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Purpose: Critically ill patients are vulnerable to penicillin allergy labels that may be incorrect. The validity of skin testing in intensive care units (ICUs) is uncertain. Many penicillin allergy labels are low risk, and validated tools exist to identify those amenable to direct oral challenge. This pilot randomised controlled trial explored the feasibility, safety, and validity of direct enteral challenge for low-risk penicillin allergy labels in critical illness., Methods: Consenting patients with a low-risk penicillin allergy label (PAL) (PEN-FAST risk assessment score < 3) in four ICUs (Melbourne, Australia) were randomised 1:1 to penicillin (250 mg amoxicillin or implicated penicillin) direct enteral challenge versus routine care (2-h post-randomisation observation for each arm). Repeat challenge was performed post -ICU in the intervention arm. Patients were reviewed at 24 h and 5 days after each challenge/observation., Results: We screened 533 patients. 130 (24.4%) were eligible and 80/130 (61.5%) enrolled (age median 64.5 years (interquartile range, IQR 53.5, 74), PEN-FAST median 1 (IQR 0,1)), with 40 (50%) randomised to direct enteral challenge. A positive challenge rate of 2.5% was identified. No antibiotic-associated serious adverse events were identified. 32/40 (80%) received a repeat challenge (zero positive). Post-randomisation, 13 (32%) of the intervention arm and 4 (10%) of the control arm received penicillin (odds ratio, OR 4.33 [1.27, 14.78] p = 0.019)., Conclusion: These findings support the safety, validity, and feasibility of direct enteral challenge for critically ill patients with PEN-FAST assessed low-risk penicillin allergy. The absence of false negative results was confirmed by subsequent negative repeat challenges. A relatively low recruitment to screened ratio suggests that more inclusive eligibility criteria and integration of allergy assessment into routine ICU processes are needed to optimise allergy delabelling in critical illness., (© 2024. The Author(s).)

Background: Patient sex affects treatment and outcomes in critical illness. Previous studies of sex differences in critical illness compared female and male patients. In this study, we describe the group of patients classified as a third sex admitted to ICUs in Australia and New Zealand., Research Question: What are the admission characteristics and outcomes of ICU patients classified as belonging to a third sex group compared with patients classified as female or male?, Study Design and Methods: Retrospective observational study of admissions to 200 ICUs, recorded in the Australian and New Zealand Intensive Care Society's Adult Patient Database from 2018 to 2022. We undertook mixed effect logistic regression to compare hospital mortality across the sex groups, adjusted for illness severity, diagnosis, treatment limitation, year, and hospital., Results: We examined 892,161 admissions, of whom 525 (0.06%) were classified as third sex. Patients classified as third sex were represented across all diagnostic categories, jurisdictions, and hospital types. On average, they were younger than the groups classified as female (59.2 ± 20.0 vs 61.3 ± 18.4 years; P = .02) or male (63.2 ± 16.7 years; P < .001), respectively. Patients classified as third sex were more likely to be admitted after orthopedic surgery (10.1% third sex admissions [95% CI, 7.7%-13.0%]; 6.2% female [95% CI, 6.1%-6.3%]; 4.8% male [95% CI, 4.7%-4.9%]) and drug overdose (8.8% third sex admissions [95% CI, 6.5%-11.5%]; 4.2% female [95% CI, 4.1%-4.2%]; 3.1% male [95% CI, 3.0%-3.1%]). There was no difference in the adjusted hospital mortality of patients classified as third sex compared with the other groups., Interpretation: Patients classified as third sex composed a small minority group of adult ICU patients. This group had a different diagnostic case mix but similar outcomes to the groups classified as female or male. Further characterizing a third sex group will require improved processes for recording sex and gender in health records., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: L. J. M. is a member of the Women in Intensive Care Medicine Network (WIN-ANZICS). M. N. C. is Executive Director of Intersex Human Rights Australia, a signatory to the Darlington Statement and a member of the Australian Bureau of Statistics Reference Group for the standard on sex, gender, variations of sex characteristics, and sexual orientation. M. N. C. is also a member of the New South Wales Ministry of Health, Australia, reference group on sex and gender. None declared (A. M. H., D. V. P., A. S. C., M. B., S. Z., R. B.)., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: A positive fluid balance (FB) is associated with harm in intensive care unit (ICU) patients with acute kidney injury (AKI). We aimed to understand how a positive balance develops in such patients., Methods: Multinational, retrospective cohort study of critically ill patients with AKI not requiring renal replacement therapy., Results: AKI occurred at a median of two days after admission in 7894 (17.3%) patients. Cumulative FB became progressively positive, peaking on day three despite only 848 (10.7%) patients receiving fluid resuscitation in the ICU. In those three days, persistent crystalloid use (median:60.0 mL/h; IQR 28.9-89.2), nutritional intake (median:18.2 mL/h; IQR 0.0-45.9) and limited urine output (UO) (median:70.8 mL/h; IQR 49.0-96.7) contributed to a positive FB. Although UO increased each day, it failed to match input, with only 797 (10.1%) patients receiving diuretics in ICU. After adjustment, a positive FB four days after AKI diagnosis was associated with an increased risk of hospital mortality (OR 1.12;95% confidence intervals 1.05-1.19;p-value <0.001)., Conclusion: Among ICU patients with AKI, cumulative FB increased after diagnosis and was associated with an increased risk of mortality. Continued crystalloid administration, increased nutritional intake, limited UO, and minimal use of diuretics all contributed to positive FB., Key Points: Question How does a positive fluid balance develop in critically ill patients with acute kidney injury? Findings Cumulative FB increased after AKI diagnosis and was secondary to persistent crystalloid fluid administration, increasing nutritional fluid intake, and insufficient urine output. Despite the absence of resuscitation fluid and an increasing cumulative FB, there was persistently low diuretics use, ongoing crystalloid use, and a progressive escalation of nutritional fluid therapy. Meaning Current management results in fluid accumulation after diagnosis of AKI, as a result of ongoing crystalloid administration, increasing nutritional fluid, limited urine output and minimal diuretic use., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To perform a post-hoc reanalysis of the Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) and the Intensity of Continuous Renal-Replacement Therapy in Critically Ill Patients (RENAL) trials through hierarchical composite endpoint analysis using win ratio (WR)., Material and Methods: All patients with complete information from the STARRT-AKI (which compared accelerated versus standard approaches for renal replacement therapy - RRT initiation) and RENAL (which compared two different RRT doses in critically ill patients) trials were selected. WR was defined as a hierarchical composite endpoint using 90-day mortality, RRT dependency at 90-days, intensive care unit (ICU) length-of-stay (LOS), and hospital LOS (primary analysis); values above the unit represent a benefit of the intervention for the hierarchical composite endpoint. A secondary analysis replacing LOS by days alive and free of RRT was performed. Stratified analyses were performed according to illness severity score, surgical status, and the presence of sepsis., Results: The WR analysis produced 2,141,830 pairs for the STARRT-AKI trial and 536,446 pairs for the RENAL trial, respectively. The WR results for STARRT-AKI and RENAL were 1.04 (95% confidence interval [CI] 0.96-1.13; p = 0.33) and 1.02 (95% CI; 0.90-1.15; p = 0.75) for the primary analysis, and 0.88 (95% CI; 0.79-0.99; p = 0.03) and 1.02 (95% CI; 0.87-1.21; p = 0.77) for the secondary analysis, respectively. The stratified analysis of the primary suggested possible benefit of the accelerated-strategy in the STARRT-AKI trial for non-surgical patients with sepsis, while the secondary analysis suggested possible harm of the accelerated-strategy for surgical patients without sepsis. There was no evidence of heterogeneity in treatment effects in stratified analyses in the RENAL trial., Conclusion: WR approach using a hierarchical composite endpoint is feasible for trials in critical care nephrology. The primary re-analyses of the STARRT-AKI and RENAL trials both yielded neutral results; however, there was suggestion of heterogeneity in treatment effect in stratified analyses of the STARRT-AKI trial by surgical status and sepsis. Selection of the endpoints and hierarchical ordering before trial design using the WR approach can have important implications for trial interpretation., Trial Registry: ClinicalTrials.gov number NCT02568722 (STARRT-AKI) and NCT00076219 (RENAL)., Competing Interests: Declaration of competing interest FGZ has received grants for investigator-initiated trials from Bactiguard (Sweden), and Ionis Pharmaceuticals (USA), unrelated to the topic of this study. RB has received honoraria and grants from Baxter. SMB has received fees from Baxter for scientific advisory and speaking; fees from BioPorto, Novartis, Sea Star Medical and SphingoTec for scientific advisory., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Among patients with severe acute kidney injury (AKI) admitted to the ICU in high-income countries, regional practice variations for fluid balance (FB) management, timing, and choice of renal replacement therapy (RRT) modality may be significant., Design: Secondary post hoc analysis of the STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial (ClinicalTrials.gov number NCT02568722)., Setting: One hundred-fifty-three ICUs in 13 countries., Patients: Altogether 2693 critically ill patients with AKI, of whom 994 were North American, 1143 European, and 556 from Australia and New Zealand (ANZ)., Interventions: None., Measurements and Main Results: Total mean FB to a maximum of 14 days was +7199 mL in North America, +5641 mL in Europe, and +2211 mL in ANZ ( p < 0.001). The median time to RRT initiation among patients allocated to the standard strategy was longest in Europe compared with North America and ANZ ( p < 0.001; p < 0.001). Continuous RRT was the initial RRT modality in 60.8% of patients in North America and 56.8% of patients in Europe, compared with 96.4% of patients in ANZ ( p < 0.001). After adjustment for predefined baseline characteristics, compared with North American and European patients, those in ANZ were more likely to survive to ICU ( p < 0.001) and hospital discharge ( p < 0.001) and to 90 days (for ANZ vs. Europe: risk difference [RD], -11.3%; 95% CI, -17.7% to -4.8%; p < 0.001 and for ANZ vs. North America: RD, -10.3%; 95% CI, -17.5% to -3.1%; p = 0.007)., Conclusions: Among STARRT-AKI trial centers, significant regional practice variation exists regarding FB, timing of initiation of RRT, and initial use of continuous RRT. After adjustment, such practice variation was associated with lower ICU and hospital stay and 90-day mortality among ANZ patients compared with other regions., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

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., Competing Interests: Dr. Modra received funding from the Graeme Clark Institute of the University of Melbourne-Women in Science Technology and Mathematics Award, and the Australia and New Zealand Intensive Care Society-Peter Hicks Fellowship Award; she disclosed that she is a member of the Women in Intensive Care Medicine Network of the Australia and New Zealand Intensive Care Society. Dr Higgins received funding from a National Health and Medical Research Council Emerging Leader Fellowship (Grant #2008447). The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Purpose: The incidence, patient features, risk factors and outcomes of surgery-associated postoperative acute kidney injury (PO-AKI) across different countries and health care systems is unclear., Methods: We conducted an international prospective, observational, multi-center study in 30 countries in patients undergoing major surgery (> 2-h duration and postoperative intensive care unit (ICU) or high dependency unit admission). The primary endpoint was the occurrence of PO-AKI within 72 h of surgery defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Secondary endpoints included PO-AKI severity and duration, use of renal replacement therapy (RRT), mortality, and ICU and hospital length of stay., Results: We studied 10,568 patients and 1945 (18.4%) developed PO-AKI (1236 (63.5%) KDIGO stage 1500 (25.7%) KDIGO stage 2209 (10.7%) KDIGO stage 3). In 33.8% PO-AKI was persistent, and 170/1945 (8.7%) of patients with PO-AKI received RRT in the ICU. Patients with PO-AKI had greater ICU (6.3% vs. 0.7%) and hospital (8.6% vs. 1.4%) mortality, and longer ICU (median 2 (Q1-Q3, 1-3) days vs. 3 (Q1-Q3, 1-6) days) and hospital length of stay (median 14 (Q1-Q3, 9-24) days vs. 10 (Q1-Q3, 7-17) days). Risk factors for PO-AKI included older age, comorbidities (hypertension, diabetes, chronic kidney disease), type, duration and urgency of surgery as well as intraoperative vasopressors, and aminoglycosides administration., Conclusion: In a comprehensive multinational study, approximately one in five patients develop PO-AKI after major surgery. Increasing severity of PO-AKI is associated with a progressive increase in adverse outcomes. Our findings indicate that PO-AKI represents a significant burden for health care worldwide., (© 2023. The Author(s).)

Background: Natural language processing (NLP) may help evaluate the characteristics, prevalence, trajectory, treatment, and outcomes of behavioural disturbance phenotypes in critically ill patients., Methods: We obtained electronic clinical notes, demographic information, outcomes, and treatment data from three medical-surgical ICUs. Using NLP, we screened for behavioural disturbance phenotypes based on words suggestive of an agitated state, a non-agitated state, or a combination of both., Results: We studied 2931 patients. Of these, 225 (7.7%) were NLP-Dx-BD positive for the agitated phenotype, 544 (18.6%) for the non-agitated phenotype and 667 (22.7%) for the combined phenotype. Patients with these phenotypes carried multiple clinical baseline differences. On time-dependent multivariable analysis to compensate for immortal time bias and after adjustment for key outcome predictors, agitated phenotype patients were more likely to receive antipsychotic medications (odds ratio [OR] 1.84, 1.35-2.51, p < 0.001) compared to non-agitated phenotype patients but not compared to combined phenotype patients (OR 1.27, 0.86-1.89, p = 0.229). Moreover, agitated phenotype patients were more likely to die than other phenotypes patients (OR 1.57, 1.10-2.25, p = 0.012 vs non-agitated phenotype; OR 4.61, 2.14-9.90, p < 0.001 vs. combined phenotype). This association was strongest in patients receiving mechanical ventilation when compared with the combined phenotype (OR 7.03, 2.07-23.79, p = 0.002). A similar increased risk was also seen for patients with the non-agitated phenotype compared with the combined phenotype (OR 6.10, 1.80-20.64, p = 0.004)., Conclusions: NLP-Dx-BD screening enabled identification of three behavioural disturbance phenotypes with different characteristics, prevalence, trajectory, treatment, and outcome. Such phenotype identification appears relevant to prognostication and trial design., (© 2023. The Author(s).)

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., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Aims: A robust climate-health projection model has the potential to improve health care resource allocation. We aim to explore the relationship between Australian intensive care unit (ICU) demand and various measures of the long-lived large-scale climate and to develop a future nationwide climate-health projection model., Methods: We investigated patients admitted to ICUs in Australia between January 2003 and December 2019 who were exposed to long-lived large-scale combined climatic measures of temperature and humidity. We analysed the projected demand for respiratory-related ICU average length of stay (in days) per capita (ICU D/C ) with four historical and one future projection dataset. These datasets included: i) Australian and New Zealand Intensive Care Society adult patient database, ii) Socioeconomic Data and Applications Center gridded global historical population, iii) Australian Bureau of Statistics national historical population, iv) Japanese 55-year Reanalysis historical climate (JRA55), and v) the fifth Coupled Model Inter-comparison Project future climate projections., Results: 148,638 patients with respiratory issues required intensive care between 2003 and 2019. The annual growth in the population density-weighted wet-bulb-globe temperature-a combined measure of temperature and humidity-is strongly correlated with the annual per capita growth ICU D/C for respiratory-related conditions (r=0.771; p<0.001). This relationship was applied to develop a model projecting future respiratory-related ICU demand with three possible future Representative Concentration Pathways (RCP). RCP2.6 (lowest carbon emission climate scenario) showed only a 33.4% increase in Australian ICU D/C demand by 2090, while the RCP8.5 (highest carbon emission climate scenario) demonstrated almost two-fold higher demand (66.1%) than RCP2.6 by 2090., Conclusions: The annual growth in population density-weighted wet-bulb-globe temperature correlates with the annual growth in Australian ICU D/C for respiratory-related conditions. A model based on possible future climate scenarios can be developed to predict changes in ICU demand in response to CO 2 changes over the coming decades., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (Copyright © 2022 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

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.

Background: Nonurban residential living is associated with adverse outcomes for a number of chronic health conditions. However, it is unclear what effect it has amongst survivors of critical illness., Objectives: The purpose of this study is to determine whether patients living greater than 50 km from the treating intensive care unit (ICU) have disability outcomes at 6 months that differ from people living within 50 km., Methods: This was a multicentre, prospective cohort study conducted in five metropolitan ICUs. Participants were adults admitted to the ICU, who received >24 h of mechanical ventilation and survived to hospital discharge. In a secondary analysis of these data, the cohort was dichotomised based on residential distance from the treating ICU: <50 km and ≥50 km. The primary outcome was patient-reported disability using the 12-item World Health Organization's Disability Assessment Schedule (WHODAS 2.0). This was recorded at 6 months after ICU admission by telephone interview. Secondary outcomes included health status as measured by EQ-5D-5L return to work and psychological function as measured by the Hospital Anxiety and Depression Scale (HADS). Multivariable logistic regression was used to assess the association between distance from the ICU and moderate to severe disability, adjusted for potential confounders. Variables included in the multivariable model were deemed to be clinically relevant and had baseline imbalance between groups (p < 0.10). These included marital status and hours of mechanical ventilation. Sensitivity analysis was also conducted using distance in kilometres as a continuous variable., Results: A total of 262 patients were enrolled, and 169 (65%) lived within 50 km of the treating ICU and 93 (35%) lived ≥50 km from the treating ICU (interquartile range [IQR] 10-664 km). There was no difference in patient-reported disability at 6 months between patients living <50 km and those living ≥50 km (WHODAS total disability % [IQR] 10.4 [2.08-25] v 14.6 [2.08-20.8], P = 0.74). There was also no difference between groups for the six major life domains of the WHODAS. There was no difference in rates of anxiety or depression as measured by HADS score (HADS anxiety median [IQR] 4 [1-7] v 3 [1-7], P = 0.60) (HADS depression median [IQR] 3 [1-6] v 3 [1-6], P = 0.62); health status as measured by EQ-5D (mean [SD] 66.7 [20] v 69.8 [22.2], P = 0.24); or health-related unemployment (% (N) 39 [26] v 25 [29.1], P = 0.61). After adjusting for confounders, living ≥50 km from the treating ICU was not associated with increased disability (odds ratio 0.61, 95% confidence interval: 0.33-1.16; P = 0.13) CONCLUSIONS: Survivors of intensive care in Victoria, Australia, who live at least 50 km from the treating ICU did not have greater disability than people living less than 50 km at 6 months after discharge. Living 50 km or more from the treating ICU was not associated with disability, nor was it associated with anxiety or depression, health status, or unemployment due to health., (Copyright © 2021 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Objectives: To evaluate and synthesize the available literature on sex differences in the treatment of adult ICU patients., Data Sources: MEDLINE and EMBASE., Study Selection: Two reviewers independently screened publications to identify observational studies of adult ICU patients that explicitly examined the association between sex and ICU treatment-specifically, mechanical ventilation, renal replacement therapy, and length of stay., Data Extraction: We extracted data independently and in duplicate: mean age, illness severity, use of mechanical ventilation and renal replacement therapy, and length of stay in ICU and hospital. We assessed risk of bias using the Newcastle-Ottawa Scale. We used a DerSimonian-Laird random-effects model to calculate pooled odds ratios (ORs) and mean differences between women and men., Data Synthesis: We screened 4,098 publications, identifying 21 eligible studies with 545,538 participants (42.7% women). The study populations ranged from 246 to 261,255 participants (median 4,420). Most studies (76.2%) were at high risk of bias in at least one domain, most commonly representativeness or comparability. Women were less likely than men to receive invasive mechanical ventilation (OR, 0.83; 95% CI, 0.77-0.89; I2 = 90.4%) or renal replacement therapy (OR, 0.79; 95% CI, 0.70-0.90; I2 = 76.2%). ICU length of stay was shorter in women than men (mean difference, -0.24 d; 95% CI, -0.37 to -0.12; I2 = 89.9%). These findings persisted in meta-analysis of data adjusted for illness severity and other confounders and also in sensitivity analysis excluding studies at high risk of bias. There was no significant sex difference in duration of mechanical ventilation or hospital length of stay., Conclusions: Women were less likely than men to receive mechanical ventilation or renal replacement therapy and had shorter ICU length of stay than men. There is substantial heterogeneity and risk of bias in the literature; however, these findings persisted in sensitivity analyses., Competing Interests: Drs. Modra and Vithanage disclosed that they are members of the Women in Intensive Care Network, Australia and New Zealand Intensive Care Society. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: Information about the epidemiology of older Internal Medicine patients receiving medical emergency team (MET) calls is limited. We assessed the prevalence, characteristics, risk factors, and outcomes of this vulnerable group., Methods: Internal Medicine patients aged >75 years who were admitted via the Emergency Department to a tertiary hospital between January 2015 to December 2018 and who activated a MET call were compared to patients without MET call activation during the same time period. Outcome measures included management post-MET call, Intensive Care Unit (ICU) admission rates, discharge disposition, length of hospital stays (LOS), and in-patient mortality., Results: There were 10,803 Internal Medical admissions involving 10,423 patients; median age 85 (IQR 81-89) years. Of these, 995 (10%) patients received at least one MET call. MET call patients had greater physiological instability in the Emergency Department and higher median Charlson comorbidity index values (2, IQR 1-3 vs. 1, IQR 0-2; p < .0001) than non-MET call patients. Overall, 10% of MET call patients were admitted to ICU. MET patients had a longer median length of stay (9 [IQR 5-14] vs. 4 days [IQR 2-7]; p < .001) and higher in-hospital mortality (29% vs. 7%; p < .001). However, mortality of MET call patients without treatment limitations was 48/357 (13%)., Conclusion: One in ten Internal Medicine patients aged >75 years and admitted via ED had a MET call. Physiological instability in ED and comorbidities were key risk factors. Mortality in MET patients approached 30%. These data can help predict at-risk patients for improving goals of care and pre-MET interventions., (© 2021 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To investigate the association between sex and illness severity and mortality of ICU patients., Methods: We performed systematic searches of MEDLINE and EMBASE for observational studies of adult ICU patients that explicitly examined the association between sex and illness severity or mortality. We used a random effects model to calculate standardised mean differences in illness severity scores and pooled odds ratios for mortality of women compared to men., Results: We identified 21 studies with 505,138 participants in total (43.1% women). There was substantial heterogeneity among studies. Only two studies were at low risk of bias overall. At ICU admission, there was a pattern of higher illness severity scores among women (standardised mean difference 0.04, 95% CI -0.01-0.09). Women had higher risk-adjusted mortality than men at ICU discharge (OR 1.25 95% CI 1.03-1.50) and 1 year (OR 1.08, 95% CI 1.02-1.13), however this finding was not robust to sensitivity analysis., Conclusions: Women tend to have higher illness severity scores at ICU admission. Women also appear to have higher risk-adjusted mortality than men at ICU discharge and at 1 year. Given the heterogeneity and risk of bias in the existing literature, additional studies are needed to confirm or refute these findings., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The COVID-19 pandemic has led to unprecedented demand for ICUs, with the need to triage admissions along with the development of ICU triage criteria. However, how these criteria relate to outcomes in patients already admitted to the ICU is unknown, as is the incremental ICU capacity that triage of these patients might create given existing admission practices., Research Question: What is the short- and long-term survival of low- vs high-priority patients for ICU admission according to current pandemic triage criteria?, Study Design and Methods: This study analyzed prospectively collected registry data (2007-2018) in 23 ICUs in Victoria, Australia, with probabilistic linkage with death registries. After excluding elective surgery, admissions were stratified according to existing ICU triage protocol prioritization as low (age ≥ 85 years, or severe chronic illness, or Sequential Organ Failure Assessment [SOFA] score = 0 or ≥ 12), medium (SOFA score = 8-11) or high (SOFA score = 1-7) priority. The primary outcome was long-term survival. Secondary outcomes were in-hospital mortality, ICU length of stay (LOS) and bed-day usage., Results: This study examined 126,687 ICU admissions. After 5 years of follow-up, 1,093 of 3,296 (33%; 95% CI, 32-34) of "low-priority" patients aged ≥ 85 years or with severe chronic illness and 86 of 332 (26%; 95% CI, 24-28) with a SOFA score ≥ 12 were still alive. Sixty-three of 290 (22%; 95% CI, 17-27) of patients in these groups followed up for 10 years were still alive. Together, low-priority patients accounted for 27% of all ICU bed-days and had lower in-hospital mortality (22%) than the high-priority patients (28%). Among nonsurvivors, low-priority admissions had shorter ICU LOS than medium- or high-priority admissions., Interpretation: Current SOFA score or age or severe comorbidity-based ICU pandemic triage protocols exclude patients with a close to 80% hospital survival, a > 30% five-year survival, and 27% of ICU bed-day use. These findings imply the need for stronger evidence-based ICU triage protocols., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Dr. Bellomo has received grants and consultancy and speaking fees from BBraun and Baxter. Dr. Ronco has received consultancy and speaking fees from ASAHI, Astute, Biomerieux, B.Braun, Baxter, FMC, Toray, GE, OCD, Jafron, and Medtronic. Dr. Kellum has received grant support and/or consulting fees from AM Pharma, Astellas, Astute Medical, Atox Bio, Baxter, bioMerieux, NxStage, and Potrero. Dr. Kellum’s institution received funding from Baxter, and he received funding from Baxter and NxStage. Dr. Baldwin has disclosed that he does not have any potential conflicts of interest.

Purpose: Patients with persistent critical illness may account for up to half of all intensive care unit (ICU) bed-days. It is unknown if there is hospital variation in the development of persistent critical illness and if hospital performance affects the incidence of persistent critical illness., Methods: This is a retrospective analysis of Veterans admitted to the Veterans Administration (VA) ICUs from 2015 to 2017. Hospital performance was defined by the risk- and reliability-adjusted 30-day mortality. Persistent critical illness was defined as an ICU length of stay of at least 11 days. We used 2-level multilevel logistic regression models to assess variation in risk- and reliability-adjusted probabilities in the development of persistent critical illness., Results: In the analysis of 100 hospitals which encompassed 153,512 hospitalizations, 4.9% (N = 7640/153,512) developed persistent critical illness. There was variation in the development of persistent critical illness despite controlling for patient characteristics (intraclass correlation: 0.067, 95% CI 0.049-0.091). Hospitals with higher risk- and reliability-adjusted 30-day mortality had higher probabilities of developing persistent critical illness (predicted probability: 0.057, 95% CI 0.051-0.063, p < 0.01) compared to those with lower risk- and reliability-adjusted 30-day mortality (predicted probability: 0.046, 95% CI 0.041-0.051, p < 0.01). The median odds ratio was 1.4 (95% CI 1.33-1.49) implying that, for two patients with the same physiology on admission at two different VA hospitals, the patient admitted to the hospital with higher adjusted mortality would have 40% greater odds of developing persistent critical illness., Conclusion: Hospitals with higher risk- and reliability-adjusted 30-day mortality have a higher probability of developing persistent critical illness. Understanding the drivers of this variation may identify modifiable factors contributing to the development of persistent critical illness.

Objectives: To evaluate what proportion of unplanned ICU admissions from hospital wards occurred after rapid response team review and compare baseline characteristics and outcomes of patients admitted after rapid response team review with non-rapid response team-related admissions., Design: Multicenter binational retrospective cohort study., Setting: One-hundred seventy-eight ICUs across Australia and New Zealand., Patients: All adults (≥ 17 yr) in the Australian and New Zealand Intensive Care Society Adult Patient Database between 2012 and 2017., Interventions: None., Measurements and Main Results: Among 97,181 unplanned ICU admissions from the ward, prior rapid response team review occurred in 55,084 cases (56.7%). Rapid response team patients were slightly older (65.4 [16.9] vs 63.3 [18]), had a higher Acute Physiology and Chronic Health Evaluation III score (64.6 [27.1] vs 54.7 [25.3]) and more frequently had limitations of medical treatment (13.1% vs 8.5%) compared with patients with no rapid response team review. The strongest independent associations with ICU admission following rapid response team review included age, ICU admission diagnosis (especially sepsis-, neurologic-, respiratory-, and cardiovascular-related), tertiary ICU status, and presence of limitations of medical treatment (p < 0.0001 all comparisons). Rapid response team-related ICU admissions had a longer median ICU (2.4 d [1.2-4.6 d] vs 2.1 d [1.0-4.2 d]) and hospital (12.8 d [7.0-23.6 d] vs 10.8 d [5.9-20.3 d]) length of stay, and were more likely to die in the ICU (12.3% vs 7.5%) and in-hospital (20.8% vs 13.5%) (p < 0.0001). After adjusting for illness severity and institution, patients admitted following rapid response team review stayed longer in hospital but were not at increased risk of dying in-hospital (adjusted odds ratio, 1.03; 0.98-1.07)., Conclusions: In Australia and New Zealand, hospital ward patients admitted to ICU following rapid response team review represent the majority of ward-based ICU admissions, are more chronically and acutely ill, and more frequently have sepsis than those admitted from the ward without rapid response team review. Their unadjusted outcomes are worse, but after adjustment their mortality is similar.

Objective: To determine the frequency, indications and complications associated with the use of faecal diversion systems (rectal tubes) in critically ill patients., Design: A single centre observational study over 15 months., Setting: Intensive care unit (ICU)., Participants: Patients admitted during this period., Main Outcome Measures: Frequency of rectal tubes utilisation in ICU, as well as associated adverse events, with major events defined as lower gastrointestinal bleeding associated with defined blood transfusion of two or more units of red cells or endoscopy or surgical intervention., Results: Of 3418 admission episodes, there were 111 episodes of rectal tubes inserted in 99 patients. Rectal tubes remained indwelling for a median of 5 days (range, 1-23) for a total of 641 patient-days. The most frequent indication for insertion was excessive bowel motions. A major adverse event was observed in three patients (3%; 0.5 events per 100 device days). Two patients underwent laparotomy and one patient sigmoidoscopy. These patients received between two and 23 units of packed red blood cells. Patients who had a rectal tube inserted had a substantially greater duration of ICU admission (mean, 14 days [SD, 14] v 2.8 days [SD, 3.7]) and hospital mortality (15% v 7.7%; risk ratio, 2.0; 95% CI, 1.2-3.4) as well as an overall higher Australian and New Zealand Risk of Death (ANZROD) score (mean, 27 [SD, 22] v 12.6 [SD, 20])., Conclusion: Rectal tubes appear to be frequently inserted and can lead to major adverse events in critically ill patients.

Rationale: The characteristics and outcomes of patients presenting with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) requiring intensive care unit (ICU) admission are poorly understood and there are sparse epidemiological data. Objectives: The objectives were to describe epidemiology and outcomes of patients admitted to an ICU with COPD and to evaluate whether outcomes varied over time. Methods: We studied adult ICU admissions across Australia and New Zealand between 2005 and 2017 with a diagnosis of AECOPD and used an admission diagnosis of asthma as comparator for trends over time. We measured changes in characteristics and outcomes over time using logistic regression, adjusting for illness severity using the Australian New Zealand Risk of Death model. Results: We studied 31,991 admissions with AECOPD and 11,096 with asthma. Mean (standard deviation) age for AECOPD patients was 68.3 (11.2) years, with 35.4% mechanically ventilated. For patients with AECOPD, the percentage of deaths in an ICU was 8.7% and in a hospital was 15.4% of admissions, with the proportion of 69.2% discharged home and 5.6% discharged to a high-level care facility. During the study period, the proportion of ICU admissions with AECOPD per 10,000 admissions decreased at an annual rate of 2.0 (95% confidence interval [CI], 0.8-3.2; P  = 0.009) but their admission rate per million population increased annually by 4.5 (95% CI, 3.7-5.3; P  < 0.0001). There was a linear reduction in mortality for AECOPD but not for asthma admissions (odds ratio annual decline: AECOPD, 0.94 [0.93-0.95] and asthma, 1.01 [0.97-1.05]; P  = 0.001) and an increase in AECOPD admissions discharged to home (odds ratio annual increase, AECOPD, 1.04 [1.03-1.05] and asthma, 1.01 [0.99-1.03]; P  = 0.01). The reduction in mortality was sustained after adjusting for illness severity. Conclusions: Across Australia and New Zealand, the rate of ICU admissions due to AECOPD is increasing but mortality rates are decreasing, with a corresponding increase in the home discharge rates.

Background: Randomised controlled trials (RCT) may be hindered by slow recruitment rates, particularly in critically ill patients. While statistical models to predict recruitment rates have been described, no systematic assessment has been conducted of the distribution of recruitment across sites, temporal trends in site participation and impact of competing trials on patient recruitment., Methods: We used recruitment and screening logs from the SAFE, NICE-SUGAR, RENAL, CHEST and ADRENAL trials, five of the largest critical care RCTs. We quantified the extent of recruitment asymmetry between sites using Lorenz curves and Gini coefficients and assessed whether the recruitment distribution across sites follow the Pareto principle, which states that 80% of effects come from 20% of causes. Peak recruitment rates and growth in participating sites were calculated., Results: In total, 25,412 patients were randomised in 99 intensive care units (ICUs) for the five trials. Distribution of recruitment was asymmetric, with a small number of ICUs recruiting a large proportion of the patients. The Gini coefficients ranged from 0.14 to 0.52. The time to peak recruitment rate ranged from 7 to 41 months and was variable (7, 31, 41, 10 and 40 months). Over time, the proportion of recruitment at non-tertiary ICUs increased from 15% to 34%., Conclusions: There is asymmetry of recruitment with a small proportion of ICUs recruiting a large proportion of patients. The distributions of recruitment were not consistent with the Pareto principle. There has been increasing participation of non-tertiary ICUs in clinical trials.

Objectives: To compare the characteristics of adults admitted to the ICU in Australia and New Zealand after trauma with nonelective, nontrauma admissions. To describe trends in hospital mortality and rates of discharge home among these two groups., Design: Retrospective review (2005-2017) of the Australia and New Zealand Intensive Care Society's Center for Outcome and Resource Evaluation Adult Patient Database., Setting: Adult ICUs in Australia and New Zealand., Patients: Adult (≥17 yr), nonelective, ICU admissions., Intervention: Observational study., Measurements and Main Results: We compared 77,002 trauma with 741,829 nonelective, nontrauma patients. Trauma patients were younger (49.0 ± 21.6 vs 60.6 ± 18.7 yr; p < 0.0001), predominantly male (73.1% vs 53.9%; p < 0.0001), and more frequently treated in tertiary hospitals (74.7% vs 45.8%; p < 0.0001). The mean age of trauma patients increased over time but was virtually static for nonelective, nontrauma patients (0.72 ± 0.02 yr/yr vs 0.03 ± 0.01 yr/yr; p < 0.0001). Illness severity increased for trauma but fell for nonelective, nontrauma patients (mean Australia and New Zealand risk of death: 0.10% ± 0.02%/yr vs -0.21% ± 0.01%/yr; p < 0.0001). Trauma patients had a lower hospital mortality than nonelective, nontrauma patients (10.0% vs 15.8%; p < 0.0001). Both groups showed an annual decline in the illness severity adjusted odds ratio (odds ratio) of hospital mortality, but this was slower among trauma patients (trauma: odds ratio 0.976/yr [0.968-0.984/yr; p < 0.0001]; nonelective, nontrauma: odds ratio 0.957/yr [0.955-0.959/yr; p < 0.0001]; interaction p < 0.0001). Trauma patients had lower rates of discharge home than nonelective, nontrauma patients (56.7% vs 64.6%; p < 0.0001). There was an annual decline in illness severity adjusted odds ratio of discharge home among trauma patients, whereas nonelective, nontrauma patients displayed an annual increase (trauma: odds ratio 0.986/yr [0.981-0.990/yr; p < 0.0001]; nonelective, nontrauma: odds ratio 1.014/yr [1.012-1.016/yr; p < 0.0001]; interaction: p < 0.0001)., Conclusions: The age and illness severity of adult ICU trauma patients in Australia and New Zealand has increased over time. Hospital mortality is lower for trauma than other nonelective ICU patients but has fallen more slowly. Trauma patients have become less likely to be discharged home than other nonelective ICU patients.

Objective : To compare the characteristics, use of invasive ventilation and outcomes of patients admitted with critical asthma syndrome (CAS) to ICUs in Australia and New Zealand (ANZ), and a large cohort of ICUs in the United States (US). Methods : We examined two large databases of ICU for patients admitted with CAS in 2014 and 2015. We obtained, analyzed, and compared information on demographic and physiological characteristics, use of invasive mechanical ventilation, and clinical outcome and derived predictive models. Results : Overall, 2202 and 762 patients were admitted with a primary diagnosis of CAS in the ANZ and US databases respectively (0.73% vs. 0.46% of all ICU admissions, P  < 0.001). A similar percentage of patients received invasive mechanical ventilation in the first 24 h (24.7% vs. 24.4%, P  = 0.87) but ANZ patients had lower respiratory rates and higher PaCO 2 levels. Overall mortality was low (1.23 for ANZ and 1.71 for USA; P  = 0.36) and even among invasively ventilated patients (2.4% for ANZ vs. 1.1% for USA; P  = 0.38). However, ANZ patients also had longer length of stay in ICU (43 vs. 37 h, P  = 0.001) and hospital (105 vs. 78 h, P  = 0.003). Conclusions : Patients admitted to ANZ and USA ICU with CAS are broadly similar and have a low and similar rate of invasive ventilation and mortality. However, ANZ patients made up a greater proportion of ICU patients and had longer ICU and hospital stays. These findings provide a modern invasive ventilation and mortality rates benchmark for future studies of CAS.

Objectives: Relative hypoglycemia is a decrease in glucose greater than or equal to 30% below prehospital admission levels (estimated by hemoglobin A1C) but not to absolute hypoglycemia levels. It is a recognized pathophysiologic phenomenon in ambulant poorly controlled diabetic patients but remains unexamined during critical illness. We examined the frequency, characteristics, and outcome associations of relative hypoglycemia in diabetic patients with critical illness., Design: Retrospective cohort study., Setting: ICU of a tertiary hospital., Patients: One-thousand five-hundred ninety-two critically ill diabetic patients between January 2013 and December 2017., Interventions: None., Measurements and Main Results: The median age of patients was 67 years (interquartile range, 60-75 yr). The median Acute Physiology and Chronic Health Evaluation III score was 53 (interquartile range, 40-68). Thirty-four percent of patients with diabetes experienced relative hypoglycemia (exposure) during their ICU admission. Such patients had higher glycemic lability, hemoglobin A1C levels, and Acute Physiology and Chronic Health Evaluation III scores. The hazard ratio for 28-day mortality of diabetic patients, censored at hospital discharge, for patients with relative hypoglycemia was 1.9 (95% CI, 1.3-2.8) and was essentially unchanged after adjustment for episodes of absolute hypoglycemia. After an episode of relative hypoglycemia, the hazard ratio for subsequent absolute hypoglycemia in the ICU was 3.5 (95% CI, 2.3-5.3)., Conclusions: In ICU patients with diabetes, relative hypoglycemia is common, increases with higher hemoglobin A1C levels, and is a modifiable risk factor for both mortality and subsequent absolute hypoglycemia. These findings provide the rationale for future interventional studies to explore new blood glucose management strategies and to substantiate the clinical relevance of relative hypoglycemia.

Introduction: Little is known about early (first 48 h) hourly and cumulative fluid balance (FB) during continuous renal replacement therapy (CRRT)., Objectives: To study the characteristics and outcome associations of early hourly and cumulative FB., Methods: We studied FB in CRRT patients (2016-2018)., Results: Among 350 patients, mean hourly FB became negative after 20 CRRT hours, but within 6 CRRT hours in patients with baseline fluid overload. A negative early FB was never achieved in patients receiving vasopressor therapy (p < 0.001). Mortality was 31%. The percentage of hourly negative FB was independently associated with decreased ICU mortality. A time-weighted hourly FB between 18.5 and -33 mL/h was also significantly and independently associated with decreased mortality., Conclusions: In CRRT patients, an early FB conservative approach is possible, modulated by patient characteristics, and associated with a low mortality. Moreover, avoidance of an early positive FB is associated with decreased mortality., (© 2019 S. Karger AG, Basel.)

Background: Hypotension following orthopaedic surgery has been associated with increased morbidity and mortality. Rapid response teams (RRT) review patients on hospital wards with hypotension., Aim: To evaluate the epidemiology of hypotensive RRT activations in adult orthopaedic patients to identify contributing factors and areas for future quality improvement., Methods: Timing of RRT activations, presumed causes of hypotension and associated treatments were assessed., Results: Among 963 RRT activations in 605 patients over 3 years, the first calls of 226 of 605 patients were due to hypotension, and 213 (94.2%) of 226 had sufficient data for analysis. The median age was 79 (interquartile range 66-87) years; 58 (27.2%) were male, and comorbidities were common. Most (68%) surgery was emergent, and 75.1% received intraoperative vasopressors for hypotension. Most activations occurred within 24 h of surgery, and hypovolaemia, infection and arrhythmias were common presumed causes. Fluid boluses occurred in 173 (81.2%), and the time between surgery and RRT activation was 10 (4.0-26.5) h. in cases where fluid boluses were given, compared with 33 (15.5-61.5) h. where they were not (P < 0.001). Blood transfusion (30, 14.1%) and withholding of medications were also common. Hospital mortality was 8.5% (18), and 13.6% (29) were admitted to critical care at some stage. In-hospital death was associated with older age, functional dependence, arrhythmia and presumed infection., Conclusions: Hypotension-related RRT calls in orthopaedic patients are common. Future interventional studies might focus on perioperative fluid therapy and vaso-active medications, as well as withholding of anti-hypertensive medications preoperatively., (© 2019 Royal Australasian College of Physicians.)

Background: Delirium is common in hospitalised patients but its epidemiology remains poorly characterised., Aims: To test the hypothesis that patient demographics, clinical phenotype, management and outcomes of patient with delirium in hospital ward patients differ from intensive care unit (ICU) patients., Methods: Retrospective cohort of patients admitted to an Australian university-affiliated hospital between March 2013 and April 2017 and coded for delirium at discharge using the International Classification of Diseases System, 10th revision, criteria., Results: Among 61 032 hospitalised patients, 2864 (4.7%) were coded for delirium. From these, we studied a random sample of 100 ward patients and 100 ICU patients. Ward patients were older (median age: 84 vs 65 years; P < 0.0001), more likely to have dementia (38% vs 2% for ICU patients; P < 0.0001) and less likely to have had surgery (24% vs 62%; P < 0.0001). Of ward patients, 74% had hypoactive delirium, while 64% of ICU patients had agitated delirium (P < 0.0001). Persistent delirium at hospital discharge was more common among ward patients (66% vs 17%, P < 0.0001). On multivariable analysis, age and dementia predicted persistent delirium, while surgery predicted recovery., Conclusions: Delirium in ward patients is profoundly different from delirium in ICU patients. It has a dominant hypoactive clinical phenotype, is preceded by dementia and is less likely to recover at hospital discharge. Therefore, delirium prevention, detection and goals of care should be adapted to the environment in which it occurs., (© 2019 Royal Australasian College of Physicians.)

Objectives: To test whether targeted therapeutic mild hypercapnia (TTMH) would attenuate cerebral oxygen desaturation detected using near-infrared spectroscopy during cardiac surgery requiring cardiopulmonary bypass (CPB)., Design: Randomized controlled trials., Setting: Operating rooms and intensive care unit of tertiary hospital., Participants: The study comprised 30 patients undergoing cardiac surgery with CPB., Interventions: Patients were randomly assigned to receive either standard carbon dioxide management (normocapnia) or TTMH (target arterial carbon dioxide partial pressure between 50 and 55 mmHg) throughout the intraoperative period and postoperatively until the onset of spontaneous ventilation., Measurements and Main Results: Relevant biochemical and hemodynamic variables were measured, and cerebral tissue oxygen saturation (SctO 2 ) was monitored with near-infrared spectroscopy. Patients were followed-up with neuropsychological testing. Patient demographics between groups were compared using the Fisher exact and Mann-Whitney tests, and SctO 2 between groups was compared using repeated measures analysis of variance. The median patient age was 67 years (interquartile range [IQR] 62-72 y), and the median EuroSCORE II was 1.1. The median CPB time was 106 minutes. The mean intraoperative arterial carbon dioxide partial pressure for each patient was significantly higher with TTMH (52.1 mmHg [IQR 49.9-53.9 mmHg] v 40.8 mmHg [IQR 38.7-41.7 mmHg]; p < 0.001) as was pulmonary artery pressure (23.9 mmHg [IQR 22.4-25.3 mmHg] v 18.5 mmHg [IQR 14.8-20.7 mmHg]; p = 0.004). There was no difference in mean percentage change in SctO 2 during CPB in the control group for both hemispheres (left: -6.7% v -2.3%; p = 0.110; right: -7.9% v -1.0%; p = 0.120). Compliance with neuropsychological test protocols was poor. However, the proportion of patients with drops in test score >20% was similar between groups in all tests., Conclusions: TTMH did not increase SctO 2 appreciably during CPB but increased pulmonary artery pressures before and after CPB. These findings do not support further investigation of TTMH as a means of improving SctO 2 during and after cardiac surgery requiring CPB., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To compare the effects of fluid bolus therapy using 20% albumin versus crystalloid on fluid balance, hemodynamic parameters, and intensive care unit (ICU) treatment effects in post-cardiac surgery patients., Design: Sequential period open-label pilot study., Setting: University teaching hospital., Participants: One hundred adult cardiac surgery patients who were prescribed fluid bolus therapy to correct hypotension or perceived hypovolemia or to optimize cardiac index during the first 24 hours in the ICU., Interventions: The first 50 patients were treated with crystalloid fluid bolus therapy in the first period (control), and 50 patients with up to 2 treatments of 100 mL of 20% albumin fluid bolus therapy in the second period (intervention), followed by crystalloid therapy if needed., Measurements and Main Results: Demographic characteristics were similar at baseline. The intervention was associated with a less positive median fluid balance in the first 24 hours (albumin: 1,100 [650-1,960] v crystalloid: 1,970 [1,430-2,550] p = 0.001), fewer episodes of fluid bolus therapy (3 [2-5] v 5 [4-7]; p < 0.0001) and a lesser volume of fluid bolus therapy (700 [200-1,450] v 1,500 mL/24 h [1,100-2,250]; p < 0.0001). The intervention also was associated with a decreased median overall dose of norepinephrine in the first 24 hours of ICU stay (19 [0-52] v 47 µg/kg/24 hours [0-134]; p = 0.025) and shorter median time to cessation of norepinephrine (17 [5-28] v 28 hours [20-48]; p = 0.002)., Conclusion: Post-cardiac surgery fluid bolus therapy with 20% albumin when compared with crystalloid fluid resulted in less positive fluid balance as well as several hemodynamic and potential ICU treatment advantages., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: We aimed to describe changes over time in admissions and outcomes, including length of stay, discharge destinations, and mortality of cirrhotic patients admitted to the ICU for variceal bleeding, and to compare it to the outcomes of those with other causes of ICU admissions., Design: Retrospective analysis of data captured prospectively in the Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation Adult Patient Database., Settings: One hundred eighty-three ICUs in Australia and New Zealand., Patients: Consecutive admissions to these ICUs for upper gastrointestinal bleeding related to varices in patients with cirrhosis between January 1, 2005, and December 31, 2016., Interventions: None., Measurements and Main Results: ICU admissions for variceal bleeding in cirrhotic patients accounted for 4,003 (0.6%) of all 720,425 nonelective ICU admissions. The proportion of ICU admissions for variceal bleeding fell significantly from 0.8% (83/42,567) in 2005 to 0.4% (53/80,388) in 2016 (p < 0.001). Hospital mortality rate was significantly higher within admissions for variceal bleeding compared with nonelective ICU admissions (20.0% vs 15.7%; p < 0.0001), but decreased significantly over time, from 24.6% in 2005 to 15.8% in 2016 (annual decline odds ratio, 0.93; 95% CI, 0.90-0.96). There was no difference in the reduction in mortality from variceal bleeding over time between liver transplant and nontransplant centers (p = 0.26)., Conclusions: Admission rate to ICU and mortality of cirrhotic patients with variceal bleeding has declined significantly over time compared with other causes of ICU admissions with the outcomes comparable between liver transplant and nontransplant centers.

Background: Critically ill patients with diabetes mellitus (DM) are at increased risk of in-hospital complications and the optimal glycemic target for such patients remains unclear. A more liberal approach to glucose control has recently been suggested for patients with DM, but uncertainty remains regarding its impact on complications., Methods: We aimed to test the hypothesis that complications would be more common with a liberal glycemic target in ICU patients with DM. Thus, we compared hospital-acquired complications in the first 400 critically ill patients with DM included in a sequential before-and-after trial of liberal (glucose target: 10-14 mmol/L) vs conventional (glucose target: 6-10 mmol/L) glucose control., Results: Of the 400 patients studied, 165 (82.5%) patients in the liberal and 177 (88.5%) in the conventional-control group were coded for at least one hospital-acquired complication (P = 0.09). When comparing clinically relevant complications diagnosed between ICU admission and hospital discharge, we found no difference in the odds for infectious (adjusted odds ratio [aOR] for liberal-control: 1.15 [95% CI: 0.68-1.96], P = 0.60), cardiovascular (aOR 1.40 [95% CI: 0.63-3.12], P = 0.41) or neurological complications (aOR: 1.07 [95% CI: 0.61-1.86], P = 0.81), acute kidney injury (aOR 0.83 [95% CI: 0.43-1.58], P = 0.56) or hospital mortality (aOR: 1.09 [95% CI: 0.59-2.02], P = 0.77) between the liberal and the conventional-control group., Conclusion: In this prospective before-and-after study, liberal glucose control was not associated with an increased risk of hospital-acquired infectious, cardiovascular, renal or neurological complications in critically ill patients with diabetes., (© 2019 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Objectives: Trials comparing the effects of transfusing RBC units of different storage durations have considered mortality or morbidity as outcomes. We perform the first economic evaluation alongside a full age of blood clinical trial with a large population assessing the impact of RBC storage duration on quality-of-life and costs in critically ill adults., Design: Quality-of-life was measured at 6 months post randomization using the EuroQol 5-dimension 3-level instrument. The economic evaluation considers quality-adjusted life year and cost implications from randomization to 6 months. A generalized linear model was used to estimate incremental costs (2016 U.S. dollars) and quality-adjusted life years, respectively while adjusting for baseline characteristics., Setting: Fifty-nine ICUs in five countries., Patients: Adults with an anticipated ICU stay of at least 24 hours when the decision had been made to transfuse at least one RBC unit., Interventions: Patients were randomized to receive either the freshest or oldest available compatible RBC units (standard practice) in the hospital transfusion service., Measurements and Main Results: EuroQol 5-dimension 3-level utility scores were similar at 6 months-0.65 in the short-term and 0.63 in the long-term storage group (difference, 0.02; 95% CI, -0.00 to 0.04; p = 0.10). There were no significant differences in resource use between the two groups apart from 3.0 fewer hospital readmission days (95% CI, -5.3 to -0.8; p = 0.01) during follow-up in the short-term storage group. There were no significant differences in adjusted total costs or quality-adjusted life years between the short- and long-term storage groups (incremental costs, -$2,358; 95% CI, -$5,586 to $711) and incremental quality-adjusted life years: 0.003 quality-adjusted life years (95% CI, -0.003 to 0.008)., Conclusions: Without considering the additional supply cost of implementing a freshest available RBC strategy for critical care patients, there is no evidence to suggest that the policy improves quality-of-life or reduces other costs compared with standard transfusion practice.

Background: Knowledge about patients with acute liver failure (ALF) in Australia and New Zealand (ANZ) is lacking., Aims: To evaluate whether the pattern of ALF would be similar to previous studies and whether, despite potentially low transplantation rates, mortality would be comparable., Methods: We obtained data from the ANZ Intensive Care Society Adult Patient Database and the ANZ Liver Transplant Registry for 10 years commencing 2005 and analysed for patient outcomes., Results: During the study period, 1 022 698 adults were admitted to intensive care units across ANZ, of which 723 had ALF. The estimated annual incidence of ALF over this period was 3.4/million people and increased over time (P = 0.001). ALF patients had high illness severity (Acute Physiology And Chronic Health Evaluation III 79.8 vs 50.1 in non-ALF patients; P < 0.0001) and were more likely to be younger, female, pregnant and immunosuppressed. ALF was an independent predictor of mortality (odds ratio 1.5 (1.26-1.79); P < 0.0001). At less than 23%, the use of liver transplantation was low, but the mortality of 39% was similar to previous studies., Conclusions: ALF is a rare but increasing diagnosis in ANZ intensive care units. Low transplantation rates in ANZ for ALF do not appear to be associated with higher mortality rates than reported in the literature., (© 2019 Royal Australasian College of Physicians.)

Objective: To assess the effects of sepsis and exogenous insulin on C-peptide levels and C-peptide to insulin ratios in intensive care unit (ICU) patients with type 2 diabetes mellitus (T2DM)., Design, Setting and Participants: In this prospective, observational, single-centre study, we enrolled 31 ICU-admitted adults with T2DM. We measured serum C-peptide and insulin levels during the first 3 days of ICU stay and recorded characteristics of exogenous insulin therapy. Patients were compared on the basis of the presence of sepsis, and their exposure to exogenous insulin therapy. C-peptide levels were also measured in eight healthy subjects., Main Outcome Measures: Serum insulin and C-peptide levels during the first 3 days in ICU., Results: Median C-peptide levels were higher in the ICU population compared with healthy subjects (10.9 [IQR, 8.2 -14.1] v 4.8 [IQR, 4.6-5.1] nmol/L, P < 0.01). Sepsis was present in 25 ICU patients (81%). Among ICU patients unexposed to exogenous insulin, the 11 patients with sepsis had higher median C-peptide levels compared with the six non-septic patients (2.5 [IQR, 1.8-3.7] v 1.7 [IQR, 0.8-2.2] nmol/L, P = 0.04), and a threefold higher C-peptide to insulin ratio (45 [IQR, 37-62] v 13 [IQR, 11-17], P = 0.03). However, septic patients exposed to exogenous insulin had lower median C-peptide levels (1.2 [IQR, 0.7-2.3] nmol/L, P = 0.01) and C-peptide to insulin ratios (5 [IQR, 2-10], P < 0.01) compared with insulin-free septic patients. The C-peptide to insulin ratio was significantly associated with white cell count and severity of illness in insulin-free septic patients., Conclusion: C-peptide levels were elevated in critically ill patients with T2DM. In this population, sepsis increased C-peptide levels and uncoupled serum C-peptide and insulin levels. Exogenous insulin decreased both C-peptide levels and C-peptide to insulin ratios.

Objective: To describe the prevalence of low-normal body temperatures in emergency department (ED) patients presenting with severe infection, and to determine whether active warming is used in this setting., Design, Setting and Participants: We performed a singlecentre retrospective cohort study in ED patients with community-acquired infection who required admission to the intensive care unit (ICU). Temperatures recorded from presentation up until 24 hours in the ICU were extracted from the patients' clinical records. Body temperatures were then classified as low (≤ 36.4°C), normothermic (36.5-37.9°C) or fever ≥ 38°C., Results: Over the study period, 574 patients were admitted to the ICU with infection. Of them, 151 fulfilled the inclusion criteria, and the in-hospital mortality rate for these patients was 8.6%. On presentation, 22.5% (34 patients) had a low body temperature (35-35.9°C for six patients, and < 35.0°C for three patients). In contrast, 26.5% (40 patients) had a temperature ≥ 38.0°C. Among those who presented with low temperature, the median time to reach normothermia was 7.9 hours (range, 3.3-14.0 hours). Active warming was only applied to one patient, (whose body temperature was < 35°C)., Conclusion: Among patients with community-acquired infection requiring ICU admission, about a quarter have a low temperature and active warming was essentially not applied. These findings suggest that active warming of such patients would likely achieve separation from usual care.

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., (© 2019 AMPCo Pty Ltd.)

Objective: To evaluate the prevalence of "likely overassistance" (categorised by respiratory rate [RR] ≤ 17 breaths/min or rapid shallow breathing index [RSBI] ≤ 37 breaths/min/L) during invasive pressure support ventilation (PSV), and the additional prevalence of fixed ventilator settings., Design: Multicentre prospective observational study of invasive PSV practice in six general Victorian intensive care units with blinding of staff members to data collection., Patients: At each hospital, investigators collected data between 11 am and 2 pm on all invasive PSV-treated patients on 60 sequential days, excluding weekends and public holidays, between 22 February and 30 August 2017. Each patient was included for maximum of 3 days., Main Results: We studied 231 patients, with a total of 379 observations episodes over the study period. There were 131 patients (56.7%) with at least one episode of RR ≤ 17 breaths/min; 146 patients (63.2%) with at least one episode of RSBI ≤ 37 breaths/min/L, and 85 patients (36.8%) with at least one episode of combined RR ≤ 17 breaths/min and RSBI ≤ 37 breaths/min/L. Moreover, the total number of observations with "likely overassistance" (RR ≤ 17 or RSBI ≤ 37 breaths/min/L) was 178 (47%) and 204 (53.8%), respectively; while for both combined criteria, it was 154 (40.6%). We also found that 10 cmH 2 O pressure support was delivered on 210 of the observations (55.4%) and adjusted in less than 25% of observations. Finally, less than half (179 observations) of all PSV-delivered tidal volumes (V T ) were at the recommended value of 6-8 mL/kg predicted body weight (PBW) and more than 20% (79 observations) were at ≥ 10 mL/kg PBW., Conclusion: In a cohort of Victorian hospitals in Australia, during invasive PSV, "likely overassistance" was common, and the pressure support level was delivered in a standardised and unadjusted manner at 10 cmH 2 O, resulting in the frequent delivery of potentially injurious V T .

Aim: Common blood tests can help identify patients at risk of death, unplanned intensive care unit (ICU) admission, or rapid response team (RRT) call. We aimed to test whether early ICU-team review triggered by such laboratory tests (lab alert) is feasible, safe, and can alter physiological variables, clinical management, and clinical outcomes., Methods: In prospective pilot randomized controlled trial in surgical wards of a tertiary hospital, we studied patients admitted for >24 h. We applied a previously validated risk assessment tool to each set of common laboratory tests to identify patients at risk and generate a "lab-alert". We randomly allocated such lab-alert patients to receive early ICU-team review (intervention) or usual care (control)., Results: We studied 205 patients (males 54.1%; average age 79 years; 103 randomized to intervention and 102 to usual care). Intervention patients were more likely to trigger RRT activation during their first lab-alert (10.7 vs. 2.0%; P < 0.001) but less likely to receive an allied health referral (18.0% vs. 24.5%; p = 0.007). They were less likely to trigger RRT activation in the 24-h before subsequent alerts (18.4 vs. 22.4%; p = 0.008) and less likely to generate further alerts (204 vs. 320; p < 0.001), but more likely to receive a not for resuscitation or endotracheal intubation status in the 24-h before subsequent alerts (26.6 vs. 17.3%; p = 0.05). Mortality at 24 h was 1.9% for the intervention group vs. 2.9% in the control group (p = 0.63). Finally, overall mortality was 19.4% for intervention patients vs. 23.5% for control patients (p = 0.50)., Conclusion: Among surgical patients, lab alerts identify patients with a high mortality. Lab alert-triggered interventions are associated with more first alert-associated RRT activations; more changes in resuscitation status toward a more conservative approach; fewer subsequent alert-associated RRT activations; fewer subsequent alerts, and decreased allied health interventions (ANZCTRN12615000146594)., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose of Review: Severe acute kidney injury in the ICU setting often requires renal replacement therapy (RRT). Intermittent hemodialysis (IHD), hybrid forms of RRT such as sustained low-efficiency dialysis (SLED), as well as continuous renal replacement therapy (CRRT) are the three common modalities of extracorporeal RRT used in the adult ICU setting in developed countries. This review summarizes recently published data regarding comparisons of these three RRT modalities on clinical outcomes (e.g., mortality and recovery of renal function) in severe acute kidney injury (AKI) patients., Recent Findings: There is still controversy on the superiority of one RRT modality over another in terms of clinical outcomes in patients with AKI in ICU. Although there is increasing acceptance that CRRT should be used in hemodynamic unstable patients, its survival advantages over IHD remains unproven because of inadequate evidence from suitably powered randomized controlled trials (RCTs). Moreover, CRRT does not show superiority to intermittent renal replacement therapy (IRRT) in hemodynamic stable patients. Although patients receiving sustained low-efficiency dialysis appear to have lower mortality than CRRT, its survival benefit is largely derived from observational studies and is confounded by selection bias. Current literature supports no differences in mortality among the three RRT modalities. However, the effect of choice of RRT modality on short-term and long-term renal outcomes need further studies, especially larger RCTs and longer duration of follow-up., Summary: There is lack of solid evidence showing superiority of any mode of RRT in patients with severe AKI in terms of patient survival. However, based on observational data, IHD treatment of AKI may delay renal recovery. Patients' hemodynamic status, coexisting medical conditions, local expertise, and availability of staff and resources as well as potential effect on long-term renal outcomes should be taken into consideration when selecting modalities of RRT for adult ICU patients.

Objective: In Australian and New Zealand (ANZ) intensive care units (ICUs), the preferred measurement methods and targets for temperature remain uncertain, but are crucial for future interventional studies. We aimed to investigate the reported use of temperature measurement methods and targets in ANZ ICUs., Design, Settings and Participants: Structured online questionnaire delivered via the email list of the Australian and New Zealand Intensive Care Society Clinical Trials Group., Main Outcome Measures: Measurements methods and targets for temperature in ANZ ICUs., Results: Of 209 respondents, 130 were nurses (62.2%) and 79 were doctors (37.8%). Only 21.5% of the respondents reported having a unit protocol for measuring body temperature. However, invasive temperature measurement methods were preferred by doctors (69.8% v 55.3%) and non-invasive methods by nurses (29.9% v 44.2%). Moreover, among non-invasive methods, tympanic measurement was preferred by doctors (66.0% v 26.9%) and axillary by nurses (11.7% v 51.9%). Both professions reported a wide range of temperature thresholds that they believed required cooling interventions, but 16.7% of doctors and 42.4% of nurses reported that, in patients with cardiac arrest, they would actively cool patients only if the temperature was ≥ 38°C., Conclusion: In ANZ ICUs, preferred temperature measurement methods and targets are typically not governed by protocol, vary greatly and differ between doctors and nurses. Targeted temperature management after cardiac arrest is not fully established. Future studies of the comparative accuracy of non-invasive temperature measurements methods and practice in patients with cardiac arrest appear important.

Background: The balance of risks and benefits with using proton pump inhibitors (PPIs) versus histamine-2 receptor blockers (H 2 RB) for stress ulcer prophylaxis in patients who are invasively ventilated in the intensive care unit (ICU) is uncertain., Objective: To describe the study protocol and statistical analysis plan for the Proton Pump Inhibitors versus Histamine-2 Receptor Blockers for Ulcer Prophylaxis Therapy in the Intensive Care Unit (PEPTIC) study., Design, Setting and Participants: Protocol for a prospective, multicentre, randomised, open-label, cluster crossover, registry-embedded trial to be conducted in 50 ICUs in Australia, Canada, Ireland, New Zealand and the United Kingdom. The PEPTIC study will compare two approaches to stress ulcer prophylaxis in mechanically ventilated adults implemented at the level of the ICU. One approach is to use PPIs as the default therapy and the other approach is to use H2RBs as the default therapy when stress ulcer prophylaxis is prescribed. Each ICU, by random allocation, will use one approach for 6 months and will then switch to the opposite approach for the next 6 months. The PEPTIC study began recruitment in August 2016 and will complete recruitment in January 2019., Main Outcome Measures: The primary end point will be in-hospital mortality. Secondary outcomes include clinically significant upper gastrointestinal bleeding, Clostridium difficile infection, ICU length of stay and hospital length of stay., Results and Conclusions: The PEPTIC study will compare the effect on in-hospital mortality of implementing, at the level of the ICU, the use of PPI as the preferred agent for stress ulcer prophylaxis in mechanically ventilated adults in the ICU with using H 2 RB as the preferred agent., Trial Registration: Australian and New Zealand Clinical Trials Registry (ANZCTRN 12616000481471).

Purpose: The purpose of this study was to characterize the organ failures that develop among patients with prolonged ICU stays, defined as those who spent a minimum of 14 days in an ICU., Methods: We retrospectively studied a cohort of consecutive patients from a university hospital who were in an ICU for a minimum of 14 days during 2014-2016. We calculated daily Sequential Organ Failure Assessment (SOFA) scores from admission to ICU day 14. The primary outcome was the number of new late organ failures, defined as occurring on ICU day 4 through 14., Results: In a retrospective cohort of 3777 consecutive patients in six ICUs, 50 patients had prolonged ICU stays. Of those 50, new cardiovascular failure occurred in 24 (62%) on day 4 or later; persistent mechanical ventilation was present in only 28 (56%)., Conclusions: Strategies aiming to reduce the development of new late organ failures may be a novel target for preventing persistent critical illness., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: To assess the feasibility, biochemical efficacy, and safety of liberal versus conventional glucose control in ICU patients with diabetes., Design: Prospective, open-label, sequential period study., Setting: A 22-bed mixed ICU of a tertiary hospital in Australia., Patients: We compared 350 consecutive patients with diabetes admitted over 15 months who received liberal glucose control with a preintervention control population of 350 consecutive patients with diabetes who received conventional glucose control., Interventions: Liberal control patients received insulin therapy if glucose was greater than 14 mmol/L (target: 10-14 mmol/L [180-252 mg/dL]). Conventional control patients received insulin therapy if glucose was greater than 10 mmol/L (target: 6-10 mmol/L [108-180 mg/dL])., Measurements and Main Results: We assessed separation in blood glucose, insulin requirements, occurrence of hypoglycemia (blood glucose ≤ 3.9 mmol/L [70 mg/dL]), creatinine and white cell count levels, and clinical outcomes. The median (interquartile range) time-weighted average blood glucose concentration was significantly higher in the liberal control group (11.0 mmol/L [8.7-12.0 mmol/L]; 198 mg/dL [157-216 mg/dL]) than in the conventional control group (9.6 mmol/L [8.5-11.0 mmol/L]; 173 mg/dL [153-198 mg/dL]; p < 0.001). Overall, 132 liberal control patients (37.7%) and 188 conventional control patients (53.7%) received insulin in ICU (p < 0.001). Hypoglycemia occurred in 6.6% and 8.6%, respectively (p = 0.32). Among 314 patients with glycated hemoglobin A1c greater than or equal to 7%, hypoglycemia occurred in 4.1% and 9.6%, respectively (p = 0.053). Trajectories of creatinine and white cell count were similar in the groups. In multivariable analyses, we found no independent association between glucose control and mortality, duration of mechanical ventilation, or ICU-free days to day 30., Conclusions: In ICU patients with diabetes, during a period of liberal glucose control, insulin administration, and among patients with hemoglobin A1c greater than or equal to 7%, the prevalence of hypoglycemia was reduced, without negatively affecting serum creatinine, the white cell count response, or other clinical outcomes. (Trial Registration: Australian New Zealand Clinical Trials Registry; ACTRN12615000216516).

Objective: To evaluate the effect of active temperature management on mortality, intensive care unit (ICU) and hospital length of stay, as well as the relative efficacy of antipyretic medications and physical cooling devices for achieving reductions in temperature in critically ill adults., Design, Setting and Participants: Systematic review and meta-analysis of randomised controlled trials (RCTs) investigating treatments administered to febrile patients in order to reduce body temperature. Fifteen studies reporting results from 13 RCTs met our eligibility criteria., Interventions: Treatments administered to reduce body temperature were defined as physical cooling, nonsteroidal anti-inflammatory drugs, paracetamol, or any combination of these., Main Outcome Measures: The primary outcome variable was all-cause mortality at the longest time point after randomisation. Secondary outcomes were ICU and hospital length of stay, and body temperature 12 hours after randomisation., Results: Active temperature control had no statistically significant association with mortality (odds ratio, 1.01; 95% confidence interval [CI], 0.81-1.28; P = 0.95, for fixed effects). There was no statistically significant association between active temperature management and ICU or hospital length of stay. Active temperature management was associated with a statistically significant reduction in temperature. The fixed effects estimate for the active minus control treatment for pharmaceutical management was -0.62C (95% CI, -0.72C to -0.51C; P < 0.001) and for physical cooling was -1.59C (95% CI, -1.82C to -1.35C; P < 0.001)., Conclusions: Active temperature management neither increased nor decreased mortality risk in critically ill adults. When the therapeutic goal is to reduce body temperature, physical cooling approaches may be more effective than pharmacological measures in critically ill adults.

Background: There are limited data on the characteristics, incidence, and mortality of patients with myasthenia gravis (MG) admitted to the ICU., Aims: To study the epidemiology, characteristics and outcome of patients with MG in Australian and New Zealand (ANZ) ICUs over a decade., Methods: We performed a retrospective observational, cross sectional study of data from the Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database (APD). We collected data on all adult patients admitted with a primary diagnosis of MG to 159 Australian and 19 New Zealand ICUs between January 1, 2005 and December 31, 2015.We extracted detailed relevant data and performed statistical assessment., Results: We identified 245 patients admitted to ICU with the primary diagnosis of MG, with an incidence increasing from 1 to 2.5 per thousand ICU admissions (P<0.0001) and from 1 to 2.2 per million people (P=0.02). Mean age was 60years with more patients being female (53.7% vs 47.3%) and 91 (37.1%) patients received mechanical ventilation. Hospital mortality occurred in 13 (5.3%) patients with a mortality rate lower than in other ICU patients., Conclusions: In ANZ, the ICU and population incidence of MG has increased over the last decade. However, its mortality rate was low., (Copyright © 2018 Elsevier Inc. All rights reserved.)