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Article ; Online: Melatonin, Ramelteon, Suvorexant, and Dexmedetomidine to Promote Sleep and Prevent Delirium in Critically Ill Patients: A Narrative Review With Practical Applications.

Fontaine, Gabriel V / Der Nigoghossian, Caroline / Hamilton, Leslie A

2020 Volume 43, Issue 2, Page(s) 232–250

Abstract: Sleep plays an important role in the recovery of critically ill patients. However, patients in the intensive care unit (ICU) often suffer sleep disturbances and abnormal circadian rhythms, which may increase delirium and lengthen ICU stay. ... ...

Abstract	Sleep plays an important role in the recovery of critically ill patients. However, patients in the intensive care unit (ICU) often suffer sleep disturbances and abnormal circadian rhythms, which may increase delirium and lengthen ICU stay. Nonpharmacologic strategies for preventing and treating sleep disturbances and delirium, such as overnight eye masks and ear plugs, are usually employed first, given the lack of adverse effects. However, a multimodal approach to care including pharmacotherapy may be necessary. Despite the limited available data supporting their use, medications such as melatonin, ramelteon, suvorexant, and dexmedetomidine may promote sleep and improve a variety of patient-centric outcomes such as delirium. This narrative review focuses on these nonbenzodiazepine agents used for sleep in the ICU. Practical application of each of these agents is described for when providers choose to utilize one of these pharmacotherapies to promote sleep or prevent delirium.
MeSH term(s)	Analgesics, Non-Narcotic/therapeutic use ; Azepines/therapeutic use ; Central Nervous System Depressants/therapeutic use ; Critical Care Nursing ; Critical Illness ; Delirium/prevention & control ; Dexmedetomidine/therapeutic use ; Humans ; Indenes/therapeutic use ; Intensive Care Units ; Melatonin/therapeutic use ; Sleep Aids, Pharmaceutical/therapeutic use ; Sleep Wake Disorders/drug therapy ; Triazoles/therapeutic use
Chemical Substances	Analgesics, Non-Narcotic ; Azepines ; Central Nervous System Depressants ; Indenes ; Sleep Aids, Pharmaceutical ; Triazoles ; suvorexant (081L192FO9) ; Dexmedetomidine (67VB76HONO) ; ramelteon (901AS54I69) ; Melatonin (JL5DK93RCL)
Language	English
Publishing date	2020-02-21
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	639095-x
ISSN	1550-5111 ; 0887-9303
ISSN (online)	1550-5111
ISSN	0887-9303
DOI	10.1097/CNQ.0000000000000304
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Article ; Online: Narrative Review of Controversies Involving Vasopressin Use in Septic Shock and Practical Considerations.

Der-Nigoghossian, Caroline / Hammond, Drayton A / Ammar, Mahmoud A

The Annals of pharmacotherapy

2020 Volume 54, Issue 7, Page(s) 706–714

Abstract: Objective: ...

Abstract	Objective:
MeSH term(s)	Arginine Vasopressin/administration & dosage ; Arginine Vasopressin/adverse effects ; Arginine Vasopressin/therapeutic use ; Arterial Pressure/drug effects ; Body Weight ; Humans ; Hypotension/drug therapy ; Norepinephrine/administration & dosage ; Norepinephrine/adverse effects ; Norepinephrine/therapeutic use ; Practice Guidelines as Topic ; Shock, Septic/drug therapy ; Vasoconstrictor Agents/administration & dosage ; Vasoconstrictor Agents/adverse effects ; Vasoconstrictor Agents/therapeutic use
Chemical Substances	Vasoconstrictor Agents ; Arginine Vasopressin (113-79-1) ; Norepinephrine (X4W3ENH1CV)
Language	English
Publishing date	2020-01-20
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1101370-9
ISSN	1542-6270 ; 1060-0280
ISSN (online)	1542-6270
ISSN	1060-0280
DOI	10.1177/1060028020901521
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Article ; Online: Acute Blood Pressure Management in Neurocritically Ill Patients.

Der-Nigoghossian, Caroline / Levasseur-Franklin, Kimberly / Makii, Jason

Pharmacotherapy

2019 Volume 39, Issue 3, Page(s) 335–345

Abstract: Optimal blood pressure (BP) management is controversial in neurocritically ill patients due to conflicting concerns of worsening ischemia with decreased BP versus cerebral edema and increased intracranial pressure with elevated BP. In addition, high- ... ...

Abstract	Optimal blood pressure (BP) management is controversial in neurocritically ill patients due to conflicting concerns of worsening ischemia with decreased BP versus cerebral edema and increased intracranial pressure with elevated BP. In addition, high-quality evidence is lacking regarding optimal BP goals in patients with most of these conditions. This review summarizes guideline recommendations and examines the literature for BP management in patients with ischemic stroke, intracerebral hemorrhage, aneurysmal subarachnoid hemorrhage, traumatic brain injury, and spinal cord injury.
MeSH term(s)	Blood Pressure/physiology ; Brain Edema/therapy ; Brain Ischemia/therapy ; Critical Illness ; Humans ; Hypertension/complications ; Hypertension/therapy ; Hypotension/complications ; Hypotension/therapy ; Intracranial Hypertension/therapy ; Nervous System Diseases/physiopathology ; Nervous System Diseases/therapy
Language	English
Publishing date	2019-03-11
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	603158-4
ISSN	1875-9114 ; 0277-0008
ISSN (online)	1875-9114
ISSN	0277-0008
DOI	10.1002/phar.2233
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Book ; Online: Interpretable Forecasting of Physiology in the ICU Using Constrained Data Assimilation and Electronic Health Record Data

Albers, David / Sirlanci, Melike / Levine, Matthew / Claassen, Jan / Der Nigoghossian, Caroline / Hripcsak, George

2023

Abstract: Prediction of physiologic states are important in medical practice because interventions are guided by predicted impacts of interventions. But prediction is difficult in medicine because the generating system is complex and difficult to understand from ... ...

Abstract	Prediction of physiologic states are important in medical practice because interventions are guided by predicted impacts of interventions. But prediction is difficult in medicine because the generating system is complex and difficult to understand from data alone, and the data are sparse relative to the complexity of the generating processes due to human costs of data collection. Computational machinery can potentially make prediction more accurate, but, working within the constraints of realistic clinical data makes robust inference difficult because the data are sparse, noisy and nonstationary. This paper focuses on prediction given sparse, non-stationary, electronic health record data in the intensive care unit (ICU) using data assimilation, a broad collection of methods that pairs mechanistic models with inference machinery such as the Kalman filter. We find that to make inference with sparse clinical data accurate and robust requires advancements beyond standard DA methods combined with additional machine learning methods. Specifically, we show that combining the newly developed constrained ensemble Kalman filter with machine learning methods can produce substantial gains in robustness and accuracy while minimizing the data requirements. We also identify limitations of Kalman filtering methods that lead to new problems to be overcome to make inference feasible in clinical settings using realistic clinical data.
Keywords	Statistics - Applications ; Quantitative Biology - Quantitative Methods
Subject code	310
Publishing date	2023-05-10
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Principles of Pharmacotherapy of Seizures and Status Epilepticus.

Der-Nigoghossian, Caroline / Tesoro, Eljim P / Strein, Micheal / Brophy, Gretchen M

Seminars in neurology

2020 Volume 40, Issue 6, Page(s) 681–695

Abstract: Status epilepticus is a neurological emergency with an outcome that is highly associated with the initial pharmacotherapy management that must be administered in a timely fashion. Beyond first-line therapy of status epilepticus, treatment is not guided ... ...

Abstract	Status epilepticus is a neurological emergency with an outcome that is highly associated with the initial pharmacotherapy management that must be administered in a timely fashion. Beyond first-line therapy of status epilepticus, treatment is not guided by robust evidence. Optimal pharmacotherapy selection for individual patients is essential in the management of seizures and status epilepticus with careful evaluation of pharmacokinetic and pharmacodynamic factors. With the addition of newer antiseizure agents to the market, understanding their role in the management of status epilepticus is critical. Etiology-guided therapy should be considered in certain patients with drug-induced seizures, alcohol withdrawal, or autoimmune encephalitis. Some patient populations warrant special consideration, such as pediatric, pregnant, elderly, and the critically ill. Seizure prophylaxis is indicated in select patients with acute neurological injury and should be limited to the acute postinjury period.
MeSH term(s)	Anticonvulsants/therapeutic use ; Benzodiazepines/therapeutic use ; Humans ; Seizures/drug therapy ; Status Epilepticus/drug therapy ; Status Epilepticus/etiology
Chemical Substances	Anticonvulsants ; Benzodiazepines (12794-10-4)
Language	English
Publishing date	2020-11-11
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	603165-1
ISSN	1098-9021 ; 0271-8235
ISSN (online)	1098-9021
ISSN	0271-8235
DOI	10.1055/s-0040-1718721
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Article ; Online: Electroencephalogram Monitoring in Critical Care.

Rubinos, Clio / Alkhachroum, Ayham / Der-Nigoghossian, Caroline / Claassen, Jan

Seminars in neurology

2020 Volume 40, Issue 6, Page(s) 675–680

Abstract: Seizures are common in critically ill patients. Electroencephalogram (EEG) is a tool that enables clinicians to provide continuous brain monitoring and to guide treatment decisions-brain telemetry. EEG monitoring has particular utility in the intensive ... ...

Abstract	Seizures are common in critically ill patients. Electroencephalogram (EEG) is a tool that enables clinicians to provide continuous brain monitoring and to guide treatment decisions-brain telemetry. EEG monitoring has particular utility in the intensive care unit as most seizures in this setting are nonconvulsive. Despite the increased use of EEG monitoring in the critical care unit, it remains underutilized. In this review, we summarize the utility of EEG and different EEG modalities to monitor patients in the critical care setting.
MeSH term(s)	Critical Care/methods ; Critical Care/standards ; Electroencephalography/methods ; Electroencephalography/standards ; Humans ; Intensive Care Units/standards ; Neurophysiological Monitoring/methods ; Neurophysiological Monitoring/standards ; Seizures/diagnosis
Language	English
Publishing date	2020-11-11
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	603165-1
ISSN	1098-9021 ; 0271-8235
ISSN (online)	1098-9021
ISSN	0271-8235
DOI	10.1055/s-0040-1719073
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Article ; Online: Markers in Status Epilepticus Prognosis.

Alkhachroum, Ayham / Der-Nigoghossian, Caroline A / Rubinos, Clio / Claassen, Jan

Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society

2020 Volume 37, Issue 5, Page(s) 422–428

Abstract: Status epilepticus (SE) is a neurologic emergency with high morbidity and mortality. The assessment of a patient's prognosis is crucial in making treatment decisions. In this review, we discuss various markers that have been used to prognosticate SE in ... ...

Abstract	Status epilepticus (SE) is a neurologic emergency with high morbidity and mortality. The assessment of a patient's prognosis is crucial in making treatment decisions. In this review, we discuss various markers that have been used to prognosticate SE in terms of recurrence, mortality, and functional outcome. These markers include demographic, clinical, electrophysiological, biochemical, and structural data. The heterogeneity of SE etiology and semiology renders development of prognostic markers challenging. Currently, prognostication in SE is limited to a few clinical scores. Future research should integrate clinical, genetic and epigenetic, metabolic, inflammatory, and structural biomarkers into prognostication models to approach "personalized medicine" in prognostication of outcomes after SE.
MeSH term(s)	Biomarkers/metabolism ; Clinical Decision-Making/methods ; Electroencephalography/methods ; Forecasting ; Humans ; Inflammation Mediators/metabolism ; Precision Medicine/methods ; Prognosis ; Recurrence ; Status Epilepticus/diagnosis ; Status Epilepticus/metabolism ; Status Epilepticus/physiopathology
Chemical Substances	Biomarkers ; Inflammation Mediators
Language	English
Publishing date	2020-09-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	605640-4
ISSN	1537-1603 ; 0736-0258
ISSN (online)	1537-1603
ISSN	0736-0258
DOI	10.1097/WNP.0000000000000761
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Article ; Online: Status epilepticus - time is brain and treatment considerations.

Der-Nigoghossian, Caroline / Rubinos, Clio / Alkhachroum, Ayham / Claassen, Jan

Current opinion in critical care

2019 Volume 25, Issue 6, Page(s) 638–646

Abstract: Purpose of review: Status epilepticus is a neurological emergency associated with high morbidity and mortality. There is a lack of robust data to guide the management of this neurological emergency beyond the initial treatment. This review examines ... ...

Abstract	Purpose of review: Status epilepticus is a neurological emergency associated with high morbidity and mortality. There is a lack of robust data to guide the management of this neurological emergency beyond the initial treatment. This review examines recent literature on treatment considerations including the choice of continuous anesthetics or adjunctive anticonvulsant, the cause of the status epilepticus, and use of nonpharmacologic therapies. Recent findings: Status epilepticus remains undertreated and mortality persists to be unchanged over the past 30 years. New anticonvulsant choices, such as levetiracetam and lacosamide have been explored as alternative emergent therapies. Anecdotal reports on the use of other generation anticonvulsants and nonpharmacologic therapies for the treatment of refractory and super-refractory status epilepticus have been described.Finally, recent evidence has examined etiology-guided management of status epilepticus in certain patient populations, such as immune-mediated, paraneoplastic or infectious encephalitis and anoxic brain injury. Summary: Randomized clinical trials are needed to determine the role for newer generation anticonvulsants and nonpharmacologic modalities for the treatment of epilepticus remains and evaluate the long-term outcomes associated with continuous anesthetics.
MeSH term(s)	Anesthetics/therapeutic use ; Anticonvulsants/therapeutic use ; Humans ; Status Epilepticus/therapy
Chemical Substances	Anesthetics ; Anticonvulsants
Language	English
Publishing date	2019-09-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1235629-3
ISSN	1531-7072 ; 1070-5295
ISSN (online)	1531-7072
ISSN	1070-5295
DOI	10.1097/MCC.0000000000000661
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Article: A methodology of phenotyping ICU patients from EHR data: high-fidelity, personalized, and interpretable phenotypes estimation.

Wang, Yanran / Stroh, J N / Hripcsak, George / Low Wang, Cecilia C / Bennett, Tellen D / Wrobel, Julia / Der Nigoghossian, Caroline / Mueller, Scott / Claassen, Jan / Albers, D J

medRxiv : the preprint server for health sciences

2023

Abstract: Objective: Computing phenotypes that provide high-fidelity, time-dependent characterizations and yield personalized interpretations is challenging, especially given the complexity of physiological and healthcare systems and clinical data quality. This ... ...

Abstract	Objective: Computing phenotypes that provide high-fidelity, time-dependent characterizations and yield personalized interpretations is challenging, especially given the complexity of physiological and healthcare systems and clinical data quality. This paper develops a methodological pipeline to estimate unmeasured physiological parameters and produce high-fidelity, personalized phenotypes anchored to physiological mechanics from electronic health record (EHR). Methods: A methodological phenotyping pipeline is developed that computes new phenotypes defined with unmeasurable computational biomarkers quantifying specific physiological properties in real time. Working within the inverse problem framework, this pipeline is applied to the glucose-insulin system for ICU patients using data assimilation to estimate an established mathematical physiological model with stochastic optimization. This produces physiological model parameter vectors of clinically unmeasured endocrine properties, here insulin secretion, clearance, and resistance, estimated for individual patient. These physiological parameter vectors are used as inputs to unsupervised machine learning methods to produce phenotypic labels and discrete physiological phenotypes. These phenotypes are inherently interpretable because they are based on parametric physiological descriptors. To establish potential clinical utility, the computed phenotypes are evaluated with external EHR data for consistency and reliability and with clinician face validation. Results: The phenotype computation was performed on a cohort of 109 ICU patients who received no or short-acting insulin therapy, rendering continuous and discrete physiological phenotypes as specific computational biomarkers of unmeasured insulin secretion, clearance, and resistance on time windows of three days. Six, six, and five discrete phenotypes were found in the first, middle, and last three-day periods of ICU stays, respectively. Computed phenotypic labels were predictive with an average accuracy of 89%. External validation of discrete phenotypes showed coherence and consistency in clinically observable differences based on laboratory measurements and ICD 9/10 codes and clinical concordance from face validity. A particularly clinically impactful parameter, insulin secretion, had a concordance accuracy of 83% Conclusion: The new physiological phenotypes computed with individual patient ICU data and defined by estimates of mechanistic model parameters have high physiological fidelity, are continuous, time-specific, personalized, interpretable, and predictive. This methodology is generalizable to other clinical and physiological settings and opens the door for discovering deeper physiological information to personalize medical care.
Language	English
Publishing date	2023-08-25
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.03.15.23287315
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Article ; Online: Common Data Elements for Disorders of Consciousness: Recommendations from the Electrophysiology Working Group.

Carroll, Elizabeth E / Der-Nigoghossian, Caroline / Alkhachroum, Ayham / Appavu, Brian / Gilmore, Emily / Kromm, Julie / Rohaut, Benjamin / Rosanova, Mario / Sitt, Jacobo Diego / Claassen, Jan

Neurocritical care

2023 Volume 39, Issue 3, Page(s) 578–585

Abstract: Background: Electroencephalography (EEG) has long been recognized as an important tool in the investigation of disorders of consciousness (DoC). From inspection of the raw EEG to the implementation of quantitative EEG, and more recently in the use of ... ...

Abstract	Background: Electroencephalography (EEG) has long been recognized as an important tool in the investigation of disorders of consciousness (DoC). From inspection of the raw EEG to the implementation of quantitative EEG, and more recently in the use of perturbed EEG, it is paramount to providing accurate diagnostic and prognostic information in the care of patients with DoC. However, a nomenclature for variables that establishes a convention for naming, defining, and structuring data for clinical research variables currently is lacking. As such, the Neurocritical Care Society's Curing Coma Campaign convened nine working groups composed of experts in the field to construct common data elements (CDEs) to provide recommendations for DoC, with the main goal of facilitating data collection and standardization of reporting. This article summarizes the recommendations of the electrophysiology DoC working group. Methods: After assessing previously published pertinent CDEs, we developed new CDEs and categorized them into "disease core," "basic," "supplemental," and "exploratory." Key EEG design elements, defined as concepts that pertained to a methodological parameter relevant to the acquisition, processing, or analysis of data, were also included but were not classified as CDEs. Results: After identifying existing pertinent CDEs and developing novel CDEs for electrophysiology in DoC, variables were organized into a framework based on the two primary categories of resting state EEG and perturbed EEG. Using this categorical framework, two case report forms were generated by the working group. Conclusions: Adherence to the recommendations outlined by the electrophysiology working group in the resting state EEG and perturbed EEG case report forms will facilitate data collection and sharing in DoC research on an international level. In turn, this will allow for more informed and reliable comparison of results across studies, facilitating further advancement in the realm of DoC research.
MeSH term(s)	Humans ; Common Data Elements ; Biomedical Research ; Consciousness Disorders/diagnosis ; Consciousness Disorders/therapy ; Data Collection ; Electrophysiology
Language	English
Publishing date	2023-08-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2381896-7
ISSN	1556-0961 ; 1541-6933
ISSN (online)	1556-0961
ISSN	1541-6933
DOI	10.1007/s12028-023-01795-1
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