Stratification of Sepsis Patients on Admission into the Intensive Care Unit According to Differential Plasma Metabolic Phenotypes.

Delayed diagnosis of patients with sepsis or septic shock is associated with increased mortality and morbidity. UPLC-MS and NMR spectroscopy were used to measure panels of lipoproteins, lipids, biogenic amines, amino acids, and tryptophan pathway metabolites in blood plasma samples collected from 152 patients within 48 h of admission into the Intensive Care Unit (ICU) where 62 patients had no sepsis, 71 patients had sepsis, and 19 patients had septic shock. Patients with sepsis or septic shock had higher concentrations of neopterin and lower levels of HDL cholesterol and phospholipid particles in comparison to nonsepsis patients. Septic shock could be differentiated from sepsis patients based on different concentrations of 10 lipids, including significantly lower concentrations of five phosphatidylcholine species, three cholesterol esters, one dihydroceramide, and one phosphatidylethanolamine. The Supramolecular Phospholipid Composite (SPC) was reduced in all ICU patients, while the composite markers of acute phase glycoproteins were increased in the sepsis and septic shock patients within 48 h admission into ICU. We show that the plasma metabolic phenotype obtained within 48 h of ICU admission is diagnostic for the presence of sepsis and that septic shock can be differentiated from sepsis based on the lipid profile.

Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19.

BACKGROUND: The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. METHODS: We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control). The primary outcome was respiratory and cardiovascular organ support-free days, on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support to day 21. The trial uses a Bayesian statistical model with predefined criteria for superiority, efficacy, equivalence, or futility. An odds ratio greater than 1 represented improved survival, more organ support-free days, or both. RESULTS: Both tocilizumab and sarilumab met the predefined criteria for efficacy. At that time, 353 patients had been assigned to tocilizumab, 48 to sarilumab, and 402 to control. The median number of organ support-free days was 10 (interquartile range, -1 to 16) in the tocilizumab group, 11 (interquartile range, 0 to 16) in the sarilumab group, and 0 (interquartile range, -1 to 15) in the control group. The median adjusted cumulative odds ratios were 1.64 (95% credible interval, 1.25 to 2.14) for tocilizumab and 1.76 (95% credible interval, 1.17 to 2.91) for sarilumab as compared with control, yielding posterior probabilities of superiority to control of more than 99.9% and of 99.5%, respectively. An analysis of 90-day survival showed improved survival in the pooled interleukin-6 receptor antagonist groups, yielding a hazard ratio for the comparison with the control group of 1.61 (95% credible interval, 1.25 to 2.08) and a posterior probability of superiority of more than 99.9%. All secondary analyses supported efficacy of these interleukin-6 receptor antagonists. CONCLUSIONS: In critically ill patients with Covid-19 receiving organ support in ICUs, treatment with the interleukin-6 receptor antagonists tocilizumab and sarilumab improved outcomes, including survival. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.).

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.

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.

Long-Term Echocardiographic and Clinical Outcomes After Invasive and Non-Invasive Therapies for Sub-Massive and Massive Acute Pulmonary Embolism.

AIM: Acute pulmonary embolism (PE) is a significant cause of mortality in the hospital setting. The objective of this study was to outline the long-term outcomes after surgical and non-surgical management for patients with massive and submassive PE. METHODS: Population cohort observational study evaluating all patients who presented to three tertiary hospitals in the state of Western Australia with access to cardiothoracic services over 5 years (2013-2018). Reviewed notes of all patients as well as radiology, linked mortality data and all available echocardiography studies at the primary hospital. RESULTS: In total, 245 patients were identified, of which 41 received surgical management and 204 non-surgical management; demographic data was similar. Clinically, the surgical group had higher rates of shock requiring vasopressors, severe bradycardia, or cardiopulmonary resuscitation prior to intervention. The 28-day mortality was not statistically significantly different between the surgical embolectomy group (2/41 [4.2%]) and the non-surgical group (17/201 [8.3%]) (p=0.382). There was no difference in 12-month mortality, including when this was adjusted for vasopressors, right ventricular (RV) strain, troponin, and brain natriuretic peptide. In the massive PE sub-group, 28-day mortality was not significantly different: 2/29 (6.9%) surgical group vs 7/34 (20.2%) non-surgical group (p=0.064). Higher rates of severe RV impairment and dilatation were present in the surgical group. All patients with available echocardiography studies at outpatient follow-up returned to normal or mild RV impairment. CONCLUSION: Patients who presented with massive or submassive PE had similar outcomes whether treated with surgical or non-surgical management. Surgical embolectomy is a safe option in a cardiothoracic centre setting.

Conservative Oxygen Therapy during Mechanical Ventilation in the ICU.

BACKGROUND: Patients who are undergoing mechanical ventilation in the intensive care unit (ICU) often receive a high fraction of inspired oxygen (Fio2) and have a high arterial oxygen tension. The conservative use of oxygen may reduce oxygen exposure, diminish lung and systemic oxidative injury, and thereby increase the number of ventilator-free days (days alive and free from mechanical ventilation). METHODS: We randomly assigned 1000 adult patients who were anticipated to require mechanical ventilation beyond the day after recruitment in the ICU to receive conservative or usual oxygen therapy. In the two groups, the default lower limit for oxygen saturation as measured by pulse oximetry (Spo2) was 90%. In the conservative-oxygen group, the upper limit of the Spo2 alarm was set to sound when the level reached 97%, and the Fio2 was decreased to 0.21 if the Spo2 was above the acceptable lower limit. In the usual-oxygen group, there were no specific measures limiting the Fio2 or the Spo2. The primary outcome was the number of ventilator-free days from randomization until day 28. RESULTS: The number of ventilator-free days did not differ significantly between the conservative-oxygen group and the usual-oxygen group, with a median duration of 21.3 days (interquartile range, 0 to 26.3) and 22.1 days (interquartile range, 0 to 26.2), respectively, for an absolute difference of -0.3 days (95% confidence interval [CI], -2.1 to 1.6; P = 0.80). The conservative-oxygen group spent more time in the ICU with an Fio2 of 0.21 than the usual-oxygen group, with a median duration of 29 hours (interquartile range, 5 to 78) and 1 hour (interquartile range, 0 to 17), respectively (absolute difference, 28 hours; 95% CI, 22 to 34); the conservative-oxygen group spent less time with an Spo2 exceeding 96%, with a duration of 27 hours (interquartile range, 11 to 63.5) and 49 hours (interquartile range, 22 to 112), respectively (absolute difference, 22 hours; 95% CI, 14 to 30). At 180 days, mortality was 35.7% in the conservative-oxygen group and 34.5% in the usual-oxygen group, for an unadjusted odds ratio of 1.05 (95% CI, 0.81 to 1.37). CONCLUSIONS: In adults undergoing mechanical ventilation in the ICU, the use of conservative oxygen therapy, as compared with usual oxygen therapy, did not significantly affect the number of ventilator-free days. (Funded by the Health Research Council of New Zealand; ICU-ROX Australian and New Zealand Clinical Trials Registry number, ACTRN12615000957594.).

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.

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.

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 accuracy of simple, feasible alternatives to polysomnography for assessing sleep in intensive care: An observational study.

BACKGROUND: Sleep disturbance is common in intensive care patients. Understanding the accuracy of simple, feasible sleep measurement techniques is essential to informing their possible role in usual clinical care. OBJECTIVE: The aim of the study was to investigate whether sleep monitoring techniques such as actigraphy (ACTG), behavioural assessments, and patient surveys are comparable with polysomnography (PSG) in accurately reporting sleep quantity and quality among conscious, intensive care patients. METHODS: An observational study was conducted in 20 patients admitted to the intensive care unit (ICU) for a minimum duration of 24 h, who underwent concurrent sleep monitoring via PSG, ACTG, nursing-based observations, and self-reported assessment using the Richards-Campbell Sleep Questionnaire. RESULTS: The reported total sleep time (TST) for the 20 participants measured by PSG was 328.2 min (±106 min) compared with ACTG (362.4 min [±62.1 min]; mean difference = 34.22 min [±129 min]). Bland-Altman analysis indicated that PSG and ACTG demonstrated clinical agreement and did not perform differently across a number of sleep variables including TST, awakening, sleep-onset latency, and sleep efficiency. Nursing observations overestimated sleep duration compared to PSG TST (mean difference = 9.95 ± 136.3 min, p > 0.05), and patient-reported TST was underestimated compared to PSG TST (mean difference = -51.81 ± 144.1 7, p > 0.05). CONCLUSIONS: Amongst conscious patients treated in the ICU, sleep characteristics measured by ACTG were similar to those measured by PSG. ACTG may provide a clinically feasible and acceptable proxy approach to sleep monitoring in conscious ICU patients.

Economic evaluations for intensive care unit randomised clinical trials in Australia and New Zealand: Practical recommendations for researchers.

OBJECTIVES: Economic evaluations of intensive care unit (ICU) interventions have specific considerations, including how to cost ICU stays and accurately measure quality of life in survivors. The aim of this article was to develop best practice recommendations for economic evaluations alongside future ICU randomised controlled trials (RCTs). REVIEW METHODS: We collated our experience based on expert consensus across several recent economic evaluations to provide best-practice, practical recommendations for researchers conducting economic evaluations alongside RCTs in the ICU. Recommendations were structured according to the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Consolidated Health Economic Evaluation Reporting Standards (CHEERS) Task Force Report. RESULTS: We discuss recommendations across the components of economic evaluations, including: types of economic evaluation, the population and sample size, study perspective, comparators, time horizon, choice of health outcomes, measurement of effectiveness, measurement and valuation of quality of life, estimating resources and costs, analytical methods, and the increment cost-effectiveness ratio. We also provide future directions for research with regard to developing more robust economic evaluations for the ICU. CONCLUSION: Economic evaluations should be built alongside ICU RCTs and should be designed a priori using appropriate follow-up and data collection to capture patient-relevant outcomes. Further work is needed to improve the quality of data available for linkage in Australia as well as developing costing methods for the ICU and appropriate quality of life measurements.

The relationship between nursing skill mix and severity of illness of patients admitted in Australian and New Zealand intensive care units.

BACKGROUND: Critically ill patients in the intensive care environment require an appropriate nursing workforce to improve quality of care and patient outcomes. However, limited information exists as to the relationship between severity of illness and nursing skill mix in the intensive care. OBJECTIVE: The aim of this study was to describe the variation in nursing skill mix across different hospital types and to determine if this was associated with severity of illness of critically ill patients admitted to adult intensive care units (ICUs) in Australia and New Zealand. DESIGN & SETTING: A retrospective cohort study using the Australia and New Zealand Intensive Care Society Adult Patient Database (to provide information on patient demographics, severity of illness, and outcome) and the Critical Care Resources Registry (to provide information on annual nursing staffing levels and hospital type) from July 2014 to June 2020. Four hospital types (metropolitan, private, rural/regional, and tertiary) and three patient groups (elective surgical, emergency surgical, and medical) were examined. MAIN OUTCOME MEASURE: The main outcome measure was the proportion of critical care specialist registered nurses (RNs) expressed as a percentage of the full-time equivalent (FTE) of total RNs working within each ICU each year, as reported annually to the Critical Care Resources Registry. RESULTS: Data were examined for 184 ICUs in Australia and New Zealand. During the 6-year study period, 770 747 patients were admitted to these ICUs. Across Australia and New Zealand, the median percentage of registered nursing FTE with a critical care qualification for each ICU (n = 184) was 59.1% (interquartile range [IQR] = 48.9-71.6). The percentage FTE of critical care specialist RNs was highest in private [63.7% (IQR = 52.6-78.2)] and tertiary ICUs [58.1% (IQR = 51.2-70.2)], followed by metropolitan ICUs [56.0% (IQR = 44.5-68.9)] with the lowest in rural/regional hospitals [55.9% (IQR = 44.9-70.0)]. In ICUs with higher percentage FTE of critical care specialist RNs, patients had higher severity of illness, most notably in tertiary and private ICUs. This relationship was persistent across all hospital types when examining subgroups of emergency surgical and medical patients and in multivariable analysis after adjusting for the type of hospital and relative percentage of each diagnostic group. CONCLUSIONS: In Australian and New Zealand ICUs, the highest acuity patients are cared for by nursing teams with the highest percentage FTE of critical care specialist RNs. The Australian and New Zealand healthcare system has a critical care nursing workforce which scales to meet the acuity of ICU patients across Australia and New Zealand.

Variation in Bed-to-Physician Ratios During Weekday Daytime Hours in ICUs in Australia and New Zealand.

OBJECTIVES: To determine common "bed-to-physician" ratios during weekday hours across ICUs and assess factors associated with variability in this ratio. DESIGN: Retrospective cohort study. SETTING: All ICUs in Australia/New Zealand that participated in a staffing survey administered in 2017-2018. PATIENTS: ICU admissions from 2016 to 2018. METHODS: We linked survey data with patient-level data. We defined: 1) bed-to-intensivist ratio as the number of usually available ICU beds divided by the number of onsite weekday daytime intensivists; and 2) bed-to-physician ratio as the number of available ICU beds divided by the total number of physicians (intensivists + nonintensivists, including trainees). We calculated the median and interquartile range (IQR) of bed-to-intensivist ratio and bed-to-physician ratios during weekday hours. We assessed variability in each by type of hospital and ICU and by severity of illness of patients, defined by the predicted hospital mortality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 123 (87.2%) of Australia/New Zealand ICUs that returned staffing surveys, 114 (92.7%) had an intensivist present during weekday daytime hours, and 116 (94.3%) reported at least one nonintensivist physician. The median bed-to-intensivist ratio was 8.0 (IQR, 6.0-11.4), which decreased to a bed-to-physician ratio of 3.0 (IQR, 2.2-4.9). These ratios varied with mean severity of illness of the patients in the unit. The median bed-to-intensivist ratio was highest (13.5) for ICUs with a mean predicted mortality > 2-4%, and the median bed-to-physician ratio was highest (5.7) for ICUs with a mean predicted mortality of > 4-6%. Both ratios decreased and plateaued in ICUs with a mean predicted mortality for patients greater than 8% (median bed-to-intensivist ratio range, 6.8-8.0, and bed-to-physician ratio range of 2.4-2.7). CONCLUSIONS: Weekday bed-to-physician ratios in Australia/New Zealand ICUs are lower than the bed-to-intensivist ratios and have a relatively fixed ratio of less than 3 for units taking care of patients with a higher average severity of illness. These relationships may be different in other countries or healthcare systems.

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.

Effect of Antiplatelet Therapy on Survival and Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial.

Importance: The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain. Objective: To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19. Design, Setting, and Participants: In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19 were enrolled between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days (final follow-up date: July 26, 2021). Interventions: Patients were randomized to receive either open-label aspirin (n = 565), a P2Y12 inhibitor (n = 455), or no antiplatelet therapy (control; n = 529). Interventions were continued in the hospital for a maximum of 14 days and were in addition to anticoagulation thromboprophylaxis. Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of intensive care unit-based respiratory or cardiovascular organ support) within 21 days, ranging from -1 for any death in hospital (censored at 90 days) to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented improved survival, more organ support-free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions. Results: The aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespecified criterion for futility was met for the pooled antiplatelet group compared with control. Among the 1557 critically ill patients randomized, 8 patients withdrew consent and 1549 completed the trial (median age, 57 years; 521 [33.6%] female). The median for organ support-free days was 7 (IQR, -1 to 16) in both the antiplatelet and control groups (median-adjusted OR, 1.02 [95% credible interval {CrI}, 0.86-1.23]; 95.7% posterior probability of futility). The proportions of patients surviving to hospital discharge were 71.5% (723/1011) and 67.9% (354/521) in the antiplatelet and control groups, respectively (median-adjusted OR, 1.27 [95% CrI, 0.99-1.62]; adjusted absolute difference, 5% [95% CrI, -0.2% to 9.5%]; 97% posterior probability of efficacy). Among survivors, the median for organ support-free days was 14 in both groups. Major bleeding occurred in 2.1% and 0.4% of patients in the antiplatelet and control groups (adjusted OR, 2.97 [95% CrI, 1.23-8.28]; adjusted absolute risk increase, 0.8% [95% CrI, 0.1%-2.7%]; 99.4% probability of harm). Conclusions and Relevance: Among critically ill patients with COVID-19, treatment with an antiplatelet agent, compared with no antiplatelet agent, had a low likelihood of providing improvement in the number of organ support-free days within 21 days. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707.

Molecular Methodologies for Improved Polymicrobial Sepsis Diagnosis.

Polymicrobial sepsis is associated with worse patient outcomes than monomicrobial sepsis. Routinely used culture-dependent microbiological diagnostic techniques have low sensitivity, often leading to missed identification of all causative organisms. To overcome these limitations, culture-independent methods incorporating advanced molecular technologies have recently been explored. However, contamination, assay inhibition and interference from host DNA are issues that must be addressed before these methods can be relied on for routine clinical use. While the host component of the complex sepsis host-pathogen interplay is well described, less is known about the pathogen's role, including pathogen-pathogen interactions in polymicrobial sepsis. This review highlights the clinical significance of polymicrobial sepsis and addresses how promising alternative molecular microbiology methods can be improved to detect polymicrobial infections. It also discusses how the application of shotgun metagenomics can be used to uncover pathogen/pathogen interactions in polymicrobial sepsis cases and their potential role in the clinical course of this condition.

Family visitation policies, facilities, and support in Australia and New Zealand intensive care units: A multicentre, registry-linked survey.

OBJECTIVE: The objective of this study was to describe family visitation policies, facilities, and support in Australia and New Zealand (ANZ) intensive care units (ICUs). METHODS: A survey was distributed to all Australian and New Zealand ICUs reporting to the Australian and New Zealand Intensive Care Society Centre for Outcomes and Resources Evaluation Critical Care Resources (CCR) Registry in 2018. Data were obtained from the survey and from data reported to the CCR Registry. For this study, open visiting (OV) was defined as allowing visitors for more than 14 h per day. SETTING AND PARTICIPANTS: This study included all Australian and New Zealand ICUs reporting to CCR in 2018. MAIN OUTCOME MEASURES: The main outcome measures were family access to the ICU and visiting hours, characteristics of the ICU waiting area, and information provided to and collected from the relatives. FINDINGS: Fifty-six percent (95/170) of ICUs contributing to CCR responded, representing 44% of ANZ ICUs and a range of rural, metropolitan, tertiary, and private ICUs. Visiting hours ranged from 1.5 to 24 h per day, with 68 (72%) respondent ICUs reporting an OV policy, of which 64 (67%) ICUs were open to visitors 24 h a day. A waiting room was part of the ICU for 77 (81%) respondent ICUs, 74 (78%) reported a separate dedicated room for family meetings, and 83 (87%) reported available social worker services. Most ICUs reported facilities for sleeping within or near the hospital. An information booklet was provided by 64 (67%) ICUs. Only six (6%) ICUs required personal protective equipment for all visitors, and 76 (80%) required personal protective equipment for patients with airborne precautions. CONCLUSIONS: In 2018, the majority of ANZ ICUs reported liberal visiting policies, with substantial facilities and family support.

Staff perceptions of family access and visitation policies in Australian and New Zealand intensive care units: The WELCOME-ICU survey.

BACKGROUND: Family-centred critical care recognises the impact of a loved one's critical illness on his relatives. Open visiting is a strategy to improve family satisfaction and psychological outcomes by permitting unrestricted or less restricted access to visit their family member in the intensive care unit (ICU). However, increased family presence may result in increased workload and a risk of burnout for ICU staff. OBJECTIVES: The objective of this study was to evaluate ICU staff perceptions regarding visiting hours and family access in Australian and New Zealand ICUs. Secondary outcomes included an evaluation of current visiting policies, witnessed events in ICUs, and barriers to implementing open visiting policies. DESIGN: A web-based survey open to all healthcare workers in Australia and New Zealand ICUs was distributed through local, state-based, and national critical care networks. Open visiting was defined as ICUs open for visiting >14 h per day. MAIN RESULTS: We received 1255 valid responses. Most respondents were nurses (n = 930, 74.1%) with a median critical care experience of 10 y. Most worked in open visiting ICUs (n = 749, 59.7%). Reported visiting hours varied greatly with a median of 20 h per day (interquartile range: 10-24 h). Open visiting was perceived as beneficial for the relatives, but less so for patients and staff (relatives: n = 845, 67.3%, patients: n = 561, 44.7%, staff: n = 257, 20.5%, p < 0.0001). Respondents from closed visiting units and nurses identified more risks from open visiting than other professional groups. Generally, staff preferred not to change from their current practice. CONCLUSION: We report that staff perceived open visiting as beneficial for relatives, but also identified risks to themselves, including increased workload, a risk of burnout, and a risk of occupational violence. Reluctance to change highlights the importance of addressing staff perceptions when implementing an open visiting policy.

Infection management processes in intensive care and their association with mortality.

BACKGROUND: ICU-specific tables of antimicrobial susceptibility for key microbial species ('antibiograms'), antimicrobial stewardship (AMS) programmes and routine rounds by infectious diseases (ID) physicians are processes aimed at improving patient care. Their impact on patient-centred outcomes in Australian and New Zealand ICUs is uncertain. OBJECTIVES: To measure the association of these processes in ICU with in-hospital mortality. METHODS: The Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database and Critical Care Resources registry were used to extract patient-level factors, ICU-level factors and the year in which each process took place. Descriptive statistics and hierarchical logistic regression were used to determine the relationship between each process and in-hospital mortality. RESULTS: The study included 799 901 adults admitted to 173 ICUs from July 2009 to June 2016. The proportion of patients exposed to each process of care was 38.7% (antibiograms), 77.5% (AMS programmes) and 74.0% (ID rounds). After adjusting for confounders, patients admitted to ICUs that used ICU-specific antibiograms had a lower risk of in-hospital mortality [OR 0.95 (99% CI 0.92-0.99), P = 0.001]. There was no association between the use of AMS programmes [OR 0.98 (99% CI 0.94-1.02), P = 0.16] or routine rounds with ID physicians [OR 0.96 (99% CI 0.09-1.02), P = 0.09] and in-hospital mortality. CONCLUSIONS: Use of ICU-specific antibiograms was associated with lower in-hospital mortality for patients admitted to ICU. For hospitals that do not perform ICU-specific antibiograms, their implementation presents a low-risk infection management process that might improve patient outcomes.

Intensive care doctors and nurses personal preferences for Intensive Care, as compared to the general population: a discrete choice experiment.

BACKGROUND: To test the hypothesis that Intensive Care Unit (ICU) doctors and nurses differ in their personal preferences for treatment from the general population, and whether doctors and nurses make different choices when thinking about themselves, as compared to when they are treating a patient. METHODS: Cross sectional, observational study conducted in 13 ICUs in Australia in 2017 using a discrete choice experiment survey. Respondents completed a series of choice sets, based on hypothetical situations which varied in the severity or likelihood of: death, cognitive impairment, need for prolonged treatment, need for assistance with care or requiring residential care. RESULTS: A total of 980 ICU staff (233 doctors and 747 nurses) participated in the study. ICU staff place the highest value on avoiding ending up in a dependent state. The ICU staff were more likely to choose to discontinue therapy when the prognosis was worse, compared with the general population. There was consensus between ICU staff personal views and the treatment pathway likely to be followed in 69% of the choices considered by nurses and 70% of those faced by doctors. In 27% (1614/5945 responses) of the nurses and 23% of the doctors (435/1870 responses), they felt that aggressive treatment would be continued for the hypothetical patient but they would not want that for themselves. CONCLUSION: The likelihood of returning to independence (or not requiring care assistance) was reported as the most important factor for ICU staff (and the general population) in deciding whether to receive ongoing treatments. Goals of care discussions should focus on this, over likelihood of survival.