Patients Under Hip, Femur, Spine OperationNCT03588988
Effect of Dexmedetomidine on Postoperative Delirium Inflammasome Activation Inhibition
A study testing Dexmedetomidine IV infusion and Normal saline in people with Patients Under Hip, Femur, Spine Operation, run by Yonsei University at 1 site in South Korea.
Trial summary
Delirium is an acute or subacute comorbid syndrome characterized by decreased awareness and cognitive dysfunction accompanied by attention deficit. It varies from 20% to 80%, depending on the report. Read more about this study
- Who is it for?
- Ages 20 years and olderHealthy volunteers can take part
- Conditions the study is for
- Patients Under Hip, Femur, Spine Operation
- What is being tested?
- Dexmedetomidine IV infusion and Normal saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteSouth Korea
- Study dates
- Mar 2019to Jul 2019
- 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 20 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- ASA class I to III adults
- aged 20 years or older who can read and understand the consent form
- patients who have been admitted to the ICU after institution of hip, femur, and spine surgery
Who cannot join
- Patients who do not understand and understand the written consent of an illiterate or foreigner
- pregnant woman
- 20 years old
- Patients with moderate to severe liver disease (AST, ALT> 200 IU / L)
- Patients with end stage renal disease (eGFR <30 or dialysis patients)
- allergy to DEX, presence of electrocardiographic atrioventricular block, hemodynamic instability
- Left ventricular ejection fraction <30%, congestive heart failure, severe coronary artery disease, hemodynamically unstable arrhythmia
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine
Seoul, 03722
Jeong Min Kim, MD, 82-2-2227-3569, ANESJEONGMIN@yuhs.ac
About this study
Delirium is an acute or subacute comorbid syndrome characterized by decreased awareness and cognitive dysfunction accompanied by attention deficit. It varies from 20% to 80%, depending on the report. If delirium occurs in intensive care unit, complications such as intubation tube and catheter removal that are not desired are increased, mechanical ventilation deviation is prolonged, and eventually the intensive care unit is extended. Prevention of delirium is therefore very important, but no medication has been found to prevent delirium.
Recent studies have shown that pro-inflammatory cytokines play an important role in the development of delirium, and as a result of the stimulation of the peripheral inflammatory reaction, proinflammatory cytokines (interleukin (IL) -6, tumor necrosis factor- ), And IL-10) secretion, resulting in the induction of inflammatory responses of the central nervous system. In addition, sleep habits have been shown to affect the pro-inflammatory pathway, and sleep induction and inactivation of the pro-inflammatory pathway may be expected to prevent and treat delirium.
Read more
Dexmedetomidine (DEX) is a highly selective a2-agonist with sedative and analgesic effects and reduces sympathetic response to stimuli. Compared to benzodiazepine and opioid, there are fewer side effects of respiratory depression.
In animal studies, the possibility of intrinsic immune suppression of DEX has been demonstrated, and recent studies have shown that intravenous DEX administration reduces IL-6, IL-8, and TNF-a levels, resulting in anti-inflammatory effects. IL-6 plays a key role in neuroinflammation with both proinflammatory cytokines and anti-inflammatory cytokines, including infection, traumatic brain injury, ischemia, and neurodegenerative disorders. DEX plays a key role in IL-6 stimulated IL-6 And inhibits mRNA expression and thus has a brain function-protecting effect. In clinical trials, DEX administration compared with propofol decreased IL-6 secretion and decreased post-operative cognitive impairment in ICU patients after primary surgery. This is closely related to the formation of inflammatory complexes (Inflammasome). In addition, low-dose DEX infusion in patients with ICU at night has a low incidence of delirium during the ICU period, and studies have shown that sleep quality is improved in the DEX group in the mechanical ventilation group. Patients who did not undergo mechanical ventilation also reported improved sleep quality with prophylactic low-dose DEX. As such, the definitive mechanism has not yet been clarified, but the use of low-dose DEX is increasingly proactively used to improve sleep quality.
The purpose of this study was to investigate the effect of DEX on the inflammatory pathway during nighttime after ICU admission and to observe the quality of sleep and the prognosis of delirium.
Read the detailed description
Delirium is an acute and subacute comorbid syndrome characterized by decreased awareness and cognitive dysfunction accompanied by attention deficit. It varies from 20% to 80% in patients entering the ICU. If delirium occurs in the intensive care unit, complications such as unintended intubation, unintentional drainage, and mechanical ventilation are prolonged. Prevention of delirium is therefore very important, but no medication has been found to prevent delirium. Recent studies have shown that the pro-inflammatory cytokine affects the etiology of delirium. In addition, sleep habits have been shown to affect the pro-inflammatory pathway, and sleep induction and inactivation of the pro-inflammatory pathway may be expected to prevent and treat delirium.
DEX is a selective alpha-2 receptor agonist with sedative and anti-anxiety effects and reduces sympathetic response due to stimulation. Recent studies have shown that intravenous DEX is effective in reducing inflammation by decreasing levels of IL-6, IL-8, and TNF-a.
This study investigated the effect of dexmedetomidine, which is continuously administered at night after ICU admission, on the development of delirium and inflammatory markers, and to observe the prognosis. Patients who underwent spine, hip or femur surgery and who were admitted to the ICU after institutional exhalation were randomly assigned to the DEX group and the control group. Both groups can be combined with remifentanil for appropriate postoperative analgesia. The DEX group injects DEX at 0.2 ug / kg / hr from 9 pm to 7 am. The control group is inoculated with saline solution. At this time, the patient's blood pressure, oxygen saturation and cardiopulmonary function are continuously monitored. If an adverse event occurs during DEX sedation, process it and record it. If hypotension occurs, 4 mg of IV ephedrine is administered. If hypotension occurs, 4 mg is added or infused with norepinephrine. If Bradycardia (HR <45 bpm) occurs, IV glycopyrrolate 0.2 mg is administered. If bradycardia persists after administration, administer 0.5 mg IV atropine at a maximum of 0.5 mg. If respiratory depression (RR <10 / min) and hypoxia (SaO2 <90%) occur, the patient may be awakened by loud or mild stimulation. If the respiratory depression and hypoxia persist despite these treatments, head extension , and maneuver for airway maintenance such as jaw thrust.
IL-1β, IL-6, TNF-α, caspase-1, NLRP3 and ASC were measured at the onset of surgery in both the DEX group and the control group. Follow up.
The following morning the subjects themselves and the researchers evaluate the quality of sleep (using RCSQ questionnaire) and delirium (ICDSC, CAM-ICU), respectively.
- Being tested
- Dexmedetomidine IV infusion, Normal saline
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dexmedetomidine IV infusionDrug
Patients who underwent spine, hip or femur surgery and who were admitted to the ICU after institutional exhalation were randomly assigned to the DEX group and the control group. Both groups can be combined with remifentanil for appropriate postoperative analgesia. The DEX group injects DEX at 0.2 ug / kg / hr from 9 pm to 7 am. At this time, the patient's blood pressure, oxygen saturation and cardiopulmonary function are continuously monitored.
Normal salineDrug
Patients who underwent spine, hip or femur surgery and who were admitted to the ICU after institutional exhalation were randomly assigned to the DEX group and the control group. Both groups can be combined with remifentanil for appropriate postoperative analgesia. The control group is inoculated with saline solution. At this time, the patient's blood pressure, oxygen saturation and cardiopulmonary function are continuously monitored.
| Study group | Role | What they receive |
|---|---|---|
| Dexmedetomidine group | Experimental | Not described Receives: Drug: Dexmedetomidine IV infusion |
| Control group | Placebo comparator | Not described Receives: Drug: Normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
CRP(C-reactive protein)
Effect of dexmedetomidine(DEX) on post-conditioning delirium and inflammasome activation
Measured: Post operative day 0
CRP(C-reactive protein)
Effect of dexmedetomidine(DEX) on post-conditioning delirium and inflammasome activation
Measured: Post operative day 1
the number of Neutrophil or Lymphocyte
Effect of dexmedetomidine(DEX) on post-conditioning delirium and inflammasome activation
Measured: Post operative day 0
the number of Neutrophil or Lymphocyte
Effect of dexmedetomidine(DEX) on post-conditioning delirium and inflammasome activation
Measured: Post operative day 1
total score of Richards-Campbell Sleep Questionnaire(RCSQ) obtained by summing each score out of 100
double-checked RCSQ; one is patient check, and the other is night nurse check.
Measured: Post operative day 0
total score of Richards-Campbell Sleep Questionnaire(RCSQ) obtained by summing each score out of 100
double-checked RCSQ; one is patient check, and the other is night nurse check.
Measured: Post operative day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2018
- Study startMar 2019 (estimated)
- Primary completionJul 2019 (estimated)
- Study completionJul 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Patients Under Hip, Femur, Spine OperationStudies of the same condition, open and under way.
- More trials run by Yonsei UniversityThe 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
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03588988
- Sponsor's protocol ID
- 4-2018-0472
- Status last verified
- Feb 2019
- First submitted
- 3 Jul 2018
- Last updated
- 8 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Dexmedetomidine on Postoperative Delirium Inflammasome Activation Inhibition
- ClinicalTrials.gov ID
- NCT03588988
- Acronym / sponsor ID
- 4-2018-0472
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Yonsei UniversityUniversity, hospital or other
- Study start
- Mar 2019 (estimated)
- Primary completion
- Jul 2019 (estimated)
- Study completion
- Jul 2019 (estimated)
- First posted
- 17 Jul 2018 (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.
Delirium is an acute or subacute comorbid syndrome characterized by decreased awareness and cognitive dysfunction accompanied by attention deficit. It varies from 20% to 80%, depending on the report. If delirium occurs in intensive care unit, complications such as intubation tube and catheter removal that are not desired are increased, mechanical ventilation deviation is prolonged, and eventually the intensive care unit is extended. Prevention of delirium is therefore very important, but no medication has been found to prevent delirium.
Recent studies have shown that pro-inflammatory cytokines play an important role in the development of delirium, and as a result of the stimulation of the peripheral inflammatory reaction, proinflammatory cytokines (interleukin (IL) -6, tumor necrosis factor- ), And IL-10) secretion, resulting in the induction of inflammatory responses of the central nervous system. In addition, sleep habits have been shown to affect the pro-inflammatory pathway, and sleep induction and inactivation of the pro-inflammatory pathway may be expected to prevent and treat delirium.
Dexmedetomidine (DEX) is a highly selective a2-agonist with sedative and analgesic effects and reduces sympathetic response to stimuli. Compared to benzodiazepine and opioid, there are fewer side effects of respiratory depression.
In animal studies, the possibility of intrinsic immune suppression of DEX has been demonstrated, and recent studies have shown that intravenous DEX administration reduces IL-6, IL-8, and TNF-a levels, resulting in anti-inflammatory effects. IL-6 plays a key role in neuroinflammation with both proinflammatory cytokines and anti-inflammatory cytokines, including infection, traumatic brain injury, ischemia, and neurodegenerative disorders. DEX plays a key role in IL-6 stimulated IL-6 And inhibits mRNA expression and thus has a brain function-protecting effect. In clinical trials, DEX administration compared with propofol decreased IL-6 secretion and decreased post-operative cognitive impairment in ICU patients after primary surgery. This is closely related to the formation of inflammatory complexes (Inflammasome). In addition, low-dose DEX infusion in patients with ICU at night has a low incidence of delirium during the ICU period, and studies have shown that sleep quality is improved in the DEX group in the mechanical ventilation group. Patients who did not undergo mechanical ventilation also reported improved sleep quality with prophylactic low-dose DEX. As such, the definitive mechanism has not yet been clarified, but the use of low-dose DEX is increasingly proactively used to improve sleep quality.
The purpose of this study was to investigate the effect of DEX on the inflammatory pathway during nighttime after ICU admission and to observe the quality of sleep and the prognosis of delirium.
Detailed description
Delirium is an acute and subacute comorbid syndrome characterized by decreased awareness and cognitive dysfunction accompanied by attention deficit. It varies from 20% to 80% in patients entering the ICU. If delirium occurs in the intensive care unit, complications such as unintended intubation, unintentional drainage, and mechanical ventilation are prolonged. Prevention of delirium is therefore very important, but no medication has been found to prevent delirium. Recent studies have shown that the pro-inflammatory cytokine affects the etiology of delirium. In addition, sleep habits have been shown to affect the pro-inflammatory pathway, and sleep induction and inactivation of the pro-inflammatory pathway may be expected to prevent and treat delirium.
DEX is a selective alpha-2 receptor agonist with sedative and anti-anxiety effects and reduces sympathetic response due to stimulation. Recent studies have shown that intravenous DEX is effective in reducing inflammation by decreasing levels of IL-6, IL-8, and TNF-a.
This study investigated the effect of dexmedetomidine, which is continuously administered at night after ICU admission, on the development of delirium and inflammatory markers, and to observe the prognosis. Patients who underwent spine, hip or femur surgery and who were admitted to the ICU after institutional exhalation were randomly assigned to the DEX group and the control group. Both groups can be combined with remifentanil for appropriate postoperative analgesia. The DEX group injects DEX at 0.2 ug / kg / hr from 9 pm to 7 am. The control group is inoculated with saline solution. At this time, the patient's blood pressure, oxygen saturation and cardiopulmonary function are continuously monitored. If an adverse event occurs during DEX sedation, process it and record it. If hypotension occurs, 4 mg of IV ephedrine is administered. If hypotension occurs, 4 mg is added or infused with norepinephrine. If Bradycardia (HR <45 bpm) occurs, IV glycopyrrolate 0.2 mg is administered. If bradycardia persists after administration, administer 0.5 mg IV atropine at a maximum of 0.5 mg. If respiratory depression (RR <10 / min) and hypoxia (SaO2 <90%) occur, the patient may be awakened by loud or mild stimulation. If the respiratory depression and hypoxia persist despite these treatments, head extension , and maneuver for airway maintenance such as jaw thrust.
IL-1β, IL-6, TNF-α, caspase-1, NLRP3 and ASC were measured at the onset of surgery in both the DEX group and the control group. Follow up.
The following morning the subjects themselves and the researchers evaluate the quality of sleep (using RCSQ questionnaire) and delirium (ICDSC, CAM-ICU), respectively.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dexmedetomidine group | Experimental | Drug: Dexmedetomidine IV infusion |
| Control group | Placebo comparator | Drug: Normal saline |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- ASA class I to III adults
- aged 20 years or older who can read and understand the consent form
- patients who have been admitted to the ICU after institution of hip, femur, and spine surgery
Key exclusion criteria (7 listed)
- Patients who do not understand and understand the written consent of an illiterate or foreigner
- pregnant woman
- 20 years old
- Patients with moderate to severe liver disease (AST, ALT> 200 IU / L)
- Patients with end stage renal disease (eGFR <30 or dialysis patients)
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 IV infusionPatients who underwent spine, hip or femur surgery and who were admitted to the ICU after institutional exhalation were randomly assigned to the DEX group and the control group. Both groups can be combined with remifentanil for appropriate postoperative analgesia. The DEX group injects DEX at 0.2 ug / kg / hr from 9 pm to 7 am. At this time, the patient's blood pressure, oxygen saturation and cardiopulmonary function are continuously monitored. | Drug | Dexmedetomidine group |
| Normal salinePatients who underwent spine, hip or femur surgery and who were admitted to the ICU after institutional exhalation were randomly assigned to the DEX group and the control group. Both groups can be combined with remifentanil for appropriate postoperative analgesia. The control group is inoculated with saline solution. At this time, the patient's blood pressure, oxygen saturation and cardiopulmonary function are continuously monitored. | Drug | Control group |
Primary outcome
CRP(C-reactive protein)
Time frame: Post operative day 0
Effect of dexmedetomidine(DEX) on post-conditioning delirium and inflammasome activation
CRP(C-reactive protein)
Time frame: Post operative day 1
Effect of dexmedetomidine(DEX) on post-conditioning delirium and inflammasome activation
the number of Neutrophil or Lymphocyte
Time frame: Post operative day 0
Effect of dexmedetomidine(DEX) on post-conditioning delirium and inflammasome activation
the number of Neutrophil or Lymphocyte
Time frame: Post operative day 1
Effect of dexmedetomidine(DEX) on post-conditioning delirium and inflammasome activation
total score of Richards-Campbell Sleep Questionnaire(RCSQ) obtained by summing each score out of 100
Time frame: Post operative day 0
double-checked RCSQ; one is patient check, and the other is night nurse check.
total score of Richards-Campbell Sleep Questionnaire(RCSQ) obtained by summing each score out of 100
Time frame: Post operative day 1
double-checked RCSQ; one is patient check, and the other is night nurse check.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2019.
- Individual participant dataSharing planned: No
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.
Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine
Seoul, South Korea
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 IV infusion and Normal saline in people with Patients Under Hip, Femur, Spine Operation, run by Yonsei University 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 7 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 8 Feb 2019. 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?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CRP(C-reactive protein) (time frame: Post operative day 0). The study lists 6 primary outcomes in all. 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 8 Feb 2019.