Acute kidney injury in critical care: complications of hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is an immune dysfunction characterized by an exaggerated and pathological inflammatory response, potentially leading to systemic inflammatory reactions and multiple-organ failure, including renal involvement. HLH can be classified as primary or secondary, with primary HLH associated with genetic mutations affecting cell degranulation capacity, and secondary HLH often linked to infections, tumors, and autoimmune diseases. The pathogenesis of HLH is not fully understood, but primary HLH is typically driven by genetic defects, whereas secondary HLH involves the activation of CD8+ T cells and macrophages, leading to the release of inflammatory cytokines and systemic inflammatory response syndrome (SIRS). The clinical presentation of HLH includes non-specific manifestations, making it challenging to differentiate from severe sepsis, particularly secondary HLH due to infections. Shared features include prolonged fever, hepatosplenomegaly, hematopenia, hepatic dysfunction, hypertriglyceridemia, and hypofibrinogenemia, along with histiocytosis and hemophagocytosis. However, distinctive markers like dual hemocytopenia, hypertriglyceridemia, hypofibrinogenemia, and elevated sCD25 levels may aid in differentiating HLH from sepsis. Indeed, no singular biomarker effectively distinguishes between hemophagocytic lymphohistiocytosis and infection. However, research on combined biomarkers provides insights into the differential diagnosis. Renal impairment is frequently encountered in both HLH and sepsis. It can result from a systemic inflammatory response triggered by an influx of inflammatory mediators, from direct damage caused by these factors, or as a consequence of the primary disease process. For instance, macrophage infiltration of the kidney can lead to structural damage affecting various renal components, precipitating disease. Presently, tubular necrosis remains the predominant form of renal involvement in HLH-associated acute kidney injury (HLH-AKI). However, histopathological changes may also encompass interstitial inflammation, glomerular abnormalities, microscopic lesions, and thrombotic microangiopathy. Treatment approaches for HLH and sepsis diverge significantly. HLH is primarily managed with repeated chemotherapy to eliminate immune-activating stimuli and suppress hypercellularity. The treatment approach for sepsis primarily focuses on anti-infective therapy and intensive symptomatic supportive care. Renal function significantly influences clinical decision-making, particularly regarding the selection of chemotherapy and antibiotic dosages, which can profoundly impact patient prognosis. Conversely, renal function recovery is a complex process influenced by factors such as disease severity, timely diagnosis, and the intensity of treatment. A crucial aspect in managing HLH-AKI is the timely diagnosis, which plays a pivotal role in reversing renal impairment and creating a therapeutic window for intervention, may have opportunity to improve patient prognosis. Understanding the clinical characteristics, underlying causes, biomarkers, immunopathogenesis, and treatment options for hemophagocytic lymphohistiocytosis associated with acute kidney injury (HLH-AKI) is crucial for improving patient prognosis.

Antidepressant drug use after intensive care: a nationwide cohort study.

Modern intensive care has improved survival rates, but emerging evidence suggests a high prevalence of post-intensive care unit (ICU) health problems, including post-traumatic stress disorder, depression and anxiety. These symptoms may have a detrimental effect on quality of life and increase mortality. The primary objective of this study is to examine the extent of initiation of antidepressant medication among ICU survivors and identify the factors associated with its usage. The secondary objective is to investigate whether the use of these medications is linked to an increased mortality. The nationwide study cohort included 125,130 ICU survivors admitted between 2010 and 2017. Within the first 3 months after ICU discharge, 7% of patients initiated antidepressant medication, by 1 year 15.5% had started medication. We found no tendency to a decrease during the 2-year follow-up period. Factors associated with antidepressant use included middle age, female sex, psychiatric and somatic comorbid conditions, substance dependence, higher illness severity, and longer ICU stay. Antidepressant users had a higher mortality rate, and deaths due to external causes and suicide were more frequent in this group. This study emphasizes the importance of detecting and addressing depression in ICU survivors to improve their quality of life and reduce mortality rates.

Barriers, Solutions, and Opportunities for Adapting Critical Care Clinical Trials in the COVID-19 Pandemic.

Importance: The COVID-19 pandemic created unprecedented challenges for clinical trials worldwide, threatening premature closure and trial integrity. Every phase of research operations was affected, often requiring modifications to protocol design and implementation. Objectives: To identify the barriers, solutions, and opportunities associated with continuing critical care trials that were interrupted during the pandemic, and to generate suggestions for future trials. Design, Setting, and Participants: This mixed-methods study performed an explanatory sequential analysis involving a self-administered electronic survey and focus groups of principal investigators (PIs) and project coordinators (PCs) conducting adult and pediatric individual-patient randomized trials of the Canadian Critical Care Trials Group during the COVID-19 pandemic. Eligible trials were actively enrolling patients on March 11, 2020. Data were analyzed between September 2023 and January 2024. Main Outcomes and Measures: Importance ratings of barriers to trial conduct and completion, solutions employed, opportunities arising, and suggested strategies for future trials. Quantitative data examining barriers were analyzed using descriptive statistics. Data addressing solutions, opportunities, and suggestions were analyzed by qualitative content analysis. Integration involved triangulation of data sources and perspectives about 13 trials, synthesized by an interprofessional team incorporating reflexivity and member-checking. Results: A total of 13 trials run by 29 PIs and PCs (100% participation rate) were included. The highest-rated barriers (on a 5-point scale) to ongoing conduct during the pandemic were decisions to pause all clinical research (mean [SD] score, 4.7 [0.8]), focus on COVID-19 studies (mean [SD] score, 4.6 [0.8]), and restricted family presence in hospitals (mean [SD] score, 4.1 [0.8]). Suggestions to enable trial progress and completion included providing scientific leadership, implementing technology for communication and data management, facilitating the informed consent process, adapting the protocol as necessary, fostering site engagement, initiating new sites, streamlining ethics and contract review, and designing nested studies. The pandemic necessitated new funding opportunities to sustain trial enrollment. It increased public awareness of critical illness and the importance of randomized trial evidence. Conclusions and Relevance: While underscoring the vital role of research in society and drawing the scientific community together with a common purpose, the pandemic signaled the need for innovation to ensure the rigor and completion of ongoing trials. Lessons learned to optimize research procedures will help to ensure a vibrant clinical trials enterprise in the future.

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).

Human-AI Teaming in Critical Care: A Comparative Analysis of Data Scientists' and Clinicians' Perspectives on AI Augmentation and Automation.

BACKGROUND: Artificial intelligence (AI) holds immense potential for enhancing clinical and administrative health care tasks. However, slow adoption and implementation challenges highlight the need to consider how humans can effectively collaborate with AI within broader socio-technical systems in health care. OBJECTIVE: In the example of intensive care units (ICUs), we compare data scientists' and clinicians' assessments of the optimal utilization of human and AI capabilities by determining suitable levels of human-AI teaming for safely and meaningfully augmenting or automating 6 core tasks. The goal is to provide actionable recommendations for policy makers and health care practitioners regarding AI design and implementation. METHODS: In this multimethod study, we combine a systematic task analysis across 6 ICUs with an international Delphi survey involving 19 health data scientists from the industry and academia and 61 ICU clinicians (25 physicians and 36 nurses) to define and assess optimal levels of human-AI teaming (level 1=no performance benefits; level 2=AI augments human performance; level 3=humans augment AI performance; level 4=AI performs without human input). Stakeholder groups also considered ethical and social implications. RESULTS: Both stakeholder groups chose level 2 and 3 human-AI teaming for 4 out of 6 core tasks in the ICU. For one task (monitoring), level 4 was the preferred design choice. For the task of patient interactions, both data scientists and clinicians agreed that AI should not be used regardless of technological feasibility due to the importance of the physician-patient and nurse-patient relationship and ethical concerns. Human-AI design choices rely on interpretability, predictability, and control over AI systems. If these conditions are not met and AI performs below human-level reliability, a reduction to level 1 or shifting accountability away from human end users is advised. If AI performs at or beyond human-level reliability and these conditions are not met, shifting to level 4 automation should be considered to ensure safe and efficient human-AI teaming. CONCLUSIONS: By considering the sociotechnical system and determining appropriate levels of human-AI teaming, our study showcases the potential for improving the safety and effectiveness of AI usage in ICUs and broader health care settings. Regulatory measures should prioritize interpretability, predictability, and control if clinicians hold full accountability. Ethical and social implications must be carefully evaluated to ensure effective collaboration between humans and AI, particularly considering the most recent advancements in generative AI.

Pediatric Cardiac Critical Care: A Vital Link in the Chain-of-Survival of Children with Congenital Heart Disease.

Despite significant strides made in childhood survival during the last 75 years, India bears the largest burden of congenital heart disease (CHD) in the world. The care of a child with CHD requires multidisciplinary collaboration and development of distinct training opportunities in developing countries to ensure outcomes similar to those achieved in high-income countries. We present a commentary on the current state of pediatric cardiac critical care in India and propose pathways to fulfil the unmet needs of Indian children. The aim is to achieve self-reliance in pediatric cardiac services and to move towards optimal outcome and intact survival of children with CHD.

Incorporating ultrasonography to the nutritional assessment process in intensive care settings to improve the prescription of enteral and parenteral nutrition: Benefits, practicality, and challenges.

The validity of the traditional nutritional assessment tools in intensive care settings might be compromised when the patient has conditions such as oedema and inflammation. Ultrasound (US) is considered a non-invasive, bedside tool that can be utilized to assess changes in muscle mass. Hence, US could guide healthcare practitioners in identifying the varying degrees of malnutrition and adjusting the nutritional prescription accordingly. This review discusses the currently available data regarding the feasibility and practicality of using US measurements in intensive care settings. Overall, the data suggest that using US as part of the standard anthropometric assessment for critically ill patients is a promising tool to track variations in muscle mass. This has the potential to enhance nutritional prescription and tailor the provision of protein and energy to critically ill patients based on their lean body mass measurements. Therefore, it is recommended to train dietitians on utilizing US for body composition measurements.

Use of intensive care, intracranial pressure monitoring, and external ventricular drainage devises in patients with bacterial meningitis, a cohort study.

BACKGROUND: Bacterial meningitis can cause a life-threatening increase in intracranial pressure (ICP). ICP-targeted treatment including an ICP monitoring device and external ventricular drainage (EVD) may improve outcomes but is also associated with the risk of complications. The frequency of use and complications related to ICP monitoring devices and EVDs among patients with bacterial meningitis remain unknown. We aimed to investigate the use of ICP monitoring devices and EVDs in patients with bacterial meningitis including frequency of increased ICP, drainage of cerebrospinal fluid (CSF), and complications associated with the insertion of ICP monitoring and external ventricular drain (EVD) in patients with bacterial meningitis. METHOD: In a single-center prospective cohort study (2017-2021), we examined the frequency of use and complications of ICP-monitoring devices and EVDs in adult patients with bacterial meningitis. RESULTS: We identified 108 patients with bacterial meningitis admitted during the study period. Of these, 60 were admitted to the intensive care unit (ICU), and 47 received an intracranial device (only ICP monitoring device N = 16; EVD N = 31). An ICP > 20 mmHg was observed in 8 patients at insertion, and in 21 patients (44%) at any time in the ICU. Cerebrospinal fluid (CSF) was drained in 24 cases (51%). Severe complications (intracranial hemorrhage) related to the device occurred in two patients, but one had a relative contraindication to receiving a device. CONCLUSIONS: Approximately half of the patients with bacterial meningitis needed intensive care and 47 had an intracranial device inserted. While some had conservatively correctable ICP, the majority needed CSF drainage. However, two patients experienced serious adverse events related to the device, potentially contributing to death. Our study highlights that the incremental value of ICP measurement and EVD in managing of bacterial meningitis requires further research.

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.

Embedding the Use of Patient Multimedia Educational Resources Into Cardiac Acute Care: Prospective Observational Study.

BACKGROUND: Multimedia interventions may play an important role in improving patient care and reducing the time constraints of patient-clinician encounters. The "MyStay Cardiac" multimedia resource is an innovative program designed to be accessed by adult patients undergoing cardiac surgery. OBJECTIVE: The purpose of this study was to evaluate the uptake of the MyStay Cardiac both during and following the COVID-19 pandemic. METHODS: A prospective observational study design was used that involved the evaluation of program usage data available from the digital interface of the multimedia program. Data on usage patterns were analyzed for a 30-month period between August 2020 and January 2023. Usage patterns were compared during and following the lifting of COVID-19 pandemic restrictions. Uptake of the MyStay Cardiac was measured via the type and extent of user activity data captured by the web-based information system. RESULTS: Intensive care unit recovery information was the most accessed information, being viewed in approximately 7 of 10 usage sessions. Ward recovery (n=124/343, 36.2%), goal (n=114/343, 33.2%), and exercise (n=102/343, 29.7%) information were routinely accessed. Most sessions involved users exclusively viewing text-based information (n=210/343, 61.2%). However, in over one-third of sessions (n=132/342, 38.5%), users accessed video information. Most usage sessions occurred during the COVID-19 restriction phase of the study (August 2020-December 2021). Sessions in which video (P=.02, phi=0.124) and audio (P=.006, phi=0.161) media were accessed were significantly more likely to occur in the restriction phase compared to the postrestriction phase. CONCLUSIONS: This study found that the use of digital multimedia resources to support patient education was well received and integrated into their practice by cardiac nurses working in acute care during the COVID-19 pandemic. There was a pattern for greater usage of the MyStay Cardiac during the COVID-19 pandemic when access to the health service for nonfrontline, essential workers was limited.

Potentially inappropriate medication as a predictor of poor prognosis of COVID-19 in older adults: a South Korean nationwide cohort study.

OBJECTIVES: To investigate the association between exposure to potentially inappropriate medication (PIM) and poor prognosis of COVID-19 in older adults, controlling for comorbidity and sociodemographic factors. DESIGN AND SETTING: Nationwide retrospective cohort study based on the national registry of COVID-19 patients, established through the linkage of South Korea's national insurance claims database with the Korea Disease Control and Prevention Agency registry of patients with COVID-19, up to 31 July 2020. PARTICIPANTS: A total of 2217 COVID-19 patients over 60 years of age who tested positive between 20 January 2022 and 4 June 2020. Exposure to PIM was defined based on any prescription record of PIM during the 30 days prior to the date of testing positive for COVID-19. PRIMARY OUTCOME MEASURES: Mortality and utilisation of critical care from the date of testing positive until the end of isolation. RESULTS: Among the 2217 COVID-19 patients over 60 years of age, 604 were exposed to PIM prior to infection. In the matched cohort of 583 pairs, PIM-exposed individuals exhibited higher rates of mortality (19.7% vs 9.8%, p<0.0001) and critical care utilisation (13.4% vs 8.9%, p=0.0156) compared with non-exposed individuals. The temporal association of PIM exposure with mortality was significant across all age groups (RR=1.68, 95% CI: 1.23~2.24), and a similar trend was observed for critical care utilisation (RR: 1.75, 95% CI: 1.26~2.39). The risk of mortality and critical care utilisation increased with exposure to a higher number of PIMs in terms of active pharmaceutical ingredients and drug categories. CONCLUSION: Exposure to PIM exacerbates the poor outcomes of older patients with COVID-19 who are already at high risk. Effective interventions are urgently needed to address PIM exposure and improve health outcomes in this vulnerable population.

Role of the Critical Care Resuscitation Unit in a Comprehensive Stroke Center: Operations for Mechanical Thrombectomy During the Pandemic.

Introduction: Standard of care for patients with acute ischemic stroke from large vessel occlusion (AIS-LVO) includes prompt evaluation for urgent mechanical thrombectomy (MT) at a comprehensive stroke center (CSC). During the start of the coronavirus 2019 pandemic (COVID-19), there were reports about disruption to emergency department (ED) operations and delays in management of patients with AIS-LVO. In this study we investigate the outcome and operations for patients who were transferred from different EDs to an academic CSC's critical care resuscitation unit (CCRU), which specializes in expeditious transfer of time-sensitive disease. Methods: This was a pre-post retrospective study using prospectively collected clinical data from our CSC's stroke registry. Adult patients who were transferred from any ED to the CCRU and underwent MT were eligible. We compared time intervals in the pre-pandemic (PP) period between January 2018- February 2020, such as ED in-out and CCRU arrival-angiography, to those during the pandemic (DP) between March 2020-May 31, 2021. We used classification and regression tree (CART) analysis to identify which time intervals, besides clinical factors, were associated with good neurological outcome (90-day modified Rankin scale 0-2). Results: We analyzed 203 patients: 135 (66.5%) in the PP group and 68 (33.5%) in the DP group. Time from ED triage to computed tomography (difference 7 minutes, 95% confidence interval [CI] -12 to -1, P < 0.01) for the DP group was statistically longer, but ED in-out was similar for both groups. Time from CCRU arrival to angiography (difference 9 minutes, 95% CI 4-13, P < 0.01) for the DP group was shorter. Forty-nine percent of the DP group achieved mRS ≤ 2 vs 32% for the PP group (difference -17%, 95% CI -0.32 to -0.03, P < 0.01). The CART identified initial National Institutes of Health Stroke Scale, age, ED in-and-out time, and CCRU arrival-to-angiography time as important predictors of good outcome. Conclusion: Overall, the care process in EDs and at this single CSC for patients requiring MT were not heavily affected by the pandemic, as certain time metrics during the pandemic were statistically shorter than pre-pandemic intervals. Time intervals such as ED in-and-out and CCRU arrival-to-angiography were important factors in achieving good neurologic outcomes. Further study is necessary to confirm our observation and improve operational efficiency in the future.