| 1. |
- Antonsson, J B, et al.
(författare)
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Changes in gut intramucosal pH and gut oxygen extraction ratio in a porcine model of peritonitis and hemorrhage.
- 1995
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Ingår i: Critical Care Medicine. - : Ovid Technologies (Wolters Kluwer Health). - 0090-3493 .- 1530-0293. ; 23:11, s. 1872-81
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To establish the relationship between gut intramucosal pH and blood flow to the gut, gut oxygen delivery, and gut oxygen extraction ratio in a porcine model of peritonitis and hemorrhage.DESIGN: Prospective, controlled study.SETTING: Experimental laboratory in a university teaching hospital.SUBJECTS: Thirty pigs of both sexes, weighing 15 to 22 kg.INTERVENTIONS: Animals were anesthetized, intubated, and mechanically ventilated. A flow probe was placed around the superior mesenteric artery for registration of blood flow. A tonometer was placed in the lumen of midileum for calculation of gut intramucosal pH. Hourly, for 5 hrs, blood samples were taken from mixed venous, mesenteric venous, and arterial blood. Five animals served as controls, ten animals had peritonitis induced by fecal instillation in the abdominal cavity, five were bled stepwise, five were bled rapidly (to a mean arterial pressure of 30 mm Hg), and five were bled rapidly and reinfused after 3 hrs.MEASUREMENTS AND MAIN RESULTS: Both peritonitis and hemorrhage caused decreases in gut blood flow and intramucosal pH. In mild peritonitis, the intramucosal pH decrease preceded that of blood flow. In all experimental groups, oxygen delivery decreased over time; in both mild and severe peritonitis, this decrease was preceded by a decrease of intramucosal pH. Intramucosal pH correlated well with gut oxygen extraction ratio in peritonitis (r2 = .86). In hemorrhage, there was a correlation of r2 = .66, but in intramucosal pH of < 7.12, a further decrease was accompanied only by minor changes in extraction ratio.CONCLUSIONS: Since a reduction in blood flow was preceded by a decrease in intramucosal pH, low intramucosal pH in peritonitis cannot be explained by low flow alone. Gut oxygen delivery proved to be a poor indicator of gut acidosis (i.e., low intramucosal pH). In peritonitis, a decreasing intramucosal pH was associated with an increasing oxygen extraction ratio. In hemorrhage, this association had a sharp deflection point below which a further decrease in intramucosal pH occurred concomitantly with an unchanged gut oxygen extraction ratio. Increased extraction ratio was not sufficient, not even initially, to maintain aerobic metabolism (i.e., unchanged intramucosal pH).
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| 2. |
- Arctaedius, Isabelle, et al.
(författare)
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2021 European Resuscitation Council/ European Society of Intensive Care Medicine Algorithm for Prognostication of Poor Neurological Outcome After Cardiac Arrest—Can Entry Criteria Be Broadened?
- 2024
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Ingår i: Critical Care Medicine. - 0090-3493. ; 52:4, s. 531-541
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To explore broadened entry criteria of the 2021 European Resuscitation Council/European Society of Intensive Care Medicine (ERC/ ESICM) algorithm for neuroprognostication including patients with ongoing sedation and Glasgow Coma Scale-Motor score (GCS-M) scores 4–5. DESIGN: Retrospective multicenter observational study. SETTING: Four ICUs, Skane, Sweden. PATIENTS: Postcardiac arrest patients managed at targeted temperature 36°C, 2014–2018. Neurologic outcome was assessed after 2–6 months according to the Cerebral Performance Category scale. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In 794 included patients, median age was 69.5 years (interquartile range, 60.6–77.0 yr), 241 (30.4%) were female, 550 (69.3%) had an out-of-hospital cardiac arrest, and 314 (41.3%) had a shockable rhythm. Four hundred ninety-five patients were dead at follow-up, 330 of 495 died after a decision on withdrawal of life-sustaining therapies. At 72 hours after cardiac arrest 218 patients remained unconscious. The entry criteria of the original algorithm (GCS-M 1–3) was fulfilled by 163 patients and 115 patients with poor outcome were identified, with false positive rate (FPR) of 0% (95% CI, 0–79.4%) and sensitivity of 71.0% (95% CI, 63.6–77.4%). Inclusion of patients with ongoing sedation identified another 13 patients with poor outcome, generating FPR of 0% (95% CI, 0–65.8%) and sensitivity of 69.6% (95% CI, 62.6–75.8%). Inclusion of all unconscious patients (GCS-M 1–5), regardless of sedation, identified one additional patient, generating FPR of 0% (95% CI, 0–22.8) and sensitivity of 62.9% (95% CI, 56.1–69.2). The few patients with true negative prediction (patients with good outcome not fulfilling guideline criteria of a poor outcome) generated wide 95% CI for FPR. CONCLUSION: The 2021 ERC/ESICM algorithm for neuroprognostication predicted poor neurologic outcome with a FPR of 0%. Broadening inclusion criteria to include all unconscious patients regardless of ongoing sedation identified an additional small number of patients with poor outcome but did not affect the FPR. Results are limited by high rate of withdrawal of life-sustaining therapies and few patients with true negative prediction.
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| 3. |
- Baker, Tim, et al.
(författare)
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Single Deranged Physiologic Parameters Are Associated With Mortality in a Low-Income Country
- 2015
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 43:10, s. 2171-2179
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate whether deranged physiologic parameters at admission to an ICU in Tanzania are associated with in-hospital mortality and compare single deranged physiologic parameters to a more complex scoring system. Design: Prospective, observational cohort study of patient notes and admission records. Data were collected on vital signs at admission to the ICU, patient characteristics, and outcomes. Cutoffs for deranged physiologic parameters were defined a priori and their association with in-hospital mortality was analyzed using multivariable logistic regression. Setting: ICU at Muhimbili National Hospital, Dar es Salaam, Tanzania. Patients: All adults admitted to the ICU in a 15-month period. Measurements and Main Results: Two hundred sixty-nine patients were included: 54% female, median age 35 years. In-hospital mortality was 50%. At admission, 69% of patients had one or more deranged physiologic parameter. Sixty-four percent of the patients with a deranged physiologic parameter died in hospital compared with 18% without (p < 0.001). The presence of a deranged physiologic parameter was associated with mortality (adjusted odds ratio, 4.64; 95% CI, 1.95-11.09). Mortality increased with increasing number of deranged physiologic parameters (odds ratio per deranged physiologic parameter, 2.24 [1.53-3.26]). Every individual deranged physiologic parameter was associated with mortality with unadjusted odds ratios between 1.92 and 16.16. A National Early Warning Score of greater than or equal to 7 had an association with mortality (odds ratio, 2.51 [1.23-5.14]). Conclusion: Single deranged physiologic parameters at admission are associated with mortality in a critically ill population in a low-income country. As a measure of illness severity, single deranged physiologic parameters are as useful as a compound scoring system in this setting and could be termed danger signs. Danger signs may be suitable for the basis of routines to identify and treat critically ill patients.
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| 4. |
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| 5. |
- Bassford, Christopher R., et al.
(författare)
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U.K. Intensivists' Preferences for Patient Admission to ICU : Evidence From a Choice Experiment
- 2019
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Ingår i: Critical Care Medicine. - : Lippincott Williams & Wilkins. - 0090-3493 .- 1530-0293. ; 47:11, s. 1522-1530
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Deciding whether to admit a patient to the ICU requires considering several clinical and nonclinical factors. Studies have investigated factors associated with the decision but have not explored the relative importance of different factors, nor the interaction between factors on decision-making. We examined how ICU consultants prioritize specific factors when deciding whether to admit a patient to ICU.DESIGN: Informed by a literature review and data from observation and interviews with ICU clinicians, we designed a choice experiment. Senior intensive care doctors (consultants) were presented with pairs of patient profiles and asked to prioritize one of the patients in each task for admission to ICU. A multinomial logit and a latent class logit model was used for the data analyses.SETTING: Online survey across U.K. intensive care.SUBJECTS: Intensive care consultants working in NHS hospitals.MEASUREMENTS AND MAIN RESULTS: Of the factors investigated, patient's age had the largest impact at admission followed by the views of their family, and severity of their main comorbidity. Physiologic measures indicating severity of illness had less impact than the gestalt assessment by the ICU registrar. We identified four distinct decision-making patterns, defined by the relative importance given to different factors.CONCLUSIONS: ICU consultants vary in the importance they give to different factors in deciding who to prioritize for ICU admission. Transparency regarding which factors have been considered in the decision-making process could reduce variability and potential inequity for patients.
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| 6. |
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| 7. |
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| 8. |
- Berg, Sören, et al.
(författare)
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Proinflammatory cytokines increase the rate of glycolysis and adenosine-5'-triphosphate turnover in cultured rat enterocytes
- 2003
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 31:4, s. 1203-1212
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Measurements of steady-state adenosine-5'-triphosphate (ATP) levels in tissue samples from patients or experimental animals with sepsis or endotoxemia provide little information about the rate of ATP production and consumption in these conditions. Accordingly, we sought to use an in vitro "reductionist" model of sepsis to test the hypothesis that proinflammatory cytokines modulate ATP turnover rate. Design: In vitro "reductionist" model of sepsis. Setting: University laboratory. Subjects: Cultured rat enterocyte-like cells. Interventions: IEC-6 nontransformed rat enterocytes were studied under control conditions or following incubation for 24 or 48 hrs with cytomix, a mixture of tumor necrosis factor-a (10 ng/mL), interleukin-1ß (1 ng/mL), and interferon-? (1000 units/mL). To measure ATP turnover rate, ATP synthesis was acutely blocked by adding to the cells a mixture of 2-deoxyglucose (10 mM), potassium cyanide (8 mM), and antimycin A (1 µM). ATP content was measured at baseline (before metabolic inhibition) and 0.5, 1, 2, 5, and 10 mins later. Log-linear ATP decay curves were generated and the kinetics of ATP utilization thereby calculated. Measurements and Main Results: ATP consumption rate was higher in cytomix-stimulated compared with control cells (3.11 ± 1.39 vs. 1.25 ± 0.66 nmol/min, respectively, p < .01). Similarly, the half-time for ATP disappearance was shorter in cytomix-stimulated compared with control cells (2.63 ± 1.00 vs. 6.21 ± 3.49, p < .05). In contrast to these findings, the rate of ATP disappearance was similar in cytokine-naïve and immunostimulated IEC-6 cells when protein and nucleic acid synthesis were inhibited by adding 50 µg/mL cycloheximide and 5 µg/mL actinomycin D to cultures for 4 hrs. The rates of glucose consumption and lactate production were significantly greater in cytomix-stimulated compared with controls cells. Conclusions: Incubation of IEC-6 cells with cytomix significantly increased ATP turnover. Increased ATP turnover rate was supported by increases in the rate of anaerobic glycolysis. These findings support the view that proinflammatory mediators impose a metabolic demand on visceral cells. In sepsis, cells may be more susceptible to dysfunction on the basis of diminished oxygen delivery and/or mitochondrial dysfunction.
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| 9. |
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| 10. |
- Borges, João Batista, et al.
(författare)
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Early inflammation mainly affects normally and poorly aerated lung in experimental ventilator-induced lung injury
- 2014
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 42:4, s. e279-e287
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The common denominator in most forms of ventilator-induced lung injury is an intense inflammatory response mediated by neutrophils. PET with [F]fluoro-2-deoxy-D-glucose can be used to image cellular metabolism, which, during lung inflammatory processes, mainly reflects neutrophil activity, allowing the study of regional lung inflammation in vivo. The aim of this study was to assess the location and magnitude of lung inflammation using PET imaging of [F]fluoro-2-deoxy-D-glucose in a porcine experimental model of early acute respiratory distress syndrome.DESIGN: Prospective laboratory investigation.SETTING: A university animal research laboratory.SUBJECTS: Seven piglets submitted to experimental ventilator-induced lung injury and five healthy controls.INTERVENTIONS: Lung injury was induced by lung lavages and 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressure and high inspiratory pressures. All animals were subsequently studied with dynamic PET imaging of [F]fluoro-2-deoxy-D-glucose. CT scans were acquired at end expiration and end inspiration.MEASUREMENTS AND MAIN RESULTS: [F]fluoro-2-deoxy-D-glucose uptake rate was computed for the whole lung, four isogravitational regions, and regions grouping voxels with similar density. Global and intermediate gravitational zones [F]fluoro-2-deoxy-D-glucose uptakes were higher in ventilator-induced lung injury piglets compared with controls animals. Uptake of normally and poorly aerated regions was also higher in ventilator-induced lung injury piglets compared with control piglets, whereas regions suffering tidal recruitment or tidal hyperinflation had [F]fluoro-2-deoxy-D-glucose uptakes similar to controls.CONCLUSIONS: The present findings suggest that normally and poorly aerated regions-corresponding to intermediate gravitational zones-are the primary targets of the inflammatory process accompanying early experimental ventilator-induced lung injury. This may be attributed to the small volume of the aerated lung, which receives most of ventilation.
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| 11. |
- Borges, Joao Batista, et al.
(författare)
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Lung Inflammation Persists After 27 Hours of Protective Acute Respiratory Distress Syndrome Network Strategy and Is Concentrated in the Nondependent Lung
- 2015
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 43:5, s. E123-E132
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Tidskriftsartikel (refereegranskat)abstract
- Objective: PET with [F-18]fluoro-2-deoxy-D-glucose can be used to image cellular metabolism, which during lung inflammation mainly reflects neutrophil activity, allowing the study of regional lung inflammation in vivo. We aimed at studying the location and evolution of inflammation by PET imaging, relating it to morphology (CT), during the first 27 hours of application of protective-ventilation strategy as suggested by the Acute Respiratory Distress Syndrome Network, in a porcine experimental model of acute respiratory distress syndrome. Design: Prospective laboratory investigation. Setting: University animal research laboratory. Subjects: Ten piglets submitted to an experimental model of acute respiratory distress syndrome. Interventions: Lung injury was induced by lung lavages and 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressure and high inspiratory pressures. During 27 hours of controlled mechanical ventilation according to Acute Respiratory Distress Syndrome Network strategy, the animals were studied with dynamic PET imaging of [F-18]fluoro-2-deoxy-D-glucose at two occasions with 24-hour interval between them. Measurements and Main Results: [F-18]fluoro-2-deoxy-D-glucose uptake rate was computed for the total lung, four horizontal regions from top to bottom (nondependent to dependent regions) and for voxels grouped by similar density using standard Hounsfield units classification. The global lung uptake was elevated at 3 and 27 hours, suggesting persisting inflammation. In both PET acquisitions, nondependent regions presented the highest uptake (p = 0.002 and p = 0.006). Furthermore, from 3 to 27 hours, there was a change in the distribution of regional uptake (p = 0.003), with more pronounced concentration of inflammation in nondependent regions. Additionally, the poorly aerated tissue presented the largest uptake concentration after 27 hours. Conclusions: Protective Acute Respiratory Distress Syndrome Network strategy did not attenuate global pulmonary inflammation during the first 27 hours after severe lung insult. The strategy led to a concentration of inflammatory activity in the upper lung regions and in the poorly aerated lung regions. The present findings suggest that the poorly aerated lung tissue is an important target of the perpetuation of the inflammatory process occurring during ventilation according to the Acute Respiratory Distress Syndrome Network strategy.
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| 12. |
- Borges, João Batista, et al.
(författare)
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Open Lung in Lateral Decubitus With Differential Selective Positive End-Expiratory Pressure in an Experimental Model of Early Acute Respiratory Distress Syndrome
- 2015
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 43:10, s. e404-e411
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: After lung recruitment, lateral decubitus and differential lung ventilation may enable the titration and application of optimum-selective positive end-expiratory pressure values for the dependent and nondependent lungs. We aimed at compare the effects of optimum-selective positive end-expiratory pressure with optimum global positive end-expiratory pressure on regional collapse and aeration distribution in an experimental model of acute respiratory distress syndrome.DESIGN: Prospective laboratory investigation.SETTING: University animal research laboratory.SUBJECTS: Seven piglets.INTERVENTIONS: A one-hit injury acute respiratory distress syndrome model was established by repeated lung lavages. After replacing the tracheal tube by a double-lumen one, we initiated lateral decubitus and differential ventilation. After maximum-recruitment maneuver, decremental positive end-expiratory pressure titration was performed. The positive end-expiratory pressure corresponding to maximum dynamic compliance was defined globally (optimum global positive end-expiratory pressure) and for each individual lung (optimum-selective positive end-expiratory pressure). After new maximum-recruitment maneuver, two steps were performed in randomized order (15 min each): ventilation applying the optimum global positive end-expiratory pressure and the optimum-selective positive end-expiratory pressure. CT scans were acquired at end expiration and end inspiration.MEASUREMENTS AND MAIN RESULTS: Aeration homogeneity was evaluated as a nondependent/dependent ratio (percent of total gas content in upper lung/percent of total gas content in lower lung) and tidal recruitment as the difference in the percent mass of nonaerated tissue between expiration and inspiration. At the end of the 15-minute optimum-selective positive end-expiratory pressure, compared with the optimum global positive end-expiratory pressure, resulted in 1) decrease in the percent mass of collapse in the lower lung at expiratory CT (19% ± 15% vs 4% ± 5%; p = 0.03); 2) decrease in the nondependent/dependent ratio between the optimum global positive end-expiratory pressure-expiratory-CT and optimum-selective positive end-expiratory pressure-expiratory-CT (3.7 ± 1.2 vs 0.8 ± 0.5; p = 0.01); 3) decrease in the nondependent/dependent ratio between the optimum global positive end-expiratory pressure-inspiratory-CT and optimum-selective positive end-expiratory pressure-inspiratory-CT (2.8 ± 1.1 vs 0.6 ± 0.3; p = 0.01); and 4) less tidal recruitment (p = 0.049).CONCLUSIONS: After maximum lung recruitment, lateral decubitus and differential lung ventilation enabled the titration of optimum-selective positive end-expiratory pressure values for the dependent and the nondependent lungs, made possible the application of an optimized regional open lung approach, promoted better aeration distribution, and minimized lung tissue inhomogeneities.
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| 13. |
- Borgquist, Ola, et al.
(författare)
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Dysglycemia, glycemic variability, and outcome after cardiac arrest and temperature management at 33°C and 36°C
- 2017
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Ingår i: Critical Care Medicine. - 0090-3493. ; 45:8, s. 1337-1343
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Dysglycemia and glycemic variability are associated with poor outcomes in critically ill patients. Targeted temperature management alters blood glucose homeostasis. We investigated the association between blood glucose concentrations and glycemic variability and the neurologic outcomes of patients randomized to targeted temperature management at 33°C or 36°C after cardiac arrest. Design: Post hoc analysis of the multicenter TTM-trial. Primary outcome of this analysis was neurologic outcome after 6 months, referred to as "Cerebral Performance Category." Setting: Thirty-six sites in Europe and Australia. Patients: All 939 patients with out-of-hospital cardiac arrest of presumed cardiac cause that had been included in the TTM-trial. Interventions: Targeted temperature management at 33°C or 36°C. Measurements and Main Results: Nonparametric tests as well as multiple logistic regression and mixed effects logistic regression models were used. Median glucose concentrations on hospital admission differed significantly between Cerebral Performance Category outcomes (p < 0.0001). Hyper- and hypoglycemia were associated with poor neurologic outcome (p = 0.001 and p = 0.054). In the multiple logistic regression models, the median glycemic level was an independent predictor of poor Cerebral Performance Category (Cerebral Performance Category, 3-5) with an odds ratio (OR) of 1.13 in the adjusted model (p = 0.008; 95% CI, 1.03-1.24). It was also a predictor in the mixed model, which served as a sensitivity analysis to adjust for the multiple time points. The proportion of hyperglycemia was higher in the 33°C group compared with the 36°C group. Conclusion: Higher blood glucose levels at admission and during the first 36 hours, and higher glycemic variability, were associated with poor neurologic outcome and death. More patients in the 33°C treatment arm had hyperglycemia.
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| 14. |
- Brauer, Kirk I, et al.
(författare)
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Hypoproteinemia does not alter plasma volume expansion in response to a 0.9% saline bolus in awake sheep
- 2010
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Ingår i: CRITICAL CARE MEDICINE. - : Williams and Wilkins. - 0090-3493 .- 1530-0293. ; 38:10, s. 2011-2015
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To test the hypothesis that hypoproteinemia reduces plasma volume expansion produced by a bolus of crystalloid solution given to awake sheep. Design: Prospective and observational. Setting: Laboratory. Subjects: Five female merino sheep (n = 5) weighing 37 +/- 3 kg were anesthetized. Interventions: Each animal was subjected to a 5-day test period: day 1: 50 mL/min 0.9% saline infusion over 20 mins. Days 2-4: daily plasmapheresis and replacement of the shed plasma with 6 L of 0.9% saline were performed in increments. Measurements and Main Results: Fractional plasma volume expansion after rapid infusion of saline on days 1 and 5 was calculated from changes in hemoglobin concentration. There was a significant reduction in total plasma protein concentration after plasmapheresis (p andlt; .05). Colloid osmotic pressures were also significantly lowered (p andlt; .05). A crystalloid infusion of 0.9% saline did not alter any of these values compared with baseline. The hemodynamic measurements did not show significant differences between the experiments. The plasma volume expansion reached approximately 20% at the end of infusion and stayed at 10-15% during the experiments. No difference was found in plasma volume expansion produced by a bolus of 50 mL/min of 0.9% in the hypoproteinemic state when compared with the euproteinemic state (p = .61). No difference in cumulative urinary output was found between the two states. Conclusions: In contrast to our hypothesis, severe acute hypoproteinemia does not reduce plasma volume expansion in response to 50 mL/min 0.9% saline infusion in nonspleenectomized sheep when compared with the resultant plasma volume expansion after a 50 mL/min of 0.9% infusion in the euproteinemic state.
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| 15. |
- Broche, Ludovic, et al.
(författare)
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Dynamic Mechanical Interactions Between Neighboring Airspaces Determine Cyclic Opening and Closure in Injured Lung
- 2017
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 45:4, s. 687-694
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Positive pressure ventilation exposes the lung to mechanical stresses that can exacerbate injury. The exact mechanism of this pathologic process remains elusive. The goal of this study was to describe recruitment/derecruitment at acinar length scales over short-time frames and test the hypothesis that mechanical interdependence between neighboring lung units determines the spatial and temporal distributions of recruitment/derecruitment, using a computational model. Design: Experimental animal study. Setting: International synchrotron radiation laboratory. Subjects: Four anesthetized rabbits, ventilated in pressure controlled mode. Interventions: The lung was consecutively imaged at - 1.5-minute intervals using phase-contrast synchrotron imaging, at positive end expiratory pressures of 12, 9, 6, 3, and 0 cm H2O before and after lavage and mechanical ventilation induced injury. The extent and spatial distribution of recruitment/derecruitment was analyzed by subtracting subsequent images. In a realistic lung structure, we implemented a mechanistic model in which each unit has individual pressures and speeds of opening and closing. Derecruited and recruited lung fractions (F-derecruaed, F-recruited) were computed based on the comparison of the aerated volumes at successive time points. Measurements and Main Results: Alternative recruitment/derecruitment occurred in neighboring alveoli over short-time scales in all tested positive end-expiratory pressure levels and despite stable pressure controlled mode. The computational model reproduced this behavior only when parenchymal interdependence between neighboring acini was accounted for. Simulations closely mimicked the experimental magnitude of F-derecruited and F-recruited when mechanical interdependence was included, while its exclusion gave F-recruited values of zero at positive end -expiratory pressure greater than or equal to 3 cm H2O. Conclusions: These findings give further insight into the microscopic behavior of the injured lung and provide a means of testing protective-ventilation strategies to prevent recruitment/derecruitment and subsequent lung damage.
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| 16. |
- Broche, Ludovic, et al.
(författare)
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Individual Airway Closure Characterized In Vivo by Phase-Contrast CT Imaging in Injured Rabbit Lung
- 2019
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Ingår i: Critical Care Medicine. - : LIPPINCOTT WILLIAMS & WILKINS. - 0090-3493 .- 1530-0293. ; 47:9, s. E774-E781
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Airway closure is involved in adverse effects of mechanical ventilation under both general anesthesia and in acute respiratory distress syndrome patients. However, direct evidence and characterization of individual airway closure is lacking. Here, we studied the same individual peripheral airways in intact lungs of anesthetized and mechanically ventilated rabbits, at baseline and following lung injury, using high-resolution synchrotron phase-contrast CT.Design: Laboratory animal investigation.Setting: European synchrotron radiation facility.Subjects: Six New-Zealand White rabbits.Interventions: The animals were anesthetized, paralyzed, and mechanically ventilated in pressure-controlled mode (tidal volume, 6 mL/kg; respiratory rate, 40; Fio(2), 0.6; inspiratory:expiratory, 1:2; and positive end-expiratory pressure, 3 cm H2O) at baseline. Imaging was performed with a 47.5 x 47.5 x 47.5 mu m voxel size, at positive end-expiratory pressure 12, 9, 6, 3, and 0 cm H2O. The imaging sequence was repeated after lung injury induced by whole-lung lavage and injurious ventilation in four rabbits. Cross-sections of the same individual airways were measured.Measurements and Main Results: The airways were measured at baseline (n = 48; radius, 1.7 to 0.21 mm) and after injury (n = 32). Closure was observed at 0 cm H2O in three of 48 airways (6.3%; radius, 0.350.08 mm at positive end-expiratory pressure 12) at baseline and five of 32 (15.6%; radius, 0.28 +/- 0.09 mm) airways after injury. Cross-section was significantly reduced at 3 and 0 cm H2O, after injury, with a significant relation between the relative change in cross-section and airway radius at 12 cm H2O in injured, but not in normal lung (R = 0.60; p < 0.001).Conclusions: Airway collapsibility increases in the injured lung with a significant dependence on airway caliber. We identify "compliant collapse" as the main mechanism of airway closure in initially patent airways, which can occur at more than one site in individual airways.
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| 17. |
- Broman, Marcus E., et al.
(författare)
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The Relationship between Heart Rate and Body Temperature in Critically Ill Patients
- 2021
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 49:3, s. 327-331
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The presence of tachycardia in critically ill patients is frequently used as an indication of severity of illness and to guide treatment decisions but can be influenced by body temperature, thus confounding its interpretation. There are few data available on the relationship between body temperature and heart rate in critically ill patients. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Mixed medical-surgical university hospital ICU. PATIENTS: All patients admitted to the ICU between November 2006 and August 2019. MEASUREMENTS AND MAIN RESULTS: Body temperature was recorded in the electronic medical records at least hourly, from invasive measurements (esophageal probe, indwelling urinary catheter, pulse contour cardiac output monitoring system, or pulmonary artery catheter) or manual tympanic recordings. Heart rate was monitored continuously and hourly values were recorded in the electronic medical record. Change in heart rate with change in body temperature was assessed by extracting pairs of simultaneous body temperature and corresponding heart rate measurements from the electronic medical record: 472,941 simultaneous pairs were obtained from the 9,046 patients admitted during the study period. Each 1°C increase in body temperature between 32.0°C and 42.0°C was associated with an 8.35 beats/min increase in heart rate. Crude linear regression showed an r2of 0.855 between body temperature and heart rate. Heart rate increased more in females than in males (9.46 vs 7.24 beats/min for each 1°C, p < 0.0001); this relationship was not affected by age or adrenergic drugs. The increase in heart rate was related to the severity of organ dysfunction. CONCLUSIONS: Increase in body temperature is associated with a linear increase in heart rate of 9.46 beats/min/°C in female and 7.24 beats/min/°C in male patients. These observations will help to correctly interpret heart rate values at different body temperatures and enable more accurate evaluation of other factors associated with tachycardia.
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| 18. |
- Brynildsen, Jon, et al.
(författare)
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Circulating Secretoneurin Concentrations After Cardiac Surgery : Data From the FINNish Acute Kidney Injury Heart Study
- 2019
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 47:5, s. E412-E419
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Tidskriftsartikel (refereegranskat)abstract
- Objectives:Secretoneurin is associated with cardiomyocyte Ca2+ handling and improves risk prediction in patients with acute myocardial dysfunction. Whether secretoneurin improves risk assessment on top of established cardiac biomarkers and European System for Cardiac Operative Risk Evaluation II in patients undergoing cardiac surgery is not known.Design:Prospective, observational, single-center sub-study of a multicenter study.Setting:Prospective observational study of survival in patients undergoing cardiac surgery.Patients:A total of 619 patients undergoing cardiac surgery.Interventions:Patients underwent either isolated coronary artery bypass graft surgery, single noncoronary artery bypass graft surgery, two procedures, or three or more procedures. Procedures other than coronary artery bypass graft were valve surgery, surgery on thoracic aorta, and other cardiac surgery.Measurements and Main Results:We measured preoperative and postoperative secretoneurin concentrations and adjusted for European System for Cardiac Operative Risk Evaluation II, N-terminal pro-B-type natriuretic peptide, and cardiac troponin T concentrations in multivariate analyses. During 961 days of follow- up, 59 patients died (9.5%). Secretoneurin concentrations were higher among nonsurvivors compared with survivors, both before (168 pmol/L [quartile 1-3, 147-206 pmol/L] vs 160 pmol/L [131-193 pmol/L]; p = 0.039) and after cardiac surgery (173 pmol/L [129-217 pmol/L] vs 143 pmol/L [111-173 pmol/L]; p < 0.001). Secretoneurin concentrations decreased from preoperative to postoperative measurements in survivors, whereas we observed no significant decrease in secretoneurin concentrations among nonsurvivors. Secretoneurin concentrations were weakly correlated with established risk indices. Patients with the highest postoperative secretoneurin concentrations had worse outcome compared with patients with lower secretoneurin concentrations (p < 0.001 by the log-rank test) and postoperative secretoneurin concentrations were associated with time to death in multivariate Cox regression analysis: hazard ratio ln secretoneurin 2.96 (95% CI, 1.46-5.99; p = 0.003). Adding postoperative secretoneurin concentrations to European System for Cardiac Operative Risk Evaluation II improved patient risk stratification, as assessed by the integrated discrimination index: 0.023 (95% CI, 0.0043-0.041; p = 0.016).Conclusions:Circulating postoperative secretoneurin concentrations provide incremental prognostic information to established risk indices in patients undergoing cardiac surgery.
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| 19. |
- Carlsson, Markus, et al.
(författare)
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Inflammatory and circulatory effects of the reduction of endotoxin concentration in established porcine endotoxemic shock : a model of endotoxin elimination
- 2009
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 37:3, s. 1031-e4
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To study whether a reduction of the endotoxin load, once a generalized inflammatory state has been established, reduces the inflammatory response and endotoxin-induced effects on circulation, hypoperfusion, and organ dysfunction.Design:Prospective parallel-grouped placebo-controlled randomized interventional experimental study.Setting:University research unit.Subjects: Healthy pigs.Interventions:The animals were subjected to a continuous endotoxin infusion rate of either 4.0 or 0.063 µg endotoxin × kg-1 × h-1 for 1, 2, or 6 hours. The 1- and 2-hour infusion groups represented the applied therapy by a reduction of the endotoxin load of 5/6 and 2/3, respectively.Measurements and Main Results:During a 6-hour experiment, laboratory and physiologic parameters were recorded hourly in 26 anesthetized and mechanically ventilated pigs. Primary end point was to detect differences in tumor necrosis factor-[alpha] (TNF-[alpha]) concentration during the last 3 hours of the experiment. Despite the early reduction of the endotoxin load, no effect on TNF-[alpha] concentration was observed. Similarly, in circulatory parameters, such as mean arterial pressure and oxygen delivery, and in platelet count and renal function, no effects were noted. However, there was some improvement in pulmonary compliance and function as determined by Pao2, Paco2, and pH. These changes were associated with slight improvements in leukocyte response and capillary leakage.Conclusions:Termination of the endotoxin infusion represents an incontestable model of endotoxin concentration reduction. Endotoxin elimination strategies applied at the TNF-[alpha] peak or later will have very little or no effect on TNF-[alpha]–mediated toxicity. Nevertheless, there was an effect on the leukocyte response that was associated with an improvement in respiratory function and microcirculation, making it impossible to rule out fully the beneficial effect of this strategy. However, the effects were limited in relation to the magnitude of the endotoxin concentration reduction and the very early application of the antiendotoxin measure.
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| 20. |
- Chen, Ke-Ling, et al.
(författare)
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Effects of Tocilizumab on Experimental Severe Acute Pancreatitis and Associated Acute Lung Injury
- 2016
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Ingår i: Critical Care Medicine. - : LIPPINCOTT WILLIAMS & WILKINS. - 0090-3493 .- 1530-0293. ; 44:8, s. E664-E677
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine the therapeutic effects of tocilizumab, an antibody against interleukin-6 receptor, on experimental severe acute pancreatitis and associated acute lung injury. The optimal dose of tocilizumab and the activation of interleukin-6 inflammatory signaling were also investigated. Design: Randomized experiment. Setting: Research laboratory at a university hospital. Subject: Experimental severe acute pancreatitis in rats. Interventions: Severe acute pancreatitis was induced by retrograde injection of sodium taurocholate (50 mg/kg) into the biliopancreatic duct. In dose-study, rats were administered with different doses of tocilizumab (1, 2, 4, 8, and 16 mg/kg) through the tail vein after severe acute pancreatitis induction. In safety-study, rats without severe acute pancreatitis induction were treated with high doses of tocilizumab (8, 16, 32, and 64 mg/kg). Serum and tissue samples of rats in time-study were collected for biomolecular and histologic evaluations at different time points (2, 6, 12, 18, and 24 hr). Measurements and Main Results: 1) Under the administration of tocilizumab, histopathological scores of pancreas and lung were decreased, and severity parameters related to severe acute pancreatitis and associated lung injury, including serum amylase, C-reactive protein, lung surfactant protein level, and myeloperoxidase activity, were all significant alleviated in rat models. 2) Dose-study demonstrated that 2 mg/kg tocilizumab was the optimal treatment dose. 3) Basing on multi-organ pathologic evaluation, physiological and biochemical data, no adverse effect and toxicity of tocilizumab were observed in safety-study. 4) Pancreatic nuclear factor-kappa B and signal transducer and activator of transcription 3 were deactivated, and the serum chemokine (C-X-C motif) ligand 1 was down-regulated after tocilizumab administration. Conclusions: Our study demonstrated tocilizumab, as a marketed drug commonly used for immune-mediated diseases, was safe and effective for the treatment of experimental severe acute pancreatitis and associated acute lung injury. Our findings provide experimental evidences for potential clinical application of tocilizumab in severe acute pancreatitis and associated complications.
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| 21. |
- Chew, Michelle, et al.
(författare)
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Pediatric cardiac output measurement using surface integration of velocity vectors : an in vivo validation study
- 2000
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Ingår i: Critical Care Medicine. - : Ovid Technologies (Wolters Kluwer Health). - 0090-3493 .- 1530-0293. ; 28:11, s. 3664-3671
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To test the accuracy and reproducibility of systemic cardiac output (CO) measurements using surface integration of velocity vectors (SIVV) in a pediatric animal model with hemodynamic instability and to compare SIVV with traditional pulsed-wave Doppler measurements.Design: Prospective, comparative study.Setting: Animal research laboratory at a university medical center.Subjects: Eight piglets weighing 10-15 kg.Interventions: Hemodynamic instability was induced by using inhalation of isoflurane and infusions of colloid and dobutamine.Measurements: SIVV CO was measured at the left ventricular outflow tract, the aortic valve, and ascending aorta. Transit time CO was used as the reference standard.Results: There was good agreement between SIVV and transit time CO. At high frame rates, the mean difference ± 2 sd between the two methods was 0.01 ± 0.27 L/min for measurements at the left ventricular outflow tract, 0.08 ± 0.26 L/min for the ascending aorta, and 0.06 ± 0.25 L/min for the aortic valve. At low frame rates, measurements were 0.06 ± 0.25, 0.19 ± 0.32, and 0.14 ± 0.30 L/min for the left ventricular outflow tract, ascending aorta, and aortic valve, respectively. There were no differences between the three sites at high frame rates. Agreement between pulsed-wave Doppler and transit time CO was poorer, with a mean difference ± 2 sd of 0.09 ± 0.93 L/min. Repeated SIVV measurements taken at a period of relative hemodynamic stability differed by a mean difference ±2 sd of 0.01 ± 0.22 L/min, with a coefficient of variation = 7.6%. Intraobserver coefficients of variation were 5.7%, 4.9%, and 4.1% at the left ventricular outflow tract, ascending aorta, and aortic valve, respectively. Interobserver variability was also small, with a coefficient of variation = 8.5%.Conclusions: SIVV is an accurate and reproducible flow measurement technique. It is a considerable improvement over currently used methods and is applicable to pediatric critical care.
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| 22. |
- Claesson, Jonas, et al.
(författare)
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Negative mesenteric effects of lung recruitment maneuvers in oleic acid lung injury are transient and short lasting.
- 2007
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 35:1, s. 230-238
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To test the hypothesis that repeated recruitment maneuvers (RMs) have sustained negative effects on mesenteric circulation, metabolism, and oxygenation 60 mins after RMs in pigs with oleic acid lung injury. Further, we aimed to test the hypothesis that an infusion of prostacyclin (PC) at 33 ng.kg.min would attenuate such possible negative mesenteric effects. DESIGN: Randomized, experimental, controlled study. SETTING: University hospital animal laboratory. SUBJECTS: A total of 31 anesthetized, fluid-resuscitated pigs with oleic acid lung injury. INTERVENTIONS: Animals were randomized to one of the following four groups: a control group (n = 7) that received no intervention, recruitment group (n = 8) that underwent the RM sequence, a prostacyclin group (n = 8) that received an infusion of PC, and a recruitment-prostacyclin group (n = 8) that received an infusion of PC and concomitant RM sequence. MEASUREMENTS AND MAIN RESULTS: We measured systemic and mesenteric hemodynamic variables, jejunal mucosal perfusion, mesenteric lactate flux, jejunal tissue oxygen tension, and mesenteric oxygen delivery, uptake, and extraction ratio. Five minutes after RMs, mesenteric oxygen extraction ratio and mesenteric lactate flux were more prominently increased in the recruitment group, giving evidence of worsened mesenteric conditions after RMs. These signs of worsened conditions were further supported by more decreased jejunal tissue oxygen tension and portal vein oxygen saturation in the recruitment group. PC preserved mesenteric oxygenation, as indicated by less of a decrease in portal vein oxygen saturation at the time corresponding to 5 mins after RM and less of a decrease in mesenteric oxygen delivery at the time corresponding to 15 mins after RM. PC preserved mesenteric oxygenation as indicated by less of a decrease in portal vein oxygen saturation at 5 mins after RM and an attenuated increase in mesenteric oxygen extraction ratio at 5 mins after RM. There was a trend toward worsened jejunal mucosal perfusion, although not significant. CONCLUSIONS: In an oleic acid lung injury model, three repeated RMs did not improve systemic oxygenation or lung mechanics. Negative effects on mesenteric oxygenation and metabolism were transient and short lasting. The intestinal effects of PC during RMs were minor and opposing, showing preserved oxygenation but a trend toward worsened mucosal perfusion.
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| 23. |
- Claesson Lingehall, Helena, et al.
(författare)
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Preoperative Cognitive Performance and Postoperative Delirium Are independently Associated With Future Dementia in Older People Who Have Undergone Cardiac Surgery : A Longitudinal Cohort Study
- 2017
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 45:8, s. 1295-1303
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate if postoperative delirium was associated with the development of dementia within 5 years after cardiac surgery.Design: Longitudinal cohort study.Setting: Cardiothoracic Division, Umeå University Hospital, Sweden.Patients: Patients aged 70 years old or older (n = 114) scheduled for routine cardiac procedures with cardiopulmonary bypass without documented dementia were enrolled in 2009.Intervention: Structured assessments were performed preoperatively, 1 and 4 days after extubation, and 1, 3, and 5 years postoperatively.Measurements and Main Results: Patients were assessed comprehensively, including cognitive and physical function, coexisting medical conditions, demographic characteristics, and medications. Diagnoses of delirium, depression, and dementia were made according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision criteria. During the 5-year period, 30 of 114 participants (26.3%) developed dementia. Postoperative delirium had occurred in 87% of those who later developed dementia. A multivariable logistic regression model showed a lower preoperative Mini-Mental State Examination score (p < 0.001; odds ratio, 0.68; 95% CI, 0.54–0.84) and the occurrence of postoperative delirium (p = 0.002; odds ratio, 7.57; 95% CI, 2.15–26.65) were associated with dementia occurrence.Conclusions: Our findings suggest that older patients with reduced preoperative cognitive functions or who develop postoperative delirium are at risk of developing dementia within 5 years after cardiac surgery. Cognitive functions should be screened for preoperatively, those who develop postoperative delirium should be followed up to enable early detection of dementia symptoms, and management should be implemented.
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| 24. |
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| 25. |
- Cronin, John N., et al.
(författare)
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Mechanical Ventilation Redistributes Blood to Poorly Ventilated Areas in Experimental Lung Injury*
- 2020
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Ingår i: Critical Care Medicine. - : LIPPINCOTT WILLIAMS & WILKINS. - 0090-3493 .- 1530-0293. ; 48:3, s. E200-E208
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Determine the intra-tidal regional gas and blood volume distributions at different levels of atelectasis in experimental lung injury. Test the hypotheses that pulmonary aeration and blood volume matching is reduced during inspiration in the setting of minimal tidal recruitment/derecruitment and that this mismatching is an important determinant of hypoxemia.Design: Preclinical study.Setting: Research laboratory.Subjects: Seven anesthetized pigs 28.7 kg (sd, 2.1 kg).Interventions: All animals received a saline-lavage surfactant depletion lung injury model. Positive end-expiratory pressure was varied between 0 and 20 cm H2O to induce different levels of atelectasis.Measurements and Main Results: Dynamic dual-energy CT images of a juxtadiaphragmatic slice were obtained, gas and blood volume fractions within three gravitational regions calculated and normalized to lung tissue mass (normalized gas volume and normalized blood volume, respectively). Ventilatory conditions were grouped based upon the fractional atelectatic mass in expiration (< 20%, 20-40%, and >= 40%). Tidal recruitment/derecruitment with fractional atelectatic mass in expiration greater than or equal to 40% was less than 7% of lung mass. In this group, inspiration-related increase in normalized gas volume was greater in the nondependent (818 mu L/g [95% CI, 729-908 mu L/g]) than the dependent region (149 mu L/g [120-178 mu L/g]). Normalized blood volume decreased in inspiration in the nondependent region (29 mu L/g [12-46 mu L/g]) and increased in the dependent region (39 mu L/g [30-48 mu L/g]). Inspiration-related changes in normalized gas volume and normalized blood volume were negatively correlated in fractional atelectatic mass in expiration greater than or equal to 40% and 20-40% groups (r(2) = 0.56 and 0.40), but not in fractional atelectatic mass in expiration less than 20% group (r(2) = 0.01). Both the increase in normalized blood volume in the dependent region and fractional atelectatic mass in expiration negatively correlated with Pao(2)/Fio(2) ratio (rho = -0.77 and -0.93, respectively).Conclusions: In experimental atelectasis with minimal tidal recruitment/derecruitment, mechanical inspiratory breaths redistributed blood volume away from well-ventilated areas, worsening Pao(2)/Fio(2).
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