Structured Weaning From the Impella Left Ventricular Micro-Axial Pump in Acute Myocardial Infarction With Cardiogenic Shock and Protected Percutaneous Coronary Intervention: Experience From a Non-Cardiac Surgical Centre.

BACKGROUND: The Impella (Abiomed, Danvers, MA, USA) temporary percutaneous left ventricular assist device is increasingly used as mechanical circulatory support in patients with acute myocardial infarction-cardiogenic shock (AMICS) or those undergoing high-risk protected percutaneous coronary intervention (PCI). The optimal weaning regimen remains to be defined. METHOD: We implemented a structured weaning protocol in a series of 10 consecutive patients receiving Impella support for protected PCI or AMICS treated with PCI in a high volume non-cardiac surgery centre. Weaning after revascularisation was titrated to native heart recovery using both haemodynamic and echocardiographic parameters. RESULTS: Ten patients (eight male, two female; aged 43-70 years) received Impella support for AMICS (80%) or protected PCI (20%). Cardiogenic shock was of Society for Cardiac Angiography & Interventions grade C-E of severity in 80%, and median left ventricular end-diastolic pressure was 31 mmHg. Protocol implementation allowed successful weaning in eight of 10 patients with a median support time of 29 hours (range, 4-48 hours). Explantation was associated with an increase in heart rate (81 vs 88 bpm; p=0.005), but no significant change in Cardiac Index (2.9 vs 2.9 L/min/m2), mean arterial pressure (79 vs 82 mmHg), vasopressor requirement (10% vs 10%), or serum lactate (1.0 vs 1.0). Median durations of intensive care and hospital stay were 3 and 6 days, respectively. At 30 days, the mortality rate was 20%, with median left ventricular ejection fraction of 40%. CONCLUSIONS: A structured and dynamic weaning protocol for patients with AMICS and protected PCI supported by the Impella device is feasible in a non-cardiac surgery centre. Larger studies are needed to assess generalisability of such a weaning protocol.

Clinician- and Patient-Identified Solutions to Reduce the Fragmentation of Post-ICU Care in Australia.

BACKGROUND: Critical care survivors experience multiple care transitions, with no formal follow-up care pathway. RESEARCH QUESTION: What are the potential solutions to improve the communication between treating teams and integration of care following an ICU admission, from the perspective of patients, their caregivers, intensivists, and general practitioners (GPs) from diverse socioeconomic areas? STUDY DESIGN AND METHODS: This study included a qualitative design using semi-structured interviews with intensivists, GPs, and patients and caregivers. Framework analysis was used to analyze data and to identify solutions to improve the integration of care following hospital discharge. Patients were previously mechanically ventilated for > 24 h in the ICU and had access to a video-enabled device. Clinicians were recruited from hospital networks and a state-wide GP network. RESULTS: Forty-six interviews with clinicians, patients, and caregivers were completed (15 intensivists, 8 GPs, 15 patients, and 8 caregivers). Three higher level feedback loops were identified that comprised 10 themes. Feedback loop 1 was an ICU and primary care collaboration. It included the following: (1) developing collaborative relationships between the ICU and primary care; (2) providing interprofessional education and resources to support primary care; and (3) improving role clarity for patient follow-up care. Feedback loop 2 was developing mechanisms for improved communication across the care continuum. It included: (4) timely, concise information-sharing with primary care on post-ICU recovery; (5) survivorship-focused information-sharing across the continuum of care; (6) empowering patients and caregivers in self-management; and (7) creation of a care coordinator role for survivors. Feedback loop 3 was learning from post-ICU outcomes to improve future care. It included: (8) developing comprehensive post-ICU care pathways; (9) enhancing support for patients following a hospital stay; and (10) integration of post-ICU outcomes within the ICU to improve clinician morale and understanding. INTERPRETATION: Practical solutions to enhance the quality of survivorship for critical care survivors and their caregivers were identified. These themes are mapped to a novel conceptual model that includes key feedback loops for health system improvements and foci for future interventional trials to improve ICU survivorship outcomes.

In-person peer support for critical care survivors: The ICU REcovery Solutions cO-Led through surVivor Engagement (ICURESOLVE) pilot randomised controlled trial.

BACKGROUND: Peer support is a promising intervention to mitigate post-ICU disability, however there is a paucity of rigorously designed studies. OBJECTIVES: The objective of this study was to establish feasibility of an in-person, co-designed, peer-support model. METHODS: Prospective, randomised, adaptive, single-centre pilot trial with blinded outcome assessment, conducted at a university-affiliated hospital in Melbourne, Australia. Intensive care unit survivors (and their nominated caregiver, where survivor and caregiver are referred to as a dyad), >18 years of age, able to speak and understand English and participate in phone surveys, were eligible. Participants were randomised to the peer-support model (six sessions, fortnightly) or usual care (no follow-up or targeted information). Two sequential models were piloted: 1. Early (2-3 weeks post hospital discharge) 2. Later (4-6 weeks post hospital discharge). Primary outcome was feasibility of implementation measured by recruitment, intervention attendance, and outcome completion. Secondary outcomes included post-traumatic stress and social support. RESULTS: Of the 231 eligible patients, 80 participants were recruited. In the early model we recruited 38 participants (28 patients, 10 carers; 18 singles, 10 dyads), with an average (standard deviation) age of 60 (18) years; 55 % were female. Twenty-two participants (58 %) were randomised to intervention. Participants in the early intervention model attended a median (interquartile range) of 0 (0-1) sessions (total 24 sessions), with 53% (n = 20) completing the main secondary outcome of interest (Impact of Event Scale) at the baseline and 37 % (n = 14) at the follow-up. For the later model we recruited 42 participants (32 patients, 10 carers; 22 singles, 10 dyads), with an average (standard deviation) age of 60.4 (15.4) years; 50 % were female. Twenty-one participants (50 %) were randomised to intervention. The later intervention model attended a median (interquartile range) of 1 (0-5) sessions (total: 44 sessions), with the main secondary outcome impact of events scale (IES-R) completed by 41 (98 %) participants at baseline and 29 (69 %) at follow-up. CONCLUSIONS: In this pilot trial, a peer-support model that required in-person attendance delivered in a later posthospital phase of recovery appeared more feasible than an early model. Further research should investigate alternative modes of intervention delivery to improve feasibility (ACTRN12621000737831).

Patient blood management guideline for adults with critical bleeding.

INTRODUCTION: The management of patients with critical bleeding requires a multidisciplinary approach to achieve haemostasis, optimise physiology, and guide blood component use. The 2011 Patient blood management guidelines: module 1 - critical bleeding/massive transfusion were updated and published. Systematic reviews were conducted for pre-specified research questions, and recommendations were based on meta-analyses of included studies. MAIN RECOMMENDATIONS: The critical bleeding/massive transfusion guideline includes seven recommendations and 11 good practice statements addressing: major haemorrhage protocols (MHPs) facilitating a multidisciplinary approach to haemorrhage control, correction of coagulopathy and normalisation of physiological derangement; measurement of physiological, biochemical and metabolic parameters in critical bleeding/massive transfusion; the optimal ratio of red blood cells to other blood components; the use of tranexamic acid; viscoelastic haemostatic assays; and cell salvage. CHANGES IN MANAGEMENT AS A RESULT OF THE GUIDELINE: The new guideline recommends MHPs be established as standard of care in all institutions managing patients with critical bleeding. In addition to routine physiological markers, the new guideline recommends temperature, biochemistry and coagulation profiles be measured early and frequently, providing parameters that define critical derangements. Ratio-based MHPs should include no fewer than four units of fresh frozen plasma and one adult unit of platelets for every eight units of red blood cells. In the setting of trauma and obstetric haemorrhage, administration of tranexamic acid within three hours of bleeding onset is recommended. The use of recombinant activated factor VII (rFVIIa) is not recommended. There was insufficient evidence to make recommendations on the use of viscoelastic haemostatic assays or cell salvage as part of MHPs.

Association Between Early External Ventricular Drain Insertion and Functional Outcomes 6 Months Following Moderate-to-Severe Traumatic Brain Injury.

Traumatic brain injury (TBI) is a leading global cause of morbidity and mortality. Intracranial hypertension following moderate-to-severe TBI (m-sTBI) is a potentially modifiable secondary cerebral insult and one of the central therapeutic targets of contemporary neurocritical care. External ventricular drain (EVD) insertion is a common therapeutic intervention used to control intracranial hypertension and attenuate secondary brain injury. However, the optimal timing of EVD insertion in the setting of m-sTBI is uncertain and practice variation is widespread. Therefore, we aimed to assess if there is an association between timing of EVD placement and functional neurological outcome at 6 months post m-sTBI. We pooled individual patient data for all relevant harmonizable variables from the Erythropoietin in Traumatic Brain Injury (EPO-TBI) and Prophylactic Hypothermia Trial to Lessen Traumatic Brain Injury (POLAR) randomized control trials, and the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) Core Study version 3.0 and Australia-Europe NeuroTrauma Effectiveness Research in TBI (Oz-ENTER) prospective observational studies to create a combined dataset. The Glasgow Coma Scale (GCS) score was used to define TBI severity and we included all patients admitted to an intensive care unit with a GCS ≤12, who were 15 years or older and underwent EVD placement within 7 days of injury. We used hierarchical multi-variable logistic regression models to study the association between EVD insertion within 24 h of injury (early) compared with EVD insertion more than 24 h after injury (late) and 6-month functional neurological outcome measured using the Glasgow Outcome Score Extended (GOSE). In total, 2536 patients were assessed. Of these, 502 (20%) underwent early EVD insertion and 145 (6%) underwent late EVD insertion. Following adjustment for the IMPACT (International Mission for Prognosis and Analysis of Clinical Trials in TBI) score extended (Core + CT), sex, injury severity score, study and treatment site, patients receiving a late EVD had higher odds of death or severe disability (GOSE 1-4) at 6 months follow-up than those receiving an early EVD adjusted odds ratio; 95% confidence interval, 2.14; 1.22-3.76; p = 0.008. Our study suggests that in patients with m-sTBI where an EVD is needed, early (≤ 24 h post-injury) insertion may result in better long-term functional outcomes. This finding supports future prospective investigation in this area.

Magnitude and time to peak oxygenation effect of prone positioning in ventilated adults with COVID-19 related acute hypoxemic respiratory failure.

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 PaO2 :FiO2 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 PaO2 :FiO2 ratio effect and time to peak PaO2 :FIO2 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 PaO2 :FIO2 ratio was 137 (±49) for all prone episodes. During the first episode. the mean PaO2 :FIO2 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 PaO2 :FIO2 ratio effect occurred during the first prone positioning episode and after 9 h. Subsequent episodes also improved oxygenation but with diminished effect on PaO2 :FIO2 ratio. This information can help guide the number and duration of prone positioning episodes.

Neuromuscular blockade and oxygenation changes during prone positioning in COVID-19.

PURPOSE: Neuromuscular blockers (NMBs) are often used during prone positioning to facilitate mechanical ventilation in COVID-19 related ARDS. However, their impact on oxygenation is uncertain. METHODS: Multi-centre observational study of invasively ventilated COVID-19 ARDS adults treated with prone positioning. We collected data on baseline characteristics, prone positioning, NMB use and patient outcome. We assessed arterial blood gas data during supine and prone positioning and after return to the supine position. RESULTS: We studied 548 prone episodes in 220 patients (mean age 54 years, 61% male) of whom 164 (75%) received NMBs. Mean PaO2:FiO2 (P/F ratio) during the first prone episode with NMBs reached 208 ± 63 mmHg compared with 161 ± 66 mmHg without NMBs (Δmean = 47 ± 5 mmHg) for an absolute increase from baseline of 76 ± 56 mmHg versus 55 ± 56 mmHg (padj < 0.001). The mean P/F ratio on return to the supine position was 190 ± 63 mmHg in the NMB group versus 141 ± 64 mmHg in the non-NMB group for an absolute increase from baseline of 59 ± 58 mmHg versus 34 ± 56 mmHg (padj < 0.001). CONCLUSION: During prone positioning, NMB is associated with increased oxygenation compared to non-NMB therapy, with a sustained effect on return to the supine position. These findings may help guide the use of NMB during prone positioning in COVID-19 ARDS.

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).

Fragmentation of care between intensive and primary care settings and opportunities for improvement.

PURPOSE: To explore the gaps in care provided across the transitions from the intensive care unit (ICU) to primary care, in order to improve post-ICU care. METHODS: Semistructured interviews with three participant groups: intensivists, general practitioners (GPs) and patients and carers with framework analysis of textual data were used to investigate experiences of transitions of care post-ICU. Participants were purposively sampled for diversity. Eligible patients were adults, mechanically ventilated for >24 hours, with access to a video-enabled device. Exclusion criteria were non-English speaking and any cognitive/neurological limitation precluding interview participation. RESULTS: A total of 46 interviews (15 patients, 8 caregivers, 15 intensivists and 8 GPs) were completed. Eight themes were identified, and categorised into three healthcare tiers. Tier 1, health system factors: (1) fragmentation of care; (2) communication gaps; (3) limited awareness and recognition of issues beyond the ICU; (4) lack of a specialised ICU follow-up pathway; Tier 2, clinician factors: (5) relationships among ICU, hospitals, GPs and patients and carers; (6) need for clinician role definition and clarity in ICU follow-up; Tier 3, patient and carer factors: (7) patient autonomy and self-actualisation and (8) the evolving caregiver role. A conceptual model was developed, highlighting bidirectional feedback loops between hospital and primary care. CONCLUSION: This study identified gaps in care between ICU discharge and reintegration with primary care from the lived experience of patients, caregivers, intensivists and GPs. These data provide foci for future interventional research to improve the integration of care for this vulnerable and underserved cohort.

Effect of Concomitant Cardiac Arrest on Outcomes in Patients With Acute Coronary Syndrome-Related Cardiogenic Shock.

Patients with acute coronary syndrome (ACS)-related cardiogenic shock (CS) with or without concomitant CA may have disparate prognoses. We compared clinical characteristics and outcomes of patients with CS secondary to ACS with and without cardiac arrest (CA). Between 2014 and 2020, 1,573 patients with ACS-related CS with or without CA who underwent percutaneous coronary intervention enrolled in a multicenter Australian registry were analyzed. Primary outcome was 30-day major adverse cardiovascular and cerebrovascular events (MACCE) (composite of mortality, myocardial infarction, stent thrombosis, target vessel revascularization and stroke). Long-term mortality was obtained through linkage to the National Death Index. Compared with the no-CA group (n = 769, 49%), the CA group (n = 804, 51%) was younger (62 vs 69 years, p <0.001) and had fewer comorbidities. Patients with CA more frequently had ST-elevation myocardial infarction (92% vs 86%), occluded left anterior descending artery (43% vs 33%), and severe preprocedural renal impairment (49% vs 42%) (all p <0.001). CA increased risk of 30-day MACCE by 45% (odds ratio 1.45, 95% confidence interval 1.05 to 2.00, p = 0.024) after adjustment. CA group had higher 30-day MACCE (55% vs 42%, p <0.001) and mortality (52% vs 37%, p <0.001). Three-year survival was lower for CA compared with no-CA patients (43% vs 52%, p <0.001). In Cox regression, CS with CA was associated with a trend toward greater long-term mortality hazard (hazard ratio 1.19, 95% confidence interval 1.00 to 1.41, p = 0.055). In conclusion, concomitant CA among patients with ACS-related CS conferred a particularly heightened short-term risk with a diminishing legacy effect over time for mortality. CS survivors continue to exhibit high sustained long-term mortality hazard regardless of CA status.

The effect of recombinant erythropoietin on long-term outcome after moderate-to-severe traumatic brain injury.

PURPOSE: Recombinant erythropoietin (EPO) administered for traumatic brain injury (TBI) may increase short-term survival, but the long-term effect is unknown. METHODS: We conducted a pre-planned long-term follow-up of patients in the multicentre erythropoietin in TBI trial (2010-2015). We invited survivors to follow-up and evaluated survival and functional outcome with the Glasgow Outcome Scale-Extended (GOSE) (categories 5-8 = good outcome), and secondly, with good outcome determined relative to baseline function (sliding scale). We used survival analysis to assess time to death and absolute risk differences (ARD) to assess favorable outcomes. We categorized TBI severity with the International Mission for Prognosis and Analysis of Clinical Trials in TBI model. Heterogeneity of treatment effects were assessed with interaction p-values based on the following a priori defined subgroups, the severity of TBI, and the presence of an intracranial mass lesion and multi-trauma in addition to TBI. RESULTS: Of 603 patients in the original trial, 487 patients had survival data; 356 were included in the follow-up at a median of 6 years from injury. There was no difference between treatment groups for patient survival [EPO vs placebo hazard ratio (HR) (95% confidence interval (CI) 0.73 (0.47-1.14) p = 0.17]. Good outcome rates were 110/175 (63%) in the EPO group vs 100/181 (55%) in the placebo group (ARD 8%, 95% CI [Formula: see text] 3 to 18%, p = 0.14). When good outcome was determined relative to baseline risk, the EPO groups had better GOSE (sliding scale ARD 12%, 95% CI 2-22%, p = 0.02). When considering long-term patient survival, there was no evidence for heterogeneity of treatment effect (HTE) according to severity of TBI (p = 0.85), presence of an intracranial mass lesion (p = 0.48), or whether the patient had multi-trauma in addition to TBI (p = 0.08). Similarly, no evidence of treatment heterogeneity was seen for the effect of EPO on functional outcome. CONCLUSION: EPO neither decreased overall long-term mortality nor improved functional outcome in moderate or severe TBI patients treated in the intensive care unit (ICU). The limited sample size makes it difficult to make final conclusions about the use of EPO in TBI.

Sodium Bicarbonate for Metabolic Acidosis in the ICU: Results of a Pilot Randomized Double-Blind Clinical Trial.

OBJECTIVES: To identify the best population, design of the intervention, and to assess between-group biochemical separation, in preparation for a future phase III trial. DESIGN: Investigator-initiated, parallel-group, pilot randomized double-blind trial. SETTING: Eight ICUs in Australia, New Zealand, and Japan, with participants recruited from April 2021 to August 2022. PATIENTS: Thirty patients greater than or equal to 18 years, within 48 hours of admission to the ICU, receiving a vasopressor, and with metabolic acidosis (pH < 7.30, base excess [BE] < -4 mEq/L, and Pa co2 < 45 mm Hg). INTERVENTIONS: Sodium bicarbonate or placebo (5% dextrose). MEASUREMENTS AND MAIN RESULT: The primary feasibility aim was to assess eligibility, recruitment rate, protocol compliance, and acid-base group separation. The primary clinical outcome was the number of hours alive and free of vasopressors on day 7. The recruitment rate and the enrollment-to-screening ratio were 1.9 patients per month and 0.13 patients, respectively. Time until BE correction (median difference, -45.86 [95% CI, -63.11 to -28.61] hr; p < 0.001) and pH correction (median difference, -10.69 [95% CI, -19.16 to -2.22] hr; p = 0.020) were shorter in the sodium bicarbonate group, and mean bicarbonate levels in the first 24 hours were higher (median difference, 6.50 [95% CI, 4.18 to 8.82] mmol/L; p < 0.001). Seven days after randomization, patients in the sodium bicarbonate and placebo group had a median of 132.2 (85.6-139.1) and 97.1 (69.3-132.4) hours alive and free of vasopressor, respectively (median difference, 35.07 [95% CI, -9.14 to 79.28]; p = 0.131). Recurrence of metabolic acidosis in the first 7 days of follow-up was lower in the sodium bicarbonate group (3 [20.0%] vs. 15 [100.0%]; p < 0.001). No adverse events were reported. CONCLUSIONS: The findings confirm the feasibility of a larger phase III sodium bicarbonate trial; eligibility criteria may require modification to facilitate recruitment.

Activin A level is associated with physical function in critically ill patients.

BACKGROUND: Activin A is a potent negative regulator of muscle mass elevated in critical illness. It is unclear whether muscle strength and physical function in critically ill humans are associated with elevated activin A levels. OBJECTIVES: The objective of this study was to investigate the relationship between serum activin A levels, muscle strength, and physical function at discharge from the intensive care unit (ICU) and hospital. METHODS: Thirty-six participants were recruited from two tertiary ICUs in Melbourne, Australia. Participants were included if they were mechanically ventilated for >48 h and expected to have a total ICU stay of >5 days. The primary outcome measure was the Six-Minute Walk Test distance at hospital discharge. Secondary outcome measures included handgrip strength, Medical Research Council Sum Score, Physical Function ICU Test Scored, Six-Minute Walk Test, and Timed Up and Go Test assessed throughout the hospital admission. Total serum activin A levels were measured daily in the ICU. RESULTS: High peak activin A was associated with worse Six-Minute Walk Test distance at hospital discharge (linear regression coefficient, 95% confidence interval, p-value: -91.3, -154.2 to -28.4, p = 0.007, respectively). Peak activin A concentration was not associated with the secondary outcome measures. CONCLUSIONS: Higher peak activin A may be associated with the functional decline of critically ill patients. Further research is indicated to examine its potential as a therapeutic target and a prospective predictor for muscle wasting in critical illness. STUDY REGISTRATION: ACTRN12615000047594.

Sex differences among patients presenting to hospital with out-of-hospital cardiac arrest and shockable rhythm.

OBJECTIVE: Sex differences in patients presenting with out-of-hospital cardiac arrest (OHCA) and shockable rhythm might be associated with disparities in clinical outcomes. METHODS: We conducted a retrospective cohort study and compared characteristics and short-term outcomes between male and female adult patients who presented with OHCA and shockable rhythm at two large metropolitan health services in Melbourne, Australia between the period of 2014-2018. Logistic regression was used to assess the effect of sex on clinical outcomes. RESULTS: Of 212 patients, 166 (78%) were males and 46 (22%) were females. Both males and females presented with similar rates of ST-elevation myocardial infarction (44% vs 36%, P = 0.29), although males were more likely to have a history of coronary artery disease (32% vs 13%) and a final diagnosis of a cardiac cause for their OHCA (89% vs 72%), both P = 0.01. Rates of coronary angiography (81% vs 71%, P = 0.23) and percutaneous coronary intervention (51% vs 42%, P = 0.37) were comparable among males and females. No differences in rates of in-hospital mortality (38% vs 37%, P = 0.90) and 30-day major adverse cardiac and cerebrovascular events (composite of all-cause mortality, myocardial infarction, coronary revascularization and nonfatal stroke) (39% vs 41%, P = 0.79) were observed between males and females, respectively. Female sex was not associated with worse in-hospital mortality when adjusted for other variables (odds ratio 0.66, 95% confidence interval 0.28-1.60, P = 0.36). CONCLUSION: Among patients presenting with OHCA and a shockable rhythm, baseline sex and sex differences were not associated with disparities in short-term outcomes in contemporary systems of care.

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.

Iron and erythropoietin to heal and recover after intensive care (ITHRIVE): A pilot randomised clinical trial.

Objective: To determine the feasibility of a pivotal randomised clinical trial of intravenous (IV) iron and erythropoietin in adult survivors of critical illness with anaemia requiring treatment in the intensive care unit. Design: An investigator-initiated, parallel group, placebo-controlled, randomised feasibility trial. Setting: A tertiary intensive care unit (ICU) in Perth, Western Australia. Participants: Adults with anaemia (haemoglobin <100 g/L), requiring ICU-level care for more than 48 h, and likely to be ready for ICU discharge within 24 h. Interventions: A single dose of IV ferric carboxymaltose and Epoetin alfa (active group) or an equal volume of 0.9% saline (placebo group). Main outcome measures: Study feasibility was considered met if the pilot achieved a recruitment rate of ≥2 participants per site per month, ≥90% of participants received their allocated study treatment, and≥ 90% of participants were followed up for the proposed pivotal trial primary outcome - days alive and at home to day 90 (DAH90). Results: The 40-participant planned sample size included twenty in each group and was enrolled between 1/9/2021 and 2/3/2022. Participants spent a median of 3.4 days (interquartile range 2.8-5.1) in the ICU prior to enrolment and had a mean baseline haemoglobin of 83.7 g/L (standard deviation 6.7). The recruitment rate was 6.7 participants per month [95% confidence interval (CI) 4.8-9.0], DAH90 follow-up was 100% (95% CI 91.2%-100%), and 39 (97.5%, 95% CI 86.8%-99.9%) participants received the allocated study intervention. No serious adverse events were reported. Conclusion: The iron and erythropoietin to heal and recover after intensive care (ITHRIVE) pilot demonstrated feasibility based on predefined participant recruitment, study drug administration, and follow-up thresholds.

Evaluation of factors associated with selection for coronary angiography and in-hospital mortality among patients presenting with out-of-hospital cardiac arrest without ST-segment elevation.

BACKGROUND: Clinical factors favouring coronary angiography (CA) selection and variables associated with in-hospital mortality among patients presenting with out-of-hospital cardiac arrest (OHCA) without ST-segment elevation (STE) remain unclear. METHODS: We evaluated clinical characteristics associated with CA selection and in-hospital mortality in patients with OHCA, shockable rhythm and no STE. RESULTS: Between 2014 and 2018, 118 patients with OHCA and shockable rhythm without STE (mean age 59; males 75%) were stratified by whether CA was performed. Of 86 (73%) patients undergoing CA, 30 (35%) received percutaneous coronary intervention (PCI). CA patients had shorter return of spontaneous circulation (ROSC) time (17 vs. 25 min) and were more frequently between 50 and 60 years (29% vs. 6.5%), with initial Glasgow Coma Scale (GCS) score >8 (24% vs. 6%) (all p < 0.05). In-hospital mortality was 33% (n = 39) for overall cohort (CA 27% vs. no-CA 50%, p = 0.02). Compared to late CA, early CA ( ≤ 2 h) was not associated with lower in-hospital mortality (32% vs. 34%, p = 0.82). Predictors of in-hospital mortality included longer defibrillation time (odds ratio 3.07, 95% confidence interval 1.44-6.53 per 5-min increase), lower pH (2.02, 1.33-3.09 per 0.1 decrease), hypoalbuminemia (2.02, 1.03-3.95 per 5 g/L decrease), and baseline renal dysfunction (1.33, 1.02-1.72 per 10 ml/min/1.73 m2 decrease), while PCI to lesion (0.11, 0.01-0.79) and bystander defibrillation (0.06, 0.004-0.80) were protective factors (all p < 0.05). CONCLUSIONS: Among patients with OHCA and shockable rhythm without STE, younger age, shorter time to ROSC and GCS >8 were associated with CA selection, while less effective resuscitation, greater burden of comorbidities and absence of treatable coronary lesion were key adverse prognostic predictors.

People in intensive care with COVID-19: demographic and clinical features during the first, second, and third pandemic waves in Australia.

OBJECTIVE: To compare the demographic and clinical features, management, and outcomes for patients admitted with COVID-19 to intensive care units (ICUs) during the first, second, and third waves of the pandemic in Australia. DESIGN, SETTING, AND PARTICIPANTS: People aged 16 years or more admitted with polymerase chain reaction-confirmed COVID-19 to the 78 Australian ICUs participating in the Short Period Incidence Study of Severe Acute Respiratory Infection (SPRINT-SARI) Australia project during the first (27 February - 30 June 2020), second (1 July 2020 - 25 June 2021), and third COVID-19 waves (26 June - 1 November 2021). MAIN OUTCOME MEASURES: Primary outcome: in-hospital mortality. SECONDARY OUTCOMES: ICU mortality; ICU and hospital lengths of stay; supportive and disease-specific therapies. RESULTS: 2493 people (1535 men, 62%) were admitted to 59 ICUs: 214 during the first (9%), 296 during the second (12%), and 1983 during the third wave (80%). The median age was 64 (IQR, 54-72) years during the first wave, 58 (IQR, 49-68) years during the second, and 54 (IQR, 41-65) years during the third. The proportion without co-existing illnesses was largest during the third wave (41%; first wave, 32%; second wave, 29%). The proportion of ICU beds occupied by patients with COVID-19 was 2.8% (95% CI, 2.7-2.9%) during the first, 4.6% (95% CI, 4.3-5.1%) during the second, and 19.1% (95% CI, 17.9-20.2%) during the third wave. Non-invasive (42% v 15%) and prone ventilation strategies (63% v 15%) were used more frequently during the third wave than during the first two waves. Thirty patients (14%) died in hospital during the first wave, 35 (12%) during the second, and 281 (17%) during the third. After adjusting for age, illness severity, and other covariates, the risk of in-hospital mortality was similar for the first and second waves, but 9.60 (95% CI, 3.52-16.7) percentage points higher during the third than the first wave. CONCLUSION: The demographic characteristics of patients in intensive care with COVID-19 and the treatments they received during the third pandemic wave differed from those of the first two waves. Adjusted in-hospital mortality was highest during the third wave.

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).

Percutaneous Coronary Intervention Volume and Cardiac Surgery Availability Effect on Acute Coronary Syndrome-Related Cardiogenic Shock.

OBJECTIVES: This study sought to assess the association between cardiac surgery availability and percutaneous coronary intervention (PCI) volume with clinical outcomes of cardiogenic shock (CS) complicating acute coronary syndrome (ACS). BACKGROUND: CS remains a grave complication of ACS with high mortality rates despite timely reperfusion and improved heart failure therapies. METHODS: The study analyzed data from consecutive patients with CS complicating ACS who underwent PCI and were prospectively enrolled in the VCOR (Victorian Cardiac Outcomes Registry) from 26 hospitals in Victoria. We compared patients treated at cardiac surgical centers (CSCs) versus non-CSCs as well as the annual CS PCI volume (stratified into tiers of <10, 10-25, and >25 cases) for in-hospital major adverse cardiac and cerebrovascular events (MACCE) and long-term mortality. RESULTS: Of 1,179 patients with CS, the mean age of patients was 65 years; males comprised 74%, and 22% had diabetes mellitus. Cardiac arrest occurred in 38% of patients, while 90% presented with ST-segment elevation myocardial infarction and 26% received intra-aortic balloon pump support. Overall, in-hospital and long-term mortality were 42% and 51%, respectively. There was no difference among patients treated non-CSCs compared with a CSCs for in-hospital MACCE and mortality (both P > 0.05). Similarly, there was no association between tiers of annual CS PCI volume with in-hospital MACCE and mortality (both P > 0.05). CONCLUSIONS: Comparable short- and long-term mortality rates among patients with ACS complicated by CS treated by PCI irrespective of cardiac surgery availability and CS PCI volume support the emergent treatment of these gravely ill patients at their presenting PCI-capable hospital.