Delirium, PostoperativeNCT06090955
Modulating Surgery-Induced Blood-Brain Barrier Disruption in Elderly
A study testing Dexmedetomidine Injection [Precedex], Lidocaine IV and normal saline in people with Delirium, Postoperative, run by Samsung Medical Center at 1 site in South Korea.
Trial 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)… Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Delirium, Postoperative
- What is being tested?
- Dexmedetomidine Injection [Precedex], Lidocaine IV and normal saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 108 participants
- Where
- 1 siteSouth Korea
- Study dates
- 25 Oct 2023to 31 Dec 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- American Society of Anesthesiologists (ASA) physical status classification I-III
- Undergoing elective open pancreatoduodenectomy
- Voluntary participation in the trial and signed informed consent
Who cannot join
- 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.
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
South Korea1 site, 1 recruiting
- Recruiting
Samsung Medical Center
Seoul, 06351
jeayoun kim, MD, +821039268786, kimjy0705@naver.com
About this study
Official title: Modulating Surgery-Induced Blood-Brain Barrier Disruption in Elderly: Impact of Dexmedetomidine and Lidocaine, a Randomized Controlled Trial
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.
Read the detailed description
Postoperative delirium (POD) negatively affects cognitive domains including memory, attention, and concentration after surgery. The incidence of POD in high-risk populations, such as aged, patients in intensive care units (ICU) and with previous cognitive impairment, the incidence of POD is as high as 50 to 60%. POD is associated with increased morbidity, mortality, and health-care costs. The 1-year survival probability is reduced by approximately 10% for each additional day of POD. Additionally, it is closely related to long-lasting postoperative cognitive dysfunction.
Surgical trauma activates the innate immune system and central nervous system (CNS) is influenced by surgical trauma by inflammatory mediators rapidly reaching the brain, which is facilitated by a transient increase in blood-brain barrier (BBB) permeability. Recent neuroimaging studies demonstrated BBB dysfunction in patients with delirium after cardiac surgery. The biomakers indicative of BBB breakdown were recently associated with the onset and intensity of delirium. These findings imply that the BBB could serve as a pivotal interface in regulating neuroinflammation and cognitive deterioration following surgical procedures.
Dexmedetomidine and lidocaine are increasingly used as part of a multimodal intraoperative anesthetic adjunct in a variety of surgical procedures. Dexmedetomidine, as a highly selective central presynaptic α2-adrenergic agonist, has sedative, sympatholytic and anti-inflammatory effects. Perioperative dexmedetomidine administration reduced delirium incidence by up to 50% and duration by 0.7 days in surgical populations. Lidocaine, an amide local anesthetic and class-1 antiarrhythmic agent, also has anti-inflammatory and opiate-sparing effects, accelerating gastrointestinal recovery and reducing hospital length of stay. In addition, previous clinical researches have suggested a beneficial effect of perioperative systemic lidocaine on postoperative neurocognitive dysfunction. Although both drugs alleviate surgery-induced systemic inflammation and animal models have indicated a potential protective effect of these agents against surgery-induced disruption of the BBB, few studies have examined the role of these different anesthetics in the interplay between peripheral and central inflammation in human subjects.
In this regard, this study 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 in a randomized, placebo-controlled, double-blind, triple-parallel clinical trial. The primary outcome measure was "cerebrospinal-plasma albumin ratio (CPAR)", which is a gold standard measure for BBB permeability, presenting in vivo evidence for the physical breakdown of the blood-CSF barrier in human. The investigators hyptothesized that the use of intraoperative continuous infusion of dexmedetomidine or lidocaine would be statistically superior to placebo control in preserving BBB integrity.
- Conditions
- Delirium, Postoperative
- Being tested
- Dexmedetomidine Injection [Precedex], Lidocaine IV, normal saline
- Keywords
- Postoperative delirium, dexmedetomidine, lidocaine, neuroinflammation, CPAR, blood brain barrier
- Medical subject headings
- Emergence Delirium, Neuroinflammatory Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dexmedetomidine Injection [Precedex]Drug
Also called Dex
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.
Lidocaine IVDrug
Also called Lido
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.
normal salineDrug
Also called Control
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: From the baseline to immediate postoperative values
Secondary outcomes (12)
The changes of inflammatory biomarker level in blood
IL-6
Measured: From the baseline to immediate postoperative state and postoperative day 2
The changes of neuronal damage biomarker level in blood
neuron specific enolase
Measured: From the baseline to immediate postoperative state and postoperative day 2
The changes of inflammatory, neuronal damage, BBB permeability biomarker level in blood
sb100 protein
Measured: From the baseline to immediate postoperative state and postoperative day 2
The incidence of postoperative delirium
Intensive Care Unit (CAM-ICU) and 3-min diagnostic interview for CAM (3D-CAM) for ICU patients and ward patients, respectively
Measured: From postoperative day 0 to 5
The subtype of postoperative delirium
hyperactive, hypoactive or mixed type will be defined by RASS score
Measured: From postoperative day 0 to 5
Delirium Rating Scale Revised (DRS-R-98)
The severity of delirium will be assessed using the Delirium Rating Scale Revised (DRS-R-98)
Measured: From postoperative day 0 to 5
Onset and duration of delirium
Intensive Care Unit (CAM-ICU) and 3-min diagnostic interview for CAM (3D-CAM)
Measured: From postoperative day 0 to 5
Pain score (NRS)
The degree of surgical pain will be assessed at rest, when taking a deep breath, and when moving by NRS.
Measured: From postoperative day 0 to 5
Subjective sleep quality
the NRS (an 11-point scale where 0 = the best sleep, and 10 = the worst sleep) once daily
Measured: From postoperative day 0 to 5
Montreal cognitive Assessment (MoCA)
Cognitive assessment
Measured: at baseline and 7 days after surgery or at discharge
Ideal outcome of pancreatoduodenectmoy
defined by the absence of In-hospital mortality, Severe complications (Clavien Dindo ≥3), Postoperative pancreatic fistula - ISGPS Grade B/C, Reoperation, Length of stay >75th percentile, or Readmission
Measured: postoperative day 30
non-delirium complications within 30 days after surgery
The severity of non-delirium complications are graded using Clavien-Dindo classification
Measured: Within 30 days after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2023
- Study start25 Oct 2023
- Primary completion30 Nov 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Delirium, PostoperativeStudies of the same condition, open and under way.
- More trials run by Samsung Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 108 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Samsung Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jiseon Jeong, Samsung Medical Center
- Investigators
- Jiseon Jeong, Principal investigator, Samsung Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06090955
- Sponsor's protocol ID
- SMC 2023-07-162
- Status last verified
- Apr 2024
- First submitted
- 3 Oct 2023
- Last updated
- 17 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Study data may be made available on request to the principal investigators with an appropriate research and data-protection plan agreed on.
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modulating Surgery-Induced Blood-Brain Barrier Disruption in Elderly: Impact of Dexmedetomidine and Lidocaine, a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT06090955
- Acronym / sponsor ID
- SMC 2023-07-162
- Conditions
- Delirium, Postoperative
- Keywords
- Postoperative delirium, dexmedetomidine, lidocaine, neuroinflammation, CPAR, blood brain barrier
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 108 participants (estimated)
- Lead sponsor
- Samsung Medical CenterUniversity, hospital or other
- Study start
- 25 Oct 2023 (actual)
- Primary completion
- 30 Nov 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 19 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Postoperative delirium (POD) negatively affects cognitive domains including memory, attention, and concentration after surgery. The incidence of POD in high-risk populations, such as aged, patients in intensive care units (ICU) and with previous cognitive impairment, the incidence of POD is as high as 50 to 60%. POD is associated with increased morbidity, mortality, and health-care costs. The 1-year survival probability is reduced by approximately 10% for each additional day of POD. Additionally, it is closely related to long-lasting postoperative cognitive dysfunction.
Surgical trauma activates the innate immune system and central nervous system (CNS) is influenced by surgical trauma by inflammatory mediators rapidly reaching the brain, which is facilitated by a transient increase in blood-brain barrier (BBB) permeability. Recent neuroimaging studies demonstrated BBB dysfunction in patients with delirium after cardiac surgery. The biomakers indicative of BBB breakdown were recently associated with the onset and intensity of delirium. These findings imply that the BBB could serve as a pivotal interface in regulating neuroinflammation and cognitive deterioration following surgical procedures.
Dexmedetomidine and lidocaine are increasingly used as part of a multimodal intraoperative anesthetic adjunct in a variety of surgical procedures. Dexmedetomidine, as a highly selective central presynaptic α2-adrenergic agonist, has sedative, sympatholytic and anti-inflammatory effects. Perioperative dexmedetomidine administration reduced delirium incidence by up to 50% and duration by 0.7 days in surgical populations. Lidocaine, an amide local anesthetic and class-1 antiarrhythmic agent, also has anti-inflammatory and opiate-sparing effects, accelerating gastrointestinal recovery and reducing hospital length of stay. In addition, previous clinical researches have suggested a beneficial effect of perioperative systemic lidocaine on postoperative neurocognitive dysfunction. Although both drugs alleviate surgery-induced systemic inflammation and animal models have indicated a potential protective effect of these agents against surgery-induced disruption of the BBB, few studies have examined the role of these different anesthetics in the interplay between peripheral and central inflammation in human subjects.
In this regard, this study 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 in a randomized, placebo-controlled, double-blind, triple-parallel clinical trial. The primary outcome measure was "cerebrospinal-plasma albumin ratio (CPAR)", which is a gold standard measure for BBB permeability, presenting in vivo evidence for the physical breakdown of the blood-CSF barrier in human. The investigators hyptothesized that the use of intraoperative continuous infusion of dexmedetomidine or lidocaine would be statistically superior to placebo control in preserving BBB integrity.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dexmedetomidine group | Experimental | Drug: Dexmedetomidine Injection [Precedex]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. |
| Lidocaine group | Experimental | Drug: Lidocaine IVPatients 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. |
| Control group | Placebo comparator | Drug: normal salinePatients in the control group will be administered equal volumes of 0.9% saline using the identical application scheme. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (3 listed)
- American Society of Anesthesiologists (ASA) physical status classification I-III
- Undergoing elective open pancreatoduodenectomy
- Voluntary participation in the trial and signed informed consent
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dexmedetomidine Injection [Precedex]Also: DexThe 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. | Drug | Dexmedetomidine group |
| Lidocaine IVAlso: LidoThe 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. | Drug | Lidocaine group |
| normal salineAlso: ControlThe 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. | Drug | Control group |
Primary outcome
Postoperative change of cerebrospinal-plasma albumin ratio (CPAR)
Time frame: From the baseline to immediate postoperative values
The change of CPAR will be calculated. CPAR was calculated using the formula 1000 x (CSF albumin (mg/dl))/(serum albumin (mg/dl).
12 secondary outcomes
The changes of inflammatory biomarker level in blood
Time frame: From the baseline to immediate postoperative state and postoperative day 2
The changes of neuronal damage biomarker level in blood
Time frame: From the baseline to immediate postoperative state and postoperative day 2
The changes of inflammatory, neuronal damage, BBB permeability biomarker level in blood
Time frame: From the baseline to immediate postoperative state and postoperative day 2
The incidence of postoperative delirium
Time frame: From postoperative day 0 to 5
The subtype of postoperative delirium
Time frame: From postoperative day 0 to 5
Delirium Rating Scale Revised (DRS-R-98)
Time frame: From postoperative day 0 to 5
Onset and duration of delirium
Time frame: From postoperative day 0 to 5
Pain score (NRS)
Time frame: From postoperative day 0 to 5
Subjective sleep quality
Time frame: From postoperative day 0 to 5
Montreal cognitive Assessment (MoCA)
Time frame: at baseline and 7 days after surgery or at discharge
Ideal outcome of pancreatoduodenectmoy
Time frame: postoperative day 30
non-delirium complications within 30 days after surgery
Time frame: Within 30 days after surgery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2024.
- Individual participant dataSharing planned: No. Study data may be made available on request to the principal investigators with an appropriate research and data-protection plan agreed on.
Related trials for Delirium, Postoperative
Not yet recruitingPhase 4
Effects of Remimazolam on Postoperative Cognitive Dysfunction and Neuroinflammatory Biomarkers in Patients Undergoing Aortic Arch Surgery
Aortic Aneurysm of the Proximal Arch, Aortic Aneurysms Arch
RecruitingPhase 4
Acetaminophen-Mannitol Injection and Postoperative Delirium
Postoperative Delirium
Not yet recruitingObservational study
Biomarkers of Postoperative Complications After Cardiac Surgery
Postoperative Complications
Recruiting
Postoperative Delirium and Analgesia in Elderly Patients
Postoperative Delirium, Postoperative Pain, Acute
Not yet recruitingObservational study
Sugammadex Timing and Recovery Profile in Pediatric Adenotonsillectomy
Neuromuscular Blockade, Delayed Emergence From Anesthesia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jiseon Jeong principal investigator
Samsung Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dexmedetomidine Injection [Precedex], Lidocaine IV and normal saline in people with Delirium, Postoperative, run by Samsung Medical Center at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact jeayoun kim (+821039268786, kimjy0705@naver.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Postoperative change of cerebrospinal-plasma albumin ratio (CPAR) (time frame: From the baseline to immediate postoperative values). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2024.