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  • Cecconi, Maurizio; Hofer, Christoph; Teboul, Jean-Louis; Pettila, Ville; Wilkman, Erika; Molnar, Zsolt; Della Rocca, Giorgio; Aldecoa, Cesar; Artigas, Antonio; Jog, Sameer; Sander, Michael; Spies, Claudia; Lefrant, Jean-Yves; De Backer, Daniel; FENICE Investigators; ESICM Trial Grp (2015)
    Fluid challenges (FCs) are one of the most commonly used therapies in critically ill patients and represent the cornerstone of hemodynamic management in intensive care units. There are clear benefits and harms from fluid therapy. Limited data on the indication, type, amount and rate of an FC in critically ill patients exist in the literature. The primary aim was to evaluate how physicians conduct FCs in terms of type, volume, and rate of given fluid; the secondary aim was to evaluate variables used to trigger an FC and to compare the proportion of patients receiving further fluid administration based on the response to the FC. This was an observational study conducted in ICUs around the world. Each participating unit entered a maximum of 20 patients with one FC. 2213 patients were enrolled and analyzed in the study. The median [interquartile range] amount of fluid given during an FC was 500 ml (500-1000). The median time was 24 min (40-60 min), and the median rate of FC was 1000 [500-1333] ml/h. The main indication for FC was hypotension in 1211 (59 %, CI 57-61 %). In 43 % (CI 41-45 %) of the cases no hemodynamic variable was used. Static markers of preload were used in 785 of 2213 cases (36 %, CI 34-37 %). Dynamic indices of preload responsiveness were used in 483 of 2213 cases (22 %, CI 20-24 %). No safety variable for the FC was used in 72 % (CI 70-74 %) of the cases. There was no statistically significant difference in the proportion of patients who received further fluids after the FC between those with a positive, with an uncertain or with a negatively judged response. The current practice and evaluation of FC in critically ill patients are highly variable. Prediction of fluid responsiveness is not used routinely, safety limits are rarely used, and information from previous failed FCs is not always taken into account.
  • Perner, Anders; Prowle, John; Joannidis, Michael; Young, Paul; Hjortrup, Peter B.; Pettilä, Ville (2017)
    Acute kidney injury (AKI) and fluids are closely linked through oliguria, which is a marker of the former and a trigger for administration of the latter. Recent progress in this field has challenged the physiological and clinical rational of using oliguria as a trigger for the administration of fluid and brought attention to the delicate balance between benefits and harms of different aspects of fluid management in critically ill patients, in particular those with AKI. This narrative review addresses various aspects of fluid management in AKI outlining physiological aspects, the effects of crystalloids and colloids on kidney function and the effect of various resuscitation and de-resuscitation strategies on the course and outcome of AKI.
  • Massy, Ziad A.; Caskey, Fergus J.; Finne, Patrik; Harambat, Jerome; Jager, Kitty J.; Nagler, Evi; Stengel, Benedicte; Sever, Mehmet Sukru; Vanholder, Raymond; Blankestijn, Peter J.; Bruchfeld, Annette; Capasso, Giovambattista; Fliser, Danilo; Fouque, Denis; Goumenos, Dimitrios; Soler, Maria Jose; Rychlik, Ivan; Spasovski, Goce; Stevens, Kathryn; Wanner, Christoph; Zoccali, Carmine (2019)
    The strengths and the limitations of research activities currently present in Europe are explored in order to outline how to proceed in the near future. Epidemiological and clinical research and public policy in Europe are generally considered to be comprehensive and successful, and the European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) is playing a key role in the field of nephrology research. The Nephrology and Public Policy Committee (NPPC) aims to improve the current situation and translation into public policy by planning eight research topics to be supported in the coming 5 years by ERA-EDTA.
  • Kinnunen, Susanna; Karhapää, Pauli; Juutilainen, Auni; Finne, Patrik; Helanterä, Ilkka (2018)
    Background and objectives Infections are the most common noncardiovascular causes of death after kidney transplantation. We analyzed the current infection-related mortality among kidney transplant recipients in a nationwide cohort in Finland. Design, setting, participants, & measurements Altogether, 3249 adult recipients of a first kidney transplant from 1990 to 2012 were included. Infectious causes of death were analyzed, and the mortality rates for infections were compared between two eras (1990-1999 and 2000-2012). Risk factors for infectious deaths were analyzed with Cox regression and competing risk analyses. Results Altogether, 953 patients (29%) died during the follow-up, with 204 infection-related deaths. Mortality rate (per 1000 patient-years) due to infections was lower in the more recent cohort (4.6; 95% confidence interval, 3.5 to 6.1) compared with the older cohort (9.1; 95% confidence interval, 7.6 to 10.7); the incidence rate ratio of infectious mortality was 0.51 (95% confidence interval, 0.30 to 0.68). The main causes of infectious deaths were common bacterial infections: septicemia in 38% and pulmonary infections in 45%. Viral and fungal infections caused only 2% and 3% of infectious deaths, respectively (such as individual patients with Cytomegalovirus pneumonia, Herpes simplex virus meningoencephalitis, Varicella zoster virus encephalitis, and Pneumocystis jirovecii infection). Similarly, opportunistic bacterial infections rarely caused death; only one deathwas caused by Listeria monocytogenes, and two were caused by Mycobacterium tuberculosis. Only 23 (11%) of infection-related deaths occurred during the first post-transplant year. Older recipient age, higher plasma creatinine concentration at the end of the first post-transplant year, diabetes as a cause of ESKD, longer pretransplant dialysis duration, acute rejection, low albumin level, and earlier era of transplantation were associated with increased risk of infectious death in multivariable analysis. Conclusions The risk of death due to infectious causes after kidney transplantation in Finland dropped by one half since the 1990s. Common bacterial infections remained the most frequent cause of infection-related mortality, whereas opportunistic viral, fungal, or unconventional bacterial infections rarely caused deaths after kidney transplantation.
  • Stel, Vianda S.; de Jong, Rianne W.; Kramer, Anneke; Andrusev, Anton M.; Baltar, Jose M.; Barbullushi, Myftar; Bell, Samira; de la Nuez, Pablo Castro; Cernevskis, Harijs; Couchoud, Cecile; De Meester, Johan; Eriksen, Bjorn O.; Garneata, Liliana; Golan, Eliezer; Helve, Jaakko; Hemmelder, Marc H.; Hommel, Kristine; Ioannou, Kyriakos; Jarraya, Faical; Kantaria, Nino; Kerschbaum, Julia; Komissarov, Kirill S.; Magaz, Angela; Mercadal, Lucile; Ots-Rosenberg, Mai; Palsson, Runolfur; Rahmel, Axel; Rydell, Helena; Savino, Manuela; Seyahi, Nurhan; Roblero, Maria F. Slon; Stojceva-Taneva, Olivera; van der Tol, Arjan; Vazelov, Evgueniy S.; Ziginskiene, Edita; Zurriaga, Oscar; Vanholder, Raymond C.; Massy, Ziad A.; Jager, Kitty J. (2021)
    The aims of this study were to determine the frequency of dialysis and kidney transplantation and to estimate the regularity of comprehensive conservative management (CCM) for patients with kidney failure in Europe. This study uses data from the ERA-EDTA Registry. Additionally, our study included supplemental data from Armenia, Germany, Hungary, Ireland, Kosovo, Luxembourg, Malta, Moldova, Montenegro, Slovenia and additional data from Israel, Italy, Slovakia using other information sources. Through an online survey, responding nephrologists estimated the frequency of CCM (i.e. planned holistic care instead of kidney replacement therapy) in 33 countries. In 2016, the overall incidence of replacement therapy for kidney failure was 132 per million population (pmp), varying from 29 (Ukraine) to 251 pmp (Greece). On 31 December 2016, the overall prevalence of kidney replacement therapy was 985 pmp, ranging from 188 (Ukraine) to 1906 pmp (Portugal). The prevalence of peritoneal dialysis (114 pmp) and home hemodialysis (28 pmp) was highest in Cyprus and Denmark respectively. The kidney transplantation rate was nearly zero in some countries and highest in Spain (64 pmp). In 28 countries with five or more responding nephrologists, the median percentage of candidates for kidney replacement therapy who were offered CCM in 2018 varied between none (Slovakia and Slovenia) and 20% (Finland) whereas the median prevalence of CCM varied between none (Slovenia) and 15% (Hungary). Thus, the substantial differences across Europe in the frequency of kidney replacement therapy and CCM indicate the need for improvement in access to various treatment options for patients with kidney failure.
  • Jansz, Thijs T.; Noordzij, Marlies; Kramer, Anneke; Laruelle, Eric; Couchoud, Cecile; Collart, Frederic; Cases, Aleix; Arici, Mustafa; Helve, Jaakko; Waldum-Grevbo, Bard; Rydell, Helena; Traynor, Jamie P.; Zoccali, Carmine; Massy, Ziad A.; Jager, Kitty J.; van Jaarsveld, Brigit C. (2020)
    Background. Previous US studies have indicated that haemodialysis with >= 6-h sessions [extended-hours haemodialysis (EHD)] may improve patient survival. However, patient characteristics and treatment practices vary between the USA and Europe. We therefore investigated the effect of EHD three times weekly on survival compared with conventional haemodialysis (CHD) among European patients. Methods. We included patients who were treated with haemodialysis between 2010 and 2017 from eight countries providing data to the European Renal Association-European Dialysis and Transplant Association Registry. Haemodialysis session duration and frequency were recorded once every year or at every change of haemodialysis prescription and were categorized into three groups: CHD (three times weekly, 3.5-4h/treatment), EHD (three times weekly, >= 6h/treatment) or other. In the primary analyses we attributed death to the treatment at the time of death and in secondary analyses to EHD if ever initiated. We compared mortality risk for EHD to CHD with causal inference from marginal structural models, using Cox proportional hazards models weighted for the inverse probability of treatment and censoring and adjusted for potential confounders. Results. From a total of 142 460 patients, 1338 patients were ever treated with EHD (three times, 7.10.8h/week) and 89 819 patients were treated exclusively with CHD (three times, 3.9 +/- 0.2h/week). Crude mortality rates were 6.0 and 13.5/100 person-years. In the primary analyses, patients treated with EHD had an adjusted hazard ratio (HR) of 0.73 [95% confidence interval (CI) 0.62-0.85] compared with patients treated with CHD. When we attributed all deaths to EHD after initiation, the HR for EHD was comparable to the primary analyses [HR 0.80 (95% CI 0.71-0.90)]. Conclusions. EHD is associated with better survival in European patients treated with haemodialysis three times weekly.
  • Pettila, Ville; Merz, Tobias; Wilkman, Erika; Karlsson, Sari; Perner, Anders; Lange, Theis; Hästbacka, Johanna; Hjortrup, Peter Buhl; Kuitunen, Anne; Jakob, Stephan M.; Takala, Jukka (2016)
    Background: Septic shock has a 90-day mortality risk of up to 50 %. The hemodynamic targets, including mean arterial pressure (MAP) are not based on robust clinical data. Both severe hypotension and high doses of vasopressors may be harmful. Hence, re-evaluation of hemodynamic targets in septic shock is relevant. Methods/design: The targeted tissue perfusion versus macrocirculation-guided standard care in patients with septic shock (TARTARE-2S) trial is a prospective, two-parallel-group, randomized, open-label, multicenter trial with assessor-blinded outcome evaluation. We will randomize at least 200 patients with septic shock in four European intensive care units (ICUs) to test whether a tissue perfusion-guided treatment strategy based on capillary refill time, peripheral temperature, arterial lactate concentrations, and accepting lower MAP levels, leads to a faster resolution of shock than macrocirculation target-guided standard care. The primary outcome measure is days alive in 30 days with normal arterial blood lactate (first value of Discussion: The TARTARE-2S trial will provide important clinical data on treatment targets in septic shock, evaluating the impact of clinical tissue perfusion-guided hemodynamic treatment on a surrogate outcome combining resolution of shock (hyperlactatemia and vasopressors/inotropes), and 30-day mortality.
  • Raj, Rahul; Bendel, Stepani; Reinikainen, Matti; Hoppu, Sanna; Luoto, Teemu; Ala-Kokko, Tero; Tetri, Sami; Laitio, Ruut; Koivisto, Timo; Rinne, Jaakko; Kivisaari, Riku; Siironen, Jari; Higgins, Alisa; Skrifvars, Markus B. (2018)
    Objective: To assess temporal trends in 1-year healthcare costs and outcome of intensive care for traumatic brain injury in Finland. Design: Retrospective observational cohort study. Setting: Multicenter study including four tertiary ICUs. Patients: Three thousand fifty-one adult patients (>= 18 yr) with significant traumatic brain injury treated in a tertiary ICU during 2003-2013. Intervention: None. Measurements and Main Results: Total 1-year healthcare costs included the index hospitalization costs, rehabilitation unit costs, and social security reimbursements. All costs are reported as 2013 U.S. dollars ($). Outcomes were 1-year mortality and permanent disability. Multivariate regression models, adjusting for case-mix, were used to assess temporal trends in costs and outcome in predefined Glasgow Coma Scale (3-8, 9-12, and 13-15) and age (18-40, 41-64, and >= 65 yr) subgroups. Overall 1-year survival was 76% (n = 2,304), and of 1-year survivors, 37% (n = 850) were permanently disabled. Mean unadjusted 1-year healthcare cost was $39,809 (95% CI, $38,144-$41,473) per patient. Adjusted healthcare costs decreased only in the Glasgow Coma Scale 13-15 and 65 years and older subgroups, due to lower rehabilitation costs. Adjusted 1-year mortality did not change in any subgroup (p <0.05 for all subgroups). Adjusted risk of permanent disability decreased significantly in all subgroups (p <0.05). Conclusion: During the last decade, healthcare costs of ICU-admitted traumatic brain injury patients have remained largely the same in Finland. No change in mortality was noted, but the risk for permanent disability decreased significantly. Thus, our results suggest that cost-effectiveness of traumatic brain injury care has improved during the past decade in Finland.
  • FINNAKI Study Grp; Törnblom, Sanna; Nisula, Sara; Petäjä, Liisa; Vaara, Suvi T.; Haapio, Mikko; Pesonen, Eero; Pettilä, Ville (2020)
    Background: Neutrophil gelatinase-associated lipocalin (NGAL) is released from kidney tubular cells under stress as well as from neutrophils during inflammation. It has been suggested as a biomarker for acute kidney injury (AKI) in critically ill patients with sepsis. To evaluate clinical usefulness of urine NGAL (uNGAL), we post-hoc applied recently introduced statistical methods to a sub-cohort of septic patients from the prospective observational Finnish Acute Kidney Injury (FINNAKI) study. Accordingly, in 484 adult intensive care unit patients with sepsis by Sepsis-3 criteria, we calculated areas under the receiver operating characteristic curves (AUCs) for the first available uNGAL to assess discrimination for four outcomes: AKI defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria, severe (KDIGO 2-3) AKI, and renal replacement therapy (RRT) during the first 3 days of intensive care, and mortality at day 90. We constructed clinical prediction models for the outcomes and used risk assessment plots and decision curve analysis with predefined threshold probabilities to test whether adding uNGAL to the models improved reclassification or decision making in clinical practice. Results: Incidences of AKI, severe AKI, RRT, and mortality were 44.8% (217/484), 27.7% (134/484), 9.5% (46/484), and 28.1% (136/484). Corresponding AUCs for uNGAL were 0.690, 0.728, 0.769, and 0.600. Adding uNGAL to the clinical prediction models improved discrimination of AKI, severe AKI, and RRT. However, the net benefits for the new models were only 1.4% (severe AKI and RRT) to 2.5% (AKI), and the number of patients needed to be tested per one extra true-positive varied from 40 (AKI) to 74 (RRT) at the predefined threshold probabilities. Conclusions: The results of the recommended new statistical methods do not support the use of uNGAL in critically ill septic patients to predict AKI or clinical outcomes.