Clinical trial NCT05279898: Perioperative Multimodal General AnesTHesia Focusing on Specific CNS Targets in Patients Undergoing carDiac surgERies
Official title: Perioperative Multimodal General AnesTHesia Focusing on Specific CNS Targets in Patients Undergoing carDiac surgERies - the PATHFINDER II Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Postoperative Delirium
Hemodynamic Instability
Pain
Neurocognitive Dysfunction
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
First posted: 2022-03-15
Enrollment: 70
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Group 1: Control - receives standard of care anesthesia and blinded EEG and Cerebral Oximetry(CO) monitoring Group 2: Intervention - receives MMGA bundle, guided by EEG monitoring, blinded CO will be passively collected
Primary purpose: PREVENTION

Brief summary: In the PATHFINDER 2 trial, the study investigators will test the intraoperative EEG-guided multimodal general anesthesia (MMGA) management strategy in combination with a postoperative protocolized analgesic approach to:

1. reduce the incidence of perioperative neurocognitive dysfunction in cardiac surgical patients
2. ensure hemodynamic stability and decrease use of vasopressors in the operating rooms
3. reduce pain and opioid consumption postoperatively

Detailed description: The investigators propose to randomize (1:1) 70 patients undergoing cardiac surgery to the perioperative EEG-guided MMGA bundle (described in full below) or standard-of-care management based primarily on the use of sevoflurane for unconsciousness and intermittent doses of fentanyl and hydromorphone for antinociception.

The team will test the intraoperative EEG-guided MMGA management strategy in combination with a postoperative protocolized analgesic approach to reduce the postoperative increase of surgical and delirium markers, reduce intraoperative abnormalities in brain health monitoring, ensure hemodynamic stability and decreased use of vasopressors in the operating rooms and reduce pain and opioid consumption postoperatively. The team will also investigate whether EEG-guided MMGA strategy reduces the incidence of perioperative neurocognitive dysfunction in cardiac surgical patients. This approach will further individualize care and minimize the use of intraoperative vasopressor-inotropic dose, dose of anesthetic medications, and postoperative opioids given to each patient potentially preventing hemodynamic complications and post-operative cognitive dysfunction after surgery.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 60 years
* Undergoing any of the following types of surgery with cardiopulmonary bypass limited to coronary artery bypass surgery (CABG), CABG+valve surgeries and isolated valve surgeries.

Exclusion Criteria:

* Preoperative left ventricular ejection fraction (LVEF) \<30%
* Emergent surgery
* Non-English speaking
* Cognitive impairment as defined by total MoCA score \< 10
* Currently enrolled in another interventional study that could impact the primary outcome, as determined by the PI
* Significant visual impairment
* Chronic opioid use for chronic pain conditions with tolerance (total dose of an opioid at or more than 30 mg morphine equivalent for more than one month within the past year)
* Hypersensitivity to any of the study medications
* Known history of alcohol (\> 2 drinks per day) or drug abuse Active (in the past year) history of alcohol abuse (≥5 drinks/day for men or ≥4 drinks/day for women) as determined by reviewing medical record and history given by the patient
* Liver dysfunction (liver enzymes \> 4 times the baseline, all patients will have a baseline liver function test evaluation), history and examination suggestive of jaundice.

Primary outcomes:
measure: Increase in plasma IL-6 levels
timeFrame: Baseline, postoperative day1 and day 2
measure: Increase in plasma Neurofilament light levels
timeFrame: Baseline, postoperative day1 and day 2
Secondary outcomes:
measure: Concurrent EEG burst suppression and cerebral desaturation
timeFrame: Intra-operative
measure: Opioid consumption and postoperative pain control
timeFrame: 48- hours, Postoperative
measure: Burst suppression
timeFrame: Introperative
measure: Postoperative delirium
timeFrame: Postoperative days till discharge
measure: Cognitive Function
timeFrame: Patients will be assessed for delirium at 1 month and 6 months following the date of surgery
measure: Hemodynamic Stability - Total Vasopressor Dose
timeFrame: Intra-operative
measure: Hemodynamic Stability - Systolic Blood pressure (SBP)
timeFrame: Intraoperative
measure: Hemodynamic Stability - Mean Arterial Blood pressure
timeFrame: Intra-operative
measure: Hemodynamic Stability - Coefficient of variation of Mean Arterial BP
timeFrame: Intraoperative
measure: Surgical and delirium markers - Plasma Cortisol
timeFrame: Baseline, and till end of surgery
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: Balachundhar Subramaniam, MD,MPH,FASA
role: PRINCIPAL_INVESTIGATOR
References:
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