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

Aneurysm, Cerebral Clinical Trial

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT03823482
• Other study ID #: 51
• Status: Enrolling by invitation
• Phase: N/A
• Start date: March 1, 2019
• Est. completion date: December 1, 2021

Study information

• Verified date: November 2020
• Source: Clinical Hospital Centre Zagreb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 40
• Est. completion date: December 1, 2021
• Est. primary completion date: March 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Aneurysm
• Aneurysm, Cerebral
• Intracranial Aneurysm

Intervention

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.

Locations

Country	Name	City	State
Croatia	UHCZagreb	Zagreb

Sponsors (1)

Lead Sponsor	Collaborator
Clinical Hospital Centre Zagreb

Country where clinical trial is conducted

Croatia, 

References & Publications (11)

Aoki T, Nishimura M. Targeting chronic inflammation in cerebral aneurysms: focusing on NF-kappaB as a putative target of medical therapy. Expert Opin Ther Targets. 2010 Mar;14(3):265-73. doi: 10.1517/14728221003586836. Review. — View Citation

Chaki T, Sugino S, Janicki PK, Ishioka Y, Hatakeyama Y, Hayase T, Kaneuchi-Yamashita M, Kohri N, Yamakage M. Efficacy and Safety of a Lidocaine and Ropivacaine Mixture for Scalp Nerve Block and Local Infiltration Anesthesia in Patients Undergoing Awake Craniotomy. J Neurosurg Anesthesiol. 2016 Jan;28(1):1-5. doi: 10.1097/ANA.0000000000000149. — View Citation

Chaudhry SR, Stoffel-Wagner B, Kinfe TM, Güresir E, Vatter H, Dietrich D, Lamprecht A, Muhammad S. Elevated Systemic IL-6 Levels in Patients with Aneurysmal Subarachnoid Hemorrhage Is an Unspecific Marker for Post-SAH Complications. Int J Mol Sci. 2017 Dec 1;18(12). pii: E2580. doi: 10.3390/ijms18122580. — View Citation

Guilfoyle MR, Helmy A, Duane D, Hutchinson PJ. Regional scalp block for postcraniotomy analgesia: a systematic review and meta-analysis. Anesth Analg. 2013 May;116(5):1093-102. doi: 10.1213/ANE.0b013e3182863c22. Epub 2013 Mar 11. Review. — View Citation

Hollmann MW, Durieux ME. Local anesthetics and the inflammatory response: a new therapeutic indication? Anesthesiology. 2000 Sep;93(3):858-75. Review. — View Citation

Hopkins SJ, McMahon CJ, Singh N, Galea J, Hoadley M, Scarth S, Patel H, Vail A, Hulme S, Rothwell NJ, King AT, Tyrrell PJ. Cerebrospinal fluid and plasma cytokines after subarachnoid haemorrhage: CSF interleukin-6 may be an early marker of infection. J Neuroinflammation. 2012 Nov 23;9:255. doi: 10.1186/1742-2094-9-255. — View Citation

Jeong HJ, Lin D, Li L, Zuo Z. Delayed treatment with lidocaine reduces mouse microglial cell injury and cytokine production after stimulation with lipopolysaccharide and interferon ?. Anesth Analg. 2012 Apr;114(4):856-61. doi: 10.1213/ANE.0b013e3182460ab5. Epub 2012 Jan 16. — View Citation

Leng T, Gao X, Dilger JP, Lin J. Neuroprotective effect of lidocaine: is there clinical potential? Int J Physiol Pathophysiol Pharmacol. 2016 Apr 25;8(1):9-13. eCollection 2016. Review. — View Citation

Mutlu LK, Woiciechowsky C, Bechmann I. Inflammatory response after neurosurgery. Best Pract Res Clin Anaesthesiol. 2004 Sep;18(3):407-24. Review. — View Citation

Osborn I, Sebeo J. "Scalp block" during craniotomy: a classic technique revisited. J Neurosurg Anesthesiol. 2010 Jul;22(3):187-94. doi: 10.1097/ANA.0b013e3181d48846. — View Citation

Pawlowska E, Szczepanska J, Wisniewski K, Tokarz P, Jaskólski DJ, Blasiak J. NF-?B-Mediated Inflammation in the Pathogenesis of Intracranial Aneurysm and Subarachnoid Hemorrhage. Does Autophagy Play a Role? Int J Mol Sci. 2018 Apr 19;19(4). pii: E1245. doi: 10.3390/ijms19041245. Review. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of meningitis, pneumonia and sepsis	Clinical signs and laboratory findings for diagnosing infectious complications	Up to one week postoperatively
Primary	Change in concentrations of interleukin-1ß	Concentrations of IL-1ß in pg/ml in cerebrospinal fluid and serum measured by enzyme-linked immunosorbent assay	Up to 24 hours after anesthesia induction.
Primary	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.
Primary	Change in concentrations of tumor necrosis factor a	Concentrations of TNF-a in pg/ml in cerebrospinal fluid and serum measured by enzyme-linked immunosorbent assay	Up to 24 hours after anesthesia induction.
Secondary	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
Secondary	Incidence of generalized epileptic seizure	Clinical assessment to diagnose generalized epileptic seizure	Up to one week postoperatively
Secondary	Incidence of vasospasm	Flow velocity over middle cerebral artery more than 180 cm/s measured by transcranial ultrasound	Up to one week postoperatively
Secondary	Incidence of pathological computerized tomography brain scan	Findings of edema, ischemia, bleeding or hydrocephalus on brain CT scan	Up to one week postoperatively