Nutrition support in children discharged from the pediatric intensive care unit: A bi-national prospective cohort study (ePICUre).

OBJECTIVES: The role of nutrition in the recovery of critically ill children has not been investigated and current nutrition provision in the post-pediatric intensive care unit (PICU) period is unknown. The primary objective of this study was to describe ward nutrition support in children following PICU discharge. METHODS: Children up to 18 years admitted to one of nine PICUs over a 2-week period with a length of stay >48 h were enrolled. Data were collected on the first full ward day following PICU discharge and on Days 7, 14, 21, and 28 following PICU admission. Data points included oral intake, enteral (EN) and parenteral nutrition (PN) support, and oral and EN energy and protein provision. RESULTS: Among the 108 children, on the first full ward day 75/108 (69%) children received EN, 54/108 (50%) oral intake, and 8/108 (7%) PN. Of those receiving oral nutrition only on the first full ward day (25/108; 23%), 9/25 (36%) received <50% of their estimated energy and protein requirements. Of those provided EN only, and where nutrition targets were known, on the first full ward day 8/46 (17%) and 7/46 (15%) met <75% of their estimated energy and protein requirements, respectively. On Day 28, this increased to 4/12 (33%) and 5/12 (42%). CONCLUSIONS: In this study of ward-based nutrition support, key findings included consistent use of EN and PN up to at least 28 days following PICU admission, and a high proportion of children receiving EN or oral intake only not meeting their estimated energy and protein requirements.

Brain tissue oxygen monitoring in moderate-to-severe traumatic brain injury: Physiological determinants, clinical interventions and current randomised controlled trial evidence.

Modern intensive care for moderate-to-severe traumatic brain injury (msTBI) focuses on managing intracranial pressure (ICP) and cerebral perfusion pressure (CPP). This approach lacks robust clinical evidence and often overlooks the impact of hypoxic injuries. Emerging monitoring modalities, particularly those capable of measuring brain tissue oxygen, represent a promising avenue for advanced neuromonitoring. Among these, brain tissue oxygen tension (PbtO2) shows the most promising results. However, there is still a lack of consensus regarding the interpretation of PbtO2 in clinical practice. This review aims to provide an overview of the pathophysiological rationales, monitoring technology, physiological determinants, and recent clinical trial evidence for PbtO2 monitoring in the management of msTBI.

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.

Characteristics of enteral and oral nutrition support among infants and young children in the pediatric intensive care unit: A descriptive cohort study.

BACKGROUND: Children who are critically ill are often reliant on enteral and oral nutrition support. However, there is limited evidence to guide "what" to prescribe, and current practice is unknown. The primary objective of this study was to describe enteral nutrition prescription in children ≤2 years of age in the pediatric intensive care unit (PICU). The secondary objectives were to describe oral nutrition support practices and factors associated with the use of increased energy and protein density nutrition support. METHODS: Children ≤2 years of age admitted to participating PICUs over a 2-week period in June 2021 were enrolled. Data were collected on PICU admission days 1 to 7, 14, 21, and 28 on the mode of nutrition, enteral and oral nutrition support prescription, and dietitian intervention. RESULTS: Eighty-four children were included (49 [58%] male; 79 [94%] ≤1 year of age). Enteral nutrition was administered to 79 (94%) children (with expressed breast milk in 45 [57%]). Forty-three children received formula as enteral nutrition. Increased energy and protein density formulas were provided to 14 (33%) children enterally, with concentrated standard infant formula powder being the most common (5 [12%]). Among children offered oral intake (22; 26%), three (14%) received oral nutrition support. Children who received increased energy and protein density enteral nutrition were more likely to receive dietitian intervention (P = 0.002). CONCLUSION: In children ≤2 years of age admitted to PICU, expressed breast milk was provided to half of those requiring enteral nutrition and oral nutrition support prescription was infrequent. One third of children receiving formula via enteral nutrition received an increased energy and protein density feed, and this was strongly associated with dietitian intervention.

Study protocol for ADAPT-TDM: A beta-lactam antibiotic Dose AdaPtation feasibility randomised controlled Trial using Therapeutic Drug Monitoring.

INTRODUCTION: Critically ill patients are at risk of suboptimal beta-lactam antibiotic (beta-lactam) exposure due to the impact of altered physiology on pharmacokinetics. Suboptimal concentrations can lead to treatment failure or toxicity. Therapeutic drug monitoring (TDM) involves adjusting doses based on measured plasma concentrations and individualising dosing to improve the likelihood of improving exposure. Despite its potential benefits, its adoption has been slow, and data on implementation, dose adaptation and safety are sparse. The aim of this trial is to assess the feasibility and fidelity of implementing beta-lactam TDM-guided dosing in the intensive care unit setting. METHODS AND ANALYSIS: A beta-lactam antibiotic Dose AdaPtation feasibility randomised controlled Trial using Therapeutic Drug Monitoring (ADAPT-TDM) is a single-centre, unblinded, feasibility randomised controlled trial aiming to enroll up to 60 critically ill adult participants (≥18 years). TDM and dose adjustment will be performed daily in the intervention group; the standard of care group will undergo plasma sampling, but no dose adjustment. The main outcomes include: (1) feasibility of recruitment, defined as the number of participants who are recruited from a pool of eligible participants, and (2) fidelity of TDM, defined as the degree to which TDM as a test is delivered as intended, from accurate sample collection, sample processing to result availability. Secondary outcomes include target attainment, uptake of TDM-guided dosing and incidence of neurotoxicity, hepatotoxicity and nephrotoxicity. ETHICS AND DISSEMINATION: This study has been approved by the Alfred Hospital human research ethics committee, Office of Ethics and Research Governance (reference: Project No. 565/22; date of approval: 22/11/2022). Prospective consent will be obtained and the study will be conducted in accordance with the Declaration of Helsinki. The finalised manuscript, including aggregate data, will be submitted for publication in a peer reviewed journal. ADAPT-TDM will determine whether beta-lactam TDM-guided dose adaptation is reproducible and feasible and provide important information required to implement this intervention in a phase III trial. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry, ACTRN12623000032651.

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.

Healthcare and economic cost burden of emergency medical services treated non-traumatic shock using a population-based cohort in Victoria, Australia.

OBJECTIVES: We aimed to assess the healthcare costs and impact on the economy at large arising from emergency medical services (EMS) treated non-traumatic shock. DESIGN: We conducted a population-based cohort study, where EMS-treated patients were individually linked to hospital-wide and state-wide administrative datasets. Direct healthcare costs (Australian dollars, AUD) were estimated for each element of care using a casemix funding method. The impact on productivity was assessed using a Markov state-transition model with a 3-year horizon. SETTING: Patients older than 18 years of age with shock not related to trauma who received care by EMS (1 January 2015-30 June 2019) in Victoria, Australia were included in the analysis. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome assessed was the total healthcare expenditure. Secondary outcomes included healthcare expenditure stratified by shock aetiology, years of life lived (YLL), productivity-adjusted life-years (PALYs) and productivity losses. RESULTS: A total of 21 334 patients (mean age 65.9 (±19.1) years, and 9641 (45.2%) females were treated by EMS with non-traumatic shock with an average healthcare-related cost of $A11 031 per episode of care and total cost of $A280 million. Annual costs remained stable throughout the study period, but average costs per episode of care increased (Ptrend=0.05). Among patients who survived to hospital, the average cost per episode of care was stratified by aetiology with cardiogenic shock costing $A24 382, $A21 254 for septic shock, $A19 915 for hypovolaemic shock and $A28 057 for obstructive shock. Modelling demonstrated that over a 3-year horizon the cohort lost 24 355 YLLs and 5059 PALYs. Lost human capital due to premature mortality led to productivity-related losses of $A374 million. When extrapolated to the entire Australian population, productivity losses approached $A1.5 billion ($A326 million annually). CONCLUSION: The direct healthcare costs and indirect loss of productivity among patients with non-traumatic shock are high. Targeted public health measures that seek to reduce the incidence of shock and improve systems of care are needed to reduce the financial burden of this syndrome.

An International Survey of the Management of Atrial Fibrillation in Critically Unwell Patients.

OBJECTIVES: To evaluate the current management of new-onset atrial fibrillation and compare differences in practice regionally. DESIGN: Cross-sectional survey. SETTING: United States, Canada, United Kingdom, Europe, Australia, and New Zealand. SUBJECTS: Critical care attending physicians/consultants and fellows. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 386 surveys were included in our analysis. Rate control was the preferred treatment approach for hemodynamically stable patients (69.1%), and amiodarone was the most used antiarrhythmic medication (70.9%). For hemodynamically unstable patients, a strategy of electrolyte supplementation and antiarrhythmic therapy was most common (54.7%). Physicians responding to the survey distributed by the Society of Critical Care Medicine were more likely to prescribe beta-blockers as a first-line antiarrhythmic medication (38.4%), use more transthoracic echocardiography than respondents from other regions (82.4%), and more likely to refer patients who survive their ICU stay for cardiology follow-up if they had new-onset atrial fibrillation (57.2%). The majority of survey respondents (83.0%) were interested in participating in future studies of atrial fibrillation in critically ill patients. CONCLUSIONS: Significant variation exists in the management of new-onset atrial fibrillation in critically ill patients, as well as geographic variation. Further research is necessary to inform guidelines in this population and establish if differences in practice impact long-term outcomes.

Nutrition provision in Australian and New Zealand PICUs: A prospective observational cohort study (ePICUre).

OBJECTIVES: The main aim of this study was to describe nutrition provision in Australian and New Zealand (ANZ) pediatric intensive care units (PICUs), including mode of nutrition and adequacy of enteral nutrition (EN) to PICU day 28. Secondary aims were to determine the proportion of children undergoing dietetics assessment, the average time to this intervention, and the methods for estimation of energy and protein requirements. METHODS: This observational study was conducted in all ANZ tertiary-affiliated specialist PICUs. All children ≤18 y of age admitted to the PICU over a 2-wk period and remaining for ≥48 h were included. Data were collected on days 1 to 7, 14, 21, and 28 (unless discharged prior). Data points included oral intake, EN and parenteral nutrition support, estimated energy and protein adequacy, and dietetics assessment details. RESULTS: We enrolled 141 children, of which 79 were boys (56%) and 84 were <2 y of age (60%). Thirty children (73%) received solely EN on day 7 with documented energy and protein targets for 22 (73%). Of these children, 14 (64%) received <75% of their estimated requirements. A dietetics assessment was provided to 80 children (57%), and was significantly higher in those remaining in the PICU beyond the median length of stay (41% in patients staying ≤4.6 d versus 72% in those staying >4.6 d; P < 0.001). CONCLUSIONS: This prospective study of nutrition provision across ANZ PICUs identified important areas for improvement, particularly in EN adequacy and nutrition assessment. Further research to optimize nutrition provision in this setting is urgently needed.

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.

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.

Nutrition care processes from intensive care unit admission to inpatient rehabilitation: A retrospective observational study.

OBJECTIVES: Extended duration of nutrition interventions in critical illness is a plausible mechanism of benefit and of interest to inform future research. The aim of this study was to describe nutrition processes of care from intensive care unit (ICU) admission to discharge from inpatient rehabilitation. METHODS: This was a single-center retrospective study conducted at a health care network in Melbourne, Australia. Adult patients in the ICU >48 h and discharged to inpatient rehabilitation within 28 d were included. Dietitian assessment data and nutrition impacting symptoms were collected until day 28. Data are presented as n (%), mean ± SD or median (interquartile range). RESULTS: Fifty patients were included. Of the 50 patients, 28 were men (56%). Patients were 65 ± 19 y of age with an Acute Physiology And Chronic Health Evaluation II score 15.5 ± 5.2. ICU length of stay (LOS) was 3 d (3-6), acute ward LOS was 10 d (7-14), and rehabilitation LOS was 17 d (8-37). Patients assessed by a dietitian and days to assessment in ICU, acute ward, and rehabilitation were 43 (86%) and 1 (0-1); 42 (84%) and 1 (1-3), and 32 (64%) and 2 (1-4) d, respectively. Oral nutrition was the most common mode: 40 (80%) in the ICU and 48 (96%) on the acute ward and rehabilitation. There was at least one nutrition impacting symptom reported in 44 patients (88%). CONCLUSIONS: Rehabilitation LOS was longer than in the ICU or acute wards, yet patients in rehabilitation were assessed the least by a dietitian and time to assessment was longest. Symptoms that impact nutrition intake were common; nutrition interventions beyond the acute care setting in critical illness need investigation.

COVID-19 related ICU admissions in paediatric and young adult patients in Australia: a national case series 2020-2022.

Background: COVID-19 pandemic research efforts have focused on disease phenotypes in adults. A distinct spectrum of illness has been documented in paediatric populations. We aimed to review paediatric intensive care unit (ICU) admissions in Australia, across differing variant predominant phases of the pandemic. Methods: Data reported to the Short PeRiod IncideNce sTudy of Severe Acute Respiratory Infection (SPRINT-SARI) Australia, across 49 ICUs from February 2020 to June 2022 were extracted. We defined 'child' as patients aged <12 years, 'adolescent' as patients aged 12-17 years, and 'young adult' as patients aged 18-25 years. Findings: We identified 226 paediatric ICU admissions with COVID-19, representing 3.9% of ICU admissions across the study period. Comorbidity was present in 34.6% of children, 51.4% of adolescents, and 48.7% of young adults. The need for respiratory support was highest in young adults. While 28.3% of patients <18 years required invasive ventilation, in-hospital mortality in paediatric patients was 3.6%. During the Omicron period, there was an increase in the annualised incidence of age-specific COVID-19 ICU admissions per 100,000 population, albeit a decrease in the incidence per 1000 SARS-CoV-2 notifications. Interpretation: This study demonstrated an appreciable burden of COVID-19 in paediatric patients. Adolescent patients presented phenotypically similar to young adults, however, illness severity was lower in younger cohorts. The Omicron phase of the pandemic demonstrated an increased age-specific population incidence of COVID-19 ICU admissions, albeit a reduced incidence when based on SARS-CoV-2 notifications. Funding: SPRINT-SARI Australia is supported by the Department of Health, Commonwealth of Australia [Standing Deed SON60002733].

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.

The impact of daptomycin therapeutic drug monitoring on clinical outcomes: a systematic review.

AIM: Daptomycin therapeutic drug monitoring (TDM) is a potentially valuable intervention for a relatively new drug. The aim of this study was to determine whether daptomycin TDM, including dose adjustment where necessary, improves the clinical outcomes of adult patients with Gram-positive infections. METHODS: A systematic review of English-language studies in MEDLINE (Ovid MEDLINE and Epub Ahead of Print, In-process, In-Data-Review & Other Non-Indexed Citations, Daily and Versions), EMBASE via OVID, Cochrane Central Register of Controlled Trials via the OVID platform, Scopus and Web of Science online databases was performed and conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. There was no discrimination on study type or time of publication. STUDY SELECTION: Adults (age ≥18 years) with a Gram-positive infection requiring treatment with daptomycin who received TDM, with subsequent reporting of serum concentrations and dose adjustment where necessary, were included. RESULTS: In total, 2869 studies were identified, of which nine met the inclusion criteria. No studies of daptomycin TDM including a relevant control arm have been published to date. All of the included studies were single-arm observational cohort studies. Broad heterogeneity was observed between the studies in terms of included pathogens, infection types, daptomycin TDM practices, reported clinical outcomes, and reporting of potential confounders. CONCLUSIONS: No studies exploring the efficacy of routine daptomycin TDM on patient-centred outcomes in comparison with fixed dosing regimens have been published to date. This represents a key knowledge gap as opposed to an inherent lack of efficacy. Further well-designed, comparative studies are required to determine the role of daptomycin TDM in patients with Gram-positive infections.

Diabetes mellitus, glycaemic control, and severe COVID-19 in the Australian critical care setting: A nested cohort study.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Diabetes is prevalent in patients admitted to Australian ICUs with severe COVID-19, highlighting the need for prevention strategies in this vulnerable population.

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.

Performance of different body weights in the Cockcroft-Gault equation in critically ill patients with and without augmented renal clearance: A multicenter cohort.

STUDY OBJECTIVE: 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). DESIGN: Multicenter, retrospective cohort. SETTING: Two ICUs in the United States and four ICUs from a previous international observational analysis. PATIENTS: 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. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the performance of the CG equation in ARC (mCrCl≥130 ml/min/1.73 m2 ) and non-ARC (mCrCl<130 ml/min/1.73 m2 ) patients. Correlation was analyzed by Pearson's correlation coefficient, bias by mean difference, and accuracy by the percentage of patients within 30% of the mCrCl. A total of 383 patients were included, which provided 1708 mCrCl values. The majority were male (n = 239, 62%), median age of 55 years [IQR 40-65] with a surgical diagnosis (n = 239, 77%). ARC was identified in 229 (60%) patients. The ARC group had lower Scr values (0.6 [0.5-0.7] vs. 0.7 [0.6-0.9] mg/dl, p < 0.001) and higher mCrCl (172.8 (SD 39.1) vs. 89.9 mL/min/1.73 m2 (SD 25.4), p < 0.001) compared with the non-ARC group, respectively. Among non-ARC patients there was a moderate correlation (r = 0.33-0.39), moderate accuracy (range 48-58%), and low bias (range of -12.9 to 17.1) among the different BW estimations with the adjusted BW having the better performance. Among ARC patients there was low correlation (r = 0.24-0.28), low to moderate accuracy (range 38-70%), and high bias (range of -58.5 to -21.6). CONCLUSIONS: The 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.

Review article: Early steroid administration for traumatic haemorrhagic shock: A systematic review.

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.

The pressure reactivity index as a measure of cerebral autoregulation and its application in traumatic brain injury management.

Severe traumatic brain injury (TBI) is a major cause of morbidity and mortality globally. The Brain Trauma Foundation guidelines advocate for the maintenance of a cerebral perfusion pressure (CPP) between 60 and 70 mmHg following severe TBI. However, such a uniform goal does not account for changes in cerebral autoregulation (CA). CA refers to the complex homeostatic mechanisms by which cerebral blood flow is maintained, despite variations in mean arterial pressure and intracranial pressure. Disruption to CA has become increasingly recognised as a key mediator of secondary brain injury following severe TBI. The pressure reactivity index is calculated as the degree of statistical correlation between the slow wave components of mean arterial pressure and intracranial pressure signals and is a validated dynamic marker of CA status following brain injury. The widespread acceptance of pressure reactivity index has precipitated the consideration of individualised CPP targets or an optimal cerebral perfusion pressure (CPPopt). CPPopt represents an alternative target for cerebral haemodynamic optimisation following severe TBI, and early observational data suggest improved neurological outcomes in patients whose CPP is more proximate to CPPopt. The recent publication of a prospective randomised feasibility study of CPPopt guided therapy in TBI, suggests clinicians caring for such patients should be increasingly familiar with these concepts. In this paper, we present a narrative review of the key landmarks in the development of CPPopt and offer a summary of the evidence for CPPopt-based therapy in comparison to current standards of care.