Patients Under Hip, Femur, Spine Operation Clinical Trial
Official title:
Effect of Dexmedetomidine on Postoperative Delirium Inflammasome Activation Inhibition
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.
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.
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