Erik Waage Nielsen

• Lynghaug, Trine; Fuskevåg, Ole Martin; Storm, Benjamin Stage; Nielsen, Erik Waage; Nilsen, Bent Aksel & Dietrichs, Erik Sveberg [Vis alle 7 forfattere av denne artikkelen] (2026). Subcutaneous Tranexamic Acid Achieves Comparable Serum Concentrations to Intramuscular Administration During Haemorrhagic Shock in a Swine Model. Acta Anaesthesiologica Scandinavica. ISSN 0001-5172. 70(6). doi: 10.1111/aas.70274. Fulltekst i vitenarkiv Vis sammendrag

  ABSTRACT Background Tranexamic acid is an antifibrinolytic agent reducing mortality when administered to trauma patients with haemorrhagic shock. This mortality reduction is time sensitive. Increased intramuscular dose administration has proven an effective alternative to intravenous administration in several studies and is used by some emergency medical services. However, subcutaneous administration has not been studied. Previous research indicates that subcutaneous tissue blood flow is more compromised during shock than muscle perfusion. Determining subcutaneous absorption is crucial to evaluate its potential as an alternative route and to assess the effect of accidental subcutaneous injection during intended intramuscular administration. Methods In this experimental study using historical intramuscular and intravenous control groups, a total of six Norwegian Landrace pigs (40–50 kg) used in a trauma surgery course were subjected to various abdominal and thoracic traumas. After 1 h of surgery, the animals received tranexamic acid 30 mg/kg subcutaneously. Serum was sampled at 0, 5, 15, 25, 35, 45, 60, and 85 min after administration. Tranexamic acid serum concentration was measured using liquid chromatography–tandem mass spectrometry and compared to intramuscular and intravenous groups from previous studies, in which animals had received tranexamic acid 30 mg/kg intramuscular ( n  = 7) or 15 mg/kg intravenous ( n  = 8). Results There was no statistical difference in serum concentrations between subcutaneous and intramuscular administration. Mean (±standard deviation) concentration after administration at 10, 45, and 85 min were 41.4 μg/mL (±19.0), 39.1 μg/mL (±8.9), and 33.4 μg/mL (±5.8), and for IM concentrations were 41.8 μg/mL (±18.9), 39.9 μg/mL (±7.8), and 44.2 μg/mL (±21.8). At 5 min, the concentration of both SC and IM administration was approximately half those observed after IV administration, but all concentrations were well above the 10–17 μg/mL concentration needed to inhibit fibrinolysis. Conclusions Although subcutaneous blood flow is sensitive to shock, serum tranexamic acid concentrations after subcutaneous administration in shocked pigs were comparable to those achieved after intramuscular administration. Intramuscular administration should remain the preferred secondary route after the standard intravenous route, but inadvertent subcutaneous injection is likely to achieve therapeutic serum concentrations. Editorial Comment This observational study in pigs undergoing hemorrhagic shock compared subcutaneous tranexamic acid administration to historical intravenous and intramuscular controls and found that plasma concentrations were comparable between routes. This suggests that inadvertent subcutaneous dosing during intramuscular injection likely achieves therapeutic levels. While promising, these results rely on historical controls and warrant further confirmatory studies. Intramuscular administration remains the preferred alternative to intravenous dosing for now.

• Hammervold, Rønnaug; Beqiri, Erta; Smielewski, Peter; Storm, Benjamin Stage; Nielsen, Erik Waage & Guérin, Claude [Vis alle 7 forfattere av denne artikkelen] (2026). Positive end-expiratory pressure increases intracranial pressure but does not affect PRx, regardless of body position, in a porcine ARDS model. Frontiers in Physiology. 17. doi: 10.3389/fphys.2026.1792273. Fulltekst i vitenarkiv Vis sammendrag

  Background: Positive end-expiratory pressure (PEEP) and prone positioning are key components in the management of acute respiratory distress syndrome (ARDS), improving gas exchange and protecting the lung via enhanced lung recruitment and homogenization of lung aeration. However, higher intrathoracic pressures may increase intracranial pressure (ICP) or impair cerebral autoregulation, as reflected by vascular reactivity. This study investigated whether stepwise PEEP elevations affect ICP, the pressure reactivity index (PRx), and brain tissue oxygenation (PbO2) in a porcine ARDS model, comparing prone and supine positions, and whether baseline physiological variables modify the ICP response.Methods: Twelve anesthetized pigs with bronchial lavage–induced ARDS were studied in a randomized crossover design with stepwise PEEP increases (5, 10, 15, and 20 cmH2O) in prone and supine positions while maintaining stable arterial carbon dioxide tension and cerebral perfusion pressure. Intracranial pressure, PRx, and PbO2 were continuously monitored, and effects of PEEP and position were analyzed using linear mixed-effects models and analysis of variance.Results: Increasing PEEP was associated with a progressive rise in ICP, whereas PRx remained unchanged across PEEP levels and body positions. PbO2 showed a non-significant upward trend with increasing PEEP, while the PbO2/PaO2 ratio remained stable. Higher baseline pulmonary artery pressure was associated with larger ICP increases, whereas higher baseline respiratory rate was associated with attenuated responses.Conclusion: In this porcine ARDS model, moderate PEEP escalation resulted in a modest increase in ICP without impairment of cerebrovascular reactivity, with similar effects in prone and supine positions, suggesting that lung protective ventilation strategies may be compatible with stable intracranial physiology when arterial carbon dioxide tension and cerebral perfusion pressure are controlled.

• Storm, Benjamin; Lappegård, Knut Tore; Ingul, Charlotte Ingeborg Björk; Nielsen, Erik Waage; Nilsen, Bent Aksel & Nyjordet, Anette [Vis alle 8 forfattere av denne artikkelen] (2026). Porcine Cardiac Arrest Model Using an Implantable Defibrillator. Journal of Visualized Experiments. 227. doi: 10.3791/69305. Fulltekst i vitenarkiv
• Hammervold, Rønnaug; Beqiri, Erta; Smielewski, Peter; Storm, Benjamin Stage; Nielsen, Erik Waage & Guérin, Claude [Vis alle 7 forfattere av denne artikkelen] (2025). Positive end-expiratory pressure increases intracranial pressure but not pressure reactivity index in supine and prone positions: a porcine model study. Frontiers in Medicine. 11. doi: 10.3389/fmed.2024.1501284. Fulltekst i vitenarkiv
• Faldaas, Bjørn Ove; Nielsen, Erik Waage; Storm, Benjamin Stage; Lappegård, Knut Tore; Nilsen, Bent Aksel & Kiss, Gabriel Hanssen [Vis alle 9 forfattere av denne artikkelen] (2024). Real-time feedback on chest compression efficacy by hands-free carotid Doppler in a porcine model. Resuscitation Plus. 18:100583. doi: 10.1016/j.resplu.2024.100583. Fulltekst i vitenarkiv Vis sammendrag

  Aim: Current guidelines for cardiopulmonary resuscitation (CPR) recommend a one-size-fits-all approach in relation to the positioning of chest compressions. We recently developed RescueDoppler, a hands-free Doppler ultrasound device for continuous monitoring of carotid blood flow velocity during CPR. The aim of the present study is to investigate whether RescueDoppler via real-time hemodynamic feedback, could identify both optimal and suboptimal compression positions. Methods: In this model of animal cardiac arrest, we induced ventricular fibrillation in five domestic pigs. Manual chest compressions were performed for ten seconds at three different positions on the sternum in random order and repeated six times. We analysed Time Average Velocity (TAV) with chest compression position as a fixed effect and animal, position, and sequential time within animals as random effects. Furthermore, we compared TAV to invasive blood pressure from the contralateral carotid artery. Results: We were able to detect changes in TAV when altering positions. The positions with the highest (range 19 to 48 cm/s) and lowest (6–25 cm/s) TAV were identified in all animals, with corresponding peak pressure 50–81 mmHg, and 46–64 mmHg, respectively. Blood flow velocity was, on average, highest at the middle position (TAV 33 cm/s), but with significant variability between animals (SD 2.8) and positions within the same animal (SD 9.3). Conclusion: RescueDoppler detected TAV changes during CPR with alternating chest compression positions, identifying the position yielding maximal TAV. Future clinical studies should investigate if RescueDoppler can be used as a real-time hemodynamical feedback device to guide compression position.

• Kristiansen, Steinar; Storm, Benjamin Stage; Emblem, Åse; Grønli, Renathe Henriksen; Pettersen, Kristin & Hilmo, Jonas Larsen [Vis alle 12 forfattere av denne artikkelen] (2024). Femoral nailing associated with bone marrow emboli in pigs induced a specific increase in blood IL-6 and broad inflammatory responses in the heart and lungs. Frontiers in Immunology. 15:1396800, s. 1–11. doi: 10.3389/fimmu.2024.1396800. Fulltekst i vitenarkiv Vis sammendrag

  Introduction: Bone marrow embolization may complicate orthopedic surgery, potentially causing fat embolism syndrome. The inflammatory potential of bone marrow emboli is unclear. We aimed to investigate the inflammatory response to femoral intramedullary nailing, specifically the systemic inflammatory effects in plasma, and local tissue responses. Additionally, the plasma response was compared to that following intravenous injection of autologous bone marrow. Methods: Twelve pigs underwent femoral nailing (previously shown to have fat emboli in lung and heart), four received intravenous bone marrow, and four served as sham controls. Blood samples were collected hourly and tissue samples postmortem. Additionally, we incubated bone marrow and blood, separately and in combination, from six pigs in vitro. Complement activation was detected by C3a and the terminal C5b-9 complement complex (TCC), and the cytokines TNF, IL-1β, IL-6 and IL-10 as well as the thrombin-antithrombin complexes (TAT) were all measured using enzyme-immunoassays. Results: After nailing, plasma IL-6 rose 21-fold, compared to a 4-fold rise in sham (p=0.0004). No plasma differences in the rest of the inflammatory markers were noted across groups. However, nailing yielded 2-3-times higher C3a, TCC, TNF, IL-1β and IL-10 in lung tissue compared to sham (p<0.0001-0.03). Similarly, heart tissue exhibited 2-times higher TCC and IL-1β compared to sham (p<0.0001-0.03). Intravenous bone marrow yielded 8-times higher TAT than sham at 30 minutes (p<0.0001). In vitro, incubation of bone marrow for four hours resulted in 95-times higher IL-6 compared to whole blood (p=0.03). Discussion: A selective increase in plasma IL-6 was observed following femoral nailing, whereas lung and heart tissues revealed a broad local inflammatory response not reflected systemically. In vitro experiments may imply bone marrow to be the primary IL-6 source.

• Faldaas, Bjørn Ove; Storm, Benjamin Stage; Lappegård, Knut Tore; How, Ole-Jakob; Nilsen, Bent Aksel & Kiss, Gabriel Hanssen [Vis alle 10 forfattere av denne artikkelen] (2024). A hands-free carotid Doppler can identify spontaneous circulation without interrupting cardiopulmonary resuscitation: an animal study. Intensive Care Medicine Experimental. 12(121). doi: 10.1186/s40635-024-00704-w. Fulltekst i vitenarkiv Vis sammendrag

  Background Identifying spontaneous circulation during cardiopulmonary resuscitation (CPR) is challenging. Current methods, which involve intermittent and time-consuming pulse checks, necessitate pauses in chest compressions. This issue is problematic in both in-hospital cardiac arrest and out-of-hospital cardiac arrest situations, where resources for identifying circulation during CPR may be limited. The fraction of chest compression plays a pivotal role in improving survival rates. To address this challenge, we evaluated a newly developed hands-free, continuous carotid Doppler system (RescueDoppler), designed to identify spontaneous circulation during chest compressions. In our study, we utilized a porcine model of cardiac arrest to investigate sequences of ventricular fbrillation, followed by defibrillation, and monitoring for the return of spontaneous circulation during chest compressions with the carotid Doppler system. We explored both manual compressions at 100 and 50 compressions per minute and mechanical compressions. To estimate the detection rate (i.e., sensitivity), we employed a logistic mixed model with animal identity as random effect. Results Offline analysis of Doppler color M-mode and spectral display successfully identified spontaneous circulation during chest compressions in all compression models. Spontaneous circulation was detected in 51 of 59 sequences, yielding an expected sensitivity of 98% with a 95% confidence interval of 59% to 99%. Conclusion The RescueDoppler, a continuous hands-free carotid Doppler system, demonstrates an expected sensitivity of 98% for identifying spontaneous circulation during both manual and mechanical chest compressions. Clinical studies are needed to further validate these findings.

• Jarmund, Anders Hagen; Kristiansen, Steinar; Leth-Olsen, Martin; Vogt, Ella Christina Stray; Nervik, Ingunn & Torp, Hans [Vis alle 8 forfattere av denne artikkelen] (2024). Perioperative Detection of Cerebral Fat Emboli From Bone Using High-Frequency Doppler Ultrasound. Ultrasound in Medicine and Biology. ISSN 0301-5629. 51(1), s. 138–148. doi: 10.1016/j.ultrasmedbio.2024.09.017. Fulltekst i vitenarkiv Vis sammendrag

  Objective - Fat embolism syndrome and cerebral fat emboli are rare yet serious conditions arising from systemic distribution of bone marrow emboli. Emboli are known to produce high-intensity transient signals (HITS) in a Doppler signal. We hypothesized that both intramedullary nailing in pigs and median sternotomy in human infants cause bone marrow release, that some of these cause cerebral emboli, and that these were detectable by a new cerebral doppler ultrasound monitoring system (NeoDoppler). We also aimed to describe the intensity of HITS generated during these procedures.<p> <p>Methods - Specific pathogen-free Norwegian landrace pigs were allocated to either bilateral femoral nailing or injection of autologous bone marrow (positive controls). Testing was carried out under continuous Doppler monitoring. Presence of cerebral emboli was confirmed with histology. NeoDoppler data from infants undergoing sternotomy prior to cardiac surgery were investigated for comparison.<p> <p>Results - Eleven of twelve pigs were monitored with cerebral Doppler ultrasound during femoral surgery. HITS were seen in five (45%). Brain biopsies demonstrated bone marrow emboli in 11 of the 12 (92%). Four positive control pigs received intraarterial injections of bone marrow, saline, or contrast, and strong HITS were detected in all pigs (100%). Median sternotomy in eight human infants was associated with a significant increase in embolic burden; the HITS intensity was lower than HITS in pigs.<p> <p>Conclusion - High-frequency cerebral Doppler ultrasound is a valuable tool for perioperative monitoring that can detect emboli in real-time, but sensitivity and specificity for bone marrow emboli may be limited and size-dependent.

• Kristiansen, Steinar; Jarmund, Anders Hagen; Hilmo, Jonas Larsen; Mollnes, Tom Eirik; Leth-Olsen, Martin & Nyrnes, Siri Ann [Vis alle 12 forfattere av denne artikkelen] (2024). Femoral Nailing in a Porcine Model Causes Bone Marrow Emboli in the Lungs and Systemic Emboli in the Heart and Brain. JBJS Open Access. 9:e23.00128(1), s. 1–8. doi: 10.2106/JBJS.OA.23.00128. Fulltekst i vitenarkiv Vis sammendrag

  Background: Shaft fractures of the femur are commonly treated with intramedullary nailing, which can release bone marrow emboli into the bloodstream. Emboli can travel to the lungs, impairing gas exchange and causing inflammation. Occasionally, emboli traverse from the pulmonary to the systemic circulation, hindering perfusion and resulting in injuries such as heart and brain infarctions, known as fat embolism syndrome. We studied the extent of systemic bone marrow embolization in a pig model. Methods: Twelve anesthetized pigs underwent bilateral intramedullary nailing of the femur, while 3 animals served as sham controls. Monitoring included transesophageal echocardiography (TEE), pulse oximetry, electrocardiography, arterial blood pressure measurement, and blood gas and troponin-I analysis. After surgery, animals were monitored for 240 minutes before euthanasia. Post mortem, the heart, lungs, and brain were biopsied. Results: Bone marrow emboli were found in the heart and lungs of all 12 of the pigs that underwent intramedullary nailing and in the brains of 11 of them. No emboli were found in the sham group. The pigs subjected to intramedullary nailing exhibited significant hypoxia (PaO2/FiO2 ratio, 410 mm Hg [95% confidence interval (CI), 310 to 510) compared with the sham group (594 mm Hg [95% CI, 528 to 660]). The nailing group exhibited ST-segment alterations consistent with myocardial ischemia and a significant increase in the troponin-I level compared with the sham group (1,580 ng/L [95% CI, 0 to 3,456] versus 241 ng/L [95% CI, 0 to 625] at the 240-minute time point; p = 0.005). TEE detected emboli in the right ventricular outflow tract, but not systemically, in the nailing group. Conclusions: Bilateral intramedullary nailing caused bone marrow emboli in the lungs and systemic emboli in the heart and brain in this pig model. The observed clinical manifestations were consistent with coronary and pulmonary emboli. TEE detected pulmonary but not systemic embolization. Clinical Relevance: Femoral intramedullary nailing in humans is likely to result in embolization as described in our pig model. Focused monitoring is necessary for detection of fat embolism syndrome. Absence of visual emboli in the left ventricle on TEE does not exclude the occurrence of systemic bone marrow emboli.

• Berg, Kristin Sandal; Seines, Ellisiv; Gâl, Petter; Løberg-Emanuelsen, Lise; Stubhaug, Audun & Nielsen, Erik Waage [Vis alle 7 forfattere av denne artikkelen] (2024). Absorption and pharmacokinetics of bupivacaine after bilateral topical administration in tonsillar fossae for posttonsillectomy pain relief. Pharmacology Research & Perspectives. 12(2). doi: 10.1002/prp2.1196. Fulltekst i vitenarkiv Vis sammendrag

  No previous studies have investigated the systemic absorption of bupivacaine when used topically for posttonsillectomy pain. The present study was undertaken to investigate the pharmacokinetics of bupivacaine after administration by a swab in the tonsillar fossae over 4 min after tonsillectomy. Eleven adult patients undergoing elective tonsillectomy were recruited. After removal of both tonsils, each of the two tonsillar fossae was covered with a swab moistened with 2 mL of bupivacaine 5 mg/mL, that is, a total of 20 mg bupivacaine. Blood samples were drawn after 0, 5, 10, 20, 30, 45, and 60 min. Bupivacaine was analyzed with an ultra-high-performance liquid chromatography–tandem mass spectrometry method. The highest single measured bupivacaine serum concentration was 23.2 ng/mL and took place 10 min after drug administration. Mean (±SD) Cmax was 11.4 ± 6.0 ng/mL and mean tmax was 11.3 ± 4.7 min. Mean t1/2 was 31.6 ± 9.3 min. As the toxic concentration threshold has been reported to be in the interval 1500–4500 ng/mL, the concentrations measured were well below 2% of the lowest cited toxic threshold. In conclusion, this study shows that applying 4 mL of bupivacaine 5 mg/mL by a swab in the tonsillar fossae posttonsillectomy yields very low plasma concentrations, suggesting its safe application without any risk of systemic toxic effects.

• Marsh, Phillip L.; Moore, Ernest E.; Moore, Hunter B.; Bunch, Connor M.; Aboukhaled, Michael & Condon, Shaun M. [Vis alle 39 forfattere av denne artikkelen] (2023). Iatrogenic air embolism: pathoanatomy, thromboinflammation, endotheliopathy, and therapies. Frontiers in Immunology. 14. doi: 10.3389/fimmu.2023.1230049. Fulltekst i vitenarkiv Vis sammendrag

  Iatrogenic vascular air embolism is a relatively infrequent event but is associated with significant morbidity and mortality. These emboli can arise in many clinical settings such as neurosurgery, cardiac surgery, and liver transplantation, but more recently, endoscopy, hemodialysis, thoracentesis, tissue biopsy, angiography, and central and peripheral venous access and removal have overtaken surgery and trauma as significant causes of vascular air embolism. The true incidence may be greater since many of these air emboli are asymptomatic and frequently go undiagnosed or unreported. Due to the rarity of vascular air embolism and because of the many manifestations, diagnoses can be difficult and require immediate therapeutic intervention. An iatrogenic air embolism can result in both venous and arterial emboli whose anatomic locations dictate the clinical course. Most clinically significant iatrogenic air emboli are caused by arterial obstruction of small vessels because the pulmonary gas exchange filters the more frequent, smaller volume bubbles that gain access to the venous circulation. However, there is a subset of patients with venous air emboli caused by larger volumes of air who present with more protean manifestations. There have been significant gains in the understanding of the interactions of fluid dynamics, hemostasis, and inflammation caused by air emboli due to in vitro and in vivo studies on flow dynamics of bubbles in small vessels. Intensive research regarding the thromboinflammatory changes at the level of the endothelium has been described recently. The obstruction of vessels by air emboli causes immediate pathoanatomic and immunologic and thromboinflammatory responses at the level of the endothelium. In this review, we describe those immunologic and thromboinflammatory responses at the level of the endothelium as well as evaluate traditional and novel forms of therapy for this rare and often unrecognized clinical condition.

• Gramstad, Olav Rogde; Schjalm, Camilla; Mollnes, Tom Eirik & Nielsen, Erik Waage (2023). Increased thromboinflammatory load in hereditary angioedema. Clinical and Experimental Immunology. ISSN 0009-9104. 214(2), s. 170–181. doi: 10.1093/cei/uxad091. Fulltekst i vitenarkiv Vis sammendrag

  C1 inhibitor (C1Inh) is a serine protease inhibitor involved in the kallikrein-kinin system, the complement system, the coagulation system, and the fibrinolytic system. In addition to the plasma leakage observed in hereditary angioedema (HAE), C1Inh deficiency may also affect these systems, which are important for thrombosis and inflammation. The aim of this study was to investigate the thromboinflammatory load in C1Inh deficiency. We measured 27 cytokines including interleukins, chemokines, interferons, growth factors, and regulators using multiplex technology. Complement activation (C4d, C3bc, and sC5b-C9/TCC), haemostatic markers (β-thromboglobulin (β-TG), thrombin-antithrombin complexes (TAT), prothrombin fragment 1 + 2 (F1 + 2), active plasminogen activator inhibitor-1 (PAI-1), and the neutrophil activation marker myeloperoxidase (MPO) were measured by enzyme immunoassays. Plasma and serum samples were collected from 20 patients with HAE type 1 or 2 in clinical remission and compared with 20 healthy age- and sex-matched controls. Compared to healthy controls, HAE patients had significantly higher levels of tumour necrosis factor (TNF), interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-7, IL-9, IL-12, and IL-17A, chemokine ligand (CXCL) 8, chemokine ligand (CCL) 3, CCL4, IL-1 receptor antagonist (IL-1RA), granulocyte-macrophage colony-stimulating factor (GM-CSF), fibroblast growth factor (FGF) 2 and platelet-derived growth factor (PDGF)-BB. HAE patients also had higher levels of TAT and F1 + 2. Although granulocyte colony-stimulating factor (G-CSF), β-TG and PAI-1 were higher in HAE patients, the differences did not reach statistical significance after correction for multiple testing. In conclusion, C1Inh deficiency is associated with an increased baseline thromboinflammatory load. These findings may reflect that HAE patients are in a subclinical attack state outside of clinically apparent oedema attacks.

• Marsh, Phillip L.; Moore, Ernest E.; Moore, Hunter B.; Bunch, Connor M.; Aboukhaled, Michael & Condon, Shaun M. [Vis alle 39 forfattere av denne artikkelen] (2023). Iatrogenic air embolism: pathoanatomy, thromboinflammation, endotheliopathy, and therapies. Frontiers in Immunology. 14:1230049, s. 1–26. doi: 10.3389/fimmu.2023.1230049. Fulltekst i vitenarkiv Vis sammendrag

  Iatrogenic vascular air embolism is a relatively infrequent event but is associated with significant morbidity and mortality. These emboli can arise in many clinical settings such as neurosurgery, cardiac surgery, and liver transplantation, but more recently, endoscopy, hemodialysis, thoracentesis, tissue biopsy, angiography, and central and peripheral venous access and removal have overtaken surgery and trauma as significant causes of vascular air embolism. The true incidence may be greater since many of these air emboli are asymptomatic and frequently go undiagnosed or unreported. Due to the rarity of vascular air embolism and because of the many manifestations, diagnoses can be difficult and require immediate therapeutic intervention. An iatrogenic air embolism can result in both venous and arterial emboli whose anatomic locations dictate the clinical course. Most clinically significant iatrogenic air emboli are caused by arterial obstruction of small vessels because the pulmonary gas exchange filters the more frequent, smaller volume bubbles that gain access to the venous circulation. However, there is a subset of patients with venous air emboli caused by larger volumes of air who present with more protean manifestations. There have been significant gains in the understanding of the interactions of fluid dynamics, hemostasis, and inflammation caused by air emboli due to in vitro and in vivo studies on flow dynamics of bubbles in small vessels. Intensive research regarding the thromboinflammatory changes at the level of the endothelium has been described recently. The obstruction of vessels by air emboli causes immediate pathoanatomic and immunologic and thromboinflammatory responses at the level of the endothelium. In this review, we describe those immunologic and thromboinflammatory responses at the level of the endothelium as well as evaluate traditional and novel forms of therapy for this rare and often unrecognized clinical condition.

• Lynghaug, Trine; Bakke, Håkon Kvåle; Fuskevåg, Ole Martin; Nielsen, Erik Waage & Dietrichs, Erik Sveberg (2023). How should tranexamic acid be administered in hemorrhagic shock? continuous serum concentration measurements in a swine model. Shock. ISSN 1073-2322. 60(5), s. 707–712. doi: 10.1097/SHK.0000000000002222. Fulltekst i vitenarkiv Vis sammendrag

  Background: Tranexamic acid (TXA) reduces mortality in trauma patients. Intramuscular (IM) administration could be advantageous in low-resource and military settings. Achieving the same serum concentration as intravenous (IV) administration is important to achieve equal mortality reduction. Therefore, we aimed to investigate whether dividing an IM dose of TXA between two injection sites and whether an increase in dose would lead to serum concentrations comparable to those achieved by IV administration. Methods: Norwegian landrace pigs (n = 29) from a course in hemostatic emergency surgery were given TXA 1 h after start of surgery. Blood samples were drawn at 0, 5, 10, 15, 20, 25, 35, 45, 60, and 85 min. The samples were centrifuged and serum TXA concentrations quantified with liquid chromatography-tandem mass spectrometry. The use of two injection sites was compared with distributing the dose on one injection site, and a dose of 15 mg/kg was compared with a dose of 30 mg/kg. All IM groups were compared with IV administration. Results: The groups were in a similar degree of shock. Increasing the IM dose from the standard of 15 mg/kg to 30 mg/kg resulted in significantly higher serum concentrations of TXA, comparable to those achieved by IV administration. Distributing the IM dose on two injection sites did not affect drug uptake, as shown by equal serum concentrations. Conclusions: For IM administration of TXA, 30 mg/kg should be the standard dose. With a short delay, IM administration will provide equal serum concentrations as IV administration, above what is considered necessary to inhibit fibrinolysis.

• Faldaas, Bjørn Ove; Nielsen, Erik Waage; Storm, Benjamin; Lappegård, Knut Tore; How, Ole-Jakob & Nilsen, Bent Aksel [Vis alle 10 forfattere av denne artikkelen] (2023). Hands-free continuous carotid Doppler ultrasound for detection of the pulse during cardiac arrest in a porcine model. Resuscitation Plus. 15:100412, s. 1–10. doi: 10.1016/j.resplu.2023.100412. Fulltekst i vitenarkiv Vis sammendrag

  Background/Purpose Pulse palpation is an unreliable method for diagnosing cardiac arrest. To address this limitation, continuous hemodynamic monitoring may be a viable solution. Therefore, we developed a novel, hands-free Doppler system, RescueDoppler, to detect the pulse continuously in the carotid artery. Methods In twelve pigs, we evaluated RescueDoppleŕs potential to measure blood flow velocity in three situations where pulse palpation of the carotid artery was insufficient: (1) systolic blood pressure below 60 mmHg, (2) ventricular fibrillation (VF) and (3) pulseless electrical activity (PEA). (1) Low blood pressure was induced using a Fogarty balloon catheter to occlude the inferior vena cava. (2) An implantable cardioverter-defibrillator induced VF. (3) Myocardial infarction after microembolization of the left coronary artery caused True-PEA. Invasive blood pressure was measured in the contralateral carotid artery. Time-averaged blood flow velocity (TAV) in the carotid artery was related to mean arterial pressure (MAP) in a linear mixed model. Results RescueDoppler identified pulsatile blood flow in 41/41 events with systolic blood pressure below 60 mmHg, with lowest blood pressure of 19 mmHg. In addition the absence of spontaneous circulation was identified in 21/21 VF events and true PEA in 2/2 events. The intraclass correlation coefficient within animals for TAV and MAP was 0.94 (95% CI. 0.85–0.98). Conclusions In a porcine model, RescueDoppler reliably identified pulsative blood flow with blood pressures below 60 mmHg. During VF and PEA, circulatory arrest was rapidly and accurately demonstrated. RescueDoppler could potentially replace unreliable pulse palpation during cardiac arrest and cardiopulmonary resuscitation.

• Storjord, Elin; Airila-Månsson, Stella; Karlsen, Katarzyna; Madsen, Martin Ragnar Skjerve; Dahl, Jim André & Landsem, Anne [Vis alle 14 forfattere av denne artikkelen] (2022). Dental and Periodontal Health in Acute Intermittent Porphyria. Life. 12:1270(8), s. 1–18. doi: 10.3390/life12081270. Fulltekst i vitenarkiv Vis sammendrag

  In the inherited metabolic disorder acute intermittent porphyria (AIP), high sugar intake prevents porphyric attacks due to the glucose effect and the following high insulin levels that may lower AIP disease activity. Insulin resistance is a known risk factor for periodontitis and sugar changes diabetogenic hormones and affects dental health. We hypothesized differences in homeostasis model assessment (HOMA) scores for insulin resistance in AIP cases vs. controls and in those with periodontitis. Our aim was to systematically study dental health in AIP as poor dental health was previously only described in case reports. Further, we aimed to examine if poor dental health and kidney failure might worsen AIP as chronic inflammation and kidney failure might increase disease activity. In 47 AIP cases and 47 matched controls, X-rays and physical examination of clinical attachment loss (CAL), probing pocket depth (PPD), and decayed missing filled teeth (DMFT) were performed. Dietary intake was evaluated through a diet logbook. Plasma cytokines and diabetogenic hormones were measured using multiplex technology and urine porphobilinogen and kidney and liver function by routine methods. An excel spreadsheet from the University of Oxford was used to estimate HOMA scores; beta cell function, HOMA%B (%B), insulin sensitivity, HOMA%S (%S), and insulin resistance HOMA-IR (IR), based on glucose and plasma (P) C-peptide. The Wilcoxon matched-pairs signed rank test, the Mann–Whitney U-test, and Spearman’s non-parametric correlation were used. Insulin (p = 0.007) and C-peptide (p = 0.006) were higher in the AIP cases with periodontitis versus those without. In AIP patients, the liver fibrosis index 4 correlated with DMFT (p < 0.001) and CAL ≥4 mm (p = 0.006); the estimated glomerular filtration rate correlated with DMFT (p < 0.001) and CAL ≥4 mm (p = 0.02). CAL ≥4 mm was correlated with chemokine ligand 11 and interleukin (IL)-13 (p = 0.04 for both), and PPD >5 mm was correlated with plasminogen activator inhibitor-1 (p = 0.003) and complement component 3 (p = 0.02). In conclusion, dental health in AIP cases was correlated with insulin resistance, inflammatory markers, and biomarkers of kidney and liver function, demonstrating that organ damage in the kidney and liver are associated with poorer dental health.

• Storm, Benjamin; Ludviksen, Judith K; Christiansen, Dorte; Fure, Hilde; Pettersen, Kristin & Landsem, Anne [Vis alle 11 forfattere av denne artikkelen] (2022). Venous Air Embolism Activates Complement C3 Without Corresponding C5 Activation and Trigger Thromboinflammation in Pigs. Frontiers in Immunology. 13:839632, s. 1–13. doi: 10.3389/fimmu.2022.839632. Fulltekst i vitenarkiv Vis sammendrag

  Introduction: Air embolism may complicate invasive medical procedures. Bubbles trigger complement C3-mediated cytokine release, coagulation, and platelet activation in vitro in human whole blood. Since these findings have not been verified in vivo, we aimed to examine the effects of air embolism in pigs on thromboinflammation. Methods: Forty-five landrace pigs, average 17 kg (range 8.5-30), underwent intravenous air infusion for 300 or 360 minutes (n=29) or served as sham (n=14). Fourteen pigs were excluded due to e.g. infections or persistent foramen ovale. Blood was analyzed for white blood cells (WBC), complement activation (C3a and terminal C5b-9 complement complex [TCC]), cytokines, and hemostatic parameters including thrombin-antithrombin (TAT) using immunoassays and rotational thromboelastometry (ROTEM). Lung tissue was analyzed for complement and cytokines using qPCR and immunoassays. Results are presented as medians with interquartile range. Results: In 24 pigs receiving air infusion, WBC increased from 17×109/L (10-24) to 28 (16-42) (p<0.001). C3a increased from 21 ng/mL (15-46) to 67 (39-84) (p<0.001), whereas TCC increased only modestly (p=0.02). TAT increased from 35 µg/mL (28-42) to 51 (38-89) (p=0.002). ROTEM changed during first 120 minutes: Clotting time decreased from 613 seconds (531-677) to 538 (399-620) (p=0.006), clot formation time decreased from 161 seconds (122-195) to 124 (83-162) (p=0.02) and α-angle increased from 62 degrees (57-68) to 68 (62-74) (p=0.02). In lungs from pigs receiving air compared to sham animals, C3a was 34 ng/mL (14-50) versus 4.1 (2.4-5.7) (p<0.001), whereas TCC was 0.3 CAU/mL (0.2-0.3) versus 0.2 (0.1-0.2) (p=0.02). Lung cytokines in pigs receiving air compared to sham animals were: IL-1β 302 pg/mL (190-437) versus 107 (66-120), IL-6 644 pg/mL (358-1094) versus 25 (23-30), IL-8 203 pg/mL (81-377) versus 21 (20-35), and TNF 113 pg/mL (96-147) versus 16 (13-22) (all p<0.001). Cytokine mRNA in lung tissue from pigs receiving air compared to sham animals increased 12-fold for IL-1β, 121-fold for IL-6, and 17-fold for IL-8 (all p<0.001). Conclusion: Venous air embolism in pigs activated C3 without a corresponding C5 activation and triggered thromboinflammation, consistent with a C3-dependent mechanism. C3-inhibition might represent a therapeutic approach to attenuate this response.

• Nielsen, Erik Waage; Miller, Yoav; Brekke, Ole Lars; Grond, Joost; Duong, Anh Hoang & Fure, Hilde [Vis alle 12 forfattere av denne artikkelen] (2022). A Novel Porcine Model of Ischemia-Reperfusion Injury After Cross-Clamping the Thoracic Aorta Revealed Substantial Cardiopulmonary, Thromboinflammatory and Biochemical Changes Without Effect of C1-Inhibitor Treatment. Frontiers in Immunology. 13:852119, s. 1–12. doi: 10.3389/fimmu.2022.852119. Fulltekst i vitenarkiv Vis sammendrag

  Ischemic injury worsens upon return of blood and innate immunity including the complement system play a central role in ischemia-reperfusion injury (IRI) as in thoracic aortic surgery. Complement component1 inhibitor (C1-INH) has been shown to reduce IRI and is a broad-acting plasma cascade inhibitor. We established a new porcine model of IRI by cross-clamping the thoracic aorta and evaluated the global changes occurring in organ function, systemic inflammatory response and organ damage with or without treatment with C1-INH-concentrate. Twenty-four piglets (8.8-11.1 kg) underwent 45 minutes clamping of the thoracic aorta at the Th8 level. Upfront 12 piglets received human saline and 12 received C1-INH (250 IU/kg) intravenously. Three sham animals received thoracic opening without clamping. Reperfusion lasted 5 hours. We studied ten cardiorespiratory markers, three hematologic markers, eleven inflammatory markers, and twelve organ damage markers over the whole experimental period. Postmortem tissue homogenates from seven organs were examined for inflammatory markers and analysed by two-way repeated-measures ANOVA, area under the curve or unpaired t-tests. By excluding sham and combining treated and untreated animals, the markers reflected a uniform, broad and severe organ dysfunction. The mean and range fold change from before cross-clamp onset to maximum change for the different groups of markers were: cardiorespiratory 1.4 (0.2-3.7), hematologic 1.9 (1.2-2.7), plasma inflammatory 19.5 (1.4-176) and plasma organ damage 2.9 (1.1-8.6). Treatment with C1-INH had only a marginal effect on the IRI-induced changes, reaching statistical significance only for the plasma complement activation product TCC (p=0.0083) and IL-4 (p=0.022) and INF-α (p=0.016) in the colon tissue. In conclusion, the present novel model of porcine global IRI is forceful with regards to central markers and could generally be applicable for pathophysiological studies. C1-INH treatment had no significant effect, but the model allows for future testing of other drugs attenuating IRI globally.

• Kristiansen, Steinar; Storm, Benjamin; Dahle, Dalia; Josefsen, Terje D.; Dybwik, Knut Gustav & Nilsen, Bent Aksel [Vis alle 7 forfattere av denne artikkelen] (2021). Intraosseous fluid resuscitation causes systemic fat emboli in a porcine hemorrhagic shock model. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. 29. doi: 10.1186/s13049-021-00986-z. Fulltekst i vitenarkiv Vis sammendrag

  Background Intraosseous cannulation can be life-saving when intravenous access cannot be readily achieved. However, it has been shown that the procedure may cause fat emboli to the lungs and brain. Fat embolization may cause serious respiratory failure and fat embolism syndrome. We investigated whether intraosseous fluid resuscitation in pigs in hemorrhagic shock caused pulmonary or systemic embolization to the heart, brain, or kidneys and if this was enhanced by open chest conditions. Methods We induced hemorrhagic shock in anesthetized pigs followed by fluid-resuscitation through bilaterally placed tibial (hind leg) intraosseous cannulas. The fluid-resuscitation was limited to intraosseous or i.v. fluid therapy, and did not involve cardiopulmonary resuscitation or other interventions. A subgroup underwent median sternotomy with pericardiectomy and pleurotomy before hemorrhagic shock was induced. We used invasive hemodynamic and respiratory monitoring including Swan Ganz pulmonary artery catheter and transesophageal echocardiography and obtained biopsies from the lungs, heart, brain, and left kidney postmortem. Results All pigs exposed to intraosseous infusion had pulmonary fat emboli in postmortem biopsies. Additionally, seven of twenty-one pigs had coronary fat emboli. None of the pigs with open chest had fat emboli in postmortem lung, heart, or kidney biopsies. During intraosseous fluid-resuscitation, three pigs developed significant ST-elevations on ECG; all of these animals had coronary fat emboli on postmortem biopsies. Conclusions Systemic fat embolism occurred in the form of coronary fat emboli in a third of the animals who underwent intraosseous fluid resuscitation. Open chest conditions did not increase the incidence of systemic fat embolization.

• Gramstad, Olav Rogde; Kandanur, Sai Priya Sarma; Etscheid, Michael; Nielsen, Erik Waage & Kanse, Sandip (2021). Factor VII activating protease (FSAP) is not essential in the pathophysiology of angioedema in patients with C1 inhibitor deficiency. Molecular Immunology. ISSN 0161-5890. 142, s. 95–104. doi: 10.1016/j.molimm.2021.11.019. Fulltekst i vitenarkiv Vis sammendrag

  Background: Excessive bradykinin (BK) generation from high molecular weight kininogen (HK) by plasma kallikrein (PK) due to lack of protease inhibition is central to the pathophysiology of hereditary angioedema (HAE). Inadequate protease inhibition may contribute to HAE through a number of plasma proteases including factor VII activating protease (FSAP) that can also cleave HK.<p> <p>Objective: To investigate the interaction between FSAP and C1 inhibitor (C1Inh) and evaluate the potential role of FSAP in HAE with C1Inh deficiency.<p> <p>Materials and methods: Plasma samples from 20 persons with HAE types 1 or 2 in remission were studied and compared to healthy controls. We measured and compared antigenic FSAP levels, spontaneous FSAP activity, FSAP generation potential, activation of plasma pre-kallikrein (PPK) by FSAP, and the formation of FSAP-C1Inh and FSAP-alpha2-antiplasmin (FSAP-α2AP) complexes. Furthermore, we measured HK cleavage and PK activation after activation of endogenous pro-FSAP and after addition of exogenous FSAP.<p> <p>Results: In plasma from HAE patients, there is increased basal FSAP activity compared to healthy volunteers. HAE plasma exhibits decreased formation of FSAP-C1Inh complexes and increased formation of FSAP-α2AP complexes in histone-activated plasma. Although exogenous FSAP can cleave HK in plasma, this was not seen when endogenous plasma pro-FSAP was activated with histones in either group. PK was also not activated by FSAP in plasma.<p> <p>Conclusion: In this study, we established that FSAP activity is increased and the pattern of FSAP-inhibitor complexes is altered in HAE patients. However, we did not find evidence suggesting that FSAP contributes directly to HAE attacks.

• Storm, Benjamin; Halvorsen, Per Steinar; Skulstad, Helge; Dybwik, Knut Gustav; Schjalm, Camilla & Christiansen, Dorte [Vis alle 11 forfattere av denne artikkelen] (2021). Open chest and pericardium facilitate transpulmonary passage of venous air emboli. Acta Anaesthesiologica Scandinavica. ISSN 0001-5172. 65(5), s. 648–655. doi: 10.1111/aas.13796. Fulltekst i vitenarkiv Vis sammendrag

  Background Transpulmonary passage of air emboli can lead to fatal brain- and myocardial infarctions. We studied whether pigs with open chest and pericardium had a greater transpulmonary passage of venous air emboli than pigs with closed thorax. Methods We allocated pigs with verified closed foramen ovale to venous air infusion with either open chest with sternotomy and opening of the pleura and pericardium (n = 8) or closed thorax (n = 16). All pigs received a five-hour intravenous infusion of ambient air, starting at 4-6 mL/kg/h and increased by 2 mL/kg/h each hour. We assessed transpulmonary air passage by transesophageal M-mode echocardiography and present the results as median with inter-quartile range (IQR). Results Transpulmonary air passage occurred in all pigs with open chest and pericardium and in nine pigs with closed thorax (56%). Compared to pigs with closed thorax, pigs with open chest and pericardium had a shorter to air passage (10 minutes (5-16) vs. 120 minutes (44-212), P < .0001), a smaller volume of infused air at the time of transpulmonary passage (12 mL (10-23) vs.170 mL (107-494), P < .0001), shorter time to death (122 minutes (48-185) vs 263 minutes (248-300, P = .0005) and a smaller volume of infused air at the time of death (264 mL (53-466) vs 727 mL (564-968), P = .001). In pigs with open chest and, infused air and time to death correlated strongly (r = 0.95, P = .001). Conclusion Open chest and pericardium facilitated the transpulmonary passage of intravenously infused air in pigs.

• Storm, Benjamin; Christiansen, Dorte; Fure, Hilde; Ludviksen, Judith K; Lau, Corinna & Lambris, John D. [Vis alle 11 forfattere av denne artikkelen] (2021). Air Bubbles Activate Complement and Trigger Hemostasis and C3-Dependent Cytokine Release Ex Vivo in Human Whole Blood. Journal of Immunology. ISSN 0022-1767. 207(11), s. 2828–2840. doi: 10.4049/jimmunol.2100308. Fulltekst i vitenarkiv Vis sammendrag

  Venous air embolism, which may complicate medical and surgical procedures, activates complement and triggers thromboinflammation. In lepirudin-anticoagulated human whole blood, we examined the effect of air bubbles on complement and its role in thromboinflammation. Whole blood from 16 donors was incubated with air bubbles without or with inhibitors of C3, C5, C5aR1, or CD14. Complement activation, hemostasis, and cytokine release were measured using ELISA and quantitative PCR. Compared with no air, incubating blood with air bubbles increased, on average, C3a 6.5-fold, C3bc 6-fold, C3bBbP 3.7-fold, C5a 4.6- fold, terminal complement complex sC5b9 3.6-fold, prothrombin fragments 1+2 (PTF1+2) 25-fold, tissue factor mRNA (TF-mRNA) 26- fold, microparticle tissue factor 6.1-fold, b-thromboglobulin 26-fold (all p < 0.05), and 25 cytokines 11-fold (range, 1.5 78-fold; all p < 0.0001). C3 inhibition attenuated complement and reduced PTF1+2 2-fold, TF-mRNA 5.4-fold, microparticle tissue factor 2-fold, and the 25 cytokines 2.7-fold (range, 1.4 4.9-fold; all p < 0.05). C5 inhibition reduced PTF1+2 2-fold and TF-mRNA 12-fold (all p < 0.05). C5 or CD14 inhibition alone reduced three cytokines, including IL-1b (p 5 0.02 and p 5 0.03). Combined C3 and CD14 inhibition reduced all cytokines 3.9-fold (range, 1.3 9.5-fold; p < 0.003) and was most pronounced for IL-1b (3.2- versus 6.4-fold), IL-6 (2.5- versus 9.3-fold), IL-8 (4.9- versus 8.6-fold), and IFN-g (5- versus 9.5-fold). Antifoam activated complement and was avoided. PTF1+2 was generated in whole blood but not in plasma. In summary, air bubbles activated complement and triggered a C3-driven thromboinflammation. C3 inhibition reduced all mediators, whereas C5 inhibition reduced only TF-mRNA. Combined C5 and CD14 inhibition reduced IL-1b release. These data have implications for future mechanistic studies and possible pharmacological interventions in patients with air embolism.

• Bakke, Håkon Kvåle; Fuskevåg, Ole Martin; Nielsen, Erik Waage & Dietrichs, Erik Sveberg (2021). Intramuscular uptake of tranexamic acid during haemorrhagic shock in a swine model. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. 29. doi: 10.1186/s13049-021-00983-2. Fulltekst i vitenarkiv Vis sammendrag

  Background: Tranexamic acid (TXA) reduce mortality in bleeding trauma patients, with greater efect if administered early. Serum concentrations above 10 µg/mL are considered sufcient to inhibit fbrinolysis. Normally administered intravenously (i.v.), TXA can also be administered intramuscularly (i.m.). This could be advantageous in low resource and military settings, if sufcient serum concentrations can be reached in shocked patients with reduced muscular blood perfusion. Accordingly, we aimed to: (1) Determine the impact of shock on the pharmacokinetics of i.m. TXA, and (2) Compare the pharmacokinetics of i.v. versus i.m. TXA in ongoing shock.<p> <p>Materials and methods: In a prospective experimental study, N=18 Norwegian landrace pigs (40–50 kg), utilised in a surgical course in haemostatic emergency surgery, were subjected to various abdominal and thoracic trauma. After 1 h of surgery the animals were given 15 mg/kg TXA either i.v. or i.m. A control group without injury, or surgery, received intramuscular TXA. Blood samples were drawn at 0, 5, 15, 25, 35, 45, 60 and 85 min. The samples were centrifuged and analysed with liquid chromatography–tandem mass spectrometry (LC–MS/MS) for TXA serum-concentrations.<p> <p>Results: In shocked pigs, i.m. administration resulted in a mean maximum serum concentration (Cmax) of 20.9 µg/mL, and i.v. administration a Cmax of 48.1 µg/mL. Cmax occurred 15 min after i.m. administration and 5 min after i.v. administration. In non-shocked swine, i.m. administration resulted in a Cmax of 36.9 µg/mL after 15 min. In all groups, mean TXA serum concentrations stayed above 10 µg/mL from administration to end of experiments.<p> <p>Conclusions: I.m. administration of TXA in shocked pigs provides serum concentrations associated with inhibition of fbrinolysis. It may be an alternative to i.v. and intraosseous administration during stabilisation and transport of trauma patients to advanced medical care.

• Storm, Benjamin; Christiansen, Dorte; Mollnes, Tom Eirik & Nielsen, Erik Waage (2020). Avoiding ambient air in test tubes during incubations of human whole-blood minimizes complement background activation. Journal of Immunological Methods (JIM). ISSN 0022-1759. 487:112876, s. 1–5. doi: 10.1016/j.jim.2020.112876. Fulltekst i vitenarkiv Vis sammendrag

  Background In vitro, the complement system can be studied in test tubes incubated with anticoagulated human whole-blood. Background activation of complement may mask inflammatory signals. Air bubbles are known to activate complement. We examined if removing ambient air from test tubes before incubation reduced background complement activation. Methods Blood from twelve donors was anticoagulated with the thrombin inhibitor lepirudin and incubated with either no air, ambient air or air bubbles in polypropylene tubes at 37 °C for 180 min on a roller mixer. After incubation, EDTA was added, plasma isolated and analyzed for seven complement activation products using ELISA. Results are presented as means with 95% confidence intervals. Results Blood incubated without air had significantly lower complement activation compared to blood incubated with ambient air; C4d 273 (192–364) vs. 379 (263–494) ng/mL (p = 0.002), C4bc 8.2 (4.1–13) vs. 12 (3.2–21) CAU/mL (p = 0.01), C3a 1351 (873–1838) vs. 2944 (2315–3572) ng/mL (p = 0.0005), C3bc 31 (17–46) vs. 68 (52–84) CAU/mL (p = 0.002), C3bBbP 134 (97–171) vs. 427 (358–506) CAU/mL (p < 0.0001), C5a 3.5 (1.9–5 0.2) vs. 15 (1.8–27)) ng/mL (p = 0.003), TCC 4.6 (2.8–6.3) vs. 9.9 (7.3–12) CAU/mL (p = 0.006). At the end of the experiment blood incubated with air bubbles had a higher complement activation than blood incubated with ambient air with an average 26 fold increase (range 1.6–59) from baseline of all activation products; C4d 551 (337–766) ng/mL, C4bc 21 (5.0–36) CAU/mL, C3a 3983 (3518–4448) ng/mL, C4bc 103 (86–121) CAU/mL, C3bBbP 626 (543–708) CAU/mL, C5a 10 (2.8–18) ng/mL and TCC 10 (6.0–14) CAU/mL. Conclusion Avoiding air in test tubes during whole-blood experiments reduced background complement activation substantially and represents an important improvement to the lepirudin whole-blood model. This could also apply to other in vitro models.

• Pischke, Søren; Hestenes, Siv Merete; Johansen, Harald Thidemann; Fure, Hilde; Bugge, Jan F & Espinoza, Andreas Westenvik [Vis alle 12 forfattere av denne artikkelen] (2019). Sepsis causes right ventricular myocardial inflammation independent of pulmonary hypertension in a porcine sepsis model. PLOS ONE. 14:e0218624(6). doi: 10.1371/journal.pone.0218624. Fulltekst i vitenarkiv Vis sammendrag

  Introduction Right ventricular (RV) myocardial dysfunction is a common feature in septic shock. It can worsen outcome, but the etiology is poorly understood. Pulmonary artery hypertension (PAH) plays a part in the pathogenesis of the right heart dysfunction in sepsis but its importance is unknown. In pigs, PAH in sepsis is substantial and the translational value of porcine sepsis models therefore questioned. We hypothesized that porcine sepsis causes a myocardial inflammatory response which leads to myocardial dysfunction independent of PAH. Materials and methods Sepsis was induced by Escherichia coli-infusion in 10 pigs resulting in PAH and increased right ventricular pressure (RVP). The same degree of RVP was achieved by external pulmonary artery banding (PAB) in a consecutive series of 6 animals. Results Sepsis, but not PAB, led to increase in endothelial damage marker PAI-1 and cytokines TNF and IL-6 (all p<0.05) in plasma. In myocardium, TNF and IL-6 were significantly elevated in sepsis, TNF in both ventricles and IL-6 mostly in RV, while IL-1β, IL-18 and C5a were significantly higher in RV compared to LV after PAB (all p<0.05). Myocardial mRNA levels of IL-1β, IL-6, IL-18, IP-10, E-selectin and PAI-1 were significantly elevated in RV and LV during sepsis compared to PAB, while Caspase-1 was decreased in septic compared to PAB animals (all p<0.05). Cathepsin L activity was increased in RV by PAB, while sepsis inhibited this response. Escherichia coli-induced sepsis caused myocardial inflammation independent of PAH. Conclusion Prominent PAH should therefore not exclude porcine sepsis models to further our understanding of human sepsis.

• Skjeflo, Espen Waage; Christiansen, Dorte; Landsem, Anne; Stenvik, Jørgen; Woodruff, T. M. & Espevik, Terje [Vis alle 8 forfattere av denne artikkelen] (2019). Phagocytosis of live and dead Escherichia coli and Staphylococcus aureus in human whole blood is markedly reduced by combined inhibition of C5aR1 and CD14. Molecular Immunology. ISSN 0161-5890. 112, s. 131–139. doi: 10.1016/j.molimm.2019.03.014. Fulltekst i vitenarkiv Vis sammendrag

  Background Sepsis is a dysregulated host response to infection. The aim of this study was to investigate the effects of complement- and CD14 inhibition on phagocytosis of live and dead Gram-negative and Gram-positive bacteria in human whole blood. Methods Lepirudin-anticoagulated blood was incubated with live or dead E. coli or S. aureus at 37 °C for 120 min with or without the C5aR1 antagonist PMX53 and/or anti-CD14. Granulocyte and monocyte phagocytosis were measured by flow cytometry, and five plasma cytokines by multiplex, yielding a total of 28 mediators of inflammation tested for. Results 16/28 conditions were reduced by PMX53, 7/28 by anti-CD14, and 24/28 by combined PMX53 and CD14 inhibition. The effect of complement inhibition was quantitatively more pronounced, in particular for the responses to S. aureus. The effect of anti-CD14 was modest, except for a marked reduction in INF-β. The responses to live and dead S. aureus were equally inhibited, whereas the responses to live E. coli were inhibited less than those to dead E. coli. Conclusion C5aR1 inhibited phagocytosis-induced inflammation by live and dead E. coli and S. aureus. CD14 blockade potentiated the effect of C5aR1 blockade, thus attenuating inflammation.

• Brønstad, Maria; Varghese, Mercy & Nielsen, Erik Waage (2018). Fatal propofol infusion syndrome in a young man with status epilepticus. Acta Anaesthesiologica Scandinavica. ISSN 0001-5172. 62(5), s. 709–711. doi: 10.1111/aas.13106. Fulltekst i vitenarkiv
• kristiansen, Steinar; Madsen, marie Rønning; Steen, Rolf & Nielsen, Erik Waage (2018). En ung traumepasient med fem frakturer og multiorgansvikt. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 138(8). doi: 10.4045/tidsskr.17.0898. Fulltekst i vitenarkiv
• Skjeflo, Espen Waage; Christiansen, Dorte; Fure, Hilde; Ludviksen, Judith K; Woodruff, Trent M. & Espevik, Terje [Vis alle 9 forfattere av denne artikkelen] (2018). Staphylococcus aureus-induced complement activation promotes tissue factor-mediated coagulation. Journal of Thrombosis and Haemostasis. ISSN 1538-7933. 16(5), s. 905–918. doi: 10.1111/jth.13979. Fulltekst i vitenarkiv Vis sammendrag

  Background There is extensive cross‐talk between the complement system, the Toll‐like receptors (TLRs), and hemostasis. Consumptive coagulopathy is a hallmark of sepsis, and is often mediated through increased tissue factor (TF) expression. Objectives To study the relative roles of complement, TLRs and TF in Staphylococcus aureus‐induced coagulation. Methods Lepirudin‐anticoagulated human whole blood was incubated with the three S. aureus strains Cowan, Wood, and Newman. C3 was inhibited with compstatin, C5 with eculizumab, C5a receptor 1 (C5aR1) and activated factor XII with peptide inhibitors, CD14, TLR2 and TF with neutralizing antibodies, and TLR4 with eritoran. Complement activation was measured by ELISA. Coagulation was measured according to prothrombin fragment 1 + 2 (PTF1 + 2) determined with ELISA, and TF mRNA, monocyte surface expression and functional activity were measured with quantitative PCR, flow cytometry, and ELISA, respectively. Results All three strains generated substantial and statistically significant amounts of C5a, terminal complement complex, PTF1 + 2, and TF mRNA, and showed substantial TF surface expression on monocytes and TF functional activity. Inhibition of C5 cleavage most efficiently and significantly inhibited all six markers in strains Cowan and Wood, and five markers in Newman. The effect of complement inhibition was shown to be completely dependent on C5aR1. The C5 blocking effect was equally potentiated when combined with blocking of CD14 or TLR2, but not TLR4. TF blocking significantly reduced PTF1 + 2 levels to baseline levels. Conclusions S. aureus‐induced coagulation in human whole blood was mainly attributable to C5a‐induced mRNA upregulation, monocyte TF expression, and plasma TF activity, thus underscoring complement as a key player in S. aureus‐induced coagulation.

• Dybwik, Knut Gustav & Nielsen, Erik Waage (2018). A successful new method for single left lobe recruitment. Clinical Case Reports. 6(12), s. 2309–2312. doi: 10.1002/ccr3.1787. Fulltekst i vitenarkiv Vis sammendrag

  Any gas will flow down the path of least resistance and highest compliance. This is a problem in the treatment of severe unilateral lung disease in the intensive care unit (ICU). Deep sedation interferes with the diaphragm’s ability to distribute air into the lower lung. Spontaneous breathing in a conscious patient, in combination with mechanical ventilation via an endotracheal tube inserted into the left main stem bronchus, can recruit collapsed alveoli.

• Hauvik, Linn Eva; Varghese, Mercy & Nielsen, Erik Waage (2018). Lactate gap: a diagnostic support in severe metabolic acidosis of unknown origin. Case Reports in Medicine. ISSN 1687-9627. 2018: 5238240, s. 1–4. doi: 10.1155/2018/5238240. Fulltekst i vitenarkiv Vis sammendrag

  Ethylene glycol poisoning is a medical emergency. The metabolites glycolate and glyoxylate give metabolic acidosis. Because of similar structure, these metabolites are misinterpreted as lactate by many point-of-care blood gas analyzers. The falsely high lactate values can lead to misdiagnosis, inappropriate laparotomies, and delayed antidotal therapy. As laboratory analyzers measure plasma lactate only, the difference or the “lactate gap” aids in early diagnosis. We present a patient with severe metabolic acidosis and elevated lactate levels on the point-of-care analyzer. A lactate gap supported the diagnosis of ethylene glycol poisoning. Hemodialysis and fomepizole treatment could be started immediately.

• Storm, Benjamin Stage; Andreasen, Stine; Hovland, Anders & Nielsen, Erik Waage (2017). Gas Embolism During Hysteroscopic Surgery?: Three Cases and a Literature Review. Anesthesia & Analgesia Case Reports. 9(5), s. 140–143. doi: 10.1213/XAA.0000000000000549. Fulltekst i vitenarkiv
• Hennø, Linda Torrissen; Storjord, Elin; Christiansen, Dorte; Bergseth, Grete; Ludviksen, Judith K & Fure, Hilde [Vis alle 10 forfattere av denne artikkelen] (2017). Effect of the anticoagulant, storage time and temperature of blood samples on the concentrations of 27 multiplex assayed cytokines ? Consequences for defining reference values in healthy humans. Cytokine. ISSN 1043-4666. 97, s. 86–95. doi: 10.1016/j.cyto.2017.05.014. Fulltekst i vitenarkiv Vis sammendrag

  Cytokines are potentially useful biomarkers of sepsis and other inflammatory conditions. Many cytokines can be released by leukocytes and platelets after sampling. The sampling and processing techniques are consequently critically important to measure the in vivo levels. We therefore examined the effects of four different anticoagulants, EDTA, citrate, lepirudin, heparin compared to serum, on the levels of 27 different cytokines. The effects of storage temperature, freezing and thawing on the plasma cytokines were examined. Cytokines were analysed using a multiplex immunoassay. The cytokine levels in serum were significantly higher compared with plasma, consistent with release of cytokines in vitro during coagulation. In general, the lowest values for all cytokines were found in EDTA samples, stored on crushed ice, centrifuged within 4 h and thereafter stored at −80 °C. MCP-1 and MIP-1β levels were highest in heparin plasma and storage of blood for up to 4 h at room temperature significantly increased the interleukin (IL)-2, IL-6, IL-8, IFN-γ and GM-CSF levels in EDTA plasma, indicating post-sampling release. In contrast, the IP-10 levels were unaffected by sample storage at both temperatures. Our results indicate that the cytokines were more stable in plasma than in whole blood after sampling. Thus, cytokines should be analysed in EDTA plasma samples stored on ice and centrifuged within 4 h. Based on these data, the reference ranges of 27 cytokines in EDTA plasma in 162 healthy human donors were calculated.

• Skjelstad, Trond; Sørensen, Marte Alsos & Nielsen, Erik Waage (2017). Turskiløper med kraftsvikt og nedsatt bevissthet. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 137(4), s. 289–291. doi: 10.4045/tidsskr.16.0267. Fulltekst i vitenarkiv
• Hovland, Anders; Nestvold, Torunn Kristin; Bohov, Pavol; Trøseid, Marius; Aukrust, Pål & Berge, Rolf Kristian [Vis alle 9 forfattere av denne artikkelen] (2017). Bariatric surgery reduces fasting total fatty acids and increases n-3 polyunsaturated fatty acids in morbidly obese individuals. Scandinavian Journal of Clinical and Laboratory Investigation. ISSN 0036-5513. 77(8), s. 628–633. doi: 10.1080/00365513.2017.1393691. Fulltekst i vitenarkiv Vis sammendrag

  Background: Obesity is a global pandemic leading to increased mortality and increased risk of cardiovascular disease. Bariatric surgery is an established treatment of obesity leading to weight loss and reduction of mortality. To further elucidate how bariatric surgery improves metabolic control, we explored the fatty acid (FA) profiles in morbidly obese subjects treated with lifestyle intervention and subsequent bariatric surgery. Methods: The intervention group consisted of 34 morbidly obese patients scheduled for bariatric surgery and the control group of 17 non-obese patients scheduled for elective laparoscopic procedures. The intervention group had to undergo lifestyle changes preoperatively. Fasting blood samples were drawn at admission, after lifestyle intervention and 1 year after bariatric surgery. Results: At admission, the morbidly obese patients had significantly higher levels of monounsaturated FAs (MUFAs) and lower levels of n-6 polyunsaturated FAs (PUFAs) and n-3 PUFAs than healthy controls (all p-values <.05). In the intervention group, there was a significantly lower level of total FAs after lifestyle intervention, and from admission to 1 year after surgical intervention (both, p < .05), primarily reflecting a lower proportion of saturated FAs (SFAs). Following bariatric surgery, but not after lifestyle changes, there was an increase in the proportion of n-3 PUFA (p < .05) reaching levels not significantly different from healthy controls. Conclusions: Our findings suggest that a reduced proportion of the proposed anti-atherogenic n-3 PUFAs characterizes morbidly obese individuals, and that this FA profile is reversed by bariatric surgery, but not by lifestyle intervention.

• Tveita, Ingrid Aune; Madsen, Martin & Nielsen, Erik Waage (2017). Dissection of the internal carotid artery and stroke after mandibular fractures: a case report and review of the literature. Journal of Medical Case Reports. 11:148, s. 1–6. doi: 10.1186/s13256-017-1316-1. Fulltekst i vitenarkiv Vis sammendrag

  Background: We present a report of a patient with blunt trauma and mandibular fractures who developed a significant cerebral infarction due to an initially unrecognized injury of her left internal carotid artery. We believe that increased knowledge of this association will facilitate early recognition and hence prevention of a devastating outcome. <br>Case presentation: A 41-year-old ethnic Norwegian woman presented to our Emergency Room after a bicycle accident that had caused a direct blow to her chin. At admittance, her Glasgow Coma Scale was 15. Initial trauma computed tomography showed triple fractures of her mandible, but no further pathology. She was placed in our Intensive Care Unit awaiting open reduction of her mandibular fractures. During the following 9 hours, she showed recurrent episodes of confusion and a progressive right-sided hemiparesis. Repeated cerebral computed tomography revealed no further pathology compared to the initial scan. She had magnetic resonance angiography 17 hours after admittance, which showed dissection and thrombus formation in her left internal carotid artery, total occlusion of her left medial cerebral artery, and left middle cerebral artery infarction was detected. <br>Conclusions: Carotid artery dissection is a rare but life-threatening condition that can develop after trauma to the head and neck. There should be a high index of suspicion in patients with a mechanism of injury that places the internal carotid artery at risk because blunt vascular injury may show delayed onset with no initial symptoms of vascular damage. By implementing an algorithm for early detection and treatment of these injuries, serious brain damage may be avoided.

• Hellerud, Bernt C; Orrem, Hilde Lang; Dybwik, Knut Gustav; Pischke, Søren Erik; Barratt-Due, Andreas & Castellheim, Albert [Vis alle 15 forfattere av denne artikkelen] (2017). Combined inhibition of C5 and CD14 efficiently attenuated the inflammatory response in a porcine model of meningococcal sepsis. Journal of Intensive Care. ISSN 2052-0492. 5:21, s. 1–9. doi: 10.1186/s40560-017-0217-0. Fulltekst i vitenarkiv Vis sammendrag

  Background Fulminant meningococcal sepsis, characterized by overwhelming innate immune activation, mostly affects young people and causes high mortality. This study aimed to investigate the effect of targeting two key molecules of innate immunity, complement component C5, and co-receptor CD14 in the Toll-like receptor system, on the inflammatory response in meningococcal sepsis. Methods Meningococcal sepsis was simulated by continuous intravenous infusion of an escalating dose of heat-inactivated Neisseria meningitidis administered over 3 h. The piglets were randomized, blinded to the investigators, to a positive control group (n = 12) receiving saline and to an interventional group (n = 12) receiving a recombinant anti-CD14 monoclonal antibody together with the C5 inhibitor coversin. Results A substantial increase in plasma complement activation in the untreated group was completely abolished in the treatment group (p = 0.006). The following inflammatory mediators were substantially reduced in plasma in the treatment group: Interferon-γ by 75% (p = 0.0001), tumor necrosis factor by 50% (p = 0.01), Interleukin (IL)-8 by 50% (p = 0.03), IL-10 by 40% (p = 0.04), IL-12p40 by 50% (p = 0.03), and granulocyte CD11b (CR3) expression by 20% (p = 0.01). Conclusion Inhibition of C5 and CD14 may be beneficial in attenuating the detrimental effects of complement activation and modulating the cytokine storm in patients with fulminant meningococcal sepsis.

• Landsem, Anne; Fure, Hilde; Mollnes, Tom Eirik; Nielsen, Erik Waage & Brekke, Ole Lars (2016). C1-inhibitor efficiently delays clot development in normal human whole blood and inhibits Escherichia coli-induced coagulation measured by thromboelastometry. Thrombosis Research. ISSN 0049-3848. 143, s. 63–70. doi: 10.1016/j.thromres.2016.04.024. Fulltekst i vitenarkiv
• Storjord, Elin; Dahl, Jim André; Landsem, Anne; Fure, Hilde; Ludviksen, Judith K & Goldbeck-Wood, Sandy [Vis alle 11 forfattere av denne artikkelen] (2016). Systemic inflammation in acute intermittent porphyria:a case–control study. Clinical and Experimental Immunology. ISSN 0009-9104. 187(3), s. 466–479. doi: 10.1111/cei.12899. Fulltekst i vitenarkiv
• Storm, Benjamin Stage; Dybwik, Knut & Nielsen, Erik Waage (2016). Late complications after percutaneous tracheostomy and oral intubation: Evaluation of 1,628 procedures. The Laryngoscope. ISSN 0023-852X. 126(5), s. 1077–1082. doi: 10.1002/lary.25766. Fulltekst i vitenarkiv
• Johansen, Harald Thidemann; Seip, Knut Fredrik & Nielsen, Erik Waage (2016). Bradykininutløste angioødemer. Norsk Farmaceutisk Tidsskrift (NFT). ISSN 0029-1935. 124(4), s. 31–35. Fulltekst i vitenarkiv
• Seip, Knut Fredrik; Evjenth, Bjørg; Hovland, Anders; Dybwik, Knut Gustav; Johansen, Harald Thidemann & Fure, Hilde [Vis alle 8 forfattere av denne artikkelen] (2016). Bradykinin-Induced Shock Increase Exhaled Nitric Oxide, Complement Activation and Cytokine Production in Pigs. Journal of Cardiology & Clinical Research. 4(2). Fulltekst i vitenarkiv Vis sammendrag

  Bradykinin is an important mediator in blood pressure regulation, ischemic precondition and capillary leakage, allergy, anaphylaxis, inflammation, and nociception, at least partly via the generation of nitric oxide (NO). Macrophages are particularly abundant in the porcine lung circulation. Upon bradykinin binding macrophages release cytokines and endothelial cells increase plasma leakage. Both cells produce NO. The complement, hemostatic, fibrinolytic and kinin plasma cascade systems crosstalk and interacts with many inflammatory systems. In the present study we investigated the effect of the shock induced by intravenously infused bradykinin on the cascade systems, cytokines, plasma leakage and exhaled NO in pigs. The metabolite of bradykinin, BK1-5, was measured in plasma by a sensitive, specific and reliable liquid chromatography-mass spectrometry method to verify exposure and in vivo metabolism of bradykinin. We show for the first time in vivo how bradykinin exposure induced shock and increased exhaled NO, activated complement and hemostasis and induced cytokine production and capillary leakage. The results broaden our understanding of how bradykinin activates endothelial cells and macrophages to induce shock and inflammation. This should encourage further studies

• Nestvold, Torunn Kristin; Nielsen, Erik Waage; Ludviksen, Judith K; Fure, Hilde; Landsem, Anne & Lappegård, Knut Tore (2015). Lifestyle changes followed by bariatric surgery lower inflammatory markers and the cardiovascular risk factors C3 and C4. Metabolic Syndrome and Related Disorders. ISSN 1540-4196. 13(1), s. 29–35. doi: 10.1089/met.2014.0099. Fulltekst i vitenarkiv
• Johnsrud, Irene Elizabeth; Kulseth, Mari Ann; Rødningen, Olaug Kristin; Landrø, Linn Aina Ysland; Helsing, Per & Nielsen, Erik Waage [Vis alle 7 forfattere av denne artikkelen] (2015). A nationwide study of Norwegian patients with hereditary angioedema with C1 inhibitor deficiency identified six novel mutations in SERPING1. PLOS ONE. 10(7). doi: 10.1371/journal.pone.0131637. Fulltekst i vitenarkiv Vis sammendrag

  Hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) is characterized by relapsing, non-pruritic swelling in skin and submucosal tissue. Symptoms can appear in early infancy when diagnosis is more difficult. In the absence of a correct diagnosis, treatment of abdominal attacks often lead to unnecessary surgery, and laryngeal edema can cause asphyxiation. A cohort study of 52 patients from 25 unrelated families in Norway was studied. Diagnosis of C1-INH-HAE was based on international consensus criteria including low functional and/or antigenic C1-INH values and antigenic C4. As SERPING1 mutations in Norwegian patients with C1-INH-HAE are largely undescribed and could help in diagnosis, we aimed to find and describe these mutations. Mutation analysis of the SERPING1 gene was performed by Sanger sequencing of all protein coding exons and exon-intron boundaries. Samples without detected mutation were further analyzed by multiplex ligation-dependent probe amplification to detect deletions and duplications. Novel mutations suspected to lead to splice defects were analyzed on the mRNA level. Fifty-two patients from 25 families were included. Forty-four (84,6%) suffered from C1-INH-HAE type I and eight (15,4%) suffered from C1-INH-HAE type II. Pathogenic or likely pathogenic mutations were found in 22/25 families (88%). Thirteen unique mutations were detected, including six previously undescribed. There were three missense mutations including one mutation affecting the reactive center loop at codon 466, three nonsense mutations, three small deletions/duplications, three gross deletions, and one splice mutation.

• Stordahl, Harald; Passas, Evangelina Helene Tønsberg; Hopland, Andreas & Nielsen, Erik Waage (2015). Nine out of ten trauma calls to a Norwegian hospital are avoidable: a retrospective analysis. BMC Emergency Medicine. 15(1). doi: 10.1186/s12873-015-0026-5. Fulltekst i vitenarkiv Vis sammendrag

  Background: Our aim was to estimate the degree of overtriage (Injury Severity Score [ISS] ≤ 15) of trauma call patients in Nordland Hospital Bodø, Norway. We also determined the transportation time from injury to hospital admission. Methods: We used data from our Acute Medical Information System, ambulance records and patient charts relating to ISS and estimation of response and transport times. Data were collected for all trauma call patients in the period from the establishment of the trauma call system in June 2008 until the 31st of December 2010. Results: We identified 421 out of 458 possible trauma call patients with sufficient clinical information available for ISS scoring. Of these 385 had an ISS ≤15. Overtriage was 91.5% (95% CI: 88.8%–94.2%). Median time from injury to the arrival of transport, and from injury to arrival in hospital, was 36 minutes and 1 hour 27 minutes, respectively. Conclusions: To our knowledge 91.5% is the highest overtriage ever published. There is a need for narrowing the trauma call criteria. This could be achieved by implementing clinical observations during the long transportation time

• Landsem, Anne; Fure, Hilde; Christiansen, Dorte; Nielsen, Erik Waage; Østerud, Bjarne & Mollnes, Tom Eirik [Vis alle 7 forfattere av denne artikkelen] (2015). The key roles of complement and tissue factor in Escherichia coli-induced coagulation in human whole blood. Clinical and Experimental Immunology. ISSN 0009-9104. 182(1), s. 81–89. doi: 10.1111/cei.12663. Fulltekst i vitenarkiv
• Trøseid, Marius; Nestvold, Torunn Kristin; Nielsen, Erik Waage; Thoresen, Hanne E. G.; Seljeflot, Ingebjørg & Lappegård, Knut Tore (2015). Soluble CD14 is associated with markers of vascular dysfunction in bariatric surgery patients. Metabolic Syndrome and Related Disorders. ISSN 1540-4196. 13(3), s. 119–124. doi: 10.1089/met.2014.0111. Fulltekst i vitenarkiv
• Hellerud, Bernt C; Olstad, Ole Kristoffer; Nielsen, Erik W.; Siebke, Anne-Marie; Skadberg, Øyvind & Thorgersen, Ebbe Billmann [Vis alle 9 forfattere av denne artikkelen] (2015). Massive organ inflammation in experimental and in clinical meningococcal septic shock. Shock. ISSN 1073-2322. 44(5), s. 458–469. doi: 10.1097/SHK.0000000000000441. Fulltekst i vitenarkiv Vis sammendrag

  Fulminant meningococcal sepsis is characterized by a massive growth of bacteria in the circulation, regarded as the primary inflammatory site, with no specific solid organ focus. Here we aimed to study the local inflammatory response in organs using a porcine model of fulminant meningococcal septic shock challenged with exponentially increasing doses of heat inactivated Neisseria meningitidis. The results were compared with those obtained in organs post mortem from three patients with lethal meningococcal septic shock. Nine patients with lethal pneumococcal disease and 14 patients with sudden infant death syndrome served as controls. Frozen tissue were thawed, homogenized and prepared for quantification of bacterial DNA by real-time polymerase chain reaction, and key inflammatory mediators were measured by ELISA in the pig material and by multiplex in the human material. In addition, gene expression assayed by Affymetrix gene expression profiling was performed in the pig study. The porcine model revealed a major influx of N. meningitidis in lungs, liver, spleen, and kidneys accompanied with major production of cardinal inflammatory mediators including tumor necrosis factor, interleukin (IL)-1[beta], IL-6, and IL-8, far exceeding the amount detected in blood. Genes encoding for these mediators revealed a similar profile. By comparing the wild-type with a lipopolysaccharide (LPS) deficient meningococcal strain, we documented that LPS was the dominant group of molecules inducing organ inflammation and was required for IL-8 production. IL-10 production was predominantly stimulated by non-LPS molecules. The massive organ inflammation in the porcine model was present in the three patients dying of meningococcal shock and differed markedly from the patients with lethal pneumococcal infections and sudden infant death syndrome. In conclusion, in meningococcal sepsis, a massive local inflammatory response occurs in specific organs.

• Skjeflo, Espen Waage; Sagatun, Caroline; Dybwik, Knut; Aam, Sturla; Urving, Sven Haakon & Nunn, Miles A. [Vis alle 14 forfattere av denne artikkelen] (2015). Combined inhibition of complement and CD14 improved outcome in porcine polymicrobial sepsis. Critical Care. ISSN 1364-8535. 19:415(1). doi: 10.1186/s13054-015-1129-9. Fulltekst i vitenarkiv Vis sammendrag

  Introduction Sepsis is an exaggerated and dysfunctional immune response to infection. Activation of innate immunity recognition systems including complement and the Toll-like receptor family initiate this disproportionate inflammatory response. The aim of this study was to explore the effect of combined inhibition of the complement component C5 and the Toll-like receptor co-factor CD14 on survival, hemodynamic parameters and systemic inflammation including complement activation in a clinically relevant porcine model of polymicrobial sepsis. Methods Norwegian landrace piglets (4 ± 0.5 kg) were blindly randomized to a treatment group (n = 12) receiving the C5 inhibitor coversin (OmCI) and anti-CD14 or to a positive control group (n = 12) receiving saline. Under anesthesia, sepsis was induced by a 2 cm cecal incision and the piglets were monitored in standard intensive care for 8 hours. Three sham piglets had a laparotomy without cecal incision or treatment. Complement activation was measured as sC5b-9 using enzyme immunoassay. Cytokines were measured with multiplex technology. Results Combined C5 and CD14 inhibition significantly improved survival (p = 0.03). Nine piglets survived in the treatment group and four in the control group. The treatment group had significantly lower pulmonary artery pressure (p = 0.04) and ratio of pulmonary artery pressure to systemic artery pressure (p < 0.001). Plasma sC5b-9 levels were significantly lower in the treatment group (p < 0.001) and correlated significantly with mortality (p = 0.006). IL-8 and IL-10 were significantly (p < 0.05) lower in the treatment group. Conclusions Combined inhibition of C5 and CD14 significantly improved survival, hemodynamic parameters and inflammation in a blinded, randomized trial of porcine polymicrobial sepsis.

• Hestenes, Siv Merete; Halvorsen, Per Steinar; Skulstad, Helge; Remme, Espen; Espinoza, Andreas Westenvik & Hyler, Stefan [Vis alle 10 forfattere av denne artikkelen] (2014). Advantages of strain echocardiography in assessment of myocardial function in severe sepsis: An experimental study. Critical Care Medicine. ISSN 0090-3493. 42(6), s. e432–e440. doi: 10.1097/CCM.0000000000000310. Fulltekst i vitenarkiv
• Warsame, Mahad Omar; Gamboa, Danil & Nielsen, Erik Waage (2014). En kvinne i 40-årene med kreft, synkope og kramper. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 134(19), s. 1855–1857. doi: 10.4045/tidsskr.13.1528. Fulltekst i vitenarkiv
• Skjeflo, Espen Waage; Christiansen, Dorte; Espevik, Terje; Nielsen, Erik Waage & Mollnes, Tom Eirik (2014). Combined inhibition of complement and CD14 efficiently attenuated the inflammatory response induced by staphylococcus aureus in a human whole blood model. Journal of Immunology. ISSN 0022-1767. 192(6), s. 2857–2864. doi: 10.4049/jimmunol.1300755. Fulltekst i vitenarkiv Vis sammendrag

  The complement and TLR systems are activated in sepsis, contributing to an unfavorable inflammatory “storm.” Combined inhibition of these systems has been documented to efficiently attenuate the inflammatory responses induced by Gram-negative bacteria. In this study, we hypothesized that the combined inhibition would attenuate the inflammatory responses induced by Gram-positive bacteria. Staphylococcus aureus bacteria (strains Cowan and Wood), as well as S. aureus cell wall lipoteichoic acid (LTA), were incubated in thrombin-inhibited human whole blood. Complement was inhibited at the level of C3 and C5, and the TLRs by inhibiting CD14 and TLR2. Thirty-four inflammatory markers were measured by multiplex technology and flow cytometry. Thirteen markers increased significantly in response to Cowan and Wood, and 12 in response to LTA. Combined inhibition with the C3 inhibitor compstatin and the anti-CD14 Ab 18D11 significantly reduced 92 (Cowan, LTA) and 85% (Wood) of these markers. Compstatin alone significantly reduced 54 (Cowan), 38 (Wood), and 83% (LTA), whereas anti-CD14 alone significantly reduced 23, 15, and 67%, respectively. Further experiments showed that the effects of complement inhibition were mainly due to inhibition of C5a interaction with the C5a receptor. The effects on inhibiting CD14 and TLR2 were similar. The combined regimen was more efficient toward the bacterial effects than either complement or anti-CD14 inhibition alone. Complement was responsible for activation of and phagocytosis by both granulocytes and monocytes. Disrupting upstream recognition by inhibiting complement and CD14 efficiently attenuated S. aureus–induced inflammation and might be a promising treatment in both Gram-negative and Gram-positive sepsis.

• Gjerløw, Ellen; Bjørgaas, Marit Ragnhild Rokne; Nielsen, Erik Waage; Olsen, Sandra Elise & Åsvold, Bjørn Olav (2014). Fear of hypoglycemia in women and men with type 1 diabetes. Nursing Research. ISSN 0029-6562. 63(2), s. 143–149. doi: 10.1097/NNR.0000000000000020. Fulltekst i vitenarkiv
• Seip, Knut Fredrik; Bjerknes, Kari Christiane; Johansen, Harald Thidemann; Nielsen, Erik Waage; Landrø, Linn Aina Ysland & Reubsaet, Leon (2014). Bradykinin analysis revived - A validated method for determination of its stable metabolite in whole blood by LC-MS/MS. Journal of chromatography. B. ISSN 1570-0232. 947-948, s. 139–144. doi: 10.1016/j.jchromb.2013.12.033. Fulltekst i vitenarkiv
• Mathisen, Marit; Olsen, Rudi Valde; Andreasen, Stine & Nielsen, Erik Waage (2014). Is it possible to detect malposition of the vertex at an early stage in labour? A case-control study. Sexual & Reproductive HealthCare. ISSN 1877-5756. 5, s. 185–187. doi: 10.1016/j.srhc.2014.04.002. Fulltekst i vitenarkiv
• Trøseid, Marius; Nestvold, Torunn Kristin; Rudi, Knut; Thoresen, Hanna; Nielsen, Erik Waage & Lappegård, Knut Tore (2013). Plasma Lipopolysaccharide Is Closely Associated With Glycemic Control and Abdominal Obesity: Evidence from bariatric surgery. Diabetes Care. ISSN 0149-5992. 36(11), s. 3627–3632. doi: 10.2337/dc13-0451. Fulltekst i vitenarkiv Vis sammendrag

  OBJECTIVE It is of vital importance to elucidate the triggering factors of obesity and type 2 diabetes to improve patient care. Bariatric surgery has been shown to prevent and even cure diabetes, but the mechanism is unknown. Elevated levels of lipopolysaccharide (LPS) predict incident diabetes, but the sources of LPS are not clarified. The objective of the current study was to evaluate the potential impact of plasma LPS on abdominal obesity and glycemic control in subjects undergoing bariatric surgery.<p> <p>RESEARCH DESIGN AND METHODS This was a prospective observational study involving a consecutive sample of 49 obese subjects undergoing bariatric surgery and 17 controls. Main assessments were plasma LPS, HbA_1c, adipose tissue volumes (computed tomography), and quantified bacterial DNA in adipose tissue compartments. <p>RESULTS Plasma levels of LPS were elevated in obese individuals compared with controls (P , 0.001) and were reduced after bariatric surgery (P = 0.010). LPS levels were closely correlated with HbA_1c (r = 0.56; P = 0.001) and intra-abdominal fat volumes (r = 0.61; P , 0.001), but only moderately correlated with subcutaneous fat volumes (r = 0.33; P = 0.038). Moreover, there was a decreasing gradient (twofold) in bacterial DNA levels going from mesenteric via omental to subcutaneous adipose tissue compartments (P = 0.041). Finally, reduced LPS levels after bariatric surgery were directly correlated with a reduction in HbA_1c (r = 0.85; P , 0.001). <p>CONCLUSIONS Our findings support a hypothesis of translocated gut bacteria as a potential trigger of obesity and diabetes, and suggest that the antidiabetic effects of bariatric surgery might be mechanistically linked to, and even the result of, a reduction in plasma levels of LPS.

• Tysvær, Gunbjørg & Nielsen, Erik Waage (2013). Nasogastrisk sonde på ville veier. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 133(5). Fulltekst i vitenarkiv
• Salomonsen, Magnus; Hardersen, Randolf; Carlsson, Maria & Nielsen, Erik Waage (2013). En mann i 70-årene funnet forvirret på treningstur. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 133(23-24), s. 2483–2487. doi: 10.4045/tidsskr.13.0189. Fulltekst i vitenarkiv
• Nestvold, Torunn Kristin; Nielsen, Erik Waage & Lappegård, Knut Tore (2013). Bariatric Surgery Reduces Risk Factors for Development of Type 2 Diabetes Mellitus in Morbidly Obese, Nondiabetic Patients. Metabolic Syndrome and Related Disorders. ISSN 1540-4196. 11(6), s. 441–446. doi: 10.1089/met.2013.0085. Fulltekst i vitenarkiv
• Brekke, Ole Lars; Waage, Knut-Christian; Christiansen, Dorte; Fure, Hilde; Qu, H & Lambris, John D. [Vis alle 9 forfattere av denne artikkelen] (2013). The Effects of Selective Complement and CD14 Inhibition on the E. coli -Induced Tissue Factor mRNA Upregulation, Monocyte Tissue Factor Expression, and Tissue Factor Functional Activity in Human Whole Blood. I Lambris, J.D. (Red.), Complement Therapeutics, Advances in Experimental Medicine and Biology. Springer Science+Business Media B.V.. ISSN 9781461441182. s. 123–136. doi: 10.1007/978-1-4614-4118-2_8. Fulltekst i vitenarkiv
• Landsem, Anne; Nielsen, Erik Waage; Fure, Hilde; Christiansen, Dorte; Ludviksen, Judith K & Lambris, J.D. [Vis alle 9 forfattere av denne artikkelen] (2013). C1-inhibitor efficiently inhibits Escherichia coli-induced tissue factor mRNA up-regulation, monocyte tissue factor expression and coagulation activation in human whole blood. Clinical and Experimental Immunology. ISSN 0009-9104. 173(2), s. 217–229. doi: 10.1111/cei.12098. Fulltekst i vitenarkiv
• Ulvin, Ole Erik & Nielsen, Erik Waage (2013). Unexplained severe lactic acidosis in emergency medicine. Journal of Medical Case Reports. 1(2). doi: 10.15744/2348-9820.1.202. Fulltekst i vitenarkiv Vis sammendrag

  Case report A 49-year-old previously healthy man was admitted to the ICU after cardiac arrest following a short history with headache, blurred speech and reduced consciousness. After cardiopulmonary resuscitation perfusion rhythm was regained, but the patient didn`t regain consciousness. The arterial blood gas analysis at the ICU revealed a severe metabolic acidosis with pH at 6.86 and lactate levels of 16 mmol/L. The white blood cells count was also markedly increased (312 * 109 /L), and blood smear showed immature cells indicating acute leukemia. The severe metabolic acidosis, at first thought to be due to systemic hypoperfusion, did not improve in spite of fluid and vasopressor resuscitation. A CT scan of the head performed the next day, revealed massive cerebellar haemorrhage, edema in both hemispheres and signs of anoxic brain damage. Immunophenotyping of peripheral blood was consistent with Acute Myeloid Leukemia (AML). Discussion Lactic acidosis is a common cause of metabolic acidosis at the ICU. Type A is most common and caused by hypoperfusion or hypoxia, whilst type B has other causes including use of the antidiabetic drug metformin and hematological malignancies. The latter should be considered when presented to persistent lactic acidosis after adequate systemic perfusion has been reestablished.

Se alle arbeider i NVA

• Seines, Ellisiv; Harneshaug, Mariann; Skjeflo, Trine; Isachsen, Fredrik & Nielsen, Erik Waage (2024). Pneumothorax under skulderkirurgi. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 144(5). doi: 10.4045/tidsskr.23.0542. Fulltekst i vitenarkiv Vis sammendrag

  A healthy man in his seventies developed left-sided tension pneumothorax with a decrease in oxygen saturation and blood pressure during shoulder arthroscopy on the same side. Perioperative ultrasound to examine lung sliding is a simple method for quickly identifying this rare but potentially dangerous situation.

• Jarmund, Anders Hagen; Kristiansen, Steinar; Leth-Olsen, Martin; Vogt, Ella Christina Stray; Nervik, Ingunn & Torp, Hans [Vis alle 8 forfattere av denne artikkelen] (2024). Perioperativ cerebral emboli-deteksjon med høy-frekvent Doppler-ultralyd. Ultraschall in der Medizin. ISSN 0172-4614. 45(5), s. 545–546. doi: 10.1055/a-2368-9156. Fulltekst i vitenarkiv
• Jarmund, Anders Hagen; Kristiansen, Steinar; Leth-Olsen, Martin; Vogt, Ella Christina Stray; Nervik, Ingunn & Torp, Hans [Vis alle 8 forfattere av denne artikkelen] (2024). Perioperativ cerebral emboli-deteksjon med høy-frekvent Doppler-ultralyd. Fulltekst i vitenarkiv
• Marsh, Phillip L.; Moore, Ernest E.; Moore, Hunter B.; Bunch, Connor M.; Aboukhaled, Michael & Condon, Shaun M. [Vis alle 39 forfattere av denne artikkelen] (2024). Corrigendum: Iatrogenic air embolism: pathoanatomy, thromboinflammation, endotheliopathy, and therapies (Front. Immunol., (2023), 14, 1230049, 10.3389/fimmu.2023.1230049). Frontiers in Immunology. 15. doi: 10.3389/fimmu.2024.1378003. Fulltekst i vitenarkiv
• Vikan, Ida Marie Nyhagen; Skogøy, Kristin; Klausen, Sofie Strand; Deu, Jordi & Nielsen, Erik Waage (2024). En kvinne i 30-årene med brystsmerter og sirkulatorisk sjokk etter fødsel. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 144(10), s. 818–822. doi: 10.4045/tidsskr.23.0774. Fulltekst i vitenarkiv Vis sammendrag

  En andregangsfødende kvinne i 30-årene ble hemodynamisk ustabil og utviklet sterke brystsmerter etter fødselen. Årsaken til symptomene viste seg å være en alvorlig komplikasjon ved vaginal fødsel etter et tidligere keisersnitt, men omfanget ble ikke avklart før over en uke senere.

• Faldaas, Bjørn Ove; Nielsen, Erik Waage; Storm, Benjamin Stage; Lappegård, Knut Tore; How, Ole-Jakob & nielsen, bent aksel [Vis alle 10 forfattere av denne artikkelen] (2023). Real Time Feedback of Chest Compressions by Hands-Free Carotid Doppler in a Porcine Model. Circulation. ISSN 0009-7322. 148. Fulltekst i vitenarkiv
• Faldaas, Bjørn Ove; Nielsen, Erik Waage; Storm, Benjamin Stage; Lappegård, Knut Tore; How, Ole-Jakob & Nilsen, Bent Aksel [Vis alle 10 forfattere av denne artikkelen] (2022). RescueDoppler: Non-invasive Handsfree Carotid Doppler Ultrasound For Continuous Hemodynamic-guided Resuscitation. Circulation. ISSN 0009-7322. 146. doi: 10.1161/circ.146.suppl_1.301. Fulltekst i vitenarkiv
• Seines, Ellisiv; Fretland, Bjørn; Gál, Peter; Berg, Kristin Sandal; Stubhaug, Audun & Løberg-Emanuelsen, L [Vis alle 8 forfattere av denne artikkelen] (2022). Low systemic concentrations of bupivacaine from topical anesthesia of the tonsillar beds after tonsillectomy. Fulltekst i vitenarkiv
• Bakke, Håkon Kvåle; Fuskevåg, Ole Martin; Nielsen, Erik Waage & Dietrichs, Erik Sveberg (2021). INTRAMUSCULAR UPTAKE OF TRANEXAMIC ACID DURING HEMORRHAGIC SHOCK IN A SWINE MODEL. Fulltekst i vitenarkiv
• Nielsen, Erik Waage & Østerud, Bjarne (2020). Measuring only pre-existing Factor VIIa. International Immunopharmacology. ISSN 1567-5769. 83. doi: 10.1016/j.intimp.2020.106424. Fulltekst i vitenarkiv
• Faldaas, Bjørn Ove; Nielsen, Erik Waage; Storm, Benjamin Stage; Lappegård, Knut Tore; How, Ole-Jakob & Nilsen, Bent Aksel [Vis alle 10 forfattere av denne artikkelen] (2020). Abstract 301: RescueDoppler: Non-invasive Handsfree Carotid Doppler Ultrasound For Continuous Hemodynamic-guided Resuscitation. Fulltekst i vitenarkiv
• Bakke, Håkon Kvåle; Fauskevåg, Ole Martin; Nielsen, Erik Waage & Dietrichs, Erik Sveberg (2020). Intramuscular uptake of tranexamic acid during haemorrhagic shock in a swine model. Fulltekst i vitenarkiv Vis sammendrag

  Intramuscular uptake of tranexamic acid during haemorrhagic shock in a swine model Bakke H.1,2, Fauskevåg O.M. 3, Nielsen E.W. 4,5,6,7, Dietrichs E.S. 8,9 1University Hospital of North Norway, Department of anaesthesia and critical care, Tromsø, Norway 2University Hospital of North Norway, Department of Traumatology, Tromsø, Norway 3University Hospital of North Norway, Division of Diagnostic Services, Tromsø, Norway 4Nordland Hospital, Bodø, Department of Anaesthesia and Critical Care, Bodø, Norway 5Univerity Nord, Bodø, Norway 6University of Oslo , Department of Immunology, Oslo, Norway 7University of Tromsø, Institute of Clinical Medicine, Norway, Norway 8University of Tromsø, Department of Experimental and Clinical Pharmacology, Tromsø, Norway 9University Hospital of North Norway, Department of Clinical Pharmacology, Tromsø, Norway Introduction: Tranexamic acid (TXA) has been shown to reduce mortality in bleeding trauma patients, with greater effect if administered early. Normally administered intravenously, TXA can also be administered intramuscularly, which could be advantageous in low resource and military settings. Intramuscular use has only been tested in healthy patients, and it is likely that shock will reduce intramuscular uptake. Material & Methods: In a prospective experimental study Norwegian landrace pigs (40-50kg)utilised in a surgical course in haemostatic emergency surgery were subjected to various abdominal and thoracic trauma. After 1 hour of surgery the pigs were injected with 15 mg/kg TXA either intravenously or intramuscularly. Blood samples were drawn at 0, 5, 15, 25, 35 ,45, 60 and 80 minutes. The samples were centrifuged and analysed with liquid chromatography-mass spectrometry (LC-MS/MS). Results: Preliminary results from 3 animals in the intramuscular and 2 animals in the intravenous group. Mean plasma concentration with SD of TXA as a function of time is shown in figure 1. Plasma concentration in the intramuscular group was near 10 ug/mL 15 minutes after administration, and rose above 14 ug/mL after 60 minutes. Conclusions: Plasma concentrations reported to inhibit fibrinolysis in vitro is 10 – 17.5 ug/ml (1,2). If this extrapolates to the clinical situation intramuscular administration would yield plasma levels within the lower end of therapeutic range after 15 minutes.In ongoing haemorrhagic shock plasma concentrations of TXA after intramuscular administration were considerably lower than after intravenous administration, but within therapeutic range . References 1. Fietchner et al. Plasma tranexamic acid concentrations during cardiopulmonary bypass. Anesth Analg 2001 May;92(5):1131-6 2. Yee et al. The effective concentration of tranexamic acid for inhibition of fibrinolysis in neonatal plasma in vitro. Anesth Analg. 2001 Oct;117(4):767-72.

• Buchmann, K.; Storm, Benjamin & Nielsen, Erik Waage (2019). BRUK AV DEKSMEDETOMIDIN VED LIVSTRUENDE HJERTESVIKT. ABSTRACTPRIS. Fulltekst i vitenarkiv
• Hansen, Tine Torjuul & Nielsen, Erik Waage (2019). Andre årsaker til postoperativt lungeødem? Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. Fulltekst i vitenarkiv
• Bakke, Victoria Desire & Nielsen, Erik Waage (2019). KLOR, DET GLEMTE ION. KARAKTERISTISKE LABORATORIEVERDIER VED ENTEROVESIKAL FISTEL. Fulltekst i vitenarkiv
• Hansen, Tine Torjuul; Storm, Benjamin & Nielsen, Erik Waage (2019). EN PASIENT MED SEKS OG EN HALV TIMES EFFEKT AV SUKSAMETONIUM OG PÅFØLGENDE STRESSINDUSERT KARDIOMYOPATI. Fulltekst i vitenarkiv
• Berg, Kristin Sandal & Nielsen, Erik Waage (2019). SELVPÅFØRT FORGIFTNING MED KOFFEINTABLETTER. HØSTMØTET I NORSK ANESTESIOLOGISK FORENING. Fulltekst i vitenarkiv
• Vikan, Ida Marie Nyhagen & Nielsen, Erik Waage (2019). LØGN, FORBANNET LØGN – OG STATISTIKK. Om reinnleggelser på Intensiv. Tidsskrift for Norsk anestesiologisk forening (NAForum). 32(1), s. 12–13. Fulltekst i vitenarkiv
• Berg, Kristin Sandal; Ofstad, Eirik Hugaas & Nielsen, Erik Waage (2019). Selvpåført forgiftning med koffeintabletter. Fulltekst i vitenarkiv
• Storm, Benjamin; Christiansen, Dorte; Fure, Hilde; Nielsen, Erik Waage & Mollnes, Tom Eirik (2019). Air bubbles induce a complement-dependent cytokine release in human whole blood in vitro and venous air embolism leads to an inflammatory response in pigs in vivo. Molecular Immunology. ISSN 0161-5890. 114, s. 441–441. Fulltekst i vitenarkiv
• Kristiansen, Steinar & Nielsen, Erik Waage (2018). Fettemboli og koagulasjon. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 138(10), s. 895–896. doi: 10.4045/tidsskr.18.0429. Fulltekst i vitenarkiv
• Nielsen, Erik Waage; Storm, Benjamin; Christiansen, Dorte & Mollnes, Tom Eirik (2018). Venous air embolism-indiced coagulation prevented by complement C5 inhibition. Molecular Immunology. ISSN 0161-5890. 102, s. 192–193. Fulltekst i vitenarkiv
• Storm, Benjamin; Thoresen, Hanne & Nielsen, Erik Waage (2018). Accidential injection of 15 ml air: Did Durant’s manoevure hinder cerebral air-emboli? European Journal of Anaesthesiology. ISSN 0265-0215. 35, s. 261–261. Fulltekst i vitenarkiv
• Hilmo, Jonas; Kayser, Ole & Nielsen, Erik Waage (2017). Fettembolisyndrom. 137(12). doi: 10.4045/tidsskr.17.0009. Fulltekst i vitenarkiv
• Storm, Benjamin Stage; Andreasen, Stine; Hovland, Anders & Nielsen, Erik Waage (2017). Underestimation of gas embolism during hysteroscopy surgery? How to recognise symptoms and reduce fatalities. Presentation of three cases. European Journal of Anaesthesiology. ISSN 0265-0215. 2017(34), s. 120–120. Fulltekst i vitenarkiv
• Storm, Benjamin Stage; Christiansen, Dorte; Dybwik, Knut Gustav; Mollnes, Tom Eirik & Nielsen, Erik Waage (2017). Gas embolism during surgery. A complement mediated condition? Fulltekst i vitenarkiv
• Storm, Benjamin Stage; Andreasen, Stine; Hovland, Anders & Nielsen, Erik Waage (2017). Underestimation of gas embolism during hysteroscopy surgery? How to recognise symptoms and reduce fatalities. Presentation of three cases. Fulltekst i vitenarkiv
• Nielsen, Erik Waage (2016). Re: En kvinne i 70-årene med rask forverring av kognitiv funksjon. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 136(18), s. 1507–1507. doi: 10.4045/tidsskr.16.0790. Fulltekst i vitenarkiv
• Nielsen, Erik Waage; Lappegård, Knut Tore & Johansen, Harald Thidemann (2015). Re: Ny og bedre medisin mot hjertesvikt. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 135(9), s. 830–831. doi: 10.4045/tidsskr.15.0486. Fulltekst i vitenarkiv
• Johnsrud, Irene Elizabeth; Kulseth, Mari Ann; Rødningen, Olaug Kristin; Landrø, Linn; Helsing, Per & Nielsen, Erik Waage [Vis alle 7 forfattere av denne artikkelen] (2015). Erratum: A nationwide study of norwegian patients with hereditary angioedema with C1 inhibitor deficiency identified six novel mutations in SERPING1 (PLOS ONE 10 :7 (e0131637) 10.1371/journal.pone.0131637)). PLOS ONE. 10(8). doi: 10.1371/journal.pone.0136011. Fulltekst i vitenarkiv
• Nielsen, Erik Waage (2015). Re: En tvillinggravid kvinne med polyuri og polydipsi. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 135(21), s. 1922–1922. doi: 10.4045/tidsskr.15.1131. Fulltekst i vitenarkiv
• Mæhle, Kirsten Vikesland; Haug, Bjørn; Flaatten, Hans & Nielsen, Erik Waage (2014). Metabolic alkalosis is the most common acid-base disorder in ICU patients. Critical Care. ISSN 1364-8535. 18(2). doi: 10.1186/cc13802. Fulltekst i vitenarkiv
• Warsame, Mahad Omar; Gamboa, Danil & Nielsen, Erik Waage (2014). M. Warsame og medarbeidere svarer:. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 134(23/24), s. 2239–2239. doi: 10.4045/tidsskr.14.1437. Fulltekst i vitenarkiv
• Landsem, A; Fure, Hilde; Nielsen, Erik Waage; Mollnes, Tom Eirik & Brekke, Ole Lars (2013). Effects of C1-inhibitor on clot development in human whole blood analyzed using rotational thromboelastography. Molecular Immunology. ISSN 0161-5890. 56(3), s. 271–271. doi: 10.1016/j.molimm.2013.05.094. Fulltekst i vitenarkiv
• Brekke, Ole Lars; Landsem, Anne; Fure, Hilde; Christiansen, Dorte; Nielsen, Erik Waage & Lambris, J.D. [Vis alle 7 forfattere av denne artikkelen] (2013). Key role of tissue factor in complement-mediated coagulation activation by Escherichia coli and LPS. Molecular Immunology. ISSN 0161-5890. 56(3), s. 250–250. doi: 10.1016/j.molimm.2013.05.036. Fulltekst i vitenarkiv
• Nielsen, Erik Waage (2013). Riktig definisjon av p-verdi? Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 133(9). Fulltekst i vitenarkiv
• Kristiansen, Steinar; Mollnes, Tom Eirik & Nielsen, Erik Waage (2026). Clinical and Inflammatory Responses to Bone Marrow Emboli: Exploring the Pathophysiological Role of Bone Marrow Embolization in Porcine Studies. UiT Norges arktiske universitet. Fulltekst i vitenarkiv Vis sammendrag

  Bone marrow embolization occurs when fat and tissue particles from the marrow enter the bloodstream. This can lead to fat embolism syndrome (FES), a potentially life-threatening condition characterized by respiratory and circulatory failure and neurological injury. The phenomenon is most often associated with major orthopedic interventions such as intramedullary nailing of long bones, trauma, or intraosseous cannulation in critically ill patients. Traditionally, emboli have been assumed to lodge in the pulmonary circulation, with the lungs serving as a protective filter. However, less is known about systemic embolization to vital organs and its inflammatory consequences. The aim of this thesis was to expand knowledge of the frequency, distribution, and effects of bone marrow embolization, using experimental porcine models, laboratory analyses, and clinical observations. Specifically, we investigated: (1) the frequency of embolization and its distribution beyond the lungs, (2) the inflammatory responses triggered, and (3) the cardiopulmonary consequences, including the utility of intraoperative transesophageal echocardiography (TEE) for real-time detection. We found that emboli were not confined to the lungs but also reached systemic circulation, including the heart and brain, more often than previously recognized. Systemic embolization was associated with impaired oxygenation, circulatory instability, and evidence of myocardial injury. Embolization elicited characteristic inflammatory responses, with systemic IL-6 elevation consistent with clinical findings. However, the most extensive inflammation occurred locally in tissues, suggesting that blood markers may underestimate the inflammatory burden. TEE detected emboli within the pulmonary circulation but failed to identify systemic embolization. In conclusion, bone marrow embolization represents a frequent and systemic phenomenon with clinical relevance. These findings provide new insights into the pathophysiology of FES and may inform future strategies for monitoring and treatment.

• Elise, Selbekk, Lotte; Ofstad, Eirik Hugaas & Nielsen, Erik Waage (2020). Akutte brystsmerter: en deskriptiv studie av pasienter innlagt ved Nordlandssykehuset over en toårsperiode. UiT Norges arktiske universitet. Fulltekst i vitenarkiv Vis sammendrag

  Tittel: Akutte brystsmerter: en deskriptiv studie av pasienter innlagt ved Nordlandssykehuset over en toårsperiode Formål: Formålet med denne oppgaven var å bruke Qlikview til å finne hva som kjennetegner pasienter innlagt med akutte brystsmerter ved NLSH i en toårs-periode når det gjelder demografi, utskrivelsesdiagnose, prosedyrer, blodprøver og overlevelse, samt finne ut i hvilken grad et datafangstverktøy (Qlikview) i kombinasjon med elektronisk pasientjournal (DIPS) kan bidra til å identifisere og beskrive denne populasjonen. Metode: Qlikview ble koblet opp med DIPS. To metoder for datainnsamling ble brukt; en tok utgangspunkt i søk i Qlikview («Populasjon 1») med inklusjonskriteriene innleggelse i akuttmottaket i tidsperioden 5. mars 2017 – 4. mars 2019, og ICD-10 diagnose enten under I-kapittelet (ekskludert I60, I73-78 og I80) eller under R07-kapittelet ved utskrivelse. «Populasjon 2» tok utgangspunkt i alle pasienter registrert i akuttmottaket med symptomdiagnose ESS5 (brystsmerter) og inklusjonskriter nevnt ovenfor. Hovedutfallene var ICD-10 utskrivelsesdiagnoser, prosedyrekoder, bosted, alder, kjønn, mortalitet (død på post, 30-dagers mortalitet og 1-års mortalitet), og blodprøver (inkludert troponin I, proBNP, CRP, Hb og D-dimer). Analyse og fremstilling av data ble gjort i Excel. Litteratursøk ble gjort i PubMed. Resultat: Prevalens av brystsmertepasienter i akuttmottaket var 6,5%. 70% var mellom 60 og 89 år. 40% kvinner (gj.snitt 71,2 år), og 60% menn (gj.snitt 66,5 år). Fem vanligste diagnoser var atrieflimmer og -flutter (prevalens 22%, gj.snitt CRP 8,2, Hb 14,5, D-dimer 1,1, proBNP 2227,1, cTnI 101, endring cTnI 18, mortalitet på post 0%, 30-dagers mortalitet 0,8%), uspesifisert brystsmerte (19%, 4,3, 14,2, 0,5, 402,9, 21, 2, 0,2%, 0,2%), akutt hjerteinfarkt (14%, 20,5, 13,7, 0,5, 3612,5, 9375, 2404, 1,1%, 5,7%), hjertesvikt (11%, 28,5, 12,4, 8491,4, 1939, 13, 0%, 11,7%) og angina pectoris (8%, 4,5, 13,9, 0,5, 834,2, 37, 6, 0%, 1,8%). Konklusjon: Brystsmertepasientene er en heterogen pasientpopulasjon med stor variasjon i diagnoser og biokjemi. Gjennomsnittsalderen var høy. Kvinnene var i snitt eldre enn menn. Pasientpopulasjonen hadde generelt lav mortalitet. Qlikview er et svært nyttig og kraftig verktøy for innsamling av store datamengder, og kan i stor grad brukes til identifisering av denne pasientpopulasjonen i kombinasjon med elektronisk pasientjournal.

Se alle arbeider i NVA