Perioperative Multimodal General AnesTHesia Focusing on Specific CNS Targets in Patients Undergoing carDiac surgERies

NCT ID: NCT05279898

Last Updated: 2025-11-26

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-02-28

Study Completion Date

2024-12-31

Brief Summary

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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

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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.

Conditions

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Postoperative Delirium Hemodynamic Instability Pain Neurocognitive Dysfunction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Participants

Study Groups

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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

Group Type EXPERIMENTAL

EEG Monitoring

Intervention Type DEVICE

Perioperative monitoring, MMGA guided by EEG for intervention group

Ropivacaine

Intervention Type DRUG

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)

Ketamine

Intervention Type DRUG

Intraoperative infusion

Remifentanil

Intervention Type DRUG

Intraoperative infusion

Dexmedetomidine

Intervention Type DRUG

Intraoperative infusion

Rocuronium

Intervention Type DRUG

Intraoperative intermittent bolus

Propofol

Intervention Type DRUG

Intraoperative infusion

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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EEG Monitoring

Perioperative monitoring, MMGA guided by EEG for intervention group

Intervention Type DEVICE

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)

Intervention Type DRUG

Ketamine

Intraoperative infusion

Intervention Type DRUG

Remifentanil

Intraoperative infusion

Intervention Type DRUG

Dexmedetomidine

Intraoperative infusion

Intervention Type DRUG

Rocuronium

Intraoperative intermittent bolus

Intervention Type DRUG

Propofol

Intraoperative infusion

Intervention Type DRUG

Other Intervention Names

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Sedline Monitoring

Eligibility Criteria

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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.
Minimum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Beth Israel Deaconess Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Balachundhar Subramaniam

Balachundhar Subramaniam MD MPH FASA, Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Balachundhar Subramaniam, MD,MPH,FASA

Role: PRINCIPAL_INVESTIGATOR

Beth Israel Deaconess Medical Center

Locations

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Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Countries

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United States

References

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Brown EN, Lydic R, Schiff ND. General anesthesia, sleep, and coma. N Engl J Med. 2010 Dec 30;363(27):2638-50. doi: 10.1056/NEJMra0808281. No abstract available.

Reference Type BACKGROUND
PMID: 21190458 (View on PubMed)

Berger M, Terrando N, Smith SK, Browndyke JN, Newman MF, Mathew JP. Neurocognitive Function after Cardiac Surgery: From Phenotypes to Mechanisms. Anesthesiology. 2018 Oct;129(4):829-851. doi: 10.1097/ALN.0000000000002194.

Reference Type BACKGROUND
PMID: 29621031 (View on PubMed)

Brown EN, Pavone KJ, Naranjo M. Multimodal General Anesthesia: Theory and Practice. Anesth Analg. 2018 Nov;127(5):1246-1258. doi: 10.1213/ANE.0000000000003668.

Reference Type BACKGROUND
PMID: 30252709 (View on PubMed)

Volkow ND, Collins FS. The Role of Science in Addressing the Opioid Crisis. N Engl J Med. 2017 Jul 27;377(4):391-394. doi: 10.1056/NEJMsr1706626. Epub 2017 May 31. No abstract available.

Reference Type BACKGROUND
PMID: 28564549 (View on PubMed)

Mulier J. Opioid free general anesthesia: A paradigm shift? Rev Esp Anestesiol Reanim. 2017 Oct;64(8):427-430. doi: 10.1016/j.redar.2017.03.004. Epub 2017 Apr 18. No abstract available. English, Spanish.

Reference Type BACKGROUND
PMID: 28431750 (View on PubMed)

MacKenzie KK, Britt-Spells AM, Sands LP, Leung JM. Processed Electroencephalogram Monitoring and Postoperative Delirium: A Systematic Review and Meta-analysis. Anesthesiology. 2018 Sep;129(3):417-427. doi: 10.1097/ALN.0000000000002323.

Reference Type BACKGROUND
PMID: 29912008 (View on PubMed)

Wildes TS, Mickle AM, Ben Abdallah A, Maybrier HR, Oberhaus J, Budelier TP, Kronzer A, McKinnon SL, Park D, Torres BA, Graetz TJ, Emmert DA, Palanca BJ, Goswami S, Jordan K, Lin N, Fritz BA, Stevens TW, Jacobsohn E, Schmitt EM, Inouye SK, Stark S, Lenze EJ, Avidan MS; ENGAGES Research Group. Effect of Electroencephalography-Guided Anesthetic Administration on Postoperative Delirium Among Older Adults Undergoing Major Surgery: The ENGAGES Randomized Clinical Trial. JAMA. 2019 Feb 5;321(5):473-483. doi: 10.1001/jama.2018.22005.

Reference Type BACKGROUND
PMID: 30721296 (View on PubMed)

Nicolini F, Agostinelli A, Vezzani A, Manca T, Benassi F, Molardi A, Gherli T. The evolution of cardiovascular surgery in elderly patient: a review of current options and outcomes. Biomed Res Int. 2014;2014:736298. doi: 10.1155/2014/736298. Epub 2014 Apr 10.

Reference Type BACKGROUND
PMID: 24812629 (View on PubMed)

Mahanna-Gabrielli E, Schenning KJ, Eriksson LI, Browndyke JN, Wright CB, Culley DJ, Evered L, Scott DA, Wang NY, Brown CH 4th, Oh E, Purdon P, Inouye S, Berger M, Whittington RA, Price CC, Deiner S. State of the clinical science of perioperative brain health: report from the American Society of Anesthesiologists Brain Health Initiative Summit 2018. Br J Anaesth. 2019 Oct;123(4):464-478. doi: 10.1016/j.bja.2019.07.004. Epub 2019 Aug 19.

Reference Type BACKGROUND
PMID: 31439308 (View on PubMed)

Maheshwari K, Ahuja S, Khanna AK, Mao G, Perez-Protto S, Farag E, Turan A, Kurz A, Sessler DI. Association Between Perioperative Hypotension and Delirium in Postoperative Critically Ill Patients: A Retrospective Cohort Analysis. Anesth Analg. 2020 Mar;130(3):636-643. doi: 10.1213/ANE.0000000000004517.

Reference Type BACKGROUND
PMID: 31725024 (View on PubMed)

Ni K, Cooter M, Gupta DK, Thomas J, Hopkins TJ, Miller TE, James ML, Kertai MD, Berger M. Paradox of age: older patients receive higher age-adjusted minimum alveolar concentration fractions of volatile anaesthetics yet display higher bispectral index values. Br J Anaesth. 2019 Sep;123(3):288-297. doi: 10.1016/j.bja.2019.05.040. Epub 2019 Jul 3.

Reference Type BACKGROUND
PMID: 31279479 (View on PubMed)

Hesse S, Kreuzer M, Hight D, Gaskell A, Devari P, Singh D, Taylor NB, Whalin MK, Lee S, Sleigh JW, Garcia PS. Association of electroencephalogram trajectories during emergence from anaesthesia with delirium in the postanaesthesia care unit: an early sign of postoperative complications. Br J Anaesth. 2019 May;122(5):622-634. doi: 10.1016/j.bja.2018.09.016. Epub 2018 Oct 25.

Reference Type BACKGROUND
PMID: 30915984 (View on PubMed)

Shanker A, Abel JH, Narayanan S, Mathur P, Work E, Schamberg G, Sharkey A, Bose R, Rangasamy V, Senthilnathan V, Brown EN, Subramaniam B. Perioperative Multimodal General Anesthesia Focusing on Specific CNS Targets in Patients Undergoing Cardiac Surgeries: The Pathfinder Feasibility Trial. Front Med (Lausanne). 2021 Oct 14;8:719512. doi: 10.3389/fmed.2021.719512. eCollection 2021.

Reference Type BACKGROUND
PMID: 34722563 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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2021-P-000889

Identifier Type: -

Identifier Source: org_study_id

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