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

Affiliated Hospital of Hebei University, Qingdao Municipal Hospital, The Second Affiliated Hospital of Air Force Medical University, Beijing Chao Yang Hospital, Beijing Shijitan Hospital, Capital Medical University, Beijing Tsinghua Chang Gung Hospital, Peking University International Hospital, Beijing Ditan 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

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 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.

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.

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