Nervous System Diseases

Symptoms and General Pathology

Behaviors and Mental Disorders

All Conditions

Delirium

Postoperative Complications

Neurobehavioral Manifestations

Neurologic Manifestations

Confusion

Neurocognitive Disorders

Mental Disorders

Psychotic Disorders

Analgesics

Central Nervous System Depressants

All Drugs and Chemicals

Dexmedetomidine

Morphine

Serotonin

Hypnotics and Sedatives

Analgesics, Non-Narcotic

Adrenergic Agents

Adrenergic alpha-Agonists

Adrenergic Agonists

Neurotransmitter Agents

Analgesics, Opioid

Narcotics

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), diluted with normal saline to a total volume of 160 ml. 5-HT3 receptor antagonist is added when necessary. 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.

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), diluted with normal saline to a total volume of 160 ml. 5-HT3 receptor antagonist is added when necessary. 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.

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 to 160 ml. 5-HT3 receptor antagonist is added when necessary. 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.

Dexmedetomidine supplemented 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 to 160 ml. 5-HT3 receptor antagonist is added when necessary. 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.

Morphine analgesia

Dong-Xin Wang, MD,PhD

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.

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.

Dexmedetomidine Supplemented Analgesia and Incidence of Postoperative Delirium

Impact of Dexmedetomidine Supplemented Analgesia on Incidence of Delirium in Elderly Patients After Cancer Surgery: a Multicenter Randomized Controlled Trial

Richmond Agitation-Sedation Scale (RASS) score during the first 5 days after surgery

Cumulative morphine consumption during the first 3 days after surgery

Numeric Rating Scale (NRS) pain score during the first 5 days after surgery

Numeric Rating Scale (NRS) sleep quality score during the first 5 days after surgery

Incidence of delirium within 5 days after surgery

Daily prevalence of delirium during the first 5 postoperative days

Incidence of non-delirium complications after surgery

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

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

Affiliated Hospital of Hebei University

Qingdao Municipal Hospital

The Second Affiliated Hospital of Air Force Medical University

Peking University International Hospital

Guizhou Provincial People's Hospital

The Third Xiangya Hospital of Central South University

Shanxi Provincial Cancer Hospital

Tianjin Hospital of ITCWM-Nankai Hospital

Zhongda Hospital

Chongqing University Fuling Hospital

Peking University First Hospital

Professor and Chairman, Department of Anesthesiology and Critical Care Medicine

Rare Diseases

Agnosia

Perceptual Disorders

Dexmedetomidine supplemented morphine analgesia is 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), diluted with normal saline to a total volume of 160 ml. 5-HT3 receptor antagonist is added when necessary. 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.

Morphine analgesia is provided for patients in this group in the form of patient-controlled intravenous analgesia. The formula contains morphine (0.5 mg/ml), diluted with normal saline to a total volume of 160 ml. 5-HT3 receptor antagonist is added when necessary. 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.

Patients in this group 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 to 160 ml. 5-HT3 receptor antagonist is added when necessary. The analgesic pump is set to administer a background infusion at a rate of 1 ml/h, with a bolus dose of 2 ml at each time and a lockout time from 6 to 8 minutes.

Patients in this group receive patient-controlled intravenous analgesia for 3 days after surgery. The formula is morphine (0.5 mg/ml), diluted with normal saline to 160 ml. 5-HT3 receptor antagonist is added when necessary. The analgesic pump is set to administer a background infusion at a rate of 1 ml/h, with a bolus dose of 2 ml at each time and a lockout time from 6 to 8 minutes.

Dong-Xin Wang, MD, PhD

A majority of the elderly patients undergo surgery for malignant tumors. For these patients, postoperative tumor recurrence and metastasis are main factors that worsen long-term outcomes. The investigators hypothesize that dexmedetomidine supplemented analgesia in elderly patients after cancer surgery may help to maintain immune function and improve long-term outcomes, possibly by relieving stress and inflammatory response, improving analgesic efficacy and sleep quality, and reducing delirium incidence.

A majority of the elderly patients undergo surgery for malignant tumors. For these patients, postoperative tumor recurrence and metastasis are main factors that worsen the quality of life and shorten the duration of survival. Perioperative immune function is a key element that influences postoperative tumor recurrence and metastasis; but it is subject to the impacts of many factors. Studies showed that elevated cortisol level and inflammation provoked by surgical stress result in suppression of immune function, whereas dexmedetomidine alleviates the elevated cortisol level and inhibit excessive inflammation; high-dose opioids inhibit the immune function and increase the invasiveness of tumor cells, whereas dexmedetomidine reduces the consumption of opioids during perioperative period; postoperative sleep disturbances also impair immune function, whereas dexmedetomidine improves sleep quality in patients after surgery; occurrence of postoperative delirium is associated with increased mortality, whereas dexmedetomidine reduces delirium incidence. The investigators hypothesize that dexmedetomidine supplemented analgesia in elderly patients after cancer surgery may improve the long-term outcomes, possibly by relieving stress and inflammatory response, improving analgesic efficacy and sleep quality, and reducing delirium incidence.

Dexmedetomidine Supplemented Analgesia and Long-term Survival After Cancer Surgery

Impact of Dexmedetomidine Supplemented Analgesia on Long-term Survival in Elderly Patients After Cancer Surgery: a Multicenter Randomized Controlled Trial

Cognitive function was assessed with Telephone Interview for Cognitive Function-Modified (TICS-M)

Quality of life was assessed with World Health Organization Quality of Life-Bref (WHOQOL-BREF)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Dexmedetomidine Supplemented Analgesia and Incidence of Postoperative Delirium	NCT03012984	Elderly Surgery Analgesia Dexmedetomidine Complication, P... Delirium	Dexmedetomidine... Morphine analge...	65 Years - 90 Years	Peking University First Hospital
Dexmedetomidine Supplemented Analgesia and Long-term Survival After Cancer Surgery	NCT03012971	Elderly Surgery Analgesia Dexmedetomidine Long-term Outco...	Dexmedetomidine... Morphine analge...	65 Years - 90 Years	Peking University First Hospital

Spots Global Cancer Trial Database for morphine analgesia