Comparison of Different Ultrasound Methods to Assess Changes in Muscle Mass in Critically ill Patients.

BACKGROUND: Muscle ultrasound represents a promising approach to aid diagnoses of neuromuscular diseases in critically ill patients. Unfortunately, standardization of ultrasound measurements in clinical research is lacking, making direct comparisons between studies difficult. Protocols are required to assess qualitative muscle changes during an ICU stay in patients at high risk for the development of neuromuscular acquired weakness (ICUAW). METHODS: We conducted a retrospective, observational analysis comprised of three prospective observational studies with the aim of diagnosing muscle changes by ultrasound measurement of the quadriceps muscle. Different protocols were used in each of the three studies. In total, 62 surgical, neurocritical care and trauma intensive care patients were serially assessed by different ultrasound protocols during the first week of critical illness. The relative change in ultrasound measurements was calculated for all possible locations, methods and sides. Comparison was obtained using mixed effect models with the location, the height and the side as influencing variables and patients as fixed effect. The relationship between variables and outcomes was assessed by multivariable regression analysis. RESULTS: Ultrasound methods and measurement sites of the quadriceps muscles from all protocols were equally effective in detecting muscle changes. During the first week of an ICU stay, two groups were identified: patients with decreased muscle mass on ultrasound (n = 42) and a cohort with enlargement (n = 23). Hospital mortality was significantly increased in the cohort with muscle swelling (8 (19%) versus 12 (52%), p = .013). CONCLUSIONS: Different approaches of ultrasound measurement during critical-illness are equally able to detect muscle changes. While some patients have a decrease in muscle mass, others show swelling, which may result in a reduced probability of surviving the hospital stay. Causative reasons for these results still remain unclear.

Multivariable haemodynamic approach to predict the fluid challenge response: A multicentre cohort study.

BACKGROUND: Beat-to-beat stroke volume (SV) results from the interplay between left ventricular function and arterial load. Fluid challenge induces time-dependent responses in cardiac performance and peripheral vascular and capillary characteristics. OBJECTIVE: To assess whether analysis of the determinants of the haemodynamic response during fluid challenge can predict the final response at 10 and 30 min. DESIGN: Observational multicentric cohort study. SETTING: Three university ICUs. PATIENTS: 85 ICU patients with acute circulatory failure diagnosed within the first 48 h of admission. INTERVENTION(S): The fluid challenge consisted of 500 ml of Ringer's solution infused over 10 min. A SV index increase at least 10% indicated fluid responsiveness. MAIN OUTCOME MEASURES: The SV, pulse pressure variation (PPV), arterial elastance, the systolic-dicrotic pressure difference (SAP-Pdic) and cardiac cycle efficiency (CCE) were measured at baseline, 1, 2, 3, 4, 5, 10, 15 and 30 min after the start of the fluid challenge. All haemodynamic data were submitted to a univariable logistic regression model and a multivariable analysis was then performed using the significant variables given by univariable analysis. RESULTS: The multivariable model including baseline PPV, and the changes of arterial elastance at 1 min and of the CCE and SAP-Pdic at 5 min when compared with their baseline values, correctly classified 80.5% of responders and 90.7% of nonresponders at 10 min. For the response 30 min after starting the fluid challenge, the model, including the changes of PPV, CCE, SAP-Pdic at 5 min and of arterial elastance at 10 min compared with their baseline values, correctly identified 93.3% of responders and 91.4% of nonresponders. CONCLUSION: In a selection of mixed ICU patients, a statistical model based on a multivariable analysis of the changes of PPV, CCE, arterial elastance and SAP-Pdic, with respect to baseline values, reliably predicts both the early and the late response to a standardised fluid challenge. TRIAL REGISTRATION: ACTRN12617000076370.

Mini fluid chAllenge aNd End-expiratory occlusion test to assess flUid responsiVEness in the opeRating room (MANEUVER study): A multicentre cohort study.

BACKGROUND: The fluid challenge response in surgical patients can be predicted by functional haemodynamic tests. Two tests, the mini-fluid challenge (mini-FC) and end-expiratory occlusion test (EEOT), have been assessed in a few small single-centre studies with conflicting results. In general, functional haemodynamic tests have not performed reliably in predicting fluid responsiveness in patients undergoing laparotomy. OBJECTIVE: This trial is designed to address and compare the reliability of the EEOT and the mini-FC in predicting fluid responsiveness during laparotomy. DESIGN: Prospective, multicentre study. SETTING: Three university hospitals in Italy. PATIENTS: A total of 103 adults patients scheduled for elective laparotomy with invasive arterial monitoring. INTERVENTIONS: The study protocol evaluated the changes in the stroke volume index (SVI) 20 s (EEOT20) and 30 s (EEOT30) after an expiratory hold and after a mini-FC of 100 ml over 1 min. Fluid responsiveness required an increase in SVI at least 10% following 4 ml kg-1 of Ringer's solution fluid challenge infused over 10 min. MAIN OUTCOME MEASUREMENTS: Haemodynamic data, including SVI, were obtained from pulse contour analysis. The area under the receiver operating characteristic curves of the tests were compared with assess fluid responsiveness. RESULTS: Fluid challenge administration induced an increase in SVI at least 10% in 51.5% of patients. The rate of fluid responsiveness was comparable among the three participant centres (P = 0.10). The area under the receiver operating characteristic curves (95% CI) of the changes in SVI after mini-FC was 0.95 (0.88 to 0.98), sensitivity 98.0% (89.5 to 99.6) and specificity 86.8% (75.1 to 93.4) for a cut-off value of 4% of increase in SVI. This was higher than the SVI changes after EEOT20, 0.67 (0.57 to 0.76) and after EEOT30, 0.73 (0.63 to 0.81). CONCLUSION: In patients undergoing laparotomy the mini-FC reliably predicted fluid responsiveness with high-sensitivity and specificity. The EEOT showed poor discriminative value and cannot be recommended for assessment of fluid responsiveness in this surgical setting. TRIAL REGISTRATION: NCT03808753.

Assessment of Fluid Responsiveness in Prone Neurosurgical Patients Undergoing Protective Ventilation: Role of Dynamic Indices, Tidal Volume Challenge, and End-Expiratory Occlusion Test.

BACKGROUND: In patients in the prone position, the reliability of pulse pressure variation and stroke volume variation (PPV and SVV) and the use of functional hemodynamic tests to predict fluid responsiveness have not previously been established. Perioperatively, in this setting, optimizing fluid management can be challenging, and fluid overload is associated with both intraoperative and postoperative complications. We designed this study to assess the sensitivity and specificity of baseline PPV and SVV, the tidal volume (VT) challenge (VTC) and the end-expiratory occlusion test (EEOT) in predicting fluid responsiveness during elective spinal surgery. METHODS: The study protocol was started during a period of intraoperative hemodynamic stability after prone positioning and before the administration of any vasopressor: (1) at baseline, the controlled ventilation was set at 6 mL/kg of predicted body weight (PBW) (T0); (2) patients underwent the first EEOT (EEOT6) by interrupting the mechanical ventilation for 30 seconds; (3) the ventilation was set again at 6 mL/kg PBW for 1 minute (T1); (4) the VTC was applied by increasing the VT up to 8 mL/kg PBW for 1 minute; (5) the ventilation was kept at 8 mL/kg PBW for 1 minute (T2); (6) a second EEOT (EEOT8) was performed; (7) the VT was reduced back to 6 mL/kg PBW for 1 minute (T3); (8) a fluid challenge of 250 mL of Ringer's solution was infused over 10 minutes. After each step, a complete set of hemodynamic measurements was recorded. RESULTS: Neither PPV and SVV values recorded at T3 nor the EEOT6 or the EEOT8 predicted fluid responsiveness. The change in PPV after VTC application predicted fluid responsiveness with an area under the curve of 0.96 (95% confidence interval, 0.87-1.00), showing a sensitivity of 95.2% and a specificity of 94.7%, using a cutoff increase of 12.2%. The change in SVV after VTC application predicted fluid responsiveness with an area under the curve 0.96 (95% confidence interval, 0.89-1.00) showing a sensitivity of 95.2% and a specificity of 94.7%, using a cutoff increase of 8.0%. A linear correlation between stroke volume index changes after fluid challenge administration and the changes in PPV and SVV after VTC application was observed (r = 0.71; P < .0001 and r = 0.68; P < .0001, respectively). CONCLUSIONS: In prone elective neurosurgical patients, the baseline values of PPV and SVV and the EEOT fail to predict fluid responsiveness, while the VTC is a very reliable functional hemodynamic test and could be helpful in guiding intraoperative fluid therapy.

Functional hemodynamic tests: a systematic review and a metanalysis on the reliability of the end-expiratory occlusion test and of the mini-fluid challenge in predicting fluid responsiveness.

BACKGROUND: Bedside functional hemodynamic assessment has gained in popularity in the last years to overcome the limitations of static or dynamic indexes in predicting fluid responsiveness. The aim of this systematic review and metanalysis of studies is to investigate the reliability of the functional hemodynamic tests (FHTs) used to assess fluid responsiveness in adult patients in the intensive care unit (ICU) and operating room (OR). METHODS: MEDLINE, EMBASE, and Cochrane databases were screened for relevant articles using a FHT, with the exception of the passive leg raising. The QUADAS-2 scale was used to assess the risk of bias of the included studies. In-between study heterogeneity was assessed through the I2 indicator. Bias assessment graphs were plotted, and Egger's regression analysis was used to evaluate the publication bias. The metanalysis determined the pooled area under the receiving operating characteristic (ROC) curve, sensitivity, specificity, and threshold for two FHTs: the end-expiratory occlusion test (EEOT) and the mini-fluid challenge (FC). RESULTS: After text selection, 21 studies met the inclusion criteria, 7 performed in the OR, and 14 in the ICU between 2005 and 2018. The search included 805 patients and 870 FCs with a median (IQR) of 39 (25-50) patients and 41 (30-52) FCs per study. The median fluid responsiveness was 54% (45-59). Ten studies (47.6%) adopted a gray zone analysis of the ROC curve, and a median (IQR) of 20% (15-51) of the enrolled patients was included in the gray zone. The pooled area under the ROC curve for the end-expiratory occlusion test (EEOT) was 0.96 (95%CI 0.92-1.00). The pooled sensitivity and specificity were 0.86 (95%CI 0.74-0.94) and 0.91 (95%CI 0.85-0.95), respectively, with a best threshold of 5% (4.0-8.0%). The pooled area under the ROC curve for the mini-FC was 0.91 (95%CI 0.85-0.97). The pooled sensitivity and specificity were 0.82 (95%CI 0.76-0.88) and 0.83 (95%CI 0.77-0.89), respectively, with a best threshold of 5% (3.0-7.0%). CONCLUSIONS: The EEOT and the mini-FC reliably predict fluid responsiveness in the ICU and OR. Other FHTs have been tested insofar in heterogeneous clinical settings and, despite promising results, warrant further investigations.

Effects of Fluids on the Macro- and Microcirculations.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2018. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2018 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901 .

Characterization of Yersinia species by protein profiling using automated microfluidic capillary electrophoresis.

Yersinia pestis is a biological agent of high risk to national security due to its ability to be easily disseminated and transmitted among humans. If Y. pestis was to be utilized in a deliberate disease outbreak it would be essential to rapidly and accurately identify the agent. Current identification methods for Yersinia species are limited by their reliance on cultivation, the time taken to achieve results and/or the use of protocols that are not amenable for field use. Faster identification methods are urgently required. Microfluidic capillary electrophoresis was used to identify seven Yersinia species based on their protein profiles. Further objectives included determining if Yersinia species could be detected in mixtures of milk products and Escherichia coli, determining if Yersinia could be detected in a blinded identification and reproducibility across two platforms. Two characteristic protein bands were detected at 50 kilodaltons (kDa) and between 50 and 75 kDa for the Yersinia species. Individual Yersinia species could be differentiated from one another and distinguished from E. coli, Bacillus anthracis Sterne strain and Dipel (containing Bacillus thuringiensis). Due to the high protein content of milk products Yersinia could not be detected when mixed with these but was detected when mixed with E. coli. Species were correctly identified with 96% success in blinded procedures using 12 individuals. Whilst protein profile patterns were reproducible across platforms there was some discrepancy in protein sizing. This study demonstrates that protein profiling using microfluidic capillary electrophoresis is able to rapidly and reproducibly identify and characterize Yersinia species. Results show this technique is a powerful front-line, rapid and broad range screening method capable of identifying and differentiating biological agents, hoax agents and environmental bacterial species.

Key steps and suggestions for a promising approach to a critical care mentoring program.

In critical care medicine, where there is a demanding career with a problematic work-life balance, mentoring is an important support tool to grow professionally, creating a network of support throughout the career. The mentoring process consists of evidence-based steps to guide critical care mentors and mentees and pair them with each other according to the correct selection and matching of participants.In order to focus on the active role of a young intensivist selected as a mentee at any level and to support their success in a mentoring relationship, the NEXT Committee of the European Society of Intensive Care Medicine (ESICM) developed 2012 a mentoring program.The critical steps of the mentoring program start from establishing a policy and program objectives, passing through the selection of participants, and matching with mentors up to the definition of the personal development plan supported by checklists, worksheets, and evaluation forms. The present manuscript provides key steps and tips for a good, essential based on our experience in the ESICM NEXT-Mentoring Program so that they guide for future mentoring programs conducted by other scientific societies. In addition, we discuss common challenges and how to avoid them.

Does the definition of fluid responsiveness affect passive leg raising reliability? A methodological ancillary analysis from a multicentric study.

BACKGROUND: Fluid challenge (FC) is often adopted as gold standard used to assess the reliability of passive leg raising (PLR) in predicting fluid responsiveness in the intensive care unit (ICU). This study aimed to address the impact of the different definitions and timings used to assess FC response on PLR reliability. METHODS: Ancillary study from a data set of a multicentric study in 85 ICU patient with acute circulatory failure who received a FC (500 mL of crystalloids in 10 minutes) within the first 48h of ICU admission, preceded by PLR in 30 patients. FC response was assessed considering the changes in Cardiac Index (CI) and Stroke Volume Index (SVI) using different thresholds and at different time-points. RESULTS: The definitions of fluid responsiveness by using CI or SVI with a 15% increase after 10 minutes were associated to the best performances of the PLR (AUC 0.94 [95% CI 0.83-1.01] vs. AUC 0.95 [95% CI 0.87-1.02]). The sensitivity of the PLR by adopting the CI or the SVI as reference variable ranged from 54.1% to 67.6% and from 81.5% to 100.0%; the specificity from 65.9% to 78.0% and from 79.5% to 100.0%, respectively. Considering all the subgroups, the number of responders 10 minutes after FC administration was higher as compared to 15 and 30 minutes (140 vs. 120 and 125, respectively, P<0.05). CONCLUSIONS: The reliability of the PLR test to predict fluid responsiveness depends on the definition of FC adopted. The timing of FC outcome assessment affected the overall fluid responsiveness.

An effective survey method for studying volant species activity and behavior at tall structures.

The effects of anthropogenic modification of air space on wildlife, particularly volant species, is not fully understood. Thus, it is essential to understand wildlife-interactions with tall structures to implement effective mitigation strategies. Yet, we are currently lacking standard protocols for visual surveys of wildlife behavior at such heights. Our study sought to determine an effective, repeatable method using readily available night vision and thermal technology to survey wildlife at tall structures. Using bats as the taxonomic group of interest, we (1) created a key to identify bats and their behavior, (2) compared the effectiveness of 2 different technologies, and (3) assessed optimal equipment placement to visually capture bat activity and behavior in proximity to wind turbine towers. For the latter, we tested thermal cameras at four distances from the base of the tower. The results of our study revealed that thermal cameras captured ∼34% more flying animals than night vision at a 2 m distance. However, due to the heat signature of the turbine towers themselves, it was challenging to identify behaviors and interactions that occurred in close proximity to the towers. In contrast, it was difficult to identify bats approaching the towers using night vision, yet we were able to clearly observe interactions with the towers themselves. With regards to equipment placement, we visually captured more bats with the thermal cameras placed 2 m from the tower base compared to farther distances. From our findings, we recommend that when using either thermal or night vision technology at tall structures, they be placed 2 m from the base to effectively observe interactions along the length of these structures. In addition, we further recommend that consideration be given to the use of these two technology types together to effectively conduct such surveys. If these survey techniques are incorporated into standard protocols, future surveys at a variety of tall structures are likely to become comparable and repeatable, thereby more effectively informing any mitigation strategies that may be required.

Distinguishing Subtypes of Mutual Violence in the Context of Self-defense: Classifying Types of Partner Violent Couples using a Modified Conflict Tactics Scale.

PURPOSE: The Revised Conflict Tactics Scale 2 (CTS2; Straus, Hamby, Boney-McCoy, & Sugarman, 1996) is the most widely used measure for assessing the frequency of intimate partner violence (IPV). However, it has been criticized for not capturing the context in which IPV takes place. This study examined follow-up items to each CTS2 physical assault item asking to clarify how often the act was perpetrated in self-defense. METHOD: A community sample of couples (N = 180) recruited for men's recent violence toward women completed the project-modified Conflict Tactics Scale with Self-Defense (CTS2SD). The majority (69.5%) reported that the physical aggression in the past year was bilateral. On the follow-up items, 27% of men's violent acts and over 22% of women's violent acts were reportedly committed in self-defense. Men's and women's CTS2 physical assault perpetration scores, along with the percentage that were committed in self-defense, were entered into two-step cluster analyses. RESULTS: Cluster analyses revealed three subgroups of bilateral violence: Male Self-defense, Female Self-defense, and Mutual Violence. The Mutual Violent cluster reported the most frequent physical assault, injury, men's controlling behavior and men's arrest for domestic violence. CONCLUSIONS: Findings suggest that Straus' (2012) tripartite conceptualization of Man-only, Woman-only, and Both-violent couples is overly simplistic and fails to capture different types of bilateral aggression.

Venoarterial extracorporeal membrane oxygenation: A systematic review of selection criteria, outcome measures and definitions of complications.

PURPOSE: The purpose of this study was to systematically investigate the reporting of selection criteria and outcome measures, and to examine definitions of complications used in venoarterial extracorporeal membrane oxygenation studies (V-A ECMO). MATERIALS AND METHODS: Medline, EMBASE and the Cochrane central register were searched for V-A ECMO studies from January 2005 to July 2017. Studies with ≤99 patients or without patient centered outcomes were excluded. Two reviewers independently assessed search results and undertook data extraction. RESULTS: Forty-six studies met the inclusion criteria, and all were retrospective, observational studies. Inconsistent reporting of selection criteria, ECMO management and outcome measures was common. In-hospital mortality was the most common primary outcome (41% of studies), followed by 30-day mortality (11%). Bleeding was the most frequent complication reported, most commonly defined as "bleeding requiring transfusion" (median ≥ 2 Units/day). Significant variation in reporting and definitions was also evident for vascular, neurological renal and infectious complications. CONCLUSION: This systematic review provides clinicians with the most commonly reported selection criteria, outcome measures and complications used in ECMO practice. However non-standardized definitions and inconsistent reporting limits their ability to inform practice. New consensus driven definitions of complications and patient centred outcomes are urgently needed.

Histological subtype of lung cancer in relation to socio-economic deprivation in South East England.

BACKGROUND: Previous studies have found differences in the histological subtypes of lung cancers affecting males and females. Our objective was to investigate trends in the incidence of histological subtypes of lung cancer in males and females in relation to socio-economic deprivation in South East England. METHODS: Data on 48,031 males and 30,454 females diagnosed with lung cancer between 1995 and 2004 were extracted from the Thames Cancer Registry database. Age-standardised incidence rates for histological subtypes were calculated for each year, using the European standard population. Using the Income Domain of the Multiple Index of Deprivation 2004, patients diagnosed between 2000 and 2004 were classified into quintiles of socio-economic deprivation based on their postcode of residence. Age-standardised rates for each histological subtype were then calculated for each deprivation quintile. A Poisson regression model was fitted to the data for males and females separately to test the hypothesis that the relationship between socio-economic deprivation and adenocarcinoma was less strong than for other subtypes. RESULTS: In males all specific histological subtypes except adenocarcinoma declined in incidence. Squamous cell carcinoma remained the most common specific subtype and large cell carcinoma the least common. In females squamous cell carcinoma was initially most common, but its incidence declined slightly and that for adenocarcinoma increased. In both sexes the overall age-standardised incidence rate of lung cancer increased with increasing deprivation. However, these trends were less strong for adenocarcinoma than for the other subtypes in both males (p < 0.001) and females (p = 0.003). CONCLUSION: The temporal trends and distribution of histological subtypes of lung cancer in males and females are similar to that reported from other western populations. In both males and females, adenocarcinoma was less strongly related to deprivation than other subtypes. This may be because its development is less strongly linked to individual smoking history.

Evaluation of cardiac function using heart-lung interactions.

Heart lung interactions can be used clinically to assist in the evaluation of cardiac function. Application of these interactions and understanding of the physiology underlying them has formed a focus of research over a number of years. The changes in preload induced by changes in intrathoracic pressure (ITP) with the respiratory cycle, have been applied to form dynamic tests of fluid responsiveness. Pulse pressure variation (PPV), stroke volume variation (SVV), end expiratory occlusion test, pleth variability index (PVI) and use of echocardiography are all clinical assessments that can be made at the bedside. However, there are limitations and pitfalls to each that restrict their use to specific situations. The haemodynamic response to treatment with continuous positive airway pressure (CPAP) in left ventricular failure is explained by the presence of heart lung interactions, and works predominately through afterload reduction. Similarly, in other disease states such as acute respiratory distress syndrome (ARDS), the effects of a change in ventilation can provide information about both the cardiac and respiratory system. This review aims to summarise how assessment of cardiac function using heart lung interactions can be performed. It introduces the underlying physiology and some of the clinical applications that are further explored in other articles within the series.

Mercury contamination in bats from the central United States.

Mercury (Hg) is a highly toxic metal that has detrimental effects on wildlife. We surveyed Hg concentrations in 10 species of bats collected at wind farms in the central United States and found contamination in all species. Mercury concentration in fur was highly variable both within and between species (range: 1.08-10.52 µg/g). Despite the distance between sites (up to 1200 km), only 2 of the 5 species sampled at multiple locations had fur Hg concentrations that differed between sites. Mercury concentrations observed in the present study all fell within the previously reported ranges for bats collected from the northeastern United States and Canada, although many of the bats we sampled had lower maximum Hg concentrations. Juvenile bats had lower concentrations of Hg in fur compared with adult bats, and we found no significant effect of sex on Hg concentrations in fur. For a subset of 2 species, we also measured Hg concentration in muscle tissue; concentrations were much higher in fur than in muscle, and Hg concentrations in the 2 tissue types were weakly correlated. Abundant wind farms and ongoing postconstruction fatality surveys offer an underutilized opportunity to obtain tissue samples that can be used to assess Hg contamination in bats. Environ Toxicol Chem 2018;37:160-165. © 2018 SETAC.

Permissive Hypercapnia, Alveolar Recruitment and Low Airway Pressure (PHARLAP): a protocol for a phase 2 trial in patients with acute respiratory distress syndrome.

BACKGROUND: Mechanical ventilation is a life-saving intervention that maintains gas exchange in patients with acute respiratory distress syndrome (ARDS); however, it is associated with high mortality and it may augment, or even initiate, lung injury. An open lung ventilation strategy that combines alveolar recruitment manoeuvres with individually titrated positive end-expiratory pressure (PEEP) and targeting lower tidal volumes, or driving pressures by a permissive approach to hypercapnia, may reduce the lung injury associated with mechanical ventilation. This protocol reports the rationale, study design and analysis plan of the Permissive Hypercapnia, Alveolar Recruitment and Low Airway Pressure (PHARLAP) trial. METHODS AND DESIGN: PHARLAP is a phase 2, international, multicentre, prospective, randomised, controlled, parallel-group clinical trial, which aims to determine if staircase alveolar recruitment and individually titrated PEEP, when combined with permissive hypercapnia and low airway pressures, increases ventilator-free days to Day 28 when compared with conventional mechanical ventilation (Acute Respiratory Distress Syndrome Clinical Network [ARDSNet] strategy) in patients with moderate to severe ARDS. This study will enrol 340 patients. The intervention group will receive daily staircase alveolar recruitment manoeuvres with incremental PEEP to a maximum of 40 cmH2O and peak pressures to a maximum of 55 cmH2O. PEEP will be titrated individually against peripheral oxygen saturation, targeting lower tidal volumes by a permissive approach to hypercapnia. In the control group, patients will receive mechanical ventilation following the ARDSNet-ARMA trial protocol, including PEEP titrated with a PEEP/fraction of inspired oxygen (FiO2) chart. Both groups will receive airway pressures ≤30 cmH2O and tidal volumes of ≤ 6 mL/kg predicted bodyweight or less. The primary outcome is ventilator-free days to Day 28. Secondary outcomes include oxygenation and lung compliance, intensive care unit (ICU) and hospital length of stay, use of rescue therapies for refractory hypoxaemia, rate of barotrauma, mortality (ICU, hospital and at 28, 90 and 180 days), quality of life and a health economic analysis at 6 months. DISCUSSION: The PHARLAP trial will determine whether the intervention strategy is effective in increasing ventilator-free days in patients with ARDS. If the PHARLAP strategy is proven to improve ventilator-free days, it will provide a strong impetus to conduct an international phase 3 trial to determine the effects of this strategy on mortality. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01667146.

Protocol summary and statistical analysis plan for the intensive care unit randomised trial comparing two approaches to oxygen therapy (ICU-ROX).

BACKGROUND: The balance of risks and benefits of conservative v standard care oxygen strategies for patients who are invasively ventilated in the intensive care unit (ICU) is uncertain. OBJECTIVE: To describe the study protocol and statistical analysis plan for the ICU randomised trial comparing two approaches to oxygen therapy (ICU-ROX). DESIGN, SETTING AND PARTICIPANTS: Protocol for a multicentre, randomised, participant and outcome assessor-blinded, standard care-controlled, parallel-group, two-sided superiority trial to be conducted in up to 22 ICUs in Australia and New Zealand. 1000 adults who are mechanically ventilated in the ICU and expected to remain ventilated beyond the day after recruitment will be randomly assigned to conservative oxygen therapy or standard care in a 1:1 ratio. ICU-ROX began with an internal pilot phase in September 2015. It is anticipated that recruitment will be completed in 2018. MAIN OUTCOME MEASURES: The primary endpoint will be alive, ventilator-free days to Day 28. Secondary outcomes include 90- and 180-day all-cause mortality, survival time to 180 days, and quality of life and cognitive function at 180 days. All analyses will be conducted on an intentionto- treat basis. RESULTS AND CONCLUSIONS: ICU-ROX will compare the effect of conservative v standard oxygen therapy in critically ill mechanically ventilated adults who are expected to be ventilated beyond the day after recruitment on ventilatorfree days to Day 28. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ANZCTRN 12615000957594).

Perioperative fluid management: From physiology to improving clinical outcomes.

Perioperative fluid management is a key component in the care of the surgical patient. It is an area that has seen significant changes and developments, however there remains a wide disparity in practice between clinicians. Historically, patients received large volumes of intravenous fluids perioperatively. The concept of goal directed therapy was then introduced, with the early studies showing significant improvements in morbidity and mortality. The current focus is on fluid therapy guided by an individual patient's physiology. A fluid challenge is commonly performed as part of an assessment of a patient's fluid responsiveness. There remains wide variation in how clinicians perform a fluid challenge and this review explores the evidence for how to administer an effective challenge that is both reliable and reproducible. The methods for monitoring cardiac output have evolved from the pulmonary artery catheter to a range of less invasive techniques. The different options that are available for perioperative use are considered. Fluid status can also be assessed by examining the microcirculation and the importance of recognising the possibility of a lack of coherence between the macro and microcirculation is discussed. Fluid therapy needs to be targeted to specific end points and individualised. Not all patients who respond to a fluid challenge will necessarily require additional fluid administration and care should be aimed at identifying those who do. This review aims to explain the underlying physiology and describe the evidence base and the changes that have been seen in the approach to perioperative fluid therapy.

Increasing evidence that bats actively forage at wind turbines.

Although the ultimate causes of high bat fatalities at wind farms are not well understood, several lines of evidence suggest that bats are attracted to wind turbines. One hypothesis is that bats would be attracted to turbines as a foraging resource if the insects that bats prey upon are commonly present on and around the turbine towers. To investigate the role that foraging activity may play in bat fatalities, we conducted a series of surveys at a wind farm in the southern Great Plains of the US from 2011-2016. From acoustic monitoring we recorded foraging activity, including feeding buzzes indicative of prey capture, in the immediate vicinity of turbine towers from all six bat species known to be present at this site. From insect surveys we found Lepidoptera, Coleoptera, and Orthoptera in consistently high proportions over several years suggesting that food resources for bats were consistently available at wind turbines. We used DNA barcoding techniques to assess bat diet composition of (1) stomach contents from 47 eastern red bat (Lasiurus borealis) and 24 hoary bat (Lasiurus cinereus) carcasses collected in fatality searches, and (2) fecal pellets from 23 eastern red bats that were found on turbine towers, transformers, and tower doors. We found that the majority of the eastern red bat and hoary bat stomachs, the two bat species most commonly found in fatality searches at this site, were full or partially full, indicating that the bats were likely killed while foraging. Although Lepidoptera and Orthoptera dominated the diets of these two bat species, both consumed a range of prey items with individual bats having from one to six insect species in their stomachs at the time of death. The prey items identified from eastern red bat fecal pellets showed similar results. A comparison of the turbine insect community to the diet analysis results revealed that the most abundant insects at wind turbines, including terrestrial insects such as crickets and several important crop pests, were also commonly eaten by eastern red and hoary bats. Collectively, these findings suggest that bats are actively foraging around wind turbines and that measures to minimize bat fatalities should be broadly implemented at wind facilities.

Intensive care unit randomised trial comparing two approaches to oxygen therapy (ICU-ROX): results of the pilot phase.

OBJECTIVE: The objective of the intensive care unit randomised trial comparing two approaches to oxygen therapy (ICU-ROX) pilot phase, which included the first 100 patients of an overall sample of 1000, was to examine feasibility. DESIGN: Investigator-initiated, prospective, parallel-group, pilot randomised controlled trial. SETTING: Six medical-surgical intensive care units (ICUs) in Australia and New Zealand, with participants recruited from September 2015 through June 2016. PARTICIPANTS: 100 patients ≥ 18 years of age who required invasive mechanical ventilation in the ICU and were expected to be receiving it beyond the next calendar day at the time of randomisation. INTERVENTIONS: Conservative oxygen therapy or standard care. MAIN OUTCOME MEASURES: Eligibility, recruitment rate, and separation in oxygen exposure (fraction of inspired oxygen [FiO2] and oxygen saturation measured by pulse oximetry [SpO2Z]). RESULTS: 94 of 99 participants (94.9%) were confirmed by study monitors to fulfil the study eligibility criteria. 3.6 patients per site per month were enrolled (95% confidence interval [CI], 2.5-4.7). Patients allocated to conservative oxygen therapy spent significantly more time on an FiO2 of 0.21 in the ICU; median, 31.5 hours (interquartile range [IQR], 7-63.5) for conservative oxygen therapy patients v 0 hours for standard oxygen therapy patients (IQR, 0-10; midpoint difference, 21.5 hours; 95% CI, 9-34; P < 0.0001). Patients allocated to conservative oxygen therapy spent less time in the ICU with an SpO2Z of ≥ 97% than patients allocated to standard oxygen therapy; median, 18.5 hours (IQR, 5-46) for conservative oxygen therapy patients v 32 hours for standard oxygen therapy (IQR, 17-80; midpoint difference, 13.5 hours; 95% CI, 2-25; P = 0.02). CONCLUSIONS: Our findings confirm the feasibility of completing the ICU-ROX trial without the need for substantive changes to the study protocol for the remaining 900 trial participants. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ANZCTRN 12615000957594).