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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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General Surgery

Intervention / Treatment
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* Other: General anesthesia
* Other: Hypno-analgesia


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |