The intrathecal morphine analgesia for full endoscopic lumbar discectomy: a prospective dose-finding study

Anesthesia for full endoscopic lumbar discectomy (FELD), typically administered locally or regionally, often fails to provide adequate analgesia, necessitating additional analgesics or even sedation. Our previous work has shown that intrathecal morphine (ITM) administration is considered an effective adjuvant approach for managing peri-operative pain for FELD, but the adverse events (AEs) for ITM remain concerns.

This study aimed to determine the effective dose of intrathecal morphine required to eliminate intraoperative pain in 90% of patients (ED₉₀) undergoing FELD under spinal anesthesia and to evaluate the safety profile of ITM within 100 µg.

A prospective, double-blind, sequential allocation dose-finding study was conducted using the biased coin up-down method. Patients undergoing single-segment FELD received ITM through the same route as spinal anesthesia. The ITM dose was adjusted using a 1/9 probability of dose reduction following an effective response, or increased for the subsequent patient if the response was ineffective. Sample size for drug dose-finding studies typically ranges between 20 and 40 participants; this study included 30 participants.

The ED₉₀ and its 95% confidence intervals were estimated by isotonic regression. The primary outcome was intraoperative pain intensity measured by visual analogue scale (VAS), while secondary outcomes included postoperative pain at various time points and AEs.

All patients underwent single-segment interlaminar or transforaminal FELD under spinal anesthesia. The ITM dosage range was established at 25, 50, 75, and 100 µg. An effective response was defined as an intraoperative VAS score of 0 with no need for additional analgesics. The dose was adjusted using a biased coin up-down method, with a 1/9 probability of dose reduction after an effective response. If an ineffective response occurred-defined as an intraoperative VAS score > 0 or the requirement for supplemental analgesics-the ITM dose was upgraded for the next patient. The study was registered in the Chinese Clinical Trial Registry (ChiCTR2200067060).

Thirty patients were enrolled and completed the study between November 2022 and August 2024. The ED₉₀ of ITM for FELD was 90.89 µg (95% CI 80.05-149.23 µg). Satisfactory analgesia (VAS = 0) was achieved in 15/16 patients at 100 µg, 11/13 patients at 75 µg, and none at 50 µg. ITM-related AEs occurred in 22/30 patients, with no significant difference in overall AE incidence between the 100 µg high-dose and lower doses. Nausea or vomiting was the most common AE during the operation and 1 h postoperatively, while pruritus was most frequent at 12 and 24 h postoperatively. More participants receiving 100 µg ITM reported pruritus compared to those receiving lower doses (7/16 vs. 1/14, p = 0.039). A total of 30% of participants required treatment for AEs, which resolved within 12 h postoperatively. No respiratory depression or motor block was observed.

ITM provides effective intraoperative analgesia for FELD. Although decreasing the ITM dose seems to lessen the likelihood of AEs such as pruritus and may hasten the resolution of the side effects, the findings suggest that an approximate dose of 90.89 µg ITM may be optimal for achieving effective intraoperative pain control in most patients. Despite observing a correlation between ITM dose and morphine-related adverse events, more investigation is crucial to accurately establish the safest and most effective dosage.