The PATHFINDER Study: A Feasibility Trial

Ketamine

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.

Intervention / Treatment

2 roll-in patients followed by 20 patients in the interventional model.
  • 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
  • Ketamine (DRUG)
    Intraoperative infusion
  • Remifentanil (DRUG)
    Intraoperative infusion
  • Dexmedetomidine (DRUG)
    Post-operative infusion
  • Rocuronium (DRUG)
    Intraoperative intermittent bolus
  • Propofol (DRUG)
    Post-operative infusion
  • Sevoflurane (DRUG)
    Intraoperative inhaled as needed
  • EEG monitoring (DEVICE)
    Perioperative monitoring

Condition or Disease

  • Coronary Artery Disease
  • Delirium

Phase

  • Early Phase 1

    • Study Design

    Study type: INTERVENTIONAL
    Status: Completed
    Study results: No Results Available
    Age: 60 Years and older   (Adult, Older Adult)
    Enrollment: 22 (ACTUAL)
    Funded by: Other
    Allocation: Non-Randomized
    Primary Purpose: Other

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    Clinical Trial Dates

    Start date: Aug 20, 2019 ACTUAL
    Primary Completion: Feb 19, 2020 ACTUAL
    Completion Date: Jul 07, 2020 ACTUAL
    Study First Posted: Jul 11, 2019 ACTUAL
    Results First Posted: Aug 31, 2020
    Last Updated: Jan 27, 2021

    Sponsors / Collaborators

    Lead Sponsor: Beth Israel Deaconess Medical Center
    Responsible Party: Balachundhar Subramaniam

    Location

    Boston, Massachusetts, USA

    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.

    Specific Aim 1: The feasibility of implementing multimodal general anesthesia strategy in the Operating Rooms (OR) Specific Aim 2: The feasibility of implementing EEG guided sedation until extubation in the Intensive Care Unit (ICU) Specific Aim 3: The enhancement of recovery after surgery (shorter ventilation time, ICU stay, hospital length of stay) Specific Aim 4: To estimate the effect size of decrease in postoperative day (POD) and postoperative cognitive dysfunction (POCD) to power future large randomized trials

    Participant Groups

    • 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

    • 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.

    Eligibility Criteria

    Sex: All
    Minimum Age: 60
    Age Groups: Adult / Older Adult
    Healthy Volunteers: Yes

    Inclusion Criteria:

    1. Age ≥ 60 years
    2. 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:

    1. Preoperative left ventricular ejection fraction (LVEF) \<30%
    2. Emergent surgery
    3. Non-English speaking
    4. Cognitive impairment as defined by total MoCA score \< 10
    5. Currently enrolled in another interventional study that could impact the primary outcome, as determined by the PI
    6. Significant visual impairment
    7. 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)
    8. Hypersensitivity to any of the study medications
    9. 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
    10. Liver dysfunction (liver enzymes \> 4 times the baseline, all patients will have a baseline liver function test evaluation), history and examination suggestive of jaundice.

    Primary Outcomes

    • 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.

    Secondary Outcomes

    • Time to extubation will be noted from ICU data

    • MoCA scores (total possible score is 30 points; a score of 26 or above is considered normal) at discharge will be reported in order to assess the occurrence of postoperative cognitive decline. Study staff trained in administering the assessments will collect the data.

    • Patient reported pain scores on a scale from 0-10 (0 no pain,10 extreme pain), until discharge for the index admission.

    • The total opioid dosage and supplemental analgesic dosage received in the first 48 hours postoperatively will be abstracted from the medical record.

    • Total duration of stay in ICU for the index admission

    • Their stay in the hospital for the index admission

    • stroke, myocardial infarction (MI), acute kidney injury, pneumonia, reintubation, congestive heart failure, sepsis, reopening of sternum and all-cause mortality

    • The follow up incidence of delirium will be analyzed at 1 month and 6 months after discharge. 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 MoCA/t-MoCA.

    More Details

    NCT Number: NCT04016740
    Acronym: PATHFINDER
    Other IDs: 2019P000407
    Study URL: https://clinicaltrials.gov/study/NCT04016740
    Last updated: Sep 29, 2023