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Intrathecal Morphine for Enhanced Recovery After Laparoscopic Colorectal Surgery: A Randomized Clinical Trial

JAMA Surg. 2025 Dec 23. doi: 10.1001/jamasurg.2025.5699. Online ahead of print.

ABSTRACT

IMPORTANCE: Despite the recovery advantages of minimally invasive surgical techniques, moderate to severe pain after laparoscopic colorectal surgery is a common barrier to improving postoperative recovery quality.

OBJECTIVE: To evaluate whether intrathecal morphine (ITM) combined with transversus abdominis plane block (TAPB) improves postoperative recovery quality after laparoscopic colorectal surgery.

DESIGN, SETTING, AND PARTICIPANTS: This prospective, double-blind randomized clinical trial was conducted at Sun Yat-sen University Cancer Center between October 15, 2024, and February 15, 2025. Adults scheduled for elective laparoscopic colorectal surgery were randomized 1:1 to ITM or saline placebo. Data were analyzed from March 1, 2025, to March 31, 2025.

INTERVENTIONS: Both groups received liposomal bupivacaine for TAPB as part of standard enhanced recovery after surgery (ERAS) protocol. The intervention group received ITM, 3 µg/kg, while the control group received intrathecal normal saline.

MAIN OUTCOMES AND MEASURES: The primary outcome was the Quality of Recovery 15 (QoR-15) score at 24 hours postoperatively. Secondary outcomes included postoperative pain scores, cumulative opioid consumption (in morphine milligram equivalents [MME]), time to first flatus, time to first ambulation, incidence of adverse effects, and length of hospital stay.

RESULTS: A total of 252 patients were included in the intention-to-treat analysis (mean [SD] age, 58.4 [11.1] years; 112 female patients [44.4%]). At 24 hours postoperatively, the intervention group had significantly higher mean (SE) QoR-15 scores compared to the control group (114.95 [1.04] vs 102.22 [0.76]; mean difference, 12.21; 95% CI, 9.91-14.51; P < .001), indicating better recovery quality. Postoperative mean (SD) morphine consumption was lower in the intervention group compared to the control group (4.4 [6.4] MME vs 10.4 [11.1] MME; mean difference, -6.59; 95% CI, -8.88 to -4.31; P < .001). The intervention group also had a reduced incidence of nausea (23.8% vs 37.3%; adjusted risk difference, -15.06%; 95% CI, -26.60% to -3.52%; P = .01), but a high incidence of pruritus was observed in the intervention group (19.0% vs 3.2%; adjusted risk difference, 15.08%; 95% CI, 7.26%-22.90%; P < .001).

CONCLUSIONS AND RELEVANCE: Per the results of this randomized clinical trial, in laparoscopic colorectal surgery, ITM combined with TAPB can significantly enhance early postoperative recovery and analgesia, albeit with an increased risk of pruritus. This strategy may be a valuable component of multimodal analgesia regimens following laparoscopic colorectal surgery.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06636864.

PMID:41433024 | DOI:10.1001/jamasurg.2025.5699

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