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  • 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. Agvald-Öhman, C
    et al.
    Lund, B
    Edlund, Charlotta
    Södertörn University, School of Chemistry, Biology, Geography and Environmental Science.
    Multiresistant coagulase-negative staphylococci disseminate frequently between intubated patients in a multidisciplinary intensive care unit2004In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 8, no 1, p. R42-R47Article in journal (Refereed)
    Abstract [en]

    Introduction The intensive care unit is burdened with a high frequency of nosocomial infections often caused by multiresistant nosocomial pathogens. Coagulase-negative staphylococci (CoNS) are reported to be the third causative agent of nosocomial infections and the most frequent cause of nosocomial bloodstream infections. CoNS are a part of the normal microflora of skin but can also colonize the nasal mucosa, the lower airways and invasive devices. The main aim of the present study was to investigate colonization and the rate of cross-transmissions of CoNS between intubated patients in a multidisciplinary intensive care unit. Materials and methods Twenty consecutive patients, ventilated for at least 3 days, were included. Samples were collected from the upper and lower airways. All samples were cultured quantitatively and CoNS were identified by morphology and biochemical tests. A total of 199 CoNS isolates from 17 patients were genetically fingerprinted by pulsed-field gel electrophoresis in order to identify clones and to monitor dissemination within and between patients. Results An unexpected high number of transmission events were detected. Five genotypes were each isolated from two or more patients, and 14/20 patients were involved in at least one and up to eight probable transmission events. Conclusions A frequent transmission of CoNS was found between patients in the intensive care unit. Although transmission of bacteria does not necessarily lead to infection, it is nevertheless an indication that infection control measures can be improved.

  • 3.
    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.

  • 4.
    Berkius, Johan
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Department of Anaesthesia and Intensive Care, Västervik County Hospital, Västervik, Sweden.
    Engerström, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Norrköping.
    Orwelius, Lotti
    Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping. Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Nordlund, Peter
    Department of Anaesthesia and Intensive Care, Ryhov Hospital, Jönköping,.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Walther, Sten M
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences.
    A prospective longitudinal multicentre study of health related quality of life in ICU survivors with COPD2013In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 17, no 5, p. R211-Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Mortality amongst COPD patients treated on the ICU is high. Health-related quality of life (HRQL) after intensive care is a relevant concern for COPD patients, their families and providers of health care. Still, there are few HRQL studies after intensive care of this patient group. Our hypothesis was that HRQL of COPD patients treated on the ICU declines rapidly with time.

    METHODS: Fifty-one COPD patients (COPD-ICU group) with an ICU stay longer than 24 hours received a questionnaire at 6, 12 and 24 months after discharge from ICU. HRQL was measured using two generic instruments: the EuroQoL instrument (EQ-5D and EQ-VAS) and the Short Form 36 Health Survey (SF-36). The results were compared to HRQL of two reference groups from the general population; an age- and sex-adjusted reference population (Non-COPD reference) and a reference group with COPD (COPD reference).

    RESULTS: HRQL of the COPD-ICU group at 6 months after discharge from ICU was lower compared to the COPD reference group: Median EQ-5D was 0.66 vs. 0.73, P=0.08 and median EQ-VAS was 50 vs.55, P<0.05. There were no significant differences in the SF-36 dimensions between the COPD-ICU and COPD-reference groups, although the difference in physical functioning (PF) approached statistical significance (P=0.059). Patients in the COPD-ICU group who were lost to follow-up after 6 months had low HRQL scores at 6 months. Scores for patients who died were generally lower compared to patients who failed to respond to the questionnaire. The PF and social functioning (SF) scores in those who died were significantly lower compared to patients with a complete follow up. HRQL of patients in the COPD-ICU group that survived a complete 24 months follow up was low but stable with no statistically significant decline from 6 to 24 months after ICU discharge. Their HRQL at 24 months was not significantly different from HRQL in the COPD reference group.

    CONCLUSIONS: HRQL in COPD survivors after intensive care was low but did not decline from 6 to 24 months after discharge from ICU. Furthermore, HRQL at 24 months was similar to patients with COPD who had not received ICU treatment.

  • 5.
    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.

  • 6. 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.

  • 7. Brück, Emily
    et al.
    Larsson, Jacob W.
    Lasselin, Julie
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Bottai, Matteo
    Hirvikoski, Tatja
    Sundman, Eva
    Eberhardson, Michael
    Sackey, Peter
    Olofsson, Peder S.
    Lack of clinically relevant correlation between subjective and objective cognitive function in ICU survivors: a prospective 12-month follow-up study2019In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 23, article id 253Article in journal (Refereed)
    Abstract [en]

    Background

    Cognitive impairment and psychological distress are common in intensive care unit (ICU) survivors. Early identification of affected individuals is important, so intervention and treatment can be utilized at an early stage. Cognitive Failures Questionnaire (CFQ) is commonly used to screen for subjective cognitive function, but it is unclear whether CFQ scores correlate to objective cognitive function in this population.

    Methods

    Between 2014 and 2018, 100 ICU survivors aged 18–70 years from the general ICU at the Karolinska University Hospital, Solna, were included in the study. Out of these, 58 patients completed follow-up at 3 months after ICU discharge, 51 at 6 months, and 45 at 12 months. Follow-up included objective cognitive function testing using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and subjective cognitive function testing with the self-rating Cognitive Failures Questionnaire (CFQ), as well as psychological self-rating with the Post-Traumatic Stress Symptoms Scale-10 (PTSS-10) and Hospital Anxiety and Depression Scale (HADS).

    Results

    The prevalence of cognitive impairment as measured by four selected CANTAB tests was 34% at 3 months after discharge, 18% at 6 months, and 16% at 12 months. There was a lack of significant correlation between CANTAB scores and CFQ scores at 3 months (r = − 0.134–0.207, p > 0.05), at 6 months (r = − 0.106–0.257, p > 0.05), and at 12 months after discharge (r = − 0.070–0.109, p > 0.05). Correlations between CFQ and PTSS-10 scores and HADS scores, respectively, were significant over the follow-up period (r = 0.372–0.710, p ≤ 0.001–0.023). In contrast, CANTAB test scores showed a weak correlation with PTSS-10 and HADS scores, respectively, at 3 months only (r = − 0.319–0.348, p = 0.008–0.015).

    Conclusion

    We found no clinically relevant correlation between subjective and objective cognitive function in this cohort of ICU survivors, while subjective cognitive function correlated significantly with psychological symptoms throughout the follow-up period. Treatment and evaluation of ICU survivors’ recovery need to consider both subjective and objective aspects of cognitive impairment, and subjective reports must be interpreted with caution as an indicator of objective cognitive function.

  • 8.
    Cajander, Sara
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Bäckman, Anders
    Örebro University, School of Medical Sciences. Clinical Research Centre, Örebro University Hospital, Örebro, Sweden.
    Tina, Elisabet
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Clinical Research Centre, Örebro University Hospital, Örebro, Sweden.
    Strålin, Kristoffer
    Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Huddinge, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Källman, Jan
    Örebro University, School of Medical Sciences. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Preliminary results in quantitation of HLA-DRA by real-time PCR: a promising approach to identify immunosuppression in sepsis2013In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 17, no 5, article id R223Article in journal (Refereed)
    Abstract [en]

    Introduction: Reduced monocyte human leukocyte antigen (mHLA)-DR surface expression in the late phase of sepsis is postulated as a general biomarker of sepsis-induced immunosuppression and an independent predictor of nosocomial infections. However, traditional monitoring of mHLA-DR by flow cytometry has disadvantages due to specific laboratory requirements. An mRNA-based HLA-DR monitoring by polymerase chain reaction (PCR) would improve the clinical usage and facilitate conduction of large multicenter studies. In this study, we evaluated an mRNA-based HLA-DR monitoring by quantitative real-time PCR (qRT-PCR) as an alternative method to traditional flow cytometry.

    Methods: Fifty-nine patients with sepsis and blood culture growing pathogenic bacteria were studied. Blood samples were collected at day 1 or 2 after admission, for measurement of mHLA-DR by flow cytometry and mRNA expression of HLA-DRA and class II transactivator (CIITA) by qRT-PCR. Blood samples from blood donors were used as controls (n = 30).

    Results: A significant reduced expression of mHLA-DR, HLA-DRA, and CIITA was seen in septic patients compared with controls. HLA-DRA mRNA level in whole blood was highly correlated with surface expression of mHLA-DR.

    Conclusions: Patients with sepsis display a diminished expression of HLA-DR at the monocyte surface as well as in the gene expression at the mRNA level. The mRNA expression level of HLA-DRA monitored by qRT-PCR correlates highly with surface expression of HLA-DR and appears to be a possible future biomarker for evaluation of immunosuppression in sepsis.

  • 9.
    Chew, Michelle
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Assessing left ventricular systolic function in shock: evaluation of echocardiographic parameters in intensive care2011In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 15, no R200Article in journal (Refereed)
    Abstract [en]

    Introduction

    Assessing left ventricular (LV) systolic function in a rapid and reliable way can be challenging in the critically ill patient. The purpose of this study was to evaluate the feasibility and reliability of, as well as the association between, commonly used LV systolic parameters, by using serial transthoracic echocardiography (TTE).

    Methods

    Fifty patients with shock and mechanical ventilation were included. TTE examinations were performed daily for a total of 7 days. Methods used to assess LV systolic function were visually estimated, "eyeball" ejection fraction (EBEF), the Simpson single-plane method, mean atrioventricular plane displacement (AVPDm), septal tissue velocity imaging (TDIs), and velocity time integral in the left ventricular outflow tract (VTI).

    Results

    EBEF, AVPDm, TDIs, VTI, and the Simpson were obtained in 100%, 100%, 99%, 95% and 93%, respectively, of all possible examinations. The correlations between the Simpson and EBEF showed r values for all 7 days ranging from 0.79 to 0.95 (P < 0.01). the Simpson correlations with the other LV parameters showed substantial variation over time, with the poorest results seen for TDIs and AVPDm. The repeatability was best for VTI (interobserver coefficient of variation (CV) 4.8%, and intraobserver CV, 3.1%), and AVPDm (5.3% and 4.4%, respectively), and worst for the Simpson method (8.2% and 10.6%, respectively).

    Conclusions

    EBEF and AVPDm provided the best, and Simpson, the worst feasibility when assessing LV systolic function in a population of mechanically ventilated, hemodynamically unstable patients. Additionally, the Simpson showed the poorest repeatability. We suggest that EBEF can be used instead of single-plane Simpson when assessing LV ejection fraction in this category of patients. TDIs and AVPDm, as markers of longitudinal function of the LV, are not interchangeable with LV ejection fraction.

  • 10. 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.

  • 11. 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.

  • 12. 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.

  • 13. 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.

  • 14. 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.

  • 15.
    de Geer, Lina
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Engvall, Jan
    Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Oscarsson Tibblin, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Strain echocardiography in septic shock - a comparison with systolic and diastolic function parameters, cardiac biomarkers and outcome2015In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 19, no 1, article id 122Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Myocardial dysfunction is a well-known complication in septic shock but its characteristics and frequency remains elusive. Here, we evaluate global longitudinal peak strain (GLPS) of the left ventricle as a diagnostic and prognostic tool in septic shock.

    METHODS: Fifty adult patients with septic shock admitted to a general intensive care unit were included. Transthoracic echocardiography was performed on the first day, and repeated during and after ICU stay. Laboratory and clinical data and data on outcome were collected daily from admission and up to 7 days, shorter in cases of death or ICU discharge. The correlation of GLPS to left ventricular systolic and diastolic function parameters, cardiac biomarkers and clinical data were compared using Spearman's correlation test and linear regression analysis, and the ability of GLPS to predict outcome was evaluated using a logistic regression model.

    RESULTS: On the day of admission, there was a strong correlation and co-linearity of GLPS to left ventricular ejection fraction (LVEF), mitral annular motion velocity (é) and to amino-terminal pro-brain natriuretic peptide (NT-proBNP) (Spearman's ρ -0.70, -0.53 and 0.54, and R(2) 0.49, 0.20 and 0.24, respectively). In LVEF and NT-proBNP there was a significant improvement during the study period (analysis of variance (ANOVA) with repeated measures, p = 0.05 and p < 0.001, respectively), but not in GLPS, which remained unchanged over time (p = 0.10). GLPS did not correlate to the improvement in clinical characteristics over time, did not differ significantly between survivors and non-survivors (-17.4 (-20.5-(-13.7)) vs. -14.7 (-19.0 - (-10.6)), p = 0.11), and could not predict mortality.

    CONCLUSIONS: GLPS is frequently reduced in septic shock patients, alone or in combination with reduced LVEF and/or é. It correlates with LVEF, é and NT-proBNP, and remains affected over time. GLPS may provide further understanding on the character of myocardial dysfunction in septic shock.

  • 16.
    de Geer, Lina
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Oscarsson, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Gustafsson, Mikael
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Lung ultrasound in quantifying lung water in septic shock patients2015In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 19, no 1, p. 140-Article in journal (Refereed)
    Abstract [en]

    Quantification of lung ultrasound (LUS) artifacts (B-lines) is used to assess pulmonary congestion in emergency medicine and cardiology [1,2]. We investigated B-lines in relation to extravascular lung-water index (EVLWI) from invasive transpulmonary thermodilution in septic shock patients. Our aim was to evaluate the role of LUS in an intensive care setting.

  • 17. 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.

  • 18.
    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.

  • 19. 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.

  • 20. 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.

  • 21.
    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.

  • 22.
    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.

  • 23.
    Hong Li, Yu
    et al.
    Zhejiang University, China.
    Bin Zhu, Hai
    Zhejiang University, China.
    Zheng, Xiaozhu
    Zhejiang Hospital, China.
    Jian Chen, Han
    Zhejiang University, China.
    Shao, Liang
    Yuhuan County Peoples Hospital, China.
    Hahn, Robert G
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Low doses of esmolol and phenylephrine act as diuretics during intravenous anesthesia2012In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 16, no 1Article in journal (Refereed)
    Abstract [en]

    Introduction

    The renal clearance of infused crystalloid fluid is very low during anaesthesia and surgery, but experiments in conscious sheep indicate that the renal fluid clearance might approach a normal rate when the adrenergic balance is modified.

    Methods

    Sixty females (mean age, 32 years) undergoing laparoscopic gynecological surgery were randomized to control group and received only the conventional anesthetic drugs and 20 ml/kg of lactated Ringer's over 30 mins. The others were also given an infusion of 50 μg/kg/min of esmolol (beta1-receptor blocker) or 0.01 μg/kg/min of phenylephrine (alpha1-adrenergic agonist) over 3 hours. The distribution and elimination of infused fluid were studied by volume kinetic analysis based on urinary excretion and blood hemoglobin level.

    Results

    Both drugs significantly increased urinary excretion while heart rate and arterial pressure remained largely unaffected. The urine flows during non-surgery were 43, 147, and 176 ml in the control, esmolol, and phenylephrine groups, respectively (medians, P < 0.03). When surgery had started the corresponding values were 34, 65 and 61 ml (P < 0.04). At 3 hours, averages of 9%, 20%, and 25% of the infused volume had been excreted in the three groups (P < 0.01). The kinetic analyses indicated that both treatments slowed down the distribution of fluid from the plasma to the interstitial fluid space, thereby preventing hypovolemia.

    Conclusions

    Esmolol doubled and phenylephrine almost tripled urinary excretion during anesthesia-induced depression of renal fluid clearance.

  • 24. 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.

  • 25. Huijben, Jilske A.
    et al.
    Wiegers, Eveline J. A.
    de Keizer, Nicolette F.
    Maas, Andrew I. R.
    Menon, David
    Ercole, Ari
    Citerio, Giuseppe
    Lecky, Fiona
    Wilson, Lindsay
    Cnossen, Maryse C.
    Polinder, Suzanne
    Steyerberg, Ewout W.
    van der Jagt, Mathieu
    Lingsma, Hester F.
    Aries, Marcel
    Badenes, Rafael
    Beishuizen, Albertus
    Bilotta, Federico
    Chieregato, Arturo
    Cingolani, Emiliano
    Cnossen, Maryse
    Coburn, Mark
    Coles, Jonathan P.
    Delargy, Mark
    Depreitere, Bart
    Flaatten, Hans
    Golyk, Volodymyr
    Grauwmeijer, Erik
    Haitsma, Iain
    Helbok, Raimund
    Hoedemaekers, Cornelia
    Jacobs, Bram
    Jellema, Korne
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Maegele, Marc
    Martin Delgado, Maria Cruz
    Moller, Kirsten
    Moreno, Rui
    Nelson, David
    Oldenbeuving, Annemarie W.
    Payen, Jean-Francois
    Pejakovic, Jasmina
    Ribbbers, Gerard M.
    Rossaint, Rolf
    Schoonman, Guus Geurt
    Steiner, Luzius A.
    Stocchetti, Nino
    Silvio, Fabio
    Takala, Riikka
    Tenovuo, Olli
    Valeinis, Eglis
    van den Bergh, Walter M.
    van Essen, Thomas
    van Leeuwen, Nikki
    Verhofstad, Michael H. J.
    Vos, Pieter E.
    Development of a quality indicator set to measure and improve quality of ICU care for patients with traumatic brain injury2019In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 23, article id 95Article in journal (Refereed)
    Abstract [en]

    Background: We aimed to develop a set of quality indicators for patients with traumatic brain injury (TBI) in intensive care units (ICUs) across Europe and to explore barriers and facilitators for implementation of these quality indicators.

    Methods: A preliminary list of 66 quality indicators was developed, based on current guidelines, existing practice variation, and clinical expertise in TBI management at the ICU. Eight TBI experts of the Advisory Committee preselected the quality indicators during a first Delphi round. A larger Europe-wide expert panel was recruited for the next two Delphi rounds. Quality indicator definitions were evaluated on four criteria: validity (better performance on the indicator reflects better processes of care and leads to better patient outcome), feasibility (data are available or easy to obtain), discriminability (variability in clinical practice), and actionability (professionals can act based on the indicator). Experts scored indicators on a 5-point Likert scale delivered by an electronic survey tool.

    Results. The expert panel consisted of 50 experts from 18 countries across Europe, mostly intensivists (N=24, 48%) and neurosurgeons (N=7, 14%). Experts agreed on a final set of 42 indicators to assess quality of ICU care: 17 structure indicators, 16 process indicators, and 9 outcome indicators. Experts are motivated to implement this finally proposed set (N=49, 98%) and indicated routine measurement in registries (N=41, 82%), benchmarking (N=42, 84%), and quality improvement programs (N=41, 82%) as future steps. Administrative burden was indicated as the most important barrier for implementation of the indicator set (N=48, 98%).

    Conclusions: This Delphi consensus study gives insight in which quality indicators have the potential to improve quality of TBI care at European ICUs. The proposed quality indicator set is recommended to be used across Europe for registry purposes to gain insight in current ICU practices and outcomes of patients with TBI. This indicator set may become an important tool to support benchmarking and quality improvement programs for patients with TBI in the future.

  • 26.
    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.

  • 27.
    Jones, Christina
    et al.
    ICU, Whiston Hospital, Prescot, UK.
    Bäckman, Carl
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Capuzzo, Maurizia
    Section of Anaesthesia and Intensive Care Medicine, University Hospital of Ferrara, Ferrara, Italy.
    Egerod, Ingrid
    Rigshospitalet Dept. 7331, University of Copenhagen, Copenhagen, Denmark.
    Flaatten, Hans
    ICU, Haukeland University Hospital, Bergen, Norway..
    Granja, Cristina
    ICU, Hospital Pedro Hispano, Matosinhos, Portugal.
    Rylander, Christian
    Sahlgrenska University Hospital, Gothenburg, Sweden..
    Griffiths, Richard D
    ICU, Whiston Hospital, Prescot, UK.
    Intensive care diaries reduce new onset post traumatic stress disorder following critical illness: a randomised, controlled trial2010In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 14, no 5, article id R168Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Patients recovering from critical illness have been shown to be at risk of developing Post Traumatic Stress disorder (PTSD). This study was to evaluate whether a prospectively collected diary of a patient's intensive care unit (ICU) stay when used during convalescence following critical illness will reduce the development of new onset PTSD.

    METHODS: Intensive care patients with an ICU stay of more than 72 hours were recruited to a randomised controlled trial examining the effect of a diary outlining the details of the patients ICU stay on the development of acute PTSD. The intervention patients received their ICU diary at 1 month following critical care discharge and the final assessment of the development of acute PTSD was made at 3 months.

    RESULTS: 352 patients were randomised to the study at 1 month. The incidence of new cases of PTSD was reduced in the intervention group compared to the control patients (5% versus 13%, P = 0.02).

    CONCLUSIONS: The provision of an ICU diary is effective in aiding psychological recovery and reducing the incidence of new PTSD.

  • 28. 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.

  • 29. 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.

  • 30.
    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).

  • 31. 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.

  • 32. 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.

  • 33.
    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.

  • 34.
    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.

  • 35.
    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.

  • 36.
    Ljungström, Lars
    et al.
    Skaraborg Hospital Skövde, Sweden.
    Karlsson, Diana
    Skaraborg Hospital Skövde, Sweden.
    Pernestig, Anna-Karin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Andersson, R.
    Institute of Biosciences, Sahlgrenska Academy at the University of Gothenburg, Sweden.
    Jacobsson, Gunnar
    Skaraborg Hospital Skövde, Sweden.
    Neutrophil to lymphocyte count ratio performs better than procalcitonin as a biomarker for bacteremia and severe sepsis in the emergency department2015In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 19, no Suppl 1, article id P66Article in journal (Refereed)
  • 37.
    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.

  • 38.
    Luhr, Robert
    et al.
    School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Cao, Yang
    Örebro University, School of Medical Sciences. Örebro University Hospital. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Söderquist, Bo
    Örebro University, School of Medical Sciences. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Cajander, Sara
    Örebro University, School of Medical Sciences. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Trends in sepsis mortality over time in randomised sepsis trials: a systematic literature review and meta-analysis of mortality in the control arm, 2002-20162019In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 23, article id 241Article, review/survey (Refereed)
    Abstract [en]

    Background: Epidemiologic data have shown an increasing incidence and declining mortality rate in sepsis. However, confounding effects due to differences in disease classification might have contributed to these trends.To assess if a declining mortality over time could be supported by data derived from high-quality prospective studies, we performed a meta-analysis using data from randomised controlled trials (RCTs) on sepsis. The primary aim was to assess whether the mortality in sepsis trials has changed over time. The secondary aim was to investigate how many of the included trials could show efficacy of the studied intervention regarding 28-day mortality.

    Methods: We searched PubMed for RCTs enrolling patients with severe sepsis and septic shock, published between 2002 and 2016. The included trials were assessed for quality and sorted by date of first inclusion. A meta-analysis was performed to synthesise data from the individual sepsis trials.

    Results: Of 418 eligible articles, 44 RCTs on sepsis were included in the analysis, enrolling 13,315 patients in the usual care arm between 1991 and 2013. In this time period, mortality decreased by 0.42% annually (p=0.04) to give a total decline of 9.24%. In subgroup analyses with adjustments for APACHE II, SAPS II and SOFA scores, the observed time trend was not significant (p=0.45, 0.23 and 0.98 respectively). Only four of the included trials showed any efficacy with regard to mortality.

    Conclusions: Data from RCTs show a declining trend in 28-day mortality in severe sepsis and septic shock patients during the years from 1991 to 2013. However, when controlling for severity at study inclusion, there was no significant change in mortality over time. The number of trials presenting new treatment options was low.

    Trial registration: PROSPERO CRD42018091100. Registered 27 August 2018.

  • 39.
    Lundberg, Oscar H. M.
    et al.
    Skåne University Hospital Malmö, Sweden.
    Bergenzaun, Lill
    Skåne University Hospital Malmö, Sweden.
    Ryden, Jorgen
    Skåne University Hospital Malmö, Sweden.
    Rosenqvist, Mari
    Skåne University Hospital Malmö, Sweden.
    Melander, Olle
    Skåne University Hospital Malmö, Sweden; Lund University, Sweden.
    Chew, Michelle
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Lund University, Sweden.
    Adrenomedullin and endothelin-1 are associated with myocardial injury and death in septic shock patients2016In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 20, no 178Article in journal (Refereed)
    Abstract [en]

    Background: Adrenomedullin and endothelin-1 are hormones with opposing effects on the cardiovascular system. Adrenomedullin acts as a vasodilator and seems to be important for the initiation and continuation of the hyperdynamic circulatory response in sepsis. Endothelin-1 is a vasoconstrictor and has been linked to decreased cardiac performance. Few studies have studied the relationship between adrenomedullin and endothelin-1, and morbidity and mortality in septic shock patients. High-sensitivity troponin T (hsTNT) is normally used to diagnose acute cardiac injury but is also prognostic for outcome in intensive care. We investigated the relationship between mid-regional pro-adrenomedullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET-1), and myocardial injury, measured using transthoracic echocardiography and hsTNT in septic shock patients. We were also interested in the development of different biomarkers throughout the ICU stay, and how early measurements were related to mortality. Further, we assessed if a positive biomarker panel, consisting of MR-proADM, CT-proET-1, and hsTNT changed the odds for mortality. Methods: A cohort of 53 consecutive patients with septic shock had their levels of MR-proADM, CT-proET-1, hsTNT, and left ventricular systolic functions prospectively measured over 7 days. The relationship between day 1 levels of MR-proADM/CT-proET-1 and myocardial injury was studied. We also investigated the relationship between biomarkers and early (7-day) and later (28-day) mortality. Likelihood ratios, and pretest and posttest odds for mortality were calculated. Results: Levels of MR-proADM and CT-proET-1 were significantly higher among patients with myocardial injury and were correlated with left ventricular systolic dysfunction. MR-proADM and hsTNT were significantly higher among 7-day and 28-day non-survivors. CT-proET-1 was also significantly higher among 28-day but not 7-day non-survivors. A positive biomarker panel consisting of the three biomarkers increased the odds for mortality 13-fold to 20-fold. Conclusions: MR-proADM and CT-proET-1 are associated with myocardial injury. A biomarker panel combining MR-proADM, CT-proET-1, and hsTNT increases the odds ratio for death, and may improve currently available scoring systems in critical care.

  • 40.
    Martinell, Louise
    et al.
    University of Gothenburg.
    Nielsen, Niklas
    Lund University.
    Herlitz, Johan
    University of Borås, Faculty of Caring Science, Work Life and Social Welfare.
    Karlsson, Thomas
    University of Gothenburg.
    Horn, Janneke
    University of Amsterdam.
    Wise, Matt P
    University Hospital of Wales.
    Undén, Johan
    Lund University.
    Rylander, Christian
    University of Gothenburg.
    Early predictors of poor outcome after out-of-hospital cardiac arrest.2017In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 21, no 1, article id 96Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Early identification of predictors for a poor long-term outcome in patients who survive the initial phase of out-of-hospital cardiac arrest (OHCA) may facilitate future clinical research, the process of care and information provided to relatives. The aim of this study was to determine the association between variables available from the patient's history and status at intensive care admission with outcome in unconscious survivors of OHCA.

    METHODS: Using the cohort of the Target Temperature Management trial, we performed a post hoc analysis of 933 unconscious patients with OHCA of presumed cardiac cause who had a complete 6-month follow-up. Outcomes were survival and neurological function as defined by the Cerebral Performance Category (CPC) scale at 6 months after OHCA. After multiple imputations to compensate for missing data, backward stepwise multivariable logistic regression was applied to identify factors independently predictive of a poor outcome (CPC 3-5). On the basis of these factors, a risk score for poor outcome was constructed.

    RESULTS: We identified ten independent predictors of a poor outcome: older age, cardiac arrest occurring at home, initial rhythm other than ventricular fibrillation/tachycardia, longer duration of no flow, longer duration of low flow, administration of adrenaline, bilateral absence of corneal and pupillary reflexes, Glasgow Coma Scale motor response 1, lower pH and a partial pressure of carbon dioxide in arterial blood value lower than 4.5 kPa at hospital admission. A risk score based on the impact of each of these variables in the model yielded a median (range) AUC of 0.842 (0.840-0.845) and good calibration. Internal validation of the score using bootstrapping yielded a median (range) AUC corrected for optimism of 0.818 (0.816-0.821).

    CONCLUSIONS: Among variables available at admission to intensive care, we identified ten independent predictors of a poor outcome at 6 months for initial survivors of OHCA. They reflected pre-hospital circumstances (six variables) and patient status on hospital admission (four variables). By using a simple and easy-to-use risk scoring system based on these variables, patients at high risk for a poor outcome after OHCA may be identified early.

  • 41.
    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.

  • 42.
    Orwelius, Lotti
    et al.
    Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping. Linköping University, Department of Clinical and Experimental Medicine.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Kristenson, Margareta
    Linköping University, Department of Medical and Health Sciences, Social Medicine and Public Health Science. Linköping University, Faculty of Health Sciences.
    Walther, Sten
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Health-related quality of life scores after intensive care are almost equal to those of the normal population: a multicenter observational study2013In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 17, no 5, p. R236-Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION:

    Health-related quality of life (HRQoL) in patients treated in intensive care has been reported to be lower compared with age- and sex-adjusted control groups. Our aim was to test whether stratifying for coexisting conditions would reduce observed differences in HRQoL between patients treated in the ICU and a control group from the normal population. We also wanted to characterize the ICU patients with the lowest HRQoL within these strata.

    METHODS:

    We did a cross-sectional comparison of scores of the short-form health survey (SF-36) questionnaire in a multicenter study of patients treated in the ICU (n = 780) and those from a local public health survey (n = 6,093). Analyses were in both groups adjusted for age and sex, and data stratified for coexisting conditions. Within each stratum, patients with low scores (below -2 SD of the control group) were identified and characterized.

    RESULTS:

    After adjustment, there were minor and insignificant differences in mean SF-36 scores between patients and controls. Eight (n = 18) and 22% (n = 51) of the patients had low scores (-2 SD of the control group) in the physical and mental dimensions of SF-36, respectively. Patients with low scores were usually male, single, on sick leave before admission to critical care, and survived a shorter time after being in ICU.

    CONCLUSIONS:

    After adjusting for age, sex, and coexisting conditions, mean HRQoL scores were almost equal in patients and controls. Up to 22% (n = 51) of the patients had, however, a poor quality of life as compared with the controls (-2 SD). This group, which more often consisted of single men, individuals who were on sick leave before admission to the ICU, had an increased mortality after ICU. This group should be a target for future support.

  • 43.
    Orwelius, Lotti
    et al.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Nordlund, Anders
    TFS Trial Form Support AB, Lund.
    Nordlund, Peter
    Department of Anaesthesia and Intensive Care, Ryhov Hospital, Jönköping, Sweden.
    Simonsson, Eva
    Department of Anaesthesia and Intensive Care, Ryhov Hospital, Jönköping, Sweden.
    Bäckman, Carl
    Department of Anaesthesia and Intensive Care, Vrinnevi Hospital, Norrköping, Sweden.
    Samuelsson, Anders
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Pre-existing disease: the most important factor for health related quality of life long-term after critical illness: a prospective, longitudinal, multicentre trial2010In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 14, no 2Article in journal (Refereed)
    Abstract [en]

    Introduction

    The aim of the present multicenter study was to assess long term (36 months) health related quality of life in patients after critical illness, compare ICU survivors health related quality of life to that of the general population and examine the impact of pre-existing disease and factors related to ICU care on health related quality of life.

    Methods

    Prospective, longitudinal, multicentre trial in three combined medical and surgical intensive care units of one university and two general hospitals in Sweden. By mailed questionnaires, health related quality of life was assessed at 6, 12, 24 and 36 months after the stay in ICU by EQ-5D and SF-36, and information of pre-existing disease was collected at the 6 months measure. ICU related factors were obtained from the local ICU database. Comorbidity and health related quality of life (EQ-5D; SF-36) was examined in the reference group. Among the 5306 patients admitted, 1663 were considered eligible (>24 hrs in the intensive care unit, and age ≥ 18 yrs, and alive 6 months after discharge). At the 6 month measure 980 (59%) patients answered the questionnaire. Of these 739 (75%) also answered at 12 month, 595 (61%) at 24 month, and 478 (47%) answered at the 36 month measure. As reference group, a random sample (n = 6093) of people from the uptake area of the hospitals were used in which concurrent disease was assessed and adjusted for.

    Results

    Only small improvements were recorded in health related quality of life up to 36 months after ICU admission. The majority of the reduction in health related quality of life after care in the ICU was related to the health related quality of life effects of pre-existing diseases. No significant effect on the long-term health related quality of life by any of the ICU-related factors was discernible.

    Conclusions

    A large proportion of the reduction in the health related quality of life after being in the ICU is attributable to pre-existing disease. The importance of the effect of pre-existing disease is further supported by the small, long term increment in the health related quality of life after treatment in the ICU. The reliability of the conclusions is supported by the size of the study populations and the long follow-up period.

     

  • 44.
    Persson, Per
    et al.
    Department of Anaesthesiology and Intensive Care, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Ahlstrand, Rebecca
    Örebro University, School of Medical Sciences. Department of Anaesthesia and Intensive Care.
    Gudmundsson, Magni
    Department of Anaesthesiology and Intensive Care, Sahlgrenska University Hospital, Gothenburg, Sweden.
    de Leon, Alex
    Department of Anaesthesiology and Intensive Care, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Anaesthesia and Intensive Care, Örebro University Hospital, Örebro, Sweden.
    Lundin, Stefan
    Department of Anaesthesiology and Intensive Care, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Detailed measurements of oesophageal pressure during mechanical ventilation with an advanced high-resolution manometry catheter2019In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 23, article id 217Article in journal (Refereed)
    Abstract [en]

    Background: Oesophageal pressure (PES) is used for calculation of lung and chest wall mechanics and transpulmonary pressure during mechanical ventilation. Measurements performed with a balloon catheter are suggested as a basis for setting the ventilator; however, measurements are affected by several factors. High-resolution manometry (HRM) simultaneously measures pressures at every centimetre in the whole oesophagus and thereby provides extended information about oesophageal pressure. The aim of the present study was to evaluate the factors affecting oesophageal pressure using HRM.

    Methods: Oesophageal pressure was measured using a high-resolution manometry catheter in 20 mechanically ventilated patients (15 in the ICU and 5 in the OR). Different PEEP levels and different sizes of tidal volume were applied while pressures were measured continuously. In 10 patients, oesophageal pressure was also measured using a conventional balloon catheter for comparison. A retrospective analysis of oesophageal pressure measured with HRM in supine and sitting positions in 17 awake spontaneously breathing patients is also included.

    Results: HRM showed large variations in end-expiratory PES (PESEE) and tidal changes in PES (PES) along the oesophagus. Mean intra-individual difference between the minimum and maximum end-expiratory oesophageal pressure (PESEE at baseline PEEP) and tidal variations in oesophageal pressure (PES at tidal volume 6ml/kg) recorded by HRM in the different sections of the oesophagus was 23.7 (7.9) cmH(2)O and 7.6 (3.9) cmH(2)O respectively. Oesophageal pressures were affected by tidal volume, level of PEEP, part of the oesophagus included and patient positioning. HRM identified simultaneous increases and decreases in PES within a majority of individual patients. Compared to sitting position, supine position increased PESEE (mean difference 12.3cmH(2)O), pressure variation within individual patients and cardiac artefacts. The pressure measured with a balloon catheter did not correspond to the average pressure measured with HRM within the same part of the oesophagus.

    Conclusions: The intra-individual variability in PESEE and PES is substantial, and as a result, the balloon on the conventional catheter is affected by many different pressures along its length. Oesophageal pressures are not only affected by lung and chest wall mechanics but are a complex product of many factors, which is not obvious during conventional measurements. For correct calculations of transpulmonary pressure, factors influencing oesophageal pressures need to be known. HRM, which is available at many hospitals, can be used to increase the knowledge concerning these factors.

    Trial registration: ClinicalTrials.gov,NCT02901158

  • 45.
    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.

  • 46.
    Rimes-Stigare, Claire
    et al.
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Frumento, Paolo
    Institute Environm Medical IMM, Sweden; Karolinska Institute, Sweden.
    Bottai, Matteo
    Institute Environm Medical IMM, Sweden; Karolinska Institute, Sweden.
    Martensson, Johan
    Karolinska Institute, Sweden; Austin Hospital, Australia.
    Martling, Claes-Roland
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Walther, Sten
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Karlstrom, Goran
    Swedish Intens Care Registry, Sweden.
    Bell, Max
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Evolution of chronic renal impairment and long-term mortality after de novo acute kidney injury in the critically ill; a Swedish multi-centre cohort study2015In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 19, no 221Article in journal (Refereed)
    Abstract [en]

    Introduction: Acute Kidney Injury (AKI) is common in critical ill populations and its association with high short-term mortality is well established. However, long-term risks of death and renal dysfunction are poorly understood and few studies exclude patients with pre-existing renal disease, meaning outcome for de novo AKI has been difficult to elicit. We aimed to compare the long-term risk of Chronic Kidney Disease (CKD), End Stage Renal Disease (ESRD) and mortality in critically ill patients with and without severe de novo AKI. Method: This cohort study was conducted between 2005 and 2011 in Swedish intensive care units (ICU). Data from 130134 adult patients listed on the Swedish intensive care register-database was linked with other national registries. Patients with pre-existing CKD (4192) and ESRD (1389) were excluded, as were cases (26771) with incomplete data. Patients were classified according to AKI exposure during ICU admission. Outcome in the de novo AKI group was compared to the non-exposed (no-AKI) intensive care control group. Primary outcome was all-cause mortality. Follow-up ranged from one to seven years (median 2.1 years). Secondary outcomes were incidence of CKD and ESRD and median follow-up was 1.3 years. Results: Of 97 782 patients, 5273 (5.4%) had de novo AKI. These patients had significantly higher crude mortality at one (48.4% vs. 24.6%) and five years (61.8% vs. 39.1%) compared to the control group. The first 30% of deaths in AKI patients occurred within 11 days of ICU admission whilst the 30-centile in the no-AKI group died by 748 days. CKD was significantly more common in AKI survivors at one year (6.0% vs. 0.44%) than in no-AKI group (adjusted incidence rate ratio (IRR) 7.6). AKI patients also had significantly higher rates of ESRD at one (2.0% vs. 0.08%) and at five years (3.9% vs. 0.3%) than those in the comparison group (adjusted IRR 22.5). Conclusion: This large cohort study demonstrated that de novo AKI is associated with increased short and long-term risk of death. AKI is independently associated with increased risk of CKD and ESRD as compared to an ICU control population. Severe de novo AKI survivors should be routinely followed-up and their renal function monitored.

  • 47.
    Rooney, Kevin D
    et al.
    Intensive Care Unit, Royal Alexandra Hospital and University of the West of Scotland, UK .
    Schilling, Ulf Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Health Care in Linköping.
    Point-of-care testing in the overcrowded emergency department - can it make a difference?2014In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 18, no 6, p. 692-Article, review/survey (Refereed)
    Abstract [en]

    Emergency departments (EDs) face several challenges in maintaining consistent quality care in the face of steadily increasing public demand. Improvements in the survival rate of critically ill patients in the ED are directly related to the advancement of early recognition and treatment. Frequent episodes of overcrowding and prolonged waiting times force EDs to operate beyond their capacity and threaten to impact upon patient care. The objectives of this review are as follows: (a) to establish overcrowding as a threat to patient outcomes, person-centered care, and public safety in the ED; (b) to describe scenarios in which point-of-care testing (POCT) has been found to ameliorate factors thought to contribute to overcrowding; and (c) to discuss how POCT can be used directly, and indirectly, to expedite patient care and improve outcomes. Various studies have shown that overcrowding in the ED has profound effects on operational efficiency and patient care. Several reports have quantified overcrowding in the ED and have described a relationship between heightened periods of overcrowding and delays in treatment, increased incidence of adverse events, and an even greater probability of mortality. In certain scenarios, POCT has been found to increase the number of patients discharged in a timely manner, expedite triage of urgent but non-emergency patients, and decrease delays to treatment initiation. This review concludes that POCT, when used effectively, may alleviate the negative impacts of overcrowding on the safety, effectiveness, and person-centeredness of care in the ED.

  • 48.
    Rydvall, Anders
    et al.
    Department of Surgical and Perioperative Sciences, Anaesthesiology, University Hospital of Northern Sweden, Lasarettsbacken SE-90185 Umeå, Sweden.
    Lynöe, Niels
    Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Berzelius vaeg 3 SE-17177 Stockholm, Sweden.
    Withholding and withdrawing life-sustaining treatment: a comparative study of the ethical reasoning of physicians and the general public2008In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 12, no 1, article id R13Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Our objective was to investigate whether a consensus exists between the general public and health care providers regarding the reasoning and values at stake on the subject of life-sustaining treatment. METHODS: A postal questionnaire was sent to a random sample of members of the adult population (n = 989) and to a random sample of intensive care doctors and neurosurgeons (n = 410) practicing in Sweden in 2004. The questionnaire was based on a case involving a severely ill patient and presented arguments for and against withholding and withdrawing treatment, and providing treatment that might hasten death. RESULTS: Approximately 70% of the physicians and 51% of the general public responded. A majority of doctors (82.3%) stated that they would withhold treatment, whereas a minority of the general public (40.2%) would do so; the arguments forwarded (for instance, belief that the first task of health care is to save life) and considerations regarding quality of life differed significantly between the two groups. Most physicians (94.1%) and members of the general public (77.7%) were prepared to withdraw treatment, and most (95.1% of physicians and 82% of members of the general public) agreed that sedation should be provided. CONCLUSION: There are indeed considerable differences in how physicians and the general public assess and reason in critical care situations, but the more hopelessly ill the patient became the more the groups' assessments tended to converge, although they prioritized different arguments. In order to avoid unnecessary dispute and miscommunication, it is important that health care providers be aware of the public's views, expectations, and preferences.

  • 49.
    Samuelsson, Anders
    et al.
    Linköping University, Department of Medicine and Care, Anaesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Intensive Care UHL.
    Steinvall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Intensive Care UHL.
    Sjöberg, Folke
    Linköping University, Department of Biomedicine and Surgery, Division of surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Microdialysis shows metabolic effects in skin during fluid resuscitation in burn-injured patients2006In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 10, no 6, p. Art.no: R172-Article in journal (Refereed)
    Abstract [en]

    Introduction: Established fluid treatment formulas for burn injuries have been challenged as studies have shown the presence of tissue hypoxia during standard resuscitation. Such findings suggest monitoring at the tissue level. This study was performed in patients with major burn injuries to evaluate the microdialysis technique for the continuous assessment of skin metabolic changes during fluid resuscitation and up to four days postburn. Methods: We conducted an experimental study in patients with a burn injury, as represented by percentage of total body surface area burned (TBSA), of more than 25% in a university eight-bed burns intensive care unit serving about 3.5 million inhabitants. Six patients with a median TBSA percentage of 59% (range 33.5% to 90%) and nine healthy controls were examined by intracutaneous MD, in which recordings of glucose, pyruvate, lactate, glycerol, and urea were performed. Results: Blood glucose concentration peaked on day two at 9.8 mmol/l (6.8 to 14.0) (median and range) and gradually declined on days three and four, whereas skin glucose in MD continued to increase throughout the study period with maximum values on day four, 8.7 mmol/l (4.9 to 11.0). Controls had significantly lower skin glucose values compared with burn patients, 3.1 mmol/l (1.5 to 4.6) (p < 0.001). Lactate from burn patients was significantly higher than controls in both injured and uninjured skin (MD), 4.6 mmol/l (1.3 to 8.9) and 3.8 mmol/l (1.6 to 7.5), respectively (p < 0.01). The skin lactate/pyruvate ratio (MD) was significantly increased in burn patients on all days (p < 0.001). Skin glycerol (MD) was significantly increased at days three and four in burn patients compared with controls (p < 0.01). Conclusion: Despite a strategy that fulfilled conventional goals for resuscitation, there were increased lactate/pyruvate ratios, indicative of local acidosis. A corresponding finding was not recorded systemically. We conclude that MD is a promising tool for depicting local metabolic processes that are not fully appreciated when examined systemically. Because the local response in glucose, lactate, and pyruvate metabolism seems to differ from that recorded systemically, this technique may offer a new method of monitoring organs. © 2006 Samuelsson et al., licensee BioMed Central Ltd.

  • 50.
    Samuelsson, Carolina
    et al.
    Skåne University Hospital, Sweden; Halland Hospital, Sweden.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Karlstrom, Goran
    Swedish Intens Care Registry, Sweden.
    Nolin, Thomas
    Kristianstad Central Hospital, Sweden.
    Walther, Sten
    Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Gender differences in outcome and use of resources do exist in Swedish intensive care, but to no advantage for women of premenopausal age2015In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 19, no 129Article in journal (Refereed)
    Abstract [en]

    Introduction: Preclinical data indicate that oestrogen appears to play a beneficial role in the pathophysiology of and recovery from critical illness. In few previous epidemiologic studies, however, have researchers analysed premenopausal women as a separate group when addressing potential gender differences in critical care outcome. Our aim was to see if women of premenopausal age have a better outcome following critical care and to investigate the association between gender and use of intensive care unit (ICU) resources. Methods: On the basis of our analysis of 127,254 consecutive Simplified Acute Physiology Score III-scored Swedish Intensive Care Registry ICU admissions from 2008 through 2012, we determined the risk-adjusted 30-day mortality, accumulated nurse workload score and ICU length of stay. To investigate associations with sex, we used logistic regression and multivariate analyses on the entire cohort as well as on two subgroups stratified by median age for menopause (up to and including 45 years and older than 45 years) and six selected diagnostic subgroups (sepsis, multiple trauma, chronic obstructive pulmonary disease, acute respiratory distress syndrome, pneumonia and cardiac arrest). Results: There was no sex difference in risk-adjusted mortality for the cohort as a whole, and there was no sex difference in risk-adjusted mortality in the group 45 years of age and younger. For the group of patients older than 45 years of age, we found a reduced risk-adjusted mortality in men admitted for cardiac arrest. For the cohort as a whole, and for those admitted with multiple trauma, male sex was associated with a higher nurse workload score and a longer ICU stay. Conclusions: Using information derived from a large multiple ICU register database, we found that premenopausal female sex was not associated with a survival advantage following intensive care in Sweden. When the data were adjusted for age and severity of illness, we found that men used more ICU resources per admission than women did.

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