The use of triiodothyronine during critical illness.

PURPOSE OF REVIEW: Thyroid hormone physiology changes during critical illness. Circulating concentration of triiodothyronine (T3), the active form of thyroid hormone decreases. It has long been uncertain whether this represents a pathologic change or if it is an adaptive phenomenon. Controlled clinical trials have been required to understand whether replacing and restoring serum T3 levels is therapeutic. RECENT FINDINGS: Clinical trials of T3 have recently been proposed with some completed. These have been conducted in patients with sepsis, myocardial infarction, infants undergoing cardiac surgery, and acute respiratory distress syndrome. Of the completed trials, T3 administration restored serum concentrations, but was not accompanied by significant clinical benefit. Importantly, restoring serum T3 levels did not cause any adverse effects. SUMMARY: If T3 is to be considered a therapeutic target in critical illness, further studies should consider the stage of disease it is administered, and whether there are other surrogate measures to assess adequacy of hormone replacement over and above serum T3 concentrations.

Trends in Childhood Oncology Admissions to ICUs in Australia and New Zealand.

OBJECTIVES: There are few robust, national-level reports of contemporary trends in pediatric oncology admissions, resource use, and mortality. We aimed to describe national-level data on trends in intensive care admissions, interventions, and survival for children with cancer. DESIGN: Cohort study using a binational pediatric intensive care registry. SETTING: Australia and New Zealand. PATIENTS: Patients younger than 16 years, admitted to an ICU in Australia or New Zealand with an oncology diagnosis between January 1, 2003, and December 31, 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We examined trends in oncology admissions, ICU interventions, and both crude and risk-adjusted patient-level mortality. Eight thousand four hundred ninety admissions were identified for 5,747 patients, accounting for 5.8% of PICU admissions. Absolute and population-indexed oncology admissions increased from 2003 to 2018, and median length of stay increased from 23.2 hours (interquartile range [IQR], 16.8-62 hr) to 38.8 hours (IQR, 20.9-81.1 hr) ( p < 0.001). Three hundred fifty-seven of 5,747 patients died (6.2%). There was a 45% reduction in risk-adjusted ICU mortality, which reduced from 3.3% (95% CI, 2.1-4.4) in 2003-2004 to 1.8% (95% CI, 1.1-2.5%) in 2017-2018 ( p trend = 0.02). The greatest reduction in mortality seen in hematological cancers and in nonelective admissions. Mechanical ventilation rates were unchanged from 2003 to 2018, while the use of high-flow nasal prong oxygen increased (incidence rate ratio, 2.43; 95% CI, 1.61-3.67 per 2 yr). CONCLUSIONS: In Australian and New Zealand PICUs, pediatric oncology admissions are increasing steadily and such admissions are staying longer, representing a considerable proportion of ICU activity. The mortality of children with cancer who are admitted to ICU is low and falling.

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).

Low prevalence of communication between intensive care unit medical staff and general practitioners: A single-centre retrospective study.

BACKGROUND: General practitioners (GPs) have a central role in delivering care to the Australian community, which includes coordinating management of chronic diseases and treatment of patients after admission to intensive care units (ICUs). Consultations between ICUs and GPs may become increasingly relevant as patients of advancing age and chronic disease burden are admitted to ICUs. However, how frequently and for what reason such consultations occur remain unclear. OBJECTIVES: The objective of this study was to determine the prevalence and themes of consultations between ICU medical staff and GPs. METHODS: Ten years of electronic medical records in the ICU of a regional Australian hospital were searched for patient admissions documenting the terms "gp", "general p∗", or "primary care∗" anywhere throughout the record. The proportion of ICU admissions in which a consultation between ICU staff members and GPs was documented was recorded along with the reason/s for the consultation and designation (resident, registrar, consultant) of those who communicated with the GP. MAIN OUTCOME MEASURES: Main outcome measures included the proportion of ICU admissions with a documented consultation between ICU staff and GPs, theme of the consultation, and designation (resident, registrar, consultant) of those who communicated with the GP. RESULTS: Of 13 402 admissions to the ICU, 137 (1.02%) had a documented consultation between ICU medical staff and GPs. Most consultations (n = 116, 85%) were initiated by junior ICU medical staff members seeking clinical information from the GPs. Few consultations were to discuss goals of care (n = 10, 7.3%) or care following ICU discharge (n = 15, 11%). CONCLUSIONS: Consultations between ICU medical staff and GPs were infrequent. Further research is required on how best to integrate the health care provided by ICUs and GPs.

Documentation of neurological status in patients admitted to an intensive care unit after cardiac arrest: A 10-year cohort study.

OBJECTIVE: The objective of this study was to describe the documented neurological assessment and investigations for neuroprognostication in patients after cardiac arrest. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study of adult patients after cardiac arrest, admitted to a tertiary intensive care unit (ICU), between January 2009 and December 2018. MAIN OUTCOME MEASURES: The main outcome measures were the proportion of patients with a documented Glasgow Coma Scale (GCS) score and investigations for neuroprognostication. RESULTS: Four hundred twenty-seven patients formed the study cohort. The GCS score was documented for 267 (63%) patients at some time during their ICU stay. The proportion of patients with the GCS score documented decreased each day of ICU stay (59% at day 1, 20% at day 5). Pupil reflex to light was recorded in 352 (82%), corneal reflex in 155 (36%), and limb reflexes in 216 (51%) patients. Twenty-eight (6.6%) patients underwent brain magnetic resonance imaging, 10 (2.3%) an electroencephalogram, and two somatosensory evoked potentials. Withdrawal of life-sustaining treatments occurred in 166 (39%) patients, and 221 (52%) patients died in hospital. CONCLUSIONS: In this single-centre study of patients admitted to the ICU after cardiac arrest, the GCS score was inconsistently documented, and investigations for neuroprognostication were infrequent.

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.

Mixed-mode versus paper surveys for patient-reported outcomes after critical illness: A randomised controlled trial.

OBJECTIVE: The aim of the study was to determine the response rate to a mixed-mode survey using email compared with that to a paper survey in survivors of critical illness. DESIGN: This is a prospective randomised controlled trial. SETTING: The study was conducted at a single-centre quaternary intensive care unit (ICU) in Adelaide, Australia. PARTICIPANTS: Study participants were patients admitted to the ICU for ≥48 h and discharged from the hospital. INTERVENTIONS: The participants were randomised to receive a survey by paper (via mail) or via online (via email, or if a non-email user, via a letter with a website address). Patients who did not respond to the initial survey received a reminder paper survey after 14 days. The survey included quality of life (EuroQol-5D-5L), anxiety and depression (Hospital Anxiety and Depression Scale), and post-traumatic symptom (Impact of Event Scale-Revised) assessment. MAIN OUTCOME MEASURES: Survey response rate, extent of survey completion, clinical outcomes at different time points after discharge, and survey cost analysis were the main outcome measures. Outcomes were stratified based on follow-up time after ICU discharge (3, 6, and 12 months). RESULTS: A total of 239 patients were randomised. The response rate was similar between the groups (mixed-mode: 78% [92/118 patients] vs. paper: 80% [97/121 patients], p = 0.751) and did not differ between time points of follow-up. Incomplete surveys were more prevalent in the paper group (10% vs 18%). The median EuroQol-5D-5L index value was 0.83 [0.71-0.92]. Depressive symptoms were reported by 25% of patients (46/187), anxiety symptoms were reported by 27% (50/187), and probable post-traumatic stress disorder was reported by 14% (25/184). Patient outcomes did not differ between the groups or time points of follow-up. The cost per reply was AU$ 16.60 (mixed-mode) vs AU$ 19.78 (paper). CONCLUSION: The response rate of a mixed-mode survey is similar to that of a paper survey and may provide modest cost savings.

Long-Term Outcomes after Severe Traumatic Brain Injury in Older Adults. A Registry-based Cohort Study.

Rationale: Older adults (≥65 yr old) account for an increasing proportion of patients with severe traumatic brain injury (TBI), yet clinical trials and outcome studies contain relatively few of these patients.Objectives: To determine functional status 6 months after severe TBI in older adults, changes in this status over 2 years, and outcome covariates.Methods: This was a registry-based cohort study of older adults who were admitted to hospitals in Victoria, Australia, between 2007 and 2016 with severe TBI. Functional status was assessed with Glasgow Outcome Scale Extended (GOSE) 6, 12, and 24 months after injury. Cohort subgroups were defined by admission to an ICU. Features associated with functional outcome were assessed from the ICU subgroup.Measurements and Main Results: The study included 540 older adults who had been hospitalized with severe TBI over the 10-year period; 428 (79%) patients died in hospital, and 456 (84%) died 6 months after injury. There were 277 patients who had not been admitted to an ICU; at 6 months, 268 (97%) had died, 8 (3%) were dependent (GOSE 2-4), and 1 (0.4%) was functionally independent (GOSE 5-8). There were 263 patients who had been admitted to an ICU; at 6 months, 188 (73%) had died, 39 (15%) were dependent, and 32 (12%) were functionally independent. These proportions did not change over longer follow-up. The only clinical features associated with a lower rate of functional independence were Injury Severity Score ≥25 (adjusted odds ratio, 0.24 [95% confidence interval, 0.09-0.67]; P = 0.007) and older age groups (P = 0.017).Conclusions: Severe TBI in older adults is a condition with very high mortality, and few recover to functional independence.

Severe acute maternal morbidity trends in Victoria, 2001-2017.

BACKGROUND: The incidence of severe acute maternal morbidity (SAMM) is one method of measuring the complexity of maternal health and monitoring maternal outcomes. Monitoring trends may provide a quantitative method for assessing health care at local, regional, or jurisdictional levels and identify issues for further investigation. AIMS: Identify temporal trends for SAMM event rates and maternal outcomes over 17 years in the state of Victoria, Australia. MATERIALS AND METHODS: All maternal public health service admissions were extracted from an administrative dataset from July 2000 to June 2017. SAMM-related diagnoses were defined by matching as closely as possible with published definitions. Outcomes included annual SAMM event rates, hospital survival, and hospital length of stay (LOS). Temporal trends were analysed using mixed-effects generalised linear models. RESULTS: There were 854 777 live births and 1.21 million pregnancy-related hospital admissions which included 34 008 SAMM events in 29 273 records and in 3.42% (95%CI = 3.39-3.46) of births. Most common were severe pre-eclampsia (0.87% of births), severe postpartum haemorrhage (0.59%), and sepsis (0.62%). SAMM-related admissions were associated with longer LOS and higher mortality risk (P < 0.001). Maternal mortality ratio remained unchanged at 8.6 fatalities per 100 000 births (P = 0.65). CONCLUSION: Over 17 years, there was a significant increase in birth rate and SAMM-related events in Victoria. Administrative data may provide a pragmatic approach for monitoring SAMM-related events in maternal health services.

Opinions and practices of blood glucose control in critically ill patients with pre-existing type 2 diabetes in Australian and New Zealand intensive care units.

BACKGROUND: Approximately 9000 patients with type-2 diabetes mellitus (T2DM) are admitted to an intensive care unit (ICU) in Australia and New Zealand annually. For these patients, recent exploratory data suggest that targeting a more liberal blood glucose range during ICU admission may be safe and potentially beneficial. However, the current approach to blood glucose management of patients with T2DM in Australia and New Zealand ICUs is not well described, and there is uncertainty about clinician equipoise for trials of liberal glycaemic control in these patients. AIM: The aim is to describe self-reported blood glucose management in patients with T2DM by intensivists working in Australian and New Zealand ICUs and to establish whether equipoise exists for a trial of liberal versus standard glycaemic control in such patients. METHOD: An online questionnaire of Australia and New Zealand intensivists conducted in July-September 2016. RESULTS: Seventy-one intensivists responded. Forty-five (63%) used a basic nomogram to titrate insulin. Sixty-six (93%) reported that insulin was commenced at blood glucose concentrations >10 mmol/L and titrated to achieve a blood glucose concentration between 6.0 and 10.0 mmol/L. A majority of respondents (75%) indicated that there was insufficient evidence to define optimal blood glucose targets in patients with T2DM, and 59 (83%) were prepared to enrol such patients in a clinical trial to evaluate a more liberal approach. CONCLUSION: A majority of respondents were uncertain about the optimal blood glucose target range for patients with T2DM and would enrol such patients in a comparative trial of conventional versus liberal blood glucose control.

Haemoglobin concentration and volume of intravenous fluids in septic shock in the ARISE trial.

BACKGROUND: Intravenous fluids may contribute to lower haemoglobin levels in patients with septic shock. We sought to determine the relationship between the changes in haemoglobin concentration and the volume of intravenous fluids administered during resuscitation from septic shock. METHODS: We performed a retrospective cohort study of patients enrolled in the Australasian Resuscitation in Sepsis Evaluation (ARISE) trial who were not transfused red blood cells (N = 1275). We determined the relationship between haemoglobin concentration, its change over time and volume of intravenous fluids administered over 6, 24 and 72 h using univariate and multivariate analysis. RESULTS: Median (IQR) haemoglobin concentration at baseline was 133 (118-146) g/L and decreased to 115 (102-127) g/L within the first 6 h of resuscitation (P < 0.001), 110 (99-122) g/L after 24 h, and 109 (97-121) g/L after 72 h. At the corresponding time points, the cumulative volume of intravenous fluid administered was 1.3 (0.7-2.2) L, 2.9 (1.8-4.3) L and 4.6 (2.7-7.1) L. Haemoglobin concentration and its change from baseline had an independent but weak association with intravenous fluid volume at each time point (R2 < 20%, P < 0.001). After adjusting for covariates, each litre of intravenous fluid administered was associated with a change in haemoglobin concentration of - 1.0 g/L (95% CI -1.5 to -0.6, P < 0.001) at 24 h and - 1.3 g/L (- 1.6 to - 0.9, P < 0.001) at 72 h. CONCLUSIONS: Haemoglobin concentration decreases during resuscitation from septic shock, and has a significant but weak association with the volume of intravenous fluids administered.

Structure and Function of the Kidney in Septic Shock. A Prospective Controlled Experimental Study.

RATIONALE: It is unclear how septic shock causes acute kidney injury (AKI) and whether this is associated with histological change. OBJECTIVES: We aimed to determine the nature and extent of changes in renal structure and function over time in an ovine model of septic shock. METHODS: Fifteen sheep were instrumented with a renal artery flow probe and renal vein cannula. Ten were given intravenous Escherichia coli to induce septic shock, and five acted as controls. Animals were mechanically ventilated for 48 hours, while receiving protocol-guided parenteral fluids and a norepinephrine infusion to maintain mean arterial pressure. Renal biopsies were taken every 24 hours or whenever animals were oliguric for 2 hours. A renal pathologist, blinded to tissue source, systematically quantified histological appearance by light and electron microscopy for 31 prespecified structural changes. MEASUREMENTS AND MAIN RESULTS: Sheep given E. coli developed septic shock, oliguria, increased serum creatinine, and reduced creatinine clearance (AKI), but there were no changes over time in renal blood flow between groups (P > 0.30) or over time within groups (P > 0.50). Renal oxygen consumption increased only in nonseptic animals (P = 0.01), but there was no between-group difference in renal lactate flux (P > 0.50). There was little structural disturbance in all biopsies and, although some cellular appearances changed over time, the only difference between septic and nonseptic animals was mesangial expansion on electron microscopy. CONCLUSIONS: In an intensive care-supported model of gram-negative septic shock, early AKI was not associated with changes in renal blood flow, oxygen delivery, or histological appearance. Other mechanisms must contribute to septic AKI.

Triiodothyronine Administration in a Model of Septic Shock: A Randomized Blinded Placebo-Controlled Trial.

OBJECTIVES: Triiodothyronine concentration in plasma decreases during septic shock and may contribute to multiple organ dysfunction. We sought to determine the safety and efficacy of administering triiodothyronine, with and without hydrocortisone, in a model of septic shock. DESIGN: Randomized blinded placebo-controlled trial. SETTING: Preclinical research laboratory. SUBJECTS: Thirty-two sheep rendered septic with IV Escherichia coli and receiving protocol-guided sedation, ventilation, IV fluids, and norepinephrine infusion. INTERVENTIONS: Two hours following induction of sepsis, 32 sheep received a 24-hour IV infusion of 1) placebo + placebo, 2) triiodothyronine + placebo, 3) hydrocortisone + placebo, or 4) triiodothyronine + hydrocortisone. MEASUREMENTS AND MAIN RESULTS: Primary outcome was the total amount of norepinephrine required to maintain a target mean arterial pressure; secondary outcomes included hemodynamic and metabolic indices. Plasma triiodothyronine levels increased to supraphysiological concentrations with hormonal therapy. Following 24 hours of study drug infusion, the amount of norepinephrine required was no different between the study groups (mean ± SD µg/kg; placebo + placebo group 208 ± 392; triiodothyronine + placebo group 501 ± 370; hydrocortisone + placebo group 167 ± 286; triiodothyronine + hydrocortisone group 466 ± 495; p = 0.20). There was no significant treatment effect on any hemodynamic variable, metabolic parameter, or measure of organ function. CONCLUSIONS: A 24-hour infusion of triiodothyronine, with or without hydrocortisone, in an ovine model of septic shock did not markedly alter norepinephrine requirement or any other physiological parameter.

Triiodothyronine supplementation in a sheep model of intensive care.

Triiodothyronine (T3) concentrations in plasma decrease during acute illness and it is unclear if this contributes to disease. Clinical and laboratory studies of T3 supplementation in disease have revealed little or no effect. It is uncertain if short term supplementation of T3 has any discernible effect in a healthy animals. Observational study of intravenous T3 (1 µg/kg/h) for 24 h in a healthy sheep model receiving protocol-guided intensive care supports (T3 group, n=5). A total of 45 endpoints were measured including hemodynamic, respiratory, renal, hematological, metabolic and endocrine parameters. Data were compared with previously published studies of sheep subject to the same support protocol without administered T3 (No T3 group, n=5). Plasma free T3 concentrations were elevated 8-fold by the infusion (pmol/l at 24 h; T3 group 34.9±9.9 vs. No T3 group 4.4±0.3, P<0.01, reference range 1.6 to 6.8). There was no significant physiological response to administration of T3 over the study duration. Supplementation of intravenous T3 for 24 h has no physiological effect on relevant physiological endpoints in healthy sheep. Further research is required to understand if the lack of effect of short-term T3 may be related to kinetics of T3 cellular uptake, metabolism and action, or acute counterbalancing hormone resistance. This information may be helpful in design of clinical T3 supplementation trials.

Twenty percent human albumin solution fluid bolus administration therapy in patients after cardiac surgery-II: a multicentre randomised controlled trial.

PURPOSE: After cardiac surgery, fluid bolus therapy (FBT) with 20% human albumin may facilitate less fluid and vasopressor administration than FBT with crystalloids. We aimed to determine whether, after cardiac surgery, FBT with 20% albumin reduces the duration of vasopressor therapy compared with crystalloid FBT. METHODS: We conducted a multicentre, parallel-group, open-label, randomised clinical trial in six intensive care units (ICUs) involving cardiac surgery patients deemed to require FBT. We randomised 240 patients to receive up to 400 mL of 20% albumin/day as FBT, followed by 4% albumin for any subsequent FBT on that day, or to crystalloid FBT for at least the first 1000 mL, with use of crystalloid or 4% albumin FBT thereafter. The primary outcome was the cumulative duration of vasopressor therapy. Secondary outcomes included fluid balance. RESULTS: Of 480 randomised patients, 466 provided consent and contributed to the primary outcome (mean age 65 years; median EuroSCORE II 1.4). The cumulative median duration of vasopressor therapy was 7 (interquartile range [IQR] 0-19.6) hours with 20% albumin and 10.8 (IQR 0-22.8) hours with crystalloids (difference - 3.8 h, 95% confidence interval [CI] - 8 to 0.4; P = 0.08). Day one fluid balance was less with 20% albumin FBT (mean difference - 701 mL, 95% CI - 872 to - 530). CONCLUSIONS: In patients after cardiac surgery, when compared to a crystalloid-based FBT, 20% albumin FBT was associated with a reduced positive fluid balance but did not significantly reduce the duration of vasopressor therapy.

Definitive management of near-hanging at major versus non-major trauma centres.

OBJECTIVES: The Victorian State Trauma System recommends that all major trauma patients receive definitive care at a major trauma service (MTS). The aim of the present study was to assess the outcomes of patients with major trauma after near-hangings who received definitive management at an MTS compared to a non-MTS. METHODS: This was a registry-based cohort study of all adult (age ≥16 years) patients with near-hanging included in the Victorian State Trauma Registry from 1 July 2010 to 30 June 2019. Outcomes of interest were death at hospital discharge, time to death and extended Glasgow Outcome Scale (GOSE) score of 5-8 (favourable) at 6 months. RESULTS: There were 243 patients included and 134 (55.1%) in-hospital deaths. Among patients presenting to a non-MTS, 24 (16.8%) were transferred to an MTS. There were 59 (47.6%) deaths at an MTS and 75 (63.0%) at a non-MTS (odds ratio [OR] 0.53; 95% confidence interval [CI] 0.32-0.89). However, more patients were managed at a non-MTS after out-of-hospital cardiac arrest (58.8% vs 50.8%) and less patients had serious neck injury (0.8% vs 11.3%). After adjustment for out-of-hospital cardiac arrests and serious neck injury, management at an MTS was not associated with mortality (adjusted OR [aOR] 0.61; 95% CI 0.23-1.65) or favourable GOSE at 6 months (aOR 1.09; 95% CI 0.40-3.03). CONCLUSIONS: After major trauma sustained from near-hanging, definitive management at an MTS did not offer a mortality benefit or better functional outcomes. Consistent with current practice, these findings suggest that most near-hanging related major trauma patients could be managed safely at a non-MTS.

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).

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.

Study protocol and statistical analysis plan for the 20% Human Albumin Solution Fluid Bolus Administration Therapy in Patients after Cardiac Surgery-ll (HAS FLAIR-II) trial.

Background: Fluid bolus therapy with 20% albumin may shorten the duration of vasopressor therapy in patients after cardiac surgery. Objective: To describe the study protocol and statistical analysis plan for the 20% Human Albumin Solution Fluid Bolus Administration Therapy in Patients after Cardiac Surgery-II (HAS FLAIR-II) trial. Design, setting, participants and intervention: HAS FLAIR-II is a phase 2b, multicentre, parallel group, openlabel, randomised controlled trial that will be conducted at six Australian intensive care units. Patients requiring fluid bolus therapy after cardiac surgery will be randomly assigned in a 1:1 ratio to the intervention of fluid bolus therapy with 20% albumin or a comparator of fluid bolus therapy with a crystalloid solution. Main outcome measures: The primary outcome measure is the cumulative duration of vasopressor therapy. Secondary outcomes include vasopressor use, service utilisation, and mortality. All analyses will be conducted on an intention-to-treat basis. Results and conclusion: The study protocol and statistical analysis plan will guide the conduct and analysis of the HAS FLAIR-II trial, such that analytical and reporting biases are minimised. Trial registration: This trial has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN No. 12620000137998).

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.