Search

Increased circulating histones correlate with sepsis severity and are a potential therapeutic target. Pre‐clinical studies showed benefit with a histone‐neutralizing polyanion molecule (STC3141). We aimed to investigate the safety, tolerability, and pharmacokinetics of STC3141 in critically ill patients with sepsis. We studied 26 patients with sepsis divided into four cohorts of one, five, ten, and ten subjects, respectively. We conducted a dose‐adjusted, open‐label study to determine the safety, tolerability, and pharmacokinetics of STC3141 administered as an IV infusion for up to 72 h, with rate adjusted to estimated creatinine clearance. Four steady‐state concentrations were targeted. Twenty of the 26 subjects (77%) in the study experienced at least one adverse event (AE). The most frequently reported study drug‐related AE was a mildly prolonged aPTT (four events). Only one AE (pulmonary hemorrhage) led to discontinuation of the drug. After excluding patients receiving renal replacement therapy (RRT) patients, clearance ranged from 3.3 to 4.2 L/h across cohorts and was essentially completely renal in nature. Half‐life values ranged from 5 to 7 h. The mean (±SD) terminal half‐life for non‐RRT subjects and for whom it was possible to calculate was approximately 9 (±4.77) h but increased to 19 (±7.94) h for subjects on RRT. Overall, 18 (69.2%) patients completed the study to day eight in the ICU, and 22 (84.6%) survived to 28 days. STC3141 administration appeared to have an acceptable degree of safety and tolerability and expected pharmacokinetics. Cautious, larger randomized efficacy trials in sepsis appear justified. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Despite high in‐hospital mortality, the epidemiology of prehospital suspected sepsis presentations is not well described. This retrospective cohort study aimed to quantify the burden of such presentations, and to determine whether such a diagnosis was independently associated with longer‐term mortality. Methods: Retrospective, observational population‐based cohort study examining all adult prehospital presentations in Victoria, between January 2015 and June 2019, who required subsequent in‐hospital assessment. Linked data were extracted from clinical and administrative datasets. Demographics, illness severity, prehospital treatment and mortality were compared between prehospital suspected sepsis and non‐sepsis patients. Multivariable logistic regression was used to determine the adjusted association between prehospital assessment (suspected sepsis vs non‐sepsis) and 6‐month mortality. Results: A total of 1 218 047 patients were included. The age‐adjusted incidence rate of prehospital suspected sepsis was 65 cases per 100 000 person‐years. Those with prehospital suspected sepsis were older (74 vs 62 years), more frequently male (55% vs 47%), with greater physiological derangement. Intravenous cannulas were more often inserted prehospital (60% vs 29%). Crude in‐hospital mortality was 6.5‐fold higher in the prehospital suspected sepsis group (11.8% vs 1.8%), and by 6 months, 22.6% had died. After adjustment for demographics, illness severity, comorbidity, treatment and hospital location, a diagnosis of prehospital suspected sepsis was associated with a 35% higher likelihood of 6‐month mortality (OR 1.35, 95% CI 1.29–1.41). Conclusions: The burden of prehospital suspected sepsis in the Australian setting is significant, with paramedics identifying patients at high‐risk of poor longer‐term outcomes. This implies the need to consider improved care pathways for this highly vulnerable group. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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/m2v 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: The Australasian Resuscitation in Sepsis Evaluation (ARISE) study researched septic shock treatment within EDs. This study aims to evaluate whether: (i) conduct of the ARISE study was associated with changes in epidemiology and care for adults (≥18 years) admitted from EDs to ICUs with sepsis in Australia and New Zealand; and (ii) such changes differed among 45 ARISE trial hospitals compared with 120 non‐trial hospitals. Methods: Retrospective study using interrupted time series analysis in three time periods; 'Pre‐ARISE' (January 1997 to December 2007), 'During ARISE' (January 2008 to May 2014) and 'Post‐ARISE' (June 2014 to December 2017) using data from the Australian and New Zealand Intensive Care Society Adult Patient Database. Results: Over 21 years there were 54 121 ICU admissions from the ED with sepsis; which increased from 8.1% to 16.4%; 54.6% male, median (interquartile range) age 66 (53–76) years. In the pre‐ARISE period, pre‐ICU ED length of stay (LOS) decreased in trial hospitals but increased in non‐trial hospitals (P = 0.174). During the ARISE study, pre‐ICU ED LOS declined more in trial hospitals (P = 0.039) as did the frequency of mechanical ventilation in the first 24 h (P = 0.003). However, ICU and hospital LOS, in‐hospital mortality and risk of death declined similarly in both trial and non‐trial hospitals. Conclusions: Sepsis‐related admissions increased from 8.1% to 16.4%. During the ARISE study, there was more rapid ICU admission and decreased early ventilation. However, these changes were not sustained nor associated with decreased risk of death or duration of hospitalisation. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background: Increased intestinal permeability (IP) is associated with sepsis in the intensive care unit (ICU). This study aimed to pilot a sensitive multisugar test to measure IP in the nonfasted state. Methods: Critically ill, mechanically ventilated adults were recruited from 2 ICUs in Australia. Measurements were completed within 3 days of admission using a multisugar test measuring gastroduodenal (sucrose recovery), small‐bowel (lactulose‐rhamnose [L‐R] and lactulose‐mannitol [L‐M] ratios), and whole‐gut permeability (sucralose‐erythritol ratio) in 24‐hour urine samples. Urinary sugar concentrations were compared at baseline and after sugar ingestion, and IP sugar recoveries and ratios were explored in relation to known confounders, including renal function. Results: Twenty‐one critically ill patients (12 males; median, 57 years) participated. Group median concentrations of all sugars were higher following sugar administration; however, sucrose and mannitol increases were not statistically significant. Within individual patients, sucrose and mannitol concentrations were higher in baseline than after sugar ingestion in 9 (43%) and 4 (19%) patients, respectively. Patients with impaired (n = 9) vs normal (n = 12) renal function had a higher L‐R ratio (median, 0.130 vs 0.047; P =.003), lower rhamnose recovery (median, 15% vs 24%; P =.007), and no difference in lactulose recovery. Conclusion: Small‐bowel and whole‐gut permeability measurements are possible to complete in the nonfasted state, whereas gastroduodenal permeability could not be measured reliably. For small‐bowel IP measurements, the L‐R ratio is preferred over the L‐M ratio. Alterations in renal function may reduce the reliability of the multisugar IP test, warranting further exploration. [ABSTRACT FROM AUTHOR]

The wide‐spread use of an initial 'Glasgow Coma Scale (GCS) 8 or less' to define and dichotomise 'severe' from 'mild' or 'moderate' traumatic brain injury (TBI) is an out‐dated research heuristic that has become an epidemiological convenience transfixing clinical care. Triaging based on GCS can delay the care of patients who have rapidly evolving injuries. Sole reliance on the initial GCS can therefore provide a false sense of security to caregivers and fail to provide timely care for patients presenting with GCS greater than 8. Nearly 50 years after the development of the GCS – and the resultant misplaced clinical and statistical definitions – TBI remains a heterogeneous entity, in which 'best practice' and 'prognoses' are poorly stratified by GCS alone. There is an urgent need for a paradigm shift towards more effective initial assessment of TBI. [ABSTRACT FROM AUTHOR]

Aim: To determine if empirical anti‐pseudomonal beta‐lactam antibiotic (BLA) dosing achieves adequate drug exposure in septic patients. Method: A single‐centre, prospective pharmacokinetic study was conducted in Intensive Care Unit (ICU) patients with sepsis, receiving empirical therapy with piperacillin/tazobactam or meropenem. The pharmacokinetic/pharmacodynamic (PK/PD) targets were free BLA concentrations above the MIC at the mid‐point (Concentration A, 50%f T > MIC) and end of the dosing interval (Concentration B, 100% fT > MIC). Sub‐therapeutic concentrations were defined as concentration A < MIC, and sub‐optimal as concentration B < MIC. The MIC breakpoint for Pseudomonas aeruginosa, as defined by The European Committee on Antimicrobial Susceptibility Testing (EUCAST) (available from ) was used. Results: Of the 37 eligible patients, 20 were receiving piperacillin/tazobactam (TZP), and 17 meropenem (MEM). PK data were available for 36 patients (concentration A) and 34 patients (concentration B). The median measured plasma concentrations (mg/L) were: piperacillin for doses 4 g 8‐hourly and 4 g 6‐hourly – concentration A 53.9 [14.38–123.71] and 36.44 [13.38–107.45], concentration B 8.01 [2.57–71.08] and 27.31 [3.32–59.76], MEM for doses 1 g 8‐hourly and 2 g 8‐hourly – concentration A 12.49 [7.35–23.63] and 30.5, concentration B 7.47 [2.97–11.33] and 9.31. 27.8% (10 of 36) of patients had sub‐therapeutic concentrations (concentration A) and 50% (17 of 34) had sub‐optimal concentrations (concentration B). Conclusion: Our study confirms that sub‐therapeutic unbound plasma anti‐pseudomonal BLA concentrations are common in critically ill septic patients and underscores the urgent need for future trials exploring the efficacy of BLA therapeutic drug monitoring in these patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 <100 mmHg) despite at least 1000 mL fluid resuscitation, were eligible. Data included baseline demographics, clinical and laboratory variables and intravenous fluid volume administered, vasopressor administration at baseline and 6‐ and 24‐h post‐enrolment, time to antimicrobial administration, intensive care admission, organ support and in‐hospital mortality. Results: A total of 4477 patients were screened and 591 were included with a mean (standard deviation) age of 62 (19) years, Acute Physiology and Chronic Health Evaluation II score 15.2 (6.6) and a median (interquartile range) systolic blood pressure of 94 mmHg (87–100). Median time to first intravenous antimicrobials was 77 min (42–148). A vasopressor infusion was commenced within 24 h in 177 (30.2%) patients, with noradrenaline the most frequently used (n = 138, 78%). A median of 2000 mL (1500–3000) of intravenous fluids was administered prior to commencing vasopressors. The total volume of fluid administered from pre‐enrolment to 24 h was 4200 mL (3000–5661), with a range from 1000 to 12 200 mL. Two hundred and eighteen patients (37.1%) were admitted to an intensive care unit. Overall in‐hospital mortality was 6.2% (95% confidence interval 4.4–8.5%). Conclusion: Current resuscitation practice in patients with sepsis and hypotension varies widely and occupies the spectrum between a restricted volume/earlier vasopressor and liberal fluid/later vasopressor strategy. [ABSTRACT FROM AUTHOR]

Parenteral nutrition (PN) is the administration of a nutritional formula by means other than the gastrointestinal (GI) tract. The formula may include carbohydrates, amino acids, lipids, electrolytes and/or micronutrients. The primary indications for PN are intestinal failure (IF) due to an underlying disease or treatment, or if the GI tract is not accessible. The goals of PN should be to ensure adequate nutrition provision to meet patient needs while minimising the risk of complications. PN should be commenced in <48 h in patients who are malnourished or otherwise within 7 days if oral or enteral nutrition is not possible or insufficient. There has been evolution in PN techniques and technology, and the risks associated with PN administration have been reduced. Monitoring clinical, laboratory and metabolic parameters in acute IF is essential to provision of safe nutritional support. When provided to appropriate patients with IF in a timely and considered manner, PN has been shown to be safe, improve nutritional parameters and reduce complications associated with malnutrition. This review aims to provide clinicians a practical guide for the management of PN in adult patients within the acute setting. [ABSTRACT FROM AUTHOR]

Objective: Vasopressor medications have traditionally been administered via central venous catheters (CVCs), primarily due to concerns of peripheral extravasation of vasoconstrictive medications. Recent studies have suggested that vasopressor administration via peripheral intravenous catheters (PiVCs) may be a feasible and safe alternative. This systematic review evaluates the safety of delivering vasopressor medications via PiVCs. Methods: We performed a systematic review to assess the frequency of complications associated with the delivery of vasopressors via PiVCs. A literature search for prospective and retrospective studies of vasopressor infusions in adults was performed. We included studies of continuous infusions of vasopressor medications (noradrenaline, adrenaline, metaraminol, phenylephrine, dopamine and vasopressin) delivered via a PiVCs that included at least 20 patients. Data on patient factors, cannulation approach, monitoring protocols, vasopressor dosing and dilutions and adverse events were collected and summarised. Results: Seven studies were identified that fulfilled the inclusion criteria, including 1382 patients. No study fulfilled all of the validity criteria. Noradrenaline was the most commonly administered agent (n = 702 episodes of administration), followed by phenylephrine (n = 546), dopamine (n = 108), metaraminol (n = 74) and vasopressin and adrenaline (<5 patients). Mean duration of infusion was 22 h (95% confidence interval [CI] 8–36 h). Extravasation occurred in 3.4% (95% CI 2.5–4.7%) of patients. There were no reported episodes of tissue necrosis or limb ischaemia. All extravasation events were successfully managed conservatively or with vasodilatory medications. Conclusions: Reports of the administration of vasopressors via PiVCs, when given for a limited duration, under close observation, suggest that extravasation is uncommon and is unlikely to lead to major complications. [ABSTRACT FROM AUTHOR]

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 < 0.001). After adjusting for baseline covariates, the estimated odds ratio for mortality for PVC‐treated patients was 1.26 (95% confidence interval 0.95–1.67, P = 0.11). Trial participants who had vasopressors commenced via PVC had a shorter median (IQR) time to commencement of antimicrobials (55 [32–96] versus 71.5 [39–119] min, P < 0.001) and a shorter median (IQR) time to commencement of vasopressors (2.4 [1.3–3.9] versus 4.9 [3.5–6.6] h, P < 0.001). Conclusion: The practice of commencing a vasopressor infusion via a PVC was common in the ARISE trial and more frequent in trial participants with higher severity of illness. Commencement of a vasopressor infusion via a PVC was associated with some improvements in processes of care and, after adjustment, was not associated with an increased risk of death. [ABSTRACT FROM AUTHOR]

Objective: To quantify the potential time saved with pre‐hospital antibiotic therapy in sepsis. Methods: Study data for adult patients transported by Ambulance Victoria (AV), and enrolled into the Australasian Resuscitation In Sepsis Evaluation (ARISE), were linked with pre‐hospital electronic records. Results: An AV record was identified for 240 of 341 ARISE patients. The pre‐hospital case notes referred to potential infection in 165 patients. The median time to first antibiotic administration from loading the patient into the ambulance was 107 (74–160) min. Conclusions: ARISE patients in Victoria were frequently identified pre‐hospital. An opportunity exists to study the feasibility of pre‐hospital antibiotic therapy. [ABSTRACT FROM AUTHOR]

Objective: There is uncertainty about the optimal i.v. fluid volume and timing of vasopressor commencement in the resuscitation of patients with sepsis and hypotension. We aim to study current resuscitation practices in EDs in Australia and New Zealand (the Australasian Resuscitation In Sepsis Evaluation: FLUid or vasopressors In Emergency Department Sepsis [ARISE FLUIDS] observational study). Methods: ARISE FLUIDS is a prospective, multicentre observational study in 71 hospitals in Australia and New Zealand. It will include adult patients presenting to the ED during a 30 day period with suspected sepsis and hypotension (systolic blood pressure <100 mmHg) despite at least 1000 mL fluid resuscitation. We will obtain data on baseline demographics, clinical and laboratory variables, all i.v. fluid given in the first 24 h, vasopressor use, time to antimicrobial administration, admission to intensive care, organ failure and in‐hospital mortality. We will specifically describe (i) the volume of fluid administered at the following time points: when meeting eligibility criteria, in the first 6 h, at 24 h and prior to vasopressor commencement and (ii) the frequency and timing of vasopressor use in the first 6 h and at 24 h. Screening logs will provide reliable estimates of the proportion of ED patients meeting eligibility criteria for a subsequent randomised controlled trial. Discussion: This multicentre, observational study will provide insight into current haemodynamic resuscitation practices in patients with sepsis and hypotension as well as estimates of practice variation and patient outcomes. The results will inform the design and feasibility of a multicentre phase III trial of early haemodynamic resuscitation in patients presenting to ED with sepsis and hypotension. [ABSTRACT FROM AUTHOR]

Background: Propofol sedation is common in critically ill patients, providing energy of 1.1 kcal/mL when administered as a 1% solution. We aimed to determine the proportion of energy administered as propofol on days 1-5 in the intensive care unit (ICU) and any association with outcomes.Methods: Retrospective observational study in a quaternary ICU from January-December 2012. Inclusion criteria were length of stay (LOS) ≥5 days, age ≥18 years, and provision of mechanical ventilation (MV) for ≥5 days. Outcome measures included proportion of total daily energy provided as propofol, overall energy balance, hospital mortality, duration of MV, and ICU LOS.Results: Data from 370 patients were analyzed, 87.8% (n = 325) of whom received propofol during days 1-5 in ICU. A median [interquartile range (IQR)] of 119 [50-730] kcal was provided as propofol per patient-day. Proportion of energy provided by propofol as a percentage of total energy delivered was 55.4%, 15.4%, 9.3%, 7.9%, and 9.9% days 1-5, respectively. Patients administered propofol received a greater proportion of their total daily energy prescription compared with those who were not (P < .01). Proportion of energy provided as propofol was not significantly different based on hospital mortality (P = .62), duration of MV (P = .50), or ICU LOS (P = .15).Conclusion: Propofol contributes to overall energy intake on days 1-5 of ICU admission. Energy balance was higher in those receiving propofol. No association was found between the proportion of energy delivered as propofol and outcomes. [ABSTRACT FROM AUTHOR]

Background: Nutrition delivered to patients with a traumatic brain injury (TBI) is typically below prescribed amounts. While the dietitian plays an important role in the assessment and provision of nutrition needs, they are part of a multidisciplinary team. The views and attitudes of medical and nursing practitioners are likely to be crucial to implementation of nutrition to patients with TBI, but there is limited information describing these.Methods: A qualitative exploratory approach was used to explore the views and attitudes of medical and nursing practitioners on nutrition for patients with TBI. Participants at 2 major neurotrauma hospitals in Australia completed individual semi-structured interviews with a set of questions and a case study. Interviews were transcribed and coded for themes.Results: Thirty-four health practitioners participated: 18 nurses and 16 physicians. Three major themes emerged: (1) nutrition practices over the hospital admission reflect the recovery course, (2) there are competing priorities when caring for patients with TBI, and (3) the implementation of nutrition therapy is influenced by practitioner roles and expectations.Conclusion: Use of qualitative inquiry in the study of attitudes toward nutrition provision to patients with TBI provided detailed insights into the challenges of operationalizing nutrition therapy. These insights can be used to clarify communication between health practitioners working with patients with TBI across the continuum of care. [ABSTRACT FROM AUTHOR]

Abstract: Significant tension surrounds the application of antibiotics in suspected infection. Guidelines stress the importance of early empirical broad‐spectrum therapy, with select observational data suggesting inferior outcomes when this is delayed. In contrast, microbiological resistance is an ever increasing global problem, with many advocating for a more restricted, culture‐driven approach to antibiotic prescription. Controlled trial data are urgently needed, although many clinicians would find withholding of antibiotic therapy unethical. A trial of prehospital antibiotic administration (by paramedics) in patients with suspected sepsis would therefore provide crucial data, and go a long way to determining whether earlier empirical therapy does actually improve outcomes. [ABSTRACT FROM AUTHOR]

Objectives To describe renal replacement therapy ( RRT) prescribing practices in Malaysian intensive care units ( ICU), and compare this with previously published data from other regions. Method A survey was sent to physicians responsible for prescribing RRT in major ICU throughout Malaysia. The questionnaire sought information on the physicians' background, and detailed information regarding RRT settings. Results Nineteen physicians from 24 sites throughout Malaysia responded to the survey (response rate 79.2%). Sixteen respondents were intensivists (84%), 2 were anaesthetists (11%) and one was a nephrologist (5%). The majority (58%) used continuous venovenous haemofiltration ( CVVH) as the treatment of choice for acute kidney injury ( AKI) in critically ill patients. RRT prescription was predominantly practitioner-dependent (63%), while 37% reported use of a dedicated protocol. The mean blood flow rate and effluent flow rate used for continuous RRT ( CRRT) were 188.9 ± 28.9 mL/min and 30.6 ± 4.7 mL/kg/h respectively. Replacement fluid solutions containing both lactate and bicarbonate were commonly used during CRRT, applied both pre- and post-dilution. Conclusion CRRT was the first-choice modality used to treat AKI in critically ill patients. CVVH was the most common CRRT technique used, while other RRT modalities were used less frequently. Overall, RRT practices were similar to those observed in other regions, although the modality and settings used were slightly different, likely due to local availability. [ABSTRACT FROM AUTHOR]

This article reports the case of a 10-year-old child with an exacerbation of asthma requiring mechanical ventilation. His immediate course was complicated by significantly elevated arterial CO2 tensions and a unilateral dilated pupil. A computed tomography scan of his brain failed to demonstrate any evidence of intracranial hypertension or cerebral edema, and he went on to make an uncomplicated recovery, with no evidence of neurological sequelae. The most likely diagnosis appeared to be local contamination with ipratropium when he was receiving frequent nebulizers prior to mechanical ventilation. Similar cases reported in the literature are reviewed, with a discussion of clinical management, implications of permissive hypercapnia and neurological complications in ventilating asthmatic patients and the importance of safe drug handling by staff members. [ABSTRACT FROM AUTHOR]

We agree that a central driver of the outcomes reported was the adequate, and at times increased, levels of staffing of intensive care units (ICUs) by experienced and highly trained critical care nurses.2 The relatively low peak occupancy of ICU beds by patients with COVID-19 (14%; interquartile range, 9-16%)2 meant that ICUs across Australia maintained normal 1:1 nurse to patient ratios for all high acuity patients (usually invasively ventilated, but not exclusively), and 1:2 for those needing less intensive care.3 Furthermore, in 7.5% of ICU days (171/2270), it was possible to increase the nursing to patient ratio even further to 2:1. Keywords: Intensive care; COVID-19; Nursing care EN Intensive care COVID-19 Nursing care 485 485 1 11/17/21 20211115 NES 211115 Acknowledgements The Short PeRiod IncideNce sTudy of Severe Acute Respiratory Infection (SPRINT-SARI) Australia receives Australian Government Department of Health funding. [Extracted from the article]

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 PaO 2 :FiO 2 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 PaO 2 :FiO 2 ratio effect and time to peak PaO 2 :FIO 2 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 PaO 2 :FIO 2 ratio was 137 (±49) for all prone episodes. During the first episode. the mean PaO 2 :FIO 2 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 PaO 2 :FIO 2 ratio effect occurred during the first prone positioning episode and after 9 h. Subsequent episodes also improved oxygenation but with diminished effect on PaO 2 :FIO 2 ratio. This information can help guide the number and duration of prone positioning episodes., (© 2023 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)