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1.
  • Bergenzaun, Lill, et al. (författare)
  • Assessing left ventricular systolic function in shock : evaluation of echocardiographic parameters in intensive care
  • 2011
  • Ingår i: Critical Care. - : BioMed Central. - 1364-8535 .- 1466-609X. ; 15:4
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Assessing left ventricular (LV) systolic function in a rapid and reliable way can be challenging in the critically ill patient. The purpose of this study was to evaluate the feasibility and reliability of, as well as the association between, commonly used LV systolic parameters, by using serial transthoracic echocardiography (TTE). METHODS: Fifty patients with shock and mechanical ventilation were included. TTE examinations were performed daily for a total of 7 days. Methods used to assess LV systolic function were visually estimated, "eyeball" ejection fraction (EBEF), the Simpson single-plane method, mean atrioventricular plane displacement (AVPDm), septal tissue velocity imaging (TDIs), and velocity time integral in the left ventricular outflow tract (VTI). RESULTS: EBEF, AVPDm, TDIs, VTI, and the Simpson were obtained in 100%, 100%, 99%, 95% and 93%, respectively, of all possible examinations. The correlations between the Simpson and EBEF showed r values for all 7 days ranging from 0.79 to 0.95 (P < 0.01). the Simpson correlations with the other LV parameters showed substantial variation over time, with the poorest results seen for TDIs and AVPDm. The repeatability was best for VTI (interobserver coefficient of variation (CV) 4.8%, and intraobserver CV, 3.1%), and AVPDm (5.3% and 4.4%, respectively), and worst for the Simpson method (8.2% and 10.6%, respectively). CONCLUSIONS: EBEF and AVPDm provided the best, and Simpson, the worst feasibility when assessing LV systolic function in a population of mechanically ventilated, hemodynamically unstable patients. Additionally, the Simpson showed the poorest repeatability. We suggest that EBEF can be used instead of single-plane Simpson when assessing LV ejection fraction in this category of patients. TDIs and AVPDm, as markers of longitudinal function of the LV, are not interchangeable with LV ejection fraction.
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2.
  • Bergenzaun, Lill, et al. (författare)
  • High-sensitive cardiac Troponin T is superior to echocardiography in predicting 1-year mortality in patients with SIRS and shock in intensive care.
  • 2012
  • Ingår i: BMC Anesthesiology. - : BioMed Central. - 1471-2253 .- 1471-2253. ; 12:25
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Left ventricular (LV) dysfunction is well documented in the critically ill. We assessed 1-year mortality in relation to cardiac biomarkers and LV function parameters by echocardiography in patients with shock. METHODS: A prospective, observational, cohort study of 49 patients. B-natriuretic peptide (BNP), highsensitive troponin T (hsTNT) and transthoracic echocardiography (TTE) were assessed within 12 h of study inclusion. LV systolic function was measured by ejection fraction (LVEF), mean atrioventricular plane displacement (AVPDm), peak systolic tissue Doppler velocity imaging (TDIs) and velocity time integral in the LV outflow tract (LVOT VTI). LV diastolic function was evaluated by transmitral pulsed Doppler (E, A, E/A, E-deceleration time), tissue Doppler indices (e, a, E/e) and left atrial volume (La volume). APACHE II (Acute Physiology and Chronic Health Evaluation) and SOFA (Sequential Organ Failure Assessment) scores were calculated. RESULTS: hsTNT was significantly higher in non-survivors than in survivors (60 [17.0-99.5] vs 168 [89.8-358] ng/l, p = 0.003). Other univariate predictors of mortality were APACHE II (p = 0.009), E/e (p = 0.023), SOFA (p = 0.024) and age (p = 0.031). Survivors and nonsurvivors did not differ regarding BNP (p = 0.26) or any LV systolic function parameter (LVEF p = 0.87, AVPDm p = 0.087, TDIs p = 0.93, LVOT VTI p = 0.18). Multivariable logistic regression analysis identified hsTNT (p = 0.010) as the only independent predictor of 1-year mortality; adjusted odds ratio 2.0 (95% CI 1.2- 3.5). CONCLUSIONS: hsTNT was the only independent predictor of 1-year mortality in patients with shock. Neither BNP nor echocardiographic parameters had an independent prognostic value. Further studies are needed to establish the clinical significance of elevated hsTNT in patients in shock.
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3.
  • Bergenzaun, Lill, et al. (författare)
  • Mitral annular plane systolic excursion (MAPSE) in shock: a valuable echocardiographic parameter in intensive care patients : Cardiovascular Ultrasound
  • 2013
  • Ingår i: Cardiovascular Ultrasound. - : BioMed Central. - 1476-7120. ; 11:16
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Assessing left ventricular (LV) dysfunction by echocardiography in ICU patients is common. The aim of this study was to investigate mitral annular plane systolic excursion (MAPSE) in critically ill patients with shock and its relation to LV systolic and diastolic function, myocardial injury and to outcome. METHODS: In a prospective, observational, cohort study we enrolled 50 patients with SIRS and shock despite fluid resuscitation. Transthoracic echocardiography (TTE) measuring LV function was performed within 12 hours after admission and daily for a 7-day observation period. TTE and laboratory measurements were related to 28-day mortality. RESULTS: MAPSE on day 1 correlated significantly with LV ejection fraction (LVEF), tissue Doppler indices of LV diastolic function (é, E/é) and high-sensitive troponin T (hsTNT) (p< 0.001, p= 0.039, p= 0.009, p= 0.003 respectively) whereas LVEF did not correlate significantly with any marker of LV diastolic function or myocardial injury. Compared to survivors, non-survivors had a significantly lower MAPSE (8 [IQR 7.5-11] versus 11 [IQR 8.9-13] mm; p= 0.028). Other univariate predictors were age (p=0.033), hsTNT (p=0.014) and Sequential Organ Failure Assessment (SOFA) scores (p=0.007). By multivariate analysis MAPSE (OR 0.6 (95% CI 0.5- 0.9), p= 0.015) and SOFA score (OR 1.6 (95% CI 1.1- 2.3), p= 0.018) were identified as independent predictors of mortality. Daily measurements showed that MAPSE, as sole echocardiographic marker, was significantly lower in most days in non-survivors (p<0.05 at day 1-2, 4-6). CONCLUSIONS: MAPSE seemed to reflect LV systolic and diastolic function as well as myocardial injury in critically ill patients with shock. The combination of MAPSE and SOFA added to the predictive value for 28-day mortality.
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5.
  • Calcagnile, Olga, et al. (författare)
  • S100B levels are affected by older age but not by alcohol intoxication following mild traumatic brain injury
  • 2013
  • Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - : Springer Science and Business Media LLC. - 1757-7241. ; 21
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Biomarkers of brain damage and head injury are potentially useful tools in the management of afflicted patients. Particularly S100B has received much attention and has been adapted into clinical guidelines. Alcohol intoxication and higher age (65 years and over) have been used as risk factors for serious complications following head injury. The effect of these factors on S100B levels has not been fully established in a relevant patient cohort. Methods: We prospectively included 621 adult patients with mild traumatic brain injury (TBI) and S100B sampling. Mild TBI was defined as Glasgow Come Scale 14-15 with loss of consciousness and/or amnesia, but without high-risk factors for intracranial complications. These patients would normally require CT scanning according to local and most international guidelines. S100B was sampled within 3 hours following trauma. Results: 280 patients (45%) were intoxicated by alcohol. Alcohol intoxication had no effect on S100B levels (p = 0.65) and the performance of S100B remained unchanged in these patients. 115 patients (22%) were 65 years or older with elevated S100B levels being more common in this group compared to patients under 65 (p = 0.029). Although the sensitivity of S100B was unchanged in older patients, the specificity was poorer. Conclusion: S100B can be used reliably in mild TBI patients with alcohol intoxication. The clinically utility of S100B in older patients may be limited by very poor specificity leading to only a small decrease in CT scanning.
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6.
  • Chew, Michelle, et al. (författare)
  • Depletion of myocardial glucose is observed during endotoxemic but not hemorrhagic shock in a porcine model
  • 2013
  • Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535. ; 17:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Metabolic dysfunction is one of the hallmarks of sepsis yet little is known about local changes in key organs such as the heart. The aim of this study was to compare myocardial metabolic changes by direct measurements of substrates, such as glucose, lactate and pyruvate, using microdialysis (MD) in in-vivo porcine endotoxemic and hemorrhagic shock. To assess whether these changes were specific to the heart, we simultaneously investigated substrate levels in skeletal muscle. Methods Twenty-six female pigs were randomized to three groups: control (C) n = 8, endotoxemic shock (E) n = 9 and hemorrhagic shock (H) n = 9. Interstitial myocardial pyruvate, lactate and glucose were measured using MD. Skeletal muscle MD was also performed in all three groups. Results Marked decreases in myocardial glucose were observed in the E group but not in the H group compared to controls (mean difference (CI) in mmol/L: C versus E -1.5(-2.2 to -0.8), P < 0.001; H versus E -1.1(-1.8 to -0.4), P = 0.004; C versus H -0.4(-1.1 to 0.3), P = 0.282). Up to four-fold increases in myocardial pyruvate and three-fold increases in lactate were seen in both shock groups with no differences between the two types of shock. There was no evidence of myocardial anaerobic metabolism, with normal lactate: pyruvate (L:P) ratios seen in all animals regardless of the type of shock. In skeletal muscle, decreases in glucose concentrations were observed in the E group only (mean difference: C versus E -0.8(-1.4 to -0.3), P = 0.007). Although skeletal muscle lactate increased in both shock groups, this was accompanied by increases in pyruvate in the E group only (mean difference: C versus E 121(46 to 195), P = 0.003; H versus E 77(7 to 147), P = 0.032; C versus H 43(-30 to 43), P = 0.229). The L:P ratio was increased in skeletal muscle in response to hemorrhagic, but not endotoxemic, shock. Conclusions Endotoxemia, but not hemorrhage, induces a rapid decrease of myocardial glucose levels. Despite the decrease in glucose, myocardial lactate and pyruvate concentrations were elevated and not different than in hemorrhagic shock. In skeletal muscle, substrate patterns during endotoxemic shock mimicked those seen in myocardium. During hemorrhagic shock the skeletal muscle response was characterized by a lack of increase in pyruvate and higher L: P ratios. Hence, metabolic patterns in the myocardium during endotoxemic shock are different than those seen during hemorrhagic shock. Skeletal muscle and myocardium displayed similar substrate patterns during endotoxemic shock but differed during hemorrhagic shock.
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8.
  • Chew, Michelle, et al. (författare)
  • Extravascular lung water index: Diagnostic accuracy and relation to lung injury and mortality in patients with shock
  • 2011
  • Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 37:1 Suppl, s. 98-98
  • Konferensbidrag (refereegranskat)abstract
    • INTRODUCTION. The diagnosis of acute lung injury may be more robust if more accurate physiological markers can be identified. Extravascular lung water index (EVLWI) may be useful and has been shown to correlate with respiratory function and mortality in patients with sepsis and ARDS. Whether this applies to a wider population, and which index performs best, are unclear. OBJECTIVES. We hypothesized that EVLWI correlates with respiratory function and mortality in patients with documented systemic inflammation and shock. We investigated EVLW indexed to actual and predicted body weight, and pulmonary blood volume. We investigated the diagnostic accuracy of EVLWI for lung injury. METHODS. In 51 patients with shock and SIRS, EVLWI was measured within 6 h of ICU admission and indexed to actual weight (EVLWI/ABW), predicted body weight (EVLWI/ PBW) and pulmonary blood volume (EVLWI/PBV). Relationships to lung injury and ICUmortality were investigated. Positive and negative likelihood ratios, pre- and post-test odds and ROC curves were calculated. RESULTS. EVLWI was higher among patients with lung injury and was significantly correlated with respiratory parameters. EVLWI/ABW was higher among non-survivors and gave the best positive likelihood ratios for diagnosing ALI/ARDS. In contrast, EVLWI/PBV gave better diagnostic value for severe lung injury according to Murray's LIS criteria. The post-test odds for ALI and ARDS increased threefold when using EVLWI/ABW as a bedside test. The post-test odds of severe lung injury increased eightfold using EVLWI/PBV. EVLWI/ABW and EVLWI/PBV generated the best ROC curves for mortality prediction with a sensitivity of 68% and specificity of 63-72%. CONCLUSIONS. EVLWI was associated with degree of lung injury, regardless of the index used, supporting its usefulness as a bedside indicator for disease severity. EVLWI/PBV and EVLW/ABW gave the best diagnostic accuracies for the diagnosis of lung injury, and generated the bestROCcurves for mortality prediction.EVLWI/ABWwas significantly increased in non-survivors. Further studies are needed to confirm the additional value of EVLWI for the early identification of lung injury.
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9.
  • Chew, Michelle, et al. (författare)
  • Extravascular lung water index improves the diagnostic accuracy of lung injury in patients with shock
  • 2012
  • Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535. ; 16:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The diagnosis of acute lung injury (ALI) may be more robust if more accurate physiological markers can be identified. Extravascular lung water (EVLW) is one possible marker, and it has been shown to correlate with respiratory function and mortality in patients with sepsis. Whether EVLW confers diagnostic value in a general population with shock, as well as which index performs best, is unclear. We investigated the diagnostic accuracy of various EVLW indices in patients with shock. Methods: We studied a prospective, observational cohort of 51 patients with shock admitted to a tertiary ICU. EVLW was measured within 6 hours of ICU admission and indexed to actual body weight (EVLW/ABW), predicted body weight (EVLW/PBW) and pulmonary blood volume (EVLW/PBV). The relationship of these indices to the diagnosis and severity of lung injury and ICU mortality were studied. Positive and negative likelihood ratios, pre- and posttest odds for diagnosis of lung injury and mortality were calculated. Results: All EVLW indices were higher among patients with lung injury and significantly correlated with respiratory parameters. Furthermore, all EVLW indices were significantly higher in nonsurvivors. The use of EVLW improves the posttest OR for the diagnosis of ALI, acute respiratory distress syndrome (ARDS) and severe lung injury (sLI) by up to eightfold. Combining increased EVLW and a diagnosis of ALI, ARDS or sLI increases the posttest odds of ICU mortality. EVLW/ABW and EVLW/PBV demonstrated the best diagnostic performance in this population. Conclusions: EVLW was associated with degree of lung injury and mortality, regardless of the index used, confirming that it may be used as a bedside indicator of disease severity. The use of EVLW as a bedside test conferred added diagnostic value for the identification of patients with lung injury.
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10.
  • Chew, Michelle, et al. (författare)
  • Haemodynamic monitoring using arterial waveform analysis.
  • 2013
  • Ingår i: Current Opinion in Critical Care. - 1531-7072. ; 19:3, s. 234-241
  • Forskningsöversikt (refereegranskat)abstract
    • PURPOSE OF REVIEW: To describe the theory behind arterial waveform analysis, the different variables that may be obtained using this method, reliability of measurements and their clinical relevance. Areas for future research are identified. RECENT FINDINGS: The precision of cardiac output (CO) measurements varies considerably and deteriorates during haemodynamic instability. Significant device-to-device differences exist. Nevertheless, most are sufficiently accurate for tracking changes in CO. Targeted intervention guided by haemodynamic monitoring reduces mortality and morbidity in high-risk surgical patients. Dynamic changes in variables such as systolic pulse variation, pulse pressure variation (PPV) and stroke volume variation (SVV) may be useful for evaluating fluid responsiveness, although important caveats exist. Newer indices such as PPV : SVV ratio may be useful in identifying preload and vasopressor-dependent patients. Peripheral arterial dP/dt has not been validated in critically ill patients and requires further investigation. SUMMARY: Despite significant limitations in measurement accuracy and inter-device differences, arterial waveform analysis is a potentially useful tool for monitoring the central circulation in critically ill patients. Future studies investigating the effects of haemodynamic management guided by arterial waveform variables in critically ill patients are urgently needed. The evaluation of cardiopulmonary interactions and usefulness of dP/dt are other areas that require further investigation.
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11.
  • Chew, Michelle (författare)
  • Haemodynamic monitoring using echocardiography in the critically ill: a review.
  • 2012
  • Ingår i: Cardiology Research and Practice. - : Hindawi Limited. - 2090-0597 .- 2090-8016. ; 2012
  • Tidskriftsartikel (refereegranskat)abstract
    • Physicians caring for the critically ill are now expected to acquire competence in echocardiography. It has become an indispensable diagnostic and monitoring tool in acute care settings where it is generally accepted to have therapeutic impact. There are a number of indications for a critical care echocardiographic study, and the most important queries include those pertaining left and right ventricular function and filling status. Focused examinations are increasing in popularity and provide a means for systematic study, and can be easily learned and practiced by novices. This paper addresses the indications, therapeutic impact, and some of the most common questions that can be answered using echocardiography the in critically ill patient.
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12.
  • Chew, Michelle, et al. (författare)
  • Increased plasma levels of heparin-binding protein in patients with shock: a prospective, cohort study.
  • 2012
  • Ingår i: Inflammation Research. - : Springer Science and Business Media LLC. - 1420-908X .- 1023-3830. ; 61:4, s. 375-379
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Heparin-binding protein (HBP) is a potent inducer of increased vascular permeability. The purpose of this study was to examine plasma levels of HBP in patients with shock. DESIGN: Fifty-three consecutive patients with septic and non-septic shock at a mixed-bed intensive care unit were included, as well as 20 age-matched controls. Patients with local infections but without signs of shock served as infectious controls. Enzyme-linked immunosorbent assay was used to determine plasma levels of HBP. RESULTS: There were no differences in serum HBP levels between healthy controls and those with local infections, including urinary tract infections, pneumonia and gastroenteritis, without shock. Levels of HBP were higher in patients with non-septic shock and septic shock than healthy controls. However, there was no difference in serum HBP levels between patients with septic shock and those with non-septic shock. Moreover, HBP levels were not different between patients with low and high APACHE II scores. Plasma levels of HBP were similar in surviving and non-surviving patients with shock. CONCLUSIONS: HBP is elevated in patients with shock from septic and non-septic etiologies. Future investigations are required to define the functional role of HBP in patients with shock.
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13.
  • Chew, Michelle, et al. (författare)
  • No beneficial effects of levosimendan in acute porcine endotoxaemia.
  • 2011
  • Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 55, s. 851-861
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Levosimendan has been proposed as an attractive alternative to adrenergic agents for the treatment of sepsis-induced heart failure and haemodynamic derangements. Its use in this setting is, however, still not well investigated. The aim of this study was to test the hypothesis that levosimendan is able to attenuate endotoxin-induced pulmonary hypertension and improve myocardial function in a porcine model. The secondary aims were to investigate its effect on renal and liver function, and the plasma cytokine response. Methods: Endotoxaemia was induced in 18 pigs, randomized to placebo and Levosimendan groups. All pigs were fluid resuscitated and Noradrenalin infusion was given according to a predefined protocol. Systemic haemodynamics and myocardial function were measured using pulmonary artery catheterization and transthoracic echocardiography. Renal and liver function tests and cytokine concentrations were measured in plasma. Results: Levosimendan did not attenuate endotoxin-induced pulmonary hypertension and did not improve myocardial function. There were no differences in renal or liver function. Increases in arterial lactate and decreases in base excess were observed in the Levosimendan group, as well as significant increases in plasma interleukin (IL)-6 and IL-8. Conclusions: Contrary to our hypothesis, levosimendan given in conjunction with a protocolized vasopressor and fluid resuscitation did not improve cardiac, renal or liver function in this model of acute porcine endotoxaemia. Hyperlactataemia, acidosis and increases in plasma pro-inflammatory cytokines were observed, the mechanisms and implications of which remain unclear.
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16.
  • Chew, Michelle, et al. (författare)
  • Soluble CD40L (CD154) is increased in patients with shock.
  • 2010
  • Ingår i: Inflammation Research. - : Springer Science and Business Media LLC. - 1420-908X .- 1023-3830. ; 59, s. 979-982
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Recent data suggest that soluble CD40L (sCD40L) plays an important role in murine sepsis. The aim of the present study was to determine plasma levels of CD40L in critically ill patients with systemic inflammatory response syndrome (SIRS) and shock, with and without sepsis. DESIGN: A prospective observational one-centre cohort study in a mixed-bed ICU of an university hospital. Fifty-three consecutive patients fulfilling the criteria for SIRS with shock as well as seven age-matched controls were included. ELISA was used to determine sCD40L in the plasma. RESULTS: The level of sCD40L in plasma from healthy controls was 0.18 +/- 0.03 ng/ml. It was found that sCD40L levels were significantly higher in patients with non-septic shock (0.72 +/- 0.18 ng/ml) and septic shock (0.50 +/- 0.1 ng/ml). However, the levels of sCD40L were not different between these two groups of patients, or in those with low and high APACHE scores. CONCLUSION: Our data show that sCD40L is increased in patients with shock from septic and non-septic etiologies. However, further studies are needed to delineate the functional significance of sCD40L in the clinical outcome in shock patients.
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17.
  • Chew, Michelle (författare)
  • TTE for fluid responsiveness?
  • 2013
  • Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 57:10, s. 1331-1331
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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18.
  • Dhanani, Jayesh, et al. (författare)
  • Antimicrobial chemotherapy and lung microdialysis: a review
  • 2010
  • Ingår i: International Journal of Antimicrobial Agents. - : Elsevier BV. - 1872-7913 .- 0924-8579. ; 36:6, s. 491-500
  • Forskningsöversikt (refereegranskat)abstract
    • Pneumonia is a form of lung infection that may be caused by various micro-organisms. The predominant site of infection in pneumonia is debatable. Advances in the fields of diagnostic and therapeutic medicine have had a less than optimal effect on the outcome of pneumonia and one of the many causes is likely to be inadequate antimicrobial concentrations at the site of infection in lung tissue. Traditional antimicrobial therapy guidelines are based on indirect modelling from blood antimicrobial levels. However, studies both in humans and animals have shown the fallacy of this concept in various tissues. Many different methods have been employed to study lung tissue antimicrobial levels with limited success, and each has limitations that diminish their utility. An emerging technique being used to study the pharmacokinetics of antimicrobial agents in lung tissue is microdialysis. Development of microdialysis catheters, along with improvement in analytical techniques, has improved the accuracy of the data. Unfortunately, very few studies have reported the use of microdialysis in lung tissue, and even fewer antimicrobial classes have been studied. These studies generally suggest that this technique is a safe and effective way of assessing the pharmacokinetics of antimicrobial agents in lung tissue. Further descriptive studies need to be conducted to study the pharmacokinetics and pharmacodynamics of different antimicrobial classes in lung tissue. Data emanating from these studies could inform decisions for appropriate dosing schedules of antimicrobial agents in pneumonia. (C) 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
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19.
  • Dias, Nuno, et al. (författare)
  • Hemodynamics and jugular venous oxygen saturation during carotid endarterectomy: a comparison between general and locoregional anesthesia.
  • 2010
  • Ingår i: International Angiology. - 1827-1839. ; 29:3, s. 232-238
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: To study hemodynamic and blood oxygenation changes in patients undergoing carotid endarterectomy (CEA) under general (GA) or locoregional (LRA) anesthesia. METHODS: Prospective non-randomized study including 50 patients undergoing CEA (31 men, mean age 72 (range 50-84) years-old under GA (N.=23) or LRA (N.=27). Systemic blood pressure, ECG, venous oxygen saturation in the ipsilateral jugular bulb and pulse-oximetry were monitored. Blood-gas analysis was done from blood obtained from the radial artery and ipsilateral jugular vein. RESULTS: Pulse rate and systemic systolic blood pressure were higher in LRA compared to the GA before, during and after cross clamping (P<0.05). Seven GA patients required dopamine-infusion to maintain systolic blood pressure >120 mmHg. Jugular venous saturation was initially identical in both groups, but decreased significantly upon cross clamping in LRA compared to GA (P<0.05). This difference remained at least 3 minutes after cross clamp release (P<0.05). CONCLUSION: Patients under LRA seem to have increased sympathetic activity compared to patients under GA, as expressed by higher pulse rates and systolic blood pressures. Jugular venous saturation was lower during clamping of LRA patients. The differences were small and concur with the near-equality findings in studies analysing the clinical outcome.
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20.
  • Enekvist, Bruno, et al. (författare)
  • Ventilation with increased apparatus dead space vs positive end-expiratory pressure : Effects on gas exchange and circulation during anesthesia in a randomized clinical study
  • 2014
  • Ingår i: AANA Journal. - 0094-6354. ; 82:2, s. 114-120
  • Tidskriftsartikel (refereegranskat)abstract
    • Atelectasis formation can be reduced by positive endexpiratory pressure (PEEP), but resulting increases in intrathoracic pressure could affect circulation. We have earlier demonstrated that increased tidal volumes with larger apparatus dead space improves oxygenation and sevoflurane uptake. In the present study, we hypothesize that isocapnic ventilation with increased tidal volumes increases oxygen and sevoflurane uptake similar to ventilation with PEEP, but with less impact on cardiac output. Thirty patients, with ASA physical status 1 or 2, scheduled for elective open colon surgery were randomly assigned to be ventilated with either PEEP at 10 cm H2O (PEEP, 15 patients) or increased tidal volumes achieved with larger apparatus dead space but with zero end-expiratory pressure (DS group, 15 patients). Oxygen tension and arterial sevoflurane concentration were significantly higher in the DS group (P < .05). Cardiac output decreased significantly less in the DS group compared with the PEEP group (5% and 33%, respectively; P < .05). Consequently, isocapnic ventilation with increased tidal volumes using apparatus dead space increased oxygen and sevoflurane tensions in arterial blood and preserved cardiac output better than did PEEP.
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21.
  • Fung, Y.L., et al. (författare)
  • Stored blood transfusion induces transient pulmonary arterial hypertension without impairing coagulation in an ovine model of nontraumatic haemorrhage.
  • 2013
  • Ingår i: Vox Sanguinis. - : Wiley. - 1423-0410 .- 0042-9007. ; 105:2, s. 150-158
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND OBJECTIVES: Transfusion of blood products in particular older products is associated with patient morbidity. Previously, we demonstrated a higher incidence of acute lung injury in lipopolysaccharide-treated sheep transfused with stored blood products. As transfusion following haemorrhage is more common, we aimed to determine whether a 'first hit' of isolated haemorrhage would precipitate similar detrimental effects following transfusion and also disrupt haemostasis. MATERIALS AND METHODS: Anaesthetized sheep had 33% of their total blood volume collected into Leukotrap bags (Pall Medical), which were processed into packed red blood cells and cross-matched for transfusion into other sheep. After 30 mins, the sheep were resuscitated with either: fresh (<5 days old) or stored (35-42 days old) ovine blood followed by 4% albumin to replacement volume, albumin alone or normal saline alone and monitored for 4 h. RESULTS: The first hit of haemorrhage precipitated substantial decreases in mean arterial pressure however haemostasis was preserved. Transfusion of stored ovine blood induced (1) transient pulmonary arterial hypertension but no oedema and (2) reduced fibrinogen levels more than fresh blood, but neither induced coagulopathy. Thus, transfusion of stored blood affected pulmonary function even in the absence of overt organ injury. CONCLUSION: The fact that stored blood transfusions: (1) did not induce acute lung injury in contrast to previous lipopolysaccharide-primed animal models identifies the 'first hit' as an important determinant of the severity of transfusion-mediated injury; (2) impaired pulmonary dynamics verifies the sensitivity and vulnerability of the pulmonary system to injury.
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22.
  • Oehmcke, Sonja, et al. (författare)
  • Stimulation of blood mononuclear cells with bacterial virulence factors leads to the release of pro-coagulant and pro-inflammatory microparticles.
  • 2012
  • Ingår i: Cellular Microbiology. - : Hindawi Limited. - 1462-5814. ; 14, s. 107-119
  • Tidskriftsartikel (refereegranskat)abstract
    • Severe infectious diseases remain a major and life-threatening health problem. In serious cases a systemic activation of the coagulation cascade and hypovolemic shock are critical complications that are associated with high mortality rates. Here we report that blood mononuclear cells, stimulated with M1 protein of Streptococcus pyogenes or other bacterial virulence factors, produce not only pro-coagulant, but also pro-inflammatory microparticles (MPs). Our results also show that activation of the contact system on MPs contributes to these two effects. Phosphatidylserine (PS) plays an important role in these processes as its up-regulation on MPs allows an assembly and activation of the contact system. This in turn results in stabilization of the tissue factor-induced clot and a processing of high-molecular weight kininogen by plasma kallikrein followed by the release of bradykinin, a potent vascular mediator. Pro-coagulant monocyte-derived MPs were identified in plasma samples from septic patients and further analysis of MPs from these patients revealed that their pro-coagulant activity is dependent on the tissue factor- and contact system-driven pathway.
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23.
  • Rahman, Milladur, et al. (författare)
  • Platelet shedding of CD40L is regulated by matrix metalloproteinase-9 in abdominal sepsis.
  • 2013
  • Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 11:7, s. 1385-1398
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and objectives: Platelet-derived CD40L is known to regulate neutrophil recruitment and lung damage in sepsis. However, the mechanism regulating shedding of CD40L from activated platelets is not known. We hypothesized that matrix metalloproteinase-9 might cleave surface expressed CD40L and regulate pulmonary accumulation of neutrophils in sepsis. Methods: Abdominal sepsis was induced by cecal ligation and puncture (CLP) in wild-type and MMP-9-deficient mice. Edema formation, CXC chemokine, myeloperoxidase levels, neutrophils in the lung as well as plasma levels of CD40L and MMP-9 were quantified. Results: CLP increased plasma levels of MMP-9 but not MMP-2. The CLP-induced decrease of platelet surface CD40L and increase of soluble CD40L levels were significantly attenuated in MMP-9 gene-deficient mice. Moreover, pulmonary MPO activity and neutrophil infiltration in the alveolar space as well as edema formation and lung injury were markedly decreased in septic animals lacking MMP-9. In vitro studies revealed that inhibition of MMP-9 decreased platelet shedding of CD40L. Moreover, recombinant MMP-9 was capable of cleaving surface expressed CD40L on activated platelets. In human studies, plasma levels of MMP-9 were significantly increased in patients with septic shock compared to healthy controls although MMP-9 levels did not correlate with organ injury score. Conclusions: Our novel data propose a role of MMP-9 in regulating platelet-dependent infiltration of neutrophils and tissue damage in septic lung injury by controlling CD40L shedding from platelets. We conclude that targeting MMP-9 may be a useful strategy to limit acute lung injury in abdominal sepsis. This article is protected by copyright. All rights reserved.
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24.
  • Simonova, G., et al. (författare)
  • A comprehensive ovine model of blood transfusion
  • 2014
  • Ingår i: Vox Sanguinis. - : Wiley. - 1423-0410 .- 0042-9007. ; 106:2, s. 153-160
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The growing awareness of transfusion-associated morbidity and mortality necessitates investigations into the underlying mechanisms. Small animals have been the dominant transfusion model but have associated limitations. This study aimed to develop a comprehensive large animal (ovine) model of transfusion encompassing: blood collection, processing and storage, compatibility testing right through to post-transfusion outcomes. Materials and methods Two units of blood were collected from each of 12 adult male Merino sheep and processed into 24 ovine-packed red blood cell (PRBC) units. Baseline haematological parameters of ovine blood and PRBC cells were analysed. Biochemical changes in ovine PRBCs were characterized during the 42-day storage period. Immunological compatibility of the blood was confirmed with sera from potential recipient sheep, using a saline and albumin agglutination cross-match. Following confirmation of compatibility, each recipient sheep (n=12) was transfused with two units of ovine PRBC. Results Procedures for collecting, processing, cross-matching and transfusing ovine blood were established. Although ovine red blood cells are smaller and higher in number, their mean cell haemoglobin concentration is similar to human red blood cells. Ovine PRBC showed improved storage properties in saline-adenine-glucose-mannitol (SAG-M) compared with previous human PRBC studies. Seventy-six compatibility tests were performed and 171% were incompatible. Only cross-match compatible ovine PRBC were transfused and no adverse reactions were observed. Conclusion These findings demonstrate the utility of the ovine model for future blood transfusion studies and highlight the importance of compatibility testing in animal models involving homologous transfusions.
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25.
  • Toft, Palle, et al. (författare)
  • Non-sedation versus sedation with a daily wake-up trial in critically ill patients receiving mechanical ventilation (NONSEDA Trial) : study protocol for a randomised controlled trial
  • 2014
  • Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 15:499, s. 1-11
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Through many years, the standard care has been to use continuous sedation of critically ill patients during mechanical ventilation. However, preliminary randomised clinical trials indicate that it is beneficial to reduce the sedation level. No randomised trial has been conducted comparing sedation with no sedation, a priori powered to have all-cause mortality as primary outcome.The objective is to assess the benefits and harms of non-sedation versus sedation with a daily wake-up trial in critically ill patients.METHODS/DESIGN: The non-sedation (NONSEDA) trial is an investigator-initiated, randomised, clinical, parallel-group, multinational trial designed to include 700 patients from at least six ICUs in Denmark, Norway and Sweden.Inclusion criteria are mechanically ventilated patients with expected duration of mechanical ventilation >24 hours.Exclusion criteria are non-intubated patients, patients with severe head trauma, coma at admission or status epilepticus, patients treated with therapeutic hypothermia, patients with PaO2/FiO2 < 9 where sedation might be necessary to ensure sufficient oxygenation or place the patient in prone position.Experimental intervention is non-sedation supplemented with pain management during mechanical ventilation.Control intervention is sedation with a daily wake-up trial.The primary outcome will be all cause mortality at 90 days after randomization. Secondary outcomes will be: days until death throughout the total observation period; coma- and delirium-free days; highest RIFLE score; days until discharge from the intensive care unit (within 28 days); days until the participant is without mechanical ventilation (within 28 days); and proportion of patients with a major cardiovascular outcome. Explorative outcomes will be: all cause mortality at 28 days after randomisation; days until discharge from the intensive care unit; days until the participant is without mechanical ventilation; days until discharge from the hospital; organ failure.Trial size: we will include 700 participants (2 × 350) in order to detect or reject 25% relative risk reduction in mortality with a type I error risk of 5% and a type II error risk of 20% (power at 80%).DISCUSSION: The trial investigates potential benefits of non-sedation. This might have large impact on the future treatment of mechanically ventilated critically ill patients.TRIAL REGISTER: ClinicalTrials.gov NCT0196768, 09.01.2014.
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