Perioperative Multimodal General AnesTHesia Focusing on Specific CNS Targets in Patients Undergoing carDiac surgERies

Pain Clinical Trial

— PATHFINDERII  

Official title:

Perioperative Multimodal General AnesTHesia Focusing on Specific CNS Targets in Patients Undergoing carDiac surgERies - the PATHFINDER II Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05279898
• Other study ID #: 2021-P-000889
• Status: Recruiting
• Phase: N/A
• Start date: February 28, 2023
• Est. completion date: November 2024

Study information

• Verified date: January 2024
• Source: Beth Israel Deaconess Medical Center
• Contact: Balachundhar Subramaniam, MD,MPH,FASA
• Phone: 617-667-2721
• Email: sadhgurucenter_research[@]bidmc.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In the PATHFINDER 2 trial, the study investigators will test the intraoperative EEG-guided multimodal general anesthesia (MMGA) management strategy in combination with a postoperative protocolized analgesic approach to:

1. reduce the incidence of perioperative neurocognitive dysfunction in cardiac surgical patients

2. ensure hemodynamic stability and decrease use of vasopressors in the operating rooms

3. reduce pain and opioid consumption postoperatively

Description:

The investigators propose to randomize (1:1) 70 patients undergoing cardiac surgery to the perioperative EEG-guided MMGA bundle (described in full below) or standard-of-care management based primarily on the use of sevoflurane for unconsciousness and intermittent doses of fentanyl and hydromorphone for antinociception.

The team will test the intraoperative EEG-guided MMGA management strategy in combination with a postoperative protocolized analgesic approach to reduce the postoperative increase of surgical and delirium markers, reduce intraoperative abnormalities in brain health monitoring, ensure hemodynamic stability and decreased use of vasopressors in the operating rooms and reduce pain and opioid consumption postoperatively. The team will also investigate whether EEG-guided MMGA strategy reduces the incidence of perioperative neurocognitive dysfunction in cardiac surgical patients. This approach will further individualize care and minimize the use of intraoperative vasopressor-inotropic dose, dose of anesthetic medications, and postoperative opioids given to each patient potentially preventing hemodynamic complications and post-operative cognitive dysfunction after surgery.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: November 2024
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Emergence Delirium
• Hemodynamic Instability
• Neurocognitive Dysfunction
• Pain
• Postoperative Delirium

Intervention

Device:
• EEG Monitoring
Perioperative monitoring, MMGA guided by EEG for intervention group

Drug:
• Ropivacaine
Intraoperative bilateral PIFB block with 20 mL of 0.2% Ropivicaine on either side of the sternum after anesthetic induction but before surgical incision (total of 40mL) PIFB on postoperative day 1 (provided they are extubated or getting ready to be extubated) to help with mobilization (for intervention group)
• Ketamine
Intraoperative infusion
• Remifentanil
Intraoperative infusion
• Dexmedetomidine
Intraoperative infusion
• Rocuronium
Intraoperative intermittent bolus
• Propofol
Intraoperative infusion

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Beth Israel Deaconess Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (13)

Berger M, Terrando N, Smith SK, Browndyke JN, Newman MF, Mathew JP. Neurocognitive Function after Cardiac Surgery: From Phenotypes to Mechanisms. Anesthesiology. 2018 Oct;129(4):829-851. doi: 10.1097/ALN.0000000000002194. — View Citation

Brown EN, Lydic R, Schiff ND. General anesthesia, sleep, and coma. N Engl J Med. 2010 Dec 30;363(27):2638-50. doi: 10.1056/NEJMra0808281. No abstract available. — View Citation

Brown EN, Pavone KJ, Naranjo M. Multimodal General Anesthesia: Theory and Practice. Anesth Analg. 2018 Nov;127(5):1246-1258. doi: 10.1213/ANE.0000000000003668. — View Citation

Hesse S, Kreuzer M, Hight D, Gaskell A, Devari P, Singh D, Taylor NB, Whalin MK, Lee S, Sleigh JW, Garcia PS. Association of electroencephalogram trajectories during emergence from anaesthesia with delirium in the postanaesthesia care unit: an early sign of postoperative complications. Br J Anaesth. 2019 May;122(5):622-634. doi: 10.1016/j.bja.2018.09.016. Epub 2018 Oct 25. Erratum In: Br J Anaesth. 2019 Aug;123(2):255. — View Citation

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. — View Citation

Mahanna-Gabrielli E, Schenning KJ, Eriksson LI, Browndyke JN, Wright CB, Culley DJ, Evered L, Scott DA, Wang NY, Brown CH 4th, Oh E, Purdon P, Inouye S, Berger M, Whittington RA, Price CC, Deiner S. State of the clinical science of perioperative brain health: report from the American Society of Anesthesiologists Brain Health Initiative Summit 2018. Br J Anaesth. 2019 Oct;123(4):464-478. doi: 10.1016/j.bja.2019.07.004. Epub 2019 Aug 19. Erratum In: Br J Anaesth. 2019 Dec;123(6):917. — View Citation

Maheshwari K, Ahuja S, Khanna AK, Mao G, Perez-Protto S, Farag E, Turan A, Kurz A, Sessler DI. Association Between Perioperative Hypotension and Delirium in Postoperative Critically Ill Patients: A Retrospective Cohort Analysis. Anesth Analg. 2020 Mar;130(3):636-643. doi: 10.1213/ANE.0000000000004517. — View Citation

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. — View Citation

Ni K, Cooter M, Gupta DK, Thomas J, Hopkins TJ, Miller TE, James ML, Kertai MD, Berger M. Paradox of age: older patients receive higher age-adjusted minimum alveolar concentration fractions of volatile anaesthetics yet display higher bispectral index values. Br J Anaesth. 2019 Sep;123(3):288-297. doi: 10.1016/j.bja.2019.05.040. Epub 2019 Jul 3. — View Citation

Nicolini F, Agostinelli A, Vezzani A, Manca T, Benassi F, Molardi A, Gherli T. The evolution of cardiovascular surgery in elderly patient: a review of current options and outcomes. Biomed Res Int. 2014;2014:736298. doi: 10.1155/2014/736298. Epub 2014 Apr 10. — View Citation

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. — View Citation

Volkow ND, Collins FS. The Role of Science in Addressing the Opioid Crisis. N Engl J Med. 2017 Jul 27;377(4):391-394. doi: 10.1056/NEJMsr1706626. Epub 2017 May 31. No abstract available. — View Citation

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. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Increase in plasma IL-6 levels	Total postoperative increase in IL-6 levels. The increase from baseline to postoperative days 1 and 2 will be quantified and compared between the two groups.	Baseline, postoperative day1 and day 2
Primary	Increase in plasma Neurofilament light levels	Total postoperative increase in Neurofilament light levels. The increase from baseline to postoperative days 1 and 2 will be quantified and compared between the two groups.	Baseline, postoperative day1 and day 2
Secondary	Concurrent EEG burst suppression and cerebral desaturation	Incidence and cumulative duration of Burst suppression (measured in minutes) will be extracted and quantified from the EEG and Cerebral oximetry records.	Intra-operative
Secondary	Opioid consumption and postoperative pain control	Total postoperative opioid dose, opioid consumption and pain scores will be quantified and compared between the two groups. The dose will be converted to morphine equivalents for standardization of the outcome and for ease of analysis. Pain will be assessed postoperatively by nursing staff every 4-8 hours and data will be collected form patient's electronic medical records	48- hours, Postoperative
Secondary	Burst suppression	3.) Duration of Burst suppression will be extracted and quantified from the EEG record and compared between both the groups.	Introperative
Secondary	Postoperative delirium	Incidence of Postoperative Delirium (POD) will be compared between both groups: POD will be diagnosed by our trained research members based on the Confusion Assessment Method (CAM) algorithm postoperatively until discharge.	Postoperative days till discharge
Secondary	Cognitive Function	Postoperative cognitive dysfunction at 1- and 6- months will be assessed with telephone version of the Montreal Cognitive Assessment (t-MoCA). It has a total score of 22 and higher score means better cognitive function.	Patients will be assessed for delirium at 1 month and 6 months following the date of surgery
Secondary	Hemodynamic Stability - Total Vasopressor Dose	Metrics of total vasopressor dose in norepinephrine equivalents (mcg/kg/min) will be collected from the intra-operative record and medical records to be quantified and compared.	Intra-operative
Secondary	Hemodynamic Stability - Systolic Blood pressure (SBP)	Amount of time the systolic blood pressure was above 130 mmHg or below 90 mmHg will be collected from the intra-operative record and medical records to be quantified and compared.	Intraoperative
Secondary	Hemodynamic Stability - Mean Arterial Blood pressure	Measurement of area under the 65 mmHg mean arterial blood pressure curve will be collected from the intraoperative record and medical records to be quantified and compared.	Intra-operative
Secondary	Hemodynamic Stability - Coefficient of variation of Mean Arterial BP	Coefficient of variation of mean arterial blood pressure will be collected from the intra-operative record and medical records to be quantified and compared.	Intraoperative
Secondary	Surgical and delirium markers - Plasma Cortisol	Blood samples will collected, stored, and analyzed at three time points to measure changes in plasma cortisol through the peri-operative course. Plasma cortisol (mcg/dl) will be quantified at baseline, end of bypass, and end of surgery.	Baseline, and till end of surgery