NEUROprotection Via optimizINg Cerebral Blood Flow afTer cArdiaC arresT (NEURO-INTACT) Study

This single-center proof of concept study aims to assess the efficacy of a blood pressure strategy targeting person- and time-specific cerebral blood flow compared with standard-of-care using neuron-specific enolase as a quantitative biomarker of brain injury. Our central hypothesis is that an individualized blood pressure strategy targeting cerebral perfusion, compared with standard-of-care, will reduce the extent of brain injury as indicated by changes in levels of neuron-specific enolase from baseline at 72 hours. To test this hypothesis, the investigators will randomly assign 90 patients to an individualized blood pressure management strategy targeting cerebral blood flow, where optimal blood pressure will be serially calculated by the ICM+ brain monitoring software (Cambridge, UK) using inputs from transcranial Doppler ultrasound and near-infrared spectroscopy (intervention), versus achieving a standard level of systemic blood pressure (standard-of-care). This is done in a 2:1 allocation (60 to intervention, 30 to standard-of-care), in the first 72 hours after return of spontaneous circulation (ROSC).

Hemodynamic optimization performed to an individualized target mean arterial pressure in the first 72 hours post ROSC based on cerebral perfusion assessed serially.

Hemodynamic optimization to a target mean arterial pressure of ≥65mmHg throughout the first 72 hours post-ROSC.

An individualized blood pressure strategy targeting cerebral blood flow, serially guided by near-infrared spectroscopy and transcranial Doppler ultrasound. Assessments are performed on admission, and at 12, 24 and 48 hours post-ROSC.

Peak concentration of myocardial injury biomarker, High-sensitive troponin (hsTNT) within 72 hours of ROSC

Peak concentration of myocardial injury biomarker - N-terminal pro b-type natriuretic peptide (NT-proBNP)

Peak concentration of myocardial injury biomarker, N-terminal pro b-type natriuretic peptide (NT-proBNP) within 72 hours of ROSC

Peak concentration of renal injury biomarker, Proenkephalin A 119-159 (penKID) within 72 hours of ROSC

Peak concentration of renal injury biomarker, Biologically active adrenomedullin (bio-ADM) within 72 hours of ROSC

Peak concentration of renal injury biomarker, Tissue inhibitor of metalloproteinases 2 (TIMP2) within 72 hours of ROSC

Peak concentration of renal injury biomarker, Insulin Like Growth Factor Binding Protein 7 (IGFBP7) within 72 hours of ROSC

Neurological outcomes measured by Cerebral Performance Category (CPC) scale on hospital discharge, and at 3, 6 and 12 months post OHCA. The CPC purports to assess domains of functioning after cardiopulmonary resuscitation (CPR) with scores ranging from 1 (good cerebral performance/normal life) to 5 (brain death).

Physical function measured by the change of Duke Activity Status Index (DASI) self-reported questionnaire on hospital discharge, and at 3, 6 and 12 months post OHCA. DASI score is the sum of the questionnaire responses, score of 34 or less means moderate-to-severe complications.

Neurocognitive is assessed by Montreal Cognitive Assessment (MOCA, global cognition) on hospital discharge, and at 3, 6 and 12 months post OHCA. Scores on the MOCA from zero to 30, while score of 26 and above is considered normal.

Neuropsychological outcome - Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)

Neuropsychological deficits is assessed by the modified local version of Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) on hospital discharge, and at 3, 6 and 12 months post OHCA. Standard scores of 70 and above will classify as average/mild impairment, scores 55 to 69 as moderate impairment and severe impairment for scores less than 55.

Depression, Anxiety, and Stress Scale (DASS-21) is used to assess neuropsychological outcome on hospital discharge, and at 3, 6 and 12 months post OHCA.

Health-related quality of life measured by EuroQol-5 Dimension-5 Level (EQ-5D-5L) questionnaire on hospital discharge, and at 3, 6 and 12 months post OHCA. EQ-5D-5L questionnaire consists of 5 dimensions (mobility, self care, usual activities, pain/comfort, anxiety/depression). There are 5 levels in each dimensions. The lowest level means normal which the highest level means extremely severe.

Neurocognitive is assessed by digital neurocognitive assessment on hospital discharge, and at 3, 6 and 12 months post OHCA.

Inclusion Criteria: At least 21 years of age Comatose defined as not being able to obey verbal commands and no verbal response to pain after sustained ROSC. Exclusion Criteria: ≥ 80 years old at time of enrolment Pregnant patients Limitations of care or life support therapy withdrawn within 24 hours of admission