BACKGROUNDIntravenous fluids are recommended for the treatment of patients who are in septic shock, but higher fluid volumes have been associated with harm in patients who are in the intensive care unit (ICU). METHODSIn this international, randomized trial, we assigned patients with septic shock in the ICU who had received at least 1 liter of intravenous fluid to receive restricted intravenous fluid or standard intravenous fluid therapy; patients were included if the onset of shock had been within 12 hours before screening. The primary outcome was death from any cause within 90 days after randomization. RESULTSWe enrolled 1554 patients; 770 were assigned to the restrictive-fluid group and 784 to the standard-fluid group. Primary outcome data were available for 1545 patients (99.4%). In the ICU, the restrictive-fluid group received a median of 1798 ml of intravenous fluid (interquartile range, 500 to 4366); the standard-fluid group received a median of 3811 ml (interquartile range, 1861 to 6762). At 90 days, death had occurred in 323 of 764 patients (42.3%) in the restrictive-fluid group, as compared with 329 of 781 patients (42.1%) in the standard-fluid group (adjusted absolute difference, 0.1 percentage points; 95% confidence interval [CI], −4.7 to 4.9; P = 0.96). In the ICU, serious adverse events occurred at least once in 221 of 751 patients (29.4%) in the restrictive-fluid group and in 238 of 772 patients (30.8%) in the standard-fluid group (adjusted absolute difference, −1.7 percentage points; 99% CI, −7.7 to 4.3). At 90 days after randomization, the numbers of days alive without life support and days alive and out of the hospital were similar in the two groups. CONCLUSIONSAmong adult patients with septic shock in the ICU, intravenous fluid restriction did not result in fewer deaths at 90 days than standard intravenous fluid therapy. (Funded by the Novo Nordisk Foundation and others; CLASSIC ClinicalTrials.gov number, NCT03668236.

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OBJECTIVES: Randomized clinical trials (RCTs) conducted in adult ICU patients increasingly include patient-important outcomes other than mortality. This comes with challenges regarding outcome choices/definitions, handling of deceased patients and missing data in analyses, and choices of effect measures and statistical methods due to complex distributions. This scoping review aimed to characterize how these challenges are handled in relevant contemporary RCTs. DATA SOURCES: We systematically searched 10 selected journals for RCTs conducted primarily in adult ICU patients published between 1 January 2018 and 5 May 2022 reporting at least one patient-important outcome other than mortality, including “days alive without”…-type outcomes, functional/cognitive/neurologic outcomes, health-related quality of life (HRQoL) outcomes, and ordinal/other outcomes. STUDY SELECTION: Abstracts and full-texts were assessed independently and in duplicate by two reviewers. DATA EXTRACTION: Data were extracted independently and in duplicate by two reviewers using predefined and pilot-tested extraction forms and subsequently categorized to facilitate analysis. DATA SYNTHESIS: We included 687 outcomes from 167 RCTs, with 32% of RCTs using a patient-important outcome other than mortality as a (co-)primary outcome, most frequently “days alive without”…-type outcomes. Many different functional/cognitive/neurologic (103) and HRQoL (29) outcomes were reported. Handling of deceased patients varied, with analyses frequently restricted to survivors only for functional/cognitive/neurologic (62%) and HRQoL (89%) outcomes. Follow-up was generally longer and missing data proportions higher for functional/cognitive/neurologic and HRQoL outcomes. Most outcomes were analyzed using nonparametric tests (31%), linear regression/t tests (27%), chi-square–like tests (12%), and proportional odds logistic regression (9%), often without presentation of actual treatment effects estimates (38%). CONCLUSIONS: In this sample of RCTs, substantial variation in practice and suboptimal methodological choices were observed. This calls for increased focus on standardizing outcome choices and definitions, adequate handling of missing data and deceased patients in analyses, and use of statistical methods quantifying effect sizes.

Managing haemostasis in patients undergoing cardiopulmonary bypass (CPB) surgery remains a challenge. There is no established laboratory test to predict transfusion requirements in cardiac surgery. We investigated whether preoperative Thromboelastography (TEG) with Platelet Mapping Assay (PMA) or Multiple Electrode Aggrometry (MEA) could predict transfusion requirements in patients undergoing elective coronary artery bypass grafting (CABG) or combined CABG with aortic or mitral valve replacement. We prospectively investigated 199 patients undergoing elective CABG or combined procedures. PMA and MEA were performed at baseline (after anaesthesia induction), upon arrival at the intensive care unit and on the first postoperative day. Patients receiving fresh frozen plasma and/or platelets (FFP/PLT) had a lower PMA maximum amplitude (MA) for adenosine diphosphate (PMA-ADP) and arachidonic acid (PMA-AA) at baseline, at arrival in the intensive care unit and the first postoperative day compared to non-transfused patients. Receiver operating characteristic curves on PMA showed that lower values predicted FFP/PLT transfusion: PMA-ActF 0.64 (p = 0.04), PMA-ADP 0.69 (p = 0.01) and PMA-AA 0.71 (p = 0.002). In contrast, MEA values were not able to predict FFP/PLT transfusions. This study shows that preoperative PMA potentially is a better screening tool for platelet inhibition associated with transfusion requirements in patients undergoing CABG or combined procedures.

Thrombocytopenia is a condition with low platelet levels in the blood, typically defined as a platelet count less than 150 × 10 9 /L, and is associated with increased rates of bleeding, transfusion requirements, and mortality. 1 Thrombocytopenia is common in hospitalised patients, including patients with haematological malignancies, 2 patients receiving chemotherapy, 3 patients with

Intravenous (IV) fluids are considered essential in the management of sepsis, and the Surviving Sepsis Campaign guideline suggests at least 30 ml/kg IV fluid volumes should be given initially to adult patients based on low quality evidence. 1 The guideline committee found that there was insufficient evidence to make recommendation on the use of restrictive versus liberal fluid strategy after initial

Background Buffered crystalloid solutions are increasingly recommended as first‐line resuscitation fluids. However, guidelines do not distinguish between different types of buffered solutions. The aim of the outlined systematic review is to summarize and assess the effects of acetate‐ vs lactate‐buffered crystalloid solutions on patient‐important outcomes. Methods We will conduct a systematic review of randomized clinical trials (RCTs) with meta‐analysis and trial sequential analysis comparing the use of acetate‐ vs lactate‐buffered crystalloid solutions in hospitalized patients. We will systematically search the Cochrane Library, MEDLINE, EMBASE, and Epistemonikos for relevant literature. We will follow the recommendations set by the Cochrane Collaboration and the Preferred Reporting Items for Systematic Review and Meta‐Analysis (PRISMA) statement. The risk of systematic errors (bias) and random errors will be assessed, and the overall quality of evidence will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Discussion The outlined systematic review will provide important data on how patient‐important outcomes are affected by intravenous administration of acetate‐ vs lactate‐buffered crystalloid solutions in hospitalized patients.

Background: Randomised clinical trials (RCTs) conducted in intensive care units (ICUs) frequently focus on all-cause mortality, but other patient-important outcomes are increasingly used and recommended. Their use, however, is not straightforward: choices and definitions, operationalisation of death, handling of missing data, choice of effect measures, and statistical analyses for these outcomes vary greatly.Methods: We will conduct a scoping review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. We will search 10 selected general and speciality journals for RCTs conducted in adult ICU patients from 2018 and onwards reporting at least 1 patientimportant outcome other than mortality (including days alive without life support/ days alive and out of hospital-type outcomes, health-related quality of life, functional/cognitive/neurological outcomes, and other general patient-important outcomes). We will summarise data on outcome measures and definitions, assessment time points, proportions and handling of death, proportions and handling of missing data, and effect measures and statistical methods used for analysis. | 1003 GRANHOLM et AL How to cite this article: Granholm A, Kaas-Hansen BS, Kjaer M-BN, et al. Patient-important outcomes other than mortality in recent ICU trials: Protocol for a scoping review. Acta