Abstract
BackgroundIntensive 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.MethodsThis 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.ResultsA 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).ConclusionsSustained 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.
Highlights
Delirium is a common neurological complication of intensive care unit (ICU), in patients requiring prolonged mechanical ventilation and sedation
The pupillary light reflex (PLR) is regulated by the cholinergic system, which mediates pupillary constriction to light stimulation [6]; quantitative measurement of the pupillary function with automated infrared pupillometry represents an attractive tool for evaluating cholinergic activity in the clinical setting [14,15,16,17,18] and is emerging as a novel monitoring and diagnostic tool in neurological conditions (e.g., Alzheimer’s and Parkinson’s disease) in which cholinergic deficit is implicated in disease pathogenesis [19,20,21]
Delirium prevalence was 59%, and median time from Intensive care unit (ICU) admission to delirium diagnosis was 8 days (IQR 5–13); 3 out of 100 patients died in the ICU, previous to Confusion Assessment Method for the ICU (CAM-ICU) assessment, and were not included in the final analysis
Summary
Delirium is a common neurological complication of intensive care unit (ICU), in patients requiring prolonged mechanical ventilation and sedation. Growing evidence demonstrates that reduced functioning of the cholinergic antiinflammatory reflex is implicated in the pathophysiology of secondary critical illness-related brain dysfunction [8], which in turn can be attenuated by therapeutic vagus nerve stimulation [9,10,11,12,13]. The objective of this study was to examine in high-risk sedated mechanically ventilated patients, without primary acute or known brain injury, whether reduced pupillary light constriction—assessed quantitatively at the early phase of ICU using automated infrared pupillometry—was associated with delirium, assessed with the Confusion Assessment Method for the ICU (CAM-ICU) [25]. 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
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