The Effect of Nimodipine on the Postoperative Cognitive Dysfunction

Study Overview
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Brief Summary
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The calcium channel blocker nimodipine dilates cerebral blood vessels and can pass through the blood-brain barrier, providing neuroprotective effects by selectively improving cerebral blood flow and inhibiting neuronal necrosis and apoptosis. Nimodipine significantly inhibited the production of tumor necrosis factor TNF-α and interleukin IL-1β, and also of nitric oxide and prostaglandin E2 from lipopolysaccharide-stimulated microglia. Abnormal cytokine networks are important in the development of nerve cell damage that leads to cognitive impairment.

Detailed Description
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All patients aged above 60 years undergoing planned neurosurgical operations in the duration up to 4 hours under general anesthesia will be included in the study. The patients will not be sedated by any type of benzodiazepine. A dose of 30 mg nimodipine or placebo will be applied 45 minutes before the surgery according to the randomization. Anesthesia will be managed according to the standardised protocol. Concentration of desflurane will be adjusted according to entropy values (target 40-50). Analgetics will be applied according to surgical pleth index (SPI) values. Sufentanil will not be applied in the last 15 minutes. Extubation will be performed at the operating theatre when meeting all extubation criteria including train of four ratio (TOFR) above 92%. Neither syntophylline, nor pharmacological decurarization (syntostigmine) will be applied to the patients.During the surgery, blood pressure will be maintained within ± 15% of the patient's normal blood pressure. Cognitive dysfunction tests will be executed on the day before the surgery, two hours after the surgery and on the third postoperative day.

Official Title
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The Effect of Nimodipine in the Preoperative Period on the Onset of Postoperative Cognitive Dysfunction in Adults

Conditions
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Mild Cognitive Impairment

Intervention / Treatment
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* Drug: Nimodipine group
* Drug: Control group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Glascow coma scale GCS 15 preoperatively American Society of Anesthesiologists ASA risk I - III planned brain surgery duration of procedure up to 4 hours. Exclusion Criteria: blood pressure below 130/80 torr preoperatively previous vascular surgery concomitant use of antiepileptic drugs, rifampicin allergy to nimodipine known liver cirrhosis

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nimodipine group<br>1 tbl of 30 mg nimodipine will be administered orally with premedication | Drug: Nimodipine group<br>* the stability of the blood pressure will be managed in interval plus minus 15% of patient's resting blood pressure<br>* Other names: nimodipine;|
| Experimental: Control group<br>1 tbl of placebo will be administered orally with premedication | Drug: Control group<br>* the stability of the blood pressure will be managed in interval plus minus 15% of patient's resting blood pressure<br>* Other names: placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cognitive behavior | measured by Addenbrooks cognitive test | within the first 3 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Postoperative cognitive dysfunction, Nimodipin, Anesthesia