Viscoelastic haemostatic assay augmented protocols for major trauma haemorrhage (ITACTIC): a randomized, controlled trial

Purpose: Contemporary trauma resuscitation prioritizes control of bleeding and uses major haemorrhage protocols (MHPs) to prevent and treat coagulopathy. We aimed to determine whether augmenting MHPs with Viscoelastic Haemostatic Assays (VHA) would improve outcomes compared to Conventional Coagulation Tests (CCTs). Methods: This was a multi-centre, randomized controlled trial comparing outcomes in trauma patients who received empiric MHPs, augmented by either VHA or CCT-guided interventions. Primary outcome was the proportion of subjects who, at 24 h after injury, were alive and free of massive transfusion (10 or more red cell transfusions). Secondary outcomes included 28-day mortality. Pre-specified subgroups included patients with severe traumatic brain injury (TBI). Results: Of 396 patients in the intention to treat analysis, 201 were allocated to VHA and 195 to CCT-guided therapy. At 24 h, there was no difference in the proportion of patients who were alive and free of massive transfusion (VHA: 67%, CCT: 64%, OR 1.15, 95% CI 0.76–1.73). 28-day mortality was not different overall (VHA: 25%, CCT: 28%, OR 0.84, 95% CI 0.54–1.31), nor were there differences in other secondary outcomes or serious adverse events. In pre-specified subgroups, there were no differences in primary outcomes. In the pre-specified subgroup of 74 patients with TBI, 64% were alive and free of massive transfusion at 24 h compared to 46% in the CCT arm (OR 2.12, 95% CI 0.84–5.34). Conclusion: There was no difference in overall outcomes between VHA- and CCT-augmented-major haemorrhage protocols

iTACTIC - implementing Treatment Algorithms for the Correction of Trauma-Induced Coagulopathy: study protocol for a multicentre, randomised controlled trial.

BACKGROUND: Traumatic injury is the fourth leading cause of death globally. Half of all trauma deaths are due to bleeding and most of these will occur within 6 h of injury. Haemorrhagic shock following injury has been shown to induce a clotting dysfunction within minutes, and this early trauma-induced coagulopathy (TIC) may exacerbate bleeding and is associated with higher mortality and morbidity. In spite of improved resuscitation strategies over the last decade, current transfusion therapy still fails to correct TIC during ongoing haemorrhage and evidence for the optimal management of bleeding trauma patients is lacking. Recent publications describe increasing the use of Viscoelastic Haemostatic Assays (VHAs) in trauma haemorrhage; however, there is insufficient evidence to support their superiority to conventional coagulation tests (CCTs). METHODS/DESIGN: This multicentre, randomised controlled study will compare the haemostatic effect of an evidence-based VHA-guided versus an optimised CCT-guided transfusion algorithm in haemorrhaging trauma patients. A total of 392 adult trauma patients will be enrolled at major trauma centres. Participants will be eligible if they present with clinical signs of haemorrhagic shock, activate the local massive haemorrhage protocol and initiate first blood transfusion. Enrolled patients will be block randomised per centre to either VHA-guided or CCT-guided transfusion therapy in addition to that therapy delivered as part of standard care, until haemostasis is achieved. Patients will be followed until discharge or 28 days. The primary endpoint is the proportion of subjects alive and free of massive transfusion (less than 10 units of red blood cells) at 24 h. Secondary outcomes include the effect of CCT- versus VHA-guided therapy on organ failure, total hospital and intensive care lengths of stay, health care resources needed and mortality. Surviving patients will be asked to complete a quality of life questionnaire (EuroQol EQ-5DTM) at day 90. DISCUSSION: CCTs have traditionally been used to detect TIC and monitor response to treatment in traumatic major haemorrhage. The use of VHAs is increasing, but limited evidence exists to support the superiority of these technologies (or comparatively) for patient-centred outcomes. This knowledge gap will be addressed by this trial. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02593877 . Registered on 15 October 2015. Trial sponsor Queen Mary University of London The contact person of the above sponsor organisation is: Dr. Sally Burtles, Director of Research Services and Business Development, Joint Research Management Office, QM Innovation Building, 5 Walden Street, London E1 2EF; phone: 020 7882 7260; Email: [email protected] Trial sites Academic Medical Centre, Amsterdam, The Netherlands Kliniken der Stadt Köln gGmbH, Cologne, Germany Rigshospitalet (Copenhagen University Hospital), Copenhagen, Denmark John Radcliff Hospital, Oxford, United Kingdom Oslo University Hospital, Oslo, Norway The Royal London Hospital, London, United Kingdom Centre for Trauma Sciences, Blizard Institute, Queen Mary University of London, London, United Kingdom Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom Sites that are planning to start recruitment in mid/late 2017 Nottingham University Hospitals, Queen's Medical Centre, Nottingham, United Kingdom University of Kansas Hospital (UKH), Kansas City, MO, USA Protocol version: 3.0/14.03.2017 (Additional file 1)

Medicine self-poisoning and the sources of the drugs in Lund, Sweden

The purpose of this study was to investigate the prevalence of toxic agents in attempted and completed suicides. The purpose was also to explore the sources of the drugs taken by suicide attempters. Verbal information on drug intake was collected from 280 suicide attempters during 1987-1990 in the Lund-Orup catchment area. Information on the sources of the drugs was collected from 143 of these attempters. The study also includes toxicological screening from 73 fatal poisonings in southern Sweden during 1989. According to verbal information, the most common drugs used by suicide attempters were benzodiazepines (51%), analgesics (29%) and antidepressants (20%). In suicide attempters, diazepam and levomepromazine were reported more than expected from prescription data. Toxicological screenings of fatal poisonings showed that benzodiazepines were most common (55%), followed by analgesics (38%), mainly propoxyphene (29%) and antidepressants (30%), mainly amitriptyline (22%). Amitriptyline and diazepam were more commonly detected in completed suicides than expected from prescription data. The most common sources of drugs to attempted suicides were physicians, and especially psychiatrists. We therefore conclude that continuous information to physicians on drug overdose is important, and it is also important to introduce alternative strategies to prevent suicidal behaviour