uu.seUppsala University Publications
Change search
Refine search result
1 - 36 of 36
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1. Abe, Toshikazu
    et al.
    Madotto, Fabiana
    Pham, Tài
    Nagata, Isao
    Uchida, Masatoshi
    Tamiya, Nanako
    Kurahashi, Kiyoyasu
    Bellani, Giacomo
    Laffey, John G
    Epidemiology and patterns of tracheostomy practice in patients with acute respiratory distress syndrome in ICUs across 50 countries.2018In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 22, no 1, article id 195Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: To better understand the epidemiology and patterns of tracheostomy practice for patients with acute respiratory distress syndrome (ARDS), we investigated the current usage of tracheostomy in patients with ARDS recruited into the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG-SAFE) study.

    METHODS: This is a secondary analysis of LUNG-SAFE, an international, multicenter, prospective cohort study of patients receiving invasive or noninvasive ventilation in 50 countries spanning 5 continents. The study was carried out over 4 weeks consecutively in the winter of 2014, and 459 ICUs participated. We evaluated the clinical characteristics, management and outcomes of patients that received tracheostomy, in the cohort of patients that developed ARDS on day 1-2 of acute hypoxemic respiratory failure, and in a subsequent propensity-matched cohort.

    RESULTS: Of the 2377 patients with ARDS that fulfilled the inclusion criteria, 309 (13.0%) underwent tracheostomy during their ICU stay. Patients from high-income European countries (n = 198/1263) more frequently underwent tracheostomy compared to patients from non-European high-income countries (n = 63/649) or patients from middle-income countries (n = 48/465). Only 86/309 (27.8%) underwent tracheostomy on or before day 7, while the median timing of tracheostomy was 14 (Q1-Q3, 7-21) days after onset of ARDS. In the subsample matched by propensity score, ICU and hospital stay were longer in patients with tracheostomy. While patients with tracheostomy had the highest survival probability, there was no difference in 60-day or 90-day mortality in either the patient subgroup that survived for at least 5 days in ICU, or in the propensity-matched subsample.

    CONCLUSIONS: Most patients that receive tracheostomy do so after the first week of critical illness. Tracheostomy may prolong patient survival but does not reduce 60-day or 90-day mortality.

    TRIAL REGISTRATION: ClinicalTrials.gov, NCT02010073 . Registered on 12 December 2013.

  • 2.
    Bachmann, M. Consuelo
    et al.
    Pontificia Univ Catolica Chile, Fac Med, Dept Med Intens, Santiago, Chile;Acute Resp & Crit Illness Ctr ARCI, Santiago, Chile.
    Morais, Caio
    Univ Sao Paulo, Inst Coracao Incor, Hosp Clin, Div Pneumol,Fac Med, Sao Paulo, Brazil.
    Bugedo, Guillermo
    Pontificia Univ Catolica Chile, Fac Med, Dept Med Intens, Santiago, Chile;Acute Resp & Crit Illness Ctr ARCI, Santiago, Chile.
    Bruhn, Alejandro
    Pontificia Univ Catolica Chile, Fac Med, Dept Med Intens, Santiago, Chile;Acute Resp & Crit Illness Ctr ARCI, Santiago, Chile.
    Morales, Arturo
    Pontificia Univ Catolica Chile, Fac Med, Dept Enfermedades Resp, Santiago, Chile.
    Batista Borges, João
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Univ Sao Paulo, Inst Coracao Incor, Hosp Clin, Div Pneumol,Fac Med, Sao Paulo, Brazil.
    Costa, Eduardo
    Univ Sao Paulo, Inst Coracao Incor, Hosp Clin, Div Pneumol,Fac Med, Sao Paulo, Brazil.
    Retamal, Jaime
    Pontificia Univ Catolica Chile, Fac Med, Dept Med Intens, Santiago, Chile;Acute Resp & Crit Illness Ctr ARCI, Santiago, Chile.
    Electrical impedance tomography in acute respiratory distress syndrome2018In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 22, article id 263Article, review/survey (Refereed)
    Abstract [en]

    Acute respiratory distress syndrome (ARDS) is a clinical entity that acutely affects the lung parenchyma, and is characterized by diffuse alveolar damage and increased pulmonary vascular permeability. Currently, computed tomography (CT) is commonly used for classifying and prognosticating ARDS. However, performing this examination in critically ill patients is complex, due to the need to transfer these patients to the CT room. Fortunately, new technologies have been developed that allow the monitoring of patients at the bedside. Electrical impedance tomography (EIT) is a monitoring tool that allows one to evaluate at the bedside the distribution of pulmonary ventilation continuously, in real time, and which has proven to be useful in optimizing mechanical ventilation parameters in critically ill patients. Several clinical applications of EIT have been developed during the last years and the technique has been generating increasing interest among researchers. However, among clinicians, there is still a lack of knowledge regarding the technical principles of EIT and potential applications in ARDS patients. The aim of this review is to present the characteristics, technical concepts, and clinical applications of EIT, which may allow better monitoring of lung function during ARDS.

  • 3.
    Borges, João Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Altering the mechanical scenario to decrease the driving pressure2015In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 19, no 1, article id 342Article in journal (Refereed)
    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.

  • 4. Boyle, Andrew J
    et al.
    Madotto, Fabiana
    Laffey, John G
    Bellani, Giacomo
    Pham, Tài
    Pesenti, Antonio
    Thompson, B Taylor
    O'Kane, Cecilia M
    Deane, Adam M
    McAuley, Daniel F
    Identifying associations between diabetes and acute respiratory distress syndrome in patients with acute hypoxemic respiratory failure: an analysis of the LUNG SAFE database.2018In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 22, no 1, article id 268Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Diabetes mellitus is a common co-existing disease in the critically ill. Diabetes mellitus may reduce the risk of acute respiratory distress syndrome (ARDS), but data from previous studies are conflicting. The objective of this study was to evaluate associations between pre-existing diabetes mellitus and ARDS in critically ill patients with acute hypoxemic respiratory failure (AHRF).

    METHODS: An ancillary analysis of a global, multi-centre prospective observational study (LUNG SAFE) was undertaken. LUNG SAFE evaluated all patients admitted to an intensive care unit (ICU) over a 4-week period, that required mechanical ventilation and met AHRF criteria. Patients who had their AHRF fully explained by cardiac failure were excluded. Important clinical characteristics were included in a stepwise selection approach (forward and backward selection combined with a significance level of 0.05) to identify a set of independent variables associated with having ARDS at any time, developing ARDS (defined as ARDS occurring after day 2 from meeting AHRF criteria) and with hospital mortality. Furthermore, propensity score analysis was undertaken to account for the differences in baseline characteristics between patients with and without diabetes mellitus, and the association between diabetes mellitus and outcomes of interest was assessed on matched samples.

    RESULTS: Of the 4107 patients with AHRF included in this study, 3022 (73.6%) patients fulfilled ARDS criteria at admission or developed ARDS during their ICU stay. Diabetes mellitus was a pre-existing co-morbidity in 913 patients (22.2% of patients with AHRF). In multivariable analysis, there was no association between diabetes mellitus and having ARDS (OR 0.93 (0.78-1.11); p = 0.39), developing ARDS late (OR 0.79 (0.54-1.15); p = 0.22), or hospital mortality in patients with ARDS (1.15 (0.93-1.42); p = 0.19). In a matched sample of patients, there was no association between diabetes mellitus and outcomes of interest.

    CONCLUSIONS: In a large, global observational study of patients with AHRF, no association was found between diabetes mellitus and having ARDS, developing ARDS, or outcomes from ARDS.

    TRIAL REGISTRATION: NCT02010073 . Registered on 12 December 2013.

  • 5. Christensen, Steffen
    et al.
    Johansen, Martin B.
    Pedersen, Lars
    Jensen, Reinhold
    Larsen, Kim M.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Tønnesen, Else
    Christiansen, Christian F.
    Sørensen, Henrik T.
    Three-year mortality among alcoholic patients after intensive care: a population-based cohort study2012In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 16, no 1, p. R5-Article in journal (Refereed)
    Abstract [en]

    Introduction: Alcoholic patients comprise a large proportion of patients in intensive care units (ICUs). However, data are limited on the impact of alcoholism on mortality after intensive care. Methods: We conducted a cohort study among 16,848 first-time ICU patients between 2001 and 2007 to examine 30-day and 3-year mortality among alcoholic patients. Alcoholic patients with and without complications of alcohol misuse (for example, alcoholic liver disease) were identified from previous hospital contacts for alcoholism-related conditions or redemption of a prescription for alcohol deterrents. Data on medication use, demographics, hospital diagnoses, and comorbidity were obtained from medical databases. We computed 30-day and 3-year mortality and mortality rate ratios (MRRs) by using Cox regression analysis, controlling for covariates. Results: In total, 1,229 (7.3%) ICU patients were current alcoholics. Among alcoholic patients without complications of alcoholism (n = 785, 4.7% of the cohort), 30-day mortality was 15.9% compared with 19.7% among nonalcoholic patients. Compared with nonalcoholic patients, the adjusted 30-day MRR was 1.04 (95% confidence interval (CI), 0.87 to 1.25). Three-year mortality was 36.2% compared with 40.9% among nonalcoholic patients, corresponding to an adjusted 3-year MRR of 1.16 (95% CI, 1.03 to 1.31). For alcoholic patients with complications (n = 444, 2.6% of the cohort), 30-day mortality was 33.6%, and 3-year mortality was 64.5%, corresponding to adjusted MRRs, with nonalcoholics as the comparator, of 1.64 (95% CI, 1.38 to 1.95) and 1.67 (95% CI, 1.48 to 1.90), respectively. Conclusions: Alcoholic ICU patients with chronic complications of alcoholism have substantially increased 30-day and 3-year mortality. In contrast, alcoholics without complications have no increased 30-day and only slightly increased 3-year mortality.

  • 6. Christensen, Steffen
    et al.
    Johansen, Martin Berg
    Tonnesen, Else
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Pedersen, Lars
    Lemeshow, Stanley
    Sorensen, Henrik Toft
    Preadmission beta-blocker use and 30-day mortality among patients in intensive care: a cohort study2011In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 15, no 2, p. R87-Article in journal (Refereed)
    Abstract [en]

    Introduction: Beta-blockers have cardioprotective, metabolic and immunomodulating effects that may be beneficial to patients in intensive care. We examined the association between preadmission beta-blocker use and 30-day mortality following intensive care. Methods: We identified 8,087 patients over age 45 admitted to one of three multidisciplinary intensive care units (ICUs) between 1999 and 2005. Data on the use of beta-blockers and medications, diagnosis, comorbidities, surgery, markers of socioeconomic status, laboratory tests upon ICU admission, and complete follow-up for mortality were obtained from medical databases. We computed probability of death within 30 days following ICU admission for beta-blocker users and non-users, and the odds ratio (OR) of death as a measure of relative risk using conditional logistic regression and also did a propensity score-matched analysis. Results: Inclusion of all 8,087 ICU patients in a logistic regression analysis yielded an adjusted OR of 0.82 (95% confidence interval (CI): 0.71 to 0.94) for beta-blocker users compared with non-users. In the propensity score-matched analysis we matched all 1,556 beta-blocker users (19.2% of the entire cohort) with 1,556 non-users; the 30-day mortality was 25.7% among beta-blocker users and 31.4% among non-users (OR 0.74 (95% CI: 0.63 to 0.87)]. The OR was 0.69 (95% CI: 0.54 to 0.88) for surgical ICU patients and 0.71 (95% CI: 0.51 to 0.98) for medical ICU patients. The OR was 0.99 (95% CI: 0.67 to 1.47) among users of non-selective beta-blockers, and 0.70 (95% CI: 0.58 to 0.83) among users of cardioselective beta-blockers. Conclusions: Preadmission beta-blocker use is associated with reduced mortality following ICU admission.

  • 7. Christensen, Steffen
    et al.
    Thomsen, Reimar W.
    Johansen, Martin B.
    Pedersen, Lars
    Jensen, Reinhold
    Larsen, Kim M.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Tønnesen, Else
    Sørensen, Henrik Toft
    Preadmission statin use and one-year mortality among patients in intensive care: a cohort study2010In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 14, no 2, p. R29-Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Statins reduce risk of cardiovascular events and have beneficial pleiotropic effects; both may reduce mortality in critically ill patients. We examined whether statin use was associated with risk of death in general intensive care unit (ICU) patients. METHODS: Cohort study of 12,483 critically ill patients > 45 yrs of age with a first-time admission to one of three highly specialized ICUs within the Aarhus University Hospital network, Denmark, between 2001 and 2007. Statin users were identified through population-based prescription databases. We computed cumulative mortality rates 0-30 days and 31-365 days after ICU admission and mortality rate ratios (MRRs), using Cox regression analysis controlling for potential confounding factors (demographics, use of other cardiovascular drugs, comorbidity, markers of social status, diagnosis, and surgery). RESULTS: 1882 (14.3%) ICU patients were current statin users. Statin users had a reduced risk of death within 30 days of ICU admission [users: 22.1% vs. non-users 25.0%; adjusted MRR = 0.76 (95% confidence interval (CI): 0.69 to 0.86)]. Statin users also had a reduced risk of death within one year after admission to the ICU [users: 36.4% vs. non-users 39.9%; adjusted MRR = 0.79 (95% CI: 0.73 to 0.86)]. Reduced risk of death associated with current statin use remained robust in various subanalyses and in an analysis using propensity score matching. Former use of statins and current use of non-statin lipid-lowering drugs were not associated with reduced risk of death. CONCLUSIONS: Preadmission statin use was associated with reduced risk of death following intensive care. The associations seen could be a pharmacological effect of statins, but unmeasured differences in characteristics of statin users and non-users cannot be entirely ruled out.

  • 8. Cortegiani, Andrea
    et al.
    Madotto, Fabiana
    Gregoretti, Cesare
    Bellani, Giacomo
    Laffey, John G
    Pham, Tai
    Van Haren, Frank
    Giarratano, Antonino
    Antonelli, Massimo
    Pesenti, Antonio
    Grasselli, Giacomo
    Immunocompromised patients with acute respiratory distress syndrome: secondary analysis of the LUNG SAFE database.2018In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 22, no 1, article id 157Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The aim of this study was to describe data on epidemiology, ventilatory management, and outcome of acute respiratory distress syndrome (ARDS) in immunocompromised patients.

    METHODS: We performed a post hoc analysis on the cohort of immunocompromised patients enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) study. The LUNG SAFE study was an international, prospective study including hypoxemic patients in 459 ICUs from 50 countries across 5 continents.

    RESULTS: Of 2813 patients with ARDS, 584 (20.8%) were immunocompromised, 38.9% of whom had an unspecified cause. Pneumonia, nonpulmonary sepsis, and noncardiogenic shock were their most common risk factors for ARDS. Hospital mortality was higher in immunocompromised than in immunocompetent patients (52.4% vs 36.2%; p < 0.0001), despite similar severity of ARDS. Decisions regarding limiting life-sustaining measures were significantly more frequent in immunocompromised patients (27.1% vs 18.6%; p < 0.0001). Use of noninvasive ventilation (NIV) as first-line treatment was higher in immunocompromised patients (20.9% vs 15.9%; p = 0.0048), and immunodeficiency remained independently associated with the use of NIV after adjustment for confounders. Forty-eight percent of the patients treated with NIV were intubated, and their mortality was not different from that of the patients invasively ventilated ab initio.

    CONCLUSIONS: Immunosuppression is frequent in patients with ARDS, and infections are the main risk factors for ARDS in these immunocompromised patients. Their management differs from that of immunocompetent patients, particularly the greater use of NIV as first-line ventilation strategy. Compared with immunocompetent subjects, they have higher mortality regardless of ARDS severity as well as a higher frequency of limitation of life-sustaining measures. Nonetheless, nearly half of these patients survive to hospital discharge.

    TRIAL REGISTRATION: ClinicalTrials.gov, NCT02010073 . Registered on 12 December 2013.

  • 9. Dahl, Michael K.
    et al.
    Vistisen, Simon T.
    Koefoed-Nielsen, Jacob
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Using an expiratory resistor, arterial pulse pressure variations predict fluid responsiveness during spontaneous breathing: an experimental porcine study2009In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 13, no 2, p. R39-Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Fluid responsiveness prediction is difficult in spontaneously breathing patients. Because the swings in intrathoracic pressure are minor during spontaneous breathing, dynamic parameters like pulse pressure variation (PPV) and systolic pressure variation (SPV) are usually small. We hypothesized that during spontaneous breathing, inspiratory and/or expiratory resistors could induce high arterial pressure variations at hypovolemia and low variations at normovolemia and hypervolemia. Furthermore, we hypothesized that SPV and PPV could predict fluid responsiveness under these conditions. METHODS: Eight prone, anesthetized and spontaneously breathing pigs (20 to 25 kg) were subjected to a sequence of 30% hypovolemia, normovolemia, and 20% and 40% hypervolemia. At each volemic level, the pigs breathed in a randomized order either through an inspiratory and/or an expiratory threshold resistor (7.5 cmH2O) or only through the tracheal tube without any resistor. Hemodynamic and respiratory variables were measured during the breathing modes. Fluid responsiveness was defined as a 15% increase in stroke volume (DeltaSV) following fluid loading. RESULTS: Stroke volume was significantly lower at hypovolemia compared with normovolemia, but no differences were found between normovolemia and 20% or 40% hypervolemia. Compared with breathing through no resistor, SPV was magnified by all resistors at hypovolemia whereas there were no changes at normovolemia and hypervolemia. PPV was magnified by the inspiratory resistor and the combined inspiratory and expiratory resistor. Regression analysis of SPV or PPV versus DeltaSV showed the highest R2 (0.83 for SPV and 0.52 for PPV) when the expiratory resistor was applied. The corresponding sensitivity and specificity for prediction of fluid responsiveness were 100% and 100%, respectively, for SPV and 100% and 81%, respectively, for PPV. CONCLUSIONS: Inspiratory and/or expiratory threshold resistors magnified SPV and PPV in spontaneously breathing pigs during hypovolemia. Using the expiratory resistor SPV and PPV predicted fluid responsiveness with good sensitivity and specificity.

  • 10. de Matos, Gustavo F. J.
    et al.
    Stanzani, Fabiana
    Passos, Rogerio H.
    Fontana, Mauricio F.
    Albaladejo, Renata
    Caserta, Raquel E.
    Santos, Durval C. B.
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Amato, Marcelo B. P.
    Barbas, Carmen S. V.
    How large is the lung recruitability in early acute respiratory distress syndrome: a prospective case series of patients monitored by computed tomography2012In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 16, no 1, p. R4-Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION:

    The benefits of higher positive end expiratory pressure (PEEP) in patients with acute respiratory distress syndrome (ARDS) have been modest, but few studies have fully tested the "open-lung hypothesis". This hypothesis states that most of the collapsed lung tissue observed in ARDS can be reversed at an acceptable clinical cost, potentially resulting in better lung protection, but requiring more intensive maneuvers. The short-/middle-term efficacy of a maximum recruitment strategy (MRS) was recently described in a small physiological study. The present study extends those results, describing a case-series of non-selected patients with early, severe ARDS submitted to MRS and followed until hospital discharge or death.

    METHODS:

    MRS guided by thoracic computed tomography (CT) included two parts: a recruitment phase to calculate opening pressures (incremental steps under pressure-controlled ventilation up to maximum inspiratory pressures of 60 cmH2O, at constant driving-pressures of 15 cmH2O); and a PEEP titration phase (decremental PEEP steps from 25 to 10 cmH2O) used to estimate the minimum PEEP to keep lungs open. During all steps, we calculated the size of the non-aerated (-100 to +100 HU) compartment and the recruitability of the lungs (the percent mass of collapsed tissue re-aerated from baseline to maximum PEEP).

    RESULTS:

    A total of 51 severe ARDS patients, with a mean age of 50.7 years (84% primary ARDS) was studied. The opening plateau-pressure was 59.6 (± 5.9 cmH2O), and the mean PEEP titrated after MRS was 24.6 (± 2.9 cmH2O). Mean PaO2/FiO2 ratio increased from 125 (± 43) to 300 (± 103; P < 0.0001) after MRS and was sustained above 300 throughout seven days. Non-aerated parenchyma decreased significantly from 53.6% (interquartile range (IQR): 42.5 to 62.4) to 12.7% (IQR: 4.9 to 24.2) (P < 0.0001) after MRS. The potentially recruitable lung was estimated at 45% (IQR: 25 to 53). We did not observe major barotrauma or significant clinical complications associated with the maneuver.

    CONCLUSIONS:

    MRS could efficiently reverse hypoxemia and most of the collapsed lung tissue during the course of ARDS, compatible with a high lung recruitability in non-selected patients with early, severe ARDS. This strategy should be tested in a prospective randomized clinical trial.

  • 11.
    Engström, Joakim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Pharyngeal oxygen administration increases the time to serious desaturation at intubation in acute lung injury: an experimental study2010In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 14, no 3, p. R93-Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Endotracheal intubation in critically ill patients is associated with severe life-threatening complications in about 20%, mainly due to hypoxemia. We hypothesized that apneic oxygenation via a pharyngeal catheter during the endotracheal intubation procedure would prevent or increase the time to life-threatening hypoxemia and tested this hypothesis in an acute lung injury animal model. METHODS: Eight anesthetized piglets with collapse-prone lungs induced by lung lavage were ventilated with a fraction of inspired oxygen of 1.0 and a positive end-expiratory pressure of 5 cmH2O. The shunt fraction was calculated after obtaining arterial and mixed venous blood gases. The trachea was extubated, and in randomized order each animal received either 10 L oxygen per minute or no oxygen via a pharyngeal catheter, and the time to desaturation to pulse oximeter saturation (SpO2) 60% was measured. If SpO2 was maintained at over 60%, the experiment ended when 10 minutes had elapsed. RESULTS: Without pharyngeal oxygen, the animals desaturated after 103 (88-111) seconds (median and interquartile range), whereas with pharyngeal oxygen five animals had a SpO2 > 60% for the 10-minute experimental period, one animal desaturated after 7 minutes, and two animals desaturated within 90 seconds (P < 0.016, Wilcoxon signed rank test). The time to desaturation was related to shunt fraction (R2 = 0.81, P = 0.002, linear regression); the animals that desaturated within 90 seconds had shunt fractions >40%, whereas the others had shunt fractions <25%. CONCLUSIONS: In this experimental acute lung injury model, pharyngeal oxygen administration markedly prolonged the time to severe desaturation during apnea, suggesting that this technique might be useful when intubating critically ill patients with acute respiratory failure.

  • 12. Fenhammar, Johan
    et al.
    Rundgren, Mats
    Hultenby, Kjell
    Forestier, Jakob
    Taavo, Micael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Kenne, Ellinor
    Weitzberg, Eddie
    Eriksson, Stefan
    Ozenci, Volkan
    Wernerson, Annika
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Renal effects of treatment with a TLR4-inhibitor in conscious septic sheep2014In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 18, no 5, p. 488-Article in journal (Refereed)
    Abstract [en]

    Introduction: Acute kidney injury (AKI) is a common and feared complication of sepsis. The pathogenesis of sepsis-induced AKI is largely unknown, and therapeutic interventions are mainly supportive. In the present study, we tested the hypothesis that pharmacological inhibition of Toll-like receptor 4 (TLR4) would improve renal function and reduce renal damage in experimental sepsis, even after AKI had already developed. Methods: Sheep were surgically instrumented and subjected to a 36-hour intravenous infusion of live Escherichia coli. After 12 hours, they were randomized to treatment with a selective TLR4 inhibitor (TAK-242) or vehicle. Results: The E. coli caused normotensive sepsis characterized by fever, increased cardiac index, hyperlactemia, oliguria, and decreased creatinine clearance. TAK-242 significantly improved creatinine clearance and urine output. The increase in N-acetyl-beta-D-glucosaminidas, a marker of tubular damage, was attenuated. Furthermore, TAK-242 reduced the renal neutrophil accumulation and glomerular endothelial swelling caused by sepsis. These effects were independent of changes in renal artery blood flow and renal microvascular perfusion in both cortex and medulla. TAK-242 had no effect per se on the measured parameters. Conclusions: These results show that treatment with a TLR4 inhibitor is able to reverse a manifest impairment in renal function caused by sepsis. In addition, the results provide evidence that the mechanism underlying the effect of TAK-242 on renal function does not involve improved macro-circulation or micro-circulation, enhanced renal oxygen delivery, or attenuation of tubular necrosis. TLR4-mediated inflammation resulting in glomerular endothelial swelling may be an important part of the pathogenesis underlying Gram-negative septic acute kidney injury.

  • 13. Ferrando, Carlos
    et al.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Gutierrez, Andrea
    Tusman, Gerardo
    Carbonell, Jose
    Garcia, Marisa
    Piqueras, Laura
    Compan, Desamparados
    Flores, Susanie
    Soro, Marina
    Llombart, Alicia
    Javier Belda, Francisco
    Adjusting tidal volume to stress index in an open lung condition optimizes ventilation and prevents overdistension in an experimental model of lung injury and reduced chest wall compliance2015In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 19, article id 9Article in journal (Refereed)
    Abstract [en]

    Introduction: The stress index ( SI), a parameter derived from the shape of the pressure-time curve, can identify injurious mechanical ventilation. We tested the hypothesis that adjusting tidal volume (VT) to a non-injurious SI in an open lung condition avoids hypoventilation while preventing overdistension in an experimental model of combined lung injury and low chest-wall compliance (Ccw). Methods: Lung injury was induced by repeated lung lavages using warm saline solution, and Ccw was reduced by controlled intra-abdominal air-insufflation in 22 anesthetized, paralyzed and mechanically ventilated pigs. After injury animals were recruited and submitted to a positive end-expiratory pressure (PEEP) titration trial to find the PEEP level resulting in maximum compliance. During a subsequent four hours of mechanical ventilation, VT was adjusted to keep a plateau pressure (Pplat) of 30 cmH2O (Pplat-group, n = 11) or to a SI between 0.95 and 1.05 (SI-group, n = 11). Respiratory rate was adjusted to maintain a 'normal' PaCO2 (35 to 65 mmHg). SI, lung mechanics, arterial-blood gases haemodynamics pro-inflammatory cytokines and histopathology were analyzed. In addition Computed Tomography (CT) data were acquired at end expiration and end inspiration in six animals. Results: PaCO2 was significantly higher in the Pplat-group (82 versus 53 mmHg, P = 0.01), with a resulting lower pH (7.19 versus 7.34, P = 0.01). We observed significant differences in VT (7.3 versus 5.4 mlKg-1, P = 0.002) and Pplat values (30 versus 35 cmH2O, P = 0.001) between the Pplat-group and SI-group respectively. SI (1.03 versus 0.99, P = 0.42) and end-inspiratory transpulmonary pressure (PTP) (17 versus 18 cmH2O, P = 0.42) were similar in the Pplat-and SI-groups respectively, without differences in overinflated lung areas at end-inspiration in both groups. Cytokines and histopathology showed no differences. Conclusions: Setting tidal volume to a non-injurious stress index in an open lung condition improves alveolar ventilation and prevents overdistension without increasing lung injury. This is in comparison with limited Pplat protective ventilation in a model of lung injury with low chest-wall compliance.

  • 14.
    Furebring, Mia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Håkansson, Lena Douhan
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Expression of the C5a receptor (CD88) on granulocytes and monocytes in patients with severe sepsis2002In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 6, no 4, p. 363-370Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Treatment of patients with severe sepsis with agents antagonising the effects of C5a has been proposed based on beneficial effects in animal experiments and in vitro studies demonstrating upregulation of the C5a receptor (CD88) on granulocytes by endotoxin.

    MATERIALS AND METHODS: CD88 expression on leukocytes from 12 patients with severe sepsis or septic shock was analysed by flow cytometer, and serum complement factors C3a and C5b-9 were measured by enzyme immunoassay techniques.

    RESULTS: The granulocyte CD88 expression on day 1 was lowered (36; range, 2-59) in comparison with controls (63; range, 25-88) (P < 0.001), despite complement activation, while the monocyte CD88 expression was unchanged. The receptor reduction correlated significantly to the APACHE II score (r2 = 0.35, P < 0.05). The recovery of CD88 expression was slow.

    DISCUSSION: In contrast to the findings in animals, it is concluded that granulocyte CD88 expression is reduced at the time when the diagnosis of severe sepsis or septic shock can clinically be made. The reason for this needs further investigation but it may be due to a previous complement activation or to cytokine effects.

  • 15.
    Heili-Frades, Sarah
    et al.
    UAM, CIBERES, IIS Fdn Jimenez Diaz, Intermediate Resp Care Unit,Pulmonol Dept, Madrid, Spain;Inst Carlos III, CIBER Enfermedades Resp, Madrid, Spain.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Hosp Univ Princesa, Serv Med Intensiva, Madrid, Spain;Inst Carlos III, CIBER Enfermedades Resp, Madrid, Spain;Uppsala Univ Hosp, Uppsala, Sweden.
    Santos, Arnoldo
    CIBER Enfermedades Resp CIBERES, ITC, Madrid, Spain.
    Pilar Carballosa, Maria
    UAM, CIBERES, IIS Fdn Jimenez Diaz, Intermediate Resp Care Unit,Pulmonol Dept, Madrid, Spain.
    Naya-Prieto, Alba
    UAM, CIBERES, IIS Fdn Jimenez Diaz, Intermediate Resp Care Unit,Pulmonol Dept, Madrid, Spain.
    Castilla-Reparaz, Carlos
    IIS Fdn Jimenez Diaz, Dept Expt Surg, Madrid, Spain.
    Jesus Rodriguez-Nieto, Maria
    UAM, CIBERES, IIS Fdn Jimenez Diaz, Intermediate Resp Care Unit,Pulmonol Dept, Madrid, Spain;Inst Carlos III, CIBER Enfermedades Resp, Madrid, Spain.
    Gonzalez-Mangado, Nicolas
    UAM, CIBERES, IIS Fdn Jimenez Diaz, Intermediate Resp Care Unit,Pulmonol Dept, Madrid, Spain;Inst Carlos III, CIBER Enfermedades Resp, Madrid, Spain.
    Peces-Barba, German
    UAM, CIBERES, IIS Fdn Jimenez Diaz, Intermediate Resp Care Unit,Pulmonol Dept, Madrid, Spain;Inst Carlos III, CIBER Enfermedades Resp, Madrid, Spain.
    Continuous monitoring of intrinsic PEEP based on expired CO2 kinetics: an experimental validation study2019In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 23, article id 192Article in journal (Refereed)
    Abstract [en]

    Background Quantification of intrinsic PEEP (PEEPi) has important implications for patients subjected to invasive mechanical ventilation. A new non-invasive breath-by-breath method (etCO(2)D) for determination of PEEPi is evaluated. MethodsIn 12 mechanically ventilated pigs, dynamic hyperinflation was induced by interposing a resistance in the endotracheal tube. Airway pressure, flow, and exhaled CO2 were measured at the airway opening. Combining different I:E ratios, respiratory rates, and tidal volumes, 52 different levels of PEEPi (range 1.8-11.7cmH(2)O; mean 8.450.32cmH(2)O) were studied. The etCO(2)D is based on the detection of the end-tidal dilution of the capnogram. This is measured at the airway opening by means of a CO2 sensor in which a 2-mm leak is added to the sensing chamber. This allows to detect a capnogram dilution with fresh air when the pressure coming from the ventilator exceeds the PEEPi. This method was compared with the occlusion method. Results The etCO(2)D method detected PEEPi step changes of 0.2cmH(2)O. Reference and etCO(2)D PEEPi presented a good correlation (R-2 0.80, P<0.0001) and good agreement, bias -0.26, and limits of agreement +/- 1.96 SD (2.23, -2.74) (P<0.0001). Conclusions The etCO(2)D method is a promising accurate simple way of continuously measure and monitor PEEPi. Its clinical validity needs, however, to be confirmed in clinical studies and in conditions with heterogeneous lung diseases.

  • 16. Hostmann, Arwed
    et al.
    Jasse, Kerstin
    Schulze-Tanzil, Gundula
    Robinson, Yohan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Oberholzer, Andreas
    Ertel, Wolfgang
    Tschoeke, Sven K
    Biphasic onset of splenic apoptosis following hemorrhagic shock: critical implications for Bax, Bcl-2, and Mcl-1 proteins2008In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 12, no 1, p. R8-Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The innate immune response to trauma hemorrhage involves inflammatory mediators, thus promoting cellular dysfunction as well as cell death in diverse tissues. These effects ultimately bear the risk of post-traumatic complications such as organ dysfunction, multiple organ failure, or adult respiratory distress syndrome. In this study, a murine model of resuscitated hemorrhagic shock (HS) was used to determine the apoptosis in spleen as a marker of cellular injury and reduced immune functions. METHODS: Male C57BL-6 mice were subjected to sham operation or resuscitated HS. At t = 0 hours, t = 24 hours, and t = 72 hours, mice were euthanized and the spleens were removed and evaluated for apoptotic changes via DNA fragmentation, caspase activities, and activation of both extrinsic and intrinsic apoptotic pathways. Spleens from untreated mice were used as control samples. RESULTS: HS was associated with distinct lymphocytopenia as early as t = 0 hours after hemorrhage without regaining baseline levels within the consecutive 72 hours when compared with sham and control groups. A rapid activation of splenic apoptosis in HS mice was observed at t = 0 hours and t = 72 hours after hemorrhage and predominantly confirmed by increased DNA fragmentation, elevated caspase-3/7, caspase-8, and caspase-9 activities, and enhanced expression of intrinsic mitochondrial proteins. Accordingly, mitochondrial pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins were inversely expressed within the 72-hour observation period, thereby supporting significant pro-apoptotic changes. Solely at t = 24 hours, expression of the anti-apoptotic Mcl-1 protein shows a significant increase when compared with sham-operated and control animals. Furthermore, expression of extrinsic death receptors were only slightly increased. CONCLUSION: Our data suggest that HS induces apoptotic changes in spleen through a biphasic caspase-dependent mechanism and imply a detrimental imbalance of pro- and anti-apoptotic mitochondrial proteins Bax, Bcl-2, and Mcl-1, thereby promoting post-traumatic immunosuppression.

  • 17.
    Höstman, Staffan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Ahlgren, Kerstin M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Engström, Joakim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    THAM reduces CO2-associated increase in pulmonary vascular resistance: an experimental study in lung-injured piglets2015In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 19, no 1, article id 331Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Low tidal volume (VT) ventilation is recommended in patients with acute respiratory distress syndrome (ARDS). This may increase arterial carbon dioxide tension (PaCO2), decrease pH, and augment pulmonary vascular resistance (PVR). We hypothesized that Tris(hydroxymethyl)aminomethane (THAM), a pure proton acceptor, would dampen these effects, preventing the increase in PVR.

    METHODS: A one-hit injury ARDS model was established by repeated lung lavages in 18 piglets. After ventilation with VT of 6 ml/kg to maintain normocapnia, VT was reduced to 3 ml/kg to induce hypercapnia. Six animals received THAM for 1 h, six for 3 h, and six serving as controls received no THAM. In all, the experiment continued for 6 h. The THAM dosage was calculated to normalize pH and exhibit a lasting effect. Gas exchange, pulmonary, and systemic hemodynamics were tracked. Inflammatory markers were obtained at the end of the experiment.

    RESULTS: In the controls, the decrease in VT from 6 to 3 ml/kg increased PaCO2 from 6.0±0.5 to 13.8±1.5 kPa and lowered pH from 7.40±0.01 to 7.12±0.06, whereas base excess (BE) remained stable at 2.7±2.3 mEq/L to 3.4±3.2 mEq/L. In the THAM groups, PaCO2 decreased and pH increased above 7.4 during the infusions. After discontinuing the infusions, PaCO2 increased above the corresponding level of the controls (15.2±1.7 kPa and 22.6±3.3 kPa for 1-h and 3-h THAM infusions, respectively). Despite a marked increase in BE (13.8±3.5 and 31.2±2.2 for 1-h and 3-h THAM infusions, respectively), pH became similar to the corresponding levels of the controls. PVR was lower in the THAM groups (at 6 h, 329±77 dyn∙s/m(5) and 255±43 dyn∙s/m(5) in the 1-h and 3-h groups, respectively, compared with 450±141 dyn∙s/m(5) in the controls), as were pulmonary arterial pressures.

    CONCLUSIONS: The pH in the THAM groups was similar to pH in the controls at 6 h, despite a marked increase in BE. This was due to an increase in PaCO2 after stopping the THAM infusion, possibly by intracellular release of CO2. Pulmonary arterial pressure and PVR were lower in the THAM-treated animals, indicating that THAM may be an option to reduce PVR in acute hypercapnia.

  • 18. Karagiannidis, Christian
    et al.
    Kampe, Kristin Aufm
    Sipmann, Fernando Suarez
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Windisch, Wolfram
    Mueller, Thomas
    Veno-venous extracorporeal CO2 removal for the treatment of severe respiratory acidosis: pathophysiological and technical considerations2014In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 18, no 3, p. R124-Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION:

    While non-invasive ventilation aimed at avoiding intubation has become the modality of choice to treat mild to moderate acute respiratory acidosis, many severely acidotic patients (pH <7.20) still need intubation. Extracorporeal veno-venous CO2 removal (ECCO2R) could prove to be an alternative. The present animal study tested in a systematic fashion technical requirements for successful ECCO2R in terms of cannula size, blood and sweep gas flow.

    METHODS:

    ECCO2R with a 0.98 m2 surface oxygenator was performed in six acidotic (pH <7.20) pigs using either a 14.5 French (Fr) or a 19Fr catheter, with sweep gas flow rates of 8 and 16 L/minute, respectively. During each experiment the blood flow was incrementally increased to a maximum of 400 mL/minute (14.5Fr catheter) and 1000 mL/minute (19Fr catheter).

    RESULTS:

    Amelioration of severe respiratory acidosis was only feasible when blood flow rates of 750 to 1000 mL/minute (19Fr catheter) were used. Maximal CO2-elimination was 146.1 ± 22.6 mL/minute, while pH increased from 7.13 ± 0.08 to 7.41 ± 0.07 (blood flow of 1000 mL/minute; sweep gas flow 16 L/minute). Accordingly, a sweep gas flow of 8 L/minute resulted in a maximal CO2-elimination rate of 138.0 ± 16.9 mL/minute. The 14.5Fr catheter allowed a maximum CO2 elimination rate of 77.9 mL/minute, which did not result in the normalization of pH.

    CONCLUSIONS:

    Veno-venous ECCO2R may serve as a treatment option for severe respiratory acidosis. In this porcine model, ECCO2R was most effective when using blood flow rates ranging between 750 and 1000 mL/minute, while an increase in sweep gas flow from 8 to 16 L/minute had less impact on ECCO2R in this setting.

  • 19. Karlsson, Viktor
    et al.
    Dankiewicz, Josef
    Nielsen, Niklas
    Kern, Karl B.
    Mooney, Michael R.
    Riker, Richard R.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Seder, David B.
    Stammet, Pascal
    Sunde, Kjetil
    Soreide, Eldar
    Unger, Barbara T.
    Friberg, Hans
    Association of gender to outcome after out-of-hospital cardiac arrest - a report from the International Cardiac Arrest Registry2015In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 19, article id 182Article in journal (Refereed)
    Abstract [en]

    Introduction: Previous studies have suggested an effect of gender on outcome after out-of-hospital cardiac arrest (OHCA), but the results are conflicting. We aimed to investigate the association of gender to outcome, coronary angiography (CAG) and adverse events in OHCA survivors treated with mild induced hypothermia (MIH). Methods: We performed a retrospective analysis of prospectively collected data from the International Cardiac Arrest Registry. Adult patients with a non-traumatic OHCA and treated with MIH were included. Good neurological outcome was defined as a cerebral performance category (CPC) of 1 or 2. Results: A total of 1,667 patients, 472 women (28%) and 1,195 men (72%), met the inclusion criteria. Men were more likely to receive bystander cardiopulmonary resuscitation, have an initial shockable rhythm and to have a presumed cardiac cause of arrest. At hospital discharge, men had a higher survival rate (52% vs. 38%, P < 0.001) and more often a good neurological outcome (43% vs. 32%, P < 0.001) in the univariate analysis. When adjusting for baseline characteristics, male gender was associated with improved survival (OR 1.34, 95% CI 1.01 to 1.78) but no longer with neurological outcome (OR 1.24, 95% CI 0.92 to 1.67). Adverse events were common; women more often had hypokalemia, hypomagnesemia and bleeding requiring transfusion, while men had more pneumonia. In a subgroup analysis of patients with a presumed cardiac cause of arrest (n = 1,361), men more often had CAG performed on admission (58% vs. 50%, P = 0.02) but this discrepancy disappeared in an adjusted analysis. Conclusions: Gender differences exist regarding cause of arrest, adverse events and outcome. Male gender was independently associated with survival but not with neurological outcome.

  • 20.
    Klarin, Bengt
    et al.
    Lund Univ, Dept Anaesthesiol & Intens Care, Lund, Sweden; Skåne Univ Hosp, Lund, Sweden.
    Adolfsson, Anne
    Lund Univ, Dept Anaesthesiol & Intens Care, Lund, Sweden; Skåne Univ Hosp, Lund, Sweden.
    Torstensson, Anders
    Cty Hosp, Dept Anaesthesiol, Halmstad, Sweden.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Can probiotics be an alternative to chlorhexidine for oral care in the mechanically ventilated patient? A multicentre, prospective, randomised controlled open trial2018In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 22, article id 272Article in journal (Refereed)
    Abstract [en]

    Background: Pathogenic enteric bacteria aspirated from the oropharynx are the main cause of ventilator-associated pneumonia (VAP). Using chlorhexidine (CHX) orally or selective decontamination has been shown to reduce VAP. In a pilot study we found that oral care with the probiotic bacterium Lactobacillus plantarum 299 (Lp299) was as effective as CHX in reducing enteric bacteria in the oropharynx. To confirm those results, in this expanded study with an identical protocol we increased the number of patients and participating centres.

    Methods: One hundred and fifty critically ill patients on mechanical ventilation were randomised to oral care with either standard 0.1% CHX solution (control group) or a procedure comprising final application of an emulsion of Lp299. Samples for microbiological analyses were taken from the oropharynx and trachea at inclusion and subsequently at defined intervals.

    Student’s t test was used for comparisons of parameters recorded daily and Fisher’s exact test was used to compare the results of microbiological cultures.

    Results: Potentially pathogenic enteric bacteria not present at inclusion were identified in oropharyngeal samples from 29 patients in the CHX group and in 31 samples in the probiotic group. Considering cultures of tracheal secretions, enteric bacteria were found in 17 and 19 samples, respectively. Risk ratios show a difference in favour of the Lp group for fungi in oropharyngeal cultures. VAP was diagnosed in seven patients in the Lp group and in 10 patients among the controls.

    Conclusions: In this multicentre study, we could not demonstrate any difference between Lp299 and CHX used in oral care procedures regarding their impact on colonisation with emerging potentially pathogenic enteric bacteria in the oropharynx and trachea.

    Trial registration: ClinicalTrials.gov, NCT01105819. Registered on 9 April 2010. First part: Current Controlled Trials, ISRCTN00472141. Registered on 22 November 2007 (published Critical Care 2008, 12:R136).

  • 21. Klarin, Bengt
    et al.
    Molin, Göran
    Jeppsson, Bengt
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Use of the probiotic Lactobacillus plantarum 299 to reduce pathogenic bacteria in the oropharynx of intubated patients: a randomised controlled open pilot study2008In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 12, no 6, p. R136-Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Ventilator-associated pneumonia (VAP) is usually caused by aspiration of pathogenic bacteria from the oropharynx. Oral decontamination with antiseptics, such as chlorhexidine (CHX) or antibiotics, has been used as prophylaxis against this complication. We hypothesised that the probiotic bacteria Lactobacillus plantarum 299 (Lp299) would be as efficient as CHX in reducing the pathogenic bacterial load in the oropharynx of tracheally intubated, mechanically ventilated, critically ill patients. METHODS: Fifty critically ill patients on mechanical ventilation were randomised to either oral mechanical cleansing followed by washing with 0.1% CHX solution or to the same cleansing procedure followed by oral application of an emulsion of Lp299. Samples for microbiological analyses were taken from the oropharynx and trachea at inclusion and at defined intervals thereafter. RESULTS: Potentially pathogenic bacteria that were not present at inclusion were identified in oropharyngeal samples from eight of the patients treated with Lp299 and 13 of those treated with CHX (p = 0.13). Analysis of tracheal samples yielded similar results. Lp299 was recovered from the oropharynx of all patients in the Lp299 group. CONCLUSIONS: In this pilot study, we found no difference between the effect of Lp299 and CHX used in oral care procedures, when we examined the effects of those agents on colonisation of potentially pathogenic bacteria in the oropharynx of intubated, mechanically ventilated patients.

  • 22. Koefoed-Nielsen, Jacob
    et al.
    Nielsen, Niels Dahlsgaard
    Kjaergaard, Anders J
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Alveolar recruitment can be predicted from airway pressure-lung volume loops: an experimental study in a porcine acute lung injury model2008In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 12, no 1, p. R7-Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION:

    Simple methods to predict the effect of lung recruitment maneuvers (LRMs) in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are lacking. It has previously been found that a static pressure-volume (PV) loop could indicate the increase in lung volume induced by positive end-expiratory pressure (PEEP) in ARDS. The purpose of this study was to test the hypothesis that in ALI (1) the difference in lung volume (DeltaV) at a specific airway pressure (10 cmH2O was chosen in this test) obtained from the limbs of a PV loop agree with the increase in end-expiratory lung volume (DeltaEELV) by an LRM at a specific PEEP (10 cmH2O), and (2) the maximal relative vertical (volume) difference between the limbs (maximal hysteresis/total lung capacity (MH/TLC)) could predict the changes in respiratory compliance (Crs), EELV and partial pressures of arterial O2 and CO2 (PaO2 and PaCO2, respectively) by an LRM.

    METHODS:

    In eight ventilated pigs PV loops were obtained (1) before lung injury, (2) after lung injury induced by lung lavage, and (3) after additional injurious ventilation. DeltaV and MH/TLC were determined from the PV loops. At all stages Crs, EELV, PaCO2 and PaO2 were registered at 0 cmH2O and at 10 cmH2O before and after LRM, and DeltaEELV was calculated. Statistics: Wilcoxon's signed rank, Pearson's product moment correlation, Bland-Altman plot, and receiver operating characteristics curve. Medians and 25th and 75th centiles are reported.

    RESULTS:

    DeltaV was 270 (220, 320) ml and DeltaEELV was 227 (177, 306) ml (P < 0.047). The bias was 39 ml and the limits of agreement were - 49 ml to +127 ml. The R2 for relative changes in EELV, Crs, PaCO2 and PaO2 against MH/TLC were 0.55, 0.57, 0.36 and 0.05, respectively. The sensitivity and specificity for MH/TLC of 0.3 to predict improvement (>75th centile of what was found in uninjured lungs) were for EELV 1.0 and 0.85, Crs 0.88 and 1.0, PaCO2 0.78 and 0.60, and PaO2 1.0 and 0.69.

    CONCLUSION:

    A PV-loop-derived parameter, MH/TLC of 0.3, predicted changes in lung mechanics better than changes in gas exchange in this lung injury model.

  • 23.
    Kostic, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Zannin, Emanuela
    Andersson Olerud, Marie
    Pompilio, Pasquale P.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Pedotti, Antonio
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Frykholm, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Dellaca, Raffaele L.
    Positive end-expiratory pressure optimization with forced oscillation technique reduces ventilator induced lung injury: a controlled experimental study in pigs with saline lavage lung injury2011In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 15, no 3, p. R126-Article in journal (Refereed)
    Abstract [en]

    Introduction: Protocols using high levels of positive end-expiratory pressure (PEEP) in combination with low tidal volumes have been shown to reduce mortality in patients with severe acute respiratory distress syndrome (ARDS). However, the optimal method for setting PEEP is yet to be defined. It has been shown that respiratory system reactance (Xrs), measured by the forced oscillation technique (FOT) at 5 Hz, may be used to identify the minimal PEEP level required to maintain lung recruitment. The aim of the present study was to evaluate if using Xrs for setting PEEP would improve lung mechanics and reduce lung injury compared to an oxygenation-based approach.

    Methods: 17 pigs, in which acute lung injury (ALI) was induced by saline lavage, were studied. Animals were randomized into two groups: in the first PEEP was titrated according to Xrs (FOT group), in the control group PEEP was set according to the ARDSNet protocol (ARDSNet group). The duration of the trial was 12 hours. In both groups recruitment maneuvers (RM) were performed every 2 hours, increasing PEEP to 20 cmH(2)O. In the FOT group PEEP was titrated by monitoring Xrs while PEEP was reduced from 20 cmH(2)O in steps of 2 cmH(2)O. PEEP was considered optimal at the step before which Xrs started to decrease. Ventilatory parameters, lung mechanics, blood gases and hemodynamic parameters were recorded hourly. Lung injury was evaluated by histopathological analysis.

    Results: The PEEP levels set in the FOT group were significantly higher compared to those set in the ARDSNet group during the whole trial. These higher values of PEEP resulted in improved lung mechanics, reduced driving pressure, improved oxygenation, with a trend for higher PaCO(2) and lower systemic and pulmonary pressure. After 12 hours of ventilation, histopathological analysis showed a significantly lower score of lung injury in the FOT group compared to the ARDSNet group.

    Conclusions: In a lavage model of lung injury a PEEP optimization strategy based on maximizing Xrs attenuated the signs of ventilator induced lung injury. The respiratory system reactance measured by FOT could thus be an important component in a strategy for delivering protective ventilation to patients with ARDS/acute lung injury.

  • 24.
    Lattuada, Marco
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Bergquist, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Maripuu, Enn
    Department of Medical Physics, University Hospital, Uppsala, Sweden.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Mechanical ventilation worsens abdominal edema and inflammation in porcine endotoxemia2013In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 17, no 3, p. R126-Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION:

    We hypothesized that mechanical ventilation per se increases abdominal edema and inflammation in sepsis and tested this in experimental endotoxemia.

    METHODS:

    Thirty anesthetized piglets were allocated to one of five groups: healthy control pigs breathing spontaneously with continuous positive pressure of 5 cm H2O or mechanically ventilated with positive end-expiratory pressure (PEEP) of 5 cm H2O, and endotoxemic piglets during mechanical ventilation for 2.5 hours and then continued on mechanical ventilation with PEEP of either 5 or 15 cm H2O or switched to spontaneous breathing with continuous positive pressure of 5 cm H2O for another 2.5 hours. Abdominal edema formation was estimated by isotope technique and inflammatory markers were measured in liver, intestine, lung and plasma.

    RESULTS:

    In the healthy controls, 5 hours of spontaneous breathing did not increase abdominal fluid whereas mechanical ventilation did (Normalized Index increased from 1.0 to 1.6;1-3.3 (median and range, p<0.05)). In endotoxemic animals, Normalized Index increased almost six-fold after 5 hours of mechanical ventilation (5.9;4.9-6.9, p<0.05) with two-fold increase from 2.5 to 5 hours whether PEEP was 5 or 15, but only by 40% with spontaneous breathing (p<0.05 vs PEEP of 5 or 15 cm H2O). Tumor Necrosis Factor alpha (TNF-alpha) and interleukin (IL)-6 in intestine and liver were 2-3 times higher with mechanical ventilation than during spontaneous breathing (p<0.05) but similar in plasma and lung. Abdominal edema formation and TNF-alpha in intestine correlated inversely with abdominal perfusion pressure.

    CONCLUSIONS:

    Mechanical ventilation with PEEP increases abdominal edema and inflammation in intestine and liver in experimental endotoxemia by increasing systemic capillary leakage and impeding abdominal lymph drainage.

  • 25.
    Lipcsey, Miklos
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Bellomo, Rinaldo
    Septic acute kidney injury: hemodynamic syndrome, inflammatory disorder, or both?2011In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 15, no 6, p. 1008-Article in journal (Refereed)
    Abstract [en]

    Septic acute kidney injury (S-AKI) is the most common cause of kidney injury in the ICU. Decreased renal blood flow and inflammation have both been suggested as mechanisms of S-AKI. Benes and colleagues present a study of S-AKI in which sepsis is induced by fecal peritonitis and bacterial infusion. In this study, although decreased renal blood flow and increased renal vascular resistance were present in some of the animals that developed S-AKI, inflammatory activation without decreased renal blood flow and increased renal vascular resistance was seen in other animals. Systemic hemodynamic findings provided little information on renal hemodynamics or risk of S-AKI. The study highlights the extraordinary complexity of S-AKI and the need for clinicians to recognize our limited understanding of its pathogenesis and the weakness of the decreased perfusion paradigm as the sole explanation for the loss of renal function seen in severe sepsis.

  • 26.
    Llano-Diez, Monica
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Renaud, Guillaume
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Andersson, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Gonzales Marrero, Humberto
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Cacciani, Nicola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Engquist, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Corpeno, Rebeca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Artemenko, Konstantin
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Larsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Mechanisms underlying intensive care unit muscle wasting and effects of passive mechanical loading2012In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 16, no 5, p. R209-Article in journal (Refereed)
    Abstract [en]

    ABSTRACT: INTRODUCTION: Critical ill intensive care unit (ICU) patients commonly develop severe muscle wasting and impaired muscle function, leading to delayed recovery, with subsequent increased morbidity and financial costs, and decreased quality of life of survivors. Critical illness myopathy (CIM) is a frequently observed neuromuscular disorder in ICU patients. Sepsis, systemic corticosteroid hormone treatment and post-synaptic neuromuscular blockade have been forwarded as the dominating triggering factors. Recent experimental results from our group using a unique experimental rat ICU model have shown that the "mechanical silencing" associated with the ICU condition is the primary triggering factor. This study aims at (1) unraveling the mechanisms underlying CIM, and (2) evaluating the effects of a specific intervention aiming at reducing the mechanical silencing in sedated and mechanically ventilated ICU patients. METHODS: Muscle gene/protein expression, post-translational modifications (PTMs), muscle membrane excitability, muscle mass measurements, and contractile properties at the single muscle fiber level were explored in seven deeply sedated and mechanically ventilated ICU patients (not exposed to systemic corticosteroid hormone treatment, post-synaptic neuromuscular blockade or sepsis) subjected to unilateral passive mechanical loading 10 hours per day (2.5 hours, 4 times) for 9 +/- 1 days. RESULTS: These patients developed a phenotype considered pathognomonic of CIM, i.e., severe muscle wasting and a preferential myosin loss (P<0.001). In addition, myosin PTMs specific to the ICU condition were observed in parallel with an increased sarcolemmal expression and cytoplasmic translocation of nNOS. Passive mechanical loading for 9 +/- 1 resulted in a 35% higher specific force (P<0.001) compared with the unloaded leg, although it was not sufficient to prevent the loss of muscle mass. CONCLUSIONS: Mechanical silencing is suggested to be a primary mechanism underlying CIM, i.e., triggering the myosin loss, muscle wasting and myosin PTMs. The higher nNOS expression found in the ICU patients and its cytoplasmic translocation are forwarded as a probable mechanism underlying these modifications. The positive effect of passive loading on muscle fiber function strongly supports the importance of early physical therapy and mobilization in deeply sedated and mechanically ventilated ICU patients.

  • 27.
    Mörer, Onnen
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Plock, Enno
    Mgbor, Uchenna
    Schmid, Alexandra
    Schneider, Heinz
    Wischnewsky, Manfred Bernd
    Burchardi, Hilmar
    A German national prevalence study on the cost of intensive care: an evaluation from 51 intensive care units2007In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 11, no 3, p. R69-Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Intensive care unit (ICU) costs account for up to 20% of a hospital's costs. We aimed to analyse the individual patient-related cost of intensive care at various hospital levels and for different groups of disease. METHODS: Data from 51 ICUs all over Germany (15 primary care hospitals and 14 general care hospitals, 10 maximal care hospitals and 12 focused care hospitals) were collected in an observational, cross-sectional, one-day point prevalence study by two external study physicians (January-October 2003). All ICU patients (length of stay > 24 hours) treated on the study day were included. The reason for admission, severity of illness, surgical/diagnostic procedures, resource consumption, ICU/hospital length of stay, outcome and ICU staffing structure were documented. RESULTS: Altogether 453 patients were included. ICU (hospital) mortality was 12.1% (15.7%). The reason for admission and the severity of illness differed between the hospital levels of care, with a higher amount of unscheduled surgical procedures and patients needing mechanical ventilation in maximal care hospital and focused care hospital facilities. The mean total costs per day were euro 791 +/- 305 (primary care hospitals, euro 685 +/- 234; general care hospitals, euro 672 +/- 199; focused care hospitals, euro 816 +/- 363; maximal care hospitals, euro 923 +/- 306), with the highest cost in septic patients (euro 1,090 +/- 422). Differences were associated with staffing, the amount of prescribed drugs/blood products and diagnostic procedures. CONCLUSION: The reason for admission, the severity of illness and the occurrence of severe sepsis are directly related to the level of ICU cost. A high fraction of costs result from staffing (up to 62%). Specialized and maximum care hospitals treat a higher proportion of the more severely ill and most expensive patients.

  • 28.
    Retamal, Jaime
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Bergamini, Bruno
    Carvalho, Alysson R
    Bozza, Fernando A
    Borzone, Gisella
    Batista Borges, João
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Bugedo, Guillermo
    Bruhn, Alejandro
    Non-lobar atelectasis generates inflammation and structural alveolar injury in the surrounding healthy tissue during mechanical ventilation2014In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 18, no 5, p. 505-Article in journal (Refereed)
    Abstract [en]

    Introduction

    When alveoli collapse the traction forces exerted on their walls by adjacent expanded units may increase and concentrate. These forces may promote its re-expansion at the expense of potentially injurious stresses at the interface between the collapsed and the expanded units. We developed an experimental model to test the hypothesis that a local non-lobar atelectasis can act as a stress concentrator, contributing to inflammation and structural alveolar injury in the surrounding healthy lung tissue during mechanical ventilation.

    Methods

    A total of 35 rats were anesthetized, paralyzed and mechanically ventilated. Atelectasis was induced by bronchial blocking: after five minutes of stabilization and pre-oxygenation with FIO2 = 1.0, a silicon cylinder blocker was wedged in the terminal bronchial tree. Afterwards, the animals were randomized between two groups: 1) Tidal volume (VT) = 10 ml/kg and positive end-expiratory pressure (PEEP) = 3 cmH2O (VT10/PEEP3); and 2) VT = 20 ml/kg and PEEP = 0 cmH2O (VT20/zero end-expiratory pressure (ZEEP)). The animals were then ventilated during 180 minutes. Three series of experiments were performed: histological (n = 12); tissue cytokines (n = 12); and micro-computed tomography (microCT; n = 2). An additional six, non-ventilated, healthy animals were used as controls.

    Results

    Atelectasis was successfully induced in the basal region of the lung of 26 out of 29 animals. The microCT of two animals revealed that the volume of the atelectasis was 0.12 and 0.21 cm3. There were more alveolar disruption and neutrophilic infiltration in the peri-atelectasis region than the corresponding contralateral lung (control) in both groups. Edema was higher in the peri-atelectasis region than the corresponding contralateral lung (control) in the VT20/ZEEP than VT10/PEEP3 group. The volume-to-surface ratio was higher in the peri-atelectasis region than the corresponding contralateral lung (control) in both groups. We did not find statistical difference in tissue interleukin-1β and cytokine-induced neutrophil chemoattractant-1 between regions.

    Conclusions

    The present findings suggest that a local non-lobar atelectasis acts as a stress concentrator, generating structural alveolar injury and inflammation in the surrounding lung tissue.

  • 29.
    Schell, Carl Otto
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Karolinska Inst, Dept Publ Hlth Sci, Global Hlth Hlth Syst & Policy, Stockholm, Sweden.
    Warnberg, Martin Gerdin
    Karolinska Inst, Dept Publ Hlth Sci, Global Hlth Hlth Syst & Policy, Stockholm, Sweden.
    Hvarfner, Anna
    Uppsala Univ, Fac Med, Uppsala, Sweden.
    Hoog, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Baker, Ulrika
    Karolinska Inst, Dept Publ Hlth Sci, Global Hlth Hlth Syst & Policy, Stockholm, Sweden;Coll Med, Blantyre, Malawi.
    Castegren, Markus
    Karolinska Univ Hosp, Perioperat Med & Intens Care PMI, Stockholm, Sweden.
    Baker, Tim
    Karolinska Inst, Dept Publ Hlth Sci, Global Hlth Hlth Syst & Policy, Stockholm, Sweden;Coll Med, Blantyre, Malawi;Karolinska Univ Hosp, Perioperat Med & Intens Care PMI, Stockholm, Sweden.
    The global need for essential emergency and critical care2018In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 22, article id 284Article in journal (Other academic)
    Abstract [en]

    Critical illness results in millions of deaths each year. Care for those with critical illness is often neglected due to a lack of prioritisation, co-ordination, and coverage of timely identification and basic life-saving treatments. To improve care, we propose a new focus on essential emergency and critical care (EECC)care that all critically ill patients should receive in all hospitals in the world. Essential emergency and critical care should be part of universal health coverage, is appropriate for all countries in the world, and is intended for patients irrespective of age, gender, underlying diagnosis, medical specialty, or location in the hospital. Essential emergency and critical care is pragmatic and low-cost and has the potential to improve care and substantially reduce preventable mortality.

  • 30.
    Seternes, Arne
    et al.
    Univ Trondheim Hosp, St Olavs Hosp, Dept Vasc Surg, Prinsesse Kristinas Gate 3, N-7030 Trondheim, Norway.;Norwegian Univ Sci & Technol NTNU, Dept Circulat & Med Imaging, Hogskoleringen 1, N-7491 Trondheim, Norway.;Norwegian Univ Sci & Technol NTNU, Dept Canc Res & Mol Med, Hogskoleringen 1, N-7491 Trondheim, Norway..
    Fasting, Sigurd
    Norwegian Univ Sci & Technol NTNU, Dept Circulat & Med Imaging, Hogskoleringen 1, N-7491 Trondheim, Norway.;Univ Trondheim Hosp, St Olavs Hosp, Dept Anesthesiol & Intens Care Med, Prinsesse Kristinas Gate 3, N-7030 Trondheim, Norway..
    Klepstad, Pål
    Norwegian Univ Sci & Technol NTNU, Dept Circulat & Med Imaging, Hogskoleringen 1, N-7491 Trondheim, Norway.;Univ Trondheim Hosp, St Olavs Hosp, Dept Anesthesiol & Intens Care Med, Prinsesse Kristinas Gate 3, N-7030 Trondheim, Norway..
    Mo, Skule
    Univ Trondheim Hosp, St Olavs Hosp, Dept Anesthesiol & Intens Care Med, Prinsesse Kristinas Gate 3, N-7030 Trondheim, Norway..
    Dahl, Torbjørn
    Univ Trondheim Hosp, St Olavs Hosp, Dept Vasc Surg, Prinsesse Kristinas Gate 3, N-7030 Trondheim, Norway.;Norwegian Univ Sci & Technol NTNU, Dept Circulat & Med Imaging, Hogskoleringen 1, N-7491 Trondheim, Norway..
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wibe, Arne
    Univ Trondheim Hosp, St Olavs Hosp, Dept Gastrointestinal Surg, Prinsesse Kristinas Gate 3, N-7030 Trondheim, Norway.;Norwegian Univ Sci & Technol NTNU, Dept Canc Res & Mol Med, Hogskoleringen 1, N-7491 Trondheim, Norway..
    Bedside dressing changes for open abdomen in the intensive care unit is safe and time and staff efficient2016In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 20, article id 164Article in journal (Refereed)
    Abstract [en]

    Background: Patients with an open abdomen (OA) treated with temporary abdominal closure (TAC) need multiple surgical procedures throughout the hospital stay with repeated changes of the vacuum-assisted closure device (VAC changes). The aim of this study was to examine if using the intensive care unit (ICU) for dressing changes in OA patients was safe regarding bloodstream infections (BSI) and survival. Secondary aims were to evaluate saved time, personnel, and costs.

    Methods: All patients treated with OA in the ICU from October 2006 to June 2014 were included. Data were retrospectively obtained from registered procedure codes, clinical and administrative patients' records and the OR, ICU, anesthesia and microbiology databases. Outcomes were 30-, 60- and 90-day survival, BSI, time used and saved personnel costs.

    Results: A total of 113 patients underwent 960 surgical procedures including 443 VAC changes as a single procedure, of which 165 (37 %) were performed in the ICU. Nine patients died before the first scheduled dressing change and six patients were closed at the first scheduled surgery after established OA, leaving 98 patients for further analysis. The mean duration for the surgical team performing a VAC change in the ICU was 63.4 (60.4-66.4) minutes and in the OR 98.2 (94.6-101.8) minutes (p < 0.001). The mean duration for the anesthesia team in the OR was 115.5 minutes, while this team was not used in the ICU. Personnel costs were reduced by (sic)682 per procedure when using the ICU. Forty-two patients had all the VAC changes done in the OR (VAC-OR), 22 in the ICU (VAC-ICU) and 34 in both OR and ICU (VAC-OR/ICU). BSI was diagnosed in eight (19 %) of the VAC-OR patients, seven (32 %) of the VAC-ICU and eight (24 %) of the VAC-OR/ICU (p = 0.509). Thirty-five patients (83 %) survived 30 days in the VAC-OR group, 17 in the VAC-ICU group (77 %) and 28 (82 %) in the VAC-OR/ICU group (p = 0.844).

    Conclusions: VAC change for OA in the ICU saved time for the OR team and the anesthesia team compared to using the OR, and it reduced personnel costs. Importantly, the use of ICU for OA dressing change seemed to be as safe as using the OR.

  • 31.
    Strandberg, Gunnar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lipcsey, Miklos
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Intraosseous blood aspirates analysed by a portable cartridge-based device2011In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 15, no Suppl 1, p. 49-49Article in journal (Refereed)
  • 32. Suarez-Sipmann, Fernando
    et al.
    Bohm, Stephan H
    Recruit the lung before titrating the right positive end-expiratory pressure to protect it2009In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 13, no 3, p. 134-Article in journal (Refereed)
    Abstract [en]

    The optimal level of positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome patients is still controversial and has gained renewed interest in the era of 'lung protective ventilation strategies'. Despite experimental evidence that higher levels of PEEP protect against ventilator-induced lung injury, recent clinical trials have failed to demonstrate clear survival benefits. The open-lung protective ventilation strategy combines lung recruitment maneuvers with a decremental PEEP trial aimed at finding the minimum level of PEEP that prevents the lung from collapsing. This approach to PEEP titration is more likely to exert its protective effects and is clearly different from the one used in previous clinical trials.

  • 33.
    Trachsel, Sebastien
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Deby-Dupont, Ginette
    Maurenbrecher, Edwige
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Nys, Monique
    Lamy, Maurice
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Association between inflammatory mediators and response to inhaled nitric oxide in a model of endotoxin-induced lung injury2008In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 12, no 5, p. R131-Article in journal (Refereed)
    Abstract [en]

    Introduction: Inhaled nitric oxide (INO) allows selective pulmonary vasodilation in acute respiratory distress syndrome and improves PaO2 by redistribution of pulmonary blood flow towards better ventilated parenchyma. One-third of patients are nonresponders to INO, however, and it is difficult to predict who will respond. The aim of the present study was to identify, within a panel of inflammatory mediators released during endotoxin-induced lung injury, specific mediators that are associated with a PaO2 response to INO.

    Methods: After animal ethics committee approval, pigs were anesthetized and exposed to 2 hours of endotoxin infusion. Levels of cytokines, prostanoid, leucotriene and endothelin-1 (ET-1) were sampled prior to endotoxin exposure and hourly thereafter. All animals were exposed to 40 ppm INO: 28 animals were exposed at either 4 hours or 6 hours and a subgroup of nine animals was exposed both at 4 hours and 6 hours after onset of endotoxin infusion.

    Results: Based on the response to INO, the animals were retrospectively placed into a responder group (increase in PaO2 >= 20%) or a nonresponder group. All mediators increased with endotoxin infusion although no significant differences were seen between responders and nonresponders. There was a mean difference in ET-1, however, with lower levels in the nonresponder group than in the responder group, 0.1 pg/ml versus 3.0 pg/ml. Moreover, five animals in the group exposed twice to INO switched from responder to nonresponder and had decreased ET-1 levels (3.0 (2.5 to 7.5) pg/ml versus 0.1 (0.1 to 2.1) pg/ml, P < 0.05). The pulmonary artery pressure and ET-1 level were higher in future responders to INO.

    Conclusions: ET-1 may therefore be involved in mediating the response to INO.

  • 34. Varelmann, Dirk
    et al.
    Muders, Thomas
    Zinserling, Jörg
    Guenther, Ulf
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Putensen, Christian
    Wrigge, Hermann
    Cardiorespiratory effects of spontaneous breathing in two different models of experimental lung injury: a randomized controlled trial2008In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 12, no 6, p. R135-Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Acute lung injury (ALI) can result from various insults to the pulmonary tissue. Experimental and clinical data suggest that spontaneous breathing (SB) during pressure-controlled ventilation (PCV) in ALI results in better lung aeration and improved oxygenation. Our objective was to evaluate whether the addition of SB has different effects in two different models of ALI. METHODS: Forty-four pigs were randomly assigned to ALI resulting either from hydrochloric acid aspiration (HCl-ALI) or from increased intra-abdominal pressure plus intravenous oleic acid injections (OA-ALI) and were ventilated in PCV mode either with SB (PCV + SB) or without SB (PCV - SB). Cardiorespiratory variables were measured at baseline after induction of ALI and after 4 hours of treatment (PCV + SB or PCV - SB). Finally, density distributions and end-expiratory lung volume (EELV) were assessed by thoracic spiral computed tomography. RESULTS: PCV + SB improved arterial partial pressure of oxygen/inspiratory fraction of oxygen (PaO2/FiO2) by a reduction in intrapulmonary shunt fraction in HCl-ALI from 27% +/- 6% to 23% +/- 13% and in OA-ALI from 33% +/- 19% to 26% +/- 18%, whereas during PCV - SB PaO2/FiO2 deteriorated and shunt fraction increased in the HCl group from 28% +/- 8% to 37% +/- 17% and in the OA group from 32% +/- 12% to 47% +/- 17% (P < 0.05 for interaction time and treatment, but not ALI type). PCV + SB also resulted in higher EELV (HCl-ALI: 606 +/- 171 mL, OA-ALI: 439 +/- 90 mL) as compared with PCV - SB (HCl-ALI: 372 +/- 130 mL, OA-ALI: 192 +/- 51 mL, with P < 0.05 for interaction of time, treatment, and ALI type). CONCLUSIONS: SB improves oxygenation, reduces shunt fraction, and increases EELV in both models of ALI.

  • 35. Yang, Runkuan
    et al.
    Zou, Xiaoping
    Koskinen, Marja-Leena
    Tenhunen, Jyrki
    Department of Intensive Care Medicine, University of Tampere Medical School, Tampere, Finland .
    Ethyl pyruvate reduces liver injury at early phase but impairs regeneration at late phase in acetaminophen overdose2012In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 16, no 1, p. R9-Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION:

    Inflammation may critically affect mechanisms of liver injury in acetaminophen (APAP) hepatotoxicity. Kupffer cells (KC) play important roles in inflammation, and KC depletion confers protection at early time points after APAP treatment but can lead to more severe injury at a later time point. It is possible that some inflammatory factors might contribute to liver damage at an early injurious phase but facilitate liver regeneration at a late time point. Therefore, we tested this hypothesis by using ethyl pyruvate (EP), an anti-inflammatory agent, to treat APAP overdose for 24-48 hours.

    METHODS:

    C57BL/6 male mice were intraperitoneally injected with a single dose of APAP (350 mg/kg dissolved in 1 mL sterile saline). Following 2 hours of APAP challenge, the mice were given 0.5 mL EP (40 mg/kg) or saline treatment every 8 hours for a total of 24 or 48 hours.

    RESULTS:

    Twenty-four hours after APAP challenge, compared to the saline-treated group, EP treatment significantly lowered serum transaminases (ALT/AST) and reduced liver injury seen in histopathology; however, at the 48-hour time point, compared to the saline therapy, EP therapy impaired hepatocyte regeneration and increased serum AST; this late detrimental effect was associated with reduced serum TNF-α concentration and decreased expression of cell cycle protein cyclin D1, two important factors in liver regeneration.

    CONCLUSIONS:

    Inflammation likely contributes to liver damage at an early injurious phase but improves hepatocyte regeneration at a late time point, and prolonged anti-inflammation therapy at a late phase is not beneficial.

  • 36. Zannin, Emanuela
    et al.
    Dellaca, Raffaele L
    Kostic, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Pompilio, Pasquale P
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Pedotti, Antonio
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Frykholm, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Optimizing positive end-expiratory pressure by oscillatory mechanics minimizes tidal recruitment and distension: an experimental study in a lavage model of lung injury2012In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 16, no 6, p. R217-Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION:

    It is well established that during mechanical ventilation of patients with acute respiratory distress syndrome cyclic recruitment/derecruitment and overdistension are potentially injurious for lung tissues. We evaluated whether the forced oscillation technique (FOT) could be used to guide the ventilator settings in order to minimize cyclic lung recruitment/derecruitment and cyclic mechanical stress in an experimental model of acute lung injury.

    METHODS:

    We studied six pigs in which lung injury was induced by bronchoalveolar lavage. The animals were ventilated with a tidal volume of 6 ml/kg. Forced oscillations at 5 Hz were superimposed on the ventilation waveform. Pressure and flow were measured at the tip and at the inlet of the endotracheal tube respectively. Respiratory system reactance (Xrs) was computed from the pressure and flow signals and expressed in terms of oscillatory elastance (EX5). Positive end-expiratory pressure (PEEP) was increased from 0 to 24 cm H2O in steps of 4 cm H2O and subsequently decreased from 24 to 0 in steps of 2 cm H2O. At each PEEP step CT scans and EX5 were assessed at end-expiration and end-inspiration.

    RESULTS:

    During deflation the relationship between both end-expiratory and end-inspiratory EX5 and PEEP was a U-shaped curve with minimum values at PEEP = 13.4 ± 1.0 cm H2O (mean ± SD) and 13.0 ± 1.0 cm H2O respectively. EX5 was always higher at end-inspiration than at end-expiration, the difference between the average curves being minimal at 12 cm H2O. At this PEEP level, CT did not show any substantial sign of intra-tidal recruitment/derecruitment or expiratory lung collapse.

    CONCLUSIONS:

    Using FOT it was possible to measure EX5 both at end-expiration and at end-inspiration. The optimal PEEP strategy based on end-expiratory EX5 minimized intra-tidal recruitment/derecruitment as assessed by CT, and the concurrent attenuation of intra-tidal variations of EX5 suggests that it may also minimize tidal mechanical stress.

1 - 36 of 36
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf