Epidural Anesthesia-analgesia and Long-term Outcome

NCT ID: NCT03012945

Last Updated: 2020-07-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 1802 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-01
• Study Completion Date: 2019-09-30

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.

Detailed Description

Surgical resection is the main treatment for potentially curable solid organ cancer. However, it is unavoidable that some cancer cells are disseminated into the circulatory or lymphatic system during surgery. And quite a number of patients develop cancer recurrence and/or metastasis after surgery, which are associated with poor long-term outcomes. The development of cancer recurrence and/or metastasis after surgery is mostly dependent on the balance between the anti-tumor immune function of the human body and the ability of implantation, proliferation and neovascularization of the residual cancer cells.

Multiple surgical factors may influence the balance between the anti-cancer immune function and cancer recurrence. For example, the presence of the primary cancer inhibits angiogenesis, whereas cancer resection eliminates this safeguard against angiogenesis; surgical manipulation releases cancer cells into the circulation; surgery-related stress response inhibits natural killer (NK) cell activity and can promote the development of cancer metastasis; local and systemic release of growth factors during surgery may also promote cancer recurrence both locally and at distant sites.

Available studies showed that general anaesthesia/anesthetics may influence the cellular immune function and long-term outcomes. For example, it was found that ketamine and thiopental, but not propofol, suppressed NK cell activity; all three drugs caused a significant reduction in NK cell number; isoflurane and halothane inhibit interferon (IFN) stimulation of NK cell cytotoxicity; nitrous oxide interferes with DNA, purine, and thymidylate synthesis and depresses neutrophil chemotaxis; opioids have been reported to suppress cell-mediated and humoral immunity.

Considering the potential harmful effects of general anesthesia/anesthetics, there is an increasing interest on the effect of regional anaesthesia. Retrospective studies investigating the relationship between epidural anesthesia and outcome after cancer surgery gave different results. In a meta-analysis, regional anesthesia is associated with improved survival (hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.74-0.96, P = 0.013), but not cancer recurrence/metastasis (HR 0.88, 95% Cl 0.64-1.22, P = 0.457). The investigators hypothesize that combined use of epidural anesthesia may produce favorable effects on the long-term survival in elderly patients undergoing major cancer surgery.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Combined epidural-general anesthesia

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

Group Type: EXPERIMENTAL

Combined epidural-general anesthesia

Intervention Type: 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.

General anesthesia

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

Group Type: ACTIVE_COMPARATOR

General anesthesia

Intervention Type: 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.

Interventions

Combined epidural-general anesthesia

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.

Intervention Type: DRUG

General anesthesia

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.

Intervention Type: DRUG

Other Intervention Names

Combined epidural-general anesthesia and postoperative epidural analgesia; General anesthesia and postoperative intravenous analgesia

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking University People's Hospital

OTHER

Sponsor Role: collaborator

Peking University Third Hospital

OTHER

Sponsor Role: collaborator

Beijing Hospital

OTHER_GOV

Sponsor Role: collaborator

Beijing Shijitan Hospital, Capital Medical University

OTHER

Sponsor Role: collaborator

Peking University

OTHER

Sponsor Role: collaborator

Peking University First Hospital

OTHER

Sponsor Role: lead

Responsible Party

Dong-Xin Wang

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dong-Xin Wang, MD

Role: PRINCIPAL_INVESTIGATOR

Peking University First Hospital

Locations

Peking University First Hospital

Beijing, Beijing Municipality, China

Beijing Shijitan Hospital

Beijing, , China

Peking University People's Hospital

Beijing, , China

Peking University Third Hospital

Beijing, , China

Beijing Hospital

Beijing, , China

Countries

China

References

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Other Identifiers

PUCRP201101-1

Identifier Type: -

Identifier Source: org_study_id