Mortality among people admitted to Australian intensive care units for reasons other than COVID-19 during the COVID-19 pandemic: a retrospective cohort study.

OBJECTIVE: To investigate in-hospital mortality among people admitted to Australian intensive care units (ICUs) with conditions other than coronavirus disease 2019 (COVID-19) during the COVID-19 pandemic. DESIGN: National, multicentre, retrospective cohort study; analysis of data in the Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation (ANZICS CORE) Adult Patient Database. SETTING, PARTICIPANTS: Adults (16 years or older) without COVID-19 admitted to Australian ICUs, 1 January 2016 - 30 June 2022. MAIN OUTCOME MEASURES: All-cause in-hospital mortality, unadjusted and relative to the January 2016 value, adjusted for illness severity (Australian and New Zealand Risk of Death [ANZROD] and hospital type), with ICU as a random effect. Points of change in mortality trends (breakpoints) were identified by segmental regression analysis. RESULTS: Data for 950 489 eligible admissions to 186 ICUs were available. In-hospital mortality declined steadily from January 2016 to March 2021 by 0.3% per month (P < 0.001; March 2021 v January 2016: adjusted odds ratio [aOR], 0.70; 95% confidence interval [CI], 0.62-0.80), but rose by 1.4% per month during March 2021 - June 2022 (P < 0.001; June 2022 v January 2016: aOR, 1.03; 95% CI, 0.90-1.17). The rise in mortality continued after the number of COVID-19-related ICU admissions had declined; mortality increased in jurisdictions with lower as well as in those with higher numbers of COVID-19-related ICU admissions. CONCLUSION: The rise in in-hospital mortality among people admitted to Australian ICUs with conditions other than COVID-19 from March 2021 reversed the improvement of the preceding five years. Changes to health service delivery during the pandemic and their consequences should be investigated further.

A Retrospective Cohort Study of Red Cell Alloimmunisation in Rural, Remote, and Aboriginal and Torres Strait Islander Peoples Admitted to Intensive Care in the Northern Territory, Australia.

Red cell (RC) alloantibodies occur on exposure to non-self RC antigens in transfusion and pregnancy (typically IgG and clinically significant) or in association with non-RC immune environmental factors (typically IgM and not clinically significant). In Australia, the risk of RC alloimmunisation in First Nations peoples is unknown. We assessed the epidemiology, specificity, and antecedents of RC alloimmunisation via a data linkage retrospective cohort study of Northern Territory (NT) intensive care unit (ICU) patients (2015-2019). Of 4183 total patients, 50.9% were First Nations. In First Nations versus non-First Nations patients, the period prevalence of alloimmunisation was 10.9% versus 2.3%, with 390 versus 72 prevalent alloantibodies detected in 232 versus 48 alloimmunised patients, of which 135 (34.6%) versus 52 (72.2%) were clinically significant specificities. Baseline and follow-up alloantibody testing were available for 1367 patients, in whom new incident clinically significant alloantibodies developed in 4.5% First Nations versus 1.1% non-First Nations patients. On Cox proportional hazards modelling, adjusted hazard ratios (HR) showed First Nations status (HR 2.67 (95% CI 1.05-6.80), p = 0.04) and cumulative RC unit transfusion exposure (HR 1.03 (95% CI 1.01-1.05), p = 0.01) were independent predictors of clinically significant alloimmunisation. First Nations Australian patients are at increased risk of alloimmunisation due to RC transfusion, underscoring the importance of very judicious use of RC transfusions and shared decision-making with patients. Further studies are recommended to explore the role of other (non-RC) immune host factors, given the relative high prevalence of non-clinically significant IgM alloantibodies within alloimmunised First Nations patients.

Twelve-month mortality outcomes for Indigenous and non-Indigenous people admitted to intensive care units in Australia: a registry-based data linkage study.

OBJECTIVE: To compare longer term (12-month) mortality outcomes for Indigenous and non-Indigenous people admitted to intensive care units (ICUs) in Australia. DESIGN, SETTING, PARTICIPANTS: Retrospective registry-based data linkage cohort study; analysis of all admissions of adults (16 years or older) to Australian ICUs, 1 January 2017 - 31 December 2019, as recorded in the Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database (APD), linked using the SLK-581 key to National Death Index data. MAIN OUTCOME MEASURES: Unadjusted and adjusted mortality risk, censored at twelve months from the start of index ICU admission. Secondary outcomes were unadjusted and adjusted mortality twelve months from admission to the ICU. RESULTS: The APD recorded 330 712 eligible ICU admissions during 2017-2019 (65% of all ICU admissions registered), of which 11 322 were of Indigenous people (3.4%). Median age at admission was lower for Indigenous patients (51.2 [IQR, 36.7-63.6] years) than for non-Indigenous patients (66.5 [IQR, 52.7-76.1] years). Unadjusted mortality risk was similar for Indigenous and non-Indigenous patients (hazard ratio, 1.01; 95% CI, 0.97-1.06), but was higher for Indigenous patients after adjusting for age, admission diagnosis, illness severity, hospital type, jurisdiction, remoteness and socio-economic status (adjusted hazard ratio, 1.20; 95% CI, 1.14-1.27). Twelve-month mortality was higher for Indigenous than non-Indigenous patients (adjusted odds ratio, 1.24; 95% CI, 1.16-1.33). CONCLUSIONS: Twelve-month mortality outcomes are poorer for people admitted to ICUs in Australia than for the general population. Further, after adjusting for age and other factors, survival outcomes are poorer for Indigenous than non-Indigenous people admitted to ICUs. Critical illness may therefore contribute to shorter life expectancy among Indigenous Australians.

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).

Characteristics and outcomes of Aboriginal and Torres Strait Islander patients with dialysis-dependent kidney disease in Australian intensive care units.

BACKGROUND: In Australia, 531 people per million population have dialysis-dependent chronic kidney disease (CKD5D). The incidence is four times higher for Aboriginal and Torres Strait Islander (indigenous) people compared with non-Indigenous Australians. CKD5D increases the risk of hospitalisation, admission to the intensive care unit (ICU) and mortality compared with patients without CKD5D. There is limited literature describing short-term outcomes of patients with CKD5D who are admitted to the ICU, comparing indigenous and non-indigenous patients. AIMS: This registry-based retrospective cohort analysis compared demographic and clinical data between indigenous and non-indigenous patients with CKD5D and tested whether indigenous status predicted short-term outcomes independently of other contributing factors. Adjusted hospital mortality was the primary outcome measure. METHODS: Data were from the Australian and New Zealand Intensive Care Society's Centre for Outcome and Resource Evaluation Adult Patient Database. Australian ICU admissions between 2010 and 2017 were included. Data from 173 ICU (2136 beds) include 1 051 697 ICU admissions, of which 23 793 had a pre-existing diagnosis of CKD5D. RESULTS: Indigenous patients comprised 11.9% of CKD5D patients in ICU. CKD5D was prevalent among 4.9% of indigenous and 2.9% of non-indigenous ICU admissions. Indigenous patients were 13.5 years younger, had fewer comorbidities and lower crude mortality despite equivalent calculated mortality risk. After adjusting for age, remoteness and severity of illness, indigenous status did not predict mortality. CONCLUSIONS: Socioeconomic disadvantage contributes to earlier development of CKD5D and the overrepresentation in ICU of indigenous people. Mortality is equivalent once correcting for confounders, but addressing inequality requires strengthening preventative care.

The effect of alcohol policy on intensive care unit admission patterns in Central Australia: A before-after cross-sectional study.

Alcohol misuse is a disproportionately large contributor to morbidity and mortality in the Northern Territory. A number of alcohol harm minimisation policies have been implemented in recent years. The effect of these on intensive care unit (ICU) admissions has not been fully explored. A retrospective before-after cross-sectional study was conducted at the Alice Springs Hospital ICU between 1 October 2017 and 30 September 2019. The primary outcome was the proportion of admissions in which alcohol misuse was a contributing factor in the 12 months before (pre-reforms phase) versus the 12 months following (post-reforms phase) implementation of alcohol legislation reforms. Secondary outcomes were measures of critical care resource use (length of stay, need for and duration of mechanical ventilation). After exclusions, 1323 ICU admissions were analysed. There was a reduction in the proportion of admissions associated with alcohol misuse between the pre-reforms and post-reforms phases (18.8% versus 11.7%, P < 0.01). This was true for both acute (10.6% versus 3.6%, P < 0.01) and chronic misuse (13.3% versus 9.6%, P = 0.03). Rates of mechanical ventilation were unchanged during the post-reforms phase (18.3% versus 14.7%). Admissions with a primary diagnosis of trauma were lower (10.5% versus 4.7%, P < 0.01). This study demonstrated a reduction in ICU admissions associated with alcohol misuse following the implementation of new alcohol harm minimisation policies. This apparent reduction in alcohol-related harm is suggestive of the effectiveness of the Northern Territory's integrated alcohol harm reduction framework.

Study protocol and statistical analysis plan for the Liberal Glucose Control in Critically Ill Patients with Pre-existing Type 2 Diabetes (LUCID) trial.

BACKGROUND: Contemporary glucose management of intensive care unit (ICU) patients with type 2 diabetes is based on trial data derived predominantly from patients without type 2 diabetes. This is despite the recognition that patients with type 2 diabetes may be relatively more tolerant of hyperglycaemia and more susceptible to hypoglycaemia. It is uncertain whether glucose targets should be more liberal in patients with type 2 diabetes. OBJECTIVE: To detail the protocol, analysis and reporting plans for a randomised clinical trial - the Liberal Glucose Control in Critically Ill Patients with Pre-existing Type 2 Diabetes (LUCID) trial - which will evaluate the risks and benefits of targeting a higher blood glucose range in patients with type 2 diabetes. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: A multicentre, parallel group, open label phase 2B randomised controlled clinical trial of 450 critically ill patients with type 2 diabetes. Patients will be randomised 1:1 to liberal blood glucose (target 10.0-14.0 mmol/L) or usual care (target 6.0-10.0 mmol/L). MAIN OUTCOME MEASURES: The primary endpoint is incident hypoglycaemia (< 4.0 mmol/L) during the study intervention. Secondary endpoints include biochemical and feasibility outcomes. RESULTS AND CONCLUSION: The study protocol and statistical analysis plan described will delineate conduct and analysis of the trial, such that analytical and reporting bias are minimised. TRIAL REGISTRATION: This trial has been registered on the Australian New Zealand Clinical Trials Registry (ACTRN No. 12616001135404) and has been endorsed by the Australian and New Zealand Intensive Care Society Clinical Trials Group.

Trauma-related admissions to intensive care units in Australia: the influence of Indigenous status on outcomes.

OBJECTIVES: To investigate the admission characteristics and hospital outcomes for Indigenous and non-Indigenous patients admitted to intensive units (ICUs) after major trauma. DESIGN, SETTING: Retrospective analysis of Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database data from 92 Australian ICUs for the 6-year period, 2010-2015. PARTICIPANTS: Patients older than 17 years of age admitted to public hospital ICUs with a primary diagnosis of trauma. MAIN OUTCOME MEASURES: ICU and overall hospital lengths of stay, hospital discharge destination, and ICU and overall hospital mortality rates for Indigenous and non-Indigenous patients. RESULTS: 23 804 people were admitted to Australian public hospital ICUs after major trauma; 1754 (7.4%) were Indigenous Australians. The population-standardised incidence of admissions was consistently higher for Indigenous Australians than for non-Indigenous Australians (847 per million v 251 per million population; incidence ratio, 3.37; 95% CI, 3.19-3.57). Overall hospital mortality rates were similar for Indigenous and non-Indigenous patients (adjusted odds ratio [aOR], 1.04; 95% CI, 0.82-1.31). Indigenous patients were more likely than non-Indigenous patients to be discharged to another hospital (non-Indigenous v Indigenous: aOR, 0.84; 95% CI, 0.72-0.96) less likely to be discharged home (non-Indigenous v Indigenous: aOR, 1.17; 95% CI, 1.04-1.31). CONCLUSION: The population rate of trauma-related ICU admissions was substantially higher for Indigenous than non-Indigenous patients, but hospital mortality rates after ICU admission were similar. Indigenous patients were more likely to be discharged to a another hospital and less likely to be discharged home than non-Indigenous patients.

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.

Long-term morbidity and mortality in survivors of critical illness: a 5-year observational follow-up study.

INTRODUCTION: This prospective observational study over 5 years aimed to quantify long-term morbidity and mortality in a prospectively recruited cohort of Central Australian survivors of critical illness. METHODS: Eligible participants are survivors of an intensive care unit (ICU) admission for a critical illness at the Alice Springs Hospital (ASH), prospectively recruited during 2009. The ASH ICU is a 10-bed unit located in Central Australia with approximately 600 admissions annually, 95% of which are emergent, and 65% Indigenous. All-cause mortality, secondary healthcare utilisation and functional outcomes were measured by 6-minute walk distance (an indicator of functional status) and the home and community care (HACC) screening tool at 5 years. RESULTS: Sixty eight percent of the cohort had died at 5 years. Median age of death was 53 years with a median time to death of 604 days following ICU admission. There was increased secondary healthcare utilisation measured by emergency department presentations and hospital re-admissions, with a median 5.22 healthcare presentations per year alive. There is evidence of ongoing functional limitation with 6-minute walk distance at 5 years significantly less than that predicted, despite high scores on the HACC screening assessment suggesting virtually full resumption of basic and domestic activities of daily living. CONCLUSIONS: A critical illness is not an isolated event, and there is evidence of ongoing high secondary healthcare utilisation, reflecting a high burden of disease. Mortality in this cohort is higher than would be expected from international data, and at a young median age, suggesting significant loss of productive life years. In addition, there is evidence of ongoing morbidity, with higher rates of healthcare utilisation than comparable international studies. This has profound implications for healthcare planners due to the ongoing economic implications, and may suggest a need for increased primary healthcare resources to pre-emptively manage chronic disease and reduce the burden of healthcare utilisation at acute care facilities.

Functional outcomes in high risk ICU patients in Central Australia: a prospective case series.

INTRODUCTION: This case series reports the functional outcomes of a prospective group of patients, thought to be at high risk for future morbidity, admitted to a rural intensive care unit (ICU) for a life-threatening illness. METHODS: This prospective longitudinal observational study conducted between February and August 2009 in the Alice Springs Hospital ICU included patients considered 'high risk', as evidenced by profound physiological derangement. The participants were prospectively recruited when pre-defined criteria were met. Functional outcomes were measured by performance in the six-minute walk test, and the ability to undertake activities of daily living. Persisting morbidity was crudely measured by hospital re-admission rate. Mortality was measured at 6 months. RESULTS: Eighteen patients consented to take part in the study. Fourteen were Indigenous, and 14 were medical patients. Six-minute walk distance did not improve between ICU discharge and 6 months, and was significantly below that predicted. Almost all patients achieved scores consistent with full independence in basic activities of daily living. Five achieved scores consistent with independence in domestic activities of daily living. Twelve required at least one re-admission, with half the Indigenous subgroup requiring three or more re-admissions. There were four deaths, all Indigenous patients, and three were homeless.< CONCLUSION: This study demonstrates that follow up in this group at 6 months is both feasible and valuable. There is evidence of persisting morbidity, and increased mortality, particularly among Indigenous patients. Further avenues of research are suggested, including the need for a large multi-centre prospective study.