Oliver Grottke

University Hospital RWTH Aachen, Aachen, North Rhine-Westphalia, Germany

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Publications (44)93.96 Total impact

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    ABSTRACT: Fibrinogen concentrate may reduce blood loss after trauma. However, its effect on endogenous fibrinogen synthesis is unknown. The authors investigated the effect of exogenous human fibrinogen on endogenous fibrinogen metabolism in a 24-h porcine trauma model.
    Anesthesiology 05/2014; · 5.16 Impact Factor
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    ABSTRACT: New oral anticoagulants are effective alternatives to warfarin. However, no specific reversal agents are available for life-threatening bleeding or emergency surgery. Using a porcine model of trauma, this study assessed the ability of prothrombin complex concentrate (PCC), activated PCC (aPCC), recombinant FVII (rFVIIa) and a specific antidote to dabigatran (aDabi-Fab) to reverse the anticoagulant effects of dabigatran. Dabigatran etexilate (DE) was given orally for 3 days (30 mg/kg bid) and intravenously on day 4 to achieve consistent, supratherapeutic concentrations of dabigatran. Blood samples were collected at baseline, after oral DE, after intravenous dabigatran, and 60 minutes post-injury. PCC (30 and 60 IU/kg), aPCC (30 and 60 U/kg), rFVIIa (90 and 180 mug/kg) and antidote (60 and 120 mg/kg) were added to blood samples ex-vivo. Coagulation was assessed by thromboelastometry, global coagulation assays and diluted thrombin time. Plasma concentrations of dabigatran were 380 +/- 106 ng/ml and 1423 +/- 432 ng/ml after oral and intravenous administration, respectively, and all coagulation parameters were affected by dabigatran. Both PCCs and aDabi-Fab, but not rFVIIa, reversed the effects of dabigatran on thromboelastometry parameters and prothrombin time. In contrast, aPTT was only normalised by aDabi-Fab. Plasma concentration (activity) of dabigatran remained elevated after PCC and rFVIIa therapy, but was not measureable after aDabi-Fab. In conclusion, PCC and aPCC were effective in reducing the anticoagulant effects of dabigatran under different conditions, while aDabi-Fab fully corrected all coagulation measures and decreased the plasma concentration of dabigatran below the limit of detection. No significant effects were observed with rFVIIa.
    Critical care (London, England) 02/2014; 18(1):R27. · 4.72 Impact Factor
  • Critical care (London, England) 01/2014; 18(3):435. · 4.72 Impact Factor
  • Joanne van Ryn, Oliver Grottke, Henri Spronk
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    ABSTRACT: Dabigatran, a direct thrombin inhibitor, is increasingly used clinically as one of the new oral anticoagulants. This review summarizes the assays available to measure its activity and includes the relative sensitivity of the different assays for this agent. In addition to plasma-based clotting tests, assays commonly used in surgical/emergency settings, such as activated clotting time and thromboelastometry/thromboelastography, are reviewed. In addition, the thrombin generation assay is discussed as an important method to determine the potential risk of thrombosis or bleeding and its relevance to the measurement of direct thrombin inhibitors.
    Clinics in Laboratory Medicine. 01/2014;
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    ABSTRACT: Rapid control of hemorrhage is one of the key aspects in trauma handling. To cope with bleeding, local hemostatic approaches are useful, along with surgical and systemic homostatic therapy. In this experimental study, we investigated the efficacy of a fibrinogen/thrombin containing collagen patch (TachoSil) in a coagulopathic pig model with blunt liver trauma under severe hypothermia. Eighteen anesthetized pigs underwent hemodilution by exchanging 70% of the blood volume with Ringer Lactate solution and hydroxyethyl starch 130/0.4 (1:1). Ten minutes after induction of a grade III blunt liver trauma, the animals randomly received treatment with TachoSil (FT-patch, n = 9) or a collagen patch (Tachotop, control group, n = 9). Blood loss, hemodynamics, and coagulation parameters were observed for 2 h. To confirm the consistency of liver trauma, pathologic examination of the liver tissue was performed. Hypothermia (33.5°C ± 0.5°C) and hemodilution led to severe coagulopathy as measured by thromboelastometry and coagulation parameters. After trauma and patch application, thromboelastometry and coagulation parameters in the control group showed further deterioration compared with the stable parameters in the FT-patch group. The total blood loss was significantly reduced in the FT-patch group (FT-patch: 1195 mL; control group: 2495 mL; P < 0.001). Concordantly, the control animals were hemodynamically jeopardized to a higher degree. Microscopy confirmed a similar degree of liver injury. Despite severe hypothermia and coagulopathy, TachoSil provided effective hemorrhage control in pigs with blunt liver injury. Therefore, TachoSil demonstrated usefulness as an additional early therapy in cases of uncontrolled bleeding following severe trauma.
    Journal of Surgical Research 11/2013; · 2.02 Impact Factor
  • Oliver Grottke, Rolf Rossaint
    Critical care medicine 11/2013; 41(11):2661-2. · 6.37 Impact Factor
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    ABSTRACT: Significant advancements in nonsurgical and surgical approaches to control bleeding in severely injured patients have also improved the treatment of critical trauma-related coagulopathy. Nonsurgical procedures such as angiographic embolization are progressively considered to terminate arterial bleeding from pelvic fractures. The disturbance of coagulation may aggravate bleeding and hamper surgical procedures. The administration of coagulation factors and factor concentrates may be useful for correcting systemic coagulopathy and reducing the need for fresh frozen plasma, platelet, and red blood cell transfusions, which are associated with various adverse outcomes. In this review, nonsurgical management of critical trauma bleeding is discussed.
    Anesthesiology Clinics 03/2013; 31(1):41-53.
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    Anasthesiologie und Intensivmedizin 03/2013; 54(3):147-157. · 0.50 Impact Factor
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    ABSTRACT: Massive bleeding with coagulopathy and hemorrhagic shock poses a potential threat to life in numerous clinical settings. Optimal treatment including the prevention of exsanguination necessitates a standardized and interdisciplinary approach. Several studies have shown the importance of massive transfusion protocols and standardized coagulation algorithms to improve survival of severely bleeding patients and to avoid secondary complications. Thus, the Helsinki declaration for patient safety in anesthesiology demands the implementation of clinical practice guidelines for the treatment of patients requiring massive transfusion. This paper introduces a standardized algorithm for the treatment of patients with massive bleeding which was developed in consensus with the German Society of Anaesthesiology and Intensive Care Medicine (DGAI).
    Der Anaesthesist 02/2013; 62:213-224. · 0.85 Impact Factor
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    ABSTRACT: The use of PCC for the treatment of trauma-induced coagulopathy potentially increase the risk of thromboembolism and disseminated intravascular coagulation, which is addressed to an imbalance of both pro- and anticoagulants. As PCCs differ in composition, we used an in vitro dilutional approach to assess the overall thrombin generation of five different PCCs through various laboratory assays. The vitamin K-dependent coagulation factors, heparin, and antithrombin were assessed in five commercially available PCCs. The procoagulant potential of the PCCs was assessed in plasma and whole blood from 4 healthy donors by means of classical coagulation assays, thrombin generation assay and thromboelastometry. In order to reflect coagulopathy, whole blood was diluted to 80, 60, 40, and 20% with Ringer's lactate solution. The five different PCCs were characterised by comparable levels of factors II, VII, IX and X (all around 20-30 IU/mL), whereas the heparin (0 to 17.6 IU/mL) and antithrombin (0.06 to 1.29 IU/mL) levels were remarkably different between manufactures. In vitro dilution of blood induced a prolongation of the PT and aPTT, and attenuation of thrombin generation and ExTem induced thromboelastometry. Overall, non- or low-heparin containing PCCs restored the in vitro dilutional coagulopathy, whereas PCCs containing heparin have an anticoagulant effect. The thrombin generation assay showed to be the most sensitive method for assessment of PCC effects. This study shows that most available PCCs are not balanced regarding their pro- and anticoagulants. The effect of measured differences in thrombin generation among different PCCs requires further investigations to elaborate the clinical meaning of this finding in the treatment of trauma induced coagulopathy.
    PLoS ONE 01/2013; 8(5):e64100. · 3.53 Impact Factor
  • Oliver Grottke
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    ABSTRACT: PURPOSE OF REVIEW: Trauma-induced coagulopathy is a frequent complication in severely injured patients. To correct coagulopathy and restore haemostasis, these patients have traditionally been treated with fresh frozen plasma, but in the last decade, there has been a shift from empirical therapy to targeted therapy with coagulation factor concentrates and other haemostatic agents. This review highlights emerging therapeutic options and controversial topics. RECENT FINDINGS: Early administration of the antifibrinolytic medication tranexamic acid was shown in the multicentre CRASH-2 trial to be an effective and inexpensive means of decreasing blood loss. Numerous retrospective and experimental studies have shown that the use of coagulation factor concentrates decreases blood loss and may be useful in reducing the need for transfusion of allogeneic blood products. In particular, early use of fibrinogen concentrate and thrombin generators has a positive impact on haemostasis. However, the use of prothrombin complex concentrate to correct trauma-induced coagulopathy has also been associated with a potential risk of serious adverse events. SUMMARY: Current evidence in trauma resuscitation indicates a potential role for coagulation factor concentrates and other haemostatic agents in correcting trauma-induced coagulopathy. Despite a shift towards such transfusion strategy, there remains a shortage of data to support this approach.
    Current opinion in critical care 10/2012; · 2.67 Impact Factor
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    ABSTRACT: The paper investigates both fresh porcine spleen and liver and the possible decomposition of these organs under a freeze-thaw cycle. The effect of tissue preservation condition is an important factor which should be taken into account for protracted biomechanical tests. In this work, tension tests were conducted for a large number of tissue specimens from twenty pigs divided into two groups of 10. Concretely, the first group was tested in fresh state; the other one was tested after a freeze-thaw cycle which simulates the conservation conditions before biomechanical experiments. A modified Fung model for isotropic behavior was adopted for the curve fitting of each kind of tissues. Experimental results show strong effects of the realistic freeze-thaw cycle on the capsule of elastin-rich spleen but negligible effects on the liver which virtually contains no elastin. This different behavior could be explained by the autolysis of elastin by elastolytic enzymes during the warmer period after thawing. Realistic biomechanical properties of elastin-rich organs can only be expected if really fresh tissue is tested. The observations are supported by tests of intestines.
    Journal of biomechanics 08/2012; 45(14):2382-6. · 2.66 Impact Factor
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    ABSTRACT: Although prothrombin complex concentrate (PCC) is increasingly used for the treatment of trauma-induced coagulopathy, few studies have investigated the impact and safety of PCC for this indication. The present study was performed to assess PCC for treatment of coagulopathy after blunt liver injury under severe hypothermia. Coagulopathy in 14 anaesthetised pigs was induced by haemodilution. Subsequently, standardised blunt liver injury was induced under severe hypothermia (32.8-33.2°C). Animals were randomised to receive either PCC (35 IU kg⁻¹) or saline (control). Coagulation was assessed over the following 2 hours by thromboelastometry and thrombin generation. Internal organs were examined to determine presence of emboli. The administration of PCC showed a significant reduction in blood loss (p=0.002 vs. controls) and a significant increase in the rate of survival (p=0.022 vs. controls). Plasma thrombin generation in the PCC group increased considerably above baseline levels, with significant increases in peak thrombin levels and endogenous thrombin potential versus controls throughout the follow-up period. In addition, PT decreased significantly in the PCC group versus the control group. However, only slight improvements in thromboelastometry variables were observed. Histology showed an equal degree of liver injury in both groups, and no thromboembolism. In severely hypothermic pigs, the application of PCC corrected trauma-induced coagulopathy and reduced blood loss. Thus, the infusion of PCC might be a reasonable approach to reduce the need for blood cell transfusion in trauma. Furthermore, the impact and safety of PCC application can be monitored through thrombin generation and thromboelastometry under hypothermia.
    Thrombosis and Haemostasis 09/2011; 106(4):724-33. · 5.76 Impact Factor
  • Vox Sanguinis 08/2011; 101(2):154-74. · 2.85 Impact Factor
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    ABSTRACT: Despite increasing use of prothrombin complex concentrate (PCC) to treat hemorrhage-associated coagulopathy, few studies have investigated PCC in trauma, and there is a particular lack of safety data. This study was performed to evaluate PCC therapy in a porcine model of coagulopathy with blunt liver injury. Coagulopathy was induced in 27 anesthetized pigs by replacing approximately 70% blood volume with hydroxyethyl starch 130/0.4 and Ringer's lactate solution; erythrocytes were collected and retransfused. Ten minutes after trauma, animals randomly received PCC (35 or 50 IU/kg) or saline. Coagulation parameters including thromboelastometry, thrombin generation, and blood loss were monitored for 2 hours. Internal organs were examined macroscopically and histologically to determine the presence of emboli and assess liver injury. Total blood loss was significantly lower and survival was higher in both PCC groups versus the control group (P < .05). These outcomes appeared to be dose-independent. Thromboembolism was found in all animals treated with 50 IU/kg PCC; 44% also showed signs of disseminated intravascular coagulation. Liver injury was similar in all animals. In conclusion, 35 IU/kg PCC safely improved coagulation and attenuated blood loss. However, the higher dose of PCC (50 IU/kg) appeared to increase the risk of thromboembolism and disseminated intravascular coagulation.
    Blood 06/2011; 118(7):1943-51. · 9.78 Impact Factor
  • O Grottke, D R Spahn, R Rossaint
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    ABSTRACT: Despite improved strategies in the treatment of polytraumatized patients the mortality rate of severely injured patients remains high. Thus, worldwide 5 million patients die due to trauma or trauma-related complications each year. As the majority of early trauma-related deaths are attributed to or caused by exsanguination the prevention and treatment of coagulopathy is of paramount significance. With the aim of developing guidelines and improve strategies to treat polytraumatized patients the multidisciplinary Task Force for Advanced Bleeding Care in Trauma was founded in 2005. Under consideration of new clinical studies, an updated version of the original publication from 2007 has recently been published. Based on a systematic review of published literature the recommendations were formed according to "Grading of Recommendations Assessment, Development and Evaluation" (GRADE). This publication summarizes the main recommendations with a special emphasis on revisions and new aspects.
    Der Anaesthesist 06/2011; 60(6):546-54. · 0.85 Impact Factor
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    ABSTRACT: In this paper, we present the results of a user study with a bimanual haptic setup. The goal of the experiment was to evaluate if Guiard's theory of the bimanual frame of reference can be applied to interaction tasks in virtual environments (VE) with haptic rendering. This theory proposes an influence of the non-dominant hand (NDH) on the dominant hand (DH). The experiment was conducted with multiple trials under two different conditions: bimanual and unimanual. The interaction task in this scenario was a sequence of pointing, alignment and docking sub-tasks for the dominant hand. In the bimanual condition, an asynchronous pointing task was added for the non-dominant hand. This additional task was primarily designed to bring the non-dominant hand closer to the other hand and thus enable the creation of a frame of reference. Our results show the potential of this task design extension (with NDH utilization). Task completion times are significantly lower in the bimanual condition compared to the unimanual case, without significant impact on overall precision. Furthermore, the bimanual condition shows better mean accuracy over several measures, e.g., lateral displacement and penetration depth. Additionally, subject performance was not only compared for all participants, but also between subgroups: medical vs. non-medical and gamer vs. non-gamer. User preference for a bimanual system over a unimanual system has been indicated with a post-test questionnaire.
    3D User Interfaces (3DUI), 2011 IEEE Symposium on; 04/2011
  • O. Grottke, D. R. Spahn, R. Rossaint
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    ABSTRACT: Zusammenfassung Die Akutbehandlung polytraumatisierter Patienten mit Massenblutungen stellt trotz verbesserter chirurgischer und konventioneller Therapien eine besondere interdisziplinäre Herausforderung dar. Die epidemiologische Bedeutung dieses komplexen Krankheitsbilds ergibt sich aus der hohen Zahl von 5 Mio. Menschen, die weltweit jährlich an den Folgen eines Traumas sterben. Da traumaassoziierte Massenblutungen auf dem Boden einer Koagulopathie potenziell vermeidbar und behandelbar sind, gilt die Exsanguination als die häufigste vermeidbare Komplikation, die zum frühen Versterben nach Trauma führt. Mit dem Ziel, Behandlungsalgorithmen nach dem aktuellen Stand der Wissenschaft für die Versorgung schwer verletzter Patienten mit Gerinnungsstörungen zu entwickeln, wurde die „Task Force for Advanced Bleeding Care in Trauma“ 2005 gegründet. Die Erstveröffentlichung aus dem Jahr 2007 wurde entsprechend den Grundsätzen der „evidence-based medicine“ unter Berücksichtigung neuer klinischer Studien in überarbeiteter Form publiziert. Der vorliegende Beitrag gibt einen Überblick über die einzelnen Empfehlungen unter besonderer Berücksichtigung wesentlicher Neuerungen.
    Der Anaesthesist 01/2011; 60(6):546-554. · 0.85 Impact Factor
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    ABSTRACT: Segmentation of multiple muscles in magnetic resonance imaging (MRI) is challenging because of the similar intensities of the tissue. In this paper, a novel approach is presented applying a scene-based discrete deformable model (simplex mesh). D segmentation is performed on a set of structures rather than on a single object. Relevant structures are modeled in a two-stage hierarchy from groups of clustered muscles (as they usually appear in MRI) to individual muscles. Collision detection is involved during mesh deformation to provide additional information of neighboring structures. The method is implemented in C++ within the Medical Imaging Interaction Toolkit (MITK) framework. As a proof of concept, we tested the approach on five datasets of the pelvis, three of which have been segmented manually. Indicating the potential impact of the method, we do not claim its general validity yet.
    Bildverarbeitung für die Medizin 2009: Algorithmen - Systeme - Anwendungen, Proceedings des Workshops vom 20. bis 22. März 2011 in Lübeck; 01/2011
  • Oliver Grottke, Rolf Rossaint
    Wiener klinische Wochenschrift 12/2010; 122 Suppl 5:S23-4. · 0.81 Impact Factor