Dexmedetomidine Supplemented Analgesia and Long-term Survival After Cancer Surgery

Peking University

Status: Completed

Conditions: Long-term Outcome; Dexmedetomidine; Surgery; Elderly; Analgesia

Treatments: Drug: Morphine analgesia; Drug: Dexmedetomidine supplemented morphine analgesia

Study type: Interventional

Funder types: Other

Identifiers

NCT03012971

2016-10-LT

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 1,500 patients

Sex: All

Ages: 65 to 90 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age >= 65 years, < 90 years;
• Scheduled to undergo curative resection 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 and serum HCO3- >= 28 mmol/L);
• 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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,500 participants in 2 patient groups, including a placebo group

Dexmedetomidine group

Experimental group

Description:

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.

Treatment:

Drug: Dexmedetomidine supplemented morphine analgesia

Control group

Placebo Comparator group

Description:

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.

Treatment:

Drug: Morphine analgesia