Novel Use of Hydromorphone as a Pretreatment Agent: A Double-blind, Randomized, Controlled Study in Adult Korean Surgical Patients

Abstract

Background: Hydromorphone is a potent μ-opioid selective agonist that has an onset time within 5 minutes and reaches peak effect between 10 and 20 minutes. However, it may show immediate analgesic effect to rocuronium-induced pain because of its peripheral analgesic property and also may attenuate noxious stimuli from tracheal intubation during induction. The opioid receptors are known to be present in peripheral sensory nerve terminals as well as in the dorsal root ganglion and the central terminal of primary afferent nerves. Therefore, we hypothesized that hydromorphone may be considered a potent pretreatment or adjuvant drug during the induction of anesthesia with its peripherally and centrally mediated analgesia.

Objective: The aim of this study was to compare the effects of pretreatment with hydromorphone in reducing rocuronium-induced withdrawal movements and hemodynamic changes during tracheal intubation with the effects of fentanyl and normal saline.

Methods: In this double-blind, randomized, controlled study, consecutive adult patients aged 20 to 70 years who were scheduled to undergo general anesthesia for elective gastric or colorectal surgery at the Samsung Seoul Hospital (Seoul, Republic of Korea) were randomly assigned to receive 5 mL hydromorphone 0.03 mg/kg or fentanyl 2 μg/kg or normal saline. Thirty seconds after administering the study drug, anesthesia was induced with 2.5% thiopental sodium 5 mg/kg. After loss of consciousness, rocuronium 0.6 mg/kg was injected and immediate withdrawal movements were recorded. Two minutes after rocuronium injection, tracheal intubation was performed and hemodynamic changes were observed.

Results: A total of 194 patients were enrolled, with 65 in the hydromorphone group, 67 in the fentanyl group, and 62 in the saline group. The overall incidence of withdrawal movements was significantly lower in the hydromorphone group (2 patients; 3.1%) and the fentanyl group (5 patients; 7.5%) (both, P < 0.001) than in the saline group (36 patients; 58.1%). The mean arterial pressure (MAP) and heart rate (HR) after intubation (median [interquartile range]) in the fentanyl group (101.5 [84-115] mm Hg; 93.5 [82-102] beats per minute [bpm]) and the hydromorphone group (93.0 [83-106] mm Hg; 90.0 [86.3-93.6] bpm) were significantly lower than these measures in the saline group (111.5 [105-123] mm Hg; 103.5 [96-113] bpm) (fentanyl group MAP and HR, P < 0.001; hydromorphone group MAP and HR, P < 0.001).

Conclusions: Pretreatment with hydromorphone and fentanyl may have similar effectiveness in reducing withdrawal movements in response to rocuronium injection pain and inducing immediate general anesthesia.

Keywords: hydromorphone; induction of anesthesia; injection pain; rocuronium; withdrawal movement.

Figure 1

CONSORT flowchart for patient allocation and participation in this study.

Figure 2

This figure delineates the (A) mean arterial pressure (MAP) and (B) heart rate (HR) on arrival (baseline) and before (1 min BI) and after (1 min AI) tracheal intubation. This box and whisker plot shows median values with interquartile ranges. There were statistically significant changes in the MAP and HR from the baseline after intubation in all groups except for the changes in the MAP after intubation in the hydromorphone group. The MAP and HR after intubation in the fentanyl (median [interquartile range]) (101.5 [84−115] mm Hg; 93.5 [82–102] beats per minute [bpm]) and hydromorphone (93.0 [83−106] mm Hg; 90.0 [86.3−93.6] bpm) groups were significantly lower than those in the saline group (111.5 [105−123] mm Hg; 103.5 [96−113] bpm) (fentanyl group MAP and HR: P < 0.001; hydromorphone group MAP and HR: P < 0.001). Baseline = upon arrival at the operating room; 1 min BI = 1 minute before intubation; 1 min AI = 1 minute after intubation. *P values compared with the baseline value within the group; ^†P values compared with the saline group; ^‡P values compared with the fentanyl group.