The PATHFINDER Study: A Feasibility Trial

NCT04016740 | Completed Early Phase 1 FDA Drug

• 1 other identifier: 2019P000407
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to determine whether a rational strategy of EEG guided multimodal general anesthesia using target specific sedative and analgesics could result in enhanced recovery after anesthesia and surgery, decrease in postoperative delirium, and decrease in long term postoperative cognitive dysfunction up to 6 months following cardiac surgery.

Conditions

Coronary Artery Disease; Delirium

Keywords

Cardiopulmonary Bypass; Cardiac Surgery; analgesics

Outcome Measures

Primary Outcomes (1)

• Incidence of Delirium

  Incidence of delirium will be analyzed in patients treated with the multi-modal approach. Delirium will be defined as an acute change in pre-operative baseline condition with additional features of inattention and either disorganized thinking and altered loss of consciousness, as defined by the Confusion Assessment Method (CAM)Assessment Method (CAM) algorithm postoperatively until discharge.

  Participants will be followed for the duration of the hospital stay, an average of 5 days

Secondary Outcomes (8)

• Time to extubation

  Time of ICU admission until time of extubation in ICU, an average of 6 hours

• Montreal Cognitive Assessment (MoCA)

  On the day of discharge, an average of 6 days

• Pain scores

  At 4-8 hourly intervals every day until discharge, an average of 6 days

• Total opioid and supplemental analgesic consumption

  48 hours, post-operative

• ICU

  Time of ICU admission until time of discharge to hospital floor; through the hospital stay, an average of 5 days

Study Arms (2)

Multimodal General Anesthesia

EXPERIMENTAL

Intraoperative The anesthesiologists involved in this study will be trained to infer differences in anti-nociception, unconsciousness movement and changes during other perioperative events by monitoring EEG. They will also be trained in titrating hypnotic and nociceptic medications based on changes in EEG. 1. Routine anesthetic induction 2. Bilateral Pectoro-interfascial block (PIFB) with 20 mL of 0.25% ropivacaine on either side of the sternum after anesthetic induction but before surgical incision 3. Ketamine (0.06 to 0.12 mg.kg/hr) 4. Remifentanil (0.05-0.2 mcg/kg/min) 5. Dexmedetomidine (0.2-1.0 mcg/kg/hr) 6. Rocuronium intermittent bolus (TOF) 7. Propofol infusion ± Sevoflurane titrated based on EEG monitoring Postoperative 1. Standard pain management protocol 2. Dexmedetomidine infusion 0.2-1.4 mcg/kg/hr (EEG guided) 3. Infusion continued till extubation 4. Propofol infusion may be added/used for sedation based on the treating physician's discretion

Drug: Ropivacaine; Drug: Ketamine; Drug: Remifentanil; Drug: Dexmedetomidine; Drug: Rocuronium; Drug: Propofol; Drug: Sevoflurane; Device: EEG monitoring

Standard Practice with EEG monitoring

OTHER

The initial 2 patients will receive standard anesthesia practice and perioperative EEG monitoring will be recorded to learn the patterns associated with our standard practice.

Device: EEG monitoring

Interventions

Ropivacaine DRUG

Intraoperative bilateral PIFB block with 20 mL of 0.25% Ropivicaine on either side of the sternum after anesthetic induction but before surgical incision

Multimodal General Anesthesia

Ketamine DRUG

Intraoperative infusion

Multimodal General Anesthesia

Remifentanil DRUG

Intraoperative infusion

Multimodal General Anesthesia

Dexmedetomidine DRUG

Intraoperative infusion

Multimodal General Anesthesia

Rocuronium DRUG

Intraoperative intermittent bolus

Multimodal General Anesthesia

Propofol DRUG

Intraoperative infusion

Multimodal General Anesthesia

Sevoflurane DRUG

Intraoperative inhaled as needed

Multimodal General Anesthesia

EEG monitoring DEVICE

Perioperative monitoring

Multimodal General Anesthesia; Standard Practice with EEG monitoring

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, 02215, United States

Location

Related Publications (24)

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• 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.

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• 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.

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• Depth of anaesthesia monitors - Bispectral Index (BIS), E-Entropy and Narcotrend-Compact M | Guidance and guidelines | NICE [Internet]. [cited 2018 Dec 24];Available from: https://www.nice.org.uk/guidance/dg6

  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.

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• Rudolph JL, Jones RN, Levkoff SE, Rockett C, Inouye SK, Sellke FW, Khuri SF, Lipsitz LA, Ramlawi B, Levitsky S, Marcantonio ER. Derivation and validation of a preoperative prediction rule for delirium after cardiac surgery. Circulation. 2009 Jan 20;119(2):229-36. doi: 10.1161/CIRCULATIONAHA.108.795260. Epub 2008 Dec 31.

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• Burkhart CS, Dell-Kuster S, Gamberini M, Moeckli A, Grapow M, Filipovic M, Seeberger MD, Monsch AU, Strebel SP, Steiner LA. Modifiable and nonmodifiable risk factors for postoperative delirium after cardiac surgery with cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 2010 Aug;24(4):555-9. doi: 10.1053/j.jvca.2010.01.003. Epub 2010 Mar 15.

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• Delirium: prevention, diagnosis and management | Guidance and guidelines | NICE [Internet]. [cited 2018 Dec 20];Available from: https://www.nice.org.uk/guidance/cg103

  BACKGROUND

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• 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 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease; Delirium

Interventions

Ropivacaine; Ketamine; Remifentanil; Dexmedetomidine; Rocuronium; Propofol; Sevoflurane

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, 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; Methyl Ethers; Ethers; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated

Study Officials

• Balachundhar Subramaniam, MD, MPH

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Anesthesia

Model Details: 2 roll-in patients followed by 20 patients in the interventional model.

Study Record Dates

• First Submitted: July 9, 2019
• First Posted: July 11, 2019
• Study Start: August 20, 2019
• Primary Completion: February 19, 2020
• Study Completion: July 7, 2020
• Last Updated: January 28, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)