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BACKGROUND: Andexanet alfa (andexanet) reverses the anticoagulant effects of factor Xa inhibitors, but it has not been assessed in clinical studies for apixaban reversal in trauma. This study evaluated andexanet for reversing apixaban anticoagulation in a porcine polytrauma model. METHODS: Oral apixaban (20 mg q.d., n=21) or placebo (n=7; sham group) was administered to male pigs for 4 days before blunt liver injury and bi-lateral femur fracture. After trauma, animals were randomised 1:1:1 to a single andexanet bolus (1000 mg), a bolus (1000 mg) plus infusion (1200 mg over 2 h), or vehicle (control). Haemodynamic and coagulation variables were monitored for 5 h or until death. The primary endpoint was blood loss. RESULTS: Mean blood loss in sham animals was 472 (standard deviation, 58) ml 12 min after injury and 658 (98) ml at 300 min, with 100% survival. Anticoagulation with apixaban significantly increased blood loss 12 min after injury [888 (133) ml, P

Background Idarucizumab is licensed to reverse dabigatran in life-threatening haemorrhage. Establishment of venous access can be challenging, and the intraosseous (IO) route is a potentially life-saving alternative. In this study, we compared the efficacy and safety of IO or intravenous (i.v.) idarucizumab for dabigatran reversal in a porcine polytrauma model. Methods Male pigs (n=21) received oral dabigatran etexilate (30 mg kg−1 bid) for 3 days. On the 4th day, animals received dabigatran infusion and were randomised 1:1:1 to receive IO saline (control), i.v. idarucizumab (60 mg kg−1), or IO idarucizumab (60 mg kg−1), or animals were included in a sham group (n=7). Study treatment was administered after polytrauma and the animals were monitored for 240 min, or until death. Coagulation status was monitored by thromboelastometry, thromboelastography, and thrombin measurements. Results Total blood loss was lowest in sham animals [521 (52) ml, P Conclusions Intravenous and intraosseous idarucizumab were comparable for reversing dabigatran in a porcine trauma model. Dabigatran reversal could be monitored using fully automated thromboelastography.

Background Recombinant factor VIIa (rFVIIa) has been successfully used in various clinical conditions to treat severe coagulopathy, but its efficacy may be affected by the underlying conditions. We therefore investigated the efficacy of rFVIIa treatment under conditions of hypofibrinogenaemia in a pig model of blunt liver injury. Methods Severe haemodilution was instigated in four groups of seven anaesthetized pigs. Before inflicting liver injury, animals were assigned to receive either 70 mg kg −1 fibrinogen (fibrinogen group) or placebo (control group). Thirty seconds after injury, rFVIIa (180 µg kg −1 ) (rFVIIa and fibrinogen+rFVIIa groups) or vehicle (control and fibrinogen groups) was administered. Haemodynamic variables, coagulation parameters, and blood loss were monitored for 2 h. Histology was examined to evaluate the presence of thrombi and the consistency of liver injury. Results At the end of the observation period, total blood loss [median (range)] decreased in all intervention groups [fibrinogen: 1275 (1221–1439) ml, P =0.036; rFVIIa: 966 (923–1136) ml, P =0.008; fibrinogen+rFVIIa: 678 (475–756) ml, P =0.008] when compared with control animals [blood loss: 1752 (1735–2221) ml]. The mortality rate in the control group was 100%, whereas only 42% of fibrinogen-substituted animals died ( P =0.023). All animals treated with rFVIIa or fibrinogen+rFVIIa ( P Conclusions rFVIIa under conditions of hypofibrinogenaemia exhibited a positive impact on coagulation parameters and a reduction in blood loss. These effects were significantly improved after prior substitution with fibrinogen.

Background Postoperative cognitive dysfunction (POCD) is being recognized as a complication contributing to perioperative morbidity and mortality of the elderly. We hypothesized that the use of the shorter-acting volatile anaesthetic desflurane would be associated with less incidence of POCD when compared with sevoflurane. Methods Approved by the local ethical committee, 80 patients (aged 65–75 yr) were enrolled in this randomized, double-blinded study. Patients were allocated to either the desflurane ( n =40) or the sevoflurane ( n =40) group. The primary outcome was the cognitive Test for Attentional Performance with its subtests Alertness, Divided Attention, Visual Scanning, Working Memory, and Reaction Change. In addition, Paper–Pencil Tests [Well-being Test BF-S, Recall of Digit Span (DST), Digit-Symbol-Substitution Test, Trail Making Tests A and B, and Spielberg State-Trait Anxiety Inventory] were measured. After baseline assessment 12–24 h before operation, patients were followed up 6–8 and 66–72 h after operation. Among other outcome parameters, emergence times from anaesthesia and modified Aldrete scores were recorded. Results There was no difference in the incidence of POCD. However, according to the Paper–Pencil Tests, significant improvements for the desflurane group could be detected (Well-being Test at 6–8 h, DST at 6–8 h, and Trail Making Test at 66–72 h). Emergence was significantly faster in the desflurane group for ‘time to open eyes' and ‘time to extubation'. Conclusions The total incidence of POCD showed no differences between the desflurane and the sevoflurane groups. However, the tests Well-being scale, DST, and Trail Making Test, emergence times, and patients' satisfaction were in favour of desflurane.

Background The safe performance of regional anaesthesia (RA) requires theoretical knowledge and good manual skills. Virtual reality (VR)-based simulators may offer trainees a safe environment to learn and practice different techniques. However, currently available VR simulators do not consider individual anatomy, which limits their use for realistic training. We have developed a VR-based simulator that can be used for individual anatomy and for different anatomical regions. Methods Individual data were obtained from magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) without contrast agent to represent morphology and the vascular system, respectively. For data handling, registration, and segmentation, an application based on the Medical Imaging Interaction Toolkit was developed. Suitable segmentation algorithms such as the fuzzy c-means clustering approach were integrated, and a hierarchical tree data structure was created to model the flexible anatomical structures of peripheral nerve cords. The simulator was implemented in the VR toolkit ViSTA using modules for collision detection, virtual humanoids, interaction, and visualization. A novel algorithm for electric impulse transmission is the core of the simulation. Results In a feasibility study, MRI morphology and MRA were acquired from five subjects for the inguinal region. From these sources, three-dimensional anatomical data sets were created and nerves modelled. The resolution obtained from both MRI and MRA was sufficient for realistic simulations. Our high-fidelity simulator application allows trainees to perform virtual peripheral nerve blocks based on these data sets and models. Conclusions Subject-specific training of RA is supported in a virtual environment. We have adapted segmentation algorithms and developed a VR-based simulator for the inguinal region for use in training for different peripheral nerve blocks. In contrast to available VR-based simulators, our simulation offers anatomical variety.