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PurposeThe Acute Disease Quality Initiative (ADQI) Workgroup recently released a consensus definition of sepsis-associated acute kidney injury (SA-AKI), combining Sepsis-3 and Kidney Disease Improving Global Outcomes (KDIGO) AKI criteria. This study aims to describe the epidemiology of SA-AKI.MethodsThis is a retrospective cohort study carried out in 12 intensive care units (ICUs) from 2015 to 2021. We studied the incidence, patient characteristics, timing, trajectory, treatment, and associated outcomes of SA-AKI based on the ADQI definition.ResultsOut of 84,528 admissions, 13,451 met the SA-AKI criteria with its incidence peaking at 18% in 2021. SA-AKI patients were typically admitted from home via the emergency department (ED) with a median time to SA-AKI diagnosis of 1 day (interquartile range (IQR) 1–1) from ICU admission. At diagnosis, most SA-AKI patients (54%) had a stage 1 AKI, mostly due to the low urinary output (UO) criterion only (65%). Compared to diagnosis by creatinine alone, or by both UO and creatinine criteria, patients diagnosed by UO alone had lower renal replacement therapy (RRT) requirements (2.8% vs 18% vs 50%; p < 0.001), which was consistent across all stages of AKI. SA-AKI hospital mortality was 18% and SA-AKI was independently associated with increased mortality. In SA-AKI, diagnosis by low UO only, compared to creatinine alone or to both UO and creatinine criteria, carried an odds ratio of 0.34 (95% confidence interval (CI) 0.32–0.36) for mortality.ConclusionSA-AKI occurs in 1 in 6 ICU patients, is diagnosed on day 1 and carries significant morbidity and mortality risk with patients mostly admitted from home via the ED. However, most SA-AKI is stage 1 and mostly due to low UO, which carries much lower risk than diagnosis by other criteria.

Purpose Sodium bicarbonate is commonly administered to treat metabolic acidosis in intensive care units (ICUs). There is limited evidence from randomized trials to support this practice, and observational studies show conflicting results. Our aim was to perform a target trial emulation evaluating the effect of bicarbonate therapy on mortality. Methods Retrospective cohort study using data from 12 Australian ICUs. Inclusion criteria were adults with pH < 7.3 and PCO 2  ≤ 45 mmHg within the first three days. We excluded repeat admissions, toxicology, diabetic ketoacidosis, and pre-existing end-stage renal failure. The treatment intervention was sodium-bicarbonate administration, and the primary outcome was 30-day ICU mortality with ICU discharge as a competing event. We evaluated multiple subgroups, including patients with acute kidney injury, requirement for vasoactive therapy, and pH < 7.2. The primary model utilized a parametric g-computation and rolling entry matching was performed as a sensitivity analysis. Results We identified 6157 eligible admissions, of which 1764 (29%) received sodium bicarbonate. Bicarbonate therapy was associated with a 1.9% absolute mortality reduction for the primary analysis [risk ratio 0.86, 95% confidence interval (CI) 0.80 to 0.91], and significant benefits were seen across all subgroups evaluated. A similar point estimate of 2.1% was observed in the sensitivity analysis, with a sustained mortality reduction seen at 30 days. Conclusion In this target trial emulation, bicarbonate administration was associated with a small but statistically significant reduction in mortality for patients with metabolic acidosis. Large sample sizes would be required to demonstrate this effect in a randomized trial.

Background In septic shock, the optimal timing of adjunctive vasopressin initiation shock is unknown. We aimed to assess the effect of its early initiation for patients with septic shock. Methods We conducted a multicenter target trial emulation to estimate the intensive care unit (ICU) mortality effect of early (≤ 6 h) adjunctive vasopressin compared with usual care. Eligible patients had septic shock diagnosed within 6 h of ICU admission. The primary outcome of this study was 30-day ICU mortality. Subgroup analyses were conducted to test the interaction of early vasopressin start with peak norepinephrine-equivalent dose (NED) at 6 h, APACHE score, peak lactate at 6 h and invasive mechanical ventilation. Secondary outcomes were the impact of delayed vasopressin introduction on 30-day ICU mortality and effect of NED at vasopressin start on 30-day ICU mortality. We used the parametric g-formula to emulate a target trial. Results Overall, 3,105 patients fulfilled the inclusion criteria. Mean age was 62 years and mean APACHE III score was 83. In the first six hours of vasopressor therapy, 1,864 (60%) patients were invasively ventilated. Estimated 30-day ICU mortality was 19.34% (95%CI, 17.0 to 21.68) in the no vasopressin group and 18.45% (95%CI, 16.26 to 20.63) in the early vasopressin group; relative risk 0.95 (95%CI, 0.93 to 0.98). The estimated 30-day ICU mortality effect of starting vasopressin was particularly strong at lower norepinephrine doses (< 0.25 µg.kg −1 .min −1 ) and significant at lower norepinephrine doses than recommended by the Surviving Sepsis Campaign Guidelines. Vasopressin administration progressively increased over the study period, from 35.2% (95%CI, 30.0 to 40.5) in 2015 to 45.1% (95%CI, 40.7 to 49.6) in 2021 (ß =  + 1.3% per year; 95%CI, + 0.46 to + 2.16, p  = 0.011). Patients had progressively lower norepinephrine equivalent dose (ß = − 0.05 µg.kg −1 .min −1 per year; 95%CI, − 0.09 to − 0.002, p  = 0.038) and lower total SOFA score (ß = − 0.1 point per year; 95%CI, − 0.18 to − 0.07, p  < 0.001) at vasopressin start. Conclusions In this emulation of a hypothetical target trial, patients with septic shock benefited from early vasopressin administration. These findings can help design prospective randomised-control trials of early adjunctive vasopressin use in septic shock.

Background The optimal transfusion threshold for patients undergoing venoarterial extracorporeal membrane oxygenation (VA-ECMO) remains uncertain. Methods We used data from OBLEX (ClinicalTrials.gov: NCT03714048), an international, prospective, observational study conducted across 12 centres in Australia, Europe, and North America between 2019 and 2022. The study collected information on patient demographics, bleeding risk factors, transfusion practices during the first seven days of ECMO, and in-hospital mortality. Using these data, we emulated a target trial comparing the effects of liberal transfusion practice (transfusion initiated at Hb ≥ 90 g/L) and restrictive transfusion practice (transfusion initiated at Hb ≤ 70 g/L) on hospital mortality within seven days of ECMO initiation. Sequential trials approach was used to estimate the causal contrast. Results A total of 534 patients were included, with 46% dying during hospitalisation. After accounting for potential confounders, the liberal transfusion practice demonstrated a modest survival benefit within the first two days of ECMO, with differences in survival probabilities of 12% (95% CI 3% to 21%) at day 2 and 13% (95% CI 2% to 25%) at day 3, corresponding to the number needed to treat (NNT) of 8 and 7 respectively. No differences in survival benefit were found after day 3. These results were consistent across sensitivity and exploratory analyses. Conclusion This target trial emulation study suggests that a liberal transfusion threshold may provide a modest survival benefit during the early course of VA-ECMO, but no benefit afterwards. Prospective studies are needed to confirm these findings, assess clinical adoption, and investigate underlying mechanism.

PurposeRecombinant erythropoietin (EPO) administered for traumatic brain injury (TBI) may increase short-term survival, but the long-term effect is unknown.MethodsWe conducted a pre-planned long-term follow-up of patients in the multicentre erythropoietin in TBI trial (2010–2015). We invited survivors to follow-up and evaluated survival and functional outcome with the Glasgow Outcome Scale-Extended (GOSE) (categories 5–8 = good outcome), and secondly, with good outcome determined relative to baseline function (sliding scale). We used survival analysis to assess time to death and absolute risk differences (ARD) to assess favorable outcomes. We categorized TBI severity with the International Mission for Prognosis and Analysis of Clinical Trials in TBI model. Heterogeneity of treatment effects were assessed with interaction p-values based on the following a priori defined subgroups, the severity of TBI, and the presence of an intracranial mass lesion and multi-trauma in addition to TBI.ResultsOf 603 patients in the original trial, 487 patients had survival data; 356 were included in the follow-up at a median of 6 years from injury. There was no difference between treatment groups for patient survival [EPO vs placebo hazard ratio (HR) (95% confidence interval (CI) 0.73 (0.47–1.14) p = 0.17]. Good outcome rates were 110/175 (63%) in the EPO group vs 100/181 (55%) in the placebo group (ARD 8%, 95% CI - 3 to 18%, p = 0.14). When good outcome was determined relative to baseline risk, the EPO groups had better GOSE (sliding scale ARD 12%, 95% CI 2–22%, p = 0.02). When considering long-term patient survival, there was no evidence for heterogeneity of treatment effect (HTE) according to severity of TBI (p = 0.85), presence of an intracranial mass lesion (p = 0.48), or whether the patient had multi-trauma in addition to TBI (p = 0.08). Similarly, no evidence of treatment heterogeneity was seen for the effect of EPO on functional outcome.ConclusionEPO neither decreased overall long-term mortality nor improved functional outcome in moderate or severe TBI patients treated in the intensive care unit (ICU). The limited sample size makes it difficult to make final conclusions about the use of EPO in TBI.

In critically ill patients with acute kidney injury (AKI), a fluid balance (FB) > 2 L at 72 h after AKI diagnosis is associated with adverse outcomes. Identification of patients at high-risk for such fluid accumulation may help prevent it. We used Australian electronic medical record (EMR)-based clinical data to develop the “AKI-FB risk score”, validated it in a British cohort and used it to predict a positive FB >2 L at 72 h after AKI diagnosis. We developed the AKI-FB score in 32,030 patients with a median age of 63 years and a median APACHE 2 score of 16. We validated it in 4465 patients, with significant differences in admission diagnoses and interventions. The key score variables were admission after trauma, sepsis or septic shock, and, on the day of AKI diagnosis, highest creatinine, daily cumulative FB, mechanical ventilation, noradrenaline use, noradrenaline equivalent dose >0.07 μg/kg/min, lactate ≥2 mmol/L, transfusion, and nutritional support. A score threshold of 32 had a sensitivity of 75 % and a specificity of 72 % for predicting a > 2 L positive FB with an AUC-ROC of 0.805; 95 % CI 0.799 to 0.810. External validation demonstrated an AUC of 0.761 (95 % CI 0.746 to 0.775). We developed and validated the “AKI-FB risk score” to predict patients who developed a positive FB >2 L within 72 h of AKI diagnosis. This prediction score was robust and facilitated the identification of high-risk AKI patients who could be the tarted for preventive measures and be included in future clinical trials of FB management. •Developed AKI-FB risk score for the prediction of a strongly positive fluid balance 72 hours after diagnosis of AKI.•The AKI-FB risk score had excellent predictive ability and was validated in a large cohort from another country.•A score of 32 or higher had high sensitivity and specificity for a positive fluid balance greater than 2L at 72 hours.

Background Although comorbid medical diseases are important determinants of outcome among the critically ill, the role of psychiatric comorbidity is not well defined. The objective of this study was to determine the occurrence of psychiatric comorbidity and its effect on the outcome of patients admitted to adult intensive care units (ICU) in Queensland. Methods Admissions among adults to 12 ICUs in Queensland during 2015–2021 were included and clinical and outcome information was obtained through linkages between the ANZICS Adult Patient Database, the state-wide Queensland Hospital Admitted Patient Data Collection, and death registry. Results A total of 89,123 admissions were included among 74,513 individuals. Overall, 7,178 (8.1%) admissions had psychiatric co-morbidity with 6,270 (7.0%) having one major psychiatric diagnosis and 908 (1%) having two or more. Individual diagnoses of mood, psychotic, anxiety, or affective disorders were present in 1,801 (2.0%), 874 (1.0%), 3,241 (3.6%) and 354 (0.4%) admissions respectively. Significant differences were observed among the main groups (mood, affective, anxiety, psychotic, or multiple disorders) and those without psychiatric comorbidity with respect to main diagnosis, Acute Physiology and Chronic Health Evaluation (APACHE II) score, sex, age, and medical comorbidity. Crude 30-day case-fatality rates were significantly lower (5.1%) compared to the general ICU population (10.1%) ( p  < 0.001). After controlling for confounding variables in the logistic regression model, patients with psychiatric comorbidity were at lower odds of death. Conclusions Psychiatric comorbidity is common among ICU presentations and is associated with a lower risk of death. This association is likely to be more complex than being a simple protective factor, and future research needs to further delineate how psychiatric comorbidity informs outcomes of specific ICU presentations.