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

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
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

Conditions
-----------------
Aneurysm, Cerebral

Intervention / Treatment
-----------------
* Drug: Lidocaine


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lidocaine group<br>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<br>* 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.<br>* Other names: Regional anesthesia;|
| No Intervention: Control group<br>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 | 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 | 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 | 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 | 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 | Clinical assessment to diagnose generalized epileptic seizure | Up to one week postoperatively | 
| Incidence of vasospasm | 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 | Findings of edema, ischemia, bleeding or hydrocephalus on brain CT scan | Up to one week postoperatively | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
aneurysm, cerebral, inflammation mediators, lidocaine, hydrochloride