Effect of Dexmedetomidine on Postoperative Delirium Inflammasome Activation Inhibition

NCT ID: NCT03588988

Last Updated: 2019-02-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-31
• Study Completion Date: 2019-07-31

Brief 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. 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.

Conditions

Patients Under Hip, Femur, Spine Operation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Dexmedetomidine group

Group Type: EXPERIMENTAL

Dexmedetomidine IV infusion

Intervention Type: DRUG

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.

Control group

Group Type: PLACEBO_COMPARATOR

Normal saline

Intervention Type: DRUG

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.

Interventions

Dexmedetomidine IV infusion

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.

Intervention Type: DRUG

Normal saline

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Yonsei University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine

Seoul, , South Korea

Countries

South Korea

Facility Contacts

Jeong Min Kim, MD

Role: primary

ANESJEONGMIN@yuhs.ac

82-2-2227-3569

Other Identifiers

4-2018-0472

Identifier Type: -

Identifier Source: org_study_id