A Prospective Randomized Dose-Finding Study of Intrathecal Opioids for Postoperative Analgesia After Minimally Invasive Colorectal Operation

Objective

To determine the optimal dose of intrathecal morphine and hydromorphone in patients undergoing minimally invasive colorectal operation for postoperative analgesia.

Patients and Methods

The study was a double-blinded clinical dosing trial that randomized patients to intrathecal morphine or hydromorphone from March 12, 2021, to February 17, 2023. Intrathecal dosing was determined by a sequential up-down method using a biased-coin design. Doses of the subsequent patients were stepped up or down based on the success or failure of the previous dose. The primary outcome was the dose effective in 90% of patients (ED₉₀) to achieve numeric rating pain scores ≤4 with postoperative opioid requirements ≤15 oral morphine equivalent at 12 hours.

Results

Eighty patients completed the study with 40 patients in each group. The ED₉₀ for intrathecal morphine and hydromorphone could not be determined for the examined dose ranges. The ED₅₀ for morphine was 100 mcg and for hydromorphone was 75 mcg. Morphine median (interquartile range [IQR]) numeric rating scale scores was 3.0 (1.5-4.5) at 12 hours and 3.0 (2.0-4.0) at 24 hours, whereas hydromorphone median (IQR) numeric rating scale were 3.0 (1.5-5.0) at 12 hours and 3.0 (2.0-5.0) at 24 hours. As the dosage of hydromorphone increased, moderate to severe pruritus increased (P=.009).

Conclusion

The study could not establish an ED₉₀ for IT dosing for minimally invasive colorectal surgical patients. However, we did determine the ED₅₀ for both agents. No serious adverse events were observed throughout the study duration.

Trial Registration

clinicaltrials.gov Identifier: NCT04752033