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

Primary Purpose

Postoperative Delirium, Hemodynamic Instability, Pain

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
EEG Monitoring
Ropivacaine
Ketamine
Remifentanil
Dexmedetomidine
Rocuronium
Propofol
Sponsored by
Beth Israel Deaconess Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Postoperative Delirium

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Beth Israel Deaconess Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Multimodal General Anesthesia (MMGA Bundle) - EEG Guided

Standard of Care/Control

Arm Description

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

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 Parasternal block (PIFB or Transversus Thoracic Plane Block) on Postoperative day 0 - currently incorporated into standard pain management after surgery based on physician discretion

Outcomes

Primary Outcome Measures

Increase in plasma IL-6 levels
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.
Increase in plasma Neurofilament light levels
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

Concurrent EEG burst suppression and cerebral desaturation
Incidence and cumulative duration of Burst suppression (measured in minutes) will be extracted and quantified from the EEG and Cerebral oximetry records.
Opioid consumption and postoperative pain control
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
Burst suppression
3.) Duration of Burst suppression will be extracted and quantified from the EEG record and compared between both the groups.
Postoperative delirium
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.
Cognitive Function
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.
Hemodynamic Stability - Total Vasopressor Dose
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)
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
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
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 - Plasma Cortisol
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.

Full Information

First Posted
February 14, 2022
Last Updated
August 8, 2023
Sponsor
Beth Israel Deaconess Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT05279898
Brief Title
Perioperative Multimodal General AnesTHesia Focusing on Specific CNS Targets in Patients Undergoing carDiac surgERies
Acronym
PATHFINDERII
Official Title
Perioperative Multimodal General AnesTHesia Focusing on Specific CNS Targets in Patients Undergoing carDiac surgERies - the PATHFINDER II Study
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 28, 2023 (Actual)
Primary Completion Date
September 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Beth Israel Deaconess Medical Center

4. Oversight

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
Data Monitoring Committee
No

5. 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: reduce the incidence of perioperative neurocognitive dysfunction in cardiac surgical patients ensure hemodynamic stability and decrease use of vasopressors in the operating rooms 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Postoperative Delirium, Hemodynamic Instability, Pain, Neurocognitive Dysfunction

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
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
Participant
Allocation
Randomized
Enrollment
70 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Multimodal General Anesthesia (MMGA Bundle) - EEG Guided
Arm Type
Experimental
Arm Description
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
Arm Title
Standard of Care/Control
Arm Type
No Intervention
Arm Description
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 Parasternal block (PIFB or Transversus Thoracic Plane Block) on Postoperative day 0 - currently incorporated into standard pain management after surgery based on physician discretion
Intervention Type
Device
Intervention Name(s)
EEG Monitoring
Other Intervention Name(s)
Sedline Monitoring
Intervention Description
Perioperative monitoring, MMGA guided by EEG for intervention group
Intervention Type
Drug
Intervention Name(s)
Ropivacaine
Intervention Description
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
Intervention Name(s)
Ketamine
Intervention Description
Intraoperative infusion
Intervention Type
Drug
Intervention Name(s)
Remifentanil
Intervention Description
Intraoperative infusion
Intervention Type
Drug
Intervention Name(s)
Dexmedetomidine
Intervention Description
Intraoperative infusion
Intervention Type
Drug
Intervention Name(s)
Rocuronium
Intervention Description
Intraoperative intermittent bolus
Intervention Type
Drug
Intervention Name(s)
Propofol
Intervention Description
Intraoperative infusion
Primary Outcome Measure Information:
Title
Increase in plasma IL-6 levels
Description
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.
Time Frame
Baseline, postoperative day1 and day 2
Title
Increase in plasma Neurofilament light levels
Description
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.
Time Frame
Baseline, postoperative day1 and day 2
Secondary Outcome Measure Information:
Title
Concurrent EEG burst suppression and cerebral desaturation
Description
Incidence and cumulative duration of Burst suppression (measured in minutes) will be extracted and quantified from the EEG and Cerebral oximetry records.
Time Frame
Intra-operative
Title
Opioid consumption and postoperative pain control
Description
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
Time Frame
48- hours, Postoperative
Title
Burst suppression
Description
3.) Duration of Burst suppression will be extracted and quantified from the EEG record and compared between both the groups.
Time Frame
Introperative
Title
Postoperative delirium
Description
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.
Time Frame
Postoperative days till discharge
Title
Cognitive Function
Description
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.
Time Frame
Patients will be assessed for delirium at 1 month and 6 months following the date of surgery
Title
Hemodynamic Stability - Total Vasopressor Dose
Description
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.
Time Frame
Intra-operative
Title
Hemodynamic Stability - Systolic Blood pressure (SBP)
Description
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.
Time Frame
Intraoperative
Title
Hemodynamic Stability - Mean Arterial Blood pressure
Description
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.
Time Frame
Intra-operative
Title
Hemodynamic Stability - Coefficient of variation of Mean Arterial BP
Description
Coefficient of variation of mean arterial blood pressure will be collected from the intra-operative record and medical records to be quantified and compared.
Time Frame
Intraoperative
Title
Surgical and delirium markers - Plasma Cortisol
Description
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.
Time Frame
Baseline, and till end of surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Balachundhar Subramaniam, MD,MPH,FASA
Phone
617-667-2721
Email
sadhgurucenter_research@bidmc.harvard.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Sepideh Hariri, Phd
Email
sadhgurucenter_research@bidmc.harvard.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Balachundhar Subramaniam, MD,MPH,FASA
Organizational Affiliation
Beth Israel Deaconess Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Balachundhar Subramaniam, MD,MPH
Phone
617-667-2721
Email
sadhgurucenter_research@bidmc.harvard.edu
First Name & Middle Initial & Last Name & Degree
Balachundhar Subramaniam, MD,MPH

12. IPD Sharing Statement

Citations:
PubMed Identifier
21190458
Citation
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.
Results Reference
background
PubMed Identifier
29621031
Citation
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.
Results Reference
background
PubMed Identifier
30252709
Citation
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.
Results Reference
background
PubMed Identifier
28564549
Citation
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.
Results Reference
background
PubMed Identifier
28431750
Citation
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.
Results Reference
background
PubMed Identifier
29912008
Citation
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.
Results Reference
background
PubMed Identifier
30721296
Citation
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.
Results Reference
background
PubMed Identifier
24812629
Citation
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.
Results Reference
background
PubMed Identifier
31439308
Citation
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. Erratum In: Br J Anaesth. 2019 Dec;123(6):917.
Results Reference
background
PubMed Identifier
31725024
Citation
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.
Results Reference
background
PubMed Identifier
31279479
Citation
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.
Results Reference
background
PubMed Identifier
30915984
Citation
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. Erratum In: Br J Anaesth. 2019 Aug;123(2):255.
Results Reference
background
PubMed Identifier
34722563
Citation
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.
Results Reference
background

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

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