Abuse potential and analgesic efficacy of different IV opioid infusion rates among patients hospitalized with cancer pain: A randomized crossover trial.
Authors: Arthur Joseph Anthony , Reddy Akhila , Halm Josiah , Rozman De Moraes Aline , Lopez-Quinones Irma , Laureano Raul , Urbauer Diana L. , Bruera Eduardo 
Published: June 2024

12077

Background: There is insufficient data on the effect of fast intravenous (IV) opioid infusion rate on their potential for abuse when administered for pain relief. No study has simultaneously evaluated the analgesic efficacy, abuse potential, and adverse effects of different IV opioid infusion rates to determine their risk-benefit ratio in routine inpatient care. We compared the abuse potential, analgesic efficacy, and adverse effect profile of the standard IV hydromorphone bolus infusion rate with a slower experimental rate among hospitalized patients with cancer pain. Methods: This double-blind, double dummy, randomized controlled, 2X2 crossover trial was conducted in the inpatient location at MD Anderson Cancer Center. Eligible patients were hospitalized patients with cancer, aged 18 years or older, who required IV opioids for moderate to severe pain. During the first period, participants were randomly assigned to receive IV hydromorphone 1mg administered over 15 minutes (experimental rate) in sequence A, or over 2 minutes (standard rate) in sequence B. Outcomes were measured at baseline, 15, 30, 60, and 120 minutes post-intervention Participants crossed over to receive treatments in the alternate sequence during the second period after a 6-hour wash out period. Abuse liability potential was measured by the Drug Effect Questionnaire (DEQ-5), change in Numerical Rating Scale pain scores, and rates of subjective and objective adverse effects. Results: Eighty-threeeligible patients were randomly allocated to sequences A (42, 51%) or B (41, 49%). There was no significant difference in the mean (SD) peak DEQ-5 “drug liking” subscale between the faster standard and slower experimental infusion rates (24.00 vs 24.34, p=0.82). Similarly, no significant differences were observed with other DEQ-5 subscales. 92% and 94% of experimental and standard IV hydromorphone rate recipients respectively had clinical improvements in pain scores over 120 minutes (OR=0.67, 95% CI: 0.06-5.82, p=0.65). No significant differences were observed in NRS pain scores between the 2 groups at all time points. Drowsiness and oxygen desaturation were the most common subjective and objective adverse events observed (up to 52% and 22% of all patients respectively). Drowsiness was more frequent in the standard group than the experimental group (50% vs 29% at 15 minutes [p= 0.03], and 52% vs 31% at 60 minutes [p=0.03]). Conclusions: The standard 2-minute IV hydromorphone bolus produced comparable abuse potential and analgesic effects but more sedation than an experimental 15-minute rate. The findings support a 2-minute bolus infusion rate for pain relief with relatively nominal abuse potential, but a slower 15-minute rate may be more desirable to minimize sedation and preserve cognition for critically important inpatient activities. Clinical trial information: NCT04296305 .