Epidural Anesthesia-analgesia and Long-term Outcome

Not Applicable

Completed

• Conditions: Malignant Tumor; Epidural Anesthesia; Surgical Resection; Long-term Outcome; Elderly
• Interventions: Drug: Combined epidural-general anesthesia; Drug: General anesthesia

• Registration Number: NCT03012945
• Lead Sponsor: Peking University First Hospital

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.

Study Timeline

• Study Start: 2014-11-01
• Study First Submitted: 2016-12-31
• Study First Submitted QC: 2017-01-05
• Study First Posted: 2017-01-06
• Primary Completion: 2019-09-30
• Study Completion: 2019-09-30
• Status Verified: 2020-07
• Last Update Submitted: 2020-07-06
• Last Update Posted: 2020-07-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1802

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Combined epidural-general anesthesia	Combined epidural-general anesthesia	Patients assigned to this group (experimental group) receive combined epidural-general anesthesia and postoperative patient-controlled epidural analgesia.
General anesthesia	General anesthesia	Patients assigned to this group (control group) receive general anesthesia and postoperative patient-controlled intravenous analgesia.

Primary Outcome Measures

Name	Time	Method
Overall survival after surgery.	Up to median 5 years after surgery.	Time from surgery to the date of all-cause death.

Secondary Outcome Measures

Name	Time	Method
Cancer-specific survival after surgery.	Up to median 5 years after surgery.	Time from surgery to the date of cancer-specific death. Patients who die from other causes will be censored at the time of death.
Recurrence-free survival after surgery.	Up to median 5 years after surgery.	Time from surgery to the date of cancer recurrence/metastasis or all-cause death, whichever come first.
Event-free survival after surgery.	Up to median 5 years after surgery.	Time from surgery to the first date of cancer recurrence/metastasis, new onset cancer, new serious non-cancer disease, or death from any cause.

Trial Locations

Locations (5)

Peking University First Hospital; 🇨🇳 Beijing, Beijing, China

Peking University People's Hospital; 🇨🇳 Beijing, China

Beijing Shijitan Hospital; 🇨🇳 Beijing, China

Beijing Hospital; 🇨🇳 Beijing, China

Peking University Third Hospital; 🇨🇳 Beijing, China