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      Neuromonitoring of delirium with quantitative pupillometry in sedated mechanically ventilated critically ill patients

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          Abstract

          Background

          Intensive care unit (ICU) delirium is a frequent secondary neurological complication in critically ill patients undergoing prolonged mechanical ventilation. Quantitative pupillometry is an emerging modality for the neuromonitoring of primary acute brain injury, but its potential utility in patients at risk of ICU delirium is unknown.

          Methods

          This was an observational cohort study of medical-surgical ICU patients, without acute or known primary brain injury, who underwent sedation and mechanical ventilation for at least 48 h. Starting at day 3, automated infrared pupillometry—blinded to ICU caregivers—was used for repeated measurement of the pupillary function, including quantitative pupillary light reflex (q-PLR, expressed as % pupil constriction to a standardized light stimulus) and constriction velocity (CV, mm/s). The relationship between delirium, using the CAM-ICU score, and quantitative pupillary variables was examined.

          Results

          A total of 59/100 patients had ICU delirium, diagnosed at a median 8 (5–13) days from admission. Compared to non-delirious patients, subjects with ICU delirium had lower values of q-PLR (25 [19–31] vs. 20 [15–28] %) and CV (2.5 [1.7–2.8] vs. 1.7 [1.4–2.4] mm/s) at day 3, and at all additional time-points tested ( p < 0.05). After adjusting for the SOFA score and the cumulative dose of analgesia and sedation, lower q-PLR was associated with an increased risk of ICU delirium (OR 1.057 [1.007–1.113] at day 3; p = 0.03).

          Conclusions

          Sustained abnormalities of quantitative pupillary variables at the early ICU phase correlate with delirium and precede clinical diagnosis by a median 5 days. These findings suggest a potential utility of quantitative pupillometry in sedated mechanically ventilated ICU patients at high risk of delirium.

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          Most cited references22

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          Molecular and Functional Neuroscience in Immunity

          The nervous system regulates immunity and inflammation. The molecular detection of pathogen fragments, cytokines, and other immune molecules by sensory neurons generates immunoregulatory responses through efferent autonomic neuron signaling. The functional organization of this neural control is based on principles of reflex regulation. Reflexes involving the vagus nerve and other nerves have been therapeutically explored in models of inflammatory and autoimmune conditions, and recently in clinical settings. The brain integrates neuro-immune communication, and brain function is altered in diseases characterized by peripheral immune dysregulation and inflammation. Here we review the anatomical and molecular basis of the neural interface with immunity, focusing on peripheral neural control of immune functions and the role of the brain in the model of the immunological homunculus. Clinical advances stemming from this knowledge within the framework of bioelectronic medicine are also briefly outlined.
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            Acute Brain Failure: Pathophysiology, Diagnosis, Management, and Sequelae of Delirium.

            Delirium is the most common psychiatric syndrome found in the general hospital setting, with an incidence as high as 87% in the acute care setting. Delirium is a neurobehavioral syndrome caused by the transient disruption of normal neuronal activity secondary to systemic disturbances. The development of delirium is associated with increased morbidity, mortality, cost of care, hospital-acquired complications, placement in specialized intermediate and long-term care facilities, slower rate of recovery, poor functional and cognitive recovery, decreased quality of life, and prolonged hospital stays. This article discusses the epidemiology, known etiological factors, presentation and characteristics, prevention, management, and impact of delirium.
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              Portable infrared pupillometry: a review.

              Portable infrared pupillometers provide an objective measure of pupil size and pupillary reflexes, which for most clinicians was previously only a visual impression. But despite the fact that pupillometry can uncover aspects of how the human pupil reacts to drugs and noxious stimulation, the use of pupillometry has not gained widespread use among anesthesiologists and critical care physicians. The present review is an introduction to the physiology of pupillary reflexes and the currently established clinical applications of infrared pupillometry, which will hopefully encourage physicians to use this diagnostic tool in their clinical practice. Portable infrared pupillometry was introduced in 1989. The technology involves flooding the eye with infrared light and then measuring the reflected image on an infrared sensor. Pupil size, along with variables of the pupillary light reflex and pupillary reflex dilation, is calculated by the instrument and displayed on a screen immediately after each time-stamped measurement. Use of these instruments has uncovered aspects of how the human pupil reacts to drugs and noxious stimulation. The primary clinical applications for portable pupillometry have been in the assessment of brainstem function. Portable pupillometry is useful in the management of pain because it allows for assessments of the effect of opioids and in the titration of combined regional-general anesthetics.
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                Author and article information

                Contributors
                mauro.oddo@chuv.ch
                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                24 February 2020
                24 February 2020
                2020
                : 24
                : 66
                Affiliations
                [1 ]ISNI 0000 0001 2165 4204, GRID grid.9851.5, Critical Care Research Unit, Centre Hospitalier Universitaire Vaudois (CHUV), , University Hospital and University of Lausanne, ; Rue du Bugnon 46, BH08-623, CH-1011 Lausanne, Switzerland
                [2 ]ISNI 0000 0001 0423 4662, GRID grid.8515.9, Department of Intensive Care Medicine, , Centre Hospitalier Universitaire Vaudois (CHUV), University Hospital and University of Lausanne, ; Rue du Bugnon 46, BH 08.623, Lausanne, Switzerland
                [3 ]ISNI 0000 0001 2165 4204, GRID grid.9851.5, Institute of Higher Education and Research in Healthcare – IUFRS, , University of Lausanne, ; Lausanne, Switzerland
                [4 ]ISNI 0000 0001 2165 4204, GRID grid.9851.5, Center for Primary Care and Public Health, , University of Lausanne, ; Lausanne, Switzerland
                Author information
                http://orcid.org/0000-0002-6155-2525
                Article
                2796
                10.1186/s13054-020-2796-8
                7041194
                32093710
                b4d6697a-fa57-4446-a284-a2468057aa18
                © The Author(s). 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 22 December 2019
                : 18 February 2020
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

                Emergency medicine & Trauma
                delirium,pupillometry,cholinergic,pupillary reactivity,mechanical ventilation

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