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Dexmedetomidine and Delirium in Patients After Cardiac Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02267538
Recruitment Status : Completed
First Posted : October 17, 2014
Results First Posted : February 5, 2018
Last Update Posted : March 5, 2018
Sponsor:
Collaborator:
Chinese Academy of Medical Sciences, Fuwai Hospital
Information provided by (Responsible Party):
Dong-Xin Wang, Peking University First Hospital

Brief Summary:
Postoperative delirium (POD) is a frequently occurring complication after cardiac surgery. Its occurrence is associated with worse outcomes of patients, including increased morbidity, prolonged hospital stay, increased medical cost, and higher mortality. It is also associated with long-term cognitive decline and decreased quality of life. However, until recently, pharmacological interventions that can effectively prevent its occurrence are still limited. The purpose of this study is to investigate whether perioperative dexmedetomidine use can decrease the incidence of postoperative delirium in patients undergoing cardiac surgery.

Condition or disease Intervention/treatment Phase
Delirium C.Surgical Procedure; Cardiac Postoperative Complications Drug: dexmedetomidine hydrochloride for injection Drug: 0.9% sodium chloride for injection Phase 4

Detailed Description:

Delirium is a state of global cerebral dysfunction manifested by acute disturbance of consciousness, attention, cognition and perception. It develops over a short period of time (usually hours to days) and tends to fluctuate during the course of the day. The reported incidences of delirium after cardiac surgery varied from 21% to 47%. The occurrence of postoperative delirium has significant harmful effects on patients' outcomes, including increased morbidity, prolonged hospital stay, increased medical cost, and higher mortality. Its occurrence is also associated with long-term cognitive decline and decreased quality of life.

The exact pathogenesis that lead to the occurrence of POD are still unclear, and possibly involves mechanisms such as inflammation, pain and sleep deprivation after surgery. Furthermore, it has been shown that anesthesia management might also have exerted some effects. Studies found that avoidance of unnecessary deep anesthesia (under the guidance of Bispectral Index monitoring) decreases the incidence of POD. Theoretically, measures that decreases the requirement of anesthetics while maintaining adequate depth of anesthesia and those that alleviates inflammation and improves postoperative analgesia as well as sleep quality will decrease the incidence of POD.

Dexmedetomidine is a highly selective alpha-2 adrenoreceptor agonists that provides anxiolysis, sedation and modest analgesia with minimal respiratory depression. Studies showed that, when used as an adjunctive anesthetics, dexmedetomidine significantly decreases the requirement of opioid analgesics and other sedatives during anesthesia. A recent study of our group found that continuous infusion of low-dose dexmedetomidine (0.2 ug/kg/h) during the first night after surgery significantly improved subjective sleep quality. Two randomized controlled trials found that, when compared with traditional sedatives (midazolam and propofol) and analgesics (such as morphine), use of dexmedetomidine in patients after cardiac surgery is associated with decreased risk of delirium. However, questions still exist as to whether dexmedetomidine prevent delirium or just does not increase its occurrence since traditional sedatives/analgesics themselves increases the risk of delirium. Furthermore, animal experiments showed that dexmedetomidine inhibits the degree of inflammation induced by endotoxins.

The investigators hypothesize that use of dexmedetomidine as an adjunctive agent during the perioperative period can decrease the incidence of postoperative delirium in patients undergoing cardiac surgery, possibly by decreasing the requirement of anesthetics during surgery, by ameliorating analgesia as well as sleep quality after surgery, and by alleviating the degree of perioperative inflammatory response.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 285 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Impact of Dexmedetomidine on the Incidence of Postoperative Delirium in Patients After Cardiac Surgery: a Randomized, Double-blinded, and Placebo-controlled Clinical Trial
Study Start Date : November 2014
Actual Primary Completion Date : August 2015
Actual Study Completion Date : November 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dex group
The intervention drug (dexmedetomidine hydrochloride for injection) will be administered during a period from before anesthesia induction until the end of mechanical ventilation after surgery.
Drug: dexmedetomidine hydrochloride for injection

Before anesthesia, dexmedetomidine hydrochloride for injection (200 ug/2 ml) will be diluted with normal saline to 50 ml (final dexmedetomidine concentration 4 ug/ml).

Before the induction of anesthesia, a loading dose will be administered by intravenous infusion at a rate of [0.9*kg] ml/h for 10 minutes (i.e., dexmedetomidine 0.6 μg/kg in 10 minutes), followed by continuous infusion at a rate of [0.1*kg] ml/h (i.e., dexmedetomidine at a rate of 0.4 μg /kg/h) until the end of surgery.

At the end of surgery, the infusion rate will be decreased to [0.025*kg] ml/h (i.e., dexmedetomidine at a rate of 0.1 ug/kg/h) and continued until the end of mechanical ventilation after surgery.

Other Name: Aibeining (trade name)

Placebo Comparator: Placebo group
The placebo drug (normal saline, i.e., 0.9% sodium chloride for injection) will be administered in the same way and rate for a same duration as that in the Dex group.
Drug: 0.9% sodium chloride for injection

Before anesthesia, 0.9% sodium chloride for injection 50 ml will be prepared.

Before the induction of anesthesia, a loading dose will be administered by intravenous infusion at a rate of [0.9*kg] ml/h for 10 minutes, followed by continuous infusion at a rate of [0.1*kg] ml/h until the end of surgery.

At the end of surgery, the infusion rate will be decreased to [0.025*kg] ml/h and continued until the end of mechanical ventilation after surgery.

Other Name: normal saline




Primary Outcome Measures :
  1. Incidence of Postoperative Delirium [ Time Frame: During the first five days after surgery ]
    Delirium was assessed with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) twice daily during the first five days after surgery.


Secondary Outcome Measures :
  1. Cognitive Function [ Time Frame: on the sixth day after surgery, and on the 30th day after surgery ]

    Cognitive function was assessed with the Mini Mental State Examination (MMSE) at baseline (the day before surgery) and on the sixth day after surgery, and with modified telephone interview for cognitive status (m-TICS) on the 30th day after surgery.

    The introduction of MMSE scale has been explained in the baseline part in the result section.

    The Telephone Interview for Cognitive Status-modified scale(m-TICS) is one of the most popular telephone interview-based screening instruments for mild cognitive impairment and dementia. It consists 11 items including wordlist memory, orientation, attention, repetition, conceptual knowledge and nonverbal praxis, which score ranges from 0 to 48, with higher scores indicating better cognitive function


  2. Incidence of Non-delirium Complications After Surgery [ Time Frame: Occurrence of non-delirium complications will be monitored until 30 days after surgery. ]
    Non-delirium complications was defined as any conditions other than delirium that occurred during the first 30 days after surgery and required therapeutic intervention.Complications listed here were not considered adverse events in this study.


Other Outcome Measures:
  1. Pain Intensity [ Time Frame: During the first five days after surgery ]
    Pain intensity was assessed daily at 8 am during the first five days after surgery with the Numeric Rating Scale (NRS, 0 = no pain, 10 = the worst possible pain).

  2. Subjective Sleep Quality [ Time Frame: During the first five days after surgery ]
    Subjective sleep quality was assessed daily at 8 am during the first five days after surgery with the Numeric Rating Scale (NRS, 0 = best sleep, 10 = the worst possible sleep).

  3. Length of Stay in the Intensive Care Unit [ Time Frame: From end of surgery until discharge from Intensive Care Unit or 30 days after surgery ]
    Results was presented as median (95% confidence interval).

  4. Length of Stay in Hospital After Surgery [ Time Frame: From end of surgery until discharge from hospital or 30 days after surgery ]
    Results was presented as median (95% confidence interval).



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Ages Eligible for Study:   60 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients of 60 years or older who are planning to receive cardiac surgery (CABG and/or valve replacement surgery)

Exclusion Criteria:

Patients will be excluded if they meet any of the following criteria:

  1. Refuse to participate;
  2. Preoperative history of schizophrenia, epilepsia, Parkinson syndrome, or severe dementia;
  3. Inability to communicate in the preoperative period because of severe visual/auditory dysfunction or language barrier;
  4. History of brain injury or neurosurgery;
  5. Preoperative sick sinus syndrome, severe bradycardia (HR < 50 bpm), second-degree or above atrioventricular block without pacemaker;
  6. Severe hepatic dysfunction (Child-Pugh class C);
  7. Severe renal dysfunction (requirement of renal replacement therapy);
  8. Other conditions that are considered unsuitable for participation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02267538


Locations
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China, Beijing
Peking University First Hospital
Beijing, Beijing, China, 100034
Sponsors and Collaborators
Peking University First Hospital
Chinese Academy of Medical Sciences, Fuwai Hospital
Investigators
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Principal Investigator: Dong-Xin Wang, MD, PhD Peking University First Hospital
Additional Information:
Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Dong-Xin Wang, Professor, Peking University First Hospital
ClinicalTrials.gov Identifier: NCT02267538    
Other Study ID Numbers: PekingUFH
First Posted: October 17, 2014    Key Record Dates
Results First Posted: February 5, 2018
Last Update Posted: March 5, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data will be available on request.
Keywords provided by Dong-Xin Wang, Peking University First Hospital:
Delirium
Cardiac Surgical Procedures
Postoperative Complications
Dexmedetomidine
Prevention
Additional relevant MeSH terms:
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Delirium
Postoperative Complications
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Pathologic Processes
Dexmedetomidine
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action