Research into the use of resuscitation and "maintenance" fluids in the intensive care unit was integral to the development of the Australian and New Zealand Intensive Care Society Clinical Trials Group (CTG) and the CTG being recognised as one of the most productive and influential trials groups in the world. Professor Rinaldo Bellomo (Rinaldo) played a central and critical role in this research and in this article; we focus on Rinaldo's many roles and contributions to the key large clinical trials that changed the critical care research landscape in Australia and New Zealand and clinical practice worldwide. With a proposed recruitment of 7000 participants, the Saline versus Albumin Fluid Evaluation study was the first large pragmatic trial conducted in intensive care units anywhere in the world. Rinaldo brought the concept of the trial to the CTG and was critical to securing funding from multiple sources at a time when Australian National Health and Medical Research Council's funding limits would cover only a fraction of the costs of such a trial. His personal contacts at CSL Ltd. and the Australian Red Cross Blood Service helped secure the supply of study fluids and made possible the seemingly impossible task of blinding a trial of two fluids that were macroscopically different with one supplied in glass bottles and the other in polyvinyl chloride bags. The successful conduct of the Saline versus Albumin Fluid Evaluation trial, the CTG's first publication in The New England Journal of Medicine and presentation at the US Food and Drugs Administration, established the CTG on the global stage and served as a template for the Crystalloid versus Hydroxyethyl Starch Study and PlasmaLyte-148® versus Saline Study trials; we can only speculate what fraction of this could have been achieved without Rinaldo.
The objective of this study was to assess the Subarachnoid Haemorrhage International Trialist (SAHIT) prediction model in a tertiary adult intensive care unit (ICU) cohort when assessing patient outcomes against predicted outcomes, firstly by assessing the discrimination and validation of the model in the Princess Alexandra Hospital (PA) intensive care cohort and secondly comparing the predicted outcomes using the SAHIT model to the actual cohort outcomes using a Monte Carlo simulation. Six logistic regression models designed by the SAHIT Collaboration Group were applied to the PA cohort considering early predictive factors such as clinical grade and treatment modality to predict the risk of both mortality and unfavourable outcome at 6 months according to the Glasgow Outcome Score. The six SAHIT logistic regression models were applied to a retrospectively collected cohort of aneurysmal subarachnoid patients who were admitted to the ICU, generating individual risk scores for mortality and poor functional outcome. Area under the curve (AUC) and calibration slope/intercept and Brier score were used to assess the strength of the model in interpreting the current data set. A Monte Carlo analysis was used to compare the actual mortality outcomes to the predicted outcomes to determine if the cohort performance was better or worse than predicted by the mortality model. Overall, the PA cohort actual mortality was higher than the predicted mortality rate based on the risk scores generated by the SAHIT models, demonstrated by Monte Carlo simulation using the SAHIT model risk scores. The core, neuroimaging, and full models for functional outcome produced AUCs of 0.719 (95% confidence interval [CI]: 0.55-0.84), 0.709 (95% CI: 0.55-0.83), and 0.738 (95% CI: 0.58-0.85). Regarding mortality, the respective AUCs were 0.684 (95% CI: 0.57-0.78), 0.678 (95% CI: 0.56-0.77), and 0.749 (95% CI: 0.64-0.84). Regarding calibration, there was modest calibration in general, with higher degrees of calibration in the fully functional outcome model. The cohort outcomes for mortality occurred at a rate higher than the risk predictions suggested using the logistic regression created by the SAHITs. Applying the externally trained model provided adequate discrimination and modest calibration, yet underestimated risk when applied to the intensive care cohort, reflected in the probability density function analysis. Using the SAHIT models in this cohort may result in underestimation of mortality for the individual patient, and the accuracy of the model is not sufficient for individual patient prediction. These results challenge the appropriateness of using admission-based models for dynamic ICU populations and highlight the urgent need for critical care-specific prognostic tools.
Examinations used to credential trainees for independent specialist practice in intensive care medicine should be evaluated to demonstrate their levels of reliability and validity. This study aimed to quantify the reliability of the College of Intensive Care Medicine of Australia and New Zealand (CICM) second part viva examination and report the variation due to candidate proficiency, station difficulty, case specificity, and examiner stringency. This retrospective analysis of the CICM examination database used generalisability theory to determine the overall reliability coefficient of the viva examination. Decision studies were used to calculate the number of stations required for a reliability coefficient of >0.8. The CICM assesses intensive care trainees in Australia and New Zealand for independent specialist practice. De-identified candidate results from 2019 to 2023 totalled 376 viva examination attempts with individual examiner scores from 2774 viva stations. The mean viva station score was 5.6 (standard deviation: 1.47). The reliability coefficient for the second part eight-station viva examination was 0.61. Sources of variance were candidate proficiency of 15.4 %, station difficulty of 22.8 %, case specificity of 51.5 %, examiner stringency of 1.4 %, and other error of 8.8 %. Twenty viva stations would be required to achieve a reliability coefficient of >0.8. The CICM second part viva examination has a reliability coefficient below the generally accepted value for a high-stakes examination. Case specificity and station difficulty made the largest contribution to score variance. Increasing the number of viva stations and introduction of pass/fail standard setting would be effective methods for increasing examination reliability.
Discrepancies between laboratory sodium and point-of-care arterial blood gas sodium values may lead to delayed interpretation of, and intervention on, the results. We studied the mean difference between these two techniques and assessed the degree of agreement. A multicentre, retrospective, observational study was conducted. Twelve intensive care units in Queensland, Australia, with tertiary-level hospitals accounting for 81% of admissions were included in the study. Adult patients with at least one paired laboratory sodium and arterial blood gas measurement during their intensive care unit admission were a part of this study. Main outcome measures included mean difference between laboratory sodium and point-of-care sodium measurement, with a positive difference demonstrating laboratory sodium values higher than arterial blood gas sodium values. A total of 65,042 patients with 224,383 paired samples were included in the analysis. The Bland-Altman mean difference of laboratory sodium and arterial blood gas sodium was 0.72 mmol/L (95% limit of agreement [LoA]: 4.35) with a Deming regression slope of 0.93 (95% confidence interval: 0.92, 0.94) and intercept +10.07 (p < 0.001). On subgroup analysis of hyponatraemia, eunatraemia and hypernatraemia a mean difference (95% LoA) of 1.53 mmol/L (4.21), 0.15 mmol/L (4.39), and -1.02 mmol/L (5.37), was calculated, respectively. Patients with severe hyperglycaemia and normal albumin had a mean difference (95% LoA) of -1.85 mmol/L (4.78). Analysis of mild, moderate, and severe subgroups within both hyponatraemic and hypernatraemic samples showed increasing mean differences, with severe hyponatraemia showing a mean difference of 2.01 mmol/L (95% LoA: 8.08) and severe hypernatraemia showing a mean difference of -4.7 mmol/L (95% LoA: 15.46). Point-of-care arterial blood gas sodium measurements show small mean differences in eunatraemia and good agreement with paired laboratory samples in adult intensive care unit patients. Caution should be applied when interchanging results between laboratory and point-of-care sodium values in patients with moderate to severe dysnatraemia, as serial measurements using different methods during treatment are unlikely to be within a clinically acceptable range. This is important when caring for patient groups with severe hyponatraemia and induced hypernatraemia, and serial measurement may be better achieved with point-of-care testing due to a combination of ease of access, repeatability, and lower cost.
The safety and feasibility of telemedicine in intensive care units (ICU) are well established. However, whether tele-ICU exerts a measurable impact on clinically relevant outcomes remains uncertain. To evaluate whether a multifaceted Tele-ICU intervention, integrating intensivist-led daily multidisciplinary rounds (DMRs), coordinated care from a multidisciplinary team, and a quality and safety management strategy focused on quality improvement can reduce ICU length of stay among patients in Brazil. Design, setting, participants, and intervention: The TELESCOPE 2 study is a multicentre, open-label, stepped-wedge cluster randomized controlled trial including 25 ICUs in Brazil from January 2024 to January 2026. In a stepped-wedge assignment, ICUs will be randomized and allocated to one of five sequences. All ICUs will receive the interventions in a staggered manner at different times. All adult patients admitted in participant ICUs will be eligible for inclusion in the study. Admissions to the ICU due to justice-related issues (since in such circumstances the ICU admission or discharge may be determined by the law rather than by medical reasons), and patients previously included in the TELESCOPE 2 study will be excluded. The trial intervention is multifaceted, comprising three components delivered in combination, via telemedicine: I) daily multidisciplinary rounds led by board-certified intensive care physicians; II) coordinated care by a multidisciplinary team, including nurses, physiotherapists, and clinical pharmacists); III) a management strategy focused on quality improvement and patient safety. The primary outcome is ICU length of stay. Secondary outcomes include ICU mortality, in-hospital mortality, ventilator-free days during the first 28 days, ICU readmission within 48 h, early reintubation, ventilator-associated events, and accidental extubation rate. The TELESCOPE 2 study will assess whether a muiltifaceted Tele-ICU intervention can reduce ICU lenght of stay among critically ill patients in Brazil. We describe the study protocol for the TELESCOPE 2 trial, finalized prior to database lock. TELESCOPE 2 will evaluate the clinical impact of a structured Tele-ICU intervention in resource-variable ICUs and may provide robust evidence regarding the optimal model for delivering Tele-ICU.
To evaluate critical care professionals' perceptions of the burden of metabolic acidosis (MA) in the intensive care unit (ICU), and assess agreement on indications, modalities, risks, and benefits of sodium bicarbonate therapy. A multinational, web-based survey administered at different times to Chinese and international ICU practitioners. The survey comprised 20 items across four domains: 1) perceived epidemiology and research relevance of MA; 2) rationale, indications, and treatment modalities; 3) potential benefits of sodium bicarbonate; and 4) potential adverse effects of sodium bicarbonate. Responses were recorded on a 5-point Likert scale and classified as "Agreed", "Disagreed", or "Uncertain". A total of 1279 responses from 20 countries were analysed. MA was widely recognised as common, clinically relevant, a frequent cause of ICU admission, and an area requiring further research. Most clinicians supported targeted therapy beyond treating underlying causes, though uncertainty remained regarding sodium bicarbonate. Chinese respondents favoured early correction and continuous infusion, while international opinions varied on timing and approach. Perceived benefits, such as reduced vasopressor use and respiratory workload, were supported by Chinese clinicians, whereas international ones remained uncertain. Opinions on adverse effects also diverged. Chinese physicians highlighted risks of hypernatraemia, severe alkalosis, and hypokalemia, while international respondents viewed sodium bicarbonate as safe regarding the risk of fluid overload or pulmonary oedema. This international survey shows broad agreement that MA is a clinically important and understudied condition in the ICU but reveals substantial variability and uncertainty in clinicians' perceptions of sodium bicarbonate therapy, with notable differences between Chinese and international respondents. These findings underscore key knowledge gaps and the need for well-designed clinical trials.
Mega-dose intravenous sodium ascorbate, the base-salt of vitamin C, is under investigation as a therapy in critical illness. At pharmacologic concentrations sodium ascorbate may interfere with point-of-care (POC) biochemical measurements. This study aims to characterise the impact of ascorbate on point-of-care (POC) lactate and glucose assays. Prospective investigator initiated in vitro study using human and ovine blood samples. Blood samples from humans were collected within the clinical trials unit of the Royal Adelaide Hospital. Blood samples from sheep were collected within the South Australian Health and Medical Research Institute (SAHMRI) Pre-clinical Imaging and Research Laboratories (PIRL). Nineteen healthy adults and three sheep. Whole blood was spiked with 30% sodium ascorbate to achieve concentrations of 5, 10, and 20mmol/L. Lactate and glucose levels were compared with baseline across multiple POC devices, blood gas analysers, and a laboratory colorimetric reference assay. Increasing ascorbate caused spurious decreases in blood lactate measured by the colorimetric assay and two POC devices (Epoc® and the StatStrip Xpress®). False increases in blood lactate were observed with one POC device (iSTAT 1®) and with two blood gas analysers (RAPIDPoint® 500 and Radiometer ABL90 Flex), although the latter was not clinically significant. The StatProfile® Prime Plus blood gas analyser showed no interference. For glucose, increasing ascorbate caused spurious elevations in glucose with four POC glucometers (FreeStyle Optium Neo, StatStrip Xpress®, HemoCue® Glucose 201, and Epoc®) and a false decrease with the RAPIDPoint® 500. No interference was observed with the StatProfile® Prime Plus, Radiometer ABL90 Flex, or laboratory assay. At pharmacologic concentrations, ascorbate can cause both falsely high and low lactate and glucose readings, depending on the device used. These findings help inform the selection of appropriate devices for future clinical trials of mega-dose ascorbate.
Vasodilatory shock remains a leading cause of morbidity and mortality in the intensive care unit. Vasopressors are the cornerstone of treatment when vasodilatory shock persists despite adequate fluid resuscitation, yet their effects on organ-specific blood flow, perfusion, and oxygenation are complex and may contribute to harm. This review summarises the extensive contributions of Professor Rinaldo Bellomo to advancing our knowledge of vasopressor therapy in clinical practice. Central to his work was the concept of personalised haemodynamic targets, introduced through the concept of "mean perfusion pressure deficit", which linked premorbid perfusion pressure to outcomes and challenged the universal application of a mean arterial pressure threshold of ≥65 mmHg. In collaboration with Professor Clive May, Bellomo established a chronically instrumented large animal model of hyperdynamic sepsis, yielding fundamental insights into the discordance between the macrocirculation and microcirculation, the vulnerability of the renal medulla to hypoxia, and the mechanisms of septic acute kidney injury. This model enabled direct comparison of vasopressor drugs in both healthy animals and during septic shock, demonstrating their heterogeneous effects on global and regional blood flow, perfusion, and tissue oxygenation. Knowledge translation to the bedside was achieved through the conduct of pivotal clinical trials, from early studies refuting the utility of "renal-dose dopamine" to landmark contributions to the ATHOS (angiotensin II treatment of high-ouput shock) program, which established angiotensin II as a novel vasopressor in refractory vasodilatory shock. Collectively, Bellomo's work has transformed vasopressor therapy from empirical convention towards individualised practice, and it continues to inform clinical investigation and guideline development.
Obtaining an accurate smoking history can be challenging in critically ill patients. The objective of this study was to determine the prevalence of nicotine exposure using a point-of-care urine cotinine test in a heterogeneous cohort of critically ill patients and to compare this to the smoking history in the medical record. In 481 adult patients we prospectively undertook a urine cotinine test within 24 h of admission using a point-of-care binary colorimetric assay with a detection threshold of 200 ng/mL. Smoking history was retrieved from the electronic medical record. Urinary cotinine was detected in 151 of 481 patients (31.4%), exceeding the 134 participants with a documented history of current smoking by 3.5% (relative increase 12.7%). A positive urine cotinine test was reported in 12% (40/347) of participants not known to be actively smoking, including 18 'former smokers', 12 'non-smokers', and 10 in whom smoking status was unknown. Cotinine-positive participants were ventilated for longer than cotinine-negative patients; a median of 71 h vs. 44 h (median difference of 30h, 95% CrI: 5.6 to 56); they were more likely to have a "code-grey" event; 34 of 151 (23%) vs. 24/330 (7.3%); median relative risk of 3.1 (95% CrI, 1.9-5.1); and were more likely to "discharge against medical advice"; 12/125 (10%) vs 3/275 (1%), with a median relative risk of 9.7 (95% CrI, 3.0-46). Urinary cotinine testing offers a point-of-care determination of current tobacco smoking status in the critically ill.
Calcium plays an essential role in myocardial contractility, excitation-contraction coupling, and vascular tone. In cardiothoracic surgery, calcium supplementation is frequently administered during weaning from cardiopulmonary bypass (CPB) and in the early postoperative period to support haemodynamics. Despite its widespread use, the evidence base underpinning this practice remains limited and inconsistent. This narrative review explores the physiological rationale for calcium supplementation in the cardiothoracic surgical population, synthesises existing experimental and clinical data, and considers potential benefits and risks relevant to contemporary intensive care practice. Animal models suggest that calcium desensitisation contributes to myocardial dysfunction following hypothermic circulatory arrest, with supplementation theoretically improving contractility. In human studies, calcium administration during CPB weaning or in the immediate post-CPB period has been associated with transient increases in mean arterial pressure, systemic vascular resistance and left ventricular stroke work index. However, these effects are short-lived and data beyond the early postoperative phase remains limited. Potential risks of calcium supplementation include exacerbation of ischaemia-reperfusion injury, arrhythmogenesis, graft vasospasm, and tissue injury related to extravasation. The absence of specific guideline recommendations, in contrast to established consensus for vasopressor therapy, likely contributes to international variability in practice. Most studies are small, dated, or proof-of-concept and no high-quality randomised controlled trials have examined patient-centred outcomes such as vasopressor duration, organ dysfunction, or length of stay. Further multicentre observational and target-trial emulation studies are warranted to clarify the role of ionised calcium use in contemporary perioperative and intensive care practice.
Patients in the intensive care unit (ICU) suffer from disturbed sleep and pharmacological sleep aids are frequently prescribed despite limited data on their efficacy. The objective of this study was to assess the effect of a single nocturnal dose of the benzodiazepine temazepam on sleep duration and quality in ICU patients. Prospective, single-centre, blinded, placebo-controlled, parallel-group, randomised clinical trial. A tertiary ICU in Australia. Adult ICU patients whose treating clinician considered that a pharmacological sleep aid was indicated. A single weight- and age-adjusted dose of temazepam (10-30 mg) or a matching placebo was administered enterally at 21:00 h. The primary outcome was total sleep time between 21:00 and 07:00 h by hourly structured nurse assessment. Secondary outcomes included the evaluation of sleep quality, independently determined by the bedside nurse and patient using the Richards-Campbell Sleep Questionnaire. Between October 2020 and May 2024, 56 patients received temazepam (n = 28) or placebo (n = 28). The mean (standard deviation) total sleep time with temazepam was 349 (120) vs. placebo 291 (124) minutes; difference = 57 min (95% confidence intervals: -11 to 130); p = 0.10. No differences in total Richards-Campbell Sleep Questionnaire sleep quality were observed when assessed by the nurse (57 (17) vs. 49 (23), p = 0.15) or by the patient (50 (28) vs. 51 (23), p = 0.70). A single dose of temazepam was not observed to improve the duration or quality of nocturnal sleep for patients in the ICU. Retrospectively registered with the Australian and New Zealand Clinical Trials Registry on 11th June 2021 (ACTRN 12621000742875).
Older critically ill women and men experience accelerated bone loss, an increased risk of fragility fracture, and the associated burden of impaired quality of life and increased risk of death. Antiresorptive therapies are commonly used, safe, and effective in preventing bone loss in ambulatory patients. There is insufficient evidence for their routine use during recovery from critical illness. The objective of this study was to describe the trial protocol and statistical analysis plan for Bone Loss Prevention with Zoledronic Acid or Denosumab in Critically Ill Adults (BONE ZONE) trial. A phase IIb, multicentre, prospective, investigator-initiated, double-blind, placebo-controlled, randomised trial, with a target sample size of 330 participants. Women aged 50 years or older and men aged 70 years or older recovering from critical illness are randomly assigned to receive zoledronic acid, denosumab, or placebo in a 1:1:1 ratio. The primary outcome is annualised change in femoral neck bone mineral density in the year after intensive care unit discharge. Secondary outcomes include change in lumbar spine bone mineral density, fracture incidence, falls, hospital readmissions, mortality, safety outcomes, and quality of life. All analyses will be conducted on an intention to treat basis. The BONE ZONE trial will evaluate the efficacy and safety of antiresorptive medication administered during recovery from critical illness to patients at higher risk of bone loss and provide robust evidence to inform the need and design for a phase III trial.
Central venous access device (CVAD) insertion is a routine procedure in intensive care units (ICUs); however, it is associated with procedural risks. While structured training enhances safety, significant variability exists in training, supervision, and competency assessment across ICUs. Standardised education and assessment frameworks are recommended to improve procedural safety and patient outcomes. This study aimed to evaluate ICU trainees' experiences with CVAD insertion training, identify any significant variation in current educational frameworks, and gather recommendations for enhancing training and assessment. A web-based survey was distributed to ICU trainees across Australia, New Zealand, Singapore, and Hong Kong. Data were analysed using descriptive statistics and regression models. Key outcomes included trainee's perceptions of training disparities, accreditation processes, and practice variations across ICUs, informing the development of a standardised CVAD training framework. Among 237 respondents, 199 responses were analysed. Fewer than two-thirds of trainees in tertiary and metropolitan ICUs and only 17% in regional and private ICUs, reported access to structured multimodal CVAD training, while 15.3% indicated no formal training was available. Fewer than a quarter (23.1%) of less experienced trainees reported having undergone competency assessments in the past 12 months. Commonly perceived challenges included coordinating ultrasound guidance and manipulating the guidewire and catheter. Most trainees (52.3%) recommended six to ten supervised insertions and competency across multiple insertion sites (∼60%) for accreditation. These findings highlight trainees' perceptions of critical gaps in CVAD training, emphasising the need for structured multimodal education, standardised competency assessments, and improved access to training resources across diverse ICU settings.
To describe current percutaneous dilatational tracheostomy (PDT) practice across Australian and New Zealand (ANZ) intensive care units (ICUs), quantify perceived procedural exposure among intensivists and trainees, and evaluate perceptions of competency and training adequacy. Cross-sectional, anonymous, online survey of 11-16 questions, depending on clinical role, investigating: frequency of PDT, demographics of respondents, their experience in performing and supervising PDT in 2024 and their opinion about processes for training and maintaining procedural competency. ANZ ICUs. College of Intensive Care Medicine trainees and specialists. Of 321 respondents, 270 complete individual survey responses were analysed. Data from 23 ICUs indicated a median PDT rate of 0.41% (interquartile range [IQR]: 0.20-0.96%) of ICU admissions. Most clinicians performed two (IQR: 0-3) PDTs in 2024 and supervised a further two (IQR: 0-3). While most specialists felt confident performing or supervising PDT, fewer believed they performed enough to maintain competency, and many reported insufficient trainee opportunities. Procedural exposure was unevenly distributed: consultants performed significantly more PDTs than trainees (median [IQR]: 2 [1-3] vs. 1 [0-2]; p = 0.004) yet only five respondents recalled procedural frequency that would have met published annual thresholds (based on expert opinion) for maintaining competency.1 Free-text analysis identified four themes: declining volume of practice; concerns about skill fade and limited trainee exposure; support for supplemental training activities; and uncertainty over whether PDT should remain a universal ICU competency. PDT is now a low-volume and variably performed procedure across ANZ ICUs. Survey respondents reported that this is affecting training and maintenance of competency.
Sodium-glucose co-transporter-2 (SGLT2) inhibitors offer benefits for patients with chronic kidney disease, heart failure, and type 2 diabetes mellitus (with cardiovascular risk factors or atherosclerotic cardiovascular disease) but concerns exist regarding euglycaemic diabetic ketoacidosis (EDKA) during acute illness and surgery. We evaluated SGLT2 inhibitor use, discontinuation patterns, and blood ketone monitoring in intensive care units (ICUs). Prospective, multicentre, cross-sectional point prevalence study as part of The George Institute for Global Health and Australian and New Zealand Intensive Care Society Clinical Trials Group Point Prevalence Program. Fifty-two ICUs in Australia and New Zealand. Critically ill adult patients in ICUs on the study day. Number of patients receiving an SGLT2 inhibitor at ICU admission, their management, serum ketone levels, and ketoacidosis monitoring procedures. Among 786 patients, 54 (6.9 %) were prescribed SGLT2 inhibitors prior to hospital admission, mostly for type 2 diabetes mellitus (75.9 %) or heart failure (18.5 %). Of these, 28 (51.9 %) had their SGLT2 inhibitor discontinued, primarily due to EDKA concerns. Only 17 (34.6 %) of the studied ICUs had documented ketone measurement policies, with 1 (1.9 %) including SGLT2 inhibitors as an indication for measurement. Of 114 patients with blood ketone measurements, 38 (33.0 %) had elevated levels, of whom 6 (5.2 %) met ketoacidosis criteria. Practice regarding discontinuation of SGLT2 inhibitors and ketone monitoring varies widely. With SGLT2 inhibitor use projected to increase, better understanding their risk-benefit profile in the ICU setting and more systematic approaches to ketone measurement are needed. Future research addressing these practice variations is essential.
The Resuscitation in Paediatric Septic Shock using Vitamin C and Hydrocortisone (RESPOND) trial is a multicentre randomised controlled trial exploring whether the use of hydrocortisone alone, or in combination with vitamin C, increases time alive and free of vasopressors for critically ill children. To present the prespecified statistical analysis plan (SAP) for the RESPOND trial prior to finalising recruitment and locking the trial dataset. The RESPOND trial is a three-arm, parallel group, open-label, randomised controlled trial, recruiting in paediatric intensive care units in Australia, New Zealand, India, and Brazil. The planned sample size is 384 participants. The primary outcome is time alive and free of inotropes/vasopressors, censored at 7 days post-randomisation. Secondary outcomes include clinical (e.g. alive and free of multi-organ dysfunction, length of stay), safety, health economics (e.g. incremental costs, quality-adjusted life years), and long-term outcomes (measured at 6 months post-randomisation; e.g. health-related quality of life). The SAP was designed by the Chief Investigators and approved by the RESPOND Steering Committee. Statistical analyses are summarised. The primary outcome will be analysed using quantile regression adjusted for stratification variables. Appropriate statistical comparisons between groups were planned and described in a way that is transparent, available to the public, verifiable, and predetermined before completion of data collection. The trial statistician, RESPOND Steering Committee members, and SAP authors remain blind to treatment allocation throughout the study. Data Safety and Monitoring Board members were provided with safety data with masked group identifiers during interim analyses. The RESPOND trial commenced recruitment in December, 2021, and aims to complete recruitment by mid-2026. ACTRN12621000247875.
The field of critical care nephrology recently lost one of its founders and champions. From his seminal and revolutionary investigations into the pathophysiology of sepsis-induced AKI to his relentless efforts to improve the care of patients with AKI through drugs and devices, Rinaldo Bellomo was a larger-than-life figure in intensive care medicine. He was a visionary leader, mentor and thinker and yes, an unrelenting challenger of conventional wisdom. He will be missed by his many friends and collaborators around the world. We are thankful to have walked alongside him and to have been inspired by his humble enthusiasm, openness, and limitless curiosity.
Sepsis is a leading cause of morbidity and mortality in hospitalised patients. Rapid Response Teams (RRTs) review clinically deteriorating patients, including those with sepsis. However, the epidemiology of sepsis in RRT calls remains unclear. This systematic review synthesised evidence on the prevalence, treatment, and outcomes of sepsis during RRT calls. Seven electronic databases (PubMed, Web of Science, Embase, CINAHL, Cochrane Library, Ovid MEDLINE, and Scopus) were searched for studies published from 1 January 2015 to 31 May 2024. All articles were independently screened and assessed for study quality using the Newcastle Ottawa Scale by two reviewers per article. The primary outcome was the prevalence of sepsis during RRT calls. Secondary outcomes included hospital mortality and length of hospitalisation. Data were pooled using random-effects meta-analyses. From 5632 studies screened, 26 studies encompassing 110,909 patients and 139,076 RRT events were included. The pooled mean age was 64.4 years (95%CI: 59.2-69.7) and 48.4 % (n = 51,720, 24 studies) were male. The pooled prevalence of sepsis among all RRT calls was 23.7 % (95%CI: 15.5 %-34.6 %), with no significant difference between studies including exclusively sepsis RRT calls and studies with all causes of RRT calls (32.7 % vs. 21.8 %; p = 0.16). Common sepsis-related RRT triggers included abnormal respiratory and heart rates. Overall hospital mortality was 12.9 % (95%CI: 7.3-21.7 %) and hospital length of stay was 18 days (95%CI: 13.9-22.1), both showing no significant differences between studies including exclusively sepsis RRT calls and studies with all causes of RRT calls. New or changes in antibiotics were initiated in 38.8 % of sepsis-related RRTs. Most patients remained on the ward, while 23.3 % were transferred to the ICU. Sepsis is a trigger for a quarter of RRT calls, associated with substantial resource use and mortality in one eighth of patients. These findings support the need for standardised recognition protocols, escalation guidelines and prospective trials to optimise outcomes.
We aimed to determine the incidence of new onset atrial fibrillation (NOAF) in a cohort of intensive care unit (ICU) patients and, further, identify commonly utilised pharmacological strategies for its management in patients with and without sepsis. A multicentre, retrospective observational study was conducted. Twelve ICUs in Queensland, Australia. Adult patients, excluding those with cardiothoracic surgical diagnoses, admitted to a participating ICU from 2015 to 2021. Main outcome measures included the incidence of NOAF in ICU, association of NOAF with illness severity and outcomes, cardiac rhythm at ICU discharge, and incidence of pharmacological intervention for NOAF in the ICU. NOAF occurred in 8.4 % of included ICU admissions, and was associated with higher illness severity, length of stay, and mortality. The majority of patients who experienced NOAF and survived their ICU stay were discharged from the ICU in a sinus rhythm (68.6 %). Patients with sepsis-associated NOAF were more likely to be in a sinus rhythm at ICU discharge than patients with NOAF without sepsis (72.2 vs 65.7 %). Amiodarone was frequently (50.4 %) prescribed to patients both with (56.5 %) and without (45.3 %) sepsis. NOAF was common amongst patients admitted to the ICU, and amiodarone is commonly prescribed. Future studies are required to determine the optimal short- and long-term management strategies for NOAF complicating critical illness.
To compare total hospital costs associated with remifentanil versus fentanyl for analgosedation in mechanically ventilated intensive care unit (ICU) patients, given increasing interest in remifentanil as a feasible alternative, but limited economic evidence. Cost analysis of a single-centre, prospective, randomised controlled trial (remi-fent1 RCT). Nepean Hospital ICU, New South Wales, Australia. Adult patients admitted between June 2020 and August 2021 requiring invasive mechanical ventilation (IMV) who were randomised to receive remifentanil or fentanyl as part of their analgosedation regimen. The primary outcome was total hospital bed-day costs (Australian Dollars), estimated from a healthcare payer perspective using the Australian Independent Hospital Pricing Authority National Pricing Model for the financial year 2020-2021. Health-related quality of life (HRQoL) at 6 months was measured using the generic EuroQoL 5-dimension 5-level (EQ-5D-5L) instrument. Pre-specified subgroup analyses examined age (arbitrary cut-off 65 years) and duration of IMV (arbitrary cut-off 72 h). A total of 210 patients were analysed (remifentanil n = 104; fentanyl n = 106). Opioid acquisition costs were comparable between groups. Total mean hospital bed-day costs were lower in the remifentanil group compared with the fentanyl ($48,301 [$38,644-$57,958] vs. $37,012 [95% confidence interval {CI}: $27,834-$46,191]; p = 0.006). The remifentanil group was associated with lower total hospital costs in older patients (≥65 years) and in those ventilated for ≤72 h. At 6 months, 110 patients were alive, with 7 lost to follow-up, (61/103 remifentanil [59.2%] vs. 59/100 fentanyl [59.0%]; p = 0.80). Among survivors, remifentanil continued to demonstrate lower overall hospital costs, but 6-month HRQoL remained similar between groups (EQ-5D-5L index 0.83 vs. 0.87; p = 0.24). Remifentanil was associated with lower total hospital costs than fentanyl, without differences in survival or HRQoL at 6 months, suggesting that remifentanil may be a lower-cost alternative for analgosedation. However, the results are exploratory and require confirmation in larger, adequately powered multicentre phase-2 trials.