Admission interleukin-6 is associated with post resuscitation organ dysfunction and predicts long-term neurological outcome after out-of-hospital ventricular fibrillation.

AIM OF THE STUDY: To study plasma concentrations of interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP) and S-100B during intensive care after out-of-hospital cardiac arrest from ventricular fibrillation (OHCA-VF), and their associations with the duration of ischemia, organ dysfunction and long-term neurological outcome. MATERIALS AND METHODS: A 12-month prospective observational multicentre study was conducted in 21 Finnish intensive care units in 2011. IL-6, hs-CRP and S-100B were measured at 0-6 h, 24 h, 48 h and 96 h after ICU admission. Associations with the time to return of spontaneous circulation (ROSC), sequential organ failure assessment (SOFA) scores divided into tertiles and 12-month cerebral performance category (CPC) were tested. RESULTS: Of 186 OHCA-VF patients included in the study, 110 (59.1%) patients survived with good neurological outcome (CPC 1-2) 12 months after cardiac arrest. Admission plasma concentrations of IL-6 but not hs-CRP were higher with prolonged time to ROSC (p<0.001, 0.203, respectively), in patients with subsequent higher SOFA scores (p<0.001, 0.069) and poor long-term neurological outcome (CPC 3-5) (p<0.001, 0.315). S-100B concentrations over time were higher in patients with CPC of 3-5 (p<0.001). The area under the curve for prediction of poor 12-month outcome for admission levels was 0.711 IL-6, 0.663 for S-100B and 0.534 for hs-CRP. With multivariate logistic regression analysis only admission IL-6 (p=0.046, OR 1.006, 95% CI 1.000-1.011/ng/L) was an independent predictor of poor neurological outcome. CONCLUSION: Admission high IL-6, but not hs-CRP or S-100B, is associated with extra-cerebral organ dysfunction and along with age and time to ROSC are independent predictors for 12-month poor neurologic outcome (CPC 3-5).

The predictive value of soluble urokinase plasminogen activator receptor (SuPAR) regarding 90-day mortality and 12-month neurological outcome in critically ill patients after out-of-hospital cardiac arrest. Data from the prospective FINNRESUSCI study.

AIM: The whole body ischaemia-reperfusion after cardiac arrest (CA) induces a systemic inflammation-reperfusion response. The expression of urokinase plasminogen activator receptor (uPAR) is known to be induced after hypoxia and increased levels of soluble form suPAR have been measured after hypoxia and ischaemia. Our aim was to evaluate, whether ischaemia/reperfusion injury after out-of-hospital cardiac arrest (OHCA) increases suPAR concentrations in serum and to evaluate the prognostic value of suPAR regarding 90-day mortality and 12-month neurological outcome. METHODS: This is a pre-determined substudy of prospective FINNRESUSCI study. Total of 287 patients treated in the intensive care units after OHCA and with consent from the next-of-kin and serum samples between baseline and day 4 were included. Outcome and neurological outcome were evaluated according the Pittsburgh Cerebral Performance Categories (CPC). Kaplan-Meier survival curves, areas under receiver operational characteristics curves and positive likelihood ratios for mortality and poor neurological outcome were calculated. RESULTS: Non-survivors had higher levels of suPAR after OHCA. Kaplan-Meier survival curves indicated high 90-day mortality in the highest concentration quintiles. LR+ for 1-year CPC 3-5 was 1.8-2.7 for the whole patient cohort and in shockable rhythms 2.0-2.4. In therapeutic hypothermia prognostic value remained. CONCLUSIONS: We found that high SuPAR concentrations were associated with poor outcome in patients with OHCA admitted to critical care. However, suPAR alone had inadequate predictive value for poor outcome and did not associate with 12-month neurological outcome.

[Update on current care guideline: sepsis (adults]. / Sepsis (aikuiset).

The incidence of severe sepsis and septic shock requiring intensive care in Finnish adult population has increased to 0.60 11000 /y. Despite improved prognosis, hospital mortality related to severe sepsis and septic shock is high 24.1%. Key recommendations include prompt administration of antimicrobial therapy, optimally after blood cultures, quantitative fluid resuscitation and imaging studies to identify possible source of infection. Crystalloids are suitable for fluid resuscitation. Norepinephrine is the first-choice vasopressor in septic shock. Hydrocortisone should be considered only if fluid and vasopressor treatment does not restore hemodynamics.

Serum MMP-8 and TIMP-1 in critically ill patients with acute respiratory failure: TIMP-1 is associated with increased 90-day mortality.

BACKGROUND: Matrix metalloproteinases (MMPs) likely have an important role in the pathophysiology of acute lung injury. In a recent study, high matrix metalloproteinases (MMP-8) levels in tracheal aspirates of pediatric acute respiratory distress syndrome (ARDS) patients were associated with worse outcome. In patients with sepsis, an imbalance between MMPs and their tissue inhibitors (TIMPs) has been associated with impaired survival. We hypothesized that the elevated systemic MMP-8 and TIMP-1 are associated with worse outcome in acute respiratory failure. METHODS: This was a substudy of the observational FINNALI study conducted in 25 Finnish intensive care units over an 8-week period. All patients older than 16 years requiring mechanical ventilation for >6 hours were included. MMP-8 and TIMP-1 levels were analyzed from blood samples taken on enrollment in the study and 48 hours later. Laboratory analyses were performed by using immunofluorometric assay for MMP-8 and ELISA for TIMP-1. MMP-8 and TIMP-1 levels were compared between 90-day survivors and nonsurvivors. Survival was compared in quartiles based on TIMP-1 levels, and ROC analysis was performed to calculate areas under the curves. The relationship between MMP-8 and TIMP-1 levels and degree of hypoxemia was examined. RESULTS: The final analyses included 563 patients. Admission TIMP-1 levels were higher in nonsurvivors, median 367 ng/mL (interquartile range 199-562), than survivors, median 240 ng/mL (interquartile range 142-412), WMWodds 1.68 (95% confidence interval [CI], 1.43-2.08). MMP-8 levels may have differed between survivors and nonsurvivors, WMWodds 1.20 (95% CI, 1.01-1.43), but no difference was found in the MMP-8/TIMP-1 molar ratio, WMWodds 0.83 (95% CI, 0.67-1.04). Difference in survival between quartiles based on TIMP-1 was significant (log-rank, P < 0.001). ROC analysis produced an area under the curve 0.63 (95% CI, 0.58-0.69) for TIMP-1. TIMP-1 was associated with severity of hypoxemia. TIMP-1 levels were higher in an ARDS subgroup than in the whole cohort, WMWodds 1.65 (95% CI, 1.15-2.44). CONCLUSIONS: MMP-8 levels were possibly higher in 90-day nonsurvivors but performed poorly in predicting outcome. Increased systemic levels of TIMP-1 were associated with more severe hypoxemia and worse outcome in a large cohort of mechanically ventilated critically ill patients and in a subgroup of ARDS patients.

Hemodynamic variables and progression of acute kidney injury in critically ill patients with severe sepsis: data from the prospective observational FINNAKI study.

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.

[Update on current care guidelines. Treatment of severe sepsis in adults]. / Aikuisten vaikean sepsiksen hoito.

According to the Finnsepsis Study, the incidence in Finland of severe sepsis requiring intensive care was 0.38/1,000 inhabitants/year. ICU and hospital mortality was 15.5% and 28.3%, respectively. The Finnsepsis Study showed that compliance with protocols was rather poor and antimicrobial treatment was often delayed. These guidelines emphasize the importance of prompt antibiotic and fluid therapy. In shock, norepinephrine is the first line vasopressor. Low-dose hydrocortisone may be used to shorten the need for vasopressors. Activated protein C should be considered in selected patients. The blood glucose target recommendation is between 5 and 8 mmol/l.

Vascular endothelial growth factor in severe sepsis and septic shock.

BACKGROUND: Vascular endothelial growth factor (VEGF) levels have been shown to be elevated in severe sepsis. We investigated the value of VEGF in predicting organ dysfunction and hospital mortality in adult patients with severe sepsis. METHODS: We conducted a prospective observational cohort study in 24 closed multidisciplinary intensive care units (ICU) in Finland. All ICU admission episodes (4500) were screened for severe sepsis from November 1, 2004, to February 28, 2005. Patients were eligible if they fulfilled the criteria for severe sepsis. RESULTS: Severe sepsis was found in 470 patients. Laboratory samples were obtained after informed consent from 250 patients at study entry (day 0) and from 215 patients after 72 h. These samples were compared with samples from 30 healthy individuals. The ICU mortality was 13.2% and hospital mortality 26%. Median serum VEGF concentrations on day 0 were 423 pg/mL (interquartile range [IQR] 159 and 858 pg/mL), and after 72 h were 521 pg/mL (IQR 182 and 1092 pg/mL), which were both higher than in healthy controls (P = 0.029 and 0.003, respectively). Low VEGF concentrations were associated with more severe renal and hematological dysfunction (Sequential Organ Failure Assessment scores 3-4 compared with scores 0-2). VEGF concentrations in day 0 and after 72 h were lower in nonsurvivors (P = 0.01 and <0.01, respectively) than in survivors, but the receiver operating characteristic curve analyses of concentrations of VEGF on day 0 and at 72 h revealed areas under the curve of 0.58 and 0.63 (95% confidence limits 0.48-0.68 and 0.54-0.72, P = 0.1 and 0.009, respectively). CONCLUSIONS: VEGF concentrations are increased in patients with severe sepsis. Low concentrations are associated with hematological and renal dysfunction. VEGF concentrations were lower in nonsurvivors than in survivors, but did not adequately predict hospital mortality in patients with severe sepsis.

Reasons, considerations, difficulties and documentation of end-of-life decisions in European intensive care units: the ETHICUS Study.

OBJECTIVE: To evaluate physicians' reasoning, considerations and possible difficulties in end-of-life decision-making for patients in European intensive care units (ICUs). DESIGN: A prospective observational study. SETTING: Thirty-seven ICUs in 17 European countries. PATIENTS AND PARTICIPANTS: A total of 3,086 patients for whom an end-of-life decision was taken between January 1999 and June 2000. The dataset excludes patients who died after attempts at cardiopulmonary resuscitation and brain-dead patients. MEASUREMENTS AND RESULTS: Physicians indicated which of a pre-determined set of reasons for, considerations in, and difficulties with end-of-life decision-making was germane in each case as it arose. Overall, 2,134 (69%) of the decisions were documented in the medical record, with inter-regional differences in documentation practice. Primary reasons given by physicians for the decision mostly concerned the patient's medical condition (79%), especially unresponsive to therapy (46%), while chronic disease (12%), quality of life (4%), age (2%) and patient or family request (2%) were infrequent. Good medical practice (66%) and best interests (29%) were the commonest primary considerations reported, while resource allocation issues such as cost effectiveness (1%) and need for an ICU bed (0%) were uncommon. Living wills were considered in only 1% of cases. Physicians in central Europe reported no significant difficulty in 81% of cases, while in northern and southern regions there was no difficulty in 92-93% of cases. CONCLUSIONS: European ICU physicians do not experience difficulties with end-of-life decisions in most cases. Allocation of limited resources is a minor consideration and autonomous choices by patient or family remain unusual. Inter-regional differences were found.

Effect of mode of hydrocortisone administration on glycemic control in patients with septic shock: a prospective randomized trial.

INTRODUCTION: Low-dose hydrocortisone treatment is widely accepted therapy for the treatment of vasopressor-dependent septic shock. The question of whether corticosteroids should be given to septic shock patients by continuous or by bolus infusion is still unanswered. Hydrocortisone induces hyperglycemia and it is possible that continuous hydrocortisone infusion would reduce the fluctuations in blood glucose levels and that tight blood glucose control could be better achieved with this approach. METHODS: In this prospective randomized study, we compared the blood glucose profiles, insulin requirements, amount of nursing workload needed, and shock reversal in 48 septic shock patients who received hydrocortisone treatment either by bolus or by continuous infusion with equivalent dose (200 mg/day). Duration of hydrocortisone treatment was five days. RESULTS: The mean blood glucose levels were similar in the two groups, but the number of hyperglycemic episodes was significantly higher in those patients who received bolus therapy (15.7 +/- 8.5 versus 10.5 +/- 8.6 episodes per patient, p = 0.039). Also, more changes in insulin infusion rate were needed to maintain strict normoglycemia in the bolus group (4.7 +/- 2.2 versus 3.4 +/- 1.9 adjustments per patient per day, p = 0.038). Hypoglycemic episodes were rare in both groups. No difference was seen in shock reversal. CONCLUSION: Strict normoglycemia is more easily achieved if the hydrocortisone therapy is given to septic shock patients by continuous infusion. This approach also reduces nursing workload needed to maintain tight blood glucose control.

Population-based audit of fresh-frozen plasma transfusion practices.

BACKGROUND: In contrast to decreasing red blood cell (RBC) consumption in Finland, the use of fresh-frozen plasma (FFP) has been increasing since the 1990s, suggesting that FFP use may not always be optimal. To improve transfusion practices, knowledge of current FFP use and regional, national, and international comparison is necessary. STUDY DESIGN AND METHODS: Nine (of 21) Finnish hospital districts participated. Data concerning FFP-transfused patients in the years 2002 and 2003 were collected from existing computerized medical records into a yearly updated database as part of a Finnish benchmarking project on blood component use. RESULTS: Data included 11,590 FFP-transfused patients and 60,240 FFP units (71.2% of Finnish FFP use) delivered to Finnish hospitals during the study period. FFP was transfused most often to surgery patients (62.8% of FFP transfusion hospital visits) with blood circulatory system problems (32.3% of surgically treated and FFP-transfused patients). In only 65.9 percent of FFP-transfused patients were coagulation variables measured at any point in the hospital episode, and FFP was usually transfused in paired doses. Mean FFP use in Finland is comparable to other countries. CONCLUSION: Although overall FFP use in Finland is similar to that of international figures, it does not ensure best practice. Perioperative staff, being the largest FFP user, should be encouraged to dose FFP based on coagulation variables and body weight. Improvement efforts should be directed to patient groups transfused with large amounts of FFP.

Comparison of entropy and complexity measures for the assessment of depth of sedation.

Entropy and complexity of the electroencephalogram (EEG) have recently been proposed as measures of depth of anesthesia and sedation. Using surrogate data of predefined spectrum and probability distribution we show that the various algorithms used for the calculation of entropy and complexity actually measure different properties of the signal. The tested methods, Shannon entropy (ShEn), spectral entropy, approximate entropy (ApEn), Lempel-Ziv complexity (LZC), and Higuchi fractal dimension (HFD) are then applied to the EEG signal recorded during sedation in the intensive care unit (ICU). It is shown that the applied measures behave in a different manner when compared to clinical depth of sedation score--the Ramsay score. ShEn tends to increase while the other tested measures decrease with deepening sedation. ApEn, LZC, and HFD are highly sensitive to the presence of high-frequency components in the EEG signal.

Communication of end-of-life decisions in European intensive care units.

OBJECTIVE: To examine end-of-life (EOL) practices in European ICUs: who makes these decisions, how they are made, communication of these decisions and questions on communication between the physicians, nurses, patients and families. DESIGN: Data collected prospectively on EOL decisions facilitated by a questionnaire including EOL decision categories, geographical regions, mental competency, information about patient wishes, and discussions with patients, families and health care professionals. SETTING: 37 European ICUs in 17 countries. PATIENTS: ICU physicians collected data on 4,248 patients. RESULTS: 95% of patients lacked decision making capacity at the time of EOL decision and patient's wishes were known in only 20% of cases. EOL decisions were discussed with the family in 68% of cases. Physicians reported having more information about patients' wishes and discussions in the northern countries (31%, 88%) than central (16%, 70%) or southern (13%, 48%) countries. The family was more often told (88%) than asked (38%) about EOL decisions. Physicians' reasons for not discussing EOL care with the family included the fact that the patient was unresponsive to therapy (39%), the family was unavailable (28%), and the family was thought not to understand (25%). CONCLUSIONS: ICU patients typically lack decision-making capacity, and physicians know patients' wishes in only 20% of EOL decisions. There were regional differences in discussions of EOL decisions with families and other physicians. In European ICUs there seems to be a need to improve communication.

End-of-life practices in European intensive care units: the Ethicus Study.

CONTEXT: While the adoption of practice guidelines is standardizing many aspects of patient care, ethical dilemmas are occurring because of forgoing life-sustaining therapies in intensive care and are dealt with in diverse ways between different countries and cultures. OBJECTIVES: To determine the frequency and types of actual end-of-life practices in European intensive care units (ICUs) and to analyze the similarities and differences. DESIGN AND SETTING: A prospective, observational study of European ICUs. PARTICIPANTS: Consecutive patients who died or had any limitation of therapy. INTERVENTION: Prospectively defined end-of-life practices in 37 ICUs in 17 European countries were studied from January 1, 1999, to June 30, 2000. MAIN OUTCOME MEASURES: Comparison and analysis of the frequencies and patterns of end-of-life care by geographic regions and different patients and professionals. RESULTS: Of 31 417 patients admitted to ICUs, 4248 patients (13.5%) died or had a limitation of life-sustaining therapy. Of these, 3086 patients (72.6%) had limitations of treatments (10% of admissions). Substantial intercountry variability was found in the limitations and the manner of dying: unsuccessful cardiopulmonary resuscitation in 20% (range, 5%-48%), brain death in 8% (range, 0%-15%), withholding therapy in 38% (range, 16%-70%), withdrawing therapy in 33% (range, 5%-69%), and active shortening of the dying process in 2% (range, 0%-19%). Shortening of the dying process was reported in 7 countries. Doses of opioids and benzodiazepines reported for shortening of the dying process were in the same range as those used for symptom relief in previous studies. Limitation of therapy vs continuation of life-sustaining therapy was associated with patient age, acute and chronic diagnoses, number of days in ICU, region, and religion (P<.001). CONCLUSION: The limiting of life-sustaining treatment in European ICUs is common and variable. Limitations were associated with patient age, diagnoses, ICU stay, and geographic and religious factors. Although shortening of the dying process is rare, clarity between withdrawing therapies and shortening of the dying process and between therapies intended to relieve pain and suffering and those intended to shorten the dying process may be lacking.