Red blood cell transfusion in southern Finland from 2011 to 2016: a quality audit.

OBJECTIVES: The current trends in RBC use and pre- and post-transfusion Hb levels were analysed to improve practice and to provide international comparison. BACKGROUND: Indications for RBC transfusion have changed with growing scientific evidence. The lowest acceptable haemoglobin (Hb) level has decreased, and transfusing single units instead of pairs has become the new standard. Evidence-based guidelines and patient blood management (PBM) programmes increase clinician awareness of rational RBC use. In Finland, however, no formal PBM programme has been established to date. METHODS: The study was registry-based, retrospective and observational. All RBC transfusions for adult patients from 2011 to 2016 in the southern region of Finland were analysed. RESULTS: RBC usage decreased from 34·9 to 27·5 units per 1000 population (P < 0·001). The percentage of single-unit transfusions increased from 57·9 to 66·7%, and the median pre- and post-transfusion Hb levels decreased from 8·4 to 8·2 g dL-1 (P < 0·001) and 9·9 to 9·6 g dL-1 (P < 0·001), respectively. The proportion of transfusions with pre-transfusion Hb ≥ 9·0 g dL-1 decreased during the study period but remained high, being 29·5% in 2011 and still 25·2% in 2016. CONCLUSIONS: Consumption of RBCs has decreased despite aging population and increasing healthcare performance demands. The results indicate more rational and evidence-based RBC use. Nevertheless, the transfusion rate and pre- and post-transfusion Hb are still sufficiently high to enable more restrictive transfusion practice.

Signalling Profiles of Blood Leucocytes in Sepsis and in Acute Pancreatitis in Relation to Disease Severity.

Intracellular signalling in blood leucocytes shows multiple aberrations in acute pancreatitis (AP) complicated by organ dysfunction (OD). We studied whether the aberrations associate with severity of AP and occur in sepsis complicated by OD. The study comprises 14 sepsis patients (11 with shock), 18 AP patients (nine mild; six moderately severe; three severe) and 28 healthy volunteers. Within 48 h after admission to hospital, phosphorylation of nuclear factor-ĸB (NF-ĸB), signal transducers and activators of transcription (STATs) 1,3, and extracellular signal-regulated kinases 1/2 were measured from stimulated or non-stimulated leucocytes using phosphospecific whole blood flow cytometry. In sepsis, as compared with healthy subjects, phosphorylated NF-ĸB levels of monocytes promoted by bacterial lipopolysaccharides, tumour necrosis factor or Escherichia coli cells were lower (P < 0.001 for all), pSTAT1 levels of monocytes promoted by IL-6 were lower (P < 0.05 for all), and STAT3 was constitutively phosphorylated in monocytes, neutrophils and lymphocytes (P < 0.001 for all). In AP, severity was associated with proportions of pSTAT1-positive monocytes and lymphocytes promoted by IL-6 (P < 0.01 for both), constitutive STAT3 phosphorylation in neutrophils (P < 0.05), but not with any of the pNF-ĸB levels. Monocyte pSTAT3 fluorescence intensity, promoted by IL-6, was lower in sepsis and AP patients with OD than in AP patients without OD (P < 0.001). Collectively, signalling aberrations in sepsis with OD mimic those described previously in AP with OD. Possibility that aberrations in STAT1 and STAT3 pathways provide novel markers predicting evolution of OD warrants studies including patients presenting without OD but developing it during follow-up.

Assessment of plasma endostatin to predict acute kidney injury in critically ill patients.

BACKGROUND: We evaluated whether plasma endostatin predicts acute kidney injury (AKI), need for renal replacement therapy (RRT), or death. METHODS: Prospective, observational, multicenter study from 1 September 2011 to 1 February 2012 with data from 17 intensive care units (ICUs) in Finland. RESULTS: A total of 1112 patients were analyzed. We measured plasma endostatin within 2 h of ICU admission. Early AKI (KDIGO stage within 12 h of ICU admission) was found in 20% of the cohort, and 18% developed late AKI (KDIGO criteria > 12 h from ICU admission). Median (IQR) admission endostatin was higher in the early AKI group, 29 (19.1, 41.9) ng/ml as compared to 22.4 (16.1, 30.1) ng/ml for the late AKI group, and 18 (14.0, 23.6) ng/ml for non-AKI patients (P < 0.001). Endostatin level increased with increasing KDIGO stage. Significantly higher endostatin levels were found in patients with sepsis as compared to those without. Predictive properties for AKI, RRT, and mortality were low with corresponding areas under the receiver operating characteristic curve (AUC) of 0.62, 0.67, and 0.59. Sensitivity analyses among patients with chronic kidney disease or sepsis did not improve the predictive ability of endostatin. Adding endostatin to a clinical AKI prediction model (illness severity score, urine output, and age) insignificantly changed the AUC from 0.67 to 0.70 (P = 0.14). CONCLUSIONS: Endostatin increases with AKI severity but has limited value as a predictor of AKI, RRT and 90-day mortality in patients admitted to ICU. Moreover, endostatin does not improve AKI risk prediction when added to a clinical risk model.

Association of plasma chloride values with acute kidney injury in the critically ill - a prospective observational study.

BACKGROUND: Chloride-rich fluids have been found to associate with an increased risk for acute kidney injury (AKI) among intensive care unit (ICU) patients. Studies evaluating the association of plasma chloride (Cl) with the development of AKI are few. We hypothesized that higher plasma Cl is associated with an increased risk for the development of AKI. METHODS: In this sub-study of the prospective FINNAKI study, we analyzed Cl values measured during ICU stay in two ICUs at a tertiary center including 445 patients. We calculated time-weighted mean values within the first 24 h in ICU for plasma Cl (ClTWM 24 ). We analyzed the association of ClTWM 24 primarily with the development of AKI, and secondarily with 90-day mortality. RESULTS: Based on the first measured Cl value, 350 of 445 patients [78.7 (95 CI, 74.8-82.5)] had hyperchloremia (P-Cl > 106 mmol/l) and 48 [10.8 (95 CI, 7.9-13.7)] severe hyperchloremia (P-Cl > 114 mmol/l). Altogether 217 of 445 [48.8% (95% CI 44.2-53.4%)] patients developed AKI. Of these 217, AKI was diagnosed in 62 (28.6%) after 24 h from ICU admission and were included in the analysis regarding development of AKI. ClTWM 24 was associated with an increased risk for the development of AKI (OR1.099; 1.003-1.205) after multivariable adjustments. According to ClTWM 24 , no difference in 90-day mortality between severely hyperchloremic patients and others existed. CONCLUSIONS: More than three of four critically ill patients had hyperchloremia and 1 of 10 had its severe form. Higher time-weighted mean chloride was independently associated with an increased risk for AKI.

Predictive value of urine interleukin-18 in the evolution and outcome of acute kidney injury in critically ill adult patients.

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.

Systemic matrix metalloproteinase-8 and tissue inhibitor of metalloproteinases-1 levels in severe sepsis-associated coagulopathy.

BACKGROUND: Matrix metalloproteinase-8 (MMP-8) and tissue inhibitor of metalloproteinases-1 (TIMP-1) have recently been suggested to be involved in coagulation process. Our objectives were to observe systemic MMP-8 and TIMP-1 levels in patients with severe sepsis with or without disseminated intravascular coagulation (DIC) and to study their relationship with coagulation markers over time. METHODS: Our prospective pilot study included 22 patients with severe sepsis, nine (41%) of whom had overt DIC. We analysed MMP-8 and TIMP-1 serum concentrations by time-resolved immunofluorometric and enzyme-linked immunosorbent assays, respectively, on days 1, 2, 4 and 7 after the intensive care unit admission. Traditional coagulation tests were taken at the same time points. The results were compared between patients with and without DIC. Blood samples from 10 healthy volunteers were used to demonstrate normal levels. RESULTS: Both patient groups had elevated levels of MMP-8 and TIMP-1 as compared with healthy controls. TIMP-1 concentration was almost twofold in DIC patients compared with those without DIC on the first 2 days. MMP-8 was elevated only on day 2. TIMP-1 correlated positively with the severity of coagulation disturbance and with disease severity scores. MMP-8 correlated negatively only with platelet count. CONCLUSION: In this first human study, we could show that TIMP-1 is elevated in the early phase of sepsis-induced overt DIC, and it correlates both with degree of coagulopathy and disease severity. These findings suggest that TIMP-1 may play a role in the pathogenesis of DIC in septic patients.

Fluid responsiveness predicted by elevation of PEEP in patients with septic shock.

BACKGROUND: The assessment of whether a patient is fluid responsive can be difficult in clinical practice. Invasive filling pressures are inadequate indicators of preload and fluid responsiveness in critically ill patients. Dynamic indices may be unreliable in clinical practice because of arrhythmias or spontaneous breathing efforts. Elevation of positive end-expiratory pressure (PEEP) causes cardiorespiratory interactions, which may produce signs of hypovolaemia. Our aim was to assess whether haemodynamic changes during a short elevation of PEEP would predict fluid responsiveness in patients with septic shock. METHODS: We performed a prospective observational study in 20 patients with septic shock on mechanical ventilation. We assessed the following changes in haemodynamic variables during a temporary elevation of PEEP from 10 cm H2O to 20 cm H2O during an end-expiratory pause: mean arterial pressure (MAP), systolic arterial pressure, pulse pressure, central venous pressure, pulmonary artery occlusion pressure, left ventricular end diastolic area and aortic velocity-time integral. We defined fluid responsiveness as an increase in cardiac output of 15% to a subsequent fluid challenge. RESULTS: Decrease in MAP related to elevation of PEEP predicted fluid responsiveness (P = 0.003). The best cut-off value of ΔMAP for clinical use was -8%, with a negative predictive value for fluid responsiveness of 100%. CONCLUSION: In patients with septic shock, the absence of decrease in MAP during an elevation of PEEP may be used to identify patients who will not increase their cardiac output in response to fluid challenge.

Association between inotrope treatment and 90-day mortality in patients with septic shock.

BACKGROUND: Administration of inotropes in septic patients with low cardiac output or low central/mixed venous saturation is recommended in current guidelines. However, the impact of inotrope use on the outcome of these patients is controversial. We aimed to analyse the association of inotrope treatment with 90-day mortality. METHODS: Data from 420 consecutive patients with septic shock were retrospectively collected from the intensive care unit (ICU) data management system. Factors associated with inotrope treatment were assessed. The association of 90-day mortality with inotrope treatment was first analysed using logistic regression analysis, and second including propensity score based on observed variables for selection to inotrope treatment. A subgroup analysis was performed for the 252 patients with pulmonary artery catheter. RESULTS: One hundred eighty-six (44.3%) patients received inotrope treatment during the first 24 h in ICU. Of those, 168 (90.3%) received dobutamine, 29 (15.6%) levosimendan, and 23 (12.4%) epinephrine. Blood lactate (P < 0.001), central venous pressure, (P < 0.001), and norepinephrine dose (P = 0.03) were independently associated with inotrope treatment. Patients with inotrope treatment had a higher 90-day mortality (42.5% vs. 23.9%, P < 0.001). Age (P < 0.001), Acute Physiology and Chronic Health Evaluation II score (P < 0.001), and inotrope treatment (P = 0.003) were independently associated with 90-day mortality also after adjustment with propensity score. CONCLUSION: The use of inotrope treatment in septic shock was associated with increased 90-day mortality without and after adjustment with propensity to receive inotrope. To differentiate between non-observed biases of severity of septic shock and an unfavourable effect of inotropes, prospective studies are needed.

Serum markers of collagen synthesis and degradation in acute respiratory failure patients.

BACKGROUND: Procollagen-derived propeptides reflect the rate of collagen synthesis and type I cross-linked collagen telopeptides (ICTP) collagen I degradation. We studied the collagen metabolism to find out if changes seen in acute respiratory distress syndrome patients are observed in patients with acute respiratory failure (ARF), and whether multiple organ dysfunction (MOD) has impact on it. METHODS: ARF patients with prolonged hospitalisation at least 21 days were included to the study. Blood samples for serum procollagen aminoterminal propeptide I (PINP) and III (PIIINP), and ICTP measurements were collected at study admission (day 0) and on days 2, 7, and 21. RESULTS: The study population comprised 68 patients. Forty-three patients (63%) developed MOD during the first week. PIIINP levels increased in all patients over time. The increase was slightly more pronounced in patients with MOD. During the first week, the synthesis of PIIINP increased more than PINP, and PINP degradation exceeded its production. By day 21, the balance of collagen metabolites returned to baseline. CONCLUSION: The collagen metabolism was altered in ARF patients. The first week was dominated by degradation of type I collagen and production of type III collagen, but by day 21, the collagen composition returned to more stable form.

Plasma neutrophil gelatinase-associated lipocalin and adverse outcome in critically ill patients with ventilatory support.

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.

Acute kidney injury in patients with severe sepsis in Finnish Intensive Care Units.

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.

Evaluation of sublingual microcirculatory blood flow in the critically ill.

BACKGROUND: The microcirculation regulates the supply of oxygen and nutrients to tissues. The sublingual region is frequently used as a window to microcirculation in critically ill patients. Numerous studies have reported impaired sublingual microcirculatory flow. We hypothesized that the quality of sidestream dark field imaging (SDF) recordings could be systematically analyzed to justify the monitoring of sublingual microcirculation in interventional studies or in clinical practice. METHODS: The sublingual microcirculation in critically ill patients with septic shock, open heart surgery, or alcoholic pancreatitis, and healthy subjects was recorded with a hand held SDF device by one trained investigator in observational setting. A total of 82 video recording sessions were performed and 240 video clips eligible for quality assessment were identified. Quality assessment was performed offline by two investigators independently and blinded for the origin of the video file. RESULTS: Of the 240 clips, pressure artifact was detected in 86 (36%), major blood in 5 (2.1%), major saliva in 21 (8.8%) and extreme brightness causing loss of visible capillaries in 16 (6.7%) clips. The dominating vessel architecture was multiple size vessels in 228 (95%) and repeating capillary loop motif in 12 (5.0%). The mean (± SD) relative size reduction during stabilization was -6.9% (± 4.7%). Excellent technical quality was detected in 74 of 240 (30.8%) recordings. CONCLUSIONS: Our findings highlight the need of a comprehensive training period and reporting of data quality before findings with SDF imaging can be accepted as surrogate end points in interventional studies or as guidance in clinical practice.

Quality of pharmacokinetic studies in critically ill patients receiving continuous renal replacement therapy.

Continuous renal replacement therapy (CRRT) is the preferred renal replacement therapy modality in the critically ill. We aimed to reveal the literature on the pharmacokinetic studies in critically ill patients receiving CRRT with special reference to quality assessment of these studies and the CRRT dose. We conducted a systematic review by searching the MEDLINE, EMBASE, and the Cochrane databases to December 2009 and bibliographies of relevant review articles. We included original studies reporting from critically ill adult subjects receiving CRRT because of acute kidney injury with a special emphasis on drug pharmacokinetics. We used the minimum reporting criteria for CRRT studies by Acute Dialysis Quality Initiative (ADQI) and, second, the Downs and Black checklist to assess the quality of the studies. We calculated the CRRT dose per study. We included pharmacokinetic parameters, residual renal function, and recommendations on drug dosing. Of 182 publications, 95 were considered relevant and 49 met the inclusion criteria. The median [interquartile range (IQR)] number of reported criteria by ADQI was 7.0 (5.0-8.0) of 12. The median (IQR) Downs and Black quality score was 15 (14-16) of 32. None of the publications reported CRRT dose directly. The median (IQR) weighted CRRT dose was 23.7 (18.8-27.9) ml/kg/h. More attention should be paid both to standardizing the CRRT dose and reporting of the CRRT parameters in pharmacokinetic studies. The general quality of the studies during CRRT in the critically ill was only moderate and would be greatly improved by reports in concordant with the ADQI recommendations.

Vascular adhesion protein-1 and syndecan-1 in septic shock.

BACKGROUND: Constituents of vascular endothelial surface layer (glycocalyx), e.g. an anchor protein syndecan-1 (SDC-1), can be detected in plasma in many inflammatory conditions. In inflammation, vascular adhesion protein-1 (VAP-1) is rapidly translocated to the apical side of the endothelial cells and may be released to plasma in a soluble form. We hypothesized that glycocalyx injury coincides with VAP-1 activation on endothelial cells. To test the hypothesis, we measured SDC-1 and VAP-1 levels in 20 patients with septic shock. METHODS: A prospective observational study was conducted in two multidisciplinary critical care units in two tertiary academic teaching hospitals with 20 mechanically ventilated adult patients with septic shock, on days 1 and 4 of treatment. Twenty healthy adults were enrolled as a control group. Plasma SDC-1 content, serum VAP-1 activity, platelets, and leukocyte count were measured in septic shock group at baseline and at 72 h and compared with those of healthy controls. RESULTS: VAP-1 activity and SDC-1 content were significantly increased in septic patients' group (P < 0.01) in comparison with controls. VAP-1 activity and SDC-1 content correlated positively to each other, and negatively to platelet count. In the septic shock group SDC-1 correlated on day 1 to SOFA score. CONCLUSIONS: We found increased VAP-1 activity and SDC-1 content in critically ill patients with septic shock. Based on our results, the role of VAP-1 in shock pathogenesis should be studied with semicarbazide-sensitive amine oxidase activity blocking agents and substrate affinity testing.

Association of ICU size and annual case volume of renal replacement therapy patients with mortality.

BACKGROUND: We aimed to reveal whether the size of an intensive care unit (ICU) or its annual case volume of patients treated with renal replacement therapy (RRT) for acute kidney injury (AKI) is associated with hospital mortality. METHODS: This was a retrospective cohort study in the Finnish Intensive Care Consortium (FICC) database in 2007-2008. We divided the 23 FICC-member ICUs first into small or large according to ICU size, and second into low, medium, or high-volume tertiles according to annual case volume of patients with RRT. We compared crude hospital mortality, Simplified Acute Physiology Score (SAPS) II-, and case-mix-adjusted hospital mortality in small vs. large ICUs and in low- or medium-volume vs. high-volume ICUs. RESULTS: The median (interquartile range) annual case volume of patients with RRT for AKI per one ICU was 25 (19-45). Patients in small or low-volume ICUs were older and less severely ill. Crude and SAPS II -adjusted hospital mortality rates were significantly higher in small ICUs but not significantly different in case volume tertiles. After adjusting for age, severity of illness, intensity of care, propensity to receive RRT, and day of RRT initiation, treatment in low or medium volume ICUs was associated with an increased risk for hospital mortality. CONCLUSIONS: Crude and adjusted hospital mortality rates of patients treated with RRT for AKI were higher in small ICUs. Patients treated in high-volume ICUs had a decreased adjusted risk for hospital mortality compared to those in low-or medium volume ICUs.

Association of automated data collection and data completeness with outcomes of intensive care. A new customised model for outcome prediction.

BACKGROUND: The Finnish Intensive Care Consortium coordinates a national intensive care benchmarking programme. Clinical information systems (CISs) that collect data automatically are widely used. The aim of this study was to explore whether the severity of illness-adjusted hospital mortality of Finnish intensive care unit (ICU) patients has changed in recent years and whether the changes reflect genuine improvements in the quality of care or are explained by changes in measuring severity of illness. METHODS: We retrospectively analysed data collected prospectively to the database of the Consortium. During the years 2001-2008, there were 116,065 admissions to the participating ICUs. We excluded readmissions, cardiac surgery patients, patients under 18 years of age and those discharged from an ICU to another hospital's ICU. The study population comprised 85,547 patients. The Simplified Acute Physiology Score II (SAPS II) was used to measure severity of illness and to calculate standardised mortality ratios (SMRs, the number of observed deaths divided by the number of expected deaths). RESULTS: The overall hospital mortality rate was 18.4%. The SAPS II-based SMRs were 0.74 in 2001-2004 and 0.64 in 2005-2008. The severity of illness-adjusted odds of death were 24% lower in 2005-2008 than in 2001-2004. One fifth of this computational difference could be explained by differences in data completeness and the automation of data collection with a CIS. CONCLUSION: The use of a CIS and improving data completeness do decrease severity-adjusted mortality rates. However, this explains only one fifth of the improvement in measured outcomes of intensive care in Finland.

Neurofilament light compared to neuron-specific enolase as a predictor of unfavourable outcome after out-of-hospital cardiac arrest.

AIM: We compared the prognostic abilities of neurofilament light (NfL) and neuron-specific enolase (NSE) in patients resuscitated from out-of-hospital cardiac arrest (OHCA) of various aetiologies. METHODS: We analysed frozen blood samples obtained at 24 and 48 hours from OHCA patients treated in 21 Finnish intensive care units in 2010 and 2011. We defined unfavourable outcome as Cerebral Performance Category (CPC) 3-5 at 12 months after OHCA. We evaluated the prognostic ability of the biomarkers by calculating the area under the receiver operating characteristic curves (AUROCs [95% confidence intervals]) and compared these with a bootstrap method. RESULTS: Out of 248 adult patients, 12-month outcome was unfavourable in 120 (48.4%). The median (interquartile range) NfL concentrations for patients with unfavourable and those with favourable outcome, respectively, were 689 (146-1804) pg/mL vs. 31 (17-61) pg/mL at 24 h and 1162 (147-4360) pg/mL vs. 36 (21-87) pg/mL at 48 h, p < 0.001 for both. The corresponding NSE concentrations were 13.3 (7.2-27.3) µg/L vs. 8.5 (5.8-13.2) µg/L at 24 h and 20.4 (8.1-56.6) µg/L vs. 8.2 (5.9-12.1) µg/L at 48 h, p < 0.001 for both. The AUROCs to predict an unfavourable outcome were 0.90 (0.86-0.94) for NfL vs. 0.65 (0.58-0.72) for NSE at 24 h, p < 0.001 and 0.88 (0.83-0.93) for NfL and 0.73 (0.66-0.81) for NSE at 48 h, p < 0.001. CONCLUSION: Compared to NSE, NfL demonstrated superior accuracy in predicting long-term unfavourable outcome after OHCA.

N-terminal-pro-BNP in critically ill patients with acute respiratory failure: a prospective cohort study.

BACKGROUND: The aim of this study was to evaluate the prognostic value of plasma N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) in unselected critically ill patients with acute respiratory failure (ARF). METHODS: Prospective, observational cohort study in 25 intensive care units in Finland. This study included a total of 602 patients with laboratory samples from 958 consecutive patients with ARF treated either with invasive or with non-invasive ventilatory support (the FINNALI study). Plasma NT-pro-BNP samples were drawn after the onset of ventilatory support (day 0) and on the morning of the second day. RESULTS: The median [interquartile ranges (IQR)] NT-pro-BNP-values were significantly higher at baseline in 90-day non-survivors than the survivors, 4378 pg/ml (1400-13,943 pg/ml) vs. 1052 pg/ml (232-4076 pg/ml), respectively. The median (IQR) NT-pro-BNP values were significantly higher in patients with chronic cardiac disease or cardiac surgery than in non-cardiac patients, 1947 pg/ml (801-4687 pg/ml) vs. 417 pg/ml (153-1735 pg/ml), respectively, if renal function was normal. With deteriorating renal function, the NT-pro-BNP values showed a significant increase. The area under curve for baseline NT-pro-BNP predicting 90-day mortality was moderate: 0.718 (95% confidence interval 0.674-0.761). Baseline NT-pro-BNP over 1765 pg/ml was independently associated with 90-day mortality by logistic regression analysis (P<0.001). CONCLUSIONS: NT-pro-BNP on admission is commonly elevated and independently associated with 90-day mortality in critically ill ARF patients. However, the routine use of NT-pro-BNP for prognostic purpose does not seem to add value to clinical data in ARF patients.