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

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ClinicalTrials.gov Identifier: NCT05279898
Recruitment Status : Recruiting
First Posted : March 15, 2022
Last Update Posted : March 9, 2023
Sponsor:
Information provided by (Responsible Party):
Balachundhar Subramaniam, Beth Israel Deaconess Medical Center

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

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 Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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
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
Actual Study Start Date : February 28, 2023
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : December 2023

Arm Intervention/treatment
Experimental: Multimodal General Anesthesia (MMGA Bundle) - EEG Guided
  1. Routine anesthetic induction
  2. 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)
  3. Ketamine (0.1 to 0.2 mg.kg/hr)
  4. Remifentanil (0.05-0.4 mcg/kg/min)
  5. Dexmedetomidine (0.2-0.5 mcg/kg/hr)
  6. Rocuronium intermittent bolus (TOF)
  7. Propofol infusion (15 to 200 mcg/kg/min)

Postop

  1. 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)
  2. Dexmedetomidine infusion (0.4-1.4 mcg/kg/hr) - EEG Guided; Infusion continued till extubation
  3. Propofol infusion may be added/used for sedation based on the treating physician's discretion
  4. PIFB on postoperative day 1 (provided they are extubated/getting ready to be extubated)(for intervention group)
  5. 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

  1. 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)
  2. Dexmedetomidine infusion (0.4-1.4 mcg/kg/hr) - EEG Guided; Infusion continued till extubation
  3. Propofol infusion may be added/used for sedation based on the treating physician's discretion
  4. Lidocaine patches
  5. Parasternal block (PIFB or Transversus Thoracic Plane Block) on Postoperative day 0 - currently incorporated into standard pain management after surgery based on physician discretion



Primary Outcome Measures :
  1. Increase in plasma IL-6 levels [ Time Frame: Baseline, postoperative day1 and day 2 ]
    Total postoperative increase in IL-6 levels. The increase from baseline to postoperative days 1 and 2 will be quantified and compared between the two groups.

  2. Increase in plasma Neurofilament light levels [ Time Frame: Baseline, postoperative day1 and day 2 ]
    Total postoperative increase in Neurofilament light levels. The increase from baseline to postoperative days 1 and 2 will be quantified and compared between the two groups.


Secondary Outcome Measures :
  1. Concurrent EEG burst suppression and cerebral desaturation [ Time Frame: Intra-operative ]
    Incidence and cumulative duration of Burst suppression (measured in minutes) will be extracted and quantified from the EEG and Cerebral oximetry records.

  2. Opioid consumption and postoperative pain control [ Time Frame: 48- hours, Postoperative ]
    Total postoperative opioid dose, opioid consumption and pain scores will be quantified and compared between the two groups. The dose will be converted to morphine equivalents for standardization of the outcome and for ease of analysis. Pain will be assessed postoperatively by nursing staff every 4-8 hours and data will be collected form patient's electronic medical records

  3. Burst suppression [ Time Frame: Introperative ]
    3.) Duration of Burst suppression will be extracted and quantified from the EEG record and compared between both the groups.

  4. Postoperative delirium [ Time Frame: Postoperative days till discharge ]
    Incidence of Postoperative Delirium (POD) will be compared between both groups: POD will be diagnosed by our trained research members based on the Confusion Assessment Method (CAM) algorithm postoperatively until discharge.

  5. Cognitive Function [ Time Frame: 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.

  6. Hemodynamic Stability - Total Vasopressor Dose [ Time Frame: 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.

  7. Hemodynamic Stability - Systolic Blood pressure (SBP) [ Time Frame: 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.

  8. Hemodynamic Stability - Mean Arterial Blood pressure [ Time Frame: 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.

  9. Hemodynamic Stability - Coefficient of variation of Mean Arterial BP [ Time Frame: 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.

  10. Surgical and delirium markers - Plasma Cortisol [ Time Frame: 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.



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Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05279898


Contacts
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Contact: Balachundhar Subramaniam, MD,MPH,FASA 617-667-2721 sadhgurucenter_research@bidmc.harvard.edu
Contact: Sepideh Hariri, Phd sadhgurucenter_research@bidmc.harvard.edu

Locations
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United States, Massachusetts
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02115
Contact: Balachundhar Subramaniam, MD,MPH    617-667-2721    sadhgurucenter_research@bidmc.harvard.edu   
Principal Investigator: Balachundhar Subramaniam, MD,MPH         
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Investigators
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Principal Investigator: Balachundhar Subramaniam, MD,MPH,FASA Beth Israel Deaconess Medical Center
Publications:

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Responsible Party: Balachundhar Subramaniam, Balachundhar Subramaniam MD MPH FASA, Principal Investigator, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT05279898    
Other Study ID Numbers: 2021-P-000889
First Posted: March 15, 2022    Key Record Dates
Last Update Posted: March 9, 2023
Last Verified: March 2023

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Cognitive Dysfunction
Neurocognitive Disorders
Mental Disorders
Cognition Disorders
Dexmedetomidine
Ketamine
Remifentanil
Propofol
Ropivacaine
Rocuronium
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anesthetics, Dissociative
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Anesthetics, Local