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Guérin, C., Beuret, P., Constantin, J. M., Bellani, G., Garcia-Olivares, P., Roca, O., . . . Mercat, A. (2018). A prospective international observational prevalence study on prone positioning of ARDS patients: the APRONET (ARDS Prone Position Network) study. Intensive Care Medicine, 44(1), 22-37
Open this publication in new window or tab >>A prospective international observational prevalence study on prone positioning of ARDS patients: the APRONET (ARDS Prone Position Network) study
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2018 (English)In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 44, no 1, p. 22-37Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: While prone positioning (PP) has been shown to improve patient survival in moderate to severe acute respiratory distress syndrome (ARDS) patients, the rate of application of PP in clinical practice still appears low.

AIM: This study aimed to determine the prevalence of use of PP in ARDS patients (primary endpoint), the physiological effects of PP, and the reasons for not using it (secondary endpoints).

METHODS: The APRONET study was a prospective international 1-day prevalence study performed four times in April, July, and October 2016 and January 2017. On each study day, investigators in each ICU had to screen every patient. For patients with ARDS, use of PP, gas exchange, ventilator settings and plateau pressure (Pplat) were recorded before and at the end of the PP session. Complications of PP and reasons for not using PP were also documented. Values are presented as median (1st-3rd quartiles).

RESULTS: Over the study period, 6723 patients were screened in 141 ICUs from 20 countries (77% of the ICUs were European), of whom 735 had ARDS and were analyzed. Overall 101 ARDS patients had at least one session of PP (13.7%), with no differences among the 4 study days. The rate of PP use was 5.9% (11/187), 10.3% (41/399) and 32.9% (49/149) in mild, moderate and severe ARDS, respectively (P = 0.0001). The duration of the first PP session was 18 (16-23) hours. Measured with the patient in the supine position before and at the end of the first PP session, PaO2/FIO2 increased from 101 (76-136) to 171 (118-220) mmHg (P = 0.0001) driving pressure decreased from 14 [11-17] to 13 [10-16] cmH2O (P = 0.001), and Pplat decreased from 26 [23-29] to 25 [23-28] cmH2O (P = 0.04). The most prevalent reason for not using PP (64.3%) was that hypoxemia was not considered sufficiently severe. Complications were reported in 12 patients (11.9%) in whom PP was used (pressure sores in five, hypoxemia in two, endotracheal tube-related in two ocular in two, and a transient increase in intracranial pressure in one).

CONCLUSIONS: In conclusion, this prospective international prevalence study found that PP was used in 32.9% of patients with severe ARDS, and was associated with low complication rates, significant increase in oxygenation and a significant decrease in driving pressure.

Keywords
ARDS, Epidemiology, Mechanical ventilation, Prone position
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-336055 (URN)10.1007/s00134-017-4996-5 (DOI)000422809000003 ()29218379 (PubMedID)
Available from: 2017-12-12 Created: 2017-12-12 Last updated: 2018-02-26Bibliographically approved
Skorup, P., Maudsdotter, L., Tano, E., Lipcsey, M., Castegren, M., Larsson, A. & Sjölin, J. (2018). Dynamics of Endotoxin, Inflammatory Variables, and Organ Dysfunction After Treatment With Antibiotics in an Escherichia coli Porcine Intensive Care Sepsis Model.. Critical Care Medicine
Open this publication in new window or tab >>Dynamics of Endotoxin, Inflammatory Variables, and Organ Dysfunction After Treatment With Antibiotics in an Escherichia coli Porcine Intensive Care Sepsis Model.
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2018 (English)In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293Article in journal (Refereed) Epub ahead of print
Abstract [en]

OBJECTIVES: To investigate the dynamics of antibiotic-induced endotoxin liberation and inflammatory response in vivo in a clinically relevant large animal intensive care sepsis model and whether the addition of an aminoglycoside to a β-lactam antibiotic affects these responses.

DESIGN: Prospective, placebo-controlled interventional experimental study.

SETTING: University research unit.

SUBJECTS: Thirty-six healthy pigs administered Escherichia coli as a 3-hour infusion.

INTERVENTIONS: After 2 hours, during E. coli infusion, the animals were exposed to cefuroxime alone, the combination of cefuroxime and tobramycin, or saline.

MEASUREMENTS AND MAIN RESULTS: Plasma endotoxin, interleukin-6, tumor necrosis factor-α, leucocytes, and organ dysfunction were recorded for 4 hours after antibiotic treatment, and differences to the values before treatment were calculated. In vitro experiments were performed to ascertain whether endotoxin is released during antibiotic-induced bacterial killing of this E. coli strain. Despite differences between the treatment arms in vitro, no differences in plasma endotoxin were observed in vivo. Antibiotic-treated animals demonstrated a higher interleukin-6 response (p < 0.001), greater leucocyte activation (p < 0.001), and more pronounced deterioration in pulmonary static compliance (p < 0.01) over time than controls. Animals treated with the combination showed a trend toward less inflammation.

CONCLUSIONS: Treatment with antibiotics may elicit an increased inflammatory interleukin-6 response that is associated with leucocyte activation and pulmonary organ dysfunction. No observable differences were detected in plasma endotoxin concentrations. The reduction in cefuroxime-induced endotoxin release after the addition of an aminoglycoside in vitro could not be reproduced in this model.

National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-349226 (URN)10.1097/CCM.0000000000003139 (DOI)29595561 (PubMedID)
Available from: 2018-04-23 Created: 2018-04-23 Last updated: 2018-05-09Bibliographically approved
Meyhoff, C. S., Larsson, A., Perchiazzi, G. & Hedenstierna, G. (2018). In Reply [Letter to the editor]. Anesthesiology, 128(1), 222-224
Open this publication in new window or tab >>In Reply
2018 (English)In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 128, no 1, p. 222-224Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2018
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-350092 (URN)10.1097/ALN.0000000000001942 (DOI)000422905300032 ()29232228 (PubMedID)
Note

Wos title: World Health Organization Responds to Concerns about Surgical Site Infection Prevention Recommendations Reply

Available from: 2018-05-04 Created: 2018-05-04 Last updated: 2018-05-09Bibliographically approved
Befekadu, R., Christiansen, K., Larsson, A. & Grenegård, M. (2018). Increased plasma cathepsin S and trombospondin-1 in patients with acute ST segment elevation myocardial infarction.. Cardiology journal
Open this publication in new window or tab >>Increased plasma cathepsin S and trombospondin-1 in patients with acute ST segment elevation myocardial infarction.
2018 (English)In: Cardiology journal, ISSN 1897-5593Article in journal (Refereed) Epub ahead of print
Abstract [en]

BACKGROUND: The role of cathepsins in the pathological progression of atherosclerotic lesions in ischemic heart disease have been defined in detail more than numerous times. This investigation examined the platelet-specific biomarker trombospondin-1 (TSP-1) and platelet function ex vivo, and compared this with cathepsin S (Cat-S; a biomarker unrelated to platelet activation but also associated this with increased mortality risk) in patients with ST segment elevation myocardial infarction (STEMI).

METHODS: The STEMI patients were divided into two groups depending on the degree of coronary vessel occlusion: those with closed (n = 90) and open culprit vessel (n = 40). Cat-S and TSP-1 were analyzed before, 1-3 days after and 3 months after percutanous coronary intervention (PCI).

RESULTS: During acute STEMI, plasma TSP-1 was significantly elevated in patients with closed culprit lesions, but rapidly declined after PCI. In fact, TSP-1 after PCI was significantly lower inpatient samples compared to healthy individuals. In comparison, plasma Cat-S was significantly elevated both before and after PCI. In patients with closed culprit lesions, Cat-S was significantly higher compared to patients with open culprit lesions 3 months after PCI. Although troponin-I were higher (p < 0.01) in patients with closed culprit lesion, there was no correlation with Cat-S and TSP-1.

CONCLUSIONS: Cat-S but not TSP-1 may be a useful risk biomarker in relation to the severity of STEMI. However, the causality of Cat-S as a predictor for long-term mortality in STEMI remains to be ascertained in future studies.

Keywords
ST segment elevation myocardial infarction, cathepsin S, percutaneous coronary intervention, platelets
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-349225 (URN)10.5603/CJ.a2018.0030 (DOI)29611169 (PubMedID)
Available from: 2018-04-23 Created: 2018-04-23 Last updated: 2018-05-09Bibliographically approved
Kostic, P., Lo Mauro, A., Larsson, A., Hedenstierna, G., Frykholm, P. & Aliverti, A. (2018). Specific anesthesia-induced lung volume changes from induction to emergence: a pilot study.. Acta Anaesthesiologica Scandinavica, 62(3), 282-292
Open this publication in new window or tab >>Specific anesthesia-induced lung volume changes from induction to emergence: a pilot study.
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2018 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 62, no 3, p. 282-292Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Studies aimed at maintaining intraoperative lung volume to reduce post-operative pulmonary complications have been inconclusive because they mixed up the effect of general anesthesia and the surgical procedure. Our aims were to study: (1) lung volume during the entire course of anesthesia without the confounding effects of surgical procedures; (2) the combination of three interventions to maintain lung volume; and (3) the emergence phase with focus on the restored activation of the respiratory muscles.

METHODS: Eighteen ASA I-II patients undergoing ENT surgery under general anesthesia without muscle relaxants were randomized to an intervention group, receiving lung recruitment maneuver (LRM) after induction, 7 cmH2 O positive end-expiratory pressure (PEEP) during anesthesia and continuous positive airway pressure (CPAP) during emergence with 0.4 inspired oxygen fraction (FiO2 ) or a control group, ventilated without LRM, with 0 cmH2 O PEEP, and 1.0 FiO2 during emergence without CPAP application. End-expiratory lung volume (EELV) was continuously estimated by opto-electronic plethysmography. Inspiratory and expiratory ribcage muscles electromyography was measured in a subset of seven patients.

RESULTS: End-expiratory lung volume decreased after induction in both groups. It remained low in the control group and further decreased at emergence, because of active expiratory muscle contraction. In the intervention group, EELV increased after LRM and remained high after extubation.

CONCLUSION: A combined intervention consisting of LRM, PEEP and CPAP during emergence may effectively maintain EELV during anesthesia and even after extubation. An unexpected finding was that the activation of the expiratory muscles may contribute to EELV reduction during the emergence phase.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-334187 (URN)10.1111/aas.13026 (DOI)000424150200001 ()29105056 (PubMedID)
Funder
Swedish Heart Lung FoundationSwedish Research Council, 5315, K2015-99X-22731-01-4
Available from: 2017-11-21 Created: 2017-11-21 Last updated: 2018-03-15Bibliographically approved
Pino, F., Ball, L., Scaramuzzo, G., Pinol Ribas, M., Pelosi, P., Hedenstierna, G., . . . Perchiazzi, G. (2017). A comparison between PEEP titration methods in a porcine ARDS model. Acta Anaesthesiologica Scandinavica, 61(8), 1024-1025
Open this publication in new window or tab >>A comparison between PEEP titration methods in a porcine ARDS model
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2017 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 61, no 8, p. 1024-1025Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
WILEY, 2017
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-342129 (URN)000407231100108 ()
Available from: 2018-02-22 Created: 2018-02-22 Last updated: 2018-02-22Bibliographically approved
Formenti, F., Bommakanti, N., Chen, R., Cronin, J., McPeak, H., Holopherne-Doran, D., . . . Farmery, A. (2017). Alveolar oxygen respiratory oscillations measured in arterial blood. Acta Physiologica, 221(SI), 20-20
Open this publication in new window or tab >>Alveolar oxygen respiratory oscillations measured in arterial blood
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2017 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 221, no SI, p. 20-20Article in journal, Meeting abstract (Other academic) Published
National Category
Physiology
Identifiers
urn:nbn:se:uu:diva-346512 (URN)000408842000038 ()
Available from: 2018-03-19 Created: 2018-03-19 Last updated: 2018-03-19Bibliographically approved
Kassebaum, N., Kyu, H. H., Zoeckler, L., Olsen, H. E., Thomas, K., Pinho, C., . . . Vos, T. (2017). Child and Adolescent Health From 1990 to 2015: Findings From the Global Burden of Diseases, Injuries, and Risk Factors 2015 Study. JAMA pediatrics, 171(6), 573-592
Open this publication in new window or tab >>Child and Adolescent Health From 1990 to 2015: Findings From the Global Burden of Diseases, Injuries, and Risk Factors 2015 Study
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2017 (English)In: JAMA pediatrics, ISSN 2168-6203, E-ISSN 2168-6211, Vol. 171, no 6, p. 573-592Article in journal (Refereed) Published
Abstract [en]

Importance: Comprehensive and timely monitoring of disease burden in all age groups, including children and adolescents, is essential for improving population health.

Objective: To quantify and describe levels and trends of mortality and nonfatal health outcomes among children and adolescents from 1990 to 2015 to provide a framework for policy discussion.

Evidence Review: Cause-specific mortality and nonfatal health outcomes were analyzed for 195 countries and territories by age group, sex, and year from 1990 to 2015 using standardized approaches for data processing and statistical modeling, with subsequent analysis of the findings to describe levels and trends across geography and time among children and adolescents 19 years or younger. A composite indicator of income, education, and fertility was developed (Socio-demographic Index [SDI]) for each geographic unit and year, which evaluates the historical association between SDI and health loss.

Findings: Global child and adolescent mortality decreased from 14.18 million (95% uncertainty interval [UI], 14.09 million to 14.28 million) deaths in 1990 to 7.26 million (95% UI, 7.14 million to 7.39 million) deaths in 2015, but progress has been unevenly distributed. Countries with a lower SDI had a larger proportion of mortality burden (75%) in 2015 than was the case in 1990 (61%). Most deaths in 2015 occurred in South Asia and sub-Saharan Africa. Global trends were driven by reductions in mortality owing to infectious, nutritional, and neonatal disorders, which in the aggregate led to a relative increase in the importance of noncommunicable diseases and injuries in explaining global disease burden. The absolute burden of disability in children and adolescents increased 4.3% (95% UI, 3.1%-5.6%) from 1990 to 2015, with much of the increase owing to population growth and improved survival for children and adolescents to older ages. Other than infectious conditions, many top causes of disability are associated with long-term sequelae of conditions present at birth (eg, neonatal disorders, congenital birth defects, and hemoglobinopathies) and complications of a variety of infections and nutritional deficiencies. Anemia, developmental intellectual disability, hearing loss, epilepsy, and vision loss are important contributors to childhood disability that can arise from multiple causes. Maternal and reproductive health remains a key cause of disease burden in adolescent females, especially in lower-SDI countries. In low-SDI countries, mortality is the primary driver of health loss for children and adolescents, whereas disability predominates in higher-SDI locations; the specific pattern of epidemiological transition varies across diseases and injuries.

Conclusions and Relevance: Consistent international attention and investment have led to sustained improvements in causes of health loss among children and adolescents in many countries, although progress has been uneven. The persistence of infectious diseases in some countries, coupled with ongoing epidemiologic transition to injuries and noncommunicable diseases, require all countries to carefully evaluate and implement appropriate strategies to maximize the health of their children and adolescents and for the international community to carefully consider which elements of child and adolescent health should be monitored.

Place, publisher, year, edition, pages
AMER MEDICAL ASSOC, 2017
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-319725 (URN)10.1001/jamapediatrics.2017.0250 (DOI)000402714300018 ()28384795 (PubMedID)
Available from: 2017-04-07 Created: 2017-04-07 Last updated: 2017-08-28Bibliographically approved
Holzgraefe, B., Andersson, C., Kalzén, H., von Bahr, V., Mosskin, M., Larsson, E.-M., . . . Larsson, A. (2017). Does permissive hypoxaemia during extracorporeal membrane oxygenation cause long-term neurological impairment?: A study in patients with H1N1-induced severe respiratory failure. European Journal of Anaesthesiology, 34(2), 98-103
Open this publication in new window or tab >>Does permissive hypoxaemia during extracorporeal membrane oxygenation cause long-term neurological impairment?: A study in patients with H1N1-induced severe respiratory failure
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2017 (English)In: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 34, no 2, p. 98-103Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The Extracorporeal Life Support Organisation accepts permissive hypoxaemia in adult patients during extracorporeal membrane oxygenation (ECMO). The neurological long-term outcome of this approach has not yet been studied.

OBJECTIVES: We investigated the prevalence of brain lesions and cognitive dysfunction in survivors from the Influenza A/H1N1 2009 pandemic treated with permissive hypoxaemia during ECMO for severe acute respiratory distress syndrome (ARDS). Our hypothesis was that this method is reasonable if tissue hypoxia is avoided.

DESIGN: Long-term follow-up study after ECMO.

SETTING: Karolinska University Hospital, Sweden, from October 2012 to July 2013.

PATIENTS: Seven patients treated with ECMO for severe influenza A/H1N1-induced ARDS were studied 3.2 years after treatment. Blood lactate concentrations were used as a surrogate for tissue oxygenation.

INTERVENTIONS: Neurocognitive outcome was studied with standardised cognitive tests and MRI of the brain.

MAIN OUTCOME MEASURES: Cognitive functioning and hypoxic brain lesions after permissive hypoxaemia during ECMO. The observation period was the first 10 days of ECMO or the entire treatment period if shorter than 10 days.

RESULTS: Eleven of 13 patients were still alive 3 years after ECMO. We were able to contact seven of these patients (mean age 31 years), who all agreed to participate in this study. Mean +/- SD peripherally measured arterial saturation during the observation period was 79 +/- 10%. Full-scale Intelligence Quotient was within one standard deviation or above from the mean of a healthy population in five patients, and was 1.5 SD below the mean in one patient. In one other patient, it could not be determined because of a lack of formal education. Memory functioning was normal in all patients. MRI showed no changes related to cerebral hypoxia.

CONCLUSIONS: Permissive hypoxaemia during ECMO might not negatively affect long-term cognitive outcome if adequate organ perfusion is maintained.

National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-310232 (URN)10.1097/EJA.0000000000000544 (DOI)000392170300008 ()28030441 (PubMedID)
Funder
Swedish Heart Lung FoundationSwedish Research Council
Available from: 2016-12-13 Created: 2016-12-13 Last updated: 2017-11-29Bibliographically approved
Broche, L., Perchiazzi, G., Porra, L., Tannoia, A., Pellegrini, M., Derosa, S., . . . Bayat, S. (2017). Dynamic Mechanical Interactions Between Neighboring Airspaces Determine Cyclic Opening and Closure in Injured Lung. Critical Care Medicine, 45(4), 687-694
Open this publication in new window or tab >>Dynamic Mechanical Interactions Between Neighboring Airspaces Determine Cyclic Opening and Closure in Injured Lung
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2017 (English)In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 45, no 4, p. 687-694Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
acute respiratory distress syndrome, assisted ventilation, imaging/computed tomography, pulmonary oedema, synchrotron
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-321336 (URN)10.1097/CCM.0000000000002234 (DOI)000396798700016 ()28107207 (PubMedID)
Funder
Swedish Heart Lung FoundationSwedish Research CouncilNIH (National Institute of Health)
Available from: 2017-05-31 Created: 2017-05-31 Last updated: 2017-05-31Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-0702-8343

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