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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.

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.