Dexmedetomidine Supplemented Analgesia and Incidence of Postoperative Delirium

ID: NCT03012984
Status: Recruiting
Phase: Phase 4
Start Date: January 01, 2017
First Submitted: December 31, 2016
Last Updated: February 22, 2018
Results: N/A
Sponsors & Collaborators: Peking University First Hospital
Location: China
Conditions: Elderly, Surgery, Analgesia, Dexmedetomidine, Complication, Postoperative, Delirium
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.

Study Description

Brief Summary

Delirium is a frequently occurred cerebral complication in elderly patients after surgery, and its occurrence is associated with worse outcomes. Sleep disturbances is considered to be one of the most important risk factors of postoperative delirium. Previous studies showed that, for elderly patients admitted to the ICU after surgery, low-dose dexmedetomidine infusion improved the quality of sleep and decreased the incidence of delirium. The investigators hypothesize that, for elderly patients after cancer surgery, dexmedetomidine supplemented analgesia can also decrease the incidence of delirium, possibly by improving sleep quality. The purpose of this multicenter, randomized controlled trial is to investigate the impact of dexmedetomidine supplemented analgesia on the incidence of delirium in elderly patients after cancer surgery.

Detailed Description

Delirium is a state of acutely occurred and transient cerebral dysfunction. It is a common complication in elderly patients after surgery. A systematic review showed that an average of 36.8% (range 0 to 73.5%) of surgical patients developed postoperative delirium, and its occurrence increased with age. According to our previous studies, postoperative delirium developed in 51.0% of patients after cardiac surgery and in 44.5% of patients after non-cardiac surgery. The occurrence of delirium is associated with worse short-term outcomes, including increased postoperative complications, prolonged hospital stay, and increased in-hospital mortality; it is also associated with worse long-term outcomes, including declined cognitive function, decreased quality of life, and increased post-hospital mortality. Delirium is the result of multiple factors. Studies showed that postoperative pain is an important risk factor of delirium, whereas good postoperative analgesia reduces the incidence of delirium. For postoperative patients, sleep disturbances occurs frequently and increases the risk of delirium, whereas improving sleep quality reduces the incidence of delirium. Furthermore, the studies found that surgery related inflammatory response also plays an important role in the development of delirium.

Dexmedetomidine is a highly selective alpha-2 (α2) adrenoreceptor agonist that provides anxiolysis, sedation, hypnosis and analgesia. It exerts the sedative and hypnotic effects by activating the endogenous sleep pathways, and produces a condition similar to phase 2 non-rapid eye movement sleep. For patients undergoing mechanical ventilation in the ICU, dexmedetomidine sedation helps to maintain a normal circadian rhythm of sleep and improves sleep architecture. Dexmedetomidine also provides analgesic effect by activating α2 adrenergic receptors in the dorsal horn of spinal cord. When used as a supplemental drug it decreases intraoperative and postoperative requirement of opioids. Moreover, animal studies showed that dexmedetomidine significantly inhibits the degree of inflammatory response induced by endotoxin or during spinal cord injury. In clinical studies, dexmedetomidine attenuates the degree of inflammatory response following Coronary Artery Bypass Grafting surgery.

These effects of dexmedetomidine make it suitable for prevention of postoperative delirium in high-risk patients. Studies have shown that, for ICU patients requiring mechanical ventilation, sedation with dexmedetomidine reduces the incidence of delirium when compared with other sedatives; for postoperative patients, dexmedetomidine administered in combined with opioids improves analgesia and reduces opioid requirements. A recent study showed that, for elderly patients admitted to the ICU after surgery, low-dose dexmedetomidine infusion (at a rate of 0.1 ug/kg/h, for an average of 15 hours) improves analgesia for up to 24 hours, ameliorates subjective sleep quality for up to 3 days, and reduces the incidence of delirium during the first 7 postoperative days. The investigators hypothesized that the use of dexmedetomidine as a supplement to patient-controlled intravenous analgesia may also reduce the incidence of postoperative delirium.
Condition or disease Intervention/treatment Phase

Analgesia

Complication, Postoperative

Delirium

Dexmedetomidine

Elderly

Surgery

Drug: Dexmedetomidine supplemented morphine analgesia
Other Names
Drug: Morphine analgesia
Other Names
Phase 4

Tracking Information

First Submitted DateDecember 31, 2016
Last Update Posted DateFebruary 22, 2018
Start DateJanuary 01, 2017
Anticipated Completion DateDecember 01, 2024
Primary Completion DateDecember 01, 2019
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Incidence of delirium within 5 days after surgery [Time Frame: During the first 5 days after surgery]

    Incidence of delirium within 5 days after surgery

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Daily prevalence of delirium during the first 5 postoperative days [Time Frame: During the first 5 postoperative days]

    Daily prevalence of delirium during the first 5 postoperative days

  • Length of stay in hospital after surgery [Time Frame: Up to 30 days after surgery]

    Length of stay in hospital after surgery

  • Incidence of non-delirium complications after surgery [Time Frame: Up to 30 days after surgery]

    Incidence of non-delirium complications after surgery

  • 30-day all-cause mortality after surgery [Time Frame: At the time of 30 days after surgery]

    30-day all-cause mortality after surgery

  • Quality of life in survival patients on the 30th day after surgery [Time Frame: On the 30th day after surgery]

    Assessed with World Health Organization Quality of Life-Bref (WHOQOL-BREF)

  • Cognitive function in survival patients on the 30th day after surgery [Time Frame: On the 30th day after surgery]

    Assessed with Telephone Interview for Cognitive Status-Modified (TICS-M)

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleDexmedetomidine Supplemented Analgesia and Incidence of Postoperative Delirium
Official TitleImpact of Dexmedetomidine Supplemented Analgesia on Incidence of Delirium in Elderly Patients After Cancer Surgery: a Multicenter Randomized Controlled Trial
Brief Summary

Delirium is a frequently occurred cerebral complication in elderly patients after surgery, and its occurrence is associated with worse outcomes. Sleep disturbances is considered to be one of the most important risk factors of postoperative delirium. Previous studies showed that, for elderly patients admitted to the ICU after surgery, low-dose dexmedetomidine infusion improved the quality of sleep and decreased the incidence of delirium. The investigators hypothesize that, for elderly patients after cancer surgery, dexmedetomidine supplemented analgesia can also decrease the incidence of delirium, possibly by improving sleep quality. The purpose of this multicenter, randomized controlled trial is to investigate the impact of dexmedetomidine supplemented analgesia on the incidence of delirium in elderly patients after cancer surgery.

Detailed Description

Delirium is a state of acutely occurred and transient cerebral dysfunction. It is a common complication in elderly patients after surgery. A systematic review showed that an average of 36.8% (range 0 to 73.5%) of surgical patients developed postoperative delirium, and its occurrence increased with age. According to our previous studies, postoperative delirium developed in 51.0% of patients after cardiac surgery and in 44.5% of patients after non-cardiac surgery. The occurrence of delirium is associated with worse short-term outcomes, including increased postoperative complications, prolonged hospital stay, and increased in-hospital mortality; it is also associated with worse long-term outcomes, including declined cognitive function, decreased quality of life, and increased post-hospital mortality. Delirium is the result of multiple factors. Studies showed that postoperative pain is an important risk factor of delirium, whereas good postoperative analgesia reduces the incidence of delirium. For postoperative patients, sleep disturbances occurs frequently and increases the risk of delirium, whereas improving sleep quality reduces the incidence of delirium. Furthermore, the studies found that surgery related inflammatory response also plays an important role in the development of delirium.

Dexmedetomidine is a highly selective alpha-2 (α2) adrenoreceptor agonist that provides anxiolysis, sedation, hypnosis and analgesia. It exerts the sedative and hypnotic effects by activating the endogenous sleep pathways, and produces a condition similar to phase 2 non-rapid eye movement sleep. For patients undergoing mechanical ventilation in the ICU, dexmedetomidine sedation helps to maintain a normal circadian rhythm of sleep and improves sleep architecture. Dexmedetomidine also provides analgesic effect by activating α2 adrenergic receptors in the dorsal horn of spinal cord. When used as a supplemental drug it decreases intraoperative and postoperative requirement of opioids. Moreover, animal studies showed that dexmedetomidine significantly inhibits the degree of inflammatory response induced by endotoxin or during spinal cord injury. In clinical studies, dexmedetomidine attenuates the degree of inflammatory response following Coronary Artery Bypass Grafting surgery.

These effects of dexmedetomidine make it suitable for prevention of postoperative delirium in high-risk patients. Studies have shown that, for ICU patients requiring mechanical ventilation, sedation with dexmedetomidine reduces the incidence of delirium when compared with other sedatives; for postoperative patients, dexmedetomidine administered in combined with opioids improves analgesia and reduces opioid requirements. A recent study showed that, for elderly patients admitted to the ICU after surgery, low-dose dexmedetomidine infusion (at a rate of 0.1 ug/kg/h, for an average of 15 hours) improves analgesia for up to 24 hours, ameliorates subjective sleep quality for up to 3 days, and reduces the incidence of delirium during the first 7 postoperative days. The investigators hypothesized that the use of dexmedetomidine as a supplement to patient-controlled intravenous analgesia may also reduce the incidence of postoperative delirium.

Study TypeInterventional
Study PhasePhase 4
Estimated Enrollment
1200
Allocation
Randomized
Interventional Model
Parallel Assignment
Masking
Quadruple
Primary Purpose
Prevention
Conditions
Analgesia
Complication, Postoperative
Delirium
Dexmedetomidine
Elderly
Surgery
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: Dexmedetomidine supplemented morphine analgesia

Patients in this group will receive patient-controlled intravenous analgesia for 3 days after surgery. The formula is a mixture of dexmedetomidine (1.25 ug/ml) and morphine (0.5 mg/ml), diluted with normal saline to160 ml. The analgesic pump is set to administer a background infusion at a rate of 1 ml/h, with a bolus dose of 2 ml each time and a lockout time from 6 to 8 minutes according to patients' condition.

Other Names
Drug: Morphine analgesia

Patients in this group will receive patient-controlled intravenous analgesia for 3 days after surgery. The formula is morphine (0.5 mg/ml), diluted with normal saline to160 ml. The analgesic pump is set to administer a background infusion at a rate of 1 ml/h, with a bolus dose of 2 ml each time and a lockout time from 6 to 8 minutes according to patients' condition.

Other Names
Study Groups/Cohorts
Dexmedetomidine group
Dexmedetomidine supplemented morphine analgesia will be provided for patients in this group in the form of patient-controlled intravenous analgesia. The formula contains a mixture of morphine (0.5 mg/ml) and dexmedetomidine (1.25 ug/ml), with a total volume of 160 ml. The analgesic pump is set to administer a background infusion at a rate of 1 ml/h, with patient-controlled bolus of 2 ml each time and a lockout time from 6 to 8 minutes.

Control group
Morphine analgesia will be provided for patients in this group in the form of patient-controlled intravenous analgesia. The formula contains morphine (0.5 mg/ml), with a total volume of 160 ml. The analgesic pump is set to administer a background infusion at a rate of 1 ml/h, with patient-controlled bolus of 2 ml each time and a lockout time from 6 to 8 minutes.

Study Arms
Placebo Comparator Control group
Morphine analgesia will be provided for patients in this group in the form of patient-controlled intravenous analgesia. The formula contains morphine (0.5 mg/ml), with a total volume of 160 ml. The analgesic pump is set to administer a background infusion at a rate of 1 ml/h, with patient-controlled bolus of 2 ml each time and a lockout time from 6 to 8 minutes.
Drug : Morphine analgesia
Patients in this group will receive patient-controlled intravenous analgesia for 3 days after surgery. The formula is morphine (0.5 mg/ml), diluted with normal saline to160 ml. The analgesic pump is set to administer a background infusion at a rate of 1 ml/h, with a bolus dose of 2 ml each time and a lockout time from 6 to 8 minutes according to patients' condition.

Experimental Dexmedetomidine group
Dexmedetomidine supplemented morphine analgesia will be provided for patients in this group in the form of patient-controlled intravenous analgesia. The formula contains a mixture of morphine (0.5 mg/ml) and dexmedetomidine (1.25 ug/ml), with a total volume of 160 ml. The analgesic pump is set to administer a background infusion at a rate of 1 ml/h, with patient-controlled bolus of 2 ml each time and a lockout time from 6 to 8 minutes.
Drug : Dexmedetomidine supplemented morphine analgesia
Patients in this group will receive patient-controlled intravenous analgesia for 3 days after surgery. The formula is a mixture of dexmedetomidine (1.25 ug/ml) and morphine (0.5 mg/ml), diluted with normal saline to160 ml. The analgesic pump is set to administer a background infusion at a rate of 1 ml/h, with a bolus dose of 2 ml each time and a lockout time from 6 to 8 minutes according to patients' condition.

Arm Intervention/Treatment
Placebo Comparator Control group
Morphine analgesia will be provided for patients in this group in the form of patient-controlled intravenous analgesia. The formula contains morphine (0.5 mg/ml), with a total volume of 160 ml. The analgesic pump is set to administer a background infusion at a rate of 1 ml/h, with patient-controlled bolus of 2 ml each time and a lockout time from 6 to 8 minutes.
Drug : Morphine analgesia
Experimental Dexmedetomidine group
Dexmedetomidine supplemented morphine analgesia will be provided for patients in this group in the form of patient-controlled intravenous analgesia. The formula contains a mixture of morphine (0.5 mg/ml) and dexmedetomidine (1.25 ug/ml), with a total volume of 160 ml. The analgesic pump is set to administer a background infusion at a rate of 1 ml/h, with patient-controlled bolus of 2 ml each time and a lockout time from 6 to 8 minutes.
Drug : Dexmedetomidine supplemented morphine analgesia

Recruitment Information

Recruitment Status:Recruiting
Enrollment1200
Completion DateDecember 01, 2024
Eligibility Criteria: Inclusion Criteria:
- Age >= 65 years, < 90 years;
- Scheduled to undergo cancer surgery under general anesthesia with an expected duration of surgery >=2 hours;
- The diagnosis is primary malignancy, without preoperative radio- or chemotherapy;
- Patient-controlled intravenous analgesia is planned for postoperative analgesia.

Exclusion Criteria:
- Refuse to participate;
- Preoperative history of schizophrenia, epilepsy, parkinsonism or myasthenia gravis;
- Inability to communicate in the preoperative period because of coma, profound dementia or language barrier;
- Presence of preoperative sleep apnea (diagnosed with sleep apnea, or a STOP-Bang score >= 3);
- Brain trauma or neurosurgery;
- Preoperative left ventricular ejection fraction < 30%, sick sinus syndrome, severe sinus bradycardia (< 50 beats per minute), or second-degree or above atrioventricular block without pacemaker;
- Severe hepatic dysfunction (Child-Pugh class C);
- Severe renal dysfunction (requirement of renal replacement therapy before surgery);
- ASA classification >= IV or unlikely to survive for more than 24 hours after surgery.
GenderAll
Age65 Years to 90 Years
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
China

Administrative Information

NCT Number:NCT03012984
Other Study ID Numbers
DEXanalgesia
Has Data Monitoring CommitteeYes
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible PartyDong-Xin Wang, Peking University First Hospital
Study Sponsor
Peking University First Hospital
Collaborators
Not Available
Investigators
Principal Investigator
Dong-Xin Wang, MD,PhD
Department of Anesthesiology and Critical Care Medicine, Peking University First Hospital

Publications