Lidocaine and Perioperative Cytokine Levels in Blood and Cerebrospinal Fluid in Cerebral Aneurysm Patients

November 10, 2020 updated by: Marijana Matas, Clinical Hospital Centre Zagreb

Effect of Regional Anesthesia With Lidocaine on Perioperative Levels of Interleukin-1β, Interleukin-6 and Tumor Necrosis Factor-α in Blood and Cerebrospinal Fluid in Cerebral Aneurysm Patients

Cerebral aneurysm surgery has significant mortality and morbidity rate. Inflammation plays a key role in the pathogenesis of intracranial aneurysms, their rupture, subarachnoid haemorrhage and neurologic complications. Brain injury activates immune cells and triggers cytokine release. Cytokine level in blood and cerebrospinal fluid is an indicator of inflammatory response. Cytokines contribute to secondary brain injury and can worsen the outcome of the treatment. Preventing secondary brain injury by modulating inflammatory response represents a therapeutic target. Lidocaine is local anesthetic that can be used in neurosurgery for regional anesthesia of the scalp and for topical anesthesia of the throat prior to direct laryngoscopy and endotracheal intubation. Except analgetic, lidocaine has systemic anti-inflammatory and neuroprotective effect. It acts through several mechanisms on various types of immune cells producing immunosuppressing effect. Lidocaine can act on activated microglia within central nervous system causing attenuation of immune response.

Primary aim of this prospective randomized trial is to determine influence of lidocaine administration on inflammatory cytokine levels in serum and cerebrospinal fluid during and following cerebral aneurysm surgery. Secondary aim is to determine possible correlation between levels of cytokines and incidence of neurologic and infectious postoperative complications. For that purpose, postoperative neurological clinical status will be recorded. Signs of vasospasm and pathological postoperative brain CT scan findings will be recorded. Incidence of meningitis, pneumonia and sepsis in postoperative period will also be analyzed.

Hypothesis of this trial is that lidocaine administration during cerebral aneurysm surgery would significantly change levels of pro-inflammatory cytokines in cerebrospinal fluid and serum. Lower concentrations of pro-inflammatory cytokines can possibly contribute to better outcome and significantly lower incidence of postoperative complications. Enzyme-immunochemical analysis will be used to measure levels of interleukin-1β, interleukin-6 and tumor necrosis factor-α in cerebrospinal fluid and serum. Investigation group will have, during cerebrovascular surgery under general anesthesia, regional anesthesia of the scalp and topical anesthesia of the throat prior to laryngoscopy, all done with lidocaine. Control group will have general anesthesia without lidocaine administration.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Croatia
      • Zagreb, Croatia, 10000
        • UHCZagreb

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 68 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • ASA ( American Society of Anesthesiologists) grading status I-III,
  • scheduled for cerebral aneurysm surgery under general anesthesia,
  • signed informed consent for participating in the research.

Exclusion Criteria:

  • poorly controlled chronic or acute cardiovascular, respiratory or autoimmune disease,
  • acute infectious disease,
  • renal or hepatic insufficiency,
  • preoperative Glasgow Coma Scale score lower than 15,
  • allergic reaction to any of the medications in protocol,
  • pregnancy
  • refusal to participate in the research.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Lidocaine group
Participants in lidocaine group, following induction to general anesthesia, will have lidocaine 2% 4 mg/kg administered as regional anesthesia of the scalp prior to Mayfield frame placement and lidocaine 1% 40 mg topically to the throat prior to direct laryngoscopy and endotracheal intubation. Maximum dosage of lidocaine won't exceed 400 mg.
Drug: Lidocaine
Administration of lidocaine 2% 4 mg/kg administered as regional anesthesia of the scalp prior to Mayfield frame placement and lidocaine 1% 40 mg topically to the throat prior to direct laryngoscopy and endotracheal intubation.
Other Names:
  • Regional anesthesia
No Intervention: Control group
Participants in control group will have general anesthesia without lidocaine administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in concentrations of interleukin-1β
Time Frame: Up to 24 hours after anesthesia induction.
Concentrations of IL-1β in pg/ml in cerebrospinal fluid and serum measured by enzyme-linked immunosorbent assay
Up to 24 hours after anesthesia induction.
Change in concentrations of interleukin-6
Time Frame: Up to 24 hours after anesthesia induction.
Concentrations of IL-6 in pg/ml in cerebrospinal fluid and serum measured by enzyme-linked immunosorbent assay
Up to 24 hours after anesthesia induction.
Change in concentrations of tumor necrosis factor α
Time Frame: Up to 24 hours after anesthesia induction.
Concentrations of TNF-α in pg/ml in cerebrospinal fluid and serum measured by enzyme-linked immunosorbent assay
Up to 24 hours after anesthesia induction.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of new motoric deficit
Time Frame: Up to one week postoperatively
Clinical assessment of neurologic status incidence of generalized epileptic seizure, incidence of vasospasm, pathological finding on brain computerized tomography ( ischemia, edema, bleeding, hydrocephalus).
Up to one week postoperatively
Incidence of generalized epileptic seizure
Time Frame: Up to one week postoperatively
Clinical assessment to diagnose generalized epileptic seizure
Up to one week postoperatively
Incidence of vasospasm
Time Frame: Up to one week postoperatively
Flow velocity over middle cerebral artery more than 180 cm/s measured by transcranial ultrasound
Up to one week postoperatively
Incidence of pathological computerized tomography brain scan
Time Frame: Up to one week postoperatively
Findings of edema, ischemia, bleeding or hydrocephalus on brain CT scan
Up to one week postoperatively

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of meningitis, pneumonia and sepsis
Time Frame: Up to one week postoperatively
Clinical signs and laboratory findings for diagnosing infectious complications
Up to one week postoperatively

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Clinical Hospital Centre Zagreb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2019

Primary Completion (Anticipated)

March 1, 2021

Study Completion (Anticipated)

December 1, 2021

Study Registration Dates

First Submitted

January 24, 2019

First Submitted That Met QC Criteria

January 29, 2019

First Posted (Actual)

January 30, 2019

Study Record Updates

Last Update Posted (Actual)

November 12, 2020

Last Update Submitted That Met QC Criteria

November 10, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 51

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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