Outcome Prognostication of Acute Brain Injury using the Neurological Pupil Index (ORANGE) study: protocol for a prospective, observational, multicentre, international cohort study

Mauro Oddo, Fabio Taccone, Stefania Galimberti, Paola Rebora, Giuseppe Citerio, Orange Study Group, R Badenes, P Bouzat, A Caricato, R M Chesnut, C Hemphill, F Rasulo, S Schwab, J I Suarez, K Sunde, Aaron Blandino, Letterio Malgeri, Eleonora Rossi, Alessia Vargiolu, Francesca Elli, Francesca Graziano, Mauro Oddo, Fabio Taccone, Stefania Galimberti, Paola Rebora, Giuseppe Citerio, Orange Study Group, R Badenes, P Bouzat, A Caricato, R M Chesnut, C Hemphill, F Rasulo, S Schwab, J I Suarez, K Sunde, Aaron Blandino, Letterio Malgeri, Eleonora Rossi, Alessia Vargiolu, Francesca Elli, Francesca Graziano

Abstract

Introduction: The pupillary examination is an important part of the neurological assessment, especially in the setting of acutely brain-injured patients, and pupillary abnormalities are associated with poor outcomes. Currently, the pupillary examination is based on a visual, subjective and frequently inaccurate estimation. The use of automated infrared pupillometry to measure the pupillary light reflex can precisely quantify subtle changes in pupillary functions. The study aimed to evaluate the association between abnormal pupillary function, assessed by the Neurological Pupil Index (NPi), and long-term outcomes in patients with acute brain injury (ABI).

Methods and analysis: The Outcome Prognostication of Acute Brain Injury using the Neurological Pupil Index study is a prospective, observational study including adult patients with ABI requiring admission at the intensive care unit. We aimed to recruit at least 420 patients including those suffering from traumatic brain injury or haemorrhagic strokes, over 12 months. The primary aim was to assess the relationship between NPi and 6-month mortality or poor neurological outcome, measured by the Extended Glasgow Outcome Score (GOS-E, poor outcome=GOS-E 1-4). Supervised and unsupervised methods and latent class mixed models will be used to identify patterns of NPi trajectories and Cox and logistic model to evaluate their association with outcome.

Ethics and dissemination: The study has been approved by the institutional review board (Comitato Etico Brianza) on 16 July 2020. Approved protocol V.4.0 dated 10 March 2020. The results of this study will be published in peer-reviewed journals and presented at conferences.

Trial registration number: NCT04490005.

Keywords: adult intensive & critical care; neurological injury; stroke.

Conflict of interest statement

Competing interests: GC reports grants, personal fees as speakers’ bureau member and advisory board member of Integra and Neuroptics, all outside the submitted work. FT received lecture fees from BD and ZOLL and personal fees as advisory board member of Nihon Khoden and Neuroptics, all outside the submitted work. MO received grants from the Swiss National Science Foundation, and is a consultant and member of the Scientific Advisory Board of Neuroptics.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

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