Highlights
- Intrathecal morphine (ITM) at a dose of 3 µg/kg, when combined with transversus abdominis plane block (TAPB), significantly improves the Quality of Recovery 15 (QoR-15) scores at 24 hours postoperatively.
- The intervention group demonstrated a significant reduction in postoperative opioid consumption (morphine milligram equivalents) compared to the control group.
- Despite the use of opioids, the ITM group experienced a lower incidence of postoperative nausea, though the incidence of pruritus was notably higher.
- These findings suggest that ITM is a highly effective component of multimodal analgesia within an Enhanced Recovery After Surgery (ERAS) framework for laparoscopic colorectal procedures.
The Challenge of Postoperative Pain in Minimally Invasive Surgery
Laparoscopic colorectal surgery has revolutionized the field of gastrointestinal surgery, offering patients smaller incisions, reduced physiological stress, and faster return to bowel function compared to open procedures. However, the assumption that minimally invasive techniques eliminate the need for robust analgesic strategies is a clinical misconception. Moderate to severe postoperative pain remains a primary barrier to achieving the full benefits of Enhanced Recovery After Surgery (ERAS) protocols. Effective pain management is not merely about patient comfort; it is a physiological necessity to facilitate early ambulation, reduce pulmonary complications, and accelerate the return of gastrointestinal motility.
While the Transversus Abdominis Plane Block (TAPB) has become a mainstay in colorectal ERAS protocols, its efficacy is primarily limited to somatic pain from the abdominal wall, often leaving visceral pain inadequately addressed. This gap has led researchers to investigate the additive benefits of neuraxial analgesia, specifically intrathecal morphine (ITM), which provides potent, long-lasting visceral and somatic analgesia through its action on the spinal cord’s dorsal horn.
Study Design: A Rigorous Evaluation of ITM and TAPB
The study, conducted at the Sun Yat-sen University Cancer Center between October 2024 and February 2025, was a prospective, double-blind randomized clinical trial. A total of 252 adult patients scheduled for elective laparoscopic colorectal surgery were randomized in a 1:1 ratio to receive either ITM or a saline placebo. This rigorous design ensured that both patients and the healthcare providers assessing outcomes remained blinded to the treatment allocation.
Both groups received a standardized ERAS protocol, which included a TAPB utilizing liposomal bupivacaine—a long-acting local anesthetic designed to extend the duration of the block. The intervention group received a specific low dose of ITM (3 µg/kg), while the control group received an equivalent volume of intrathecal normal saline. The primary endpoint was the Quality of Recovery 15 (QoR-15) score at 24 hours post-surgery. The QoR-15 is a validated patient-reported outcome measure that assesses five dimensions of recovery: pain, physical comfort, physical independence, psychological support, and emotional state.
Primary and Secondary Outcomes: Quantifying the Recovery Benefit
The results of the trial, analyzed in March 2025, revealed a clear and statistically significant advantage for the ITM group. At 24 hours postoperatively, the mean QoR-15 score in the ITM group was 114.95, compared to 102.22 in the control group. This represents a mean difference of 12.21 (95% CI, 9.91-14.51; P < .001). Given that a difference of 6.0 to 8.0 points is generally considered clinically meaningful on the QoR-15 scale, the 12.21-point improvement underscores a substantial enhancement in the patient's perceived quality of recovery.
Opioid Sparing and Functional Recovery
Beyond the primary recovery score, the ITM intervention demonstrated a powerful opioid-sparing effect. Cumulative morphine consumption was significantly lower in the ITM group (4.4 MME) compared to the control group (10.4 MME). This reduction is particularly relevant in the context of ERAS, as systemic opioids are well-known to contribute to postoperative ileus and cognitive dysfunction. Furthermore, the ITM group showed improved functional milestones, including a trend toward faster return of bowel function and ambulation, although the most striking differences were observed in the immediate 24-hour analgesic profile.
Safety and Adverse Effects: Balancing Efficacy with Side Effects
A critical consideration with the use of intrathecal opioids is the side-effect profile, specifically nausea, vomiting, pruritus, and the rare but serious risk of respiratory depression. Interestingly, the trial found that the ITM group actually had a lower incidence of nausea (23.8% vs 37.3%; P = .01) than the control group. This counterintuitive finding is likely explained by the significant reduction in the need for systemic rescue opioids in the ITM group, suggesting that the localized spinal delivery of morphine may be more emetogenic-neutral than systemic administration in this clinical context.
However, the incidence of pruritus was significantly higher in the ITM group (19.0% vs 3.2%; P < .001). While pruritus is often considered a minor side effect by clinicians, it can be distressing for patients. No cases of clinically significant respiratory depression were reported, which supports the safety of the 3 µg/kg low-dose regimen used in this study.
Expert Commentary: Integrating Findings into Clinical Practice
The findings by Zheng et al. provide high-level evidence for the inclusion of low-dose ITM in multimodal analgesic regimens for laparoscopic colorectal surgery. The use of liposomal bupivacaine in the TAP block for both groups is a notable strength of this study, as it demonstrates that ITM provides additive benefits even when a high-quality regional block is already in place. This suggests that the visceral analgesia provided by ITM addresses a component of surgical stress that peripheral nerve blocks cannot reach.
Clinicians should note the specific dose of 3 µg/kg. Historically, higher doses of ITM (e.g., 100-200 µg) were associated with a higher risk of complications. The weight-based low-dose approach used here appears to optimize the benefit-to-risk ratio. The increased risk of pruritus should be managed proactively with prophylactic or early symptomatic treatment (such as low-dose naloxone or antihistamines) to ensure that the gains in recovery quality are not offset by patient discomfort.
Conclusion: A Shift Toward Multimodal Precision
This randomized clinical trial confirms that intrathecal morphine is a valuable adjunct to the ERAS toolkit for laparoscopic colorectal surgery. By significantly improving the quality of early postoperative recovery and reducing the reliance on systemic opioids, ITM helps bridge the gap between surgical success and patient-perceived wellness. While the risk of pruritus must be managed, the overall improvement in recovery scores and the reduction in postoperative nausea make this strategy a compelling option for anesthesiologists and surgical teams aiming for excellence in perioperative care.
Funding and Clinical Trial Information
This study was conducted at Sun Yat-sen University Cancer Center. ClinicalTrials.gov Identifier: NCT06636864. Data analysis was completed in March 2025.
References
- Zheng L, Lu Y, Lu X, et al. Intrathecal Morphine for Enhanced Recovery After Laparoscopic Colorectal Surgery: A Randomized Clinical Trial. JAMA Surg. 2025 Dec 23. doi: 10.1001/jamasurg.2025.5699.
- Stark PA, Myles PS, Burke JA. Development and psychometric evaluation of a 15-item quality of recovery score (QoR-15). Br J Anaesth. 2013;111(3):454-462.
- Gustafsson UU, Scott MJ, Hubner M, et al. Guidelines for Perioperative Care in Elective Colorectal Surgery: Enhanced Recovery After Surgery (ERAS) Society Recommendations: 2018. World J Surg. 2019;43(3):659-695.
