Interventions for Silent Brain Infarction and Perioperative Neurocognitive Disorders in Cardiovascular Surgery

Official title

Interventions for Silent Brain Infarction and Perioperative Neurocognitive Disorders in Cardiovascular Surgery (the INSPIRE Study)

Overview

the purpose of the study is to investigate whether a combined anesthetic targets bundle, known as the NeuroFirst strategy, focused on neurological protection, can reduce the incidence of silent brain infarction (SBI) and perioperative neurocognitive disorders (PND) in patients undergoing cardiac surgery. Additionally, the trial will assess the safety of this strategy. The NeuroFirst target bundle incorporates multiple parameters, including mean arterial pressure (MAP), bispectral index (BIS), regional cerebral oxygen saturation (rSO2), and arterial inflow temperature during cardiopulmonary bypass. The primary question this study seeks to answer is: Does the NeuroFirst strategy reduce the incidence of SBI and PND in cardiac surgery? To address this, researchers will compare the NeuroFirst strategy with routine institutional practices based on published guidelines. Participants will be randomly assigned to either the NeuroFirst group or the routine care group. All participants will undergo magnetic resonance imaging (MRI), be assessed using the Confusion Assessment Method (CAM) and the Montreal Cognitive Assessment (MoCA), and be followed for up to one year postoperatively.

Interventions

• Other Managements for NeuroFirst target bundle
  In the intervention group, patient management aims to achieve the NeuroFirst target bundle, including 1) mean arterial pressure (MAP) 65-90 mmHg, 2) bispectral index (BIS) 40-60, 3) regional cerebral oxygen saturation (rSO2)≥ 60% , and 4) arterial inflow temperature \<37 ℃ and rewarming rate \< 0.5 ℃/min after exceeding 30℃ during CPB. To achieve this target bundle, pharmacologic agents, fluid resuscitation, blood transfusion, and other therapeutic modalities will be utilized. These interventio
• Other Managements for institutional routine
  MAP, BIS, cerebral rSO2 and arterial inflow temperature during CPB rewarming, will be managed according to institutional routine in accordance with published guidelines.

Primary outcome measures

• the 7-day incidence of new-onset silent brain infarction (SBI) [Time frame: within 7 days postoperatively]

Secondary outcome measures (9)

• Key Secondary Outcome: the 30-day incidence of perioperative neurocognitive disorders (PND) [Time frame: within 30 days postoperatively]
• the 5-day incidence of postoperative delirium [Time frame: within five days postoperatively]
• the 30-day incidence of new-onset overt stroke [Time frame: within 30 days postoperatively]
• the 1-year incidence of new-onset overt stroke [Time frame: within 1 year postoperatively]
• the 1-year incidence of perioperative neurocognitive disorders (PND) [Time frame: within 1 year postoperatively]
• the 30-day composite incidence of major adverse events [Time frame: within 30 days postoperatively]
• the 1-year composite incidence of major adverse events [Time frame: within 1 year postoperatively]
• the 30-day incidence of transient ischemic attack (TIA) [Time frame: within 30 days postoperatively]
• the 1-year incidence of transient ischemic attack (TIA) [Time frame: within 1 year postoperatively]

Eligibility criteria

Inclusion criteria

• Male or female adult patients aged 60 years or older
• Receiving elective cardiovascular surgery with cardiopulmonary bypass
• Written Informed consent provided

Exclusion criteria

• Contraindication to MRI scanning
• Not suitable for receiving interventions to achieve NeuroFirst target bundle
• Unable to receive neuro-cognitive evaluation due to language, vision, or hearing impairments
• Breastfeeding or pregnancy
• Terminal illness with a life expectancy of less than 3 months
• Mental or legal disability
• current enrollment in other interventional study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Prevention

Study locations

China · 5 centers

• Beijing Chaoyang Hospital，Capital Medical University — Beijing
• State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardio — Beijing
• Xuanwu Hospital,Capital Medical University — Beijing
• Beijing Tiantan Hospital, Capital Medical University — Beijing
• The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and — Wuhan

Publications

• Uysal S, Lin HM, Trinh M, Park CH, Reich DL. Optimizing cerebral oxygenation in cardiac surgery: A randomized controlled trial examining neurocognitive and perioperative outcomes. J Thorac Cardiovasc Surg. 2020 Mar;159(3):943-953.e3. doi: 10.1016/j.jtcvs.2019.03.036. Epub 2019 Mar 29. PMID 31056357
• Maheshwari A, McCormick PJ, Sessler DI, Reich DL, You J, Mascha EJ, Castillo JG, Levin MA, Duncan AE. Prolonged concurrent hypotension and low bispectral index ('double low') are associated with mortality, serious complications, and prolonged hospitalization after cardiac surgery. Br J Anaesth. 2017 Jul 1;119(1):40-49. doi: 10.1093/bja/aex095. PMID 28974062
• Descamps R, Amour J, Besnier E, Bougle A, Charbonneau H, Charvin M, Cholley B, Desebbe O, Fellahi JL, Frasca D, Labaste F, Lena D, Mahjoub Y, Mertes PM, Molliex S, Moury PH, Moussa MD, Oilleau JF, Ouattara A, Provenchere S, Rozec B, Parienti JJ, Fischer MO; OPTIPAM investigators. Perioperative individualized hemodynamic optimization according to baseline mean arterial pressure in cardiac surgery p PMID 36934980
• Gerstenecker A, Norling AM, Jacob A, Lazar RM. Silent Brain Infarction, Delirium, and Cognition in Three Invasive Cardiovascular Procedures: a Systematic Review. Neuropsychol Rev. 2023 Jun;33(2):474-491. doi: 10.1007/s11065-022-09548-1. Epub 2022 Jul 8. PMID 35804216
• Newman MF, Kirchner JL, Phillips-Bute B, Gaver V, Grocott H, Jones RH, Mark DB, Reves JG, Blumenthal JA; Neurological Outcome Research Group and the Cardiothoracic Anesthesiology Research Endeavors Investigators. Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery. N Engl J Med. 2001 Feb 8;344(6):395-402. doi: 10.1056/NEJM200102083440601. PMID 11172175
• Brown CH 4th, Probert J, Healy R, Parish M, Nomura Y, Yamaguchi A, Tian J, Zehr K, Mandal K, Kamath V, Neufeld KJ, Hogue CW. Cognitive Decline after Delirium in Patients Undergoing Cardiac Surgery. Anesthesiology. 2018 Sep;129(3):406-416. doi: 10.1097/ALN.0000000000002253. PMID 29771710
• Cheng C, Wan H, Cong P, Huang X, Wu T, He M, Zhang Q, Xiong L, Tian L. Targeting neuroinflammation as a preventive and therapeutic approach for perioperative neurocognitive disorders. J Neuroinflammation. 2022 Dec 12;19(1):297. doi: 10.1186/s12974-022-02656-y. PMID 36503642
• Indja B, Woldendorp K, Vallely MP, Grieve SM. Silent Brain Infarcts Following Cardiac Procedures: A Systematic Review and Meta-Analysis. J Am Heart Assoc. 2019 May 7;8(9):e010920. doi: 10.1161/JAHA.118.010920. PMID 31017035

Identifiers

NCT: NCT07048002 · The INSPIRE study

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗