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Objective: Frequent measurement of creatinine by point-of-care testing (POCT) may facilitate the earlier detection of acute kidney injury (AKI) in critically ill patients. However, no robust data exist to confirm its equivalence to central laboratory testing. We aimed to conduct a multicenter study to compare POCT with central laboratory creatinine (CrC) measurement., Design: Retrospective observational study, using hospital electronic medical records. Obtained paired point-of-care creatinine (CrP) from arterial blood gas machines and CrC., Setting: Four intensive care units in Queensland, Australia., Participants: Critically ill patients, where greater than 50% of POCT contained creatinine., Main Outcome Measures: Mean difference, bias, and limits of agreement between two methods, and biochemical confounders., Results: We studied 79,767 paired measurements in 19,118 patients, with a median Acute Physiology and Chronic Health Evaluation 3 score of 51. The mean CrC was 115.5 μmol/L (standard deviation: 100.2) compared to a CrP mean of 115 μmol/L (standard deviation: 100.7) (Pearson coefficient of 0.99). The mean difference between CrP and CrC was 0.49 μmol/L with 95% limits of agreement of -27 μmol/L and +28 μmol/L. Several biochemical variables were independently associated with the difference between tests (e.g., pH, potassium, lactate, glucose, and bilirubin), but their impact was small., Conclusion: In critically ill patients, measurement of creatinine by POCT yields clinically equivalent values to those obtained by central laboratory measurement and can be easily used for more frequent monitoring of kidney function in such patients. These findings open the door to the use of POCT for the earlier detection of acute kidney injury in critically ill patients., (© 2024 The Authors.)

Objective: To describe the proportion of patients admitted to intensive care who have anaphylaxis as a principal diagnosis and their subsequent outcomes in Australia and New Zealand., Design: Retrospective observational study of ICU admissions for severe anaphylaxis., Setting: ICU admissions recorded in the Australian and New Zealand Intensive Care Society Adult Patient Database between 2012 and 2022., Participants: Adults 16 years or older with severe anaphylaxis admitted to the ICU., Interventions: None., Main Outcome Measures: Proportion of patients admitted to ICU who have anaphylaxis as a principal diagnosis, mortality rate, ICU and hospital length of stay., Results: 7189 of the 7270 ICU admissions for severe anaphylaxis recorded between 2012 and 2022, were included in the analysis. This represented a proportion from 0.25% in 2012 to 0.43% in 2022. ICU and hospital mortality were 0.4% and 0.8%, respectively. The proportion of ICUs reporting at least one severe anaphylaxis each year increased from 61.7% in 2012 to 83.0% in 2022. Most of the patients were discharged home (92.6%, n = 6660). Increasing age (OR = 1.055; 95%CI: 1.008-1.105) and SOFA scores (OR = 1.616; 95%CI: 1.265-2.065), an immunosuppressive chronic condition (OR = 16.572; 95%CI: 3.006-91.349) and an increasing respiratory rate above 16 breaths/min (OR = 1.116; 95%CI: 1.057-1.178) predicted in-hospital mortality in patients with anaphylaxis, while higher GCS decreased in-hospital mortality (OR = 0.827; 95%CI: 0.705-0.969)., Conclusions: The overall proportion of patients admitted to ICU who have anaphylaxis as a principal diagnosis has increased. In-hospital mortality remains low despite the need for vital organ support. Further studies should investigate these identified factors that may predict in-hospital mortality among these patients., Trial Registration: Not applicable., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ashwin Subramaniam and David Pilcher are associate editors for critical care and resuscitation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective: Critically ill patients suffer disrupted sleep. Hypnotic medications may improve sleep; however, local epidemiological data regarding the amount of nocturnal time awake and the use of such medications is needed., Design: Point prevalence study., Setting: Adult ICUs in Australia and New Zealand., Participants: All adult patients admitted to participating Intensive Care Units (ICUs) on the study day., Main Outcome Measures: Time awake overnight (22:00-06:00) was determined by structured nurse observation. The use of enterally administered sedative-hypnotic drugs prior to and during ICU admission was recorded, as was the use of a unit policy and non-pharmacological sleep promotion strategies., Results: Data were available for 532 patients admitted to 40 ICUs (median age 60 years, 336 (63.2%) male, and 222 (41.7%) invasively ventilated). Forty-eight patients (9.0%) received an enteral pharmacological sleep aid, of which melatonin (28, 5.2%) was most frequently used. Patients not invasively ventilated were observed to be awake overnight for a median of 4.0 h (interquartile range (IQR): 2.5, 5.5), with no difference in those receiving an enteral hypnotic (p = 0.9). Non-pharmacological sleep aids were reportedly not offered or available for 52% (earplugs) and 63% of patients (eye masks). Only 7 (17.5%) participating ICUs had a policy informing sleep-optimising interventions., Conclusions: Patients not receiving invasive ventilation appeared to spend many nocturnal hours awake. Pharmacological sleep aid administration was not associated with a greater observed time asleep. Most patients did not receive any non-pharmacological aid, and most ICUs did not have a local guideline or unit policy on sleep promotion., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The following authors declare that they are part of the CC&R editorial team as associate editors:1. Adam Deane2. Naomi Hammond3. Ed Litton4. Manoj Saxena5. Bala Venkatesh6. Paul Young7. Yasmine Ali Abdelhamid, (© 2024 The Authors.)

Objective: To determine the perceived barriers and enablers to efficient completion of the College of Intensive Care Medicine (CICM) of Australia and New Zealand Formal Project - a trainee research project mandated for award of CICM Fellowship - and to develop consensus-based recommendations to support Intensive Care trainees and supervisors., Design: A two-stage modified Delphi study was conducted. In stage one, an anonymous electronic survey was distributed with three targeted open-ended questions relating to perceived key steps, barriers to, and improvements for efficient completion of the Formal Project. A thematic analysis used the survey results to generate a list of close-ended questions.In stage two, a consensus panel comprising of 30 panellists including CICM trainees, Formal Project supervisors and assessors, and critical care researchers, underwent a Delphi process with two rounds of voting and discussion to generate consensus-based recommendations., Setting: Surveys were distributed to Intensive Care Units across Australia and New Zealand. The consensus panel convened at the Queensland Critical Care Research Network Annual Scientific Meeting in Redcliffe, Queensland, Australia, on 9 June 2023., Participants: CICM trainees, Formal Project supervisors and assessors, and critical care researchers in Australia and New Zealand., Main Outcome Measures: Consensus-based recommendations for the CICM Formal Project., Results: We received 88 responses from the stage one survey. Stage two finalised 22 consensus-based recommendations, centring on key steps of the research process, resources for trainees, and support and training for supervisors., Conclusions: Twenty-two recommendations were developed aiming to make the process of completing the mandatory CICM research project more efficient, and to improve the quality of research produced from these projects., Competing Interests: None., (© 2024 The Authors.)

Objective: Targeted mild hypercapnia is a potential neuroprotective therapy after cardiac arrest. In this exploratory observational study, we aimed to explore the effects of targeted mild hypercapnia on cerebral microvascular resistance assessed by middle cerebral artery pulsatility index (MCA PI) and intracranial pressure estimated by optic nerve sheath diameter (ONSD) in resuscitated out-of-hospital cardiac arrest (OHCA) patients., Design Setting Participants and Interventions: Comatose adults resuscitated from OHCA were randomly allocated to targeted mild hypercapnia (PaCO 2 50-55 mmHg) or targeted normocapnia (PaCO 2 35-45 mmHg) for 24 h in the TAME trial., Main Outcome Measures: Using transcranial Doppler and transorbital ultrasound, we obtained MCA PI and ONSD at 4, 24, and 48 h after randomization. Ultrasound parameters were compared between groups using a linear mixed effects model., Results: Twelve consecutive patients were included, with seven patients in the mild hypercapnia group. MCA PI decreased from 4 to 24 h (p = 0.019) and was lower over the first 24 h in patients allocated to targeted mild hypercapnia compared with targeted normocapnia (p = 0.047). ONSD did not differ between groups or over time., Conclusion: Cerebral microvascular resistance assessed by MCA PI decreased over 24 h and was lower in OHCA patients treated with targeted mild hypercapnia compared with targeted normocapnia. Targeted mild hypercapnia did not exert substantial effect on intracranial pressure as estimated by ONSD., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Modern intensive care for moderate-to-severe traumatic brain injury (msTBI) focuses on managing intracranial pressure (ICP) and cerebral perfusion pressure (CPP). This approach lacks robust clinical evidence and often overlooks the impact of hypoxic injuries. Emerging monitoring modalities, particularly those capable of measuring brain tissue oxygen, represent a promising avenue for advanced neuromonitoring. Among these, brain tissue oxygen tension (PbtO 2 ) shows the most promising results. However, there is still a lack of consensus regarding the interpretation of PbtO 2 in clinical practice. This review aims to provide an overview of the pathophysiological rationales, monitoring technology, physiological determinants, and recent clinical trial evidence for PbtO 2 monitoring in the management of msTBI., (© 2024 The Authors.)

Objective: This article aims to examine the impact of nursing workforce skill-mix (percentage of critical care registered nurses [CCRN]) in the intensive care unit (ICU) during a patient's stay., Design: Registry linked cohort study of the Australian and New Zealand Intensive Care Society Adult Patient Database and the Critical Health Resources Information System using real-time nursing workforce data., Settings: Fifteen public and 5 private hospital ICUs in Victoria, Australia., Participants: There were 16,618 adult patients admitted between 1 December 2021 and 30 September 2022., Main Outcome Measures: Primary outcome: in-hospital mortality. Secondary outcomes: in-ICU mortality, development of delirium, pressure injury, duration of stay in-ICU and hospital, after-hours discharge from ICU and readmission to ICU., Results: In total, 6563 (39.5%) patients were cared for in ICUs with >75% CCRN, 7695 (46.3%) in ICUs with 50-75% CCRN, and 2360 (14.2%) in ICUs with <50% CCRN. In-hospital mortality was 534 (8.1%) vs. 859 (11.2%) vs. 252 (10.7%) respectively. After adjusting for confounders, patients cared for in ICUs with 50-75% CCRN (adjusted OR 1.21 [95% CI 1.02-1.45]) were more likely to die compared to patients in ICUs with >75% CCRN. A similar but non-significant trend was seen in ICUs with <50% CCRN (adjusted OR 1.21 [95% CI 0.94-1.55]), when compared to patients in ICUs with >75% CCRN. In-ICU mortality, delirium, pressure injuries, after-hours discharge and ICU length of stay were lower in ICUs with CCRN>75%., Conclusion: The nursing skill-mix in ICU impacts outcomes and should be routinely monitored. Health system regulators, hospital administrators and ICU leaders should ensure nursing workforce planning and education align with these findings to maximise patient outcomes., (© 2024 The Authors.)

Objective: Determine the prevalence and outcomes of patients with life-limiting illness (LLI) admitted to Australian and New Zealand Intensive Care Units (ICUs)., Design Setting Participants: Retrospective registry-linked observational cohort study of all adults admitted to Australian and New Zealand ICUs from 1st January 2018 until 31st December 2020 (New Zealand) and 31st March 2022 (Australia), recorded in the Australian and New Zealand Intensive Care Society Adult Patient Database., Main Outcome Measures: The primary outcome was 1-year mortality. Secondary outcomes included ICU and hospital mortality, ICU and hospital length of stay, and 4-year survival., Results: A total of 566,260 patients were included, of whom 129,613 (22.9%) had one or more LLI. Mortality at one year was 28.1% in those with LLI and 10.4% in those without LLI (p < 0.001). Mortality in intensive care (6.8% v 3.4%, p < 0.001), hospital (11.8% v 5.0%, p < 0.001), and at two (36.6% v 14.1%, p < 0.001), three (43.7% v 17.7%, p < 0.001) and four (55.6% v 24.5%, p < 0.001) years were all higher in the cohort of patients with LLI. Patients with LLI had a longer ICU (1.9 [0.9, 3.7] v 1.6 [0.9, 2.9] days, p < 0.001) and hospital length of stay (8.8 [49,16.0] v 7.2 [3.9, 12.9] days, p < 0.001), and were more commonly readmitted to ICU during the same hospitalisation than patients without LLI (5.2% v 3.7%, p < 0.001). After multivariate analysis the LLI with the strongest adverse effect on survival was frailty (HR 2.08, 95% CI 2.03 to 2.12, p < 0.001), followed by the presence of metastatic cancer (HR 1.97, 95% CI 1.92 to 2.02, p < 0.001), and chronic liver disease (HR 1.65, 95% CI 1.65 to 1.71, p < 0.001)., Conclusion: Patients with LLI account for almost a quarter of ICU admissions in Australia and New Zealand, require prolonged ICU and hospital care, and have high mortality in subsequent years. This knowledge should be used to identify this vulnerable cohort of patients, and to ensure that treatment is aligned to each patient's values and realistic goals., (Crown Copyright © 2024 Published by Elsevier B.V. on behalf of College of Intensive Care Medicine of Australia and New Zealand.)

Objective: Acute respiratory distress syndrome (ARDS) is associated with significant mortality, morbidity, and cost. We aimed to describe characteristics and management of adult patients admitted to intensive care units (ICUs) in Australia and New Zealand with moderate-severe ARDS, to better understand contemporary practice., Design: Bi-national, prospective, observational, multi-centre study., Setting: 19 ICUs in Australia and New Zealand., Participants: Mechanically ventilated patients with moderate-severe ARDS., Main Outcome Measures: Baseline demographic characteristics, ventilation characteristics, use of adjunctive support therapy and all-cause mortality to day 28. Data were summarised using descriptive statistics., Results: 200 participants were enrolled, mean (±SD) age 55.5 (±15.9) years, 40% (n = 80) female. Around half (51.5%) had no baseline comorbidities and 45 (31%) tested positive for COVID-19. On day 1, mean SOFA score was 9 ± 3; median (IQR) PaO 2 /FiO 2 ratio 119 (89, 142), median (IQR) FiO 2 70% (50%, 99%) and mean (±SD) positive end expiratory pressure (PEEP) 11 (±3) cmH 2 O. On day one, 10.5% (n = 21) received lung protective ventilation (LPV) (tidal volume ≤6.5 mL/kg predicted body weight and plateau pressure or peak pressure ≤30 cm H 2 O). Adjunctive therapies were received by 86% (n = 172) of patients at some stage from enrolment to day 28. Systemic steroids were most used (n = 127) followed by neuromuscular blockers (n = 122) and prone positioning (n = 27). Median ventilator-free days (IQR) to day 28 was 5 (0, 20). In-hospital mortality, censored at day 28, was 30.5% (n = 61)., Conclusions: In Australia and New Zealand, compliance with evidence-based practices including LPV and prone positioning was low in this cohort. Therapies with proven benefit in the treatment of patients with moderate-severe ARDS, such as lung protective ventilation and prone positioning, were not routinely employed., (© 2024 The Authors.)

Objective: Intensive care unit (ICU) cost estimates are critical to achieving healthcare system efficiency and sustainability. We aimed to review the published literature describing ICU costs in Australia., Design: A systematic review was conducted to identify studies that estimated the cost of ICU care in Australia. Studies conducted in specific patient cohorts or on specific treatments were excluded., Data Sources: Relevant studies were sourced from a previously published review (1970-2016), a systematic search of MEDLINE and EMBASE (2016-5 May 2023), and reference checking., Review Methods: A tool was developed to assess study quality and risk of bias (maximum score 57/57). Total and component costs were tabulated and indexed to 2022 Australian Dollars. Costing methodologies and study quality assessments were summarised., Results: Six costing studies met the inclusion criteria. Study quality scores were low (15/41 to 35/47). Most studies were conducted only in tertiary metropolitan public ICUs; sample sizes ranged from 100 to 10,204 patients. One study used data collected within the past 10 years. Mean daily ICU costs ranged from $966 to $5381 and mean total ICU admission costs $4888 to $14,606. Three studies used a top-down costing approach, deriving cost estimates from budget reports. The other three studies used both bottom-up and top-down costing approaches. Bottom-up approaches collected individual patient resource use., Conclusions: Available ICU cost estimates are largely outdated and lack granular data. Future research is needed to estimate ICU costs that better reflect current practice and patient complexity and to determine the best methods for generating these estimates., (© 2024 The Authors.)

Objective: Fluid bolus therapy (FBT) is ubiquitous in intensive care units (ICUs) after cardiac surgery. However, its physiological effects remain unclear., Design: : We performed an electronic health record-based quasi-experimental ICU study after cardiac surgery. We applied propensity score matching and compared the physiological changes after FBT episodes to matched control episodes where despite equivalent physiology no fluid bolus was given., Setting: The study was conducted in a multidisciplinary ICU of a tertiary-level academic hospital., Participants: The study included 2,736 patients who underwent Coronary Artery Bypass Grafting and/or heart valve surgery., Main Outcome Measures: Changes in cardiac output (CO) and mean arterial pressure (MAP) during the 60 minutes following FBT., Results: We analysed 3572 matched fluid bolus (FB) episodes. After FBT, but not in control episodes, CO increased within 10 min, with a maximum increase of 0.2 l/min (95%CI 0.1 to 0.2) or 4% above baseline at 40 min (p < 0.0001 vs. controls). CO increased by > 10% from baseline in 60.6% of FBT and 49.1% of control episodes (p < 0.0001). MAP increased by > 10% in 51.7% of FB episodes compared to 53.4% of controls. Finally, FBT was not associated with changes in acid-base status or oxygen delivery., Conclusion: In this quasi-experimental comparative ICU study in cardiac surgery patients, FBT was associated with statistically significant but numerically small increases in CO. Nearly half of FBT failed to induce a positive CO or MAP response., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Objectives: Opioid use disorder is extremely common. Many long-term opioid users will have their first exposure to opioids in hospitals. We aimed to compare long-term opioid use in patients who received fentanyl vs. morphine analgosedation and assess ICU related risk factors for long-term opioid use., Design: We performed a post-hoc analysis of the Assessment of Opioid Administration to Lead to Analgesic Effects and Sedation in Intensive Care (ANALGESIC) cluster randomised crossover trial of fentanyl and morphine infusions for analgosedation in mechanically ventilated patients., Setting: Two mixed, adult, university affiliated intensive care units in Melbourne, Australia., Participants: Adult patients who were mechanically ventilated and received fentanyl or morphine for analgosedation in the ANALGESIC trial., Main Outcome Measures: We assessed discharge and long-term (90-365 days) opioid use in opioid-naïve patients at hospital admission according to the agent used for analgosedation., Results: We studied 477 patients (242 fentanyl and 235 morphine). There were no differences between discharge (16.5% vs. 14.0%, p = 0.45), 90-180 day post-discharge use (3.7% vs 2.1%, p = 0.30) or 180-365 day post-discharge use (3.4% vs 1.3%, p = 0.22) of opioids when comparing those patients who received fentanyl vs. those who received morphine. Surgical diagnosis and one chronic condition were associated with increased hospital discharge prescription of opioids, whereas increasing APACHE II score was associated with decreased discharge prescription. No ICU-related factors were associated with long-term opioid use., Conclusions: Approximately one in seven opioid-naïve patients who receive analgosedation for mechanical ventilation in ICU will be prescribed opioid medications at hospital discharge. There was no difference in discharge prescription or long-term use of opioids depending on whether fentanyl or morphine was used for analgosedation., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ary Serpa Neto reports a relationship with Drager that includes: consulting or advisory and speaking and lecture fees. Ary Serpa Neto is an Associate Editor of Critical Care and Resuscitation (voluntary role) If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2023 Published by Elsevier B.V. on behalf of College of Intensive Care Medicine of Australia and New Zealand.)

Severe traumatic brain injury (TBI) is a major cause of morbidity and mortality globally. The Brain Trauma Foundation guidelines advocate for the maintenance of a cerebral perfusion pressure (CPP) between 60 and 70 mmHg following severe TBI. However, such a uniform goal does not account for changes in cerebral autoregulation (CA). CA refers to the complex homeostatic mechanisms by which cerebral blood flow is maintained, despite variations in mean arterial pressure and intracranial pressure. Disruption to CA has become increasingly recognised as a key mediator of secondary brain injury following severe TBI. The pressure reactivity index is calculated as the degree of statistical correlation between the slow wave components of mean arterial pressure and intracranial pressure signals and is a validated dynamic marker of CA status following brain injury. The widespread acceptance of pressure reactivity index has precipitated the consideration of individualised CPP targets or an optimal cerebral perfusion pressure (CPPopt). CPPopt represents an alternative target for cerebral haemodynamic optimisation following severe TBI, and early observational data suggest improved neurological outcomes in patients whose CPP is more proximate to CPPopt. The recent publication of a prospective randomised feasibility study of CPPopt guided therapy in TBI, suggests clinicians caring for such patients should be increasingly familiar with these concepts. In this paper, we present a narrative review of the key landmarks in the development of CPPopt and offer a summary of the evidence for CPPopt-based therapy in comparison to current standards of care., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Co-author Professor Andrew Udy holds the position of Associate Editor for Critical Care and Resuscitation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Objective: Though frailty is associated with mortality, its impact on long-term survival after an ICU admission with COVID-19 is unclear. We aimed to investigate the association between frailty and long-term survival in patients after an ICU admission with COVID-19., Design Setting and Participants: This registry-based multicentre, retrospective, cohort study included all patients ≥16 years discharged alive from the hospital following an ICU admission with COVID-19 and documented clinical frailty scale (CFS). Data from 118 ICUs between 01/01/2020 through 31/12/2020 in New Zealand and 31/12/2021 in Australia were reported in the Australian and New Zealand Intensive Care Society Adult Patient Database. The patients were categorised as 'not frail' (CFS 1-3), 'mildly frail' (CFS 4-5) and 'moderately-to-severely frail' (CFS 6-8)., Main Outcome Measures: The primary outcome was survival time up to two years, which we analysed using Cox regression models., Results: We included 4028 patients with COVID-19 in the final analysis. 'Moderately-to-severely frail' patients were older (66.6 [56.3-75.8] vs. 69.9 [60.3-78.1]; p < 0.001) than those without frailty (median [interquartile range] 53.0 [40.1-64.6]), had higher sequential organ failure assessment scores (p < 0.001), and less likely to receive mechanical ventilation (p < 0.001) than patients without frailty or mild frailty. After adjusting for confounders, patients with mild frailty (adjusted hazards ratio: 2.31, 95%-CI: 1.75-3.05) and moderate-to-severe frailty (adjusted hazards ratio: 2.54, 95%-CI: 1.89-3.42) had higher mortality rates than those without frailty., Conclusions: Frailty was independently associated with shorter survival times to two years in patients with severe COVID-19 in ANZ following hospital discharge. Recognising frailty provides individualised patient intervention in those with frailty admitted to ICUs with severe COVID-19., Clinical Trial Registration: Not applicable., Competing Interests: All three authors declare no support from any organization for the submitted work. All authors declare no financial or non-financial competing interests concerning the submitted work., (© 2023 The Authors.)

Objective: We aimed to describe the characteristics, outcomes and resource utilisation of patients being cared for in an ICU after undergoing elective surgery in Australia and New Zealand (ANZ)., Methods: This was a point prevalence study involving 51 adult ICUs in ANZ in June 2021. Patients met inclusion criteria if they were being treated in a participating ICU on he study dates. Patients were categorised according to whether they had undergone elective surgery, admitted directly from theatre or unplanned from the ward. Descriptive and comparative analysis was performed according to the source of ICU admission. Resource utilisation was measured by Length of stay, organ support and occupied bed days., Results: 712 patients met inclusion criteria, with 172 (24%) have undergone elective surgery. Of these, 136 (19%) were admitted directly to the ICU and 36 (5.1%) were an unplanned admission from the ward. Elective surgical patients occupied 15.8% of the total ICU patient bed days, of which 44.3% were following unplanned admissions. Elective surgical patients who were an unplanned admission from the ward, compared to those admitted directly from theatre, had a higher severity of illness (AP2 17 vs 13, p<0.01), require respiratory or vasopressor support (75% vs 44%, p<0.01) and hospital mortality (16.7% vs 2.2%, p < 0.01)., Conclusions: ICU resource utilisation of patients who have undergone elective surgery is substantial. Those patients admitted directly from theatre have good outcomes and low resource utilisation. Patient admitted unplanned from the ward, although fewer, were sicker, more resource intensive and had significantly worse outcomes., (Crown Copyright © 2023 Published by Elsevier B.V. on behalf of College of Intensive Care Medicine of Australia and New Zealand.)

Objective: To describe current transfusion practices in intensive care units (ICUs) in Australia and New Zealand, compare them against national guidelines, and describe how viscoelastic haemostatic assays (VHAs) are used in guiding transfusion decisions., Design Setting and Participants: Prospective, multicentre, binational point-prevalence study. All adult patients admitted to participating ICUs on a single day in 2021., Main Outcome Measures: Transfusion types, amounts, clinical reasons, and triggers; use of anti-platelet medications, anti-coagulation, and VHA., Results: Of 712 adult patients in 51 ICUs, 71 (10%) patients received a transfusion during the 24hr period of observation. Compared to patients not transfused, these patients had higher Acute Physiology and Chronic Health Evaluation II scores (19 versus 17, p  = 0.02), a greater proportion were mechanically ventilated (49.3% versus 37.3%, p  < 0.05), and more had systemic inflammatory response syndrome (70.4% versus 51.3%, p  < 0.01). Overall, 63 (8.8%) patients received red blood cell (RBC) transfusions, 10 (1.4%) patients received platelet transfusions, 6 (0.8%) patients received fresh frozen plasma (FFP), and 5 (0.7%) patients received cryoprecipitate. VHA was available in 42 (82.4%) sites but only used in 6.6% of transfusion episodes when available. Alignment with guidelines was found for 98.6% of RBC transfusions, but only 61.6% for platelet, 28.6% for FFP, and 20% for cryoprecipitate transfusions., Conclusions: Non-RBC transfusion decisions are often not aligned with guidelines and VHA is commonly available but rarely used to guide transfusions. Better evidence to guide transfusions in ICUs is needed., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Andrew Flint reports financial support was provided by Australian and New Zealand Society of Blood Transfusion. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Objective: To evaluate the feasibility of conducting a prospective randomised controlled trial (pRCT) comparing remifentanil and fentanyl as adjuncts to sedate mechanically ventilated patients., Design: Single-center, open-labelled, pRCT with blinded analysis., Setting: Australian tertiary intensive care unit (ICU)., Participants: Consecutive adults between June 2020 and August 2021 expected to receive invasive ventilation beyond the next day and requiring opioid infusion were included. Exclusion criteria were pregnant/lactating women, intubation >12 h , or study-drug hypersensitivity., Interventions: Open-label fentanyl and remifentanil infusions per existing ICU protocols., Outcomes: Primary outcomes were feasibility of recruiting ≥1 patient/week and >90 % compliance, namely no other opioid infusion used during the study period. Secondary outcomes included complications, ICU-, ventilator- and hospital-free days, and mortality (ICU, hospital). Blinded intention-to-treat analysis was performed concealing the allocation group., Results: 208 patients were enrolled (mean 3.7 patients/week). Compliance was 80.6 %. More patients developed complications with fentanyl than remifentanil: bradycardia (n = 44 versus n = 21; p < 0.001); hypotension (n = 78 versus n = 53; p < 0.01); delirium (n = 28 versus n = 15; p = 0.001). No differences were seen in ICU (24.3 % versus 27.6 %,p = 0.60) and hospital mortalities (26.2 % versus 30.5 %; p = 0.50). Ventilator-free days were higher with remifentanil (p = 0.01)., Conclusions: We demonstrated the feasibility of enrolling patients for a pRCT comparing remifentanil and fentanyl as sedation adjuncts in mechanically ventilated patients. We failed to attain the study-opioid compliance target, likely because of patients with complex sedative/analgesic requirements. Secondary outcomes suggest that remifentanil may reduce mechanical ventilation duration and decrease the incidence of complications. An adequately powered multicentric phase 2 study is required to evaluate these results., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Objective: The impact of obesity on long-term survival after intensive care unit (ICU) admission with severe coronavirus disease 2019 (COVID-19) is unclear. We aimed to quantify the impact of obesity on time to death up to two years in patients admitted to Australian and New Zealand ICUs., Design: Retrospective multicentre study., Setting: 92 ICUs between 1st January 2020 through to 31st December 2020 in New Zealand and 31st March 2022 in Australia with COVID-19, reported in the Australian and New Zealand Intensive Care Society adult patient database., Participants: All patients with documented height and weight to estimate the body mass index (BMI) were included. Obesity was classified patients according to the World Health Organization recommendations., Interventions and Main Outcome Measures: The primary outcome was survival time up to two years after ICU admission. The effect of obesity on time to death was assessed using a Cox proportional hazards model. Confounders were acute illness severity, sex, frailty, hospital type and jurisdiction for all patients., Results: We examined 2,931 patients; the median BMI was 30.2 (IQR 25.6-36.0) kg/m 2 . Patients with a BMI ≥30 kg/m 2  were younger (median [IQR] age 57.7 [46.2-69.0] vs. 63.0 [50.0-73.6]; p < 0.001) than those with a BMI <30 kg/m 2 . Most patients (76.6%; 2,244/2,931) were discharged alive after ICU admission. The mortality at two years was highest for BMI categories <18.5 kg/m 2  (35.4%) and 18.5-24.9 kg/m 2  (31.1%), while lowest for BMI ≥40 kg/m 2  (14.5%). After adjusting for confounders and with BMI 18.5-24.9 kg/m 2  category as a reference, only the BMI ≥40 kg/m 2  category patients had improved survival up to 2 years (hazard ratio = 0.51; 95%CI: 0.34-0.76)., Conclusions: The obesity paradox appears to exist beyond hospital discharge in critically ill patients with COVID-19 admitted in Australian and New Zealand ICUs. A BMI ≥40 kg/m 2 was associated with a higher survival time of up to two years., Competing Interests: The authors declare the following financial interests/personal relationships that may be considered as potential competing interests: n/a If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Intravenous vitamin C is known to interfere with some point-of-care blood glucose meters. We aimed to determine the concentrations at which ascorbate interferes with glucose concentrations measured using a point-of-care blood glucose meter. We also compared the point-of-care meter and an arterial blood gas (ABG) analyser in the intensive care unit with laboratory glucose monitoring in septic patients receiving intravenous vitamin C infusions. Methods: Blood samples containing normal, depleted and supplemented glucose and increasing concentrations of ascorbate (0.1-1.0 mmol/L) were tested using an Accu-Chek Inform II (Roche Diagnostics, USA) glucometer. For the in vivo study, 41 individual blood samples were drawn daily from septic patients (n = 16) receiving infusions of 25 mg/kg of vitamin C every 6 hours. The glucose values of matched blood samples were assessed using Accu-Chek, ABG and laboratory glucose methods. Results: For every 1 mmol/L of ascorbate added, the glucose concentration measured by the point-of-care monitor increased by 1.4 mmol/L (95% CI, 1.0-1.8; P < 0.001). Analysis of matched blood samples collected following intravenous vitamin C infusion indicated that 98% of the ABG and 83% of the Accu-Chek values met the International Organization for Standardization (ISO) 15197:2013 accuracy criteria. One patient had severe renal impairment, which contributed to elevated plasma vitamin C concentrations (median, 0.95 mmol/L; range, 0.64-1.10 mmol/L), resulting in elevated Accu-Chek readings and presenting a moderate clinical risk for the highest value. Conclusions: Vitamin C concentrations < 0.8 mmol/L do not interfere with point-of-care glucose monitoring. Intravenous vitamin C infusion of 25 mg/kg every 6 hours does not interfere with point-of-care glucose monitoring unless the patient has renal impairment, in which case laboratory glucose tests should be used., Competing Interests: All authors declare that they do not have any potential conflict of interest in relation to this manuscript., (© 2022 College of Intensive Care Medicine of Australia and New Zealand.)

Objective: It is uncertain whether psychological distress in the family members of patients who die during an intensive care unit (ICU) admission may be improved by bereavement interventions. In this trial, relatives' symptoms of anxiety and depression after 6 months were measured when allocated to three commonly used bereavement follow-up strategies. Design: Single-centre, randomised, three parallel-group trial. Setting: A tertiary ICU in Australia. Participants: Relatives of patients who died in the ICU. Interventions: Relatives received bereavement follow-up 4 weeks after the death using a condolence letter, short telephone call or no contact. Main outcome measures: The primary outcome was the total Hospital Anxiety and Depression Scale (HADS-T) score. Secondary outcomes estimated anxiety, depression, complicated grief, post-traumatic stress, and satisfaction with ICU care. Results: Seventy-one relatives participated (24 had no contact, 19 were contacted by letter and 28 by telephone 4 weeks after the death). The mean HADS-T score for no contact was 16.1 (95% CI, 12.4-19.8). Receipt of a letter was associated with a mean HADS-T increase of 1.4 (4.0 decrease to 6.8 increase), and a condolence call was accompanied by a mean decrease of 1.6 (6.6 decrease to 3.4 increase; P > 0.5). Non-significant differences were observed for all secondary outcomes. Conclusions: Anxiety and depression at 6 months in the relatives of patients who died in the ICU was not meaningfully alleviated by receipt of either a condolence letter or telephone call. Trial registration: Australia New Zealand Clinical Trials Registry (ACTRN12619000917134)., Competing Interests: All authors declare that they do not have any potential conflict of interest in relation to this manuscript., (© 2022 College of Intensive Care Medicine of Australia and New Zealand.)

Objectives : To evaluate the epidemiology of rapid response team (RRT) reviews that led to intensive care unit (ICU) admissions, and to evaluate the frequency of in-hospital cardiac arrests (IHCAs) among ICU patients with confirmed coronavirus disease 2019 (COVID-19) in Australia . Design : Multicentre, retrospective cohort study. Setting: All adults (aged ≥ 16 years) with confirmed COVID-19 admitted to participating ICUs between 25 January and 31 October 2020, as part of SPRINT-SARI (Short PeRiod IncideNce sTudy of Severe Acute Respiratory Infection) Australia, which were linked with ICUs contributing to the Australian and New Zealand Intensive Care Society Adult Patient Database (ANZICS APD). Participants: Of the 413 critically ill patients with COVID-19 who were analysed, 48.2% (199/413) were admitted from the ward and 30.5% (126/413) were admitted to the ICU following an RRT review. Patients admitted following an RRT review had higher Acute Physiology and Chronic Health Evaluation (APACHE) scores, fewer days from symptom onset to hospitalisation (median, 5.4 [interquartile range (IQR), 3.2-7.6] Main outcome measures and results: Of the 413 critically ill patients with COVID-19 who were analysed, 48.2% (199/413) were admitted from the ward and 30.5% (126/413) were admitted to the ICU following an RRT review. Patients admitted following an RRT review had higher Acute Physiology and Chronic Health Evaluation (APACHE) scores, fewer days from symptom onset to hospitalisation (median, 5.4 [interquartile range (IQR), 3.2-7.6] v 7.1 days [IQR, 4.1-9.8]; P < 0.001) and longer hospitalisations (median, 18 [IQR, 11-33] v < 0.001) compared with those not admitted via an RRT review. Admissions following RRT review comprised 60.3% (120/199) of all ward-based admissions. Overall, IHCA occurred in 1.9% (8/413) of ICU patients with COVID-19, and most IHCAs (6/8, 75%) occurred during ICU admission. There were no differences in IHCA rates or in ICU or hospital mortality rates based on whether a patient had a prior RRT review or not. P < 0.001) compared with those not admitted via an RRT review. Admissions following RRT review comprised 60.3% (120/199) of all ward-based admissions. Overall, IHCA occurred in 1.9% (8/413) of ICU patients with COVID-19, and most IHCAs (6/8, 75%) occurred during ICU admission. There were no differences in IHCA rates or in ICU or hospital mortality rates based on whether a patient had a prior RRT review or not. Conclusions : This study found that RRT reviews were a common way for deteriorating ward patients with COVID-19 to be admitted to the ICU, and that IHCA was rare among ICU patients with COVID-19., Competing Interests: All authors declare that they do not have any potential conflict of interest in relation to this manuscript., (© 2022 College of Intensive Care Medicine of Australia and New Zealand.)

Objective: It remains unclear whether balanced solutions improve patient-centred outcomes in critically ill patients overall and whether the treatment effect is heterogeneous, with evidence that some populations of patients may be helped and others harmed. To provide the most up-to-date and comprehensive assessment of the totality of the evidence, we will perform an ongoing living systematic review with aggregated and individual patient data meta-analysis (IPDMA) comparing the use of balanced solutions with saline in critically ill adults. Design: Living systematic review using aggregated and individual patient data from randomised controlled trials. Data sources: We will conduct annual searches of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials. gov, the Australian New Zealand Clinical Trials Registry (ANZCTR), Japan's University Hospital Medical Information Network (UMIN) Center, and the Brazilian Registry of Clinical Trials (ReBEC). The first search was completed on 1 March 2022 and will be repeated annually. Authors of eligible trials will be invited to provide individual data for the IPDMA. The initial analysis will use all data received up to 30 June 2022. Review methods: We will include randomised controlled trials in adults treated in an intensive care unit that allocated individuals or clusters of patients to a balanced crystalloid solution or 0.9% saline for intravenous fluid therapy. Studies that used colloids as part of the intervention or that recruited only elective surgical patients will be excluded. The primary endpoint will be in-hospital mortality. The key secondary endpoint will be survival at longest follow-up for each trial. Data will be synthesised using both a random effect Bayesian meta-analysis and using hierarchical Bayesian models for individual patient data. Discussion: The use of balanced crystalloid solutions may reduce mortality and improve other outcomes in some critically ill patients. We will assess the totality of current and future evidence by performing an ongoing living systematic review with aggregated data and IPDMA. Protocol registration: CRD42022299282., Competing Interests: FGZ reports receiving grants for investigator-initiated trial from Ionis Pharmaceuticals (USA) and logistics support from Baxter Hospitalar (Brazil) for the BaSICS trial. SF / JM / NH / SM received unrestricted grants from Baxter and CSL (Paid to their institution)., (© 2022 College of Intensive Care Medicine of Australia and New Zealand.)

Background: The effect of conservative versus liberal oxygen therapy on 90-day in-hospital mortality in patients who require unplanned invasive mechanical ventilation in an intensive care unit (ICU) is uncertain and will be evaluated in the mega randomised registry trial research program (Mega-ROX). Objective: To summarise the protocol and statistical analysis plan for Mega-ROX. Design, setting and participants: Mega-ROX is a 40 000-patient parallel-group, registry-embedded clinical trial in which adults who require unplanned invasive mechanical ventilation in an ICU will be randomly assigned to conservative or liberal oxygen therapy. Within this overarching trial research program, three nested parallel randomised controlled trials will be conducted. These will include patients with suspected hypoxic ischaemic encephalopathy (HIE) following resuscitation from a cardiac arrest, patients with sepsis, and patients with non-HIE acute brain injuries or conditions. Main outcome measures: The primary outcome is in-hospital allcause mortality up to 90 days from the date of randomisation. Secondary outcomes include duration of survival, duration of mechanical ventilation, ICU length of stay, hospital length of stay, and proportion of patients discharged home. Results and conclusions: Mega-ROX will compare the effect of conservative versus liberal oxygen therapy on 90-day in-hospital mortality in critically ill adults who receive unplanned invasive mechanical ventilation in an ICU. The protocol and a pre-specified approach to analyses are reported here to mitigate analysis bias. Trial registration: Australian and New Zealand Clinical Trials Registry (ANZCTRN 12620000391976)., Competing Interests: All authors declare that they do not have any potential conflict of interest in relation to this manuscript., (© 2022 College of Intensive Care Medicine of Australia and New Zealand.)

Background: Acute pulmonary oedema is a life-threatening syndrome diagnosed based on radiological and clinical findings. However, to our knowledge, no studies have investigated this syndrome in critically ill patients. Objective: To describe the prevalence of radiologically and clinically diagnosed pulmonary oedema (RCDPO) in critically ill patients, characteristics of diagnosed patients, and treatments and outcomes in this patient population. Methods: We conducted a retrospective study using natural language processing to identify all radiological reports of pulmonary oedema among patients who had been admitted to single tertiary intensive care unit (ICU) over a 1-year period (January 2015 to January 2016). We reviewed clinical data, discharge diagnosis, treatment and outcomes for such patients, and used multivariable logistic regression analysis to identify the association of RCDPO with various outcomes. Results: Out of 2001 ICU patients, we identified 238 patients (11.9%) with RCDPO. Patients with RCDPO were more acutely ill, had more chronic liver disease and had more chronic renal failure than critically ill patients who did not have RCDPO. They were typically admitted with acute cardiovascular disease; were more likely to receive invasive mechanical ventilation and continuous renal replacement therapy; had longer duration of ICU and hospital stay; were more likely to die in hospital; and, if discharged alive, were more likely to be admitted to a chronic care facility. In total, 46 RCDPO patients (19.3%) died in hospital. On multivariable analysis, only age and continuous renal replacement therapy were independently associated with mortality. In contrast, invasive mechanical ventilation was associated with a 2.5 times greater odds of radiological resolution. Conclusion: RCDPO affected about one in eight ICU patients. Such patients were sicker and had more comorbidities. The presence of RCDPO was independently associated with higher risk of death. Invasive mechanical ventilation was the only intervention independently associated with greater odds of radiological resolution., Competing Interests: No relevant disclosures., (© 2021 College of Intensive Care Medicine of Australia and New Zealand.)

Background: To our knowledge, the use and management of pressure support ventilation (PSV) in patients receiving prolonged (≥ 7 days) invasive mechanical ventilation has not previously been described. Objective: To collect and analyse data on the use and management of PSV in critically ill patients receiving prolonged ventilation. Design, setting and participants: We performed a multicentre retrospective observational study in Australia, with a focus on PSV in patients ventilated for ≥ 7 days. Main outcome measures: We obtained detailed data on ventilator management twice daily (8am and 8pm moments) for the first 7 days of ventilation. Results: Among 143 consecutive patients, 90/142 (63.4%) had received PSV by Day 7, and PSV accounted for 40.5% (784/1935) of ventilation moments. The most common pressure support level was 10 cmH 2 O (352/780) observations [45.1%]) with little variation over time, and 37 of 114 patients (32.4%) had no change in pressure support. Mean tidal volume during PSV was 8.3 (7.0-9.5) mL/kg predicted bodyweight (PBW) compared with 7.5 (7.0-8.3) mL/kg PBW during mandatory ventilation (P < 0.001). For 74.6% (247/331) of moments, despite a tidal volume of more than 8 mL/kg PBW, the pressure support level was not changed. Among 122 patients exposed to PSV, 97 (79.5%) received likely over-assistance according to rapid shallow breathing index criteria. Of 784 PSV moments, 411 (52.4%) were also likely over-assisted according to rapid shallow breathing index criteria, and 269/346 (77.7%) having no subsequent adjustment of pressure support. Conclusions: In patients receiving prolonged ventilation, almost two-thirds received PSV, which accounted for 40.5% of mechanical ventilation time. Half of the PSV-treated patients were exposed to high tidal volume and two-thirds to likely over-assistance. These observations provide evidence that can be used to inform interventional studies of PSV management., Competing Interests: No relevant disclosures., (© 2021 College of Intensive Care Medicine of Australia and New Zealand.)

Objectives: The 12-item World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) provides a standardised method for measuring health and disability. This study aimed to determine its reliability, validity and responsiveness and to establish the minimum clinically important difference (MCID) in critically ill patients. Design: Prospective, multicentre cohort study. Setting: Intensive care units of six metropolitan hospitals. Participants: Adults mechanically ventilated for > 24 hours. Main outcome measures: Reliability was assessed by measuring internal consistency. Construct validity was assessed by comparing WHODAS 2.0 scores at 6 months with the EuroQoL visual analogue scale (EQ VAS) and Lawton Instrumental Activities of Daily Living (IADL) scale scores. Responsiveness was evaluated by assessing change over time, effect sizes, and percentage of patients showing no change. The MCID was calculated using both anchor and distribution-based methods with triangulation of results. Main results: A baseline and 6-month WHODAS 2.0 score were available for 448 patients. The WHODAS 2.0 demonstrated good correlation between items with no evidence of item redundancy. Cronbach α coefficient was 0.91 and average split-half coefficient was 0.91. There was a moderate correlation between the WHODAS 2.0 and the EQ VAS scores ( r = -0.72; P < 0.001) and between the WHODAS 2.0 and the Lawton IADL scores ( r = -0.66; P < 0.001) at 6 months. The effect sizes for change in the WHODAS 2.0 score from baseline to 3 months and from 3 to 6 months were low. Ceiling effects were not present and floor effects were present at baseline only. The final MCID estimate was 10%. Conclusion: The 12-item WHODAS 2.0 is a reliable, valid and responsive measure of disability in critically ill patients. A change in the total WHODAS 2.0 score of 10% represents the MCID., Competing Interests: None declared., (© 2021 College of Intensive Care Medicine of Australia and New Zealand.)

Objective: To study the temperature and haemodynamic effects of room versus body temperature 20% albumin fluid bolus therapy (FBT). Design: Single-centre, prospective, before-after trial. Setting: A tertiary intensive care unit (ICU) in Australia. Participants: Sixty ventilated post-cardiac surgery patients. Intervention: Room versus body temperature 100 mL 20% albumin FBT. Main outcome measures: We recorded haemodynamic data from FBT start to 30 minutes after FBT. The cardiac index (CI) response was defined by a CI increase > 15%, and the mean arterial pressure (MAP) response was defined by a MAP increase > 10%. Outcomes: Immediately after FBT, median blood temperature decreased by -0.1°C (interquartile range [IQR], -0.1 to 0.0°C) with room temperature albumin versus 0.0°C (IQR, -0.1 to 0.0°C) with body temperature albumin ( P < 0.001). The CI or MAP responses were similar. There was, however, a time and study group interaction for blood temperature ( P < 0.001) for absolute and relative changes. In addition, mean pulmonary arterial pressure (PAP) ( P = 0.002) increased more with body temperature albumin and remained higher for most of the observation period. Conclusion: Compared with room temperature albumin FBT, body temperature 20% albumin FBT prevents FBT-associated blood temperature fall and increases mean PAP. However, CI and MAP changes were the similar between the two groups, implying that fluid temperature has limited haemodynamic effects in these patients., Competing Interests: None declared., (© 2021 College of Intensive Care Medicine of Australia and New Zealand.)

Objective: To investigate the environment and care in the intensive care unit (ICU) and its relationship to patient circadian temperature disruption. Design: 30-day, prospective period prevalence study. Setting: 27-bed tertiary ICU. Participants: Patients expected to remain in the ICU for at least 24 hours. Main outcome measures: Temperature, relative humidity, light and sound intensity in the ICU; nursing interventions (using the Therapeutic Intervention Scoring System-28); and core body temperature of ICU patients. Results: Of 28 patients surveyed, 20 (71%) were mechanically ventilated. Median (interquartile range [IQR]) light intensity peaked at 07:00 at 165 (12-1218) lux with a trough at 23:00 of 15 (12-51) lux and was consistently < 100 lux between 21:00 and 06:00. Peak median (IQR) sound intensity was at 07:00 (62.55 [57.87-68.03] dB) while 58.84 (54.81-64.71) dB at 02:00. Ambient temperature and humidity varied with median (IQR) peaks of 23.11°C (22.74-23.31°C) at 16:00 and 44.07% (32.76-51.08%) at 11:00 and median troughs of 22.37°C (21.79-22.88°C) at 05:00 and 39.95% (31.53-47.95%) at 14:00, respectively. Disturbances to sleep during the night occurred due to care activities including linen changes (15 patients, 54%) and bathing (13, 46%). On the day before and the day of the study, 13 patients (47%) and 10 patients (36%), respectively, had a circadian rhythm on core body temperature without an association with illness severity, nursing intervention or environmental measures. Conclusions: The ICU has low light intensity with relative humidity and ambient temperature not aligned to normal human circadian timing. Noise levels are commonly equivalent to conversational speech while patient care procedures interrupt overnight sleep. The contribution of these factors to disrupted CBT rhythmicity is unclear., Competing Interests: None declared., (© 2020 College of Intensive Care Medicine of Australia and New Zealand.)

Objective: To evaluate the haemodynamic effects of rapid fluid bolus therapy (FBT) (500 mL of 4% albumin over several minutes) versus combined FBT (rapid 200 mL FBT followed by a 300 mL infusion over 30 minutes). Design: Single centre, prospective, before-and-after trial. Setting: A tertiary intensive care unit in Australia. Participants: Fifty mechanically ventilated post-cardiac surgery patients. Interventions: Rapid 4% albumin FBT versus combined FBT. Main outcome measures: We recorded haemodynamic parameters from before FBT to 30 minutes after FBT. A mean arterial pressure (MAP) response was defined by a MAP increase > 10%, and a cardiac index (CI) response was defined by a CI increase > 15%. Results: Immediately after rapid FBT versus combined FBT, there was a CI response in 13 patients (52%) compared with five patients (20%) respectively ( P = 0.038), and a MAP response in 11 patients (44%) in each group. However, from FBT administration to 30 minutes, there was a time and group interaction such that MAP was higher in the rapid FBT group ( P = 0.003), as was the case for central venous pressure ( P = 0.002) and mean pulmonary artery pressure ( P < 0.001). Body temperature fell immediately and was lower with rapid FBT but became warmer than with combined FBT later ( P < 0.001). At 30 minutes, a MAP response was seen in ten patients (40%) compared with nine patients (36%) ( P < 0.99) and a CI response was present in eight patients (32%) compared with 11 patients (44%) ( P = 0.56) in the rapid versus combined FBT groups respectively. Conclusion: Rapid FBT was superior to combined FBT in terms of mean MAP levels and immediate CI response. However, the number of MAP responders or CI responders was similar at 30 minutes., Competing Interests: No relevant disclosures., (© 2021 College of Intensive Care Medicine of Australia and New Zealand.)

Objective: To characterise the assessment and management of delirium in patients admitted to intensive care units (ICUs) in Australia and New Zealand. Methods: We conducted a multicentre observational point prevalence study across 44 adult Australian and New Zealand ICUs. Data were extracted for all patients in the ICU in terms of assessment and treatment of delirium. ICU-level data were collected regarding the use of explicit protocols related to delirium. Results: We studied 627 patients, with 54% (336/627) having at least one delirium screening assessment performed. The Confusion Assessment Method for the ICU (CAM-ICU) was the most frequently used tool (88%, 296/336). Of patients assessed, 20% (68) were identified to have delirium. Eighteen per cent (111) of patients were administered a drug to manage delirium, with 41% (46) of those receiving a drug having no recorded assessment for delirium on that day. Of the drugs used to treat delirium, quetiapine was the most frequently administered. Physical restraints were applied to 8% (48/626) of patients, but only 17% (8/48) of such patients had been diagnosed with delirium. Most physically restrained patients either did not have delirium diagnosed (31%, 15/48) or had no formal assessment recorded (52%, 25/48) on that day. Conclusions: On the study day, more than 50% of patients had a delirium screening assessment performed, with 20% of screened patients deemed to have delirium. Drugs that are prescribed to treat delirium and physical restraints were frequently used in the absence of delirium or the formal assessment for its presence., Competing Interests: None declared., (© 2020 College of Intensive Care Medicine of Australia and New Zealand.)

Objective: The accuracy of different non-invasive body temperature measurement methods in intensive care unit (ICU) patients is uncertain. We aimed to study the accuracy of three commonly used methods. Design: Prospective observational study. Setting: ICUs of two tertiary Australian hospitals. Participants: Critically ill patients admitted to the ICU. Interventions: Invasive (intravascular and intra-urinary bladder catheter) and non-invasive (axillary chemical dot, tympanic infrared, and temporal scanner) body temperature measurements were taken at study inclusion and every 4 hours for the following 72 hours. Main outcome measures: Accuracy of non-invasive body temperature measurement methods was assessed by the Bland-Altman approach, accounting for repeated measurements and significant explanatory variables that were identified by regression analysis. Clinical adequacy was set at limits of agreement (LoA) of 1°C compared with core temperature. Results: We studied 50 consecutive critically ill patients who were mainly admitted to the ICU after cardiac surgery. From over 375 observations, invasive core temperature (mostly pulmonary artery catheter) ranged from 33.9°C to 39°C. On average, the LoA between invasive and non-invasive measurements methods were about 3°C. The temporal scanner showed the worst performance in estimating core temperature (bias, 0.66°C; LoA, -1.23°C, +2.55°C), followed by tympanic infrared (bias, 0.44°C; LoA, -1.73°C, +2.61°C) and axillary chemical dot methods (bias, 0.32°C; LoA, -1.64°C, +2.28°C). No methods achieved clinical adequacy even accounting for significant explanatory variables. Conclusions: The axillary chemical dot, tympanic infrared and temporal scanner methods are inaccurate measures of core temperature in ICU patients. These non-invasive methods appeared unreliable for use in ICU patients., Competing Interests: No relevant disclosures., (© 2021 College of Intensive Care Medicine of Australia and New Zealand.)

Background: The β-Lactam Infusion Group (BLING) III study is a prospective, multicentre, open, phase 3 randomised controlled trial comparing continuous infusion with intermittent infusion of β-lactam antibiotics in 7000 critically ill patients with sepsis. Objective: To describe a statistical analysis plan for the BLING III study. Methods: The statistical analysis plan was designed by the trial statistician and chief investigators and approved by the BLING III management committee before the completion of data collection. Statistical analyses for primary, secondary and tertiary outcomes and planned subgroup analyses are described in detail. Interim analysis by the Data Safety and Monitoring Committee (DSMC) has been conducted in accordance with a pre-specified DSMC charter. Results and conclusions: The statistical analysis plan for the BLING III study is published before completion of data collection and unblinding to minimise analysis bias and facilitate public access and transparent analysis and reporting of study findings. Trial registration: ClinicalTrials.gov Registry NCT03212990., Competing Interests: Jeffrey Lipman has served as a board member for the Bayer ESICM and MSD Antibacterials Advisory Boards and given lectures with honoraria from Pfizer and MSD. Stephen Brett has received a speaker’s fee and attended an Advisory Board from Orion Pharma. Jan De Waele has attended Advisory Boards, acted as a consultant to, or given lectures with honoraria from Accelerate, Bayer Healthcare, Grifols, MSD and Pfizer. David Paterson has received research grants from AstraZeneca and has attended Advisory Boards, acted as a consultant to, or given lectures with honoraria from Three Rivers Pharmaceuticals, Merck, AstraZeneca, SanofiAventis, Pfizer, Johnson and Johnson, Shionogi, Sumitomo and Leo Pharmaceuticals. Jason Roberts has served as a consultant for MSD, Bayer, Astellas, bioMerieux and Accelerate Diagnostics and has received research grants from MSD, The Medicines Company, Pfizer, Astellas and Cardeas Pharma. Claire Roger has received speaker’s fees from Pfizer and MSD. Colman Taylor owns a company, Health Technology Analysts, which provides consulting services to pharmaceutical companies, medical device companies and the Australian Government., (© 2021 College of Intensive Care Medicine of Australia and New Zealand.)

Objective: To compare the characteristics, treatments and 6-month functional outcomes of patients with coronavirus disease 2019 (COVID-19) versus non-COVID-19 viral pneumonitis supported by venovenous extracorporeal membrane oxygenation (VV-ECMO). Design: Prospective, observational cohort study in seven intensive care units (ICUs) across Australia. Participants: Patients admitted to participating ICUs with laboratory-confirmed COVID-19 or viral pneumonitis requiring VV-ECMO. Results: From 30 March 2019 to 31 December 2020, 13 patients were initiated on VV-ECMO for COVID-19 and 23 were initiated for non-COVID-19 viral pneumonitis. Patients with COVID-19 were older and had a longer duration from intubation to ECMO initiation, but had similar illness severity and APACHE IV scores at the time of initiation. Overall disability, health-related quality of life, and mortality were similar, but ICU and hospital length of stay were significantly longer in patients with COVID-19. Conclusions: Six-month functional outcomes and mortality were similar between COVID-19 and viral pneumonitis patients treated with VV-ECMO. However, length of stay was longer in COVID-19 patients, which may have resource implications., Competing Interests: All authors declare that they do not have any potential conflict of interest in relation to this manuscript., (© 2022 College of Intensive Care Medicine of Australia and New Zealand.)

Background: The NITric oxide during cardiopulmonary bypass (CPB) to improve Recovery in Infants with Congenital heart defects (NITRIC) trial, a 1320-patient, multicentre, randomised controlled trial, is aiming to improve survival free of ventilation after CPB by using nitric oxide delivered into the oxygenator of the CPB. Objective: To provide a statistical analysis plan before completion of patient recruitment and data monitoring. Final analyses for this study will adhere to this statistical analysis plan, which details all key pre-planned analyses. Stata scripts for analyses have been prepared alongside this statistical analysis plan. Methods: The statistical analysis plan was designed collaboratively by the chief investigators and trial statistician and builds on the previously published study protocol. All authors remain blinded to treatment allocation. Detail is provided on statistical analyses including cohort description, analysis of primary and secondary outcomes and adverse events. Statistical methods to compare outcomes are planned in detail to ensure methods are verifiable and reproducible. Results: The statistical analysis plan developed provides the trial outline, list of mock tables, and analysis scripts. The plan describes statistical analyses on cohort and baseline description, primary and secondary outcome analyses, process of care measures, physiological descriptors, and safety and adverse event reporting. We define the pre-specified subgroup analyses and the respective statistical tests used to compare subgroups. Conclusion: The statistical analysis plan for the NITRIC trial establishes detailed pre-planned analyses alongside Stata scripts to analyse the largest trial in the field of neonatal and paediatric heart surgery. The plan ensures standards for trial analysis validity aiming to minimise bias of analyses. Trial registration: ACTRN12617000821392., Competing Interests: Yves d’Udekem receives consultancy fees from Actelion (Janssen) and travel fees from Berlin Heart., (© 2021 College of Intensive Care Medicine of Australia and New Zealand.)

Competing Interests: Balasubramanian Venkatesh is the Chair of the Queensland Statewide Sepsis Steering Committee.

Objective: To report longitudinal differences in baseline characteristics, treatment, and outcomes in patients with coronavirus disease 2019 (COVID-19) admitted to intensive care units (ICUs) between the first and second waves of COVID-19 in Australia. Design, setting and participants: SPRINT-SARI Australia is a multicentre, inception cohort study enrolling adult patients with COVID-19 admitted to participating ICUs. The first wave of COVID-19 was from 27 February to 30 June 2020, and the second wave was from 1 July to 22 October 2020. Results: A total of 461 patients were recruited in 53 ICUs across Australia; a higher number were admitted to the ICU during the second wave compared with the first: 255 (55.3%) versus 206 (44.7%). Patients admitted to the ICU in the second wave were younger (58.0 v 64.0 years; P = 0.001) and less commonly male (68.9% v 60.0%; P = 0.045), although Acute Physiology and Chronic Health Evaluation (APACHE) II scores were similar (14 v 14; P = 0.998). High flow oxygen use (75.2% v 43.4%; P < 0.001) and non-invasive ventilation (16.5% v 7.1%; P = 0.002) were more common in the second wave, as was steroid use (95.0% v 30.3%; P < 0.001). ICU length of stay was shorter (6.0 v 8.4 days; P = 0.003). In-hospital mortality was similar (12.2% v 14.6%; P = 0.452), but observed mortality decreased over time and patients were more likely to be discharged alive earlier in their ICU admission (hazard ratio, 1.43; 95% CI, 1.13-1.79; P = 0.002). Conclusion: During the second wave of COVID-19 in Australia, ICU length of stay and observed mortality decreased over time. Multiple factors were associated with this, including changes in clinical management, the adoption of new evidence-based treatments, and changes in patient demographic characteristics but not illness severity., Competing Interests: No relevant disclosures., (© 2021 College of Intensive Care Medicine of Australia and New Zealand.)

Background and objectives: The effect of initiating continuous renal replacement therapy (CRRT) on urine output, fluid balance and mean arterial pressure (MAP) in adult intensive care unit (ICU) patients is unclear. We aimed to evaluate the impact of CRRT on urine output, MAP, vasopressor requirements and fluid balance, and to identify factors affecting urine output during CRRT. Design: Retrospective cohort study using data from existing databases and CRRT machines. Setting: Medical and surgical ICUs at a single university-associated centre. Participants: Patients undergoing CRRT between 2015 and 2018. Main outcome measures: Hourly urine output, fluid balance, MAP and vasopressor dose 24 hours before and after CRRT commencement. Missing values were estimated via Kaplan smoothing univariate time-series imputation. Mixed linear modelling was performed with noradrenaline equivalent dose and urine output as outcomes. Results: In 215 patients, CRRT initiation was associated with a reduction in urine output. Multivariate analysis confirmed an immediate urine output decrease (-0.092 mL/kg/h; 95% confidence interval [CI], -0.150 to -0.034 mL/kg/h) and subsequent progressive urine output decline (effect estimate, -0.01 mL/kg/h; 95% CI, -0.02 to -0.01 mL/kg/h). Age and greater vasopressor dose were associated with lower post-CRRT urine output. Higher MAP and lower rates of net ultrafiltration were associated with higher post-CRRT urine output. With MAP unchanged, vasopressor dose increased in the 24 hours before CRRT, then plateaued and declined in the 24 hours thereafter (effect estimate, -0.004 μg/kg/ min per hour; 95% CI, -0.005 to -0.004 μg/kg/min per hour). Fluid balance remained positive but declined towards neutrality following CRRT implementation. Conclusions: CRRT was associated with decreased urine output despite a gradual decline in vasopressor and a positive fluid balance. The mechanisms behind the reduction in urine output associated with commencement of CRRT requires further investigation., Competing Interests: All authors declare that they do not have any potential conflict of interest in relation to this manuscript., (© 2022 College of Intensive Care Medicine of Australia and New Zealand.)

Objective: To describe the pattern of acute illness and 6-month mortality and health-related quality-of-life outcomes for a cohort of Aboriginal and Torres Strait Islander patients presenting with septic shock. Design: Nested cohort study of Aboriginal and Torres Strait Islander participants recruited to a large randomised controlled trial of corticosteroid treatment in patients with septic shock. Setting: Royal Darwin Hospital, Northern Territory. Participants: All Aboriginal and Torres Strait Islander patients recruited to the Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock (ADRENAL) trial at Royal Darwin Hospital were compared with a non-Indigenous cohort drawn from the same site, and a cohort matched for age, sex and severity of disease. Main outcome measures: Mortality at 90 days and 6 months, time to shock resolution, mechanical ventilation requirement, renal replacement therapy requirement, and five-domain, five-level EuroQol questionnaire (EQ-5D-5L) score at 6 months. Results: Aboriginal and Torres Strait Islander patients had significantly reduced risk of death at 90 days when compared with non-Indigenous patients recruited to ADRENAL at Royal Darwin Hospital (12/60 v 23/62; adjusted odds ratio, 0.40 [95% CI, 0.17 to 0.94]) which was robust to additional adjustment for baseline covariates (odds ratio, 0.35 [95% CI, 0.14 to 0.90]). When compared with the matched population drawn from the broader ADRENAL cohort, there was no significant difference in 90-day mortality (12/60 v 16/61; adjusted odds ratio, 1.43 [95% CI, 0.60 to 3.39]; P = 0.42). Only nine Aboriginal and Torres Strait Islander patients provided 6-month health-related quality-of-life data. Conclusions: Aboriginal and Torres Strait Islander patients had reduced risk of death at 90 days when compared with non- Indigenous patients recruited to the ADRENAL trial at Royal Darwin Hospital, which was robust to adjustment for covariates, but similar outcomes when compared with a cohort matched for age, sex and severity of disease., Competing Interests: All authors declare that they do not have any potential conflict of interest in relation to this manuscript., (© 2022 College of Intensive Care Medicine of Australia and New Zealand.)

Competing Interests: No relevant disclosures.

Objective: To assess the incidence and impact of metabolic acidosis in Indigenous and non-Indigenous patients Design: Retrospective study. Setting: Adult intensive care units (ICUs) from Australia and New Zealand. Participants: Patients aged 16 years or older admitted to an Australian or New Zealand ICU in one of 195 contributing ICUs between January 2019 and December 2020 who had metabolic acidosis, defined as pH < 7.30, base excess (BE) < - 4 mEq/L and PaCO 2 ≤ 45 mmHg. Main outcome measures: The primary outcome was the prevalence of metabolic acidosis. Secondary outcomes included ICU length of stay, hospital length of stay, receipt of renal replacement therapy (RRT), major adverse kidney events at 30 days (MAKE30), and hospital mortality. Results: Overall, 248 563 patients underwent analysis, with 11 537 (4.6%) in the Indigenous group and 237 026 (95.4%) in the non-Indigenous group. The prevalence of metabolic acidosis was higher in Indigenous patients (9.3% v 6.1%; P < 0.001). Indigenous patients with metabolic acidosis received RRT more often (28.2% v 22.0%; P < 0.001), but hospital mortality was similar between the groups (25.8% in Indigenous v 25.8% in non-Indigenous; P = 0.971). Conclusions: Critically ill Indigenous ICU patients are more likely to have a metabolic acidosis in the first 24 hours of their ICU admission, and more often received RRT during their ICU admission compared with non-Indigenous patients. However, hospital mortality was similar between the groups., Competing Interests: All authors declare that they do not have any potential conflict of interest in relation to this manuscript., (© 2022 College of Intensive Care Medicine of Australia and New Zealand.)

Objectives: To validate a real-time Intensive Care Unit (ICU) Activity Index as a marker of ICU strain from daily data available from the Critical Health Resource Information System (CHRIS), and to investigate the association between this Index and the need to transfer critically ill patients during the coronavirus disease 2019 (COVID-19) pandemic in Victoria, Australia. Design: Retrospective observational cohort study. Setting: All 45 hospitals with an ICU in Victoria, Australia. Participants: Patients in all Victorian ICUs and all critically ill patients transferred between Victorian hospitals from 27 June to 6 September 2020. Main outcome measure: Acute interhospital transfer of one or more critically ill patients per day from one site to an ICU in another hospital. Results: 150 patients were transported over 61 days from 29 hospitals (64%). ICU Activity Index scores were higher on days when critical care transfers occurred (median, 1.0 [IQR, 0.4-1.7] v 0.6 [IQR, 0.3-1.2]; P < 0.001). Transfers were more common on days of higher ICU occupancy, higher numbers of ventilated or COVID-19 patients, and when more critical care staff were unavailable. The highest ICU Activity Index scores were observed at hospitals in north-western Melbourne, where the COVID-19 disease burden was greatest. After adjusting for confounding factors, including occupancy and lack of available ICU staff, a rising ICU Activity Index score was associated with an increased risk of a critical care transfer (odds ratio, 4.10; 95% CI, 2.34-7.18; P < 0.001). Conclusions: The ICU Activity Index appeared to be a valid marker of ICU strain during the COVID-19 pandemic. It may be useful as a real-time clinical indicator of ICU activity and predict the need for redistribution of critical ill patients., Competing Interests: No relevant disclosures., (© 2021 College of Intensive Care Medicine of Australia and New Zealand.)

Objective: To determine the cost-effectiveness of early goal-directed therapy (EGDT) for patients with early septic shock. Design: Within-trial cost-effectiveness evaluation. Setting: Nineteen hospitals in Australia and New Zealand. Participants and interventions: Patients with early septic shock enrolled in the Australasian Resuscitation in Sepsis Evaluation (ARISE) trial were randomly assigned to EGDT versus usual care. A subgroup of patients participated in a nested economic evaluation study in which detailed resource use data were collected until 12 months after randomisation. Outcome measures: Clinical outcomes included lives saved, life-years gained and quality-adjusted life-years (QALYs), with mortality collected until 12 months and health-related quality of life assessed at baseline, 6 and 12 months using the 3-level EuroQol five dimensions questionnaire (EQ-5D-3L). Economic outcomes included health care resource use, costs and cost-effectiveness from the Australian health care payer perspective. Results: A total of 205 patients (100 EGDT, 105 usual care) participated in the nested economic evaluation study, of which 203 had complete resource use data. Unadjusted mean health care costs to 12 months were $67 223 (standard deviation [SD], $72 397) in the EGDT group and $54 179 (SD, $61 980) in the usual care group, with a mean difference of $13 044 (95% CI, -$5791 to $31 878). There was no difference between groups with regards to lives saved (EGDT, 69.4% v usual care, 68.6%; P = 1.0), life-years gained (mean EGDT, 0.746 [SD, 0.406] v usual care, 0.725 [SD, 0.417]; P = 0.72) or QALYs (mean EGDT, 0.318 [SD, 0.291] v usual care, 0.367 [SD, 0.295]; P = 0.24). EGDT was dominated (higher costs, lower effectiveness) by usual care in 80.4% of bootstrap replications. For a willingness-to-pay threshold of $50 000 per QALY, the probability of EGDT being cost-effective was only 6.4%. Conclusions: In patients presenting to the emergency department with early septic shock, EGDT compared with usual care was not cost-effective. Clinical trial registration: ClinicalTrials.gov number NCT00975793., Competing Interests: No relevant disclosures., (© 2021 College of Intensive Care Medicine of Australia and New Zealand.)

Objective: The use of angiotensin II in invasively ventilated patients with coronavirus disease 2019 (COVID-19) is controversial. Its effect on organ function is unknown. Design: Prospective observational study. Setting: Intensive care unit (ICU) of a tertiary academic hospital in Milan, Italy. Participants: Adult patients receiving mechanical ventilation due to COVID-19. Interventions: Use angiotensin II either as rescue vasopressor agent or as low dose vasopressor support. Main outcome measures: Patients treated before angiotensin II was available or treated in an adjacent COVID-19 ICU served as controls. For data analysis, we applied Bayesian modelling as appropriate. We assessed the effects of angiotensin II on organ function. Results: We compared 46 patients receiving angiotensin II therapy with 53 controls. Compared with controls, angiotensin II increased the mean arterial pressure (median difference, 9.05 mmHg; 95% CI, 1.87-16.22; P = 0.013) and the PaO 2 /FiO 2 ratio (median difference, 23.17; 95% CI, 3.46-42.88; P = 0.021), and decreased the odds ratio (OR) of liver dysfunction (OR, 0.32; 95% CI, 0.09-0.94). However, angiotensin II had no effect on lactate, urinary output, serum creatinine, C-reactive protein, platelet count, or thromboembolic complications. In patients with abnormal baseline serum creatinine, Bayesian modelling showed that angiotensin II carried a 95.7% probability of reducing the use of renal replacement therapy (RRT). Conclusions: In ventilated patients with COVID-19, angiotensin II therapy increased blood pressure and PaO 2 /FiO 2 ratios, decreased the OR of liver dysfunction, and appeared to decrease the risk of RRT use in patients with abnormal baseline serum creatinine. However, all of these findings are hypothesis-generating only. Trial registration: ClinicalTrials.gov NCT04318366., Competing Interests: No relevant disclosures., (© 2021 College of Intensive Care Medicine of Australia and New Zealand.)