Effects of Epidural Anesthesia and Analgesia on the Prognosis in Patients Undergoing Pancreatic Cancer Surgery

Study Overview
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Brief Summary
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The purpose of this randomized controlled trial is to investigate the effects of epidural anesthesia and analgesia on the overall survival，disease-free survival and recovery in patients undergoing pancreatic cancer surgery. This study will also evaluate the effects of this technique on neuroendocrine, stress and inflammatory response in these patients.

Official Title
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Effects of Epidural Anesthesia and Analgesia on the Prognosis in Patients Undergoing Pancreatic Cancer Surgery: A Multi-center Randomized Controlled Trial

Conditions
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Cancer of Pancreas

Intervention / Treatment
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* Drug: GEA
* Drug: PCEA
* Drug: GA
* Drug: PCIA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Undergoing elective pancreaticoduodenectomy for pancreatic cancer . ASA statusⅠ-Ⅲ. 18 years to 80 years （adults）. Able to understand, communicate and sign an informed consent form. Exclusion Criteria: Laparoscopic surgery. Preoperative chemotherapy or radiotherapy. Pregnancy. Allergic to any drugs used during the study. Long-term receiving β-blockers. Complicated with chronic inflammatory diseases, autoimmune diseases, or long-term receiving glucocorticoids or other immunosuppressants before surgery. Abnormal coagulation functions (platelet count prior to surgery <100000/ μL , APTT value is more than the normal value, INR > 1.3 or clopidogrel that cannot be discontinued 7 days prior to surgery). Complicated with severe heart disease (NYHA classification >3), severe renal insufficiency (serum creatinine >1.8mg/dL or receiving renal replacement therapy), severe hepatic disease (Child-Pugh classification = C), diabetes (fasting blood glucose not in the range of 3.9-13.8 mmol/L ), or acute infectious diseases (WBC>10000/μL) before surgery. BMI > 35. All contraindications to epidural anesthesia and analgesia. Chronic opiate medication/drug abuse. Complicated with severe mental illness, cognitive disorder or unable to collaborate during the study. Refuse to sign an informed consent form.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GEA+PCEA<br>General anesthesia combined with epidural anesthesia will be performed during surgery and patient-controlled epidural analgesia (PCEA) will be provided after surgery. | Drug: GEA<br>* Thoracic epidural catheterization will be performed and epidural anesthesia will be maintained with 0.25% ropivacaine during surgery. General anesthesia will be maintained with inhalation (sevoflurane) and muscle relaxants will be administered when considered necessary.<br>* Other names: General anesthesia combined with epidural anesthesia;Drug: PCEA<br>* Patient-controlled epidural analgesia (0.15% ropivacaine infusion) will be provided after surgery.<br>* Other names: Patient-controlled epidural analgesia;|
| Other: GA+PCIA<br>General anesthesia will be performed during surgery and patient-controlled intravenous analgesia (PCIA) will be provided after surgery. | Drug: GA<br>* General anesthesia will be maintained with inhalation (sevoflurane) and sufentanil infusion, and muscle relaxants will be administered when considered necessary.<br>* Other names: General anesthesia;Drug: PCIA<br>* Patient-controlled intravenous analgesia (1ug/ml sufentanil) will be provided after surgery.<br>* Other names: Patient-controlled intravenous analgesia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | Defined and calculated as the time from the date of surgery to death related to all reasons | During 2 years after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival (DFS ) | Defined and calculated as the time from the date of surgery to the first time of pancreatic cancer recurrence or metastasis or cancer-related death | During 2 years after surgery | 
| Postoperative pain score and side effects of patient-controlled analgesia | Assessed with visual analogue score ( 0 is no pain and 10 is the most severe pain) | During the first 48 hours after surgery | 
| Incidence of delirium | Assessed for delirium using the 3D-CAM instrument | During the first 1 week after surgery | 
| Incidence of persistent post-surgical pain (PPSP) after surgery | Assessed with visual analogue score ( 0 is no pain and 10 is the most severe pain) | During 2 years after surgery | 
| Length of stay in hospital after surgery and total costs after surgery |  | During the first 30 days after surgery | 
| Return of bowel function | Measured by the time of first flatus | During the first 30 days after surgery | 
| Start of enteral tube feeding | Measured by the time of first enteral tube feeding after surgery | During the first 30 days after surgery | 
| Removal of Perianastomotic drains |  | During the first 30 days after surgery | 
| Removal of Urinary drainage |  | During the first 30 days after surgery | 
| Removal of nasogastric tube |  | During the first 30 days after surgery | 
| Removal of enteral feeding tube |  | During the first 30 days after surgery | 
| Blood level of neuroendocrine, stress and inflammatory response | Changes of blood epinephrine, norepinephrine, cortisol, VEGF, interleukin-6 (IL-6)、interleukin-8 (IL-8), peripheral blood NLR ( neutrophil-lymphocyte ratio) | During surgery and the first 24 hours after surgery (post-operative day 1) | 
| Serum CA19-9 、CA125、CEA、CA72-4、CA242、AFP、CA15-3、CA50 levels |  | During 2 years after surgery | 
| Plasma levels of ropivacaine and sufentanil |  | During surgery and the first 24 hours after surgery (post-operative day 1) |