PATHFINDER-II: Perioperative Multimodal General AnesTHesia Focusing on Specific CNS Targets in Patients Undergoing carDiac surgERies - the PATHFINDER II Study

Sponsor

Beth Israel Deaconess Medical Center (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05279898

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

5.4

Patients Per Site Per Month

Study Details

Study Description

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:

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

Condition or Disease	Intervention/Treatment	Phase
Postoperative Delirium Hemodynamic Instability Pain Neurocognitive Dysfunction	Device: EEG Monitoring Drug: Ropivacaine Drug: Ketamine Drug: Remifentanil Drug: Dexmedetomidine Drug: Rocuronium Drug: Propofol	N/A

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 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

70 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Group 1: Control - receives standard of care anesthesia and blinded EEG monitoring Group 2: Intervention - receives MMGA bundle, guided by EEG monitoringGroup 1: Control - receives standard of care anesthesia and blinded EEG monitoring Group 2: Intervention - receives MMGA bundle, guided by EEG monitoring

Masking:

Single (Participant)

Primary Purpose:

Prevention

Official Title:

Perioperative Multimodal General AnesTHesia Focusing on Specific CNS Targets in Patients Undergoing carDiac surgERies - the PATHFINDER II Study

Anticipated Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Aug 1, 2023

Anticipated Study Completion Date :

Sep 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Multimodal General Anesthesia (MMGA Bundle) - EEG Guided Routine anesthetic induction Bilateral Pectoro-interfascial block (PIFB) with 20 mL of 0.2% ropivacaine on both sides of the sternum after anesthetic induction but before surgical incision (total of 40mL) Ketamine (0.1 to 0.2 mg.kg/hr) Remifentanil (0.05-0.4 mcg/kg/min) Dexmedetomidine (0.2-0.5 mcg/kg/hr) Rocuronium intermittent bolus (TOF) Propofol infusion (15 to 200 mcg/kg/min) Postop Standard pain management protocol IV Acetaminophen IV Hydromorphone/fentanyl boluses as needed per current practice for rescue analgesia Other oral pain medications as per standard of care (Oxycodone, etc) Dexmedetomidine infusion (0.4-1.4 mcg/kg/hr) - EEG Guided; Infusion continued till extubation Propofol infusion may be added/used for sedation based on the treating physician's discretion PIFB on postoperative day 1 (provided they are extubated/getting ready to be extubated)(for intervention group) Lidocaine patches	Device: EEG Monitoring Perioperative monitoring, MMGA guided by EEG for intervention group Drug: Ropivacaine Intraoperative bilateral PIFB block with 20 mL of 0.2% Ropivicaine on either side of the sternum after anesthetic induction but before surgical incision (total of 40mL) PIFB on postoperative day 1 (provided they are extubated or getting ready to be extubated) to help with mobilization (for intervention group) Drug: Ketamine Intraoperative infusion Drug: Remifentanil Intraoperative infusion Drug: Dexmedetomidine Intraoperative infusion Drug: Rocuronium Intraoperative intermittent bolus Drug: Propofol Intraoperative infusion
No Intervention: Standard of Care/Control EEG monitoring will be blinded, and not guide anesthesiologists. Patients will receive standard/routine anesthesia practice intraoperatively. Postoperative Propofol infusion (15 to 200 mcg/kg/min) ± Sevoflurane Standard pain management protocol IV Acetaminophen (1 gram) x 4 doses at 6 hour intervals starting from 1 hr after ICU arrival IV Hydromorphone/fentanyl boluses as needed per current practice for rescue analgesia Other oral pain medications as per standard of care (Oxycodone, etc) Dexmedetomidine infusion (0.4-1.4 mcg/kg/hr) - EEG Guided; Infusion continued till extubation Propofol infusion may be added/used for sedation based on the treating physician's discretion Lidocaine patches

Arm

Intervention/Treatment

Experimental: Multimodal General Anesthesia (MMGA Bundle) - EEG Guided

Routine anesthetic induction Bilateral Pectoro-interfascial block (PIFB) with 20 mL of 0.2% ropivacaine on both sides of the sternum after anesthetic induction but before surgical incision (total of 40mL) Ketamine (0.1 to 0.2 mg.kg/hr) Remifentanil (0.05-0.4 mcg/kg/min) Dexmedetomidine (0.2-0.5 mcg/kg/hr) Rocuronium intermittent bolus (TOF) Propofol infusion (15 to 200 mcg/kg/min) Postop Standard pain management protocol IV Acetaminophen IV Hydromorphone/fentanyl boluses as needed per current practice for rescue analgesia Other oral pain medications as per standard of care (Oxycodone, etc) Dexmedetomidine infusion (0.4-1.4 mcg/kg/hr) - EEG Guided; Infusion continued till extubation Propofol infusion may be added/used for sedation based on the treating physician's discretion PIFB on postoperative day 1 (provided they are extubated/getting ready to be extubated)(for intervention group) Lidocaine patches

Device: EEG Monitoring

Perioperative monitoring, MMGA guided by EEG for intervention group

Drug: Ropivacaine

Intraoperative bilateral PIFB block with 20 mL of 0.2% Ropivicaine on either side of the sternum after anesthetic induction but before surgical incision (total of 40mL) PIFB on postoperative day 1 (provided they are extubated or getting ready to be extubated) to help with mobilization (for intervention group)

Drug: Ketamine

Intraoperative infusion

Drug: Remifentanil

Intraoperative infusion

Drug: Dexmedetomidine

Intraoperative infusion

Drug: Rocuronium

Intraoperative intermittent bolus

Drug: Propofol

Intraoperative infusion

No Intervention: Standard of Care/Control

EEG monitoring will be blinded, and not guide anesthesiologists. Patients will receive standard/routine anesthesia practice intraoperatively. Postoperative Propofol infusion (15 to 200 mcg/kg/min) ± Sevoflurane Standard pain management protocol IV Acetaminophen (1 gram) x 4 doses at 6 hour intervals starting from 1 hr after ICU arrival IV Hydromorphone/fentanyl boluses as needed per current practice for rescue analgesia Other oral pain medications as per standard of care (Oxycodone, etc) Dexmedetomidine infusion (0.4-1.4 mcg/kg/hr) - EEG Guided; Infusion continued till extubation Propofol infusion may be added/used for sedation based on the treating physician's discretion Lidocaine patches

Outcome Measures

Primary Outcome Measures

Opioid consumption [48-hours, Post-operative]
Total postoperative opioid dose in morphine milligram equivalents (MME - reported in milligrams). Opioid consumption will be quantified and compared between the two groups. Total dose of opioids consumed by all the study patients in the 48 hours post-operative period will be obtained from the medical records. This will be converted to morphine equivalents (MME- Morphine milligram equivalents) for standardization of the outcome and for ease of analysis.
Postoperative pain control [48-hours, Post-operative]
Pain scores will be quantified and compared between the two groups. Pain will be assessed postoperatively by nursing staff every 4-8 hours and data will be collected form patient's electronic medical records. Pain score will be based off of numerical rating scale (NRS) of 0-10 (0 being no pain at all, and 10 being worst pain imaginable), verbally asked to patients.

Secondary Outcome Measures

Duration of Burst suppression [Intra-operative]
Duration of Burst suppression (measured in minutes) will be extracted and quantified from the EEG record.
Incidence of Postoperative Delirium (POD) [Participants will be followed for the duration of the hospital stay, an average of 5 days]
POD will be diagnosed by our trained research members based on the Confusion Assessment Method (CAM) algorithm postoperatively until discharge. There are four features (variables) in the CAM algorithm and the diagnosis of delirium requires the presence of features 1 and 2 and either 3 or 4. Outcomes will be reported in terms of presence or absence of delirium based on the CAM algorithm.
Cognitive Function [Patients will be assessed for delirium at 1 month and 6 months following the date of surgery]
Postoperative cognitive dysfunction at 1- and 6- months will be assessed with telephone version of the Montreal Cognitive Assessment (t-MoCA). It has a total score of 22 and higher score means better cognitive function.
Sedation Titration [Time between patient admission to ICU and extubation, an average of 6-8 hours]
Providers will be taught to titrate the sedative medications - dexmedetomidine and/or propofol (given as an infusion - dexmedetomidine in mcg/kg/hr and propofol in mcg/kg/min) using EEG as a surrogate for level of unconsciousness in the cardiovascular intensive care unit. The total amount of sedatives given as an infusion during the time period till extubation will be noted for the two groups and the time spent in EEG suppression between the two groups will be compared.
Hemodynamic Stability - Total Vasopressor Dose [Intra-operative]
Metrics of total vasopressor dose in norepinephrine equivalents (mcg/kg/min) will be collected from the intra-operative record and medical records to be quantified and compared.
Hemodynamic Stability - Systolic Blood pressure (SBP) [Intraoperative]
Amount of time the systolic blood pressure was above 130 mmHg or below 90 mmHg will be collected from the intra-operative record and medical records to be quantified and compared.
Hemodynamic Stability - Mean Arterial Blood pressure [Intra-operative]
Measurement of area under the 65 mmHg mean arterial blood pressure curve will be collected from the intraoperative record and medical records to be quantified and compared.
Hemodynamic Stability - Coefficient of variation of Mean Arterial BP [Intraoperative]
Coefficient of variation of mean arterial blood pressure will be collected from the intra-operative record and medical records to be quantified and compared.
Surgical and delirium markers - Neurofilament Light [Baseline, and till postoperative day 2]
Blood samples will collected, stored, and analyzed at three time points to measure changes in neurofilament light (NfL) through the perioperative course. Neurofilament light (pg/mL) will be quantified at baseline, postoperative day 1, and postoperative day 2. Neurofilament light is a bio-marker of axonal injury and higher values signify greater degree of axonal injury.
Surgical and delirium markers - Plasma Cortisol [Baseline, and till end of surgery]
Blood samples will collected, stored, and analyzed at three time points to measure changes in plasma cortisol through the peri-operative course. Plasma cortisol (mcg/dl) will be quantified at baseline, end of bypass, and end of surgery.

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.