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Background: Reports of the prevalence and impact of hazardous alcohol use among intensive care unit (ICU) patients are contradictory. We aimed to study the prevalence of hazardous alcohol use among ICU patients and its association with ICU length of stay (LOS) and mortality., Methods: Finnish ICUs have been using the Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) to evaluate and record patients' alcohol use into the Finnish Intensive Care Consortium's Database (FICC). We retrieved data from the FICC from a 3-month period. We excluded data from centers with an AUDIT-C recording rate of less than 70% of admissions. We defined hazardous alcohol use as a score of 5 or more for women and 6 or more for men from a maximum score of 12 points., Results: Two thousand forty-five patients were treated in the 10 centers with an AUDIT-C recording rate of 70% or higher. AUDIT-C was available for 1576 (77%) patients and indicated hazardous alcohol use for 334 (21%) patients who were more often younger (median age 55 [interquartile range 42-65] vs 67 [57-74] [P < .001]) and male (78.1% vs 61.3% [P < .001]) compared to other patients. We found no difference in LOS or hospital mortality between hazardous and non-hazardous alcohol users. Among the non-abstinent, risk of death within a year increased with increasing AUDIT-C scores adjusted odds ratio 1.077 (95% confidence interval, 1.006-1.152) per point., Conclusion: The prevalence of hazardous alcohol use in Finnish ICUs was 21%. Patients with hazardous alcohol use were more often younger and male compared with non-hazardous alcohol users., (© 2021 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

ATP and adenosine are important signaling molecules involved in vascular remodeling, retinal function, and neurovascular coupling in the eye. Current knowledge on enzymatic pathways governing the duration and magnitude of ocular purinergic signaling is incompletely understood. By employing sensitive analytical assays, this study dissected ocular purine homeostasis as a complex and coordinated network. Along with previously characterized ecto-5'-nucleotidase/CD73 and adenylate kinase activities, other enzymes have been identified in vitreous fluids, including nucleoside triphosphate diphosphohydrolase (NTPDase), adenosine deaminase, and alkaline phosphatase. Strikingly, activities of soluble adenylate kinase, adenosine deaminase, ecto-5'-nucleotidase/CD73, and alkaline phosphatase, as well as intravitreal concentrations of ATP and ADP, were concurrently upregulated in patients suffering from diabetic retinopathy (DR) with non-clearing vitreous hemorrhage (VH), when compared to DR eyes without VH and control eyes operated due to macular hole or pucker. Additional histochemical analysis revealed selective distribution of key ecto-nucleotidases (NTPDase1/CD39, NTPDase2, ecto-5'-nucleotidase/CD73, and alkaline phosphatase) in the human sensory neuroretina and optic nerve head, and also in pathological neofibrovascular tissues surgically excised from patients with advanced proliferative DR. Collectively, these data provide evidence for specific hemorrhage-related shifts in purine homeostasis in DR eyes from the generation of anti-inflammatory adenosine towards a pro-inflammatory and pro-angiogenic ATP-regenerating phenotype. In the future, identifying the exact mechanisms by which a broad spectrum of soluble and membrane-bound enzymes coordinately regulates ocular purine levels and the further translation of purine-converting enzymes as potential therapeutic targets in the treatment of proliferative DR and other vitreoretinal diseases will be an area of intense interest. KEY MESSAGES: NTPDase, alkaline phosphatase, and adenosine deaminase circulate in human vitreous. Purinergic enzymes are up-regulated in diabetic eyes with vitreous hemorrhage. Soluble adenylate kinase maintains high ATP levels in diabetic retinopathy eyes. Ecto-nucleotidases are co-expressed in the human retina and optic nerve head. Alkaline phosphatase is expressed on neovascular tissues excised from diabetic eyes.

Background: Studies reporting renal and overall survival after acute kidney injury (AKI) treated exclusively with intermittent modalities of renal replacement therapy (IRRT) are rare. This study focused on outcomes of AKI patients treated with IRRT both in intensive care units (ICUs) and non-ICU dialysis units., Methods: This prospective observational study was carried on during a 5-month period in 17 ICUs and 17 non-ICUs. ICU and non-ICU patients (total n = 138; 65 ICU, 73 non-ICU) requiring RRT for AKI and chosen to receive IRRT were included. Patient and RRT characteristics as well as outcomes at 90 days, 1 year, and 3 years were registered., Results: Characteristics of ICU and non-ICU patients differed markedly. Pre-existing chronic kidney disease (CKD) and chronic heart failure were significantly more common among non-ICU patients. At 1 year, RRT dependence was significantly more common in the non-ICU group. At 3 years, there was no significant difference between the groups either in RRT dependence or mortality., Conclusion: Outcome of AKI patients treated with IRRT is dismal with regard to 3-year kidney function and mortality. Although pre-existing CKD emerged as a major risk factor for end-stage renal disease after AKI, the poor kidney survival was also seen in patients without prior CKD., (© 2018 The Acta Anaesthesiologica Scandinavica Founzdation. Published by John Wiley & Sons Ltd.)

Objectives: Acute kidney injury (AKI) occurs frequently after cardiac surgery and is associated with increased mortality. The Kidney Disease: Improving Global Outcomes (KDIGO) criteria for diagnosing AKI include creatinine and urine output values. However, the value of the latter is debated. The authors aimed to evaluate the incidence of AKI after cardiac surgery and the independent association of KDIGO criteria, especially the urine output criterion, and 2.5-year mortality., Design: Prospective, observational, cohort study., Setting: Single-center study in a university hospital., Participants: The study comprised 638 cardiac surgical patients from September 1, 2011, to June 20, 2012., Interventions: None., Measurements and Main Results: Hourly urine output, daily plasma creatinine, risk factors for AKI, and variables for EuroSCORE II were recorded. AKI occurred in 183 (28.7%) patients. Patients with AKI diagnosed using only urine output had higher 2.5-year mortality than did patients without AKI (9/53 [17.0%] v 23/455 [5.1%], p = 0.001). AKI was associated with mortality (hazard ratios [95% confidence intervals]: 3.3 [1.8-6.1] for KDIGO 1; 5.8 [2.7-12.1] for KDIGO 2; and 7.9 [3.5-17.6]) for KDIGO 3. KDIGO stages and AKI diagnosed using urine output were associated with mortality even after adjusting for mortality risk assessed using EuroSCORE II and risk factors for AKI., Conclusions: AKI diagnosed using only the urine output criterion without fulfilling the creatinine criterion and all stages of AKI were associated with long-term mortality. Preoperatively assessed mortality risk using EuroSCORE II did not predict this AKI-associated mortality., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The role of an episode of acute kidney injury (AKI) in long-term mortality among initial survivors of critical illness is controversial. We aimed to determine whether AKI is independently associated with decreased survival at 3 years among 30-day survivors of intensive care., Results: We included 2336 30-day survivors of intensive care enrolled in the FINNAKI study conducted in seventeen medical-surgical ICUs in Finland during a 5-month period in 2011-2012. The incidence of AKI, defined by the Kidney Disease: Improving Global Outcomes criteria, was 34.6%, and 192 (8.3%) commenced RRT. The 3-year mortality among AKI patients was 23.5% (95% CI 20.6-26.4%) compared to 18.9% (17.0-20.9%) of patients without AKI, p = 0.01. However, after adjustments using Cox proportional hazards regression, AKI was not associated with decreased 3-year survival (HR 1.05; CI 95% 0.86-1.27), whereas advanced age, poor pre-morbid functional performance, and presence of several comorbidities were. Additionally, we matched AKI patients to non-AKI patients 1:1 according to age, gender, presence of severe sepsis, and a propensity score to develop AKI. In the well-balanced matched cohort, 3-year mortality among AKI patients was 136 of 662 (20.5%; 17.5-23.6%) and among matched non-AKI patients 143 of 662 (21.6%; 18.5-24.7%), p = 0.687. Neither AKI nor RRT was associated with decreased survival at 3 years in the sensitivity analyses that excluded patients (1) with chronic kidney disease, (2) with AKI not commenced renal replacement therapy (RRT), and (3) with estimated pre-admission creatinine, chronic kidney disease, or AKI stage 1., Conclusion: AKI was not an independent risk factor for 3-year mortality among 30-day survivors. Increased 3-year mortality among patients with AKI who survive critical illness may not be related to AKI per se, but rather to advanced age and pre-existing comorbidities.

Background: CD73 dephosphorylates adenosine monophosphate to adenosine that is an anti-inflammatory molecule inhibiting immune activation and vascular leakage. Therefore, CD73 could be an interesting mediator both in sepsis and acute kidney injury (AKI). We aimed to explore the soluble CD73 (sCD73) levels and their evolution in critically ill patients with severe sepsis and, second, to scrutinize the potential association of sCD73 levels with AKI and 90-day mortality., Methods: This was a post-hoc laboratory analysis of the prospective, observational FINNAKI study conducted in 17 Finnish ICU during 5 months in 2011-2012. Plasma samples of 588 patients admitted with severe sepsis/shock or with developing severe sepsis were analyzed at 0h (ICU admission) and 24h, and additionally, on day 3 or day 5 from a subset of the patients., Results: The median [IQR] sCD73 levels at 0h were 5.11 [3.29-8.28] ng/mL and they decreased significantly from 0h to 4.14 [2.88-7.11] ng/mL at 24h, P<0.001. From 24h to Day 3 (n = 132) the sCD73 levels rose to 5.18 [2.98-8.83] ng/mL (P = 0.373) and from 24h to Day 5 (n = 224) to 5.52 [3.57-8.90] ng/mL (P<0.001). Patients with AKI had higher sCD73 values at 0h and at 24h compared to those without AKI. Non-survivors with severe sepsis, but not with septic shock, had higher CD73 levels at each time-point compared to survivors. After multivariable adjustments, sCD73 levels at 0h associated independently neither with the development of AKI nor 90-day mortality., Conclusions: Compared to normal population, the sCD73 levels were generally low at 0h, showed a decrease to 24h, and later an increase by day 5. The sCD73 levels do not seem useful in predicting the development of AKI or 90-day mortality among patients with severe sepsis or shock., Competing Interests: VP is a Steering Committee member for INTEREST study in ARDS patients. SJ, MH, MM and MS own stocks of Faron Pharmaceuticals. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The other authors declare no competing interests.

Purpose: Current reports on acute kidney injury (AKI) in the intensive care unit (ICU) show wide variation in occurrence rate and are limited by study biases such as use of incomplete AKI definition, selected cohorts, or retrospective design. Our aim was to prospectively investigate the occurrence and outcomes of AKI in ICU patients., Methods: The Acute Kidney Injury-Epidemiologic Prospective Investigation (AKI-EPI) study was an international cross-sectional study performed in 97 centers on patients during the first week of ICU admission. We measured AKI by Kidney Disease: Improving Global Outcomes (KDIGO) criteria, and outcomes at hospital discharge., Results: A total of 1032 ICU patients out of 1802 [57.3%; 95% confidence interval (CI) 55.0-59.6] had AKI. Increasing AKI severity was associated with hospital mortality when adjusted for other variables; odds ratio of stage 1 = 1.679 (95% CI 0.890-3.169; p = 0.109), stage 2 = 2.945 (95% CI 1.382-6.276; p = 0.005), and stage 3 = 6.884 (95% CI 3.876-12.228; p < 0.001). Risk-adjusted rates of AKI and mortality were similar across the world. Patients developing AKI had worse kidney function at hospital discharge with estimated glomerular filtration rate less than 60 mL/min/1.73 m(2) in 47.7% (95% CI 43.6-51.7) versus 14.8% (95% CI 11.9-18.2) in those without AKI, p < 0.001., Conclusions: This is the first multinational cross-sectional study on the epidemiology of AKI in ICU patients using the complete KDIGO criteria. We found that AKI occurred in more than half of ICU patients. Increasing AKI severity was associated with increased mortality, and AKI patients had worse renal function at the time of hospital discharge. Adjusted risks for AKI and mortality were similar across different continents and regions.

Background: Interleukin-18 (IL-18) is a pro-inflammatory protein, which mediates ischaemic tubular injury, and has been suggested to be a sensitive and specific biomarker for acute kidney injury (AKI). The predictive value of IL-18 in the diagnosis, evolution, and outcome of AKI in critically ill patients is still unclear., Methods: We measured urine IL-18 from critically ill patients at intensive care unit (ICU) admission and 24 h. We evaluated the association of IL-18 with developing new AKI, renal replacement therapy (RRT), and 90-day mortality. We calculated areas under receiver operating characteristics curves (AUCs), best cut-off values, and positive likelihood ratios (LR+) for IL-18 concerning these endpoints. Additionally, we compared the predictive value of IL-18 at ICU admission to that of urine neutrophil gelatinase-associated lipocalin (NGAL)., Results: In this study population of 1439 patients the highest urine IL-18 during the first 24 h in the ICU associated with the development of AKI with an AUC [95% confidence interval (CI)] of 0.586 (0.546-0.627) and with the development of Stage 3 AKI with an AUC (95% CI) of 0.667 (0.591-0.774). IL-18 predicted the initiation of RRT with an AUC (95% CI) of 0.655 (0.572-0.739), and 90-day mortality with an AUC (95% CI) of 0.536 (0.497-0.574)., Conclusions: IL-18 had poor-to-moderate ability to predict AKI, RRT, or 90-day mortality in this large cohort of critically ill patients. Thus, it should be used with caution for diagnostic or predictive purposes in the critically ill., (© The Author 2014. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

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

Objective: Acute kidney injury in the critically ill is an independent risk factor for adverse outcome. The magnitude of the impact of acute kidney injury on outcome, however, is still unclear. This study aimed to estimate the excess mortality attributable to acute kidney injury., Design: We performed a sequentially matched analysis according to the day of acute kidney injury diagnosis after ICU admission. Patients with acute kidney injury and those without acute kidney injury were matched according to age, sex, ICU admission diagnosis, Simplified Acute Physiology Score II without renal and age components, and the propensity to develop acute kidney injury at each of the four matching time points., Setting: Cohort of 16 participating ICUs from the prospective Finnish Acute Kidney Injury study., Patients: Cohort of 2,719 consecutive patients with either emergency admission or elective postsurgical patients with an expected ICU stay greater than 24 hours., Interventions: None., Measurements and Main Results: Of the 2,719 patients included in the study, acute kidney injury developed in 1,081 patients (39.8%) according to the Kidney Disease: Improving Global Outcomes-definition during ICU treatment on days 1-5. Of these, 477 patients were successfully matched to 477 patients who did not develop acute kidney injury. The 90-day mortality of the matched patients with acute kidney injury was 125 of 477 (26.2%) compared with 84 of 477 (17.6%) for their matched controls without acute kidney injury. Thus, the absolute excess 90-day mortality attributable to acute kidney injury was estimated at 8.6 percentage points (95% CI, 2.6-17.6 percentage points). The population attributable risk (95% CI) of 90-day mortality associated with acute kidney injury was 19.6% (10.3-34.1%)., Conclusions: In general ICU patients, the absolute excess 90-day mortality statistically attributable to acute kidney injury is substantial (8.6%), and the population attributable risk was nearly 20%. Our findings are useful in planning suitably powered future clinical trials to prevent and treat acute kidney injury in critically ill patients.

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.

Introduction: Knowledge of the association of hemodynamics with progression of septic acute kidney injury (AKI) is limited. However, some recent data suggest that mean arterial pressure (MAP) exceeding current guidelines (60-65 mmHg) may be needed to prevent AKI. We hypothesized that higher MAP during the first 24 hours in the intensive care unit (ICU), would be associated with a lower risk of progression of AKI in patients with severe sepsis., Methods: We identified 423 patients with severe sepsis and electronically recorded continuous hemodynamic data in the prospective observational FINNAKI study. The primary endpoint was progression of AKI within the first 5 days of ICU admission defined as new onset or worsening of AKI by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We evaluated the association of hemodynamic variables with this endpoint. We included 53724 10-minute medians of MAP in the analysis. We analysed the ability of time-adjusted MAP to predict progression of AKI by receiver operating characteristic (ROC) analysis., Results: Of 423 patients, 153 (36.2%) had progression of AKI. Patients with progression of AKI had significantly lower time-adjusted MAP, 74.4 mmHg [68.3-80.8], than those without progression, 78.6 mmHg [72.9-85.4], P < 0.001. A cut-off value of 73 mmHg for time-adjusted MAP best predicted the progression of AKI. Chronic kidney disease, higher lactate, higher dose of furosemide, use of dobutamine and time-adjusted MAP below 73 mmHg were independent predictors of progression of AKI., Conclusions: The findings of this large prospective multicenter observational study suggest that hypotensive episodes (MAP under 73 mmHg) are associated with progression of AKI in critically ill patients with severe sepsis.

Introduction: Acute kidney injury (AKI) has high incidence among the critically ill and associates with dismal outcome. Not only the long-term survival, but also the quality of life (QOL) of patients with AKI is relevant due to substantial burden of care regarding these patients. We aimed to study the long-term outcome and QOL of patients with AKI treated in intensive care units., Methods: We conducted a predefined six-month follow-up of adult intensive care unit (ICU) patients from the prospective, observational, multi-centre FINNAKI study. We evaluated the QOL of survivors with the EuroQol (EQ-5D) questionnaire. We included all participating sites with at least 70% rate of QOL measurements in the analysis., Results: Of the 1,568 study patients, 635 (40.5%, 95% confidence interval (CI) 38.0-43.0%) had AKI according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Of the 635 AKI patients, 224 (35.3%), as compared to 154/933 (16.5%) patients without AKI, died within six months. Of the 1,190 survivors, 959 (80.6%) answered the EQ-5D questionnaire at six months. The QOL (median with Interquartile range, IQR) measured with the EQ-5D index and compared to age- and sex-matched general population was: 0.676 (0.520-1.00) versus 0.826 (0.812-0.859) for AKI patients, and 0.690 (0.533-1.00) versus 0.845 (0.812-0.882) for patients without AKI (P <0.001 in both). The EQ-5D at the time of ICU admission was available for 774 (80.7%) of the six-month respondents. We detected a mean increase of 0.017 for non-AKI and of 0.024 for AKI patients in the EQ-5D index (P = 0.728). The EQ-5D visual analogue scores (median with IQR) of patients with AKI (70 (50-83)) and patients without AKI (75 (60-87)) were not different from the age- and sex-matched general population (69 (68-73) and 70 (68-77))., Conclusions: The health-related quality of life of patients with and without AKI was already lower on ICU admission than that of the age- and sex-matched general population, and did not change significantly during critical illness. Patients with and without AKI rate their subjective health to be as good as age and sex-matched general population despite statistically significantly lower QOL indexes measured by EQ-5D.

Objective: Plasma neutrophil gelatinase-associated lipocalin (pNGAL) has been introduced as an early and sensitive biomarker of acute kidney injury (AKI), with an increased risk for renal replacement therapy (RRT) and adverse outcome in selected critically ill patient groups. Acute respiratory failure is the most common organ dysfunction in critically ill patients with an increased risk for AKI. Accordingly, we hypothesized that pNGAL would independently predict adverse outcome in a heterogeneous group of critically ill adult patients with acute respiratory failure., Design and Setting: Prospective, multi-centre study in 25 Finnish intensive care units., Patients and Methods: pNGAL was measured from critically ill patients with acute respiratory failure. We evaluated the predictive value of pNGAL for RRT, and hospital and 90-day mortality first separately, second in addition to the Simplified Acute Physiology Score (SAPS II), and third to RIFLE (Risk, Injury, Failure, Loss, End-Stage Renal Disease) AKI classification. Additionally, we assessed the factors associated with pNGAL by linear regression analysis., Interventions: None., Measurements and Main Results: We included 369 patients. Median (interquartile range) baseline pNGAL was 169 (92-370) ng/ml. The areas under receiver operating characteristic curves of baseline pNGAL were as follows: 0.733 [95% confidence interval (CI) 0.656-0.810] for RRT, 0.627 (95% CI 0.561-0.693) for hospital, and 0.582 (95% CI 0.520-0.645) for 90-day mortality. Present infection, baseline creatinine, operative status, and pancreatitis were independently associated with baseline pNGAL., Conclusions: Baseline pNGAL gives no additional value into prediction of hospital and 90-day mortality compared with RIFLE or SAPS II, and has only moderate predictive power regarding RRT in critically ill adult patients with acute respiratory failure., (© 2013 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Severe sepsis is one of the leading causes of acute kidney injury (AKI). Patients with sepsis-associated AKI demonstrate high-hospital mortality. We evaluated the incidence of severe sepsis-associated AKI and its association with outcome in intensive care units (ICUs) in Finland., Methods: This was a predetermined sub-study of the prospective, observational, multicentre FINNAKI study conducted in 17 ICUs during 1 September 2011 and 1 February 2012. All emergency ICU admissions and elective admissions exceeding 24 hours in the ICU were screened for presence of severe sepsis and AKI up to 5 days in ICU. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria and severe sepsis according to the American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) criteria., Results: Of the 2901 included patients, severe sepsis was diagnosed in 918 (31.6%, 95% confidence interval [CI] 29.9-33.4%) patients. Of these 918 patients, 488 (53.2% [95% CI 49.9-56.5%]) had AKI. The 90-day mortality rate was 38.1% (95% CI 33.7-42.5%) for severe sepsis patients with AKI and 24.7% (95% CI 20.5-28.8%) for those without AKI. After adjusting for covariates, KDIGO stage 3 AKI was associated with an increased risk for 90-day mortality with an adjusted odds ratio (OR) of 1.94 (95% CI 1.28-2.94), but stages 1 and 2 were not., Conclusions: More than half of the patients with severe sepsis had AKI according to the KDIGO classification, and AKI stage 3 was independently associated with 90-day mortality., (© 2013 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: We aimed to determine the incidence, risk factors and outcome of acute kidney injury (AKI) in Finnish ICUs., Methods: This prospective, observational, multi-centre study comprised adult emergency admissions and elective patients whose stay exceeded 24 h during a 5-month period in 17 Finnish ICUs. We defined AKI first by the Acute Kidney Injury Network (AKIN) criteria supplemented with a baseline creatinine and second with the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We screened the patients' AKI status and risk factors for up to 5 days., Results: We included 2,901 patients. The incidence (95 % confidence interval) of AKI was 39.3 % (37.5-41.1 %). The incidence was 17.2 % (15.8-18.6 %) for stage 1, 8.0 % (7.0-9.0 %) for stage 2 and 14.1 % (12.8-15.4 %) for stage 3 AKI. Of the 2,901 patients 296 [10.2 % (9.1-11.3 %)] received renal replacement therapy. We received an identical classification with the new KDIGO criteria. The population-based incidence (95 % CI) of ICU-treated AKI was 746 (717-774) per million population per year (reference population: 3,671,143, i.e. 85 % of the Finnish adult population). In logistic regression, pre-ICU hypovolaemia, diuretics, colloids and chronic kidney disease were independent risk factors for AKI. Hospital mortality (95 % CI) for AKI patients was 25.6 % (23.0-28.2 %) and the 90-day mortality for AKI patients was 33.7 % (30.9-36.5 %). All AKIN stages were independently associated with 90-day mortality., Conclusions: The incidence of AKI in the critically ill in Finland was comparable to previous large multi-centre ICU studies. Hospital mortality (26 %) in AKI patients appeared comparable to or lower than in other studies.

Introduction: Positive fluid balance has been associated with an increased risk for mortality in critically ill patients with acute kidney injury with or without renal replacement therapy (RRT). Data on fluid accumulation prior to RRT initiation and mortality are limited. We aimed to study the association between fluid accumulation at RRT initiation and 90-day mortality., Methods: We conducted a prospective, multicenter, observational cohort study in 17 Finnish intensive care units (ICUs) during a five-month period. We collected data on patient characteristics, RRT timing, and parameters at RRT initiation. We studied the association of parameters at RRT initiation, including fluid overload (defined as cumulative fluid accumulation > 10% of baseline weight) with 90-day mortality., Results: We included 296 RRT-treated critically ill patients. Of 283 patients with complete data on fluid balance, 76 (26.9%) patients had fluid overload. The median (interquartile range) time from ICU admission to RRT initiation was 14 (3.3 to 41.5) hours. The 90-day mortality rate of the whole cohort was 116 of 296 (39.2%; 95% confidence interval 38.6 to 39.8%). The crude 90-day mortality of patients with or without fluid overload was 45 of 76 (59.2%) vs. 65 of 207 (31.4%), P < 0.001. In logistic regression, fluid overload was associated with an increased risk for 90-day mortality (odds ratio 2.6) after adjusting for disease severity, time of RRT initiation, initial RRT modality, and sepsis. Of the 168 survivors with data on RRT use at 90 days, 34 (18.9%, 95% CI 13.2 to 24.6%) were still dependent on RRT., Conclusions: Patients with fluid overload at RRT initiation had twice as high crude 90-day mortality compared to those without. Fluid overload was associated with increased risk for 90-day mortality even after adjustments.

In cases with severe anemia and significant hemorrhages, intensive care of a person refusing blood products is challenging. Owing to ethical aspects associated with conviction, treatment is easily subject to prejudice. Research data on this particular topic are insufficient, thus, treatment decisions are based on case reports. Treatment modalities that can be approved by the patients should be scrutinized as early as possible and individuality taken into consideration. Epoetin, iron and vitamins are readily started. Attempts have to be made to guarantee adequate blood volume, oxygen transport and hemostasis. Mechanical ventilation, high fraction of inspired oxygen and sedation are utilized as supportive treatments, when severe anemia is improving.

Introduction: Concentrations of plasma cell-free DNA are increased in various diseases and have shown some prognostic value in many patient groups, including critically ill patients. Pathophysiological processes behind the need for mechanical ventilation and the treatment itself could raise plasma levels of cell-free DNA. We evaluated levels of plasma cell-free DNA and their prognostic value in patients needing mechanical ventilation., Methods: We studied prospectively 580 mechanically ventilated critically ill patients. Blood samples were taken at study admission (Day 0) and on Day 2. Plasma cell-free DNA concentrations were measured by real-time quantitative PCR assay for the β-globin gene and are expressed as genome equivalents (GE)/ml., Results: Median (interquartile range, IQR) plasma cell-free DNA concentration was 11,853 GE/ml (5,304 to 24,620 GE/mL) at study admission, and 11,610 GE/mL (6,411 to 21,558 GE/mL) on Day 2. Concentrations at admission were significantly higher in 90-day non-survivors than survivors, 16,936 GE/mL (7,262 to 46,866 GE/mL) versus 10,026 GE/mL (4,870 to 19,820 GE/mL), P < 0.001. In a multivariate logistic regression analysis plasma cell-free DNA concentration over 16,000 GE/ml remained an independent predictor of 90-day mortality (adjusted odds ratio 2.16, 95% confidence interval CI 1.37 to 3.40). Positive likelihood ratio of plasma cell-free DNA at admission for the prediction of 90-day mortality was 1.72 (95% CI 1.40 to 2.11)., Conclusions: Plasma levels of cell-free DNA were significantly higher in non-survivors than survivors. Plasma DNA level at baseline was an independent predictor of 90-day mortality. However, its clinical benefit as a prognostic marker seems to be limited.

Horner's syndrome is a rare complication following insertion of a central catheter into the internal jugular vein (IJV). A 5-year-old boy, who developed unilateral Horner's syndrome postoperatively following IJV cannulation, is presented. The Horner's syndrome resolved completely after 5 months.

Purpose of Review: An increasing number of day-case surgical patients is challenging the presently used methods of anaesthesia: reliable surgical anaesthesia should be fast, with rapid recovery and minimal side effects. To compete with modern ambulatory general anaesthesia a knowledge of special spinal anaesthesia techniques is essential. This review brings together important issues concerning the spinal technique, anaesthetic agents and benefits as well as the disadvantages of spinal anaesthesia in outpatients., Recent Findings: For surgical procedures in one lower limb, a low dose of hyperbaric bupivacaine with standardized spinal anaesthesia technique produces a reliable block, with low incidence of side effects and home-readiness equal to spinal anaesthesia with lidocaine (50 mg) or general anaesthesia (desflurane), whereas ropivacaine has not shown benefits over spinal anaesthesia with bupivacaine. 'Walk-in, walk-out' spinals with an extremely low dose of lidocaine and opioids for gynaecological laparoscopy created the concept of selective spinal anaesthesia. Reintroduction of chloroprocaine may provide a solution for bilateral, short-acting spinal anaesthesia in the future., Summary: To produce reliable spinal anaesthesia with a reasonable recovery time it is essential to understand the factors affecting the spread of spinal block and to choose the optimal drug and adequate dose for specific surgical procedures.

Background: We tested the hypothesis that selective spinal anesthesia for ambulatory knee arthroscopy can be accomplished with a small dose of bupivacaine at the L3/4 interspace with or without a head-down tilt of 5 degrees when the patients were in the lateral decubitus position., Methods: In this double-blind study, 123 patients were randomly allocated to receive spinal anesthesia with 4 mg of hyperbaric bupivacaine inserted at either the L2/3 interspace, while the vertebral column was kept horizontal (L2/3 group), or the L3/4 level, with the vertebral column horizontal (L3/4H) or tilted 5 degrees head-down (L3/4T). At 7 min, an additional head down tilt was used in all groups if the sensory block was inadequate., Results: In the L3/4T group the sensory block (Th8) reached a significantly higher level 30 min after spinal injection, compared with both the L2/3 (Th10) and L3/4H (Th11) groups. In the L3/4H group, 39% of the patients needed an additional tilt for 3 min at 7 min, compared with 10% (P=0.004) in the L3/4T group. Sacral block developed later and recovered faster (P<0.05) in the L3/4T group compared to the L3/4H group. Home-readiness was achieved equally fast in all groups., Conclusion: When producing selective spinal anesthesia, the posture of the vertebral column is a major determinant of both sensory and motor segments to be blocked. A 4-mg dose of hyperbaric bupivacaine at the L3/4 interspace with a 5 degrees head-down tilt of the vertebral column for 6 min is recommended for knee arthroscopy.

In this randomized and controlled trial, 64 adult ambulatory knee arthroscopy patients received either selective spinal anesthesia (SSA) with 4 mg of hyperbaric bupivacaine or general anesthesia (GA) with desflurane. We conducted the study to determine whether SSA with small-dose bupivacaine provides equal fast-tracking possibilities, a shorter stay in the postanesthesia care unit, and earlier discharge home compared with GA with desflurane. Patients with a high risk for postoperative nausea and vomiting received prophylaxis in the GA group. No difference was seen in the fast-tracking possibilities or time in the postanesthesia care unit between the groups. Home readiness was achieved after 114 (31-174) and 129 (28-245) min (NS) in the SSA and GA groups, respectively. In the hospital, the pain scores were significantly (P < 0.001) lower in the SSA group compared with the GA group and the need for postoperative opioids was significantly (P = 0.008) larger after GA. The incidence of postoperative nausea and vomiting was 0% versus 19% in the SSA and GA groups (P = 0.024), respectively. We conclude that for outpatients undergoing knee arthroscopy, SSA with hyperbaric bupivacaine provides equal recovery times with less frequent side effects compared with GA with desflurane.

Background: Addition of an opioid to low-dose spinal anesthesia with bupivacaine improves the quality and success of anesthesia. However, the intrathecal fentanyl-induced pruritus is as high as 75%. We hypothesized that after administration of 4 or 8 mg of prophylactic IV ondansetron, the incidence of pruritus induced by low-dose intrathecal fentanyl would be significantly lower than after placebo., Methods: In this double-blind study, 90 outpatients undergoing knee arthroscopy received 3 mg of bupivacaine + 10 micro g fentanyl intrathecally. Before spinal puncture, the patients received randomly either saline (P) or ondansetron 4 mg (O4) or 8 mg (O8) IV. They were asked about pruritus frequently, and they estimated its severity on a scale of 0-10., Results: There was no difference in the incidence of pruritus between the three groups: pruritus occurred in 17 (57%), in 21 (75%) and in 19 patients (70%) in P, O4 and O8 groups, respectively. The pruritus was mostly mild. Four patients in the placebo group, three in the O4 and four patients in the O8 groups considered it severe. One patient in each group requested treatment for pruritus; after IV naloxone their pruritus was relieved. Neither time to pruritus nor duration of pruritus differed between the groups. One patient in each group developed a long-lasting (>10 h) pruritus., Conclusions: After prophylactic administration of 4 or 8 mg of ondansetron IV, the incidence, duration and severity of pruritus were similar to placebo. Ondansetron does not prevent pruritus induced by low-dose intrathecal fentanyl.

The aim of this study was to investigate the potential of computerized nuclear morphometry and DNA image cytometry in characterizing the apocrine change of mammary epithelium in fine-needle aspiration biopsy (FNAB). The effect of two different sample processing techniques on the results was also studied. Mean nuclear areas in air-dried smears ranged from 59.0 microm2 to 151.0 microm2 and in ethanol-fixed samples from 32.3 microm2 to 63.4 microm2. The DNA histograms of apocrine cells usually showed a dominant peak in the diploid region. In some cases the mode of the peak was slightly shifted to the right or left in respect to the control peak. One case had a tetraploid cell population, suggesting atypical apocrine change. After histological investigation this case was diagnosed as infiltrating carcinoma. The patient had earlier been treated with x-ray irradiation for a mediastinal lymphoma. Findings of nuclear morphometry and DNA cytometry in apocrine metaplasia are here described in a systematic study for the first time. The data suggest that these methods may help in distinguishing premalignant and malignant apocrine lesions from typical apocrine metaplasia of mammary epithelial cells.

Background: Combination of local anesthetic and opioid enables the use of less spinal anesthetic and increases the success of anesthesia. Intrathecal opioid does not prolong motor recovery and thus should not delay discharge home. We hypothesized that 3 mg of hyperbaric bupivacaine with 10 microg of fentanyl permits fast-tracking or shorter stay in post anesthesia care unit (PACU), and earlier discharge home, compared with 4 mg of hyperbaric bupivacaine., Methods: In this double-blind study, 100 outpatients undergoing knee arthroscopy received randomly either 4 mg of bupivacaine (B4) or 3 mg of bupivacaine + 10 microg fentanyl (B3F) intrathecally. The volume of 0.8 ml was injected at the L2/3 interspace over a 2-min period. A lateral decubitus position was maintained for 10 min. The sensory block was recorded by using thermal stimuli, and motor block was assessed according to a modified Bromage scale. Fast-tracking criteria were complete recovery of motor block, sensory block Th12 or lower and stable vital signs., Results: One block (1%) failed. Motor recovery was faster in the B3F group: 60% of the patients recovered in 80 min or less compared with 28% in group B4 (P = 0.002). The PACU-time was shorter: 36 (10-103) vs. 55 (10-140) min, respectively (P = 0.005). Seventeen (B3F) vs. nine patients (B4) could bypass PACU (NS). Time to discharge home was similar in both groups. In the B3F group, 75% of the patients developed pruritus., Conclusion: Both solutions produced reliable spinal anesthesia for outpatient knee arthroscopy. The PACU-time was shorter in the bupivacaine-fentanyl group, but both groups reached home-readiness equally.

Implications: A low-dose (4 mg), low-volume (0.8 mL), low-flow (2 min) technique with hyperbaric bupivacaine toward the dependent side oriented injection and maintenance of the lateral decubitus position for 10 min produced selective spinal anesthesia with rapid recession of motor block and early discharge home.

Objective: To evaluate the origin and identification of mysterious particles in Papanicolaou smears from healthy, asymptomatic women participating in a local mass screening program., Study Design: The material consisted of 16,000 cerricovaginal smears studied at the cytology laboratory of Pathology Laboratory of South-Western Finland Ltd. Unidentified particles were found in four apparently independent smears. All the slides were rescreened, but no further positive cases were found., Results: Several swab samples were collected from the investigation room, but all were negative. Attempts at identification included numerous consultations. A telepathology consultation with the Cellular Division, Armed Forces Institute of Pathology, Washington, D.C., U.S.A., was conducted. Another teleconsultation with the reference laboratoryfor intestinal parasites in Iceland was conducted. Finally, the Aerobiology Unit, University of Turku, was consulted. The aerobiologist suggested that the particles were most probably summer spores of birch rust fungus (Melampsoridium betulinum). To confirm this we obtained a reference specimen of the fungus from the herbarium at the University of Turku. The morphology of the spore particles was identical to that in the cervicovaginal smears, proving that the smears were contaminated with birch rust fungus spores., Conclusion: Birch rust is ubiqutitous in Finland. Outside the hospital window there is a wide lawn behind which, at a distance of 70 m, there is a forest of birch trees. It is most likely that the rust spores flew in through the open window, to settle down on the surface of material that was used in sample taking. Airborne dust may cause misleading and surprising artefacts. Protection of specimens and instruments against dust should minimize the problem.

Cortical evoked potentials were measured to visual, auditory and somatosensory stimuli in 20 subjects with serious neurodevelopmental impairments due to various etiologies. The results were compared with behavioral observations to find out whether the absence/presence of the responses corresponded to the level of social functioning. No cortical evoked potentials were elicited in two subjects, responses to the stimulation of one modality were missing in three subjects (retinal b-waves and brainstem auditory and somatosensory evoked potentials were, however, preserved in them). No communicative behavior was observed in subjects with absent responses. Ten subjects had marked deviations in the evoked potentials, the behavioral observations in them, ranging from no communication to sentenced speech. Five subjects had normal response patterns and they showed a great variety of communicative skills, including speech. The results support the view that bilateral loss of cortical somatosensory, visual, and auditory evoked potentials is a sign of loss of neural substrates of communication.