Effect of Dexmedetomidine on Postoperative Delirium Inflammasome Activation Inhibition

NCT03588988 | Unknown

• 1 other identifier: 4-2018-0472
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Patients Under Hip, Femur, Spine Operation

Outcome Measures

Primary Outcomes (6)

• CRP(C-reactive protein)

  Effect of dexmedetomidine(DEX) on post-conditioning delirium and inflammasome activation

  Post operative day 0

• CRP(C-reactive protein)

  Effect of dexmedetomidine(DEX) on post-conditioning delirium and inflammasome activation

  Post operative day 1

• the number of Neutrophil or Lymphocyte

  Effect of dexmedetomidine(DEX) on post-conditioning delirium and inflammasome activation

  Post operative day 0

• the number of Neutrophil or Lymphocyte

  Effect of dexmedetomidine(DEX) on post-conditioning delirium and inflammasome activation

  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.

  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.

  Post operative day 1

Study Arms (2)

Dexmedetomidine group

EXPERIMENTAL

Drug: Dexmedetomidine IV infusion

Control group

PLACEBO COMPARATOR

Drug: Normal saline

Interventions

Dexmedetomidine IV infusion 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.

Dexmedetomidine group

Normal saline 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.

Control group

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Patients who do not understand and understand the written consent of an illiterate or foreigner
• pregnant woman
• 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

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

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

Seoul, 03722, South Korea

Location

MeSH Terms

Interventions

Saline Solution

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

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: SPONSOR

Study Record Dates

• First Submitted: July 3, 2018
• First Posted: July 17, 2018
• Study Start: March 1, 2019
• Primary Completion: July 1, 2019
• Study Completion: July 1, 2019
• Last Updated: February 8, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)