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  • 1.
    Acosta, Cecilia M.
    et al.
    Univ Nacl Mar Del Plata, Hosp Privado Comunidad, Dept Anaesthesiol, Mar Del Plata, Argentina.
    Lopez Vargas, Maria Paz
    Univ Nacl Mar Del Plata, Hosp Privado Comunidad, Dept Anaesthesiol, Mar Del Plata, Argentina.
    Oropel, Facundo
    Univ Nacl Mar Del Plata, Hosp Privado Comunidad, Dept Anaesthesiol, Mar Del Plata, Argentina.
    Valente, Lisandro
    Univ Nacl Mar Del Plata, Hosp Privado Comunidad, Dept Anaesthesiol, Mar Del Plata, Argentina.
    Ricci, Lila
    Univ Nacl Mar Del Plata, Fac Ciencias Exactas, Dept Math, Mar Del Plata, Argentina.
    Natal, Marcela
    Univ Nacl Mar Del Plata, Fac Ciencias Exactas, Dept Math, Mar Del Plata, Argentina.
    Suarez Sipmann, Fernando
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Univ Autonoma Madrid, Hosp Univ Princesa, Inst Carlos III, CIBERES, Madrid, Spain; Univ Autonoma Madrid, Hosp Univ Princesa, Dept Crit Care, Madrid, Spain.
    Tusman, Gerardo
    Univ Nacl Mar Del Plata, Hosp Privado Comunidad, Dept Anaesthesiol, Mar Del Plata, Argentina.
    Prevention of atelectasis by continuous positive airway pressure in anaesthetised children: A randomised controlled study2021Ingår i: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 38, nr 1, s. 41-48Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND 

    Continuous positive airway pressure (CPAP) prevents peri-operative atelectasis in adults, but its effect in children has not been quantified.

    OBJECTIVE 

    The aim of this study was to evaluate the role of CPAP in preventing postinduction and postoperative atelectasis in children under general anaesthesia.

    DESIGN 

    A randomised controlled study.

    SETTING 

    Single-institution study, community hospital, Mar del Plata. Argentina.

    PATIENTS 

    We studied 42 children, aged 6 months to 7 years, American Society of Anesthesiologists physical status class I, under standardised general anaesthesia.

    INTERVENTIONS 

    Patients were randomised into two groups: Control group (n = 21): induction and emergence of anaesthesia without CPAP; and CPAP group (n = 21): 5 cmH2O of CPAP during induction and emergence of anaesthesia. Lung ultrasound (LUS) imaging was performed before and 5 min after anaesthesia induction. Children without atelectasis were ventilated in the same manner as the Control group with standard ventilatory settings including 5 cmH2O of PEEP. Children with atelectasis received a recruitment manoeuvre followed by standard ventilation with 8 cmH2O of PEEP. Then, at the end of surgery, LUS images were repeated before tracheal extubation and 60 min after awakening.

    MAIN OUTCOME MEASURES 

    Lung aeration score and atelectasis assessed by LUS.

    RESULTS 

    Before anaesthesia, all children were free of atelectasis. After induction, 95% in the Control group developed atelectasis compared with 52% of patients in the CPAP group (P < 0.0001). LUS aeration scores were higher (impaired aeration) in the Control group than the CPAP group (8.8 ± 3.8 vs. 3.5 ± 3.3 points; P < 0.0001). At the end of surgery, before tracheal extubation, atelectasis was observed in 100% of children in the Control and 29% of the CPAP group (P < 0.0001) with a corresponding aeration score of 9.6 ± 3.2 and 1.8 ± 2.3, respectively (P < 0.0001). After surgery, 30% of children in the Control group and 10% in the CPAP group presented with residual atelectasis (P < 0.0001) also corresponding to a higher aeration score in the Control group (2.5 ± 3.1) when compared with the CPAP group (0.5 ± 1.5; P < 0.01).

    CONCLUSION 

    The use of 5 cmH2O of CPAP in healthy children of the studied age span during induction and emergence of anaesthesia effectively prevents atelectasis, with benefits maintained during the first postoperative hour.

    TRIAL REGISTRY 

    Clinicaltrials.gov NCT03461770.

  • 2.
    Acosta, Cecilia M.
    et al.
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, Cordoba 4545, RA-7600 Buenos Aires, DF, Argentina..
    Tusman, Gerardo
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, Cordoba 4545, RA-7600 Buenos Aires, DF, Argentina..
    Costantini, Mauro
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, Cordoba 4545, RA-7600 Buenos Aires, DF, Argentina..
    Echevarria, Camila
    Hosp Privado Comunidad Mar Del Plata, Dept Radiol, Buenos Aires, DF, Argentina..
    Pollioto, Sergio
    Hosp Privado Comunidad Mar Del Plata, Dept Pediat Surg, Buenos Aires, DF, Argentina..
    Abrego, Diego
    Hosp Privado Comunidad Mar Del Plata, Dept Pediat Surg, Buenos Aires, DF, Argentina..
    Suarez-Sipmann, Fernando
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain..
    Bohm, Stephan H.
    Swisstom AG, Landquart, Switzerland..
    Doppler images of intra-pulmonary shunt within atelectasis in anesthetized children2016Ingår i: Critical Ultrasound Journal, ISSN 2036-3176, E-ISSN 2036-7902, Vol. 8, artikel-id 19Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Doppler images of pulmonary vessels in pulmonary diseases associated with subpleural consolidations have been described. Color Doppler easily identifies such vessels within consolidations while spectral Doppler analysis allows the differentiation between pulmonary and bronchial arteries. Thus, Doppler helps in diagnosing the nature of consolidations. To our knowledge, Doppler analysis of pulmonary vessels within anesthesia-induced atelectasis has never been described before. The aim of this case series is to demonstrate the ability of lung ultrasound to detect the shunting of blood within atelectatic lung areas in anesthetized children.

    Findings: Three anesthetized and mechanically ventilated children were scanned in the supine position using a high-resolution linear probe of 6-12 MHz. Once subpleural consolidations were detected in the most dependent posterior lung regions, the probe was rotated such that its long axis followed the intercostal space. In this oblique position, color Doppler mapping was performed to detect blood flow within the consolidation. Thereafter, pulsed waved spectral Doppler was applied in the previously identified vessels during a short expiratory pause, which prevented interferences from respiratory motion. Different flow patterns were identified which corresponded to both, pulmonary and bronchial vessels. Finally, a lung recruitment maneuver was performed which leads to the complete resolution of the aforementioned consolidation thereby confirming the pathophysiological entity of anesthesia-induced atelectasis.

    Conclusions: Lung ultrasound is a non-invasive imaging tool that not only enables the diagnosis of anesthesia-induced atelectasis in pediatric patients but also analysis of shunting blood within this consolidation.

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  • 3.
    Ahlström, Björn
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna.
    Frithiof, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    Hultström, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Ing-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Strandberg, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    One-year functional recovery from severe Covid-19 is severely affected in the Swedish intensive care and hospital admitted working age cohortManuskript (preprint) (Övrigt vetenskapligt)
  • 4.
    Ahlström, Björn
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna.
    Frithiof, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hultström, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Ing-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Strandberg, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    The swedish covid-19 intensive care cohort: Risk factors of ICU admission and ICU mortality2021Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 65, nr 4, s. 525-533Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Several studies have recently addressed factors associated with severe Coronavirus disease 2019 (COVID-19); however, some medications and comorbidities have yet to be evaluated in a large matched cohort. We therefore explored the role of relevant comorbidities and medications in relation to the risk of intensive care unit (ICU) admission and mortality.

    Methods: All ICU COVID-19 patients in Sweden until 27 May 2020 were matched to population controls on age and gender to assess the risk of ICU admission. Cases were identified, comorbidities and medications were retrieved from high-quality registries. Three conditional logistic regression models were used for risk of ICU admission and three Cox proportional hazards models for risk of ICU mortality, one with comorbidities, one with medications and finally with both models combined, respectively.

    Results: We included 1981 patients and 7924 controls. Hypertension, type 2 diabetes mellitus, chronic renal failure, asthma, obesity, being a solid organ transplant recipient and immunosuppressant medications were independent risk factors of ICU admission and oral anticoagulants were protective. Stroke, asthma, chronic obstructive pulmonary disease and treatment with renin-angiotensin-aldosterone inhibitors (RAASi) were independent risk factors of ICU mortality in the pre-specified primary analyses; treatment with statins was protective. However, after adjusting for the use of continuous renal replacement therapy, RAASi were no longer an independent risk factor.

    Conclusion: In our cohort oral anticoagulants were protective of ICU admission and statins was protective of ICU death. Several comorbidities and ongoing RAASi treatment were independent risk factors of ICU admission and ICU mortality.

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  • 5.
    Ahlström, Björn
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Falun Cent Hosp, Ctr Clin Res Dalarna, Reg Dalarna, Nissers V6g 3, S-79182 Falun, Sweden..
    Frithiof, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Ing-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Strandberg, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    Hultström, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    A comparison of impact of comorbidities and demographics on 60-day mortality in ICU patients with COVID-19, sepsis and acute respiratory distress syndrome2022Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 12, artikel-id 15703Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Severe Coronavirus disease 2019 (COVID-19) is associated with several pre-existing comorbidities and demographic factors. Similar factors are linked to critical sepsis and acute respiratory distress syndrome (ARDS). We hypothesized that age and comorbidities are more generically linked to critical illness mortality than a specific disease state. We used national databases to identify ICU patients and to retrieve comorbidities. The relative importance of risk factors for 60-day mortality was evaluated using the interaction with disease group (Sepsis, ARDS or COVID-19) in logistic regression models. We included 32,501 adult ICU patients. In the model on 60-day mortality in sepsis and COVID-19 there were significant interactions with disease group for age, sex and asthma. In the model on 60-day mortality in ARDS and COVID-19 significant interactions with cohort were found for acute disease severity, age and chronic renal failure. In conclusion, age and sex play particular roles in COVID-19 mortality during intensive care but the burden of comorbidity was similar between sepsis and COVID-19 and ARDS and COVID-19.

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  • 6.
    Ahlström, Björn
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Ctr Clin Res Dalarna, Reg Dalarna, Nissers Vag 3, S-79182 Falun, Sweden..
    Larsson, Ing-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Strandberg, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala Univ, Dept Surg Sci, Uppsala, Sweden.;Uppsala Univ, CIRRUS, Dept Surg Sci, Hedenstierna Lab,Anesthesiol & Intens Care, Uppsala, Sweden..
    A nationwide study of the long-term prevalence of dementia and its risk factors in the Swedish intensive care cohort2020Ingår i: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 24, nr 1, artikel-id 548Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BackgroundDeveloping dementia is feared by many for its detrimental effects on cognition and independence. Experimental and clinical evidence suggests that sepsis is a risk factor for the later development of dementia. We aimed to investigate whether intensive care-treated sepsis is an independent risk factor for a later diagnosis of dementia in a large cohort of intensive care unit (ICU) patients.MethodsWe identified adult patients admitted to an ICU in 2005 to 2015 and who survived without a dementia diagnosis 1year after intensive care admission using the Swedish Intensive Care Registry, collecting data from all Swedish general ICUs. Comorbidity, the diagnosis of dementia and mortality, was retrieved from the Swedish National Patient Registry, the Swedish Dementia Registry, and the Cause of Death Registry. Sepsis during intensive care served as a covariate in an extended Cox model together with age, sex, and variables describing comorbidities and acute disease severity.ResultsOne year after ICU admission 210,334 patients were alive and without a diagnosis of dementia; of these, 16,115 (7.7%) had a diagnosis of sepsis during intensive care. The median age of the cohort was 61years (interquartile range, IQR 43-72). The patients were followed for up to 11years (median 3.9years, IQR 1.7-6.6). During the follow-up, 6312 (3%) patients were diagnosed with dementia. Dementia was more common in individuals diagnosed with sepsis during their ICU stay (log-rank p<0.001), however diagnosis of sepsis during critical care was not an independent risk factor for a later dementia diagnosis in an extended Cox model: hazard ratio (HR) 1.01 (95% confidence interval 0.91-1.11, p=0.873). Renal replacement therapy and ventilator therapy during the ICU stay were protective. High age was a strong risk factor for later dementia, as was increasing severity of acute illness, although to a lesser extent. However, the severity of comorbidities and the length of ICU and hospital stay were not independent risk factors in the model.ConclusionAlthough dementia is more common among patients treated with sepsis in the ICU, sepsis was not an independent risk factor for later dementia in the Swedish national critical care cohort.Trial registrationThis study was registered a priori with the Australian and New Zeeland Clinical Trials Registry (registration no. ACTRN12618000533291).

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  • 7.
    Ahlström, Björn
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna.
    Larsson, Ing-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Strandberg, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    Association of sepsis with long-term mortality and causes of death in the Swedish intensive care cohortManuskript (preprint) (Övrigt vetenskapligt)
  • 8.
    Ahlström, J. Zebialowicz
    et al.
    Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Massaro, F.
    Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden.
    Mikolka, P.
    Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden;Comenius Univ, Jessenius Fac Med Martin, Biomed Ctr Martin, Martin, TN USA;Comenius Univ, Jessenius Fac Med Martin, Dept Physiol, Martin, TN USA.
    Feinstein, R.
    Swedish Natl Vet Inst, Dept Pathol, Uppsala, Sweden.
    Perchiazzi, Gaetano
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala Univ, Dept Surg Sci, Hedenstierna Lab, Uppsala, Sweden.
    Basabe-Burgos, O.
    Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Curstedt, T.
    Karolinska Inst, Karolinska Univ Hosp, Dept Mol Med & Surg, Stockholm, Sweden.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Johansson, J.
    Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Rising, A.
    Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden;Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden.
    Synthetic surfactant with a recombinant surfactant protein C analogue improves lung function and attenuates inflammation in a model of acute respiratory distress syndrome in adult rabbits2019Ingår i: Respiratory Research, ISSN 1465-9921, E-ISSN 1465-993X, Vol. 20, artikel-id 245Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AimIn acute respiratory distress syndrome (ARDS) damaged alveolar epithelium, leakage of plasma proteins into the alveolar space and inactivation of pulmonary surfactant lead to respiratory dysfunction. Lung function could potentially be restored with exogenous surfactant therapy, but clinical trials have so far been disappointing. These negative results may be explained by inactivation and/or too low doses of the administered surfactant. Surfactant based on a recombinant surfactant protein C analogue (rSP-C33Leu) is easy to produce and in this study we compared its effects on lung function and inflammation with a commercial surfactant preparation in an adult rabbit model of ARDS.MethodsARDS was induced in adult New Zealand rabbits by mild lung-lavages followed by injurious ventilation (V-T 20m/kg body weight) until P/F ratio<26.7kPa. The animals were treated with two intratracheal boluses of 2.5mL/kg of 2% rSP-C33Leu in DPPC/egg PC/POPG, 50:40:10 or poractant alfa (Curosurf (R)), both surfactants containing 80mg phospholipids/mL, or air as control. The animals were subsequently ventilated (V-T 8-9m/kg body weight) for an additional 3h and lung function parameters were recorded. Histological appearance of the lungs, degree of lung oedema and levels of the cytokines TNF alpha IL-6 and IL-8 in lung homogenates were evaluated.ResultsBoth surfactant preparations improved lung function vs. the control group and also reduced inflammation scores, production of pro-inflammatory cytokines, and formation of lung oedema to similar degrees. Poractant alfa improved compliance at 1h, P/F ratio and PaO2 at 1.5h compared to rSP-C33Leu surfactant.ConclusionThis study indicates that treatment of experimental ARDS with synthetic lung surfactant based on rSP-C33Leu improves lung function and attenuates inflammation.

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  • 9.
    Andersson, Hanna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Elias, Eerola
    Frykholm, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Preoperative weight loss, hypoglycaemia and ketosis in elective paediatric patients, preliminary results from a prospective observational studyManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Background

    New paediatric fasting guidelines allow free clear fluids up until one hour prior to surgery. At the paediatric anaesthesia department of Uppsala University Hospital, children are fasted six hours for solids, four hours for breast milk and are allowed free clear fluids up until called to theatre. Preoperative fasting is necessary to avoid perioperative pulmonary aspiration. However, extended fasting times have detrimental effects for fluid homeostasis and may cause hypoglycaemia and ketone bodies.

    Aim

    The aim of the current study was to investigate if preoperative weight loss, glucose level and ketone bodies were related to preoperative fasting times.

    Methods

    Paediatric patients aged 0-72 months were included in this prospective, observational study. All children included were instructed to fast from midnight for solids, four hours for breast milk or semi-solids and from when they are called to theatre for clear fluids. Fasting times were registered, and patient weight was measured in the evening prior to surgery, and before induction. Blood glucose and ketone body levels were measured before induction. Multiple regression was used to determine how fasting time affected the outcomes weight change, blood glucose level and ketone bodies, respectively.

    Results

    43 patients were enrolled. Three children had a weight loss of more than 5 %, five children presented with blood glucose level < 3.3 mmol l-1, and 11 children presented with ketone bodies > 0.6 mmol l-1. There was no correlation between fasting time and the respective outcomes.

    Conclusion

    Even with a lenient preoperative fasting regimen, mild dehydration or hypoglycaemia may occur. This methodology may be used in further studies of the effects of preoperative fasting in settings where dehydration may be more significant.

  • 10.
    Aneman, Anders
    et al.
    Liverpool Hosp, South Western Sydney Local Hlth Dist, Intens Care Unit, Sydney, NSW, Australia.;Univ New South Wales, South Western Sydney Clin Sch, Sydney, NSW, Australia.;Macquarie Univ, Fac Med & Hlth Sci, Sydney, NSW, Australia..
    Wilander, Petter
    Hallands Hosp, Dept Anaesthesiol & Intens Care Med, Halmstad, Sweden.;Linköping Univ, Fac Hlth Sci, Dept Med & Hlth Sci, Div Drug Res, Linköping, Sweden..
    Zoerner, Frank
    Liverpool Hosp, South Western Sydney Local Hlth Dist, Intens Care Unit, Sydney, NSW, Australia..
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Chew, Michelle S.
    Linköping Univ, Fac Hlth Sci, Biomed & Clin Sci, Dept Anaesthesia & Intens Care, Linköping, Sweden..
    Vasopressor Responsiveness Beyond Arterial Pressure: A Conceptual Systematic Review Using Venous Return Physiology2021Ingår i: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 56, nr 3, s. 352-359Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    We performed a systematic review to investigate the effects of vasopressor-induced hemodynamic changes in adults with shock. We applied a physiological approach using the interacting domains of intravascular volume, heart pump performance, and vascular resistance to structure the interpretation of responses to vasopressors. We hypothesized that incorporating changes in determinants of cardiac output and vascular resistance better reflect the vasopressor responsiveness beyond mean arterial pressure alone. We identified 28 studies including 678 subjects in Pubmed, EMBASE, and CENTRAL databases. All studies demonstrated significant increases in mean arterial pressure (MAP) and systemic vascular resistance during vasopressor infusion. The calculated mean systemic filling pressure analogue increased (16 +/- 3.3 mmHg to 18 +/- 3.4 mmHg; P = 0.02) by vasopressors with variable effects on central venous pressure and the pump efficiency of the heart leading to heterogenous changes in cardiac output. Changes in the pressure gradient for venous return and cardiac output, scaled by the change in MAP, were positively correlated (r (2) = 0.88, P < 0.001). Changes in the mean systemic filling pressure analogue and heart pump efficiency were negatively correlated (r (2) = 0.57, P < 0.001) while no correlation was found between changes in MAP and heart pump efficiency. We conclude that hemodynamic changes induced by vasopressor therapy are inadequately represented by the change in MAP alone despite its common use as a clinical endpoint. The more comprehensive analysis applied in this review illustrates how vasopressor administration may be optimized.

  • 11. Artigas, Antonio
    et al.
    Noël, Julie-Lyn
    Brochard, Laurent
    Busari, Jamiu O
    Dellweg, Dominic
    Ferrer, Miguel
    Geiseler, Jens
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Nava, Stefano
    Navalesi, Paolo
    Orfanos, Stylianos
    Palange, Paolo
    Pelosi, Paolo
    Rohde, Gernot
    Schoenhofer, Bernd
    Vassilakopoulos, Theodoros
    Simonds, Anita K
    Defining a training framework for clinicians in respiratory critical care2014Ingår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 44, nr 3, s. 572-577Artikel i tidskrift (Refereegranskat)
  • 12.
    Asif, Sana
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Frithiof, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Franzén, Stephanie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Bülow Anderberg, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Kristensen, Bjarne
    Thermo Fisher Scientific, DK-84 3450 Alleröd, Denmark..
    Hultström, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    Immuno-Modulatory Effects of Dexamethasone in Severe COVID-19: A Swedish Cohort Study2023Ingår i: Biomedicines, E-ISSN 2227-9059, Vol. 11, nr 1, artikel-id 164Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Dexamethasone (Dex) has been shown to decrease mortality in severe coronavirus disease 2019 (COVID-19), but the mechanism is not fully elucidated. We aimed to investigate the physiological and immunological effects associated with Dex administration in patients admitted to intensive care with severe COVID-19. A total of 216 adult COVID-19 patients were included-102 (47%) received Dex, 6 mg/day for 10 days, and 114 (53%) did not. Standard laboratory parameters, plasma expression of cytokines, endothelial markers, immunoglobulin (Ig) IgA, IgM, and IgG against SARS-CoV-2 were analyzed post-admission to intensive care. Patients treated with Dex had higher blood glucose but lower blood lactate, plasma cortisol, IgA, IgM, IgG, D-dimer, cytokines, syndecan-1, and E-selectin and received less organ support than those who did not receive Dex (Without-Dex). There was an association between Dex treatment and IL-17A, macrophage inflammatory protein 1 alpha, syndecan-1 as well as E-selectin in predicting 30-day mortality. Among a subgroup of patients who received Dex early, within 14 days of COVID-19 debut, the adjusted mortality risk was 0.4 (95% CI 0.2-0.8), i.e., 40% compared with Without-Dex. Dex administration in a cohort of critically ill COVID-19 patients resulted in altered immunological and physiologic responses, some of which were associated with mortality.

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  • 13.
    Asif, Sana
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Frithiof, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Kristensen, Bjarne
    Alving, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Pediatrisk inflammations- och metabolismforskning samt barnhälsa.
    Hultström, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Weak anti-SARS-CoV-2 antibody response is associated with mortality in a Swedish cohort of COVID-19 patients in critical care2020Ingår i: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 24, nr 1, artikel-id 639Artikel i tidskrift (Refereegranskat)
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  • 14.
    Asif, Sana
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Ruge, Thoralph
    Department of Clinical Sciences, Lund University, Malmö, Sweden, Lund, 221 00, Sweden..
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Bülow Anderberg, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    Frithiof, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hultström, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Plasma endostatin correlates with hypoxia and mortality in COVID-19-associated acute respiratory failure2021Ingår i: Biomarkers in Medicine, ISSN 1752-0363, E-ISSN 1752-0371, Vol. 15, nr 16, s. 1509-1517Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The contribution of endothelial injury in the pathogenesis of COVID-19-associated acute respiratory distress syndrome (ARDS) and resulting respiratory failure remains unclear. Plasma endostatin, an endogenous inhibitor of angiogenesis and endothelial dysfunction is upregulated during hypoxia, inflammation and progress of pulmonary disease.

    Aim: To investigate if plasma endostatin is associated to hypoxia, inflammation and 30-day mortality in patients with severe COVID-19 infection.

    Method: Samples for blood analysis and plasma endostatin quantification were collected from adult patients with ongoing COVID-19 (n = 109) on admission to intensive care unit (day 1). Demographic characteristics and 30-day mortality data were extracted from medical records. The ability of endostatin to predict mortality was analyzed using receiving operating characteristics and Kaplan-Meier analysis with a cutoff at 46.2 ng/ml was used to analyze the association to survival.

    Results: Plasma endostatin levels correlated with; PaO2/FiO2 (r = -0.3, p < 0.001), arterial oxygen tension (r = -0.2, p = 0.01), lactate (r = 0.2, p = 0.04), C-reactive protein (r = 0.2, p = 0.04), ferritin (r = 0.2, p = 0.09), D-dimer (r = 0.2, p = 0.08) and IL-6 (r = 0.4, p < 0.001). Nonsurvivors at 30 days had higher plasma endostatin levels than survivors (72 ± 26 vs 56 ± 16 ng/ml, p = 0.01). Receiving operating characteristic curve (area under the curve 0.7) showed that plasma endostatin >46.2 ng/ml predicts mortality with a sensitivity of 92% and specificity of 71%. In patients with plasma endostatin >46.2 ng/ml probability of survival was lower (p = 0.02) in comparison to those with endostatin <46.2 ng/ml.

    Conclusion: Our results suggest that plasma endostatin is an early biomarker for disease severity in COVID-19.

  • 15.
    Asswad, Amjad Ghazal
    et al.
    Newcastle Upon Tyne Hosp NHS Fdn Trust, Freeman Hosp, Cardiol Dept, Freeman Rd, Newcastle Upon Tyne NE7 7DN, Tyne & Wear, England..
    Holm, Sebastian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Plastikkirurgi. Department of Plastic and Maxillofacial Surgery, Burn Centre, Uppsala University Hospital, 751 85, Uppsala, Sweden.
    Engström, Olof
    Department of Plastic and Maxillofacial Surgery, Burn Centre, Uppsala University Hospital, 751 85, Uppsala, Sweden.
    Huss, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Plastikkirurgi. Department of Plastic and Maxillofacial Surgery, Burn Centre, Uppsala University Hospital, 751 85, Uppsala, Sweden.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    Rudolph, Andre
    Karolinska Univ Hosp, Pediat Heart Ctr Stockholm Uppsala, Stockholm, Sweden.;Karolinska Univ Hosp, Karolinska Inst, Dept Med, Stockholm, Sweden..
    Delayed, Unprovoked, Hemodynamic Collapse with Following Asystole in a Pediatric Patient Following a High-Voltage Injury: A Case Report and Literature Review2022Ingår i: Pediatric Cardiology, ISSN 0172-0643, E-ISSN 1432-1971, Vol. 43, nr 5, s. 1163-1168Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Electrical incidents are common and mostly uneventful, though can be severe and sometimes lethal. Aside from skin, muscle and soft tissue damage, electrical injuries can cause cardiac arrhythmias, the most common cardiac complication. The case of a 14-year-old girl who sustained 48.5% TBSA burns following a high-voltage electrical injury is described. She suffered five episodes of asystole 78 h following the injury, requiring extracorporeal membrane oxygenation. The cause of the delayed asystole was investigated and a PubMed literature search was conducted to explore late presenting cardiac sequelae following electrical injuries. This yielded fifteen studies, identified as relevant, of high quality and in the English language. These studies included a total of 1411 patients of whom only 3 were found to have had late potentially lethal arrhythmias, all manifesting within the first 24 h after the injury. Of these patients, 32 suffered cardiac arrests shortly after the electrical injury, 11 of which were documented as asystolic arrests though these were all from a single study with the rural locale and prolonged delay in arrival to the hospital setting contributing to this finding. To our knowledge, this is the only pediatric cardiac arrest developing in a stable patient over 72 h following the initial electrical injury. No other patient has suffered any significant cardiac complications first presenting outside the initial 24-h period following the electrical injury. Guidelines and recommendations on post electrical injury observation of patient vary and further research into this field is required to allow for guidance unification.

  • 16.
    Auckburally, Adam
    et al.
    Swedish Univ Agr Sci, Fac Vet Med & Anim Sci, Dept Clin Sci, Uppsala, Sweden..
    Wiklund, Maja K.
    Swedish Univ Agr Sci, Fac Vet Med & Anim Sci, Dept Clin Sci, Uppsala, Sweden..
    Lord, Peter F.
    Swedish Univ Agr Sci, Fac Vet Med & Anim Sci, Dept Clin Sci, Uppsala, Sweden..
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    Nyman, Gorel
    Swedish Univ Agr Sci, Fac Vet Med & Anim Sci, Dept Clin Sci, Uppsala, Sweden..
    Effects of pulsed inhaled nitric oxide delivery on the distribution of pulmonary perfusion in spontaneously breathing and mechanically ventilated anesthetized ponies2022Ingår i: American Journal of Veterinary Research, ISSN 0002-9645, E-ISSN 1943-5681, Vol. 83, nr 2, s. 171-179Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To measure changes in pulmonary perfusion during pulsed inhaled nitric oxide (PiNO) delivery in anesthetized, spontaneously breathing and mechanically ventilated ponies positioned in dorsal recumbency.

    Animals: 6 adult ponies.

    Procedures: Ponies were anesthetized, positioned in dorsal recumbency in a CT gantry, and allowed to breathe spontaneously. Pulmonary artery, right atrial, and facial artery catheters were placed. Analysis time points were baseline, after 30 minutes of PiNO, and 30 minutes after discontinuation of PiNO. At each time point, iodinated contrast medium was injected, and CT angiography was used to measure pulmonary perfusion. Thermodilution was used to measure cardiac output, and arterial and mixed venous blood samples were collected simultaneously and analyzed. Analyses were repeated while ponies were mechanically ventilated.

    Results: During PiNO delivery, perfusion to aerated lung regions increased, perfusion to atelectatic lung regions decreased, arterial partial pressure of oxygen increased, and venous admixture and the alveolar-arterial difference in partial pressure of oxygen decreased. Changes in regional perfusion during PiNO delivery were more pronounced when ponies were spontaneously breathing than when they were mechanically ventilated.

    Clinical relevance: In anesthetized, dorsally recumbent ponies, PiNO delivery resulted in redistribution of pulmonary perfusion from dependent, atelectatic lung regions to nondependent aerated lung regions, leading to improvements in oxygenation. PiNO may offer a treatment option for impaired oxygenation induced by recumbency.

  • 17.
    Bahnasawy, Salma M.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Skorup, Paul
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin.
    Hanslin, Katja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Friberg, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    Nielsen, Elisabet I.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Predicting cytokine kinetics during sepsis; a modelling framework from a porcine sepsis model with live Escherichia coli2023Ingår i: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 169, artikel-id 156296Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Describing the kinetics of cytokines involved as biomarkers of sepsis progression could help to optimise interventions in septic patients. This work aimed to quantitively characterise the cytokine kinetics upon exposure to live E. coli by developing an in silico model, and to explore predicted cytokine kinetics at different bacterial exposure scenarios.

    Methods: Data from published in vivo studies using a porcine sepsis model were analysed. A model describing the time courses of bacterial dynamics, endotoxin (ETX) release, and the kinetics of TNF and IL-6 was developed. The model structure was extended from a published model that quantifies the ETX-cytokines relationship. An external model evaluation was conducted by applying the model to literature data. Model simulations were performed to explore the sensitivity of the host response towards differences in the input rate of bacteria, while keeping the total bacterial burden constant.

    Results: The analysis included 645 observations from 30 animals. The blood bacterial count was well described by a one-compartment model with linear elimination. A scaling factor was estimated to quantify the ETX release by bacteria. The model successfully described the profiles of TNF, and IL-6 without a need to modify the ETXcytokines model structure. The kinetics of TNF, and IL-6 in the external datasets were well predicted. According to the simulations, the ETX tolerance development results in that low initial input rates of bacteria trigger the lowest cytokine release.

    Conclusion: The model quantitively described and predicted the cytokine kinetics triggered by E. coli exposure. The host response was found to be sensitive to the bacterial exposure rate given the same total bacterial burden.

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  • 18.
    Balintescu, Anca
    et al.
    Section of Anaesthesia and Intensive Care, Department of Clinical Science and Education Södersjukhuset, Karolinska Institute, Stockholm, Sweden..
    Palmgren, Ida
    Section of Anaesthesia and Intensive Care, Hudiksvall Hospital, Hudiksvall, Sweden..
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Oldner, Anders
    Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden..
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Cronhjort, Maria
    Section of Anaesthesia and Intensive Care, Department of Clinical Science and Education Södersjukhuset, Karolinska Institute, Stockholm, Sweden..
    Lind, Marcus
    Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden..
    Wernerman, Jan
    Division of Anaesthesia and Intensive Care, Department of Clinical Science Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden..
    Mårtensson, Johan
    n of Anaesthesia and Intensive Care, Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden..
    Prevalence and impact of chronic dysglycemia in intensive care unit patients-A retrospective cohort study.2021Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 65, nr 1, s. 82-91Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The prevalence of chronic dysglycemia (diabetes and prediabetes) in patients admitted to Swedish intensive care units (ICUs) is unknown. We aimed to determine the prevalence of such chronic dysglycemia and asses its impact on blood glucose control and patient-centered outcomes in critically ill patients.

    METHODS: In this retrospective observational cohort study, we obtained glycated hemoglobin A1c (HbA1c) in patients admitted to four tertiary ICUs in Sweden between March and August 2016. Based on previous diabetes history and HbA1c we determined the prevalence of chronic dysglycemia. We used multivariable regression analyses to study the association of chronic dysglycemia with the time-weighted average blood glucose concentration, glycemic lability index (GLI), and development of hypoglycemia (co-primary outcomes), and with ICU length of stay, mechanical ventilation duration, renal replacement therapy (RRT) use, vasopressor use, ICU-acquired infections, and mortality (exploratory clinical outcomes).

    RESULTS: Of 943 patients, 312 (33%) had chronic dysglycemia. Of these 312 patients, 84 (27%) had prediabetes, 43 (14%) had undiagnosed diabetes and 185 (59%) had known diabetes. Chronic dysglycemia was independently associated with higher time-weighted average blood glucose concentration (P < .001), higher GLI (P < .001), and hypoglycemia (P < .001). Chronic dysglycemia was independently associated with RRT use (adjusted odds ratio 1.97, 95% CI 1.24-3.13, P = .004) but not with other exploratory clinical outcomes.

    CONCLUSIONS: In four tertiary Swedish ICUs, measurement of HbA1c showed that one-third of patients had chronic dysglycemia. Chronic dysglycemia was associated with marked derangements in glycemic control, and a greater need for renal replacement therapy.

  • 19.
    Ball, Lorenzo
    et al.
    Univ Genoa, Dept Surg Sci & Integrated Diagnost, IRCCS San Martino IST, Genoa, Italy.
    Pelosi, Paolo
    Univ Genoa, Dept Surg Sci & Integrated Diagnost, IRCCS San Martino IST, Genoa, Italy.
    de Abreu, Marcelo Gama
    Tech Univ Dresden, Dept Anesthesiol & Intens Care Therapy, Dresden, Germany.
    Rocco, Patricia R. M.
    Univ Fed Rio de Janeiro, Carlos Chagas Filho Inst Biophys, Lab Pulm Invest, Rio De Janeiro, Brazil.
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Injurious Ventilation and Post-Operative Residual Curarization: A Dangerous Combination Reply2017Ingår i: TURKISH JOURNAL OF ANAESTHESIOLOGY AND REANIMATION, ISSN 2149-0937, Vol. 45, nr 1, s. 61-62Artikel i tidskrift (Övrigt vetenskapligt)
  • 20.
    Bandert, Anna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg. Department of Anaesthesiology and Intensive Care, Gävle Hospital, Lasarettvägen 1, 80324, Gävle, Sweden.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    Frithiof, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Smekal, David
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    In an endotoxaemic model, antibiotic clearance can be affected by different central venous catheter positions, during renal replacement therapy2023Ingår i: Intensive Care Medicine Experimental, E-ISSN 2197-425X, Vol. 11, nr 1, artikel-id 32Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: In intensive care, different central venous catheters (CVC) are often used for infusion of drugs. If a patient is treated with continuous renal replacement therapy (CRRT) a second catheter, a central venous dialysis catheter (CVDC), is needed. Placing the catheters close together might pose a risk that a drug infused in a CVC could be directly aspirated into a CRRT machine and cleared from the blood without giving the effect intended. The purpose of this study was to elucidate if drug clearance is affected by different catheter placement, during CRRT. In this endotoxaemic animal model, an infusion of antibiotics was administered in a CVC placed in the external jugular vein (EJV). Antibiotic clearance was compared, whether CRRT was through a CVDC placed in the same EJV, or in a femoral vein (FV). To reach a target mean arterial pressure (MAP), noradrenaline was infused through the CVC and the dose was compared between the CDVDs.

    RESULTS: The main finding in this study was that clearance of antibiotics was higher when both catheter tips were in the EJV, close together, compared to in different vessels, during CRRT. The clearance of gentamicin was 21.0 ± 7.3 vs 15.5 ± 4.2 mL/min (p 0.006) and vancomycin 19.3 ± 4.9 vs 15.8 ± 7.1 mL/min (p 0.021). The noradrenaline dose to maintain a target MAP also showed greater variance with both catheters in the EJV, compared to when catheters were placed in different vessels.

    CONCLUSION: The results in this study indicate that close placement of central venous catheter tips could lead to unreliable drug concentration, due to direct aspiration, during CRRT.

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  • 21.
    Bark, Lovisa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Ing-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Wallin, Ewa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Simren, Joel
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Mölndal, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, Mölndal, Sweden..
    Zetterberg, Henrik
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Mölndal, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, Mölndal, Sweden.;UCL Inst Neurol, Dept Neurodegenerat Dis, Queen Sq, London, England.;UK Dementia Res Inst UCL, London, England.;Hong Kong Ctr Neurodegenerat Dis, Clear Water Bay, Hong Kong, Peoples R China..
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    Frithiof, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Rostami, Elham
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Förvärvade hjärnskador. Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Hultström, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada.;Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ, Canada..
    Central nervous system biomarkers GFAp and NfL associate with post-acute cognitive impairment and fatigue following critical COVID-192023Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 13, artikel-id 13144Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A high proportion of patients with coronavirus disease 2019 (COVID-19) experience post-acute COVID-19, including neuropsychiatric symptoms. Objective signs of central nervous system (CNS) damage can be investigated using CNS biomarkers such as glial fibrillary acidic protein (GFAp), neurofilament light chain (NfL) and total tau (t-tau). We have examined whether CNS biomarkers can predict fatigue and cognitive impairment 3-6 months after discharge from the intensive care unit (ICU) in critically ill COVID-19 patients. Fifty-seven COVID-19 patients admitted to the ICU were included with analysis of CNS biomarkers in blood at the ICU and at follow up. Cognitive dysfunction and fatigue were assessed with the Montreal Cognitive Assessment (MoCA) and the Multidimensional Fatigue inventory (MFI-20). Elevated GFAp at follow-up 3-6 months after ICU discharge was associated to the development of mild cognitive dysfunction (p = 0.01), especially in women (p = 0.005). Patients who experienced different dimensions of fatigue at follow-up had significantly lower GFAp in both the ICU and at follow-up, specifically in general fatigue (p = 0.009), physical fatigue (p = 0.004), mental fatigue (p = 0.001), and reduced motivation (p = 0.001). Women showed a more pronounced decrease in GFAp compared to men, except for in mental fatigue where men showed a more pronounced GFAp decrease compared to women. NfL concentration at follow-up was lower in patients who experienced reduced motivation (p = 0.004). Our findings suggest that GFAp and NfL are associated with neuropsychiatric outcome after critical COVID-19.

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  • 22.
    Barrueta Tenhunen, Annelie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Massaro, Fabrizia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Anthea Hosp, GVM Care & Res, Cardiac Anesthesia & Intens Care, Bari, Italy.
    Hansson, Hans Arne
    Univ Gothenburg, Inst Biomed, Gothenburg, Sweden.
    Feinstein, Ricardo
    Natl Vet Inst, Dept Pathol & Wildlife Dis, Uppsala, Sweden.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Perchiazzi, Gaetano
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Does the antisecretory peptide AF-16 reduce lung oedema in experimental ARDS?2019Ingår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, nr 4, s. 246-253Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Acute respiratory distress syndrome (ARDS) is an acute inflammatory condition with pulmonary capillary leakage and lung oedema formation. There is currently no pharmacologic treatment for the condition. The antisecretory peptide AF-16 reduces oedema in experimental traumatic brain injury. In this study, we tested AF-16 in an experimental porcine model of ARDS.

    Methods: Under surgical anaesthesia 12 piglets were subjected to lung lavage followed by 2 hours of injurious ventilation. Every hour for 4 hours, measurements of extravascular lung water (EVLW), mechanics of the respiratory system, and hemodynamics were obtained.

    Results: There was a statistically significant (p = 0.006, two-way ANOVA) reduction of EVLW in the AF-16 group compared with controls. However, this was not mirrored in any improvement in the wet-to-dry ratio of lung tissue samples, histology, inflammatory markers, lung mechanics, or gas exchange.

    Conclusions: This pilot study suggests that AF-16 might improve oedema resolution as indicated by a reduction in EVLW in experimental ARDS.

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  • 23.
    Barrueta Tenhunen, Annelie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    van der Heijden, Jaap
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Blokhin, Ivan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Massaro, Fabrizia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Cardiac Anesthesia and Intensive Care, Anthea Hospital, GVM Care & Research, Bari, Italy.
    Hansson, Hans Arne
    Institute of Biomedicine, University of Gothenburg, Göteborg, Sweden.
    Feinstein, Ricardo
    Department of Pathology and Wildlife Diseases, National Veterinary Institute, Uppsala, Sweden.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    The antisecretory peptide AF-16 may modulate tissue edema but not inflammation in experimental peritonitis induced sepsis2020Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 15, nr 8, artikel-id e0232302Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Sepsis is a life-threatening condition due to a dysregulated immunological response to infection. Apart from source control and broad-spectrum antibiotics, management is based on fluid resuscitation and vasoactive drugs. Fluid resuscitation implicates the risk of volume overload, which in turn is associated with longer stay in intensive care, prolonged use of mechanical ventilation and increased mortality. Antisecretory factor (AF), an endogenous protein, is detectable in most tissues and in plasma. The biologically active site of the protein is located in an 8-peptide sequence, contained in a synthetic 16-peptide fragment, named AF-16. The protein as well as the peptide AF-16 has multiple modulatory effects on abnormal fluid transport and edema formation/resolution as well as in a variety of inflammatory conditions. Apart from its' anti-secretory and anti-inflammatory characteristics, AF is an inhibitor of capillary leakage in intestine. It is not known whether the protein AF or the peptide AF-16 can ameliorate symptoms in sepsis. We hypothesized that AF-16 decreases the degree of hemodynamic instability, the need of fluid resuscitation, vasopressor dose and tissue edema in fecal peritonitis. To test the hypothesis, we induced peritonitis and sepsis by injecting autologous fecal solution into abdominal cavity of anesthetized pigs, and randomized (in a blind manner) the animals to intervention (AF-16, n = 8) or control (saline, n = 8) group. After the onset of hemodynamic instability (defined as mean arterial pressure < 60 mmHg maintained for > 5 minutes), intervention with AF-16 (20 mg/kg (50 mg/ml) in 0.9% saline) intravenously (only the vehicle in the control group) and a protocolized resuscitation was started. We recorded respiratory and hemodynamic parameters hourly for twenty hours or until the animal died and collected post mortem tissue samples at the end of the experiment. No differences between the groups were observed regarding hemodynamics, overall fluid balance, lung mechanics, gas exchange or histology. However, liver wet-to-dry ratio remained lower in AF-16 treated animals as compared to controls, 3.1 ± 0.4, (2.7-3.5, 95% CI, n = 8) vs 4.0 ± 0.6 (3.4-4.5, 95% CI, n = 8), p = 0.006, respectively. Bearing in mind the limited sample size, this experimental pilot study suggests that AF-16 may inhibit sepsis induced liver edema in peritonitis-sepsis.

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  • 24.
    Barrueta Tenhunen, Annelie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    van der Heijden, Jaap
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Skorup, Paul
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin.
    Maccarana, Marco
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    Perchiazzi, Gaetano
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Fluid restrictive resuscitation with high molecular weight hyaluronan infusion in early peritonitis sepsis2023Ingår i: Intensive Care Medicine Experimental, E-ISSN 2197-425X, Vol. 11, nr 1, artikel-id 63Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Sepsis is a condition with high morbidity and mortality. Prompt recognition and initiation of treatment is essential. Despite forming an integral part of sepsis management, fluid resuscitation may also lead to volume overload, which in turn is associated with increased mortality. The optimal fluid strategy in sepsis resuscitation is yet to be defined. Hyaluronan, an endogenous glycosaminoglycan with high affinity to water is an important constituent of the endothelial glycocalyx. We hypothesized that exogenously administered hyaluronan would counteract intravascular volume depletion and contribute to endothelial glycocalyx integrity in a fluid restrictive model of peritonitis. In a prospective, blinded model of porcine peritonitis sepsis, we randomized animals to intervention with hyaluronan (n = 8) or 0.9% saline (n = 8). The animals received an infusion of 0.1% hyaluronan 6 ml/kg/h, or the same volume of saline, during the first 2 h of peritonitis. Stroke volume variation and hemoconcentration were comparable in the two groups throughout the experiment. Cardiac output was higher in the intervention group during the infusion of hyaluronan (3.2 ± 0.5 l/min in intervention group vs 2.7 ± 0.2 l/min in the control group) (p = 0.039). The increase in lactate was more pronounced in the intervention group (3.2 ± 1.0 mmol/l in the intervention group and 1.7 ± 0.7 mmol/l in the control group) at the end of the experiment (p < 0.001). Concentrations of surrogate markers of glycocalyx damage; syndecan 1 (0.6 ± 0.2 ng/ml vs 0.5 ± 0.2 ng/ml, p = 0.292), heparan sulphate (1.23 ± 0.2 vs 1.4 ± 0.3 ng/ml, p = 0.211) and vascular adhesion protein 1 (7.0 ± 4.1 vs 8.2 ± 2.3 ng/ml, p = 0.492) were comparable in the two groups at the end of the experiment. In conclusion, hyaluronan did not counteract intravascular volume depletion in early peritonitis sepsis. However, this finding is hampered by the short observation period and a beneficial effect of HMW-HA in peritonitis sepsis cannot be discarded based on the results of the present study.

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  • 25.
    Batista Borges, João
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Univ Sao Paulo, Hosp Clin, Pulm Div Heart Inst InCor, Sao Paulo, Brazil..
    Hansen, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    The "normal" ventilated airspaces suffer the most damaging effects of mechanical ventilation2017Ingår i: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 43, nr 7, s. 1057-1058Artikel i tidskrift (Övrigt vetenskapligt)
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  • 26.
    Batista Borges, João
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Bergman, J. S.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet.
    Dussault, C.
    Armed Forces Biomed Res Inst, Bretigny Sur Orge, France..
    Amato, M. B. P.
    Univ Sao Paulo, Sch Med, Sao Paulo, Brazil..
    Montmerle-Borgdorff, S.
    Armed Forces Biomed Res Inst, Bretigny Sur Orge, France..
    First-Time Monitoring Of Simultaneous Effects Of Hypergravity On Heart And Lung By Electrical Impedance Tomography2016Ingår i: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 193Artikel i tidskrift (Refereegranskat)
  • 27.
    Batista Borges, João
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Santos, Arnoldo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lucchetta, L.
    Hosp San Matteo, Pavia, Italy..
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Suarez-Sipmann, Fernando
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Redistribution Of Regional Lung Perfusion During Mechanical Ventilation With An Open Lung Approach Impacts Pulmonary Vascular Mechanics2017Ingår i: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 195, artikel-id A3751Artikel i tidskrift (Övrigt vetenskapligt)
  • 28.
    Baumgardner, James E.
    et al.
    Univ Pittsburgh, Med Ctr, Dept Anesthesiol & Perioperat Med, Pittsburgh, PA 15213 USA.;Oscill LLC, Pittsburgh, PA USA..
    Kretzschmar, Moritz
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Otto von Guericke Univ, Dept Anesthesiol & Intens Care Med, Magdeburg, Germany..
    Kozian, Alf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Otto von Guericke Univ, Dept Anesthesiol & Intens Care Med, Magdeburg, Germany..
    Hachenberg, Thomas
    Otto von Guericke Univ, Dept Anesthesiol & Intens Care Med, Magdeburg, Germany..
    Schilling, Thomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Otto von Guericke Univ, Dept Anesthesiol & Intens Care Med, Magdeburg, Germany..
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Effect of Global Ventilation to Perfusion Ratio, for Normal Lungs, on Desflurane and Sevoflurane Elimination Kinetics2021Ingår i: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 135, nr 6, s. 1042-1054Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Kinetics of the uptake of inhaled anesthetics have been well studied, but the kinetics of elimination might be of more practical importance. The objective of the authors' study was to assess the effect of the overall ventilation/perfusion ratio (V-A/Q), for normal lungs, on elimination kinetics of desflurane and sevoflurane.

    Methods: The authors developed a mathematical model of inhaled anesthetic elimination that explicitly relates the terminal washout time constant to the global lung V-A/Q ratio. Assumptions and results of the model were tested with experimental data from a recent study, where desflurane and sevoflurane elimination were observed for three different V-A/Q conditions: normal, low, and high.

    Results: The mathematical model predicts that the global V-A/Q ratio, for normal lungs, modifies the time constant for tissue anesthetic washout throughout the entire elimination. For all three V-A/Q conditions, the ratio of arterial to mixed venous anesthetic partial pressure P-art/P-mv reached a constant value after 5 min of elimination, as predicted by the retention equation. The time constant corrected for incomplete lung clearance was a better predictor of late-stage kinetics than the intrinsic tissue time constant.

    Conclusions: In addition to the well-known role of the lungs in the early phases of inhaled anesthetic washout, the lungs play a long-overlooked role in modulating the kinetics of tissue washout during the later stages of inhaled anesthetic elimination. The V-A/Q ratio influences the kinetics of desflurane and sevoflurane elimination throughout the entire elimination, with more pronounced slowing of tissue washout at lower V-A/Q ratios.

  • 29.
    Bayat, S.
    et al.
    Grenoble Univ Hosp, Clin Physiol Sommeil & Exercice, Grenoble, France; Grenoble Univ Hosp, RSRM EA 7442, Grenoble, France; Univ Grenoble Alpes, Grenoble, France.
    Fardin, L.
    European Synchrotron Radiat Facil, Biomed Beamline ID17, Grenoble, France.
    Broche, L.
    European Synchrotron Radiat Facil, Biomed Beamline ID17, Grenoble, France.
    Lovric, G.
    Paul Scherrer Inst, Swiss Light Source, Villigen, Switzerland.
    Larsson, Anders S.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Bravin, A.
    European Synchrotron Radiat Facil, Biomed Beamline ID17, Grenoble, France.
    High-Resolution Time-Resolved Phase-Contrast Synchrotron CT for Mapping Cardiac-Induced Lung Motion2018Ingår i: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 197Artikel i tidskrift (Övrigt vetenskapligt)
  • 30.
    Bayat, Sam
    et al.
    Univ Grenoble Alpes, Inserm UA07, STROBE Lab, Grenoble, France.;Grenoble Univ Hosp, Departmentof Pulmonol & Clin Physiol, Grenoble, France..
    Fardin, Luca
    European Synchrotron Radiat Facil, Grenoble, France..
    Cercos-Pita, Jose Luis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    Perchiazzi, Gaetano
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    Bravin, Alberto
    Univ Milano Bicocca, Dept Phys, Milan, Italy..
    Imaging Regional Lung Structure and Function in Small Animals Using Synchrotron Radiation Phase-Contrast and K-Edge Subtraction Computed Tomography2022Ingår i: Frontiers in Physiology, E-ISSN 1664-042X, Vol. 13, artikel-id 825433Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Synchrotron radiation offers unique properties of coherence, utilized in phase-contrast imaging, and high flux as well as a wide energy spectrum which allow the selection of very narrow energy bands of radiation, used in K-edge subtraction imaging (KES) imaging. These properties extend X-ray computed tomography (CT) capabilities to quantitatively assess lung morphology, and to map regional lung ventilation, perfusion, inflammation, aerosol particle distribution and biomechanical properties, with microscopic spatial resolution. Four-dimensional imaging, allows the investigation of the dynamics of regional lung functional parameters simultaneously with structural deformation of the lung as a function of time. These techniques have proven to be very useful for revealing the regional differences in both lung structure and function which is crucial for better understanding of disease mechanisms as well as for evaluating treatment in small animal models of lung diseases. Here, synchrotron radiation imaging methods are described and examples of their application to the study of disease mechanisms in preclinical animal models are presented.

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  • 31.
    Bellani, Giacomo
    et al.
    Univ Milano Bicocca, Sch Med & Surg, Monza, Italy.;San Gerardo Hosp, Dept Emergency & Intens Care, Monza, Italy..
    Laffey, John G.
    St Michaels Hosp, Dept Anesthesia & Crit Care Med, Keenan Res Ctr Biomed Sci, Toronto, ON, Canada.;Univ Toronto, Dept Anesthesia, 30 Bond St, Toronto, ON M5B 1W8, Canada.;Univ Toronto, Dept Physiol, 30 Bond St, Toronto, ON M5B 1W8, Canada.;Univ Toronto, Interdept Div Crit Care Med, 30 Bond St, Toronto, ON M5B 1W8, Canada..
    Pham, Tai
    Grp Hosp Hop Univ Est Parisien, Hop Tenon, AP HP, Unite Reanimat Med Chirurgicale,Pole Thorax Voies, Paris, France.;Univ Paris Diderot, Sorbonne Paris Cite, ECSTRA Team, UMR 1153,Inserm, Paris, France.;Univ Paris Est Creteil, UMR 915, INSERM, Creteil, France..
    Fan, Eddy
    Univ Toronto, Interdept Div Crit Care Med, 30 Bond St, Toronto, ON M5B 1W8, Canada.;Univ Hlth Network, Dept Med, Toronto, ON, Canada.;Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada.;Univ Toronto, Inst Hlth Policy Management & Evaluat, 30 Bond St, Toronto, ON M5B 1W8, Canada..
    Brochard, Laurent
    Univ Toronto, Interdept Div Crit Care Med, 30 Bond St, Toronto, ON M5B 1W8, Canada.;St Michaels Hosp, Keenan Res Ctr, Li Ka Shing Knowledge Inst, 30 Bond St, Toronto, ON M5B 1W8, Canada..
    Esteban, Andres
    Univ Toronto, Interdept Div Crit Care Med, 30 Bond St, Toronto, ON M5B 1W8, Canada.;Hosp Univ Getafe, CIBER Enfermedades Respiratorias, Madrid, Spain..
    Gattinoni, Luciano
    Univ Milan, Ist Anestesia & Rianimaz, Osped Maggiore, Ist Ricovero & Cura Carattere Sci, Milan, Italy..
    van Haren, Frank
    Canberra Hosp, Intens Care Unit, Canberra, ACT, Australia.;Australian Natl Univ, Canberra, ACT, Australia..
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    McAuley, Daniel F.
    Queens Univ Belfast, Ctr Med Expt, Belfast, Antrim, North Ireland.;Wellcome Wolfson Inst Expt Med, Belfast, Antrim, North Ireland.;Royal Victoria Hosp, Reg Intens Care Unit, Grosvenor Rd, Belfast BT12 6BA, Antrim, North Ireland..
    Ranieri, Marco
    Policlin Umberto 1, SAPIENZA Univ ROMA, Dipartimento Anestesia & Rianimaz, Viale Policlin 155, I-00161 Rome, Italy..
    Rubenfeld, Gordon
    Univ Toronto, Interdept Div Crit Care Med, 30 Bond St, Toronto, ON M5B 1W8, Canada.;Sunnybrook Hlth Sci Ctr, Program Trauma Emergency & Crit Care, Toronto, ON M4N 3M5, Canada..
    Thompson, B. Taylor
    Harvard Univ, Sch Med, Div Pulm, Boston, MA USA.;Harvard Univ, Massachusetts Gen Hosp, Sch Med, Crit Care Unit,Dept Med, Boston, MA USA..
    Wrigge, Hermann
    Univ Leipzig, Dept Anesthesiol & Intens Care Med, Liebigstr 20, D-04103 Leipzig, Germany..
    Slutsky, Arthur S.
    Univ Toronto, Interdept Div Crit Care Med, 30 Bond St, Toronto, ON M5B 1W8, Canada.;Univ Toronto, St Michaels Hosp, Keenan Res Ctr, Li Ka Shing Knowledge Inst, 30 Bond St, Toronto, ON M5B 1W8, Canada..
    Pesenti, Antonio
    Univ Milan, Ist Anestesia & Rianimaz, Osped Maggiore, Ist Ricovero & Cura Carattere Sci, Milan, Italy..
    Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries2016Ingår i: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 315, nr 8, s. 788-800Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    IMPORTANCE Limited information exists about the epidemiology, recognition, management, and outcomes of patients with the acute respiratory distress syndrome (ARDS). OBJECTIVES To evaluate intensive care unit (ICU) incidence and outcome of ARDS and to assess clinician recognition, ventilation management, and use of adjuncts-for example prone positioning-in routine clinical practice for patients fulfilling the ARDS Berlin Definition. DESIGN, SETTING, AND PARTICIPANTS The Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients undergoing invasive or noninvasive ventilation, conducted during 4 consecutive weeks in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across 5 continents. EXPOSURES Acute respiratory distress syndrome. MAIN OUTCOMES AND MEASURES The primary outcome was ICU incidence of ARDS. Secondary outcomes included assessment of clinician recognition of ARDS, the application of ventilatory management, the use of adjunctive interventions in routine clinical practice, and clinical outcomes from ARDS. RESULTS Of 29 144 patients admitted to participating ICUs, 3022 (10.4%) fulfilled ARDS criteria. Of these, 2377 patients developed ARDS in the first 48 hours and whose respiratory failure was managed with invasive mechanical ventilation. The period prevalence of mild ARDS was 30.0%(95% CI, 28.2%-31.9%); of moderate ARDS, 46.6%(95% CI, 44.5%-48.6%); and of severe ARDS, 23.4%(95% CI, 21.7%-25.2%). ARDS represented 0.42 cases per ICU bed over 4 weeks and represented 10.4%(95% CI, 10.0%-10.7%) of ICU admissions and 23.4% of patients requiring mechanical ventilation. Clinical recognition of ARDS ranged from 51.3% (95% CI, 47.5%-55.0%) in mild to 78.5%(95% CI, 74.8%-81.8%) in severe ARDS. Less than two-thirds of patients with ARDS received a tidal volume 8 of mL/kg or less of predicted body weight. Plateau pressure was measured in 40.1%(95% CI, 38.2-42.1), whereas 82.6%(95% CI, 81.0%-84.1%) received a positive end-expository pressure (PEEP) of less than 12 cm H2O. Prone positioning was used in 16.3%(95% CI, 13.7%-19.2%) of patients with severe ARDS. Clinician recognition of ARDS was associated with higher PEEP, greater use of neuromuscular blockade, and prone positioning. Hospital mortality was 34.9%(95% CI, 31.4%-38.5%) for those with mild, 40.3%(95% CI, 37.4%-43.3%) for those with moderate, and 46.1%(95% CI, 41.9%-50.4%) for those with severe ARDS. CONCLUSIONS AND RELEVANCE Among ICUs in 50 countries, the period prevalence of ARDS was 10.4% of ICU admissions. This syndrome appeared to be underrecognized and undertreated and associated with a high mortality rate. These findings indicate the potential for improvement in the management of patients with ARDS.

  • 32. Bellani, Giacomo
    et al.
    Laffey, John G
    Pham, Tài
    Madotto, Fabiana
    Fan, Eddy
    Brochard, Laurent
    Esteban, Andres
    Gattinoni, Luciano
    Bumbasirevic, Vesna
    Piquilloud, Lise
    van Haren, Frank
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    McAuley, Daniel F
    Bauer, Philippe R
    Arabi, Yaseen M
    Ranieri, Marco
    Antonelli, Massimo
    Rubenfeld, Gordon D
    Thompson, B Taylor
    Wrigge, Hermann
    Slutsky, Arthur S
    Pesenti, Antonio
    Noninvasive Ventilation of Patients with Acute Respiratory Distress Syndrome. Insights from the LUNG SAFE Study.2017Ingår i: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 195, nr 1, s. 67-77Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Rationale: Noninvasive ventilation (NIV) is increasingly used in patients with acute respiratory distress syndrome (ARDS). The evidence supporting NIV use in patients with ARDS remains relatively sparse.

    Objectives: To determine whether, during NIV, the categorization of ARDS severity based on the PaO2/FiO2 Berlin criteria is useful.

    Methods: The LUNG SAFE (Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure) study described the management of patients with ARDS. This substudy examines the current practice of NIV use in ARDS, the utility of the PaO2/FiO2 ratio in classifying patients receiving NIV, and the impact of NIV on outcome.

    Measurements and Main Results: Of 2,813 patients with ARDS, 436 (15.5%) were managed with NIV on Days 1 and 2 following fulfillment of diagnostic criteria. Classification of ARDS severity based on PaO2/FiO2 ratio was associated with an increase in intensity of ventilatory support, NIV failure, and intensive care unit (ICU) mortality. NIV failure occurred in 22.2% of mild, 42.3% of moderate, and 47.1% of patients with severe ARDS. Hospital mortality in patients with NIV success and failure was 16.1% and 45.4%, respectively. NIV use was independently associated with increased ICU (hazard ratio, 1.446 [95% confidence interval, 1.159–1.805]), but not hospital, mortality. In a propensity matched analysis, ICU mortality was higher in NIV than invasively ventilated patients with a PaO2/FiO2 lower than 150 mm Hg.

    Conclusions: NIV was used in 15% of patients with ARDS, irrespective of severity category. NIV seems to be associated with higher ICU mortality in patients with a PaO2/FiO2 lower than 150 mm Hg.

  • 33.
    Berghäll, Elisabeth
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hultström, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Frithiof, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    Hahn-Strömberg, Victoria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    The Evolution of Blood Cell Phenotypes, Intracellular and Plasma Cytokines and Morphological Changes in Critically Ill COVID-19 Patients2022Ingår i: Biomedicines, E-ISSN 2227-9059, Vol. 10, nr 5, artikel-id 934Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Severe coronavirus disease 2019 (COVID-19) causes a strong inflammatory response. To obtain an overview of inflammatory mediators and effector cells, we studied 25 intensive-care-unit patients during the timeframe after off-label chloroquine treatment and before an introduction of immunomodulatory drugs.

    Material and methods: Blood samples were weekly examined with flow cytometry (FCM) for surface and intracytoplasmic markers, cytokine assays were analyzed for circulating interleukins (ILs), and blood smears were evaluated for morphological changes. Samples from healthy volunteers were used for comparison. Organ function data and 30-day mortality were obtained from medical records.

    Results: Compared to that of the healthy control group, the expression levels of leukocyte surface markers, i.e., the cluster of differentiation (CD) markers CD2, CD4, CD8, CD158d, CD25, CD127, and CD19, were lower (p < 0.001), while those of leukocytes expressing CD33 were increased (p < 0.05). An aberrant expression of CD158d on granulocytes was found on parts of the granulocyte population. The expression levels of intracellular tumor necrosis factor alpha (TNF alpha) and IL-1 receptor type 2 in leukocytes were higher (p < 0.001) as well as plasma levels of TNF alpha, IL-2, IL-6, IL-8, IL-10 (p < 0.001), interferon gamma (IFN gamma) (p < 0.01), and granulocyte-macrophage colony-stimulating factor (GM-CSF) (p < 0.05). The expression levels of CD33+ leukocytes and circulating IL-6 were higher (p < 0.05) among patients with arterial oxygen partial pressure-to-fractional inspired oxygen (PaO2/FiO(2)) ratios below 13.3 kPa compared to in the remaining patients. The expression levels of TNF alpha, IL-2, IL-4, IL-6, IL-8, and IL-10 were higher in patients treated with continuous renal replacement therapy (CRRT) (p < 0.05), and the levels of the maximum plasma creatinine and TNF alpha Spearman's rank-order correlation coefficient (rho = 0.51, p < 0.05) and IL-8 (rho = 0.44, p < 0.05) correlated. Blood smears revealed neutrophil dysplasia with pseudo-Pelger forms being most common.

    Conclusion: These findings suggest that patients with severe COVID-19, in addition to augmented ILs, lymphopenia, and increased granulocytes, also had effects on the bone marrow.

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  • 34.
    Bergmann, Astrid
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Department of Anesthesiology and Intensive Care Medicine, Otto-von-Guericke-University Magdeburg, Germany.
    Breitling, Christian
    Department of Anesthesiology and Intensive Care Medicine, Otto-von-Guericke-University Magdeburg, Germany.
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Kretzschmar, Moritz
    Department of Anesthesiology and Intensive Care Medicine, Otto-von-Guericke-University Magdeburg, Germany.
    Kozian, Alf
    Department of Anesthesiology and Intensive Care Medicine, Otto-von-Guericke-University Magdeburg, Germany.
    Hachenberg, Thomas
    Department of Anesthesiology and Intensive Care Medicine, Otto-von-Guericke-University Magdeburg, Germany.
    Schilling, Thomas
    Department of Anesthesiology and Intensive Care Medicine, Otto-von-Guericke-University Magdeburg, Germany.
    Data on the effects of remote ischemic preconditioning in the lungs after one-lung ventilation2018Ingår i: Data in Brief, E-ISSN 2352-3409, Vol. 21, s. 441-448Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This article contains data on experimental endpoints of a randomized controlled animal trial. Fourteen healthy piglets underwent mechanical ventilation including injurious one-lung ventilation (OLV), seven of them experienced four cycles of remote ischemic preconditioning (RIP) on one hind limb immediately before OLV, seven of them did not receive RIP and served as controls, in a randomized manner. The two major endpoints were (1) pulmonary damage assessed with the diffuse alveolar damage (DAD) score and (2) the inflammatory response assessed by cytokine concentrations in serum and in bronchoalveolar lavage fluids (BAL). The cytokine levels in the homogenized lung tissue samples are presented in the original article. Further interpretation and discussion of these data can be found in Bergmann et al. (in press).

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  • 35.
    Bergmann, Astrid
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Otto von Guericke Univ, Cardiothorac Anesthesia, Dept Anesthesiol & Intens Care Med, Magdeburg, Germany.
    Jovanovska, Elena
    Otto von Guericke Univ, Dept Anesthesiol & Intens Care Med, Anesthesiol, Magdeburg, Germany.
    Schilling, Thomas
    Otto von Guericke Univ, Dept Anesthesiol & Intens Care Med, Anesthesia, Magdeburg, Germany.
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Follner, Sebastian
    Otto von Guericke Univ, Dept Pulmonol, Magdeburg, Germany.
    Schreiber, Jens
    Otto von Guericke Univ, Dept Pulmonol, Pulmonol, Magdeburg, Germany.
    Hachenberg, Thomas
    Otto von Guericke Univ, Anesthesia, Magdeburg, Germany;Otto von Guericke Univ, Dept Anesthesiol & Intens Care Med, Leipziger Str 44, D-39120 Magdeburg, Germany.
    Early and late effects of remote ischemic preconditioning on spirometry and gas exchange in healthy volunteers2020Ingår i: Respiratory Physiology & Neurobiology, ISSN 1569-9048, E-ISSN 1878-1519, Vol. 271, artikel-id 103287Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: Remote ischemic preconditioning (RIP) may protect remote organs from ischemia-reperfusion-injury (IRI) in surgical and non-surgical patients. There are few data available on RIP and lung function, especially not in healthy volunteers. The null-hypothesis was tested that RIP does not have an effect on pulmonary function when applied on healthy volunteers that were breathing spontaneously and did not experience any intervention. After approval of the Ethics Committee and informed consent of the study subjects, 28 healthy non-smoking volunteers were included and randomized in either the RIP group (n = 13) or the control group (n = 15). In the RIP group, lower limb ischemia was induced by inflation of a blood pressure cuff to a pressure 20 mmHg above the systolic blood pressure. After five minutes the blood pressure cuff was released for five minutes rest. The procedure was repeated three times resulting in 40 min ischemia and reperfusion. Capillary blood samples were taken, and lung function tests were performed at baseline (T1) and 60 min (T2) and 24 h (T3) after RIP. The control group was treated in the same fashion, but the RIP procedure was replaced by a sham protocol.

    Results: 60 min after RIP capillary pO(2) decreased significantly and returned to baseline level after 24 h in the RIP group. This did not occur in the control group. Capillary pCO(2), variables of lung function tests and pulmonary capillary blood volume remained unchanged throughout the experiment in both groups.

    Conclusion: Oxygenation is impaired early after RIP which is possibly induced by transient ventilation-perfusion inequality. No late effects of RIP were observed. The null hypothesis has to be rejected that RIP has no effect on respiratory variables in healthy volunteers.

  • 36.
    Bergmann, Astrid
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Department of Anesthesiology and Intensive Care Medicine, Otto-von-Guericke-University Magdeburg, Germany.
    Schilling, Thomas
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Ahlgren, Kerstin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    Kretzschmar, Moritz
    Kozian, Alf
    Hachenberg, Thomas
    Pulmonary effects of remote ischemic preconditioning in a porcine model of ventilation-induced lung injury2019Ingår i: Respiratory Physiology & Neurobiology, ISSN 1569-9048, E-ISSN 1878-1519, Vol. 259, s. 111-118Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: One-lung ventilation (OLV) may result in lung injury due to increased mechanical stress and tidal recruitment. As a result, a pulmonary inflammatory response is induced. The present randomized, controlled, animal experiment was undertaken to assess the effects of remote ischemic preconditioning (RIP) on diffuse alveolar damage and immune response after OLV.

    METHODS: Fourteen piglets (26 ± 2 kg) were randomized to control (n = 7) and RIP group (n = 7). For RIP, a blood pressure cuff at hind limb was inflated up to 200 mmHg for 5 min and deflated for another 5 min, this being done four times before OLV. Mechanical ventilation settings were constant throughout the experiment: VT = 10 ml/kg, FIO2 = 0.40, PEEP = 5cmH2O. OLV was performed by left-sided bronchial blockade. Number of cells was counted from BAL fluid; cytokines were assessed by immunoassays in lung tissue and serum samples. Lung tissue samples were obtained for histological analysis and assessment of diffuse alveolar damage (DAD) score.

    RESULTS: Hemodynamic and respiratory data were similar in both groups. Likewise, no differences in pulmonary tissue TNF-α and protein content were found, but fewer leukocytes were counted in the ventilated lung after RIP. DAD scores were high without any differences between controls and RIP. On the other hand, alveolar edema and microhemorrhage were significantly increased after RIP.

    CONCLUSIONS: OLV results in alveolar injury, possibly enhanced by RIP. On the other hand, RIP attenuates the immunological response and decreased alveolar leukocyte recruitment in a porcine model of OLV.

  • 37.
    Bergmann, Astrid
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Department of Anesthesiology and Intensive Care Medicine, Otto-von-Guericke-University Magdeburg, Germany.
    Schilling, Thomas
    Perchiazzi, Gaetano
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Kretzschmar, Moritz
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Hachenberg, Thomas
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Effect of remote ischemic preconditioning on exhaled nitric oxide concentration in piglets during and after one-lung ventilation2020Ingår i: Respiratory Physiology & Neurobiology, ISSN 1569-9048, E-ISSN 1878-1519, Vol. 276, artikel-id 103426Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Remote ischemic preconditioning (RIP) may protect target organs from ischemia - reperfusion injury, however, little is known on pulmonary effects of RIP prior to, immediately after and several hours after one-lung ventilation (OLV). The present randomized, controlled, animal experiment was undertaken to analyze these issues.

    METHODS: After animal ethics committee approval, twelve piglets (26 ± 2 kg) were anesthetized and randomly assigned to a control (n = 6) or to a RIP group (n = 6). For RIP, arterial perfusion of a hind limb was suspended by an inflated blood pressure cuff (200 mmHg for 5 min) and deflated for another 5 min, this was repeated four times. After intubation, mechanical ventilation (MV) was kept constant with tidal volume 10 ml/kg, inspired oxygen fraction (FIO2) 0.40, and positive end-expiratory pressure (PEEP) 5cmH2O. FIO2 was increased to 1 after RIP in the RIP group and after the sham procedure in the control group, respectively, for the time of OLV. OLV was established by left-sided bronchial blockade. After OLV, TLV was re-established until the end of the protocol. Exhaled nitric oxide (NO) was measured by ozon chemiluminiscense and ventilatory and hemodynamic variables were assessed according to the protocol.

    RESULTS: Hemodynamic and respiratory data were similar in both groups. Arterial pO2 was higher in the RIP group after two hours of OLV. In the control group, exhaled NO decreased during OLV and remained at low levels for the rest of the protocol. In the RIP group, exhaled NO decreased as well during OLV but returned to baseline levels when TLV was re-established.

    CONCLUSIONS: RIP has no effects on hemodynamic and respiratory variables in juvenile, healthy piglets. RIP improves the oxygenation after OLV and prevents the decline of exhaled NO after OLV.

  • 38.
    Bergquist, Maria
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi. Univ Gothenburg, Sahlgrenska Acad, Dept Rheumatol & Inflammat Res, Gothenburg, Sweden.
    Hastbacka, Johanna
    Univ Helsinki, Intens Care Med, Dept Anesthesiol Intens Care Med & Pain Med, Helsinki, Finland;Helsinki Univ Hosp, Helsinki, Finland.
    Glaumann, Christian
    Uppsala Univ Hosp, Burn Ctr, Dept Plast & Maxillofacial Surg, Uppsala, Sweden.
    Fredén, Filip
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Huss, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Plastikkirurgi. Uppsala Univ Hosp, Burn Ctr, Dept Plast & Maxillofacial Surg, Uppsala, Sweden.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    The time-course of the inflammatory response to major burn injury and its relation to organ failure and outcome2019Ingår i: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 45, nr 2, s. 354-363Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Burn injury causes major inflammatory activation and cytokine release, however, the temporal resolution of the acute and sub-acute inflammatory response has not yet been fully delineated. To this end, we have quantified 20 inflammatory mediators in plasma from 44 adult patients 0-21 days after burn injury and related the time course of these mediators to % total body surface area (TBSA) burned, clinical parameters, organ failure and outcome. Of the cytokines analyzed in these patients, interleukin 6 (IL-6), IL-8, IL-10 and monocyte chemoattractant protein 1 (MCP-1) correlated to the size of the injury at 24-48h after burn injury. In our study, the concentration of IL-10 had prognostic value in patients with burn injury both measured at admission and at 24-48h after injury. However, simple demographic data such as age, % burned TBSA, inhalation injury and their combination, the Baux score and modified Baux score, outperform most of the cytokines, with the exception of IL-8 and MCP1 levels on admission, in predicting death.

  • 39.
    Bergquist, Maria
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Huss, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Plastikkirurgi. Uppsala Burn Center, Uppsala University Hospital, Uppsala, Sweden.
    Fredén, Filip
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala Burn Center, Uppsala University Hospital, Uppsala, Sweden.
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Hästbacka, Johanna
    Intensive Care Medicine Department of Perioperative, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Finland.
    Rockwood, Alan L.
    ARUP Institute for Clinical & Experimental Pathology, 500 Chipeta Way, Salt Lake City, UT 84108-1221, USA;Department of Pathology, University of Utah School of Medicine, Salt Lake City, USA.
    Kushnir, Mark M.
    ARUP Institute for Clinical & Experimental Pathology, 500 Chipeta Way, Salt Lake City, UT 84108-1221, USA;Department of Pathology, University of Utah School of Medicine, Salt Lake City, USA.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Department of Pathology, University of Utah School of Medicine, Salt Lake City, USA.
    Altered adrenal and gonadal steroids biosynthesis in patients with burn injury2016Ingår i: Clinical Mass Spectrometry, ISSN 2213-8005, E-ISSN 2376-9998, Vol. 1, s. 19-26Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Burn injury inevitably leads to changes in the endogenous production of cytokines, as well as adrenal and gonadal steroids. Previous studies have reported gender-related differences in outcome following burn injury, which suggests that gonadal steroids may play a role. The aim of this study was to assess alterations in concentration of endogenous steroids in patients with burn injury.

    Methods: For this single-center, prospective descriptive study, high-sensitivity liquid chromatography tandem mass spectrometry (LC-MS/MS)-based steroid quantification was used to determine longitudinal profiles of the concentrations of endogenous steroids in plasma from sixteen adult male patients with burn injury (14.5-72% of total body surface area). Steroids were extracted from plasma samples and analyzed using multiple reaction monitoring acquisition, with electrospray ionization on a triple quadruple mass spectrometer. Total protein concentration was measured in the samples using spectrophotometry.

    Results: Steroid and total protein concentration distributions were compared to reference intervals characteristic of healthy adult men. Concentrations of the following steroids in plasma of burn injured patients were found to correlate positively to the area of the burn injury: cortisol (r = 0.84), corticosterone (r = 0.73), 11-deoxycortisol (r = 0.72), androstenedione (r = 0.72), 17OH-progesterone (r = 0.68), 17OH-pregnenolone (r = 0.64) and pregnenolone (r = 0.77). Concentrations of testosterone decreased during the acute phase and were up to ten-times lower than reference values for healthy adult men, while concentrations of estrone were elevated. By day 21 after injury, testosterone concentrations were increased in younger, but not older, patients. The highest concentrations of estrone were observed on day 3 after the injury and then declined by day 21 to concentrations comparable to those observed on the day of the injury.

    Conclusion: Burn injury alters endogenous steroid biosynthesis, with decreased testosterone concentrations and elevated estrone concentrations, during the first 21 days after the injury. Concentrations of glucocorticoids, progestagens and androgen precursors correlated positively with the area of burn injury. The finding of increased estrone following burn injury needs to be confirmed in a larger hypothesis driven study.

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  • 40.
    Bergquist, Maria
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Jonasson, Sofia
    Hjoberg, Josephine
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Hanrieder, Joerg
    Comprehensive multiplexed protein quantitation delineates eosinophilic and neutrophilic experimental asthma2014Ingår i: BMC Pulmonary Medicine, E-ISSN 1471-2466, Vol. 14, s. 110-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Improvements in asthma diagnosis and management require deeper understanding of the heterogeneity of the complex airway inflammation. We hypothesise that differences in the two major inflammatory phenotypes of asthma; eosinophilic and neutrophilic asthma, will be reflected in the lung protein expression profile of murine asthma models and can be delineated using proteomics of bronchoalveolar lavage (BAL). Methods: BAL from mice challenged with ovalbumin (OVA/OVA) alone (standard model of asthma, here considered eosinophilic) or OVA in combination with endotoxin (OVA/LPS, model of neutrophilic asthma) was analysed using liquid chromatography coupled to high resolution mass spectrometry, and compared with steroid-treated animals and healthy controls. In addition, conventional inflammatory markers were analysed using multiplexed ELISA (Bio-Plex T assay). Multivariate statistics was performed on integrative proteomic fingerprints using principal component analysis. Proteomic data were complemented with lung mechanics and BAL cell counts. Results: Several of the analysed proteins displayed significant differences between the controls and either or both of the two models reflecting eosinophilic and neutrophilic asthma. Most of the proteins found with mass spectrometry analysis displayed a considerable increase in neutrophilic asthma compared with the other groups. Conversely, the larger number of the inflammatory markers analysed with Bio-Plex T analysis were found to be increased in the eosinophilic model. In addition, major inflammation markers were correlated to peripheral airway closure, while commonly used asthma biomarkers only reflect central inflammation. Conclusion: Our data suggest that the commercial markers we are currently relying on to diagnose asthma subtypes are not giving us comprehensive or specific enough information. The analysed protein profiles allowed to discriminate the two models and may add useful information for characterization of different asthma phenotypes.

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  • 41.
    Bergquist, Maria
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Samuelsson, Line
    Department of Surgical and Perioperative Sciences, Anaesthesiology and Critical Care Medicine (Östersund), Umeå University, Umeå, Sweden.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Tydén, Jonas
    Department of Surgical and Perioperative Sciences, Anaesthesiology and Critical Care Medicine (Östersund), Umeå University, Umeå, Sweden.
    Johansson, Joakim
    Department of Surgical and Perioperative Sciences, Anaesthesiology and Critical Care Medicine (Östersund), Umeå University, Umeå, Sweden.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    TNFR1, TNFR2, neutrophil gelatinase-associated lipocalin and heparin binding protein in identifying sepsis and predicting outcome in an intensive care cohort2020Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 10, nr 1, artikel-id 15350Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To date no biomarkers can aid diagnosing sepsis with adequate accuracy. We set out to assess the ability of Tumor necrosis factor receptor (TNFR) 1 and 2, Neutrophil gelatinase-associated lipocalin (NGAL) and Heparin binding protein (HBP) to discriminate sepsis from non-infected critically ill patients in a large ICU cohort, and to evaluate their value to predict mortality at 30 days. Adult patients admitted to the ICU with an arterial catheter were included. Clinical data and blood samples were prospectively recorded daily. Diagnoses were set retrospectively. Descriptive statistics and logistic regression models were used. NGAL, TNFR1 and TNFR2 were higher in sepsis patients compared to other diagnoses, as well as in non-survivors compared to survivors. In addition, these biomarkers increased with increasing stages of acute kidney injury. TNFR1 and TNFR2 performed similarly to NGAL and CRP in identifying sepsis patients, but they performed better than CRP in predicting 30-day mortality in this ICU cohort. Thus, TNFR1 and TNFR2 may be particularly useful in identifying high risk sepsis patients and facilitate relevant health care actions in this group of sepsis patients.

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  • 42. Bergström, Anna
    et al.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Yang, Bei
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Engblom, David
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden..
    Chew, Michelle S.
    Elander, Louise
    Acetaminophen Attenuates Pulmonary Vascular Resistance and Pulmonary Arterial Pressure and Inhibits Cardiovascular Collapse in a Porcine Model of Endotoxemia2023Ingår i: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 59, nr 3, s. 442-448Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Acetaminophen (paracetamol) is often used in critically ill patients with fever and pain; however, little is known about the effects of acetaminophen on cardiovascular function during systemic inflammation. Here, we investigated the effect of acetaminophen on changes in the systemic and pulmonary circulation induced by endotoxin (0.5 μg/kg/h) in anesthetized pigs. Endotoxin infusion led to a rapid increase in pulmonary artery (PA)-pressure and pulmonary vascular resistance index (PVRI). Acetaminophen delayed and attenuated this increase. Furthermore, acetaminophen reduced tachycardia and decreased stroke volume, accompanied by systemic inflammation, without affecting inflammatory parameters such as white blood cell count and TNF-α in blood. As a proof of concept, we injected a high dose of endotoxin (100 μg), which induced rapid cardiovascular collapse in pigs. Pigs treated with acetaminophen survived with no obvious hemodynamic instability during the 50 min observation period. In conclusion, acetaminophen attenuates the effects of endotoxin on pulmonary circulation in anesthetized pigs. This may play a role in severe systemic inflammation.

  • 43. Bluth, Thomas
    et al.
    Serpa Neto, Ary
    Schultz, Marcus J
    Pelosi, Paolo
    Gama de Abreu, Marcelo
    Bluth, T
    Bobek, I
    Canet, J C
    Cinnella, G
    de Baerdemaeker, L
    Gama de Abreu, M
    Gregoretti, C
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Hemmes, S N T
    Hiesmayr, M
    Hollmann, M W
    Jaber, S
    Laffey, J
    Licker, M J
    Markstaller, K
    Matot, I
    Mills, G H
    Mulier, J P
    Pelosi, P
    Putensen, C
    Rossaint, R
    Schmitt, J
    Schultz, M J
    Senturk, M
    Serpa Neto, A
    Severgnini, P
    Sprung, J
    Vidal Melo, M F
    Wrigge, H
    Effect of Intraoperative High Positive End-Expiratory Pressure (PEEP) With Recruitment Maneuvers vs Low PEEP on Postoperative Pulmonary Complications in Obese Patients: A Randomized Clinical Trial.2019Ingår i: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 321, nr 23, s. 2292-2305Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Importance: An intraoperative higher level of positive end-expiratory positive pressure (PEEP) with alveolar recruitment maneuvers improves respiratory function in obese patients undergoing surgery, but the effect on clinical outcomes is uncertain.

    Objective: To determine whether a higher level of PEEP with alveolar recruitment maneuvers decreases postoperative pulmonary complications in obese patients undergoing surgery compared with a lower level of PEEP.

    Design, Setting, and Participants: Randomized clinical trial of 2013 adults with body mass indices of 35 or greater and substantial risk for postoperative pulmonary complications who were undergoing noncardiac, nonneurological surgery under general anesthesia. The trial was conducted at 77 sites in 23 countries from July 2014-February 2018; final follow-up: May 2018.

    Interventions: Patients were randomized to the high level of PEEP group (n = 989), consisting of a PEEP level of 12 cm H2O with alveolar recruitment maneuvers (a stepwise increase of tidal volume and eventually PEEP) or to the low level of PEEP group (n = 987), consisting of a PEEP level of 4 cm H2O. All patients received volume-controlled ventilation with a tidal volume of 7 mL/kg of predicted body weight.

    Main Outcomes and Measures: The primary outcome was a composite of pulmonary complications within the first 5 postoperative days, including respiratory failure, acute respiratory distress syndrome, bronchospasm, new pulmonary infiltrates, pulmonary infection, aspiration pneumonitis, pleural effusion, atelectasis, cardiopulmonary edema, and pneumothorax. Among the 9 prespecified secondary outcomes, 3 were intraoperative complications, including hypoxemia (oxygen desaturation with Spo2 ≤92% for >1 minute).

    Results: Among 2013 adults who were randomized, 1976 (98.2%) completed the trial (mean age, 48.8 years; 1381 [69.9%] women; 1778 [90.1%] underwent abdominal operations). In the intention-to-treat analysis, the primary outcome occurred in 211 of 989 patients (21.3%) in the high level of PEEP group compared with 233 of 987 patients (23.6%) in the low level of PEEP group (difference, -2.3% [95% CI, -5.9% to 1.4%]; risk ratio, 0.93 [95% CI, 0.83 to 1.04]; P = .23). Among the 9 prespecified secondary outcomes, 6 were not significantly different between the high and low level of PEEP groups, and 3 were significantly different, including fewer patients with hypoxemia (5.0% in the high level of PEEP group vs 13.6% in the low level of PEEP group; difference, -8.6% [95% CI, -11.1% to 6.1%]; P < .001).

    Conclusions and Relevance: Among obese patients undergoing surgery under general anesthesia, an intraoperative mechanical ventilation strategy with a higher level of PEEP and alveolar recruitment maneuvers, compared with a strategy with a lower level of PEEP, did not reduce postoperative pulmonary complications.

    Trial Registration: ClinicalTrials.gov Identifier: NCT02148692.

  • 44.
    Borges, Joao Batista
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Costa, Eduardo L. V.
    Bergquist, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Lucchetta, Luca
    Widström, Charles
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Avdelningen för sjukhusfysik.
    Maripuu, Enn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Avdelningen för sjukhusfysik.
    Suarez-Sipmann, Fernando
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Amato, Marcelo B. P.
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Lung Inflammation Persists After 27 Hours of Protective Acute Respiratory Distress Syndrome Network Strategy and Is Concentrated in the Nondependent Lung2015Ingår i: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 43, nr 5, s. E123-E132Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 45.
    Borges, Joao Batista
    et al.
    Kings Coll London, Ctr Human & Appl Physiol Sci, London, England.
    Cronin, John N.
    Kings Coll London, Ctr Human & Appl Physiol Sci, London, England.
    Crockett, Douglas C.
    Univ Oxford, Nuffield Div Anaesthet, Oxford, England.
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Formenti, Federico
    Kings Coll London, Ctr Human & Appl Physiol Sci, London, England;Univ Oxford, Nuffield Div Anaesthet, Oxford, England.
    Real-time effects of PEEP and tidal volume on regional ventilation and perfusion in experimental lung injury2020Ingår i: Intensive Care Medicine Experimental, E-ISSN 2197-425X, Vol. 8, nr 1, artikel-id 10Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Real-time bedside information on regional ventilation and perfusion during mechanical ventilation (MV) may help to elucidate the physiological and pathophysiological effects of MV settings in healthy and injured lungs. We aimed to study the effects of positive end-expiratory pressure (PEEP) and tidal volume (V-T) on the distributions of regional ventilation and perfusion by electrical impedance tomography (EIT) in healthy and injured lungs. Methods One-hit acute lung injury model was established in 6 piglets by repeated lung lavages (injured group). Four ventilated piglets served as the control group. A randomized sequence of any possible combination of three V-T (7, 10, and 15 ml/kg) and four levels of PEEP (5, 8, 10, and 12 cmH(2)O) was performed in all animals. Ventilation and perfusion distributions were computed by EIT within three regions-of-interest (ROIs): nondependent, middle, dependent. A mixed design with one between-subjects factor (group: intervention or control), and two within-subjects factors (PEEP and V-T) was used, with a three-way mixed analysis of variance (ANOVA). Results Two-way interactions between PEEP and group, and V-T and group, were observed for the dependent ROI (p = 0.035 and 0.012, respectively), indicating that the increase in the dependent ROI ventilation was greater at higher PEEP and V-T in the injured group than in the control group. A two-way interaction between PEEP and V-T was observed for perfusion distribution in each ROI: nondependent (p = 0.030), middle (p = 0.006), and dependent (p = 0.001); no interaction was observed between injured and control groups. Conclusions Large PEEP and V-T levels were associated with greater pulmonary ventilation of the dependent lung region in experimental lung injury, whereas they affected pulmonary perfusion of all lung regions both in the control and in the experimental lung injury groups.

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  • 46.
    Borges, Joao Batista
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Bergman, Jakob S.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Amato, Marcelo B. P.
    Avenel, Jacques
    Montmerle-Borgdorff, Stephanie
    First-time imaging of effects of inspired oxygen concentration on regional lung volumes and breathing pattern during hypergravity2015Ingår i: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 115, nr 2, s. 353-363Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aeroatelectasis can develop in aircrew flying the latest generation high-performance aircraft. Causes alleged are relative hyperoxia, increased gravity in the head-to-foot direction (+G(z)), and compression of legs and stomach by anti-G trousers (AGT). We aimed to assess, in real time, the effects of hyperoxia, +G(z) accelerations and AGT inflation on changes in regional lung volumes and breathing pattern evaluated in an axial plane by electrical impedance tomography (EIT). The protocol mimicked a routine peacetime flight in combat aircraft. Eight subjects wearing AGT were studied in a human centrifuge during 1 h 15 min exposure of +1 to +3.5G(z). They performed this sequence three times, breathing AIR, 44.5 % O-2 or 100 % O-2. Continuous recording of functional EIT enabled uninterrupted assessment of regional lung volumes at the 5th intercostal level. Breathing pattern was also monitored. EIT data showed that +3.5G(z), compared with any moment without hypergravity, caused an abrupt decrease in regional tidal volume (V-T) and regional end-expiratory lung volume (EELV) measured in the EIT slice, independently of inspired oxygen concentration. Breathing AIR or 44.5 % O-2, sub-regional EELV measured in the EIT slice decreased similarly in dorsal and ventral regions, but sub-regional V-T measured in the EIT slice decreased significantly more dorsally than ventrally. Breathing 100 % O-2, EELV and V-T decreased similarly in both regions. Inspired tidal volume increased in hyperoxia, whereas breathing frequency increased in hypergravity and hyperoxia. Our findings suggest that hypergravity and AGT inflation cause airway closure and air trapping in gravity-dependent lung regions, facilitating absorption atelectasis formation, in particular during hyperoxia.

  • 47.
    Borges, João Batista
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Regional Lung Kinetics of Ventilator-Induced Lung Injury and Protective-Ventilation Strategies Studied by Dynamic Positron Emission Tomography2014Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Mechanical ventilation in itself can harm the lung and cause ventilator-induced lung injury (VILI), which can induce or aggravate acute respiratory distress syndrome (ARDS). Much debate remains over pivotal concepts regarding the pathophysiology of VILI, especially about the precise contribution, kinetics, and primary role of potential VILI mechanisms. Consequently, it remains largely unknown how best to design a well-timed and full-bodied mechanical ventilation strategy. Little is known also about small airways dysfunction in ARDS. Dynamic positron emission tomography (PET) with [18F]fluoro-2-deoxy-D-glucose (18F-FDG) 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 studied the regional evolution of inflammation using dynamic PET/CT imaging of 18F-FDG in VILI and during different lung-protective mechanical ventilation strategies. By dynamic CT we investigated also the location and magnitude of peripheral airway closure and alveolar collapse under high and low distending pressures and high and low inspiratory oxygen fraction. Piglets were submitted to an experimental model of early ARDS combining repeated lung lavages and injurious mechanical ventilation. The animals were subsequently studied during sustained VILI, or submitted to distinct approaches of lung-protective mechanical ventilation: the one recommended by the ARDS Network (ARDSNet), or to one defined as open lung approach (OLA). The normally and poorly aerated regions - corresponding to intermediate gravitational zones - were the primary targets of the inflammatory process accompanying early VILI, which may be attributed to the small volume of the aerated lung that receives most of ventilation. The ARDSNet strategy did not attenuate global pulmonary inflammation during 27h and led to a concentration of inflammatory activity in the upper and poorly aerated lung regions. The OLA, in comparison with the ARDSNet approach, resulted in sustained and better gas exchange and lung mechanics. Moreover, the OLA strategy resulted in less global and regional inflammation. Dynamic CT data suggested that a significant amount of airway closure and related reabsorption atelectasis occurs in acute lung injury. Whether potential distal bronchioles injury (“bronchiolotrauma”) is a critical and decisive element in ventilator-associated lung injury is a matter for future studies.

    Delarbeten
    1. Early inflammation mainly affects normally and poorly aerated lung in experimental ventilator-induced lung injury
    Öppna denna publikation i ny flik eller fönster >>Early inflammation mainly affects normally and poorly aerated lung in experimental ventilator-induced lung injury
    Visa övriga...
    2014 (Engelska)Ingår i: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 42, nr 4, s. e279-e287Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    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.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Forskningsämne
    Klinisk fysiologi
    Identifikatorer
    urn:nbn:se:uu:diva-223348 (URN)10.1097/CCM.0000000000000161 (DOI)000332839700003 ()24448197 (PubMedID)
    Tillgänglig från: 2014-04-17 Skapad: 2014-04-17 Senast uppdaterad: 2022-01-28Bibliografiskt granskad
    2. Lung inflammation persists after 27 hours of protective ARDSNet strategy and concentrated in the nondependent lung.
    Öppna denna publikation i ny flik eller fönster >>Lung inflammation persists after 27 hours of protective ARDSNet strategy and concentrated in the nondependent lung.
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-230045 (URN)
    Tillgänglig från: 2014-08-19 Skapad: 2014-08-19 Senast uppdaterad: 2018-11-12Bibliografiskt granskad
    3. Molecular Imaging in an Animal Model of Early Acute Respiratory Distress Syndrome: Rethinking the Lung-Protective Mechanical Ventilation Strategy
    Öppna denna publikation i ny flik eller fönster >>Molecular Imaging in an Animal Model of Early Acute Respiratory Distress Syndrome: Rethinking the Lung-Protective Mechanical Ventilation Strategy
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-230046 (URN)
    Tillgänglig från: 2014-08-19 Skapad: 2014-08-19 Senast uppdaterad: 2015-01-22Bibliografiskt granskad
    4. Reabsorption atelectasis in a porcine model of ARDS: regional and temporal effects of airway closure, oxygen, and distending pressure
    Öppna denna publikation i ny flik eller fönster >>Reabsorption atelectasis in a porcine model of ARDS: regional and temporal effects of airway closure, oxygen, and distending pressure
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    2013 (Engelska)Ingår i: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 115, nr 10, s. 1464-1473Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Little is known about the small airways dysfunction in acute respiratory distress syndrome (ARDS). By computed tomography (CT) imaging in a porcine experimental model of early ARDS, we aimed at studying the location and magnitude of peripheral airway closure and alveolar collapse under high and low distending pressures and high and low inspiratory oxygen fraction (FIO2). Six piglets were mechanically ventilated under anesthesia and muscle relaxation. Four animals underwent saline-washout lung injury, and two served as healthy controls. Beyond the site of assumed airway closure, gas was expected to be trapped in the injured lungs, promoting alveolar collapse. This was tested by ventilation with an FIO2 of 0.25 and 1 in sequence during low and high distending pressures. In the most dependent regions, the gas/tissue ratio of end-expiratory CT, after previous ventilation with FIO2 0.25 low-driving pressure, was significantly higher than after ventilation with FIO2 1; with high-driving pressure, this difference disappeared. Also, significant reduction in poorly aerated tissue and a correlated increase in nonaerated tissue in end-expiratory CT with FIO2 1 low-driving pressure were seen. When high-driving pressure was applied or after previous ventilation with FIO2 0.25 and low-driving pressure, this pattern disappeared. The findings suggest that low distending pressures produce widespread dependent airway closure and with high FIO2, subsequent absorption atelectasis. Low FIO2 prevented alveolar collapse during the study period because of slow absorption of gas behind closed airways.

    Nyckelord
    small airways dysfunction, absorption atelectasis, acute respiratory distress syndrome
    Nationell ämneskategori
    Medicin och hälsovetenskap Fysiologi
    Identifikatorer
    urn:nbn:se:uu:diva-213823 (URN)10.1152/japplphysiol.00763.2013 (DOI)000327398600007 ()
    Tillgänglig från: 2014-01-05 Skapad: 2014-01-04 Senast uppdaterad: 2018-01-11Bibliografiskt granskad
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  • 48.
    Borges, João Batista
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Costa, Eduardo L V
    Suarez-Sipmann, Fernando
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Widström, Charles
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Avdelningen för sjukhusfysik.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Amato, Marcelo
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Early inflammation mainly affects normally and poorly aerated lung in experimental ventilator-induced lung injury2014Ingår i: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 42, nr 4, s. e279-e287Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 49.
    Borges, João Batista
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Eduardo, Costa LV
    Bergquist, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Lucchetta, Luca
    Widström, Charles
    Maripuu, Enn
    Suarez-Sipmann, Fernando
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Marcelo, Amato
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Lung inflammation persists after 27 hours of protective ARDSNet strategy and concentrated in the nondependent lung.Manuskript (preprint) (Övrigt vetenskapligt)
  • 50.
    Borges, João Batista
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Suarez-Sipmann, Fernando
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Altering the mechanical scenario to decrease the driving pressure2015Ingår i: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 19, nr 1, artikel-id 342Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Ventilator settings resulting in decreased driving pressure (ΔP) are positively associated with survival. How to further foster the potential beneficial mediator effect of a reduced ΔP? One possibility is promoting the active modification of the lung's "mechanical scenario" by means of lung recruitment and positive end-expiratory pressure selection. By taking into account the individual distribution of the threshold-opening airway pressures to achieve maximal recruitment, a redistribution of the tidal volume from overdistended to newly recruited lung occurs. The resulting more homogeneous distribution of transpulmonary pressures may induce a relief of overdistension in the upper regions. The gain in lung compliance after a successful recruitment rescales the size of the functional lung, potentially allowing for a further reduction in ΔP.

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