Epidural Anesthesia-analgesia and Long-term Outcome

NCT03012945 | Completed DMC

• 1 other identifier: PUCRP201101-1
• Study Type: interventional
• Target: 1,802
• Locations: 1 country
• Sites: 5

Brief Summary

Surgical resection is one of the most important treatments for resectable cancer; on the other hand, cancer recurrence and/or metastasis are the major reasons of treatment failure. The development of recurrence/metastasis after cancer surgery mostly depends on the balance between the immunity of human body and the capability of implantation, proliferation and neovascularization of the residual cancer. Preclinical and retrospective clinical studies suggest that anaesthetic management may affect the long-term outcomes after cancer surgery. The investigators hypothesize that use of epidural anesthesia-analgesia may improve long-term survival in elderly patients after major surgery for cancer.

Conditions

Elderly; Malignant Tumor; Surgical Resection; Epidural Anesthesia; Long-term Outcome

Keywords

Elderly; Cancer surgery; Epidural anesthesia and analgesia; Long-term survival

Outcome Measures

Primary Outcomes (1)

• Overall survival after surgery.

  Time from surgery to the date of all-cause death.

  Up to median 5 years after surgery.

Secondary Outcomes (3)

• Cancer-specific survival after surgery.

  Up to median 5 years after surgery.

• Recurrence-free survival after surgery.

  Up to median 5 years after surgery.

• Event-free survival after surgery.

  Up to median 5 years after surgery.

Other Outcomes (6)

• Overall survival after surgery (cancer patients).

  Up to median 5 years after surgery.

• Cancer-specific survival after surgery (cancer patients).

  Up to median 5 years after surgery.

• Recurrence-free survival after surgery (cancer patients).

  Up to median 5 years after surgery.

Study Arms (2)

Combined epidural-general anesthesia

EXPERIMENTAL

Patients assigned to this group (experimental group) receive combined epidural-general anesthesia and postoperative patient-controlled epidural analgesia.

Drug: Combined epidural-general anesthesia

General anesthesia

ACTIVE COMPARATOR

Patients assigned to this group (control group) receive general anesthesia and postoperative patient-controlled intravenous analgesia.

Drug: General anesthesia

Interventions

Combined epidural-general anesthesia DRUG

Combined epidural-general anesthesia and postoperative epidural analgesia. General anesthesia is performed as that in the general anesthesia group. Epidural anesthesia is performed with ropivacaine. Epidural analgesia is performed with a mixture of ropivacaine and sufentanil.

Also known as: Combined epidural-general anesthesia and postoperative epidural analgesia

Combined epidural-general anesthesia

General anesthesia DRUG

General anesthesia and postoperative intravenous analgesia. General anesthesia is performed with propofol induction and propofol and/or sevoflurane maintenance. Intravenous analgesia is performed with morphine.

Also known as: General anesthesia and postoperative intravenous analgesia

General anesthesia

Eligibility Criteria

• Age: 60 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Elderly patients (age 60-90 years);
• Scheduled to undergo noncardiac thoracic or abdominal surgery with an expected duration of 2 hours or longer. For those who undergo thoracoscopic or laparoscopic surgery, the expected length of incision must be 5 centimeters or more;
• Agree to receive patient-controlled postoperative analgesia.

You may not qualify if:

• Refuse to participate;
• Previous history of schizophrenia, epilepsy or Parkinson disease, or unable to complete preoperative assessment due to severe dementia, language barrier or end-stage disease;
• History of myocardial infarction or stroke within 3 months before surgery;
• Presence of any contraindication to epidural anesthesia and analgesia, including abnormal vertebral anatomy, previous spinal trauma or surgery, severe chronic back pain, coagulation disorder (prothrombin time or activated partial prothrombin time longer than 1.5 times of the upper normal limit, or platelet count of less than 80 \* 10\^9/L), local infection near the site of puncture, and severe sepsis;
• Severe heart dysfunction (New York Heart Association functional classification 3 or above), severe hepatic insufficiency (Child-Pugh grade C), or severe renal insufficiency (serum creatinine of 442 umol/L or above, with or without serum potassium of 6.5 mmol/L or above, or requirement of renal replacement therapy);
• Any other conditions that are considered unsuitable for study participation.

Sponsors & Collaborators

• Peking University First Hospital: lead
• Peking University People's Hospital: collaborator
• Peking University Third Hospital: collaborator
• Beijing Hospital: collaborator
• Beijing Shijitan Hospital, Capital Medical University: collaborator
• Peking University: collaborator

Study Sites (5)

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

Location

Beijing Shijitan Hospital

Beijing, 100038, China

Location

Peking University People's Hospital

Beijing, 100044, China

Location

Peking University Third Hospital

Beijing, 100191, China

Location

Beijing Hospital

Beijing, 100730, China

Location

Related Publications (12)

• Yamaguchi K, Takagi Y, Aoki S, Futamura M, Saji S. Significant detection of circulating cancer cells in the blood by reverse transcriptase-polymerase chain reaction during colorectal cancer resection. Ann Surg. 2000 Jul;232(1):58-65. doi: 10.1097/00000658-200007000-00009.

  PMID: 10862196 BACKGROUND

• Shakhar G, Ben-Eliyahu S. Potential prophylactic measures against postoperative immunosuppression: could they reduce recurrence rates in oncological patients? Ann Surg Oncol. 2003 Oct;10(8):972-92. doi: 10.1245/aso.2003.02.007.

  PMID: 14527919 BACKGROUND

• Sessler DI. Long-term consequences of anesthetic management. Anesthesiology. 2009 Jul;111(1):1-4. doi: 10.1097/ALN.0b013e3181a913e1. No abstract available.

  PMID: 19512884 BACKGROUND

• Buggy DJ, Smith G. Epidural anaesthesia and analgesia: better outcome after major surgery?. Growing evidence suggests so. BMJ. 1999 Aug 28;319(7209):530-1. doi: 10.1136/bmj.319.7209.530. No abstract available.

  PMID: 10463878 BACKGROUND

• Melamed R, Bar-Yosef S, Shakhar G, Shakhar K, Ben-Eliyahu S. Suppression of natural killer cell activity and promotion of tumor metastasis by ketamine, thiopental, and halothane, but not by propofol: mediating mechanisms and prophylactic measures. Anesth Analg. 2003 Nov;97(5):1331-1339. doi: 10.1213/01.ANE.0000082995.44040.07.

  PMID: 14570648 BACKGROUND

• Mitsuhata H, Shimizu R, Yokoyama MM. Suppressive effects of volatile anesthetics on cytokine release in human peripheral blood mononuclear cells. Int J Immunopharmacol. 1995 Jun;17(6):529-34. doi: 10.1016/0192-0561(95)00026-x.

  PMID: 7499031 BACKGROUND

• Markovic SN, Knight PR, Murasko DM. Inhibition of interferon stimulation of natural killer cell activity in mice anesthetized with halothane or isoflurane. Anesthesiology. 1993 Apr;78(4):700-6. doi: 10.1097/00000542-199304000-00013.

  PMID: 8466070 BACKGROUND

• Gupta K, Kshirsagar S, Chang L, Schwartz R, Law PY, Yee D, Hebbel RP. Morphine stimulates angiogenesis by activating proangiogenic and survival-promoting signaling and promotes breast tumor growth. Cancer Res. 2002 Aug 1;62(15):4491-8.

  PMID: 12154060 BACKGROUND

• Beilin B, Martin FC, Shavit Y, Gale RP, Liebeskind JC. Suppression of natural killer cell activity by high-dose narcotic anesthesia in rats. Brain Behav Immun. 1989 Jun;3(2):129-37. doi: 10.1016/0889-1591(89)90013-5.

  PMID: 2477090 BACKGROUND

• Gaspani L, Bianchi M, Limiroli E, Panerai AE, Sacerdote P. The analgesic drug tramadol prevents the effect of surgery on natural killer cell activity and metastatic colonization in rats. J Neuroimmunol. 2002 Aug;129(1-2):18-24. doi: 10.1016/s0165-5728(02)00165-0.

  PMID: 12161016 BACKGROUND

• O'Riain SC, Buggy DJ, Kerin MJ, Watson RWG, Moriarty DC. Inhibition of the stress response to breast cancer surgery by regional anesthesia and analgesia does not affect vascular endothelial growth factor and prostaglandin E2. Anesth Analg. 2005 Jan;100(1):244-249. doi: 10.1213/01.ANE.0000143336.37946.7D.

  PMID: 15616085 BACKGROUND

• Chen WK, Miao CH. The effect of anesthetic technique on survival in human cancers: a meta-analysis of retrospective and prospective studies. PLoS One. 2013;8(2):e56540. doi: 10.1371/journal.pone.0056540. Epub 2013 Feb 20.

  PMID: 23437162 BACKGROUND

MeSH Terms

Conditions

Neoplasms; Agnosia

Interventions

Anesthesia, General

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Anesthesia; Anesthesia and Analgesia

Study Officials

• Dong-Xin Wang, MD

  Peking University First Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 31, 2016
• First Posted: January 6, 2017
• Study Start: November 1, 2014
• Primary Completion: September 30, 2019
• Study Completion: September 30, 2019
• Last Updated: July 8, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5)