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Item Acute Kidney Injury Interacts With Coma, Acidosis, and Impaired Perfusion to Significantly Increase Risk of Death in Children With Severe Malaria(Oxford University Press, 2022) Namazzi, Ruth; Opoka, Robert; Datta, Dibyadyuti; Bangirana, Paul; Batte, Anthony; Berrens, Zachary; Goings, Michael J.; Schwaderer, Andrew L.; Conroy, Andrea L.; John, Chandy C.; Pediatrics, School of MedicineBackground: Mortality in severe malaria remains high in children treated with intravenous artesunate. Acute kidney injury (AKI) is a common complication of severe malaria, but the interactions between AKI and other complications on the risk of mortality in severe malaria are not well characterized. Methods: Between 2014 and 2017, 600 children aged 6-48 months to 4 years hospitalized with severe malaria were enrolled in a prospective clinical cohort study evaluating clinical predictors of mortality in children with severe malaria. Results: The mean age of children in this cohort was 2.1 years (standard deviation, 0.9 years) and 338 children (56.3%) were male. Mortality was 7.3%, and 52.3% of deaths occurred within 12 hours of admission. Coma, acidosis, impaired perfusion, AKI, elevated blood urea nitrogen (BUN), and hyperkalemia were associated with increased mortality (all P < .001). AKI interacted with each risk factor to increase mortality (P < .001 for interaction). Children with clinical indications for dialysis (14.4% of all children) had an increased risk of death compared with those with no indications for dialysis (odds ratio, 6.56; 95% confidence interval, 3.41-12.59). Conclusions: AKI interacts with coma, acidosis, or impaired perfusion to significantly increase the risk of death in severe malaria. Among children with AKI, those who have hyperkalemia or elevated BUN have a higher risk of death. A better understanding of the causes of these complications of severe malaria, and development and implementation of measures to prevent and treat them, such as dialysis, are needed to reduce mortality in severe malaria.Item Biomarkers of Delirium Duration and Delirium Severity in the ICU(Wolters Kluwer, 2020-03) Khan, Babar A.; Perkins, Anthony J.; Prasad, Nagendra K.; Shekhar, Anantha; Campbell, Noll L.; Gao, Sujuan; Wang, Sophia; Khan, Sikandar H.; Marcantonio, Edward R.; Twigg, Homer L., III.; Boustani, Malaz A.; Medicine, School of MedicineObjectives: Both delirium duration and delirium severity are associated with adverse patient outcomes. Serum biomarkers associated with delirium duration and delirium severity in ICU patients have not been reliably identified. We conducted our study to identify peripheral biomarkers representing systemic inflammation, impaired neuroprotection, and astrocyte activation associated with delirium duration, delirium severity, and in-hospital mortality. Design: Observational study. Setting: Three Indianapolis hospitals. Patients: Three-hundred twenty-one critically ill delirious patients. Interventions: None. Measurements and main results: We analyzed the associations between biomarkers collected at delirium onset and delirium-/coma-free days assessed through Richmond Agitation-Sedation Scale/Confusion Assessment Method for the ICU, delirium severity assessed through Confusion Assessment Method for the ICU-7, and in-hospital mortality. After adjusting for age, gender, Acute Physiology and Chronic Health Evaluation II score, Charlson comorbidity score, sepsis diagnosis and study intervention group, interleukin-6, -8, and -10, tumor necrosis factor-α, C-reactive protein, and S-100β levels in quartile 4 were negatively associated with delirium-/coma-free days by 1 week and 30 days post enrollment. Insulin-like growth factor-1 levels in quartile 4 were not associated with delirium-/coma-free days at both time points. Interleukin-6, -8, and -10, tumor necrosis factor-α, C-reactive protein, and S-100β levels in quartile 4 were also associated with delirium severity by 1 week. At hospital discharge, interleukin-6, -8, and -10 retained the association but tumor necrosis factor-α, C-reactive protein, and S-100β lost their associations with delirium severity. Insulin-like growth factor-1 levels in quartile 4 were not associated with delirium severity at both time points. Interleukin-8 and S-100β levels in quartile 4 were also associated with higher in-hospital mortality. Interleukin-6 and -10, tumor necrosis factor-α, and insulin-like growth factor-1 were not found to be associated with in-hospital mortality. Conclusions: Biomarkers of systemic inflammation and those for astrocyte and glial activation were associated with longer delirium duration, higher delirium severity, and in-hospital mortality. Utility of these biomarkers early in delirium onset to identify patients at a higher risk of severe and prolonged delirium, and delirium related complications during hospitalization needs to be explored in future studies.Item Delirium management in critically ill patients(2013) Calvo-Ayala, Enrique; Khan, Babar; Medicine, School of MedicineDelirium among critically ill patients is common. Presence of delirium imparts a poorer prognosis to patients, including longer ICU and hospital length of stay, increased risk of institutionalization, higher health related costs, and elevated mortality. Even with such grave consequences, the rates of delirium diagnosis are dire. The importance of early recognition through validated tools and appropriate management of this life-threatening condition cannot be over emphasized. This article provides an overview of delirium pathophysiology, diagnosis, and management with a focus on critically ill patients.Item Proceedings of the Second Curing Coma Campaign NIH Symposium: Challenging the Future of Research for Coma and Disorders of Consciousness(Springer, 2022) Mainali, Shraddha; Aiyagari, Venkatesh; Alexander, Sheila; Bodien, Yelena; Boerwinkle, Varina; Boly, Melanie; Brown, Emery; Brown, Jeremy; Claassen, Jan; Edlow, Brian L.; Fink, Ericka L.; Fins, Joseph J.; Foreman, Brandon; Frontera, Jennifer; Geocadin, Romergryko G.; Giacino, Joseph; Gilmore, Emily J.; Gosseries, Olivia; Hammond, Flora; Helbok, Raimund; Hemphill, J. Claude; Hirsch, Karen; Kim, Keri; Laureys, Steven; Lewis, Ariane; Ling, Geoffrey; Livesay, Sarah L.; McCredie, Victoria; McNett, Molly; Menon, David; Molteni, Erika; Olson, DaiWai; O’Phelan, Kristine; Park, Soojin; Polizzotto, Len; Provencio, Jose Javier; Puybasset, Louis; Venkatasubba Rao, Chethan P.; Robertson, Courtney; Rohaut, Benjamin; Rubin, Michael; Sharshar, Tarek; Shutter, Lori; Silva, Gisele Sampaio; Smith, Wade; Steven, Robert D.; Thibaut, Aurore; Vespa, Paul; Wagner, Amy K.; Ziai, Wendy C.; Zink, Elizabeth; Suarez, Jose I.; Physical Medicine and Rehabilitation, School of MedicineThis proceedings article presents actionable research targets on the basis of the presentations and discussions at the 2nd Curing Coma National Institutes of Health (NIH) symposium held from May 3 to May 5, 2021. Here, we summarize the background, research priorities, panel discussions, and deliverables discussed during the symposium across six major domains related to disorders of consciousness. The six domains include (1) Biology of Coma, (2) Coma Database, (3) Neuroprognostication, (4) Care of Comatose Patients, (5) Early Clinical Trials, and (6) Long-term Recovery. Following the 1st Curing Coma NIH virtual symposium held on September 9 to September 10, 2020, six workgroups, each consisting of field experts in respective domains, were formed and tasked with identifying gaps and developing key priorities and deliverables to advance the mission of the Curing Coma Campaign. The highly interactive and inspiring presentations and panel discussions during the 3-day virtual NIH symposium identified several action items for the Curing Coma Campaign mission, which we summarize in this article.Item Relationship Among Clinically Obtained Biomarkers of Inflammation, Hypercoagulability, and Macrophage Activation, and Delirium in Critically Ill Patients With COVID-19(Wolters Kluwer, 2023-01-18) Khan, Sikandar H.; Perkins, Anthony J.; Chi, Rosalyn; Seyffert, Sarah; Conrad, Peter; Lindroth, Heidi; Wang, Sophia; Mulkey, Malissa; Gao, Sujuan; Khan, Babar; Medicine, School of MedicineCritically ill patients with COVID-19 experience high rates of delirium and coma. Whether delirium occurs through novel mechanisms in COVID-19 is not known. We analyzed the relationship among biomarkers of inflammation (C-reactive protein [CRP]), hypercoagulability (d-dimer), and lung macrophage activation (ferritin), and the primary composite outcome of delirium/coma next day. We also measured associations between biomarkers and next day delirium and coma independently, and delirium severity. Design: Retrospective, observational cohort study. Setting: ICUs at two large, urban, academic referral hospitals. Patients: All consecutive adult patients admitted to the ICU from March 1, 2020, to June 7, 2020, with COVID-19 with clinical biomarkers and delirium assessments performed. Interventions: None. Measurements and main results: Daily concentrations of CRP, d-dimer, and ferritin were obtained. Coma (assessed by Richmond Agitation-Sedation Scale) and delirium (assessed by Confusion Assessment Method for the ICU/Confusion Assessment Method for the ICU-7) were measured bid. A cohort of 197 ICU patients with COVID-19 were included. Higher d-dimer (odds ratio [OR], 1.57; 95% CI, 1.17-2.12; p < 0.01) and ferritin quartiles (OR, 1.36; 95% CI, 1.02-1.81; p < 0.01) were associated with greater odds of the composite outcome of delirium/coma next day. d-dimer was associated with greater odds of next day delirium (OR, 1.49; 95% CI, 1.14-1.94; p < 0.01) and coma independently (OR, 1.52; 95% CI, 1.08-2.14; p = 0.017). Higher ferritin quartiles were associated with greater odds of next day delirium (OR, 1.33; 95% CI, 1.04-1.70; p = 0.026) and coma independently (OR, 1.59; 95% CI, 1.14-2.23; p < 0.01). Higher CRP quartiles were associated with coma (OR, 1.36; 95% CI, 1.03-1.79; p = 0.030) and delirium severity the next day (β = 0.30; se, 0.07; p ≤ 0.01). Conclusions: Our hypothesis-generating study found d-dimer and ferritin were associated with delirium/coma the following day, as well as delirium and coma independently. CRP was associated with next day coma and delirium severity. Larger studies to validate these results are needed.Item Research Needs for Prognostic Modeling and Trajectory Analysis in Patients with Disorders of Consciousness(Springer, 2021) Hammond, Flora M.; Katta-Charles, Sheryl; Russell, Mary Beth; Zafonte, Ross D.; Claassen, Jan; Wagner, Amy K.; Puybasset, Louis; Egawa, Satoshi; Laureys, Steven; Diringer, Michael; Stevens, Robert D.; Curing Coma Campaign and its Contributing Members; Physical Medicine and Rehabilitation, School of MedicineBackground: The current state of the science regarding the care and prognosis of patients with disorders of consciousness is limited. Scientific advances are needed to improve the accuracy, relevance, and approach to prognostication, thereby providing the foundation to develop meaningful and effective interventions. Methods: To address this need, an interdisciplinary expert panel was created as part of the Coma Science Working Group of the Neurocritical Care Society Curing Coma Campaign. Results: The panel performed a gap analysis which identified seven research needs for prognostic modeling and trajectory analysis ("recovery science") in patients with disorders of consciousness: (1) to define the variables that predict outcomes; (2) to define meaningful intermediate outcomes at specific time points for different endotypes; (3) to describe recovery trajectories in the absence of limitations to care; (4) to harness big data and develop analytic methods to prognosticate more accurately; (5) to identify key elements and processes for communicating prognostic uncertainty over time; (6) to identify health care delivery models that facilitate recovery and recovery science; and (7) to advocate for changes in the health care delivery system needed to advance recovery science and implement already-known best practices. Conclusion: This report summarizes the current research available to inform the proposed research needs, articulates key elements within each area, and discusses the goals and advances in recovery science and care anticipated by successfully addressing these needs.Item Understanding Disorders of Consciousness: Opportunities for Critical Care Nurses(American Association of Critical Care Nurses, 2021) Mulkey, Malissa A.; School of NursingBackground: Disorders of consciousness are powerful predictors of outcomes including mortality among critically ill patients. Encephalopathy, delirium, and coma are disorders of consciousness frequently encountered by critical care nurses but often classified incorrectly. Objective: To provide a greater understanding of disorders of consciousness and to provide standardized assessments and nursing interventions for these disorders. Methods: A literature search was conducted by using the terms consciousness, mental status, awareness, arousal, wakefulness, assessment, disorders of consciousness, delirium, encephalopathy, coma, vegetative state, and minimal consciousness. Articles were published in the past 10 years in CINAHL and PubMed. Articles were excluded if they were not in English or directly related to caring for patients with a disorder of consciousness. The remaining 142 articles were evaluated for inclusion; 81 articles received full review. Results: A disorder of consciousness signifies that the threshold for compensation has been surpassed with potentially irreversible damage. Altered thalamocortical interactions and reduced cortical activity impair communication networks across the various parts of the brain, causing a disturbance in consciousness. Discussion: The cue-response theory is a model that describes the process and impact of nursing care on recovery from acute brain injury. Appropriate standardized assessments and interventions must be used to manage altered levels of consciousness in critically ill patients. Conclusions: Paying close attention to neurological changes and monitoring them with standardized assessments are critical to implementing early measures to prevent complications.