| 1. |
- Jungner, Mårten, et al.
(författare)
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Blood-brain barrier permeability following traumatic brain injury.
- 2016
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Ingår i: Minerva Anestesiologica. - 1827-1596. ; 82:5, s. 525-533
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Brain edema and intracranial hypertension is deleterious after traumatic brain injury (TBI), but the underlying pathophysiology is complex and poorly understood. One major subject of controversy is the time course and extent of blood-brain barrier (BBB) dysfunction following trauma, and previous studies in humans have only provided semi-quantitative data. The objective of the present study was therefore to quantify changes in BBB-permeability in the early course of TBI, when brain edema is still evolving. METHODS: Sixteen non-consecutive brain trauma patients and two controls were included. Following i.v. injection of iohexol and CT perfusion scans, patients were scanned eight times from 4 to 25 minutes. Blood to brain transfer constant (Ki) for iohexol (molecular weight 821 D), reflecting permeability and available area for diffusion, was calculated offline by Patlak plot analysis of the enhancement curves of intracerebral large venous vessels and pericontusional brain parenchyma. RESULTS : In non-ischemic tissue surrounding contusions and hematomas Ki was increased 2-to 10-fold compared to normal tissue, reaching maximal values of 0.5 mL/min/100 g. In non-injured areas and in controls Ki was about 0.06 mL/min/100 g. The increase was more pronounced in the most severely injured patients, and was detectable within 24 hours after trauma and up to five days after. CONCLUSIONS: Our results suggest that traumatic brain injury is associated with early focal increases in small molecular BBB-permeability. The results indicate that in the injured brain, capillary hydrostatic and oncotic pressures may influence edema formation.
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| 2. |
- Mohanty, Tirthankar, et al.
(författare)
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Neutrophil extracellular traps in the central nervous system hinder bacterial clearance during pneumococcal meningitis
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1667-1667
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Tidskriftsartikel (refereegranskat)abstract
- Neutrophils are crucial mediators of host defense that are recruited to the central nervous system (CNS) in large numbers during acute bacterial meningitis caused by Streptococcus pneumoniae. Neutrophils release neutrophil extracellular traps (NETs) during infections to trap and kill bacteria. Intact NETs are fibrous structures composed of decondensed DNA and neutrophil-derived antimicrobial proteins. Here we show NETs in the cerebrospinal fluid (CSF) of patients with pneumococcal meningitis, and their absence in other forms of meningitis with neutrophil influx into the CSF caused by viruses, Borrelia and subarachnoid hemorrhage. In a rat model of meningitis, a clinical strain of pneumococci induced NET formation in the CSF. Disrupting NETs using DNase I significantly reduces bacterial load, demonstrating that NETs contribute to pneumococcal meningitis pathogenesis in vivo. We conclude that NETs in the CNS reduce bacterial clearance and degrading NETs using DNase I may have significant therapeutic implications.
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| 3. |
- Adrian, Maria, et al.
(författare)
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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
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 9:10, s. 029301-029301
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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.
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| 4. |
- Bentzer, Peter, et al.
(författare)
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Advances in Sepsis Research.
- 2015
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Ingår i: Clinics in Chest Medicine. - : Elsevier BV. - 1557-8216 .- 0272-5231. ; 36:3, s. 521-530
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Forskningsöversikt (refereegranskat)abstract
- Recent research has identified promising targets for therapeutic interventions aimed at modulating the inflammatory response in sepsis. Herein, the authors describe mechanisms involved in the clearance of pathogen toxin from the circulation and potential interventions aimed at enhancing clearance mechanisms. The authors also describe advances in the understanding of the innate immune response as potential therapeutic targets. Finally, novel potential treatment strategies aimed at decreasing vascular leak are discussed.
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| 5. |
- Bentzer, Peter, et al.
(författare)
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Effect of dextran-70 on outcome in severe sepsis; A propensity-score matching study
- 2017
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Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - : Springer Science and Business Media LLC. - 1757-7241. ; 25:1
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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.
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| 6. |
- Bentzer, Peter, et al.
(författare)
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Heparin-binding protein is important for vascular leak in sepsis
- 2016
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Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Elevated plasma levels of heparin-binding protein (HBP) are associated with risk of organ dysfunction and mortality in sepsis, but little is known about causality and mechanisms of action of HBP. The objective of the present study was to test the hypothesis that HBP is a key mediator of the increased endothelial permeability observed in sepsis and to test potential treatments that inhibit HBP-induced increases in permeability.METHODS: Association between HBP at admission with clinical signs of increased permeability was investigated in 341 patients with septic shock. Mechanisms of action and potential treatment strategies were investigated in cultured human endothelial cells and in mice.RESULTS: Following adjustment for comorbidities and Acute Physiology and Chronic Health Evaluation (APACHE) II, plasma HBP concentrations were weakly associated with fluid overload during the first 4 days of septic shock and the degree of hypoxemia (PaO2/FiO2) as measures of increased systemic and lung permeability, respectively. In mice, intravenous injection of recombinant human HBP induced a lung injury similar to that observed after lipopolysaccharide injection. HBP increased permeability of vascular endothelial cell monolayers in vitro, and enzymatic removal of luminal cell surface glycosaminoglycans (GAGs) using heparinase III and chondroitinase ABC abolished this effect. Similarly, unfractionated heparins and low molecular weight heparins counteracted permeability increased by HBP in vitro. Intracellular, selective inhibition of protein kinase C (PKC) and Rho-kinase pathways reversed HBP-mediated permeability effects.CONCLUSIONS: HBP is a potential mediator of sepsis-induced acute lung injury through enhanced endothelial permeability. HBP increases permeability through an interaction with luminal GAGs and activation of the PKC and Rho-kinase pathways. Heparins are potential inhibitors of HBP-induced increases in permeability.
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| 7. |
- Bentzer, Peter, et al.
(författare)
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Isolated Brain Trauma in Cats Triggers Rapid Onset of Hypovolemia
- 2017
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Ingår i: Neurocritical Care. - : Springer Science and Business Media LLC. - 1541-6933 .- 1556-0961. ; 26:3, s. 450-456
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hemodynamic instability responsive to fluid resuscitation is common after a traumatic brain injury (TBI), also in the absence of systemic hemorrhage. The present study tests if an isolated severe TBI induces a decrease in plasma volume (PV). Methods: The study was performed in three groups of anesthetized and tracheostomized male cats (n = 21). In one group (n = 8), the cats were prepared with a cranial borehole (10 mm i.d) used to expose the brain to a fluid percussion brain injury (FPI) (1.90–2.20 bar), and two smaller cranial boreholes (4 mm i.d) for insertion of an intracranial pressure (ICP) and a microdialysis catheter. To differentiate the effect of FPI from that of the surgical preparation, a sham group was exposed to the same surgical preparation but no FPI trauma (n = 8). A control group had no brain trauma and no surgical preparation (n = 5). PV was determined by a 125I-albumin dilution technique. PV, electrolytes, pH, BE (base excess), hematocrit (Hct), PaO2, and PaCO2 were measured at baseline and after 3 h. Mean arterial pressure (MAP) was measured continuously. ICP was measured in the FPI and the sham group. Results: In the FPI group, PV decreased by 11.2 mL/kg from 31.7 mL/kg (p < 0.01) with a simultaneous increase in Hct and decrease in pH. In the sham group, PV decreased by 5.7 mL/kg from 32.7 mL/kg (p < 0.01). The control group showed no PV reduction. Conclusions: The results support that an isolated severe head trauma triggers a significant and rapid reduction in PV, most likely due to vascular leak.
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| 8. |
- Bentzer, Peter, et al.
(författare)
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Plasma cytokine levels predict response to corticosteroids in septic shock
- 2016
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 42:12, s. 1970-1979
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate if plasma cytokine concentrations predict a beneficial response to corticosteroid treatment in septic shock patients. Methods: A cohort of septic shock patients in whom a panel of 39 cytokines had been measured at baseline (n = 363) was included. Patients who received corticosteroids were propensity score matched to non-corticosteroid-treated patients. An optimal threshold to identify responders to corticosteroid treatment for each cytokine was defined as the concentration above which the odds ratio for 28-day survival between corticosteroid- and non-corticosteroid-treated patients was highest. Results: Propensity score matching partitioned 165 patients into 61 sets; each set contained matched corticosteroid- and non-corticosteroid-treated patients. For 13 plasma cytokines threshold concentrations were found where the odds ratio for survival between corticosteroid- and non-corticosteroid-treated patients was significant (P <0.05). CD40 ligand was associated with the highest odds ratio and identified 21 % of the patients in the propensity score matched cohort as responders to corticosteroid treatment. Combinations of triplets of cytokines with a significant odds ratio, using the thresholds identified above, were tested to find a higher proportion of responders. IL3, IL6, and CCL4 identified 50 % of the patients in the propensity score matched cohort as responders to corticosteroid treatment. The odds ratio for 28-day survival was 19 (95 % CI 3.5–140, P = 0.02) with a concentration above threshold for a least one of these cytokines. Conclusion: Plasma concentration of selected cytokines is a potential predictive biomarker to identify septic shock patients that may benefit from treatment with corticosteroids.
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| 9. |
- Bentzer, Peter, et al.
(författare)
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Will this hemodynamically unstable patient respond to a bolus of intravenous fluids?
- 2016
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Ingår i: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484. ; 316:12, s. 1298-1309
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Fluid overload occurring as a consequence of overly aggressive fluid resuscitation may adversely affect outcome in hemodynamically unstable critically ill patients. Therefore, following the initial fluid resuscitation, it is important to identify which patients will benefit from further fluid administration. OBJECTIVE To identify predictors of fluid responsiveness in hemodynamically unstable patients with signs of inadequate organ perfusion. DATA SOURCES AND STUDY SELECTION Search of MEDLINE and EMBASE (1966 to June 2016) and reference lists from retrieved articles, previous reviews, and physical examination textbooks for studies that evaluated the diagnostic accuracy of tests to predict fluid responsiveness in hemodynamically unstable adult patients who were defined as having refractory hypotension, signs of organ hypoperfusion, or both. Fluid responsiveness was defined as an increase in cardiac output following intravenous fluid administration. DATA EXTRACTION Two authors independently abstracted data (sensitivity, specificity, and likelihood ratios [LRs]) and assessed methodological quality. A bivariate mixed-effects binary regression model was used to pool the sensitivities, specificities, and LRs across studies. RESULTS A total of 50 studies (N = 2260 patients) were analyzed. In all studies, indices were measured before assessment of fluid responsiveness. The mean prevalence of fluid responsiveness was 50% (95%CI, 42%-56%). Findings on physical examination were not predictive of fluid responsiveness with LRs and 95%CIs for each finding crossing 1.0. A low central venous pressure (CVP) (mean threshold 8mmHg) was associated with fluid responsiveness (positive LR, 2.6 [95%CI, 1.4-4.6]; pooled specificity, 76%), but a CVP greater than the threshold made fluid responsiveness less likely (negative LR, 0.50 [95%CI, 0.39-0.65]; pooled sensitivity, 62%). Respiratory variation in vena cava diameter measured by ultrasound (distensibility index >15%) predicted fluid responsiveness in a subgroup of patients without spontaneous respiratory efforts (positive LR, 5.3 [95%CI, 1.1-27]; pooled specificity, 85%). Patients with less vena cava distensibility were not as likely to be fluid responsive (negative LR, 0.27 [95%CI, 0.08-0.87]; pooled sensitivity, 77%). Augmentation of cardiac output or related parameters following passive leg raising predicted fluid responsiveness (positive LR, 11 [95%CI, 7.6-17]; pooled specificity, 92%). Conversely, the lack of an increase in cardiac output with passive leg raising identified patients unlikely to be fluid responsive (negative LR, 0.13 [95%CI, 0.07-0.22]; pooled sensitivity, 88%). CONCLUSIONS AND RELEVANCE Passive leg raising followed by measurement of cardiac output or related parameters may be the most useful test for predicting fluid responsiveness in hemodynamically unstable adults. The usefulness of respiratory variation in the vena cava requires confirmatory studies.
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| 10. |
- Björkander, Malin, et al.
(författare)
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Mechanical complications of central venous catheter insertions : A retrospective multicenter study of incidence and risks
- 2019
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 63:1, s. 61-68
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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.
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