The PATHFINDER Study: A Feasibility Trial

Coronary Artery Disease Clinical Trial

— PATHFINDER  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04016740
• Other study ID #: 2019P000407
• Status: Completed
• Phase: Early Phase 1
• Start date: August 20, 2019
• Est. completion date: July 7, 2020

Study information

• Verified date: January 2021
• Source: Beth Israel Deaconess Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: July 7, 2020
• Est. primary completion date: February 19, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Coronary Artery Disease
• Delirium

Intervention

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
• Ketamine
Intraoperative infusion
• Remifentanil
Intraoperative infusion
• Dexmedetomidine
Intraoperative infusion
• Rocuronium
Intraoperative intermittent bolus
• Propofol
Intraoperative infusion
• Sevoflurane
Intraoperative inhaled as needed
• Dexmedetomidine
Post-operative infusion
• Propofol
Post-operative infusion

Device:
• EEG monitoring
Perioperative monitoring

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 (23)

Arora RC, Djaiani G, Rudolph JL. Detection, Prevention, and Management of Delirium in the Critically Ill Cardiac Patient and Patients Who Undergo Cardiac Procedures. Can J Cardiol. 2017 Jan;33(1):80-87. doi: 10.1016/j.cjca.2016.08.020. Epub 2016 Oct 5. Review. — View Citation

Ballard C, Jones E, Gauge N, Aarsland D, Nilsen OB, Saxby BK, Lowery D, Corbett A, Wesnes K, Katsaiti E, Arden J, Amoako D, Prophet N, Purushothaman B, Green D. Optimised anaesthesia to reduce post operative cognitive decline (POCD) in older patients undergoing elective surgery, a randomised controlled trial. PLoS One. 2012;7(6):e37410. doi: 10.1371/journal.pone.0037410. Epub 2012 Jun 15. Erratum in: PLoS One. 2012;7(9). doi:10.1371/annotation/1cc38e55-23e8-44a5-ac2b-43c7b2a880f9. Amaoko, Derek [corrected to Amoako, Derek]. PLoS One. 2013;8(9). doi:10.1371/annotation/c0569644-bea1-4c38-af9a-75d1168e3142. — 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. Review. — 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. Review. — View Citation

Burkhart CS, Dell-Kuster S, Gamberini M, Moeckli A, Grapow M, Filipovic M, Seeberger MD, Monsch AU, Strebel SP, Steiner LA. Modifiable and nonmodifiable risk factors for postoperative delirium after cardiac surgery with cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 2010 Aug;24(4):555-9. doi: 10.1053/j.jvca.2010.01.003. Epub 2010 Mar 15. — View Citation

Chan MT, Cheng BC, Lee TM, Gin T; CODA Trial Group. BIS-guided anesthesia decreases postoperative delirium and cognitive decline. J Neurosurg Anesthesiol. 2013 Jan;25(1):33-42. doi: 10.1097/ANA.0b013e3182712fba. — View Citation

Delirium: prevention, diagnosis and management | Guidance and guidelines | NICE [Internet]. [cited 2018 Dec 20];Available from: https://www.nice.org.uk/guidance/cg103

Depth of anaesthesia monitors - Bispectral Index (BIS), E-Entropy and Narcotrend-Compact M | Guidance and guidelines | NICE [Internet]. [cited 2018 Dec 24];Available from: https://www.nice.org.uk/guidance/dg6

Jia Y, Jin G, Guo S, Gu B, Jin Z, Gao X, Li Z. Fast-track surgery decreases the incidence of postoperative delirium and other complications in elderly patients with colorectal carcinoma. Langenbecks Arch Surg. 2014 Jan;399(1):77-84. doi: 10.1007/s00423-013-1151-9. Epub 2013 Dec 13. — View Citation

Lurati Buse GA, Schumacher P, Seeberger E, Studer W, Schuman RM, Fassl J, Kasper J, Filipovic M, Bolliger D, Seeberger MD. Randomized comparison of sevoflurane versus propofol to reduce perioperative myocardial ischemia in patients undergoing noncardiac surgery. Circulation. 2012 Dec 4;126(23):2696-704. doi: 10.1161/CIRCULATIONAHA.112.126144. Epub 2012 Nov 7. — 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

McNicol E, Horowicz-Mehler N, Fisk RA, Bennett K, Gialeli-Goudas M, Chew PW, Lau J, Carr D; Americal Pain Society. Management of opioid side effects in cancer-related and chronic noncancer pain: a systematic review. J Pain. 2003 Jun;4(5):231-56. Review. — 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. English, Spanish. — View Citation

Papaioannou A, Fraidakis O, Michaloudis D, Balalis C, Askitopoulou H. The impact of the type of anaesthesia on cognitive status and delirium during the first postoperative days in elderly patients. Eur J Anaesthesiol. 2005 Jul;22(7):492-9. — View Citation

Pesonen A, Suojaranta-Ylinen R, Hammarén E, Kontinen VK, Raivio P, Tarkkila P, Rosenberg PH. Pregabalin has an opioid-sparing effect in elderly patients after cardiac surgery: a randomized placebo-controlled trial. Br J Anaesth. 2011 Jun;106(6):873-81. doi: 10.1093/bja/aer083. Epub 2011 Apr 6. — View Citation

Purdon PL, Sampson A, Pavone KJ, Brown EN. Clinical Electroencephalography for Anesthesiologists: Part I: Background and Basic Signatures. Anesthesiology. 2015 Oct;123(4):937-60. doi: 10.1097/ALN.0000000000000841. Review. — View Citation

Rudolph JL, Jones RN, Levkoff SE, Rockett C, Inouye SK, Sellke FW, Khuri SF, Lipsitz LA, Ramlawi B, Levitsky S, Marcantonio ER. Derivation and validation of a preoperative prediction rule for delirium after cardiac surgery. Circulation. 2009 Jan 20;119(2):229-36. doi: 10.1161/CIRCULATIONAHA.108.795260. Epub 2008 Dec 31. — View Citation

Sauër AM, Slooter AJ, Veldhuijzen DS, van Eijk MM, Devlin JW, van Dijk D. Intraoperative dexamethasone and delirium after cardiac surgery: a randomized clinical trial. Anesth Analg. 2014 Nov;119(5):1046-52. doi: 10.1213/ANE.0000000000000248. — View Citation

Stoppe C, Fahlenkamp AV, Rex S, Veeck NC, Gozdowsky SC, Schälte G, Autschbach R, Rossaint R, Coburn M. Feasibility and safety of xenon compared with sevoflurane anaesthesia in coronary surgical patients: a randomized controlled pilot study. Br J Anaesth. 2013 Sep;111(3):406-16. doi: 10.1093/bja/aet072. Epub 2013 Apr 11. — View Citation

Urban MK, Ya Deau JT, Wukovits B, Lipnitsky JY. Ketamine as an adjunct to postoperative pain management in opioid tolerant patients after spinal fusions: a prospective randomized trial. HSS J. 2008 Feb;4(1):62-5. doi: 10.1007/s11420-007-9069-9. Epub 2007 Dec 19. — View Citation

Volkow ND, Collins FS. The Role of Science in the Opioid Crisis. N Engl J Med. 2017 Nov 2;377(18):1798. doi: 10.1056/NEJMc1711494. — 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

Wilson PT, Spitzer RL. Major changes in psychiatric nomenclature. Reconciling existing psychiatric medical records with the new American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders. Hosp Community Psychiatry. 1968 Jun;19(6):169-74. — View Citation

* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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