Spinal Hydromorphone Outperforms TAP Block for Gastrectomy Pain

In a combined preclinical and clinical study published in Anesthesiology and Perioperative Science, researchers determined that intrathecal hydromorphone provides superior early postoperative pain relief compared to transversus abdominis plane (TAP) block in patients undergoing gastrectomy. The study, conducted at West China Hospital in Sichuan University, Chengdu, China, integrated animal experiments with a two-part clinical trial to identify the optimal dose of hydromorphone for spinal administration. The primary finding was that a dose of 150 micrograms of intrathecal hydromorphone significantly reduced cumulative pain intensity and opioid consumption in the first 48 hours after surgery, offering a more effective alternative for managing the severe pain associated with upper abdominal procedures.

Gastrectomy, a standard surgical intervention for gastric malignancies, is frequently associated with intense postoperative pain in up to 75% of patients. This pain is primarily driven by visceral nociception resulting from peritoneal irritation and organ manipulation. Inadequate pain relief, particularly during the first postoperative day, can increase the risk of respiratory complications, the development of chronic pain, and prolonged hospitalization. While current perioperative guidelines recommend regional anesthesia as a cornerstone of multimodal analgesia, no specific regional technique has been formally endorsed for gastrectomy due to insufficient high-quality evidence. Thoracic epidural analgesia, traditionally considered the gold standard, has seen a decline in use due to technical barriers and high failure rates, prompting the exploration of alternatives such as TAP blocks and intrathecal opioids.

The TAP block targets the terminal branches of the anterior rami of spinal nerves T6–L1 in the plane between the internal oblique and transversus abdominis muscles. Although it effectively reduces incisional somatic pain and is valued for its simplicity, the TAP block has notable limitations. It does not block visceral pain, and its analgesic duration is limited by the short persistence of local anesthetics after a single injection. In contrast, intrathecal opioids act directly on the dorsal horn of the spinal cord, modulating both somatic and visceral pain pathways. However, the broader application of intrathecal opioids is often tempered by concerns over adverse effects, particularly respiratory depression. Hydromorphone is considered to have a more favorable pharmacological profile than morphine, including higher lipid solubility, faster onset, and fewer side effects.

To address the unclear spinal mechanisms and optimal dosing of intrathecal hydromorphone, the research team first conducted animal experiments using a rat model of acute pain. Adult Sprague–Dawley male rats were subjected to a Complete Freund’s Adjuvant-induced inflammatory pain model. The researchers found that intrathecal hydromorphone produced dose-dependent antinociceptive effects primarily mediated by spinal μ-receptors. Low-dose administration produced analgesia restricted to the hind paws, which was completely reversed by intrathecal naloxone, confirming a spinal-restricted mechanism of action. Higher doses extended the analgesic effects to the forepaws, indicating rostral spread within the cerebrospinal fluid and engagement of more cephalad spinal segments. This graded rostrocaudal spread provides the mechanistic rationale for selecting a higher intrathecal dose in upper abdominal surgery, where extensive visceral and somatic innervation from thoracic segments necessitates broader spinal coverage.

Following the animal studies, the researchers conducted a clinical dose-finding trial to determine the 95% effective dose (ED95) of intrathecal hydromorphone for gastrectomy. This phase involved 51 patients aged 18 years or older, classified as American Society of Anesthesiologists (ASA) I-III, who underwent elective gastrectomy under general anesthesia. The study used a double-blind, biased-coin sequential trial design. Dose exploration was initiated at 50 micrograms, with adjustments made based on individual patient responses. Isotonic regression analysis estimated the ED95 of intrathecal hydromorphone at 131.7 micrograms, with a 95% confidence interval of 113.2 to 150.0 micrograms. No patient in this phase experienced respiratory depression.

Based on the dose-finding results, the researchers selected 150 micrograms, the upper limit of the 95% confidence interval, as the intervention dose for a subsequent randomized controlled trial (RCT). This selection was intended to ensure analgesic coverage in at least 95% of patients. The RCT was a prospective, single-center, randomized, and assessor-blind trial with two parallel groups. Between July 21, 2023, and March 30, 2024, 96 patients were randomly assigned in a 1:1 ratio to receive either intrathecal hydromorphone at the 150-microgram dose or a four-point TAP block using 60 milliliters of 0.2% ropivacaine. The primary outcome was cumulative pain intensity during mobilization within the first 24 postoperative hours, determined by the area under the curve of NRS scores recorded at 0.5, 2, 6, 12, and 24 hours after surgery.

For the modified intention-to-treat analysis, 89 patients were included after excluding five due to surgery cancellation and two who were lost to follow-up. Baseline characteristics were comparable between the two groups. The results demonstrated that patients in the intrathecal hydromorphone group reported significantly lower cumulative pain intensity during mobilization within the first 24 hours compared to the TAP block group. The median cumulative pain intensity was 65.0 cm·h in the intrathecal group versus 93.0 cm·h in the TAP block group. This difference was statistically significant with a P-value of 0.001. The analgesic advantage persisted throughout the first 48 hours for both rest and mobilization, and the benefit during mobilization remained statistically significant at 72 hours. Cumulative pain intensity at rest over the first 24 hours was also significantly reduced in the intrathecal group.

In addition to pain intensity, rescue opioid consumption was significantly lower in the intrathecal hydromorphone group. At 24 hours postoperatively, the median rescue opioid consumption was 4.2 mg in the intrathecal group compared to 5.2 mg in the TAP block group. At 48 hours, the consumption was 8.4 mg in the intrathecal group versus 10.0 mg in the TAP block group. No significant difference was observed at 72 hours. Trajectory analysis identified four distinct pain trajectories during mobilization: persistent moderate-to-severe pain, poor control with recovery, well-controlled pain, and rebound pain. Notably, persistent moderate-to-severe pain occurred in 9.3% of TAP patients but in none of those receiving intrathecal hydromorphone. However, the intrathecal group had a higher incidence of mild rebound pain after 24 hours, occurring in 56.5% of patients compared to 23.3% in the TAP group. Despite this rebound, pain scores during this later period were consistently lower than in the TAP group.

Postoperative recovery quality was comparable between the two groups, with no respiratory depression observed in either group. Mild pruritus occurred in three patients in the intrathecal hydromorphone group, requiring no treatment. Postoperative nausea and vomiting were more frequent in the intrathecal group but did not reach statistical significance. The study authors noted that while intrathecal hydromorphone provided significantly improved analgesia and reduced systemic opioid consumption, it did not result in a concurrent improvement in postoperative recovery outcomes. This finding is consistent with prior evidence suggesting that, within a comprehensive Enhanced Recovery After Surgery protocol, optimizing analgesia alone may be insufficient to meaningfully enhance functional recovery.

The study has several limitations that must be considered when interpreting the results. First, the CFA-induced inflammatory pain model used in the animal experiments does not fully mimic the complex nature of postoperative pain after gastrectomy. Second, the dose-finding phase excluded patients with a body mass index below 18 or above 30 kg/m², meaning the estimated ED95 may not be generalizable to underweight or obese populations. Third, although outcome assessors were blinded to treatment allocation, the lack of formal assessment of patient blinding means that potential unblinding cannot be ruled out, which may have influenced self-reported pain scores. Fourth, the primary outcome lacks an established minimal clinically important difference, so the researchers interpreted its clinical relevance using the NRS minimal clinically important difference as a reference. Finally, the trial was conducted at a single center and enrolled only patients undergoing gastrectomy, limiting the extrapolation of results to other types of upper abdominal surgery.

These findings support the use of intrathecal hydromorphone as a safe and effective component of multimodal analgesic regimens for post-gastrectomy pain management. The optimized dose of 150 micrograms provides superior postoperative analgesia compared to TAP block, with increased but mild pruritus and postoperative nausea and vomiting, yet without compromising respiratory safety. The study highlights the importance of precise dose selection in achieving effective postoperative analgesia and provides a mechanistic rationale for the use of intrathecal opioids in upper abdominal surgery.

Subject of Research: Intrathecal hydromorphone for postoperative pain management in gastrectomy: a dose-finding and randomized controlled study

Article Title: Intrathecal hydromorphone for postoperative pain management in gastrectomy: a dose-finding and randomized controlled study

Article References: Ding, L., Leng, Y., Liu, H., Jiang, X., Ma, J., Gong, Z., Li, C., Zhou, C., & Li, Q. (2026). Intrathecal hydromorphone for postoperative pain management in gastrectomy: a dose-finding and randomized controlled study. Anesthesiology and Perioperative Science, 4(1), Article 28. https://doi.org/10.1007/s44254-026-00174-1

Image Credits: AI Generated

DOI: 10.1007/s44254-026-00174-1

Keywords: Intrathecal, hydromorphone, postoperative, pain, management, gastrectomy, dose-finding, randomized, controlled, scientific research