Ubiquitin C-terminal hydrolase L1 after out-of-hospital cardiac arrest.

BACKGROUND: We studied the prognostic ability of serum ubiquitin C-terminal hydrolase L1 (UCH-L1) after out-of-hospital cardiac arrest (OHCA), compared to that of neuron-specific enolase (NSE). METHODS: In this post-hoc analysis of the FINNRESUSCI study, we measured serum concentrations of UCH-L1 in 249 OHCA patients treated in 21 Finnish intensive care units in 2010-2011. We evaluated the ability of UCH-L1 to predict unfavourable outcome at 12 months (defined as cerebral performance category 3-5) by assessing the area under the receiver operating characteristic curve (AUROC), in comparison with NSE. RESULTS: The concentrations of UCH-L1 were higher in patients with unfavourable outcome than for those with favourable outcome: median concentration 10.8 ng/mL (interquartile range, 7.5-18.5 ng/mL) versus 7.8 ng/mL (5.9-11.8 ng/mL) at 24 h (p < .001), and 16.2 ng/mL (12.2-27.7 ng/mL) versus 11.5 ng/mL (9.0-17.2 ng/mL) (p < .001) at 48 h after OHCA. For UCH-L1 as a 12-month outcome predictor, the AUROC was 0.66 (95% confidence interval, 0.60-0.73) at 24 h and 0.66 (0.59-0.74) at 48 h. For NSE, the AUROC was 0.66 (0.59-0.73) at 24 h and 0.72 (0.65-0.80) at 48 h. The prognostic ability of UCH-L1 was not different from that of NSE at 24 h (p = .82) and at 48 h (p = .23). CONCLUSION: Concentrations of UCH-L1 in serum were higher in patients with unfavourable outcome than in those with favourable outcome. However, the ability of UCH-L1 to predict unfavourable outcome after OHCA was only moderate and not superior to that of NSE.

Exposure to bacterial and fungal bioaerosols in facilities processing biodegradable waste.

The aim of the study was to determine the exposure of workers within biodegradable waste processing facilities to bacteria and fungi to identify any exposures of potential concern to health. Occupational measurements were performed in six composting and three bioenergy (bioethanol or methane/biogas) producing facilities. Bioaerosols were measured from breathing zones with Button aerosol or open face cassette filter samplers, and swab specimens were taken from the nasal mucous membranes of the workers. Aspergillus fumigatus, Bacillus cereus group, Campylobacter spp., Salmonella spp., Streptomyces spp., and Yersinia spp. were determined by real-time polymerase chain reaction (qPCR). A. fumigatus, and mesophilic and thermophilic actinobacteria were also cultivated from filters. Bacterial airborne endotoxins collected by IOM samplers were analyzed using a Limulus assay. Bioaerosol levels were high, especially in composting compared to bioenergy producing facilities. Endotoxin concentrations in composting often exceeded the occupational exposure value of 90 EU/m3, which may be harmful to the health. In addition to endotoxins, the concentrations of A. fumigatus (up to 2.4 × 105 copies/m3) and actinobacteria/Streptomyces spp. (up to 1.6 × 106 copies/m3) in the air of composting facilities were often high. Microbial and endotoxin concentrations were typically highest in waste reception and pre-treatment, equal or decreased during processing and handling of treated waste, and lowest in wheel loader cabins and control rooms/outdoors. Still, the parameters measured in wheel loader cabins were often higher than in the control sites, which suggests that the use of preventive measures could be improved. B. cereus group, Salmonella spp., and Yersinia spp. were rarely detected in bioaerosols or nasal swabs. Although Campylobacter spp. DNA was rarely detected in air, as a new finding, Campylobacter ureolyticus DNA was frequently detected in the nasal mucous membranes of workers, based on partial 16S rDNA sequencing. Moreover, especially A. fumigatus and C. ureolyticus spp. DNA concentrations in swabs after the work shift were significantly higher than before the shift, which indicates their inhalation or growth during the work shift. Microbial qPCR analysis of bioaerosols and swab samples of nasal mucosa allowed measuring exposure in various work operations and during the work shift, identifying problems for health risk assessment to improve working conditions, and evaluating the effectiveness of preventive measures and personal protection of workers.

ARTS: A Large, International Trial of Thromboprophylaxis in Intra-abdominal, Gynecologic, and Urologic Surgery.

ARTS will be the first trial to compare anticoagulation with a direct oral anticoagulant (apixaban) versus no anticoagulation among patients undergoing intra-abdominal, gynecologic, or urologic surgery at sufficiently similar risk of deep vein thrombosis or pulmonary embolism and major bleeding.

Time course of signaling profiles of blood leukocytes in acute pancreatitis and sepsis.

Activation of intracellular signaling pathways in circulating leukocytes represents an early step in systemic immune-inflammatory response occurring e.g. in acute pancreatitis (AP) and sepsis. Previously, we found aberrations in the phosphorylation of leukocyte signaling proteins in patients with sepsis or AP (measured <48 h from hospital admission) resembling each other and associating with AP severity. Of these patients, those with sepsis or severe AP complicated by persistent organ dysfunction (OD+, n = 17) and patients with moderately severe AP (OD-, n = 6) were followed up in this study by measuring the phosphorylations at two additional time points (2-4 and 5-8 days after the initial sample) using phosphospecific whole blood flow cytometry. Twenty-eighty healthy subjects served as controls (HC). Constitutive STAT3 phosphorylation (pSTAT3) declined in monocytes and neutrophils of OD-/OD + and in lymphocytes of OD + and remained higher in OD- than HC. Monocytes of OD-/OD + showed low pSTAT3 and pSTAT1 levels in response to IL-6 through follow-up. Monocyte pNF-κB levels in response to TNF, LPS and E. coli in OD+, to E. coli in OD-, and lymphocyte pNF-κB levels in response to TNF in OD- increased during follow-up but remained lower than in HC, and neutrophil pNF-κB levels in response to TNF declined in OD-. Phorbol myristate acetate + Ca2+ ionophore-stimulated pERK1/2 decreased in neutrophils of OD-/OD+. To conclude, in patients with moderately severe or severe AP or sepsis, improvement and molecular events contributing to OD can be assessed at the level of blood leukocyte signaling.

Usefulness of neuron specific enolase in prognostication after cardiac arrest: Impact of age and time to ROSC.

AIM OF THE STUDY: We evaluated the impact of patient age and time from collapse to return of spontaneous circulation (ROSC) on the prognostic accuracy of neuron specific enolase (NSE) after out-of-hospital cardiac arrest (OHCA). METHODS: Using electrochemiluminescence immunoassay, we measured serum concentrations of NSE in 249 patients who were admitted to intensive care units after resuscitation from OHCA. In each quartile according to age and time to ROSC, we evaluated the ability of NSE at 48 h after OHCA to predict poor outcome (Cerebral Performance Category 3-5) at 12 months. RESULTS: The outcome at 12 months was poor in 121 (49%) patients. The prognostic performance of NSE was excellent (area under the receiver operating characteristic curve, AUROC, 0.91 [95% confidence interval, 0.81-1.00]) in the youngest quartile (18-56 years), but worsened with increasing age, and was poor (AUROC 0.53 [0.37-0.70]) in the oldest quartile (72 years or more). The prognostic performance of NSE was worthless (AUROC 0.45 [0.30-0.61]) in the quartile with the shortest time to ROSC (1-13 min), but improved with increasing time to ROSC, and was good (AUROC 0.84 [0.74-0.95]) in the quartile with the longest time to ROSC (29 min or over). CONCLUSION: NSE at 48 h after OHCA is a useful predictor of 12-month-prognosis in young patients and in patients with a long time from collapse to ROSC, but not in old patients or patients with a short time to ROSC.

The systemic inflammatory response syndrome criteria and their differential association with mortality.

PURPOSE: Despite the recent Sepsis-3 consensus, the Systemic Inflammatory Response Syndrome (SIRS) criteria continue to be assessed and recommended. Such use implies equivalence and interchangeability of criteria. Thus, we aimed to test whether such criteria are indeed equivalent and interchangeable. MATERIALS AND METHODS: From 2000 to 2015, we identified patients with infection, organ failure, and at least one SIRS criterion in 179 Intensive Care Units in Australia and New. Zealand. We studied the association of different SIRS criteria with hospital mortality. RESULTS: Among 131,016 patients with infection and organ failure, mortality increased from 10.6% for the respiratory rate criterion to 15.8% for the heart rate criterion (P<0.01); from 10.1% for the high leukocyte count criterion to 20.0% for a low count and from 10.1% for a high temperature to 14.4% for a low temperature criterion. With any two SIRS criteria, hospital mortality varied from 11.5% to 30.8% depending on the combination of criteria. This difference remained unchanged after adjustments and was consistent over time. CONCLUSIONS: Different individual and combinations of SIRS criteria were associated with marked differences in hospital mortality. These differences remained unchanged after adjustment and over time and imply that individual SIRS criteria are not equivalent or interchangeable.

Age of Red Cells for Transfusion and Outcomes in Critically Ill Adults.

BACKGROUND: It is uncertain whether the duration of red-cell storage affects mortality after transfusion among critically ill adults. METHODS: In an international, multicenter, randomized, double-blind trial, we assigned critically ill adults to receive either the freshest available, compatible, allogeneic red cells (short-term storage group) or standard-issue (oldest available), compatible, allogeneic red cells (long-term storage group). The primary outcome was 90-day mortality. RESULTS: From November 2012 through December 2016, at 59 centers in five countries, 4994 patients underwent randomization and 4919 (98.5%) were included in the primary analysis. Among the 2457 patients in the short-term storage group, the mean storage duration was 11.8 days. Among the 2462 patients in the long-term storage group, the mean storage duration was 22.4 days. At 90 days, there were 610 deaths (24.8%) in the short-term storage group and 594 (24.1%) in the long-term storage group (absolute risk difference, 0.7 percentage points; 95% confidence interval [CI], -1.7 to 3.1; P=0.57). At 180 days, the absolute risk difference was 0.4 percentage points (95% CI, -2.1 to 3.0; P=0.75). Most of the prespecified secondary measures showed no significant between-group differences in outcome. CONCLUSIONS: The age of transfused red cells did not affect 90-day mortality among critically ill adults. (Funded by the Australian National Health and Medical Research Council and others; TRANSFUSE Australian and New Zealand Clinical Trials Registry number, ACTRN12612000453886 ; ClinicalTrials.gov number, NCT01638416 .).

Acute Kidney Injury After Cardiac Surgery by Complete KDIGO Criteria Predicts Increased Mortality.

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.

Predictive value of high-sensitivity troponin T in addition to EuroSCORE II in cardiac surgery.

OBJECTIVES: Plasma troponins, measured by fourth-generation assays, are associated with increased mortality and morbidity after cardiac surgery. They also offer predictive information in addition to EuroSCORE, a widely used risk model after cardiac surgery. However, preoperatively measured troponin has provided no additional information to postoperative values. Whether these facts hold true also for the high-sensitivity fifth-generation troponin assay and the better calibrated risk model, EuroSCORE II, is unknown. We hypothesized that preoperative and/or postoperative high-sensitivity troponin T (hs-TnT) would increase the predictive value of EuroSCORE II. METHODS: Consecutive coronary artery bypass grafting (CABG) and other cardiac surgical patients were prospectively enrolled in a university hospital. Plasma samples and EuroSCORE II variables were collected. The primary and secondary end-points were 180-day mortality and any major adverse event within 30 days, and 961-day mortality. The data were analysed by Kaplan-Meier survival curves, regression analyses, receiver operator characteristic curves and decision curve analysis. RESULTS: Mortality rates in 180 days were 3.5% (15/428) in CABG and 6.4% (14/220) in other cardiac surgical patients. Survival curves differed only in patients with not only high postoperative hs-TnT value (>500 ng/l), but also high preoperative hs-TnT value (>14 ng/l), compared with patients with both hs-TnT values low. Adding hs-TnT to EuroSCORE II improved the prediction of 180-day mortality in other cardiac surgical patients (maximum net benefit of 1.5%), but not in CABG patients. Regarding major adverse events, adding hs-TnT to EuroSCORE II improved the prediction in both CABG patients and other cardiac surgical patients (maximum net benefits of 3 and 7%). CONCLUSIONS: Elevated postoperative hs-TnT was predictive of mortality only when combined with elevated preoperative hs-TnT. Hs-TnT measurements added information to the EuroSCORE II regarding major adverse events in all cardiac surgical patients and regarding 180-day mortality in non-CABG patients.

Evaluation of patients' sleep by nurses in an ICU.

AIMS AND OBJECTIVES: To determine how intensive care unit evaluations of patients' sleep by nurses correspond to polysomnography and if changes in patients' physiologic parameters could be helpful in sleep evaluation. BACKGROUND: The evaluations of patients' sleep by nurses have not corresponded very well with objective sleep recordings, so there is a need for further knowledge in this field. DESIGN: Correlational study of patients' sleep, nurses' sleep evaluations and the sleep-related heart rate and blood pressure changes. METHODS: The standard overnight polysomnography was recorded on 21 patients. Simultaneously, nurses marked into an electronic patient care documentation system all the changes noted in the patients' sleep status. Patients' arterial blood pressure and heart-rate data were automatically saved into the electronic patient care documentation. RESULTS: The evaluations of patients' sleep/wake state by nurses corresponded to polysomnography 68% of the time. A correlation was found between nurses' evaluations and polysomnography recordings only on total sleep time. There was no correlation in the other sleep aspects (sleep latency, amount of awakenings or movements during sleep). Most patients' blood pressures and heart rate varied according to sleep/wake state. There was less variation if the patient had received noradrenalin for blood pressure control. CONCLUSION: The evaluations of patients' sleep/wake state by nurses only correspond to the polysomnography two-thirds of the time. Thus, more sophisticated evaluation methods should be developed to aid nurses in sleep evaluations. Sleep-related changes in blood pressure and heart rate can be seen in intensive care unit patients, so using these parameters as part of the patients' sleep evaluation should be further explored. RELEVANCE TO CLINICAL PRACTICE: The nurses' evaluation practices of intensive care unit patients' sleep need further development. Monitoring the changes in patients' heart rate and blood pressure may aid in evaluating his/her sleep.

Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort.

OBJECTIVES: We utilized the database of the Defining Antibiotic Levels in Intensive care unit patients (DALI) study to statistically compare the pharmacokinetic/pharmacodynamic and clinical outcomes between prolonged-infusion and intermittent-bolus dosing of piperacillin/tazobactam and meropenem in critically ill patients using inclusion criteria similar to those used in previous prospective studies. METHODS: This was a post hoc analysis of a prospective, multicentre pharmacokinetic point-prevalence study (DALI), which recruited a large cohort of critically ill patients from 68 ICUs across 10 countries. RESULTS: Of the 211 patients receiving piperacillin/tazobactam and meropenem in the DALI study, 182 met inclusion criteria. Overall, 89.0% (162/182) of patients achieved the most conservative target of 50% fT>MIC (time over which unbound or free drug concentration remains above the MIC). Decreasing creatinine clearance and the use of prolonged infusion significantly increased the PTA for most pharmacokinetic/pharmacodynamic targets. In the subgroup of patients who had respiratory infection, patients receiving ß-lactams via prolonged infusion demonstrated significantly better 30 day survival when compared with intermittent-bolus patients [86.2% (25/29) versus 56.7% (17/30); P = 0.012]. Additionally, in patients with a SOFA score of ≥9, administration by prolonged infusion compared with intermittent-bolus dosing demonstrated significantly better clinical cure [73.3% (11/15) versus 35.0% (7/20); P = 0.035] and survival rates [73.3% (11/15) versus 25.0% (5/20); P = 0.025]. CONCLUSIONS: Analysis of this large dataset has provided additional data on the niche benefits of administration of piperacillin/tazobactam and meropenem by prolonged infusion in critically ill patients, particularly for patients with respiratory infections.

Femoral Access and Delivery of Continuous Renal Replacement Therapy Dose.

AIMS: The study aims to describe the use of dialysis catheters in critically ill patients treated with continuous renal replacement therapy (CRRT) and to study the impact of femoral versus non-femoral access on CRRT dose. METHODS: Statistical analysis and predictive modelling of data from the Randomized Evaluation of Normal vs. Augmented Level renal replacement therapy trial. RESULTS: The femoral vein was the first access site in 937 (67%) of 1,399 patients. These patients had higher Acute Physiology and Chronic Health Evaluation and Sequential Organ Failure Assessment scores (p = 0.009) and lower pH (p < 0.001) but similar mortality to patients with non-femoral access (44 vs. 45%; p = 0.63). Lower body weight was independently associated with femoral access placement (OR 0.97, 95% CI 0.96-0.98). Femoral access was associated with a 1.03% lower CRRT dose (p = 0.05), but a 4.20% higher dose was achieved with 13.5 Fr catheters (p = 0.03). CONCLUSIONS: Femoral access was preferred in lighter and sicker patients. Catheter gauge had greater impact than catheter site in CRRT dose delivery. Video Journal Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=439581.

Epidemiology of RBC Transfusions in Patients With Severe Acute Kidney Injury: Analysis From the Randomized Evaluation of Normal Versus Augmented Level Study.

OBJECTIVE: To assess the epidemiology and outcomes associated with RBC transfusion in patients with severe acute kidney injury requiring continuous renal replacement therapy. DESIGN: Post hoc analysis of data from a multicenter, randomized, controlled trial. SETTING: Thirty-five ICUs in Australia and New Zealand. PATIENTS: Cohort of 1,465 patients enrolled in the Randomized Evaluation of Normal versus Augmented Level replacement therapy study. INTERVENTIONS: Daily information on morning hemoglobin level and amount of RBC transfused were prospectively collected in the Randomized Evaluation of Normal versus Augmented Level study. We analyzed the epidemiology of such transfusions and their association with clinical outcomes. MEASUREMENTS AND MAIN RESULTS: Overall, 977 patients(66.7%) received a total of 1,192 RBC units. By day 5, 785 of 977 transfused patients (80.4%) had received at least one RBC transfusion. Hemoglobin at randomization was lower in transfused than in nontransfused patients (94 vs 111 g/L; p < 0.001). Mean daily hemoglobin was 88 ± 7 and 99 ± 12 g/L in transfused and nontransfused patients. Among transfused patients, 228 (46.7%) had died by day 90 when compared with 426 (43.6%) of nontransfused patients (p = 0.27). Survivors received on average 316 ± 261 mL of RBC, whereas nonsurvivors received 302 ± 362 mL (p = 0.42). On multivariate Cox regression analysis, RBC transfusion was independently associated with lower 90-day mortality (hazard ratio, 0.55; 95% CI, 0.38-0.79). However, we found no independent association between RBC transfusions and mortality when the analyses were restricted to patients surviving at least 5 days (hazard ratio, 1.29; 95% CI, 0.90-1.85). We found no independent association between RBC transfusion and renal replacement therapy-free days, mechanical ventilator-free days, or length of stay in ICU or hospital. CONCLUSIONS: In patients with severe acute kidney injury treated with continuous renal replacement therapy, we found no association of RBC transfusion with 90-day mortality or other patient-centered outcomes. The optimal hemoglobin threshold for RBC transfusion in such patients needs to be determined in future randomized controlled trials.

Dexmedetomidine versus standard care sedation with propofol or midazolam in intensive care: an economic evaluation.

INTRODUCTION: Dexmedetomidine was shown in two European randomized double-blind double-dummy trials (PRODEX and MIDEX) to be non-inferior to propofol and midazolam in maintaining target sedation levels in mechanically ventilated intensive care unit (ICU) patients. Additionally, dexmedetomidine shortened the time to extubation versus both standard sedatives, suggesting that it may reduce ICU resource needs and thus lower ICU costs. Considering resource utilization data from these two trials, we performed a secondary, cost-minimization analysis assessing the economics of dexmedetomidine versus standard care sedation. METHODS: The total ICU costs associated with each study sedative were calculated on the basis of total study sedative consumption and the number of days patients remained intubated, required non-invasive ventilation, or required ICU care without mechanical ventilation. The daily unit costs for these three consecutive ICU periods were set to decline toward discharge, reflecting the observed reduction in mean daily Therapeutic Intervention Scoring System (TISS) points between the periods. A number of additional sensitivity analyses were performed, including one in which the total ICU costs were based on the cumulative sum of daily TISS points over the ICU period, and two further scenarios, with declining direct variable daily costs only. RESULTS: Based on pooled data from both trials, sedation with dexmedetomidine resulted in lower total ICU costs than using the standard sedatives, with a difference of €2,656 in the median (interquartile range) total ICU costs-€11,864 (€7,070 to €23,457) versus €14,520 (€7,871 to €26,254)-and €1,649 in the mean total ICU costs. The median (mean) total ICU costs with dexmedetomidine compared with those of propofol or midazolam were €1,292 (€747) and €3,573 (€2,536) lower, respectively. The result was robust, indicating lower costs with dexmedetomidine in all sensitivity analyses, including those in which only direct variable ICU costs were considered. The likelihood of dexmedetomidine resulting in lower total ICU costs compared with pooled standard care was 91.0% (72.4% versus propofol and 98.0% versus midazolam). CONCLUSIONS: From an economic point of view, dexmedetomidine appears to be a preferable option compared with standard sedatives for providing light to moderate ICU sedation exceeding 24 hours. The savings potential results primarily from shorter time to extubation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00479661 (PRODEX), NCT00481312 (MIDEX).

Pharmacokinetic variability and exposures of fluconazole, anidulafungin, and caspofungin in intensive care unit patients: Data from multinational Defining Antibiotic Levels in Intensive care unit (DALI) patients Study.

INTRODUCTION: The objective of the study was to describe the pharmacokinetics (PK) of fluconazole, anidulafungin, and caspofungin in critically ill patients and to compare with previously published data. We also sought to determine whether contemporary fluconazole doses achieved PK/pharmacodynamic (PD; PK/PD) targets in this cohort of intensive care unit patients. METHODS: The Defining Antibiotic Levels in Intensive care unit patients (DALI) study was a prospective, multicenter point-prevalence PK study. Sixty-eight intensive care units across Europe participated. Inclusion criteria were met by critically ill patients administered fluconazole (n = 15), anidulafungin (n = 9), and caspofungin (n = 7). Three blood samples (peak, mid-dose, and trough) were collected for PK/PD analysis. PK analysis was performed by using a noncompartmental approach. RESULTS: The mean age, weight, and Acute Physiology and Chronic Health Evaluation (APACHE) II scores of the included patients were 58 years, 84 kg, and 22, respectively. Fluconazole, caspofungin, and anidulafungin showed large interindividual variability in this study. In patients receiving fluconazole, 33% did not attain the PK/PD target, ratio of free drug area under the concentration-time curve from 0 to 24 hours to minimum inhibitory concentration (fAUC(0-24)/MIC) ≥100. The fluconazole dose, described in milligrams per kilogram, was found to be significantly associated with achievement of fAUC(0-24)/MIC ≥100 (P = 0.0003). CONCLUSIONS: Considerable interindividual variability was observed for fluconazole, anidulafungin, and caspofungin. A large proportion of the patients (33%) receiving fluconazole did not attain the PK/PD target, which might be related to inadequate dosing. For anidulafungin and caspofungin, dose optimization also appears necessary to minimize variability.

Systemic inflammatory response syndrome criteria in defining severe sepsis.

BACKGROUND: The consensus definition of severe sepsis requires suspected or proven infection, organ failure, and signs that meet two or more criteria for the systemic inflammatory response syndrome (SIRS). We aimed to test the sensitivity, face validity, and construct validity of this approach. METHODS: We studied data from patients from 172 intensive care units in Australia and New Zealand from 2000 through 2013. We identified patients with infection and organ failure and categorized them according to whether they had signs meeting two or more SIRS criteria (SIRS-positive severe sepsis) or less than two SIRS criteria (SIRS-negative severe sepsis). We compared their characteristics and outcomes and assessed them for the presence of a step increase in the risk of death at a threshold of two SIRS criteria. RESULTS: Of 1,171,797 patients, a total of 109,663 had infection and organ failure. Among these, 96,385 patients (87.9%) had SIRS-positive severe sepsis and 13,278 (12.1%) had SIRS-negative severe sepsis. Over a period of 14 years, these groups had similar characteristics and changes in mortality (SIRS-positive group: from 36.1% [829 of 2296 patients] to 18.3% [2037 of 11,119], P<0.001; SIRS-negative group: from 27.7% [100 of 361] to 9.3% [122 of 1315], P<0.001). Moreover, this pattern remained similar after adjustment for baseline characteristics (odds ratio in the SIRS-positive group, 0.96; 95% confidence interval [CI], 0.96 to 0.97; odds ratio in the SIRS-negative group, 0.96; 95% CI, 0.94 to 0.98; P=0.12 for between-group difference). In the adjusted analysis, mortality increased linearly with each additional SIRS criterion (odds ratio for each additional criterion, 1.13; 95% CI, 1.11 to 1.15; P<0.001) without any transitional increase in risk at a threshold of two SIRS criteria. CONCLUSIONS: The need for two or more SIRS criteria to define severe sepsis excluded one in eight otherwise similar patients with infection, organ failure, and substantial mortality and failed to define a transition point in the risk of death. (Funded by the Australian and New Zealand Intensive Care Research Centre.).

Sleep and nursing care activities in an intensive care unit.

This study aimed to describe the quality of sleep of non-intubated patients and the night-time nursing care activities in an intensive care unit. The study also aimed to evaluate the effect of nursing care activities on the quality of sleep. An overnight polysomnography was performed in 21 alert, non-intubated, non-sedated adult patients, and all nursing care activities that involved touching the patient were documented by the bedside nurse. The median (interquartile range) amount of sleep was 387 (170, 486) minutes. The portion of deep non-rapid-eye-movement (non-REM) sleep varied from 0% to 42% and REM sleep from 0% to 65%. The frequency of arousals and awakenings varied from two to 73 per hour. The median amount of nursing care activities was 0.6/h. Every tenth activity presumably awakened the patient. Patients who had more care activities had more light N1 sleep, less light N2 sleep, and less deep sleep. Nursing care was often performed while patients were awake. However, only 31% of the intervals between nursing care activities were over 90 min. More attention should be paid to better clustering of care activities.

Functional outcome, cognition and quality of life after out-of-hospital cardiac arrest and therapeutic hypothermia: data from a randomized controlled trial.

BACKGROUND: To study functional neurologic and cognitive outcome and health-related quality of life (HRQoL) in a cohort of patients included in a randomised controlled trial on glucose control following out-of-hospital cardiac arrest (OHCA) from ventricular fibrillation (VF) treated with therapeutic hypothermia. METHODS: Patients alive at 6 months after being discharged from the hospital underwent clinical neurological and extensive neuropsychological examinations. Functional outcome was evaluated with the Cerebral Performance Category scale, the modified Rankin scale and the Barthel Index. Cognitive outcome was evaluated by neuropsychological test battery including two measures of each cognitive function: cognitive speed, execution, memory, verbal skills and visuospatial performance. We also assessed quality of life with a HRQoL 15D questionnaire. RESULTS: Of 90 OHCA-VF patients included in the original trial, 57 were alive at 6 months. Of these, 52 (91%) were functionally independent and 54 (95%) lived at their previous home. Focal neurological deficits were scarce. Intact cognitive performance was observed in 20 (49%), mild to moderate deficits in 14 (34%) and severe cognitive deficits in 7 (17%) of 41 patients assessed by a neuropsychologist. Cognitive impairments were most frequently detected in executive and memory functions. HRQoL of the CA survivors was comparable to that of age- and gender matched population. CONCLUSIONS: Functional outcome six months after OHCA and therapeutic hypothermia was good in the great majority of the survivors, and half of them were cognitively intact. Of note, the HRQoL of CA survivors did not differ from that of age- and gender matched population.

A randomised controlled trial of standard transfusion versus fresher red blood cell use in intensive care (TRANSFUSE): protocol and statistical analysis plan.

OBJECTIVE: To determine if using freshest available rather than standard-issue red blood cells (RBCs) can reduce mortality in critically ill intensive care unit patients. Our study is the largest ongoing randomised controlled trial (RCT) of RBC age in critically ill patients and will help determine if the use of the freshest available RBCs should become standard policy for the critically ill. DESIGN, SETTING AND PARTICIPANTS: A double-blind, multicentre, Phase III RCT of 5000 adult ICU patients in Australia, New Zealand, Europe and the Middle East. INTERVENTIONS: Transfusion of the freshest available RBCs in place of standard-care RBCs until hospital discharge. MAIN OUTCOME MEASURES: The primary outcome measure is 90-day all-cause mortality. Secondary outcome measures are time to death, 28-day and 180-day mortality, persistent organ dysfunction combined with death, days alive and free of mechanical ventilation and renal replacement therapy, bloodstream infection in the ICU, length of stay in the ICU and in hospital, proportion of patients with febrile non-haemolytic transfusion reactions, and quality of life at Day 180. RESULTS: A detailed statistical analysis plan with predefined subgroups and secondary analyses has been finalised before results being available, to ensure an unbiased final analysis. CONCLUSIONS: The pragmatic protocol design has been chosen to facilitate translation of the trial results into practice. The TRANSFUSE trial will have important clinical and policy implications, regardless of the outcome.