Neurotoxicity of Spinal Anesthesia With Ropivacaine and Bupivacaine (BuRoNe)

Inflammatory Mediators, Neural Tissue Injury Markers and the Markers of Oxidative Stress in the CSF of Patients Undergoing Spinal Anesthesia With Ropivacaine and Bupivacaine

Consenting patients, scheduled for orthopaedic surgery under spinal anesthesia will be randomly assigned (1:1) to receive ropivacaine or bupivacaine as a single shot before the start of surgery, followed by bolus doses of the same local anesthetic as required during the surgery, and continuous infusion of the same local anesthetic for 24 hours postoperatively.

Primary Outcome Measures: Evaluation of changes in concentrations of glutamate in the cerebrospinal fluid and in the blood. Secondary outcomes: : Evaluation of changes in concentrations of selected mediators of inflammatory response (IL-1β, IL-6, TNF and others) and selected chemokines as markers of the glia damage.

Hemodynamic stability during the surgery, and efficacy of postoperative analgesia will be also evaluated.

Study Overview

• Status: Unknown
• Conditions: Anesthesia; Adverse Effect, Spinal and Epidural; Anaesthetic Complication Neurological
• Intervention / Treatment: Drug: Ropivacaine; Drug: Bupivacaine

Detailed Description

With the approval from the Bioethical Committee of the University of Rzeszow, informed written consent will be obtained from all patients.

A sample size of 60 patients was calculated to obtain at least 25% reduction of glutamate concentration in the cerebrospinal fluid in the ropivacaine group with 0,05 significance and power of 0,8.

Consenting patients, scheduled for orthopaedic surgery under spinal anesthesia will be randomly (1:1) assigned using closed envelopes to receive intrathecally ropivacaine or bupivacaine as a single shot before the start of surgery, followed by bolus doses of the same local anesthetic as required during the surgery, and continuous infusion of the same local anesthetic for 24 h for postoperative pain relief. All block will be performed in the sitting position, and the drug will be administered in supine position through the catheter in the intrathecal space. Blood and cerebrospinal fluid samples will be drawn at predetermined time intervals centrifuged as required and frosen in -70deg C until analysis.

Eligibility Ages eligible for study 18 years and older (Adult, Senior) Sexes Eligible for the Study: All Accepts Healthy Volunteers: No

Inclusion Criteria:

Orthopedic procedures in the lower limbs Written informed consent Exclusion criteria Patients' refusal Known allergies to study medications Anatomic, posttraumatic and postoperative deformations of the spinal column making placement of intrathecal catheter impossible Neurological contraindications Any other contraindications for spinal anesthesia (coagulations disorders, antiplatelet or anticoagulant treatment, infection at the puncture site.

Inability to comprehend or participate in pain scoring scale

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Marek Wojtaszek, M.D., Ph.D.; Phone Number: +48-17-872-1195; Email: wojtaaszek@gmail.com
• Study Contact Backup: Name: Bogumila Woloszczuk-Gebicka, M.D., Ph.D.; Phone Number: +48-17-872-1195; Email: gebicka@hotmail.com

Study Locations

• Poland
  • Rzeszów, Poland, 35310
    • Recruiting
    • University of Rzeszów
    • Contact: Bogumila Woloszczuk-Gebicka, M.D., Ph.D.; Phone Number: +48-17-872-1195; Email: gebicka@hotmail.com
    • Contact: Marek Wojtaszek, M.D.; Phone Number: +48-17-872-1195; Email: wojtaaszek@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

- Orthopedic procedures in the lower limbs Written informed consent

Exclusion Criteria:

• Patients' refusal Known allergies to study medications Inability to comprehend or participate in pain scoring scale Anatomic, posttraumatic and postoperative deformations of the spinal column making placement of intrathecal catheter impossible Neurological contraindications Any other contraindications for spinal anesthesia (coagulations disorders, antiplatelet or anticoagulant treatment, infection at the puncture site.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ropivacaine; Experimental: 0.5% ropivacaine (isobaric) 4.5 ml for the patients < 160 cm tall, 5.0 ml for 161-170 cm tall, 5.5 ml for 171-180 cm tall, and 6.0 ml > 180 cm. supplementary bolus doses of ropivacaine as required, followed by 0.2% ropivacaine, 1 ml/h for the postoperative period	Drug: Ropivacaine; Procedure: Continuous Epidural Anesthesia Local anesthetic injection to the cerebrospinal fluid (subarachnoid space) at the L3-L4 or L4-L5 level Drug: ropivacaine Other name: Ropimol 0.5% ropivacaine (isobaric) 4.5 ml for the patients < 160 cm tall, 5.0 ml for 161-170 cm tall, 5.5 ml for 171-180 cm tall, and 6.0 ml > 180 cm, supplementary ropivacaine bolus doses as required, followed by 0.2% ropivacaine, 1 ml/h for the postoperative period Device : The Wiley Spinal Catheter-Over-Needle System for Continuous Spinal Anesthesia 4-6" 23-gauge intrathecal cannula over a 27-gauge pencil-point spinal needle; Other Names: Ropimol
Active Comparator: Bupivacaine; 0.5% v Bupivacaine mg (isobaric) loading dose of 0.5% bupivacaine, 3.0 ml for the patients < 160 cm tall, 3.3 ml for 161-170 cm tall, 3.6 ml for 171-180 cm tall, and 4.0 ml > 180 cm. and supplementary bupivacaine bolus dose as required, followed by 0,12% bupivacaine 1 ml/h for the postoperative period	Drug: Bupivacaine; Procedure: Continuous Epidural Anesthesia Local anesthetic injection to the subarachnoid space at the L3-L4 or L4-L5 level Drug: bupivacaine Loading dose of bupivacaine followed by 0.12% bupivacaine, 1 ml/h Other name: bupivacaine Device: The Wiley Spinal Catheter-Over-Needle System for Continuous Spinal Anesthesia 4-6" 23-gauge intrathecal cannula over a 27-gauge pencil-point spinal needle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammatory mediators, neural tissue injury markers and the markers of oxidative stress in the cerebrospinal fluid of patients undergoing spinal anesthesia with ropivacaine and bupivacaine.	Evaluation of changes in concentrations of • glutamate in the cerebrospinal fluid and in the blood of patients undergoing orthopaedic surgery under spinal anesthesia with either ropivacaine or bupivacaine	24 h

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammatory mediators, neural tissue injury markers and the markers of oxidative stress in the cerebrospinal fluid of patients undergoing spinal anesthesia with ropivacaine and bupivacaine.	Evaluation of changes in concentrations of selected mediators of inflammatory response (IL-1β, IL-6, tumor necrosis factor and others)	24 h
Inflammatory mediators, neural tissue injury markers and the markers of oxidative stress in the cerebrospinal fluid of patients undergoing spinal anesthesia with ropivacaine and bupivacaine.	Evaluation of changes in concentrations of • selected chemokines as markers of the glia damage in the cerebrospinal fluid and in the blood of patients undergoing orthopaedic surgery under continuous spinal anesthesia with either ropivacaine or bupivacaine	24 h

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammatory mediators, neural tissue injury markers and the markers of oxidative stress in the CSF of patients undergoing spinal anesthesia with ropivacaine and bupivacaine.	Assessment of hemodynamic stability in patients anaesthetized with continuous epidural infusion of ropivacaine and bupivacaine	24 h
Inflammatory mediators, neural tissue injury markers and the markers of oxidative stress in the CSF of patients undergoing spinal anesthesia with ropivacaine and bupivacaine.	Postoperative pain severity in Numerical Rating Scale (NRS) in the first 24 hours after surgery [Time Frame: 24 h] NRS range from 0 for no pain to 10 for worst pain imaginable	24h

Collaborators and Investigators

• Sponsor: University of Rzeszow
• Collaborators: Department of Anesthesiology, Intensive Therapy, District Hospital No2 in Rzeszow

Publications and helpful links

General Publications

• Wille M. Intrathecal use of ropivacaine: a review. Acta Anaesthesiol Belg. 2004;55(3):251-9.
• Kuthiala G, Chaudhary G. Ropivacaine: A review of its pharmacology and clinical use. Indian J Anaesth. 2011 Mar;55(2):104-10. doi: 10.4103/0019-5049.79875.
• Sung CM, Hah YS, Kim JS, Nam JB, Kim RJ, Lee SJ, Park HB. Cytotoxic effects of ropivacaine, bupivacaine, and lidocaine on rotator cuff tenofibroblasts. Am J Sports Med. 2014 Dec;42(12):2888-96. doi: 10.1177/0363546514550991. Epub 2014 Oct 8.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2017
• Primary Completion (Anticipated): December 30, 2019
• Study Completion (Anticipated): December 31, 2019

Study Registration Dates

• First Submitted: September 21, 2017
• First Submitted That Met QC Criteria: September 21, 2017
• First Posted (Actual): September 26, 2017

Study Record Updates

• Last Update Posted (Actual): December 18, 2017
• Last Update Submitted That Met QC Criteria: December 14, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Bupivacaine; Ropivacaine
• Other Study ID Numbers: URzeszow

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
• product manufactured in and exported from the U.S.: No