Serum Neurofilament Light (NFL) in Surgery Under General Anaesthesia (GA) Compared to Surgery With Hypno-analgesia (Hyp)

Release of Serum Neurofilament Light (NFL), Biomarker of Neuronal Injury, in Surgery Under General Anaesthesia (GA) Compared to Surgery With Hypno-analgesia (Hyp): A Prospective, Non-inferiority Study

Experimental studies have shown that inhalational anesthetics may be neurotoxic by for example causing amyloid beta deposition. Otherwise a pre-clinical study reported an increase in tau phosphorylation with the use of propofol.

Whether anesthesia and surgery contribute to the development of long-term cognitive decline remains however controversial. A meta-analysis concluded that general anesthesia could increase the risk of postoperative cognitive decline (POCD) compared with regional or combined anesthesia but this was not shown for Postoperative delirium (POD). This conclusion should be interpreted with caution as these studies showed many shortcomings.

Currently no study has compared the release of Neurofilament Light, a biomarker of neuronal injury, in patients undergoing surgery under general anesthesia compared to surgery with Hypno-analgesia and thus without anesthetic drugs.

Study Overview

• Status: Recruiting
• Conditions: General Surgery
• Intervention / Treatment: Other: General anesthesia; Other: Hypno-analgesia

Detailed Description

POD and POCD are manifestations of cognitive dysfunction occurring in the perioperative period. Whether surgery and specifically anesthesia contribute to the development of perioperative cognitive dysfunctions is not clear.

Cell culture and animal studies have suggested detrimental effects of anesthetic exposure.1,2,3 Otherwise, it has been shown in animals that surgery plus anesthesia produced worse POCD than anesthesia alone.4 Proinflammatory cytokine levels increase during surgery. These elevated levels of inflammatory markers associated with the activation of microglial cells may induce neuroinflammation enhancing ongoing neurodegeneration.5 However, anesthetics may be capable of modulating inflammation and may alter the neuroinflammatory response.

Clinical studies associating the effects of general anesthesia with POCD and POD are conflicting.6 These varying results could be due to heterogeneity of patients' baseline status (e.g. cognitive status, education, associated diseases), type of surgery, as well as methods used to determine POCD and POD.

The use of serum neurobiomarkers, sensitive and specific for neuronal cell injury will address the hypothesis of general anesthesia neurotoxicity. Serum Neurofilament Light (NFL) is such a neurobiomarker.Currently no study has compared the release of Neurofilament Light, a biomarker of neuronal injury, in patients undergoing surgery under general anesthesia compared to surgery with Hypno-analgesia and thus without anesthetic drugs. Our hypothesis is that surgery under GA compared to hypnosis does not statistically increase the risk of neuronal injury as measured by serum NFL.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mona Momeni, MD, PhD; Phone Number: 003227647029; Email: mona.momeni@uclouvain.be

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Recruiting
    • Cliniques Universitaires Saint Luc
    • Principal Investigator: MONA MOMENI, M.D.; PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients undergoing thyroid or breast cancer surgery and necessitating one night of hospital stay

Exclusion Criteria:

• Renal insufficiency with a GFR < 30 mL/min
• Mammectomy
• Preoperative psychiatric problems
• Patients not speaking fluently French
• Patients at risk of postoperative hyperalgesia (Kalkman score > 4/15)
• Allergy to local anesthetics, NSAID and to Rocuronium
• Patients undergoing one day surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: General Anesthesia (GA); Patients undergoing thyroid or breast cancer surgery under general anesthesia	Other: General anesthesia; Surgery under general anesthesia with the use of propofol
Placebo Comparator: Hypno-analgesia (Hyp); Patients undergoing thyroid or breast cancer surgery under Hypno-analgesia; i.e.hypnosis combined with the use of analgesics.	Other: Hypno-analgesia; Surgery under Hypnosis session and analgesics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Neurofilament Light at first postoperative day (18 - 24 hours) postoperatively) between both groups	Comparison of postoperative serum Neurofilament Light between both groups	18 hours to 24 hours postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total postoperative analgesic consumption between both groups	Comparison of total consumed analgesics in the postoperative period	24 hours postoperatively
Postoperative C-reactive protein between both groups	Comparison of postoperative highest C-reactive protein between both groups	24 hours postoperatively
Postoperative serum Neurofilament Light in function of type of surgery	Analysis of postoperative serum Neurofilament Light in function of type of surgery	24 hours postoperatively
Comparison of postoperative Montreal Cognitive Assessment on a scale of 30 (higher scores are better) between both groups	Postoperative Montreal Cognitive Assessment	Day 8 to day 10
Postoperative serum Neurofilament Light at postoperative day 8 - 10	Analysis of postoperative serum Neurofilament Light between both groups	Day 8 to day 10
Quality of Recovery F15 questionnaire with 15 questions on a scale of 10 (higher scores are better) between both groups	Comparison of quality of recovery between both groups based on a validated questionnaire with 15 items	Day 8 to day 10

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frontal EEG analysis of patients under hypnosis	Analysis of raw frontal EEG power (in slow, delta, theta, alpha, beta and gamma band) from the depth-of-anesthesia monitor as a sub-analysis of this study	Intraoperatively

Collaborators and Investigators

• Sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
• Investigators: Principal Investigator: Mona Momeni, MD, PhD, Cliniques universitaires Saint-Luc

Publications and helpful links

General Publications

• Wan Y, Xu J, Ma D, Zeng Y, Cibelli M, Maze M. Postoperative impairment of cognitive function in rats: a possible role for cytokine-mediated inflammation in the hippocampus. Anesthesiology. 2007 Mar;106(3):436-43. doi: 10.1097/00000542-200703000-00007.
• Eckenhoff RG, Johansson JS, Wei H, Carnini A, Kang B, Wei W, Pidikiti R, Keller JM, Eckenhoff MF. Inhaled anesthetic enhancement of amyloid-beta oligomerization and cytotoxicity. Anesthesiology. 2004 Sep;101(3):703-9. doi: 10.1097/00000542-200409000-00019.
• Whittington RA, Virag L, Marcouiller F, Papon MA, El Khoury NB, Julien C, Morin F, Emala CW, Planel E. Propofol directly increases tau phosphorylation. PLoS One. 2011 Jan 31;6(1):e16648. doi: 10.1371/journal.pone.0016648.
• Mason SE, Noel-Storr A, Ritchie CW. The impact of general and regional anesthesia on the incidence of post-operative cognitive dysfunction and post-operative delirium: a systematic review with meta-analysis. J Alzheimers Dis. 2010;22 Suppl 3:67-79. doi: 10.3233/JAD-2010-101086.
• Wei H, Xie Z. Anesthesia, calcium homeostasis and Alzheimer's disease. Curr Alzheimer Res. 2009 Feb;6(1):30-5. doi: 10.2174/156720509787313934.
• Riedel B, Browne K, Silbert B. Cerebral protection: inflammation, endothelial dysfunction, and postoperative cognitive dysfunction. Curr Opin Anaesthesiol. 2014 Feb;27(1):89-97. doi: 10.1097/ACO.0000000000000032.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): February 28, 2023

Study Registration Dates

• First Submitted: July 22, 2020
• First Submitted That Met QC Criteria: July 31, 2020
• First Posted (Actual): August 5, 2020

Study Record Updates

• Last Update Posted (Actual): April 22, 2022
• Last Update Submitted That Met QC Criteria: April 21, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics
• Other Study ID Numbers: 2020/14MAI/273

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All data will be available at the moment of publication of results

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No