Non-COVID-19 intensive care admissions during the pandemic: a multinational registry-based study.

BACKGROUND: The COVID-19 pandemic resulted in a large number of critical care admissions. While national reports have described the outcomes of patients with COVID-19, there is limited international data of the pandemic impact on non-COVID-19 patients requiring intensive care treatment. METHODS: We conducted an international, retrospective cohort study using 2019 and 2020 data from 11 national clinical quality registries covering 15 countries. Non-COVID-19 admissions in 2020 were compared with all admissions in 2019, prepandemic. The primary outcome was intensive care unit (ICU) mortality. Secondary outcomes included in-hospital mortality and standardised mortality ratio (SMR). Analyses were stratified by the country income level(s) of each registry. FINDINGS: Among 1 642 632 non-COVID-19 admissions, there was an increase in ICU mortality between 2019 (9.3%) and 2020 (10.4%), OR=1.15 (95% CI 1.14 to 1.17, p<0.001). Increased mortality was observed in middle-income countries (OR 1.25 95% CI 1.23 to 1.26), while mortality decreased in high-income countries (OR=0.96 95% CI 0.94 to 0.98). Hospital mortality and SMR trends for each registry were consistent with the observed ICU mortality findings. The burden of COVID-19 was highly variable, with COVID-19 ICU patient-days per bed ranging from 0.4 to 81.6 between registries. This alone did not explain the observed non-COVID-19 mortality changes. INTERPRETATION: Increased ICU mortality occurred among non-COVID-19 patients during the pandemic, driven by increased mortality in middle-income countries, while mortality decreased in high-income countries. The causes for this inequity are likely multi-factorial, but healthcare spending, policy pandemic responses, and ICU strain may play significant roles.

Oxygenation During Venoarterial Extracorporeal Membrane Oxygenation: Physiology, Current Evidence, and a Pragmatic Approach to Oxygen Titration.

OBJECTIVES: This review aims to: 1) identify the key circuit and patient factors affecting systemic oxygenation, 2) summarize the literature reporting the association between hyperoxia and patient outcomes, and 3) provide a pragmatic approach to oxygen titration, in patients undergoing peripheral venoarterial extracorporeal membrane oxygenation (ECMO). DATA SOURCES: Searches were performed using PubMed, SCOPUS, Medline, and Google Scholar. STUDY SELECTION: All observational and interventional studies investigating the association between hyperoxia, and clinical outcomes were included, as well as guidelines from the Extracorporeal Life Support Organization. DATA EXTRACTION: Data from relevant literature was extracted, summarized, and integrated into a concise narrative review. For ease of reference a summary of relevant studies was also produced. DATA SYNTHESIS: The extracorporeal circuit and the native cardiorespiratory circuit both contribute to systemic oxygenation during venoarterial ECMO. The ECMO circuit's contribution to systemic oxygenation is, in practice, largely determined by the ECMO blood flow, whereas the native component of systemic oxygenation derives from native cardiac output and residual respiratory function. Interactions between ECMO outflow and native cardiac output (as in differential hypoxia), the presence of respiratory support, and physiologic parameters affecting blood oxygen carriage also modulate overall oxygen exposure during venoarterial ECMO. Physiologically those requiring venoarterial ECMO are prone to hyperoxia. Hyperoxia has a variety of definitions, most commonly Pa o2 greater than 150 mm Hg. Severe hypoxia (Pa o2 > 300 mm Hg) is common, seen in 20%. Early severe hyperoxia, as well as cumulative hyperoxia exposure was associated with in-hospital mortality, even after adjustment for disease severity in both venoarterial ECMO and extracorporeal cardiopulmonary resuscitation. A pragmatic approach to oxygenation during peripheral venoarterial ECMO involves targeting a right radial oxygen saturation target of 94-98%, and in selected patients, titration of the fraction of oxygen in the mixture via the air-oxygen blender to target postoxygenator Pa o2 of 150-300 mm Hg. CONCLUSIONS: Hyperoxia results from a range of ECMO circuit and patient-related factors. It is common during peripheral venoarterial ECMO, and its presence is associated with poor outcome. A pragmatic approach that avoids hyperoxia, while also preventing hypoxia has been described for patients receiving peripheral venoarterial ECMO.

Sex Differences in Vital Organ Support Provided to ICU Patients.

OBJECTIVES: Critically ill women may receive less vital organ support than men but the mortality impact of this differential treatment remains unclear. We aimed to quantify sex differences in vital organ support provided to adult ICU patients and describe the relationship between sex, vital organ support, and mortality. DESIGN: In this retrospective observational study, we examined the provision of invasive ventilation (primary outcome), noninvasive ventilation, vasoactive medication, renal replacement therapy, extracorporeal membrane oxygenation (ECMO), or any one of these five vital organ supports in women compared with men. We performed logistic regression investigating the association of sex with each vital organ support, adjusted for illness severity, diagnosis, preexisting treatment limitation, year, and hospital. We performed logistic regression for hospital mortality adjusted for the same variables, stratified by vital organ support (secondary outcome). SETTING AND PATIENTS: ICU admissions in the Australia and New Zealand Intensive Care Society Adult Patient Database 2018-2021. This registry records admissions from 90% of ICUs in the two nations. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We examined 699,535 ICU admissions (43.7% women) to 199 ICUs. After adjustment, women were less likely than men to receive invasive ventilation (odds ratio [OR], 0.64; 99% CI, 0.63-0.65) and each other organ support except ECMO. Women had lower adjusted hospital mortality overall (OR, 0.94; 99% CI, 0.91-0.97). Among patients who did not receive any organ support, women had significantly lower adjusted hospital mortality (OR, 0.82; 99% CI, 0.76-0.88); among patients who received any organ support women and men were equally likely to die (OR, 1.01; 99% CI, 0.97-1.04). CONCLUSIONS: Women received significantly less vital organ support than men in ICUs in Australia and New Zealand. However, our findings suggest that women may not be harmed by this conservative approach to treatment.

National ICU Registries as Enablers of Clinical Research and Quality Improvement.

OBJECTIVES: Clinical quality registries (CQRs) have been implemented worldwide by several medical specialties aiming to generate a better characterization of epidemiology, treatments, and outcomes of patients. National ICU registries were created almost 3 decades ago to improve the understanding of case-mix, resource use, and outcomes of critically ill patients. This narrative review describes the challenges, proposed solutions, and evidence generated by National ICU registries as facilitators for research and quality improvement. DATA SOURCES: English language articles were identified in PubMed using phrases related to ICU registries, CQRs, outcomes, and case-mix. STUDY SELECTION: Original research, review articles, letters, and commentaries, were considered. DATA EXTRACTION: Data from relevant literature were identified, reviewed, and integrated into a concise narrative review. DATA SYNTHESIS: CQRs have been implemented worldwide by several medical specialties aiming to generate a better characterization of epidemiology, treatments, and outcomes of patients. National ICU registries were created almost 3 decades ago to improve the understanding of case-mix, resource use, and outcomes of critically ill patients. The initial experience in European countries and in Oceania ensured that through locally generated data, ICUs could assess their performances by using risk-adjusted measures and compare their results through fair and validated benchmarking metrics with other ICUs contributing to the CQR. The accomplishment of these initiatives, coupled with the increasing adoption of information technology, resulted in a broad geographic expansion of CQRs as well as their use in quality improvement studies, clinical trials as well as international comparisons, and benchmarking for ICUs. CONCLUSIONS: ICU registries have provided increased knowledge of case-mix and outcomes of ICU patients based on real-world data and contributed to improve care delivery through quality improvement initiatives and trials. Recent increases in adoption of new technologies (i.e., cloud-based structures, artificial intelligence, machine learning) will ensure a broader and better use of data for epidemiology, healthcare policies, quality improvement, and clinical trials.

Epidemiology of Renal Replacement Therapy for Critically Ill Patients across Seven Health Jurisdictions.

INTRODUCTION: Acute kidney injury (AKI) requiring treatment with renal replacement therapy (RRT) is a common complication after admission to an intensive care unit (ICU) and is associated with significant morbidity and mortality. However, the prevalence of RRT use and the associated outcomes in critically patients across the globe are not well described. Therefore, we describe the epidemiology and outcomes of patients receiving RRT for AKI in ICUs across several large health system jurisdictions. METHODS: Retrospective cohort analysis using nationally representative and comparable databases from seven health jurisdictions in Australia, Brazil, Canada, Denmark, New Zealand, Scotland, and the USA between 2006 and 2023, depending on data availability of each dataset. Patients with a history of end-stage kidney disease receiving chronic RRT and patients with a history of renal transplant were excluded. RESULTS: A total of 4,104,480 patients in the ICU cohort and 3,520,516 patients in the mechanical ventilation cohort were included. Overall, 156,403 (3.8%) patients in the ICU cohort and 240,824 (6.8%) patients in the mechanical ventilation cohort were treated with RRT for AKI. In the ICU cohort, the proportion of patients treated with RRT was lowest in Australia and Brazil (3.3%) and highest in Scotland (9.2%). The in-hospital mortality for critically ill patients treated with RRT was almost fourfold higher (57.1%) than those not receiving RRT (16.8%). The mortality of patients treated with RRT varied across the health jurisdictions from 37 to 65%. CONCLUSION: The outcomes of patients who receive RRT in ICUs throughout the world vary widely. Our research suggests that differences in access to and provision of this therapy are contributing factors.

Sepsis mortality among patients with haematological malignancy admitted to intensive care 2000-2022: a binational cohort study.

BACKGROUND: Sepsis occurs in 12-27% of patients with haematological malignancy within a year of diagnosis. Sepsis mortality has improved in non-cancer patients in the last two decades, but longitudinal trends in patients with haematological malignancy are not well characterised. We aimed to compare outcomes, including temporal changes, in patients with and without a haematological malignancy admitted to ICU with a primary diagnosis of sepsis in Australia and New Zealand over the past two decades. METHODS: We performed a retrospective cohort study of 282,627 patients with a primary intensive care unit (ICU) admission diagnosis of sepsis including 17,313 patients with haematological malignancy, admitted to 216 intensive care units (ICUs) in Australia or New Zealand between January 2000 and December 2022. Annual crude and adjusted in-hospital mortality were reported. Risk factors for in-hospital mortality were determined using a mixed methods logistic regression model and were used to calculate annual changes in mortality. RESULTS: In-hospital sepsis mortality decreased in patients with haematological malignancy, from 55.6% (95% CI 46.5-64.6%) in 2000 to 23.1% (95% CI 20.8-25.5%) in 2021. In patients without haematological malignancy mortality decreased from 33.1% (95% CI 31.3-35.1%) to 14.4% (95% CI 13.8-14.8%). This decrease remained significant after adjusting for mortality predictors including age, SOFA score and comorbidities, as estimated by adjusted annual odds of in-hospital death. The reduction in odds of death was of greater magnitude in patients with haematological malignancy than those without (OR 0.954, 95% CI 0.947-0.961 vs. OR 0.968, 95% CI 0.966-0.971, p < 0.001). However, absolute risk of in-hospital mortality remained higher in patients with haematological malignancy. Older age, higher SOFA score, presence of comorbidities, and mechanical ventilation were associated with increased mortality. Leukopenia (white cell count < 1.0 × 109 cells/L) was not associated with increased mortality in patients with haematological malignancy (p = 0.60). CONCLUSIONS: Sepsis mortality has improved in patients with haematological malignancy admitted to ICU. However, mortality remains higher in patients with haematological malignancy than those without.

Outcomes for people admitted to Australian and New Zealand intensive care units with primary, exacerbating, or incidental SARS-CoV-2 infections, 2022-23: a retrospective analysis of ANZICS data.

OBJECTIVES: To compare in-hospital mortality and intensive care unit (ICU) length of stay for people admitted to Australian and New Zealand ICUs during 2022-23 with coronavirus disease 2019 (COVID-19) pneumonitis, incidental or exacerbating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, or without SAR-CoV-2 infections. STUDY DESIGN: Retrospective cohort study; analysis of Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database data. SETTING, PARTICIPANTS: Adults (16 years or older) admitted to participating ICUs in Australia or New Zealand, 1 January 2022 - 30 June 2023. MAJOR OUTCOME MEASURES: The primary outcome was in-hospital mortality, the secondary outcome ICU length of stay, each by SARS-CoV-2 infection attribution classification: primary COVID-19; exacerbating SARS-CoV-2 infection (SARS-CoV-2 infection was a contributing factor to the primary cause of ICU admission); incidental SARS-CoV-2 infections (SARS-CoV-2 infection detected during ICU admission but did not contribute to admission diagnosis); no SARS-CoV-2 infection. RESULTS: A total of 207 684 adults were admitted to 195 Australian and New Zealand ICUs during 2022-23; 2674 people (1.3%) had incidental SARS-CoV-2 infections, 4923 (2.4%) exacerbating infections, and 3620 (1.7%) primary COVID-19. Unadjusted in-hospital mortality for people with incidental SARS-CoV-2 infections (288 deaths, 10.8%) was lower than for those with exacerbating infections (928 deaths, 18.8%) or primary COVID-19 (830 deaths, 22.9%), but higher than for patients without SARS-CoV-2 infections (15 486 deaths, 7.9%). After adjusting for illness severity, frailty, geographic region, and type of hospital, mortality was higher for patients with incidental SARS-CoV-2 infections (adjusted odds ratio [aOR], 1.28; 95% confidence interval [CI], 1.10-1.50), exacerbating infections (aOR, 1.35; 95% CI, 1.22-1.48), or primary COVID-19 (aOR, 2.54; 95% CI, 2.30-2.81) than for patients without SARS-CoV-2 infections. After adjusting for diagnosis and illness severity, ICU stays were longer for people with incidental (mean difference, 3.3 hours; 95% CI, 2.4-4.2 hours) or exacerbating infections (0.8 hours; 95% CI, 0.2-1.5 hours) than for those without SARS-CoV-2 infections. CONCLUSION: Risk-adjusted in-hospital mortality and ICU length of stay are higher for people admitted to intensive care who have concomitant SARS-CoV-2 infections than for people who do not.

FRailty in Australian patients admitted to Intensive care unit after eLective CANCER-related SURGery: a retrospective multicentre cohort study (FRAIL-CANCER-SURG study).

BACKGROUND: The association between frailty and short-term and long-term outcomes in patients receiving elective surgery for cancer remains unclear, particularly in those admitted to the ICU. METHODS: In this multicentre retrospective cohort study, we included adults ≥16 yr old admitted to 158 ICUs in Australia from January 1, 2018 to March 31, 2022 after elective surgery for cancer. We investigated the association between frailty and survival time up to 4 yr (primary outcome), adjusting for a prespecified set of covariates. We analysed how this association changed in specific subgroups (age categories [<65, 65-80, ≥80 yr], and those who survived hospitalisation), and over time by splitting the survival information at monthly intervals. RESULTS: We included 35,848 patients (median follow-up: 18.1 months [inter-quartile range: 8.3-31.1 months], 19,979 [56.1%] male, median age 69.0 yr [inter-quartile range: 58.8-76.0 yr]). Some 3502 (9.8%) patients were frail (defined as clinical frailty scale ≥5). Frailty was associated with lower survival (hazard ratio: 1.72, 95% confidence interval [CI]: 1.59-1.86 compared with clinical frailty scale ≤4); this was concordant across several sensitivity analyses. Frailty was most strongly associated with mortality early on in follow-up, up to 10 months (hazard ratio: 1.39, 95% CI: 1.03-1.86), but this association plateaued, and its predictive capacity subsequently diminished with time up until 4 yr (1.96, 95% CI: 0.73-5.28). Frailty was associated with similar effects when stratified based on age, and in those who survived hospitalisation. CONCLUSIONS: Frailty was associated with poorer outcomes after an ICU admission after elective surgery for cancer, particularly in the short term. However, its predictive capacity with time diminished, suggesting a potential need for longitudinal reassessment to ensure appropriate prognostication in this population.

The interplay between frailty status and persistent critical illness on the outcomes of patients with critical COVID-19: A population-based retrospective cohort study.

OBJECTIVES: Persistent critical illness (PerCI) occurs when the patient's prolonged intensive care unit (ICU) stay results in complications that become the primary drivers of their condition, rather than the initial reason for their admission. Patients with frailty have a higher risk of developing and dying from PerCI. We aimed to investigate the interplay of frailty and PerCI in critically ill patients with COVID-19. METHOD: We conducted a retrospective multicentre cohort study including 103 Australian and New Zealand ICUs over the period of January 2020 to December 2021. We included all adult patients with COVID-19 and documented the Clinical Frailty Scale (frail ≥ 5). PerCI is defined as an ICU length of stay of ≥10 days. We aimed to investigate the hospital mortality with and without PerCI across varying degrees of frailty and examined the potential interaction effect between frailty status and PerCI. RESULTS: The prevalence of PerCI was similar between patients with and without frailty (25.4% vs. 27.9%; p = 0.44). Hospital mortality was higher in patients with PerCI than in those without (28.8% vs. 9.3%; p < 0.001). Mortality in patients with PerCI also increased with increasing frailty (p < 0.001). Frailty independently predicted hospital mortality. When adjusted for Australia and New Zealand risk of death mortality prediction model and sex, the impact of frailty was no different in patients with and without PerCI (odds ratio = 1.30 [95% confidence interval: 1.14-1.49] vs. (odds ratio = 1.46 [95% confidence interval: 1.29-1.64]). Furthermore, increasing frailty did not influence mortality in patients with PerCI more (or less) than in those without PerCI (pinteraction = 0.82). CONCLUSIONS: The presence of frailty independently predicted hospital mortality in patients with PerCI with COVID-19, but the impact of frailty on mortality was no different in those who developed PerCI from those without PerCI.

An exploration of intensive care nurses' perceptions of workload in providing extracorporeal membrane oxygenation (ECMO) support: A descriptive qualitative study.

BACKGROUND: There is increasing use of extracorporeal membrane oxygenation (ECMO) in intensive care, where nurses provide the majority of the required ongoing care of cannulas, circuit, and console. Limited evidence currently exists that details nursing perspectives, experiences, and challenges with workload in the provision of ECMO care. OBJECTIVE: The objective of this study was to investigate intensive care nurses' perceptions of workload in providing specialist ECMO therapy and care in a high-volume ECMO centre. METHODS: The study used a qualitative descriptive methodology through semistructured interviews. Data were analysed using an inductive thematic analysis approach following Braun and Clarke's iterative process. This study was conducted in an intensive care unit within an Australian public, quaternary, university-affiliated hospital, which provides specialist state-wide service for ECMO. FINDINGS: Thirty ECMO-specialist trained intensive care nurses were interviewed. This study identified three key themes: (i) opportunity; (ii) knowledge and responsibilities; and (iii) systems and structures impacting on intensive care nurses' workload in providing ECMO supportive therapy. CONCLUSIONS: Intensive care nurses require advanced clinical and critical thinking skills. Intensive care nurses are motivated and engaged to learn and acquire ECMO skills and competency as part of their ongoing professional development. Providing bedside ECMO management requires constant monitoring and surveillance from nurses to care for the one of the most critically unwell patient populations in the intensive care unit setting. As such, ECMO nursing services require a suitably trained and educated workforce of intensive care trained nurses. ECMO services provide clinical development opportunities for nurses, increase their scope of practice, and create advanced practice-specialist roles.

Characteristics and Outcomes of Very Elderly Patients Admitted to Intensive Care: A Retrospective Multicenter Cohort Analysis.

OBJECTIVES: To characterize and compare trends in ICU admission, hospital outcomes, and resource utilization for critically ill very elderly patients (≥ 80 yr old) compared with the younger cohort (16-79 yr old). DESIGN: A retrospective multicenter cohort study. SETTING: One-hundred ninety-four ICUs contributing data to the Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation Adult Patient Database between January 2006 and December 2018. PATIENTS: Adult (≥ 16 yr) patients admitted to Australian and New Zealand ICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Very elderly patients with a mean ± sd age of 84.8 ± 3.7 years accounted for 14.8% (232,582/1,568,959) of all adult ICU admissions. They had higher comorbid disease burden and illness severity scores compared with the younger cohort. Hospital (15.4% vs 7.8%, p < 0.001) and ICU mortality (8.5% vs 5.2%, p < 0.001) were higher in the very elderly. They stayed fewer days in ICU, but longer in hospital and had more ICU readmissions. Among survivors, a lower proportion of very elderly was discharged home (65.2% vs 82.4%, p < 0.001), and a higher proportion was discharged to chronic care/nursing home facilities (20.1% vs 7.8%, p < 0.001). Although there was no change in the proportion of very elderly ICU admissions over the study period, they showed a greater decline in risk-adjusted mortality (6.3% [95% CI, 5.9%-6.7%] vs 4.0% [95% CI, 3.7%-4.2%] relative reduction per year, p < 0.001) compared with the younger cohort. The mortality of very elderly unplanned ICU admissions improved faster than the younger cohort ( p < 0.001), whereas improvements in mortality among elective surgical ICU admissions were similar in both groups ( p = 0.45). CONCLUSIONS: The proportion of ICU admissions greater than or equal to 80 years old did not change over the 13-year study period. Although their mortality was higher, they showed improved survivorship over time, especially in the unplanned ICU admission subgroup. A higher proportion of survivors were discharged to chronic care facilities.

Measuring the Impact of ICU Strain on Mortality, After-Hours Discharge, Discharge Delay, Interhospital Transfer, and Readmission in Australia With the Activity Index.

OBJECTIVES: ICU resource strain leads to adverse patient outcomes. Simple, well-validated measures of ICU strain are lacking. Our objective was to assess whether the "Activity index," an indicator developed during the COVID-19 pandemic, was a valid measure of ICU strain. DESIGN: Retrospective national registry-based cohort study. SETTING: One hundred seventy-five public and private hospitals in Australia (June 2020 through March 2022). SUBJECTS: Two hundred seventy-seven thousand seven hundred thirty-seven adult ICU patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data from the Australian and New Zealand Intensive Care Society Adult Patient Database were matched to the Critical Health Resources Information System. The mean daily Activity index of each ICU (census total of "patients with 1:1 nursing" + "invasive ventilation" + "renal replacement" + "extracorporeal membrane oxygenation" + "active COVID-19," divided by total staffed ICU beds) during the patient's stay in the ICU was calculated. Patients were categorized as being in the ICU during very quiet (Activity index < 0.1), quiet (0.1 to < 0.6), intermediate (0.6 to < 1.1), busy (1.1 to < 1.6), or very busy time-periods (≥ 1.6). The primary outcome was in-hospital mortality. Secondary outcomes included after-hours discharge from the ICU, readmission to the ICU, interhospital transfer to another ICU, and delay in discharge from the ICU. Median Activity index was 0.87 (interquartile range, 0.40-1.24). Nineteen thousand one hundred seventy-seven patients died (6.9%). In-hospital mortality ranged from 2.4% during very quiet to 10.9% during very busy time-periods. After adjusting for confounders, being in an ICU during time-periods with higher Activity indices, was associated with an increased risk of in-hospital mortality (odds ratio [OR], 1.49; 99% CI, 1.38-1.60), after-hours discharge (OR, 1.27; 99% CI, 1.21-1.34), readmission (OR, 1.18; 99% CI, 1.09-1.28), interhospital transfer (OR, 1.92; 99% CI, 1.72-2.15), and less delay in ICU discharge (OR, 0.58; 99% CI, 0.55-0.62): findings consistent with ICU strain. CONCLUSIONS: The Activity index is a simple and valid measure that identifies ICUs in which increasing strain leads to progressively worse patient outcomes.

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.

Mortality and costs related to severe acute pancreatitis in the intensive care units of Australia and New Zealand (ANZ), 2003-2020.

BACKGROUND AND OBJECTIVE: Comprehensive data on the burden of severe acute pancreatitis (SAP) in global intensive care units (ICUs) and trends over time are lacking. Our objective was to compare trends in hospital and ICU mortality, in-hospital and ICU length of stay, and costs related to ICU admission in Australia and New Zealand (ANZ) for SAP. METHODS: We performed a retrospective, observational, cohort study of ICU admissions reported to the ANZ Intensive Care Society Adult Patient Database over three consecutive six-year time periods from 2003 to 2020. RESULTS: 12,635 patients with SAP from 189 ICUs in ANZ were analysed. No difference in adjusted hospital mortality (11.4% vs 11.5% vs 11.0%, p = 0.85) and ICU mortality rates (7.5% vs 8.0% vs 8.1%, p = 0.73) were noted over the study period. Median length of hospital admission reduced over time (13.9 days in 2003-08, 13.1 days in 2009-14 and 12.5 days in 2015-20; p < 0.01). No difference in length of ICU stay was noted over the study period (p = 0.13). The cost of managing SAP in ANZ ICUs remained constant over the three time periods. CONCLUSIONS: In critically-ill SAP patients in ANZ, no change in mortality has been noted over nearly two decades. There was a slight reduction in hospital stay (1 day), while the length of ICU stay remained unchanged. Given the significant costs related to care of patients with SAP in ICU, these findings highlight the need to prioritise resource allocation for healthcare delivery and targeted clinical research to identify treatments aimed at reducing mortality.

Improved survival of cirrhotic patients with infections in Australian and New Zealand ICUs between 2005 and 2017.

BACKGROUND & AIMS: Changes in outcomes of cirrhotic patients admitted to intensive care units (ICUs) with infections are poorly understood. We aimed to describe changes over time in outcomes for such patients and to compare them to other ICU admissions. METHODS: Analysis of consecutive admissions to 188 ICUs between 2005 and 2017 as recorded in the Australian and New Zealand Intensive Care Society Centre for Outcome and Research Evaluation Adult Patient Database. RESULTS: Admissions for cirrhotic patients with infections accounted for 4645 (0.6%) of 813 189 non-elective ICU admissions. Hospital mortality rate (35.5%) was significantly higher compared with other cirrhotic patients' admissions (28.5%), and other ICU admissions for infection (17.1%, p < .0001), and increased to 52.2% in the presence of acute-on-chronic liver failure (ACLF). Hospital mortality in cirrhotic patients' ICU admissions for infection decreased significantly over time (annual decline odds ratio, 0.97; 95% CI, 0.95-0.99, p = .002). There was a comparable reduction in-hospital mortality rates over time in other ICU admissions for infections and other cirrhotic patients' ICU admissions. However, mortality rates did not change over time in the ACLF subgroup. Median hospital and ICU length of stays for cirrhotic patients' ICU admissions for infections were 12.1 and 3.5 days, respectively, and decreased significantly by 1 day every 4 years in-hospital survivors(p < .0001). CONCLUSION: Hospital mortality in ICU admissions for cirrhotic patients with infection is double that of non-cirrhotic patients with infection but has declined significantly over time. Outcomes in the subgroup with ACLF remained poor without significant improvement over the study period.

Mortality data from omission of early thromboprophylaxis in critically ill patients highlights the importance of an individualised diagnosis-related approach.

BACKGROUND: Venous thromboembolism (VTE) prophylaxis is effective in reducing VTE events, however, its impact on mortality is unclear. We examined the association between omission of VTE prophylaxis within the first 24 h after intensive care unit (ICU) admission and hospital mortality. METHODS: Retrospective analysis of prospectively collected data from the Australian New Zealand Intensive Care Society Adult Patient Database. Data were obtained for adult admissions between 2009 and 2020. Mixed effects logistic regression models were used to evaluate the association between omission of early VTE prophylaxis and hospital mortality. RESULTS: Of the 1,465,020 ICU admissions, 107,486 (7.3%) did not receive any form of VTE prophylaxis within the first 24 h after ICU admission without documented contraindication. Omission of early VTE prophylaxis was independently associated with 35% increased odds of in-hospital mortality (odds ratios (OR): 1.35; 95% CI: 1.31-1.41). The associations between omission of early VTE prophylaxis and mortality varied by admission diagnosis. In patients diagnosed with stroke (OR: 1.26, 95% CI: 1.05-1.52), cardiac arrest (OR: 1.85, 95% CI: 1.65-2.07) or intracerebral haemorrhage (OR: 1.48, 95% CI: 1.19-1.84), omission of VTE prophylaxis was associated with increased risk of mortality, but not in patients diagnosed with subarachnoid haemorrhage or head injury. CONCLUSIONS: Omission of VTE prophylaxis within the first 24 h after ICU admission was independently associated with increased risk of mortality that varied by admission diagnosis. Consideration of early thromboprophylaxis may be required for patients with stroke, cardiac arrest and intracerebral haemorrhage but not in those with subarachnoid haemorrhage or head injury. The findings highlight the importance of individualised diagnosis-related thromboprophylaxis benefit-harm assessments.

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.

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.

Renin-angiotensin-aldosterone system dynamics after targeted blood pressure control using angiotensin II or norepinephrine in cardiac surgery: mechanistic randomised controlled trial.

BACKGROUND: The role of the renin-angiotensin-aldosterone axis in vasoplegia after cardiac surgery remains unclear. We tested the hypothesis that, compared with norepinephrine, infusion of angiotensin II titrated to achieve similar mean arterial pressure (MAP) would suppress plasma renin concentration (PRC) while maintaining aldosterone levels. METHODS: In a double-blind, randomised controlled trial, subjects received either an infusion of angiotensin II or norepinephrine to maintain MAP 70-80 mm Hg from induction of anaesthesia. We compared PRC, aldosterone, dipeptidyl peptidase-3, and angiotensin-converting enzyme 2 activity between treatment groups, before surgery, on ICU admission, and 24 h after surgery. RESULTS: In 60 patients (11.7% female; mean age 68 yr [11 yr]), norepinephrine increased median PRC at ICU admission (median difference [MD] 46 [inter-quartile range, IQR, 3-88] µU ml-1; P<0.001) but angiotensin II did not (MD -3 [IQR -62 to 35] µU ml-1; P=0.36). Aldosterone levels increased with both. The aldosterone:PRC ratio did not change with norepinephrine (MD -0.01 [IQR -0.14 to 0.03] µU ml-1 per ng dl-1, P=0.76) but increased with angiotensin II (MD 0.05 [IQR 0.004-0.26] µU ml-1 per ng dl-1, P<0.001). The upper quartile of PRC before surgery was associated with higher vasopressor requirements when norepinephrine was used to maintain MAP, but not angiotensin II. Dipeptidyl peptidase-3 levels and angiotensin-converting enzyme 2 activities were similar at all time points. CONCLUSIONS: Angiotensin II suppressed renin release while maintaining aldosterone levels compared with norepinephrine. Higher plasma renin concentration before surgery was associated with greater vasopressor requirement for norepinephrine, but not angiotensin II. CLINICAL TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry-ACTRN12621000195853 23/02/2021.

Sex Differences in Mortality of ICU Patients According to Diagnosis-related Sex Balance.

Rationale: Women have worse outcomes than men in several conditions more common in men, including cardiac surgery and burns. Objectives: To describe the relationship between sex balance within each diagnostic group of ICU admissions, defined as the percentage of patients who were women, and hospital mortality of women compared with men with that same diagnosis. Methods: We studied ICU patients in the Australian and New Zealand Intensive Care Society's Adult Patient Database (2011-2020). We performed mixed effects logistic regression for hospital mortality adjusted for sex, illness severity, ICU lead time, admission year, and hospital site. We compared sex balance with the adjusted hospital mortality of women compared with men for each diagnosis using weighted linear regression. Measurements and Main Results: There were 1,450,782 admissions (42.1% women), with no difference in the adjusted hospital mortality of women compared with men overall (odds ratio, 0.99; 99% confidence interval [CI], 0.97 to 1). As the percentage of women within each diagnosis increased, the adjusted mortality of women compared with men with that same diagnosis decreased (regression coefficient, -0.015; 99% CI; -0.020 to -0.011; P < 0.001), and the illness severity of women compared with men at ICU admission decreased (regression coefficient, -0.0026; 99% CI, -0.0035 to -0.0018; P < 0.001). Conclusions: Sex balance in diagnostic groups was inversely associated with both the adjusted mortality and illness severity of women compared with men. In diagnoses with relatively few women, women were more likely than men to die. In diagnoses with fewer men, men were more likely than women to die.