Browsing by Subject "SEPSIS"

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  • Turunen, A.; Kuuliala, K.; Kuuliala, A.; Tervahartiala, T.; Mustonen, H.; Puolakkainen, P.; Kylänpää, A. L.; Sorsa, T. (2021)
    Objectives: Severe acute pancreatitis (SAP) has high morbidity and mortality but there are no widely accepted predictive biomarkers in clinical use. Matrix metalloproteinases (MMPs) are active in tissue destruction and inflammatory responses. We studied whether serum levels of activated MMP-8 (aMMP8), MMP-9 and their regulators tissue inhibitor of matrix metalloproteinases (TIMP)-1, myeloperoxidase (MPO) and human neutrophil elastase (HNE) could predict the development of SAP. Methods: The study comprised 214 AP patients (revised Atlanta classification: 142 mild, MAP; 54 moderately severe, MSAP; 18 SAP) referred to Helsinki University Hospital. A venous blood sample was taken within 72 h from the onset of symptoms. Serum levels of aMMP-8 were determined using immunofluorometric assay, and those of MMP-9, TIMP-1, MPO and HNE using enzyme-linked immunosorbent assay. AP groups were compared using Jonckheere-Terpstra test and predictive value for SAP was analyzed using receiver operating characteristics (ROC) analysis. Results: Serum aMMP-8 levels were higher in SAP (median 657 ng/ml, interquartile range 542-738 ng/ ml) compared to MSAP (358 ng/ml, 175-564 ng/ml; p < 0.001) and MAP (231 ng/ml, 128-507 ng/ml; p < 0.001). Similar trend was seen with TIMP-1 and MPO. In ROC analysis aMMP-8, MPO and TIMP-1 emerged as potential markers for the development of SAP (areas under ROC curves 0.83, 0.71 and 0.69, respectively). Conclusions: Serum aMMP-8 measured early in the course of AP (within 72 h of symptom onset) predicted the development of SAP. (c) 2021 The Authors. Published by Elsevier B.V. on behalf of IAP and EPC. This is an open access article under the CC BY-NC-ND license (
  • Möller, Vidar; Östholm-Balkhed, Åse; Berild, Dag; Fredriksson, Mats; Gottfredsson, Magnus; Holmbom, Martin; Järvinen, Asko; Kristjansson, Mar; Rydell, Ulf; Sonksen, Ute Wolff; Kolmos, Hans Joern; Hanberger, Håkan (2021)
    Background The Nordic countries have comparable nationwide antibiotic resistance surveillance systems and individual antibiotic stewardship programmes. The aim of this study was to assess antibiotic resistance among major pathogens in relation to practice guidelines for hospital antibiotic treatment and antibiotic use in Nordic countries 2010-2018. Methods Antibiotic resistance among invasive isolates from 2010-2018 and aggregated antibiotic use were obtained from the European Centre for Disease Prevention and Control. Hospital practice guidelines were obtained from national or regional guidelines. Results Antibiotic resistance levels among Escherichia coli and Klebsiella pneumoniae were similar in all Nordic countries in 2018 and low compared to the European mean. Guidelines for acute pyelonephritis varied; 2nd generation cephalosporin (Finland), 3rd generation cephalosporins (Sweden, Norway), ampicillin with an aminoglycoside or aminoglycoside monotherapy (Denmark, Iceland and Norway). Corresponding guidelines for sepsis of unknown origin were 2nd (Finland) or 3rd (Sweden, Norway, Iceland) generation cephalosporins, carbapenems, (Sweden) combinations of penicillin with an aminoglycoside (Norway, Denmark), or piperacillin-tazobactam (all Nordic countries). Methicillin-resistant Staphylococcus aureus rates were 0-2% and empirical treatment with anti-MRSA antibiotics was not recommended in any country. Rates of penicillin non-susceptibility among Streptococcus pneumoniae were low (
  • Lankelma, Jacqueline M.; Belzer, Clara; Hoogendijk, Arie J.; de Vos, Alex F.; de Vos, Willem M.; van der Poll, Tom; Wiersinga, W. Joost (2016)
    OBJECTIVES: Broad-spectrum antibiotics disrupt the intestinal microbiota. The microbiota is essential for physiological processes, such as the development of the gut immune system. Recent murine data suggest that the intestinal microbiota also modulates systemic innate immune responses; however, evidence in humans is lacking. METHODS: Twelve healthy young men were given oral broad-spectrum antibiotics (ciprofloxacin 500 mg bid, vancomycin 500 mg tid and metronidazole 500 mg tid) for 7 days. At baseline, 1 day, and 6 weeks after antibiotics, blood and feces were sampled. Whole blood and isolated mononuclear cells were stimulated with selected Toll-like receptor agonists and heat-killed bacteria. Microbiota diversity and composition was determined using bacterial 16S rDNA sequencing. RESULTS: One day after the antibiotic course, microbial diversity was significantly lower compared with baseline. After antibiotic therapy, systemic mononuclear cells produced lower levels of tumor necrosis factor (TNF)-alpha after ex vivo stimulation with lipopolysaccharide (LPS). This diminished capacity to produce TNF-alpha was restored 6 weeks after cessation of antibiotic therapy. In whole blood, a reduced capacity to release interleukin (IL)-1 beta and IL-6 was observed after LPS stimulation. Antibiotic treatment did not impact on differential leukocyte counts, phagocytosis, and cell surface markers of neutrophils and monocytes. CONCLUSIONS: In this proof-of-principle study of healthy subjects, microbiota disruption by broad-spectrum antibiotics is reversibly associated with decreased systemic cellular responsiveness towards LPS. The implications of these findings in a clinical setting remain to be determined.
  • Turunen, Antti; Kuuliala, Antti; Mustonen, Harri; Puolakkainen, Pauli; Kylänpää, Leena; Kuuliala, Krista (2021)
    Objectives Clinical practice lacks biomarkers to predict the severity of acute pancreatitis (AP). We studied if intracellular signaling of circulating leukocytes could predict persistent organ dysfunction (OD) and secondary infections in AP. Methods A venous blood sample was taken from 174 patients with AP 72 hours or less from onset of symptoms and 31 healthy controls. Phosphorylation levels (p) of appropriately stimulated signal transducer and activator of transcription 1 (STAT1), STAT6, nuclear factor-kappa B (NF-kappa B), Akt, and nonstimulated STAT3 in monocytes, neutrophils, and lymphocytes was measured using phosphospecific flow cytometry. Results The patients showed higher pSTAT3 and lower pSTAT1, pSTAT6, pNF-kappa B, and pAkt than healthy controls. pSTAT3 in all leukocyte subtypes studied increased, and pSTAT1 in monocytes and T cells decreased in an AP severity-wise manner. In patients without OD at sampling, high pSTAT3 in monocytes and T lymphocytes were associated with development of persistent OD. In patients with OD, low interleukin-4-stimulated pSTAT6 in monocytes and neutrophils and Escherichia coli-stimulated pNF-kappa B in neutrophils predicted OD persistence. High pSTAT3 in monocytes, CD8(+) T cells, and neutrophils; low pSTAT1 in monocytes and T cells; and low pNF-kappa B in lymphocytes predicted secondary infections. Conclusions Leukocyte STAT3, STAT1, STAT6, and NF-kappa Beta phosphorylations are potential predictors of AP severity.
  • Kuusela, Pentti I; Saraswat, Mayank; Joenväärä, Sakari; Kaartinen, Johanna; Järvinen, Asko; Renkonen, Risto (2017)
    Blood culture is the primary diagnostic test performed in a suspicion of bloodstream infection to detect the presence of microorganisms and direct the treatment. However, blood culture is slow and time consuming method to detect blood stream infections or separate septic and/or bacteremic patients from others with less serious febrile disease. Plasma proteomics, despite its challenges, remains an important source for early biomarkers for systemic diseases and might show changes before direct evidence from bacteria can be obtained. We have performed a plasma proteomic analysis, simultaneously at the time of blood culture sampling from ten blood culture positive and ten blood culture negative patients, and quantified 172 proteins with two or more unique peptides. Principal components analysis, Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) and ROC curve analysis were performed to select protein(s) features which can classify the two groups of samples. We propose a number of candidates which qualify as potential biomarkers to select the blood culture positive cases from negative ones. Pathway analysis by two methods revealed complement activation, phagocytosis pathway and alterations in lipid metabolism as enriched pathways which are relevant for the condition. Data are available via ProteomeXchange with identifier PXD005022.
  • Nieminen, Anne; Maksimow, Mikael; Mentula, Panu; Kyhala, Lea; Kylänpää, Leena; Puolakkainen, Pauli; Kemppainen, Esko; Repo, Heikki; Salmi, Marko (2014)
  • SICS Study Grp; Hiemstra, Bart; Eck, Ruben J.; Wiersema, Renske; Pettilä, Ville; van der Horst, Iwan C. C. (2019)
    Objectives: Caregivers use clinical examination to timely recognize deterioration of a patient, yet data on the prognostic value of clinical examination are inconsistent. In the Simple Intensive Care Studies-I, we evaluated the association of clinical examination findings with 90-day mortality in critically ill patients. Design: Prospective single-center cohort study. Setting: ICU of a single tertiary care level hospital between March 27, 2015, and July 22, 2017. Patients: All consecutive adults acutely admitted to the ICU and expected to stay for at least 24 hours. Interventions: A protocolized clinical examination of 19 clinical signs conducted within 24 hours of admission. Measurements Main Results: Independent predictors of 90-day mortality were identified using multivariable logistic regression analyses. Model performance was compared with established prognostic risk scores using area under the receiver operating characteristic curves. Robustness of our findings was tested by internal bootstrap validation and adjustment of the threshold for statistical significance. A total of 1,075 patients were included, of whom 298 patients (28%) had died at 90-day follow-up. Multivariable analyses adjusted for age and norepinephrine infusion rate demonstrated that the combination of higher respiratory rate, higher systolic blood pressure, lower central temperature, altered consciousness, and decreased urine output was independently associated with 90-day mortality (area under the receiver operating characteristic curves = 0.74; 95% CI, 0.71-0.78). Clinical examination had a similar discriminative value as compared with the Simplified Acute Physiology Score-II (area under the receiver operating characteristic curves = 0.76; 95% CI, 0.73-0.79; p = 0.29) and Acute Physiology and Chronic Health Evaluation-IV (using area under the receiver operating characteristic curves = 0.77; 95% CI, 0.74-0.80; p = 0.16) and was significantly better than the Sequential Organ Failure Assessment (using area under the receiver operating characteristic curves = 0.67; 95% CI, 0.64-0.71; p <0.001). Conclusions: Clinical examination has reasonable discriminative value for assessing 90-day mortality in acutely admitted ICU patients. In our study population, a single, protocolized clinical examination had similar prognostic abilities compared with the Simplified Acute Physiology Score-II and Acute Physiology and Chronic Health Evaluation-IV and outperformed the Sequential Organ Failure Assessment score.
  • Vilander, Laura M.; Vaara, Suvi T.; Kaunisto, Mari A.; Pettilä, Ville; FINNAKI Study Grp; Laru-Sompa, Raili; Pulkkinen, Anni; Saarelainen, Minna; Reilama, Mikko; Tolmunen, Sinikka; Rantalainen, Ulla; Miettinen, Marja; Suvela, Markku; Pesola, Katrine; Saastamoinen, Pekka; Kauppinen, Sirpa; Kaukonen, Kirsi-Maija; Korhonen, Anna-Maija; Nisula, Sara; Vaara, Suvi; Suojaranta-Ylinen, Raili; Mildh, Leena; Haapio, Mikko; Nurminen, Laura; Sutinen, Sari; Pettilä, Leena; Laitinen, Helinä; Syrja, Heidi; Henttonen, Kirsi; Lappi, Elina; Boman, Hillevi; Varpula, Tero; Porkka, Päivi; Sivula, Mirka; Rahkonen, Mira; Tsurkka, Anne; Prittinen, Niina; Alaspaa, Ari; Salanto, Ville; Juntunen, Hanna; Sanisalo, Teija; Parviainen, Ilkka; Uusaro, Ari; Ruokonen, Esko; Bendel, Stepani; Rissanen, Niina; Lång, Maarit; Rahikainen, Sari; Rissanen, Saija; Ahonen, Merja; Halonen, Elina; Vaskelainen, Eija; Poukkanen, Meri; Lintula, Esa; Suominen, Sirpa; Heikkinen, Jorma; Lavander, Timo; Heinonen, Kirsi; Juopperi, Anne-Mari; Kaminski, Tadeusz; Gäddnäs, Fiia; Kuusela, Tuija; Roiko, Jane; Karlsson, Sari; Reinikainen, Matti; Surakka, Tero; Jyrkönen, Helena; Eiserbeck, Tanja; Kallinen, Jaana; Lund, Vesa; Tuominen, Päivi; Perkola, Pauliina; Tuominen, Riikka; Hietaranta, Marika; Johansson, Satu; Hovilehto, Seppo; Kirsi, Anne; Tiainen, Pekka; Myllärinen, Tuija; Leino, Pirjo; Toropainen, Anne; Kuitunen, Anne; Leppänen, Ilona; Levoranta, Markus; Hoppu, Sanna; Sauranen, Jukka; Tenhunen, Jyrki; Kukkurainen, Atte; Kortelainen, Samuli; Varila, Simo; Inkinen, Outi; Koivuviita, Niina; Kotamäki, Jutta; Laine, Anu; Ala-Kokko, Tero; Laurila, Jouko J.; Sälkiö, Sinikka; Koivisto, Simo-Pekka; Hautamäki, Raku; Skinnar, Maria (2019)
    Acute kidney injury (AKI) is a syndrome with high incidence among the critically ill. Because the clinical variables and currently used biomarkers have failed to predict the individual susceptibility to AKI, candidate gene variants for the trait have been studied. Studies about genetic predisposition to AKI have been mainly underpowered and of moderate quality. We report the association study of 27 genetic variants in a cohort of Finnish critically ill patients, focusing on the replication of associations detected with variants in genes related to inflammation, cell survival, or circulation. In this prospective, observational Finnish Acute Kidney Injury (FINNAKI) study, 2647 patients without chronic kidney disease were genotyped. We defined AKI according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We compared severe AKI (Stages 2 and 3, n = 625) to controls (Stage 0, n = 1582). For genotyping we used iPLEX(TM) Assay (Agena Bioscience). We performed the association analyses with PLINK software, using an additive genetic model in logistic regression. Despite the numerous, although contradictory, studies about association between polymorphisms rs1800629 in TNFA and rs1800896 in IL10 and AKI, we found no association (odds ratios 1.06 (95% CI 0.89-1.28, p = 0.51) and 0.92 (95% CI 0.80-1.05, p = 0.20), respectively). Adjusting for confounders did not change the results. To conclude, we could not confirm the associations reported in previous studies in a cohort of critically ill patients.
  • Sartelli, Massimo; Catena, Fausto; Ansaloni, Luca; Coccolini, Federico; Corbella, Davide; Moore, Ernest E.; Malangoni, Mark; Velmahos, George; Coimbra, Raul; Koike, Kaoru; Leppaniemi, Ari; Biffl, Walter; Balogh, Zsolt; Bendinelli, Cino; Gupta, Sanjay; Kluger, Yoram; Agresta, Ferdinando; Di Saverio, Salomone; Tugnoli, Gregorio; Jovine, Elio; Ordonez, Carlos A.; Whelan, James F.; Fraga, Gustavo P.; Gomes, Carlos Augusto; Pereira Junior, Gerson Alves; Yuan, Kuo-Ching; Bala, Miklosh; Peev, Miroslav P.; Ben-Ishay, Offir; Cui, Yunfeng; Marwah, Sanjay; Zachariah, Sanoop; Wani, Imtiaz; Rangarajan, Muthukumaran; Sakakushev, Boris; Kong, Victor; Ahmed, Adamu; Abbas, Ashraf; Teixeira Gonsaga, Ricardo Alessandro; Guercioni, Gianluca; Vettoretto, Nereo; Poiasina, Elia; Diaz-Nieto, Rafael; Massalou, Damien; Skrovina, Matej; Gerych, Ihor; Augustin, Goran; Kenig, Jakub; Khokha, Vladimir; Trana, Cristian; Kok, Kenneth Yuh Yen; Mefire, Alain Chichom; Lee, Jae Gil; Hong, Suk-Kyung; Lohse, Helmut Alfredo Segovia; Ghnnam, Wagih; Verni, Alfredo; Lohsiriwat, Varut; Siribumrungwong, Boonying; El Zalabany, Tamer; Tavares, Alberto; Baiocchi, Gianluca; Das, Koray; Jarry, Julien; Zida, Maurice; Sato, Norio; Murata, Kiyoshi; Shoko, Tomohisa; Irahara, Takayuki; Hamedelneel, Ahmed O.; Naidoo, Noel; Adesunkanmi, Abdul Rashid Kayode; Kobe, Yoshiro; Ishii, Wataru; Oka, Kazuyuki; Izawa, Yoshimitsu; Hamid, Hytham; Khan, Iqbal; Attri, A. K.; Sharma, Rajeev; Sanjuan, Juan; Badiel, Marisol; Barnabe, Rita (2014)
  • Ristagno, Giuseppe; Masson, Serge; Tiainen, Marjaana; Bendel, Stepani; Bernasconi, Roberto; Varpula, Tero M; Milani, Valentina; Vaahersalo, Jukka; Magnoli, Michela; Spanuth, Eberhard; Barlera, Simona; Latini, Roberto; Hoppu, Sanna; Pettila, Ville; Skrifvars, Markus; FINNRESUSCI Study Grp (2016)
    Background: An intense systemic inflammatory response is observed following reperfusion after cardiac arrest. Heparin-binding protein (HBP) is a granule protein released by neutrophils that intervenes in endothelial permeability regulation. In the present study, we investigated plasma levels of HBP in a large population of patients resuscitated from out-of-hospital cardiac arrest. We hypothesized that high circulating levels of HBP are associated with severity of post-cardiac arrest syndrome and poor outcome. Methods: Plasma was obtained from 278 patients enrolled in a prospective multicenter observational study in 21 intensive care units (ICU) in Finland. HBP was assayed at ICU admission and 48 h later. Multiple organ dysfunction syndrome (MODS) was defined as the 24 h Sequential Organ Failure Assessment (SOFA) score >= 12. ICU death and 12-month Cerebral Performance Category (CPC) were evaluated. Multiple linear and logistic regression tests and receiver operating characteristic curves with area under the curve (AUC) were performed. Results: Eighty-two percent of patients (229 of 278) survived to ICU discharge and 48 % (133 of 276) to 1 year with a favorable neurological outcome (CPC 1 or 2). At ICU admission, median plasma levels of HBP were markedly elevated, 15.4 [9.6-31.3] ng/mL, and persisted high 48 h later, 14.8 [9.8-31.1] ng/mL. Admission levels of HBP were higher in patients who had higher 24 h SOFA and cardiovascular SOFA score (p <0.0001) and in those who developed MODS compared to those who did not (29.3 [13.7-60.1] ng/mL vs. 13.6 [9.1-26.2] ng/mL, p <0.0001; AUC = 0.70 +/- 0.04, p = 0.0001). Admission levels of HBP were also higher in patients who died in ICU (31.0 [17.7-78.2] ng/mL) compared to those who survived (13.5 [9.1-25.5] ng/mL, p <0.0001) and in those with an unfavorable 12-month neurological outcome compared to those with a favorable one (18.9 [11.3-44.3] ng/mL vs. 12.8 [8.6-30.4] ng/mL, p <0.0001). Admission levels of HBP predicted early ICU death with an AUC of 0.74 +/- 0. 04 (p <0.0001) and were independently associated with ICU death (OR [95 %CI] 1.607 [1.076-2.399], p = 0.020), but not with unfavorable 12-month neurological outcome (OR [95 %CI] 1.154 [0.834-1.596], p = 0.387). Conclusions: Elevated plasma levels of HBP at ICU admission were independently associated with early death in ICU.
  • Perner, Anders; Hjortrup, Peter B.; Pettila, Ville (2017)
  • Perner, Anders; Hjortrup, Peter B.; Pettilä, Ville (2018)
  • Forsblom, Erik; Frilander, Hanna; Ruotsalainen, Eeva; Järvinen, Asko (2019)
    Background. Formal infectious diseases specialist (IDS) consultation has been shown to improve short-term outcomes in Staphylococcus aureus bacteremia (SAB), but its effect on long-term outcomes lacks evaluation. Methods. This retrospective study followed 367 methicillin-sensitive (MS) SAB patients for 10 years. The impact of formal IDS consultation on risk for new bacteremia and outcome during long-term follow-up was evaluated. Patients who died within 90 days were excluded to avoid interference from early deceased patients. Results. Three hundred four (83%) patients had formal IDS consultation, whereas 63 (17%) received informal or no IDS consultation. Formal consultation, compared with informal or lack of consultation, was associated with a reduced risk of new bacteremia caused by any pathogen within 1 year (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.18-0.84; P = .014; 8% vs 17%) and within 3 years (OR, 0.39; 95% CI, 0.19-0.80; P = .010; 9% vs 21%), whereas a trend toward lower risk was observed within 10 years (OR, 0.56; 95% CI, 0.29-1.08; P = .079; 16% vs 25%). Formal consultation, compared with informal or lack of consultation, improved outcomes at 1 year (OR, 0.16; 95% CI, 0.06-0.44; P <.001; 3% vs 14%), at 3 years (OR, 0.19; 95% CI, 0.09-0.42; P <.001; 5% vs 22%), and at 10 years (OR, 0.43; 95% CI, 0.24-0.74; P = .002; 27% vs 46%). Considering all prognostic parameters, formal consultation improved outcomes (HR, 0.42; 95% CI, 0.27-0.65; P <.001) and lowered risk for any new bacteremia (OR, 0.45; 95% CI, 0.23-0.88; P = .02) during 10 years of follow-up. Conclusions. MS-SAB management by formal IDS consultation, compared with informal or lack of IDS consultation, reduces risk for new bacteremia episodes and improves long-term prognosis up to 10 years.
  • Vilander, Laura; Kaunisto, Mari A.; Vaara, Suvi; Pettila, Ville; FINNAKI Study Grp (2017)
    Background: Acute kidney injury (AKI) is a multifactorial syndrome, but knowledge about its pathophysiology and possible genetic background is limited. Recently the first hypothesis-free genetic association studies have been published to explore individual susceptibility to AKI. We aimed to replicate the previously identified associations between five candidate single nucleotide polymorphisms (SNP) in apoptosis-related genes BCL2, SERPINA4, SERPINA5, and SIK3 and the development of AKI, using a prospective cohort of critically ill patients with sepsis/ septic shock, in Finland. Methods: This is a prospective, observational multicenter study. Of 2567 patients without chronic kidney disease and with genetic samples included in the Finnish Acute Kidney Injury (FINNAKI) study, 837 patients had sepsis and 627 patients had septic shock. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, considering stages 2 and 3 affected (severe AKI), stage 0 unaffected, and stage 1 indecisive. Genotyping was done using iPLEX (TM) Assay (Agena Bioscience). The genotyped SNPs were rs8094315 and rs12457893 in the intron of the BCL2 gene, rs2093266 in the SERPINA4 gene, rs1955656 in the SERPINA5 gene and rs625145 in the SIK3 gene. Association analyses were performed using logistic regression with PLINK software. Results: We found no significant associations between the SNPs and severe AKI in patients with sepsis/ septic shock, even after adjustment for confounders. Among patients with septic shock (252 with severe AKI and 226 without AKI (149 with KDIGO stage 1 excluded)), the SNPs rs2093266 and rs1955656 were significantly (odds ratio 0.63, p = 0.04276) associated with stage 2-3 AKI after adjusting for clinical and demographic variables. Conclusions: The SNPs rs2093266 in the SERPINA4 and rs1955656 in the SERPINA5 were associated with the development of severe AKI (KDIGO stage 2-3) in critically ill patients with septic shock. For the other SNPs, we did not confirm the previously reported associations.
  • HOT-ICU Investigators; Schjorring, Olav L.; Perner, Anders; Wetterslev, Jorn; Lange, Theis; Keus, Frederik; Laake, Jon H.; Okkonen, Marjatta; Siegemund, Martin; Morgan, Matthew; Thormar, Katrin M.; Rasmussen, Bodil S. (2019)
    Background Acutely ill adults with hypoxaemic respiratory failure are at risk of life-threatening hypoxia, and thus oxygen is often administered liberally. Excessive oxygen use may, however, increase the number of serious adverse events, including death. Establishing the optimal oxygenation level is important as existing evidence is of low quality. We hypothesise that targeting an arterial partial pressure of oxygen (PaO2) of 8 kPa is superior to targeting a PaO2 of 12 kPa in adult intensive care unit (ICU) patients with acute hypoxaemic respiratory failure. Methods The Handling Oxygenation Targets in the ICU (HOT-ICU) trial is an outcome assessment blinded, multicentre, randomised, parallel-group trial targeting PaO2 in acutely ill adults with hypoxaemic respiratory failure within 12 hours after ICU admission. Patients are randomised 1:1 to one of the two PaO2 targets throughout ICU stay until a maximum of 90 days. The primary outcome is 90-day mortality. Secondary outcomes are serious adverse events in the ICU, days alive without organ support and days alive out of hospital in the 90-day period; mortality, health-related quality-of-life at 1-year follow-up as well as 1-year cognitive and pulmonary function in a subgroup; and an overall health economic analysis. To detect or reject a 20% relative risk reduction, we aim to include 2928 patients. An interim analysis is planned after 90-day follow-up of 1464 patients. Conclusion The HOT-ICU trial will test the hypothesis that a lower oxygenation target reduces 90-day mortality compared with a higher oxygenation target in adult ICU patients with acute hypoxaemic respiratory failure.
  • Forsblom, Erik; Aittoniemi, Janne; Ruotsalainen, Eeva; Helmijoki, Visa; Huttunen, Reetta; Jylhava, Juulia; Hurme, Mikko; Jarvinen, Asko (2014)
  • Efraim Investigators; Nine-I Study Grp; Martin-Loeches, Ignacio; Valkonen, Miia; Azoulay, Elie (2019)
    BackgroundIt is unclear whether influenza infection and associated co-infection are associated with patient-important outcomes in critically ill immunocompromised patients with acute respiratory failure.MethodsPreplanned secondary analysis of EFRAIM, a prospective cohort study of 68 hospitals in 16 countries. We included 1611 patients aged 18years or older with non-AIDS-related immunocompromise, who were admitted to the ICU with acute hypoxemic respiratory failure. The main exposure of interest was influenza infection status. The primary outcome of interest was all-cause hospital mortality, and secondary outcomes ICU length of stay (LOS) and 90-day mortality.ResultsInfluenza infection status was categorized into four groups: patients with influenza alone (n=95, 5.8%), patients with influenza plus pulmonary co-infection (n=58, 3.6%), patients with non-influenza pulmonary infection (n=820, 50.9%), and patients without pulmonary infection (n=638, 39.6%). Influenza infection status was associated with a requirement for intubation and with LOS in ICU (P
  • Kjaer, Maj-Brit N.; Meyhoff, Tine S.; Madsen, Martin B.; Hjortrup, Peter B.; Moller, Morten Hylander; Egerod, Ingrid; Wetterslev, Jorn; Lange, Theis; Cronhjort, Maria; Laake, Jon H.; Jakob, Stephan M.; Nalos, Marek; Pettilä, Ville; van der Horst, Iwan C. C.; Ostermann, Marlies; Mouncey, Paul; Cecconi, Maurizio; Ferrer, Ricard; Malbrain, Manu L. N. G.; Ahlstedt, Christian; Hoffmann, Soren; Bestle, Morten H.; Gyldensted, Louise; Nebrich, Lars; Russell, Lene; Vang, Marianne; Solling, Christoffer; Brochner, Anne C.; Rasmussen, Bodil S.; Perner, Anders (2020)
    BackgroundIn patients with septic shock, mortality is high, and survivors experience long-term physical, mental and social impairments. The ongoing Conservative vs Liberal Approach to fluid therapy of Septic Shock in Intensive Care (CLASSIC) trial assesses the benefits and harms of a restrictive vs standard-care intravenous (IV) fluid therapy. The hypothesis is that IV fluid restriction improves patient-important long-term outcomes. AimTo assess the predefined patient-important long-term outcomes in patients randomised into the CLASSIC trial. MethodsIn this pre-planned follow-up study of the CLASSIC trial, we will assess all-cause mortality, health-related quality of life (HRQoL) and cognitive function 1 year after randomisation in the two intervention groups. The 1-year mortality will be collected from electronic patient records or central national registries in most participating countries. We will contact survivors and assess EuroQol 5-Dimension, -5-Level (EQ-5D-5L) and EuroQol-Visual Analogue Scale and Montreal Cognitive Assessment 5-minute protocol score. We will analyse mortality by logistic regression and use general linear models to assess HRQoL and cognitive function. DiscussionWith this pre-planned follow-up study of the CLASSIC trial, we will provide patient-important data on long-term survival, HRQoL and cognitive function of restrictive vs standard-care IV fluid therapy in patients with septic shock.
  • Rakkolainen, Ilmari; Elmasry, Moustafa; Steinvall, Ingrid; Vuola, Jyrki (2018)
    B-type natriuretic peptide has shown promising results as a biomarker for acute kidney injury in general intensive care patients. It may also indirectly reflect fluid balance of the circulation. Among burn patients, it has been observed to indicate excessive fluid resuscitation and organ dysfunction, although its clinical use to indicate acute kidney injury or guide fluid resuscitation has not been validated. The aim of this study was to evaluate whether the N-terminal pro-brain natriuretic peptide values are related to the amount of fluids given after severe burn injury and whether it can act as a novel biomarker for acute kidney injury in these patients. Nineteen consecutive burn patients were included. Plasma N-terminal pro-brain natriuretic peptide was measured daily during 1 week from admission. Other variables such as laboratory values and intravenous infusions were also recorded. The association between acute kidney injury and N-terminal pro-brain natriuretic peptide values was analyzed with a multivariable panel regression model, adjusted for burned total body surface area, age, body mass index, and laboratory values. N-terminal pro-brain natriuretic peptide values varied between single patients, and even more between the patients who developed acute kidney injury. Older age, lower body mass index, and cumulative infusions were independently associated with higher N-terminal pro-brain natriuretic peptide values, whereas acute kidney injury was not. N-terminal pro-brain natriuretic peptide values correlated with cumulative infusions given during the first week. The authors could not validate the role of N-terminal probrain natriuretic peptide as a biomarker for acute kidney injury in burns.
  • Törnblom, Sanna; Nisula, Sara; Vaara, Suvi T.; Poukkanen, Meri; Andersson, Sture; Pettilä, Ville; Pesonen, Eero (2019)
    Background Inflammation, reflected by high plasma interleukin-6 concentration, is associated with acute kidney injury (AKI) in septic patients. Neutrophil activation has pathophysiological significance in experimental septic AKI. We hypothesized that neutrophil activation is associated with AKI in critically ill sepsis patients. Methods We measured plasma (n = 182) and urine (n = 118) activin A (a rapidly released cytosolic neutrophil protein), interleukin-8 (a chemotactic factor for neutrophils), myeloperoxidase (a neutrophil biomarker released in tissues), and interleukin-6 on intensive care unit admission (plasma and urine) and 24 hours later (plasma) in sepsis patients manifesting their first organ dysfunction between 24 hours preceding admission and the second calendar day in intensive care unit. AKI was defined by the Kidney Disease: Improving Global Outcomes criteria. Results Plasma admission interleukin-8 (240 [60-971] vs 50 [19-164] pg/mL, P <.001) and activin A (845 [554-1895] vs 469 [285-862] pg/mL, P <.001) were but myeloperoxidase (169 [111-300] vs 144 [88-215] ng/mL, P = .059) was not higher among patients with AKI compared with those without. Urine admission interleukin-8 (50.4 [19.8-145.3] vs 9.5 [2.7-28.7] ng/mL, P <.001) and myeloperoxidase (7.7 [1.5-12.6] vs 1.9 [0.4-6.9] ng/mL, P <.001) were but activin A (9.7 [1.4-42.6] vs 4.0 [0.0-33.0] ng/mL, P = .064) was not higher in AKI than non-AKI patients. Urine myeloperoxidase correlated with urine interleukin-8 (R = .627, P <.001) but not with plasma myeloperoxidase (R = .131, P = .158). Conclusion Interleukin-8 in plasma and urine was associated with septic AKI. Elevated plasma activin A indicates intravascular neutrophil activation in septic AKI. Concomitant plasma and urine myeloperoxidase measurements suggest neutrophil accumulation into injured kidneys.