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1.	Anthon, Carl Thomas, et al. (författare) Platelet transfusions in adult ICU patients with thrombocytopenia : A sub-study of the PLOT-ICU inception cohort study Ingår i: Acta Anaesthesiologica Scandinavica. - 0001-5172. Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Platelet transfusions are frequently used in the intensive care unit (ICU), but current practices including used product types, volumes, doses and effects are unknown.STUDY DESIGN AND METHODS: Sub-study of the inception cohort study 'Thrombocytopenia and Platelet Transfusions in the ICU (PLOT-ICU)', including acutely admitted, adult ICU patients with thrombocytopenia (platelet count <150 × 10 9/L). The primary outcome was the number of patients receiving platelet transfusion in ICU by product type. Secondary outcomes included platelet transfusion details, platelet increments, bleeding, other transfusions and mortality. RESULTS: Amongst 504 patients with thrombocytopenia from 43 hospitals in 10 countries in Europe and the United States, 20.8% received 565 platelet transfusions; 61.0% received pooled products, 21.9% received apheresis products and 17.1% received both with a median of 2 (interquartile range 1-4) days from admission to first transfusion. The median volume per transfusion was 253 mL (180-308 mL) and pooled products accounted for 59.1% of transfusions, however, this varied across countries. Most centres (73.8%) used fixed dosing (medians ranging from 2.0 to 3.5 × 10 11 platelets/transfusion) whilst some (mainly in France) used weight-based dosing (ranging from 0.5 to 0.7 × 10 11 platelets per 10 kg body weight). The median platelet count increment for a single prophylactic platelet transfusion was 2 (-1 to 8) × 10 9/L. Outcomes of patients with thrombocytopenia who did and did not receive platelet transfusions varied. CONCLUSIONS: Among acutely admitted, adult ICU patients with thrombocytopenia, 20.8% received platelet transfusions in ICU of whom most received pooled products, but considerable variation was observed in product type, volumes and doses across countries. Prophylactic platelet transfusions were associated with limited increases in platelet counts.
2.	Anthon, Carl Thomas, et al. (författare) Thrombocytopenia and platelet transfusions in ICU patients : an international inception cohort study (PLOT-ICU) 2023 Ingår i: Intensive Care Medicine. - 0342-4642. ; 49:11, s. 1327-1338 Tidskriftsartikel (refereegranskat)abstract PURPOSE: Thrombocytopenia (platelet count < 150 × 10 9/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. METHODS: We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses.RESULTS: We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4-46.1) had thrombocytopenia; 23.4% (20-26) had thrombocytopenia at ICU admission, and 19.8% (17.6-22.2) developed thrombocytopenia during their ICU stay. Absence of acquired immune deficiency syndrome (AIDS), non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19-2.42).CONCLUSION: Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic.
3.	Anthon, Carl Thomas, et al. (författare) Platelet transfusions and thrombocytopenia in intensive care units : Protocol for an international inception cohort study (PLOT-ICU) 2022 Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 66:9, s. 1146-1155 Tidskriftsartikel (refereegranskat)abstract Introduction: Thrombocytopenia is frequent in intensive care unit (ICU) patients and has been associated with worse outcome. Platelet transfusions are often used in the management of ICU patients with severe thrombocytopenia. However, the reported frequencies of thrombocytopenia and platelet transfusion practices in the ICU vary considerably. Therefore, we aim to provide contemporary epidemiological data on thrombocytopenia and platelet transfusion practices in the ICU. Methods: We will conduct an international inception cohort, including at least 1000 acutely admitted adult ICU patients. Routinely available data will be collected at baseline (ICU admission), and daily during ICU stay up to a maximum of 90 days. The primary outcome will be the number of patients with thrombocytopenia (a recorded platelet count < 150 × 109/L) at baseline and/or during ICU stay. Secondary outcomes include mortality, days alive and out of hospital, days alive without life-support, the number of patients with at least one bleeding episode, at least one thromboembolic event and at least one platelet transfusion in the ICU, the number of platelet transfusions and the indications for transfusion. The primary and secondary outcomes will be presented descriptively. In addition, we will assess risk factors for developing thrombocytopenia during ICU stay and the association between thrombocytopenia at baseline and 90-day mortality using logistic regression analyses. Conclusion: The outlined international PLOT-ICU cohort study will provide contemporary epidemiological data on the burden and clinical significance of thrombocytopenia in adult ICU patients and describe the current platelet transfusion practice.
4.	Anthon, Carl Thomas, et al. (författare) Platelet transfusions in adult thrombocytopenic ICU patients : Protocol for a sub-study of the PLOT-ICU cohort Ingår i: Acta Anaesthesiologica Scandinavica. - 0001-5172. Tidskriftsartikel (refereegranskat)abstract INTRODUCTION: Platelet transfusions are frequently used in intensive care unit (ICU) patients, but contemporary epidemiological data are sparse. We aim to present contemporary international data on the use of platelet transfusions in adult ICU patients with thrombocytopenia.METHODS: This is a protocol and statistical analysis plan for a post hoc sub-study of 504 thrombocytopenic patients from the 'Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU)'. The primary outcome will be the number of patients receiving platelet transfusion in the ICU reported according to the type of product received (apheresis-derived versus pooled whole-blood-derived transfusions). Secondary platelet transfusion outcomes will include platelet transfusion volumes; timing of platelet transfusion; approach to platelet transfusion dosing (fixed dosing versus weight-based dosing) and platelet count increments for prophylactic transfusions. Secondary clinical outcomes will include the number of patients receiving red blood cell- and plasma transfusions during ICU stay; the number of patients who bled in the ICU, the number of patients who had a new thrombosis in the ICU, and the number of patients who died. The duration of follow-up was 90 days. Baseline characteristics and secondary clinical outcomes will be stratified according to platelet transfusion status in the ICU and severity of thrombocytopenia. Data will be presented descriptively.CONCLUSIONS: The outlined study will provide detailed epidemiological data on the use of platelet transfusions in adult ICU patients with thrombocytopenia using data from the large international PLOT-ICU cohort study. The findings will inform the design of future randomised trials evaluating platelet transfusions in ICU patients.
5.	Robba, Chiara, et al. (författare) Oxygen targets and 6-month outcome after out of hospital cardiac arrest : a pre-planned sub-analysis of the targeted hypothermia versus targeted normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial 2022 Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 26, s. 1-13 Tidskriftsartikel (refereegranskat)abstract Background: Optimal oxygen targets in patients resuscitated after cardiac arrest are uncertain. The primary aim of this study was to describe the values of partial pressure of oxygen values (PaO2) and the episodes of hypoxemia and hyperoxemia occurring within the first 72 h of mechanical ventilation in out of hospital cardiac arrest (OHCA) patients. The secondary aim was to evaluate the association of PaO2 with patients’ outcome. Methods: Preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after OHCA (TTM2) trial. Arterial blood gases values were collected from randomization every 4 h for the first 32 h, and then, every 8 h until day 3. Hypoxemia was defined as PaO2 < 60 mmHg and severe hyperoxemia as PaO2 > 300 mmHg. Mortality and poor neurological outcome (defined according to modified Rankin scale) were collected at 6 months. Results: 1418 patients were included in the analysis. The mean age was 64 ± 14 years, and 292 patients (20.6%) were female. 24.9% of patients had at least one episode of hypoxemia, and 7.6% of patients had at least one episode of severe hyperoxemia. Both hypoxemia and hyperoxemia were independently associated with 6-month mortality, but not with poor neurological outcome. The best cutoff point associated with 6-month mortality for hypoxemia was 69 mmHg (Risk Ratio, RR = 1.009, 95% CI 0.93–1.09), and for hyperoxemia was 195 mmHg (RR = 1.006, 95% CI 0.95–1.06). The time exposure, i.e., the area under the curve (PaO2-AUC), for hyperoxemia was significantly associated with mortality (p = 0.003). Conclusions: In OHCA patients, both hypoxemia and hyperoxemia are associated with 6-months mortality, with an effect mediated by the timing exposure to high values of oxygen. Precise titration of oxygen levels should be considered in this group of patients. Trial registration: clinicaltrials.gov NCT02908308, Registered September 20, 2016.
6.	Robba, Chiara, et al. (författare) Ventilatory settings in the initial 72 h and their association with outcome in out-of-hospital cardiac arrest patients : a preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (TTM2) trial 2022 Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 48:8, s. 1024-1038 Tidskriftsartikel (refereegranskat)abstract Purpose: The optimal ventilatory settings in patients after cardiac arrest and their association with outcome remain unclear. The aim of this study was to describe the ventilatory settings applied in the first 72 h of mechanical ventilation in patients after out-of-hospital cardiac arrest and their association with 6-month outcomes. Methods: Preplanned sub-analysis of the Target Temperature Management-2 trial. Clinical outcomes were mortality and functional status (assessed by the Modified Rankin Scale) 6 months after randomization. Results: A total of 1848 patients were included (mean age 64 [Standard Deviation, SD = 14] years). At 6 months, 950 (51%) patients were alive and 898 (49%) were dead. Median tidal volume (VT) was 7 (Interquartile range, IQR = 6.2–8.5) mL per Predicted Body Weight (PBW), positive end expiratory pressure (PEEP) was 7 (IQR = 5–9) cmH20, plateau pressure was 20 cmH20 (IQR = 17–23), driving pressure was 12 cmH20 (IQR = 10–15), mechanical power 16.2 J/min (IQR = 12.1–21.8), ventilatory ratio was 1.27 (IQR = 1.04–1.6), and respiratory rate was 17 breaths/minute (IQR = 14–20). Median partial pressure of oxygen was 87 mmHg (IQR = 75–105), and partial pressure of carbon dioxide was 40.5 mmHg (IQR = 36–45.7). Respiratory rate, driving pressure, and mechanical power were independently associated with 6-month mortality (omnibus p-values for their non-linear trajectories: p < 0.0001, p = 0.026, and p = 0.029, respectively). Respiratory rate and driving pressure were also independently associated with poor neurological outcome (odds ratio, OR = 1.035, 95% confidence interval, CI = 1.003–1.068, p = 0.030, and OR = 1.005, 95% CI = 1.001–1.036, p = 0.048). A composite formula calculated as [(4*driving pressure) + respiratory rate] was independently associated with mortality and poor neurological outcome. Conclusions: Protective ventilation strategies are commonly applied in patients after cardiac arrest. Ventilator settings in the first 72 h after hospital admission, in particular driving pressure and respiratory rate, may influence 6-month outcomes.
7.	Schott, Ulf, et al. (författare) Time to peak effect of aspirin-induced platelet inhibition and ex vivo effects of desmopressin: An observational study 2021 Ingår i: Journal of Integrative Cardiology. - 2058-3702. ; 7, s. 1-6 Tidskriftsartikel (refereegranskat)abstract Objective: To investigate time to maximal platelet inhibition after an oral loading dose of ASA. The effect of ex vivo reversal platelet inhibition by desmopressin (DDAVP) was also studied. Methods: Ten healthy volunteers were given a 300 mg ASA-tablet. Blood was sampled at 0, 15, 30, 60, 120 and 180 minutes. DDAVP was added to the samples taken at 120 minutes. Samples were analysed with a Multiplate® platelet aggregometer (MEA) using arachidonic acid (AA), collagen and thrombin aggregation agonists. Results: Platelet inhibition was observed in the sample activated by AA at 15 minutes but not until 120 minutes in the samples activated by collagen. No platelet inhibition was seen in the samples activated by thrombin. The median time to maximal AA-induced platelet inhibition of <30 U was 30 (interquartile range 15-90) minutes. Ex vivo DDAVP did not reverse platelet inhibition. Subgroup analysis did not show any gender differences. Conclusions: ASA induces a strong platelet inhibition within 30 minutes of oral ingestion, with no gender differences. Ex vivo DDAVP did not reverse ASA’s platelet inhibition.
8.	Adrian, Maria, et al. (författare) Mechanical complications after central venous catheterisation in the ultrasound-guided era : a prospective multicentre cohort study 2022 Ingår i: British Journal of Anaesthesia. - : Elsevier BV. - 1471-6771 .- 0007-0912. ; 129:6, s. 843-850 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Limited data are available on the incidence of mechanical complications after ultrasound-guided central venous catheterisation. We aimed to determine the incidence of mechanical complications in hospitals where real-time ultrasound guidance is clinical practice for central venous access and to identify variables associated with mechanical complications.METHODS: All central venous catheter insertions in patients ≥16 yr at four emergency care hospitals in Sweden from March 2, 2019 to December 31, 2020 were eligible for inclusion. Every insertion was monitored for complete documentation and occurrence of mechanical complications within 24 h after catheterisation. Multivariable logistic regression analyses were used to determine associations between predefined variables and mechanical complications.RESULTS: In total, 12 667 catheter insertions in 8586 patients were included. The incidence (95% confidence interval [CI]) of mechanical complications was 7.7% (7.3-8.2%), of which 0.4% (0.3-0.5%) were major complications. The multivariable analyses showed that patient BMI <20 kg m -2 (odds ratio 2.69 [95% CI: 1.17-5.62]), male operator gender (3.33 [1.60-7.38]), limited operator experience (3.11 [1.64-5.77]), and increasing number of skin punctures (2.18 [1.59-2.88]) were associated with major mechanical complication. Subclavian vein catheterisation was associated with pneumothorax (5.91 [2.13-17.26]). CONCLUSIONS: The incidence of major mechanical complications is low in hospitals where real-time ultrasound guidance is the standard of care for central venous access. Several variables independently associated with mechanical complications can be used for risk stratification before catheterisation procedures, which might further reduce complication rates.CLINICAL TRIAL REGISTRATION: NCT03782324.
9.	Adrian, Maria, et al. (författare) Minimal guidewire length for central venous catheterization of the right subclavian vein : A CT-based consecutive case series 2022 Ingår i: Journal of Vascular Access. - : SAGE Publications. - 1129-7298 .- 1724-6032. ; 23:3, s. 375-382 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Central venous catheter (CVC) misplacement occurs frequently after right subclavian vein catheterization. It can be avoided by using ultrasound to confirm correct guidewire tip position in the lower superior vena cava prior to CVC insertion. However, retraction of the guidewire during the CVC insertion may dislocate the guidewire tip from its desired and confirmed position, thereby resulting in CVC misplacement. The aim of this study was to determine the minimal guidewire length required to maintain correct guidewire tip position in the lower superior vena cava throughout an ultrasound-guided CVC placement in the right subclavian vein.METHODS: One hundred adult patients with a computed tomography scan of the chest were included. By using multiplanar reconstructions from thin-sliced images, the distance from the most plausible distal puncture site of the right subclavian vein to the optimal guidewire tip position in the lower superior vena cava was measured (vessel length). In addition, measurements of equipment in common commercial over-the-wire percutaneous 15-16 cm CVC kits were performed. The 95th percentile of the vessel length was used to calculate the required minimal guidewire length for each CVC kit.RESULTS: The 95th percentile of the vessel length was 153 mm. When compared to the calculated minimal guidewire length, the guidewires were up to 108 mm too short in eight of eleven CVC kits.CONCLUSION: After confirmation of a correct guidewire position, retraction of the guidewire tip above the junction of the brachiocephalic veins should be avoided prior to CVC insertion in order to preclude dislocation of the catheter tip towards the right internal jugular vein or the left subclavian vein. This study shows that many commercial over-the-wire percutaneous 15-16 cm CVC kits contain guidewires that are too short for right subclavian vein catheterization, i.e., guidewire retraction is needed prior to CVC insertion.
10.	Adrian, Maria, et al. (författare) Research protocol for mechanical complications after central venous catheterisation : a prospective controlled multicentre observational study to determine incidence and risk factors of mechanical complications within 24 hours after cannulation 2019 Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 9:10, s. 029301-029301 Tidskriftsartikel (refereegranskat)abstract INTRODUCTION: Central venous catheterisation is a common procedure in intensive care therapy and the use of central venous catheters is essential for treatment of many medical disorders. Although rare, central venous catheterisation is associated with mechanical complications that can be life-threatening if untreated. Real-time ultrasound guidance reduces the incidence of mechanical complications when compared with the anatomic landmark method. The purpose of this study is to determine the incidence of and potential risk factors associated with early mechanical complications of central venous catheterisation in an era where real-time ultrasound guidance has become clinical practice. METHODS AND ANALYSIS: This is a prospective, controlled, multicentre, observational study. All participating hospitals follow the same clinical guidelines for central venous catheterisation. Each central venous catheter insertion will be recorded in the common electronic chart system according to a recently revised template. An automated script-based search will identify all recorded central venous catheter insertion templates during the study period and relevant variables will be extracted. Outcome measures and independent variables are pre-defined in this study protocol. Multivariable and univariable logistic regression analysis will be used to determine associations and risk factors of mechanical complications. ETHICS AND DISSEMINATION: The Regional Ethical Review Board in Lund, Sweden has approved this study. The results will be submitted for publication in peer-reviewed medical journals and presented at national and international scientific meetings. TRIAL REGISTRATION NUMBER: NCT03782324.
11.	Amado-Rodríguez, Laura, et al. (författare) Mechanical ventilation in patients with cardiogenic pulmonary edema : a sub-analysis of the LUNG SAFE study 2022 Ingår i: Journal of Intensive Care. - : Springer Science and Business Media LLC. - 2052-0492. ; 10:1 Tidskriftsartikel (refereegranskat)abstract Background: Patients with acute respiratory failure caused by cardiogenic pulmonary edema (CPE) may require mechanical ventilation that can cause further lung damage. Our aim was to determine the impact of ventilatory settings on CPE mortality. Methods: Patients from the LUNG SAFE cohort, a multicenter prospective cohort study of patients undergoing mechanical ventilation, were studied. Relationships between ventilatory parameters and outcomes (ICU discharge/hospital mortality) were assessed using latent mixture analysis and a marginal structural model. Results: From 4499 patients, 391 meeting CPE criteria (median age 70 [interquartile range 59–78], 40% female) were included. ICU and hospital mortality were 34% and 40%, respectively. ICU survivors were younger (67 [57–77] vs 74 [64–80] years, p < 0.001) and had lower driving (12 [8–16] vs 15 [11–17] cmH2O, p < 0.001), plateau (20 [15–23] vs 22 [19–26] cmH2O, p < 0.001) and peak (21 [17–27] vs 26 [20–32] cmH2O, p < 0.001) pressures. Latent mixture analysis of patients receiving invasive mechanical ventilation on ICU day 1 revealed a subgroup ventilated with high pressures with lower probability of being discharged alive from the ICU (hazard ratio [HR] 0.79 [95% confidence interval 0.60–1.05], p = 0.103) and increased hospital mortality (HR 1.65 [1.16–2.36], p = 0.005). In a marginal structural model, driving pressures in the first week (HR 1.12 [1.06–1.18], p < 0.001) and tidal volume after day 7 (HR 0.69 [0.52–0.93], p = 0.015) were related to survival. Conclusions: Higher airway pressures in invasively ventilated patients with CPE are related to mortality. These patients may be exposed to an increased risk of ventilator-induced lung injury. Trial registration Clinicaltrials.gov NCT02010073.
12.	Andersson, E., et al. (författare) Analgesic efficacy of sleep-promoting pharmacotherapy in patients with chronic pain : a systematic review and meta-analysis 2023 Ingår i: Pain Rep. - : Lippincott Williams & Wilkins. - 2471-2531. ; 8:1, s. e1061- Tidskriftsartikel (refereegranskat)abstract Dysregulation of sleep heightens pain sensitivity and may contribute to pain chronification. Interventions which consolidate and lengthen sleep have the potential to improve pain control. The main objective of this systematic review was to examine the effects of sleep-promoting pharmacotherapy on pain intensity in patients with chronic pain. Multiple electronic databases were searched from inception to January 2022 to identify relevant randomized controlled trials (RCTs). Two independent reviewers screened titles, abstracts, and full-text articles; extracted data; and assessed risk of bias for each included study. The GRADE approach was used to determine the strength of evidence. The search identified 624 articles. After full-text screening, 10 RCTs (n = 574 randomized participants) involving 3 pharmacologic interventions (melatonin, zopiclone, and eszopiclone) and 7 different chronic pain populations were included. Minimum clinically significant pain reduction >/=30% was reported in 4 studies. There is low-quality evidence (downgraded due to inconsistency and imprecision) that 2 to 8 weeks treatment with a sleep-promoting medication alone or in combination with an analgesic (6 trials, n = 397) decreases pain intensity compared with placebo or the same analgesic treatment alone (SMD -0.58 [95% confidence interval -1.00, -0.17], P = 0.006). Analyses of associations between changes in sleep and pain outcomes were only provided in 2 articles, with inconsistent findings. Notably, pain-relieving effects were most consistent in melatonin trials. Only 3 studies implemented polysomnography to obtain objective sleep measures. Low-quality evidence indicates that pharmacologic sleep promotion may decrease pain intensity in chronic pain populations. More research is needed to fully understand the influence of sleep-targeting interventions on pain control.
13.	Bagge, August, et al. (författare) Effects of naturopathic medicines on Multiplate and ROTEM: a prospective experimental pilot study in healthy volunteers. 2016 Ingår i: BMC Complementary and Alternative Medicine. - : Springer Science and Business Media LLC. - 1472-6882. ; 16:1 Tidskriftsartikel (refereegranskat)abstract Of patients undergoing surgery, 22 to 57 % have been reported to be using naturopathic medicines. Several of these medicines have been reported to increase bleeding or enhance the effect of other drugs that increase bleeding. The Swedish Medical Products Agency recommends cessation of the use of the naturopathic medicines echinacea, fish oil, ginkgo biloba, ginseng, St. John's wort, valeriana and garlic 2 weeks before surgery. The aim of this pilot study was to examine the effects of these 7 naturopathic medicines in healthy humans by utilising multiple electrode aggregometer (Multiplate) and viscoelastic rotational thromboelastometer (ROTEM) to obtain data for sample size calculation before a larger trial.
14.	Bagge, August, et al. (författare) High-dose omega-3 fatty acids have no effect on platelet aggregation or coagulation measured with static and flow-based aggregation instruments and Sonoclot; an observational study in healthy volunteers 2018 Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 78:7-8, s. 539-545 Tidskriftsartikel (refereegranskat)abstract The effect of omega-3 fatty acids on platelet aggregation and coagulation is highly unclear. Studies both support and refute the impacts of omega-3 fatty acids on prolonged bleeding time and platelet inhibition as well as its purported positive effects on cardiovascular disease. In a previous pilot study we suggested an inhibition of platelet aggregation measured with multiple electrode aggregometry. Following on that, the aim of the present study was to investigate the effects of supplementary high doses of omega-3 fatty acids on platelet aggregation and coagulation in a sample-size calculated number of healthy volunteers using Sonoclot, multiple electrode aggregometry, and flow-based Cellix instruments after 10 days of omega-3 fatty acid intake. Twelve healthy human volunteers ingested 2520 mg of supplementary omega-3 fatty acids per day for 10 days. Venous blood was sampled and platelet aggregation and coagulation were measured before and after the treatment period. The viscoelastic test instrument Sonoclot, multiple electrode aggregometry, and flow-based Cellix instruments with collagen-coated channels were used to evaluate platelet aggregation and coagulation. There were no differences in any of the measured variables after the treatment period as compared to before. In this well-powered study on healthy volunteers, no effects of high doses of omega-3 fatty acids after 10 days of intake could be demonstrated, either on coagulation or platelet function. Further studies are needed to clarify whether omega-3 fatty acids have a role in the regulation of the putative complex processes in vivo.
15.	Bagger, Harald, et al. (författare) Synergistic platelet inhibition between Omega-3 and acetylsalicylic acid dose titration; an observational study 2020 Ingår i: BMC Complementary Medicine and Therapies. - : Springer Science and Business Media LLC. - 2662-7671. ; 20, s. 1-9 Tidskriftsartikel (refereegranskat)abstract Background: Omega-3 and acetylsalicylic acid (ASA) are two widely used “over-the-counter” drugs. Previous researchhas shown multiple electrode aggregometry (MEA) can detect ASA and varying Omega-3 platelet inhibiting effects.Synergistic platelet inhibiting effects of ASA and Omega-3 have been found using other methods than MEA. The aimof this study was to investigate the antiplatelet effects of Omega-3, and ASA synergism with MEA.Methods: Ten healthy male volunteers ingested Omega-3 (1260mg/day) for 5 days. MEA was used to analyse plateletfunction before and after Omega-3 intake. Aggregation was initiated using three different agonists and measured asarea under the curve (AUC): adenosine diphosphate (ADP), thrombin receptor activating peptide (TRAP) andarachidonic acid (ASPI). Two concentrations of ASA were dose titrated ex vivo to 2 out of 3 ASPI test cells in order tomeasure synergism between Omega-3 and ASA.Results: Following 5 days Omega-3 intake, ADP, TRAP and ASPI AUC did not change significantly. In vitro ASA beforeOmega-3 intake, reduced ASPI AUC < 30 U, indicating a strong platelet inhibiting effect. Below this AUC level, the 5 daysOmega-3 intake increased ASPI-AUC with the ex vivo added low dose ASA (P = 0.02) and high dose ASA (P = 0.04).Conclusions: No synergism between ASA and Omega-3 was found using the MEA ASPI test. The surprising increase inASPI-AUC following Omega-3 intake and ex vivo ASA suggest that there are methodological issuses with the MEA ASPI test.
16.	Benediktsson, Sigurdur, et al. (författare) Coagulation tests on admission correlate with mortality and morbidity in general ICU-patients : an observational study 2020 Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 64:5, s. 628-634 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: It is well known that low platelet count on admission to intensive care units (ICU) is associated with increased mortality. However, it is unknown whether prothrombin time (PT-INR) and activated partial thromboplastin time (APTT) on admission correlate with mortality and organ failure. Therefore, the aim of this study was to investigate if PT-INR and APTT at admission can predict outcome in the critically ill patient after adjusting for severity of illness measured with Simplified Acute Physiology Score 3 (SAPS 3).MATERIALS AND METHODS: Data were retrospectively collected. APTT and PT-INR taken on admission and SAPS 3 score, were independent variables in all regression analyses. Survival analysis was done with Cox regression. Organ failure was reported as days alive and free (DAF) of vasopressors and invasive ventilation, need of continuous renal replacement therapy (CRRT) and Acute Kidney Injury Network creatinine score (AKIN-crea).RESULTS: 3585 ICU-patients were included. Prolonged APTT correlated with mortality with 95% confidence interval (CI) of hazard ratio 1.001-1.010. Prolonged APTT also correlated with DAF vasopressor, CRRT, and AKIN-crea with 95% CI of odds ratio (OR) 1.009-1.034, 1.016-1.037 and 1.009-1.028, respectively. Increased PT-INR correlated with DAF vasopressor and DAF ventilator with 95% CI of OR 1.112-2.014 and 1.135-1.847, respectively.CONCLUSIONS: APTT prolongation was associated with mortality and all morbidity outcomes except the DAF ventilator. PT-INR increase at admission was associated with DAF vasopressor and DAF ventilator. APTT and PT-INR at admission correlate with morbidity, which is not accounted for in the SAPS 3 model.
17.	Benediktsson, Sigurdur, et al. (författare) Linear decline of corrected platelet count increment within 24 hours after platelet transfusion in haematological patients : a prospective observational study 2017 Ingår i: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; , s. 559-568 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: The aim of the present study was to prospectively explore the detailed longitudinal development of platelet increments in patients with chemotherapy-induced bone marrow aplasia during the first 24 hours after platelet transfusion.METHODS: Patients admitted to the Haematology department during 7 months and fulfilled inclusion criteria were divided into 4 groups: Group 1, patients with acute leukaemia; Group 2, patients after autologous stem cell transplantation (SCT); Group 3, patients after allogeneic SCT; Group 4, patients given platelet transfusion prior to intervention. We used frequent blood sampling within 24 hours after platelet transfusion to investigate the kinetics of platelet counts following transfusion.RESULTS AND CONCLUSIONS: 54 platelet transfusion occasions in patients with chemotherapy-induced bone marrow aplasia were included. The decrease of corrected count increment (CCI) 1-24 hours after platelet transfusions in all groups could be described as linear functions. For patients in the aggregated Groups 1-3, the decline was 2.0%± 0.6% (mean± standard deviation) per hour. For patients in Group 4, the decline of CCI was 2.8%± 1.2% per hour. We found no differences between the groups, either in the rate of platelet elimination from the bloodstream or in the mean CCI, in the first 24 hours post-transfusion. This article is protected by copyright. All rights reserved.
18.	Benediktsson, S., et al. (författare) Platelet increment is not associated with endothelial damage in haematological patients : a prospective observational study 2019 Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 79:6, s. 395-403 Tidskriftsartikel (refereegranskat)abstract The aim of this study was to investigate if thrombocytopenic haematology patients show signs of endothelial damage when transfused with platelets and if that damage correlates with platelet increment measured with corrected count increment (CCI). Endothelial damage secondary to radiation or chemotherapy may lead to consumption of transfused platelets but research in this field is scarce. Patients were divided into four groups: Group 1: Acute leukaemia; Group 2: Autologous stem cell transplantation (SCT); Group 3: Allogenic SCT; and Group 4: patients receiving platelets prior to interventions. Blood was sampled before (baseline) and immediately after (0 h) transfusion and then at 1, 4, 8, 16 and 24 h after transfusion. The biomarkers syndecan-1, soluble thrombomodulin (sTM) and vascular endothelial growth factor (VEGF) were analysed. The plasma concentration differences between baseline and later sampling times were referred to as delta (Δ). Fifty-four platelet transfusion events were studied. All biomarkers were within the normal ranges both before and after the transfusions. The Δsyndecan-1 increased at 0 h (p =.02), but there was no significant correlation between Δsyndecan-1 and CCI. There was no change in any of the other biomarkers after transfusion compared to before. There were no differences between the groups and no correlations were found between CCI and C-reactive protein, Δsyndecan-1, ΔsTM or ΔVEGF. There were no signs of endothelial damage before or after platelet transfusions. A transient significant change in syndecan-1 immediately after platelet transfusion did not influence platelet count or platelet CCI.
19.	Bentzer, Peter, et al. (författare) Effect of dextran-70 on outcome in severe sepsis; A propensity-score matching study 2017 Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - : Springer Science and Business Media LLC. - 1757-7241. ; 25:1 Tidskriftsartikel (refereegranskat)abstract Background: Albumin may be beneficial in patients with septic shock but availability is limited and cost is high. The objective of the present study was to investigate if the use of dextran-70 in addition to albumin and crystalloids influences organ failure or mortality in patients with severe sepsis or septic shock. Methods: Patients with severe sepsis or septic shock (n = 778) admitted to a university hospital intensive care unit (ICU) between 2007 and 2015 that received dextran-70 during resuscitation were propensity score matched to controls at a 1 to 1 ratio. Outcomes were highest acute kidney injury network (AKIN) score the first 10 days in the ICU, use of renal replacement therapy, days alive and free of organ support the first 28 days after admission to ICU, mortality and events of severe bleeding. Outcomes were assessed using paired hypothesis testing. Results: Propensity score matching resulted in two groups of patients with 245 patients in each group. The dextran group received a median volume of 1483 ml (interquartile range, 1000-2000 ml) of dextran-70 during the ICU stay. Highest AKIN score did not differ between the control- and dextran groups (1 (0-3) versus 2 (0-3), p = 0.06). Incidence of renal replacement therapy in the control- and dextran groups was similar (19% versus 22%, p = 0.42, absolute risk reduction -2.9% [95% CI: -9.9 to 4.2]). Days alive and free of renal replacement, vasopressors and mechanical ventilation did not differ between the control- and dextran groups. The 180-day mortality was 50.2% in the control group and 41.6% in the dextran group (p = 0.046, absolute risk reduction 8.6% [-0.2 to 17.4]). Fraction of patients experiencing a severe bleeding in the first 10 days in the ICU did not differ between the control and dextran groups (14% versus 18%, p = 0.21). Discussion: There is a paucity of high quality data regarding effects of dextran solutions on outcome in sepsis. In the present study, propensity score matching was used in attempt to reduce bias. Conclusion: No evidence to support a detrimental effect of dextran-70 on mortality or on organ failures in patients with severe sepsis or septic shock could be detected.
20.	Bjurström, Martin F., et al. (författare) Adherence to a restrictive red blood cell transfusion strategy in critically ill patients : An observational study 2024 Ingår i: Acta Anaesthesiologica Scandinavica. - : John Wiley & Sons. - 0001-5172 .- 1399-6576. Tidskriftsartikel (refereegranskat)abstract BackgroundRandomized controlled trials relatively consistently show that restrictive red blood cell (RBC) transfusion strategies are safe and associated with similar outcomes compared to liberal transfusion strategies in critically ill patients. Based on these data, the general threshold for RBC transfusion was changed to 70 g/L at a 9-bed tertiary level intensive care unit in September 2020. Implementation measures included lectures, webinars and feedback during clinical practice. The aim of this study was to investigate how implementation of a restrictive transfusion strategy influenced RBC usage, haemoglobin trigger levels and adherence to prescribed trigger levels.MethodsIn this registry-based, observational study, critically ill adult patients without massive bleeding were included and divided into a pre-cohort, with admissions prior to the change of transfusion strategy, and a post-cohort, with admissions following the change of transfusion strategy. These cohorts were compared regarding key RBC transfusion-related variables.ResultsIn total 5626 admissions were included in the analyses (pre-cohort n = 4373, post-cohort n = 1253). The median volume (interquartile range, IQR) of RBC transfusions per 100 admission days, in the pre-cohort was 6120 (4110–8110) mL versus 3010 (2890–4970) mL in the post-cohort (p < .001). This corresponds to an estimated median saving of 1128 € per 100 admission days after a restrictive RBC transfusion strategy was implemented. In total, 26% of the admissions in the pre-cohort and 19% in the post-cohort (p < .001) received RBC transfusion(s) during days 0–10. Both median (IQR) prescribed trigger levels (determined by intensivist) and actual haemoglobin trigger levels (i.e., levels prior to actual administration of transfusion) were higher in the pre- versus post-cohort (90 [80–100] vs. 80 [72–90] g/L, p < .001 and 89 [82–96] g/L vs. 83 [79–94], p < .001, respectively). Percentage of days without compliance with the prescribed transfusion trigger was higher in the pre-cohort than in the post-cohort (23% vs. 14%, p < .001). Sensitivity analyses, excluding patients with traumatic brain injury, ischemic heart disease and COVID-19 demonstrated similar results.ConclusionsImplementation of a restrictive transfusion trigger in a critical care setting resulted in lasting decreased RBC transfusion use and costs, decreased prescribed and actual haemoglobin trigger levels and improved adherence to prescribed haemoglobin trigger levels.
21.	Bjurström, Martin F, et al. (författare) Audio podcast and procedural video use in anaesthesiology and intensive care : A nationwide survey of Swedish anaesthetists 2024 Ingår i: Acta Anaesthesiologica Scandinavica. - 0001-5172 .- 1399-6576. Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Digital modalities which enable asynchronous learning, such as audio podcasts and videos demonstrating procedures, may benefit acquisition and retention of knowledge and clinical skills. The main objective of this nationwide cross-sectional survey study was to evaluate key aspects and factors related to usage of audio podcasts and procedural videos in anaesthesiology and intensive care.METHODS: A 20-item multiple-choice-question online survey was created through a consensus process including pilot testing among residents and consultants. Data were collected over a 3-month period, September-November 2023.RESULTS: The survey was completed by 466 anaesthetists. More than a third reported using procedural videos ≥1 time per week, whereas fewer than one in four participants used audio podcasts at least once per week. Multivariable logistic regression analysis showed that working at a university hospital, male sex, and younger age were independently associated with podcast use ≥1 time per week, with the highest odds ratio (OR) for younger age (<40 years vs. ≥40 years old; OR 5.86 (95% confidence interval 3.55-9.67), p < .001). Younger age was also significantly associated with higher frequency of video use (OR 1.71 (1.13-2.58), p = .011), while working predominantly in intensive care was associated with a lower frequency of video use. Podcasts were often used during commuting (42.3%), household work (30.7%), and exercise (24.9%), indicating a role in multi-tasking. Approximately half of respondents expressed that audio podcast-based learning has a moderate to very large positive impact on acquisition of theoretical knowledge, as well as practical skills. A vast majority, 85.2%, reported that procedural videos have a moderate to very large impact on development of clinical skills.CONCLUSION: Audio podcasts and procedural videos are appreciated tools with potential to supplement more traditional didactic techniques in anaesthesiology and intensive care. Procedural video use is common, with perceived large effects on development of clinical skills. Further data are needed to fully understand learning outcomes, quality of peer-review processes, and potential sex-differences.
22.	Björck, Viveka, et al. (författare) Morbidity and mortality in critically ill patients with invasive group A streptococcus infection : an observational study 2020 Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535. ; 24:1 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Group A streptococci (GAS) are known to cause serious invasive infections, but little is known about outcomes when patients with these infections are admitted to intensive care. We wanted to describe critically ill patients with severe sepsis or septic shock due to invasive GAS (iGAS) and compare them with other patients with severe sepsis or septic shock. METHODS: Adult patients admitted to a general intensive care unit (ICU) in Sweden (2007-2019) were screened for severe sepsis or septic shock according to Sepsis 2 definition. Individuals with iGAS infection were identified. The outcome variables were mortality, days alive and free of vasopressors and invasive mechanical ventilation, maximum acute kidney injury score for creatinine, use of continuous renal replacement therapy and maximum Sequential Organ Failure Assessment score during the ICU stay. Age, Simplified Acute Physiology Score (SAPS 3) and iGAS were used as independent, explanatory variables in regression analysis. Cox regression was used for survival analyses. RESULTS: iGAS was identified in 53 of 1021 (5.2%) patients. Patients with iGAS presented a lower median SAPS 3 score (62 [56-72]) vs 71 [61-81]), p < 0.001), had a higher frequency of cardiovascular cause of admission to the ICU (38 [72%] vs 145 [15%], p < 0.001) and had a higher median creatinine score (173 [100-311] vs 133 [86-208] μmol/L, p < 0.019). Of the GAS isolates, 50% were serotyped emm1/T1 and this group showed signs of more pronounced circulatory and renal failure than patients with non-emm1/T1 (p = 0.036 and p = 0.007, respectively). After correction for severity of illness (SAPS 3) and age, iGAS infection was associated with lower mortality risk (95% confidence interval (CI) of hazard ratio (HR) 0.204-0.746, p < 0.001). Morbidity analyses demonstrated that iGAS patients were more likely to develop renal failure. CONCLUSION: Critically ill patients with iGAS infection had a lower mortality risk but a higher degree of renal failure compared to similarly ill sepsis patients. emm1/T1 was found to be the most dominant serotype, and patients with emm1/T1 demonstrated more circulatory and renal failure than patients with other serotypes of iGAS.
23.	Björkander, Malin, et al. (författare) Mechanical complications of central venous catheter insertions : A retrospective multicenter study of incidence and risks 2019 Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 63:1, s. 61-68 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Incidence and risk factors for complications after insertion of central venous catheters have previously been reported for smaller cohorts. The aim of this observational multicenter study was to study risk factors for mechanical complications in a large, recently collected cohort of patients.METHODS: Records of central venous catheter insertions from 8 hospitals in southern Sweden from 2013 to 2016 were collected from the regional chart system. Data on blood coagulation tests, use of ultrasonography, central venous catheter location, bore size, number of needle passes, arterial puncture, the chronological order of the central venous catheter insertion, and mechanical complications were extracted. Only one insertion/patient was included using worst-case selection criteria. Predefined primary outcome was mechanical complications defined as bleeding, pneumothorax, nerve injury, or malignant arrhythmia. Severe mechanical complications were defined as bleeding requiring intervention or transfusion, pneumothorax, persistent nerve injury, or non-self-limiting arrhythmias.RESULTS: We included 10 949 insertions and identified 118 (1.1%) incidents of mechanical complication, of which 85 (0.8%) were bleedings, 21 (0.2%) were pneumothoraces, 7 (0.06%) were transient nerve injuries, and 5 (0.05%) were self-limiting arrhythmias. Severe mechanical complications occurred in 23 (0.2%) cases.CONCLUSIONS: In this retrospective, multicenter observational study on 10 949 central venous catheter insertions, mechanical complications were rare. Preprocedural coagulopathy, number of needle passes, and arterial puncture were associated with grade 2-4 bleeding. Subclavian vein insertions, arterial puncture, and chronological order of the central venous catheter insertion were associated with pneumothorax.
24.	Borgquist, Ola, et al. (författare) Central venous stenosis after subclavian versus internal jugular dialysis catheter insertion (CITES) in adults in need of a temporary central dialysis catheter : study protocol for a two-arm, parallel-group, non-inferiority randomised controlled trial 2023 Ingår i: Trials. - 1745-6215. ; 24:1 Tidskriftsartikel (refereegranskat)abstract Background: The right internal jugular vein is currently recommended for temporary central dialysis catheters (tCDC) based on results from previous studies showing a lower incidence of central vein stenosis compared to the subclavian vein. Data is however conflicting, and there are several advantages when the subclavian route is used for tCDCs. This prospective, controlled, randomised, non-inferiority study aims to compare the incidence of post-catheterisation central vein stenosis between the right subclavian and the right internal jugular routes. Methods: Adult patients needing a tCDC will be included from several hospitals and randomised to either subclavian or internal jugular vein catheterisation with a silicone tCDC. Inclusion continues until 50 patients in each group have undergone a follow-up CT venography. The primary outcome is the incidence of post-catheterisation central vein stenosis detected by a CT venography performed 1.5 to 3 months after removal of the tCDC. Secondary outcomes include between-group comparisons of (I) the patients’ experience of discomfort and pain, (II) any dysfunction of the tCDC during use, (III) catheterisation success rate and (IV) the number of mechanical complications. Furthermore, the ability to detect central vein stenosis by a focused ultrasound examination will be evaluated using the CT venography as golden standard. Discussion: The use of the subclavian route for tCDC placement has largely been abandoned due to older studies with various methodological issues. However, the subclavian route offers several advantages for the patient. This trial is designed to provide robust data on the incidence of central vein stenosis after silicone tCDC insertion in the era of ultrasound-guided catheterisations. Trial registration: Clinicaltrials.gov; NCT04871568. Prospectively registered on May 4, 2021.
25.	Dahlberg, Sofia, et al. (författare) Desphospho-Uncarboxylated Matrix-Gla Protein Is Increased Postoperatively in Cardiovascular Risk Patients 2018 Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 10:1 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Matrix Gla protein (MGP) is an extrahepatic protein that is dependent on glutamate carboxylation, a vitamin K-dependent process. Its dysfunctional form, desphospho-uncarboxylated-MGP, has been associated with increased arterial calcification and stiffness. The aim of this study was to measure the degree of postoperative carboxylation of MGP and two other Gla proteins in patients scheduled for abdominal or orthopaedic surgery.METHODS: Forty patients undergoing abdominal or orthopaedic surgery were included. Blood samples were collected preoperatively and four days after the surgery. Desphospho-carboxylated MGP (dp-cMGP), desphospho-uncarboxylated MGP (dp-ucMGP), carboxylated osteocalcin (OC) (cOC), uncarboxylated OC (ucOC), and uncarboxylated prothrombin (PIVKA-II) were analysed.RESULTS: Preoperatively, 29 patients had dp-ucMGP levels above the reference values. Patients with pre-existing cardiovascular comorbidities had higher dp-ucMGP preoperatively compared with patients with no record of cardiovascular disease. Postoperatively, this number increased to 36 patients, and median dp-ucMGP levels increased (p < 0.0001) and correlated to a PIVKA-II increase (r = 0.44). On the other hand, dp-cMGP levels did not significantly alter. Decreased levels of ucOC and cOC were seen after surgery (p = 0.017 and p = 0.0033, respectively). Comorbidities, possible nutritional defects, and complications affecting Gla protein activity and function were identified.CONCLUSIONS: Dp-ucMGP was high preoperatively, and had further increased postoperatively. This pattern was linked to several comorbidities, possible nutritional defects, and postoperative complications, which motivates further research about potential interactions between perioperative corrective treatments with vitamin K supplements, cardiovascular biomarkers, and incidents of stroke and myocardial infarction events.
26.	Dahlberg, Sofia, et al. (författare) Detection of subclinical vitamin K deficiency in neurosurgery with PIVKA-II 2017 Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 77:4, s. 267-274 Tidskriftsartikel (refereegranskat)abstract Vitamin K is known for supporting the carboxylation of hepatic coagulation proteins. Levels of proteins induced by vitamin K absence for factor II (PIVKA-II) reflect hypocarboxylated prothrombin and can be used to detect subclinical vitamin K deficiency. The aim of this study was to determine the prevalence of perioperative subclinical vitamin K deficiency among neurosurgical patients using PIVKA-II and investigate the existence of any correlation to standard coagulation assays. Also, the antitumor effects of vitamin K were reviewed. Thirty-five patients undergoing brain tumor resection were included. Blood samples were drawn preoperatively, at the end of surgery and in the morning after surgery. In addition to PIVKA-II, factor II and the Owren and Quick prothrombin times were analyzed. Seventeen of 35 patients had elevated PIVKA-II levels before surgery, which continued to be above normal range postoperatively. Median PIVKA-II and Owren prothrombin time (PT-INR) were increased on the morning day 1 postoperatively compared to before surgery, whereas Quick end-stage prothrombin time (EPT) decreased and factor II was unaffected. Postoperative complications were connected to high PIVKA-II increases. Positive correlations between PIVKA-II and factor II and body mass index (BMI) were found. In conclusion, PIVKA-II was increased in many patients preoperatively and then increased by the morning following surgery. Standard coagulation assays were largely non-pathological. Correlations were demonstrated between PIVKA-II and factor II and BMI. The effect of perioperative treatment with different vitamin K supplements should be investigated in future studies, as well as clinical trials evaluating their antitumor effects.
27.	Dahlberg, Sofia, et al. (författare) Effekt av intravenöst givet K-vitamin till kritiskt sjuka patienter med spontant förlängd protrombintid. 2019 Konferensbidrag (refereegranskat)abstract Studien demonstrerar att protrombintid(PT) och aktivitet av K-vitaminberoende koagulationsfaktorer hos kritiskt sjuka patienter med spontanförlängda PT-värden har förstärkts 24 timmar efter Konakion.
28.	Dahlberg, Sofia, et al. (författare) Intravenous Vitamin K1 for the Correction of Prolonged Prothrombin Times in Non-Bleeding Critically Ill Patients: A Prospective Observational Study 2021 Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 13:8, s. 1-12 Tidskriftsartikel (refereegranskat)abstract The aim of this study was to evaluate the effects of vitamin K1 on various vitamin K-dependent proteins in critically ill patients with prolonged Owren PT. We included critically ill non-bleeding adult patients without liver failure or anticoagulation treatment, with Owren PT > 1.2, who were prescribed intravenous vitamin K1. Blood was drawn at baseline and at 20–28 h after vitamin K1 administration. At both time points, we measured various vitamin K-dependent proteins and coagulation assays. ClinicalTrials.gov; Identifier: NTC3782025. In total, 52 patients were included. Intravenous vitamin K1 reduced Owren PT, Quick PT, protein induced by vitamin K absence/antagonist-II and desphospho-uncarboxylated matrix Gla protein (dp-ucMGP), but not to normal levels. Concomitantly, there were increases in thrombin generation and the activity of coagulation factors II, VII, IX and X that was only counteracted with a small increase in Protein C activity. In conclusion, the results suggest that vitamin K1 strengthens coagulation as measured by PT decrease and increases in the activity of vitamin K-dependent clotting factors and thrombin generation. The decreased dp-ucMGP, and its potential positive short- and long-term non-coagulative effects, merits further research.
29.	Dahlberg, Sofia, et al. (författare) The effect of vitamin K on prothrombin time in critically ill patients: an observational registry study. 2021 Ingår i: Journal of Intensive Care. - : Springer Science and Business Media LLC. - 2052-0492. ; 1, s. 11-17 Tidskriftsartikel (refereegranskat)abstract Background Previous studies have indicated that vitamin K deficiency is common in non-bleeding critically ill patients with slightly prolonged prothrombin time-international normalized ratio (PT-INR). It has never been investigated thoroughly whether the administration of vitamin K to these patients could affect their PT-INR. Therefore, the aim of this registry study was to evaluate changes in PT-INR in response to vitamin K in critically ill patients with PT-INR in the range of 1.3–1.9. Methods Patients admitted to a mixed 9-bed general intensive care unit at a University Hospital, between 2013 and 2019 (n = 4541) with a PT-INR between 1.3 and 1.9 at any time during the stay were identified. Patients who received vitamin K with appropriate sampling times for PT-INR and without exclusion criteria were matched with propensity score to patients from the same cohort who did not receive vitamin K (controls). PT-INR was measured at admission, within 12 h before vitamin K administration and 12–36 h following vitamin K administration. Exclusion criteria included pre-existing liver cirrhosis, any plasma or platelet transfusion, or > 1 unit red blood cell transfusion between PT-INR samplings. Results Propensity score matching resulted in two groups of patients with 129 patients in each group. PT-INR decreased in both groups (1.4 [1.3–1.4] in the vitamin K group and 1.4 [1.3–1.6] in the controls, p < 0.001 and p = 0.004, respectively). The decrease in PT-INR was slightly more pronounced in patients who received vitamin K (delta PT-INR − 0.10 [− 0.30 to − 0.10] in the vitamin K group and − 0.10 [− 0.20 to 0.10] in the controls, p = 0.01). Conclusion In critically ill patients with a PT-INR of 1.3–1.9, the administration of vitamin K resulted in a slightly larger decrease of PT-INR 12–36 h after administration compared to controls. Future studies should focus on identifying which patient populations may benefit most from vitamin K administration as well as whether vitamin K could be a better alternative than plasma or prothrombin complex concentrate to improve PT-INR before non-emergent invasive procedures.
30.	Dahlberg, Sofia, et al. (författare) Vitamin K deficiency in critical ill patients; a prospective observational study 2019 Ingår i: Journal of Critical Care. - : Elsevier BV. - 1557-8615 .- 0883-9441. ; 49, s. 105-109 Tidskriftsartikel (refereegranskat)abstract Background: Vitamin K is a cofactor for proteins involved in cardiovascular health, bone metabolism and cancer. Measuring uncarboxylated prothrombin, also termed as “protein induced by vitamin K absence or antagonism for factor II (PIVKA-II)”, has been used to assess vitamin K status. High levels may indicate vitamin K deficiency. The aim of this study was to measure PIVKA-II and prothrombin time (PT-INR) in intensive care (ICU) patients and correlate vitamin K status with mortality. Methods: Ninety-five patients admitted to the ICU had blood samples taken near admission and every third day. In addition to PIVKA-II and PT-INR, critical-care severity scores were computed. Results: The median baseline PIVKA-II was 4.97 μg/L compared to the upper reference of 2.0 μg/L. PIVKA-II further increased at days 3 and 6, (median 7.88 μg/L, p = .047 and median 8.14 μg/L, p = .011) predominantly in cardiac arrest patients (median 21.4 μg/L, day 3). Conclusion: Intensive care patients have increased PIVKA-II levels at admission, which increases during the ICU stay, especially in cardiac arrest patients. There were no correlations between PIVKA-II and PT-INR, SOFA score or mortality. Further studies are needed to determine why PIVKA-II increases and whether high PIVKA-II levels in ICU patients affect long-term mortality or morbidity. Previous article in issue
31.	Dahlberg, Sofia, et al. (författare) Vitamin K: Nutrition, Metabolism and Current Evidence from Clinical Trials. 2018 Ingår i: Nutrition and Metabolism: An Open Access. ; , s. 1-13 Forskningsöversikt (refereegranskat)
32.	Fisher, Jane, et al. (författare) The Dynamics of Circulating Heparin-Binding Protein : Implications for Its Use as a Biomarker 2022 Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 14:5, s. 447-460 Tidskriftsartikel (refereegranskat)abstract Heparin-binding protein (HBP) is a promising biomarker for the development and severity of sepsis. To guide its use, it is important to understand the factors that could lead to false-positive or negative results, such as inappropriate release and inadequate clearance of HBP. HBP is presumably released only by neutrophils, and the organs responsible for its elimination are unknown. In this study, we aimed to determine whether non-neutrophil cells can be a source of circulating HBP and which organs are responsible for its removal. We found that in two cohorts of neutropenic patients, 12% and 19% of patients in each cohort, respectively, had detectable plasma HBP levels. In vitro, three leukemia-derived monocytic cell lines and healthy CD14+ monocytes constitutively released detectable levels of HBP. When HBP was injected intravenously in rats, we found that plasma levels of HBP decreased rapidly, with a distribution half-life below 10 min and an elimination half-life of 1-2 h. We measured HBP levels in the liver, spleen, kidneys, lungs, and urine using both ELISA and immunofluorescence quantitation, and found that the majority of HBP was present in the liver, and a small amount was present in the spleen. Immunofluorescence imaging indicated that HBP is associated mainly with hepatocytes in the liver and monocytes/macrophages in the spleen. The impact of hematologic malignancies and liver diseases on plasma HBP levels should be explored further in clinical studies.
33.	Ingefors, Sofia, et al. (författare) Major immediate insertion-related complications after central venous catheterisation and associations with mortality, length of hospital stay, and costs : A prospective observational study Ingår i: Journal of Vascular Access. - 1129-7298. ; , s. 1-10 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: It is well-known that infectious complications after central venous catheterisation are associated with increased mortality, length of hospital stay and costs. However, there are limited data regarding such associations for immediate insertion-related complications. Therefore, the aim of this study was to investigate whether major immediate insertion-related complications are associated with mortality, length of hospital stay and costs.METHODS: This was a preplanned substudy to the CVC-MECH trial on immediate insertion-related complications after central venous catheterisation in the ultrasound-guided era. Patients receiving central venous catheters at Skåne University Hospital from 2 March 2019 to 31 December 2020 were prospectively included. Patient characteristics, clinical data and costs were automatically collected from medical journals and the patient administration system. Associations between major immediate insertion-related complications and mortality, length of hospital stay and costs were studied by multivariable logistic and linear regression analyses.RESULTS: In total, 6671 patients were included, of whom 0.5% suffered major immediate insertion-related complications. Multivariable analyses, including surrogates for general morbidity, showed associations between major immediate insertion-related complications and 30-day (odds ratio 2.46 [95% CI 1.05-5.77]), 90-day (2.90 [1.35-6.21]) and 180-day (2.26 [1.05-4.83]) mortality. There were no associations between major immediate insertion-related complications and increased length of hospital stay or costs.CONCLUSION: This study showed that major immediate insertion-related complications, although not directly responsible for any death, were associated with increased 30-day, 90-day and 180-day mortality. These findings clearly demonstrate the importance of using all possible means to prevent avoidable insertion-related complications after central venous catheterisation.
34.	Jansohn, Erik, et al. (författare) A pilot study on the applicability of thromboelastometry in detecting brain tumour-induced hypercoagulation 2017 Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 77:4, s. 289-294 Tidskriftsartikel (refereegranskat)abstract Patients with intracranial tumours have an increased risk of venous thromboembolism, particularly during the first month after neurosurgery. A proposed explanation for this increased risk, are procoagulant tumour-derived substances, such as tissue factor, usually measured in peripheral blood. The aim of the present study is to investigate whether a rotational thromboelastometry (ROTEM) can measure the procoagulative activity of tumour tissue. The study included 21 patients who were undergoing a craniotomy and complete tumour resection after written consent and ethical approval were obtained. Tumour tissue was biopsied during surgery and used for in vitro spiking of patients own citrated whole blood. Blood samples with or without spiking were analyzed with ROTEM using different activating reagents. ROTEM clotting time significantly decreased (p < .001), indicating a hypercoagulative response on clot initiation that was strongest for glioma tumours. However, ROTEM clot formation time was significantly prolonged (p < .001), which was an opposite response that indicated poor initial clot propagation. ROTEM maximum lysis was increased in the tumour tissue-spiked samples (p < .001), indicating a strong fibrinolytic activity in brain tumour tissue. Tissue extracts from intracranial tumours have both procoagulant and fibrinolytic effects that are detectable with ROTEM. Glioma tumours had the strongest hypercoagulative response in our in vitro model. Larger studies are necessary to test the clinical relevance and accuracy of tumour extract spiked viscoelastic tests to predict the individual patient risk for developing a thrombotic complication.
35.	Jonmarker, Sandra, et al. (författare) A retrospective multicenter cohort study of the association between anti-Factor Xa values and death, thromboembolism, and bleeding in patients with critical COVID-19 2023 Ingår i: Thrombosis Journal. - 1477-9560. ; 21, s. 1-11 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Patients with critical COVID-19 have a high risk of thromboembolism, but intensified thromboprophylaxis has not been proven beneficial. The activity of low-molecular-weight heparins can be monitored by measuring anti-Factor Xa. We aimed to study the association between anti-Factor Xa values and death, thromboembolism, and bleeding in patients with critical COVID-19.METHOD: This retrospective cohort study included adult patients with critical COVID-19 admitted to an intensive care unit at three Swedish hospitals between March 2020 and May 2021 with at least one valid peak and/or trough anti-Factor Xa value. Within the peak and trough categories, patients' minimum, median, and maximum values were determined. Logistic regressions with splines were used to assess associations.RESULTS: In total, 408 patients had at least one valid peak and/or trough anti-Factor Xa measurement, resulting in 153 patients with peak values and 300 patients with trough values. Lower peak values were associated with thromboembolism for patients' minimum (p = 0.01), median (p = 0.005) and maximum (p = 0.001) values. No association was seen between peak values and death or bleeding. Higher trough values were associated with death for median (p = 0.03) and maximum (p = 0.002) values and with both bleeding (p = 0.01) and major bleeding (p = 0.02) for maximum values, but there were no associations with thromboembolism.CONCLUSIONS: Measuring anti-Factor Xa activity may be relevant for administrating low-molecular-weight heparin to patients with critical COVID-19. Lower peak values were associated with an increased risk of thromboembolism, and higher trough values were associated with an increased risk of death and bleeding. Prospective studies are needed to confirm the results.TRIAL REGISTRATION: The study was retrospectively registered at Clinicaltrials.gov, NCT05256524, February 24, 2022.
36.	Kander, Astrid, et al. (författare) National greenhouse-gas accounting for effective climate policy on international trade 2015 Ingår i: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-6798 .- 1758-678X. ; 5:5, s. 431-435 Tidskriftsartikel (refereegranskat)abstract National greenhouse-gas accounting should reflect how countries’ policies and behaviours affect global emissions. Actions that contribute to reduced global emissions should be credited, and actions that increase them should be penalized. This is essential if accounting is to serve as accurate guidance for climate policy. Yet this principle is not satisfied by the two most common accounting methods. Production-based accounting used under the Kyoto Protocol does not account for carbon leakage — the phenomenon of countries reducing their domestic emissions by shifting carbon-intensive production abroad1. Consumption-based accounting2,3 (also called carbon footprinting) does not credit countries for cleaning up their export industries, and it also punishes some types of trade that could contribute to more carbon efficient production worldwide. We propose an improvement to consumption-based carbon accounting that takes technology differences in export sectors into account and thereby tends to more correctly reflect how national policy changes affect total global emissions. We also present empirical results showing how this new measure redraws the global emissions map.
37.	Kander, Astrid, et al. (författare) Reply to 'Consistency of technology-adjusted consumption-based accounting' 2016 Ingår i: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-678X .- 1758-6798. ; 6:8, s. 730-730 Tidskriftsartikel (refereegranskat)
38.	Kander, Thomas, et al. (författare) ABO and RhD blood group are not associated with mortality and morbidity in critically ill patients; a multicentre observational study of 29 512 patients 2022 Ingår i: BMC Anesthesiol. - : Springer Science and Business Media LLC. - 1471-2253. ; 22:1, s. 91- Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The ABO and RhD blood group represent antigens on the surface of erythrocytes. The ABO blood group antigens are also present on multiple other cells. Interestingly, previous studies have demonstrated associations between the blood group and many types of disease. The present study aimed to identifying associations between the ABO blood group, the RhD blood group, and morbidity and mortality in a mixed cohort and in six pre-defined subgroups of critically ill patients. METHODS: Adult patients admitted to any of the five intensive care units (ICUs) in the Scania Region, Sweden, between February 2007 and April 2021 were eligible for inclusion. The outcomes were mortality analysed at 28- and 90-days as well as at the end of observation and morbidity measured using days alive and free of (DAF) invasive ventilation (DAF ventilation) and DAF circulatory support, including vasopressors or inotropes (DAF circulation), maximum Sequential Organ Failure Assessment score (SOFAmax) the first 28 days after admission and length of stay. All outcomes were analysed in separate multivariable regression models adjusted for age and sex. In addition, in a sensitivity analysis, five subgroups of patients with the main diagnoses sepsis, septic shock, acute respiratory distress syndrome, cardiac arrest and trauma were analysed using the same separate multivariable regression models. RESULTS: In total, 29,512 unique patients were included in the analyses. There were no significant differences for any of the outcomes between non-O blood groups and blood group O, or between RhD blood groups. In the sensitivity analysis of subgroups, there were no differences in mortality between non-O blood groups and blood group O or between the RhD blood groups. AB was the most common blood group in the COVID-19 cohort. CONCLUSIONS: The ABO and RhD blood group do not influence mortality or morbidity in a general critically ill patient population.
39.	Kander, Thomas (författare) Aspects of bleeding complications and hemostasis at central line insertion and mild induced hypothermia 2014 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Bleeding complications range from 0.5 to 1.6% in connection with central venous catheter insertions but are more frequent in patients with bone marrow failure and severe thrombocytopenia. Although supportive evidence is scarce, prophylactic platelet transfusion is sometimes performed in these patients before catheter insertion. Furthermore, the ideal threshold platelet count and timing of transfusion remain controversial among clinical studies. Hypothermia is generally considered to reduce coagulation and platelet function. However, studies performed in animals, healthy volunteers, and patients have shown conflicting results. Paper I, a retrospective study in non-intensive care unit patients, showed that serious bleeding complications in association with central line insertions were uncommon and that insertion of a large bore catheter may be an independent risk factor for mild bleeding complications in this population. Paper II, a prospective observational study, evaluated the efficacy of prophylactic platelet transfusions in thrombocytopenic patients with bone marrow failure. Transfusion improved hemostatic parameters in ROTEM and Multiplate tests by increasing the number of platelets and not by enhancing platelet function. Improved clotting parameters persisted between 1 and 4 hours after transfusion. Paper III demonstrated increased platelet aggregation and strengthened clot formation over time in out-of-hospital cardiac arrest patients treated with hypothermia. In patients with dual platelet inhibition, including ticagrelor and aspirin, this effect was offset by powerful P2Y12 blockade, confirmed by analysis of vasodilator-stimulated phosphoprotein. The effect of ticagrelor was delayed in survivors of cardiac arrest, probably due to slow gastric emptying. Paper IV demonstrated prolonged clot initiation and decreased clot propagation in ROTEM testing (EXTEM, FIBTEM, and APTEM assays) in whole blood from out-of-hospital cardiac arrest patients treated with mild induced hypothermia. Paper V investigated whole blood from acute coronary syndrome patients treated with ticagrelor and aspirin. In vitro applied hypothermia to 33 degrees C markedly increased platelet activity measured by flow cytometry, whereas a viscoelastic coagulation test (Sonoclot) revealed a hypocoagulative response.
40.	Kander, Thomas (författare) Aspects of bleeding complications and hemostasis at central line insertion and mild induced hypothermia. 2014 Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. Tidskriftsartikel (refereegranskat)
41.	Kander, Thomas, et al. (författare) Assessment of Haemostasis in Disseminated Intravascular Coagulation by Use of Point-of-Care Assays and Routine Coagulation Tests, in Critically Ill Patients; A Prospective Observational Study. 2016 Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:3 Tidskriftsartikel (refereegranskat)abstract Disseminated intravascular coagulopathy (DIC) relates to the consumption of coagulation factors and platelets with bleeding and micro thrombosis events.
42.	Kander, Thomas, et al. (författare) Bleeding complications after cardiac arrest and targeted temperature management, a post hoc study of the targeted temperature management trial 2019 Ingår i: Therapeutic hypothermia and temperature management. - : Mary Ann Liebert Inc. - 2153-7933 .- 2153-7658. ; 9:3, s. 177-183 Tidskriftsartikel (refereegranskat)abstract Target Temperature Management (TTM) is standard care following out of hospital cardiac arrest (OHCA). The aim of the study was to evaluate if treatment temperature (33°C or 36°C) or other predefined variables were associated with the occurrence of bleeding in the TTM study. This study is a predefined, post hoc analysis of the TTM trial, a multinational randomized controlled trial comparing treatment at 33°C and 36°C for 24 hours after OHCA with return of spontaneous circulation. Bleeding events from several locations were registered daily. The main outcome measure was occurrence of any bleeding during the first 3 days of intensive care. Risk factors for bleeding, including temperature allocation, were evaluated. Complete data were available for 722/939 patients. Temperature allocation was not associated with bleeding either in the univariable (p = 0.95) or in the primary multivariable analysis (odds ratio [OR] 0.95; 95% confidence interval [CI] 0.64–1.41, p = 0.80). A multiple imputation model, including all patients, was used as a sensitivity analysis, rendering similar results (OR 0.98; 95% CI 0.69–1.38, p = 0.92). Factors associated with bleeding were increasing age, female sex, and angiography with percutaneous coronary intervention (PCI) within 36 hours of cardiac arrest (CA) in both the primary and the sensitivity analysis. TTM at 33°C, when compared to TTM at 36°C, was not associated with an increased incidence of bleeding during the first 3 days of intensive care after CA. Increasing age, female gender, and PCI were independently associated with any bleeding the first 3 days after CA.
43.	KANDER, THOMAS, et al. (författare) Bleeding complications after central line insertions and the relevance of pre-procedure coagulation tests and blood component therapy 2013 Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535. ; 17:Suppl 2 Konferensbidrag (refereegranskat)
44.	Kander, Thomas, et al. (författare) Bleeding complications after central line insertions: relevance of pre-procedure coagulation tests and institutional transfusion policy. 2013 Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 57:5, s. 573-579 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The aim of this study was to map pre-procedural variables for insertion of a central venous catheter, prophylactic blood component use and to investigate whether any independent variable could be identified as an independent risk factor for associated bleeding complications in patients outside the intensive care unit. METHODS: In this retrospective study, we investigated 1737 consecutive insertions of central venous catheters in 1444 patients in a large university hospital during 2009-2010. Pre-procedural coagulation status, blood component use, type of catheter, insertion site and complications during insertion were recorded and compared with bleeding complications documented on electronic charts. RESULTS: No serious bleeding complications were recorded in connection with the insertion of central venous catheters. Sixteen of 1769 (0.9%) insertions caused grade 2 bleeding, defined as bleeding requiring prolonged compression at the insertion site. Insertion of a large bore central dialysis catheter was found to be an independent risk factor for bleeding complications. Neither conventional coagulation tests nor accidental arterial puncture or the number of needle passes could predict bleeding complications in this study. CONCLUSION: This retrospective study, in non-ICU patients, shows that serious bleeding complications in association with central line insertions are uncommon and that insertion of a large bore catheter is likely to be an independent risk factor for mild-bleeding complications in this population.
45.	Kander, Thomas (författare) Coagulation disorder in COVID-19 2020 Ingår i: The Lancet Haematology. - 2352-3026. ; 7:9, s. 630-632 Tidskriftsartikel (refereegranskat)
46.	KANDER, THOMAS, et al. (författare) Dose-response effects of omega-3 on platelet aggregation: an observational study 2018 Ingår i: Journal of International Medical Research. - : SAGE Publications. - 1473-2300 .- 0300-0605. ; 46:12, s. 5074-5082 Tidskriftsartikel (refereegranskat)abstract ObjectiveThis study aimed to evaluate the dose-response effects of supplemental omega-3 fatty acids on platelet function in healthy volunteers.MethodsTwelve healthy volunteers ingested a normal supplemental dose of 1260 mg omega-3 fatty acids daily for 5 days, followed by a high dose of 2520 mg daily for another 5 days. Multiple electrode aggregometry (MEA) with four different agonists was used to measure platelet aggregation before and after the normal- and high-dose regimes. In vitro spiking using physiological doses of omega-3 fatty acids was also performed to determine whether MEA is capable of detecting a platelet-inhibiting effect due to omega-3 fatty acids.ResultsThere were no differences in platelet aggregation measured by the MEA assay in healthy volunteers after intake of either the normal or high dose of omega-3 fatty acids. In the in vitro experiment, a platelet-inhibiting effect of omega-3 fatty acids was shown by an arachidonic acid agonist in MEA .ConclusionsSupplemental omega-3 fatty acids do not evoke their positive health effects through inhibition of platelet aggregation measurable with MEA.
47.	Kander, Thomas, et al. (författare) Effect and duration of prophylactic platelet transfusions before insertion of central venous catheter in patients with bone marrow failure evaluated with point of care methods and flow cytometry. 2013 Konferensbidrag (refereegranskat)
48.	KANDER, THOMAS, et al. (författare) Effect of hypothermia on haemostasis and bleeding risk : a narrative review 2019 Ingår i: Journal of International Medical Research. - : SAGE Publications. - 0300-0605 .- 1473-2300. ; 47:8, s. 3559-3568 Forskningsöversikt (refereegranskat)abstract It must be remembered that clinically important haemostasis occurs in vivo and not in a tube, and that variables such as the number of bleeding events and bleeding volume are more robust measures of bleeding risk than the results of analyses. In this narrative review, we highlight trauma, surgery, and mild induced hypothermia as three clinically important situations in which the effects of hypothermia on haemostasis are important. In observational studies of trauma, hypothermia (body temperature <35°C) has demonstrated an association with mortality and morbidity, perhaps owing to its effect on haemostatic functions. Randomised trials have shown that hypothermia causes increased bleeding during surgery. Although causality between hypothermia and bleeding risk has not been well established, there is a clear association between hypothermia and negative outcomes in connection with trauma, surgery, and accidental hypothermia; thus, it is crucial to rewarm patients in these clinical situations without delay. Mild induced hypothermia to ≥33°C for 24 hours does not seem to be associated with either decreased total haemostasis or increased bleeding risk.
49.	Kander, Thomas, et al. (författare) Effects of red blood cell transfusions given to non-septic critically ill patients : a propensity score matched study 2021 Ingår i: Anaesthesiology Intensive Therapy. - : Termedia Sp. z.o.o.. - 1642-5758. ; 53:5, s. 390-397 Tidskriftsartikel (refereegranskat)abstract Background: Previous studies have demonstrated that low-grade red blood cell transfusions (RBC) given to septic patients are harmful. The objectives of the present study were to compare mortality and morbidity in non-septic critically ill patients who were given low-grade RBC transfusions at haemoglobin level > 70 g L–1 with patients without RBC-transfusions any of the first 5 days in intensive care. Methods: Adult patients admitted to a general intensive care unit between 2007 and 2018 at a university hospital were eligible for inclusion. Patients who received > 2 units RBC transfusion per day during the first 5 days after admisasion, with pre-transfusion haemoglobin level < 70 g L–1 or with severe sepsis or septic shock, were excluded. Results: In total, 9491 admissions were recorded during the study period. Propensity score matching resulted in 2 well matched groups with 674 unique patients in each. Median pre-transfusion haemoglobin was 98 g L–1 (interquartile range 91–107 g L–1). Mortality was higher in the RBC group with an absolute risk increase for death at 180 days of 5.9% (95% CI: 3.6–8.3; P< 0.001). Low-grade RBC-transfusion was also associated with renal, circulatory, and respiratory failure as well as a higher SOFA-max score. Sensitivity analyses suggested that disease trajectories during the exposure time did not significantly differ between the groups. Conclusions: Low-grade RBC-transfusions given to non-septic critically ill patients without significant anaemia were associated with increased mortality, increased kidney, circulatory, and respiratory failure, as well as higher SOFA-max score.
50.	Kander, Thomas, et al. (författare) Platelet aggregation and clot formation in comatose survivors of cardiac arrest treated with induced hypothermia and dual platelet inhibition with aspirin and ticagrelor; a prospective observational study 2014 Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535. ; 18:5 Tidskriftsartikel (refereegranskat)abstract Introduction: We conducted a prospective observational study in cardiac arrest survivors treated with mild induced hypothermia, evaluating different platelet function tests at hypo-and normothermia. We also investigated the relation between gastric emptying and vasodilator stimulated phosphoprotein (VASP). Methods: Comatose survivors of out of hospital cardiac arrest were included and divided into two groups, depending on whether dual platelet inhibition with peroral ticagrelor and aspirin was given or not. The first blood samples (T1) were collected 12-24 hours after reaching target temperature (33 degrees C) and were compared to blood samples collected 12-28 hours after reaching normothermia (37 degrees C) (T2) within each group. All samples were analysed by Sonoclot viscoelasticity, flow cytometry based VASP and with multiple electrode aggregometry, Multiplate (R); adenosine diphosphate (ADP), collagen (COL), thrombin receptor agonist peptide (TRAP) and arachidonic acid (ASPI). Sonoclot and Multiplate (R) instruments were set on in vivo temperatures. Gastric secretion from the nasogastric tube was measured to assess absorption of per orally administered antiplatelet drugs. Differences between T1 and T2 within each group were calculated using Wilcoxon matched pairs signed test. Significance levels were set at P < 0.01. Results: In total, 23 patients were included. In patients with dual platelet inhibition (n = 14) Multiplate (R)-analyses showed no changes in ADP stimulated platelets. COL, TRAP and ASPI aggregations were higher at T2 compared to T1. Sonoclot-analyses showed that activated clotting time (ACT) was unchanged but both clot rate (CR) and platelet function (PF) were higher at T2 compared to T1. VASP decreased from 53 +/- 28(T1) to 24 +/- 22(T2), (P < 0.001). The average volume of gastric secretion aspirated before T1 correlated well with VASP (T1), r = 0.81 (P < 0.001). In patients with no platelet inhibition, (n = 9) similar changes between T1 and T2 were seen as in patients with dual platelet inhibition while VASP was unchanged. Conclusions: We have demonstrated increased platelet aggregation and strengthened clot formation over time in out of hospital cardiac arrest patients treated with hypothermia. In patients on oral dual platelet inhibition, the effect of ticagrelor was delayed, probably due to slow gastric emptying.

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