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ImportanceNeurocritical care (NCC) aims to improve the outcomes of critically ill patients with brain injury, although the benefits of such subspecialized care are yet to be determined.ObjectiveTo evaluate the association of NCC with patient-centered outcomes in adults with acute brain injury who were admitted to intensive care units (ICUs). The protocol was preregistered on PROSPERO (CRD42020177190).Data SourcesThree electronic databases were searched (Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials) from inception through December 15, 2021, and by citation chaining.Study SelectionStudies were included for interventions of neurocritical care units (NCCUs), neurointensivists, or NCC consulting services compared with general care in populations of neurologically ill adults or adults with acute brain injury in ICUs.Data Extraction and SynthesisData extraction was performed in keeping with PRISMA guidelines and risk of bias assessed through the ROBINS-I Cochrane tool by 2 independent reviewers. Data were pooled using a random-effects model.Main Outcomes and MeasuresThe primary outcome was all-cause mortality at longest follow-up until 6 months. Secondary outcomes were ICU length of stay (LOS), hospital LOS, and functional outcomes. Data were measured as risk ratio (RR) if dichotomous or standardized mean difference if continuous. Subgroup analyses were performed for disease and models of NCC delivery.ResultsAfter 5659 nonduplicated published records were screened, 26 nonrandomized observational studies fulfilled eligibility criteria. A meta-analysis of mortality outcomes for 55 792 patients demonstrated a 17% relative risk reduction (RR, 0.83; 95% CI, 0.75-0.92; P = .001) in those receiving subspecialized care (n = 27 061) compared with general care (n = 27 694). Subgroup analyses did not identify subgroup differences. Eight studies including 4667 patients demonstrated a 17% relative risk reduction (RR, 0.83; 95% CI, 0.70-0.97; P = .03) for an unfavorable functional outcome with subspecialized care compared with general care. There were no differences in LOS outcomes. Heterogeneity was substantial in all analyses.Conclusions and RelevanceSubspecialized NCC is associated with improved survival and functional outcomes for critically ill adults with brain injury. However, confidence in the evidence is limited by substantial heterogeneity. Further investigations are necessary to determine the specific aspects of NCC that contribute to these improved outcomes and its cost-effectiveness.

Haemorrhagic shock after trauma is a leading cause of death worldwide, particularly in young individuals. Despite advances in trauma systems and resuscitation strategies, mortality from haemorrhagic shock has not declined over the previous two decades. A proportion of shocked trauma patients may experience a deficiency of cortisol relative to the severity of their injury. The benefit of exogenous steroid administration in patients suffering haemorrhagic shock as a result of injury is unclear. A systematic review of four databases (Ovid Medline, Ovid Embase, Cochrane, Scopus) was undertaken. Inclusion and exclusion criteria were pre-determined and two reviewers independently screened the articles with disagreements arbitrated by a third reviewer. The primary outcome variable was 28-day mortality. Quality of studies were assessed using the Cochrane-risk-of-bias (RoB 2) tool. Of the 2919 studies yielded by the search strategy, 1274 duplicates were removed and 1645 screened on title and abstract. After the full text of 33 studies were assessed, two articles were included. Both studies were over 30 years old with small numbers of participants and with primary outcomes not including mortality. Of the data available, no statistically significant difference in mortality was detected. Hospital length of stay, reversal of shock or adverse events were not reported. Both studies were at risk of bias. There are no high quality or recent studies in the English literature investigating the use of steroids for haemorrhagic shocked trauma patients. PROSPERO: CRD42021239656.

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.

Therapeutic drug monitoring (TDM) of beta-lactam antibiotics is recommended to address the variability in exposure observed in critical illness. However, the impact of TDM-guided dosing on clinical outcomes remains unknown. We conducted a systematic review and meta-analysis on TDM-guided dosing and clinical outcomes (all-cause mortality, clinical cure, microbiological cure, treatment failure, hospital and intensive care unit length of stay, target attainment, antibiotic-related adverse events, and emergence of resistance) in critically ill patients with suspected or proven sepsis. Eleven studies (n = 1463 participants) were included. TDM-guided dosing was associated with improved clinical cure (relative risk, 1.17; 95% confidence interval [CI], 1.04 to 1.31), microbiological cure (RR, 1.14; 95% CI, 1.03 to 1.27), treatment failure (RR, 0.79; 95% CI, .66 to .94), and target attainment (RR, 1.85; 95% CI, 1.08 to 3.16). No associations with mortality and length of stay were found. TDM-guided dosing improved clinical and microbiological cure and treatment response. Larger, prospective, randomized trials are required to better assess the utility of beta-lactam TDM in critically ill patients.

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating form of stroke frequently affecting young to middle-aged adults, with an unmet need to improve outcome. This special report focusses on the development of intrathecal haptoglobin supplementation as a treatment by reviewing current knowledge and progress, arriving at a Delphi-based global consensus regarding the pathophysiological role of extracellular hemoglobin and research priorities for clinical translation of hemoglobin-scavenging therapeutics. After aneurysmal subarachnoid hemorrhage, erythrocyte lysis generates cell-free hemoglobin in the cerebrospinal fluid, which is a strong determinant of secondary brain injury and long-term clinical outcome. Haptoglobin is the body’s first-line defense against cell-free hemoglobin by binding it irreversibly, preventing translocation of hemoglobin into the brain parenchyma and nitric oxide-sensitive functional compartments of cerebral arteries. In mouse and sheep models, intraventricular administration of haptoglobin reversed hemoglobin-induced clinical, histological, and biochemical features of human aneurysmal subarachnoid hemorrhage. Clinical translation of this strategy imposes unique challenges set by the novel mode of action and the anticipated need for intrathecal drug administration, necessitating early input from stakeholders. Practising clinicians (n=72) and scientific experts (n=28) from 5 continents participated in the Delphi study. Inflammation, microvascular spasm, initial intracranial pressure increase, and disruption of nitric oxide signaling were deemed the most important pathophysiological pathways determining outcome. Cell-free hemoglobin was thought to play an important role mostly in pathways related to iron toxicity, oxidative stress, nitric oxide, and inflammation. While useful, there was consensus that further preclinical work was not a priority, with most believing the field was ready for an early phase trial. The highest research priorities were related to confirming haptoglobin’s anticipated safety, individualized versus standard dosing, timing of treatment, pharmacokinetics, pharmacodynamics, and outcome measure selection. These results highlight the need for early phase trials of intracranial haptoglobin for aneurysmal subarachnoid hemorrhage, and the value of early input from clinical disciplines on a global scale during the early stages of clinical translation.

Rapid reductions in P a CO 2 during extracorporeal membrane oxygenation (ECMO) are associated with poor neurologic outcomes. Understanding what factors determine P a CO 2 may allow a gradual reduction, potentially improving neurologic outcome. A simple and intuitive arithmetic expression was developed, to describe the interactions between the major factors determining P a CO 2 during venovenous ECMO. This expression was tested using a wide range of input parameters from clinically feasible scenarios. The difference between P a CO 2 predicted by the arithmetic equation and P a CO 2 predicted by a more robust and complex in-silico mathematical model, was10 mm Hg for more than 95% of the scenarios tested. With no CO 2 in the sweep gas, P a CO 2 is proportional to metabolic CO 2 production and inversely proportional to the "total effective expired ventilation" (sum of alveolar ventilation and oxygenator ventilation). Extracorporeal blood flow has a small effect on P a CO 2 , which becomes more important at low blood flows and high recirculation fractions. With CO 2 in the sweep gas, the increase in P a CO 2 is proportional to the concentration of CO 2 administered. P a CO 2 also depends on the fraction of the total effective expired ventilation provided via the oxygenator. This relationship offers a simple intervention to control P a CO 2 using titration of CO 2 in the sweep gas.

The primary objective was to evaluate the performance of the Cockcroft-Gault (CG) equation with different body weights (BWs) compared to a measured creatinine clearance (mCrCl) in an intensive care unit (ICU) population with and without augmented renal clearance (ARC).Multicenter, retrospective cohort.Two ICUs in the United States and four ICUs from a previous international observational analysis.Adult ICU patients admitted from January 1, 2010 to July 30, 2020 with at least one mCrCl collected within the initial 10 days of hospitalization were eligible for inclusion.The primary outcome was the performance of the CG equation in ARC (mCrCl≥130 ml/min/1.73 mThe CG-adjusted BW had the best performance in the non-ARC patients, while CG performed poorly with any BW in ARC patients. Although the CG equation remains the standard equation for estimating CrCl in the ICU setting, a new, validated equation is needed for patients with ARC.

OBJECTIVE: To report longitudinal differences in baseline characteristics, treatment, and outcomes in patients with coronavirus disease 2019 (COVID-19) admitted to intensive care units (ICUs) between the first and second waves of COVID-19 in Australia. DESIGN, SETTING AND PARTICIPANTS: SPRINT-SARI Australia is a multicentre, inception cohort study enrolling adult patients with COVID-19 admitted to participating ICUs. The first wave of COVID-19 was from 27 February to 30 June 2020, and the second wave was from 1 July to 22 October 2020. RESULTS: A total of 461 patients were recruited in 53 ICUs across Australia; a higher number were admitted to the ICU during the second wave compared with the first: 255 (55.3%) versus 206 (44.7%). Patients admitted to the ICU in the second wave were younger (58.0 v 64.0 years; P = 0.001) and less commonly male (68.9% v 60.0%; P = 0.045), although Acute Physiology and Chronic Health Evaluation (APACHE) II scores were similar (14 v 14; P = 0.998). High flow oxygen use (75.2% v 43.4%; P < 0.001) and non-invasive ventilation (16.5% v 7.1%; P = 0.002) were more common in the second wave, as was steroid use (95.0% v 30.3%; P < 0.001). ICU length of stay was shorter (6.0 v 8.4 days; P = 0.003). In-hospital mortality was similar (12.2% v 14.6%; P = 0.452), but observed mortality decreased over time and patients were more likely to be discharged alive earlier in their ICU admission (hazard ratio, 1.43; 95% CI, 1.13–1.79; P = 0.002). CONCLUSION: During the second wave of COVID-19 in Australia, ICU length of stay and observed mortality decreased over time. Multiple factors were associated with this, including changes in clinical management, the adoption of new evidence-based treatments, and changes in patient demographic characteristics but not illness severity.

Summary Background Hypophosphatemia may be a useful biomarker to identify thiamine deficiency in critically ill enterally-fed patients. The objective was to determine whether intravenous thiamine affects blood lactate, biochemical and clinical outcomes in this group. Method This randomized clinical trial was conducted across 5 Intensive Care Units. Ninety critically ill adult patients with a serum phosphate ≤0.65 mmol/L within 72 h of commencing enteral nutrition were randomized to intravenous thiamine (200 mg every 12 h for up to 14 doses) or usual care (control). The primary outcome was blood lactate over time and data are median [IQR] unless specified. Results Baseline variables were well balanced (thiamine: lactate 1.2 [1.0, 1.6] mmol/L, phosphate 0.56 [0.44, 0.64] mmol/L vs. control: lactate 1.0 [0.8, 1.3], phosphate 0.54 [0.44, 0.61]). Patients randomized to the intervention received a median of 11 [7.5, 13.5] doses for a total of 2200 [1500, 2700] mg of thiamine. Blood lactate over the entire 7 days of treatment was similar between groups (mean difference = −0.1 (95 % CI -0.2 to 0.1) mmol/L; P = 0.55). The percentage change from lactate pre-randomization to T = 24 h was not statistically different (thiamine: −32 (−39, −26) vs. control: −24 (−31, −16) percent, P = 0.09). Clinical outcomes were not statistically different (days of vasopressor administration: thiamine 2 [1, 4] vs. control 2 [0, 5.5] days; P = 0.37, and deaths 9 (21 %) vs. 5 (11 %); P = 0.25). Conclusions In critically ill enterally-fed patients who developed hypophosphatemia, intravenous thiamine did not cause measurable differences in blood lactate or clinical outcomes. Trial registration Australian and New Zealand Clinical Trials Registry (ACTRN12619000121167).

Rationale: Both 2009 pandemic influenza A (H1N1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are transmitted by respiratory secretions and in severe cases result in a viral pneumonitis, requiring intensive care unit (ICU) admission. However, no studies have compared the clinical characteristics and outcomes of such patients. Objectives: To report and compare the demographic characteristics, treatments, use of critical care resources, and outcomes of patients admitted to an Australian ICU with H1N1 influenza during the winter of 2009, and SARS-CoV-2 during the winter of 2020. Methods: This was a multicenter project, using national data from previous and ongoing epidemiological studies concerning severe acute respiratory infections in Australia. All ICUs admitting patients with H1N1 or coronavirus disease (COVID-19) were included and contributed data. We compared clinical characteristics and outcomes of patients with H1N1 admitted to ICU in the winter of 2009 versus patients with COVID-19 admitted to ICU in the winter of 2020. The primary outcome was in-hospital mortality. Potential years of life lost (PYLL) were calculated according to sex-adjusted life expectancy in Australia. Results: Across the two epochs, 861 patients were admitted to ICUs; 236 (27.4%) with COVID-19 and 625 (72.6%) with H1N1 influenza. The number of ICU admissions and bed-days occupied were higher with 2009 H1N1 influenza. Patients with COVID-19 were older, more often male and overweight, and had lower Acute Physiology and Chronic Health Evaluation II scores at ICU admission. The highest age-specific incidence of ICU admission was among infants (0–1 yr of age) for H1N1, and among the elderly (≥65 yr) for COVID-19. Unadjusted in-hospital mortality was similar (11.5% in COVID-19 vs. 16.1% in H1N1; odds ratio, 0.68 [95% confidence interval (95% CI), 0.42–1.06]; P = 0.10). The PYLL was greater with H1N1 influenza than with COVID-19 at 154.1 (95% CI, 148.7–159.4) versus 13.6 (95% CI, 12.2–15.1) PYLL per million inhabitants. Conclusions: In comparison with 2009 H1N1 influenza, COVID-19 admissions overwinter in Australia resulted in fewer ICU admissions, and lower bed-day occupancy. Crude in-hospital mortality was similar, but because of demographic differences in affected patients, deaths due to 2009 H1N1 influenza led to an 11-fold increase in the number of PYLL in critically ill patients.

ObjectiveTo report intensive care unit admission outcomes for head and neck cancer patients.MethodsA retrospective, observational cohort analysis of all Australian and New Zealander head and neck cancer patient intensive care unit admissions from January 2000 to June 2016, including data from 192 intensive care units.ResultsThere were 10 721 head and neck cancer patients, with a median age of 64 years (71.6 per cent male). Of admissions, 76.4 per cent were in public hospitals, 96.9 per cent were post-operative and 43.6 per cent required mechanical ventilation. Annual head and neck cancer admissions increased from 2000 to 2015 (from 348 to 1132 patients), but the overall proportion of intensive care unit admissions remained constant. In-hospital mortality was 2.7 per cent, and intensive care unit mortality was 0.7 per cent. The in-hospital mortality risk decreased three-fold (p < 0.001).ConclusionHead and neck cancer patients had low mortality in the intensive care unit and in hospital. Risk of dying decreased despite more intensive care unit admissions. This is the first large-scale cohort study quantifying intensive care unit utilisation by head and neck cancer patients. It informs future work investigating alternatives to the intensive care unit for these patients.

There is growing interest in not only intensive care unit (ICU) outcomes but also the resources required to deliver this care and itscost-effectiveness. The most available metric of resource utilisation is ICU length of stay, which is influenced by casemix, illness severity, and institutional characteristics, including delays in discharge. For instance, ICU length of stay is generally longer for more severely ill patients. Comparison of length of stay between units must therefore account for differences in baseline patient characteristics.

Internationally, diabetes mellitus is recognised as a risk factor for severe COVID-19. The relationship between diabetes mellitus and severe COVID-19 has not been reported in the Australian population.The objective of this study was to determine the prevalence of and outcomes for patients with diabetes admitted to Australian intensive care units (ICUs) with COVID-19.This is a nested cohort study of four ICUs in Melbourne participating in the Short Period Incidence Study of Severe Acute Respiratory Infection (SPRINT-SARI) Australia project. All adult patients admitted to the ICU with COVID-19 from 20 February 2020 to 27 February 2021 were included. Blood glucose and glycated haemoglobin (HbA1c) data were retrospectively collected. Diabetes was diagnosed from medical history or an HbA1c ≥6.5% (48 mmol/mol). Hospital mortality was assessed using logistic regression.There were 136 patients with median age 58 years [48-68] and median Acute Physiology and Chronic Health Evaluation II (APACHE II) score of 14 [11-19]. Fifty-eight patients had diabetes (43%), 46 patients had stress-induced hyperglycaemia (34%), and 32 patients had normoglycaemia (23%). Patients with diabetes were older, were with higher APACHE II scores, had greater glycaemic variability than patients with normoglycaemia, and had longer hospital length of stay. Overall hospital mortality was 16% (22/136), including nine patients with diabetes, nine patients with stress-induced hyperglycaemia, and two patients with normoglycaemia.Diabetes is prevalent in patients admitted to Australian ICUs with severe COVID-19, highlighting the need for prevention strategies in this vulnerable population.

Objective: To characterise the assessment and management of delirium in patients admitted to intensive care units (ICUs) in Australia and New Zealand. Methods: We conducted a multicentre observational point prevalence study across 44 adult Australian and New Zealand ICUs. Data were extracted for all patients in the ICU in terms of assessment and treatment of delirium. ICU-level data were collected regarding the use of explicit protocols related to delirium. Results: We studied 627 patients, with 54% (336/627) having at least one delirium screening assessment performed. The Confusion Assessment Method for the ICU (CAM-ICU) was the most frequently used tool (88%, 296/336). Of patients assessed, 20% (68) were identified to have delirium. Eighteen per cent (111) of patients were administered a drug to manage delirium, with 41% (46) of those receiving a drug having no recorded assessment for delirium on that day. Of the drugs used to treat delirium, quetiapine was the most frequently administered. Physical restraints were applied to 8% (48/626) of patients, but only 17% (8/48) of such patients had been diagnosed with delirium. Most physically restrained patients either did not have delirium diagnosed (31%, 15/48) or had no formal assessment recorded (52%, 25/48) on that day. Conclusions: On the study day, more than 50% of patients had a delirium screening assessment performed, with 20% of screened patients deemed to have delirium. Drugs that are prescribed to treat delirium and physical restraints were frequently used in the absence of delirium or the formal assessment for its presence.

This study aimed to evaluate the utility of the 11-variable modified Frailty Index (mFI) in prognosticating elderly patients with traumatic acute subdural hematomas (aSDHs). A state-service level 1 trauma center registry was interrogated to investigate consecutive patients ≥65 years of age presenting with traumatic aSDH, with or without major extracranial injury, between January 2013 and December 2017. mFI on admission, demographics, and admission details, including Glasgow Coma Scale (GCS) and pupillary status and radiological findings, were retrospectively retrieved from institutional records. Clinical outcome data were retrieved from medical records and the Victorian State Trauma Registry (VSTR). Outcome measures were 1) 30-day mortality and 2) 6-month unfavorable outcome, defined by the Extended Glasgow Outcome Scale (GOS-E). Five hundred twenty-nine consecutive cases were identified from the registry. Demographic data included: 1) age (median; interquartile range) = 80.46; 74.17-85.89; 2) mFI (mean ± standard deviation) = 1.96 ± 1.42 of 11 variables. Four hundred sixteen cases (79%) had complete outcome data. As mFI increased from 0/11 variables to ≥5/11 variables (≥0.45), 30-day mortality risk increased from 17.72% to 39.29% (

Background/Objective: Dysnatremia is common in severe traumatic brain injury (TBI) patients and may contribute to mortality. However, serum sodium variability has not been studied in TBI patients. We hypothesized that such variability would be independently associated with mortality. Methods: We collected 6-hourly serum sodium levels for the first 7 days of ICU admission from 240 severe TBI patients in 14 neurotrauma ICUs in Europe and Australia. We evaluated the association between daily serum sodium standard deviation (dNaSD), an index of variability, and 28-day mortality. Results: Patients were 46 ± 19 years of age with a median initial GCS of 6 [4–8]. Overall hospital mortality was 28%. Hypernatremia and hyponatremia occurred in 64% and 24% of patients, respectively. Over the first 7 days in ICU, serum sodium standard deviation was 2.8 [2.0–3.9] mmol/L. Maximum daily serum sodium standard deviation (dNaSD) occurred at a median of 2 [1–4] days after admission. There was a significant progressive decrease in dNaSD over the first 7 days (coefficient − 0.15 95% CI [− 0.18 to − 0.12], p < 0.001). After adjusting for baseline TBI severity, diabetes insipidus, the use of osmotherapy, the occurrence of hypernatremia, and hyponatremia and center, dNaSD was significantly independently associated with 28-day mortality (HR 1.27 95% CI (1.01–1.61), p = 0.048). Conclusions: Our study demonstrates that daily serum sodium variability is an independent predictor of 28-day mortality in severe TBI patients. Further prospective investigations are necessary to confirm the significance of sodium variability in larger cohorts of TBI patients and test whether attenuating such variability confers outcome benefits to such patients.

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).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.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. 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.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.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is an invasive procedure used to support critically ill patients with the most severe forms of cardiac or respiratory failure in the short term, but long-term effects on incidence of death and disability are unknown. We aimed to assess incidence of death or disability associated with ECMO up to 6 months (180 days) after treatment. METHODS: This prospective, multicentre, registry-embedded cohort study was done at 23 hospitals in Australia from Feb 15, 2019, to Dec 31, 2020. The EXCEL registry included all adults (≥18 years) in Australia who were admitted to an intensive care unit (ICU) in a participating centre at the time of the study and who underwent ECMO. All patients who received ECMO support for respiratory failure, cardiac failure, or cardiac arrest during their ICU stay were eligible for this study. The primary outcome was death or moderate-to-severe disability (defined using the WHO Disability Assessment Schedule 2.0, 12-item survey) at 6 months after ECMO initiation. We used Fisher's exact test to compare categorical variables. This study is registered with ClinicalTrials.gov, NCT03793257. FINDINGS: Outcome data were available for 391 (88%) of 442 enrolled patients. The primary outcome of death or moderate-to-severe disability at 6 months was reported in 260 (66%) of 391 patients: 136 (67%) of 202 who received veno-arterial (VA)-ECMO, 60 (54%) of 111 who received veno-venous (VV)-ECMO, and 64 (82%) of 78 who received extracorporeal cardiopulmonary resuscitation (eCPR). After adjustment for age, comorbidities, Acute Physiology and Chronic Health Evaluation (APACHE) IV score, days between ICU admission and ECMO start, and use of vasopressors before ECMO, death or moderate-to-severe disability was higher in patients who received eCPR than in those who received VV-ECMO (VV-ECMO vs eCPR: risk difference [RD] -32% [95% CI -49 to -15]; p

It is plausible that a longer duration of nutrition intervention may have a greater impact on clinical and patient-centred outcomes. The Intensive Nutrition care Therapy comparEd to usual care iN criTically ill adults (INTENT) trial will determine if a whole hospital nutrition intervention is feasible and will deliver more total energy compared with usual care in critically ill patients with at least one organ system failure.This study is a prospective, multicentre, unblinded, parallel-group, phase II randomised controlled trial (RCT) conducted in 23 hospitals in Australia and New Zealand. Mechanically ventilated critically ill adult patients with at least one organ failure who have been in intensive care unit (ICU) for 72-120 hours and meet all of the inclusion and none of the exclusion criteria will be randomised to receive either intensive or usual nutrition care. INTENT started recruitment in October 2018 and a sample size of 240 participants is anticipated to be recruited in 2022. The study period is from randomisation to hospital discharge or study day 28, whichever occurs first, and the primary outcome is daily energy delivery from nutrition therapy. Secondary outcomes include daily energy and protein delivery during ICU and in the post-ICU period, duration of ventilation, ventilator-free days, total bloodstream infection rate and length of hospital stay. All other outcomes are considered tertiary and results will be analysed on an intention-to-treat basis.Ethics approval has been received in Australia (Alfred Hospital Ethics Committee (HREC/18/Alfred/101) and Human Research Ethics Committee of the Northern Territory Department of Health (2019-3372)) and New Zealand (Northern A Health and Disability Ethics Committee (18/NTA/222). Results will be disseminated in an international peer-reviewed journal(s), at scientific meetings and via social media.NCT03292237.

Induction of ketosis by manipulation of nutrition intake has been proposed as an adjunctive treatment for super-refractory status epilepticus (SRSE). However, the classical 4:1 ketogenic ratio may not meet the nutrition needs, specifically protein for critically ill adults. The aim of this study was to analyze the outcomes of adults with SRSE who received a lower ketogenic ratio of 2:1 grams of fat to non-fat grams, including 20%-30% of energy from medium chain triglycerides.We reviewed patients aged ≥18 years with SRSE treated with ketogenic therapy between July 2015 and December 2020 at two quaternary teaching hospitals in Melbourne, Australia. Data collected from medical records included patient demographics, nutrition prescription, clinical outcomes, and ketogenic therapy-related complications. The primary outcome of the study was to assess tolerability of ketogenic therapy.Twelve patients (female = 7) were treated with ketogenic therapy for SRSE. Patients received between 4 and 8 antiseizure medications and 1-5 anesthetic agents prior to commencement of ketogenic therapy. Blood beta-hydroxybutyrate concentrations were variable (median = 0.5 mmol/L, range: 0.0-6.1 mmol/L). SRSE resolved in 10 cases (83%) after a median of 9 days (range: 2-21 days) following commencement of ketogenic therapy. Ketogenic therapy-associated complications were reported in five patients, leading to cessation in two patients.Despite the challenge in maintaining ketosis during critical illness, low ratio 2:1 ketogenic therapy incorporating medium chain triglycerides is tolerable for adults with SRSE. Further studies are required to determine the optimal timing, nutrition prescription and duration of ketogenic therapy for SRSE treatment.

Contains fulltext : 248999.pdf (Publisher’s version ) (Closed access) BACKGROUND: The SARS-CoV-2 (COVID-19) pandemic has impacted many facets of critical care delivery. METHODS: An electronic survey was distributed to explore the pandemic's perceived impact on neurocritical care delivery between June 2020 and March 2021. Variables were stratified by World Bank country income level, presence of a dedicated neurocritical care unit (NCCU) and experiencing a COVID-19 patient surge. RESULTS: Respondents from 253 hospitals (78.3% response rate) from 47 countries (45.5% low/middle income countries; 54.5% with a dedicated NCCU; 78.6% experienced a first surge) participated in the study. Independent of country income level, NCCU and surge status, participants reported reductions in NCCU admissions (67%), critical care drug shortages (69%), reduction in ancillary services (43%) and routine diagnostic testing (61%), and temporary cancellation of didactic teaching (44%) and clinical/basic science research (70%). Respondents from low/middle income countries were more likely to report lack of surge preparedness (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.8-5.8) and struggling to return to prepandemic standards of care (OR, 12.2; 95% CI, 4.4-34) compared with respondents from high-income countries. Respondents experiencing a surge were more likely to report conversion of NCCUs and general-mixed intensive care units (ICUs) to a COVID-ICU (OR 3.7; 95% CI, 1.9-7.3), conversion of non-ICU beds to ICU beds (OR, 3.4; 95% CI, 1.8-6.5), and deviations in critical care and pharmaceutical practices (OR, 4.2; 95% CI 2.1-8.2). Respondents from hospitals with a dedicated NCCU were less likely to report conversion to a COVID-ICU (OR, 0.5; 95% CI, 0.3-0.9) or conversion of non-ICU to ICU beds (OR, 0.5; 95% CI, 0.3-0.9). CONCLUSION: This study reports the perceived impact of the COVID-19 pandemic on global neurocritical care delivery, and highlights shortcomings of health care infrastructures and the importance of pandemic preparedness.

We aimed to compare the effects of vitamin C, glucocorticoids, vitamin B1, combinations of these drugs, and placebo or usual care on longer-term mortality in adults with sepsis or septic shock. MEDLINE, Embase, CENTRAL, ClinicalTrials.gov and WHO-ICTRP were searched. The final search was carried out on September 3rd, 2021. Multiple reviewers independently selected randomized controlled trials (RCTs) comparing very-high-dose vitamin C (≥ 12 g/day), high-dose vitamin C (

BACKGROUND: Contemporary glucose management of intensive care unit (ICU) patients with type 2 diabetes is based on trial data derived predominantly from patients without type 2 diabetes. This is despite the recognition that patients with type 2 diabetes may be relatively more tolerant of hyperglycaemia and more susceptible to hypoglycaemia. It is uncertain whether glucose targets should be more liberal in patients with type 2 diabetes. OBJECTIVE: To detail the protocol, analysis and reporting plans for a randomised clinical trial — the Liberal Glucose Control in Critically Ill Patients with Pre-existing Type 2 Diabetes (LUCID) trial — which will evaluate the risks and benefits of targeting a higher blood glucose range in patients with type 2 diabetes. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: A multicentre, parallel group, open label phase 2B randomised controlled clinical trial of 450 critically ill patients with type 2 diabetes. Patients will be randomised 1:1 to liberal blood glucose (target 10.0–14.0 mmol/L) or usual care (target 6.0–10.0 mmol/L). MAIN OUTCOME MEASURES: The primary endpoint is incident hypoglycaemia (< 4.0 mmol/L) during the study intervention. Secondary endpoints include biochemical and feasibility outcomes. RESULTS AND CONCLUSION: The study protocol and statistical analysis plan described will delineate conduct and analysis of the trial, such that analytical and reporting bias are minimised. TRIAL REGISTRATION: This trial has been registered on the Australian New Zealand Clinical Trials Registry (ACTRN No. 12616001135404) and has been endorsed by the Australian and New Zealand Intensive Care Society Clinical Trials Group.

Objectives To describe haemodynamic resuscitation practices in ED patients with suspected sepsis and hypotension. Methods This was a prospective, multicentre, observational study conducted in 70 hospitals in Australia and New Zealand between September 2018 and January 2019. Consecutive adults presenting to the ED during a 30‐day period at each site, with suspected sepsis and hypotension (systolic blood pressure

Background This study aimed to compare recommendations in the American Society for Parenteral and Enteral Nutrition (ASPEN) Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient with measured energy expenditure in obese, critically ill adults. Methods After enrollment, measured energy expenditure was attempted at baseline and twice weekly to extubation or day 14. Data are reported as median [interquartile range]. Results Twenty patients were included. The median baseline and subsequent measured energy expenditures were 2438 [1807-2703] kcal and 2919 [2318-3362] kcal, respectively. Baseline measured energy expenditures were -491 [-788 to -323] kcal lower than subsequent measurements, and week 1 measurements were lower than those of week 2. The median bias between the guideline recommendation of 11-14 kcal/kg of actual body weight and measured expenditure at baseline was -950 [-1254 to -595] kcal/d and -1618 [-1820 to -866] kcal/d at subsequent measurements. Conclusion Clinically significant variation was observed between measured expenditure and guideline recommendations at all time points.

Objective To quantify the pharmacodynamic (PD) activity of daily subcutaneous (SC) enoxaparin as venous thromboembolism (VTE) prophylaxis in high-risk trauma patients admitted to the intensive care unit (ICU). Methods This was a prospective observational PD study conducted in the ICU of a state-wide major trauma referral centre. The study cohort included adult patients admitted to the ICU with a high risk of VTE, as defined by at least one of the following: age > 40 years, prior VTE, spinal cord injury (SCI), traumatic brain injury (TBI), major venous injury, pelvic fractures, spinal fractures requiring treatment, severe lower limb injuries, and major surgery >2 h in duration. Standard prophylactic enoxaparin dosing was 40 mg SC daily, unless amended by the treating clinician. Plasma anti-Xa activity was measured approximately 60 min before dosing (trough activity), and at 3–5 h after dosing (peak activity). Target peak and trough activity were defined as >0.2 IU/mL and >0.1 IU/mL respectively. Clinical data including the development of VTE and haemorrhagic complications were collected. Results Twenty-five patients were enrolled. Median [IQR] age, weight, and plasma creatinine were 59 years [36,70], 85 kg [76.5,93.5] and 70μmol/L [60.5,109] respectively. Median APACHE III and Injury Severity Score were 54 [42.5,66.5] and 27 [17,34] respectively. Thirteen patients suffered a TBI, in 12 cases surgery extended beyond two hours, and five patients had spinal fractures requiring treatment. Twenty-two patients received enoxaparin 40 mg SC daily, two 60 mg, and one 20 mg. Median peak and trough anti-Xa activity was 0.21 IU/mL [0.125,0.25] and 0.01 IU/mL [0,0.05] respectively. Twelve (12/25; 48%) patients had low peak activity ≤0.2 IU/mL. Twenty-one (21/23; 91%) patients had low trough activity (≤0.1 IU/mL) and in six (6/23; 26%) cases, these were undetectable. Eight (8/25; 32%) patients had documented VTE of whom seven had low trough activity. There were no major haemorrhagic complications. Conclusions In a cohort of high risk critically ill trauma patients receiving daily SC enoxaparin as VTE chemoprophylaxis, measured peak and trough plasma anti-Xa activity was inadequate in a significant proportion. On this basis, further systematic investigation concerning dose optimisation in this patient population appears warranted.

Objective: To assess whether the initiation of vasopressor infusions via peripheral venous catheters (PVC) compared to central venous catheters (CVC) in ED patients with early septic shock was associated with differences in processes of care and outcomes. Methods: We conducted a post‐hoc analysis of the ARISE trial. We compared participants who had a vasopressor infusion first commenced via a PVC versus a CVC. The primary outcome was 90 day mortality. Results: We studied 937 participants. Of these, 389 (42%) had early vasopressor infusion commenced via a PVC and 548 (58%) via a CVC. Trial participants who received a vasopressor infusion via a PVC were more severely ill, with higher median (interquartile range [IQR]) Acute Physiology And Chronic Health Evaluation (APACHE II) scores (17 [13–23] versus 16 [12–21], P = 0.003), and higher median (IQR) lactate (mmol/L) (3.6 [1.9–5.8] versus 2.5 [1.5–4.5], P

Background Metabolic acidosis is a major complication of critical illness. However, its current epidemiology and its treatment with sodium bicarbonate given to correct metabolic acidosis in the ICU are poorly understood. Method This was an international retrospective observational study in 18 ICUs in Australia, Japan, and Taiwan. Adult patients were consecutively screened, and those with early metabolic acidosis (pH Results We screened 9437 patients. Of these, 1292 had early metabolic acidosis (14.0%). Early sodium bicarbonate was given to 18.0% (233/1292) of these patients. Dosing, physiological, and clinical outcome data were assessed in 360 patients. The median dose of sodium bicarbonate in the first 24 h was 110 mmol, which was not correlated with bodyweight or the severity of metabolic acidosis. Patients who received early sodium bicarbonate had higher APACHE III scores, lower pH, lower base excess, lower PaCO2, and a higher lactate and received higher doses of vasopressors. After adjusting for confounders, the early administration of sodium bicarbonate was associated with an adjusted odds ratio (aOR) of 0.85 (95% CI, 0.44 to 1.62) for ICU mortality. In patients with vasopressor dependency, early sodium bicarbonate was associated with higher mean arterial pressure at 6 h and an aOR of 0.52 (95% CI, 0.22 to 1.19) for ICU mortality. Conclusions Early metabolic acidosis is common in critically ill patients. Early sodium bicarbonate is administered by clinicians to more severely ill patients but without correction for weight or acidosis severity. Bicarbonate therapy in acidotic vasopressor-dependent patients may be beneficial and warrants further investigation.

Objective(s) To use machine learning (ML) to predict short-term requirements for invasive ventilation in patients with COVID-19 admitted to Australian intensive care units (ICUs). Design A machine learning study within a national ICU COVID-19 registry in Australia. Participants Adult patients who were spontaneously breathing and admitted to participating ICUs with laboratory-confirmed COVID-19 from 20 February 2020 to 7 March 2021. Patients intubated on day one of their ICU admission were excluded. Main outcome measures Six machine learning models predicted the requirement for invasive ventilation by day three of ICU admission from variables recorded on the first calendar day of ICU admission; (1) random forest classifier (RF), (2) decision tree classifier (DT), (3) logistic regression (LR), (4) K neighbours classifier (KNN), (5) support vector machine (SVM), and (6) gradient boosted machine (GBM). Cross-validation was used to assess the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of machine learning models. Results 300 ICU admissions collected from 53 ICUs across Australia were included. The median [IQR] age of patients was 59 [50–69] years, 109 (36%) were female and 60 (20%) required invasive ventilation on day two or three. Random forest and Gradient boosted machine were the best performing algorithms, achieving mean (SD) AUCs of 0.69 (0.06) and 0.68 (0.07), and mean sensitivities of 77 (19%) and 81 (17%), respectively. Conclusion Machine learning can be used to predict subsequent ventilation in patients with COVID-19 who were spontaneously breathing and admitted to Australian ICUs.

Purpose To assess the feasibility and physiological efficacy of adjunctive midodrine in patients with vasopressor-dependent hypotension. Materials and methods This was a pilot, open label, randomised controlled trial. Patients were enrolled from two tertiary intensive care units on low dose intravenous vasopressor therapy for more than 24 h. We randomly assigned patients to receive either adjunctive midodrine (10 mg every 8 h) or usual care. The primary efficacy outcome was time to cessation of intravenous vasopressor therapy. Secondary outcomes included protocol compliance, ICU and hospital length of stay. Results We screened 381 patients over 22-months and enrolled 62 (32 in midodrine group, 30 in usual care group). Median time to cessation of vasopressor infusion was 16.5 h for midodrine vs 19 h for usual care (p = 0.22). Time in ICU (50 [25.50, 74.00] hours for midodrine v 59 [38.50, 93.25] hours for usual care, p = 0.14) and hospital length of stay (9 days vs. 7.5 days, p = 0.92) were similar. Protocol compliance was 96.9%. One patient ceased midodrine early due to symptomatic bradycardia. Conclusions Adjunctive midodrine therapy was feasible with acceptable compliance, duration of therapy, and safety profile. However, at the chosen dose, there was no evidence of physiological or clinical efficacy.

Background To test the hypothesis that Intensive Care Unit (ICU) doctors and nurses differ in their personal preferences for treatment from the general population, and whether doctors and nurses make different choices when thinking about themselves, as compared to when they are treating a patient. Methods Cross sectional, observational study conducted in 13 ICUs in Australia in 2017 using a discrete choice experiment survey. Respondents completed a series of choice sets, based on hypothetical situations which varied in the severity or likelihood of: death, cognitive impairment, need for prolonged treatment, need for assistance with care or requiring residential care. Results A total of 980 ICU staff (233 doctors and 747 nurses) participated in the study. ICU staff place the highest value on avoiding ending up in a dependent state. The ICU staff were more likely to choose to discontinue therapy when the prognosis was worse, compared with the general population. There was consensus between ICU staff personal views and the treatment pathway likely to be followed in 69% of the choices considered by nurses and 70% of those faced by doctors. In 27% (1614/5945 responses) of the nurses and 23% of the doctors (435/1870 responses), they felt that aggressive treatment would be continued for the hypothetical patient but they would not want that for themselves. Conclusion The likelihood of returning to independence (or not requiring care assistance) was reported as the most important factor for ICU staff (and the general population) in deciding whether to receive ongoing treatments. Goals of care discussions should focus on this, over likelihood of survival.

Purpose To determine the frequency of nosocomial infections including hospital-acquired pneumonia (HAP) and bloodstream infection (BSI), among critically ill patients with COVID-19 infection in Australian ICUs and to evaluate associations with mortality and length of stay (LOS). Methods The effect of nosocomial infections on hospital mortality was evaluated using hierarchical logistic regression models to adjust for illness severity and mechanical ventilation. Results There were 490 patients admitted to 55 ICUs during the study period. Adjusted odds ratio (OR) for hospital mortality was 1.61 (95% confidence interval (CI) 0.61-4.27, p=0.3) when considering BSI, and 1.76 (95% CI 0.73-4.21, p=0.2) for HAP. The average adjusted ICU LOS was significantly longer for patients with BSI (geometric mean 9.0 days vs 6.3 days, p=0.04) and HAP (geometric mean 13.9 days vs 6.0 days p Conclusion Nosocomial infection rates among patients with COVID-19 were low and their development was associated with a significantly longer ICU LOS.

To the Editor: The coronavirus disease 2019 (COVID-19) pandemic has resulted in 38 394 169 cases and 1 089 047 deaths worldwide as of 15 October 2020, although to date, Australia has been relatively spared, with only 11 441 cases and 118deaths. Globally, health care systems and intensive care units (ICUs) have been under immense pressure and wide regional variation in mortality has been observed, both between and within countries. It has been suggested that a higher ICU case volume of COVID-19 may be associated with increased mortality, although this has not yet been systematically investigated. Intuitively, a negative volume–outcome association is plausible under pandemic conditions, as a stretched system running above maximal capacity may not be able to deliver its usual standard of care.