| 1. |
- Borges, Joao Batista, et al.
(författare)
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Real-time effects of PEEP and tidal volume on regional ventilation and perfusion in experimental lung injury
- 2020
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Ingår i: Intensive Care Medicine Experimental. - : SPRINGEROPEN. - 2197-425X. ; 8:1
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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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| 2. |
- Fisher, Jane, et al.
(författare)
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A functional observational battery for evaluation of neurological outcomes in a rat model of acute bacterial meningitis
- 2020
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Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 8
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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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| 3. |
- Hahn, RG
(författare)
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Water content of the endothelial glycocalyx layer estimated by volume kinetic analysis
- 2020
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Ingår i: Intensive care medicine experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 8:1, s. 29-
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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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| 4. |
- Pellegrini, Mariangela, et al.
(författare)
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Expiratory Resistances Prevent Expiratory Diaphragm Contraction, Flow Limitation, and Lung Collapse
- 2020
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - : AMER THORACIC SOC. - 1073-449X .- 1535-4970. ; 3:7
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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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| 5. |
- Svensson, Robert, et al.
(författare)
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Electrolyte-based calculation of fluid shifts after infusing 0.9% saline in severe hyperglycemia
- 2020
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Ingår i: Intensive Care Medicine Experimental. - : SPRINGER. - 2197-425X. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Early treatment of severe hyperglycemia involves large shifts of body fluids that entail a risk of hemodynamic instability. We studied the feasibility of applying a new electrolyte equation that estimates the degree of volume depletion and the distribution of infused 0.9% saline in this setting. Methods The new equation was applied to plasma and urinary concentrations of sodium and chloride measured before and 30 min after a 30-min infusion of 1 L of 0.9% saline on two consecutive days in 14 patients with severe hyperglycemia (mean age 50 years). The extracellular fluid (ECF) volume was also estimated based on the volume dilution kinetics of chloride. Results On day 1, the baseline ECF volume amounted to 11.5 L. The saline infusion expanded the ECF space by 160 mL and the intracellular fluid space by 375 mL. On day 2, the ECF volume was 15.5 L, and twice as much of the infused fluid remained in the ECF space. The chloride dilution kinetics yielded baseline ECF volumes of 11.6 and 15.2 L on day 1 and day 2, respectively. No net uptake of glucose to the cells occurred during the two 1-h measurement periods despite insulin administration in the intervening time period. Conclusions The electrolyte equation was feasible to apply in a group of hyperglycemic patients. The ECF space was 3 L smaller than expected on admission but normal on the second day. Almost half of the infused fluid was distributed intracellularly.
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| 6. |
- Tverring, Jonas, et al.
(författare)
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Repeated measures of Heparin-binding protein (HBP) and procalcitonin during septic shock : biomarker kinetics and association with cardiovascular organ dysfunction
- 2020
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Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Heparin-binding protein (HBP) is a neutrophil-derived pro-inflammatory protein, an inducer of endothelial dysfunction and vascular permeability and a promising prognostic biomarker in sepsis. This exploratory study aims to describe the kinetics of plasma HBP during septic shock and investigate an association between repeated measures of HBP concentration and cardiovascular organ dysfunction severity.METHODS: We included patients at or above 18 years with suspected septic shock on admission to the intensive care unit (ICU) during 2014 and 2016 to 2018. Plasma samples were collected from ICU admission and every 4 h for 72 h or until death or ICU discharge and batch analysed for HBP. Mean arterial blood pressure (MAP) and noradrenaline dose (NA dose) were recorded at each sampling time point, and systemic vascular resistance index (SVRI) was recorded when available from non-invasive monitoring. The association between HBP, NA dose, MAP and SVRI was assessed respectively using mixed-effects linear regression models. Procalcitonin (PCT) was used as a comparator.RESULTS: A total of 24 patients were included. The kinetics of plasma HBP was highly variable over time, with occasional >2-fold increases and decreases in between 4-h measurements. Every 100 ng/mL increase in HBP corresponded to a 30% increase in NA dose in a crude model (95% CI 3 to 60%, p = 0.03, nobs = 340), a 1.4-mmHg decrease in MAP in an adjusted model (95% CI - 1 to - 2.3 mmHg, p = 0.04) or a 99 dyne s cm-5 m-2 decrease in SVRI in another adjusted model (95% CI - 36 to - 162, p = 0.002, npat = 13). PCT had a stronger association to NA dose than HBP in a crude model but was not significantly associated to NA dose, MAP or SVRI in any time-adjusted model.CONCLUSIONS: Plasma HBP displayed a highly variable kinetic pattern during septic shock and was significantly associated to cardiovascular organ dysfunction severity over time.
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