Assessing the relationship between near-infrared spectroscopy-derived regional cerebral oxygenation and neurological dysfunction in critically ill adults: a prospective observational multicentre protocol, on behalf of the Canadian Critical Care Trials Group

Abstract

Introduction: Survivors of critical illness frequently exhibit acute and chronic neurological complications. The underlying aetiology of this dysfunction remains unknown but may be associated with cerebral ischaemia. This study will use near-infrared spectroscopy to non-invasively quantify regional cerebral oxygenation (rSO2) to assess the association between poor rSO2 during the first 72 hours of critical illness with delirium severity, as well as long-term sensorimotor and cognitive impairment among intensive care unit (ICU) survivors. Further, the physiological determinants of rSO2 will be examined.

Methods and analysis: This multicentre prospective observational study will consider adult patients (≥18 years old) eligible for enrolment if within 24 hours of ICU admission, they require mechanical ventilation and/or vasopressor support. For 72 hours, rSO2 will be continuously recorded, while vital signs (eg, heart rate) and peripheral oxygenation saturation will be concurrently captured with data monitoring software. Arterial and central venous gases will be sampled every 12 hours for the 72 hours recording period and will include: pH, PaO2, PaCO2, and haemoglobin concentration. Participants will be screened daily for delirium with the confusion assessment method (CAM)-ICU, whereas the brief-CAM will be used on the ward. At 3 and 12 months post-ICU discharge, neurological function will be assessed with the Repeatable Battery for the Assessment of Neuropsychological Status and KINARM sensorimotor and cognitive robot-based behavioural tasks.

Ethics and dissemination: The study protocol has been approved in Ontario by a central research ethics board (Clinical Trials Ontario); non-Ontario sites will obtain local ethics approval. The study will be conducted under the guidance of the Canadian Critical Care Trials Group (CCCTG) and the results of this study will be presented at national meetings of the CCCTG for internal peer review. Results will also be presented at national/international scientific conferences. On completion, the study findings will be submitted for publication in peer-reviewed journals.

Trial registration number: NCT03141619.

Keywords: cerebral autoregulation; delirium; kinarm; near-infrared spectroscopy; post-intensive care syndrome; rbans.

Conflict of interest statement

Competing interests: JM is the scientific director of the Canadian Frailty Network. SHS is the cofounder of BKIN Technologies, the manufacturer of the KINARM device. IB receives a stipend from the Trillium Gift of Life Network to support his role as a Regional Medical Lead. NO received funding from the Academic Medical Organization of Southwestern Ontario. MS receives a stipend from the Trillium Gift of Life Network to support his role as a Hospital Donation Physician. DG is funded through a Health-Professional Investigator Award from the Michael Smith Foundation for Health Research. JGB receives a stipend from the Trillium Gift of Life Network to support his role as a Regional Medical Lead.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

A visual representation of the CONFOCAL2 study design from enrolment to 3 and 12 months follow-up assessments. APACHE II, Acute Physiology and Chronic Health Evaluation II; Hb, haemoglobin; ICU, intensive care unit; NIRS, near-infrared spectroscopy; pCO2, partial arterial pressure of carbon dioxide; pO2, partial arterial pressure of oxygen; RBANS, Repeatable Battery for the Assessment of Neuropsychological Status.

Figure 2

Three-dimensional animated representation of the KINARM endpoint robotic set-up used at 3 and 12 months follow-up assessments.

Figure 3

(A) Simplified line graph (24 hours instead of the full 72 hours recording period) illustrating the sliding window correlation between mean arterial pressure (MAP) and regional cerebral oxygenation (rSO2) for an individual patient over a 24 period of recording. The black rectangle represents a 60 min window that moves forward 1 min at a time until the recording period is completed. (B) Scatter plot illustrating a time dependent positive association between MAP and rSO2. Black dots represent data collected for an individual patient over 24 hours, with the blue line representing a linear model fit to the data, and the grey shaded region representing the 95% CI. (C) Scatter plot indicating the time varying association between MAP and rSO2 represented as the Cerebral Oximetry Index (COx) over an individual patient’s 24 hours recording period. Statistically significant (p<0.0001) positive COx values represent dysfunctional cerebral autoregulation, with negative or near zero values indicating intact cerebral autoregulation.

Figure 4

Line graph of the high frequency vital sign recordings indicates the highly variable relationships with regional cerebral oxygenation over the 72 hours period of recording. The figure represents a single patient’s ICU recording. artMAP, mean arterial pressure from an arterial line; HR, heart rate; ICU, intensive care unit; rSO2, regional cerebral oxygenation; SpO2, peripheral oxygen saturation.

Figure 5

A power curve indicating the study sample size, and the respective statistical power, to asses the primary study outcome. Red dots represent the sample size needed for a given statistical power. The primary sample size was calculated using the following multivariate regression model parameters: 10 independent variables tested, controlling for 9 additional covariates, power=0.90, R2=0.050, α=0.05, which would require a sample size of 400.