Therapeutics for Vancomycin-Resistant Enterococcal Bloodstream Infections.

Vancomycin-resistant enterococci (VRE) are common causes of bloodstream infections (BSIs) with high morbidity and mortality rates. They are pathogens of global concern with a limited treatment pipeline. Significant challenges exist in the management of VRE BSI, including drug dosing, the emergence of resistance, and the optimal treatment for persistent bacteremia and infective endocarditis. Therapeutic drug monitoring (TDM) for antimicrobial therapy is evolving for VRE-active agents; however, there are significant gaps in the literature for predicting antimicrobial efficacy for VRE BSIs. To date, TDM has the greatest evidence for predicting drug toxicity for the three main VRE-active antimicrobial agents daptomycin, linezolid, and teicoplanin. This article presents an overview of the treatment options for VRE BSIs, the role of antimicrobial dose optimization through TDM in supporting clinical infection management, and challenges and perspectives for the future.

Composite outcome measures in high-impact critical care randomised controlled trials: a systematic review.

BACKGROUND: The use of composite outcome measures (COM) in clinical trials is increasing. Whilst their use is associated with benefits, several limitations have been highlighted and there is limited literature exploring their use within critical care. The primary aim of this study was to evaluate the use of COM in high-impact critical care trials, and compare study parameters (including sample size, statistical significance, and consistency of effect estimates) in trials using composite versus non-composite outcomes. METHODS: A systematic review of 16 high-impact journals was conducted. Randomised controlled trials published between 2012 and 2022 reporting a patient important outcome and involving critical care patients, were included. RESULTS: 8271 trials were screened, and 194 included. 39.1% of all trials used a COM and this increased over time. Of those using a COM, only 52.6% explicitly described the outcome as composite. The median number of components was 2 (IQR 2-3). Trials using a COM recruited fewer participants (409 (198.8-851.5) vs 584 (300-1566, p = 0.004), and their use was not associated with increased rates of statistical significance (19.7% vs 17.8%, p = 0.380). Predicted effect sizes were overestimated in all but 6 trials. For studies using a COM the effect estimates were consistent across all components in 43.4% of trials. 93% of COM included components that were not patient important. CONCLUSIONS: COM are increasingly used in critical care trials; however effect estimates are frequently inconsistent across COM components confounding outcome interpretations. The use of COM was associated with smaller sample sizes, and no increased likelihood of statistically significant results. Many of the limitations inherent to the use of COM are relevant to critical care research.

Outcomes for people admitted to Australian and New Zealand intensive care units with primary, exacerbating, or incidental SARS-CoV-2 infections, 2022-23: a retrospective analysis of ANZICS data.

OBJECTIVES: To compare in-hospital mortality and intensive care unit (ICU) length of stay for people admitted to Australian and New Zealand ICUs during 2022-23 with coronavirus disease 2019 (COVID-19) pneumonitis, incidental or exacerbating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, or without SAR-CoV-2 infections. STUDY DESIGN: Retrospective cohort study; analysis of Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database data. SETTING, PARTICIPANTS: Adults (16 years or older) admitted to participating ICUs in Australia or New Zealand, 1 January 2022 - 30 June 2023. MAJOR OUTCOME MEASURES: The primary outcome was in-hospital mortality, the secondary outcome ICU length of stay, each by SARS-CoV-2 infection attribution classification: primary COVID-19; exacerbating SARS-CoV-2 infection (SARS-CoV-2 infection was a contributing factor to the primary cause of ICU admission); incidental SARS-CoV-2 infections (SARS-CoV-2 infection detected during ICU admission but did not contribute to admission diagnosis); no SARS-CoV-2 infection. RESULTS: A total of 207 684 adults were admitted to 195 Australian and New Zealand ICUs during 2022-23; 2674 people (1.3%) had incidental SARS-CoV-2 infections, 4923 (2.4%) exacerbating infections, and 3620 (1.7%) primary COVID-19. Unadjusted in-hospital mortality for people with incidental SARS-CoV-2 infections (288 deaths, 10.8%) was lower than for those with exacerbating infections (928 deaths, 18.8%) or primary COVID-19 (830 deaths, 22.9%), but higher than for patients without SARS-CoV-2 infections (15 486 deaths, 7.9%). After adjusting for illness severity, frailty, geographic region, and type of hospital, mortality was higher for patients with incidental SARS-CoV-2 infections (adjusted odds ratio [aOR], 1.28; 95% confidence interval [CI], 1.10-1.50), exacerbating infections (aOR, 1.35; 95% CI, 1.22-1.48), or primary COVID-19 (aOR, 2.54; 95% CI, 2.30-2.81) than for patients without SARS-CoV-2 infections. After adjusting for diagnosis and illness severity, ICU stays were longer for people with incidental (mean difference, 3.3 hours; 95% CI, 2.4-4.2 hours) or exacerbating infections (0.8 hours; 95% CI, 0.2-1.5 hours) than for those without SARS-CoV-2 infections. CONCLUSION: Risk-adjusted in-hospital mortality and ICU length of stay are higher for people admitted to intensive care who have concomitant SARS-CoV-2 infections than for people who do not.

Magnitude and time to peak oxygenation effect of prone positioning in ventilated adults with COVID-19 related acute hypoxemic respiratory failure.

BACKGROUND: Prone positioning may improve oxygenation in acute hypoxemic respiratory failure and was widely adopted in COVID-19 patients. However, the magnitude and timing of its peak oxygenation effect remain uncertain with the optimum dosage unknown. Therefore, we aimed to investigate the magnitude of the peak effect of prone positioning on the PaO2 :FiO2 ratio during prone and secondly, the time to peak oxygenation. METHODS: Multi-centre, observational study of invasively ventilated adults with acute hypoxemic respiratory failure secondary to COVID-19 treated with prone positioning. Baseline characteristics, prone positioning and patient outcome data were collected. All arterial blood gas (ABG) data during supine, prone and after return to supine position were analysed. The magnitude of peak PaO2 :FiO2 ratio effect and time to peak PaO2 :FIO2 ratio effect was measured. RESULTS: We studied 220 patients (mean age 54 years) and 548 prone episodes. Prone positioning was applied for a mean (±SD) 3 (±2) times and 16 (±3) hours per episode. Pre-proning PaO2 :FIO2 ratio was 137 (±49) for all prone episodes. During the first episode. the mean PaO2 :FIO2 ratio increased from 125 to a peak of 196 (p < .001). Peak effect was achieved during the first episode, after 9 (±5) hours in prone position and maintained until return to supine position. CONCLUSIONS: In ventilated adults with COVID-19 acute hypoxemic respiratory failure, peak PaO2 :FIO2 ratio effect occurred during the first prone positioning episode and after 9 h. Subsequent episodes also improved oxygenation but with diminished effect on PaO2 :FIO2 ratio. This information can help guide the number and duration of prone positioning episodes.

Early Net Ultrafiltration during Continuous Renal Replacement Therapy: Impact of Admission Diagnosis and Association with Mortality.

INTRODUCTION: Continuous renal replacement therapy (CRRT) is common in the intensive care unit (ICU) but a high net ultrafiltration rate (UFNET) calculated with daily data may increase mortality. We aimed to study early UFNET practice using minute-by-minute CRRT machine recordings and to assess its association with admission diagnosis and mortality. METHODS: We studied CRRT treatments in three adult ICUs over 7 years. We calculated early UFNET rates minute-by-minute and categorized UFNET into tertiles of mean UFNET in the first 72 h and admission diagnosis. We applied Cox-proportional hazards modelling with censoring of patients who died within 72 h. RESULTS: We studied 1,218 patients, 154,712 h, and 9,282,729 min of CRRT (5,702 circuits). Mean early UFNET was 1.52 (1.46-1.57) mL/kg/h. Early UFNET tertiles were similar to, but somewhat higher than, previously reported values at 0.00-1.20 mL/kg/h, 1.21-1.93 mL/kg/h, and >1.93 mL/kg/h. UFNET values were similar whether evaluated at 24 or 72 h or for the entire duration of CRRT. There was, however, significant variation in UFNET practice by admission diagnosis: higher in respiratory diseases (pneumonia p = 0.01, other p < 0.0001) and cardiovascular disease (p = 0.005) but lower in cardiothoracic surgery (p = 0.04), renal (p = 0.0003) and toxicology-associated diagnoses (p = 0.01). Higher UFNET was associated with an increased hazard of death, HR 1.24 (1.13-1.37), independent of admission diagnosis, weight, age, sex, presence of end-stage kidney disease, and severity of illness. CONCLUSION: Early UFNET practice varies significantly by admission diagnosis. Higher early UFNET is independently associated with mortality. Impacts of UFNET on mortality may vary by admission diagnosis. Further work is required to elucidate the nature and mechanisms responsible for this association.

The Impact of Sedative Choice in the Management of Aneurysmal Subarachnoid Hemorrhage: A Scoping Review.

Aneurysmal subarachnoid hemorrhage (aSAH) is characterized by high mortality and morbidity. This scoping review assesses the current evidence regarding the use of sedatives and analgesics in the acute intensive care unit management of aSAH. We conducted a systematic search of Ovid MEDLINE, Ovid Embase, Ovid EmCare, APA PsycInfo, CINAHL, and the Cochrane Database of Systematic Reviews from inception to June 2023. Studies were included if they enrolled intensive care unit patients aged 18 or older with a significant proportion (> 20%) who had aSAH and evaluated the impact of one or more commonly used analgosedatives on physiological parameters in the management of aSAH. The methodological quality of the studies was assessed using the Methodological Index for Nonrandomized Studies score. Of 2,583 articles, 11 met the inclusion criteria. The median sample size was 47 (interquartile range 10-127), and the median Methodological Index for Nonrandomized Studies score was 9.5 (interquartile range 8-11). The studies' publication years ranged from 1980 to 2023. Dexmedetomidine and ketamine showed potential benefits in reducing the incidence of cortical spreading depolarization and delayed cerebral ischemia. Propofol and opioids appeared safe but lacked robust evidence for efficacy. Benzodiazepines were associated with increased delayed cerebral ischemia-related cerebral infarctions and cortical spreading depolarization events. The evidence available to guide the use of analgosedative medications in aSAH is critically inadequate. Dexmedetomidine and ketamine warrant further exploration in large-scale prospective studies because of their potential benefits. Improved study designs with consistent definitions and a focus on patient-centered outcomes are necessary to inform clinical practice.

Development of a Quality Indicator Set for the Optimal Acute Management of Moderate to Severe Traumatic Brain Injury in the Australian Context.

BACKGROUND: The aim of this study was to develop a consensus-based set of indicators of high-quality acute moderate to severe traumatic brain injury (msTBI) clinical management that can be used to measure structure, process, and outcome factors that are likely to influence patient outcomes. This is the first stage of the PRECISION-TBI program, which is a prospective cohort study that aims to identify and promote optimal clinical management of msTBI in Australia. METHODS: A preliminary set of 45 quality indicators was developed based on available evidence. An advisory committee of established experts in the field refined the initial indicator set in terms of content coverage, proportional representation, contamination, and supporting evidence. The refined indicator set was then distributed to a wider Delphi panel for assessment of each indicator in terms of validity, measurement feasibility, variability, and action feasibility. Inclusion in the final indicator set was contingent on prespecified inclusion scoring. RESULTS: The indicator set was structured according to the care pathway of msTBI and included prehospital, emergency department, neurosurgical, intensive care, and rehabilitation indicators. Measurement domains included structure indicators, logistic indicators, and clinical management indicators. The Delphi panel consisted of 44 participants (84% physician, 12% nursing, and 4% primary research) with a median of 15 years of practice. Of the 47 indicators included in the second round of the Delphi, 32 indicators were approved by the Delphi group. CONCLUSIONS: This study identified a set of 32 quality indicators that can be used to structure data collection to drive quality improvement in the clinical management of msTBI. They will also be used to guide feedback to PRECISION-TBI's participating sites.

Beta-blockade for the treatment of refractory hypoxaemia during venovenous extracorporeal membrane oxygenation: An in-silico study.

INTRODUCTION: Venovenous extracorporeal membrane oxygenation (VV ECMO) is used for refractory hypoxemia, although despite this, in high cardiac output states, hypoxaemia may persist. The administration of beta-blockers has been suggested as an approach in this scenario, however the physiological consequences of this intervention are not clear. METHODS: We performed an in-silico study using a previously described mathematical model to evaluate the effect of beta-blockade on mixed venous and arterial saturations (Sv¯O2, SaO2), in three different clinical scenarios and considered the potential effects of beta-blockers on, cardiac output, oxygen consumption and recirculation. Additionally we assessed the interaction of beta-blockade with haemoglobin concentration. RESULTS: In scenario 1: simulating a patient with high cardiac output and partial lung shunt Sv¯O2 decreased from increased 53.5% to 44.7% despite SaO2 rising from 74.2% to 79.2%. In scenario 2 simulating a patient with high cardiac output and complete lung shunt Sv¯O2 remained unchanged at 52.2% and SaO2 rose from 71.9% to 85%. In scenario 3 a patient with normal cardiac output and high recirculation Sv¯O2 fell from 50.8% to 25.5% and also fell from 82.4% to to 78.3%. Across the remaining modelling examples the effect on Sv¯O2 varied but oxygen delivery was consistently reduced across all scenarios. CONCLUSION: The administration of beta-blockers for refractory hypoxemia during VV ECMO are unpredictable and may reduce oxygen delivery, although this will vary with patient and circuit features. This study does not support the use of beta-blockers for this indication.

An exploration of intensive care nurses' perceptions of workload in providing extracorporeal membrane oxygenation (ECMO) support: A descriptive qualitative study.

BACKGROUND: There is increasing use of extracorporeal membrane oxygenation (ECMO) in intensive care, where nurses provide the majority of the required ongoing care of cannulas, circuit, and console. Limited evidence currently exists that details nursing perspectives, experiences, and challenges with workload in the provision of ECMO care. OBJECTIVE: The objective of this study was to investigate intensive care nurses' perceptions of workload in providing specialist ECMO therapy and care in a high-volume ECMO centre. METHODS: The study used a qualitative descriptive methodology through semistructured interviews. Data were analysed using an inductive thematic analysis approach following Braun and Clarke's iterative process. This study was conducted in an intensive care unit within an Australian public, quaternary, university-affiliated hospital, which provides specialist state-wide service for ECMO. FINDINGS: Thirty ECMO-specialist trained intensive care nurses were interviewed. This study identified three key themes: (i) opportunity; (ii) knowledge and responsibilities; and (iii) systems and structures impacting on intensive care nurses' workload in providing ECMO supportive therapy. CONCLUSIONS: Intensive care nurses require advanced clinical and critical thinking skills. Intensive care nurses are motivated and engaged to learn and acquire ECMO skills and competency as part of their ongoing professional development. Providing bedside ECMO management requires constant monitoring and surveillance from nurses to care for the one of the most critically unwell patient populations in the intensive care unit setting. As such, ECMO nursing services require a suitably trained and educated workforce of intensive care trained nurses. ECMO services provide clinical development opportunities for nurses, increase their scope of practice, and create advanced practice-specialist roles.

Dietitian and nutrition-related practices and resources in Australian and New Zealand PICUs: A clinician survey.

BACKGROUND: Recommendations to facilitate evidence-based nutrition provision for critically ill children exist and indicate the importance of nutrition in this population. Despite these recommendations, it is currently unknown how well Australian and New Zealand (ANZ) paediatric intensive care units (PICUs) are equipped to provide nutrition care. OBJECTIVES: The objectives of this project were to describe the dietitian and nutrition-related practices and resources in ANZ PICUs. METHODS: A clinician survey was completed as a component of an observational study across nine ANZ PICUs in June 2021. The online survey comprised 31 questions. Data points included reporting on dietetics resourcing, local feeding-related guidelines and algorithms, nutrition screening and assessment practices, anthropometry practices, and indirect calorimetry (IC) device availability and local technical expertise. Data are presented as frequency (%), mean (standard deviation), or median (interquartile range). RESULTS: Survey responses were received from all nine participating sites. Dietetics staffing per available PICU bed ranged from 0.01 to 0.07 full-time equivalent (median: 0.03 [interquartile range: 0.02-0.04]). Nutrition screening was established in three (33%) units, all of which used the Paediatric Nutrition Screening Tool. Dietitians consulted all appropriate patients (or where capacity allowed) in six (66%) units and on a request or referral basis only in three (33%) units. All units possessed a local feeding guideline or algorithm. An IC device was available in two (22%) PICUs and was used in one of these units. CONCLUSIONS: This is the first study to describe the dietitian and nutrition-related practices and resources of ANZ PICUs. Areas for potential improvement include dietetics full-time equivalent, routine nutrition assessment, and access to IC.

Nutrition delivery across hospitalisation in critically ill patients with COVID-19: An observational study of the Australian experience.

BACKGROUND: Data on nutrition delivery over the whole hospital admission in critically ill patients with COVID-19 are scarce, particularly in the Australian setting. OBJECTIVES: The objective of this study was to describe nutrition delivery in critically ill patients admitted to Australian intensive care units (ICUs) with coronavirus disease 2019 (COVID-19), with a focus on post-ICU nutrition practices. METHODS: A multicentre observational study conducted at nine sites included adult patients with a positive COVID-19 diagnosis admitted to the ICU for >24 h and discharged to an acute ward over a 12-month recruitment period from 1 March 2020. Data were extracted on baseline characteristics and clinical outcomes. Nutrition practice data from the ICU and weekly in the post-ICU ward (up to week four) included route of feeding, presence of nutrition-impacting symptoms, and nutrition support received. RESULTS: A total of 103 patients were included (71% male, age: 58 ± 14 years, body mass index: 30±7 kg/m2), of whom 41.7% (n = 43) received mechanical ventilation within 14 days of ICU admission. While oral nutrition was received by more patients at any time point in the ICU (n = 93, 91.2% of patients) than enteral nutrition (EN) (n = 43, 42.2%) or parenteral nutrition (PN) (n = 2, 2.0%), EN was delivered for a greater duration of time (69.6% feeding days) than oral and PN (29.7% and 0.7%, respectively). More patients received oral intake than the other modes in the post-ICU ward (n = 95, 95.0%), and 40.0% (n = 38/95) of patients were receiving oral nutrition supplements. In the week after ICU discharge, 51.0% of patients (n = 51) had at least one nutrition-impacting symptom, most commonly a reduced appetite (n = 25; 24.5%) or dysphagia (n = 16; 15.7%). CONCLUSION: Critically ill patients during the COVID-19 pandemic in Australia were more likely to receive oral nutrition than artificial nutrition support at any time point both in the ICU and in the post-ICU ward, whereas EN was provided for a greater duration when it was prescribed. Nutrition-impacting symptoms were common.

Sodium Bicarbonate for Metabolic Acidosis in the ICU: Results of a Pilot Randomized Double-Blind Clinical Trial.

OBJECTIVES: To identify the best population, design of the intervention, and to assess between-group biochemical separation, in preparation for a future phase III trial. DESIGN: Investigator-initiated, parallel-group, pilot randomized double-blind trial. SETTING: Eight ICUs in Australia, New Zealand, and Japan, with participants recruited from April 2021 to August 2022. PATIENTS: Thirty patients greater than or equal to 18 years, within 48 hours of admission to the ICU, receiving a vasopressor, and with metabolic acidosis (pH < 7.30, base excess [BE] < -4 mEq/L, and Pa co2 < 45 mm Hg). INTERVENTIONS: Sodium bicarbonate or placebo (5% dextrose). MEASUREMENTS AND MAIN RESULT: The primary feasibility aim was to assess eligibility, recruitment rate, protocol compliance, and acid-base group separation. The primary clinical outcome was the number of hours alive and free of vasopressors on day 7. The recruitment rate and the enrollment-to-screening ratio were 1.9 patients per month and 0.13 patients, respectively. Time until BE correction (median difference, -45.86 [95% CI, -63.11 to -28.61] hr; p < 0.001) and pH correction (median difference, -10.69 [95% CI, -19.16 to -2.22] hr; p = 0.020) were shorter in the sodium bicarbonate group, and mean bicarbonate levels in the first 24 hours were higher (median difference, 6.50 [95% CI, 4.18 to 8.82] mmol/L; p < 0.001). Seven days after randomization, patients in the sodium bicarbonate and placebo group had a median of 132.2 (85.6-139.1) and 97.1 (69.3-132.4) hours alive and free of vasopressor, respectively (median difference, 35.07 [95% CI, -9.14 to 79.28]; p = 0.131). Recurrence of metabolic acidosis in the first 7 days of follow-up was lower in the sodium bicarbonate group (3 [20.0%] vs. 15 [100.0%]; p < 0.001). No adverse events were reported. CONCLUSIONS: The findings confirm the feasibility of a larger phase III sodium bicarbonate trial; eligibility criteria may require modification to facilitate recruitment.

The clinical application of beta-lactam antibiotic therapeutic drug monitoring in the critical care setting.

Critically ill patients have increased variability in beta-lactam antibiotic (beta-lactam) exposure due to alterations in their volume of distribution and elimination. Therapeutic drug monitoring (TDM) of beta-lactams, as a dose optimization and individualization tool, has been recommended to overcome this variability in exposure. Despite its potential benefit, only a few centres worldwide perform beta-lactam TDM. An important reason for the low uptake is that the evidence for clinical benefits of beta-lactam TDM is not well established. TDM also requires the availability of specific infrastructure, knowledge and expertise. Observational studies and systematic reviews have demonstrated that TDM leads to an improvement in achieving target concentrations, a reduction in potentially toxic concentrations and improvement of clinical and microbiological outcomes. However, a small number of randomized controlled trials have not shown a mortality benefit. Opportunities for improved study design are apparent, as existing studies are limited by their inclusion of heterogeneous patient populations, including patients that may not even have infection, small sample size, variability in the types of beta-lactams included, infections caused by highly susceptible bacteria, and varied sampling, analytical and dosing algorithm methods. Here we review the fundamentals of beta-lactam TDM in critically ill patients, the existing clinical evidence and the practical aspects involved in beta-lactam TDM implementation.

Implementation Strategies Addressing Stakeholder-Perceived Barriers and Enablers to the Establishment of a Beta-Lactam Antibiotic Therapeutic Drug Monitoring Program: A Qualitative Analysis.

BACKGROUND: Therapeutic drug monitoring (TDM) of beta-lactam antibiotics (beta-lactams) is increasingly recommended for optimizing antibiotic exposure in intensive care patients with sepsis. However, limited data are available on the implementation of beta-lactam TDM in complex health care settings. Theory-based approaches were used to systematically explore barriers and enablers perceived by key stakeholders in the implementation of beta-lactam TDM in the intensive care unit. METHODS: In this qualitative descriptive study, the authors interviewed key stakeholders (n = 40): infectious disease physicians, intensive care unit physicians, pharmacists, clinical leaders, scientists, and nurses. The data were thematically analyzed and coded using the theoretical domains framework, and the codes and themes were mapped to the relevant domains of the capability, opportunity, and motivation behavior-change wheel model. RESULTS: Barriers included a lack of knowledge, experience, evidence, and confidence, which led to concerns about capability, lack of resources, and harm in straying from standard practice. Access to education and guidelines, on-site assays with short turnaround times, communication among teams, and workflow integration were identified as enablers. A focus on patient care, trust in colleagues, and endorsement by hospital leaders were strong motivators. Pharmacist and nursing stakeholder groups emerged as key targets in the implementation of strategies. CONCLUSIONS: Using theory-based approaches, the authors identified the key barriers and enablers to establishing beta-lactam TDM. These data were used to identify strategies, policies, and key target groups for the implementation of interventions.

Inter-hospital transfer and clinical outcomes for people with COVID-19 admitted to intensive care units in Australia: an observational cohort study.

OBJECTIVES: To examine the association between inter-hospital transfer and in-hospital mortality among people with coronavirus disease 2019 (COVID-19) admitted to intensive care units (ICUs) in Australia. DESIGN: Retrospective cohort study; analysis of data collected for the Short Period Incidence Study of Severe Acute Respiratory Illness (SPRINT-SARI) Australia study. SETTING, PARTICIPANTS: People with COVID-19 admitted to 63 ICUs, 1 January 2020 - 1 April 2022. MAIN OUTCOME MEASURES: Primary outcome: in-hospital mortality; secondary outcomes: ICU and hospital lengths of stay and frequency of selected complications. RESULTS: Of 5207 people with records in the SPRINT-SARI Australia database at 1 April 2022, 328 (6.3%) had been transferred between hospitals, 305 (93%) during the third pandemic wave. Compared with patients not transferred, their median age was lower (53 years; interquartile range [IQR], 45-61 years v 60 years; IQR, 46-70 years), their median body mass index higher (32.5 [IQR, 27.2-39.0] kg/m2 v 30.1 [IQR, 25.7-35.7] kg/m2 ), and fewer had received a COVID-19 vaccine (22% v 44.9%); their median APACHE II scores were similar (14.0; IQR, 12.0-18.0 v 14.0; IQR, 10.0-19.0). Bacterial pneumonia (64.7% v 29.0%) and bacteraemia (27% v 8%) were more frequent in transferred patients, as was the need for more intensive ICU interventions, including invasive mechanical ventilation (71.2% v 38.1%) and extra-corporeal membrane oxygenation (26% v 1.7%). Crude ICU (19% v 14.9%) and in-hospital mortality (19% v 18.4%) were similar for patients who were or were not transferred; median lengths of ICU (20.0 [IQR, 11.2-40.3] days v 4.6 [IQR, 2.1-10.1] days) and hospital stay (29.7 [IQR, 18.1-49.6] days v 12.3 [IQR, 7.3-21.0] days) were longer for transferred patients. In the multivariable regression analysis, in-hospital mortality risk was lower for transferred patients (risk difference [RD], -5.0 percentage points; 95% confidence interval [CI] -10 to -0.03 percentage points), but not in the propensity score-adjusted analysis (RD, -3.4 [95% CI, -8.9 to 2.1] percentage points). CONCLUSIONS: Among people with COVID-19 admitted to ICUs, patients transferred from another hospital required more intense interventions and remained in hospital longer, but were not at greater risk of dying in hospital than the patients who were not transferred.

Mental health and wellbeing of health and aged care workers in Australia, May 2021 - June 2022: a longitudinal cohort study.

OBJECTIVES: To assess the mental health and wellbeing of health and aged care workers in Australia during the second and third years of the coronavirus disease 2019 (COVID-19) pandemic, overall and by occupation group. DESIGN, SETTING, PARTICIPANTS: Longitudinal cohort study of health and aged care workers (ambulance, hospitals, primary care, residential aged care) in Victoria: May-July 2021 (survey 1), October-December 2021 (survey 2), and May-June 2022 (survey 3). MAIN OUTCOME MEASURES: Proportions of respondents (adjusted for age, gender, socio-economic status) reporting moderate to severe symptoms of depression (Patient Health Questionnaire-9, PHQ-9), anxiety (Generalized Anxiety Disorder scale, GAD-7), or post-traumatic stress (Impact of Event Scale-6, IES-6), burnout (abbreviated Maslach Burnout Inventory, aMBI), or high optimism (10-point visual analogue scale); mean scores (adjusted for age, gender, socio-economic status) for wellbeing (Personal Wellbeing Index-Adult, PWI-A) and resilience (Connor Davidson Resilience Scale 2, CD-RISC-2). RESULTS: A total of 1667 people responded to at least one survey (survey 1, 989; survey 2, 1153; survey 3, 993; response rate, 3.3%). Overall, 1211 survey responses were from women (72.6%); most respondents were hospital workers (1289, 77.3%) or ambulance staff (315, 18.9%). The adjusted proportions of respondents who reported moderate to severe symptoms of depression (survey 1, 16.4%; survey 2, 22.6%; survey 3, 19.2%), anxiety (survey 1, 8.8%; survey 2, 16.0%; survey 3, 11.0%), or post-traumatic stress (survey 1, 14.6%; survey 2, 35.1%; survey 3, 14.9%) were each largest for survey 2. The adjusted proportions of participants who reported moderate to severe symptoms of burnout were higher in surveys 2 and 3 than in survey 1, and the proportions who reported high optimism were smaller in surveys 2 and 3 than in survey 1. Adjusted mean scores for wellbeing and resilience were similar at surveys 2 and 3 and lower than at survey 1. The magnitude but not the patterns of change differed by occupation group. CONCLUSION: Burnout was more frequently reported and mean wellbeing and resilience scores were lower in mid-2022 than in mid-2021 for Victorian health and aged care workers who participated in our study. Evidence-based mental health and wellbeing programs for workers in health care organisations are needed. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12621000533897 (observational study; retrospective).

Continuous Renal Replacement Therapy during Extracorporeal Membrane Oxygenation: Circuit Haemodynamics and Circuit Failure.

INTRODUCTION: Treatment with continuous renal replacement therapy (CRRT) is common during extracorporeal membrane oxygenation (ECMO). Such ECMO-CRRT has specific technical characteristics, which may affect circuit life. Accordingly, we studied CRRT haemodynamics and circuit life during ECMO. METHODS: ECMO and non-ECMO-CRRT treatments in two adult intensive care units were compared using data collected over a 3-year period. A potential predictor of circuit survival identified in a 60% training data subset as a time-varying covariate within a Cox proportional hazard model was subsequently assessed in the complementary remaining data (40%). RESULTS: Median [interquartile range] CRRT circuit life was greater when associated with ECMO (28.8 [14.0-65.2] vs. 20.2 [9.8-40.2] h, p < 0.0001). Access, return, prefilter, and effluent pressures were also greater during ECMO. Higher ECMO flows were associated with higher access and return pressures. Classification and regression tree analysis identified an association between high access pressures and accelerated circuit failure, while both first access pressures ≥190 mm Hg (HR 1.58 [1.09-2.30]) and patient weight (HR 1.85 [1.15-2.97] third tertile vs. first tertile) were independently associated with circuit failure in a multivariable Cox model. Access dysfunction was associated with a stepwise increase in transfilter pressure, suggesting a potential mechanism of membrane injury. CONCLUSION: CRRT circuits used in conjunction with ECMO have a longer circuit life than usual CRRT despite exposure to higher circuit pressures. Markedly elevated access pressures, however, may predict early CRRT circuit failure during ECMO, possibly via progressive membrane thrombosis as evidenced by increased transfilter pressure gradients.

The Effect of a Liberal Approach to Glucose Control in Critically Ill Patients with Type 2 Diabetes: A Multicenter, Parallel-Group, Open-Label Randomized Clinical Trial.

Rationale: Blood glucose concentrations affect outcomes in critically ill patients, but the optimal target blood glucose range in those with type 2 diabetes is unknown. Objectives: To evaluate the effects of a "liberal" approach to targeted blood glucose range during ICU admission. Methods: This mutlicenter, parallel-group, open-label randomized clinical trial included 419 adult patients with type 2 diabetes expected to be in the ICU on at least three consecutive days. In the intervention group intravenous insulin was commenced at a blood glucose >252 mg/dl and titrated to a target range of 180-252 mg/dl. In the comparator group insulin was commenced at a blood glucose >180 mg/dl and titrated to a target range of 108-180 mg/dl. The primary outcome was incident hypoglycemia (<72 mg/dl). Secondary outcomes included glucose metrics and clinical outcomes. Measurements and Main Results: By Day 28, at least one episode of hypoglycemia occurred in 10 of 210 (5%) patients assigned the intervention and 38 of 209 (18%) patients assigned the comparator (incident rate ratio, 0.21 [95% confidence interval (CI), 0.09 to 0.49]; P < 0.001). Those assigned the intervention had greater blood glucose concentrations (daily mean, minimum, maximum), less glucose variability, and less relative hypoglycemia (P < 0.001 for all comparisons). By Day 90, 62 of 210 (29.5%) in the intervention and 52 of 209 (24.9%) in the comparator group had died (absolute difference, 4.6 percentage points [95% CI, -3.9% to 13.2%]; P = 0.29). Conclusions: A liberal approach to blood glucose targets reduced incident hypoglycemia but did not improve patient-centered outcomes. Clinical trial registered with Australian New Zealand Clinical Trials Registry (ACTRN 12616001135404).

Comparison of 6-Month Outcomes of Survivors of COVID-19 versus Non-COVID-19 Critical Illness.

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).

Clinical characteristics and outcomes of critically ill patients with one, two and three doses of vaccination against COVID-19 in Australia.

BACKGROUND: Vaccination has been shown to be highly effective in preventing death and severe disease from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Currently, few studies have directly compared vaccinated and unvaccinated patients with severe COVID-19 in the intensive care unit (ICU). AIMS: To compare the clinical characteristics and outcomes of vaccine recipients and unvaccinated patients with SARS-CoV-2 infection admitted to the ICU in a nationwide setting. METHODS: Data were extracted from the Short PeRiod IncideNce sTudy of Severe Acute Respiratory Infection Australia, in 57 ICU during Delta and Omicron predominant periods of the COVID-19 pandemic. The primary outcome was inhospital mortality. Secondary outcomes included duration of mechanical ventilation, ICU length of stay, hospital length of stay and ICU mortality. RESULTS: There were 2970 patients admitted to ICU across participating sites from 26 June 2021 to 8 February 2022; 1134 (38.2%) patients were vaccine recipients, and 1836 (61.8%) patients were unvaccinated. Vaccine recipients were older, more comorbid and less likely to require organ support. Unadjusted inhospital mortality was greater in the vaccinated cohort. After adjusting for age, gender and comorbid status, no statistically significant association between inhospital or ICU mortality, and vaccination status, was apparent. CONCLUSION: We found COVID-19 infection can cause severe disease and death in vaccine recipients, though comorbid status and older age were significant contributors to mortality. Organ support requirements and the number of deaths were highest in the unvaccinated cohort.