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Background <p>Single-dose intrathecal hydromorphone or transversus abdominis plane (TAP) block has garnered growing interest as components of multimodal analgesia for gastrectomy. However, the spinal mechanisms of intrathecal hydromorphone and its optimal dosing remain unclear. This study aimed to confirm the spinal mechanism of intrathecal hydromorphone using animal models, precisely determine its 95% effective dose (ED<sub>95</sub>) in clinical settings, and compare its analgesic efficacy with TAP block.</p> Methods <p>In a rat model of acute pain, we determined the dose–response relationship of intrathecal hydromorphone. Clinically, the ED<sub>95</sub> of hydromorphone for patients undergoing gastrectomy was identified through a double-blind, biased-coin sequential trial involving 51 patients aged 18&#xa0;years or older who were classified as ASA I-III. In subsequent randomized controlled trial (RCT), 96 gastrectomy patients were randomly assigned to receive either intrathecal hydromorphone at its ED<sub>95</sub> dose or a four-point TAP block (15&#xa0;mL of 0.2% ropivacaine per point). The primary outcomes were ED₉₅ and cumulative pain intensity during mobilization within 24 postoperative hours.</p> Results <p>Animal studies demonstrated that intrathecal hydromorphone produces dose-dependent antinociceptive effects primarily mediated by spinal μ-receptors. Clinically, the calculated ED<sub>95</sub> for intrathecal hydromorphone in gastrectomy was 131.67&#xa0;μg (95% CI 113.19–150 μg). Based on these findings, we selected 150&#xa0;μg (the upper limit of the 95% CI) as the intervention dose for the subsequent RCT to ensure analgesic coverage in at least 95% of patients. In this RCT, 89 patients completed the modified intention-to-treat analysis. Patients in the intrathecal hydromorphone group reported significantly lower cumulative pain intensity (65.0 [48.0–89.0] cm·h) compared to the TAP block group (93.0 [64.0–131.0] cm·h; <i>P</i> = 0.001). Furthermore, rescue opioid consumption was reduced at both 24 and 48&#xa0;h postoperatively in the intrathecal hydromorphone group (<i>P</i> &lt; 0.05). Trajectory analysis showed that the TAP group had a higher incidence of inadequate early pain control, while the intrathecal group maintained better initial analgesia but demonstrated mild rebound pain after 24&#xa0;h. Recovery profiles and adverse events were comparable between groups.</p> Conclusion <p>Intrathecal hydromorphone exerts dose-dependent antinociceptive effects through spinal μ-receptor mechanisms. At a dose of 150&#xa0;μg (upper 95% CI of the ED<sub>95</sub>) for gastrectomy, intrathecal hydromorphone provides superior postoperative analgesia compared to TAP block, with reduced opioid consumption.</p> Trial registration <p>ChiCTR2300069163 Part I for the dose-finding trial on March 8, 2023; ChiCTR2300073827 for the randomized controlled trial on July 21, 2023. (<a href="http://www.chictr.org.cn">http://www.chictr.org.cn</a>).</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月19日

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  • Lin Ding,
  • Yu Leng,
  • Hongxin Liu,
  • Xiaojuan Jiang,
  • Jun Ma,
  • Zhichao Gong,
  • Chengyu Li,
  • Cheng Zhou,
  • Qian Li

摘要

Background

Single-dose intrathecal hydromorphone or transversus abdominis plane (TAP) block has garnered growing interest as components of multimodal analgesia for gastrectomy. However, the spinal mechanisms of intrathecal hydromorphone and its optimal dosing remain unclear. This study aimed to confirm the spinal mechanism of intrathecal hydromorphone using animal models, precisely determine its 95% effective dose (ED95) in clinical settings, and compare its analgesic efficacy with TAP block.

Methods

In a rat model of acute pain, we determined the dose–response relationship of intrathecal hydromorphone. Clinically, the ED95 of hydromorphone for patients undergoing gastrectomy was identified through a double-blind, biased-coin sequential trial involving 51 patients aged 18 years or older who were classified as ASA I-III. In subsequent randomized controlled trial (RCT), 96 gastrectomy patients were randomly assigned to receive either intrathecal hydromorphone at its ED95 dose or a four-point TAP block (15 mL of 0.2% ropivacaine per point). The primary outcomes were ED₉₅ and cumulative pain intensity during mobilization within 24 postoperative hours.

Results

Animal studies demonstrated that intrathecal hydromorphone produces dose-dependent antinociceptive effects primarily mediated by spinal μ-receptors. Clinically, the calculated ED95 for intrathecal hydromorphone in gastrectomy was 131.67 μg (95% CI 113.19–150 μg). Based on these findings, we selected 150 μg (the upper limit of the 95% CI) as the intervention dose for the subsequent RCT to ensure analgesic coverage in at least 95% of patients. In this RCT, 89 patients completed the modified intention-to-treat analysis. Patients in the intrathecal hydromorphone group reported significantly lower cumulative pain intensity (65.0 [48.0–89.0] cm·h) compared to the TAP block group (93.0 [64.0–131.0] cm·h; P = 0.001). Furthermore, rescue opioid consumption was reduced at both 24 and 48 h postoperatively in the intrathecal hydromorphone group (P < 0.05). Trajectory analysis showed that the TAP group had a higher incidence of inadequate early pain control, while the intrathecal group maintained better initial analgesia but demonstrated mild rebound pain after 24 h. Recovery profiles and adverse events were comparable between groups.

Conclusion

Intrathecal hydromorphone exerts dose-dependent antinociceptive effects through spinal μ-receptor mechanisms. At a dose of 150 μg (upper 95% CI of the ED95) for gastrectomy, intrathecal hydromorphone provides superior postoperative analgesia compared to TAP block, with reduced opioid consumption.

Trial registration

ChiCTR2300069163 Part I for the dose-finding trial on March 8, 2023; ChiCTR2300073827 for the randomized controlled trial on July 21, 2023. (http://www.chictr.org.cn).