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Effect of Dexmedetomidine on Postoperative Delirium Inflammasome Activation Inhibition

7 febbraio 2019 aggiornato da: Yonsei University

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.

Panoramica dello studio

Stato

Sconosciuto

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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.

Tipo di studio

Interventistico

Iscrizione (Anticipato)

100

Fase

  • Non applicabile

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Corea, Repubblica di
      • Seoul, Corea, Repubblica di, 03722
        • Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

20 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

Sì

Sessi ammissibili allo studio

Tutto

Descrizione

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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Prevenzione
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Quadruplicare

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Comparatore placebo: Gruppo di controllo
Droga: 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.
Sperimentale: Gruppo dexmedetomidina
Droga: 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.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
CRP(C-reactive protein)
Lasso di tempo: Post operative day 0
Effect of dexmedetomidine(DEX) on post-conditioning delirium and inflammasome activation
Post operative day 0
CRP(C-reactive protein)
Lasso di tempo: Post operative day 1
Effect of dexmedetomidine(DEX) on post-conditioning delirium and inflammasome activation
Post operative day 1
the number of Neutrophil or Lymphocyte
Lasso di tempo: Post operative day 0
Effect of dexmedetomidine(DEX) on post-conditioning delirium and inflammasome activation
Post operative day 0
the number of Neutrophil or Lymphocyte
Lasso di tempo: Post operative day 1
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
Lasso di tempo: Post operative day 0
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
Lasso di tempo: Post operative day 1
double-checked RCSQ; one is patient check, and the other is night nurse check.
Post operative day 1

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Yonsei University

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Anticipato)

1 marzo 2019

Completamento primario (Anticipato)

1 luglio 2019

Completamento dello studio (Anticipato)

1 luglio 2019

Date di iscrizione allo studio

Primo inviato

3 luglio 2018

Primo inviato che soddisfa i criteri di controllo qualità

15 luglio 2018

Primo Inserito (Effettivo)

17 luglio 2018

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

8 febbraio 2019

Ultimo aggiornamento inviato che soddisfa i criteri QC

7 febbraio 2019

Ultimo verificato

1 febbraio 2019

Maggiori informazioni

Termini relativi a questo studio

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • 4-2018-0472

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

NO

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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