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

NCT05279898 | Completed Results FDA Device

• 1 other identifier: 2021-P-000889
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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

Conditions

Postoperative Delirium; Hemodynamic Instability; Pain; Neurocognitive Dysfunction

Outcome Measures

Primary Outcomes (2)

• Increase in Plasma IL-6 Levels

  Plasma interleukin-6 (IL-6) levels will be measured at baseline, postoperative day 1, and postoperative day 2. The change in IL-6 concentration from baseline to each postoperative time point will be calculated and compared between the study groups.

  Baseline, postoperative day 1, and postoperative day 2

• Increase in Plasma Neurofilament Light Levels

  Plasma neurofilament light (NfL) levels will be measured at baseline, postoperative day 1, and postoperative day 2. The change in NfL concentration from baseline to each postoperative time point will be calculated and compared between the study groups.

  Baseline, postoperative day 1, and postoperative day 2

Secondary Outcomes (6)

• Opioid Consumption

  From end of surgery to 48 hours postoperatively

• Pain Scores

  From end of surgery to 48 hours postoperatively

• Burst Suppression

  intraoperative period, from anesthetic induction until the end of surgery

• Postoperative Delirium

  From postoperative day 1 until hospital discharge, an average of 4 days

• Cognitive Function

  Patients will be assessed for cognitive function at 1 month and 6 months following the date of surgery

Study Arms (2)

Multimodal General Anesthesia (MMGA Bundle) - EEG Guided

EXPERIMENTAL

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; Drug: Ropivacaine; Drug: Ketamine; Drug: Remifentanil; Drug: Dexmedetomidine; Drug: Rocuronium; Drug: Propofol

Standard of Care/Control

NO INTERVENTION

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

Interventions

EEG Monitoring DEVICE

Perioperative monitoring, MMGA guided by EEG for intervention group

Also known as: Sedline Monitoring

Multimodal General Anesthesia (MMGA Bundle) - EEG Guided

Ropivacaine 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)

Multimodal General Anesthesia (MMGA Bundle) - EEG Guided

Ketamine DRUG

Intraoperative infusion

Multimodal General Anesthesia (MMGA Bundle) - EEG Guided

Remifentanil DRUG

Intraoperative infusion

Multimodal General Anesthesia (MMGA Bundle) - EEG Guided

Dexmedetomidine DRUG

Intraoperative infusion

Multimodal General Anesthesia (MMGA Bundle) - EEG Guided

Rocuronium DRUG

Intraoperative intermittent bolus

Multimodal General Anesthesia (MMGA Bundle) - EEG Guided

Propofol DRUG

Intraoperative infusion

Multimodal General Anesthesia (MMGA Bundle) - EEG Guided

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Related Publications (13)

• 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.

  PMID: 21190458 BACKGROUND

• 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.

  PMID: 29621031 BACKGROUND

• 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.

  PMID: 30252709 BACKGROUND

• 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.

  PMID: 28564549 BACKGROUND

• 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.

  PMID: 28431750 BACKGROUND

• 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.

  PMID: 29912008 BACKGROUND

• 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.

  PMID: 30721296 BACKGROUND

• 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.

  PMID: 24812629 BACKGROUND

• 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.

  PMID: 31439308 BACKGROUND

• 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.

  PMID: 31725024 BACKGROUND

• 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.

  PMID: 31279479 BACKGROUND

• 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.

  PMID: 30915984 BACKGROUND

• 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.

  PMID: 34722563 BACKGROUND

MeSH Terms

Conditions

Emergence Delirium; Pain; Cognition Disorders

Interventions

Ropivacaine; Ketamine; Remifentanil; Dexmedetomidine; Rocuronium; Propofol

Condition Hierarchy (Ancestors)

Delirium; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Propionates; Acids, Acyclic; Carboxylic Acids; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Imidazoles; Azoles; Androstanols; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic

Limitations and Caveats

This single-center trial enrolled a small sample and was not powered for clinical outcomes such as delirium. Some biomarker and EEG data were missing or artifact-limited, and anesthesia depth may have differed between groups. These factors may limit generalizability and interpretation of results.

Results Point of Contact

• Title: Balachundhar Subramaniam
• Organization: Beth Israel Deaconess Medical Center

bsubrama@bidmc.harvard.edu

617-278-8000

Study Officials

• Balachundhar Subramaniam, MD,MPH,FASA

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Balachundhar Subramaniam MD MPH FASA, Principal Investigator

Model Details: 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

Study Record Dates

• First Submitted: February 14, 2022
• First Posted: March 15, 2022
• Study Start: February 28, 2023
• Primary Completion: June 30, 2024
• Study Completion: December 31, 2024
• Last Updated: November 26, 2025
• Results First Posted: November 26, 2025

Record last verified: 2025-11

Locations

US (1)