Dexmedetomidine Supplemented Analgesia and Incidence of Postoperative Delirium

Surgery Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03012984
• Other study ID #: 2016-10
• Status: Completed
• Phase: N/A
• Start date: January 6, 2017
• Est. completion date: June 11, 2022

Study information

• Verified date: July 2023
• Source: Peking University First Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1500
• Est. completion date: June 11, 2022
• Est. primary completion date: May 12, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years to 90 Years

Eligibility

Inclusion Criteria:

• Age >= 65 years, < 90 years;

• Scheduled to undergo surgery for primary solid organ cancer under general anesthesia, with an expected duration of surgery >=2 hours;

• Planned to use patient-controlled intravenous analgesia after surgery;

• Provide written informed consent.

Exclusion Criteria:

• Preoperative history of schizophrenia, epilepsy, parkinsonism or myasthenia gravis;

• Preoperative radio- or chemotherapy;

• Inability to communicate in the preoperative period because of coma, profound dementia or language barrier;

• Preoperative obstructive sleep apnea (previously diagnosed as obstructive 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) or severe renal dysfunction (requirement of renal replacement therapy before surgery);

• ASA classification >= IV.

Related Conditions & MeSH terms

• Analgesia
• Complication, Postoperative
• Delirium
• Dexmedetomidine
• Elderly
• Postoperative Complications
• Surgery

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 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
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.

Locations

Country	Name	City	State
China	Affiliated Hospital of Hebei University	Baoding	Hebei
China	Peking University First Hospital	Beijing	Beijing
China	Peking University International Hospital	Beijing	Beijing
China	The Third Xiangya Hospital of Central South University	Changsha	Hunan
China	Chongqing University Fuling Hospital	Chongqing	Chongqing
China	Guizhou Provincial People's Hospital	Guiyang	Guizhou
China	Zhongda Hospital Southeast University	Nanjing	Jiangsu
China	Qingdao Municipal Hospital	Qingdao	Shandong
China	Shanxi Provincial Cancer Hospital	Taiyuan	Shanxi
China	Tianjin Hospital of ITCWM-Nankai Hospital	Tianjin	Tianjin
China	The Second Affiliated Hospital of Air Force Medical University	Xi'an	Shaanxi

Sponsors (11)

Lead Sponsor

Collaborator

Peking University First Hospital

Affiliated Hospital of Hebei University, Chongqing University Fuling Hospital, Guizhou Provincial People's Hospital, Peking University International Hospital, Qingdao Municipal Hospital, Shanxi Provincial Cancer Hospital, The Second Affiliated Hospital of Air Force Medical University, The Third Xiangya Hospital of Central South University, Tianjin Hospital of ITCWM-Nankai Hospital, Zhongda Hospital

Country where clinical trial is conducted

China, 

References & Publications (45)

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* Note: There are 45 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Richmond Agitation-Sedation Scale (RASS) score during the first 5 days after surgery	Richmond Agitation-Sedation Scale (RASS) score during the first 5 days after surgery	During the first 5 days after surgery
Other	Cumulative morphine consumption during the first 3 days after surgery	Cumulative morphine consumption during the first 3 days after surgery	During the first 3 days after surgery
Other	Numeric Rating Scale (NRS) pain score during the first 5 days after surgery	Numeric Rating Scale (NRS) pain score during the first 5 days after surgery	During the first 5 days after surgery
Other	Numeric Rating Scale (NRS) sleep quality score during the first 5 days after surgery	Numeric Rating Scale (NRS) sleep quality score during the first 5 days after surgery	During the first 5 days after surgery
Primary	Incidence of delirium within 5 days after surgery	Incidence of delirium within 5 days after surgery	During the first 5 days after surgery
Secondary	Daily prevalence of delirium during the first 5 postoperative days	Daily prevalence of delirium during the first 5 postoperative days	During the first 5 postoperative days
Secondary	Length of stay in hospital after surgery	Length of stay in hospital after surgery	Up to 30 days after surgery
Secondary	Incidence of non-delirium complications after surgery	Incidence of non-delirium complications after surgery	Up to 30 days after surgery
Secondary	30-day all-cause mortality after surgery	30-day all-cause mortality after surgery	At the time of 30 days after surgery
Secondary	Quality of life in survival patients on the 30th day after surgery	Assessed with World Health Organization Quality of Life-Bref (WHOQOL-BREF)	On the 30th day after surgery
Secondary	Cognitive function in survival patients on the 30th day after surgery	Assessed with Telephone Interview for Cognitive Status-Modified (TICS-M)	On the 30th day after surgery