PragmaTic, prospEctive, randomized, controlled, double-blind, mulTi-centre, multinational study on the safety and efficacy of a 6% HydroxYethyl Starch (HES) solution versus an electrolyte solution in trauma patients: study protocol for the TETHYS study.

BACKGROUND: Trauma may be associated with significant to life-threatening blood loss, which in turn may increase the risk of complications and death, particularly in the absence of adequate treatment. Hydroxyethyl starch (HES) solutions are used for volume therapy to treat hypovolemia due to acute blood loss to maintain or re-establish hemodynamic stability with the ultimate goal to avoid organ hypoperfusion and cardiovascular collapse. The current study compares a 6% HES 130 solution (Volulyte 6%) versus an electrolyte solution (Ionolyte) for volume replacement therapy in adult patients with traumatic injuries, as requested by the European Medicines Agency to gain more insights into the safety and efficacy of HES in the setting of trauma care. METHODS: TETHYS is a pragmatic, prospective, randomized, controlled, double-blind, multicenter, multinational trial performed in two parallel groups. Eligible consenting adults ≥ 18 years, with an estimated blood loss of ≥ 500 ml, and in whom initial surgery is deemed necessary within 24 h after blunt or penetrating trauma, will be randomized to receive intravenous treatment at an individualized dose with either a 6% HES 130, or an electrolyte solution, for a maximum of 24 h or until reaching the maximum daily dose of 30 ml/kg body weight, whatever occurs first. Sample size is estimated as 175 patients per group, 350 patients total (α = 0.025 one-tailed, power 1-ß = 0.8). Composite primary endpoint evaluated in an exploratory manner will be 90-day mortality and 90-day renal failure, defined as AKIN stage ≥ 2, RIFLE injury/failure stage, or use of renal replacement therapy (RRT) during the first 3 months. Secondary efficacy and safety endpoints are fluid administration and balance, changes in vital signs and hemodynamic status, changes in laboratory parameters including renal function, coagulation, and inflammation biomarkers, incidence of adverse events during treatment period, hospital, and intensive care unit (ICU) length of stay, fitness for ICU or hospital discharge, and duration of mechanical ventilation and/or RRT. DISCUSSION: This pragmatic study will increase the evidence on safety and efficacy of 6% HES 130 for treatment of hypovolemia secondary to acute blood loss in trauma patients. TRIAL REGISTRATION: Registered in EudraCT, No.: 2016-002176-27 (21 April 2017) and ClinicalTrials.gov, ID: NCT03338218 (09 November 2017).

Posttraumatic Natural Killer Cell Decrease is Associated with Septic Complications.

BACKGROUND: There has been paucity in prospective studies investigating trauma-induced changes in the cellular immunity of HIV-seropositive patients and their impact on the clinical outcome after trauma surgery. The role of natural killer (NK) cells especially has not yet been fully elucidated, and the function of this lymphocyte subtype in the immune defense after trauma is still under debate. METHODS: This prospective study included patients requiring surgery for abdominal gunshot wounds. A blood specimen was obtained on admission, 48 hours after the index operation and, in case of damage control surgery, 48 hours after the first planned second look operation. The quantity and changes of T-, B- and NK cells were analyzed via flow cytometry to investigate whether these numbers had an impact on the postoperative outcome. RESULTS: A total of 62 patients were recruited in the analysis of which 38 were HIV-negative and 24 HIV-seropositive. After surgery, HIV-negative patients had a more severe decrease of their CD4+ T cells compared to the HIV-seropositive patients. Trauma resulted in a severe decrease of NK cells irrespective of the HIV-serostatus. Patients with more extensive NK cell drop had a significantly higher postoperative complication rate. CONCLUSIONS: Our data support the association of trauma-induced NK cell decrease with a subsequent significantly higher rate of septic and surgical complications and suggest that these immune cells might play an important role in antibacterial immunity. Strengthening the NK cell function or limiting their decrease in the postoperative course might be of therapeutic value in severely injured trauma patients.

Compromised Gut Associated Lymphoid Tissue is a Risk Factor for Postoperative Septic Complications in HIV-Seropositive Trauma Patients.

BACKGROUND: The gut associated lymphoid tissue (GALT) is an important part of the immune system and compromised in HIV treatment-naïve as well as in HIV-seropositive patients on antiretroviral treatment (ART) due to HIV-induced changes. The influence of the impaired GALT on the postoperative complication rate after surgery for penetrating abdominal trauma has not been investigated and the hypothesis that the HIV-induced changes of the GALT contribute to septic complications postoperatively was tested. MATERIAL AND METHODS: This prospective study included patients who required a small bowel resection due to abdominal gunshot wounds. A bowel specimen was obtained in the index operation, and the T-lymphocytic quantity in the specimen was analyzed via immunohistochemistry to scrutinize whether these lymphocyte numbers had an impact on the postoperative outcome. Septic and postoperative complications were documented during the in-hospital course and the first month after discharge. RESULTS: In total, 62 patients were included in the study of which 38 patients were HIV-seronegative and 24 were HIV-seropositive. HIV-seropositive patients had a significantly lower quantity of CD4 + T cells in the GALT compared to the HIV-seronegative patients (p = 0.0001), which was also associated with a significantly higher rate of septic complications in the postoperative course. In the HIV-seropositive group, no significant differences were detected for T-lymphocytic quantity in the GALT between the HIV-treatment naïve and antiretroviral treatment groups. CONCLUSION: The compromised GALT in HIV-seropositive patients may predispose these patients to postoperative septic complications. Antiretroviral therapy does not result in an adequate immune reconstitution in this tissue.

Trauma results in immune cell-induced intestinal epithelial damage with subsequently increased sepsis rate.

BACKGROUND: The detrimental effect of trauma on the immune system has been a subject of interest for decades. The gut-associated lymphoid tissue (GALT) of the bowel that encompasses different lymphocyte subpopulations may be an important pillar of human immunity in the context of trauma. Neither the short-term histological trauma-induced changes in the GALT nor its impact on the outcome after trauma surgery has been investigated. METHODS: This prospective, longitudinal proof-of-concept study included patients who required damage-control surgery after abdominal gunshot wounds with small bowel involvement. Bowel specimens were obtained during the index and relook operations, and the T-lymphocytic quantity therein was analyzed via immunohistochemistry. We scrutinized how the lymphocyte structure and numbers of the GALT altered, and whether the extent and nature of these changes had an impact on the postoperative outcome with regard to septic and surgical complications. RESULTS: A total of 31 damage-control patients were recruited for the study. The main histological changes between the index and relook specimen was a shift of CD8+ T cells from the lamina propria (LP) into the epithelium and a decrease of T lymphocytes in the LP. The significant increase of the intraepithelial CD8+ T cells was associated with a more extensive enterocyte apoptosis, and correlated significantly, positively with the number of postoperative septic complications. CONCLUSION: Our data support that trauma induces an immune cell-driven impairment of the intestinal epithelium, as well as an increased apoptosis of lymphocytes in the LP, which is associated with a worse clinical outcome. The underlying mechanism suggests that a therapeutic approach to minimize apoptosis in the intestine may impact the outcome of severely injured trauma patients. LEVEL OF EVIDENCE: Therapeutic/care/management, level lV.

Postoperative CD4 counts predict anastomotic leaks in patients with penetrating abdominal trauma.

INTRODUCTION: The influence of trauma- and surgical stress-induced decrease of CD4 count on anastomotic leaks after penetrating abdominal trauma has to date not been investigated. A prospective study was performed to explore the effect of CD4 count 24 h after surgery on the anastomotic leak rate and to identify risk factors for anastomotic leaks. METHODS: This was a prospective study including 98 patients with small or large bowel resection and subsequent anastomosis due to penetrating abdominal trauma. Univariate analysis identified risk factors for the development of anastomotic leak and also investigated the predictive value of the CD4 count for this complication. RESULTS: Of the 98 patients 23 patients (23%) were HIV-infected. The overall leak rate was 13%. Univariate analysis including all potential risk factors with p-values<0.05 identified six factors leading to a significantly higher rate of anastomotic complications: postoperative CD4 count<250 cells/µl, postoperative albumin <30 g/L, penetrating abdominal trauma index≥25, gunshot wound as mechanism of injury, blood transfusion requirement >6units and delayed anastomosis after damage control surgery. Survival rates were analysed with the χ2 test and did not show a significantly higher mortality rate in patients with low CD4 count. The negative impact of trauma and subsequent surgery on the cell mediated immunity was demonstrated by the fact that 55 (73%) of the HIV-negative patients had a CD4 count less than 500 cells/µl 24 h postoperatively. HIV-infection had no significant influence on the leak rate, however all HIV infected patients that developed an anastomotic leak died. CONCLUSION: A low post-operative CD4 count is a predictor for anastomotic leaks irrespective of HIV-serostatus. Low postoperative serum albumin, high injury severity, gunshot wound as mechanism of injury, blood transfusion requirement >6 units and delayed anastomosis were further risk factors for anastomotic complications. Postoperative CD4 count and serum albumin should be considered in the decision making process of performing an anastomosis or diverting stoma for patients after "clip and drop" of the bowel as part of damage control surgery.

On a knife-edge: clinical uncertainty with an extensive knife blade in situ in the craniofacial region.

A 25-year-old man presented to the trauma department following a penetrating stab wound to his left infraorbital margin with retained knife blade causing superoposterior displacement of the globe. Plain skull X-ray revealed an extensive retained blade with subsequent CT imaging revealing the tip of the blade had reached the right styloid process with no neurovascular compromise. Initial concern was primarily for the left eye leading to ophthalmology being the first specialty requested to review the patient. However, once the extent of the injury was established, ophthalmology requested further review from maxillofacial, ENT and neurosurgery. This resulted in an 84 hours wait between the initial injury and the removal of the knife blade. Incredibly, the patient had no initial sequelae from such an extensive injury and had an unremarkable recovery with no further complications aside from a laceration to the left inferior rectus muscle that was conservatively managed.

The challenges of developing a trauma system for Indigenous people.

Trauma systems have been shown to provide the best trauma care for injured patients. A trauma system developed for Indigenous people should take into account many factors including geographical remoteness and cultural diversity. Indigenous people suffer from a significant intentional and non-intentional burden of injury, often greater than non-Indigenous populations, and a public health approach in dealing with trauma can be adopted. This includes transport issues, prevention and control of intentional violence, cultural sensitization of health providers, community emergency responses, community rehabilitation and improving resilience. The ultimate aim is to decrease the trauma burden through a trauma system with which indigenous people can fully identify.

The use of low dosage X-ray (Lodox/Statscan) in major trauma: comparison between low dose X-ray and conventional x-ray techniques.

BACKGROUND: Patients presenting with major trauma normally require resuscitation, usually carried out according to techniques laid down by the Advanced Trauma Life Support (ATLS) Program of the American College of Surgeons. Techniques normally suggested include the routine radiology of the cervical spine, chest and pelvis. This can sometimes be time consuming and may not return helpful information in all cases. METHODS: This paper describes the use of a new low dose X-ray technique (Lodox/Statscan to perform these X-rays, and compares their interpretation by both radiologists and trauma surgeons with images obtained from conventional X-rays. The time taken for the respective images to be obtained was measured. RESULTS: There was no difference in the amount of information obtained. CONCLUSION: The use of the Lodox allowed a substantial reduction in the time taken for resuscitation, without prejudice to diagnostic radiology.

Death and injury on duty--a study of South African police officers.

OBJECTIVES: Sections of contemporary South African society are characterised by high levels of crime and interpersonal conflict. The South African Police Service (SAPS) is in the front line, with many deaths and injuries occuring among serving officers in recent years. The circumstances and nature of the injuries sustained by these officers have received little attention in the medical literature. DESIGN: A retrospective review of all injured SAPS members was undertaken at a single level one trauma centre in Johannesburg between June 1993 and June 2002. The following factors were recorded: demographics, mechanism and anatomical site of injury, mode of transportation to hospital, whether personal protection had been used, mortality, and return to work. RESULTS: One hundred and thirty-four SAPS personnel were admitted over a 9-year period. The majority (95%) were male and the median age was 31 years. One hundred and thirty-two were on duty and two were in transit to a place of duty when injured. Ninety-two (69%) were injured by gunshot, (including 3 attempted suicides and 9 injuries due to negligent discharge), 2 members were stabbed, 31 were involved in motor vehicle accidents, 2 in motorbike accidents, 1 member was struck by a car while directing traffic, 3 officers were injured by falls from a height, 2 members were injured in helicopter crashes, and 1 member required treatment for gas inhalation. Documentation on whether some form of personal protection was worn at the time of injury was only available for 43 of the 92 cases of gunshot wounds (47%); of these, only 15 (35%) were wearing a bulletproof vest. Use or non-use of a seat belt was documented by hospital staff for only 6 of the 31 officers (19%) injured in motor vehicle accidents. None of the 6 officers had been restrained by a seatbelt. Nineteen SAPS personnel (14%) died of their injuries, but the majority of surviving members returned to duty. CONCLUSION: There is an unacceptably high level of violence in South African society today and SAPS members regularly have to deal with dangerous or violent situations. There is a clear need to introduce a reporting system within the SAPS to record the use of personal protection by officers. Education needs to target SAPS members in order to enhance their use of personal protection. There is a further need to design and implement personal protection that will be universally acceptable by SAPS members.

Intubated, ventilating patients with complete tracheal transection: a diagnostic challenge.

Tracheal transection is a rare injury after blunt trauma. The presence of complete tracheal transection in the intubated, ventilating patient is even more rare and constitutes a major diagnostic challenge. The liberal use of computed tomography (CT) scans as an adjunct to endoscopy is paramount.