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  • 1. Antonen, Jaakko
    et al.
    Leppanen, Ilona
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Arvola, Pertti
    Makela, Satu
    Vaheri, Antti
    Mustonen, Jukka
    A severe case of Puumala hantavirus infection successfully treated with bradykinin receptor antagonist icatibant2013Ingår i: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 45, nr 6, s. 494-496Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A patient with severe capillary leakage syndrome caused by a Puumala hantavirus infection was treated with a single dose of icatibant, a bradykinin receptor antagonist, with a dramatic positive response. We suggest that this drug should be tested in a larger number of patients with severe hantavirus infection.

  • 2. Backes, Yara
    et al.
    van der Sluijs, Koenraad F
    Mackie, David P
    Tacke, Frank
    Koch, Alexander
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Schultz, Marcus J
    Usefulness of suPAR as a biological marker in patients with systemic inflammation or infection: a systematic review2012Ingår i: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 38, nr 9, s. 1418-1428Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    PURPOSE:

    Systemic levels of soluble urokinase-type plasminogen activator receptor (suPAR) positively correlate with the activation level of the immune system. We reviewed the usefulness of systemic levels of suPAR in the care of critically ill patients with sepsis, SIRS, and bacteremia, focusing on its diagnostic and prognostic value.

    METHODS:

    A PubMed search on suPAR was conducted, including manual cross-referencing. The list of papers was narrowed to original studies of critically ill patients. Ten papers on original studies of critically ill patients were identified that report on suPAR in sepsis, SIRS, or bacteremia.

    RESULTS:

    Systematic levels of suPAR have little diagnostic value in critically ill patients with sepsis, SIRS, or bacteremia. Systemic levels of suPAR, however, have superior prognostic power over other commonly used biological markers in these patients. Mortality prediction by other biological markers or severity-of-disease classification system scores improves when combining them with suPAR. Systemic levels of suPAR correlate positively with markers of organ dysfunction and severity-of-disease classification system scores. Finally, systemic levels of suPAR remain elevated for prolonged periods after admission and only tend to decline after several weeks. Notably, the type of assay used to measure suPAR as well as the age of the patients and underlying disease affect systemic levels of suPAR.

    CONCLUSIONS:

    The diagnostic value of suPAR is low in patients with sepsis. Systemic levels of suPAR have prognostic value, and may add to prognostication of patients with sepsis or SIRS complementing severity-of-disease classification systems and other biological markers.

  • 3.
    Hellevuo, H.
    et al.
    Tampere Univ Hosp, Dept Intens Care Med, POB 2000, FI-33521 Tampere, Finland.;Univ Tampere, Tampere, Finland..
    Sainio, M.
    Tampere Univ Hosp, Dept Intens Care Med, POB 2000, FI-33521 Tampere, Finland.;Univ Tampere, Tampere, Finland.;Univ Turku, Dept Emergency Med, Emergency Med Serv, Turku, Finland.;Turku Univ Hosp, Turku, Finland..
    Huhtala, H.
    Univ Tampere, Fac Social Sci, Tampere, Finland..
    Olkkola, K. T.
    Univ Helsinki, Dept Anaesthesiol Intens Care & Pain Med, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland..
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hoppu, S.
    Tampere Univ Hosp, Dept Intens Care Med, POB 2000, FI-33521 Tampere, Finland.;Univ Tampere, Tampere, Finland..
    Good quality of life before cardiac arrest predicts good quality of life after resuscitation2018Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 62, nr 4, s. 515-521Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The survival rate of cardiac arrest patients is increasing. Our aim was to compare the quality of life before and after cardiac arrest and analyse the factors associated with outcome.

    Methods. All adult cardiac arrest patients admitted to the Tampere University Hospital intensive care unit between 2009 and 2011 were included in a retrospective follow-up study if surviving to discharge and were asked to return a questionnaire after 6 months. Data on patient demographics and pre-arrest quality of life were retrieved from medical records. Data are given as means (SD) or medians [Q(1), Q(3)]. We used logistic regression to identify factors associated with better quality of life after cardiac arrest.

    Results. Six months after cardiac arrest, 36% (79/222) were alive and 70% (55/79) of those patients completed the follow-up EuroQoL (EQ-5D) quality of life questionnaire. Median values for the EQ-5D before and after cardiac arrest were 0.89 [0.63, 1] and 0.89 [0.62, 1], respectively (P = 0.75). Only the EQ-5D prior to cardiac arrest was associated with better quality of life afterwards (OR 1.2; 95% CI 1.0-1.3; P = 0.02).

    Conclusions. Quality of life remained good after cardiac arrest especially in those patients who had good quality of life before cardiac arrest.

  • 4. Hellevuo, H
    et al.
    Sainio, M
    Huhtala, H
    Olkkola, K T
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hoppu, S
    The quality of manual chest compressions during transport: effect of the mattress assessed by dual accelerometers2014Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 58, nr 3, s. 323-328Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND

    The quality of cardiopulmonary resuscitation (CPR) has an impact on survival. The quality may be impaired if the patient needs to be transported to the hospital with ongoing CPR. The aim of this study was to analyse whether the quality of CPR can be improved during transportation by using real-time audiovisual feedback. In addition, we sought to evaluate the real compression depths taking into account the mattress and stretcher effect.

    METHODS

    Paramedics (n = 24) performed standard CPR on a Resusci Anne Mannequin in a moving ambulance. Participants were instructed to perform CPR according to European Resuscitation Council Resuscitation guidelines 2010. Each pair acted as their own controls performing CPR first without and then with the feedback device. Compression depth, rate and no-flow fraction and also the mattress effect were recorded by using dual accelerometers by two Philips, HeartStart MRx Q-CPR defibrillators.

    RESULTS

    In the feedback phase, the mean compression depth increased from 51 (10) to 56 (5) mm (P < 0.001), and the percentage of compression fractions with adequate depth was 60% vs. 89% (P < 0.001). However, taking account of the mattress effect, the real depth was only 41 (8) vs. 44 (5) mm without and with feedback, respectively (P < 0.001). The values for compression rate did not differ.

    CONCLUSIONS

    CPR quality was good during transportation in general. However, the results suggest that the feedback system improves CPR quality. Dual accelerometer measurements show, on the other hand, that the mattress effect may be a clinically relevant impediment to high quality CPR.

  • 5. Hellevuo, Heidi
    et al.
    Sainio, Marko
    Nevalainen, Riikka
    Huhtala, Heini
    Olkkola, Klaus T.
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hoppu, Sanna
    Deeper chest compression - More complications for cardiac arrest patients?2013Ingår i: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 84, nr 6, s. 760-765Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim of the study: Sternal and rib fractures are frequent complications caused by chest compressions during cardiopulmonary resuscitation (CPR). This study aimed to investigate the potential association of CPR-related thoracic and abdominal injuries and compression depth measured with an accelerometer. Methods: We analysed the autopsy records, CT scans or chest radiographs of 170 adult patients, suffering in-hospital cardiac arrest at the Tampere University Hospital during the period 2009-2011 to investigate possible association of chest compressions and iatrogenic injuries. The quality of manual compressions during CPR was recorded on a Philips, HeartStart MRx Q-CPR (TM)-defibrillator. Results: Patients were 110 males and 60 females. Injuries were found in 36% of male and 23% of female patients. Among male patients CPR-related injuries were associated with deeper mean - and peak compression depths (p < 0.05). No such association was observed in women. The frequency of injuries in mean compression depth categories <5, 5-6 and >6 cm, was 28%, 27% and 49% (p = 0.06). Of all patients 27% sustained rib fractures, 11% sternal fracture and eight patients had haematomas/ruptures in the myocardium. In addition, we observed one laceration of the stomach without bleeding, one ruptured spleen, one mediastinal haemorrhage and two pneumothoraxes. Conclusion: The number of iatrogenic injuries in male patients was associated with chest compressions during cardiopulmonary resuscitation increased as the measured compression depth exceeded 6 cm. While there is an increased risk of complications with deeper compressions it is important to realize that the injuries were by and large not fatal. 

  • 6. Jalkanen, V.
    et al.
    Yang, R.
    Vaahersalo, J.
    Kurola, J.
    Ruokonen, E.
    Huhtala, H.
    Kuitunen, A.
    Pettila, V.
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Low Serum Super Concentration Predicts 90-Day Survival after Out-Of-Hospital Cardiac Arrest2014Ingår i: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 40, s. S213-S214Artikel i tidskrift (Övrigt vetenskapligt)
  • 7. Jalkanen, Ville
    et al.
    Vaahersalo, Jukka
    Pettila, Ville
    Kurola, Jouni
    Varpula, Tero
    Tiainen, Marjaana
    Huhtala, Heini
    Alaspaa, Ari
    Hovilehto, Seppo
    Kiviniemi, Outi
    Kuitunen, Anne
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    The predictive value of soluble urokinase plasminogen activator receptor (SuPAR) regarding 90-day mortality and 12-month neurological outcome in critically ill patients after out-of-hospital cardiac arrest. Data from the prospective FINNRESUSCI study2014Ingår i: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 85, nr 11, s. 1562-1567Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim: The whole body ischaemia-reperfusion after cardiac arrest (CA) induces a systemic inflammation-reperfusion response. The expression of urokinase plasminogen activator receptor (uPAR) is known to be induced after hypoxia and increased levels of soluble form suPAR have been measured after hypoxia and ischaemia. Our aim was to evaluate, whether ischaemia/reperfusion injury after out-of-hospital cardiac arrest (OHCA) increases suPAR concentrations in serum and to evaluate the prognostic value of suPAR regarding 90-day mortality and 12-month neurological outcome. Methods: This is a pre-determined substudy of prospective FINNRESUSCI study. Total of 287 patients treated in the intensive care units after OHCA and with consent from the next-of-kin and serum samples between baseline and day 4 were included. Outcome and neurological outcome were evaluated according the Pittsburgh Cerebral Performance Categories (CPC). Kaplan-Meier survival curves, areas under receiver operational characteristics curves and positive likelihood ratios for mortality and poor neurological outcome were calculated. Results: Non-survivors had higher levels of suPAR after OHCA. Kaplan-Meier survival curves indicated high 90-day mortality in the highest concentration quintiles. LR+ for 1-year CPC 3-5 was 1.8-2.7 for the whole patient cohort and in shockable rhythms 2.0-2.4. In therapeutic hypothermia prognostic value remained. Conclusions: We found that high SuPAR concentrations were associated with poor outcome in patients with OHCA admitted to critical care. However, suPAR alone had inadequate predictive value for poor outcome and did not associate with 12-month neurological outcome.  

  • 8. Jalkanen, Ville
    et al.
    Yang, Runkuan
    Linko, Rita
    Huhtala, Heini
    Okkonen, Marjatta
    Varpula, Tero
    Pettilä, Ville
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    SuPAR and PAI-1 in critically ill, mechanically ventilated patients2013Ingår i: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 39, nr 3, s. 489-496Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE:

    SuPAR (soluble urokinase plasminogen activator receptor) and PAI-1 (plasminogen activator inhibitor 1) are active in the coagulation-fibrinolysis pathway. Both have been suggested as biomarkers for disease severity. We evaluated them in prediction of mortality, acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), sepsis and renal replacement therapy (RRT) in operative and non-operative ventilated patients.

    METHODS:

    We conducted a prospective, multicenter, observational study. Blood samples and data of intensive care were collected. Mechanically ventilated patients with baseline suPAR and PAI-1 measurements were included in the analysis, and healthy volunteers were analysed for comparison. Receiver operating characteristics (ROC), logistic regression, likelihood ratios and Kaplan-Meier analysis were performed.

    RESULTS:

    Baseline suPAR was 11.6 ng/ml (quartiles Q1-Q3, 9.6-14.0), compared to healthy volunteers with suPAR of 0.6 ng/ml (0.5-11.0). PAI-1 concentrations were 2.67 ng/ml (1.53-4.69) and 0.3 ng/ml (0.3-0.4), respectively. ROC analysis for suPAR 90-day mortality areas under receiver operating characteristic curves (AUC) 0.61 (95 % confidence interval (CI): 0.55-0.67), sepsis 0.68 (0.61-0.76), ALI/ARDS 0.64 (0.56-0.73) and RRT 0.65 (0.56-0.73). Patients with the highest quartile of suPAR concentrations had an odds ratio of 2.52 (1.37-4.64, p = 0.003) for 90-day mortality and 3.16 (1.19-8.41, p = 0.02) for ALI/ARDS. In non-operative patients, the AUC's for suPAR were 90-day mortality 0.61 (0.54-0.68), RRT 0.73 (0.64-0.83), sepsis 0.70 (0.60-0.80), ALI/ARDS 0.61 (0.51-0.71). Predictive value of PAI-1 was negligible.

    CONCLUSIONS:

    In non-operative patients, low concentrations of suPAR were predictive for survival and high concentrations for RRT and mortality. SuPAR may be used for screening for patients with potentially good survival. The association with RRT may supply an early warning sign for acute renal failure.

  • 9.
    Kai, Lehtimaki
    et al.
    Tampere Univ Hosp, Dept Neurosci & Rehabil, POB 2000,Teiskontie 35,Bldg A, Tampere 33521, Finland..
    Jaakko, W. Langsjo
    Tampere Univ Hosp, Intens Care Unit, Tampere, Finland..
    Jyrki, Ollikainen
    Tampere Univ Hosp, Dept Neurosci & Rehabil, POB 2000,Teiskontie 35,Bldg A, Tampere 33521, Finland..
    Hanna, Heinonen
    Tampere Univ Hosp, Dept Clin Neurophysiol, Tampere, Finland..
    Timo, Mottonen
    Tampere Univ Hosp, Dept Neurosci & Rehabil, POB 2000,Teiskontie 35,Bldg A, Tampere 33521, Finland..
    Timo, Tahtinen
    Tampere Univ Hosp, Dept Neurosci & Rehabil, POB 2000,Teiskontie 35,Bldg A, Tampere 33521, Finland..
    Joonas, Haapasalo
    Tampere Univ Hosp, Dept Neurosci & Rehabil, POB 2000,Teiskontie 35,Bldg A, Tampere 33521, Finland..
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Jani, Katisko
    Oulu Univ Hosp, Dept Neurosurg, Oulu, Finland..
    Juha, Ohman
    Tampere Univ Hosp, Dept Neurosci & Rehabil, POB 2000,Teiskontie 35,Bldg A, Tampere 33521, Finland..
    Jukka, Peltola
    Tampere Univ Hosp, Dept Neurosci & Rehabil, POB 2000,Teiskontie 35,Bldg A, Tampere 33521, Finland..
    Successful management of super-refractory status epilepticus with thalamic deep brain stimulation2017Ingår i: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 81, nr 1, s. 142-146Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Super-refractory status epilepticus is a condition characterized by recurrence of status epilepticus despite use of deep general anesthesia, and it has high morbidity and mortality rates. We report a case of a 17-year-old boy with a prolonged super-refractory status epilepticus that eventually resolved after commencing deep brain stimulation of the centromedian nucleus of the thalamus. Later attempt to reduce stimulation parameters resulted in immediate relapse of status epilepticus, suggesting a pivotal role of deep brain stimulation in the treatment response. Deep brain stimulation may be a treatment option in super-refractory status epilepticus when other treatment options have failed. ANN NEUROL 2017;81:142-146

  • 10.
    Kiiski, Heikki
    et al.
    Tampere Univ Hosp, Dept Intens Care, Crit Care Med Res Grp, Tampere, Finland..
    Jalkanen, Ville
    Tampere Univ Hosp, Dept Intens Care, Crit Care Med Res Grp, Tampere, Finland..
    Ala-Peijari, Marika
    Tampere Univ Hosp, Dept Intens Care, Crit Care Med Res Grp, Tampere, Finland..
    Hamalainen, Mari
    Univ Tampere, Tampere Univ Hosp, Fac Med & Life Sci, Immunopharmacol Res Grp, Tampere, Finland..
    Moilanen, Eeva
    Univ Tampere, Tampere Univ Hosp, Fac Med & Life Sci, Immunopharmacol Res Grp, Tampere, Finland..
    Peltola, Jukka
    Univ Tampere, Tampere Univ Hosp, Dept Neurol, Tampere, Finland..
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Tampere Univ Hosp, Dept Intens Care, Crit Care Med Res Grp, Tampere, Finland..
    Plasma soluble Urokinase-Type Plasminogen activator receptor is not associated with neurological Outcome in Patients with aneurysmal subarachnoid hemorrhage2017Ingår i: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 8, artikel-id 144Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Object: Aneurysmal subarachnoid hemorrhage (aSAH) is a common cause of death or long-term disability. Despite advances in neurocritical care, there is still only a very limited ability to monitor the development of secondary brain injury or to predict neurological outcome after aSAH. Soluble urokinase-type plasminogen activator receptor (suPAR) has shown potential as a prognostic and as an inflammatory biomarker in a wide range of critical illnesses since it displays an association with overall immune system activation. This is the first time that suPAR has been evaluated as a prognostic biomarker in aSAH. Methods: In this prospective population-based study, plasma suPAR levels were measured in aSAH patients (n = 47) for up to 5 days. suPAR was measured at 0, 12, and 24 h after patient admission to the intensive care unit (ICU) and daily thereafter until he/ she was transferred from the ICU. The patients' neurological outcome was evaluated with the modified Rankin Scale (mRS) at 6 months after aSAH. Results: suPAR levels (n = 47) during the first 24 h after aSAH were comparable in groups with a favorable (mRS 0-2) or an unfavorable (mRS 3-6) outcome. suPAR levels during the first 24 h were not associated with the findings in the primary brain CT, with acute hydrocephalus, or with antimicrobial medication use during 5-days' follow-up. suPAR levels were associated with generally accepted inflammatory biomarkers (C-reactive protein, leukocyte count). Conclusion: Plasma suPAR level was not associated with either neurological outcome or selected clinical conditions. While suPAR is a promising biomarker for prognostication in several conditions requiring intensive care, it did not reveal any value as a prognostic biomarker after aSAH.

  • 11.
    Kiiski, Heikki
    et al.
    Tampere Univ Hosp, Dept Intens Care, Crit Care Med Res Grp, Tampere, Finland.
    Långsjö, Jaakko
    Tampere Univ Hosp, Dept Intens Care, Crit Care Med Res Grp, Tampere, Finland.
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Tampere Univ Hosp, Dept Intens Care, Crit Care Med Res Grp, Tampere, Finland.
    Ala-Peijari, Marika
    Tampere Univ Hosp, Dept Intens Care, Crit Care Med Res Grp, Tampere, Finland.
    Huhtala, Heini
    Univ Tampere, Fac Social Sci, Tampere, Finland.
    Hämäläinen, Mari
    Univ Tampere, Tampere Univ Hosp, Fac Med & Life Sci, Immunopharmacol Res Grp, Tampere, Finland.
    Moilanen, Eeva
    Univ Tampere, Tampere Univ Hosp, Fac Med & Life Sci, Immunopharmacol Res Grp, Tampere, Finland.
    Peltola, Jukka
    Univ Tampere, Dept Neurol, Tampere, Finland;Tampere Univ Hosp, Tampere, Finland.
    S100B, NSE and MMP-9 fail to predict neurologic outcome while elevated S100B associates with milder initial clinical presentation after aneurysmal subarachnoid hemorrhage2018Ingår i: Journal of the Neurological Sciences, ISSN 0022-510X, E-ISSN 1878-5883, Vol. 390, s. 129-134Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Despite advances in the treatment of aneurysmal subarachnoid hemorrhage (aSAH) one-year mortality remains approximately 50%. Making an accurate prognosis at the early phase of the disease is notoriously difficult. A clinically reliable biomarker that could be used for better prediction of prognosis and/or as a surrogate for developing complications after aSAH is still lacking. In this study, we evaluated the prognostic values of three promising biomarkers, i.e. S100B, NSE, and MMP-9 in aSAH.

    Methods: In this prospective population-based study, S100B, NSE, and MMP-9 levels were measured in 47 aSAH patients for up to five days. Blood samples were taken at 0, 12 and 24 h after the admission to the intensive care unit (ICU) and daily after that until the patient was transferred from the ICU. The patients' neurological outcome was evaluated with the modified Rankin Scale (mRS) at six months after aSAH.

    Results: Biomarker-levels measured during the first 24 h were not associated with neurological outcome. S100B levels during the first 24 h were elevated in patients with a non-severe initial clinical presentation. Otherwise, there was no association between selected clinical variables and the early biomarker levels. In 22 patients, whose ICU follow-up lasted for up to five days, the total release of biomarkers was not associated with the neurological outcome.

    Conclusions: None of the measured biomarkers were associated with the neurological outcome evaluated at six months after aSAH. Elevated levels of S100B in patients with non-severe initial presentation suggest an adaptive role of this biomarker in aSAH. Based on our findings it is not advisable to use these biomarkers to guide clinical decision-making in patients with aSAH.

  • 12.
    Kiiski, Heikki
    et al.
    Tampere Univ Hosp, Dept Intens Care, Crit Care Med Res Grp, Tampere, Finland.;Univ Tampere, NeuroGrp, BioMediTech, FIN-33101 Tampere, Finland..
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Tampere Univ Hosp, Dept Intens Care, Crit Care Med Res Grp, Tampere, Finland..
    Ala-Peijari, Marika
    Tampere Univ Hosp, Dept Intens Care, Crit Care Med Res Grp, Tampere, Finland..
    Huhtala, Heini
    Univ Tampere, Sch Hlth Sci, FIN-33101 Tampere, Finland..
    Hamalainen, Mari
    Univ Tampere, Tampere Univ Hosp, Sch Med, Immunopharmacol Res Grp, FIN-33101 Tampere, Finland..
    Langsjo, Jaakko
    Tampere Univ Hosp, Dept Intens Care, Crit Care Med Res Grp, Tampere, Finland..
    Moilanen, Eeva
    Univ Tampere, Tampere Univ Hosp, Sch Med, Immunopharmacol Res Grp, FIN-33101 Tampere, Finland..
    Narkilahti, Susanna
    Univ Tampere, NeuroGrp, BioMediTech, FIN-33101 Tampere, Finland..
    Ohman, Juha
    Tampere Univ Hosp, Dept Neurosci & Rehabil, Tampere, Finland..
    Peltola, Jukka
    Tampere Univ Hosp, Dept Neurosci & Rehabil, Tampere, Finland..
    Increased plasma UCH-L1 after aneurysmal subarachnoid hemorrhage is associated with unfavorable neurological outcome2016Ingår i: Journal of the Neurological Sciences, ISSN 0022-510X, E-ISSN 1878-5883, Vol. 361, s. 144-149Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Aneurysmal subarachnoid hemorrhage (aSAH) is a common cause of long-term disability and death. After primary hemorrhage, secondary brain injury is the main cause of mortality and morbidity. Despite extensive research, reliable prognostic biomarkers are lacking. We measured ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) levels in aSAH patients to evaluate its prognostic potential. This is the first time that plasma UCH-L1 has been studied as a potential prognostic biomarker in patients with aSAH. Methods: In this prospective population-based study, UCH-L1 levels were measured in aSAH patients (n = 47) for up to five days. UCH-L1 was measured at 0, 12 and 24 h after the admission to the intensive care unit (ICU) and daily thereafter until the patient was transferred from the ICU. Only patients whose UCH-L1 was measured within 24 h from aSAH were included in the study. The patients' neurological outcome was evaluated with the modified Rankin Scale (mRS) at six months after aSAH. Results: UCH-L1 levels during the first 24 h after aSAH were not significantly different between the groups with favorable (mRS 0-2) and unfavorable (mRS 3-6) neurological outcome. In 22 patients, UCH-L1 levels were obtained for up to five days. In this subgroup, UCH-L1 measured at day five showed significant elevation from baseline levels in patients with unfavorable outcome (p = 0.026). Elevated UCH-L1 levels at day five were higher in patients with unfavorable outcome than in patients with favorable outcome (p = 0.001). Conclusions: Elevated UCH-L1 levels during the five-day follow-up were associated with unfavorable neurological outcome. Repetitive measurements of UCH-L1 concentrations with an emphasis on change relative to the individual baseline could be the optimal approach for future clinical studies.

  • 13. Kiiski, Heikki
    et al.
    Äänismaa, Riikka
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Critical Care Medicine Research Group, Department of Intensive Care Unit, Tampere University Hospital, FI-33521 Tampere, Finland .
    Hagman, Sanna
    Ylä-Outinen, Laura
    Aho, Antti
    Yli-Hankala, Arvi
    Bendel, Stepani
    Skottman, Heli
    Narkilahti, Susanna
    Healthy human CSF promotes glial differentiation of hESC-derived neural cells while retaining spontaneous activity in existing neuronal networks2013Ingår i: Biology open, ISSN 2046-6390, Vol. 2, nr 6, s. 605-612Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The possibilities of human pluripotent stem cell-derived neural cells from the basic research tool to a treatment option in regenerative medicine have been well recognized. These cells also offer an interesting tool for in vitro models of neuronal networks to be used for drug screening and neurotoxicological studies and for patient/disease specific in vitro models. Here, as aiming to develop a reductionistic in vitro human neuronal network model, we tested whether human embryonic stem cell (hESC)-derived neural cells could be cultured in human cerebrospinal fluid (CSF) in order to better mimic the in vivo conditions. Our results showed that CSF altered the differentiation of hESC-derived neural cells towards glial cells at the expense of neuronal differentiation. The proliferation rate was reduced in CSF cultures. However, even though the use of CSF as the culture medium altered the glial vs. neuronal differentiation rate, the pre-existing spontaneous activity of the neuronal networks persisted throughout the study. These results suggest that it is possible to develop fully human cell and culture-based environments that can further be modified for various in vitro modeling purposes.

  • 14. Kämäräinen, Antti
    et al.
    Sainio, Marko
    Olkkola, Klaus T
    Huhtala, Heini
    Tenhunen, Jyrki
    Critical Care Medicine Research Group, Department of Critical Care Medicine, Tampere University Hospital and University of Tampere, Tampere, Finland.
    Hoppu, Sanna
    Quality controlled manual chest compressions and cerebral oxygenation during in-hospital cardiac arrest2012Ingår i: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 83, nr 1, s. 138-142Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM:

    The quality of cardiopulmonary resuscitation (CPR) is associated with the rate of return of spontaneous circulation (ROSC) during human cardiac arrest. Current advances in defibrillator technology enable measurement of CPR quality during resuscitation, but it is not known whether this is directly reflected in cerebral oxygenation. In this descriptive study we aimed to evaluate whether the quality of feedback-monitored CPR during in-hospital cardiac arrest is reflected in near infrared frontal cerebral spectroscopy (NIRS).

    METHODS:

    Nine patients suffering an in-hospital cardiac arrest in a university hospital were included. All patients underwent quality-controlled CPR performed by a dedicated medical emergency team using a Philips HeartStart MRx defibrillator (Philips, Eindhoven, Netherlands) with a CPR quality (Q-CPR, Laerdal Medical, Stavanger, Norway) analysis feature. Simultaneously, bilateral frontal cerebral oximetry was measured using INVOS 5100c (Somanetics, Troy, MI, USA) NIRS.

    RESULTS:

    During quality controlled resuscitation, regional cerebral oxygenation (rSO2) as measured with NIRS was low but it improved during CPR (p = 0.043) and 8 min after ROSC (p = 0.022). After the onset of NIRS recording, there were four episodes exceeding 30 s, during which the quality of CPR was substandard. When CPR technique was corrected and maintained for 2 min, a minor non-significant increase in rSO2 was observed in two cases.

    CONCLUSIONS:

    High quality CPR was not significantly reflected in cerebral oxygenation as quantified using NIRS. Even after ROSC and subsequent significant increase in cerebral oxygenation, rSO2 readings were below previously suggested threshold of cerebral ischaemia. Improving CPR technique after an episode of low quality CPR did not significantly increase rSO2.

  • 15. Linko, R
    et al.
    Pettilä, V
    Ruokonen, E
    Varpula, T
    Karlsson, S
    Tenhunen, Jyrki
    Critical Care Medicine Research Group, Department of Intensive Care Medicine, Tampere University Hospital, Tampere, Finland.
    Reinikainen, M
    Saarinen, K
    Perttilä, J
    Parviainen, I
    Ala-Kokko, T
    Corticosteroid therapy in intensive care unit patients with PCR-confirmed influenza A(H1N1) infection in Finland2011Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 55, nr 8, s. 971-979Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE:

    To evaluate the incidence, treatment, and outcome of influenza A(H1N1) in Finnish intensive care units (ICUs) with special reference to corticosteroid treatment.

    METHODS:

    During the H1N1 outbreak in Finland between 11 October and 31 December 2009, we prospectively evaluated all consecutive ICU patients with high suspicion of or confirmed pandemic influenza A(H1N1) infection. We assessed severity of acute disease and daily organ dysfunction. Ventilatory support and other concomitant treatments were evaluated and recorded daily throughout the ICU stay. The primary outcome was hospital mortality.

    RESULTS:

    During the 3-month period altogether 132 ICU patients were tested polymerase chain reaction-positive for influenza A(H1N1). Of these patients, 78% needed non-invasive or invasive ventilatory support. The median (interquartile) length of ICU stay was 4 [2-12] days. Hospital mortality was 10 of 132 [8%, 95% confidence interval (CI) 3-12%]. Corticosteroids were administered to 72 (55%) patients, but rescue therapies except prone positioning were infrequently used. Simplified Acute Physiology Score II and Sequential Organ Failure Assessment scores in patients with and without corticosteroid treatment were 31 [24-36] and 6 [2-8] vs. 22 [5-30] and 3 [2-6], respectively. The crude hospital mortality was not different in patients with corticosteroid treatment compared to those without: 8 of 72 (11%, 95% CI 4-19%) vs. 2 of 60 (3%, 95% CI 0-8%) (P = 0.11).

    CONCLUSIONS:

    The majority of H1N1 patients in ICUs received ventilatory support. Corticosteroids were administered to more than half of the patients. Despite being more severely ill, patients given corticosteroids had comparable hospital outcome with patients not given corticosteroids.

  • 16.
    Lipcsey, Miklós
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Frithiof, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Bendel, Stepani
    Kuopio Univ Hosp, Dept Intens Care, Kuopio, Finland..
    Flaatten, Hans
    UiB, Haukeland Univ Hosp, Dept Clin Med, Bergen, Norway..
    Kawati, Rafael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Kuitunen, Anne
    Tampere Univ Hosp, Crit Care Med Res Grp, POB 200033521, Tampere, Finland..
    Tonnessen, Tor Inge
    Oslo Univ Hosp, Div Emergencies & Crit Care, N-0450 Oslo, Norway.;Inst Clin Med, N-0450 Oslo, Norway..
    Rubertsson, Sten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Abdominal Septic Shock - Endotoxin Adsorption Treatment (ASSET) - endotoxin removal in abdominal and urogenital septic shock with the Alteco (R) LPS Adsorber: study protocol for a double-blinded, randomized placebo-controlled trial2016Ingår i: Trials, ISSN 1745-6215, E-ISSN 1745-6215, Vol. 17, artikel-id 587Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Severe sepsis and septic shock are common in intensive care and carry high mortality rates. In patients with Gram-negative infections, early and extensive removal of endotoxin may limit the inflammatory response that characterizes septic shock. The Alteco (R) LPS Adsorber (hereafter referred to cited as the lipopolysaccharide (LPS) Adsorber) can be used for endotoxin removal and attenuate the deleterious inflammatory and clinical responses seen in septic shock. Methods/design: The Abdominal Septic Shock - Endotoxin Adsorption Treatment (ASSET) trial is a pilot study investigating the feasibility and safety of LPS Adsorber therapy. This pilot, multicenter, stratified, parallel, double-blinded, randomized, phase IIa, feasibility clinical investigation will be performed in five Scandinavian intensive care units. Thirty-two subjects with early septic shock and organ failure, following adequate resuscitation, will be randomized to receive either: extracorporeal veno-venous hemoperfusion therapy with the LPS Adsorber or veno-venous hemoperfusion therapy with a placebo adsorber (without active LPS-binding peptide). Patients will be stratified by infection focus such that 20 subjects with an abdominal focus (stratum A) and 12 subjects with a urogenital focus (stratum B) will be included in a parallel design. Thereafter, an interim analysis will be performed and an additional 12 patients may be included in the study. The study is designed as adaptive a priori: the patients from this study can be included in a later phase IIb study. The aim of the study is to investigate the feasibility of LPS Adsorber therapy commenced early in the time-course of septic shock. The primary endpoint will be a characterization of all reported unanticipated serious adverse device effects and anticipated serious adverse device effects. Secondary outcomes are decrease in endotoxin plasma concentration, impact on clinical outcome measures and impact on inflammatory response by LPS Adsorber therapy, as well as detailed description of the relevant mediators bound to the LPS Adsorber. Recruitment of patients will start in September 2015. Discussion: The ASSET trial will give insight into the feasibility and safety of this LPS Adsorber therapy and preliminary data on its potential clinical effects in septic shock. Moreover, this pilot trial will provide with necessary data for designing future studies.

  • 17. Liuhanen, Sasu
    et al.
    Sallisalmi, Marko
    Pettilä, Ville
    Oksala, Niku
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Indirect measurement of the vascular endothelial glycocalyx layer thickness in human submucosal capillaries with a plug-in for ImageJ2013Ingår i: Computer Methods and Programs in Biomedicine, ISSN 0169-2607, E-ISSN 1872-7565, Vol. 110, nr 1, s. 38-47Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    The thickness of vascular endothelial glycocalyx layer can be measured indirectly during a spontaneous leukocyte passage from oral submucosal capillaries in humans. The subsequent differences in red blood cell (RBC) column widths, before a spontaneous white blood cell passage (pre-WBC) and after a spontaneous WBC passage (post-WBC) can be used in off-line analysis to measure glycocalyx thickness: [pre-WBC width-post-WBC width]/2. We created and validated a semi-automatic plug-in for ImageJ to measure the endothelial glycocalyx layer thickness.

    METHODS:

    Video clips presenting human sublingual microvasculature were created with a side-stream dark field imaging device. Spontaneous leukocyte passages in capillaries were analyzed from video clips with ImageJ. The capillary glycocalyx layer thickness was measured by the indirect approach with two manual and two semi-automatic methods.

    RESULTS:

    There were no statistically significant differences between glycocalyx layer thicknesses measured with different methods, even though small inter-method differences in RBC column thicknesses could be detected. Inter-rater differences were systematically smaller with both semi-automatic methods. Intra-rater coefficient of variation [CV] (95% CI) was largest when measurements were made completely manually [9.2% (8.4-10.0)], but improved significantly with automatic image enhancement prior to manual measurement [7.2% (6.4-8.0)]. CV could be improved further when using semi-automatic analysis with an in-frame median filter radius of 1 pixel [5.8% (5.0-6.6)], or a median filter radius of 2 pixels [4.3% (3.5-5.1)].

    CONCLUSIONS:

    Semi-automatic analysis of glycocalyx decreased the intra-rater CV and the inter-rater differences compared to the manual method. On average, each of the four methods yielded equal results for the glycocalyx thickness. Being the only feasible bed side method in most clinical scenarios, indirect measurement of glycocalyx thickness with orthogonal polarization spectral imaging or side-stream dark field imaging device and our plug-in can advance the study of glycocalyx layer pathology in man.

  • 18. Maddison, Liivi
    et al.
    Karjagin, Juri
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Kirsimaegi, Uelle
    Starkopf, Joel
    Moderate Intra-Abdominal Hypertension Leads to Anaerobic Metabolism in the Rectus Abdominis Muscle Tissue of Critically Ill Patients: A Prospective Observational Study2014Ingår i: BioMed Research International, ISSN 2314-6133, s. 857492-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose. We hypothesize that intra-abdominal hypertension (IAH) is associated with the presence of anaerobic metabolism in the abdominal rectus muscle (RAM) tissue of critically ill patients. Methods. We included 10 adult, critically ill patients with intra-abdominal pressure (IAP) above 12 mm Hg. Microdialysis catheters (CMA 60) were inserted into the RAM tissue. The samples were collected up to 72 hours after enrollment. Results. The patients' median (IQR) APACHE II at inclusion was 29 (21-37); 7 patients were in shock. IAP was 14.5 (12.5-17.8) mmHg at baseline and decreased significantly over time, concomitantly with arterial lactate and vasopressors requirements. The tissue lactate-to-pyruvate (L/P) ratio was 49 (36-54) at the beginning of the study and decreased significantly throughout the study. Additionally, the tissue lactate, lactate-to-glucose (L/G) ratio, and glutamate concentrations changed significantly during the study. The correlation analysis showed that lower levels of pyruvate and glycerol were associated with higher MAP and abdominal perfusion pressures (APP) and that higher levels of glutamate were correlated to elevated IAP. Conclusions. Moderate IAH leads to RAM tissue anaerobic metabolism suggestive for hypoperfusion in critically ill patients. Correlation analysis supports the concept of using APP as the primary endpoint of resuscitation in addition to MAP and IAP.

  • 19. Maddison, Liivi
    et al.
    Karjagin, Juri
    Tenhunen, Jyrki
    Critical Care Medicine Research Group, Department of Intensive Care Medicine, Tampere University Hospital, Tampere, Finland.
    Starkopf, Joel
    Moderate intra-abdominal hypertension is associated with an increased lactate-pyruvate ratio in the rectus abdominis muscle tissue: a pilot study during laparoscopic surgery2012Ingår i: Annals of intensive care, ISSN 2110-5820, Vol. 2, nr Suppl 1, s. S14-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    The development of intra-abdominal hypertension [IAH] in critically ill patients admitted to the ICU is an independent predictor of mortality. In an attempt to find an early, clinically relevant metabolic signal of modest IAH, we investigated abdominal wall metabolite concentrations in a small group of patients undergoing laparoscopic surgery. We hypothesized that elevated intra-abdominal pressure [IAP] due to pneumoperitoneum leads to an increased lactate/pyruvate [L/P] ratio in the rectus abdominis muscle [RAM], indicating anaerobic metabolism.

    METHOD:

    Six patients scheduled for elective laparoscopic gastric fundoplication were studied. Two hours before surgery, a microdialysis catheter (CMA 60, CMA Small Systems AB, Solna, Sweden) was inserted into the RAM under local anaesthesia. Catheter placement was confirmed by ultrasound. The microdialysis perfusion rate was set at 0.3 μL/min. Dialysate was collected hourly prior to pneumoperitoneum, during pneumoperitoneum, and for 2 h after pneumoperitoneum resolution. IAP was maintained at 12 to 13 mmHg during the surgery. The glucose, glycerol, pyruvate and lactate contents of the dialysate were measured.

    RESULTS:

    The median (interquartile range) L/P ratio was 10.3 (7.1 to 15.5) mmol/L at baseline. One hour of pneumoperitoneum increased the L/P ratio to 16.0 (13.6 to 35.3) mmol/L (p = 0.03). The median pneumoperitoneum duration was 86 (77 to 111) min. The L/P ratio at 2 h post-pneumoperitoneum was not different from that at baseline (p = 1.0). No changes in glycerol or glucose levels were observed.

    CONCLUSIONS:

    IAH of 12 to 13 mmHg, even for a relatively short duration, is associated with metabolic changes in the abdominal wall muscle tissue of patients undergoing laparoscopic surgery. We suggest that tissue hypoperfusion occurs even during a modest increase in IAP, and intramuscular metabolic monitoring could therefore serve as an early warning sign of deteriorating tissue perfusion.

  • 20. Nisula, S.
    et al.
    Yang, R.
    Poukkanen, M.
    Vaara, S. T.
    Kaukonen, K. M.
    Tallgren, M.
    Haapio, M.
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Korhonen, A. M.
    Pettila, V.
    Predictive value of urine interleukin-18 in the evolution and outcome of acute kidney injury in critically ill adult patients2015Ingår i: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 114, nr 3, s. 460-468Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. Interleukin-18 (IL-18) is a pro-inflammatory protein, which mediates ischaemic tubular injury, and has been suggested to be a sensitive and specific biomarker for acute kidney injury (AKI). The predictive value of IL-18 in the diagnosis, evolution, and outcome of AKI in critically ill patients is still unclear. Methods. We measured urine IL-18 from critically ill patients at intensive care unit (ICU) admission and 24 h. We evaluated the association of IL-18 with developing new AKI, renal replacement therapy (RRT), and 90-day mortality. We calculated areas under receiver operating characteristics curves (AUCs), best cut-off values, and positive likelihood ratios (LR+) for IL-18 concerning these endpoints. Additionally, we compared the predictive value of IL-18 at ICU admission to that of urine neutrophil gelatinase-associated lipocalin (NGAL). Results. In this study population of 1439 patients the highest urine IL-18 during the first 24 h in the ICU associated with the development of AKI with an AUC [95% confidence interval (CI)] of 0.586 (0.546-0.627) and with the development of Stage 3 AKI with an AUC (95% CI) of 0.667 (0.591-0.774). IL-18 predicted the initiation of RRT with an AUC (95% CI) of 0.655 (0.572-0.739), and 90-day mortality with an AUC (95% CI) of 0.536 (0.497-0.574). Conclusions. IL-18 had poor-to-moderate ability to predict AKI, RRT, or 90-day mortality in this large cohort of critically ill patients. Thus, it should be used with caution for diagnostic or predictive purposes in the critically ill.

  • 21. Nisula, Sara
    et al.
    Kaukonen, Kirsi-Maija
    Vaara, Suvi T
    Korhonen, Anna-Maija
    Poukkanen, Meri
    Karlsson, Sari
    Haapio, Mikko
    Inkinen, Outi
    Parviainen, Ilkka
    Suojaranta-Ylinen, Raili
    Laurila, Jouko J
    Tenhunen, Jyrki
    Department of Intensive Care Medicine, Tampere University Hospital, Tampere, Finland .
    Reinikainen, Matti
    Ala-Kokko, Tero
    Ruokonen, Esko
    Kuitunen, Anne
    Pettilä, Ville
    Incidence, risk factors and 90-day mortality of patients with acute kidney injury in Finnish intensive care units: the FINNAKI study2013Ingår i: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 39, nr 3, s. 420-428Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE

    We aimed to determine the incidence, risk factors and outcome of acute kidney injury (AKI) in Finnish ICUs.

    METHODS

    This prospective, observational, multi-centre study comprised adult emergency admissions and elective patients whose stay exceeded 24 h during a 5-month period in 17 Finnish ICUs. We defined AKI first by the Acute Kidney Injury Network (AKIN) criteria supplemented with a baseline creatinine and second with the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We screened the patients' AKI status and risk factors for up to 5 days.

    RESULTS

    We included 2,901 patients. The incidence (95 % confidence interval) of AKI was 39.3 % (37.5-41.1 %). The incidence was 17.2 % (15.8-18.6 %) for stage 1, 8.0 % (7.0-9.0 %) for stage 2 and 14.1 % (12.8-15.4 %) for stage 3 AKI. Of the 2,901 patients 296 [10.2 % (9.1-11.3 %)] received renal replacement therapy. We received an identical classification with the new KDIGO criteria. The population-based incidence (95 % CI) of ICU-treated AKI was 746 (717-774) per million population per year (reference population: 3,671,143, i.e. 85 % of the Finnish adult population). In logistic regression, pre-ICU hypovolaemia, diuretics, colloids and chronic kidney disease were independent risk factors for AKI. Hospital mortality (95 % CI) for AKI patients was 25.6 % (23.0-28.2 %) and the 90-day mortality for AKI patients was 33.7 % (30.9-36.5 %). All AKIN stages were independently associated with 90-day mortality.

    CONCLUSIONS

    The incidence of AKI in the critically ill in Finland was comparable to previous large multi-centre ICU studies. Hospital mortality (26 %) in AKI patients appeared comparable to or lower than in other studies.

  • 22. Nisula, Sara
    et al.
    Yang, Runkuan
    Kaukonen, Kirsi-Maija
    Vaara, Suvi T.
    Kuitunen, Anne
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Pettila, Ville
    Korhonen, Anna-Maija
    The Urine Protein NGAL Predicts Renal Replacement Therapy, but Not Acute Kidney Injury or 90-Day Mortality in Critically III Adult Patients2014Ingår i: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 119, nr 1, s. 95-102Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Urine neutrophil gelatinase-associated lipocalin (uNGAL) is increasingly used as a biomarker for acute kidney injury (AKI). However, the clinical value of uNGAL with respect to AKI, renal replacement therapy (RRT), or 90-day mortality in critically ill patients is unclear. Accordingly, we tested the hypothesis that uNGAL is a clinically relevant biomarker for these end points in a large, nonselected cohort of critically ill adult patients. METHODS: We prospectively obtained urine samples from 1042 adult patients admitted to 15 Finnish intensive care units. We analyzed 3 samples (on admission, at 12 hours, and at 24 hours) with NGAL ELISA Rapid Kits (BioPorto (R) Diagnostics, Gentofte, Denmark). We chose the highest uNGAL (uNGAL24) for statistical analyses. We calculated the areas under receiver operating characteristics curves (AUC) with 95% confidence intervals (95% CIs), the best cutoff points with the Youden index, positive likelihood ratios (LR+), continuous net reclassification improvement (NRI), and the integrated discrimination improvement (IDI). We performed sensitivity analyses excluding patients with AKI or RRT on day 1, sepsis, or with missing baseline serum creatinine concentration. RESULTS: In this study population, the AUG of uNGAL24 (95% CI) for development of AKI (defined by the Kidney Disease: Improving Global Outcomes [KDIGO] criteria) was 0.733(0.701-0.765), and the continuous NRI for AKI was 56.9%. For RRT, the AUG of uNGAL24 (95% CI) was 0.839 (0.797-0.880), and NRI 56.3%. For 90-day mortality, the AUG of uNGAL24 (95% CI) was 0.634 (0.593 to 0.675), and NRI 15.3%. The LR+ (95% CI) for RRT was 3.81 (3.26-4.47). CONCLUSION: In this study, we found that uNGAL associated well with the initiation of RRT but did not provide additional predictive value regarding AKI or 90-day mortality in critically ill patients.

  • 23. Perner, Anders
    et al.
    Haase, Nicolai
    Guttormsen, Anne B.
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Klemenzson, Gudmundur
    Åneman, Anders
    Madsen, Kristian R.
    Moller, Morten H.
    Elkjaer, Jeanie M.
    Poulsen, Lone M.
    Bendtsen, Asger
    Winding, Robert
    Steensen, Morten
    Berezowicz, Pawel
    Søe-Jensen, Peter
    Bestle, Morten
    Strand, Kristian
    Wiis, Jørgen
    White, Jonathan O.
    Thornberg, Klaus J.
    Quist, Lars
    Nielsen, Jonas
    Andersen, Lasse H.
    Holst, Lars B.
    Thormar, Katrin
    Kjaeldgaard, Anne-Lene
    Fabritius, Maria L.
    Mondrup, Frederik
    Pott, Frank C.
    Møller, Thea P.
    Winkel, Per
    Wetterslev, Jørn
    Hydroxyethyl Starch 130/0.4 versus Ringer's Acetate in Severe Sepsis2012Ingår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 367, nr 2, s. 124-134Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND Hydroxyethyl starch (HES) 130/0.4 is widely used for fluid resuscitation in intensive care units (ICUs), but its safety and efficacy have not been established in patients with severe sepsis. METHODS In this multicenter, parallel-group, blinded trial, we randomly assigned patients with severe sepsis to fluid resuscitation in the ICU with either 6% HES 130/0.4 or Ringer's acetate at a dose of up to 33 ml per kilogram of ideal body weight per day. The primary outcome measure was either death or end-stage kidney failure (dependence on dialysis) at 90 days after randomization. RESULTS Of the 804 patients who underwent randomization, 798 were included in the modified intention-to-treat population. The two intervention groups had similar baseline characteristics. At 90 days after randomization, 201 of 398 patients (51%) assigned to HES 130/0.4 had died, as compared with 172 of 400 patients (43%) assigned to Ringer's acetate (relative risk, 1.17; 95% confidence interval [CI], 1.01 to 1.36; P=0.03); 1 patient in each group had end-stage kidney failure. In the 90-day period, 87 patients (22%) assigned to HES 130/0.4 were treated with renal-replacement therapy versus 65 patients (16%) assigned to Ringer's acetate (relative risk, 1.35; 95% CI, 1.01 to 1.80; P=0.04), and 38 patients (10%) and 25 patients (6%), respectively, had severe bleeding (relative risk, 1.52; 95% CI, 0.94 to 2.48; P=0.09). The results were supported by multivariate analyses, with adjustment for known risk factors for death or acute kidney injury at baseline. CONCLUSIONS Patients with severe sepsis assigned to fluid resuscitation with HES 130/0.4 had an increased risk of death at day 90 and were more likely to require renal-replacement therapy, as compared with those receiving Ringer's acetate. 

  • 24. Perner, Anders
    et al.
    Haase, Nicolai
    Winkel, Per
    Guttormsen, Anne B.
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Klemenzson, Gudmundur
    Muller, Rasmus G.
    Aneman, Anders
    Wetterslev, Jorn
    Long-term outcomes in patients with severe sepsis randomised to resuscitation with hydroxyethyl starch 130/0.42 or Ringer's acetate2014Ingår i: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 40, nr 7, s. 927-934Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We assessed long-term mortality and hospitalisation in patients with severe sepsis resuscitated with hydroxyethyl starch (HES) or Ringer's acetate. This was an investigator-initiated, parallel-grouped, blinded randomised trial using computer-generated allocation sequence and centralised allocation data that included 804 patients with severe sepsis needing fluid resuscitation in 26 general intensive care units (ICUs) in Scandinavia. Patients were allocated to fluid resuscitation using either 6 % HES 130/0.42 or Ringer's acetate during ICU admission. We assessed mortality rates at 6 months, 1 year and at the time of longest follow-up and days alive and out of hospital at 1 year. The vital status of all patients was obtained at a median of 22 (range 13-36) months after randomisation. Mortality rates in the HES versus Ringer's groups at 6 months were 53.3 (212/398 patients) versus 47.5 % (190/400) [relative risk 1.12; 95 % confidence interval (CI) 0.98-1.29; P = 0.10], respectively; at 1 year, 56.0 (223/398) versus 51.5 % (206/400) (1.09; 95 % CI 0.96-1.24; P = 0.20), respectively; at the time of longest follow-up, 59.8 (238/398) versus 56.3 % (225/400) (1.06; 95 % CI 0.94-1.20; P = 0.31), respectively. Percentage of days alive and out of hospital at 1 year in the HES versus Ringer's groups was 24 (0-87 days) versus 63 % (0-90) (P = 0.07). The long-term mortality rates did not differ in patients with severe sepsis assigned to HES 130/0.42 versus Ringer's acetate, but we could not reject a 24 % relative increased or a 4 % relative decreased mortality at 1 year with HES at the 95 % confidence level.

  • 25. Pynnonen, Lauri
    et al.
    Minkkinen, Minna
    Raty, Sari
    Sand, Juhani
    Nordback, Isto
    Perner, Anders
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Luminal lactate in acute pancreatitis - validation and relation to disease severity2012Ingår i: BMC Gastroenterology, ISSN 1471-230X, E-ISSN 1471-230X, Vol. 12, s. 40-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Increased rectal luminal lactate concentration may be associated with the severity of the septic shock and high dose of vasopressors. It suggests hypoperfusion of the gut mucosa. This is potentially associated with bacterial translocation from the gut leading to local and systemic inflammation. In acute pancreatitis (AP) bacterial translocation is considered as the key event leading to infection of necrotic pancreatic tissue and high severity of illness. Methods: We used rectal luminal equilibration dialysis for the measurement of gut luminal lactate in 30 consecutive patients admitted to hospital due to acute pancreatitis to test the hypothesis that a single measurement of rectal luminal lactate predicts the severity of acute pancreatitis, the length of hospital stay, the need of intensive care and ultimately, mortality. We also tested the physiological validity of luminal lactate concentration by comparing it to luminal partial tension of oxygen. Additionally, a comparison between two different L-lactate analyzers was performed. Results: High rectal luminal lactate was associated with low mucosal partial tension of oxygen (R = 0.57, p = 0.005) thereby indicating the physiological validity of the method. Rectal luminal lactate at the hospital admission was not associated with the first day or the highest SOFA score, CRP level, hospital length of stay, length of stay in intensive care or mortality. In this cohort of unselected consecutive patients with acute pancreatitis we observed a tendency of increased rectal lactate in the severe cases. Low precision and high bias was observed between two lactate analyzers. Conclusions: The association between rectal luminal lactate and oxygen tension indicates that luminal lactate is a marker mucosal anaerobiosis. Comparison between two different analyzers showed poor, non-constant precision over the range of lactate concentrations. Rectal luminal lactate concentration at the time of hospital admission did not predict the severity of pancreatitis.

  • 26. Pynnönen, Lauri
    et al.
    Minkkinen, Minna
    Perner, Anders
    Räty, Sari
    Nordback, Isto
    Sand, Juhani
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Validation of Intraluminal and Intraperitoneal microdialysis in ischemic small intestine2013Ingår i: BMC Gastroenterology, ISSN 1471-230X, E-ISSN 1471-230X, Vol. 13, s. 170-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND

    We sought to define the sensitivity and specificity of intraperitoneal (IP) and intraluminal (IL) microdialysate metabolites in depicting ex vivo small intestinal total ischemia during GI-tract surgery. We hypothesized that IL as opposed to IP microdialysis detects small intestinal ischemia with higher sensitivity and specificity.

    METHODS

    IL and IP microdialysate lactate, pyruvate, glucose and glycerol were analysed from small intestine of pancreaticoduodenectomy patients before and after occluding the mesenteric vasculature and routine resection of a segment of small intestine. Ex vivo time sequences of microdialysate metabolites were described and ROC analyses after 0-30, 31-60, 61-90 and 91-120 minutes after the onset ischemia were calculated.

    RESULTS

    IL lactate to pyruvate ratio (L/P ratio) indicated ischemia after 31-60 minutes with 0.954 ROC AUC (threshold: 109) in contrast to IP L/P (ROC AUC of 0.938 after 61-90 minutes, threshold: 18). At 31-60 minutes IL glycerol concentration indicated ischemia with 0.903 ROC AUCs (thresholds: 69 μmol/l). IP glycerol was only moderately indicative for ischemia after 91-120 minutes with 0,791 ROC AUCs (threshold 122 μmol/l). After 31-60 minutes IL and IP lactate to glucose ratios (L/G ratio) indicated ischemia with 0.956 and 0,942 ROC AUCs (thresholds: 48,9 and 0.95), respectively.

    CONCLUSIONS

    The results support the hypothesis that intraluminal application of microdialysis and metabolic parameters from the small intestinal lumen indicate onset of ischemia earlier than intraperioneal microdialysis with higher sensitivity and specificity.

  • 27. Raittinen, Lassi P.
    et al.
    Berg, Leena
    Nunes, Silvia
    Ahonen, Heikki
    Parviainen, Ilkka
    Laranne, Jussi
    Tenhunen, Jyrki J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Sympathetic innervation does not contribute to glycerol release in ischemic flaps2012Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 72, nr 5, s. 420-426Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. Extracellular glycerol as detected by microdialysis has been used as a surrogate marker for (ischemic) tissue damage and cellular membrane breakdown in the monitoring of free microvascular musculocutaneous flaps. One confounding factor for glycerol as a marker of ischemic cell damage is the effect of lipolysis and associated glycerol release as induced by sympathetic signalling alone. We hypothesized that extracellular glycerol concentrations in a microvascular flap with sympathetic innervation would be confounded by intact innervation per se as compared to denervated flap. Clinical relevance is related to the use of both free and pedicled flaps in reconstructive surgery. We tested the hypothesis in an experimental model of microvascular musculocutaneal flaps.

    Methods. Twelve pigs were anesthetized and mechanically ventilated. Two identical rectus abdominis musculocutaneal flaps were raised for the investigation. In the A-flaps the adventitia of the artery and accompanying innervation was carefully stripped, while in the B-flaps it was left untouched. Flap ischemia was induced by clamping both vessels for 60 minutes. The ischemia was confirmed by measuring tissue oxygen pressure, while extracellular lactate to pyruvate ratio indicated the accompanying anaerobic metabolism locally.

    Results. Intramuscular and sub-cutaneal extracellular glycerol concentrations were measured by microdialysate analyzer. Contrary to our hypothesis, glycerol concentrations were comparable between the two ischemia groups at 60 minutes (p = 0.089, T-test).

    Conclusions. In this experimental model of vascular flap ischemia, intact innervation of the flap did not confound ischemia detection by glycerol. Extrapolation of the results to clinical setting warrants further studies.

  • 28. Ranieri, V. Marco
    et al.
    Thompson, B. Taylor
    Barie, Philip S.
    Dhainaut, Jean-Francois
    Douglas, Ivor S.
    Finfer, Simon
    Gardlund, Bengt
    Marshall, John C.
    Rhodes, Andrew
    Artigas, Antonio
    Payen, Didier
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Al-Khalidi, Hussein R.
    Thompson, Vivian
    Janes, Jonathan
    Macias, William L.
    Vangerow, Burkhard
    Williams, Mark D.
    Drotrecogin Alfa (Activated) in Adults with Septic Shock2012Ingår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 366, nr 22, s. 2055-2064Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND There have been conflicting reports on the efficacy of recombinant human activated protein C, or drotrecogin alfa (activated) (DrotAA), for the treatment of patients with septic shock.

    METHODS In this randomized, double-blind, placebo-controlled, multicenter trial, we assigned 1697 patients with infection, systemic inflammation, and shock who were receiving fluids and vasopressors above a threshold dose for 4 hours to receive either DrotAA (at a dose of 24 mu g per kilogram of body weight per hour) or placebo for 96 hours. The primary outcome was death from any cause 28 days after randomization.

    RESULTS At 28 days, 223 of 846 patients (26.4%) in the DrotAA group and 202 of 834 (24.2%) in the placebo group had died (relative risk in the DrotAA group, 1.09; 95% confidence interval [CI], 0.92 to 1.28; P = 0.31). At 90 days, 287 of 842 patients (34.1%) in the DrotAA group and 269 of 822 (32.7%) in the placebo group had died (relative risk, 1.04; 95% CI, 0.90 to 1.19; P = 0.56). Among patients with severe protein C deficiency at baseline, 98 of 342 (28.7%) in the DrotAA group had died at 28 days, as compared with 102 of 331 (30.8%) in the placebo group (risk ratio, 0.93; 95% CI, 0.74 to 1.17; P = 0.54). Similarly, rates of death at 28 and 90 days were not significantly different in other predefined subgroups, including patients at increased risk for death. Serious bleeding during the treatment period occurred in 10 patients in the DrotAA group and 8 in the placebo group (P = 0.81).

    CONCLUSIONS DrotAA did not significantly reduce mortality at 28 or 90 days, as compared with placebo, in patients with septic shock.

  • 29. Sainio, Marko
    et al.
    Hellevuo, Heidi
    Huhtala, Heini
    Hoppu, Sanna
    Eilevstjonn, Joar
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Olkkola, Klaus T.
    Effect of mattress and bed frame deflection on real chest compression depth measured with two CPR sensors2014Ingår i: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 85, nr 6, s. 840-843Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim: Implementation of chest compression (CC) feedback devices with a single force and deflection sensor (FDS) may improve the quality of CPR. However, CC depth may be overestimated if the patient is on a compliant surface. We have measured the true CC depth during in-hospital CPR using two FDSs on different bed and mattress types. Methods: This prospective observational study was conducted at Tampere University Hospital between August 2011 and September 2012. During in-hospital CPR one FDS was placed between the rescuer's hand and the patient's chest, with the second attached to the backboard between the patient's back and the mattress. The real CC depth was calculated as the difference between the total depth from upper FDS to lower FDS. Results: Ten cardiac arrests on three different bed and mattress types yielded 10,868 CCs for data analyses. The mean (SD) mattress/bed frame effect was 12.8 (4) mm on a standard hospital bed with a gel mattress, 12.4 (4) mm on an emergency room stretcher with a thin gel mattress and 14.1 (3) mm on an ICU bed with an emptied air mattress. The proportion of CCs with an adequate depth (>= 50 mm) decreased on all mattress types after compensating for the mattress/bed frame effect from 94 to 64%, 98 to 76% and 91 to 17%, in standard hospital bed, emergency room stretcher and ICU bed, respectively (p < 0.001). Conclusion: The use of FDS without real-time correction for deflection may result in CC depth not reaching the recommended depth of 50 mm.

  • 30.
    Sainio, Marko
    et al.
    Tampere Univ Hosp, Dept Intens Care Med, Crit Care Med Res Grp, FI-33521 Tampere, Finland.;Turku Univ Hosp, Dept Emergency Med, Emergency Med Serv, FI-20521 Turku, Finland..
    Hoppu, Sanna
    Tampere Univ Hosp, Dept Intens Care Med, Crit Care Med Res Grp, FI-33521 Tampere, Finland..
    Huhtala, Heini
    Univ Tampere, Sch Hlth Sci, FI-33014 Tampere, Finland..
    Eilevstjonn, Joar
    Laerdal Med AS, N-4002 Stavanger, Norway..
    Olkkola, Klaus T.
    Univ Helsinki, Dept Anaesthesiol Intens Care Emergency Care & Pa, FI-00029 Helsinki, Finland.;Univ Helsinki, Cent Hosp, Meilahti Hosp, FI-00029 Helsinki, Finland..
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Tampere Univ Hosp, Dept Intens Care Med, Crit Care Med Res Grp, FI-33521 Tampere, Finland..
    Simultaneous beat-to-beat assessment of arterial blood pressure and quality of cardiopulmonary resuscitation in out-of-hospital and in-hospital settings2015Ingår i: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 96, s. 163-169Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: The current recommendation for depth and rate of chest compression (CC) during cardiopulmonary resuscitation (CPR) is based on limited hemodynamic data recorded during human CPR. We have evaluated the possible association between CC depth and rate and continuously measured arterial blood pressure during adult CPR. Methods: This prospective study included data from 104 patients resuscitated inside or outside hospital. Adequate data on continuously measured invasive arterial blood pressure (BP) and the quality of CPR from a defibrillator capable recording CPR quality parameters was successful in 39 patients. We used logistic regression and mixed effects modeling to identify CC depths and rates associated with systolic blood pressure (SBP) >= 85 mmHg and diastolic blood pressure (DBP) >= 30 mmHg. Results: We analyzed 41,575 compression-BP pairs. The values for blood pressure varied greatly between the patients. SBP varied from 25 to 225 mmHg and DBP from 2 to 59 mmHg. CC rate 100-120/min and CC depth >= 60 mm (without mattress deflection correction) was associated with DBP >= 30 mmHg in both femoral (OR 1.14; 95% CI 1.03, 1.26; p < 0.05) and radial (OR 4.70; 95% CI 3.92, 5.63; p < 0.001) recordings. For any given subject there was a weak upward trend in blood pressure as CC depth increased. Conclusion: Deeper CC does not equal higher BP in every patient. The heterogeneity of patients creates a challenge to find the optimal way to resuscitate patients individually.

  • 31. Sainio, Marko
    et al.
    Kämäräinen, Antti
    Huhtala, Heini
    Aaltonen, Petri
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Olkkola, Klaus T.
    Hoppu, Sanna
    Real-time audiovisual feedback system in a physician-staffed helicopter emergency medical service in Finland: the quality results and barriers to implementation2013Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, E-ISSN 1757-7241, Vol. 21, s. 50-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: To evaluate the quality of cardiopulmonary resuscitation (CPR) in a physician staffed helicopter emergency medical service (HEMS) using a monitor-defibrillator with a quality analysis feature. As a post hoc analysis, the potential barriers to implementation were surveyed. Methods: The quality of CPR performed by the HEMS from November 2008 to April 2010 was analysed. To evaluate the implementation rate of quality analysis, the HEMS database was screened for all cardiac arrest missions during the study period. As a consequence of the observed low implementation rate, a survey was sent to physicians working in the HEMS to evaluate the possible reasons for not utilizing the automated quality analysis feature. Results: During the study period, the quality analysis was used for 52 out of 187 patients (28%). In these cases the mean compression depth was < 40 mm in 46% and < 50 mm in 96% of the 1-min analysis intervals, but otherwise CPR quality corresponded with the 2005 resuscitation guidelines. In particular, the no-flow fraction was remarkably low 0.10 (0.07, 0.16). The most common reasons for not using quality-controlled CPR were that the device itself was not taken to the scene, or not applied to the patient, because another EMS unit was already treating the patient with another defibrillator. Conclusions: When quality-controlled CPR technology was used, the indicators of good quality CPR as described in the 2005 resuscitation guidelines were mostly achieved albeit with sufficient compression depth. The use of the well-described technology in improving patient care was low. Wider implementation of the automated quality control and feedback feature in defibrillators could further improve the quality of CPR on the field.

  • 32. Sainio, Marko
    et al.
    Sutton, Robert M.
    Huhtala, Heini
    Eilevstjonn, Joar
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Olkkola, Klaus T.
    Nadkarni, Vinay M.
    Hoppu, Sanna
    Association of arterial blood pressure and CPR quality in a child using three different compression techniques, a case report2013Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, E-ISSN 1757-7241, Vol. 21, s. 51-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A 2-year-old boy found in cardiac arrest secondary to drowning received standard CPR for 35 minutes and was transported to a tertiary hospital for rewarming from hypothermia. Chest compressions in hospital were started using two-thumb encircling hands technique. Subsequently two-thumbs direct sternal compression technique and after sternal force/depth sensor placement, chest compression with classic one-hand technique were done. By using CPR recording/feedback defibrillator, quantitative CPR quality data and invasive arterial pressures were available for analyses for 5 hours and 35 minutes. 316 compressions with the two-thumb encircling hands technique provided a mean (SD) systolic arterial pressure (SAP) of 24 (4) mmHg, mean arterial pressure (MAP) 18 (3) and diastolic arterial pressure (DAP) of 15 (3) mmHg. similar to 6000 compressions with the two thumbs direct compression technique created a mean SAP of 45 (7) mmHg, MAP 35 (4) mmHg and DAP of 30 (3) mmHg. similar to 20,000 compressions with the sternal accelerometer in place produced SAP 50 (10) mmHg, MAP 32 (5) mmHg and DAP 24 (4) mmHg. Restoration of spontaneous circulation (ROSC) was achieved at the point when the child achieved normothermia by using peritoneal dialysis. Unfortunately, the child died ten hours after ROSC without any signs of neurological recovery. This case demonstrates improved hemodynamic parameters with classic one-handed technique with real-time quantitative quality of CPR feedback compared to either the two-thumbs encircling hands or two-thumbs direct sternal compression techniques. We speculate that the improved arterial pressures were related to improved chest compression depth when a real-time CPR recording/feedback device was deployed.

  • 33. Sallisalmi, M
    et al.
    Oksala, N
    Pettilä, V
    Tenhunen, Jyrki
    Critical Care Medicine Research Group, Department of Intensive Care Medicine, Tampere University Hospital, Tampere, Finland.
    Evaluation of sublingual microcirculatory blood flow in the critically ill2012Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 56, nr 3, s. 298-306Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    The microcirculation regulates the supply of oxygen and nutrients to tissues. The sublingual region is frequently used as a window to microcirculation in critically ill patients. Numerous studies have reported impaired sublingual microcirculatory flow. We hypothesized that the quality of sidestream dark field imaging (SDF) recordings could be systematically analyzed to justify the monitoring of sublingual microcirculation in interventional studies or in clinical practice.

    METHODS:

    The sublingual microcirculation in critically ill patients with septic shock, open heart surgery, or alcoholic pancreatitis, and healthy subjects was recorded with a hand held SDF device by one trained investigator in observational setting. A total of 82 video recording sessions were performed and 240 video clips eligible for quality assessment were identified. Quality assessment was performed offline by two investigators independently and blinded for the origin of the video file.

    RESULTS:

    Of the 240 clips, pressure artifact was detected in 86 (36%), major blood in 5 (2.1%), major saliva in 21 (8.8%) and extreme brightness causing loss of visible capillaries in 16 (6.7%) clips. The dominating vessel architecture was multiple size vessels in 228 (95%) and repeating capillary loop motif in 12 (5.0%). The mean (± SD) relative size reduction during stabilization was -6.9% (± 4.7%). Excellent technical quality was detected in 74 of 240 (30.8%) recordings.

    CONCLUSIONS:

    Our findings highlight the need of a comprehensive training period and reporting of data quality before findings with SDF imaging can be accepted as surrogate end points in interventional studies or as guidance in clinical practice.

  • 34. Sallisalmi, M
    et al.
    Tenhunen, Jyrki
    Critical Care Medicine Research Group, Department of Intensive Care Medicine, Tampere University Hospital, Tampere, Finland.
    Yang, R
    Oksala, N
    Pettilä, V
    Vascular adhesion protein-1 and syndecan-1 in septic shock2012Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 56, nr 3, s. 316-322Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    Constituents of vascular endothelial surface layer (glycocalyx), e.g. an anchor protein syndecan-1 (SDC-1), can be detected in plasma in many inflammatory conditions. In inflammation, vascular adhesion protein-1 (VAP-1) is rapidly translocated to the apical side of the endothelial cells and may be released to plasma in a soluble form. We hypothesized that glycocalyx injury coincides with VAP-1 activation on endothelial cells. To test the hypothesis, we measured SDC-1 and VAP-1 levels in 20 patients with septic shock.

    METHODS:

    A prospective observational study was conducted in two multidisciplinary critical care units in two tertiary academic teaching hospitals with 20 mechanically ventilated adult patients with septic shock, on days 1 and 4 of treatment. Twenty healthy adults were enrolled as a control group. Plasma SDC-1 content, serum VAP-1 activity, platelets, and leukocyte count were measured in septic shock group at baseline and at 72 h and compared with those of healthy controls.

    RESULTS:

    VAP-1 activity and SDC-1 content were significantly increased in septic patients' group (P < 0.01) in comparison with controls. VAP-1 activity and SDC-1 content correlated positively to each other, and negatively to platelet count. In the septic shock group SDC-1 correlated on day 1 to SOFA score.

    CONCLUSIONS:

    We found increased VAP-1 activity and SDC-1 content in critically ill patients with septic shock. Based on our results, the role of VAP-1 in shock pathogenesis should be studied with semicarbazide-sensitive amine oxidase activity blocking agents and substrate affinity testing.

  • 35. Sallisalmi, Marko
    et al.
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Kultti, Anne
    Tammi, Markku
    Pettilä, Ville
    Plasma hyaluronan and hemorheology in patients with septic shock: a clinical and experimental study2014Ingår i: Clinical hemorheology and microcirculation, ISSN 1386-0291, E-ISSN 1875-8622, Vol. 56, nr 2, s. 133-144Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND

    Total plasma hyaluronan concentration is increased in septic shock. High-molecular-weight hyaluronan has a high intrinsic viscosity. Excessive release of high-molecular-weight hyaluronan in sepsis may induce hyperviscosity.

    METHODS

    Plasma viscosity and the molecular size of plasma hyaluronan were determined in 20 patients with septic shock and in 20 healthy controls. Ex vivo, the effects of 0.4% and 0.047% high-molecular-weight hyaluronan 1560 kDa, 0.9% saline, and 6% hydroxy-ethyl-starch 130 kDa were compared to plasma and whole blood viscosity and red blood cell aggregation at a systemic hematocrit of 0.4, and at a microcirculatory hematocrit of 0.2.

    RESULTS

    Plasma viscosity and total plasma protein content were low in septic shock patients on days one and four of treatment. Hyaluronan concentration was 10-fold higher in sepsis on day 1. Molecular weight of hyaluronan was relatively low, mostly 50-500 kDa, and did not change significantly in sepsis. Ex vivo, 0.4% high-molecular-weight hyaluronan 1560 kDa increased blood viscosity but did not promote red blood cell aggregation. Dilutions of 6% hydroxyl-ethyl-starch 130 kDa and 0.047% high-molecular-weight hyaluronan 1560 kDa had comparable effects on blood viscosity and red blood cell aggregation.

    CONCLUSIONS

    Plasma viscosity of the septic patients remained low for four days despite markedly elevated concentration of relatively small-molecular-weight hyaluronan.

  • 36. Tirkkonen, J.
    et al.
    Nurmi, J.
    Olkkola, K. T.
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hoppu, S.
    Cardiac arrest teams and medical emergency teams in Finland: a nationwide cross- sectional postal survey2014Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 58, nr 4, s. 420-427Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BackgroundThe implementation, characteristics and utilisation of cardiac arrest teams (CATs) and medical emergency teams (METs) in Finland are unknown. We aimed to evaluate how guidelines on advanced in-hospital resuscitation have been translated to practice. MethodsA cross-sectional postal survey including all public hospitals providing anaesthetic services. ResultsOf the 55 hospitals, 51 (93%) participated in the study. All hospitals with intensive care units (university and central hospitals, n=24) took part. In total, 88% of these hospitals (21/24) and 30% (8/27) of the small hospitals had CATs. Most hospitals with CATs (24/29) recorded team activations. A structured debriefing after a resuscitation attempt was organised in only one hospital. The median incidence of in-hospital cardiac arrest in Finland was 1.48 (Q(1)=0.93, Q(3)=1.93) per 1000 hospital admissions. METs had been implemented in 31% (16/51) of the hospitals. A physician participated in MET activation automatically in half (8/16) of the teams. Operating theatres (13/16), emergency departments (10/16) and paediatric wards (7/16) were the most common sites excluded from the METs' operational areas. The activation thresholds for vital signs varied between hospitals. The lower upper activation threshold for respiratory rate was associated with a higher MET activation rate. The national median MET activation rate was 2.3 (1.5, 4.8) per 1000 hospital admissions and 1.5 (0.96, 4.0) per every cardiac arrest. ConclusionsCurrent guidelines emphasise the preventative actions on in-hospital cardiac arrest. Practices are changing accordingly but are still suboptimal especially in central and district hospitals. Unified guidelines on rapid response systems are required.

  • 37. Tirkkonen, J.
    et al.
    Olkkola, K. T.
    Huhtala, H.
    Tenhunen, J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hoppu, S.
    Vital dysfunctions after intensive care discharge: prevalence and impact on patient outcome2013Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 57, nr 1, s. 56-62Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Patients discharged from the intensive care unit (ICU) are at increased risk for serious adverse events (SAEs). Recording vital functions and comprehending the consequences of altered vitals on general wards may be suboptimal. This potentially endangers recovery after successful intensive care. We aimed to determine the prevalence of vital dysfunctions after ICU discharge and their effect on patient outcome. Methods A prospective observational study. Adult patients discharged from a tertiary referral hospital ICU to general wards without treatment limitations were visited 24?h afterwards; their vitals were measured and reported to ward staff. Attending ward nurse responsible for patient was interviewed. Results The cohort consisted of 184 patients who had survived the first 24?h on the ward without complications (age: 57 +/- 16 years; male: 68%). The prevalence of objectively measured vital dysfunctions was 15%, and the attending nurse had been unusually concerned about the patient in 19% of cases. Of the 184 patients, 9.8% subsequently suffered an SAE. In a multivariate logistic regression model, only vital dysfunctions (odds ratio 3.79; 95% confidence interval 1.18-12.2) and nurse concern (3.63; 1.17-11.3) were independently associated with an increased incidence of SAE. Medical emergency team (MET) assistance was never considered necessary by ward staff. Sensitivity of observed altered vitals on SAEs was 50% and specificity 89%. Sensitivity of nurse concern was 26%, specificity 84%. Conclusions Simple vital function measurement and attending ward nurse's subjective assessment facilitate early detection of post-ICU patients at risk. The threshold in seeking assistance through MET remains high.

  • 38. Tirkkonen, Joonas
    et al.
    Olkkola, Klaus T.
    Huhtala, Heini
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hoppu, Sanna
    Medical emergency team activation: performance of conventional dichotomised criteria versus national early warning score2014Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 58, nr 4, s. 411-419Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BackgroundTo activate the hospital's medical emergency team (MET), either conventional dichotomised activation criteria or an early warning scoring system may be used. The relative performance of these different activation patterns to discriminate high risk patients in a heterogenic general ward population after adjustment for multiple confounding factors has not been evaluated. We aimed to evaluate the dichotomised activation criteria used at our institution and the recently published national early warning score (NEWS, United Kingdom). Materials and MethodsProspective point prevalence study at a university hospital in Finland. On two separate days, the vital signs of all adult patients without treatment limitations were measured. Data on cumulative comorbidity (Charlson comorbidity index), age, gender, admission characteristics and subsequent mortality were collected. Univariate and multivariate logistic regression models were used for unadjusted and adjusted performance testing. ResultsThe cohort consisted of 615 patients. The dichotomised activation criteria were not associated with in-hospital serious adverse events (odds ratio 1.87, 95% confidence interval 0.55-6.30) or 30-day mortality (2.13, 0.79-5.72) after adjustments. For a NEWS of seven or more (the suggested trigger level for immediate MET activation), the adjusted odds ratios for the above mentioned outcomes were 7.45 (2.39-23.3) and 11.4 (4.40-29.6), respectively. Unlike the dichotomised activation criteria, NEWS was also independently associated with a higher 60- and 180-day mortality after adjustments. ConclusionsNEWS discriminates high risk patients in a heterogenic general ward population independently of multiple confounding factors. The conventional dichotomised activation criteria were not able to detect high risk patients.

  • 39.
    Tirkkonen, Joonas
    et al.
    Tampere Univ Hosp, Dept Intens Care Med, POB 2000, FI-33521 Tampere, Finland.;Tampere Univ Hosp, Crit Care Med Res Grp, POB 2000, FI-33521 Tampere, Finland.;Seinajoki Cent Hosp, Dept Anaesthesiol, Seinajoki, Finland..
    Olkkola, Klaus T.
    Univ Helsinki, Cent Hosp, Dept Anaesthesiol Intens Care Emergency Care & Pa, Helsinki, Finland.;Univ Helsinki, Helsinki, Finland..
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Tampere Univ Hosp, Dept Intens Care Med, POB 2000, FI-33521 Tampere, Finland.;Tampere Univ Hosp, Crit Care Med Res Grp, POB 2000, FI-33521 Tampere, Finland..
    Hoppu, Sanna
    Tampere Univ Hosp, Dept Intens Care Med, POB 2000, FI-33521 Tampere, Finland.;Tampere Univ Hosp, Crit Care Med Res Grp, POB 2000, FI-33521 Tampere, Finland..
    Ethically justified treatment limitations in emergency situations2016Ingår i: European journal of emergency medicine, ISSN 0969-9546, E-ISSN 1473-5695, Vol. 23, nr 3, s. 214-218Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective Medical emergency teams (METs) implement do not attempt cardiopulmonary resuscitation (DNACPR) orders and other limitations of medical treatment (LOMTs) in hospitals regularly. However, METs operate in emergency situations with limited or no patient information at the scene. We aimed to study the medical ethics of LOMTs implemented in in-hospital emergency situations.

    Methods: This was a prospective observational study with retrospect case-note analysis conducted in a single Finnish university hospital over 16 months. Data were collected according to the Utstein-style scientific statement.

    Results: There were 774 reviews on 640 patients without preceding LOMT. During the reviews MET assigned LOMTs (including 55 DNACPR orders) for a group of 59 patients who were older (median 77 vs. 68 years; P<0.001) and had higher cumulative comorbidity (median Charlson comorbidity index 2 vs. 1; P=0.001) compared with patients without LOMTs (no-LOMT). Most reviews (71%) leading to new LOMTs occurred during on-call time. In the majority of LOMT cases at least two physicians (86%) and the patient/relatives (76%) were involved in the decision-making. All but one (98%) of the LOMT reviews were documented in the electronic patient records and included clearly described rationale for the LOMT. The median durations of the MET groups. Age alone was never recorded as a reason for LOMT.

    Conclusion: LOMTs were implemented in a decent and ethically justified manner in emergency situations following the code of conduct recommended by guidelines, even though MET operated under highly suboptimal circumstances for end-of-life care planning.

  • 40. Tirkkonen, Joonas
    et al.
    Ylä-Mattila, Jari
    Olkkola, Klaus T
    Huhtala, Heini
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hoppu, Sanna
    Factors associated with delayed activation of medical emergency team and excess mortality: An Utstein-style analysis2013Ingår i: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 84, nr 2, s. 173-178Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM:

    We used the Utstein template, with special reference to patients having automated patient monitoring, and studied the factors which are associated with delayed medical emergency team (MET) activation and increased hospital mortality.

    DESIGN AND SETTING:

    A prospective observational study in a tertiary hospital with 45 of 769 general ward beds (5.9%) equipped with automated monitoring.

    COHORT:

    569 MET reviews for 458 patients.

    RESULTS:

    Basic MET review characteristics were comparable to literature. We found that 41% of the reviews concerned monitored ward patients. These patients' vitals had been more frequently documented during the 6h period preceding MET activation compared to patients in normal ward areas (96% vs. 74%, p<0.001), but even when adjusted to the documentation frequency of vitals, afferent limb failure (ALF) occurred more often among monitored ward patients (81% vs. 53%, p<0.001). In MET population, factors associated with increased hospital mortality were non-elective hospital admission (OR 6.25, 95% CI 2.77-14.11), not-for-resuscitation order (3.34, 1.78-6.35), ICD XIV genitourinary diseases (2.42, 1.16-5.06), ICD II neoplasms (2.80, 1.59-4.91), age (1.02, 1.00-1.04), preceding length of hospital stay (1.04, 1.01-1.07), ALF (1.67, 1.02-2.72) and transfer to intensive care (1.85, 1.05-3.27).

    CONCLUSIONS:

    Documentation of vital signs before MET activation is suboptimal. Documentation frequency seems to increase if automated monitors are implemented, but our results suggest that benefits of intense monitoring are lost without appropriate and timely interventions, as afferent limb failure, delay to call MET when predefined criteria are fulfilled, was independently associated to increased hospital mortality.

  • 41. Vaahersalo, Jukka
    et al.
    Hiltunen, Pamela
    Tiainen, Marjaana
    Oksanen, Tuomas
    Kaukonen, Kirsi-Maija
    Kurola, Jouni
    Ruokonen, Esko
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Ala-Kokko, Tero
    Lund, Vesa
    Reinikainen, Matti
    Kiviniemi, Outi
    Silfvast, Tom
    Kuisma, Markku
    Varpula, Tero
    Pettila, Ville
    Therapeutic hypothermia after out-of-hospital cardiac arrest in Finnish intensive care units: the FINNRESUSCI study2013Ingår i: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 39, nr 5, s. 826-837Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We aimed to evaluate post-resuscitation care, implementation of therapeutic hypothermia (TH) and outcomes of intensive care unit (ICU)-treated out-of-hospital cardiac arrest (OHCA) patients in Finland. We included all adult OHCA patients admitted to 21 ICUs in Finland from March 1, 2010 to February 28, 2011 in this prospective observational study. Patients were followed (mortality and neurological outcome evaluated by Cerebral Performance Categories, CPC) within 1 year after cardiac arrest. This study included 548 patients treated after OHCA. Of those, 311 patients (56.8 %) had a shockable initial rhythm (incidence of 7.4/100,000/year) and 237 patients (43.2 %) had a non-shockable rhythm (incidence of 5.6/100,000/year). At ICU admission, 504 (92 %) patients were unconscious. TH was given to 241/281 (85.8 %) unconscious patients resuscitated from shockable rhythms, with unfavourable 1-year neurological outcome (CPC 3-4-5) in 42.0 % with TH versus 77.5 % without TH (p < 0.001). TH was given to 70/223 (31.4 %) unconscious patients resuscitated from non-shockable rhythms, with 1-year CPC of 3-4-5 in 80.6 % (54/70) with TH versus 84.0 % (126/153) without TH (p = 0.56). This lack of difference remained after adjustment for propensity to receive TH in patients with non-shockable rhythms. One-year unfavourable neurological outcome of patients with shockable rhythms after TH was lower than in previous randomized controlled trials. However, our results do not support use of TH in patients with non-shockable rhythms.

  • 42. Wang, Zanxin
    et al.
    Li, Hongyan
    Vuohelainen, Vilma
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hämäläinen, Mari
    Rinne, Timo
    Moilanen, Eeva
    Paavonen, Timo
    Tarkka, Matti
    Mennander, Ari
    Confined ischemia may improve remote myocardial outcome after rat cardiac arrest2014Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 74, nr 1, s. 27-36Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Confined ongoing ischemia after ischemia-reperfusion injury (IRI) may alter myocardial recovery. We evaluated in a rat cardiac transplantation model whether distal persistent myocardial ischemia (dMI) and remote preconditioning (RPreC) have a remote myocardial impact after IRI.

    Material and methods

    Syngeneic heterotopic cardiac transplantation was performed on 29 Fischer344 rats to induce IRI, including nine rats which underwent distal ligation of the left anterior coronary artery (LAD) to yield distal MI (IRI+ dMI). RPreC was applied by occluding the left renal artery 5 min prior to reperfusion in six rats with IRI (IRI+ RPreC) as well as in seven with distal MI (IRI+ dMI+ RPreC). Microdialysis, histology and qRT-PCR for inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) were performed after graft harvesting.

    Results

    In contrast to IRI + dMI + RPreC (39 ± 7 μmol), glutamate decreased in IRI + RPreC and IRI + dMI as compared with IRI (26 ± 3 and 31 ± 8 vs 91 ± 20, μmol respectively, p < 0.007). The relative number of vacuolated intramyocardial artery nuclei decreased in IRI + dMI as compared with IRI (0.02 ± 0.01, range 0-12 vs. 0.42 ± 0.31, range 0-3.25 PSU respectively, p < 0.04). iNOS expression decreased in IRI + RPreC as compared with IRI (p < 0.04), and eNOS expression decreased in IRI + dMI + RPreC as compared with IRI + dMI (p < 0.006) along with increased glycerol release.

    Conclusions

    dMI after IRI has a potentially beneficial myocardial impact after cardiac arrest, which is hampered by RPreC.

  • 43.
    Yang, Runkuan
    et al.
    Univ Tampere, Tampere Univ Hosp, Dept Intens Care Med, 10 Biokatu, Tampere 33014, Finland.;Univ Pittsburgh, Sch Med, Dept Crit Care Med, 3550 Terrace St, Pittsburgh, PA 15261 USA.;Oslo Univ Hosp, Dept Emergencies & Crit Care, 4950 Nydalen, N-0424 Oslo, Norway..
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Univ Tampere, Tampere Univ Hosp, Dept Intens Care Med, 10 Biokatu, Tampere 33014, Finland..
    Tonnessen, Tor Inge
    Oslo Univ Hosp, Dept Emergencies & Crit Care, 4950 Nydalen, N-0424 Oslo, Norway.;Univ Oslo, Inst Clin Med, N-0316 Oslo, Norway..
    HMGB1 and Histones Play a Significant Role in Inducing Systemic Inflammation and Multiple Organ Dysfunctions in Severe Acute Pancreatitis2017Ingår i: INTERNATIONAL JOURNAL OF INFLAMMATION, ISSN 2090-8040, artikel-id UNSP 1817564Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Severe acute pancreatitis (SAP) starts as a local inflammation of pancreatic tissue that induces the development of multiple extrapancreatic organs dysfunction; however, the underlying mechanisms are still not clear. Ischemia-reperfusion, circulating inflammatory cytokines, and possible bile cytokines significantly contribute to gut mucosal injury and intestinal bacterial translocation (BT) during SAP. Circulating HMGB1 level is significantly increased in SAP patients and HMGB1 is an important factor that mediates (at least partly) gut BT during SAP. Gut BT plays a critical role in triggering/inducing systemic inflammation/sepsis in critical illness, and profound systemic inflammatory response syndrome (SIRS) can lead to multiple organ dysfunction syndrome (MODS) during SAP, and systemic inflammation with multiorgan dysfunction is the cause of death in experimental SAP. Therefore, HMGB1 is an important factor that links gut BT and systemic inflammation. Furthermore, HMGB1 significantly contributes to multiple organ injuries. The SAP patients also have significantly increased circulating histones and cell-free DNAs levels, which can reflect the disease severity and contribute to multiple organ injuries in SAP. Hepatic Kupffer cells (KCs) are the predominant source of circulating inflammatory cytokines in SAP, and new evidence indicates that hepatocyte is another important source of circulating HMGB1 in SAP; therefore, treating the liver injury is important in SAP.

  • 44. Yang, Runkuan
    et al.
    Zhang, Shutian
    Cotoia, Antonella
    Oksala, Niku
    Zhu, Shengtao
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    High mobility group B1 impairs hepatocyte regeneration in acetaminophen hepatotoxicity2012Ingår i: BMC Gastroenterology, ISSN 1471-230X, E-ISSN 1471-230X, Vol. 12, artikel-id 45Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    Acetaminophen (APAP) overdose induces massive hepatocyte necrosis. Necrotic tissue releases high mobility group B1 (HMGB1), and HMGB1 contributes to liver injury. Even though blockade of HMGB1 does not protect against APAP-induced acute liver injury (ALI) at 9 h time point, the later time points are not studied and the role of HMGB1 in APAP overdose is unknown, it is possible that neutralization of HMGB1 might improve hepatocyte regeneration. This study aims to test whether blockade of HMGB1 improves hepatocyte regeneration after APAP overdose.

    METHODS:

    Male C57BL/6 mice were treated with a single dose of APAP (350 mg/kg). 2 hrs after APAP administration, the APAP challenged mice were randomized to receive treatment with either anti-HMGB1 antibody (400 μg per dose) or non-immune (sham) IgG every 24 hours for a total of 2 doses.

    RESULTS:

    24 hrs after APAP injection, anti-HMGB1 therapy instead of sham IgG therapy significantly improved hepatocyte regeneration microscopically; 48 hrs after APAP challenge, the sham IgG treated mice showed 14.6% hepatic necrosis; in contrast, blockade of HMGB1 significantly decreased serum transaminases (ALT and AST), markedly reduced the number of hepatic inflammatory cells infiltration and restored liver structure to nearly normal; this beneficial effect was associated with enhanced hepatic NF-κB DNA binding and increased the expression of cyclin D1, two important factors related to hepatocyte regeneration.

    CONCLUSION:

    HMGB1 impairs hepatocyte regeneration after APAP overdose; Blockade of HMGB1 enhances liver recovery and may present a novel therapy to treat APAP overdose.

  • 45. Yang, Runkuan
    et al.
    Zhang, Shutian
    Kajander, Henri
    Zhu, Shengtao
    Koskinen, Marja-Leena
    Tenhunen, Jyrki
    Department of Intensive Care Medicine, University of Tampere Medical School, Finland.
    Ringer's lactate improves liver recovery in a murine model of acetaminophen toxicity2011Ingår i: BMC Gastroenterology, ISSN 1471-230X, E-ISSN 1471-230X, Vol. 11, s. 125-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    Acetaminophen (APAP) overdose induces massive hepatocyte necrosis. Liver regeneration is a vital process for survival after a toxic insult. Since hepatocytes are mostly in a quiescent state (G0), the regeneration process requires the priming of hepatocytes by cytokines such as TNF-α and IL-6. Ringer's lactate solution (RLS) has been shown to increase serum TNF-α and IL-6 in patients and experimental animals; in addition, RLS also provides lactate, which can be used as an alternative metabolic fuel to meet the higher energy demand by liver regeneration. Therefore, we tested whether RLS therapy improves liver recovery after APAP overdose.

    METHODS:

    C57BL/6 male mice were intraperitoneally injected with a single dose of APAP (300 mg/kg dissolved in 1 mL sterile saline). Following 2 hrs of APAP challenge, the mice were given 1 mL RLS or Saline treatment every 12 hours for a total of 72 hours.

    RESULTS:

    72 hrs after APAP challenge, compared to saline-treated group, RLS treatment significantly lowered serum transaminases (ALT/AST) and improved liver recovery seen in histopathology. This beneficial effect was associated with increased hepatic tissue TNF-α concentration, enhanced hepatic NF-κB DNA binding and increased expression of cell cycle protein cyclin D1, three important factors in liver regeneration.

    CONCLUSION:

    RLS improves liver recovery from APAP hepatotoxicity.

  • 46. Yang, Runkuan
    et al.
    Zou, Xiaoping
    Koskinen, Marja-Leena
    Tenhunen, Jyrki
    Department of Intensive Care Medicine, University of Tampere Medical School, Tampere, Finland .
    Ethyl pyruvate reduces liver injury at early phase but impairs regeneration at late phase in acetaminophen overdose2012Ingår i: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 16, nr 1, s. R9-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION:

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

    METHODS:

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

    RESULTS:

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

    CONCLUSIONS:

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

  • 47.
    Yang, Runkuan
    et al.
    University of Tampere; University of Pittsburgh; Oslo University Hospital.
    Zou, Xiaoping
    Nanjing University.
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. University of Tampere.
    Tonnessen, Tor Inge
    Oslo Univ Hosp; University of Oslo.
    HMGB1 and Extracellular Histones Significantly Contribute to Systemic Inflammation and Multiple Organ Failure in Acute Liver Failure2017Ingår i: Mediators of Inflammation, ISSN 0962-9351, artikel-id 5928078Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Acute liver failure (ALF) is the culmination of severe liver cell injury from a variety of causes. ALF occurs when the extent of hepatocyte death exceeds the hepatic regenerative capacity. ALF has a high mortality that is associated with multiple organ failure (MOF) and sepsis; however, the underlying mechanisms are still not clear. Emerging evidence shows that ALF patients/animals have high concentrations of circulating HMGB1, which can contribute to multiple organ injuries and mediate gut bacterial translocation (BT). BT triggers/induces systemic inflammatory responses syndrome (SIRS), which can lead to MOF in ALF. Blockade of HMGB1 significantly decreases BT and improves hepatocyte regeneration in experimental acute fatal liver injury. Therefore, HMGB1 seems to be an important factor that links BT and systemic inflammation in ALF. ALF patients/animals also have high levels of circulating histones, which might be the major mediators of systemic inflammation in patients with ALF. Extracellular histones kill endothelial cells and elicit immunostimulatory effect to induce multiple organ injuries. Neutralization of histones can attenuate acute liver, lung, and brain injuries. In conclusion, HMGB1 and histones play a significant role in inducing systemic inflammation and MOF in ALF.

  • 48. Yang, Runkuan
    et al.
    Zou, Xiaoping
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Zhu, Shengtao
    Kajander, Henri
    Koskinen, Marja-Leena
    Tonnessen, Tor Inge
    HMGB1 neutralization is associated with bacterial translocation during acetaminophen hepatotoxicity2014Ingår i: BMC Gastroenterology, ISSN 1471-230X, E-ISSN 1471-230X, Vol. 14, s. 66-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Acetaminophen (APAP) hepatotoxicity is associated with a high rate of gram- negative enteric bacterial infection; however, the underlying mechanism is still unknown. APAP overdose induces massive hepatocyte necrosis, necrotic tissue releases high mobility group B1 (HMGB1) and exogenous HMGB1 is able to induce gut bacterial translocation (BT) in normal mice; therefore, it is possible that HMGB1 mediates gut BT in APAP hepatotoxicity. This study aims to test this hypothesis by using anti-HMGB1 neutralizing antibody to treat APAP overdose for 24-48 hours. Methods: Male C57BL/6 mice were intraperitoneally (i.p.) injected with a single dose of APAP (350 mg/ kg dissolved in 1 mL sterile saline). 2 hrs after APAP injection, the APAP challenged mice were randomized to receive treatment with either anti-HMGB1 antibody (400 mu g per dose) or non-immune (sham) IgG every 24 h for a total of 2 doses. Results: 24 and 48 hrs after APAP challenge, anti-HMGB1 treatment instead of sham IgG therapy significantly decreased serum HMGB1 concentrations and reduced BT by 85%; serum HMGB1 levels were positively correlated with the amount of BT; anti-HMGB1 therapy decreased hepatic BT at 48 h, which was associated with better recovered liver structure and better restored hepatic immune system that was shown by enhanced hepatic mRNA expression of TNF-alpha, IL-6 and extensive proliferation of inflammatory and reticuloendothelial cells; however, anti- HMGB1 treatment did not decrease gut mucosal permeability as compared to the sham IgG therapy at either 24 or 48 hrs. Conclusion: HMGB1 neutralization is associated with bacterial translocation during APAP hepatotoxicity.

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