Clinical trial NCT04500236: Serum Neurofilament Light (NFL) in Surgery Under General Anaesthesia (GA) Compared to Surgery With Hypno-analgesia (Hyp)
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: General Surgery
Lead sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Sponsor class: OTHER
First posted: 2020-08-05
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Serum Neurofilament Light at first postoperative day (18 - 24 hours) postoperatively) between both groups
timeFrame: 18 hours to 24 hours postoperatively
Secondary outcomes:
measure: Total postoperative analgesic consumption between both groups
timeFrame: 24 hours postoperatively
measure: Postoperative C-reactive protein between both groups
timeFrame: 24 hours postoperatively
measure: Postoperative serum Neurofilament Light in function of type of surgery
timeFrame: 24 hours postoperatively
measure: Comparison of postoperative Montreal Cognitive Assessment on a scale of 30 (higher scores are better) between both groups
timeFrame: Day 8 to day 10
measure: Postoperative serum Neurofilament Light at postoperative day 8 - 10
timeFrame: Day 8 to day 10
measure: Quality of Recovery F15 questionnaire with 15 questions on a scale of 10 (higher scores are better) between both groups
timeFrame: Day 8 to day 10
Other outcomes:
measure: Frontal EEG analysis of patients under hypnosis
timeFrame: Intraoperatively
Locations:
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint Luc
Study officials:
affiliation: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
name: Mona Momeni, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: Wei H, Xie Z. Anesthesia, calcium homeostasis and Alzheimer's disease. Curr Alzheimer Res. 2009 Feb;6(1):30-5. doi: 10.2174/156720509787313934.
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. doi: 10.1097/00000542-200703000-00007.
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.
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.