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

General Surgery Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04500236
• Other study ID #: 2020/14MAI/273
• Status: Recruiting
• Phase: N/A
• Start date: September 1, 2020
• Est. completion date: February 28, 2023

Study information

• Verified date: April 2022
• Source: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
• Contact: Mona Momeni, MD, PhD
• Phone: 003227647029
• Email: mona.momeni[@]uclouvain.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: February 28, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• General Surgery

Intervention

Other:
• General anesthesia
Surgery under general anesthesia with the use of propofol
• Hypno-analgesia
Surgery under Hypnosis session and analgesics

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint Luc	Brussels

Sponsors (1)

Lead Sponsor	Collaborator
Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Country where clinical trial is conducted

Belgium, 

References & Publications (6)

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. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. — View Citation

Wei H, Xie Z. Anesthesia, calcium homeostasis and Alzheimer's disease. Curr Alzheimer Res. 2009 Feb;6(1):30-5. Review. — View Citation

Whittington RA, Virág 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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	Total postoperative analgesic consumption between both groups	Comparison of total consumed analgesics in the postoperative period	24 hours postoperatively
Secondary	Postoperative C-reactive protein between both groups	Comparison of postoperative highest C-reactive protein between both groups	24 hours postoperatively
Secondary	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
Secondary	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
Secondary	Postoperative serum Neurofilament Light at postoperative day 8 - 10	Analysis of postoperative serum Neurofilament Light between both groups	Day 8 to day 10
Secondary	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