Neurotoxicity of Spinal Anesthesia With Ropivacaine and Bupivacaine

Anesthesia; Adverse Effect, Spinal and Epidural Clinical Trial

— BuRoNe  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03293472
• Other study ID #: URzeszow
• Status: Recruiting
• Phase: Phase 4
• First received: September 21, 2017
• Last updated: December 14, 2017
• Start date: December 1, 2017
• Est. completion date: December 31, 2019

Study information

• Verified date: December 2017
• Source: University of Rzeszow
• Contact: Marek Wojtaszek, M.D., Ph.D.
• Phone: +48-17-872-1195
• Email: wojtaaszek[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 31, 2019
• Est. primary completion date: December 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Anaesthetic Complication Neurological
• Anesthesia; Adverse Effect, Spinal and Epidural

Intervention

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
• 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

Locations

Country	Name	City	State
Poland	University of Rzeszow	Rzeszów

Sponsors (2)

Lead Sponsor	Collaborator
University of Rzeszow	Department of Anesthesiology, Intensive Therapy, District Hospital No2 in Rzeszow

Country where clinical trial is conducted

Poland, 

References & Publications (3)

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. — View Citation

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. — View Citation

Wille M. Intrathecal use of ropivacaine: a review. Acta Anaesthesiol Belg. 2004;55(3):251-9. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Primary	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	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-1ß, IL-6, tumor necrosis factor and others)	24 h
Secondary	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