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The PATHFINDER Study: A Feasibility Trial

Early Phase 1
Completed
Conditions
Delirium
Coronary Artery Disease
Interventions
Registration Number
NCT04016740
Lead Sponsor
Beth Israel Deaconess Medical Center
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.

Detailed Description

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

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
22
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Multimodal General AnesthesiaEEG monitoringIntraoperative 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
Standard Practice with EEG monitoringEEG monitoringThe initial 2 patients will receive standard anesthesia practice and perioperative EEG monitoring will be recorded to learn the patterns associated with our standard practice.
Multimodal General AnesthesiaRopivacaineIntraoperative 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
Multimodal General AnesthesiaKetamineIntraoperative 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
Multimodal General AnesthesiaRemifentanilIntraoperative 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
Multimodal General AnesthesiaDexmedetomidineIntraoperative 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
Multimodal General AnesthesiaRocuroniumIntraoperative 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
Multimodal General AnesthesiaPropofolIntraoperative 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
Multimodal General AnesthesiaSevofluraneIntraoperative 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
Primary Outcome Measures
NameTimeMethod
Incidence of DeliriumParticipants will be followed for the duration of the hospital stay, an average of 5 days

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 Outcome Measures
NameTimeMethod
Time to extubationTime of ICU admission until time of extubation in ICU, an average of 6 hours

Time to extubation will be noted from ICU data

ICU/hospital length of stayTime of stay in the hospital until discharge to floor or rehab, an average of 5 days

Their stay in the hospital for the index admission

In-hospital complications7 days post-op on an average

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

Montreal Cognitive Assessment (MoCA)On the day of discharge, an average of 6 days

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.

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

Total duration of stay in ICU for the index admission

Follow up incidence of deliriumPatients will be assessed for delirium at 1 month and 6 months following the date of surgery

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.

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

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

Total opioid and supplemental analgesic consumption48 hours, post-operative

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

Trial Locations

Locations (1)

Beth Israel Deaconess Medical Center

🇺🇸

Boston, Massachusetts, United States

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