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

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.