Anesthetic Methods and Gene Expression Profile

NCT03585647 | Completed

• 1 other identifier: 12630
• Study Type: observational
• Target: 99
• Locations: 1 country
• Sites: 1

Brief Summary

The study will analyze differentially regulated genes involved in oxidative stress and toxicology in peripheral blood mononuclear cells (PBMCs) of patients who underwent arthroplasty under three different anesthetic methods. The investigator hypothesized that anesthesia procedures trigger toxicity, thus inducing changes in the messenger ribonucleic acid (mRNA) profile. The results may provide a more profound understanding of the molecular mechanism of anesthesia and in overcoming the adverse effects arising from their use.

Conditions

Hip Arthroplasty

Keywords

General anesthesia; Regional anesthesia; Integrated anesthesia; Hip arthroplasty; Toxicological gene expression

Outcome Measures

Primary Outcomes (1)

• Changes of Gene expression profile from baseline at time points

  Effect of anesthesia techniques on the expression of genes indicative of stress and toxicity

  Gene expression will be evaluated in PBMCs at baseline (T0), up-30 min after surgery (T1) and on the third day (T2) after surgery.

Secondary Outcomes (1)

• Relationship between deregulated genes and hepatic/renal cytotoxicity from baseline at time points

  Biochemical analysis have been evaluated in blood collected at baseline (T0), up-30 min after surgery (T1) and on the third day (T2) after surgery.

Study Arms (3)

GA-group

Patients undergoing elective hip arthroplasty included in the GA-group received general anesthesia. GA was induced by intravenous fentanyl (1 mcg/kg) and propofol (2 mg/kg), followed by vecuronium bromide (0.1 mg/kg) to facilitate tracheal intubation, then GA was maintained using a 50% air/oxygen mixture and sevoflurane.The end-tidal concentration of sevoflurane was adjusted to maintain heart rate and blood pressure values within 20% of baseline. Mechanical ventilation was regulated to maintain the end-tidal carbon dioxide partial pressure ranging between 4.3 and 5.1 kilopascal.

Procedure: hip arthroplasty

RA-group

Patients undergoing elective hip arthroplasty included in the RA-group received regional anesthesia. Regional anaesthesia included continuous lumbar plexus block, performed by or under supervision of an experienced operator using a nerve stimulator (Stimulax, B. Braun) and Continued Peripheral Nerve Block Set. A total dose of 20 ml of 0.5% Levobupivacaine was administered at the time of catheter placement. Dural puncture was performed at the L3-L4 interspace using a 25-Gauge whitaker spinal needle (Becton-Dickinson, New Jersey, USA) with the midline approach using 3 ml of 0.5% Levobupivacaine.

Procedure: hip arthroplasty

IA-group

Patients undergoing elective hip arthroplasty included in the IA-group received integrated anesthesia. The patients received regional anaesthesia (lumbar plexus block + spinal anaesthesia) as described protocol. General anaesthesia was induced by propofol 1% and a laryngeal mask airway of appropriate size was inserted. General anaesthesia and mechanical ventilation were maintained as standard protocol.

Procedure: hip arthroplasty

Interventions

hip arthroplasty PROCEDURE

Hip replacement is a surgery for people with severe hip damage. The most common cause of damage is osteoarthritis.

Also known as: Hip prosthesis

GA-group; IA-group; RA-group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

patients undergoing elective hip arthroplasty

You may qualify if:

• \- American Society of Anesthesiologists Classification (ASA Class) = I-II.

You may not qualify if:

• American Society of Anesthesiologists Classification (ASA Class) \> III
• contraindication to spinal anaesthesia or lumbar catheter placement
• arterial hypertension not controlled by oral medication
• severe pulmonary
• cardiovascular disease
• renal disease
• hepatic disease
• cerebrovascular disease
• psychiatric diseases

Sponsors & Collaborators

• University of Bologna: lead

Study Sites (1)

Rizzoli Orthopaedic Institute

Bologna, 40136, Italy

Location

Related Publications (5)

• Alleva R, Tomasetti M, Solenghi MD, Stagni F, Gamberini F, Bassi A, Fornasari PM, Fanelli G, Borghi B. Lymphocyte DNA damage precedes DNA repair or cell death after orthopaedic surgery under general anaesthesia. Mutagenesis. 2003 Sep;18(5):423-8. doi: 10.1093/mutage/geg013.

  PMID: 12960410 RESULT

• Borghi B, Casati A, Iuorio S, Celleno D, Michael M, Serafini PL, Alleva R. Effect of different anesthesia techniques on red blood cell endogenous recovery in hip arthroplasty. J Clin Anesth. 2005 Mar;17(2):96-101. doi: 10.1016/j.jclinane.2004.05.005.

  PMID: 15809124 RESULT

• Nakazato K, Yoshida Y, Takemori K, Kobayashi K, Sakamoto A. Expressions of genes encoding drug-metabolizing enzymes are altered after sevoflurane, isoflurane, propofol or dexmedetomidine anesthesia. Biomed Res. 2009 Feb;30(1):17-24. doi: 10.2220/biomedres.30.17.

  PMID: 19265259 RESULT

• Ishikawa M, Tanaka S, Arai M, Genda Y, Sakamoto A. Differences in microRNA changes of healthy rat liver between sevoflurane and propofol anesthesia. Anesthesiology. 2012 Dec;117(6):1245-52. doi: 10.1097/ALN.0b013e3182746676.

  PMID: 23090150 RESULT

• Alleva R, Tognu A, Tomasetti M, Benassi MS, Pazzaglia L, van Oven H, Vigano E, De Simone N, Pacini I, Giannone S, Gagic S, Borghi R, Picone S, Borghi B. Effect of different anaesthetic techniques on gene expression profiles in patients who underwent hip arthroplasty. PLoS One. 2019 Jul 25;14(7):e0219113. doi: 10.1371/journal.pone.0219113. eCollection 2019.

  PMID: 31344051 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood samples will be obtained from all enrolled patients. The samples will be collected in heparin tubes and peripheral blood mononuclear cell (PBMC) fraction will be isolated for total RNA extraction.

MeSH Terms

Interventions

Arthroplasty, Replacement, Hip; Hip Prosthesis

Intervention Hierarchy (Ancestors)

Arthroplasty, Replacement; Arthroplasty; Orthopedic Procedures; Surgical Procedures, Operative; Plastic Surgery Procedures; Prosthesis Implantation; Joint Prosthesis; Prostheses and Implants; Equipment and Supplies

Study Officials

• Battista Borghi, MD

  Rizzoli Orthopaedic Institute

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD

Study Record Dates

• First Submitted: June 14, 2018
• First Posted: July 13, 2018
• Study Start: September 15, 2014
• Primary Completion: June 20, 2015
• Study Completion: November 30, 2016
• Last Updated: April 17, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)