Dexmedetomidine and Delirium in Patients After Cardiac Surgery

February 3, 2018 updated by: Dong-Xin Wang, Peking University First Hospital

Impact of Dexmedetomidine on the Incidence of Postoperative Delirium in Patients After Cardiac Surgery: a Randomized, Double-blinded, and Placebo-controlled Clinical Trial

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

285

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100034
        • Peking University First Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
During the first five days after surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
on the sixth day after surgery, and on the 30th day after surgery
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.
Occurrence of non-delirium complications will be monitored until 30 days after surgery.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
During the first five days after surgery
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).
During the first five days after surgery
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).
From end of surgery until discharge from Intensive Care Unit or 30 days after surgery
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).
From end of surgery until discharge from hospital or 30 days after surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking University First Hospital

Collaborators

Chinese Academy of Medical Sciences, Fuwai Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2014

Primary Completion (Actual)

August 1, 2015

Study Completion (Actual)

November 1, 2015

Study Registration Dates

First Submitted

October 9, 2014

First Submitted That Met QC Criteria

October 14, 2014

First Posted (Estimate)

October 17, 2014

Study Record Updates

Last Update Posted (Actual)

March 5, 2018

Last Update Submitted That Met QC Criteria

February 3, 2018

Last Verified

February 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PekingUFH

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data will be available on request.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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