Unresponsive Low Mixed Venous Oxygen Saturation During Early Intensive Care Unit Stay is Associated With Increased Risk of Organ Dysfunction After Cardiac Surgery: A Single-Center Retrospective Study.

OBJECTIVES: The aim of the study was to determine if unresponsive mixed venous oxygen saturation (SvO2) values during early postoperative hours are associated with postoperative organ dysfunction. DESIGN: A single-center retrospective observational study. SETTING: A university hospital. PARTICIPANTS: A total of 6,282 adult patients requiring cardiac surgery who underwent surgery in a University Hospital from 2007 to 2020. INTERVENTIONS: A pulmonary artery catheter was used to gather SvO2 samples after surgery at admission to the intensive care unit (ICU) and 4 hours later. For the analysis, patients were divided into 4 groups according to their SvO2 values. The rate of organ dysfunctions categorized according to the SOFA score was then studied among these subgroups. MEASUREMENTS AND MAIN RESULTS: The crude mortality rate for the cohort at 1 year was 4.3%. Multiple organ dysfunction syndrome (MODS) was present in 33.0% of patients in the early postoperative phase. During the 4-hour initial treatment period, 43% of the 931 patients with low SvO2 on admission responded to goal-directed therapy to increase SvO2 >60%; whereas, in 57% of the 931 patients, the low SvO2 was sustained. According to the adjusted logistic regression analyses, the odds ratio for MODS (4.23 [95% CI 3.41-5.25]), renal- replacement therapy (4.97 [95% CI 3.28-7.52]), time on a ventilator (2.34 [95% CI 2.17-2.52]), and vasoactive-inotropic score >30 (3.62 [95% CI 2.96-4.43]) were the highest in the group with sustained low SvO2. CONCLUSIONS: Patients with SvO2 <60% at ICU admission and 4 hours later had the greatest risk of postoperative MODS. Responsiveness to a goal-directed therapy protocol targeting maintaining or increasing SvO2 ≥60% at and after ICU admission may be beneficial.

Association of low mixed venous oxygen saturations during early ICU stay with increased 30-day and 1-year mortality after cardiac surgery: a single-center retrospective study.

BACKGROUND: Low postoperative mixed venous oxygen saturation (SvO2) values have been linked to poor outcomes after cardiac surgery. The present study was designed to assess whether SvO2 values of < 60% at intensive care unit (ICU) admission and 4 h after admission are associated with increased mortality after cardiac surgery. METHODS: During the years 2007-2020, 7046 patients (74.4% male; median age, 68 years [interquartile range, 60-74]) underwent cardiac surgery at an academic medical center in Finland. All patients were monitored with a pulmonary artery catheter. SvO2 values were obtained at ICU admission and 4 h later. Patients were divided into four groups for analyses: SvO2 ≥ 60% at ICU admission and 4 h later; SvO2 ≥ 60% at admission but < 60% at 4 h; SvO2 < 60% at admission but ≥ 60% at 4 h; and SvO2 < 60% at both ICU admission and 4 h later. Kaplan-Meier survival curves, Cox regression models, and receiver operating characteristic curve analysis were used to assess differences among groups in 30-day and 1-year mortality. RESULTS: In the overall cohort, 52.9% underwent coronary artery bypass grafting (CABG), 29.1% valvular surgery, 12.1% combined CABG and valvular procedures, 3.5% surgery of the ascending aorta or aortic dissection, and 2.4% other cardiac surgery. The 1-year crude mortality was 4.3%. The best outcomes were associated with SvO2 ≥ 60% at both ICU admission and 4 h later. Hazard ratios for 1-year mortality were highest among patients with SvO2 < 60% at both ICU admission and 4 h later, regardless of surgical subgroup. CONCLUSION: SvO2 values < 60% at ICU admission and 4 h after admission are associated with increased 30-day and 1-year mortality after cardiac surgery. Goal-directed therapy protocols targeting SvO2 ≥ 60% may be beneficial. Prospective studies are needed to confirm these observational findings.

Use and outcome of empiric echinocandins in critically ill patients.

BACKGROUND: Echinocandins are recommended as a first-line empiric treatment for fungal infections of patients in an intensive care unit (ICU) with critical illness. The primary aim of the study was to compare outcomes among ICU patients treated with empiric anidulafungin (ANI), caspofungin (CASPO), or micafungin (MICA). METHODS: A retrospective cohort study in a mixed adult ICU. Patient demographics, reason for ICU admission, ICU risk scores and organ support therapies were analyzed. Outcome parameters included ICU and hospital stay, 30-day mortality and 1-year mortality. RESULTS: Empiric echinocandin therapy was given to 367 patients (ANI; 73 patients, CASPO; 84 patients, and MICA; 210 patients) with a median duration of 3 days in an ICU. Patient median age was 60.7 years. As a first-line therapy, 52% of patients received fluconazole. Positive Candida cultures were found in the following samples: blood, 16 (4.4%); central line, 27 (7.4%); deep site, 92 (25.1%). Median ICU stay (ANI 6.4 days, CASPO 5.3 days, MICA 8.1 days), hospital stay (ANI 33 days, CASPO 30 days, MICA 30 days), 30-day mortality (ANI 27%, CASPO 32%, MICA 32%), and 1-year mortality (ANI 33%, CASPO 44%, MICA 45%) did not differ between the groups . The cost of antifungal therapy during the ICU period was similar in the three echinocandin groups (ANI; €1 872, CASPO; €1 799, and MICA; €1783). CONCLUSION: Our results show that ICU, hospital stay, and mortality (hospital, 30-day and 1-year) did not differ among patients with empiric anidulafungin, caspofungin, or micafungin treatment in a mixed adult ICU.

School Performance After Pediatric Intensive Care-Association of Mental Well-Being, Chronic Illnesses, and Family Socioeconomic Status.

OBJECTIVES: To describe school performance in pediatric intensive care survivors, as well as the influence of chronic diseases, psychological well-being, and family socioeconomic status on poor school performance. DESIGN: Register-based observational descriptive follow-up study. SETTING: A multicenter national study. PATIENTS: All pediatric patients who were admitted to an ICU in Finland in 2009-2010. Children and adolescents of or beyond school age. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Questionnaires regarding the child's coping in school classes, chronic illnesses, as well as family socioeconomic factors were sent to every child alive 6 years after discharge from intensive care in Finland. Mental well-being was measured with the Strengths and Difficulties Questionnaire. There were 1,109 responders in an ICU group of 3,674 children. Seven-hundred fifty-three of the respondents were of school age or older. Of these, 13% (101/753) demonstrated poor school performance. Children with difficulties in school more often had a need for regular medication (71.3% vs 32.4%; p < 0.001), healthcare visits (91.1% vs 80.6%; p = 0.01), some regular therapy (60.4% vs 13.7%; p < 0.001), chronic illnesses (86.3% vs 48.4%; p < 0.001), or additional ICU admissions (36.5% vs 14.9%; p = 0.003). Schooling difficulties were reported more often in children with abnormal Strengths and Difficulties Questionnaire scores compared to those with normal or borderline scores (24.8% vs 5.4%; p < 0.001). In an adjusted logistic regression model, which included age, number of chronic diseases, and need for therapy, poor school performance was predicted by abnormal Strengths and Difficulties Questionnaire scores, nonacademic parental education, and paternal manual labor status. CONCLUSIONS: Difficulties in school were more frequent when the child had chronic comorbid illnesses, especially neurologic or chromosomal abnormalities, had poor mental health, father was employed in manual labor, or parents were uneducated.

Strengths and Difficulties Questionnaire Assessment of Long-Term Psychological Outcome in Children After Intensive Care Admission.

OBJECTIVES: We investigated the long-term psychologic symptoms of patients who survived pediatric intensive care admission. DESIGN: Longitudinal follow-up study. SETTING: Nationwide cohort study based on a national ICU register and a questionnaire survey. PATIENTS: All pediatric patients (0-16 yr old) who were admitted to an ICU in Finland in 2009-2010. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Six years after ICU admission, all surviving patients were sent the Strengths and Difficulties Questionnaire, and questionnaires regarding chronic diseases and need for medication and therapy. At the end of the follow-up period, there were 3,674 surviving children who had been admitted to an ICU in 2009-2010. Of these children, 1,105 completed the Strengths and Difficulties Questionnaire 6 years after admission. Strengths and Difficulties Questionnaire scores were abnormal for 84 children (7.6%), borderline for 80 (7.2%), and normal for 941 (85.2%). Participants with abnormal scores were younger at admission to the ICU (3.06 vs 4.70 yr; p = 0.02), and more commonly had a chronic disease (79.5% vs 47.4%; p < 0.001), a need for continuous medication (49.4% vs 31.7%; p < 0.001), a need for therapy (58.5% vs 15.9%; p < 0.001), and a need for annual healthcare visits (91.4% vs 85.2%; p = 0.05). Abnormal Strengths and Difficulties Questionnaire scores were associated with higher rates of neurologic (32.1% vs 10.2%), gastrointestinal (7.1% vs 3.9%), psychiatric (3.6% vs 0.5%), and chromosomal disorders (9.5% vs 1.3%), as well as with long-term pain (1.2% vs 0.6%). CONCLUSIONS: Participants with abnormal Strengths and Difficulties Questionnaire scores (poor psychologic outcome) at 6 years after childhood ICU admission more commonly suffered neurologic, chromosomal, or psychiatric diagnoses or long-term pain, and generally required higher levels of healthcare services, therapies, and medication.

Inhibitory effects of serum from sepsis patients on epithelial cell migration in vitro: a case control study.

BACKGROUND: Sepsis delays wound re-epithelialization. In this study we explored the effect of human sepsis sera as well as the effects of cytokines, growth factors and exosomes of sepsis sera treated normal fibroblasts (NF) on keratinocyte migration and proliferation in vitro. METHODS: Serum samples were taken on days 1, 4, and 9 from 44 patients diagnosed with severe sepsis, and from 14 matching healthy controls. We evaluated the effects of sepsis serum with or without TNF-α, EGF, EGF receptor inhibitor or exosomes of sepsis sera treated NF on human keratinocyte (HaCaT) proliferation (BrdU assay), viability (MTT assay), and migration (horizontal wound healing model). Cytokine levels of sepsis and healthy sera were measured by multiplex assay. Comparisons between groups were carried out using SPSS statistics and P < 0.05 was considered significant. RESULTS: Severe-sepsis sera collected on days 1, 4, and 9 reduced keratinocyte proliferation by 6% (P = 0.005), 20% (P = 0.001), and 18% (P = 0.002), respectively, compared to control sera. Cell viability in cultures exposed to sepsis sera from days 4 and 9 was reduced by 38% (P = 0.01) and 58% (P < 0.001), respectively. Open-surface wounds exposed to sepsis sera from days 1 and 4 were larger than those exposed to sera from healthy controls (60 vs. 31%, P = 0.034 and 66 vs. 31%, P = 0.023, respectively). Exosomes of sepsis or healthy sera treated NF inhibited keratinocyte migration. We detected higher serum levels of cytokines TNF-α (5.7 vs. 0.7 pg/ml, P < 0.001), IL-6 (24.8 vs. 3.8 pg/ml, P < 0.001), IL-10 (30.0 vs. 11.9 pg/ml, P = 0.040), and VEGF (177.9 vs. 48.1 pg/ml, P = 0.018) in sepsis sera. Levels of EGF were significantly lower in sepsis sera than in that of healthy controls (6.5 vs. 115.6 pg/ml, P < 0.001). Sepsis serum supplemented with EGF 5 ng/ml and TNF-α in all concentrations improved keratinocyte migration. CONCLUSIONS: Keratinocyte viability, proliferation and migration were reduced in severe sepsis in vitro. Exosomes from NF added in healthy or sepsis serum media inhibited keratinocyte migration. Decreased levels of EGF in sepsis sera may partially explain the delay of wound healing with severe-sepsis patients. Increased levels of TNF-α in sepsis sera do not explain diminished keratinocyte migration.

ICU-treated influenza A(H1N1) pdm09 infections more severe post pandemic than during 2009 pandemic: a retrospective analysis.

BACKGROUND: We compared in a single mixed intensive care unit (ICU) patients with influenza A(H1N1) pdm09 between pandemic and postpandemic periods. METHODS: Retrospective analysis of prospectively collected data in 2009-2016. Data are expressed as median (25th-75th percentile) or number (percentile). RESULTS: Seventy-six influenza A(H1N1) pdm09 patients were admitted to the ICU: 16 during the pandemic period and 60 during the postpandemic period. Postpandemic patients were significantly older (60 years vs. 43 years, p < 0.001) and less likely to have epilepsy or other neurological diseases compared with pandemic patients (5 [8.3%] vs. 6 [38%], respectively; p = 0.009). Postpandemic patients were more likely than pandemic patients to have cardiovascular disease (24 [40%] vs. 1 [6%], respectively; p = 0.015), and they had higher scores on APACHE II (17 [13-22] vs. 14 [10-17], p = 0.002) and SAPS II (40 [31-51] vs. 31 [25-35], p = 0.002) upon admission to the ICU. Postpandemic patients had higher maximal SOFA score (9 [5-12] vs. 5 [4-9], respectively; p = 0.03) during their ICU stay. Postpandemic patients had more often septic shock (40 [66.7%] vs. 8 [50.0%], p = 0.042), and longer median hospital stays (15.0 vs. 8.0 days, respectively; p = 0.006). During 2015-2016, only 18% of the ICU- treated patients had received seasonal influenza vaccination. CONCLUSIONS: Postpandemic ICU-treated A(H1N1) pdm09 influenza patients were older and developed more often septic shock and had longer hospital stays than influenza patients during the 2009 pandemic.

Effects of simulation education on oral care practices - a randomized controlled trial.

BACKGROUND: Implementation of evidence-based oral care protocols, nurse education programmes and assessment tools may reduce the risk of developing ventilator-associated pneumonia by increasing critical care nurses' knowledge and skills in adhering to current oral care recommendations. AIMS: To evaluate the longitudinal effects of single-dose simulation education with structured debriefing and verbal feedback on critical care nurses' knowledge and skills in adhering to current oral care recommendations. DESIGN: A randomized controlled trial with repeated measurements. METHOD: The data for the study were collected in a single academic centre in a 22-bed adult, mixed, medical-surgical intensive care unit in Finland from February 2012 to March 2014. The effectiveness of simulation education was evaluated through the validated Ventilator Bundle Questionnaire and Observation Schedule at baseline (n = 30) and 24 months (n = 17) after simulation education. Data were analysed using a linear mixed model and intention-to-treat analyses. RESULTS: During the study period, the average knowledge score in the intervention group increased significantly (44·0% to 56·0% of the total score) in the final post-intervention measurement (pt = 0·51, pg = 0·002, pt*g = 0·023). However, single-dose simulation education with structured debriefing and verbal feedback had no impact on critical care nurses' skill scores. CONCLUSION: Single-dose simulation education had only a minimal effect on critical care nurses' knowledge and skills in adhering to current oral care recommendations. Despite increased awareness, there was no significant difference in oral care practices between the study groups after simulation education. RELEVANCE FOR CLINICAL PRACTICE: The need for regularly repeated educational sessions with theoretical training and practical exercises and direct feedback is evident. Certain aspects of oral care, such as prevention of microaspiration of oropharyngeal secretions and moistening of oral mucosa and lips, require more reinforcement than others.

Variation in the use of renal replacement therapy in patients with septic shock: a substudy of the prospective multicenter observational FINNAKI study.

INTRODUCTION: Indications for renal replacement therapy (RRT) have not been generally standardized and vary among intensive care units (ICUs). We aimed to assess the proportion, indications, and modality of RRT, as well as the association between the proportion of RRT use and 90-day mortality in patients with septic shock in Finnish adult ICUs. METHODS: We identified patients with septic shock from the prospective observational multicenter FINNAKI study conducted between 1 September 2011 and 1 February 2012. We divided the ICUs into high-RRT and low-RRT ICUs according to the median of the proportion of RRT-treated patients with septic shock. Differences in indications, and modality of RRT between ICU groups were assessed. Finally, we performed an adjusted logistic regression analysis to evaluate the possible association of the ICU group (high vs. low-RRT) with 90-day mortality. RESULTS: Of the 726 patients with septic shock, 131 (18.0%, 95% CI 15.2 to 20.9%) were treated with RRT. The proportion of RRT-treated patients varied from 3% up to 36% (median 19%) among ICUs. High-RRT ICUs included nine ICUs (354 patients) and low-RRT ICUs eight ICUs (372 patients). In the high-RRT ICUs patients with septic shock were older (P = 0.04), had more cardiovascular (P <0.001) and renal failures (P = 0.003) on the first day in the ICU, were more often mechanically ventilated, and received higher maximum doses of norepinephrine (0.25 µg/kg/min vs. 0.18 µg/kg/min, P <0.001) than in the low-RRT ICUs. No significant differences in indications for or modality of RRT existed between the ICU groups. The crude 90-day mortality rate for patients with septic shock was 36.2% (95% CI 31.1 to 41.3%) in the high-RRT ICUs compared to 33.9% (95% CI 29.0 to 38.8%) in the low-RRT ICUs, P = 0.5. In an adjusted logistic regression analysis the ICU group (high-RRT or low-RRT ICUs) was not associated with 90-day mortality. CONCLUSIONS: Patients with septic shock in ICUs with a high proportion of RRT had more severe organ dysfunctions and received more organ-supportive treatments. Importantly, the ICU group (high-RRT or low-RRT group) was not associated with 90-day mortality.

Colectomy in intensive care patients: operative findings and outcomes.

BACKGROUND: With a critical illness, intestinal complications are associated with high morbidity and mortality. METHODS: Operative findings and outcomes of 77 intensive care unit (ICU) patients treated with colectomy are described. RESULTS: Three conditions led to colectomy: sepsis (S group; n = 31), fulminant Clostridium difficile colitis (Cl group; n = 25), and cardiovascular surgery (CV group; n = 21). The median Acute Physiology and Chronic Health score was >25 in all groups. Thickening and distension of the colon was more frequent in the Cl group (p = 0.001), and ischemia was more frequent in the S and CV groups (p < 0.001). Widespread necrosis was more frequent in the CV patients (p = 0.001). The kappa value for ischemic operative findings and histologic necrosis was 0.64 (95 % confidence interval 0.49-0.79). Hospital mortality was 35 % without multiple organ failure (MOF) (n = 31) and 74 % with MOF (n = 46) (p < 0.001). Overall, 38 % were alive at the 1-year follow-up. CONCLUSIONS: Although colectomy in ICU patients is associated with high hospital mortality, patients who survive beyond their hospital stay have a good 1-year outcome.

Impact of preoperative organ failures on survival in intensive care unit patients with colectomy.

BACKGROUND: The present study aimed to evaluate the prognostic value of preoperative changes in sequential organ failure assessment (SOFA) score, daily norepinephrine (NE) dose, lactate, C-reactive protein, and white blood cell count among patients with colectomy in the intensive care unit (ICU). METHODS: We performed a retrospective analysis of 77 colectomized patients (30 female, 47 male) who were treated in a single tertiary-level mixed ICU during 2000-2009. RESULTS: The underlying conditions leading to colectomy included sepsis (31 patients), cardiovascular operations (21 patients), and fulminant Clostridium difficile colitis (25 patients). The 28-day mortality was 53.3 % (41/77). Nonsurvivors had significantly higher median values than survivors (p < 0.05) for the following parameters: admission SOFA [10.0 (25th-75th percentile 8.0-13.0) vs. 9.0 (6.5-10.0)], highest SOFA [14.0 (12.0-16.0) vs. 12.5 (9.5-14.5)], operative day lactate level (6.3 vs. 2.2 mmol/L), and NE dose (16.8 vs. 9.3 total mg/day). During the last three preoperative days, significant increases were observed in total SOFA score (p < 0.001) and in cardiovascular (p < 0.001), coagulation (p = 0.017), renal (p < 0.01), and respiratory (p < 0.001) SOFA subscores, without statistically significant differences between nonsurvivors and survivors. Increasing Glasgow Coma Scale score, preoperative lactate level, and NE dose were significantly associated with mortality. CONCLUSIONS: It should be prospectively studied whether preoperatively increasing lactate level and NE dose are surrogate markers for early laparotomy among ICU patents with colitis.

Comparison of the epidemiology, risk factors, outcome and degree of organ failures of patients with candidemia acquired before or during ICU treatment.

INTRODUCTION: The aim of this study was to compare the epidemiology, risk factors, severity and outcome of two types of ICU-treated candidemias: namely, ICU-acquired candidemia (acquired after 48-hour ICU stay) (ICUAC group), and those needing ICU treatment for candidemia acquired before ICU admission or during the first 48-hour ICU stay (non-ICUAC group). METHODS: A retrospective cohort study was conducted between 2000 and 2009 in a mixed tertiary ICU among patients with blood-culture-confirmed candidemia. RESULTS: The study involved 82 patients (53 men). The ICUAC group consisted of 38 patients (46.3%) and the non- ICUA group included 44 patients (53.6). The ICUAC group had undergone previous surgery more often and had ICU stays that were 3.7 times longer than the non-ICUAC group, whose members more often had co-morbidities (95.6% versus 73.7%, P = 0.001). The ICUAC group had significantly more frequent organ failures with cardiovascular, renal, central nervous and coagulation systems than the non-ICUAC group. ICU, hospital and one-year mortality rates did not differ between the groups (23%, 36.8% and 65.8%, respectively, in the ICUAC group and 26%, 44.4% and 64.4%, respectively, in the non-ICUAC group). Among patients with APACHE II scores greater than 25, the ICUAC group had lower one-year mortality (65.0% versus 87.5%). Among patients with APACHE II scores of 25 or less, the ICUAC group had higher mortality (66.7% versus 50.0). Candida albicans was most common cause of candidemia in both groups (76.3% and 68.9%, respectively). CONCLUSIONS: More than half of the ICU-treated candidemias were acquired prior to admission to the ICU. Patients with ICU- and non-ICU-acquired candidemias had different risk factors and different needs for ICU resources. Hospital mortality was similar in both groups; however, the groups had different mortality rates when the severity of disease and underlying diseases were taken into account.

Growth factor expression is enhanced, and extracellular matrix proteins are depressed in healing skin wounds in septic patients compared with healthy controls.

Sepsis manifests as a dysregulated immune response to infection, damaging organs. Skin has a critical role in protecting the body. In sepsis, skin wound healing is impaired. The mechanisms behind it have been poorly studied. In this study, suction blister wounds were induced on intact abdominal skin in 15 septic patients. A single blister wound was biopsied from each patient and from 10 healthy controls. Immunohistochemical staining of growth factors and extracellular matrix (ECM) proteins was performed. Significance (p < 0.05) of the differences was calculated. The following growth factors were overexpressed in the skin of septic patients compared with healthy controls: epithelial growth factor (intact epithelium p = 0.007, migrating epithelium p = 0.038), vascular epithelial growth factor (intact epithelium p < 0.001, migrating epithelium p = 0.011) and transforming growth factor beta (migrating epithelium p = 0.002). The expression of syndecan-1 was upregulated in the skin of septic patients compared with healthy controls (intact epithelium p = 0.048, migrating epithelium p = 0.028). The following ECM proteins had lower expression in the epithelium in septic patients than in healthy controls: tenascin-C (migrating epithelium p = 0.03) and laminin-332 (intact epithelium p = 0.036). In sepsis, growth factor and syndecan expression was enhanced, while ECM and basement membrane proteins were mostly depressed.

Changes in the incidence and outcome of multiple organ failure in emergency non-cardiac surgical admissions: a 10-year retrospective observational study.

BACKGROUND: During the past decades, epidemiologic data of independent predictors of multiple organ failure (MOF), incidence, and mortality have changed. The aim of the study was to assess the potential changes in the incidence and outcomes of MOF for one decade (2008-2017). In addition, resource utilization was considered. METHODS: Patients were eligible for inclusion if they were adults, admitted to the ICU between January 1, 2008 and December 31, 2017, and had complete data sets regarding MOF. MOF was defined as organ failure separately with and without central nervous system (CNS) failure. The onset of MOF was defined as being early (≤48 h of ICU admission) and late (>48 h after ICU admission). RESULTS: Of a total of 13,270 patients enclosed in this study, 44.6% of the patients developed MOF with and 31.4% without CNS failure. MOF-related mortality decreased in patients with (adjusted IRR 0.972 [95% CI 0.948 to 0.996], P=0.022) and without (adjusted IRR 0.957 [95% CI 0.931 to 0.983], P=0.0013) CNS failure. In addition, the incidence (adjusted IRR 0.970 [95% CI 0.950 to 0.991], P=0.006) and mortality (adjusted IRR 0.968 [95% CI 0.940 to 0.996], P=0.025) of early-onset MOF decreased, while the incidence and mortality of late-onset MOF remained constant. The length of ICU (P=0.024) and hospital (P=0.032) stays decreased while the length of mechanical ventilation remained constant (P=0.41). CONCLUSIONS: Despite all improvements in intensive care during the last decades, the incidence of late-onset MOF remains a resource-intensive, morbid, and lethal condition. More research on etiologies, signs of organ failure, and where and when to start treatment is needed to improve the prognosis of late-onset MOF.

Matrix-metalloproteinase-2, -8 and -9 in serum and skin blister fluid in patients with severe sepsis.

INTRODUCTION: Matrix metalloproteinases (MMPs) have various roles in inflammatory states. They seem to be able to modulate endothelial barriers and regulate the activity of chemokines and cytokines. The timely development of the levels during severe sepsis and thereafter have not been investigated. In addition it was of interest to study alterations of MMP-levels in intact skin, as the skin is the largest barrier against external pathogens and MMPs have not been studied at organ level in human sepsis. The aim of this study was to investigate the timely development of serum and skin MMP-2, -8 and -9 levels in human severe sepsis and their association with disease severity and mortality. METHODS: Forty-four patients with severe sepsis and fifteen healthy controls were included in this prospective longitudinal study. The amounts of MMP-2, -8 and -9 were analyzed from serum at days 1, 4, 6, 8, and 10, and from skin suction blister fluid at days 1 and 5 from the beginning of severe sepsis. Additionally, samples from the survivors were obtained after three and six months. RESULTS: The levels of MMP-2 and -8 were up-regulated in severe sepsis in comparison to healthy controls in skin blister fluid and serum. Compared to the controls MMP-9 levels were lower in sepsis from the fourth day on in serum and both the first and fifth day in skin blister fluid. Active forms of MMP-2 and -9 were present only in severe sepsis. The non-survivors had higher pro- and active MMP-2 levels than the survivors in skin blister fluid samples. Furthermore, MMP-2 levels were more pronounced in blister fluid and serum samples in patients with more severe organ failures. In the survivors at 3 and 6 month follow-up the MMP levels had returned to normal. CONCLUSIONS: MMP-2 and -8 are elevated in serum and blister fluid in severe sepsis, implying that they may play a significant role in the pathogenesis of severe sepsis and organ dysfunctions. Active forms of MMP-2 and 9 were only present in patients with severe sepsis, and higher MMP-2 levels in skin blister and serum were associated with more severe organ dysfunctions.

1H NMR Based Metabolomics in Human Sepsis and Healthy Serum.

Early diagnosis is essential but challenging in severe sepsis. Quantifying and comparing metabolite concentrations in serum has been suggested as a new diagnostic tool. Here we used proton nuclear magnetic resonance spectroscopy (1H NMR) based metabolomics to analyze the possible differences in metabolite concentrations between sera taken from septic patients and healthy controls, as well as between sera of surviving and non-surviving sepsis patients. We took serum samples from 44 sepsis patients when the first sepsis induced organ dysfunction was found. Serum samples were also collected from 14 age and gender matched healthy controls. The samples were analyzed by quantitative 1H NMR spectroscopy for non-lipid metabolites. We found that the serum levels of glucose, glycine, 3-hydroxybutyrate, creatinine and glycoprotein acetyls (mostly alpha-1-acid glycoprotein, AGP) were significantly (p < 0.05) higher in sepsis compared to healthy sera, whereas citrate and histidine were significantly (p < 0.05) lower in sepsis patients compared to healthy controls. We found statistically significantly higher serum lactate and citrate concentrations in non-survivors compared to 30-day survivors. According to our study, 3-hydroxybutyrate, citrate, glycine, histidine, and AGP are candidates for further studies to enable identification of phenotype association in the early stages of sepsis.

Nutrition deficit during intensive care stay: incidence, predisposing factors and outcomes.

BACKGROUND: Adequate nutrition support during intensive care has several benefits including lower amount of infectious complications, improved wound healing, shorter length of stay (LOS) and decreased morbidity. The aim of the present study was to survey the adequacy of nutrition throughout Intensive Care Unit (ICU) stay and to examine various factors associated to cumulative nutrition inadequacy during ICU stay. METHODS: The study was a retrospective single center cohort study. The study population consisted of 1771 ICU adult (≥18 years) patients with emergency admission to ICU who had LOS between three and 40 days. Nutrition adequacy and factors associated to inadequate nutrition support during ICU stay were analyzed. RESULTS: Factors related to impaired energy balance were prescribed energy less than 25kcal/kg (OR 11.794 (9.017-15.427), P<0.001) and higher median CRP (OR 1.003 (1.001-1.004), P<0.001). Factors related to improved energy balance were length of stay (OR 0.975 (0.953-0.997), P=0.024), more than 30% Bolus enteral nutrition days (OR 0.314 (0.187-0.526), P<0.001) and Enteral/Parenteral -Ratio (OR 0.970 (0.953-0.987), P=0.001). CONCLUSIONS: The majority of ICU patients did not reach 60% of nutrition adequacy. Nutrition inadequacy was a common finding throughout the study population. Nutrition inadequacy might be partially avoidable since adequacy less than 60% was related to underprescription and failure to administer the prescribed nutrition. Bolus enteral nutrition might be an efficient method to deliver energy in ICU setting.

Long-term outcome and quality-adjusted life years after severe sepsis.

OBJECTIVE: To study long-term mortality, quality of life (QOL), quality-adjusted life years (QALYs), and costs per QALY in an unselected intensive care unit (ICU) patient population with severe sepsis. DESIGN: Prospective observational cohort study. SETTING: Twenty-four ICUs in Finland. PATIENTS: A total of 470 adult patients with severe sepsis who were treated in ICUs between November 1, 2004 and February 28, 2005. The QOL before critical illness was assessed in 252 patients and QOL after severe sepsis in 156 patients (58% of the patients surviving in April 30, 2006). Ninety-eight patients responded to both questionnaires. QOL was assessed by a generic EuroQol-5D (EQ-5D) measurement with summary index (EQsum) and visual analogue scale (VAS). MEASUREMENTS AND MAIN RESULTS: The 2-year mortality after severe sepsis was 44.9% (211 of 470). The median response time for QOL assessment after severe sepsis was 17 months (interquartile range [IQR] 16-18). The median EQsum (75, IQR 56-92) and EQ VAS (66, IQR 50-80) were lower after severe sepsis than age- and sex-adjusted reference values (p < 0.001 and p < 0.001). The decrease between the mean EQsum reference value and that of severe sepsis patients was 12 (95% confidence interval [CI], 9-16). The difference between the mean EQ VAS reference values and the mean EQ VAS was 8 (95% CI, 5-11). The mean calculated QALYs after severe sepsis were 10.9 (95% CI, 9.7-12.1) and the calculated cost for one QALY was only 2139 [Euro sign] for all survivors and nonsurvivors. CONCLUSIONS: Two-year mortality after severe sepsis was high (44.9%) and the QOL was lower after severe sepsis than before critical illness as assessed by EQ-5D. However, the mean QALYs for the surviving patients were reasonable and the cost for one QALY was reasonably low, which makes intensive care in patients with severe sepsis cost effective.

Epidermal wound healing in severe sepsis and septic shock in humans.

INTRODUCTION: The effect of sepsis on epidermal wound healing has not been previously studied. It was hypothesised that epidermal wound healing is disturbed in severe sepsis. METHODS: Blister wounds were induced in 35 patients with severe sepsis and in 15 healthy controls. The healing of the wounds was followed up by measuring transepidermal water loss and blood flow in the wound, reflecting the restoration of the epidermal barrier function and inflammation, respectively. The first set of suction blisters (early wound) was made within 48 hours of the first sepsis-induced organ failure and the second set (late wound) four days after the first wound. In addition, measurements were made on the intact skin. RESULTS: The average age of the whole study population was 62 years (standard deviation [SD] 12). The mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score on admission was 25 (SD 8). The two most common causes of infections were peritonitis and pneumonia. Sixty-six percent of the patients developed multiple organ failure. The decrease in water evaporation from the wound during the first four days was lower in septic patients than in the control subjects (56 g/m2 per hour versus 124 g/m2 per hour, P = 0.004). On the fourth day, septic patients had significantly higher blood flow in the wound compared with the control subjects (septic patients 110 units versus control subjects 47 units, P = 0.001). No difference in transepidermal water loss from the intact skin was found between septic patients and controls. Septic patients had higher blood flow in the intact skin on the fourth and on the eighth day of study compared with the controls. CONCLUSIONS: The restoration of the epidermal barrier function is delayed and wound blood flow is increased in patients with severe sepsis.

Implementation of strategies to liberate patients from mechanical ventilation in a tertiary-level medical center.

BACKGROUND: Considerable discrepancies have been observed in the implementation of strategies to liberate patients from mechanical ventilation. The aim of this study was to describe critical care nurses' knowledge of and self-reported and documented adherence to lung-protective ventilation, daily sedation interruption, and daily assessment of readiness to extubate and evaluate how these practices differ between patients with and without ventilator-associated pneumonia and between survivors and nonsurvivors. METHODS: The survey was conducted in a tertiary-level hospital in Finland from October 2014 to June 2015. Actual adherence was evaluated based on documentation of performed practices. RESULTS: A total of 86 critical care nurses responded to the survey, and 85 patients were followed. The levels of knowledge of and self-reported adherence to low tidal ventilation were 84.5% and 90.2%, respectively, and the median tidal volume was at a target level in 74.4% of patients. Regarding daily sedation interruption, the level of knowledge was 85.7%, the level of self-reported adherence was 77.3%, and documented adherence was 33.3%. The levels of knowledge and self-reported adherence regarding spontaneous breathing trials were 61.9% and 71.6%, respectively. Adherence to lung-protective ventilation, daily sedation interruption, and daily assessment of readiness to extubate did not differ between patients with (n = 20) and without (n = 65) ventilator-associated pneumonia and between survivors (n = 55) and nonsurvivors (n = 30). CONCLUSIONS: Lung-protective ventilation, including low-tidal ventilation and avoidance of high inspiratory plateau pressures, was well implemented and adhered to. The levels of knowledge and self-reported adherence versus documented adherence regarding daily sedation interruption and spontaneous breathing trial demonstrated insufficient implementation of local guidelines. There was no effect on the outcome.