Browsing by Subject "SEVERE SEPSIS"

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  • Efraim Investigators Nine; Mokart, Djamel; Darmon, Michael; Schellongowski, Peter; Valkonen, Miia; Azoulay, Elie (2020)
    Background The impact of neutropenia in critically ill immunocompromised patients admitted in a context of acute respiratory failure (ARF) remains uncertain. The primary objective was to assess the prognostic impact of neutropenia on outcomes of these patients. Secondary objective was to assess etiology of ARF according to neutropenia. Methods We performed a post hoc analysis of a prospective multicenter multinational study from 23 ICUs belonging to the Nine-I network. Between November 2015 and July 2016, all adult immunocompromised patients with ARF admitted to the ICU were included in the study. Adjusted analyses included: (1) a hierarchical model with center as random effect; (2) propensity score (PS) matched cohort; and (3) adjusted analysis in the matched cohort. Results Overall, 1481 patients were included in this study of which 165 had neutropenia at ICU admission (11%). ARF etiologies distribution was significantly different between neutropenic and non-neutropenic patients, main etiologies being bacterial pneumonia (48% vs 27% in neutropenic and non-neutropenic patients, respectively). Initial oxygenation strategy was standard supplemental oxygen in 755 patients (51%), high-flow nasal oxygen in 165 (11%), non-invasive ventilation in 202 (14%) and invasive mechanical ventilation in 359 (24%). Before adjustment, hospital mortality was significantly higher in neutropenic patients (54% vs 42%;p = 0.006). After adjustment for confounder and center effect, neutropenia was no longer associated with outcome (OR 1.40, 95% CI 0.93-2.11). Similar results were observed after matching (52% vs 46%, respectively;p = 0.35) and after adjustment in the matched cohort (OR 1.04; 95% CI 0.63-1.72). Conclusion Neutropenia at ICU admission is not associated with hospital mortality in this cohort of critically ill immunocompromised patients admitted for ARF. In neutropenic patients, main ARF etiologies are bacterial and fungal infections.
  • Khanna, Ashish; English, Shane W.; Wang, Xueyuan S.; Ham, Kealy; Tumlin, James; Szerlip, Harold; Busse, Laurence W.; Altaweel, Laith; Albertson, Timothy E.; Mackey, Caleb; McCurdy, Michael T.; Boldt, David W.; Chock, Stefan; Young, Paul J.; Krell, Kenneth; Wunderink, Richard G.; Ostermann, Marlies; Murugan, Raghavan; Gong, Michelle N.; Panwar, Rakshit; Hastbacka, Johanna; Favory, Raphael; Venkatesh, Balasubramanian; Thompson, B. Taylor; Bellomo, Rinaldo; Jensen, Jeffrey; Kroll, Stew; Chawla, Lakhmir S.; Tidmarsh, George F.; Deane, Adam M.; ATHOS-3 Investigators (2017)
    BACKGROUND Vasodilatory shock that does not respond to high-dose vasopressors is associated with high mortality. We investigated the effectiveness of angiotensin II for the treatment of patients with this condition. METHODS We randomly assigned patients with vasodilatory shock who were receiving more than 0.2 mu g of norepinephrine per kilogram of body weight per minute or the equivalent dose of another vasopressor to receive infusions of either angiotensin II or placebo. The primary end point was a response with respect to mean arterial pressure at hour 3 after the start of infusion, with response defined as an increase from baseline of at least 10 mm Hg or an increase to at least 75 mm Hg, without an increase in the dose of background vasopressors. RESULTS A total of 344 patients were assigned to one of the two regimens; 321 received a study intervention (163 received angiotensin II, and 158 received placebo) and were included in the analysis. The primary end point was reached by more patients in the angiotensin II group (114 of 163 patients, 69.9%) than in the placebo group (37 of 158 patients, 23.4%) (odds ratio, 7.95; 95% confidence interval [CI], 4.76 to 13.3; P<0.001). At 48 hours, the mean improvement in the cardiovascular Sequential Organ Failure Assessment (SOFA) score (scores range from 0 to 4, with higher scores indicating more severe dysfunction) was greater in the angiotensin II group than in the placebo group (-1.75 vs. -1.28, P = 0.01). Serious adverse events were reported in 60.7% of the patients in the angiotensin II group and in 67.1% in the placebo group. Death by day 28 occurred in 75 of 163 patients (46%) in the angiotensin II group and in 85 of 158 patients (54%) in the placebo group (hazard ratio, 0.78; 95% CI, 0.57 to 1.07; P = 0.12). CONCLUSIONS Angiotensin II effectively increased blood pressure in patients with vasodilatory shock that did not respond to high doses of conventional vasopressors. (Funded by La Jolla Pharmaceutical Company; ATHOS-3 number, NCT02338843.)
  • Pettilä, Ville; Kyhälä, Lea; Kylänpää, Marja-Leena; Leppäniemi, Ari; Tallgren, Minna; Markkola, Antti Thor Olavi; Puolakkainen, Pauli; Repo, Heikki; Kemppainen, Esko (2010)
  • Pölkki, Anssi; Pekkarinen, Pirkka T.; Takala, Jukka; Selander, Tuomas; Reinikainen, Matti (2022)
    Background Sequential Organ Failure Assessment (SOFA) is a practical method to describe and quantify the presence and severity of organ system dysfunctions and failures. Some proposals suggest that SOFA could be employed as an endpoint in trials. To justify this, all SOFA component scores should reflect organ dysfunctions of comparable severity. We aimed to investigate whether the associations of different SOFA components with in-hospital mortality are comparable. Methods We performed a study based on nationwide register data on adult patients admitted to 26 Finnish intensive care units (ICUs) during 2012-2015. We determined the SOFA score as the maximum score in the first 24 hours after ICU admission. We defined organ failure (OF) as an organ-specific SOFA score of three or higher. We evaluated the association of different SOFA component scores with mortality. Results Our study population comprised 63,756 ICU patients. Overall hospital mortality was 10.7%. In-hospital mortality was 22.5% for patients with respiratory failure, 34.8% for those with coagulation failure, 40.1% for those with hepatic failure, 14.9% for those with cardiovascular failure, 26.9% for those with neurologic failure and 34.6% for the patients with renal failure. Among patients with comparable total SOFA scores, the risk of death was lower in patients with cardiovascular OF compared with patients with other OFs. Conclusions All SOFA components are associated with mortality, but their weights are not comparable. High scores of other organ systems mean a higher risk of death than high cardiovascular scores. The scoring of cardiovascular dysfunction needs to be updated.
  • Heliste, Maria; Pettilä, Ville; Berger, David; Jakob, Stephan M.; Wilkman, Erika (2022)
    Background Critical illness may lead to activation of the sympathetic system. The sympathetic stimulation may be further increased by exogenous catecholamines, such as vasopressors and inotropes. Excessive adrenergic stress has been associated with organ dysfunction and higher mortality. beta-Blockers may reduce the adrenergic burden, but they may also compromise perfusion to vital organs thus worsening organ dysfunction. To assess the effect of treatment with beta-blockers in critically ill adults, we conducted a systematic review and meta-analysis of randomized controlled trials. Materials and methods We conducted a search from three major databases: Ovid Medline, the Cochrane Central Register for Controlled Trials and Scopus database. Two independent reviewers screened, selected, and assessed the included articles according to prespecified eligibility criteria. We assessed risk of bias of eligible articles according to the Cochrane guidelines. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results Sixteen randomized controlled trials comprising 2410 critically ill patients were included in the final review. A meta-analysis of 11 trials including 2103 patients showed a significant reduction in mortality in patients treated with beta-blockers compared to control (risk ratio 0.65, 95%CI 0.53-0.79; p < .0001). There was no significant difference in mean arterial pressure or vasopressor load. Quality of life, biventricular ejection fraction, blood lactate levels, cardiac biomarkers and mitochondrial function could not be included in meta-analysis due to heterogenous reporting of outcomes. Conclusions In this systematic review we found that beta-blocker treatment reduced mortality in critical illness. Use of beta-blockers in critical illness thus appears safe after initial hemodynamic stabilization. High-quality RCT's are needed to answer the questions concerning optimal target group of patients, timing of beta-blocker treatment, choice of beta-blocker, and choice of physiological and hemodynamic parameters to target during beta-blocker treatment in critical illness. KEY MESSAGES A potential outcome benefit of beta-blocker treatment in critical illness exists according to the current review and meta-analysis. Administration of beta-blockers to resuscitated patients in the ICU seems safe in terms of hemodynamic stability and outcome, even during concomitant vasopressor administration. However, further studies, preferably large RCTs on beta-blocker treatment in the critically ill are needed to answer the questions concerning timing and choice of beta-blocker, patient selection, and optimal hemodynamic targets.
  • Hiemstra, Bart; Eck, Ruben J.; Koster, Geert; Wetterslev, Jorn; Perner, Anders; Pettila, Ville; Snieder, Harold; Hummel, Yoran M.; Wiersema, Renske; de Smet, Anne Marie G. A.; Keus, Frederik; van der Horst, Iwan C. C.; SICS Study Grp (2017)
    Purpose In the Simple Intensive Care Studies-I (SICS-I), we aim to unravel the value of clinical and haemodynamic variables obtained by physical examination and critical care ultrasound (CCUS) that currently guide daily practice in critically ill patients. We intend to (1) measure all available clinical and haemodynamic variables, (2) train novices in obtaining values for advanced variables based on CCUS in the intensive care unit (ICU) and (3) create an infrastructure for a registry with the flexibility of temporarily incorporating specific (haemodynamic) research questions and variables. The overall purpose is to investigate the diagnostic and prognostic value of clinical and haemodynamic variables. Participants The SICS-I includes all patients acutely admitted to the ICU of a tertiary teaching hospital in the Netherlands with an ICU stay expected to last beyond 24 hours. Inclusion started on 27 March 2015. Findings to date On 31 December 2016, 791 eligible patients fulfilled our inclusion criteria of whom 704 were included. So far 11 substudies with additional variables have been designed, of which six were feasible to implement in the basic study, and two are planned and awaiting initiation. All researchers received focused training for obtaining specific CCUS images. An independent Core laboratory judged that 632 patients had CCUS images of sufficient quality. Future plans We intend to optimise the set of variables for assessment of the haemodynamic status of the critically ill patient used for guiding diagnostics, prognosis and interventions. Repeated evaluations of these sets of variables are needed for continuous improvement of the diagnostic and prognostic models. Future plans include: (1) more advanced imaging; (2) repeated clinical and haemodynamic measurements; (3) expansion of the registry to other departments or centres; and (4) exploring possibilities of integration of a randomised clinical trial superimposed on the registry. Study registration number NCT02912624; Pre-results.
  • Forsblom, E.; Kakriainen, A.; Ruotsalainen, E.; Järvinen, A. (2018)
    Background Sex-related treatment inequalities are suggested to explain outcome differences between men and women in Staphylococcus aureus bacteremia (SAB). We compared patient characteristics, clinical management, infectious specialist consultation (ISC) and outcome in men and women with SAB. Methods Multicenter retrospective study of methicillin-sensitive (MS-) SAB patients categorized according to sex and ISC consultation provided within 7 days of diagnosis. Results Altogether 617 SAB patients were included in the analysis: 62% males and 38% females. Male sex was associated less often to nosocomial bacteremia (OR 0.69, 95% CI 0.50-0.96, p = 0.029) and more often to alcoholism (OR 2.25, 95% CI 1.31-3.87, p = 0.003). No sex-related differences were seen in basic or immunologic laboratory tests, illness severity, intensive care unit treatment or thromboembolic events. ISC was provided to most patients (94%) irrespective of sex. No differences were seen in clinical management of men or women: Transthoracic or -esophageal echocardiography (61% vs. 65%), deep infection (77% vs. 72%), infection removal (30% vs. 27%) and anti-staphylococcal antibiotics as first-line treatment (54% vs. 51%). However, male sex was connected to more frequent adjunctive rifampicin treatment (52% vs. 41%, p = 0.025). No difference in 28- or 90-day mortality (13% vs. 13% and 18% vs. 20%) or SAB relapse (0% vs. 1%) was observed between men and women. Propensity-score adjusted Cox proportional analysis gave no connection of sex to mortality within 90 days. Conclusion Patient characteristics, clinical management, ISC guidance, bacteremia relapse, and outcome did not differ in men and women with MS-SAB.
  • Pettilä, Ville; Hjortrup, Peter Buhl; Jakob, Stephan M.; Wilkman, Erika; Perner, Anders; Takala, Jukka (2016)
    The interpretation of septic shock trial data is profoundly affected by patients, control intervention, co-interventions and selected outcome measures. We evaluated the reporting of control groups in recent septic shock trials. We searched for original articles presenting randomized clinical trials (RCTs) in adult septic shock patients from 2006 to 2016. We included RCTs focusing on septic shock patients with at least two parallel groups and at least 50 patients in the control group. We selected and evaluated data items regarding patients, control group characteristics, and mortality outcomes, and calculated a data completeness score to provide an overall view of quality of reporting. A total of 24 RCTs were included (mean n = 287 patients and 71 % of eligible patients were randomized). Of the 24 studies, 14 (58 %) presented baseline data on vasopressors and 58 % the proportion of patients with elevated lactate values. Five studies (21 %) provided data to estimate the proportion of septic shock patients fulfilling the Sepsis-3 definition. The mean data completeness score was 19 out of 36 (range 8-32). Of 18 predefined control group characteristics, a mean of 8 (range 2-17) were reported. Only 2 (8 %) trials provided adequate data to confirm that their control group treatment represented usual care. Recent trials in septic shock provide inadequate data on the control group treatment and hemodynamic values. We propose a standardized trial dataset to be created and validated, comprising characteristics of patient population, interventions administered, hemodynamic values achieved, surrogate organ dysfunction, and mortality outcomes, to allow better analysis and interpretation of future trial results.
  • Lankelma, Jacqueline M.; van Vught, Lonneke A.; Belzer, Clara; Schultz, Marcus J.; van der Poll, Tom; de Vos, Willem M.; Wiersinga, W. Joost (2017)
    The intestinal microbiota has emerged as a virtual organ with essential functions in human physiology. Antibiotic-induced disruption of the microbiota in critically ill patients may have a negative influence on key energy resources and immunity. We set out to characterize the fecal microbiota composition in critically ill patients both with and without sepsis and to explore the use of microbiota-derived markers for clinical outcome measurements in this setting. In this prospective observational cohort study we analyzed the fecal microbiota of 34 patients admitted to the intensive care unit. Fifteen healthy subjects served as controls. The fecal microbiota was phylogenetically characterized by 16S rRNA gene sequencing, and associations with clinical outcome parameters were evaluated. A marked shift in fecal bacterial composition was seen in all septic and non-septic critically ill patients compared with controls, with extreme interindividual differences. In 13 of the 34 patients, a single bacterial genus made up > 50% of the gut microbiota; in 4 patients this was even > 75%. A significant decrease in bacterial diversity was observed in half of the patients. No associations were found between microbiota diversity, Firmicutes/Bacteroidetes ratio, or Gram-positive/Gram-negative ratio and outcome measurements such as complications and survival. We observed highly heterogeneous patterns of intestinal microbiota in both septic and non-septic critically ill patients. Nevertheless, some general patterns were observed, including disappearance of bacterial genera with important functions in host metabolism. More detailed knowledge of the short- and long-term health consequences of these major shifts in intestinal bacterial communities is needed.
  • Glassford, Neil J.; Martensson, Johan; Eastwood, Glenn M.; Jones, Sarah L.; Tanaka, Aiko; Wilkman, Erica; Bailey, Michael; Bellomo, Rinaldo; Arabi, Yaseen; Bagshaw, Sean M.; Bannard-Smith, Jonathan; Bin, Du; Dubin, Arnaldo; Duranteau, Jacques; Echeverri, Jorge; Hoste, Eric; Joannidis, Michael; Kashani, Kianoush; Kellum, John; Kulkarni, Atul P.; Landoni, Giovanni; Candal, Christina Lluch; Matejovic, Martin; Yunos, Norazim Modh; Anaes, M.; Nichol, Alistair; Oudemans van Straaten, Heleen; Perner, Anders; Pettila, Ville; Phua, Jason; Hernandez, Glenn; Puxty, Alex; Reinhart, Konrad; Richards, Guy; Schneider, Antoine; Tsuji, Isabella; Uchino, Shigehiko; GLobal OBservational Evaluations I (2016)
    Purpose: The purpose of the study is to understand what clinicians believe defines fluid bolus therapy (FBT) and the expected response to such intervention. Methods: We asked intensive care specialists in 30 countries to participate in an electronic questionnaire of their practice, definition, and expectations of FBT. Results: We obtained 3138 responses. Despite much variation, more than 80% of respondents felt that more than 250 mL of either colloid or crystalloid fluid given over less than 30 minutes defined FBT, with crystalloids most acceptable. The most acceptable crystalloid and colloid for use as FBT were 0.9% saline and 4% albumin solution, respectively. Most respondents believed that one or more of the following physiological changes indicates a response to FBT: a mean arterial pressure increase greater than 10 mm Hg, a heart rate decrease greater than 10 beats per minute, an increase in urinary output by more than 10 mL/h, an increase in central venous oxygen saturation greater than 4%, or a lactate decrease greater than 1 mmol/L. Conclusions: Despite wide variability between individuals and countries, clear majority views emerged to describe practice, define FBT, and identify a response to it. Further investigation is now required to describe actual FBT practice and to identify the magnitude and duration of the physiological response to FBT and its relationship to patient-centered outcomes. (C) 2016 Elsevier Inc. All rights reserved.
  • 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.
  • ARISE Investigators; Luethi, Nora; Bailey, Michael; Harjola, V-P; Okkonen, M.; Pettilä, V.; Sutinen, E.; Wilkman, E. (2020)
    Purpose: To assess the impact of gender and pre-menopausal state on short- and long-term outcomes in patients with septic shock. Material and methods: Cohort study of the Australasian Resuscitation in Sepsis Evaluation (ARISE) trial, an international randomized controlled trial comparing early goal-directed therapy (EGDT) to usual care in patients with early septic shock, conducted between October 2008 and April 2014. The primary exposure in this analysis was legal gender and the secondary exposure was pre-menopausal state defined by chronological age ( Results: 641 (40.3%) of all 1591 ARISE trial participants in the intention-to-treat population were females and overall, 337 (21.2%) (146 females) patients were 50 years of age or younger. After risk-adjustment, we could not identify any survival benefit for female patients at day 90 in the younger (50 years) age-group (aOR: 1.10 (0.81-1.49), p = .56). Similarly, there was no gender-difference in ICU, hospital, 1-year mortality nor quality of life measures. Conclusions: This post-hoc analysis of a large multi-center trial in early septic shock has shown no short- or long-term survival effect for women overall as well as in the pre-menopausal age-group. (C) 2019 Elsevier Inc. All rights reserved.
  • Moller, Morten Hylander; Skrifvars, Markus B.; Azoulay, Elie (2017)
  • Kylänpää, Marja-Leena; Repo, Heikki; Puolakkainen, Pauli Antero (2010)
  • Wallgren, Ulrika Margareta; Antonsson, Viktor Erik; Castren, Maaret; Kurland, Lisa (2016)
    Background: The presentation of sepsis is varied and our hypotheses were that septic patients with non-specific presentations such as decreased general condition (DGC) have a less favourable outcome, and that a screening tool could increase identification of these patients. We aimed to: 1) assess time to antibiotics and in-hospital mortality among septic patients with ED chief complaint DGC, as compared with septic patients with other ED chief complaints, and 2) determine whether a screening tool could improve identification of septic patients with non-specific presentations such as DGC. Methods: Cross sectional study comparing time to antibiotics (Mann Whitney and Kaplan-Meier tests), and in-hospital mortality (logistic regression), between 61 septic patients with ED chief complaint DGC and 516 septic patients with other ED chief complaints. The sensitivity and specificity of the modified Robson screening tool was compared with that of ED doctor clinical judgment (McNemar's two related samples test) among 122 patients presenting to the ED with chief complaint DGC, of which 61 were discharged with ICD code sepsis. Results: Septic patients presenting to the ED with the chief complaint DGC had a longer median time to antibiotics (05: 26 h: minutes; IQR 4: 00-10: 40, vs. 03: 56 h: minutes; IQR 2: 21-7: 32) and an increased in-hospital mortality (crude OR = 4.01; 95 % CI, 2.19-7.32), compared to septic patients with other ED chief complaints. This association remained significant when adjusting for sex, age, priority, comorbidity and fulfilment of the Robson score (OR 4.31; 95 % CI, 2.12-8.77). The modified Robson screening tool had a higher sensitivity (63.0 vs. 24.6 %, p <0.001), but a lower specificity (68.3 vs. 100.0 %, p <0.001), as compared to clinical judgment. Discussion: This is, to the best of our knowledge, the first study comparing outcome of septic patients according to ED chief complaint. Septic patients presenting with a non-specific ED presentation, here exemplified as the chief complaint DGC, have a less favourable outcome. Our results indicate that implementation of a screening tool may increase the identification of septic patients.
  • Forsblom, Erik; Tervahartiala, Taina; Ruotsalainen, Eeva; Järvinen, Asko; Sorsa, Timo (2021)
    Background Matrix metalloproteinase-8 (MMP-8) and tissue inhibitor of metalloproteinases-1 (TIMP-1) have been shown to predict prognosis in sepsis. However, MMP-8 and TIMP-1 in Staphylococcus aureus bacteremia (SAB) lacks evaluation and their role in the pathogenesis of SAB is unclear. Methods MMP-8 and TIMP-1 and MMP-8/TIMP-1 molar ratio were determined at days 3, 5 and 28 from positive blood cultures in patients with methicillin-sensitive SAB and the connection to disease severity and early mortality was determined. Results Altogether 395 SAB patients were included. Patients with severe sepsis or infection focus presented higher MMP-8 levels at day 3 and 5 (p Conclusion MMP-8 and MMP-8/TIMP-1 ratio were high 3-5 days after MS-SAB diagnosis in patients with an infection focus, severe sepsis or mortality within 14 days suggesting that matrix metalloproteinase activation might play a role in severe SAB.
  • Hästbacka, Johanna; Freden, Filip; Hult, Maarit; Bergquist, Maria; Wilkman, Erika; Vuola, Jyrki; Sorsa, Timo; Tervahartiala, Taina; Huss, Fredrik (2015)
    Introduction Matrix metalloproteinases (MMPs) -8 and -9 are released from neutrophils in acute inflammation and may contribute to permeability changes in burn injury. In retrospective studies on sepsis, levels of MMP-8, MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) differed from those of healthy controls, and TIMP-1 showed an association with outcome. Our objective was to investigate the relationship between these proteins and disease severity and outcome in burn patients. Methods In this prospective, observational, two-center study, we collected plasma samples from admission to day 21 post-burn, and burn blister fluid samples on admission. We compared MMP-8, -9, and TIMP-1 levels between TBSA20% (N = 30) injured patients and healthy controls, and between 90-day survivors and non-survivors. MMP-8, -9, and TIMP-1 levels at 24-48 hours from injury, their maximal levels, and their time-adjusted means were compared between groups. Correlations with clinical parameters and the extent of burn were analyzed. MMP-8, -9, and TIMP-1 levels in burn blister fluids were also studied. Results Plasma MMP-8 and -9 were higher in patients than in healthy controls (P20% groups. MMP-8 and -9 were not associated with clinical severity or outcome measures. TIMP-1 differed significantly between patients and controls (P20% groups (P
  • Inkinen, Nina; Selander, Tuomas; Pettila, Ville; Valkonen, Miia; Bäcklund, Minna; Wennervirta, Johanna; Pulkkinen, Anni; Hästbacka, Johanna; Vaara, Suvi T. (2020)
    Background Oliguria is a frequent trigger for administering a fluid bolus, but the effect of fluid bolus in improving urine output is inadequately demonstrated. Here, we summarize the protocol and detailed statistical analysis plan of the randomized, controlled RESPONSE trial comparing follow-up as the experimental group and a 500 mL crystalloid fluid bolus as the control group for oliguria in critically ill oliguric patients. Methods Our trial is an investigator-initiated, randomized, controlled, pilot trial conducted in three ICUs in two centers. We aim to randomize 1:1 altogether 130 hemodynamically stable oliguric patients either to a 2-hour follow-up without interventions or to receive a crystalloid bolus of 500 mL over 30 minutes. The primary outcome is the change in individual urine output during the 2-hour period compared to 2 hours preceding randomization. Doubling of the urine output is considered clinically significant. Additionally, we record the duration of oliguria, physiological and biochemical variables, adverse events, and the incidences of acute kidney injury and renal replacement therapy. Conclusions Oliguria is a frequent trigger for potentially harmful fluid loading. Therefore, the RESPONSE trial will give information of the potential effect of fluid bolus on oliguria in critically ill patients. Trial registration, NCT02860572.