The PATHFINDER Study: A Feasibility Trial

Study Overview
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Brief Summary
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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
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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

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

Conditions
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Coronary Artery Disease, Delirium

Intervention / Treatment
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* Drug: Ropivacaine
* Drug: Ketamine
* Drug: Remifentanil
* Drug: Dexmedetomidine
* Drug: Rocuronium
* Drug: Propofol
* Drug: Sevoflurane
* Drug: Dexmedetomidine
* Drug: Propofol
* Device: EEG monitoring


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: 2 roll-in patients followed by 20 patients in the interventional model.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multimodal General Anesthesia<br>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<br>* Intraoperative bilateral PIFB block with 20 mL of 0.25% Ropivicaine on either side of the sternum after anesthetic induction but before surgical incision<br>Drug: Ketamine<br>* Intraoperative infusion<br>Drug: Remifentanil<br>* Intraoperative infusion<br>Drug: Dexmedetomidine<br>* Intraoperative infusion<br>Drug: Rocuronium<br>* Intraoperative intermittent bolus<br>Drug: Propofol<br>* Intraoperative infusion<br>Drug: Sevoflurane<br>* Intraoperative inhaled as needed<br>Drug: Dexmedetomidine<br>* Post-operative infusion<br>Drug: Propofol<br>* Post-operative infusion<br>Device: EEG monitoring<br>* Perioperative monitoring<br>|
| Other: Standard Practice with EEG monitoring<br>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<br>* Perioperative monitoring<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to extubation | Time to extubation will be noted from ICU data | Time of ICU admission until time of extubation in ICU, an average of 6 hours | 
| Montreal Cognitive Assessment (MoCA) | 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. | On the day of discharge, an average of 6 days | 
| Pain scores | Patient reported pain scores on a scale from 0-10 (0 no pain,10 extreme pain), until discharge for the index admission. | At 4-8 hourly intervals every day until discharge, an average of 6 days | 
| Total opioid and supplemental analgesic consumption | The total opioid dosage and supplemental analgesic dosage received in the first 48 hours postoperatively will be abstracted from the medical record. | 48 hours, post-operative | 
| ICU | Total duration of stay in ICU for the index admission | Time of ICU admission until time of discharge to hospital floor; through the hospital stay, an average of 5 days | 
| ICU/hospital length of stay | Their stay in the hospital for the index admission | Time of stay in the hospital until discharge to floor or rehab, an average of 5 days | 
| In-hospital complications | stroke, myocardial infarction (MI), acute kidney injury, pneumonia, reintubation, congestive heart failure, sepsis, reopening of sternum and all-cause mortality | 7 days post-op on an average | 
| Follow up incidence of delirium | 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. | Patients will be assessed for delirium at 1 month and 6 months following the date of surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiopulmonary Bypass, Cardiac Surgery, analgesics