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Objective: To compare the demographic and clinical features, management, and outcomes for patients admitted with COVID-19 to intensive care units (ICUs) during the first, second, and third waves of the pandemic in Australia., Design, Setting, and Participants: People aged 16 years or more admitted with polymerase chain reaction-confirmed COVID-19 to the 78 Australian ICUs participating in the Short Period Incidence Study of Severe Acute Respiratory Infection (SPRINT-SARI) Australia project during the first (27 February - 30 June 2020), second (1 July 2020 - 25 June 2021), and third COVID-19 waves (26 June - 1 November 2021)., Main Outcome Measures: Primary outcome: in-hospital mortality., Secondary Outcomes: ICU mortality; ICU and hospital lengths of stay; supportive and disease-specific therapies., Results: 2493 people (1535 men, 62%) were admitted to 59 ICUs: 214 during the first (9%), 296 during the second (12%), and 1983 during the third wave (80%). The median age was 64 (IQR, 54-72) years during the first wave, 58 (IQR, 49-68) years during the second, and 54 (IQR, 41-65) years during the third. The proportion without co-existing illnesses was largest during the third wave (41%; first wave, 32%; second wave, 29%). The proportion of ICU beds occupied by patients with COVID-19 was 2.8% (95% CI, 2.7-2.9%) during the first, 4.6% (95% CI, 4.3-5.1%) during the second, and 19.1% (95% CI, 17.9-20.2%) during the third wave. Non-invasive (42% v 15%) and prone ventilation strategies (63% v 15%) were used more frequently during the third wave than during the first two waves. Thirty patients (14%) died in hospital during the first wave, 35 (12%) during the second, and 281 (17%) during the third. After adjusting for age, illness severity, and other covariates, the risk of in-hospital mortality was similar for the first and second waves, but 9.60 (95% CI, 3.52-16.7) percentage points higher during the third than the first wave., Conclusion: The demographic characteristics of patients in intensive care with COVID-19 and the treatments they received during the third pandemic wave differed from those of the first two waves. Adjusted in-hospital mortality was highest during the third wave., (© 2022 The Authors. Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

Background: Data on long-term outcomes after sepsis-associated critical illness have mostly come from small cohort studies, with no information about the incidence of new disability. We investigated whether sepsis-associated critical illness was independently associated with new disability at 6 months after ICU admission compared with other types of critical illness., Methods: We conducted a secondary analysis of a multicenter, prospective cohort study in six metropolitan intensive care units in Australia. Adult patients were eligible if they had been admitted to the ICU and received more than 24 h of mechanical ventilation. There was no intervention., Results: The primary outcome was new disability measured with the WHO Disability Assessment Schedule 2.0 (WHODAS) 12 level score compared between baseline and 6 months. Between enrollment and follow-up at 6 months, 222/888 (25%) patients died, 100 (35.5%) with sepsis and 122 (20.1%) without sepsis (P < 0.001). Among survivors, there was no difference for the incidence of new disability at 6 months with or without sepsis, 42/106 (39.6%) and 106/300 (35.3%) (RD, 0.00 (- 10.29 to 10.40), P = 0.995), respectively. In addition, there was no difference in the severity of disability, health-related quality of life, anxiety and depression, post-traumatic stress, return to work, financial distress or cognitive function., Conclusions: Compared to mechanically ventilated patients of similar acuity and length of stay without sepsis, patients with sepsis admitted to ICU have an increased risk of death, but survivors have a similar risk of new disability at 6 months. Trial registration NCT03226912, registered July 24, 2017., (© 2022. The Author(s).)

Predicting and optimizing outcomes after traumatic brain injury (TBI) remains a major challenge because of the breadth of injury characteristics and complexity of brain responses. AUS-TBI is a new Australian Government-funded initiative that aims to improve personalized care and treatment for children and adults who have sustained a TBI. The AUS-TBI team aims to address a number of key knowledge gaps, by designing an approach to bring together data describing psychosocial modulators, social determinants, clinical parameters, imaging data, biomarker profiles, and rehabilitation outcomes in order to assess the influence that they have on long-term outcome. Data management systems will be designed to track a broad range of suitable potential indicators and outcomes, which will be organized to facilitate secure data collection, linkage, storage, curation, management, and analysis. It is believed that these objectives are achievable because of our consortium of highly committed national and international leaders, expert committees, and partner organizations in TBI and health informatics. It is anticipated that the resulting large-scale data resource will facilitate personalization, prediction, and improvement of outcomes post-TBI., Competing Interests: No competing financial interests exist., (© Melinda Fitzgerald et al., 2022; Published by Mary Ann Liebert, Inc.)

Rationale: The outcomes of survivors of critical illness due to coronavirus disease (COVID-19) compared with non-COVID-19 are yet to be established. Objectives: We aimed to investigate new disability at 6 months in mechanically ventilated patients admitted to Australian ICUs with COVID-19 compared with non-COVID-19. Methods: We included critically ill patients with COVID-19 and non-COVID-19 from two prospective observational studies. Patients were eligible if they were adult (age ⩾ 8 yr) and received ⩾24 hours of mechanical ventilation. In addition, patients with COVID-19 were eligible with a positive laboratory PCR test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Measurements and Main Results: Demographic, intervention, and hospital outcome data were obtained from electronic medical records. Survivors were contacted by telephone for functional outcomes with trained outcome assessors using the World Health Organization Disability Assessment Schedule 2.0. Between March 6, 2020, and April 21, 2021, 120 critically ill patients with COVID-19, and between August 2017 and January 2019, 199 critically ill patients without COVID-19, fulfilled the inclusion criteria. Patients with COVID-19 were older (median [interquartile range], 62 [55-71] vs. 58 [44-69] yr; P  = 0.019) with a lower Acute Physiology and Chronic Health Evaluation II score (17 [13-20] vs. 19 [15-23]; P  = 0.011). Although duration of ventilation was longer in patients with COVID-19 than in those without COVID-19 (12 [5-19] vs. 4.8 [2.3-8.8] d; P  < 0.001), 180-day mortality was similar between the groups (39/120 [32.5%] vs. 70/199 [35.2%]; P  = 0.715). The incidence of death or new disability at 180 days was similar (58/93 [62.4%] vs. 99/150 [66/0%]; P  = 0.583). Conclusions: At 6 months, there was no difference in new disability for patients requiring mechanical ventilation for acute respiratory failure due to COVID-19 compared with non-COVID-19. Clinical trial registered with www.clinicaltrials.gov (NCT04401254).

Background: Medical emergency teams use medications to rescue deteriorating patients. Medication management is the system of steps and processes, including prescribing, distribution, administration, and monitoring, to achieve the best outcomes from medication use. Systems or standards for medication management by medical emergency teams have not been defined., Objectives: The aim of the study was to propose potential solutions to improve medical emergency team medication management by evaluating medication supply and related medication management practices during medical emergency team activations and understanding clinicians' perceptions about medical emergency team medication management in acute hospitals., Methods: A prospective multicentre audit of intensive care unit-equipped hospitals in Victoria, Australia, was conducted. After advertisement and invitation via scheduled email newsletters to hospitals, a representative of the medical emergency team from each hospital self-administered an online audit tool during December 2019 and January 2020. Audit data were analysed descriptively, and perceptions were analysed using content analysis., Results: Responses were received from 32 of the 44 (72.7%) eligible hospitals. At 17 of the 32 (53.1%) hospitals, arrest trolleys provided medications for medical emergency team activations, in addition to arrest calls. At 15 of the 32 (46.9%) hospitals, separate, dedicated medical emergency team medication supplies were used to care for deteriorating patients. Dedicated medical emergency team supplies contained a median of 20 (range = 8-37) medications, predominantly cardiovascular (median = 8, mode = 7, range = 4-16) and neurological medications (median and mode = 6, range = 0-11). Variation was observed in all storage and other supply-related medication management practices studied. The four most frequent categories of clinicians' perceptions described systematic challenges with availability of the right medication in the right place at the right time., Conclusions: Current supply and related medication management practices and clinicians' perceptions demonstrated further development is necessary for medication management to meet the needs of medical emergency team clinicians and their patients., (Copyright © 2021 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Studies comparing mortality following massive transfusion (MT) with fresher versus longer-stored red blood cells (RBCs) have focused on trauma patients. The Australian and New Zealand Massive Transfusion Registry collects data on all adult MT cases (≥5 RBCs within 4 hours, any bleeding context, ≥18 years) at participating hospitals., Methods: Years 2007 to 2018 data from 29 hospitals were analyzed to quantify the association between mortality and RBC storage time in adult MT cases. We ran three logistic regression models separately on each of seven bleeding contexts, with in-hospital mortality as the outcome and, in turn, (1) mean storage time (STmean) quartiles, (2) proportion of RBCs ≥30 days old (propOLD), and (3) scalar age of blood index as predictors., Results: A total of 8,685 adult MT cases involving transfusion of 126,622 RBCs were analyzed with Australian and New Zealand data analyzed separately. Mean storage times for these cases were (by quartile in ascending order) as follows: Australia, 12.5 days (range, 3.1-15.5 days), 17.7 (15.5-19.9), 22.3 (19.9-24.9), and 29.8 (24.9-41.7); New Zealand, 11.3 days (3.6-13.7), 15.3 (13.7-16.8), 18.7 (16.8-20.7), and 24.5 (20.7-35.6). The odds ratios comparing in-hospital mortality for each quartile with that of the control first quartile (freshest blood), proportion of longer-stored (≥30 days) RBCs, and scalar age of blood index were not statistically significant across all bleeding contexts., Conclusion: We find no correlation between in-hospital mortality and storage time of transfused RBCs in a large cohort of adult MT patients representing all bleeding contexts. These results are consistent with those of recent large multicenter trials., Level of Evidence: Epidemiologic, level III; Therapeutic, level IV., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To investigate the association between plasma sodium concentrations and 6-month neurologic outcome in critically ill patients with aneurysmal subarachnoid hemorrhage., Design: Prospective cohort study., Setting: Eleven ICUs in Australia and New Zealand., Participants: Three-hundred fifty-six aneurysmal subarachnoid hemorrhage patients admitted to ICU between March 2016 and June 2018. The exposure variable was daily measured plasma sodium., Interventions: None., Measurements and Main Results: Six-month neurologic outcome as measured by the modified Rankin Scale. A poor outcome was defined as a modified Rankin Scale greater than or equal to 4. The mean age was 57 years (± 12.6 yr), 68% were female, and 32% ( n = 113) had a poor outcome. In multivariable analysis, including age, illness severity, and process of care measures as covariates, higher mean sodium concentrations (odds ratio, 1.17; 95% CI, 1.05-1.29), and greater overall variability-as measured by the sd (odds ratio, 1.53; 95% CI, 1.17-1.99)-were associated with a greater likelihood of a poor outcome. Multivariable generalized additive modeling demonstrated, specifically, that a high initial sodium concentration, followed by a gradual decline from day 3 onwards, was also associated with a poor outcome. Finally, greater variability in sodium concentrations was associated with a longer ICU and hospital length of stay: mean ICU length of stay ratio (1.13; 95% CI, 1.07-1.20) and mean hospital length of stay ratio (1.08; 95% CI, 1.01-1.15)., Conclusions: In critically ill aneurysmal subarachnoid hemorrhage patients, higher mean sodium concentrations and greater variability were associated with worse neurologic outcomes at 6 months, despite adjustment for known confounders. Interventional studies would be required to demonstrate a causal relationship., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background & Aims: Prophylactic hypothermia, often used in critically ill patients with traumatic brain injury, reduces energy expenditure and may affect energy delivered by nutrition therapy. The primary objective of this study was to measure energy expenditure in hypothermic patients over the first 3 days after traumatic brain injury (TBI). Secondary objectives included comparison of measured energy expenditure and nutrition delivery to day 7., Methods: A prospective sub-study of a randomized controlled trial conducted in patients with severe TBI, investigating prophylactic hypothermia (33-35 °C) as a neuroprotective therapy. In two centers, indirect calorimetry was initiated within 24 h of randomization and repeated up to twice daily to day 7. Data are presented as n (%), mean (standard deviation (SD)), median [interquartile range (IQR)], and mean difference (95% confidence interval (CI))., Results: Forty patients were included (20 in each group), with 17 patients in the hypothermic and 16 in the normothermic group having an indirect calorimetry measurement in the first 3 days. Over the first 3 days, the mean temperature in the hypothermic and normothermic groups was 33.5 (0.6) ºC (n = 17) and 37 (0.5) ºC (n = 16), p < 0.0001, and the mean measured energy expenditure, was 21 (5) and 27 (4) kcal/kg, p = 0.002, representing a mean difference of 5 (95% CI: 2-8) kcal/kg. Energy expenditure was 20% (95% CI: 9.5-29%) less in hypothermia patients compared to normothermia patients. Hypothermia patients also had higher gastric residual volumes across the 7 day study period (438 (237) mls vs 184 (103) mls, p < 0.0001) and higher use of metoclopramide and erythromycin as prokinetics. Despite enteral nutrition intolerance, hypothermia patients received 93% of measured energy expenditure over 7 days., Conclusion: In TBI patients, energy expenditure was 20% less when receiving prophylactic hypothermia compared to normothermia. Greater gastric residual volumes, use of prokinetics and energy delivery that approximated measured energy expenditure was also observed in hypothermia patients., Trial Registry Number: POLAR-RCT: clinicaltrials.gov Identifier: NCT00987688; Anzctr.org.au Identifier: ACTRN12609000764235. This sub-study was not registered separately., Competing Interests: Conflicts of interest None declared., (Copyright © 2021. Published by Elsevier Ltd.)

Therapeutic hypothermia has been a treatment option for patients with severe traumatic brain injury (TBI) for many years. There has, however, been uncertainty whether hypothermia in this context also increased clinical bleeding risk, perhaps due to platelet dysfunction. Standard coagulation tests do not allow accurate assessment of in vivo coagulation. We studied specific coagulation abnormalities in patients undergoing therapeutic hypothermia for severe TBI using bedside thromboelastography (TEG).We studied 20 patients with severe blunt TBI from a single tertiary ICU who were enrolled in the prophylactic hypothermia to lessen traumatic brain injury (POLAR) trial. Ten patients had been randomized to hypothermia, and 10 were controls receiving normothermic standard care. TEG was undertaken during and after therapeutic hypothermia, and at the same time points in controls. Coagulation profiles were then compared between the hypothermic and control patients, and also between hypothermia and later normothermia in the study patients. Patients were primarily young (mean age 34 years) and male (85%). Measures of injury severity, including Glasgow coma score and injury severity scale, were not different between groups. Using TEG, the median alpha angle was reduced in hypothermic patients compared with controls (69.2° vs. 72.0°, p  = 0.02), although both were within the normal range. LY30 was also reduced (0.0% vs. 0.5%, p  < 0.01). Both differences persisted when hypothermic patients were compared with themselves during later normothermia. Therapeutic hypothermia during severe TBI causes a small decrease in the rate of clot formation. However, this decrease is within the normal range, and is unlikely to be clinically significant.

Functional outcomes at 12 months were a secondary outcome of the randomized DECRA trial of early decompressive craniectomy for severe diffuse traumatic brain injury (TBI) and refractory intracranial hypertension. In the DECRA trial, patients were randomly allocated 1:1 to either early decompressive craniectomy or intensive medical therapies (standard care). We conducted planned secondary analyses of the DECRA trial outcomes at 6 and 12 months, including all 155 patients. We measured functional outcome using the Glasgow Outcome Scale-Extended (GOS-E). We used ordered logistic regression, and dichotomized the GOS-E using logistic regression, to assess outcomes in patients overall and in survivors. We adjusted analyses for injury severity using the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) model. At 12 months, the odds ratio (OR) for worse functional outcomes in the craniectomy group (OR 1.68; 95% confidence interval [CI]: 0.96-2.93; p  = 0.07) was no longer significant. Unfavorable functional outcomes after craniectomy were 11% higher (59% compared with 48%), but were not significantly different from standard care (OR 1.58; 95% CI: 0.84-2.99; p  = 0.16). Among survivors after craniectomy, there were fewer good (OR 0.33; 95% CI: 0.12-0.91; p  = 0.03) and more vegetative (OR 5.12; 95% CI: 1.04-25.2; p  = 0.04) outcomes. Similar outcomes in survivors were found at 6 months after injury. Vegetative (OR 5.85; 95% CI: 1.21-28.30; p  = 0.03) and severely disabled outcomes (OR 2.49; 95% CI: 1.21-5.11; p  = 0.01) were increased. Twelve months after severe diffuse TBI and early refractory intracranial hypertension, decompressive craniectomy did not improve outcomes and increased vegetative survivors.

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., (Copyright © 2019. Published by Elsevier Inc.)

Background: Tranexamic acid reduces blood loss and transfusion requirements in cardiac surgery but may increase the risk of coronary graft thrombosis. We previously reported the 30-day results of a trial evaluating tranexamic acid for coronary artery surgery. Here we report the 1-year clinical outcomes., Methods: Using a factorial design, we randomly assigned patients undergoing coronary artery surgery to receive aspirin or placebo and tranexamic acid or placebo. The results of the tranexamic acid comparison are reported here. The primary 1-year outcome was death or severe disability, the latter defined as living with a modified Katz activities of daily living score of less than 8. Secondary outcomes included a composite of myocardial infarction, stroke, and death from any cause through to 1 year after surgery., Results: The rate of death or disability at 1 year was 3.8% in the tranexamic acid group and 4.4% in the placebo group (relative risk, 0.85; 95% confidence interval, 0.64-1.13; P = .27), and this did not significantly differ according to aspirin exposure at the time of surgery (interaction P = .073). The composite rate of myocardial infarction, stroke, and death up to 1 year after surgery was 14.3% in the tranexamic acid group and 16.4% in the placebo group (relative risk, 0.87; 95% CI, 0.76-1.00; P = .053)., Conclusions: In this trial of patients having coronary artery surgery, tranexamic acid did not affect death or severe disability through to 1 year after surgery. Further work should be done to explore possible beneficial effects on late cardiovascular events., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Aspirin may reduce the risk of vascular graft thrombosis after cardiovascular surgery. We previously reported the 30-day results of a trial evaluating aspirin use before coronary artery surgery. Here we report the 1-year outcomes evaluating late thrombotic events and disability-free survival., Methods: Using a factorial design, we randomly assigned patients undergoing coronary artery surgery to receive aspirin or placebo and tranexamic acid or placebo. The results of the aspirin comparison are reported here. The primary 1-year outcome was death or severe disability, the latter defined as living with a modified Katz activities of daily living score < 8. Secondary outcomes included a composite of myocardial infarction, stroke and death from any cause through to 1 year after surgery., Results: Patients were randomly assigned to aspirin (1059 patients) or placebo (1068 patients). The rate of death or severe disability was 4.1% in the aspirin group and 3.5% in the placebo group (relative risk, 1.17; 95% confidence interval, 0.76-1.81; P = .48). There was no significant difference in the rates of myocardial infarction (P = .11), stroke (P = .086), or death (P = .24), or a composite of these cardiovascular end points (P = .68). With the exception of those with a low European System for Cardiac Operative Risk Evaluation score (P = .03), there were no interaction effects on these outcomes with tranexamic acid (all tests of interaction P > .10)., Conclusions: In patients undergoing coronary artery surgery, preoperative aspirin did not reduce death or severe disability, or thrombotic events through to 1 year after surgery., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Erythropoietin (EPO) may reduce mortality after traumatic brain injury (TBI). Secondary brain injury is exacerbated by multiple trauma, and possibly modifiable by EPO. We hypothesized that EPO decreases mortality more in TBI patients with multiple trauma, than in patients with TBI alone., Methods: A post hoc analysis of the EPO-TBI randomized controlled trial conducted in 2009 to 2014. To evaluate the impact of injuries outside the brain, we calculated an extracranial Injury Severity Score (ISS) that included the same components of the ISS, excluding head and face components. We defined multiple trauma as two injured body regions with an Abbreviated Injury Scale (AIS) score of 3 or higher. Cox regression analyses, allowing for potential differential responses per the presence or absence of extracranial injury defined by these injury scores, were used to assess the effect of EPO on time to mortality., Results: Of 603 included patients, the median extracranial ISS was 6 (interquartile range, 1-13) and 258 (43%) had an AIS score of 3 or higher in at least two body regions. On Cox regression, EPO was associated with decreased mortality in patients with greater extracranial ISS (interaction p = 0.048) and weakly associated with differential mortality with multiple trauma (AIS score > 3 or in two regions, interaction p = 0.17). At 6 months in patients with extracranial ISS higher than 6, 10 (6.8%) of 147 EPO-treated patients compared with 26 (17%) of 154 placebo-treated patients died (risk reduction, 10%; 95% confidence interval, 2.9-17%; p = 0.007)., Conclusion: In this post hoc analysis, EPO administration was associated with a potential differential improvement in 6-month mortality in TBI patients with more severe extracranial injury. These findings need confirmation in future clinical and experimental studies., Level of Evidence: Therapeutic study, level III.

Introduction: Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Prophylactic hypothermia is effective in laboratory models, but clinical studies to date have been inconclusive, partly because of methodological limitations. Our Prophylactic Hypothermia Trial to Lessen Traumatic Brain Injury (POLAR) randomised controlled trial is currently underway comparing early, sustained hypothermia versus standard care in patients with severe TBI. We describe our study protocol and the challenges in conducting prophylactic hypothermia research in TBI., Design: We aim to randomise 500 patients to either prophylactic 33°C hypothermia initiated within 3 hours of injury and continued for at least 72 hours, or standard normothermic management. Patients will be enrolled by paramedic services in the prehospital setting, or by emergency department staff at participating sites in Australia, New Zealand and Europe. The primary outcome will be the eight-level extended Glasgow outcome scale (GOSE), dichotomised to favourable and unfavourable outcomes at 6 months after injury. Secondary outcomes will include mortality at hospital discharge and at 6 months, ordinal analyses of 6-month GOSE outcomes, quality of life with health economic evaluations and the differential proportion of adverse events. We will predefine subgroup and interaction analyses., Discussion: After a run-in phase, recruitment for our main study began in December 2010. When the study is completed, we aim to provide evidence on the efficacy of prophylactic hypothermia in TBI to guide clinicians in their management of this devastating condition.

Background: Early goal-directed therapy (EGDT) has been endorsed in the guidelines of the Surviving Sepsis Campaign as a key strategy to decrease mortality among patients presenting to the emergency department with septic shock. However, its effectiveness is uncertain., Methods: In this trial conducted at 51 centers (mostly in Australia or New Zealand), we randomly assigned patients presenting to the emergency department with early septic shock to receive either EGDT or usual care. The primary outcome was all-cause mortality within 90 days after randomization., Results: Of the 1600 enrolled patients, 796 were assigned to the EGDT group and 804 to the usual-care group. Primary outcome data were available for more than 99% of the patients. Patients in the EGDT group received a larger mean (±SD) volume of intravenous fluids in the first 6 hours after randomization than did those in the usual-care group (1964±1415 ml vs. 1713±1401 ml) and were more likely to receive vasopressor infusions (66.6% vs. 57.8%), red-cell transfusions (13.6% vs. 7.0%), and dobutamine (15.4% vs. 2.6%) (P<0.001 for all comparisons). At 90 days after randomization, 147 deaths had occurred in the EGDT group and 150 had occurred in the usual-care group, for rates of death of 18.6% and 18.8%, respectively (absolute risk difference with EGDT vs. usual care, -0.3 percentage points; 95% confidence interval, -4.1 to 3.6; P=0.90). There was no significant difference in survival time, in-hospital mortality, duration of organ support, or length of hospital stay., Conclusions: In critically ill patients presenting to the emergency department with early septic shock, EGDT did not reduce all-cause mortality at 90 days. (Funded by the National Health and Medical Research Council of Australia and the Alfred Foundation; ARISE ClinicalTrials.gov number, NCT00975793.).

Purpose: To assess the relationship between early daily fluid balance (FB) and 90-day outcome in adult patients treated with extracorporeal membrane oxygenation (ECMO)., Design: Retrospective observational study., Setting: Tertiary referral centre for ECMO., Patients: 115 patients treated with ECMO for refractory heart failure and 57 patients treated with ECMO for refractory respiratory failure., Methods: We analysed the association between early daily FB versus hospital and 90-day mortality using multivariable logistic regression model, Cox proportional-hazards model and propensity score., Results: We obtained detailed demographic, clinical, and biochemical data, daily FB, and continuous renal replacement days. Fifty-seven per cent of patients had acute kidney injury (AKI) at ECMO initiation, and 60 % (n = 103) of patients received continuous renal replacement therapy (CRRT) during ECMO course, beginning at a median of 1 (0-3.5) days after ECMO initiation. Overall 90-day mortality was 24 %. Survivors exhibited lower daily FB from day 3 to day 5. After adjustments, Acute Physiology and Chronic Health Evaluation (APACHE) III, CRRT during the first 3 days, major bleeding event at day 1 and positive FB on day 3 were independent predictors of 90-day mortality. Positive FB at ECMO day 3 remained an independent predictor of hospital and 90-day mortality, regardless of the statistical model used or the inclusion of a propensity score to have positive FB., Conclusions: Positive FB at ECMO day 3 is an independent predictor of 90-day mortality. Further interventional studies aimed at testing the value of strategy of tight control of FB during the early ECMO period are now warranted.

Background: There are conflicting data that suggest that hyperoxia may be associated with either worse or better outcomes in patients suffering a stroke., Objectives: To investigate the association between PaO(2) in the first 24 hours in the intensive care unit and mortality among ventilated patients with acute ischaemic stroke., Design: Retrospective cohort study., Setting: Data were extracted from the Australian and New Zealand Intensive Care Society Adult Patient Database., Participants: Adults ventilated for ischaemic stroke in 129 ICUs in Australia and New Zealand, 2000-2009., Main Outcome Measures: The primary outcome was the odds ratio for in hospital mortality associated with "worst" PaO(2) considered as a categorical variable, with data divided into deciles and compared with the mortality of the 10th decile. For patients on an FiO(2) of &#95;50% at any time in the first 24 hours, "worst" PaO(2) was defined as the PaO(2) associated with the highest alveolar-arterial (A-a) gradient. For patients on an FiO(2) of <50%, it was defined as the lowest PaO(2). Secondary outcomes were ICU and hospital length of stay and the proportion of patients in each decile discharged home., Results: Of the 2643 patients eligible for study inclusion, 1507 (57%) died in hospital. The median "worst" PaO(2) was 117mmHg (interquartile range, 87-196mmHg). There was no association between worst PaO(2) and mortality, length of stay or likelihood of discharge home., Conclusions: We found no association between worst arterial oxygen tension in the first 24 hours in ICU and outcome in ventilated patients with ischaemic stroke.

Background: Intensive care patients with traumatic brain injury (TBI) are at high risk of developing deep vein thrombosis (DVT). A high rate of DVT was reported before routine thromboprophylaxis, but the current DVT rate in TBI patients receiving best-practice mechanical and pharmacological prophylaxis is unknown., Objectives: To determine the prevalence of DVT among TBI patients., Design, Participants and Setting: A prospective observational pilot study of adult patients admitted to the intensive care unit of a level 1 trauma centre within 72 hours of sustaining a TBI (Glasgow Coma Scale score &#95;14)., Main Outcome Measures: Rate of DVT determined using twice-weekly compression ultrasound; rate of pulmonary embolism (PE) and length of stay., Results: 36 patients (28 men; mean age, 40.3 years) were included. Six had moderate and 21 had severe TBI. Two patients (6%) developed a DVT and two patients (6%) developed a PE. The proximal leg DVT rate was 3%, but the overall venous thromboembolism rate was 11% (4 patients)., Conclusions: Mechanical and pharmacological prophylaxis appeared to be effective. The incidence of clinically identified PE is of concern and suggests that thromboembolic sources other than large leg veins may not be being adequately controlled by modern thromboprophylaxis regimens.

Study Objective: We aim to determine the prevalence and factors associated with cervical discoligamentous injuries detected on magnetic resonance imaging (MRI) in acute, alert, neurologically intact trauma patients with computed tomography (CT) imaging negative for acute injury and persistent midline cervical spine tenderness. We present the cross-sectional analysis of baseline information collected as a component of a prospective observational study., Methods: Alert, neurologically intact trauma patients presenting to a Level I trauma center with CT negative for acute injury, who underwent MRI for investigation of persistent midline cervical tenderness, were prospectively recruited. Deidentified images were assessed, and injuries were identified and graded. Outcome measures included the presence and extent of MRI-detected injury of the cervical ligaments, intervertebral discs, spinal cord and associated soft tissues., Results: There were 178 patients recruited during a 2-year period to January 2009. Of these, 78 patients (44%) had acute cervical injury detected on MRI. There were 48 single-column injuries, 15 two-column injuries, and 5 three-column injuries. Of the remaining 10 patients, 6 had isolated posterior muscle edema, 2 had alar ligamentous edema, 1 had epidural hematoma, and 1 had atlanto-occipital edema. The injuries to 38 patients (21%) were managed clinically; 33 patients were treated in cervical collars for 2 to 12 weeks, and 5 patients (2.8%) underwent operative management, 1 of whom had delayed instability. Ordinal logistic regression revealed that factors associated with a higher number of spinal columns injured included advanced CT-detected cervical spondylosis (odds ratio [OR] 11.6; 95% confidence interval [CI] 3.9 to 34.3), minor isolated thoracolumbar fractures (OR 5.4; 95% CI 1.5 to 19.7), and multidirectional cervical spine forces (OR 2.5; 95% CI 1.2 to 5.2)., Conclusion: In patients with cervical midline tenderness and negative acute CT findings, we found that a subset of patients had MRI-detected cervical discoligamentous injuries and that advanced cervical spine degeneration evident on CT, minor thoracolumbar fracture, and multidirectional cervical spine forces were associated with increased injury extent. However, a larger study is required to validate which variables may reliably predict clinically important injury in such patients, thereby indicating the need for further radiographic assessment., (Copyright © 2011 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.)

Background: Critically ill patients are at high risk of morbidity and mortality caused by venous thromboembolism (VTE). In addition to premorbid predisposing conditions, critically ill patients may be exposed to prolonged immobility, invasive intravascular catheters and frequent operative procedures, and further may have contraindications to pharmaceutical prophylactic measures designed to attenuate VTE risk. There are limited data describing current VTE prophylaxis regimens in Australia and New Zealand., Objective: To document current Australian and New Zealand management of VTE prophylaxis in a large mixed cohort of critically ill patients., Design: Prospective, multicentre point prevalence survey endorsed by the Australian and New Zealand Intensive Care Society Clinical Trials Group (ANZICS CTG)., Setting: 30 public hospital ICUs in Australia and New Zealand surveyed on Wednesday 9 May 2007., Methods: For all patients in each ICU on the study day, demographic data, admission diagnosis and information on VTE prophylaxis were prospectively collected., Results: 502 patients were included in the survey, and 431 of these (86%) received VTE prophylaxis. Of these, 64% (276/431) received pharmacological prophylaxis and 80% (345/431) received mechanical prophylaxis, with 44% (190/431) receiving both. Of those receiving pharmacological prophylaxis, unfractionated heparin was used in 74%, and enoxaparin (low molecular weight heparin) in 23%. Contraindications to pharmacological prophylaxis were reported in 122 patients. Overall, pharmacological prophylaxis was administered to 87% of potentially suitable patients., Conclusions: We observed a high prevalence of VTE prophylaxis, with many critically ill patients receiving two or more modalities of prophylaxis. These results show that the potential risk of VTE in critically ill patients is recognised in Australia and New Zealand, and strategies to mitigate this serious complication are widely implemented.

Objective: To compare the effects of vasopressin versus norepinephrine infusion on the outcome of kidney injury in septic shock., Design and Setting: Post-hoc analysis of the multi-center double-blind randomized controlled trial of vasopressin versus norepinephrine in adult patients who had septic shock (VASST)., Patients and Intervention: Seven hundred seventy-eight patients were randomized to receive a blinded infusion of either low-dose vasopressin (0.01-0.03 U/min) or norepinephrine infusion (5-15 microg/min) in addition to open-label vasopressors and were included in the outcome analysis. All vasopressors were titrated and weaned to maintain a target blood pressure., Measurement and Results: RIFLE criteria for acute kidney injury were used to compare the effects of vasopressin versus norepinephrine. In view of multiple simultaneous comparisons, a p value of 0.01 was considered statistically significant. Kidney injury was present in 464 patients (59.6%) at study entry. In patients in the RIFLE "Risk" category (n = 106), vasopressin as compared with norepinephrine was associated with a trend to a lower rate of progression to renal "Failure" or "Loss" categories (20.8 vs. 39.6%, respectively, p = 0.03), and a lower rate of use of renal replacement therapy (17.0 vs. 37.7%, p = 0.02). Mortality rates in the "Risk" category patients treated with vasopressin compared to norepinephrine were 30.8 versus 54.7%, p = 0.01, but this did not reach significance in a multiple logistic regression analysis (OR = 0.33, 99% CI 0.10-1.09, p = 0.02). The interaction of treatment group and RIFLE category was significant in predicting mortality., Conclusions: Vasopressin may reduce progression to renal failure and mortality in patients at risk of kidney injury who have septic shock.

Aims: To explore whether fluid resuscitation with normal saline or 4% albumin is associated with differential changes in routine clinical coagulation tests., Design: Substudy from a large double-blind randomised controlled trial, the SAFE (Saline versus Albumin Fluid Evaluation) study., Setting: Three general intensive care units., Patients: Cohort of 687 critically ill patients., Intervention: We randomly allocated patients to receive either 4% human albumin or normal saline for fluid resuscitation, and collected demographic and haematological data., Methods and Main Results: Albumin was administered to 338 patients and saline to 349. At baseline, the two groups had similar mean activated partial thromboplastin time (APTT) of 37.2 s (albumin) v 39.1 s (saline); mean international normalised ratio (INR) of 1.38 v 1.34, and mean platelet count of 244 x 10(9)/L v 249 x 10(9)/L. After randomisation, during the first day of treatment, the APTT in the albumin group was prolonged by a mean of 2.7 s, but shortened slightly by a mean of -0.9 s in the saline group. The INR did not change in either group, while the platelet count decreased transiently in both groups. Using multivariate analysis of covariance to account for baseline coagulation status, albumin fluid resuscitation (P = 0.01) and a greater overall volume of resuscitation (P = 0.03) were independently associated with prolongation of APTT during the first day., Conclusions: Administration of albumin or of larger fluid volumes is associated with a prolongation of APTT. In ICU patients, the choice and amount of resuscitation fluid may affect a routinely used coagulation test.

Objective: To assess and describe postoperative complications of single dilator percutaneous dilatational tracheostomy (PDT) and surgical tracheostomy (ST) in a large series of critically ill patients., Methods: A prospective observational study was conducted in 1163 critically ill patients in a university affiliated tertiary referral hospital between 2002 and 2007. PDT was the procedure of choice for all critically ill patients requiring tracheostomy except for those with an anatomic abnormality or refractory coagulopathy, who underwent ST. Demographic and postoperative complication data were collected in a web-based database., Results: 913 patients (79%) underwent PDT at the bedside in the ICU, and 250 (21%) underwent ST in the operating theatre. The tracheostomy tube was larger, and the duration of tracheostomy cannulation was shorter after PDT than after ST. The postoperative complication rate for PDT was 9.6% compared with 19.6% for ST (P<0.001). Tracheal tube obstruction and displacement were significantly less frequent after PDT (obstruction 1.0% for PDT v 3.6% for ST, P = 0.007; displacement, 1.3% for PDT v 4.8% for ST, P = 0.002)., Conclusions: In a large heterogeneous group of critically ill patients, single dilator PDT was safe and had few postoperative complications. Although ST was used in higher-risk patients, those who underwent PDT were more likely to receive a larger-sized tracheostomy tube; they were also less likely to experience obstruction or displacement of the postoperative tracheostomy tube. These differences are probably related to a combination of patient selection, smaller, shorter tracheostomy tubes, and larger tissue incision size with ST.

Purpose: The aims of this study were to test the feasibility and to assess potential recruitment rates in a pilot study preliminary to a phase III randomized trial of decompressive craniectomy surgery in patients with diffuse traumatic brain injury (TBI) and refractory intracranial hypertension., Materials and Methods: A study protocol was developed, inclusion and exclusion criteria were defined, and a standardized surgical technique was established. Neurologic outcomes were assessed 6 months after injury with a validated structured questionnaire and a single trained assessor blind to treatment group., Results: During the 8-month pilot study at a level 1 trauma center in Melbourne, Australia, 69 intensive care patients with severe TBI were assessed for inclusion. Six patients were eligible, and 5 (8%) were randomized. Six months after injury, 100% of patients received outcome assessments. Key improvements to the multicenter Decompressive Craniectomy study protocol were enabled by the pilot study., Conclusions: In patients with severe TBI and refractory intracranial hypertension, the frequency of favorable neurologic outcomes (independent living) was low and similar to predicted values (40% favorable). A future multicenter phase III trial involving 18 neurotrauma centers with most sites conservatively recruiting at just 25% of the pilot study rate would require at least 5 years to achieve an estimated 210-patient sample size. Collaboration with neurotrauma centers in countries other than Australia and New Zealand would be required for such a phase III trial to be successful.

Complex interventions, such as the introduction of medical emergency teams or an early goal-directed therapy protocol, are developed from a number of components that may act both independently and inter-dependently. There is an emerging body of literature advocating the use of integrated complex interventions to optimise the treatment of critically ill patients. As with any other treatment, complex interventions should undergo careful evaluation prior to widespread introduction into clinical practice. During the development of an international collaboration of researchers investigating protocol-based approaches to the resuscitation of patients with severe sepsis, we examined the specific issues related to the evaluation of complex interventions. This review outlines some of these issues. The issues specific to trials of complex interventions that require particular attention include determining an appropriate study population and defining current treatments and outcomes in that population, defining the study intervention and the treatment to be used in the control group, and deploying the intervention in a standardised manner. The context in which the research takes place, including existing staffing levels and existing protocols and procedures, is crucial. We also discuss specific details of trial execution, in particular randomization, blinded outcome adjudication and analysis of the results, which are key to avoiding bias in the design and interpretation of such trials. These aspects of study design impact upon the evaluation of complex interventions in critical care. Clinicians should also consider these specific issues when implementing new complex interventions into their practice.

Background: The Saline versus Albumin Fluid Evaluation study suggested that patients with traumatic brain injury resuscitated with albumin had a higher mortality rate than those resuscitated with saline. We conducted a post hoc follow-up study of patients with traumatic brain injury who were enrolled in the study., Methods: For patients with traumatic brain injury (i.e., a history of trauma, evidence of head trauma on a computed tomographic [CT] scan, and a score of < or =13 on the Glasgow Coma Scale [GCS]), we recorded baseline characteristics from case-report forms, clinical records, and CT scans and determined vital status and functional neurologic outcomes 24 months after randomization., Results: We followed 460 patients, of whom 231 (50.2%) received albumin and 229 (49.8%) received saline. The subgroup of patients with GCS scores of 3 to 8 were classified as having severe brain injury (160 [69.3%] in the albumin group and 158 [69.0%] in the saline group). Demographic characteristics and indexes of severity of brain injury were similar at baseline. At 24 months, 71 of 214 patients in the albumin group (33.2%) had died, as compared with 42 of 206 in the saline group (20.4%) (relative risk, 1.63; 95% confidence interval [CI], 1.17 to 2.26; P=0.003). Among patients with severe brain injury, 61 of 146 patients in the albumin group (41.8%) died, as compared with 32 of 144 in the saline group (22.2%) (relative risk, 1.88; 95% CI, 1.31 to 2.70; P<0.001); among patients with GCS scores of 9 to 12, death occurred in 8 of 50 patients in the albumin group (16.0%) and 8 of 37 in the saline group (21.6%) (relative risk, 0.74; 95% CI, 0.31 to 1.79; P=0.50)., Conclusions: In this post hoc study of critically ill patients with traumatic brain injury, fluid resuscitation with albumin was associated with higher mortality rates than was resuscitation with saline. (Current Controlled Trials number, ISRCTN76588266 [controlled-trials.com].)., (Copyright 2007 Massachusetts Medical Society.)

Study Design: Retrospective medical record and electronic database audit to ascertain the incidence and predictors of cervical collar-related decubitus ulceration (CRU)., Objective: To determine the incidence and risk factors associated with the development of CRU in major trauma patients immobilized in Philadelphia cervical collars., Summary of Background Data: Cervical spine immobilization requires the utilization of a cervical collar before spinal clearance, which may be complicated by CRU and increased morbidity., Methods: From a trauma registry database at a level 1 trauma center, 299 major trauma patients admitted over a 6-month period were identified. Predictors of CRU were retrospectively examined and assessed for relative importance using medical records and prospective infection control and radiology databases., Results: Clinically significant predictors of CRU were ICU admission (P = 0.007), mechanical ventilation (P = 0.005), the necessity for cervical MRI (P < or = 0.001), and time to cervical spine clearance (P < or = 0.001). Time to cervical spine clearance was the major indicator, such that the risk of CRU increased by 66% for every 1 day increase in cervical collar time., Conclusion: In major trauma patients at a level 1 trauma center, the risk of CRU development increased significantly for every day of Philadelphia cervical collar time. Associated increased morbidity may be reduced by measures aimed at earlier cervical spine clearance.

Context: Prehospital hypertonic saline (HTS) resuscitation of patients with traumatic brain injury (TBI) may increase survival but whether HTS improves neurological outcomes is unknown., Objective: To determine whether prehospital resuscitation with intravenous HTS improves long-term neurological outcome in patients with severe TBI compared with resuscitation with conventional fluids., Design, Setting, and Patients: Double-blind, randomized controlled trial of 229 patients with TBI who were comatose (Glasgow Coma Scale score, <9) and hypotensive (systolic blood pressure, <100 mm Hg). The patients were enrolled between December 14, 1998, and April 9, 2002, in Melbourne, Australia., Interventions: Patients were randomly assigned to receive a rapid intravenous infusion of either 250 mL of 7.5% saline (n = 114) or 250 mL of Ringer's lactate solution (n = 115; controls) in addition to conventional intravenous fluid and resuscitation protocols administered by paramedics. Treatment allocation was concealed., Main Outcome Measure: Neurological function at 6 months, measured by the extended Glasgow Outcome Score (GOSE)., Results: Primary outcomes were obtained in 226 (99%) of 229 patients enrolled. Baseline characteristics of the groups were equivalent. At hospital admission, the mean serum sodium level was 149 mEq/L for HTS patients vs 141 mEq/L for controls (P<.001). The proportion of patients surviving to hospital discharge was similar in both groups (n = 63 [55%] for HTS group and n = 57 [50%] for controls; P =.32); at 6 months, survival rates were n = 62 (55%) in the HTS group and n = 53 (47%) in the control group (P =.23). At 6 months, the median (interquartile range) GOSE was 5 (3-6) in the HTS group vs 5 (5-6) in the control group (P =.45). There was no significant difference between the groups in favorable outcomes (moderate disability and good outcome survivors [GOSE of 5-8]) (risk ratio, 0.99; 95% confidence interval, 0.76-1.30; P =.96) or in any other measure of postinjury neurological function., Conclusion: In this study, patients with hypotension and severe TBI who received prehospital resuscitation with HTS had almost identical neurological function 6 months after injury as patients who received conventional fluid.