OBJECTIVES:The role of ketamine for analgosedation in the ICU remains unclear. This study aimed to assess the efficacy of low-dose ketamine infusion for adjunct analgosedation in adults receiving mechanical ventilation. DESIGN:A prospective, double blind, randomized, placebo-controlled trial. SETTING:The study was conducted at two university-affiliated ICUs in Melbourne, Australia, between September 2022 and December 2024. PATIENTS:Adult patients receiving mechanical ventilation in the ICU who were also receiving opioid infusion for analgosedation (excluding cardiac surgical patients). INTERVENTIONS:Patients were randomized to receive low-dose ketamine infusion (0.15 mg/kg/hr) or placebo during the period of mechanical ventilation. MEASUREMENTS AND MAIN RESULTS:The primary outcome was the hourly dose of opioids. Secondary outcomes included, among others, delirium, as well as ventilator, ICU, and hospital-free days to day 28. A total of 538 patients were screened for inclusion. Of these, 413 patients were ineligible based on exclusion criteria. A further five patients had consent withdrawn, leaving 120 patients (59 ketamine and 61 placebo) included for primary analysis. The median (interquartile range) hourly dose of opioids in fentanyl equivalents was 64 µg/hr (36-89 µg/hr) in the ketamine group and 77 µg/hr (47-100 µg/hr) in the placebo group (median difference, -13.0 [95% credible interval, -26.6 to 2.4]; probability of benefit, 95.1%). There were no differences between groups for most of the secondary outcomes, including delirium and significant adverse events. CONCLUSIONS:Low-dose ketamine infusion appeared safe and was associated with a reduction in hourly opioid requirements in ICU patients receiving mechanical ventilation. Larger randomized controlled trials are required to assess effects on other patient-centered outcomes.

OBJECTIVES:To assess whether high flow nasal oxygen (HFNO) therapy reduces the need for endotracheal intubation in adults with acute hypoxaemic respiratory failure (AHRF) in the intensive care unit (ICU). METHODS:Systematic reviews were identified through a structured search of MEDLINE, EMBASE, CINAHL, Cochrane Central, and Web of Science from inception to August 2024. Two reviewers independently screened studies, extracted data, and assessed methodological quality (AMSTAR-2), risk of bias (ROBIS), and review overlap using the corrected covered area method. RESULTS:Twenty systematic reviews met inclusion criteria, comprising 331 primary trials. Methodological quality in the reviews was low to moderate, and ROBIS was high. Variability was evident in heterogeneous patient cohorts, intervention implementation, outcome assessment, and follow-up, in the context of a high degree of study overlap (26.3%) across reviews. Four trials (5 intervention arms) within reviews included ICU patients with AHRF. There was no difference in effect when comparing HFNO with noninvasive ventilation (NIV) on intubation: pooled relative risk (RR) = 0.82, 95% confidence interval (CI) = 0.58-1.16, p = 0.172, I2 = 43.2%. Two trials demonstrated no difference in effect when comparing HFNO with conventional oxygen therapy (COT) on intubation: pooled RR = 0.812, 95% CI: 0.588, 1.120, p = 0.204, I2 = 0.0%. HFNO was associated with a 49% relative reduction in mortality when compared with NIV in two trials (RR = 0.49; 95% CI = 0.310-0.787, p = 0.003, I2 = 0.0%), indicating a clear beneficial effect of HFNO on mortality in this population. CONCLUSIONS:Current reviews suggest HFNO may reduce the risk of intubation compared with COT or NIV, but the overall strength of this evidence is questionable. In practice, HFNO is often applied uniformly across highly variable patient groups, despite limited clarity regarding, which subpopulations derive the greatest benefit. These limitations underscore the need for more rigorous, well-designed trials and focused systematic reviews to guide tailored, evidence-informed use of HFNO and optimise clinical decision-making.

PURPOSE:The impact of augmenting enteral protein delivery on nitrogen balance, urea generation, and kidney function in critically ill patients remains poorly defined. This study aimed to investigate these effects in a nested cohort within the TARGET Protein trial. METHODS:We conducted a single-center study nested within a cluster randomized crossover trial. Consecutive patients were enrolled during either the usual protein intake period (n = 52) or the augmented protein intake period (n = 55). Nitrogen balance, its components, plasma urea concentrations, and urea nitrogen accumulation were compared between groups. Multivariable analyses identified factors independently associated with nitrogen balance and incident acute kidney injury (AKI). A causal mediation analysis was performed to assess whether the effect of augmented protein delivery on urea concentrations was mediated through incident AKI. RESULTS:From day 1 to day 7, mean protein intake was 0.84 ± 0.73 g·kg-1·day-1 in the usual-protein group and 1.35 ± 0.94 g·kg-1·day-1 in the augmented-protein group. Patients receiving augmented protein achieved a less negative nitrogen balance than those receiving usual protein (mean difference, +5 g per day; 95% confidence interval [CI], 0.4 to 10; P = 0.033), driven by greater nitrogen intake (mean difference, +7 g per day; 95% CI, 5 to 10; P < 0.001). Independent predictors of nitrogen balance were ideal body weight (-0.18 g.kg-1; 95% CI, -0.35 to -0.01; P = 0.040), AKI at ICU admission (+4.7 g; 95% CI, 0.10 to 9.3; P = 0.046), and allocation to augmented protein therapy (+5.1 g; 95% CI, 0.43 to 9.7; P = 0.033). Compared with usual protein delivery, augmented protein delivery resulted in higher plasma urea concentrations (median, 14 vs. 11 mmol/L) and greater urea nitrogen accumulation (+3 g; 95% CI, 1.0 to 6.0; P = 0.035). Approximately 60% of the additional positive nitrogen balance was accounted for by urea generation. Among patients without AKI at ICU admission, augmented protein delivery was independently associated with incident AKI (odds ratio, 4.79; 95% CI, 1.14 to 26.4; P = 0.046). In mediation analyses, most of the increase in urea concentrations associated with augmented protein delivery was attributable to a direct effect rather than mediation through incident AKI. CONCLUSIONS:In critically ill patients, augmented protein delivery resulted in a less negative nitrogen balance but substantially increased urea generation and plasma urea concentrations. These findings suggest that a substantial proportion of additional protein intake may be directed toward nitrogen waste production rather than net anabolic utilization.

Sepsis survivors may experience ongoing health challenges after hospitalization for sepsis. Patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) are important endpoints to assess patient health status and health system performance. This review aimed to (1) identify and describe the PROMs and PREMs used in randomized controlled trials (RCTs) of critically ill adults with sepsis and (2) determine the "survivor-centricity" of these measures. MEDLINE, Embase, CINAHL Plus, and PsycINFO were searched on November 18, 2024. Studies were included if they (1) were conducted in adult patients admitted to the intensive care unit (ICU) with sepsis; (2) were RCTs (or a follow-up study of an RCT); (3) included at least 1 PROM or PREM; and (4) were published since January 1, 2000, in English, and available in full text. A total of 7667 studies were screened for eligibility. Eighteen studies were included (n = 21 439 patients). Nine (50%) studies were RCTs, and 9 (50%) were RCT follow-up studies. A total of 21 PROMs, and 1 PREM were identified in these 18 studies. The most common PROM was health-related quality of life (HRQoL), measured in 17 (94%) studies, via the EuroQol-5D-5L (n = 10, 56%). Most PROMs (n = 13, 62%) were aligned with the survivor-centricity health domain of psychological impairment. Only 1 study reported a PREM that captured the patient experience of chronic care. In RCTs of patients admitted to the ICU with sepsis, HRQoL was the most frequently measured PROM. Only 1 PREM was identified. Health-related QoL captured the most survivor-centricity domains. INPLASY Registration: INPLASY (International Platform of Registered Systematic Reviewsand Meta-Analysis Protocols), INPLASY Protocol 5756 - INPLASY, INPLASY202410064.

Objective: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. Design:A multinational, web-based survey administered at different times to Chinese and international ICU practitioners. Main outcome measures: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". Results: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. Conclusions: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.

Guidelines for temperature control following out-of-hospital cardiac arrest (OHCA) are based on trials with end points of 180 days or fewer. To investigate if targeted hypothermia, compared with targeted normothermia with early treatment of fever, affects functional outcome focusing on societal participation or cognitive functioning at 24 months in initially comatose OHCA survivors. An additional objective was to explore recovery trajectories up to 24 months post arrest. The randomized clinical Targeted Hypothermia vs Targeted Normothermia After OHCA (TTM2) trial (November 2017-2020) included blinded follow-up at 1, 6, and 24 months post randomization (December 2017-June 2022), with analyses performed in 2024. TTM2 was an international, multicenter study conducted at 61 hospitals in 14 countries. The study included 1861 adults with OHCA of presumed cardiac or unknown cause who were initially comatose. There were 992 survivors at 1 month, 943 at 6 months, and 835 at 24 months. Nonparticipation rates at follow-up were 44 (4%), 107 (11%), and 165 (20%), respectively. Participants were randomized 1:1 to undergo temperature control via targeted hypothermia (33 °C) or targeted normothermia and early treatment of fever (≥37.8 °C). The functional outcome, including societal participation, was assessed using the Glasgow Outcome Scale-Extended (GOSE). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and the Symbol Digit Modalities Test (SDMT). Of the participants who were followed up, 84% were male, with a mean (SD) age of 60 (14) years, and clinical variables were similar between the hypothermia and normothermia temperature groups. No significant differences were found between temperature groups regarding societal participation (GOSE: odds ratio, 0.97 [95% CI, 0.72-1.30]) or cognitive function (MoCA: mean difference, −0.02 [95% CI, −0.67 to 0.63]; SDMT: mean difference, −0.09 [95% CI, −0.33 to 0.16]) at 24 months. Improvement for GOSE was significant within the first 6 months (1 to 6 months: n = 1707 [95% CI, −2.00 to −1.50]; P < .001; 6 to 24 months: n = 1606 [95% CI, −0.50 to <0.001]; P = .10). Intraindividual improvement and decline corresponding to thresholds for minimal important differences were observed for societal participation and cognitive function up to 24 months. Targeted hypothermia, compared with targeted normothermia, did not affect societal participation or cognitive function at 24 months, suggesting no longer-term effect of hypothermia for the explored outcomes. The intraindividual changes observed indicate variability in recovery. ClinicalTrials.gov Identifier: NCT02908308

The urine albumin-to-creatinine ratio (UACR) is a well-established marker for chronic kidney disease, but its utility in predicting acute kidney injury remains uncertain. This systematic review and meta-analysis aimed to evaluate predictive performance for AKI development and prognostic performance for AKI progression in hospitalized adults. A comprehensive search of Ovid MEDLINE, Embase, and CENTRAL databases identified 13 studies (n = 10,438) on AKI incidence and three studies (n = 1596) on AKI progression. Elevated UACR was associated with an increased risk of AKI (pooled OR 1.39; 95% CI 1.08-1.79) and AKI progression (pooled OR 3.76; 95% CI 2.59-5.45). The pooled sensitivity and specificity for AKI prediction were 0.71 (95% CI 0.59-0.80) and 0.67 (95% CI 0.56-0.76), respectively, with an area under the curve (AUC) of 0.74. However, there was high heterogeneity across studies, and UACR thresholds for AKI prediction varied widely. Despite these limitations, UACR appears to be a promising, low-cost biomarker for predicting AKI, particularly in high-risk settings such as cardiac surgery. Standardization of thresholds and further validation are needed to support its clinical implementation.

BACKGROUND:Targeting mild hypercapnia reduced myocardial injury in a single-centre cohort of STelevation myocardial infarction (STEMI) patients from the multinational Targeted Therapeutic Mild Hypercapnia after Resuscitated Cardiac Arrest (TAME) trial. We examined the effect of mild hypercapnia on myocardial injury and outcomes in all acute myocardial infarction (AMI) patients of the TAME trial. METHODS:Post-hoc exploratory study of the TAME trial that compared the effect of targeted mild hypercapnia or normocapnia in comatose adults after out-of-hospital cardiac arrest (OHCA). The primary outcome was myocardial injury assessed by peak high-sensitivity cardiac troponin T (hs-cTnT) or troponin I (cTnI) levels during hospitalisation in STEMI and successfully percutaneous coronary intervention (PCI) treated STEMI patients. Secondary outcomes included lactate clearance, in-hospital mortality, and neurological outcome at six months. RESULTS:We studied 810 of 1700 TAME patients (49%) that were diagnosed with AMI. Of these, 593 had STEMI (73%), with 287 patients (48%) in the mild hypercapnia group and 306 (52%) in the normocapnia group. Troponin levels were available for 562 STEMI patients (95%). There was no difference in troponin level (ratio of geometric means (95% (CI) (mild hypercapnia/normocapnia) cTnI 1.18 (0.79-1.77), hs-cTnT 1.20 (0.88-1.63)) or lactate clearance over the first 24 h according to treatment allocation. In-hospital mortality in STEMI patients was 112 of 287 (39%) vs. 124 of 306 (40.5%) patients in the mild hypercapnia group vs. normocapnia group, respectively (Relative Risk 0.97, 95% CI, 0.82-1.14). At six months, 129 of 267 (44.3%) vs. 125 of 282 (48.5%) patients in the mild hypercapnia group vs normocapnia group had a favourable neurological outcome (Relative Risk 1.09, 95% CI, 0.92-1.29). For successful PCI STEMI patients there were no significant differences in any outcomes according to treatment allocation. CONCLUSION:Among STEMI patients of the TAME trial, myocardial injury, in-hospital mortality, and neurological outcome at six months were not modified by allocation to targeted mild hypercapnia.

AIM:This study aimed to assess the characteristics, transfusion events, and clinical outcomes of cardiac surgery patients treated with three-factor prothrombin complex concentrate (3F-PCC). METHOD:A retrospective observational study was performed in three cardiac surgery centres in Australia. We studied sequential cardiac surgeries and collected data on 3F-PCC, fresh frozen plasma (FFP) and red blood cell (RBC) use from blood banks and clinical outcomes from the Australian Society of Cardiothoracic Surgery database. We compared 3F-PCC treated to PCC-untreated patients. RESULTS:For 1,698 patients, 254 (15%) received 3F-PCC, with a median dose of 2,000 IU (Interquartile range [IQR]: 1,000 to 2,000), administered almost exclusively in the operating theatre. After adjustment by overlap weighting, 3F-PCC was associated with a reduction in post-surgical FFP transfusions (Relative risk [RR]: 0.47; 95% confidence interval [CI] 0.29 to 0.77). Similarly, 14% of 3F-PCC patients needed ≥2 RBC units after surgery compared to 21% in controls (RR: 0.63; 95% CI 0.45 to 0.88). Both groups displayed similar safety profiles and clinical outcomes. However, pulmonary embolism occurred in 1.8% of 3F-PCC patients versus 0.8% of controls. CONCLUSIONS:In a multicentre study, 3F-PCC use during cardiac surgery was independently associated with a significantly reduction of postoperative FFP and RBC transfusions. A phase III trial of early PCC at 2,000 IU appears justified.

OBJECTIVE:To describe the incidence, management, and outcomes of segmental and subsegmental pulmonary embolism (PE) in intensive care unit (ICU) patients and to explore associations between therapeutic-dose anticoagulation and clinical outcomes. DESIGN:Single-center retrospective cohort study. SETTING:Tertiary academic hospital ICU between January 2019 and June 2025. PATIENTS:Critically ill adults (≥18 years) who underwent computed tomography pulmonary angiography (CTPA) during ICU admission and had radiologically confirmed segmental or subsegmental PE. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Radiology reports of all CTPA examinations performed in ICU-admitted patients were screened to identify the most proximal level of thrombus. Clinical records were reviewed for demographics, illness severity, radiologic characteristics, anticoagulation practice, bleeding, venous thromboembolism (VTE) recurrence, and mortality. Among 896 CTPA examinations performed in 804 patients, 164 examinations (18.3%) identified PE. Of these, 115 scans (12.8% of all CTPAs) demonstrated distal PE only, corresponding to 104 patients (12.9%) (61 segmental, 43 subsegmental). Overall, 96% of patients with distal PE received anticoagulation and 86% of anticoagulated patients received therapeutic-dose regimens. Bleeding occurred in 15% (major bleeding 12%), 90-day VTE recurrence in 7.8%, and 90-day mortality in 24%. No statistically significant association was found between the use of therapeutic-dose anticoagulation and 90-day mortality (adjusted odds ratio [OR], 0.70; 95% CI, 0.21-2.45), bleeding episodes (adjusted OR, 2.34; 95% CI, 0.47-19.2), or VTE recurrence (adjusted OR, 0.69; 95% CI, 0.11-6.22). CONCLUSIONS:In critically ill adults, segmental and subsegmental PE are commonly detected on CTPA and are usually treated with therapeutic-dose anticoagulation. Although VTE recurrence was less frequent than bleeding episodes and mortality, our study did not find a significant association between therapeutic-dose anticoagulation and bleeding episodes, recurrent VTE, or mortality. Larger prospective studies are needed to define optimal anticoagulation strategies for ICU patients with distal PE.

Importance:Guidelines for temperature control following out-of-hospital cardiac arrest (OHCA) are based on trials with end points of 180 days or fewer. Objectives:To investigate if targeted hypothermia, compared with targeted normothermia with early treatment of fever, affects functional outcome focusing on societal participation or cognitive functioning at 24 months in initially comatose OHCA survivors. An additional objective was to explore recovery trajectories up to 24 months post arrest. Design, Setting, and Participants:The randomized clinical Targeted Hypothermia vs Targeted Normothermia After OHCA (TTM2) trial (November 2017-2020) included blinded follow-up at 1, 6, and 24 months post randomization (December 2017-June 2022), with analyses performed in 2024. TTM2 was an international, multicenter study conducted at 61 hospitals in 14 countries. The study included 1861 adults with OHCA of presumed cardiac or unknown cause who were initially comatose. There were 992 survivors at 1 month, 943 at 6 months, and 835 at 24 months. Nonparticipation rates at follow-up were 44 (4%), 107 (11%), and 165 (20%), respectively. Intervention:Participants were randomized 1:1 to undergo temperature control via targeted hypothermia (33 °C) or targeted normothermia and early treatment of fever (≥37.8 °C). Main Outcomes and Measures:The functional outcome, including societal participation, was assessed using the Glasgow Outcome Scale-Extended (GOSE). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and the Symbol Digit Modalities Test (SDMT). Results:Of the participants who were followed up, 84% were male, with a mean (SD) age of 60 (14) years, and clinical variables were similar between the hypothermia and normothermia temperature groups. No significant differences were found between temperature groups regarding societal participation (GOSE: odds ratio, 0.97 [95% CI, 0.72-1.30]) or cognitive function (MoCA: mean difference, -0.02 [95% CI, -0.67 to 0.63]; SDMT: mean difference, -0.09 [95% CI, -0.33 to 0.16]) at 24 months. Improvement for GOSE was significant within the first 6 months (1 to 6 months: n = 1707 [95% CI, -2.00 to -1.50]; P < .001; 6 to 24 months: n = 1606 [95% CI, -0.50 to <0.001]; P = .10). Intraindividual improvement and decline corresponding to thresholds for minimal important differences were observed for societal participation and cognitive function up to 24 months. Conclusions and Relevance:Targeted hypothermia, compared with targeted normothermia, did not affect societal participation or cognitive function at 24 months, suggesting no longer-term effect of hypothermia for the explored outcomes. The intraindividual changes observed indicate variability in recovery. Trial Registration:ClinicalTrials.gov Identifier: NCT02908308.

OBJECTIVE:The aim of this study was to investigate the association between socioeconomic status (SES) and sepsis survival in Australian intensive care unit (ICU) admissions. METHODS:We conducted a retrospective cohort study of adult sepsis ICU admissions between 2018 and 2023, using ICU registry and national death data. SES was derived using the Australian Bureau of Statistics Index of Relative Socioeconomic Advantage and Disadvantage deciles mapped from residential postcodes and categorised as low, middle, or high. Unadjusted survival to 180 days and in-hospital 30-day survival were described using Kaplan-Meier estimates. Cox proportional hazard models, adjusted for age, sex, organ failure, ICU admission source, elective surgical status, chronic conditions, admission year, study site, and the presence of septic shock, were used to determine associations between SES and survival. RESULTS:Of 794,756 admissions, 80,422 (10.1%) were sepsis admissions; 180-day mortality was 7570 of 31,528 (24·0%) in low SES admissions compared to 5109 of 22262 (22.9%) and 6009 of 26,088 (23·0%) in middle and high SES admissions, respectively. In-hospital 30-day mortality was 4662 of 31,613 (14·7%) in low SES admissions compared to 3079 of 22348 (13.7%) and 3695 of 26,221 (14·1%) in middle and high SES admissions, respectively. In adjusted Cox regression models, high SES was associated with greater 180-day and in-hospital 30-day survival (adjusted hazard ratio: 0·86, 95% confidence interval: 0·83-0·90; p < 0·001 and adjusted hazard ratio: 0·88, 95% confidence interval: 0·84-0·93; p < 0·001, respectively). CONCLUSION:People living in areas of socioeconomic disadvantage had lower survival to day 180 after an ICU admission for sepsis than people living in other areas.

There is limited published data on metaraminol dosing, duration of therapy and clinical outcomes for critically ill patients. We conducted a retrospective cohort study across two tertiary intensive care units (ICUs) and included all patients who received a metaraminol infusion between 26 August 2016 and 31 December 2021. The primary outcome of this study was to describe the characteristics and outcomes of patients who receive metaraminol in ICU. Secondary outcomes included a range of pharmacological and physiological measures. We studied 1261 patients, which represented 6.7% of ICU admissions during the study period. Most (85.4%) patients were unplanned admissions and less than 40% required mechanical ventilation. ICU and hospital mortality were low (7.4% and 12.4% respectively). Median total infusion duration for metaraminol was 10 (interquartile range, 3-24) h. Median dose range was 1 mg/h (16 µg/min) to 6 mg/h (100 µg/min). Almost three-fifths of these patients subsequently transitioned to norepinephrine (noradrenaline), which commenced at a median time of 7 h after initiation of metaraminol. Hourly heart rate, mean arterial pressure and respiratory rate remained very stable during infusion of metaraminol and median urine output remained greater than 30 ml/h for the first 24 h. In conclusion, patients who received metaraminol by infusion in the ICU had a low severity of illness and risk of mortality. Dosing of metaraminol was conservative and clinicians frequently transitioned to norepinephrine early despite the low doses infused. Metaraminol effectively maintained blood pressure with no associated tachycardia or significant drop in urine output and no clinical evidence of tachyphylaxis.

Background Survivors of an intensive care unit (ICU) admission frequently experience long-term physical, cognitive, and psychological challenges. ICU follow-up services may be an important mechanism to address post-ICU morbidity, but services in Australia and New Zealand are poorly defined. Objectives The aim of this study was to assess the prevalence and characteristics of ICU follow-up services in Australia and New Zealand. Methods A cross-sectional online survey, open from February to August 2025, was distributed via email to ICU medical directors across 227 public and private ICUs in Australia and New Zealand, with follow-up phone calls at 3 months. The survey comprised questions on timing, frequency, methods of delivery, professionals involved, outcome measures utilised, and barriers and enablers to ICU follow-up service provision. Questions were predominantly close ended with predefined response options, with some allowing additional free-text responses. Data were number (%). Free-text responses were analysed descriptively and grouped into existing or newly generated categories where appropriate. Results Of a possible 227 ICUs, 83 participated (37% response rate). Although 67 sites (81%) acknowledged the importance of follow-up services, only 24 (29%) offered such a service for patients and 21 (25%) for caregivers. Referral timing varied from during hospital admission to 6 months post discharge. Follow-up was predominantly nurse led (n = 13, 48%) and mostly delivered face-to-face (n = 13, 48%). Only seven (27%) of ICUs collected patient-related outcome data, with a wide variety of tools used. The primary barriers to providing follow-up were funding (n = 62, 75%) and limited ICU clinicians to staff a follow-up service (n = 53, 64%). Conclusions Approximately a third of participating ICUs in Australia and New Zealand had a follow-up service, limited by financial and ICU clinician staffing constraints. Where follow-up was provided, service characteristics varied greatly. Further data to identify effective models of ICU follow-up care will improve the consistency, equitability, and impact of post-ICU support.

Background Acute kidney injury (AKI) is common in the intensive care unit (ICU) but is often detected only after creatinine rises or oliguria develops. Although novel biomarkers allow earlier detection, their cost limits use. The urine albumin-to-creatinine ratio (uACR) is inexpensive, yet its role in AKI risk stratification remains uncertain. Methods In a prospective single-centre cohort of mixed ICU patients, adults with existing AKI or at high risk (modified AKI Risk Based on Creatinine [ARBOC] score ≥ 3) were enrolled. uACR was measured at enrollment (uACR at Time 0) and 24 h (uACR at Time 1). Outcomes included the prevalence and prognostic value of elevated uACR (≥ 3.4 mg/mmol) for incident, progressive, or persistent AKI (> 48 h), and for ≥30% decline in estimated glomerular filtration rate (eGFR) at discharge. Predictive performance was assessed using the area under the receiver operating characteristic curve (AUC), change in AUC, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision-curve analysis. Results Of 1010 patients screened, 203 were analysed (89 with and 114 without AKI at enrollm). Elevated uACR was frequent (72% with AKI; 52% without). In AKI patients, high uACR correlated with longer and more persistent AKI. Discrimination for incident AKI was modest (AUC 0.61 and 0.66 for uACR at Time 0 and uACR at Time 1) but higher for persistent AKI (both AUC 0.68). Adding uACR at Time 0 to ARBOC improved reclassification (NRI 0.48; IDI 0.04) and clinical net benefit. Conclusions uACR modestly identified incident AKI and more strongly predicted persistent AKI. As a simple biomarker, uACR may serve as a low-cost adjunct to existing ICU risk stratification tools, but requires further validation before consideration for routine clinical use.

Background:Data on long-term survival after intensive care unit (ICU) admission for sepsis and septic shock are limited. This study aimed to evaluate survival over five years among critically ill sepsis or septic shock patients discharged alive from hospital. Methods:This retrospective cohort study of adults who survived to hospital discharge after non-elective ICU admission (2018-2024) used Australian and New Zealand Intensive Care Society Adult Patient Database. Sepsis, septic shock, or non-sepsis patients were classified using diagnostic codes and physiological/laboratory criteria during first 24-h of ICU admission. Mixed-effects Cox models with time-varying covariate effects were used, adjusting for demographics, comorbidities, frailty, illness severity, and ICU interventions. Findings:Of 557,538 hospital survivors, 7.3% had sepsis without shock, 11.5% septic shock, and 81.2% non-sepsis conditions. At five-years, unadjusted survival was lowest for septic shock (68.0%, 95% confidence interval/CI = 67.6-68.4%), sepsis without shock (74.2%, 73.7-74.6%), and non-sepsis (78.2%, 78.1-78.3%). After adjustment, hazards ratio/HR for sepsis without shock remained at or below the null relative to non-sepsis; 0-1 year: HR = 0.95, 0.92-0.98; 1-3 years: 0.96, 0.93-1.00; 3-5 years: 1.03, 0.97-1.08, while septic shock showed persistent independent excess mortality; 0-1 year: HR = 1.05,1.03-1.08; 1-3 years: 1.03, 1.00-1.06; and 3-5 years:1.09,1.05-1.14. Major predictors of mortality included age, frailty, comorbidities, and organ support. Interpretation:Septic shock was associated with persistent independent excess mortality over five years after hospital discharge, whereas in sepsis without shock, this was largely explained by pre-existing comorbidity and frailty. Funding:Medical Research Future Fund.

BACKGROUND:In patients who are unresponsive after resuscitation from cardiac arrest, limiting oxygen exposure to that necessary to achieve acceptable oxygenation may increase the likelihood of survival with a favorable functional outcome. METHODS:We randomly assigned unresponsive adults receiving mechanical ventilation in the intensive care unit (ICU) after cardiac arrest to conservative or liberal oxygen therapy. In the two groups, the default lower limit of arterial oxygen saturation as measured by pulse oximetry (Spo2) was 90%. In the conservative-oxygen group, the alarm for the upper limit of the Spo2 was set at 95%, and the fraction of inspired oxygen (Fio2) was decreased to 0.21 provided that the Spo2 was above the lower limit. In the liberal-oxygen group, there were no measures limiting the upper Spo2, but the minimum Fio2 permitted during mechanical ventilation was 0.3. The primary outcome was survival with a favorable functional outcome at 180 days, assessed with the Extended Glasgow Outcome Scale (GOS-E). Levels on the GOS-E range from 1 (death) to 8 ("upper good recovery"). We defined survival with a favorable functional outcome as a GOS-E level of 5 ("lower moderate disability") or higher. RESULTS:A total of 1840 patients were recruited from 53 ICUs in Australia, New Zealand, and Ireland, with 882 assigned to conservative oxygen therapy and 958 assigned to liberal oxygen therapy. A favorable functional outcome at 180 days was observed for 313 of 819 patients (38.2%) in the conservative-oxygen group and 353 of 890 patients (39.7%) in the liberal-oxygen group (relative risk, 0.97; 95% confidence interval, 0.87 to 1.09; P = 0.65). No adverse events were reported. CONCLUSIONS:Among unresponsive adults undergoing mechanical ventilation in the ICU after a cardiac arrest, the percentage who survived with a favorable functional outcome was not higher with conservative oxygen therapy than with liberal oxygen therapy. (Funded by the Health Research Council of New Zealand and others; LOGICAL Australian New Zealand Clinical Trials Registry number, ACTRN12621000518864.).

Objective:To evaluate whether structured education combined with target-aligned arterial pressure alarm limits improved alignment between documented achieved and clinician-prescribed mean arterial pressure (MAP) during vasopressor therapy. Design:Multicentre pre-post quality-improvement evaluation. Setting:Three tertiary intensive care units in Australia and New Zealand. Participants:Adult intensive care unit patients receiving continuous vasopressor infusion with invasive arterial pressure monitoring, a documented clinician-prescribed MAP target, and available MAP and alarm-limit data during 24 h of vasopressor therapy. Intervention:A centre-level bundled implementation strategy comprising structured education, target-aligned arterial pressure alarm-limit configuration, and bedside implementation support, without mandating MAP targets or altering prescribing practice. Main outcome measures:The primary outcome was MAP gap, defined as documented achieved MAP minus prescribed MAP at four-hourly observation points during vasopressor therapy. Secondary outcomes included alarm window configuration, inter-site variation in MAP gap, exposure to MAP <60 mmHg, and exploratory short-term clinical outcomes. Results:After the intervention, alarm window width was narrower and more consistently aligned with prescribed MAP targets (median difference in width -40 mmHg, 95% confidence interval [CI]: -45 to -35). The post-intervention phase was associated with a lower documented MAP gap (median difference: -4 mmHg, 95% CI: -5.0 to -3.0; p < 0.001), reflecting reduced overshoot above target. The proportion of observations with MAP <60 mmHg did not increase. Clinical outcome data were exploratory and incompletely captured. Conclusions:Structured education combined with target-aligned arterial pressure alarm limits and bedside implementation support was associated with improved alignment between documented achieved and clinician-prescribed MAP. Further evaluation should include continuous pressure-time exposure, vasopressor dose, alarm burden, and longitudinal adherence to target-aligned alarm limits.

PURPOSE:In intensive care unit (ICU) patients receiving unfractionated heparin (UFH) infusion, activated partial thromboplastin time (aPTT) and anti-factor Xa (anti-Xa) levels have limited correlation and significant discordance. We aimed to test whether thromboelastographic-derived citrated kaolin reaction time (CKR) and/or the difference (R-difference) and/or ratio (R-ratio) between CKR and heparinase-corrected CKR might help resolve such discordance METHODS: We obtained simultaneous triple-paired samples for aPTT, anti-Xa and thromboelastography (TEG) in ICU patients receiving UFH infusion. We assessed correlation between UFH dose and R-difference and concordance for therapeutic ranges between aPTT, anti-Xa, and CKR or R-difference or R-ratio. On multivariate analysis, we assessed factors associated with TEG R-based measurements RESULTS: We studied 136 samples from 24 patients with a median APACHE III score of 50 and median UFH dose of 14.6 [10.5, 18.3] units/kg/h. for each 1 unit/kg increase in UFH dose, the R-difference increased by 2 min (95% C.I. 0.23-3.7, p < 0.05) but the correlation was weak (R2 = 0.1). The Cohen's kappa coefficient for agreement was 0.39 for CKR-aPTT and 0.17 for CKR-anti-Xa. Similar results were seen for R-difference and R-ratio. When aPTT and anti-Xa were discordant for therapeutic ranges, TEG did not resolve discordance. On multivariate analysis, CKR, R-difference and R-ratio were independently positively associated with UFH dose but also with APACHE III score and, negatively, with iCa CONCLUSIONS: In ICU patients receiving UFH infusion, TEG R-based measurements have limited correlation and concordance with anti-Xa and aPTT for defined therapeutic ranges and do not help resolve their discordance.