The PATHFINDER Study: A Feasibility Trial

Sponsor

Beth Israel Deaconess Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT04016740

Collaborator

(none)

Enrollment

Location

Arms

10.6

Actual Duration (Months)

2.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease Delirium	Drug: Ropivacaine Drug: Ketamine Drug: Remifentanil Drug: Dexmedetomidine Drug: Rocuronium Drug: Propofol Drug: Sevoflurane Drug: Dexmedetomidine Drug: Propofol Device: EEG monitoring	Early Phase 1

Detailed Description

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

Study Design

Study Type:

Interventional

Actual Enrollment :

22 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

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

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

Perioperative Multimodal General Anesthesia Focusing on Specific CNS Targets in Patients Undergoing Cardiac Surgeries

Actual Study Start Date :

Aug 20, 2019

Actual Primary Completion Date :

Feb 19, 2020

Actual Study Completion Date :

Jul 7, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Multimodal General Anesthesia 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. Routine anesthetic induction 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 Ketamine (0.06 to 0.12 mg.kg/hr) Remifentanil (0.05-0.2 mcg/kg/min) Dexmedetomidine (0.2-1.0 mcg/kg/hr) Rocuronium intermittent bolus (TOF) Propofol infusion ± Sevoflurane titrated based on EEG monitoring Postoperative Standard pain management protocol Dexmedetomidine infusion 0.2-1.4 mcg/kg/hr (EEG guided) Infusion continued till extubation Propofol infusion may be added/used for sedation based on the treating physician's discretion	Drug: Ropivacaine Intraoperative bilateral PIFB block with 20 mL of 0.25% Ropivicaine on either side of the sternum after anesthetic induction but before surgical incision Drug: Ketamine Intraoperative infusion Drug: Remifentanil Intraoperative infusion Drug: Dexmedetomidine Intraoperative infusion Drug: Rocuronium Intraoperative intermittent bolus Drug: Propofol Intraoperative infusion Drug: Sevoflurane Intraoperative inhaled as needed Drug: Dexmedetomidine Post-operative infusion Drug: Propofol Post-operative infusion Device: EEG monitoring Perioperative monitoring
Other: Standard Practice with EEG monitoring 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 Perioperative monitoring

Arm

Intervention/Treatment

Experimental: Multimodal General Anesthesia

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. Routine anesthetic induction 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 Ketamine (0.06 to 0.12 mg.kg/hr) Remifentanil (0.05-0.2 mcg/kg/min) Dexmedetomidine (0.2-1.0 mcg/kg/hr) Rocuronium intermittent bolus (TOF) Propofol infusion ± Sevoflurane titrated based on EEG monitoring Postoperative Standard pain management protocol Dexmedetomidine infusion 0.2-1.4 mcg/kg/hr (EEG guided) Infusion continued till extubation Propofol infusion may be added/used for sedation based on the treating physician's discretion

Drug: Ropivacaine

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

Drug: Ketamine

Intraoperative infusion

Drug: Remifentanil

Intraoperative infusion

Drug: Dexmedetomidine

Intraoperative infusion

Drug: Rocuronium

Intraoperative intermittent bolus

Drug: Propofol

Intraoperative infusion

Drug: Sevoflurane

Intraoperative inhaled as needed

Drug: Dexmedetomidine

Post-operative infusion

Drug: Propofol

Post-operative infusion

Device: EEG monitoring

Perioperative monitoring

Other: Standard Practice with EEG monitoring

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

Perioperative monitoring

Outcome Measures

Primary Outcome Measures

Incidence of Delirium [Participants 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

Time to extubation [Time of ICU admission until time of extubation in ICU, an average of 6 hours]
Time to extubation will be noted from ICU data
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.
Pain scores [At 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 consumption [48 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.
ICU [Time 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
ICU/hospital length of stay [Time 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 complications [7 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
Follow up incidence of delirium [Patients 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years and Older

Sexes Eligible for Study:

All

Accepts 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.