Data collection in randomized trials is expensive and labor intensive. With the rise in ongoing pragmatic trials, the use of electronic medical records (EMR) as a source of data has increased. Although potentially faster and cheaper, EMR use can lead to errors. Therefore, to ensure accurate data collection and to avoid systematic errors we performed a study comparing automated data extraction (ADE) with manual data extraction (MDE). We performed a retrospective cohort study to compare the accuracy of ADE using Structured Query Language with MDE by blinded physicians from our EMR. We tested the interrater agreement and intraclass correlation coefficient of clinical baseline data and outcomes of a random sample of 30 patients admitted to the ICU, on mechanical ventilation, requiring opioids for analgosedation for an upcoming pragmatic clinical trial. Key data compared included, but not limited to, patient’s demographics, laboratory and vital signs, daily morphine milligram equivalent (MME), days alive and free of mechanical ventilation, days alive and free of hospitalization, days alive and free of ICU, days alive and free of vasopressors, and death. Among 238 patients screened over 1-month period, 72 fulfilled inclusion criteria and 30 were randomly selected to be included in the evaluation. We blindly collected 1320 baseline data, 2160 categorical outcomes and 705 continuous outcomes for a total of 4185 data points. The intraclass correlation coefficient and the Cohen’s Kappa were perfect or almost perfect for all data, including outcomes such as daily MME, days alive and free of mechanical ventilation, days alive and free of ICU and days alive and free of hospital with p < 0.001. Among all rechecked data, the ADE was correct in 53 (77.9

Phenobarbital (PB) is historically used for management of seizure disorders but more recently has emerged as a prominent option for the management of alcohol withdrawal syndrome given data suggesting its benefit over benzodiazepines. An important consideration of PB therapy is its induction of cytochrome-P 450 enzymes (CYP450), which may lead to underrecognized drug-drug interactions (DDIs). Knowledge of these PB DDIs, including their onset and offset, is important to better elucidate how to manage these DDIs. To identify published literature evaluating the relevance of DDIs between PB and selected medications, a systematic review was performed including literature published through January 2026, focused on the administration of both PB and a list of medications based on tertiary medication database review as well as clinical relevance, including anticoagulants, antimicrobials, and immunosuppressants. Included articles had to identify outcomes of interest, which were focused on laboratory, pharmacokinetic, and clinical outcomes, and had to be in humans. Data extraction included the onset and offset of PB DDIs and potential PB dose-response and magnitude of induction of target medication. A total of 3271 articles were identified, with 50 studies meeting inclusion criteria, which included both adult and pediatric populations. Thirteen studies evaluated onset of PB induction, which ranged from 6 h to 30 days. Eight studies evaluated offset of PB induction, which ranged from 2 to 8 weeks. Limited data demonstrated a PB dose-response relationship in terms of magnitude of CYP induction. We found that 86% of the included studies demonstrated an impact by PB on outcomes, which were often related to therapeutic drug monitoring. Data suggest that PB does lead to clinically significant DDIs in multiple classes of medications. Future areas of research include focused evaluations on clinical outcomes, as well as studies specifically evaluating single high-dose PB and impact on DDI outcomes.

INTRODUCTION:Critical care ultrasound (CCUS) is an essential tool for managing critically ill patients at bedside, improving diagnostic accuracy and reducing procedural risks. However, its global adoption remains inconsistent due to variability in training, certification, and organizational support. This study explores current CCUS use, training practices, and associated facilitators and barriers, aiming to identify opportunities for improving its implementation. METHODS:A worldwide online survey was conducted between June 2023 and June 2024. The survey was endorsed and distributed by several (inter)national critical care societies. Participation was fully anonymous and open to all healthcare professionals affiliated with a critical care department. The survey consisted of four sections: demographic data, CCUS practice, CCUS training, and possible facilitators and barriers to CCUS. Facilitators and barriers were assessed using an evidence-based framework: the Measurement Instrument for Determinants of Innovation (MIDI). RESULTS:A total of 277 participants (73.3% intensivists, 60.3% European) across 62 countries completed the survey. Most participants (93.5%) used CCUS, predominantly for lung, vascular and basic cardiac assessments (>95% for each). However, the majority lacked formal CCUS certification (73.6%). Facilitators included CCUS's perceived value in improving patient outcomes, including faster diagnosis or treatment. Key barriers included lack of adequate training, absence of formal certification, and limited organizational support. CONCLUSION:Despite widespread recognition of CCUS's clinical benefits, significant barriers in training, certification, and organizational infrastructure hinder its full implementation. Addressing these challenges and engaging identified facilitators provides a strong foundation for promoting the introduction and integration of CCUS into routine clinical practice.

BACKGROUND:Long-term benzodiazepine (BZD) use in the intensive care unit (ICU) is associated with negative patient outcomes, while data on short-term BZD use are limited. OBJECTIVES:This study evaluated ICU outcomes associated with short-term midazolam infusion (<24 h) compared to propofol in emergency department (ED) patients who were mechanically ventilated. METHODS:This was a retrospective cohort study of mechanically ventilated patients in the ED who received either midazolam or propofol infusions from 1/1/2020 to 3/15/2022. Patients with either status epilepticus, acute pancreatitis, or status postcardiac arrest, had continuous midazolam for >24 h, or concurrent midazolam and propofol use for >2 h, were excluded. The primary outcome was ventilator-free days (VFDs) at day 7. Secondary outcomes were duration of mechanical ventilation, incidence of delirium within 48 h, and in-hospital mortality. RESULTS:A total of 137 patients were included (midazolam, n = 82; propofol, n = 55). Patients were older in the midazolam group (65 vs. 59 years), while baseline Acute Physiology and Chronic Health Evaluation II scores were comparable between the two groups. Midazolam was most often initiated due to need for vasopressors (25.6%), with a median norepinephrine equivalent of 0.15 mcg/kg/min (IQR 0.07-0.29) at initiation. In the midazolam group, 36.6% were changed to propofol within 60 minutes of ICU admission. No significant differences were observed in VFDs at day 7 between the propofol and midazolam groups (difference 0, 95% CI -0.69 to +0.58; p = 0.75). We also did not find differences in duration of mechanical ventilation (p = 0.53), incidence of delirium at 48 h (p = 0.85), or in-hospital mortality (p = 0.49). CONCLUSION:Short-term midazolam use (i.e., <24 h) was not associated with longer VFDs at day 7 in this retrospective study. No significant differences were observed in duration of mechanical ventilation, delirium incidence, or in-hospital mortality. Further research is warranted to validate these findings.

BACKGROUND:Alcohol withdrawal syndrome (AWS) is a complication of alcohol use disorder that manifests as a range of symptoms. Symptom-triggered benzodiazepines (BZDs) are often used as first-line treatment of AWS. However, recent literature suggests phenobarbital (PHB) may be safer and more efficacious, but studies are limited by exclusion of patients with neurological injuries. OBJECTIVE:We aimed to evaluate the safety of PHB compared to BZDs for the management of AWS among patients with primary neurologic injuries. METHODS:Retrospective cohort study of patients with primary neurologic injuries admitted to an ICU who received PHB or symptom-triggered BZD for AWS between December 2013 and February 2020. The primary outcome was incidence of oversedation, defined as Richmond Agitation Sedation Scale (RASS) scores from -5 to -3 within 24 hours of initial PHB or BZD dose. Secondary outcomes included largest decrease in RASS, need for mechanical ventilation, and additional sedative use within 24 hours of initial PHB or BZD dose. A multivariable analysis was performed to evaluate the association of PHB administration with the primary outcome. RESULTS:Among 600 patients treated for AWS, 84 patients were included in our analysis (PHB, n = 56; BZD, n = 28). In the unadjusted analysis, there were no differences between the PHB and BZD groups for the primary outcome of oversedation (21.4 vs. 7.1%, P = 0.13), or secondary outcomes of decrease in RASS (P = 0.34), or new ventilator requirement (P = 0.55). Patients who received PHB had higher rates of additional sedative use (P < 0.01). Multivariable regression revealed an increase in oversedation among intubated patients (P = 0.014), while PHB administration was not independently associated with oversedation (P = 0.516). CONCLUSION AND RELEVANCE:Phenobarbital did not independently increase the risk of oversedation compared to BZD for AWS in patients with primary neurologic injuries. Future studies should determine optimal dosing of PHB in this population.

The advancements in cardiovascular imaging over the past two decades have been significant. The miniaturization of ultrasound devices has greatly contributed to their widespread adoption in operating rooms and intensive care units. The integration of AI-enabled tools has further transformed the field by simplifying echocardiographic evaluations and enhancing the reproducibility of hemodynamic measurements, even for less experienced operators. Speckle tracking echocardiography offers a direct, visual, and quantitative assessment of myocardial shortening, serving as a compelling alternative to traditional methods for evaluating right and left ventricular systolic function. In critically ill patients, sublingual microcirculation imaging has revealed a high prevalence of microvascular alterations, which are markers of disease severity. The use of handheld vital microscopes enables the quantification of several key parameters, including vessel density, perfusion, red blood cell velocity, and the perfused vascular density. Such metrics are useful for evaluating microcirculatory health. The development of automated software marks a significant advance toward real-time bedside microvascular assessment. These advancements could eventually allow shock resuscitation to be tailored based on microvascular responses. In parallel with imaging advances, cardiac output monitors have evolved significantly. Once cumbersome devices displaying basic numerical data in tabular form, they now feature sleek, touch-screen interfaces integrated with visual decision-support tools. These tools synthesize hemodynamic data into intuitive graphical formats, allowing clinicians to quickly grasp the determinants of circulatory shock. This visual clarity supports more efficient and accurate decision-making, which may ultimately lead to improved patient care and outcomes.

BACKGROUND:Early mobilisation (EM) within the first 72 h of ICU admission is essential for preventing ICU-acquired weakness; however, mobilisation rates remained low among mechanically ventilated (MV) COVID-19 patients during the pandemic waves. This study aimed to characterise the association between EM and 60-day outcomes. METHODS:A multicentre observational study conducted by the European Society of Intensive Care Medicine (ESICM) examined mobilisation strategies during the second COVID-19 wave (UNITE-COVIDed2021). All patients with confirmed SARS-COV-2 infection who were in the ICU on the peak day between 1st January and 1st June 2021 were included. The analysis expanded on the UNITE-COVIDed2020 study, comparing the first and second COVID-19 waves using a combined dataset. RESULTS:Data from 2053 patients during the second wave across 103 ICUs in 35 countries were analysed and compared with 4190 patients from the first wave. EM was achieved in 801 (39%) vs. 1114 (27%), p < 0.001, respectively. In the combined cohort, MV on admission significantly reduced the likelihood of EM (OR 0.29, 95% CI: 0.25-0.33, p = 0.001). While EM did not improve ICU or hospital length of stay, it was associated with reduced 60-day mortality (OR 0.74, 95% CI: 0.64-0.86, p = 0.001) and transfer rates to other care facilities (OR 0.74, 95% CI: 0.59-0.94, p = 0.001). CONCLUSION:EM is feasible and beneficial for critically ill COVID-19 patients. It was associated with reduced mortality and lower transfer rates to other care facilities, which underscores the critical role of EM in enhancing patient recovery during a pandemic.

PURPOSE OF REVIEW:Despite advances in critical care medicine, the incidence of clinically important upper gastrointestinal bleeding (UGIB) remains consistent. One therapy that reduces UGIB is the use of stress ulcer prophylaxis (SUP). In the past year, several key manuscripts have been published regarding SUP, providing updated recommendations for its prescription. In this review, we provide commentary on these recommendations and areas for future research. RECENT FINDINGS:Risk factors for UGIB include chronic liver disease, coagulopathy, severe neurologic illness or injury, and shock. The prescription of SUP is associated with a decreased occurrence of UGIB but no benefit in mortality. Although both histamine-2 receptor antagonists and proton pump inhibitors (PPIs) are recommended for SUP, it is possible that PPIs may be associated with increased mortality in critically ill patients. The short-term use of SUP is not expected to be associated with most adverse drug events, but inappropriate continuation of SUP increases this risk. SUMMARY:Patient-specific considerations based on recent data help with improving the prescription of SUP, although additional research is necessary. The use of artificial intelligence may be able to predict at risk patients with the potential to influence appropriate prescription of SUP and reduce the occurrence of UGIB.

Acute kidney injury (AKI) in the intensive care unit (ICU) occurs in up to 60% of patients globally. Of this population, approximately 15% to 25% receive renal replacement therapy (RRT). Modes of RRT include intermittent hemodialysis (IHD) or continuous renal replacement therapy (CRRT). CRRT offers the potential advantage of continuous removal of fluid and solutes, reducing potential fluctuations in electrolytes, fluid balance, and providing hemodynamic stability, compared to IHD. Although there is ongoing debate regarding the optimal use and application of RRT in the ICU, its frequent use necessitates drug dosing considerations. Along with the numerous comorbidities and physiologic factors that may affect drug dosing in critically ill patients, RRT only adds to the complicated nature of these patients.

BACKGROUND:Early detection of mild neurocognitive disorder (NCD) enables timely and targeted interventions, especially before progression to major neurocognitive disorder. This study aims to develop a sensitive and simple digitalised screening tool, using artificial intelligence to capture and interpret spoken language, for the detection of mild NCD. METHOD:The Digitalised Combined Objective-Subjective (DCOS) cognitive screening tool was developed based on DSM-5 criteria, which includes subjective and objective cognitive impairment for the diagnosis of mild NCD. We developed and validated on two independent cohorts: a dementia speech biomarkers cohort (n = 977) for development and the Screening for Early Alzheimer's Disease Study cohort (n = 127) for validation. Mild NCD is defined using the Hong Kong List Learning Test (HKLLT with below 1SD cutoff; see Table 1). DCOS items were selected through ROC analysis from existing validated cognitive assessments, incorporating both subjective and objective domains, with the criteria that the items must be assessed using spoken language for the development of the digitalised tool. The scoring weights were calculated according to the estimated coefficients of a multivariate logistic regression model. RESULT:The new tool DCOS comprises six items (three subjective, three objective) with a maximum score of 16 points. In the development cohort, DCOS demonstrated good diagnostic accuracy (AUC=0.75) comparable to Hong Kong Montreal Cognitive Assessment-5min (MoCA-5min) (AUC=0.77) and superior to Ascertain Dementia 8 (AD8) (AUC=0.58). At the optimal cutoff score of 9.5, DCOS achieved a better balanced performance (F1=0.56) than both HK MoCA-5min (F1=0.48) and AD8 (F1=0.44). External validation confirmed robust performance with improved diagnostic accuracy (AUC=0.87), achieving 88% sensitivity and 69% specificity (see Table 2). The sampling of the items and and the nature of the test has shown the feasibility of developing into a digitalised test. CONCLUSION:DCOS is a novel screening tool that assesses cognitive impairment from both subjective and objective domains. It presents a potential discriminative performance for mild NCD detection. The brief administration time (<5 minutes) makes it particularly suitable for primary health care. As a next step, DCOS will be incorporated with artificial intelligence and be applied on a digital platform to enhance its utility in large-scale settings.

Patients with septic shock are high risk for developing acute kidney injury (AKI), with its associated morbidity. This systematic review assessed the evidence for an effect on renal outcomes from choice of vasopressor. Searches were conducted on Medline, Embase, Cochrane Central, congress abstracts and trial registries. The search strategy included septic shock, vasopressor agents and renal impairment. Inclusion criteria were non-crossover randomised controlled trials of adult septic shock comparing individual or combinations of vasopressors and placebo controlled trials. Primary outcome was the incidence of AKI in study participants. Secondary outcomes were AKI duration, renal replacement therapy (RRT) rate, RRT duration, renal failure free days, requirement for long term RRT and Major Adverse Kidney Events (MAKE) at 30 and 90 days. A total of 4259 patients, from 17 studies, were included. Vasopressin and terlipressin studies predominated. In 8 studies reporting AKI rate, no effect was seen relating to vasopressor choice. RRT rate was the most reported secondary outcome. Of five studies that investigated the role of vasopressin, only one showed significant benefit. Alongside limited reporting, no conclusive benefit was demonstrated in other secondary outcomes. No studies reported requirement for long term RRT, MAKE 30 or 90. This is the first systematic review focussed on renal outcomes with differential vasopressor therapy in septic shock. It illustrates the paucity of evidence supporting a particular vasopressor. Also highlighted are problems of population and study heterogeneity, as well as the focus on RRT as a proxy for renal outcomes. Standardised renal outcome reporting, large and appropriately powered trials and focussed sub-population studies are required to further inform renal focussed vasopressor research and practice. This systematic review was prospectively registered on PROSPERO (CRD42023481778).

Background: Phenobarbital (PHB) has been shown to be an effective treatment of alcohol withdrawal syndrome (AWS), with multiple dosing strategies used (e.g., single-dose and symptom-triggered). Studies have often used tapered doses, typically following a front-loaded dose, despite PHB’s long half-life which should lead to an ability to auto-taper. Objective: The purpose of this study was to compare clinical outcomes associated with two PHB dosing strategies (taper [T], no taper [NT]) for AWS. Methods: This retrospective cohort study compared adult patients admitted to the ICU from October 2017 to May 2019 who received an initial loading dose of PHB for AWS. The use of PHB was at the discretion of the clinician per our institutional guidelines. Prior to November 2018, patients were prescribed a PHB taper, while after this period, the taper was no longer recommended. The primary outcome was the proportion of patients requiring rescue PHB or adjunctive medications for AWS. Secondary outcomes included number of adjunctive agents used, prevalence of severe manifestations of AWS, ICU and hospital lengths of stay, and incidence of potentially significant drug interactions. Results: A total of 172 patients were included (T: n = 81, NT: n = 91). Baseline characteristics were similar between groups, including history of severe AWS and cumulative benzodiazepine dose pre-PHB. There was no difference in the primary outcome between groups (T: 70.4% vs NT: 59.3%, P = 0.152). The median number of adjunctive agents per patient, severe manifestations, and ICU and hospital length of stay did not differ between groups. Twenty-five patients (14.5%) had potentially significant drug interactions. Conclusion and Relevance: The use of a PHB loading dose without a taper may be comparable to a taper strategy on clinical outcomes. Prospective studies are needed to further delineate the optimal dose of PHB for AWS.

ImportanceCerebral small vessel disease (SVD) is associated with various cerebrovascular outcomes, but data on sex differences in SVD are scarce.ObjectiveTo investigate whether the frequency, severity, and distribution of cerebral microbleeds (CMB), other SVD markers on magnetic resonance imaging (MRI), and outcomes differ by sex.Design, Setting, and ParticipantsThis cohort study used pooled individual patient data from the Microbleeds International Collaborative Network, including patients from 38 prospective cohort studies in 18 countries between 2000 and 2018, with clinical follow-up of at least 3 months (up to 5 years). Participants included patients with acute ischemic stroke or transient ischemic attack with available brain MRI. Data were analyzed from April to December 2023.Main Outcomes and MeasuresOutcomes of interest were presence of CMB, lacunes, and severe white matter hyperintensities determined on MRI. Additionally, mortality, recurrent ischemic stroke, and intracranial hemorrhage during follow-up were assessed. Multivariable random-effects logistic regression models, Cox regression, and competing risk regression models were used to investigate sex differences in individual SVD markers, risk of recurrent cerebrovascular events, and death.ResultsA total of 20 314 patients (mean [SD] age, 70.1 [12.7] years; 11 721 [57.7%] male) were included, of whom 5649 (27.8%) had CMB. CMB were more frequent in male patients, and this was consistent throughout different age groups, locations, and in multivariable models (female vs male adjusted odds ratio [aOR], 0.86; 95% CI, 0.80-0.92; P < .001). Female patients had fewer lacunes (aOR, 0.82; 95% CI, 0.74-0.90; P < .001) but a higher prevalence of severe white matter hyperintensities (aOR, 1.10; 95% CI, 1.01-1.20; P = .04) compared with male patients. A total of 2419 patients (11.9%) died during a median (IQR) follow-up of 1.4 (0.7-2.5) years. CMB presence was associated with a higher risk of mortality in female patients (hazard ratio, 1.15; 95% CI, 1.02-1.31), but not male patients (hazard ratio, 0.95; 95% CI, 0.84-1.07) (P for interaction = .01). A total of 1113 patients (5.5%) had recurrent ischemic stroke, and 189 patients (0.9%) had recurrent intracranial hemorrhage, with no sex differences.Conclusions and RelevanceThis cohort study using pooled individual patient data found varying frequencies of individual SVD markers between female and male patients, indicating potential pathophysiological differences in manifestation and severity of SVD. Further research addressing differences in pathomechanisms and outcomes of SVD between female and male patients is required.

OBJECTIVES:To summarize the effectiveness of implementation strategies for ICU execution of recommendations from the 2013 Pain, Agitation/Sedation, Delirium (PAD) or 2018 PAD, Immobility, Sleep Disruption (PADIS) guidelines.DATA SOURCES:PubMed, CINAHL, Scopus, and Web of Science were searched from January 2012 to August 2023. The protocol was registered with PROSPERO (CRD42020175268).STUDY SELECTION:Articles were included if: 1) design was randomized or cohort, 2) adult population evaluated, 3) employed recommendations from greater than or equal to two PAD/PADIS domains, and 4) evaluated greater than or equal to 1 of the following outcome(s): short-term mortality, delirium occurrence, mechanical ventilation (MV) duration, or ICU length of stay (LOS).DATA EXTRACTION:Two authors independently reviewed articles for eligibility, number of PAD/PADIS domains, quality according to National Heart, Lung, and Blood Institute assessment tools, implementation strategy use (including Assess, prevent, and manage pain; Both SAT and SBT; Choice of analgesia and sedation; Delirium: assess, prevent, and manage; Early mobility and exercise; Family engagement and empowerment [ABCDEF] bundle) by Cochrane Effective Practice and Organization of Care (EPOC) category, and clinical outcomes. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation.DATA SYNTHESIS:Among the 25 of 243 (10.3%) full-text articles included (n = 23,215 patients), risk of bias was high in 13 (52%). Most studies were cohort (n = 22, 88%). A median of 5 (interquartile range [IQR] 4-7) EPOC strategies were used to implement recommendations from two (IQR 2-3) PAD/PADIS domains. Cohort and randomized studies were pooled separately. In the cohort studies, use of EPOC strategies was not associated with a change in mortality (risk ratio [RR] 1.01; 95% CI, 0.9-1.12), or delirium (RR 0.92; 95% CI, 0.82-1.03), but was associated with a reduction in MV duration (weighted mean difference [WMD] -0.84 d; 95% CI, -1.25 to -0.43) and ICU LOS (WMD -0.77 d; 95% CI, -1.51 to 0.04). For randomized studies, EPOC strategy use was associated with reduced mortality and MV duration but not delirium or ICU LOS.CONCLUSIONS:Using multiple implementation strategies to adopt PAD/PADIS guideline recommendations may reduce mortality, duration of MV, and ICU LOS. Further prospective, controlled studies are needed to identify the most effective strategies to implement PAD/PADIS recommendations.

OBJECTIVES:Septic shock is a common condition necessitating timely management including hemodynamic support with vasopressors. Despite the high prevalence and mortality, there is limited data characterizing patients who require three or more vasopressors. We sought to define the demographics, outcomes, and prognostic determinants associated with septic shock requiring three or more vasopressors. DESIGN:This is a multicenter retrospective cohort of two ICU databases, Medical Information Mart for Intensive Care IV (MIMIC-IV) and electronic ICU-Clinical Research Database, which include over 400,000 patients admitted to 342 ICUs. PATIENTS:Inclusion criteria entailed patients who were: 1) age 18 years old and older, 2) admitted to any ICU, 3) administered at least three vasopressors for at least 2 hours at any time during their ICU stay, and 4) identified to have sepsis based on the Sepsis-3 criteria. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:A total of 3447 patients met inclusion criteria. The median age was 67 years, 60.5% were male, and 96.6% had full code orders at the time of the third vasopressor initiation. Septic shock requiring three or more vasopressors was associated with 57.6% in-hospital mortality. Code status changes occurred in 23.9% of patients following initiation of a third vasopressor. Elevated lactate upon ICU admission (odds ratio [95% CI], 2.79 [2.73-2.85]), increased duration of time between ICU admission and third vasopressor initiation (1.78 [1.69-1.87]), increased serum creatinine (1.61 [1.59-1.62]), and age above 60 years (1.47 [1.41-1.54]) were independently associated with an increased risk of mortality based on analysis of the MIMIC-IV database. Non-White race and Richmond Agitation-Sedation Scale scores were not associated with mortality. CONCLUSIONS:Septic shock requiring three vasopressors is associated with exceptionally high mortality. Knowledge of patients at highest risk of mortality in this population may inform management and expectations conveyed in shared decision-making.

OBJECTIVES: Clinical decision support systems (CDSSs) are used in various aspects of healthcare to improve clinical decision-making, including in the ICU. However, there is growing evidence that CDSS are not used to their full potential, often resulting in alert fatigue which has been associated with patient harm. Clinicians in the ICU may be more vulnerable to desensitization of alerts than clinicians in less urgent parts of the hospital. We evaluated facilitators and barriers to appropriate CDSS interaction and provide methods to improve currently available CDSS in the ICU. DESIGN: Sequential explanatory mixed-methods study design, using the BEhavior and Acceptance fRamework. SETTING: International survey study. PATIENT/SUBJECTS: Clinicians (pharmacists, physicians) identified via survey, with recent experience with clinical decision support. INTERVENTIONS: An initial survey was developed to evaluate clinician perspectives on their interactions with CDSS. A subsequent in-depth interview was developed to further evaluate clinician (pharmacist, physician) beliefs and behaviors about CDSS. These interviews were then qualitatively analyzed to determine themes of facilitators and barriers with CDSS interactions. MEASUREMENTS AND MAIN RESULTS: A total of 48 respondents completed the initial survey (estimated response rate 15.5%). The majority believed that responding to CDSS alerts was part of their job (75%) but felt they experienced alert fatigue (56.5%). In the qualitative analysis, a total of five facilitators (patient safety, ease of response, specificity, prioritization, and feedback) and four barriers (excess quantity, work environment, difficulty in response, and irrelevance) were identified from the in-depth interviews. CONCLUSIONS: In this mixed-methods survey, we identified areas that institutions should focus on to improve appropriate clinician interactions with CDSS, specific to the ICU. Tailoring of CDSS to the ICU may lead to improvement in CDSS and subsequent improved patient safety outcomes.