Epidural Anesthesia and Long-term Outcomes in Elderly Patients After Surgery

Impact of Epidural Anesthesia-analgesia on Long-term Outcomes in Elderly Patients After Surgery: 5-year Follow-up of a Multicenter Randomized Controlled Trial

Surgical resection is one of the most important treatments for solid organ cancer. Whereas cancer recurrence and/or metastasis are the major reasons of treatment failure. The outcomes after surgery are mainly dependent on the balance between the immune function of the body and the invasiveness of residual cancer. Preclinical and retrospective studies suggest that anaesthetic techniques and drugs may affect the long-term outcomes in patients undergoing cancer surgery. The investigators hypothesize that epidural anesthesia-analgesia may improve long-term survival in the elderly who undergo major surgery for cancer.

Surgical resection is the main treatment for potentially curable solid organ cancer. However, long-term survival after cancer surgery is far from satisfactory. Quite a number of patients develop tumor metastasis and/or recurrence after surgery, which are associated with poor long-term outcomes. The development of tumor recurrence and/or metastasis after surgery is mostly dependent on the balance between the anti-tumor immune function of the body and the ability of implantation, proliferation and neovascularization of the residual cancer cells.

Studies showed that anaesthetic techniques and drugs may influence the cellular immune function and long-term outcomes. For example, it was found that ketamine and thiopental, but not propofol, suppresses natural killer (NK) cell activity; all three drugs caused a significant reduction in NK cell number; isoflurane and halothane inhibit interferon stimulation of NK cell cytotoxicity; nitrous oxide interferes with deoxyribonucleic acid, purine, and thymidylate synthesis and depresses neutrophil chemotaxis; opioids have been shown to suppress cell-mediated and humoral immunity.

Considering the potential harmful effects of general anesthesia/anesthetics, there is increasing interest on the effect of regional anaesthesia. Retrospective studies investigating the relationship between epidural anesthesia and outcomes after cancer surgery provide different results. In a meta-analysis of retrospective studies, regional anesthesia was associated with improved survival, but had no effect on the occurrence of cancer recurrence/metastasis. The investigators hypothesize that epidural anesthesia may produce favorable effects on long-term survival in the elderly who undergo major surgery for cancer under general anesthesia. However, there are no sufficient evidences in this aspect.

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:

• Refused 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 were considered unsuitable for study participation.