Study protocol for ADAPT-TDM: A beta-lactam antibiotic Dose AdaPtation feasibility randomised controlled Trial using Therapeutic Drug Monitoring.

INTRODUCTION: Critically ill patients are at risk of suboptimal beta-lactam antibiotic (beta-lactam) exposure due to the impact of altered physiology on pharmacokinetics. Suboptimal concentrations can lead to treatment failure or toxicity. Therapeutic drug monitoring (TDM) involves adjusting doses based on measured plasma concentrations and individualising dosing to improve the likelihood of improving exposure. Despite its potential benefits, its adoption has been slow, and data on implementation, dose adaptation and safety are sparse. The aim of this trial is to assess the feasibility and fidelity of implementing beta-lactam TDM-guided dosing in the intensive care unit setting. METHODS AND ANALYSIS: A beta-lactam antibiotic Dose AdaPtation feasibility randomised controlled Trial using Therapeutic Drug Monitoring (ADAPT-TDM) is a single-centre, unblinded, feasibility randomised controlled trial aiming to enroll up to 60 critically ill adult participants (≥18 years). TDM and dose adjustment will be performed daily in the intervention group; the standard of care group will undergo plasma sampling, but no dose adjustment. The main outcomes include: (1) feasibility of recruitment, defined as the number of participants who are recruited from a pool of eligible participants, and (2) fidelity of TDM, defined as the degree to which TDM as a test is delivered as intended, from accurate sample collection, sample processing to result availability. Secondary outcomes include target attainment, uptake of TDM-guided dosing and incidence of neurotoxicity, hepatotoxicity and nephrotoxicity. ETHICS AND DISSEMINATION: This study has been approved by the Alfred Hospital human research ethics committee, Office of Ethics and Research Governance (reference: Project No. 565/22; date of approval: 22/11/2022). Prospective consent will be obtained and the study will be conducted in accordance with the Declaration of Helsinki. The finalised manuscript, including aggregate data, will be submitted for publication in a peer reviewed journal. ADAPT-TDM will determine whether beta-lactam TDM-guided dose adaptation is reproducible and feasible and provide important information required to implement this intervention in a phase III trial. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry, ACTRN12623000032651.

Vitamin K: a potential missing link in critical illness-a scoping review.

BACKGROUND: Vitamin K is essential for numerous physiological processes, including coagulation, bone metabolism, tissue calcification, and antioxidant activity. Deficiency, prevalent in critically ill ICU patients, impacts coagulation and increases the risk of bleeding and other complications. This review aims to elucidate the metabolism of vitamin K in the context of critical illness and identify a potential therapeutic approach. METHODS: In December 2023, a scoping review was conducted using the PRISMA Extension for Scoping Reviews. Literature was searched in PubMed, Embase, and Cochrane databases without restrictions. Inclusion criteria were studies on adult ICU patients discussing vitamin K deficiency and/or supplementation. RESULTS: A total of 1712 articles were screened, and 13 met the inclusion criteria. Vitamin K deficiency in ICU patients is linked to malnutrition, impaired absorption, antibiotic use, increased turnover, and genetic factors. Observational studies show higher PIVKA-II levels in ICU patients, indicating reduced vitamin K status. Risk factors include inadequate intake, disrupted absorption, and increased physiological demands. Supplementation studies suggest vitamin K can improve status but not normalize it completely. Vitamin K deficiency may correlate with prolonged ICU stays, mechanical ventilation, and increased mortality. Factors such as genetic polymorphisms and disrupted microbiomes also contribute to deficiency, underscoring the need for individualized nutritional strategies and further research on optimal supplementation dosages and administration routes. CONCLUSIONS: Addressing vitamin K deficiency in ICU patients is crucial for mitigating risks associated with critical illness, yet optimal management strategies require further investigation. IMPACT RESEARCH: To the best of our knowledge, this review is the first to address the prevalence and progression of vitamin K deficiency in critically ill patients. It guides clinicians in diagnosing and managing vitamin K deficiency in intensive care and suggests practical strategies for supplementing vitamin K in critically ill patients. This review provides a comprehensive overview of the existing literature, and serves as a valuable resource for clinicians, researchers, and policymakers in critical care medicine.

Priorities for Clinical Research in Pediatric Extracorporeal Membrane Oxygenation Anticoagulation From the Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

OBJECTIVES: To identify and prioritize research questions for anticoagulation and hemostasis management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus. DATA SOURCES: Systematic review was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial consensus conferences of international, interprofessional experts in the management of ECMO for critically ill neonates and children. STUDY SELECTION: The management of ECMO anticoagulation for critically ill neonates and children. DATA EXTRACTION: Within each of the eight subgroups, two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts. DATA SYNTHESIS: Following the systematic review of MEDLINE, EMBASE, and Cochrane Library databases from January 1988 to May 2021, and the consensus process for clinical recommendations and consensus statements, PEACE panel experts constructed research priorities using the Child Health and Nutrition Research Initiative methodology. Twenty research topics were prioritized, falling within five domains (definitions and outcomes, therapeutics, anticoagulant monitoring, protocolized management, and impact of the ECMO circuit and its components on hemostasis). CONCLUSIONS: We present the research priorities identified by the PEACE expert panel after a systematic review of existing evidence informing clinical care of neonates and children managed with ECMO. More research is required within the five identified domains to ultimately inform and improve the care of this vulnerable population.

Nasogastric tube versus postpyloric tube feeding for critical illness: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Gastric tube feeding and postpyloric tube feeding are two common forms of enteral nutrition in critically ill patients. This study aimed to compare the efficacy and safety of gastric tube feeding with that of postpyloric tube feeding in critically ill patients. METHODS AND STUDY DESIGN: PubMed, Embase, and Cochrane Library were systematically searched for eligible trials from their inception until March 2023. Relative risks (RRs) or weighted mean differences (WMDs) with 95% confidence intervals (CIs) were used to estimate categorical and continuous outcomes using the random-effects model. RESULTS: Sixteen trials involving 1,329 critically ill patients were selected for the final meta-analysis. Overall, we noted that gastric tube feeding showed no significant difference from post-pyloric tube feeding in mortality (p = 0.891), whereas the risk of pneumonia was significantly increased in patients who received gastric tube feeding (RR: 1.45; p = 0.021). Furthermore, we noted that gastric tube feeding was associated with a shorter time required to start feeding (WMD: -11.05; p = 0.007). CONCLUSIONS: This research revealed that initiating feeding through the gastric tube required less time compared to postpyloric tube feeding. However, it was also associated with a heightened risk of pneumonia among critically ill patients.

Executive Summary: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE (PEACE) Consensus Conference.

OBJECTIVES: To present recommendations and consensus statements with supporting literature for the clinical management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus conference. DATA SOURCES: Systematic review was performed using PubMed, Embase, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial meetings of international, interprofessional experts in the management ECMO for critically ill children. STUDY SELECTION: The management of ECMO anticoagulation for critically ill children. DATA EXTRACTION: Within each of eight subgroup, two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts. DATA SYNTHESIS: A systematic review was conducted using MEDLINE, Embase, and Cochrane Library databases, from January 1988 to May 2021. Each panel developed evidence-based and, when evidence was insufficient, expert-based statements for the clinical management of anticoagulation for children supported with ECMO. These statements were reviewed and ratified by 48 PEACE experts. Consensus was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed 23 recommendations, 52 expert consensus statements, and 16 good practice statements covering the management of ECMO anticoagulation in three broad categories: general care and monitoring; perioperative care; and nonprocedural bleeding or thrombosis. Gaps in knowledge and research priorities were identified, along with three research focused good practice statements. CONCLUSIONS: The 91 statements focused on clinical care will form the basis for standardization and future clinical trials.

Core socioDemographic data variables in ICU Trials (CoDe-IT): a protocol for generating core data variables using a Delphi consensus process.

INTRODUCTION: Sociodemographic variables influence health outcomes, either directly (ie, gender identity) or indirectly (eg, structural/systemic racism based on ethnoracial group). Identification of how sociodemographic variables can impact the health of critically ill adults is important to guide care and research design for this population. However, despite the growing recognition of the importance of collecting sociodemographic measures that influence health outcomes, insufficient and inconsistent data collection of sociodemographic variables persists in critical care studies. We aim to develop a set of core data variables (CoDaV) for social determinants of health specific to studies involving critically ill adults. METHODS AND ANALYSIS: We will conduct a scoping review to generate a list of possible sociodemographic measures to be used for round 1 of the modified Delphi processes. We will engage relevant knowledge users (previous intensive care unit patients and family members, critical care researchers, critical care clinicians and research co-ordinators) to participate in the modified Delphi consensus survey to identify the CoDaV. A final consensus meeting will be held with knowledge user representatives to discuss the final CoDaV, how each sociodemographic variable will be collected (eg, level of granularity) and how to disseminate the CoDaV for use in critical care studies. ETHICS AND DISSEMINATION: The University of Calgary conjoint health research ethics board has approved this study protocol (REB22-1648).

Resilience after severe critical illness: a prospective, multicentre, observational study (RESIREA).

BACKGROUND: Critical-illness survivors may experience post-traumatic stress disorder (PTSD) and quality-of-life impairments. Resilience may protect against psychological trauma but has not been adequately studied after critical illness. We assessed resilience and its associations with PTSD and quality of life, and also identified factors associated with greater resilience. METHODS: This prospective, multicentre, study in patients recruited at 41 French ICUs was done in parallel with the NUTRIREA-3 trial in patients given mechanical ventilation and vasoactive amines for shock. Three months to one year after intensive-care-unit admission, survivors completed the Connor-Davidson Resilience Scale (CD-RISC-25), Impact of Event-Revised scale for PTSD symptoms (IES-R), SF-36 quality-of-life scale, Multidimensional Scale of Perceived Social Support (MSPSS), and Brief Illness Perception Questionnaire (B-IPQ). RESULTS: Of the 382 included patients, 203 (53.1%) had normal or high resilience (CD-RISC-25 ≥ 68). Of these resilient patients, 26 (12.8%) had moderate to severe PTSD symptoms (IES-R ≥ 24) vs. 45 (25.4%) patients with low resilience (p = 0.002). Resilient patients had higher SF-36 scores. Factors independently associated with higher CD-RISC-25 scores were higher MSPSS score indicating stronger social support (OR, 1.027; 95%CI 1.008-1.047; p = 0.005) and lower B-IPQ scores indicating a more threatening perception of the illness (OR, 0.973; 95%CI 0.950-0.996; p = 0.02). CONCLUSIONS: Resilient patients had a lower prevalence of PTSD symptoms and higher quality of life scores, compared to patients with low resilience. Higher scores for social support and illness perception were independently associated with greater resilience. Thus, our findings suggest that interventions to strengthen social support and improve illness perception may help to improve resilience. Such interventions should be evaluated in trials with PTSD mitigation and quality-of-life improvement as the target outcomes.

Anabolic Strategies for ICU-Acquired Weakness. What Can We Learn from Bodybuilders?

The study aimed to show the potential clinical application of supplements used among sportsmen for patients suffering from Intensive Care Unit-acquired Weakness (ICUAW) treatment. ICUAW is a common complication affecting approximately 40% of critically ill patients, often leading to long-term functional disability. ICUAW comprises critical illness polyneuropathy, critical illness myopathy, or a combination of both, such as critical illness polyneuromyopathy. Muscle degeneration begins shortly after the initiation of mechanical ventilation and persists post-ICU discharge until proteolysis and autophagy processes normalize. Several factors, including prolonged bedrest and muscle electrical silencing, contribute to muscle weakness, resulting from an imbalance between protein degradation and synthesis. ICUAW is associated with tissue hypoxia, oxidative stress, insulin resistance, reduced glucose uptake, lower adenosine triphosphate (ATP) formation, mitochondrial dysfunction, and increased free-radical production. Several well-studied dietary supplements and pharmaceuticals commonly used by athletes are proven to prevent the aforementioned mechanisms or aid in muscle building, regeneration, and maintenance. While there is no standardized treatment to prevent the occurrence of ICUAW, nutritional interventions have demonstrated the potential for its mitigation. The use of ergogenic substances, popular among muscle-building sociates, may offer potential benefits in preventing muscle loss and aiding recovery based on their work mechanisms.

Fulfilling last wishes: improving the compassionate discharge process.

BACKGROUND: Compassionate discharges (ComD), commonly known as rapid discharges, are urgent one-way discharges for critically ill hospitalised patients with death expected within hours or less than 7 days, to die at their place of choice-usually in their own home. Challenges abound in this time-sensitive setting when multiple parties must work together to prepare medically unstable patients for discharge, yet healthcare staff are largely unaware of the process, resulting in delays. METHODS: Process mapping, an Ishikawa diagram and a Pareto chart were used to identify barriers, which included timely acquisition of home equipment and medication and poor communication among stakeholders. In May 2020, the Quality Improvement (QI) team embarked on a pilot project to reduce family caregiver anxiety and delays in the ComD process while maintaining a success rate above 90% over a 12-month period. INTERVENTIONS: Three Plan-Do-Study-Act (PDSA) cycles were used to refine a ComD resource package that was developed; this consisted of a checklist, a kit and caregiver resources. This was to support nurses, doctors and families during this difficult and emotional transition. Items in the ComD resource package were revised iteratively based on user feedback, with further data collected to measure its usefulness. RESULTS: The 12-month ComD success rate over 3 PDSA cycles were 88.9%, 94.2% and 96.7%, respectively, after each cycle. There was a consistent reduction in the level of family anxiety before and after caregiver training and resources. Reasons for failed ComD included acute clinical deterioration or delays in obtaining home oxygen support. CONCLUSION: The ComD resource package allowed collaborative work across different disciplines, strengthening the safety and utility of ComD and allowing patients to die in their place of choice. These are ubiquitous across settings; this QI problem is thus relevant beyond our local institution.

Observational study of missing SOFA score data frequency in RCTs relative to ICU length of stay.

The Sequential Organ Failure Assessment, also known as SOFA score, was introduced to assess organ dysfunction of critical ill patients. However, understanding the impact of missing SOFA scores in randomized controlled trials and how this affect the validity and applicability of the SOFA score as a surrogate endpoint for predicting mortality has been a matter of interest. To address this, a secondary analysis of a systematic review was conducted to quantify the relationship between SOFA scores and the prediction of mortality in critically ill adults in randomized controlled trials (RCTs). The systematic review being referred to included 87 RCTs with a total of 12,064 critically ill patients. This analysis focused on missing SOFA score data in relation to the length of stay on the intensive care unit (ICU) and the methods used to handle missing data. SOFA score measurements from the included studies were categorized into three time frames: Early (t ≤ 4 days), Intermediate (t = 5-10 days) and Late (t > 10 days) measurement. Only one study reported a complete data set for calculating the SOFA score for an Early measurement. When considering all methods used to address missing data, 32% of studies still had missing data for Early measurements, and this percentage increased to 64% for Late measurements. These findings suggested that, over time, the number of studies with incomplete data sets has been increasing. The longer a patient is treated on the ICU, the higher the number of missing data which can impact the validity of SOFA score analyses. There was no clear trend towards a specific method for compensating missing data. An exemplary calculation demonstrated that ignoring missing data may lead to an underestimated variability of the treatment effect. This, in turn, could bias the interpretation of study results by policy- and clinical decision-makers. Overall, there are several limitations that need to be considered when using SOFA score as a surrogate endpoint for mortality. When employed as an outcome, the SOFA score is frequently missing and most studies do not adequately describe the amount or nature of missing data, or the methods used to handle missing data in the analysis.

Design and construct of an assessment tool for the handover of critical patient the in urgent care and emergency setting.

OBJECTIVES: To design and construct an assessment tool for the handover of critical patients in the urgent care and emergency setting. RESEARCH METHODOLOGY: This metric and descriptive study comprised two phases in accordance with the Clinical practice guidelines for A Reporting Tool for Adapted Guidelines in Health Care: The RIGHT-Ad@pt Checklist. In the first phase, the identification and selection of items related to the handover of critical patients were performed by consensus of a group of experts. The second phase consisted of two stages. In the first stage, the items were selected by applying the e-Delphi technique across two assessment rounds and in the second stage, the items were subjected a pilot test in a real critical patient handover scenario. Professionals from different disciplines and work areas (hospital and prehospital) caring for critically ill patients in the urgency and emergency setting participated in each of the phases. RESULTS: A total of 58 critical patient care, and urgent and emergency care professionals participated in the design and construction of the assessment tool. The initial list consisted of 14 categories and 57 items, which were reduced to 28 items grouped into five categories after the intervention of the participants. The content validity index (CVI) of the instrument was 0.966. CONCLUSIONS: This study describes an assessment tool developed in Spanish-language designed to assess the handover of critical patients in the urgent care and emergency setting. This tool has a high CVI, and is the only currently available tool that consider all of the dimensions and characteristics of the handover process. IMPLICATIONS FOR CLINICAL PRACTICE: The assessment tool developed in this study could enable critical care professionals in their clinical practice to work in a systematic way, universalizing the handover of critically ill patients in the urgent care and emergency setting through scientifically proven guidelines.

Utility and rationale for continuous EEG monitoring: a primer for the general intensivist.

This review offers a comprehensive guide for general intensivists on the utility of continuous EEG (cEEG) monitoring for critically ill patients. Beyond the primary role of EEG in detecting seizures, this review explores its utility in neuroprognostication, monitoring neurological deterioration, assessing treatment responses, and aiding rehabilitation in patients with encephalopathy, coma, or other consciousness disorders. Most seizures and status epilepticus (SE) events in the intensive care unit (ICU) setting are nonconvulsive or subtle, making cEEG essential for identifying these otherwise silent events. Imaging and invasive approaches can add to the diagnosis of seizures for specific populations, given that scalp electrodes may fail to identify seizures that may be detected by depth electrodes or electroradiologic findings. When cEEG identifies SE, the risk of secondary neuronal injury related to the time-intensity "burden" often prompts treatment with anti-seizure medications. Similarly, treatment may be administered for seizure-spectrum activity, such as periodic discharges or lateralized rhythmic delta slowing on the ictal-interictal continuum (IIC), even when frank seizures are not evident on the scalp. In this setting, cEEG is utilized empirically to monitor treatment response. Separately, cEEG has other versatile uses for neurotelemetry, including identifying the level of sedation or consciousness. Specific conditions such as sepsis, traumatic brain injury, subarachnoid hemorrhage, and cardiac arrest may each be associated with a unique application of cEEG; for example, predicting impending events of delayed cerebral ischemia, a feared complication in the first two weeks after subarachnoid hemorrhage. After brief training, non-neurophysiologists can learn to interpret quantitative EEG trends that summarize elements of EEG activity, enhancing clinical responsiveness in collaboration with clinical neurophysiologists. Intensivists and other healthcare professionals also play crucial roles in facilitating timely cEEG setup, preventing electrode-related skin injuries, and maintaining patient mobility during monitoring.

Health care workers' experiences of calling-for-help when taking care of critically ill patients in hospitals in Tanzania and Kenya.

BACKGROUND: When caring for critically ill patients, health workers often need to 'call-for-help' to get assistance from colleagues in the hospital. Systems are required to facilitate calling-for-help and enable the timely provision of care for critically ill patients. Evidence around calling-for-help systems is mostly from high income countries and the state of calling-for-help in hospitals in Tanzania and Kenya has not been formally studied. This study aims to describe health workers' experiences about calling-for-help when taking care of critically ill patients in hospitals in Tanzania and Kenya. METHODS: Ten hospitals across Kenya and Tanzania were visited and in-depth interviews conducted with 30 health workers who had experience of caring for critically ill patients. The interviews were transcribed, translated and the data thematically analyzed. RESULTS: The study identified three thematic areas concerning the systems for calling-for-help when taking care of critically ill patients: 1) Calling-for-help structures: there is lack of functioning structures for calling-for-help; 2) Calling-for-help processes: the calling-for-help processes are innovative and improvised; and 3) Calling-for-help outcomes: the help that is provided is not as requested. CONCLUSION: Calling-for-help when taking care of a critically ill patient is a necessary life-saving part of care, but health workers in Tanzanian and Kenyan hospitals experience a range of significant challenges. Hospitals lack functioning structures, processes for calling-for-help are improvised and help that is provided is not as requested. These challenges likely cause delays and decrease the quality of care, potentially resulting in unnecessary mortality and morbidity.

Use of the DMAIC Lean Six Sigma quality improvement framework to improve beta-lactam antibiotic adequacy in the critically ill.

Beta-lactam antibiotics are widely used in the intensive care unit due to their favorable effectiveness and safety profiles. Beta-lactams given to patients with sepsis must be delivered as soon as possible after infection recognition (early), treat the suspected organism (appropriate), and be administered at a dose that eradicates the infection (adequate). Early and appropriate antibiotic delivery occurs in >90% of patients, but less than half of patients with sepsis achieve adequate antibiotic exposure. This project aimed to address this quality gap and improve beta-lactam adequacy using the Define, Measure, Analyze, Improve, and Control Lean Six Sigma quality improvement framework. A multidisciplinary steering committee was formed, which completed a stakeholder analysis to define the gap in practice. An Ishikawa cause and effect (Fishbone) diagram was used to identify the root causes and an impact/effort grid facilitated prioritization of interventions. An intervention that included bundled education with the use of therapeutic drug monitoring (TDM; i.e. drug-level testing) was projected to have the highest impact relative to the amount of effort and selected to address beta-lactam inadequacy in the critically ill. The education and TDM intervention were deployed through a Plan, Do, Study, Act cycle. In the 3 months after "go-live," 54 episodes of beta-lactam TDM occurred in 41 unique intensive care unit patients. The primary quality metric of beta-lactam adequacy was achieved in 94% of individuals after the intervention. Ninety-four percent of clinicians gauged the education provided as sufficient. The primary counterbalance of antimicrobial days of therapy, a core antimicrobial stewardship metric, was unchanged over time (favorable result; P = .73). Application of the Define, Measure, Analyze, Improve, and Control Lean Six Sigma quality improvement framework effectively improved beta-lactam adequacy in critically ill patients. The approach taken in this quality improvement project is widely generalizable to other drugs, drug classes, or settings to increase the adequacy of drug exposure.

Post-Intensive Care Syndrome - An Opportunity For Collaborative Transition Between the Intensive and Primary Settings.

Critical care advancements have allowed clinicians to discover the many functional disabilities that survivors suffer. Recent research has focused on improving the long-term outcomes of critical illness survivors and optimizing their functional recovery. Post-intensive care syndrome (PICS) describes the disability that remains in those surviving critical illness following discharge from the intensive care unit (ICU). This comprises impairment in cognition, neuropsychiatric health, and physical function of the ICU survivor. Consequent to this, the health of family members of the survivor may also be affected adversely, termed PICS-family. PICS is defined as a new or worsening impairment in physical (ICU-acquired neuromuscular weakness), cognitive (thinking and judgment), or mental health status arising after critical illness and persisting beyond discharge from the acute care setting.

From Traditional Typing to Intelligent Insights: A Narrative Review of Directions Toward Targeted Therapies in Delirium.

Delirium is a heterogeneous syndrome characterized by an acute change in level of consciousness that is associated with inattention and disorganized thinking. Delirium affects most critically ill patients and is associated with poor patient-oriented outcomes such as increased mortality, longer ICU and hospital length of stay, and worse long-term cognitive outcomes. The concept of delirium and its subtypes has existed since nearly the beginning of recorded medical literature, yet robust therapies have yet to be identified. Analogous to other critical illness syndromes, we suspect the lack of identified therapies stems from patient heterogeneity and prior subtyping efforts that do not capture the underlying etiology of delirium. The time has come to leverage machine learning approaches, such as supervised and unsupervised clustering, to identify clinical and pathophysiological distinct clusters of delirium that will likely respond differently to various interventions. We use sedation in the ICU as an example of how precision therapies can be applied to critically ill patients, highlighting the fact that while for some patients a sedative drug may cause delirium, in another cohort sedation is the specific treatment. Finally, we conclude with a proposition to move away from the term delirium, and rather focus on the treatable traits that may allow precision therapies to be tested.