Enzymatic Evaluation of General Anesthetic Induced Neurotoxicity in Patients With Aneurysmal Subarachnoid Hemorrhage

NCT03213392 | Completed FDA Drug

• 1 other identifier: NK/2677/DM/351
• Study Type: observational
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

General anesthetic induced neurotoxicity has received considerable attention in the past decade from various pre-clinical studies in rodents and non-human primates. Which demonstrated that exposure to general anesthetic agents for a longer duration can induce neuronal cell death that can lead to adverse neurodevelopmental outcomes. The neuroapoptosis and impairment of neurodevelopmental processes has been postulated as the underlying mechanism, but the molecular mechanisms was not completely understood. Various hypothesis has been proposed they are- Antagonistic effect on N-methyl-D-aspartate receptors and agonistic effect on gamma-aminobutyric acid type A receptors; mitochondrial perturbations and activation of reactive oxygen species and dysregulation of intracellular calcium homeostasis. They trigger neuroapoptosis and cell death through the activation of caspases.3 Caspases, a group of cysteine proteases, plays an important role in regulation and execution of apoptosis. Caspase-3 is most important since it is activated by many cell death signals and cleaves a variety of important cellular proteins.4 Various anesthetic agents like isoflurane, halothane, sevoflurane, nitrous oxide and propofol causes neurotoxicity by activation of caspase-3. Which has been proven from various animal studies western blot analysis, immunohistochemical analysis and flow cytometric analysis.3, 5-9 Though it is documented that exposure to general anesthetics causes neurotoxicity during active brain growth in animals, there is no evidence of such effects in adult humans.10 and it is difficult to separate the effects of anesthetics from surgical impact and other factors associated with diseases.11 The patients with aneurysmal subarachnoid hemorrhage (SAH) have variable degree of neurological insults and it is possible, based on the evidence from animal models that administration of general anesthetics could add to the neuronal insults.

Conditions

Neurotoxicity

Outcome Measures

Primary Outcomes (1)

• Estimation of changes in caspase 3 levels as a marker of neurotoxicity in patients with aneurysmal SAH following exposure to general anaesthetics.

  enzyme Caspase-3 is used as a marker of apoptosis and will be used as an indirect marker for neurotoxicity caused by general anesthetic agents

  baseline( pre- induction), one hour after the exposure to anesthetic agents and after extubation

Study Arms (1)

SUPRA ORBITAL KEYHOLE CLIPPING/ COILING

Aneurysms should be either clipped or coiled to prevent re rupture general anesthesia is required to carry out these procedures.various anesthetic agents are used as an maintenance agents.

Drug: Anesthetic Agents

Interventions

Anesthetic Agents DRUG

four different anesthetic agents will be used during the surgical clipping or coiling of the aneurysm for the maintenance of anesthesia.

Also known as: ANESTHETIC AGENTS FOR MAINTENANCE OF SURGERY

SUPRA ORBITAL KEYHOLE CLIPPING/ COILING

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

the study population includes the patients with aneurysmal subarchnoid haemorraghe coming to PGIMER for either supra orbital keyhole approach for aneurysmal clipping or endovascular coiling of the aneurysm

You may qualify if:

• Patients with aneurysmal SAH who are scheduled for surgical or endovascular intervention.
• Age between 18 to 65 yrs.
• WFNS grade 1 or 2
• Fischer grade 1 or 2
• ASA grade 1 or 2.

You may not qualify if:

• Patients with giant aneurysms of the internal carotid artery that require external carotid-internal carotid bypass or intra operative ligation of internal carotid artery.
• Patients with known psychiatric disease.
• Patients with any other neurological or neuro degenerative disorders.
• History of drug abuse.
• Patients with any history of carcinoma or any immune deficiency diseases.
• Intra-operative surgical complications like massive blood loss, prolonged clipping time (\>20 minutes), severe intra-operative brain swelling requiring extended craniotomy or lobectomy or precluding replacement of bone flap.

Sponsors & Collaborators

• Mukilan Balu: lead

Study Sites (1)

Postgraduate Institute of Medical Education and Research

Chandigarh, 160012, India

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

serum from blood samples and cerebrospinal fluid

MeSH Terms

Conditions

Neurotoxicity Syndromes

Interventions

Anesthetics

Condition Hierarchy (Ancestors)

Nervous System Diseases; Poisoning; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Central Nervous System Depressants; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Central Nervous System Agents; Therapeutic Uses

Study Officials

• MUKILAN BALASUBRAMANIAN, MD

  PGIMER, chandigarh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Month
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: principal investigator-resident in the department of neuroanesthesia

Study Record Dates

• First Submitted: July 5, 2017
• First Posted: July 11, 2017
• Study Start: January 1, 2016
• Primary Completion: July 31, 2017
• Study Completion: July 31, 2017
• Last Updated: September 19, 2017

Record last verified: 2017-09

Locations

IN (1)