Intrathecal Morphine for Quality of Recovery After Open Abdominal Surgery Within an Enhanced Recovery Pathway

Intrathecal Morphine for Quality of Recovery After Open Abdominal Surgery Within an Enhanced Recovery Pathway: A Prospective, Multicenter, Randomized, Placebo-Controlled Trial

Pain management after open abdominal surgery still faces severe challenges, with the incidence of moderate to severe pain after surgery as high as 50 - 90%. Insufficient analgesia can hinder early mobilization of patients, delay gastrointestinal function recovery, increase the risk of complications, thereby reducing the quality of patient recovery and prolonging hospital stay.

The Enhanced Recovery after Surgery (ERAS) pathway has significantly improved surgical outcomes. Multimodal analgesia based on transversus abdominis plane block (TAPB) analgesia is the core of ERAS for abdominal surgery. However, the existing multimodal analgesia regimens still inade-quately control visceral pain, resulting in the failure to significantly reduce the dosage of opioid drugs, which has become a key bottleneck restricting the smooth recovery of patients.

Intrathecal morphine (ITM) directly delivers the drug to the dorsal horn of the spinal cord through cerebrospinal fluid, providing potent and long-lasting visceral analgesia. Although its analgesic effect is clear, in the context of modern ERAS with routine application of TAPB, there is still insufficient evidence regarding the impact of ITM on the quality of recovery - a multi-dimensional core outcome - in patients undergoing open abdominal surgery. In addition, whether its effect is affected by key factors such as age (e.g., >60 years) or surgical site (upper abdomen vs. lower abdomen) also remains to be clarified.

Therefore, in this prospective, multicenter, randomized, double-blind, placebo-controlled trial, we aimed to evaluate whether single-dose preoperative ITM can further improve the quality of recovery in the ERAS pathway based on TAPB and to verify the efficacy differences of ITM in important subgroups.

Study Overview

• Status: Not yet recruiting
• Conditions: Open Abdominal Surgery
• Intervention / Treatment: Procedure: Intrathecal Morphine; Procedure: TAPB; Procedure: Intrathecal saline injection

Detailed Description

Pain management after open abdominal surgery still faces severe challenges, with the incidence of moderate to severe pain after surgery as high as 50 - 90%. Insufficient analgesia can hinder early mobilization of patients, delay gastrointestinal function recovery, increase the risk of complications, thereby reducing the quality of patient recovery and prolonging hospital stay.

The Enhanced Recovery after Surgery (ERAS) pathway has significantly improved surgical outcomes. Multimodal analgesia based on transversus abdominis plane block (TAPB) analgesia is the core of ERAS for abdominal surgery. However, the existing multimodal analgesia regimens still inadequately control visceral pain, resulting in the failure to significantly reduce the dosage of opioid drugs, which has become a key bottleneck restricting the smooth recovery of patients.

Intrathecal morphine (ITM) directly delivers the drug to the dorsal horn of the spinal cord through cerebrospinal fluid, providing potent and long-lasting visceral analgesia. Although its analgesic effect is clear, in the context of modern ERAS with routine application of TAPB, there is still insufficient evidence regarding the impact of ITM on the quality of recovery - a multi-dimensional core outcome - in patients undergoing open abdominal surgery. In addition, whether its effect is affected by key factors such as age (e.g., >60 years) or surgical site (upper abdomen vs. lower abdomen) also remains to be clarified.

Therefore, in this prospective, multicenter, randomized, double-blind, placebo-controlled trial, we aimed to evaluate whether single-dose preoperative ITM can further improve the quality of recovery in the ERAS pathway based on TAPB and to verify the efficacy differences of ITM in important subgroups.

The anesthesia scheme was endotracheal intubation general anesthesia combined with bupivacaine liposome plane block of transverse abdominal muscle, experimental group combined with intrathecal morphine, control group injected with intrathecal saline. After the patient enters the operating room, establish an intravenous access in the healthy upper limb and perform standard monitoring (electrocardiogram, non-invasive blood pressure, and oxygen saturation). Before lumbar puncture, intravenous infusion of dexmedetomidine 30 μg is given for conscious sedation, and then the patient takes a lateral position for ultrasound-guided lumbar puncture. Inject the drug labeled "Study drug for intrathecal injection" of 5ml.

After the intrathecal injection is completed, general anesthesia will be implemented for the patient. All patients receive sufentanil (0.2 μg/kg, maximum dose 20μg ), propofol 2-3 mg/kg, rocuronium 0.6 mg/kg and butorphanol 0.1mg-0.2mg are used for general anesthesia induction for pruritus prevention followed by endotracheal intubation. After endotracheal intubation, sevoflurane or desflurane is used to maintain general anesthesia, and the bispectral index is maintained at 40-60; remifentanil is used for analgesia during surgery to maintain hemodynamic stability within ±20% of the preoperative level. The ventilation strategy is to use a mixture of air and oxygen ( FiO2 50%) for mechanical ventilation and adjust to maintain the PetCO2 concentration at 35-45 mmHg. The antiemetic regimen is a dual prophylactic regimen, that is, dexamethasone 8mg is injected intravenously after general anesthesia induction, and palononsetron 0.25 mg is injected intravenously at the end of the surgery. After the surgery is completed, sugammadex is used to reverse the muscle relaxation effect and then the endotracheal tube is removed.

After the patient is transferred to the PACU, postoperative monitoring is carried out by the PACU nurse (who is blinded). After meeting the criteria for transfer out of the PACU, the patient is transferred to the surgical ward. Observation in the PACU, vital sign monitoring, pain and PONV assessment and treatment. If the patient's NRS > 4 at rest or the patient requires additional analgesic medications, all patients use a standardized analgesic rescue protocol (morphine 1 mg iv, q5min, maximum dose 5 mg). Similarly, if nausea persists for more than 10 minutes or the patient experiences 2 or more vomiting episodes, intravenous injection of palononsetron 0.25 mg. Use the Aldrete score. The score is performed every 15 minutes. When the patient reaches an Aldrete score of 9 (out of 10), they can be transferred to the surgical ward. When the patient is in the PACU, a blinded research nurse collects postoperative data. Pain and nausea scores are performed once upon entry into the PACU and once upon transfer out of the PACU. The NRS 0-10 score (0 = no pain to 10 = the most severe pain imaginable) is used to evaluate pain at rest and movement pain during coughing. The NRS 0-10 score (0 = no nausea to 10 = the most severe nausea imaginable) is used to evaluate nausea and record the number of vomiting episodes.

The analgesia protocol after the patient returns to the ward is patient-controlled intravenous morphine analgesia for 0-72 hours, 150 mg morphine + 150 mL NS, the background dose is 1mg/h , the Bolus is 2mg , the lockout time is 5min , and the pain rescue protocol is patient-controlled intravenous analgesia (morphine 1 mg iv, q5min, maximum dose 5 mg). After 72 hours postoperatively, it is changed to oral celecoxib. If the patient's NRS > 4 or requires additional analgesic medications, tramadol 75 mg q6h orally is given as rescue analgesia. If nausea persists for more than 10 minutes or there are 2 or more vomiting episodes, palononsetron 0.25 mg is given by intravenous injection. The research nurse will regularly collect postoperative data within 48 hours after surgery. At within 72 hours after surgery, the patient needs to complete the QoR-15 score at 10 am on the same day, once a day. The main outcome was QoR15 score 24 hours after operation.

• Study Type: Interventional
• Enrollment (Estimated): 756
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Renchun Lai, MD; Phone Number: +8613660012343; Email: lairch@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years.
2. Scheduled for elective open abdominal surgery (upper or lower abdomen).
3. American Society of Anesthesiologists classification I-III.
4. Signed informed consent form.

Exclusion Criteria:

1. Allergic to opioids or any drug in the trial.
2. Presence of contraindications to intrathecal injection (such as abnormal coagulation function, puncture site infection, increased intracranial pressure).
3. History of chronic pain, long-term use of opioids.
4. Severe hepatic and renal insufficiency (Child-Pugh C grade or eGFR < 30 mL/min).
5. Severe respiratory diseases (such as non-invasive ventilation required for sleep apnea syndrome).
6. Cognitive dysfunction, unable to complete the questionnaire.
7. Pregnant or lactating women.

Withdrawal criteria:

1. The patient or legal representative requests withdrawal.
2. Serious complications occur during the study, and continued participation is not in the best in-terest of the patient.
3. Other situations where the researcher believes withdrawal is necessary.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Normal saline group; Before anesthesia induction, the control group received intrathecal injection of normal saline.	Procedure: TAPB; The patient was in a supine position. The rectus muscle was confirmed to be warping under the guidance of color photography, and the needle was injected with bupivacaine liposomes.; Procedure: Intrathecal saline injection; After the patient was asked to lie on his side, the injection point was determined with the aid of ultrasound guidance. After local anesthesia, the needle was injected into the subarachnoid space and then normal saline was injected.
Experimental: Intrathecal morphine group; Before induction of anesthesia, the experimental group received intrathecal morphine in the lumbar segment. For our preliminary clinical application, the intrathecal morphine was 3ug/kg.	Procedure: Intrathecal Morphine; The patient was asked to lie on the side, the needle insertion point was located under the guidance of color ultrasound, and after local anesthesia, the needle was inserted into the subarachnoid space at the puncture point and morphine was injected.; Procedure: TAPB; The patient was in a supine position. The rectus muscle was confirmed to be warping under the guidance of color photography, and the needle was injected with bupivacaine liposomes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
QoR15 score at 24 hours after surgery	Lower scores represent a worse outcome.	Day 1 after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
QoR15 scores 48 and 72 hours after surgery	Lower scores represent a worse outcome.	Day 2, Day 3 after surgery
Pain score (NRS)	The pain scores during rest and movement (cough) were recorded using the Numerical Rating Scale (NRS) during the waking period, at 24, 48, and 72 hours after surgery. Higher scores represent a worse outcome.	Baseline, Day 1, Day 2, Day 3 after surgery
Morphine consumption equivalent 24, 48, 72 hours after surgery		Baseline, Day 1, Day 2, Day 3 after surgery
Recovery indicators	The time to first ambulation (h), the time to first flatus (h), the time to first tolerance of liquid diet (h), the length of time to meet the discharge criteria (d), and the length of hospital stay (d).	Up to 4 weeks after surgery
Safety endpoints	The occurrence of nausea, vomiting, skin itching (grading of nausea and vomiting, grading of itching), respiratory depression (respiratory rate less than 8 breaths/min or SpO2 < 90%),and excessive sedation (Ramsay score ≥ 4) were recorded at 24, 48, and 72 hours after surgery.	Day 1, Day 2, Day 3 after surgery
Postoperative complications	Clavien-Dindo classification	Baseline, Day 1, Day 2, Day 3 after surgery
Percentage of adhered core ERAS elements	Rate of adherence to core ERAS elements (such as preoperative carbohydrates, multimodal analgesia, early ambulation, early feeding, etc.). ERAS compliance is calculated as (number of actually completed items/ total core items)× 100%	Baseline, Day 1, Day 2, Day 3 after surgery
Age-adjusted Charlson Comorbidity Index (aCCI) score (range 0-41, higher scores indicate worse outcome)	The age-adjusted Charlson Comorbidity Index (aCCI) is calculated by adding age-related points to the original Charlson Comorbidity Index (CCI) score. Age adjustment is commonly performed by adding 1 point per decade after age 40 years (e.g., 1 point for 41-50 years, up to 4 points for >80 years). The total aCCI score ranges from 0 to 41, where 0 indicates no comorbidity and the lowest age risk, and higher scores indicate greater comorbidity burden and higher predicted mortality risk. Higher scores represent a worse outcome.	Baseline, Day 1, Day 2, Day 3 after surgery

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: First Affiliated Hospital, Sun Yat-Sen University; Cancer Hospital of Guangxi Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: April 23, 2026
• First Submitted That Met QC Criteria: May 2, 2026
• First Posted (Actual): May 8, 2026

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 2, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Intrathecal morphine; ERAS; QoR-15; Open Abdominal surgery
• Additional Relevant MeSH Terms: 1,3-bis(4-amidinophenoxy)-2-(4-amidinophenoxymethyl)ethylpropane
• Other Study ID Numbers: 2025-FXY-534

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No