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Intrathecal Hydromorphone and Morphine for Postcesarean Delivery Analgesia: Determination of the ED90 Using a Sequential Allocation Biased-Coin Method

Sviggum, Hans P. MD; Arendt, Katherine W. MD; Jacob, Adam K. MD; Niesen, Adam D. MD; Johnson, Rebecca L. MD; Schroeder, Darrell R. MS; Tien, Michael BS; Mantilla, Carlos B. MD, PhD

doi: 10.1213/ANE.0000000000001229
Obstetric Anesthesiology: Original Clinical Research Report

BACKGROUND: Intrathecal (IT) morphine is considered the “gold standard” for analgesia after cesarean delivery under spinal anesthesia, most commonly administered at a dose of 100 to 200 μg. There is less experience with IT hydromorphone for postcesarean analgesia and limited information on its optimal analgesic dose. We conducted this study to determine the effective analgesic dose for 90% patients (ED90) of IT hydromorphone that provides effective analgesia for women undergoing elective cesarean delivery and its potency ratio to IT morphine.

METHODS: In this dose-finding trial, 80 patients received spinal anesthesia for cesarean delivery. Participants were randomized to receive IT morphine or IT hydromorphone at a dose determined using up–down sequential allocation with a biased-coin design to determine ED90. All patients received standardized multimodal analgesia postoperatively in addition to IT opioid. An effective dose was defined as a numeric response score for pain of ≤3 (scale 0–10) 12 hours after spinal injection.

RESULTS: The ED90 was 75 μg (95% confidence interval [CI], 46–93 μg) for IT hydromorphone and 150 μg (95% CI, 145–185 μg) for IT morphine. At these doses, the 95% CI for the percentage of patients with effective analgesia (numeric rating scale ≤3) was 64% to 100% for hydromorphone and 68% to 100% for morphine. Exploratory findings showed that the incidence of nausea and pruritus was not different among the most commonly used doses of IT hydromorphone (P = 0.44 and P = 0.74) or IT morphine (P = 0.67 and P = 0.38, respectively). When administering IT opioids at ED90 doses or higher, 100% (21/21) of IT hydromorphone and 95% (37/39) of IT morphine patients were satisfied with their analgesia.

CONCLUSIONS: The ratio of IT morphine to IT hydromorphone for effective postcesarean analgesia is 2:1. Patient satisfaction was high with both medications.

Published ahead of print March 11, 2016

From the Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota.

Accepted for publication January 18, 2016.

Published ahead of print March 11, 2016

Funding: Department of Anesthesiology, Mayo Clinic, Rochester, MN.

The authors declare no conflicts of interest.

Reprints will not be available from the authors.

Address correspondence to Hans P. Sviggum, MD, Department of Anesthesiology, Mayo Clinic, 200 1st St. SW, Rochester, MN 55905. Address e-mail to

© 2016 International Anesthesia Research Society