Anesthetic Neurotoxicity: the Association Between General Anesthesia and the Level of Plasma Neurofilament Light (ANESTOX-2019)

A prospective controlled single centre study designed to determine the association between the exposure to anesthetic agents and the pre and postoperative changes in plasma Neurofilament Light levels, biomarkers of neurological injury, in patients with similar surgical intervention but different anesthetic techniques.

Secondary endpoints: Association between the changes in plasma Neurofilament Light levels and the development of post-operative neurocognitive disorders as acute delirium.

Study Overview

• Status: Unknown
• Conditions: General Anesthetics Toxicity
• Intervention / Treatment: Drug: General anesthetic

Detailed Description

Our intent is to evaluate the impact of the general anesthesia on the Central Nervous System, trying to minimize the surgical bias as much as possible. For this purpose, it is necessary to consider two groups of patients who undergo to similar surgical intervention, but with exposed to different anesthetic techniques. In particular, one group with local anesthesia and one group with general anesthesia.

The population sample will be composed of all patients who satisfy the inclusion and exclusion criteria and scheduled for the implantation of pacemaker (PM) - a procedure that require a local anesthesia - and the implantation of a cardioverter defibrillator (ICD), a cardiac resynchronization therapy pacemaker (CRT-P) and a cardiac resynchronization therapy defibrillator (CRT-D) at the Cardiocentro Ticino Lugano, procedures usually realize under general anesthesia.

The population sample will be divided in two groups: the non-exposed group, or control group, will be composed by the patients undergo PM implantation (without anesthesia) and the exposed group will be composed by the patients that undergo CRT/ICD implantation (general anesthesia).

Inclusion criteria:

• Same type of surgery: ICD,CRT-P, CRT-D and PM implantation;
• Age > 18 years old
• Patients who have expressed their consent to the participation of the study

Exclusion criteria:

- Patients with history of neurodegenerative diseases and neurocognitive disorders: the presence of these disorders could influence the level of the neuro-markers.

No change will be applied to normal clinical practice: we'll collect two blood samples, taken from routine samples already performed in our clinical practice, for the dosage of Neurofilament Light plasma levels before (t0) and after the procedure (t+24h).

Our intent is to compare the NF-L plasma levels delta (pre or t0 - postoperative or t24) between the exposed group (general anesthesia) and the not exposed group (local anesthesia).

Blood samples will be collected and stored in EDTA at the times specified above and anonymized. The samples, post anonymization, will be send to the University Hospital of Basel (Basel, Switzerland) where the plasma concentration of neurodegeneration markers will be blindly measured using the SiMoA neurology 4-plex assay.

The neurological status of the patients will be monitored daily during the first 2 days of the post-operative course in intensive care or in the ward. The screening of the phenomenon will be carried out by the nursing staff through the CAM-ICU and CAM (screening), in accordance with the internal protocols. The screening will be performed and documented at least three times a day or when the need is detected by the nursing staff. Any diagnosis of delirium will be certified by the neurologist.

Exams or procedures that differ from normal clinical practice will not be performed, except for the dosage of Neurofilament Light.

• Study Type: Observational
• Enrollment (Anticipated): 120

Contacts and Locations

Study Locations

• Switzerland
  • Canton Ticino
    • Lugano, Canton Ticino, Switzerland, 6900
      • Recruiting
      • Cardiocentro Ticino
      • Contact: Tiziano TC Cassina, MD; Phone Number: +41 (0)91 8053183; Email: tiziano.cassina@cardiocentro.org
      • Sub-Investigator: Stefania SB Buson, DR
      • Sub-Investigator: Michele MV Villa, RN

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The population sample will be composed of all patients who satisfy the inclusion and exclusion criteria and scheduled for the implantation of pacemaker (PM) - a procedure that require a local anesthesia - and the implantation of a cardioverter defibrillator (ICD), a cardiac resynchronization therapy pacemaker (CRT-P) and a cardiac resynchronization therapy defibrillator (CRT-D) at the Cardiocentro Ticino Lugano, procedures usually realize under general anesthesia.

Description

Inclusion Criteria:

• Same type of surgery: ICD,CRT-P, CRT-D and PM implantation;
• Age > 18 years old
• Patients who have expressed their consent to the participation of the study

Exclusion Criteria:

- Patients with history of neurodegenerative diseases and neurocognitive disorders: the presence of these disorders could influence the level of the neuro-markers.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Exposed group; The exposed group will be composed by the patients that undergo CRT/ICD implantation (general anesthesia).	Drug: General anesthetic; General anesthesia (propofol, fentanyl, sevorane, remifentanyl, rocuronium)
Not exposed group; The non-exposed group, or control group, will be composed by the patients undergo PM implantation (without anesthesia)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in plasma Neurofilament Light levels	Comparison of changes in plasma Neurofilament Light levels pre and postoperative in patients exposed and not exposed to general anesthesia.	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in plasma Neurofilament Light levels and acute postoperative neurocognitive disorders	Association between the changes in plasma Neurofilament Light levels and the development of post-operative neurocognitive disorders as acute delirium.	48 hours

Collaborators and Investigators

• Sponsor: Cardiocentro Ticino
• Investigators: Principal Investigator: Tiziano TC Cassina, Professor, Cardiocentro Ticino; Principal Investigator: Stefania SB Buson, Dr.ssa, Cardiocentro Ticino

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 11, 2019
• Primary Completion (ANTICIPATED): October 31, 2020
• Study Completion (ANTICIPATED): October 31, 2020

Study Registration Dates

• First Submitted: November 13, 2019
• First Submitted That Met QC Criteria: November 14, 2019
• First Posted (ACTUAL): November 15, 2019

Study Record Updates

• Last Update Posted (ACTUAL): November 18, 2019
• Last Update Submitted That Met QC Criteria: November 15, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: anesthesia; Neurofilament Light; Neurotoxicity
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Nervous System Diseases; Poisoning; Neurotoxicity Syndromes; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics; Anesthetics, General
• Other Study ID Numbers: 2019-01739

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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