobin, local oxygen consumption, and saturation values in the microcirculation were observed significantly lower during shock, however, no changes in the microcirculatory blood flow and microcirculatory oxygen delivery were observed. After resuscitation, the microcirculatory blood flow and relative haemoglobin increased and remained elevated during the whole observation period (72 h). In this study, we observed changes in microcirculation during the trauma and shock phases. Furthermore, we also measured persistent dysfunction of the microcirculation over the observation period of 3 days after resuscitation and haemorrhagic shock.

Analysis of skeletal muscle microcirculation in a porcine polytrauma model with haemorrhagic shock

Polytraumatised patients with haemorrhagic shock are prone to develop systemic complications, such as SIRS (systemic inflammatory response syndrome), ARDS (acute respiratory distress syndrome) and MOF (multiple organ failure). The pathomechanism of severe complications following trauma is multifactorial, and it is believed that microcirculatory dysfunction plays an important role. The aim of this study was to determine the changes in the microcirculation in musculature over time during shock and subsequent resuscitation in a porcine model of haemorrhagic shock and polytrauma. Twelve pigs (German Landrace) underwent femur fracture, liver laceration, blunt chest trauma, and haemorrhagic shock under standard anaesthesia and intensive care monitoring. Microcirculation data were measured from the vastus lateralis muscle using a combined white light spectrometry and laser spectroscopy system every 15 min during the shock and resuscitation period, and at 24, 48, and 72 h. Oxygen delivery and oxygen consumption were calculated and compared to baseline. The relative haemoglobin, local oxygen consumption, and saturation values in the microcirculation were observed significantly lower during shock, however, no changes in the microcirculatory blood flow and microcirculatory oxygen delivery were observed. After resuscitation, the microcirculatory blood flow and relative haemoglobin increased and remained elevated during the whole observation period (72 h). In this study, we observed changes in microcirculation during the trauma and shock phases. Furthermore, we also measured persistent dysfunction of the microcirculation over the observation period of 3 days after resuscitation and haemorrhagic shock.

Comparative Analysis of the Regulatory T Cells Dynamics in Peripheral Blood in Human and Porcine Polytrauma

Background Severely injured patients experience substantial immunological stress in the aftermath of traumatic insult, which often results in systemic immune dysregulation. Regulatory T cells (Treg) play a key role in the suppression of the immune response and in the maintenance of immunological homeostasis. Little is known about their presence and dynamics in blood after trauma, and nothing is known about Treg in the porcine polytrauma model. Here, we assessed different subsets of Treg in trauma patients (TP) and compared those to either healthy volunteers (HV) or data from porcine polytrauma. Methods Peripheral blood was withdrawn from 20 TP with injury severity score (ISS) ≥16 at the admittance to the emergency department (ED), and subsequently on day 1 and at day 3. Ten HV were included as controls (ctrl). The porcine polytrauma model consisted of a femur fracture, liver laceration, lung contusion, and hemorrhagic shock resulting in an ISS of 27. After polytrauma, the animals underwent resuscitation and surgical fracture fixation. Blood samples were withdrawn before and immediately after trauma, 24 and 72 h later. Different subsets of Treg, CD4+CD25+, CD4+CD25+FoxP3+, CD4+CD25+CD127−, and CD4+CD25+CD127−FoxP3+ were characterized by flow cytometry. Results Absolute cell counts of leukocytes were significantly increasing after trauma, and again decreasing in the follow-up in human and porcine samples. The proportion of human Treg in the peripheral blood of TP admitted to the ED was lower when compared to HV. Their numbers did not recover until 72 h after trauma. Comparable data were found for all subsets. The situation in the porcine trauma model was comparable with the clinical data. In porcine peripheral blood before trauma, we could identify Treg with the typical immunophenotype (CD4+CD25+CD127−), which were virtually absent immediately after trauma. Similar to the human situation, most of these cells expressed FoxP3, as assessed by intracellular FACS stain. Conclusion Despite minor percental differences in the recovery of Treg populations after trauma, our findings show a comparable decrease of Treg early after polytrauma, and strengthen the immunological significance of the porcine polytrauma model. Furthermore, the Treg subpopulation CD4+CD25+CD127− was characterized in porcine samples.

Dose-dependent effects of peroxisome proliferator-activated receptors β/δ agonist on systemic inflammation after haemorrhagic shock

Introduction PPAR&bgr;/&dgr; agonists are known to modulate the systemic inflammatory response after sepsis. In this study, inflammation modulation effects of PPAR&bgr;/&dgr; are investigated using the selective PPAR&bgr;/&dgr; agonist (GW0742) in a model of haemorrhagic shock (HS)‐induced sterile systemic inflammation. Methods Blood pressure‐controlled (35 ± 5 mmHg) HS was performed in C57/BL6 mice for 90 min. Low‐dose GW0742 (0.03 mg/kg/BW) and high‐dose GW0742 (0.3 mg/kg/BW) were then administered at the beginning of resuscitation. Mice were sacrificed 6 h after induction of HS. Plasma levels of IL‐6, IL‐1&bgr;, IL‐10, TNF&agr;, KC, MCP‐1, and GM‐CSF were determined by ELISA. Myeloperoxidase (MPO) activity in pulmonary and liver tissues was analysed with standardised MPO kits. Results In mice treated with high‐dose GW0742, plasma levels of IL‐6, IL‐1&bgr;, and MCP‐1 were significantly increased compared to the control group mice. When compared to mice treated with low‐dose GW0742 plasma levels of IL‐6, IL‐1&bgr;, GM‐CSF, KC, and MCP‐1 were significantly elevated in high‐dose‐treated mice. Low‐dose GW0742 treatment was associated with a non‐significant downtrend of inflammatory factors in mice with HS. No significant changes of MPO activity in lung and liver were observed between the control group and the GW0742 treatment groups. Conclusion This study identified dose‐dependent effects of GW0742 on systemic inflammation after HS. While high‐dose GW0742 substantially enhanced the systemic inflammatory response, low‐dose GW0742 led to a downtrend of pro‐inflammation cytokine expression. The exact mechanisms are yet unknown and need to be assessed in further studies. HighlightsHigh dosage of GW0742 enhanced the plasma pro‐inflammatory cytokines levels.Low‐dose treatment of GW0742 induced a downtrend of inflammation cytokine levels.GW0742 treatment has no effect on the remote organ neutrophil infiltration.