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This is a prospective randomized open-label noninferiority trial that compares intrathecal morphine injection and continuous wound infiltration after open pancreaticoduodenectomy.
Open pancreaticoduodenectomy causes severe postoperative pain due to the relatively large incision and tissue damage compared to other abdominal surgeries. Current Enhanced Recovery After Surgery (ERAS) guidelines recommend continuous wound infiltration for pancreaticoduodenectomy as an effective analgesic modality along with thoracic epidural analgesia. However, continuous wound infiltration is effective for somatic pain in the abdominal wall but not for visceral pain from the incision of internal organs. It also requires the placement of a catheter for several days after surgery, which can be inconvenient for patients.
Intrathecal morphine injection has been recommended as an effective analgesic method for abdominal surgery because they provide potent, long-lasting analgesia with a single injection and can provide equivalent analgesia with a much smaller dose compared to intravenous or oral morphine. Several previous studies have reported on the analgesic efficacy of a single intrathecal morphine injection including pancreaticoduodenectomy. However, no studies have compared a single intrathecal morphine injection with continuous wound infiltration for pancreaticoduodenectomy. To date, studies comparing the two methods of analgesia have only been reported in cesarean section and donor hepatectomy, and these studies either found no significant difference between the two methods of analgesia or reported that intrathecal morphine injection provided better analgesia in early postoperative period.
Therefore, the investigators will examine the effect of single intrathecal morphine injection for postoperative pain control in patients undergoing open pancreaticoduodenectomy to improve postoperative pain management and to explore its potential as one of the effective analgesic methods in ERAS protocol. To this end, the investigators will test non-inferiority between intrathecal morphine injection and continuous wound infiltration.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intrathecal morphine injection | Experimental | A single dose of intrathecal morphine is administered prior to induction of general anesthesia. Other postoperative pain management follows the institution's protocol including intravenous patient controlled analgesia. |
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| Continuous wound infiltration | Active Comparator | A catheter is inserted at preperitoneal space at the end of surgery and ropivacaine is continuously infused until postoperative day 3. Other postoperative pain management follows the institution's protocol including intravenous patient controlled analgesia. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Intrathecal morphine injection | Drug | A single dose of intrathecal morphine is administered prior to induction of general anesthesia. The patient is placed in the lateral decubitus position on the bed and a 25 guage quincke spinal needle is inserted intrathecally at the L4/5 median or paramedian approach to administer 0.2 mg of morphine. |
| Measure | Description | Time Frame |
|---|---|---|
| Mean pain intensity on cough assessed by K-DVRPS at 24, 48, and 72 hours from the end of anesthesia | The K-DVPRS (Korean version of Defense and Veterans Pain Rating Scale), ranging from 0 to 10, is used to assess postoperative pain on cough at 24, 48, and 72 hours after the end of anesthesia. The mean K-DVPRS pain score for 3 time points is compared between two groups. | Postoperative days 1 to 3 |
| Measure | Description | Time Frame |
|---|---|---|
| Mean pain intensity at rest assessed by K-DVRPS at 24, 48, and 72 hours from the end of anesthesia | The K-DVPRS is used to assess postoperative pain at rest at 24, 48, and 72 hours after the end of anesthesia. The mean K-DVPRS pain score for 3 time points is compared between two groups. | Postoperative days 1 to 3 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ho-jin Lee, M.D., PhD. | Contact | +82-2-2072-0039 | hjpainfree@snu.ac.kr |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Seoul National University Hospital | Recruiting | Seoul | Seoul | KS013 | South Korea |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42403225 | Derived | Yoon S, Kim T, Lee HJ, Park N, Jung HS, Cho YJ, Kwon W, Park JS, Jung CW, Jang JY. A randomized, noninferiority clinical trial of Single-Shot Intrathecal Morphine versus Continuous Wound Infiltration for postoperative pain control after open pancreatoduodenectomy. Br J Surg. 2026 Jul 6:znag088. doi: 10.1093/bjs/znag088. Online ahead of print. |
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| ID | Term |
|---|---|
| D000377 | Agnosia |
| D010149 | Pain, Postoperative |
| ID | Term |
|---|---|
| D010468 | Perceptual Disorders |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
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Stratify patients who receive preoperative chemotherapy and those who do not in a 1:3 ratio, so that 26 and 78 patients are assigned to each stratum out of a total of 104 patients. Then, within each stratum, block randomization is performed, with blocks of size 4 containing two intrathecal morphine and two wound infiltration groups, and blocks of size 6 containing three intrathecal morphine and three wound infiltration groups.
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| Continuous wound infiltration | Device | Prior to closure of the abdominal wall, a catheter is placed in the preperitoneal space lateral to the surgical incision through the tunneler. The catheter is connected to a prepared infusion pump (275 ml of 0.5% ropivacaine, 4 ml/hr/catheter), and the remaining catheter protruding from the abdomen is secured with a catheterization dressing. The preperitoneal catheter is removed in the afternoon of postoperative day 3. |
|
| Pain intensity at rest and on cough assessed at 2, 24, 48, and 72 hours from end of anesthesia |
The K-DVPRS is used to assess postoperative pain at rest and on cough at 2, 24, 48, and 72 hours after the end of anesthesia, respectively. |
| Postoperative days 0 to 3 |
| Cumulative dose of opioid use at 6, 12, 24, 48, and 72 hours after end of anesthesia | The cumulative fentanyl equivalent dose used at 6, 12, 24, 48, and 72 hours after the end of anesthesia is assessed. | Postoperative days 0 to 3 |
| Quality of recovery at 24, 48, and 72 hours from the end of anesthesia | Quality of recovery is assessed with the Korean version of the EQ-5D-5L at 24, 48, and 72 hours after the end of anesthesia. | Postoperative days 1 to 3 |
| Postoperative complications | Postoperative complications are assessed with the comprehensive complication index. | Within 1 week after surgery |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D010146 | Pain |