Modulating Surgery-Induced Blood-Brain Barrier Disruption in Elderly

NCT06090955 | Recruiting DMC

• 1 other identifier: SMC 2023-07-162
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

Postoperative delirium (POD) is the most common complications (\~50-60%) in elderly and major challenges to our rapidly growing aging population. Growing evidence suggests a possible role for neuroinflammation in the development of delirium, which is facilitated by a transient increase in blood-brain barrier (BBB) permeability. Lidocaine and dexmedetomidine, commonly used anesthetic adjuncts, have anti-inflammatory properties. Both drugs are reported to have modulatory effect on the intergrity of BBB and associated with a beneficial effect on postoperative neurocognitive dysfunction. In this regard, The investigators aimed to prospectively compare the modulatory effect of the intraoperative administration of dexmedetomidine or lidocaine with a sham control group (normal saline solution) on surgery-induced BBB disruption.

Conditions

Delirium, Postoperative

Keywords

Postoperative delirium; dexmedetomidine; lidocaine; neuroinflammation; CPAR; blood brain barrier

Outcome Measures

Primary Outcomes (1)

• Postoperative change of cerebrospinal-plasma albumin ratio (CPAR)

  The change of CPAR will be calculated. CPAR was calculated using the formula 1000 x (CSF albumin (mg/dl))/(serum albumin (mg/dl).

  From the baseline to immediate postoperative values

Secondary Outcomes (12)

• The changes of inflammatory biomarker level in blood

  From the baseline to immediate postoperative state and postoperative day 2

• The changes of neuronal damage biomarker level in blood

  From the baseline to immediate postoperative state and postoperative day 2

• The changes of inflammatory, neuronal damage, BBB permeability biomarker level in blood

  From the baseline to immediate postoperative state and postoperative day 2

• The incidence of postoperative delirium

  From postoperative day 0 to 5

• The subtype of postoperative delirium

  From postoperative day 0 to 5

Study Arms (3)

Dexmedetomidine group

EXPERIMENTAL

Patients in the dexmedetomidine group will be administered a bolus of 0.3 ug/kg intravenous dexmedetomidine over 10 min before anesthetic induction. After bolus injection, a continuous infusion of 0.3 ug/kg/hr of intravenous dexmedetomidine will be administered until the end of surgery.

Drug: Dexmedetomidine Injection [Precedex]

Lidocaine group

EXPERIMENTAL

Patients in the lidocaine group will receive a bolus of 1.5 mg/kg intravenous lidocaine over 10 min before induction of anesthesia. A continuous infusion of 1.5 mg/kg/hour of systemic lidocaine will be administered until the end of the surgery.

Drug: Lidocaine IV

Control group

PLACEBO COMPARATOR

Patients in the control group will be administered equal volumes of 0.9% saline using the identical application scheme.

Drug: normal saline

Interventions

Dexmedetomidine Injection [Precedex] DRUG

The study drugs(dexmedetomidine 80 μg/20 mL) will be prepared with 20 mL syringe and marked as 'trial drug', which are identical in appearance with control and active comparator. In order to avoid anaesthesiologists' speculation about the randomised assignment, the study drugs will be infused at the same rate.

Also known as: Dex

Dexmedetomidine group

Lidocaine IV DRUG

The study drugs(lidocaine 400 mg/20 mL) will be prepared with 20 mL syringe and marked as 'trial drug', which are identical in appearance with control and active comparator. In order to avoid anaesthesiologists' speculation about the randomised assignment, the study drugs will be infused at the same rate.

Also known as: Lido

Lidocaine group

normal saline DRUG

The study drugs(normal saline) will be prepared with 20 mL syringe and marked as 'trial drug', which are identical in appearance with control and active comparator. In order to avoid anaesthesiologists' speculation about the randomised assignment, the study drugs will be infused at the same rate.

Also known as: Control

Control group

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• American Society of Anesthesiologists (ASA) physical status classification I-III
• Undergoing elective open pancreatoduodenectomy
• Voluntary participation in the trial and signed informed consent

You may not qualify if:

• Sinus bradycardia (heart rate (HR) \<50 beats per minute (bpm)), Adams-Stokes syndrome, sick sinus or Wolff-Parkinson-White syndrome, or second-degree trioventricular block and over.
• Concurrent treatment with a class 1 antiarrhythmic or amiodarone)
• History of hypersensitivity reactions or contraindications to the study drugs (dexmedetomidine or lidocaine).
• Patient at personal of familial risk of malignant hyperthermia and porphyria
• Body mass index (BMI) ˃40 kg/m2
• Patients with coagulopathy (INR 1.5 or more, platelet count less than 75000/ul) or other contraindications to spinal tapping, or on anticoagulants that would preclude safe lumbar punctures.
• History of severe hepatic (Childs-Pugh Score \> Class A ) or renal (glomerular filtration rate \<30m)/min×1.73m2) disorders.
• Severe audio-visual impairments, or inability to speak precluding communication.
• Evidence of preoperative delirium (Confusion Assessment Method, CAM)
• History of uncontrolled seizures.
• Patients on immunosuppressants (e.g., steroids) or immunomodulatory therapy, chemotherapeutic agents with known cognitive effects.
• Patients taking the following drugs that are moderate-strong inhibitors of the CYP1A2 and CYP3A4 metabolic pathways within 72 hours prior to surgery

Sponsors & Collaborators

• Samsung Medical Center: lead

Study Sites (1)

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

MeSH Terms

Conditions

Emergence Delirium; Neuroinflammatory Diseases

Interventions

Dexmedetomidine; Saline Solution

Condition Hierarchy (Ancestors)

Delirium; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Inflammation

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Jiseon Jeong

  Samsung Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

jeayoun kim

CONTACT

+821039268786; kimjy0705@naver.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: October 3, 2023
• First Posted: October 19, 2023
• Study Start: October 25, 2023
• Primary Completion: November 30, 2024
• Study Completion: December 31, 2024
• Last Updated: April 17, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)