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1.
  • Bark, Björn, et al. (författare)
  • The effect of vitamin C on plasma volume in the early stage of sepsis in the rat.
  • 2014
  • Ingår i: Intensive Care Medicine Experimental. - 2197-425X. ; 2:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous experimental studies have shown that vitamin C has several beneficial effects in sepsis and burns, such as decreased tissue oedema, improved endothelial barrier function and decreased transcapillary leakage of plasma markers. It has still not been investigated, though, if vitamin C has any impact specifically on plasma volume. The present study aims at testing the hypothesis that vitamin C decreases plasma volume loss in sepsis.
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3.
  • Bandert, Anna, et al. (författare)
  • Different distances between central venous catheter tips can affect antibiotic clearance during continuous renal replacement therapy
  • 2024
  • Ingår i: Intensive Care Medicine Experimental. - : Springer Nature. - 2197-425X. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The aim of this experimental study was to elucidate whether different distances between central venous catheter tips can affect drug clearance during continuous renal replacement therapy (CRRT). Central venous catheters (CVCs) are widely used in intensive care patients for drug infusion. If a patient receives CRRT, a second central dialysis catheter (CDC) is required. Where to insert CVCs is directed by guidelines, but recommendations regarding how to place multiple catheters are scarce. There are indications that a drug infused in a CVC with the tip close to the tip of the CDC, could be directly aspirated into the dialysis machine, with a risk of increased clearance. However, studies on whether clearance is affected by different CVC and CDC tip positions, when the two catheters are in the same vessel, are few.METHODS: In this model with 18 piglets, gentamicin (GM) and vancomycin (VM) were infused through a CVC during CRRT. The CVC tip was placed in different positions in relation to the CDC tip from caudal, i.e., proximal to the heart, to cranial, i.e., distal to the heart. Serum and dialysate concentrations were sampled after approximately 30 min of CRRT at four different positions: when the CVC tip was 2 cm caudally (+ 2), at the same level (0), and at 2 (- 2) and 4 (- 4) cm cranially of the tip of the CDC. Clearance was calculated. A mixed linear model was performed, and level of significance was set to p < 0.05.RESULTS: Clearance of GM had median values at + 2 cm, 0 cm, - 2 cm and - 4 cm of 17.3 (5.2), 18.6 (7.4), 20.0 (16.2) and 26.2 (12.2) ml/min, respectively (p = 0.04). Clearance of VM had median values at + 2 cm, 0 cm, - 2 cm and - 4 cm of 16.2 (4.5), 14.7 (4.9), 19.0 (10.2) and 21.2 (11.4) ml/min, respectively (p = 0.02).CONCLUSIONS: The distance between CVC and CDC tips can affect drug clearance during CRRT. A cranial versus a caudal tip position of the CVC in relation to the tip of the CDC led to the highest clearance.
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4.
  • Bandert, Anna, et al. (författare)
  • In an endotoxaemic model, antibiotic clearance can be affected by different central venous catheter positions, during renal replacement therapy
  • 2023
  • Ingår i: Intensive Care Medicine Experimental. - : Springer Nature. - 2197-425X. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: In intensive care, different central venous catheters (CVC) are often used for infusion of drugs. If a patient is treated with continuous renal replacement therapy (CRRT) a second catheter, a central venous dialysis catheter (CVDC), is needed. Placing the catheters close together might pose a risk that a drug infused in a CVC could be directly aspirated into a CRRT machine and cleared from the blood without giving the effect intended. The purpose of this study was to elucidate if drug clearance is affected by different catheter placement, during CRRT. In this endotoxaemic animal model, an infusion of antibiotics was administered in a CVC placed in the external jugular vein (EJV). Antibiotic clearance was compared, whether CRRT was through a CVDC placed in the same EJV, or in a femoral vein (FV). To reach a target mean arterial pressure (MAP), noradrenaline was infused through the CVC and the dose was compared between the CDVDs.RESULTS: The main finding in this study was that clearance of antibiotics was higher when both catheter tips were in the EJV, close together, compared to in different vessels, during CRRT. The clearance of gentamicin was 21.0 ± 7.3 vs 15.5 ± 4.2 mL/min (p 0.006) and vancomycin 19.3 ± 4.9 vs 15.8 ± 7.1 mL/min (p 0.021). The noradrenaline dose to maintain a target MAP also showed greater variance with both catheters in the EJV, compared to when catheters were placed in different vessels.CONCLUSION: The results in this study indicate that close placement of central venous catheter tips could lead to unreliable drug concentration, due to direct aspiration, during CRRT.
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5.
  • Barrueta Tenhunen, Annelie, et al. (författare)
  • Fluid restrictive resuscitation with high molecular weight hyaluronan infusion in early peritonitis sepsis
  • 2023
  • Ingår i: Intensive Care Medicine Experimental. - : Springer Nature. - 2197-425X. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Sepsis is a condition with high morbidity and mortality. Prompt recognition and initiation of treatment is essential. Despite forming an integral part of sepsis management, fluid resuscitation may also lead to volume overload, which in turn is associated with increased mortality. The optimal fluid strategy in sepsis resuscitation is yet to be defined. Hyaluronan, an endogenous glycosaminoglycan with high affinity to water is an important constituent of the endothelial glycocalyx. We hypothesized that exogenously administered hyaluronan would counteract intravascular volume depletion and contribute to endothelial glycocalyx integrity in a fluid restrictive model of peritonitis. In a prospective, blinded model of porcine peritonitis sepsis, we randomized animals to intervention with hyaluronan (n = 8) or 0.9% saline (n = 8). The animals received an infusion of 0.1% hyaluronan 6 ml/kg/h, or the same volume of saline, during the first 2 h of peritonitis. Stroke volume variation and hemoconcentration were comparable in the two groups throughout the experiment. Cardiac output was higher in the intervention group during the infusion of hyaluronan (3.2 ± 0.5 l/min in intervention group vs 2.7 ± 0.2 l/min in the control group) (p = 0.039). The increase in lactate was more pronounced in the intervention group (3.2 ± 1.0 mmol/l in the intervention group and 1.7 ± 0.7 mmol/l in the control group) at the end of the experiment (p < 0.001). Concentrations of surrogate markers of glycocalyx damage; syndecan 1 (0.6 ± 0.2 ng/ml vs 0.5 ± 0.2 ng/ml, p = 0.292), heparan sulphate (1.23 ± 0.2 vs 1.4 ± 0.3 ng/ml, p = 0.211) and vascular adhesion protein 1 (7.0 ± 4.1 vs 8.2 ± 2.3 ng/ml, p = 0.492) were comparable in the two groups at the end of the experiment. In conclusion, hyaluronan did not counteract intravascular volume depletion in early peritonitis sepsis. However, this finding is hampered by the short observation period and a beneficial effect of HMW-HA in peritonitis sepsis cannot be discarded based on the results of the present study.
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6.
  • Bentzer, Peter, et al. (författare)
  • Heparin-binding protein is important for vascular leak in sepsis
  • 2016
  • Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 4:1
  • 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.
  • Bergquist, Maria, et al. (författare)
  • Impairment of neutrophilic glucocorticoid receptor function in patients treated with steroids for septic shock
  • 2015
  • Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 3:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Glucocorticoid (GC) treatment has variable effect in sepsis. This may be explained by decreased expression or function of the glucocorticoid receptor (GR). The aim of this study was to determine GR expression and binding capacity in patients during and after sepsis.METHODS: In this prospective, non-interventional clinical study, peripheral blood and clinical data were collected from 20 adult patients at five timepoints during sepsis and 5-13 months after recovery. GR expression and binding capacity were assessed by flow cytometry.RESULTS: GR expression was higher in T lymphocytes from patients with septic shock compared to healthy subjects (p = 0.01). While there was no difference in GR expression between GC-treated and non-treated patients, GR binding capacity was lower in GC-treated patients at admission compared to healthy subjects (p ≤ 0.03). After the acute inflammation inflammatory phase, GR binding capacity was still lower in neutrophils of GC-treated patients, compared to healthy subjects (p = 0.01). On admission, GR binding capacity in T lymphocytes and neutrophils was inversely correlated with noradrenaline dose and lactate (p ≤ 0.03).CONCLUSIONS: Our data suggest that GR expression is increased in T lymphocytes during septic shock regardless of GC treatment, while GR binding capacity is decreased in neutrophils in GC-treated patients. As neutrophils are the predominant circulating leucocyte in septic shock, their decreased GR binding capacity may impede the response to exogenous or endogenous glucocorticoids.
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8.
  • Borges, Joao Batista, et al. (författare)
  • Real-time effects of PEEP and tidal volume on regional ventilation and perfusion in experimental lung injury
  • 2020
  • Ingår i: Intensive Care Medicine Experimental. - : SPRINGEROPEN. - 2197-425X. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Real-time bedside information on regional ventilation and perfusion during mechanical ventilation (MV) may help to elucidate the physiological and pathophysiological effects of MV settings in healthy and injured lungs. We aimed to study the effects of positive end-expiratory pressure (PEEP) and tidal volume (V-T) on the distributions of regional ventilation and perfusion by electrical impedance tomography (EIT) in healthy and injured lungs. Methods One-hit acute lung injury model was established in 6 piglets by repeated lung lavages (injured group). Four ventilated piglets served as the control group. A randomized sequence of any possible combination of three V-T (7, 10, and 15 ml/kg) and four levels of PEEP (5, 8, 10, and 12 cmH(2)O) was performed in all animals. Ventilation and perfusion distributions were computed by EIT within three regions-of-interest (ROIs): nondependent, middle, dependent. A mixed design with one between-subjects factor (group: intervention or control), and two within-subjects factors (PEEP and V-T) was used, with a three-way mixed analysis of variance (ANOVA). Results Two-way interactions between PEEP and group, and V-T and group, were observed for the dependent ROI (p = 0.035 and 0.012, respectively), indicating that the increase in the dependent ROI ventilation was greater at higher PEEP and V-T in the injured group than in the control group. A two-way interaction between PEEP and V-T was observed for perfusion distribution in each ROI: nondependent (p = 0.030), middle (p = 0.006), and dependent (p = 0.001); no interaction was observed between injured and control groups. Conclusions Large PEEP and V-T levels were associated with greater pulmonary ventilation of the dependent lung region in experimental lung injury, whereas they affected pulmonary perfusion of all lung regions both in the control and in the experimental lung injury groups.
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9.
  • Broberg, Ellen, et al. (författare)
  • A new way of monitoring mechanical ventilation by measurement of particle flow from the airways using Pexa method in vivo and during ex vivo lung perfusion in DCD lung transplantation
  • 2018
  • Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Different mechanical ventilation settings are known to affect lung preservation for lung transplantation. Measurement of particle flow in exhaled air may allow online assessment of the impact of ventilation before changes in the tissue can be observed. We hypothesized that by analyzing the particle flow, we could understand the impact of different ventilation parameters. Methods: Particle flow was monitored in vivo, post mortem, and in ex vivo lung perfusion (EVLP) in six porcines with the Pexa (particles in exhaled air) instrument. Volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV) were used to compare small versus large tidal volumes. The surfactant lipids dipalmitoylphosphatidylcholine (DPPC) and phosphatidylcholine (PC) were quantified by mass spectrometry. Results: In vivo the particle mass in VCV1 was significantly lower than in VCV2 (p= 0.0186), and the particle mass was significantly higher in PCV1 than in VCV1 (p= 0.0322). In EVLP, the particle mass in VCV1 was significantly higher than in PCV1 (p= 0.0371), and the particle mass was significantly higher in PCV2 than in PCV1 (p= 0.0127). DPPC was significantly higher in EVLP than in vivo. Conclusions: Here, we introduce a new method for measuring particle flow during mechanical ventilation and confirm that these particles can be collected and analyzed. VCV resulted in a lower particle flow in vivo but not in EVLP. In all settings, large tidal volumes resulted in increased particle flow. We found that DPPC was significantly increased comparing in vivo with EVLP. This technology may be useful for developing strategies to preserve the lung and has a high potential to detect biomarkers.
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10.
  • Broberg, Ellen, et al. (författare)
  • Releasing high positive end-expiratory pressure to a low level generates a pronounced increase in particle flow from the airways
  • 2023
  • Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Detecting particle flow from the airways by a non-invasive analyzing technique might serve as an additional tool to monitor mechanical ventilation. In the present study, we used a customized particles in exhaled air (PExA) technique, which is an optical particle counter for the monitoring of particle flow in exhaled air. We studied particle flow while increasing and releasing positive end-expiratory pressure (PEEP). The aim of this study was to investigate the impact of different levels of PEEP on particle flow in exhaled air in an experimental setting. We hypothesized that gradually increasing PEEP will reduce the particle flow from the airways and releasing PEEP from a high level to a low level will result in increased particle flow. Methods: Five fully anesthetized domestic pigs received a gradual increase of PEEP from 5 cmH2O to a maximum of 25 cmH2O during volume-controlled ventilation. The particle count along with vital parameters and ventilator settings were collected continuously and measurements were taken after every increase in PEEP. The particle sizes measured were between 0.41 µm and 4.55 µm. Results: A significant increase in particle count was seen going from all levels of PEEP to release of PEEP. At a PEEP level of 15 cmH2O, there was a median particle count of 282 (154–710) compared to release of PEEP to a level of 5 cmH2O which led to a median particle count of 3754 (2437–10,606) (p < 0.009). A decrease in blood pressure was seen from baseline to all levels of PEEP and significantly so at a PEEP level of 20 cmH2O. Conclusions: In the present study, a significant increase in particle count was seen on releasing PEEP back to baseline compared to all levels of PEEP, while no changes were seen when gradually increasing PEEP. These findings further explore the significance of changes in particle flow and their part in pathophysiological processes within the lung.
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11.
  • Cronin, John N, et al. (författare)
  • Dynamic single-slice CT estimates whole-lung dual-energy CT variables in pigs with and without experimental lung injury
  • 2019
  • Ingår i: Intensive Care Medicine Experimental. - : Springer. - 2197-425X. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Dynamic single-slice CT (dCT) is increasingly used to examine the intra-tidal, physiological variation in aeration and lung density in experimental lung injury. The ability of dCT to predict whole-lung values is unclear, especially for dual-energy CT (DECT) variables. Additionally, the effect of inspiration-related lung movement on CT variables has not yet been quantified.METHODS: Eight domestic pigs were studied under general anaesthesia, including four following saline-lavage surfactant depletion (lung injury model). DECT, dCT and whole-lung images were collected at 12 ventilatory settings. Whole-lung single energy scans images were collected during expiratory and inspiratory apnoeas at positive end-expiratory pressures from 0 to 20 cmH2O. Means and distributions of CT variables were calculated for both dCT and whole-lung images. The cranio-caudal displacement of the anatomical slice was measured from whole-lung images.RESULTS: Mean CT density and volume fractions of soft tissue, gas, iodinated blood, atelectasis, poor aeration, normal aeration and overdistension correlated between dCT and the whole lung (r2 0.75-0.94) with agreement between CT density distributions (r 0.89-0.97). Inspiration increased the matching between dCT and whole-lung values and was associated with a movement of 32% (SD 15%) of the imaged slice out of the scanner field-of-view. This effect introduced an artefactual increase in dCT mean CT density during inspiration, opposite to that caused by the underlying physiology.CONCLUSIONS: Overall, dCT closely approximates whole-lung aeration and density. This approximation is improved by inspiration where a decrease in CT density and atelectasis can be interpreted as physiological rather than artefactual.
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12.
  • Cronin, John N., et al. (författare)
  • Intra-tidal PaO2 oscillations associated with mechanical ventilation : a pilot study to identify discrete morphologies in a porcine model
  • 2023
  • Ingår i: Intensive Care Medicine Experimental. - : Springer Nature. - 2197-425X. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Within-breath oscillations in arterial oxygen tension (PaO2) can be detected using fast responding intra-arterial oxygen sensors in animal models. These PaO2 signals, which rise in inspiration and fall in expiration, may represent cyclical recruitment/derecruitment and, therefore, a potential clinical monitor to allow titration of ventilator settings in lung injury. However, in hypovolaemia models, these oscillations have the potential to become inverted, such that they decline, rather than rise, in inspiration. This inversion suggests multiple aetiologies may underlie these oscillations. A correct interpretation of the various PaO2 oscillation morphologies is essential to translate this signal into a monitoring tool for clinical practice. We present a pilot study to demonstrate the feasibility of a new analysis method to identify these morphologies.Methods Seven domestic pigs (average weight 31.1 kg) were studied under general anaesthesia with muscle relaxation and mechanical ventilation. Three underwent saline-lavage lung injury and four were uninjured. Variations in PEEP, tidal volume and presence/absence of lung injury were used to induce different morphologies of PaO2 oscillation. Functional principal component analysis and k-means clustering were employed to separate PaO2 oscillations into distinct morphologies, and the cardiorespiratory physiology associated with these PaO2 morphologies was compared.Results PaO2 oscillations from 73 ventilatory conditions were included. Five functional principal components were sufficient to explain = 95% of the variance of the recorded PaO2 signals. From these, five unique morphologies of PaO2 oscillation were identified, ranging from those which increased in inspiration and decreased in expiration, through to those which decreased in inspiration and increased in expiration. This progression was associated with the estimates of the first functional principal component (P < 0.001, R-2 = 0.88). Intermediate morphologies demonstrated waveforms with two peaks and troughs per breath. The progression towards inverted oscillations was associated with increased pulse pressure variation (P = 0.03).Conclusions Functional principal component analysis and k-means clustering are appropriate to identify unique morphologies of PaO2 waveform associated with distinct cardiorespiratory physiology. We demonstrated novel intermediate morphologies of PaO2 waveform, which may represent a development of zone 2 physiologies within the lung. Future studies of PaO2 oscillations and modelling should aim to understand the aetiologies of these morphologies.
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  • Dhanani, Jayesh A, et al. (författare)
  • A research pathway for the study of the delivery and disposition of nebulised antibiotics: an incremental approach from in vitro to large animal models
  • 2018
  • Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 6:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Nebulised antibiotics are frequently used for the prevention or treatment of ventilator-associated pneumonia. Many factors may influence pulmonary drug concentrations with inaccurate dosing schedules potentially leading to therapeutic failure and/or the emergence of antibiotic resistance. We describe a research pathway for studying the pharmacokinetics of a nebulised antibiotic during mechanical ventilation using in vitro methods and ovine models, using tobramycin as the study antibiotic.
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14.
  • Fisher, Jane, et al. (författare)
  • A functional observational battery for evaluation of neurological outcomes in a rat model of acute bacterial meningitis
  • 2020
  • Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Acute bacterial meningitis is a disease with a high mortality and a high incidence of neurological sequelae in survivors. There is an acute need to develop new adjuvant therapies. To ensure that new therapies evaluated in animal models are translatable to humans, studies must evaluate clinically relevant and patient-important outcomes, including neurological symptoms and sequelae. Methods We developed and tested a functional observational battery to quantify the severity of a variety of relevant neurological and clinical symptoms in a rat model of bacterial meningitis. The functional observational battery included symptoms relating to general clinical signs, gait and posture abnormalities, involuntary motor movements, focal neurological signs, and neuromotor abnormalities which were scored according to severity and summed to obtain a combined clinical and neurological score. To test the functional observational battery, adult Sprague-Dawley rats were infected by intracisternal injection of a clinical isolate of Streptococcus pneumoniae. Rats were evaluated for 6 days following the infection. Results Pneumococcal meningitis was not lethal in this model; however, it induced severe neurological symptoms. Most common symptoms were hearing loss (75% of infected vs 0% of control rats; p = 0.0003), involuntary motor movements (75% of infected vs 0% of control rats; p = 0.0003), and gait and posture abnormality (67% of infected vs 0% of control rats; p = 0.0013). Infected rats had a higher combined score when determined by the functional observational battery than control rats at all time points (24 h 12.7 ± 4.0 vs 4.0 ± 2.0; 48 h 17.3 ± 7.1 vs 3.4 ± 1.8; 6 days 17.8 ± 7.4 vs 1.7 ± 2.4; p < 0.0001 for all). Conclusions The functional observational battery described here detects clinically relevant neurological sequelae of bacterial meningitis and could be a useful tool when testing new therapeutics in rat models of meningitis.
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15.
  • Fisher, Jane, et al. (författare)
  • Elevated plasma glypicans are associated with organ failure in patients with infection
  • 2019
  • Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Increased vascular permeability is a key feature in the pathophysiology of sepsis and the development of organ failure. Shedding of the endothelial glycocalyx is increasingly being recognized as an important pathophysiological mechanism but at present it is unclear if glypicans contribute to this response. We hypothesized that plasma levels of glypicans (GPC) are elevated in patients with sepsis. Methods Plasma GPC 1–6 levels were measured by ELISA in 10 patients with sepsis and 10 healthy controls as an initial screening. Plasma GPC 1, 3, and 4 were further measured in a cohort of 184 patients with a clinically confirmed infection. Patients were divided into groups of those who had sepsis and those who had an infection without organ failure. To determine whether plasma glypicans could predict the development of organ failure, patients were further subdivided to those who had organ failure at enrolment and those who developed it after enrollment. The association of plasma GPC 1, 3, and 4 with organ failure and with various markers of inflammation, disease severity, and glycocalyx shedding was investigated. Results In the pilot study, only GPC 1, 3, and 4 were detectable in the plasma of sepsis patients. In the larger cohort, GPC 1, 3, and 4 levels were significantly higher (p < 0.001) in patients with sepsis than in those with infection without organ failure. GPC 1, 3, and 4 were significantly positively correlated with plasma levels of the disease severity markers C-reactive protein, lactate, procalcitonin, and heparin binding protein, and with the marker of glycocalyx degradation syndecan 1. They were significantly negatively correlated with plasma levels of the glycocalyx-protective factors apolipoprotein M and sphingosine-1-phosphate. Conclusions We show that GPC 1, 3, and 4 are elevated in plasma of patients with sepsis and correlate with markers of disease severity, systemic inflammation, and glycocalyx damage.
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16.
  • Frigyesi, Attila, et al. (författare)
  • Plasma proenkephalin A 119-159 on intensive care unit admission is a predictor of organ failure and 30-day mortality
  • 2021
  • Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Proenkephalin A 119-159 (penKid) has been suggested as a marker of renal failure and poor outcome. We aimed to investigate the association of penKid on ICU admission with organ dysfunction and mortality in a mixed ICU population. In this retrospective, observational study, admission penKid levels from prospectively collected blood samples of consecutive patients admitted to four Swedish ICUs were analysed. The association of penKid with day-two sequential organ failure assessment (SOFA) scores and 30-day mortality was investigated using (ordinal) logistic regression. The predictive power of penKid for 30-day mortality and dialysis was assessed using the area under the receiver operating characteristic curve (AUC).RESULTS: Of 1978 included patients, 632 fulfilled the sepsis 3-criteria, 190 had a cardiac arrest, and 157 had experienced trauma. Admission penKid was positively associated with 30-day mortality with an odds ratio of 1.95 (95% confidence interval 1.75-2.18, p < 0.001), and predicted 30-day mortality in the entire ICU population with an AUC of 0.71 (95% confidence interval 0.68-0.73) as well as in the sepsis, cardiac arrest and trauma subgroups (AUCs of 0.61-0.84). Correction for admission plasma creatinine revealed that penKid correlated with neurological dysfunction.CONCLUSION: Plasma penKid on ICU admission is associated with day-two organ dysfunction and predictive of 30-day mortality in a mixed ICU-population, as well as in sepsis, cardiac arrest and trauma subgroups. In addition to being a marker of renal dysfunction, plasma penKid is associated with neurologic dysfunction in the entire ICU population, and cardiovascular dysfunction in sepsis.
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18.
  • Froese, Logan, et al. (författare)
  • The impact of sedative and vasopressor agents on cerebrovascular reactivity in severe traumatic brain injury
  • 2023
  • Ingår i: Intensive Care Medicine Experimental. - : Springer. - 2197-425X. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The aim of this study is to evaluate the impact of commonly administered sedatives (Propofol, Alfentanil, Fentanyl, and Midazolam) and vasopressor (Dobutamine, Ephedrine, Noradrenaline and Vasopressin) agents on cerebrovascular reactivity in moderate/severe TBI patients. Cerebrovascular reactivity, as a surrogate for cerebral autoregulation was assessed using the long pressure reactivity index (LPRx). We evaluated the data in two phases, first we assessed the minute-by-minute data relationships between different dosing amounts of continuous infusion agents and physiological variables using boxplots, multiple linear regression and ANOVA. Next, we assessed the relationship between continuous/bolus infusion agents and physiological variables, assessing pre-/post- dose of medication change in physiology using a Wilcoxon signed-ranked test. Finally, we evaluated sub-groups of data for each individual dose change per medication, focusing on key physiological thresholds and demographics.Results: Of the 475 patients with an average stay of 10 days resulting in over 3000 days of recorded information 367 (77.3%) were male with a median Glasgow coma score of 7 (4-9). The results of this retrospective observational study confirmed that the infusion of most administered agents do not impact cerebrovascular reactivity, which is confirmed by the multiple linear regression components having p value > 0.05. Incremental dose changes or bolus doses in these medications in general do not lead to significant changes in cerebrovascular reactivity (confirm by Wilcoxon signed-ranked p value > 0.05 for nearly all assessed relationships). Within the sub-group analysis that separated the data based on LPRx pre-dose, a significance between pre-/post-drug change in LPRx was seen, however this may be more of a result from patient state than drug impact.Conclusions: Overall, this study indicates that commonly administered agents with incremental dosing changes have no clinically significant influence on cerebrovascular reactivity in TBI (nor do they impair cerebrovascular reactivity). Though further investigation in a larger and more diverse TBI patient population is required.
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21.
  • Hahn, RG (författare)
  • Water content of the endothelial glycocalyx layer estimated by volume kinetic analysis
  • 2020
  • Ingår i: Intensive care medicine experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 8:1, s. 29-
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThe water volume of the endothelial glycocalyx layer has been estimated at 0.7 to 1.7 L using tracer methods of unclear value. The present study attempts to measure this fluid volume by analyzing the kinetics of a crystalloid fluid load.MethodsAn intravenous infusion of approximately 1 L of Ringer’s acetate was administered to 35 healthy volunteers, and the central volume of distribution of the water volume was calculated from the urinary excretion and frequent measurements of the fluid-induced hemodilution using mixed-effects modeling software. Comparisons were made with the plasma volume derived from three published anthropometric regression equations based on isotope measurements. In a second analysis, up to 2.5 L of Ringer’s was administered to 60 volunteers selected from a cohort of 160 to have as similar hematocrits as possible to the volunteers whose data were used to create the anthropometric equations.ResultsVolume kinetics showed that the infused crystalloid fluid occupied a larger central fluid space than was estimated with the isotope measurements. The first analysis of the 35 subjects indicated a mean difference of 0.51 L in males and 0.49 L in females. The second, larger analysis showed a mean excess volume of 0.43 L, which was approximately 15% of the circulating plasma volume.ConclusionsA crystalloid fluid load expands a 0.4–0.5 L larger central fluid space than the circulating plasma volume. The excess volume is probably located in the glycocalyx layer.
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22.
  • Hanslin, Katja, et al. (författare)
  • The impact of the systemic inflammatory response on hepatic bacterial elimination in experimental abdominal sepsis
  • 2019
  • Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Bacterial translocation from the gut has been suggested to induce a systemic inflammatory response syndrome (SIRS) and organ dysfunction. The liver has a pivotal role in eliminating circulating bacteria entering from the gut. We investigated whether pre-existing inflammation affects hepatic bacterial elimination.METHODS: Fifteen anaesthetised piglets were infused with E. coli in the portal vein for 3 h. The naive group (n = 6) received the bacterial infusion without endotoxin exposure. SIRS (SIRS group, n = 6) was induced by endotoxin infusion 24 h before the bacterial infusion. For effects of anaesthesia, controls (n = 3) received saline instead of endotoxin for 24 h. Bacterial counts and endotoxin levels in the portal and hepatic veins were analysed during bacterial infusion.RESULTS: The bacterial killing rate was higher in the naive group compared with the SIRS group (p = 0.001). The ratio of hepatic to portal venous bacterial counts, i.e. the median bacterial influx from the splanchnic circulation, was 0.06 (IQR 0.01-0.11) in the naive group and 0.71 (0.03-1.77) in the SIRS group at 3 h, and a magnitude lower in the naive group during bacteraemia (p = 0.03). Similar results were seen for hepatic endotoxin elimination. Peak log tumour necrosis factor alpha was higher in the naive 4.84 (4.77-4.89) vs. the SIRS group 3.27 (3.26-3.32) mg/L (p < 0.001).CONCLUSIONS: Our results suggest that hepatic bacterial and endotoxin elimination is impaired in pigs with pre-existing SIRS while the inflammatory response to bacterial infusion is diminished. If similar mechanisms operate in human critical illness, the hepatic elimination of bacteria from the gut could be impaired by SIRS.
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23.
  • Hurtsén, Anna Stene, 1992-, et al. (författare)
  • A randomized porcine study of hemorrhagic shock comparing end-tidal carbon dioxide targeted and proximal systolic blood pressure targeted partial resuscitative endovascular balloon occlusion of the aorta in the mitigation of metabolic injury
  • 2023
  • Ingår i: Intensive Care Medicine Experimental. - : Springer. - 2197-425X. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The definition of partial resuscitative endovascular balloon occlusion of the aorta (pREBOA) is not yet determined and clinical markers of the degree of occlusion, metabolic effects and end-organ injury that are clinically monitored in real time are lacking. The aim of the study was to test the hypothesis that end-tidal carbon dioxide (ETCO2) targeted pREBOA causes less metabolic disturbance compared to proximal systolic blood pressure (SBP) targeted pREBOA in a porcine model of hemorrhagic shock.MATERIALS AND METHODS: Twenty anesthetized pigs (26-35 kg) were randomized to 45 min of either ETCO2 targeted pREBOA (pREBOAETCO2, ETCO2 90-110% of values before start of occlusion, n = 10) or proximal SBP targeted pREBOA (pREBOASBP, SBP 80-100 mmHg, n = 10), during controlled grade IV hemorrhagic shock. Autotransfusion and reperfusion over 3 h followed. Hemodynamic and respiratory parameters, blood samples and jejunal specimens were analyzed.RESULTS: ETCO2 was significantly higher in the pREBOAETCO2 group during the occlusion compared to the pREBOASBP group, whereas SBP, femoral arterial mean pressure and abdominal aortic blood flow were similar. During reperfusion, arterial and mesenteric lactate, plasma creatinine and plasma troponin concentrations were higher in the pREBOASBP group.CONCLUSIONS: In a porcine model of hemorrhagic shock, ETCO2 targeted pREBOA caused less metabolic disturbance and end-organ damage compared to proximal SBP targeted pREBOA, with no disadvantageous hemodynamic impact. End-tidal CO2 should be investigated in clinical studies as a complementary clinical tool for mitigating ischemic-reperfusion injury when using pREBOA.
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24.
  • Jakobsen, Rasmus Peter, et al. (författare)
  • Effects of norepinephrine infusion on cerebral energy metabolism during experimental haemorrhagic shock
  • 2022
  • Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The use of norepinephrine in the case of life-threatening haemorrhagic shock is well established but widely discussed. The present study was designed to compare the effects of early norepinephrine treatment vs. no treatment on cerebral energy metabolism during haemorrhagic shock. Methods: Twelve pigs were subjected to haemorrhagic shock, 4 in the control group and 8 in the norepinephrine (NE) group. Following a 60 min baseline period haemorrhagic shock was achieved by bleeding all animals to a pre-defined mean arterial blood pressure (MAP) of approximately 40 mm Hg. When mean arterial pressure had decreased to 40 mmHg NE infusion started in the treatment group. After 90 min, NE infusion stopped, and all pigs were resuscitated with autologous blood and observed for 2.5 h. During the experiment cerebral tissue oxygenation (PbtO2) was monitored continuously and variables reflecting cerebral energy metabolism (glucose, lactate, pyruvate, glutamate, glycerol) were measured by utilizing intracerebral microdialysis. Results: All 12 pigs completed the protocol. NE infusion resulted in significantly higher MAP (p < 0.001). During the shock period lactate/pyruvate (LP) ratio group increased from 20 (15–29) to 66 (38–82) (median (IQR)) in the control group but remained within normal limits in the NE group. The significant increase in LP ratio in the control group remained after resuscitation. After induction of shock PbtO2 decreased markedly in the control group and was significantly lower than in the NE group during the resuscitation phase. Conclusion: NE infusion during haemorrhagic shock improved cerebral energy metabolism compared with no treatment.
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25.
  • Johnsson, Patrik, et al. (författare)
  • Plasma bioactive adrenomedullin on intensive care unit admission is associated with acute respiratory distress syndrome : an observational study
  • 2023
  • Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 11, s. 1-15
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Bioactive adrenomedullin (bio-ADM) is a vasoactive peptide with a key role in reducing vascular hyperpermeability and improving endothelial stability during infection, but it also has vasodilatory properties. Bioactive ADM has not been studied in conjunction with acute respiratory distress syndrome (ARDS), but it has recently been shown to correlate with outcomes after severe COVID-19. Therefore, this study investigated the association between circulating bio-ADM on intensive care unit (ICU) admission and ARDS. The secondary aim was the association between bio-ADM and ARDS mortality. Methods: We analysed bio-ADM levels and assessed the presence of ARDS in adult patients admitted to two general intensive care units in southern Sweden. Medical records were manually screened for the ARDS Berlin criteria. The association between bio-ADM levels and ARDS and mortality in ARDS patients was analysed using logistic regression and receiver-operating characteristics analysis. The primary outcome was an ARDS diagnosis within 72 h of ICU admission, and the secondary outcome was 30-day mortality. Results: Out of 1224 admissions, 11% (n = 132) developed ARDS within 72 h. We found that elevated admission bio-ADM level was associated with ARDS independently of sepsis status and of organ dysfunction as measured by the Sequential organ failure assessment (SOFA) score. Both lower levels (< 38 pg/L) and high (> 90 pg/L) levels of bio-ADM were independently (of the Simplified acute physiology score, SAPS-3) predictive of mortality. Patients with indirect mechanisms of lung injury had higher bio-ADM levels than those with a direct mechanism of injury, and bio-ADM increased with increasing ARDS severity. Conclusions: High levels of bio-ADM on admission are associated with ARDS, and bio-ADM levels significantly differ depending on the injury mechanism. In contrast, both high and low levels of bio-ADM are associated with mortality, possibly due to the dual action of bio-ADM in stabilising the endothelial barrier and causing vasodilation. These findings could lead to improved diagnostic accuracy of ARDS and potentially lead to new therapeutic strategies.
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26.
  • Jungner, Åsa, et al. (författare)
  • Cardiopulmonary bypass in the newborn: effects of circulatory cell-free hemoglobin and hyperoxia evaluated in a novel rat pup model
  • 2017
  • Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 5:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Infants with congenital heart defects (CHD) are at risk for white matter brain injury. This novel rat pup model characterizes the systemic effects of intravasal cell-free hemoglobin and hyperoxia, hypothesizing that immature endogenous scavenging systems relate to increased vulnerability to conditions present during cardiopulmonary bypass (CPB).Methods: Plasma pharmacokinetics of cell-free human hemoglobin (Hb) was determined after intraperitoneal (i.p.) administration in postnatal day 6 (P6) rat pups. Cell-free hemoglobin degradation, scavenger- and oxidative stress responses in altered oxygen environments were evaluated in P6 rat pups exposed to i.p. cell-free Hb or vehicle and subjected to hyperoxia or normoxia for 24 h. Plasma and liver were analyzed for free heme, haptoglobin, hemopexin, heme-oxygenase 1, and 8-OHdG at 3–120 h post-injection. Baseline scavenging properties were evaluated in P0-P12 rat pups.Results: Cell-free Hb displayed peak plasma concentrations of 3.6 ± 0.5 mg/mL (mean ± SD) at 3 h post-administration. Animals exposed to cell-free Hb demonstrated a 30-fold increase in plasma haptoglobin and a decrease in plasma hemopexin to 1/6 of concentrations observed in pups exposed to vehicle. Exposure to cell-free Hb and hyperoxia mediated increased plasma concentrations of free heme (72.7 ± 19.5 μM, mean ± SD) compared to exposure to cell-free Hb and normoxia (49.3 ± 13.1 μM) at 3 h, and an elevated hepatic mRNA expression of heme-oxygenase 1. mRNA expression of haptoglobin and hemopexin was increased in animals exposed to hemoglobin with a mitigated response in pups exposed to hemoglobin and hyperoxia. Animals exposed to hyperoxia displayed an increase in hepatic transcription of scavenger proteins at 24 h. Combined exposure to cell-free Hb and hyperoxia mediated an increased DNA- oxidation at 6 h, whereas all insults conveyed a decrease in DNA-oxidation at 120 h.Conclusions: In this study, we present a novel rat pup model with scavenging characteristics and brain maturation similar to newborns with CHD. We have confirmed a distinct scavenger response after exposure to systemic cell-free hemoglobin. We have indications of an accelerated metabolism of cell-free Hb and of an altered transcription of scavenger proteins in a hyperoxic environment. We believe that this model will prove valuable in future delineation of inflammatory and oxidative end-organ damage following CPB.
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27.
  • Jörg, Matthias, et al. (författare)
  • Agreement of pCO2 in venous to arterial blood gas conversion models in undifferentiated emergency patients
  • 2023
  • Ingår i: Intensive Care Medicine Experimental. - : SPRINGER. - 2197-425X. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Venous blood gas sampling has replaced arterial sampling in many critically ill patients, though interpretation of venous pCO(2) still remains a challenge. Lemoel et al., Farkas and Zeserson et al. have proposed models to estimate arterial pCO(2) based on venous pCO(2). Our objective was to externally validate these models with a new dataset. This was a prospective cross-sectional study of consecutive adult patients with a clinical indication for blood gas analysis in an academic emergency department in Sweden. Agreement of pairs was reported as mean difference with limits of agreement (LoA). Vital signs and lead times were recorded.Results Two hundred and fifty blood gas pairs were collected consecutively between October 2021 and April 2022, 243 valid pairs were used in the final analysis [mean age 72.8 years (SD 17.8), 47% females]. Respiratory distress was the most common clinical indication (84% of all cases). The model of Farkas showed the best metrics with a mean difference between estimated and arterial pCO(2) of - 0.11 mmHg (95% LoA - 6.86, + 6.63). For Lemo & euml;l the difference was 2.57 mmHg (95% LoA - 5.65, + 10.8), Zeserson 2.55 mmHg (95% LoA - 7.43, + 12.53). All three models showed a decrease in precision in patients with ongoing supplemental oxygen therapy.Conclusion Arterial pCO(2) may be accurately estimated in most patients based on venous blood gas samples. Additional consideration is required in patients with hypo- or hypercapnia or oxygen therapy. Thus, conversion of venous pCO(2) may be considered as an alternative to arterial blood gas sampling with the model of Farkas being the most accurate.
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28.
  • Karagiannidis, Christian, et al. (författare)
  • Impact of membrane lung surface area and blood flow on extracorporeal CO2 removal during severe respiratory acidosis
  • 2017
  • Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Veno-venous extracorporeal CO2 removal (vv-ECCO2R) is increasingly being used in the setting of acute respiratory failure. Blood flow rates through the device range from 200 ml/min to more than 1500 ml/min, and the membrane surface areas range from 0.35 to 1.3 m2. The present study in an animal model with similar CO2 production as an adult patient was aimed at determining the optimal membrane lung surface area and technical requirements for successful vv-ECCO2R.METHODS: Four different membrane lungs, with varying lung surface areas of 0.4, 0.8, 1.0, and 1.3m2 were used to perform vv-ECCO2R in seven anesthetized, mechanically ventilated, pigs with experimentally induced severe respiratory acidosis (pH 7.0-7.1) using a 20Fr double-lumen catheter with a sweep gas flow rate of 8 L/min. During each experiment, the blood flow was increased stepwise from 250 to 1000 ml/min.RESULTS: Amelioration of severe respiratory acidosis was only feasible when blood flow rates from 750 to 1000 ml/min were used with a membrane lung surface area of at least 0.8 m2. Maximal CO2 elimination was 150.8 ml/min, with pH increasing from 7.01 to 7.30 (blood flow 1000 ml/min; membrane lung 1.3 m2). The membrane lung with a surface of 0.4 m2 allowed a maximum CO2 elimination rate of 71.7 mL/min, which did not result in the normalization of pH, even with a blood flow rate of 1000 ml/min. Also of note, an increase of the surface area above 1.0 m2 did not result in substantially higher CO2 elimination rates. The pressure drop across the oxygenator was considerably lower (<10 mmHg) in the largest membrane lung, whereas the smallest revealed a pressure drop of more than 50 mmHg with 1000 ml blood flow/min.CONCLUSIONS: In this porcine model, vv-ECCO2R was most effective when using blood flow rates ranging between 750 and 1000 ml/min, with a membrane lung surface of at least 0.8 m2. In contrast, low blood flow rates (250-500 ml/min) were not sufficient to completely correct severe respiratory acidosis, irrespective of the surface area of the membrane lung being used. The converse was also true, low surface membrane lungs (0.4 m2) were not capable of completely correcting severe respiratory acidosis across the range of blood flows used in this study.
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29.
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30.
  • Krifors, Anders, et al. (författare)
  • An experimental porcine model of invasive candidiasis
  • 2023
  • Ingår i: Intensive Care Medicine Experimental. - : Springer Nature. - 2197-425X. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundInvasive candidiasis (IC) is a severe and often fatal fungal infection that affects critically ill patients. The development of animal models that mimic human disease is essential for advancing our understanding of IC pathophysiology and testing experimental or novel treatments. We aimed to develop a large animal model of IC that could provide a much-needed addition to the widely used murine models.ResultsA total of 25 pigs (including one control), aged between 9 and 12 weeks, with a median weight of 25.1 kg (IQR 24.1–26.2), were used to develop the porcine IC model. We present the setup, the results of the experiments, and the justification for the changes made to the model. The experiments were conducted in an intensive care setting, using clinically relevant anaesthesia, monitoring and interventions. The final model used corticosteroids, repeated Candida inoculation, and continuous endotoxin. The model consistently demonstrated quantifiable growth of Candida in blood and organs. The registered physiological data supported the development of the sepsis-induced circulatory distress observed in IC patients in the ICU.ConclusionsOur proposed porcine model of IC offers a potential new tool in the research of IC.
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31.
  • Lagebrant, Alice, et al. (författare)
  • Brain injury markers in blood associate with generalised oedema on computed tomography after cardiac arrest
  • 2021
  • Ingår i: - : Springer Science and Business Media LLC. ; , s. 203-204
  • Konferensbidrag (refereegranskat)abstract
    • Introduction. According to the 2021 ERC/ESICM guideline recommen-dations, elevated neuron-specific enolase [NSE] levels as well as diffuseand extensive anoxic damage on neuroimaging are predictors of poorneurological outcome after cardiac arrest.(1) We previously describedthat NSE is elevated in patients with generalised oedema on com-puted tomography [CT]. (2).Objectives. In this study, we aim to examine the novel brain injurymarkers serum neurofilament light [NFL], glial fibrillary acidic protein[GFAP] and total-tau [tau] to predict the presence of generalised brainoedema.Methods. Retrospective analysis of patients examined with CT onclinical indication within the Target Temperature Management afterout-of-hospital cardiac arrest [TTM] trial. (2,3) Serum samples fromthe biobank sub study were prospectively collected at 48 h post arrestand analysed after trial completion as published. (4–7) The neuronalmarker NSE, the neuroaxonal injury markers NFL and tau and theastrocytic injury marker GFAP were correlated with the presence ofgeneralised oedema on CT, assessed by local radiologists through vis-ual evaluation. The prognostic accuracy of NSE ≥ 60 ug/l for predictinggeneralised oedema was also analysed.Results. 192 patients had data available on all four biomarkers at 48 hand were examined with CT < 168 h post arrest. Brain injury markerswere significantly higher in patients with generalised oedema as com-pared to patients without oedema on CT scans performed 24–168 hafter ROSC (p < 0.001) (Fig. 1A–D). For CT scans performed < 24 h, onlyNSE levels showed a significant correlation (p < 0.05). Biomarkers pre -dicted generalised oedema with area under the receiver operatingcharacteristics curve [AUC] 67.5–73.2% for CT scans performed < 24 h(n = 111), with no statistically significant difference between themarkers ( Fig. 2A). For scans performed 24–168 h (n = 81) AUC for pre -dicting generalised oedema was 78.1%-82.9%, with no statisticallysignificant difference between the markers. NSE ≥ 60 ug/l at 48 h, asrecommended by guidelines, predicted generalised oedema with 81%(95%CI 67–90%) sensitivity and 77% (95%CI 62–87%) specificity.Conclusion. Concentrations of all evaluated brain injury markerswere significantly higher in patients with generalised oedema on CTperformed after the first 24 h post arrest. Biomarker concentrationsindicate whether generalised oedema on CT is likely and may thus beclinically useful for deciding if a CT scan is sufficient for prognostica-tion or if a MRI is more appropriate.
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32.
  • Lileikyte, Gabriele, et al. (författare)
  • Serum proteome profiles in patients treated with targeted temperature management after out-of-hospital cardiac arrest
  • 2023
  • Ingår i: Intensive Care Medicine Experimental. - 2197-425X. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Definition of temporal serum proteome profiles after out-of-hospital cardiac arrest may identify biological processes associated with severe hypoxia-ischaemia and reperfusion. It may further explore intervention effects for new mechanistic insights, identify candidate prognostic protein biomarkers and potential therapeutic targets. This pilot study aimed to investigate serum proteome profiles from unconscious patients admitted to hospital after out-of-hospital cardiac arrest according to temperature treatment and neurological outcome.METHODS: Serum samples at 24, 48, and 72 h after cardiac arrest at three centres included in the Target Temperature Management after out-of-hospital cardiac arrest trial underwent data-independent acquisition mass spectrometry analysis (DIA-MS) to find changes in serum protein concentrations associated with neurological outcome at 6-month follow-up and targeted temperature management (TTM) at 33 °C as compared to 36 °C. Neurological outcome was defined according to Cerebral Performance Category (CPC) scale as "good" (CPC 1-2, good cerebral performance or moderate disability) or "poor" (CPC 3-5, severe disability, unresponsive wakefulness syndrome, or death).RESULTS: Of 78 included patients [mean age 66 ± 12 years, 62 (80.0%) male], 37 (47.4%) were randomised to TTM at 36 °C. Six-month outcome was poor in 47 (60.3%) patients. The DIA-MS analysis identified and quantified 403 unique human proteins. Differential protein abundance testing comparing poor to good outcome showed 19 elevated proteins in patients with poor outcome (log 2-fold change (FC) range 0.28-1.17) and 16 reduced proteins (log 2(FC) between - 0.22 and - 0.68), involved in inflammatory/immune responses and apoptotic signalling pathways for poor outcome and proteolysis for good outcome. Analysis according to level of TTM showed a significant protein abundance difference for six proteins [five elevated proteins in TTM 36 °C (log 2(FC) between 0.33 and 0.88), one reduced protein (log 2(FC) - 0.6)] mainly involved in inflammatory/immune responses only at 48 h after cardiac arrest. CONCLUSIONS: Serum proteome profiling revealed an increase in inflammatory/immune responses and apoptosis in patients with poor outcome. In patients with good outcome, an increase in proteolysis was observed, whereas TTM-level only had a modest effect on the proteome profiles. Further validation of the differentially abundant proteins in response to neurological outcome is necessary to validate novel biomarker candidates that may predict prognosis after cardiac arrest.
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33.
  • Lindén, Anja, et al. (författare)
  • Blood volume in patients likely to be preload responsive : a post hoc analysis of a randomized controlled trial
  • 2023
  • Ingår i: Intensive Care Medicine Experimental. - 2197-425X. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Preload responsive postoperative patients with signs of inadequate organ perfusion are commonly assumed to be hypovolemic and therefore treated with fluids to increase preload. However, preload is influenced not only by blood volume, but also by venous vascular tone and the contribution of these factors to preload responsiveness in this setting is unknown. Based on this, the objective of this study was to investigate blood volume status in preload-responsive postoperative patients. Methods: Data from a clinical trial including postoperative patients after major abdominal surgery were analyzed. Patients with signs of inadequate organ perfusion and with data from a passive leg raising test (PLR) were included. An increase in pulse pressure by ≥ 9% was used to identify patients likely to be preload responsive. Blood volume was calculated from plasma volume measured using radiolabelled albumin and hematocrit. Patients with a blood volume of at least 10% above or below estimated normal volume were considered hyper- and hypovolemic, respectively. Results: A total of 63 patients were included in the study. Median (IQR) blood volume in the total was 57 (50–65) ml/kg, and change in pulse pressure after PLR was 14 (7–24)%. A total of 43 patients were preload responsive. Of these patients, 44% were hypovolemic, 28% euvolemic and 28% hypervolemic. Conclusions: A large fraction of postoperative patients with signs of hypoperfusion that are likely to be preload responsive, are hypervolemic. In these patients, treatments other than fluid administration may be a more rational approach to increase cardiac output.
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34.
  • Marchesi, Silvia, MD, 1985-, et al. (författare)
  • Duodenum edema due to reduced lymphatic drainage leads to increased inflammation in a porcine endotoxemic model.
  • 2022
  • Ingår i: Intensive care medicine experimental. - : Springer Nature. - 2197-425X. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Interventions, such as mechanical ventilation with high positive end-expiratory pressure (PEEP), increase inflammation in abdominal organs. This effect could be due to reduced venous return and impaired splanchnic perfusion, or intestinal edema by reduced lymphatic drainage. However, it is not clear whether abdominal edema per se leads to increased intestinal inflammation when perfusion is normal. The aim of the presented study was to investigate if an impaired thoracic duct function can induce edema of the abdominal organs and if it is associated to increase inflammation when perfusion is maintained normal. In a porcine model, endotoxin was used to induce systemic inflammation. In the Edema group (n = 6) the abdominal portion of the thoracic duct was ligated, while in the Control group (7 animals) it was maintained intact. Half of the animals underwent a diffusion weighted-magnetic resonance imaging (DW-MRI) at the end of the 6-h observation period to determine the abdominal organ perfusion. Edema in abdominal organs was assessed using wet-dry weight and with MRI. Inflammation was assessed by measuring cytokine concentrations in abdominal organs and blood as well as histopathological analysis of the abdominal organs.RESULTS: Organ perfusion was similar in both groups, but the Edema group had more intestinal (duodenum) edema, ascites, higher intra-abdominal pressure (IAP) at the end of observation time, and higher cytokine concentration in the small intestine. Systemic cytokines (from blood samples) correlated with IAP.CONCLUSIONS: In this experimental endotoxemic porcine model, the thoracic duct's ligation enhanced edema formation in the duodenum, and it was associated with increased inflammation.
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35.
  • Masterson, C. H., et al. (författare)
  • Mesenchymal stem/stromal cell-based therapies for severe viral pneumonia: therapeutic potential and challenges
  • 2021
  • Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 9:61, s. 1-21
  • Forskningsöversikt (refereegranskat)abstract
    • Severe viral pneumonia is a significant cause of morbidity and mortality globally, whether due to outbreaks of endemic viruses, periodic viral epidemics, or the rarer but devastating global viral pandemics. While limited anti-viral therapies exist, there is a paucity of direct therapies to directly attenuate viral pneumonia-induced lung injury, and management therefore remains largely supportive. Mesenchymal stromal/stem cells (MSCs) are receiving considerable attention as a cytotherapeutic for viral pneumonia. Several properties of MSCs position them as a promising therapeutic strategy for viral pneumonia-induced lung injury as demonstrated in pre-clinical studies in relevant models. More recently, early phase clinical studies have demonstrated a reassuring safety profile of these cells. These investigations have taken on an added importance and urgency during the COVID-19 pandemic, with multiple trials in progress across the globe. In parallel with clinical translation, strategies are being investigated to enhance the therapeutic potential of these cells in vivo, with different MSC tissue sources, specific cellular products including cell-free options, and strategies to ‘licence’ or ‘pre-activate’ these cells, all being explored. This review will assess the therapeutic potential of MSC-based therapies for severe viral pneumonia. It will describe the aetiology and epidemiology of severe viral pneumonia, describe current therapeutic approaches, and examine the data suggesting therapeutic potential of MSCs for severe viral pneumonia in pre-clinical and clinical studies. The challenges and opportunities for MSC-based therapies will then be considered.
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36.
  • Messina, Antonio, et al. (författare)
  • Pathophysiology of fluid administration in critically ill patients
  • 2022
  • Ingår i: Intensive Care Medicine Experimental. - : Springer. - 2197-425X. ; 10:1
  • Forskningsöversikt (refereegranskat)abstract
    • Fluid administration is a cornerstone of treatment of critically ill patients. The aim of this review is to reappraise the pathophysiology of fluid therapy, considering the mechanisms related to the interplay of flow and pressure variables, the systemic response to the shock syndrome, the effects of different types of fluids administered and the concept of preload dependency responsiveness. In this context, the relationship between preload, stroke volume (SV) and fluid administration is that the volume infused has to be large enough to increase the driving pressure for venous return, and that the resulting increase in end-diastolic volume produces an increase in SV only if both ventricles are operating on the steep part of the curve. As a consequence, fluids should be given as drugs and, accordingly, the dose and the rate of administration impact on the final outcome. Titrating fluid therapy in terms of overall volume infused but also considering the type of fluid used is a key component of fluid resuscitation. A single, reliable, and feasible physiological or biochemical parameter to define the balance between the changes in SV and oxygen delivery (i.e., coupling "macro" and "micro" circulation) is still not available, making the diagnosis of acute circulatory dysfunction primarily clinical.
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37.
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38.
  • Mälberg, Johan, et al. (författare)
  • Continuous chest compressions are associated with higher peak inspiratory pressures when compared to 30:2 in an experimental cardiac arrest model
  • 2023
  • Ingår i: Intensive Care Medicine Experimental. - : Springer. - 2197-425X. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Ventilation during cardiopulmonary resuscitation (CPR) has long been a part of the standard treatment during cardiac arrests. Ventilation is usually given either during continuous chest compressions (CCC) or during a short pause after every 30 chest compressions (30:2). There is limited knowledge of how ventilation is delivered if it effects the hemodynamics and if it plays a role in the occurrence of lung injuries. The aim of this study was to compare ventilation parameters, hemodynamics, blood gases and lung injuries during experimental CPR given with CCC and 30:2 in a porcine model.METHODS: Sixteen pigs weighing approximately 33 kg were randomized to either receive CPR with CCC or 30:2. Ventricular fibrillation was induced by passing an electrical current through the heart. CPR was started after 3 min and given for 20 min. Chest compressions were provided mechanically with a chest compression device and ventilations were delivered manually with a self-inflating bag and 12 l/min of oxygen. During the experiment, ventilation parameters and hemodynamics were sampled continuously, and arterial blood gases were taken every five minutes. After euthanasia and cessation of CPR, the lungs and heart were removed in block and visually examined followed by sampling of lung tissue which were examined using microscopy.RESULTS: In the CCC group and the 30:2 group, peak inspiratory pressure (PIP) was 58.6 and 35.1 cmH2O (p < 0.001), minute volume (MV) 2189.6 and 1267.1 ml (p < 0.001), peak expired carbon dioxide (PECO2) 28.6 and 39.4 mmHg (p = 0.020), partial pressure of carbon dioxide (PaCO2) 50.2 and 61.1 mmHg (p = 0.013) and pH 7.3 and 7.2 (p = 0.029), respectively. Central venous pressure (CVP) decreased more over time in the 30:2 group (p = 0.023). All lungs were injured, but there were no differences between the groups.CONCLUSIONS: Ventilation during CCC resulted in a higher PIP, MV and pH and lower PECO2 and PaCO2, showing that ventilation mode during CPR can affect ventilation parameters and blood gases.
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39.
  • Nelson, Axel, et al. (författare)
  • Effects of fresh frozen plasma, Ringer's acetate and albumin on plasma volume and on circulating glycocalyx components following haemorrhagic shock in rats.
  • 2016
  • Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 4:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Early use of fresh frozen plasma (FFP) in haemorrhagic shock is associated with improved outcome. This effect may partly be due to protection of the endothelial glycocalyx and/or secondary to a superior efficacy of FFP as a plasma volume expander compared to crystalloids. The objective of the present study was to investigate if protection of the glycocalyx by FFP can be demonstrated when potential differences in plasma volume (PV) following resuscitation are accounted for.
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40.
  • Nilsson, Kristofer F., 1981-, et al. (författare)
  • The novel nitric oxide donor PDNO attenuates ovine ischemia-reperfusion induced renal failure
  • 2017
  • Ingår i: Intensive Care Medicine Experimental. - London, UK : Springer Science and Business Media LLC. - 2197-425X. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Renal ischemia-reperfusion injury is a common cause of acute kidney injury in intensive care and surgery. Recently, novel organic mononitrites of 1,2-propanediol (PDNO) were synthesized and shown to rapidly and controllably deploy nitric oxide in the circulation when administered intravenously. We hypothesized that intravenous infusion of PDNO during renal ischemia reperfusion would improve post-ischemic renal function and microcirculation.METHODS: Sixteen sheep were anesthetized, mechanically ventilated, and surgically instrumented. The left renal artery was clamped for 90 min, and the effects of ischemia were studied for a total of 8 h. Fifteen minutes prior to the release of the clamp, intravenous infusions of PDNO (n = 8) or vehicle (1,2 propanediol + inorganic nitrite, n = 8) were initiated (180 nmol/kg/min for 30 min, thereafter 60 nmol/kg/min for the remainder of the experiment).RESULTS: Renal artery blood flow, cortical and medullary perfusion, and diuresis and creatinine clearance decreased in the left kidney post ischemia. However, in the sheep treated with PDNO, diuresis and creatinine clearance in the left kidney were significantly higher post ischemia compared to vehicle-treated animals (1.7 ± 0.5 vs 0.7 ± 0.3 ml/kg/h, p = 0.04 and 7.5 ± 2.1 vs 1.7 ± 0.6 ml/min, p = 0.02, respectively). Left renal medullary perfusion and oxygen uptake were higher in the PDNO group (73 ± 9 vs 37 ± 5% of baseline, p = 0.004 and 2.6 ± 0.4 vs 1.6 ± 0.3 ml/min, p = 0.02, respectively). PDNO significantly increased renal oxygen consumption and reduced the oxygen utilization for sodium reabsorption (p = 0.03 for both). Mean arterial blood pressure was significantly reduced by PDNO (83 ± 3 vs 94 ± 3 mmHg, p = 0.02) but was still within normal limits. Total renal blood flow was not affected, and there were no signs of increased blood methemoglobin concentrations or tachyphylaxis.CONCLUSIONS: The novel nitric oxide donor PDNO improved renal function after ischemia. PDNO also prevented the persistent reduction in medullary perfusion during reperfusion and improved renal oxygen utilization without severe side effects.
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41.
  •  
42.
  • Otterbeck, Alexander, et al. (författare)
  • Inhalation of specific anti-Pseudomonas aeruginosa IgY antibodies transiently decreases P. aeruginosa colonization of the airway in mechanically ventilated piglets
  • 2019
  • Ingår i: Intensive Care Medicine Experimental. - : SPRINGEROPEN. - 2197-425X. ; 7:24
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: P. aeruginosa is a pathogen frequently resistant to antibiotics and a common cause of ventilator-associated pneumonia (VAP). Non-antibiotic strategies to prevent or treat VAP are therefore of major interest. Specific polyclonal avian IgY antibodies have previously been shown to be effective against pneumonia caused by P. aeruginosa in rodents and against P. aeruginosa airway colonization in patients.Objectives: To study the effect of specific polyclonal anti-P. aeruginosa IgY antibodies (Pa-IgY) on colonization of the airways in a porcine model.Method: The pigs were anesthetized, mechanically ventilated, and subject to invasive hemodynamic monitoring and allocated to either receive 10(9) CFU nebulized P. aeruginosa (control, n=6) or 10(9) CFU nebulized P. aeruginosa + 200 mg Pa-IgY antibodies (intervention, n=6). Physiological measurement, blood samples, and tracheal cultures were then secured regularly for 27 h, after which the pigs were sacrificed and lung biopsies were cultured.Results: After nebulization, tracheal growth of P. aeruginosa increased in both groups during the experiment, but with lower growth in the Pa-IgY-treated group during the experiment (p = 0.02). Tracheal growth was 4.6 x 10(3) (9.1 x 10(2)-3.1 x 10(4)) vs. 4.8 x 10(4) (7.5 x 10(3)-1.4 x 10(5)) CFU/mL in the intervention group vs. the control group at 1h and 5.0 x 10(0) (0.0 x 10(0)-3.8 x 10(2)) vs. 3.3 x 10(4) (8.0 x 10(3)-1.4 x 10(5)) CFU/mL at 12 h in the same groups. During this time, growth in the intervention vs. control group was one to two orders of ten lower. After 12 h, the treatment effect disappeared and bacterial growth increased in both groups. The intervention group had lower body temperature and cardiac index and higher static compliance compared to the control group.Conclusion: In this porcine model, Pa-IgY antibodies lessen bacterial colonization of the airways.
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43.
  • Parenmark, Fredric, et al. (författare)
  • Increased risk of dying if discharged with inter-hospital transfer due to lack of ICU beds. A nationwide study from the Swedish Intensive Care Registry
  • 2019
  • Ingår i: Intensive Care Medicine Experimental. - : Springer. - 2197-425X. ; 7:Supplement 3, s. 634-634
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • INTRODUCTION. Most patients admitted to intensive care are discharged to a general ward in the same hospital, but some patients require transfer to another hospital. Indications for interhospital transfers (IHT) include referral for specialist treatment, lack of intensive care beds at the referring ICU and repatriation to ICU in home hospital [1].OBJECTIVES. To review mortality of ICU-patients undergoing IHT and analyse whether different indications for transfer render different mortalities.METHODS. Retrospective cohort register study using the Swedish Intensive Care Registry (SIR) during 2016-2018. The SIR collects data from 98.8% of Swedish ICUs including data on discharge from ICUs to other hospitals/ICUs. Transfers were divided into three categories: transfer due to medical reasons, lack of ICU beds or repatriation to ICU in home hospital. We analysed odds ratios (ORs) for dying within 30 days after discharge from ICU using risk adjusted (SAPS3 score) multi-level mixed effect logistic regression with ICUs as random effect.RESULTS. We identified 12,356 patients who were discharged to another ICU and hospital, i.e. inter-hospital transfers. The unadjusted mortality 30 days after IHT was 17.2 % compared to 12.4 % if discharged to ward in the same hospital. Mortality after IHT varied with the cause of discharge (Figure).Main diagnoses for transfer due to specialist treatment were subarachnoid haemorrhage, head injury and multi-trauma whilst for lack of ICU beds post cardiac arrest, respiratory failure and pneumonia dominated. Risk adjusted analysis showed a significantly increased risk of dying after discharge due to lack of ICU-beds in comparison with other reasons for IHTsCONCLUSION. The adjusted risk of dying within 30 days after interhospital transfer was greater among critically ill patients when the transfer was due to lack of beds in the referring ICU. The increased mortality lingered for at least 6 months underlining the importance to identify causes and intervene to avoid unnecessary loss of life.
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44.
  • Pellegrini, Mariangela, et al. (författare)
  • Expiratory Resistances Prevent Expiratory Diaphragm Contraction, Flow Limitation, and Lung Collapse
  • 2020
  • Ingår i: American Journal of Respiratory and Critical Care Medicine. - : AMER THORACIC SOC. - 1073-449X .- 1535-4970. ; 3:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Rationale: Tidal expiratory flow limitation (tidal-EFL) is not completely avoidable by applying positive end-expiratory pressure and may cause respiratory and hemodynamic complications in ventilated patients with lungs prone to collapse. During spontaneous breathing, expiratory diaphragmatic contraction counteracts tidal-EFL. We hypothesized that during both spontaneous breathing and controlled mechanical ventilation, external expiratory resistances reduce tidal-EFL.Objectives: To assess whether external expiratory resistances 1) affect expiratory diaphragmatic contraction during spontaneous breathing, 2) reduce expiratory flow and make lung compartments more homogeneous with more similar expiratory time constants, and 3) reduce tidal atelectasis, preventing hyperinflation.Methods: Three positive end-expiratory pressure levels and four external expiratory resistances were tested in 10 pigs after lung lavage. We analyzed expiratory diaphragmatic electric activity and respiratory mechanics. On the basis of computed tomography scans, four lung compartments-not inflated (atelectasis), poorly inflated, normally inflated, and hyperinflated-were defined.Measurements and Main Results: Consequently to additional external expiratory resistances, and mainly in lungs prone to collapse (at low positive end-expiratory pressure), 1) the expiratory transdiaphragmatic pressure decreased during spontaneous breathing by >10%, 2) expiratory flow was reduced and the expiratory time constants became more homogeneous, and 3) the amount of atelectasis at end-expiration decreased from 24% to 16% during spontaneous breathing and from 32% to 18% during controlled mechanical ventilation, without increasing hyperinflation.Conclusions: The expiratory modulation induced by external expiratory resistances preserves the positive effects of the expiratory brake while minimizing expiratory diaphragmatic contraction. External expiratory resistances optimize lung mechanics and limit tidal-EFL and tidal atelectasis, without increasing hyperinflation.
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45.
  • Piel, Sarah, et al. (författare)
  • Bioenergetic bypass using cell-permeable succinate, but not methylene blue, attenuates metformin-induced lactate production
  • 2018
  • Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 6:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Metformin is the most common pharmacological treatment for type 2 diabetes. It is considered safe but has been associated with the development of lactic acidosis under circumstances where plasma concentrations exceed therapeutic levels. Metformin-induced lactic acidosis has been linked to the drug's toxic effect on mitochondrial function. Current treatment strategies aim to remove the drug and correct for the acidosis. With a mortality of 20%, complementary treatment strategies are needed. In this study, it was investigated whether targeting mitochondria with pharmacological agents that bypass metformin-induced mitochondrial dysfunction can counteract the energetic deficit linked to toxic doses of metformin.METHODS: The redox agent methylene blue and the cell-permeable succinate prodrug NV118 were evaluated by measuring mitochondrial respiration and lactate production of human platelets exposed to metformin and co-treated with either of the two pharmacological bypass agents.RESULTS: The cell-permeable succinate prodrug NV118 increased mitochondrial respiration which was linked to phosphorylation by the ATP-synthase and alleviated the increase in lactate production induced by toxic doses of metformin. The redox agent methylene blue, in contrast, failed to mitigate the metformin-induced changes in mitochondrial respiration and lactate generation.CONCLUSIONS: The cell-permeable succinate prodrug NV118 bypassed the mitochondrial dysfunction and counteracted the energy deficit associated with toxic doses of metformin. If similar effects of NV118 prove translatable to an in vivo effect, this pharmacological strategy presents as a promising complementary treatment for patients with metformin-induced lactic acidosis.
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46.
  • Santos, Arnoldo, et al. (författare)
  • Impact of respiratory cycle during mechanical ventilation on beat-to-beat right ventricle stroke volume estimation by pulmonary artery pulse wave analysis
  • 2024
  • Ingår i: Intensive Care Medicine Experimental. - : Springer. - 2197-425X. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The same principle behind pulse wave analysis can be applied on the pulmonary artery (PA) pressure waveform to estimate right ventricle stroke volume (RVSV). However, the PA pressure waveform might be influenced by the direct transmission of the intrathoracic pressure changes throughout the respiratory cycle caused by mechanical ventilation (MV), potentially impacting the reliability of PA pulse wave analysis (PAPWA). We assessed a new method that minimizes the direct effect of the MV on continuous PA pressure measurements and enhances the reliability of PAPWA in tracking beat-to-beat RVSV.Methods: Continuous PA pressure and flow were simultaneously measured for 2-3 min in 5 pigs using a high-fidelity micro-tip catheter and a transonic flow sensor around the PA trunk, both pre and post an experimental ARDS model. RVSV was estimated by PAPWA indexes such as pulse pressure (SVPP), systolic area (SVSystAUC) and standard deviation (SVSD) beat-to-beat from both corrected and non-corrected PA signals. The reference RVSV was derived from the PA flow signal (SVref).Results: The reliability of PAPWA in tracking RVSV on a beat-to-beat basis was enhanced after accounting for the direct impact of intrathoracic pressure changes induced by MV throughout the respiratory cycle. This was evidenced by an increase in the correlation between SVref and RVSV estimated by PAPWA under healthy conditions: rho between SVref and non-corrected SVSD - 0.111 (0.342), corrected SVSD 0.876 (0.130), non-corrected SVSystAUC 0.543 (0.141) and corrected SVSystAUC 0.923 (0.050). Following ARDS, correlations were SVref and non-corrected SVSD - 0.033 (0.262), corrected SVSD 0.839 (0.077), non-corrected SVSystAUC 0.483 (0.114) and corrected SVSystAUC 0.928 (0.026). Correction also led to reduced limits of agreement between SVref and SVSD and SVSystAUC in the two evaluated conditions.Conclusions: In our experimental model, we confirmed that correcting for mechanical ventilation induced changes during the respiratory cycle improves the performance of PAPWA for beat-to-beat estimation of RVSV compared to uncorrected measurements. This was demonstrated by a better correlation and agreement between the actual SV and the obtained from PAPWA.
  •  
47.
  • Sievert, Theodor, et al. (författare)
  • Neurofilament light chain on intensive care admission is an independent predictor of mortality in COVID-19: a prospective multicenter study.
  • 2023
  • Ingår i: Intensive care medicine experimental. - 2197-425X. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and total-tau protein (tau) are novel blood biomarkers of neurological injury, and may be used to predict outcomes in critical COVID-19.A prospective multicentre cohort study of 117 consecutive and critically ill COVID-19 patients in six intensive care units (ICUs) in southern Sweden between May and November 2020. Serial NfL, GFAP and tau were analysed in relation to mortality, the Glasgow Outcome Scale Extended (GOSE) and the physical (PCS) and mental (MCS) components of health-related quality of life at one year.NfL, GFAP and tau on ICU admission predicted one-year mortality with an area under the curve (AUC) of 0.82 (95% confidence interval [CI] 0.74[Formula: see text]0.90), 0.72 (95% CI 0.62[Formula: see text]0.82) and 0.66 (95% CI 0.54[Formula: see text]0.77). NfL on admission was an independent predictor of one-year mortality (p= 0.039). Low NfL and GFAP values were associated with good PCS ([Formula: see text]45) at one year but not with good MCS ([Formula: see text]45) or GOSE ([Formula: see text]5).NfL on ICU admission was an independent predictor of mortality. High levels of NfL, GFAP and tau were associated with mortality but not with poor GOSE in survivors at one year. Low levels of NfL and GFAP were associated with improved physical health-related quality of life.
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48.
  • Skorup, Paul, et al. (författare)
  • Evaluation of an extracorporeal ozone-based bactericide system for the treatment of Escherichia coli sepsis
  • 2022
  • Ingår i: Intensive Care Medicine Experimental. - : Springer Nature. - 2197-425X. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Sepsis is associated with substantial mortality rates. Antibiotic treatment is crucial, but global antibiotic resistance is now classified as one of the top ten global public health risks facing humanity. Ozone (O-3) is an inorganic molecule with no evident function in the body. We investigated the bactericide properties of ozone, using a novel system of extracorporeal ozone blood treatment. We hypothesized that ozone would decrease the concentration of viable Escherichia coli (E. coli) in human whole blood and that the system would be technically feasible and physiologically tolerable in a clinically relevant model of E. coli sepsis in swine. Methods: The E. coli strain B09-11822, a clinical isolate from a patient with septic shock was used. The in vitro study treated E. coli infected human whole blood (n = 6) with ozone. The in vivo 3.5-h sepsis model randomized swine to E. coli infusion and ozone treatment (n = 5) or E. coli infusion and no ozone treatment (n = 5). Live E. coli, 5 x 10(7) colony-forming units (CFU/mL) was infused in a peripheral vein. Ozone treatment was initiated with a duration of 30 min after 1.5 h. Results: The single pass in vitro treatment decreased E. coli by 27%, mean 1941 to 1422 CFU/mL, mean of differences - 519.0 (95% CI - 955.0 to - 82.98,P= 0.0281). pO(2) increased (95% CI 31.35 to 48.80, P= 0.0007), pCO(2) decreased (95% CI -3.203 to - 1.134, P= 0.0069), oxyhemoglobin increased (95% CI 1.010 to 3.669, P= 0.0113). Methemoglobin was not affected. In the sepsis model, 9/10 swine survived. One swine randomized to ozone treatment died from septic shock before initiation of the treatment. Circulatory, respiratory, and metabolic parameters were not affected by the ozone treatment. E. coli in arterial blood, in organs and in aerobic and anaerobic blood cultures did not differ. Hemoglobin, leucocytes, and methemoglobin were not affected by the treatment. Conclusions: Ozone decreased the concentration of viable E. coli in human whole blood. The system was technically feasible and physiologically tolerable in porcine sepsis/septic shock and should be considered for further studies towards clinical applications.
  •  
49.
  • Sondergaard, S, et al. (författare)
  • The haemodynamic effects of crystalloid and colloid volume resuscitation on primary, derived and efficiency variables in post-CABG patients.
  • 2019
  • Ingår i: Intensive care medicine experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent studies in haemodynamic management have focused on fluid management and assessed its effects in terms of increase in cardiac output based on fluid challenges or variations in pulse pressure caused by cyclical positive pressure ventilation. The theoretical scope may be characterised as Starling-oriented. This approach ignores the actual events of right-sided excitation and left-sided response which is consistently described in a Guyton-oriented model of the cardiovascular system.Based on data from a previous study, we aim to elucidate the primary response to crystalloid and colloid fluids in terms of cardiac output, mean blood pressure and right atrial pressure as well as derived and efficiency variables defined in terms of Guyton venous return physiology.Re-analyses of previously published data.Cardiac output invariably increased on infusion of crystalloid and colloid solutions, whereas static and dynamic efficiency measures declined in spite of increasing pressure gradient for venous return.We argue that primary as well as derived and efficiency measures should be reported and discussed when haemodynamic studies are reported involving fluid administrations.
  •  
50.
  • Sperber, Jesper, et al. (författare)
  • Protective ventilation reduces Pseudomonas aeruginosa growth in lung tissue in a porcine pneumonia model
  • 2017
  • Ingår i: Intensive & Critical Care Nursing. - : Springer Science and Business Media LLC. - 0964-3397 .- 1532-4036. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Mechanical ventilation with positive end expiratory pressure and low tidal volume, i.e. protective ventilation, is recommended in patients with acute respiratory distress syndrome. However, the effect of protective ventilation on bacterial growth during early pneumonia in non-injured lungs is not extensively studied. The main objectives were to compare two different ventilator settings on Pseudomonas aeruginosa growth in lung tissue and the development of lung injury.METHODS: A porcine model of severe pneumonia was used. The protective group (n = 10) had an end expiratory pressure of 10 cm H2O and a tidal volume of 6 ml x kg-1. The control group (n = 10) had an end expiratory pressure of 5 cm H2O and a tidal volume of 10 ml x kg-1. 1011 colony forming units of Pseudomonas aeruginosa were inoculated intra-tracheally at baseline, after which the experiment continued for 6 h. Two animals from each group received only saline, and served as sham animals. Lung tissue samples from each animal were used for bacterial cultures and wet-to-dry weight ratio measurements.RESULTS: The protective group displayed lower numbers of Pseudomonas aeruginosa (p < 0.05) in the lung tissue, and a lower wet-to-dry ratio (p < 0.01) than the control group. The control group deteriorated in arterial oxygen tension/inspired oxygen fraction, whereas the protective group was unchanged (p < 0.01).CONCLUSIONS: In early phase pneumonia, protective ventilation with lower tidal volume and higher end expiratory pressure has the potential to reduce the pulmonary bacterial burden and the development of lung injury.
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