The identification of an optimal body size parameter to adjust skeletal muscle area on chest CT in COVID-19 patients.

Objectives: The most efficient way to adjust skeletal muscle area (SMA) derived from chest CT to body size remains unclear. We hypothesized that vertebral body area (VBA) measurement would allow such efficient adjustment. Methods: We conducted a retrospective observational study of chest CT imaging in a cohort of critically ill COVID-19 patients. We measured paravertebral SMA at T5 level and T5 vertebral body anteroposterior length, width, and area. We used linear regression and multivariable modelling to assess the association of VBA with SMA. Results: In 48 COVID-19 patients in ICU, T5 VBA could be easily derived from simple width and anteroposterior length linear measurements. T5 VBA (measured manually or estimated from width and length) performed similarly to height (R2 of 0.22) as an adjustment variable for SMA, with R2 of 0.23 and 0.22, respectively. Gender had the strongest correlation with SMA (R2 = 0.28). Adding height or age to a model using gender and VBA did not improve correlation. Conclusions: Gender and estimated VBA from simple linear measurements at T5 level on CT images can be utilized for adjustment of SMA without the need for height. Validation of these findings in larger cohorts of critically ill patients is now needed.

Study protocol for TARGET protein: The effect of augmented administration of enteral protein to critically ill adults on clinical outcomes: A cluster randomised, cross-sectional, double cross-over, clinical trial.

Background: It is unknown whether increasing dietary protein to 1.2-2.0 g/kg/day as recommended in international guidelines compared to current practice improves outcomes in intensive care unit (ICU) patients. The TARGET Protein trial will evaluate this. Objective: To describe the study protocol for the TARGET Protein trial. Design setting and participants: TARGET Protein is a cluster randomised, cross-sectional, double cross-over, pragmatic clinical trial undertaken in eight ICUs in Australia and New Zealand. Each ICU will be randomised to use one of two trial enteral formulae for three months before crossing over to the other formula, which is then repeated, with enrolment continuing at each ICU for 12 months. All patients aged ≥16 years in their index ICU admission commencing enteral nutrition will be eligible for inclusion. Eligible patients will receive the trial enteral formula to which their ICU is allocated. The two trial enteral formulae are isocaloric with a difference in protein dose: intervention 100g/1000 ml and comparator 63g/1000 ml. Staggered recruitment commenced in May 2022. Main outcomes measures: The primary outcome is days free of the index hospital and alive at day 90. Secondary outcomes include days free of the index hospital at day 90 in survivors, alive at day 90, duration of invasive ventilation, ICU and hospital length of stay, incidence of tracheostomy insertion, renal replacement therapy, and discharge destination. Conclusion: TARGET Protein aims to determine whether augmented enteral protein delivery reduces days free of the index hospital and alive at day 90. Trial registration: Australian New Zealand Clinical Trials Registry (ACTRN12621001484831).

Early sepsis in Australia and New Zealand: A point-prevalence study of haemodynamic resuscitation practices.

OBJECTIVE: Optimal resuscitation of sepsis-induced hypotension is uncertain, particularly the role of restrictive fluid strategies, leading to variability in usual practice. The objective of this study is to understand resuscitation practices in patients presenting to ED with early sepsis. METHODS: Design, participants and setting: Prospective, observational, multicentre, single-day, point-prevalence study enrolling adult patients present in 51 Australian and New Zealand ICUs at 10.00 hours, 8 June 2021. MAIN OUTCOME MEASURES: Site-level data on sepsis policies and patient-level demographic data, presence of sepsis and fluid and vasopressor administration in the first 24 h post-ED presentation. RESULTS: A total of 722 patients were enrolled. ED was the ICU admission source for 222 of 722 patients (31.2%) and 78 of 222 patients (35%) met the criteria for sepsis within 24 h of ED presentation. Median age of the sepsis cohort was 61 (48-72) years, 58% were male and respiratory infection was the commonest cause (53.8%). The sepsis cohort had a higher severity of illness than the non-sepsis cohort (144/222 patients) and chronic immunocompromise was more common. Of 78 sepsis patients, 55 (71%) received ≥1 fluid boluses with 500 and 1000 mL boluses equally common (both 49%). In the first 24 h, 2335 (1409-3125) mL (25.3 [13.2-42.9] mL/kg) was administered. Vasopressors were administered in 53 of 78 patients (68%) and for 25 patients (47%) administration was peripheral. CONCLUSIONS: ICU patients presenting to the ED with sepsis receive less fluids than current international recommendations and peripheral vasopressor administration is common. This finding supports the conduct of clinical trials evaluating optimal fluid dose and vasopressor timing for early sepsis-induced hypotension.

Blood Pressure Management Goals in Critically Ill Aneurysmal Subarachnoid Hemorrhage Patients in Australia and New Zealand.

INTRODUCTION: Blood pressure (BP) management is common in patients with aneurysmal subarachnoid hemorrhage (SAH) admitted to an intensive care unit. However, the practice patterns of BP management (timing, dose, and duration) have not been studied locally. METHODS: This post hoc analysis explored BP management goals (defined as the setting of a minimum systolic BP target or application of induced hypertension) in patients enrolled into the PROMOTE-SAH study in eleven neurosurgical centers in Australia and New Zealand. The primary outcome was 'dead or disabled' (modified Rankin Score ≥4) at 6 months, with the hypothesis being that setting BP management goals would be associated with improved outcomes. RESULTS: BP management goals were recorded in 266 of 357 (75%) patients, of which 149 were recorded as receiving induced hypertension for delayed cerebral ischemia (DCI) or vasospasm on 738 (19%) study days. In patients with a minimum systolic BP goal recorded (on 2067 d), the indication for the BP management goal was vasospasm or DCI on 651 (32%) days; no indication for BP management goals was documented on 1416 (69%) days. Crude analysis demonstrated an association between setting BP management goals and reduced death or disability (P=0.03), but this association was not significant after adjustment for the presence of DCI or vasospasm and clustered by the site. CONCLUSIONS: BP management goals are commonly 'prescribed' to aSAH patients admitted to an intensive care unit in Australia and New Zealand, but BP management goal setting was not associated with improved outcomes in the adjusted analysis.

Relationship of blood thiamine pyrophosphate to plasma phosphate and the response to enteral nutrition plus co-administration of intravenous thiamine during critical illness.

BACKGROUND: Hypovitamin B1 occurs frequently during critical illness but is challenging to predict or rapidly diagnose. The aim of this study was to evaluate whether plasma phosphate concentrations predict hypovitamin B1, enteral nutrition prevents hypovitamin B1 and intravenous thiamine supplementation achieves supraphysiological concentrations in critically ill patients. METHODS: Thirty-two enterally fed critically ill patients, with a plasma phosphate concentration ≤0.65 mmol/L, formed a nested cohort within a larger randomised clinical trial. Patients were assigned to receive intravenous thiamine (200 mg) twice daily, and controls were not administered intravenous thiamine. Thiamine pyrophosphate concentrations were measured at four time points (pre- and post-infusion and 4- and 6-h post-infusion) on days 1 and 3 in those allocated to thiamine and once in the control group. RESULTS: Baseline thiamine pyrophosphate concentrations were similar (intervention 88 [67, 93] vs. control 89 [62, 110] nmol/L, p = 0.49). Eight (25%) patients had hypovitamin B1 (intervention 3 vs. control 5), with two patients in the control group remaining insufficient at day 3. There was no association between baseline phosphate and thiamine pyrophosphate concentrations. Intravenous thiamine achieved supraphysiological concentrations 6 h post first infusion, with concentrations increasing to day 3. In the control group, thiamine pyrophosphate concentrations were not statistically different between baseline and day 3 (mean change: 8.6 [-6.0, 23.1] nmol/L, p = 0.25). CONCLUSIONS: Phosphate concentrations did not predict hypovitamin B1, which was observed in 25% of the participants. Enteral nutrition alone prevented the development of new hypovitamin B1. Administration of a single 200-mg dose of intravenous thiamine achieved supraphysiological concentrations of thiamine pyrophosphate, with repeated dosing sustaining this effect.

Impact of time of intensive care unit transfer and outcomes in patients with septic shock: An observational study.

OBJECTIVE: To evaluate the association between time from ED presentation to intensive care unit (ICU) transfer on mortality in patients presenting with septic shock. METHODS: Adult patients with suspected septic shock enrolled in the Australasian Resuscitation in Sepsis Evaluation trial were included. The primary outcome of this post-hoc analysis was 90-day mortality. ED-to-ICU time was analysed as both a continuous variable and a binary variable (≤ vs >4 h). Analysis incorporated mixed effects regression, with ICU site as a random effect, time-to-event analysis and competing risks regression; all with and without inverse probability of treatment weighting to account for confounding baseline covariates. RESULTS: Data from 1301 patients were included. Median (interquartile range [IQR]) ED-to-ICU time was 4.3 (3.1, 6.3) hours, with 588 patients (45%) transferred within 4 h. The ≤4-h group were younger, 64 (51, 74) versus 67 (52, 76) years (P = 0.04), with higher APACHE III scores, 50 (37, 65) versus 47 (35, 62) (P = 0.002), and higher unadjusted 90-day mortality, odds ratio (OR) 1.53 (95% confidence interval 1.15, 2.03), P = 0.01. After adjustment for pre-specified confounders, the 90-day mortality OR was 1.09 (0.83, 1.44), P = 0.52. Adjusted for death as a competing event and illness severity, hospital length of stay was similar between groups, whereas ICU duration remained longer for the ≤4-h group. CONCLUSION: In patients presenting to the ED with septic shock, ED-to-ICU time less than 4 h was not associated with altered 90-day mortality, although this should be interpreted with caution due to study limitations.

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.

Cerebrospinal fluid and plasma ascorbate concentrations following subarachnoid haemorrhage.

Background: Ascorbate, the biologically active form of vitamin C, is the primary neural anti-oxidant. Ascorbate concentrations have never been quantified following aneurysmal subarachnoid haemorrhage (aSAH). Objective: To quantify plasma and cerebrospinal fluid (CSF) ascorbate concentrations in patients following SAH. Design Setting Participants Main Outcome Measures: Cohort study in which plasma and CSF ascorbate concentrations were measured longitudinally in 12 aSAH patients admitted to a quaternary referral intensive care unit and compared to one-off samples obtained from 20 pregnant women prior to delivery in a co-located obstetric hospital. Data are median [interquartile range] or median (95 % confidence intervals). Results: Forty-eight plasma samples were obtained from the 12 aSAH patients (eight females, age 62 [53-68] years). Eight participants with extra-ventricular drains provided 31 paired CSF-plasma samples. Single plasma and CSF samples were obtained from 20 pregnant women (age 35 [31-37] years). Initial plasma and CSF ascorbate concentrations post aSAH were less than half those in pregnant controls (plasma: aSAH: 31 [25-39] µmol/L vs. comparator: 64 [59-77] µmol/L; P < 0.001 and CSF: 116 [80-142] µmol/L vs. 252 [240-288] µmol/L; P < 0.001). Post aSAH there was a gradual reduction in the CSF:plasma ascorbate ratio from ∼4:1 to ∼1:1. Six (50 %) patients developed vasospasm and CSF ascorbate concentrations were lower in these patients (vasospasm: 61 (25, 97) vs. no vasospasm: 110 (96, 125) µmol/L; P = 0.01). Conclusion: Post aSAH there is a marked reduction in CSF ascorbate concentration that is most prominent in those who develop vasospasm.

A multicentre observational study of the use of antiseizure medication in patients with aneurysmal subarachnoid haemorrhage in the PROMOTE-SAH study.

Our objective was to describe antiseizure medication (ASM) prescription patterns, and associations between ASM use and death and disability outcomes in patients with aneurysmal subarachnoid haemorrhage (aSAH) admitted to ICU. This was a multi-centre prospective observational study. The study took place in eleven ICUs across Australia and New Zealand. Data was collected from 1 April 2017 to 1 October 2018. Three hundred and fifty-seven adult patients with aSAH were enrolled. The primary outcome was to describe patterns of ASM prescription. The secondary outcome of interest was death or disability (modified Rankin Scale (mRS) score ≥ 4) at six months, and its association with ASM therapy, and relevant clinical subgroups. Forty percent of patients received an ASM and the most commonly used agent was levetiracetam. The median length of ASM administration was eight days (IQR 4.5-12.5). A number of patients with prehospital seizures did not receive ASM therapy (14/55, 2725%). There was a tendency towards ASM prescription with both higher radiological and clinical grade aSAH. There was no significant association between death or disability at six month (mRS ≥ 4) and ASM vs No ASM prescription. Testing for an interaction effect between ASM administration and WFNS grade suggested inferior outcomes with ASM use in lower aSAH grades (p = 0.04). In conclusion, the prescription of ASM for aSAH in Australia is variable across and within sites, with the majority of patients not receiving ASM chemoprophylaxis. We demonstrated no significant association between death or disability at six months and the use of ASM. There may be an association with poorer outcomes in patients with lower grade aSAH. This finding requires further exploration.

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

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

Venous blood for the analysis of acid-base status in a model of septic shock.

OBJECTIVE: To determine the relationship between arterial and venous acid-base status in a model of septic shock. METHODS: Paired samples (n = 435) of arterial and femoral venous blood from 57 sheep (47 septic, 10 non-septic) managed with protocol-guided ventilation, sedation, parenteral fluids and inotropic support. RESULTS: The arterial-venous difference in acid-base parameters was similar with and without sepsis. There was a consistent arterio-venous relationship for metabolic (pH, lactate, bicarbonate, base excess), but not respiratory parameters (partial pressures of oxygen, carbon dioxide, and haemoglobin-oxygen saturation), independent of sepsis. CONCLUSIONS: Venous blood provides a reliable measure of metabolic but not respiratory disturbance.

The use of smartphone-derived location data to evaluate participation following critical illness: A pilot observational cohort study.

BACKGROUND: Disability is common following critical illness, impacting the quality of life of survivors, and is difficult to measure. 'Participation' can be quantified as involvement in life outside of their home requiring movement from their home to other locations. Participation restriction is a key element of disability, and following critical illness, participation may be diminished. It may be possible to quantify this change using pre-existing smartphone data. OBJECTIVES: The feasibility of extracting location data from smartphones of survivors of intensive care unit (ICU) admission and assessing participation, using location-based outcomes, during recovery from critical illness was evaluated. METHODS: Fifty consecutively admitted, consenting adult survivors of non-elective admission to ICU of greater than 48-h duration were recruited to a prospective observational cohort study where they were followed up at 3 and 6 months following discharge. The feasibility of extracting location data from survivors' smartphones and creating location-derived outcomes assessing participation was investigated over three 28-d study periods: pre-ICU admission and at 3 and 6 months following discharge. The following were calculated: time spent at home; the number of destinations visited; linear distance travelled; and two 'activity spaces', a minimum convex polygon and standard deviation ellipse. RESULTS: Results are median [interquartile range] or n (%). The number of successful extractions was 9/50 (18%), 12/39 (31%), and 13/33 (39%); the percentage of time spent at home was 61 [56-68]%, 77 [66-87]%, and 67 [58-77]% (P = 0.16); the number of destinations visited was 34 [18-64], 38 [22-63], and 65 [46-88] (P = 0.02); linear distance travelled was 367 [56-788], 251 [114-323], and 747 [326-933] km over 28 d (P = 0.02), pre-ICU admission and at 3 and 6 months following ICU discharge, respectively. Activity spaces were successfully created. CONCLUSION: Limited smartphone ownership, missing data, and time-consuming data extraction limit current implementation of mass extraction of location data from patients' smartphones to aid prognostication or measure outcomes. The number of journeys taken and the linear distance travelled increased between 3 and 6 months, suggesting participation may improve over time.

Frailty is not independently associated with intensive care unit length of stay: An observational study.

BACKGROUND: Frailty is independently associated with morbidity and mortality in critically ill patients. However, the association between preadmission frailty and the degree of treatment received in the intensive care unit (ICU) remains unclear. OBJECTIVE: To describe patient length of stay in an ICU and the treatments provided according to the extent of patient frailty. METHODS: Single-centre retrospective cohort study of adult patients admitted to a tertiary ICU between January 2018 and December 2019. Frailty was assessed using the Clinical Frailty Scale (CFS). The primary outcome was ICU length of stay stratified by CFS score (1-8). Secondary outcomes were the proportion of patients with each CFS score treated with vasoactive agents, invasive ventilation, noninvasive ventilation, renal replacement therapy, and tracheostomy. Poisson regression and competing risks regression was used to analyse associations between ICU length of stay and potential confounders. RESULTS: The study cohort comprised 2743 patients, with CFS scores known for 2272 (83%). Length of stay in the ICU increased with each increment in the CFS up to a score of 5, beyond which it decreased with higher frailty scores. After adjusting for age, illness severity, admission type, and treatment limitation, CFS scores were not independently associated with length of stay in the ICU (P = 0.31). The proportion of patients receiving specific ICU treatments peaked at different CFS scores, being highest for vasoactive agents at CFS 5 (47%), invasive ventilation CFS 3 (51%), noninvasive ventilation CFS 6 (11%), renal replacement therapy CFS 6 (8.2%), and tracheostomy CFS 5 (2.2%). Increasing frailty was associated with increased mortality and discharge to a destination other than home. CONCLUSIONS: The extent of frailty is not independently associated with length of stay in the ICU. The proportion of patients receiving specific ICU treatments peaked at different CFS scores.

Hyperoncotic Albumin Solution in Continuous Renal Replacement Therapy Patients.

AIM: The aim of this study was to investigate the association of hyperoncotic (20%) human albumin solution (HAS) with outcomes among critically ill patients receiving continuous renal replacement therapy (RRT). METHODS: Analysis of the Randomized Evaluation of Normal versus Augmented Level (RENAL) RRT trial data. RESULTS: Of 1,508 patients, 771 (51%) received albumin. Of these, 345 (45%) received 4% HAS only, 155 (20%) received 20% HAS only, and 271 (35%) received both. Patients who received combined 4% and 20% HAS were more severely ill, received more days of RENAL trial therapy and required mechanical ventilation for longer. Mean daily fluid balance was -288 mL (-904 to 261) with 20% HAS only versus 245 mL (-248 to 1,050) with 4% HAS only (p < 0.001). On Cox proportional hazards regression, 20% HAS exposure was not associated with greater 90-day mortality (odds ratio 1.12, 95% confidence interval [CI]: 0.77-1.62; p = 0.55) or longer recovery to RRT independence (sub-hazard ratio 1.04, 95% CI: 0.84-1.30; p = 0.70) compared to those who received 4% HAS only. CONCLUSIONS: RENAL trial patients commonly received albumin in varying concentrations. The administration of 20% HAS was associated with a more negative fluid balance but was not independently associated with increased mortality or RRT dependence when compared to 4% HAS only.

A multicenter randomized clinical trial of pharmacological vitamin B1 administration to critically ill patients who develop hypophosphatemia during enteral nutrition (The THIAMINE 4 HYPOPHOSPHATEMIA trial).

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).

Dysnatremia and 6-Month Functional Outcomes in Critically Ill Patients With Aneurysmal Subarachnoid Hemorrhage: A Prospective Cohort Study.

OBJECTIVES: To investigate the association between plasma sodium concentrations and 6-month neurologic outcome in critically ill patients with aneurysmal subarachnoid hemorrhage. DESIGN: Prospective cohort study. SETTING: Eleven ICUs in Australia and New Zealand. PARTICIPANTS: Three-hundred fifty-six aneurysmal subarachnoid hemorrhage patients admitted to ICU between March 2016 and June 2018. The exposure variable was daily measured plasma sodium. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Six-month neurologic outcome as measured by the modified Rankin Scale. A poor outcome was defined as a modified Rankin Scale greater than or equal to 4. The mean age was 57 years (± 12.6 yr), 68% were female, and 32% (n = 113) had a poor outcome. In multivariable analysis, including age, illness severity, and process of care measures as covariates, higher mean sodium concentrations (odds ratio, 1.17; 95% CI, 1.05-1.29), and greater overall variability-as measured by the sd (odds ratio, 1.53; 95% CI, 1.17-1.99)-were associated with a greater likelihood of a poor outcome. Multivariable generalized additive modeling demonstrated, specifically, that a high initial sodium concentration, followed by a gradual decline from day 3 onwards, was also associated with a poor outcome. Finally, greater variability in sodium concentrations was associated with a longer ICU and hospital length of stay: mean ICU length of stay ratio (1.13; 95% CI, 1.07-1.20) and mean hospital length of stay ratio (1.08; 95% CI, 1.01-1.15). CONCLUSIONS: In critically ill aneurysmal subarachnoid hemorrhage patients, higher mean sodium concentrations and greater variability were associated with worse neurologic outcomes at 6 months, despite adjustment for known confounders. Interventional studies would be required to demonstrate a causal relationship.

Urinary and renal oxygenation during dexmedetomidine infusion in critically ill adults with mechanistic insights from an ovine model.

PURPOSE: Examine effects of dexmedetomidine on bladder urinary oxygen tension (PuO2) in critically ill patients and delineate mechanisms in an ovine model. MATERIALS AND METHODS: In 12 critically ill patients: oxygen-sensing probe inserted in the bladder catheter and dexmedetomidine infusion at a mean (SD) rate of 0.9 ± 0.3 µg/kg/h for 24-h. In 9 sheep: implantation of flow probes around the renal and pulmonary arteries, and oxygen-sensing probes in the renal cortex, renal medulla and bladder catheter; dexmedetomidine infusion at 0.5 µg/kg/h for 4-h and 1.0 µg/kg/h for 4-h then 16 h observation. RESULTS: In patients, dexmedetomidine decreased bladder PuO2at 2 (-Δ11 (95% CI 7-16)mmHg), 8 (-Δ 7 (0.1-13)mmHg) and 24 h (-Δ 11 (0.4-21)mmHg). In sheep, dexmedetomidine at 1 µg/kg/h reduced renal medullary oxygenation (-Δ 19 (14-24)mmHg) and bladder PuO2 (-Δ 12 (7-17)mmHg). There was moderate correlation between renal medullary oxygenation and bladder PuO2; intraclass correlation co-efficient 0.59 (0.34-0.80). Reductions in renal medullary oxygenation were associated with reductions in blood pressure, cardiac output and renal blood flow (P < 0.01). CONCLUSIONS: Dexmedetomidine decreases PuO2in critically ill patients and in sheep. In sheep this reflects a decrease in renal medullary oxygenation, associated with reductions in cardiac output, blood pressure and renal blood flow.

Long-term outcomes of patients admitted to an intensive care unit with intentional self-harm.

Self-harm is one of the most common reasons for admission to an intensive care unit (ICU). While most patients with self-harm survive the ICU admission, little is known about their outcomes after hospital discharge. We conducted a retrospective cohort study of patients in the Barwon region in Victoria admitted to the ICU with self-harm (between 1998 and 2018) who survived to hospital discharge. The primary objective was to determine mortality after hospital discharge, and secondarily estimate relative survival, years of potential life lost, cause of death and factors associated with death. Over the 20-year study period, there were 710 patients in the cohort. The median patient age was 37 years (interquartile range (IQR) 26-48 years). A total of 406 (57%) were female, and 527 (74%) had a prior psychiatric diagnosis. The incidence of ICU admission increased over time (incidence rate ratio 1.05; 95% confidence interval (CI) 1.03-1.06 per annum). There were 105 (15%) patients who died after hospital discharge. Relative survival decreased each year after discharge, with the greatest decrement during the first 12 months. At ten years, relative survival was 0.85 (95% CI 0.81-0.88). The median years of potential life lost was 35 (IQR 22-45). Cause of death was self-harm in 27%, possible self-harm in 32% and medical disease in 41%. The only factors associated with mortality were male sex, older age and re-admission to ICU with self-harm. Further population studies are required to confirm these findings, and to understand what interventions may improve long-term survival in this relatively young group of critically ill patients.

Use of a High-Protein Enteral Nutrition Formula to Increase Protein Delivery to Critically Ill Patients: A Randomized, Blinded, Parallel-Group, Feasibility Trial.

BACKGROUND: International guidelines recommend critically ill adults receive more protein than most receive. We aimed to establish the feasibility of a trial to evaluate whether feeding protein to international recommendations would improve outcomes, in which 1 group received protein doses representative of international guideline recommendations (high protein) and the other received doses similar to usual practice. METHODS: We conducted a prospective, randomized, blinded, parallel-group, feasibility trial across 6 intensive care units. Critically ill, mechanically ventilated adults expected to receive enteral nutrition (EN) for ≥2 days were randomized to receive EN containing 63 or 100 g/L protein for ≤28 days. Data are mean (SD) or median (interquartile range). RESULTS: The recruitment rate was 0.35 (0.13) patients per day, with 120 patients randomized and data available for 116 (n = 58 per group). Protein delivery was greater in the high-protein group (1.52 [0.52] vs 0.99 [0.27] grams of protein per kilogram of ideal body weight per day; difference, 0.53 [95% CI, 0.38-0.69] g/kg/d protein), with no difference in energy delivery (difference, -26 [95% CI, -190 to 137] kcal/kg/d). There were no between-group differences in the duration of feeding (8.7 [7.3] vs 8.1 [6.3] days), and blinding of the intervention was confirmed. There were no differences in clinical outcomes, including 90-day mortality (14/55 [26%] vs 15/56 [27%]; risk difference, -1.3% [95% CI, -17.7% to 15.0%]). CONCLUSION: Conducting a multicenter blinded trial is feasible to compare protein delivery at international guideline-recommended levels with doses similar to usual care during critical illness.

Time to antimicrobial therapy in septic shock patients treated with an early goal-directed resuscitation protocol: A post-hoc analysis of the ARISE trial.

OBJECTIVE: Intravenous antimicrobial therapy within 1 h of the diagnosis of septic shock is recommended in international sepsis guidelines. We aimed to evaluate the association between antimicrobial timing and mortality in patients presenting to the ED with septic shock. METHODS: Post-hoc analysis of 1587 adult participants enrolled in the Australasian Resuscitation in Sepsis Evaluation (ARISE) multicentre trial of early goal-directed therapy for whom the time of initial antimicrobial therapy was recorded. We compared participants who had initiation of antimicrobials within the first hour (early) or later (delayed) of ED presentation. A propensity score model using inverse probability of treatment weighting was constructed to account for confounding baseline covariates. The primary outcome was 90-day mortality. RESULTS: The median (interquartile range) time to initiating antimicrobials was 69 (39-112) min with 712 (44.9%) participants receiving the first dose within the first hour of ED presentation. Compared with delayed therapy, early administration was associated with increased baseline illness severity score and greater intensity of resuscitation pre-randomisation (fluid volumes, vasopressors, invasive ventilation). All-cause 90-day mortality was also higher; 22.6% versus 15.5%; unadjusted odds ratio (OR) 1.58 (95% confidence interval [CI] 1.16-2.15), P = 0.004. After inverse probability of treatment weighting, the mortality difference was non-significant; OR 1.30 (95% CI 0.95-1.76), P = 0.1. Live discharge rates from ICU (OR 0.81, 95% CI 0.72-0.91; P = 0.80) and hospital (OR 0.93, 95% CI 0.82-1.06; P = 0.29) were also not different between groups. CONCLUSION: In this post-hoc analysis of the ARISE trial, early antimicrobial therapy was associated with increased illness severity, but 90-day adjusted mortality was not reduced.