Summary
In urgent clinical situations, such as trauma, urgent surgery or before thrombolysis, rapid quantification of direct oral anticoagulant plasma drug levels is warranted. Using the ClotPro® ...analyser, we assessed two novel viscoelastic tests for detection of clinically‐relevant plasma drug levels in trauma patients. The ecarin clotting time was used to assess the plasma concentration of dabigatran and Russell´s viper venom clotting time to determine the plasma concentration of direct factor Xa inhibitors. In parallel, plasma concentrations were analysed using plasma‐based chromogenic assays. A total of 203 simultaneous measurements were performed. Strong to very strong linear correlations were detected between ecarin clotting time and plasma concentration of dabigatran (r = 0.9693), and between Russell´s viper venom clotting time and plasma concentrations of apixaban (r = 0.7391), edoxaban (r = 0.9251) and rivaroxaban (r = 0.8792), all p < 0.001. An ecarin clotting time ≥ 189 seconds provided 100% sensitivity and 90% specificity for detecting plasma dabigatran concentrations ≥ 50 ng.ml‐1. Corresponding Russell´s viper venom clotting time cut‐off values were ≥ 136 seconds for apixaban (80% sensitivity, 88% specificity), ≥ 168 seconds for edoxaban (100% sensitivity, 100% specificity) and ≥ 177 seconds for rivaroxaban (90% sensitivity, 100% specificity). Detection of drug levels ≥ 100 ng.ml‐1 was also investigated: for dabigatran, an ecarin clotting time ≥ 315 seconds yielded 92% sensitivity and 100% specificity; while Russell´s viper venom clotting time cut‐offs of 191, 188 and 196 seconds were calculated for apixaban (67% sensitivity, 88% specificity), edoxaban (100% sensitivity, 75% specificity) and rivaroxaban (100% sensitivity, 91% specificity), respectively. We have demonstrated strong positive correlations between plasma drug levels and clotting time values in the specific ClotPro assays. Cut‐off values for detecting clinically‐relevant drug levels showed high levels of sensitivity and specificity.
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.
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.
Total blood loss was lowest in sham animals 521 (52) ml, P<0.01 vs all other groups, and comparable in the two idarucizumab groups IO: 1085 (102) ml vs i.v.: 1142 (125) ml, and highest in the control group 4065 (557) ml, P<0.001 vs all other groups. Survival to 240 min was 100% in the sham group and both idarucizumab groups, and 14% in the control group. IO and i.v. idarucizumab promptly normalised global coagulation assays and thrombin generation. Thromboelastography showed a strong correlation between dabigatran concentrations and R-time (R2=0.90 and 0.89) in idarucizumab-treated animals.
Intravenous and intraosseous idarucizumab were comparable for reversing dabigatran in a porcine trauma model. Dabigatran reversal could be monitored using fully automated thromboelastography.
Compared to conventional coagulation assays, as prothrombin time (PT) or activated partial thromboplastin time (aPTT), viscoelastic methods of coagulation analysis, including rotational ...thromboelastometry (ROTEM®, Tem International GmbH, Munich, Germany), yield prognostic benefits. Results of ROTEM® in citrated whole blood could be generated within 10-12 min and allow for a qualitative and semiquantitative characterisation of clot kinetics. Based on ROTEM® results, the switch between empiric approaches of treating coagulopathy to a goal-directed approach could be accelerated. Introduction of ROTEM® reduces transfusion requirements and the need for single factor concentrates. Thus, ROTEM® reduces transfusion-related adverse events, and additionally implement therapeutic cost effectiveness.
This review provides a short introduction in the methodology of ROTEM®, showing how the combination of assays with different commercially available ROTEM® reagents allows for rapid differential diagnosis of common coagulopathies in clinical practice. Furthermore, prognostic benefits and limitations of ROTEM® diagnostics are described. Finally, we discuss the potential fields of ROTEM® application in different surgical settings.
ROTEM® appears to be a contemporary, applicable and effective method in diagnosing coagulopathy and for subsequent algorithm-based goal-directed therapy.
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.
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.
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’.
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.
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.
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.
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.
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.
To elaborate the impact of new haemostatic agents we developed an instrument for the pressure-controlled induction of blunt liver injuries in a porcine animal model.
A dilutional coagulopathy of 80% ...of animal blood volume was induced in 9 anaesthetized pigs. Animals were randomly assigned to be injured with a force of 112 Newton (N) (n = 1), 224 +/- 19 N (n = 4) or 355 +/- 35 N (n = 4). The impact of injury was measured by blood loss, survival time and coagulation parameters. Liver histology was obtained to evaluate the degree of liver injury.
The profound haemodilution resulted in a significant alteration of all coagulation parameters. After inflicting the injury with 355 +/- 35 N, both the survival time (30 +/- 9 min; p = 0.006) and blood loss (68 +/- 16 ml min(-1), p = 0.002) were significantly different as compared to injuries with 224 +/- 19 N (survival time: 76 +/- 20 min, blood loss: 23 +/- 4 ml min(-1)). In contrast, an injury with 112 N led to an insignificant blood loss of only 239 ml.
We developed a pressure-controlled clamp that allows for the induction of blunt liver traumas with highly reproducible injuries with a positive correlation with blood loss and survival.
PDF
