Pain management/original research
Safety and Efficacy of Hydromorphone as an Analgesic Alternative to Morphine in Acute Pain: A Randomized Clinical Trial

https://doi.org/10.1016/j.annemergmed.2006.03.005Get rights and content

Study objective

We compare a standard weight-based dose of intravenous hydromorphone (Dilaudid) to a standard weight-based dose of intravenous morphine in adults presenting to the ED with acute severe pain.

Methods

This was a prospective, randomized, double-blind, clinical trial conducted in an academic medical center. Of the 198 adult patients presenting to the ED with acute severe pain who were randomized to receive either intravenous hydromorphone at 0.015 mg/kg or intravenous morphine at 0.1 mg/kg, 191 patients had sufficient data for analysis. The main outcome measure was the difference between the 2 groups in pain reduction at 30 minutes as measured on a validated numeric rating scale. Adverse effects, pain reduction at 5 minutes and 2 hours postbaseline, and additional analgesics and antiemetics were tracked as secondary outcome measures.

Results

The mean change of pain from baseline to 30 minutes postbaseline in patients allocated to intravenous hydromorphone was −5.5 numeric rating scale units versus −4.1 in patients allocated to intravenous morphine (difference −1.3; 95% confidence interval −2.2 to −0.5). Adverse effects were similar in both groups, with the exception of pruritus, which did not occur in patients receiving hydromorphone (0% versus 6% [difference −6%; 95% confidence interval −11% to −1%]). No patient required naloxone.

Conclusion

For the treatment of acute, severe pain in the emergency department, intravenous hydromorphone at 0.015 mg/kg represents a feasible alternative to intravenous morphine at 0.1 mg/kg.

Introduction

There are 4 main parenteral opioids used to treat pain in the emergency department (ED): morphine, meperidine (Demerol), fentanyl, and hydromorphone (Dilaudid). Morphine is considered the standard for the management of severe cancer pain.1 It is also the most frequently used parenteral opioid in emergency practice, followed closely by meperidine,2 whose use is constrained by accumulation of the toxic metabolite normeperidine.3 Because of its short half-life, fentanyl is primarily used for procedural sedation. For unclear reasons, hydromorphone is not commonly used by emergency physicians.2

Hydromorphone is a semisynthetic opioid introduced in the 1920s, approximately 10 years before meperidine was synthesized. Hydromorphone has been used extensively for the management of postoperative pain 4, 5, 6 and morphine-resistant cancer-related pain.7 A recent Cochrane review on the use of hydromorphone found 32 studies that focused on acute pain.8 Of these 32 studies, only 9 involved intravenous forms of hydromorphone.9, 10, 11, 12, 13, 14, 15, 16, 17 Five of these 9 studies examined patient-controlled analgesia.12, 13, 14, 15, 16, 17 The only study directly comparing intravenous hydromorphone to intravenous morphine was conducted in 1975 among postoperative patients.9 We could locate only 1 study of hydromorphone in the ED setting, and this compared intravenous hydromorphone to intravenous meperidine in patients with ureteral colic.10 Although this study showed that hydromorphone was superior at all periods and had fewer adverse effects, the study used fixed rather than weight-based doses of hydromorphone (1 mg) and meperidine (50 mg). The Cochrane review concluded that there are substantive gaps in our understanding of the efficacy and potency of hydromorphone.8

There is widespread agreement that pain is undertreated in the ED.18 The current recommended treatment of acute pain in the ED setting is administration of an initial bolus of morphine, followed by titration until adequate analgesia is achieved.19, 20 Two studies have shown that even 0.1 mg/kg intravenous morphine (7 to 10 mg administered to the average 70- to 100-kg patient) inadequately treats many patients’ acute pain.21, 22 Despite this undertreatment, we have observed that many emergency physicians and nurses are hesitant to give 7 to 10 mg of morphine as an initial intravenous dose. In contrast, we observed that these same health care providers were not similarly reluctant to administer a roughly equianalgesic dose of hydromorphone (1 to 1.5 mg), perhaps because the more potent hydromorphone is given in much smaller milligram quantities than morphine, thus providing the illusion of substantially less opioid administered to the patient. Having repeatedly observed this phenomenon, we reasoned that if a smaller milligram dose of hydromorphone were shown to provide an efficacy, safety, and adverse-effect profile comparable or superior to that of a larger milligram dose of morphine, it would provide evidence supporting use of hydromorphone as an alternative first-line opioid in the treatment of acute pain presenting to the ED. As a practical corollary to this, we reasoned further that the increased willingness of health care providers to use hydromorphone might contribute to reducing one component of the multifaceted problem of oligoanalgesia in the ED.18

The aim of this study was to determine the between-group difference in before-after improvements in pain numeric rating scale scores at 30 minutes in patients randomized to receive either intravenous hydromorphone at 0.015 mg/kg or intravenous morphine at 0.1 mg/kg.

Section snippets

Study Design

This was a prospective, randomized, double-blind, clinical trial designed to compare intravenous hydromorphone to intravenous morphine in the treatment of acute pain presenting to the ED. The study was approved by the institutional review board of the Montefiore Medical Center.

Setting

The study was conducted in an adult urban academic ED with an annual census of approximately 85,000 patients.

Selection of Participants

The study population consisted of adults between the ages of 21 and 65 years who presented to the ED with acute

Characteristics of Study Subjects

One hundred ninety-eight patients were enrolled in the study (Figure 1, CONSORT diagram). Three data collection forms were lost (all were from the morphine group). Outcome data at 30 minutes were missing for 2 patients in the hydromorphone group and 1 patient in the morphine group. One patient who was randomized into the morphine group received oxycodone/acetaminophen prebaseline and was excluded. Thus, there were 97 patients in the hydromorphone group and 94 patients in the morphine group

Limitations

Any comparative study of opioid analgesics is intrinsically limited by the imprecision of the definition of equianalgesia. Historically, there is little consensus in the literature on the ratio of hydromorphone to morphine that constitutes analgesic equivalency, ranging from as little as 2 to as much as 12 times the potency.9 Lacking evidence-based consensus, we calculated our doses according to the ratio suggested in the most recent edition of Goodman & Gilman.24 We chose this as the most

Discussion

We found that ED patients who received intravenous hydromorphone had a greater decrease in mean pain score than those who received intravenous morphine. The CI around this difference of −1.3 ranges from −2.2 to −0.5, with the upper end of the CI only half a numeric rating scale unit below 0. Thus, despite the fact that the point estimate of the difference between groups, 1.3, is one that has been thought to be a minimally clinically significant difference, we are hesitant to conclude that this

References (31)

  • S.R. Chaplan et al.

    Morphine and hydromorphone epidural analgesia

    Anesthesiology

    (1992)
  • M. Goodarzi

    Comparison of epidural morphine, hydromorphone and fentanyl for postoperative pain control in children undergoing orthopaedic surgery

    Paediatr Anaesth.

    (1999)
  • C. Hanna et al.

    An evaluation of dihydromorphinone in treating postoperative pain

    Anesth Analg.

    (1962)
  • A. Jacox et al.

    New clinical practice guidelines for the management of pain in patients with cancer

    N Engl J Med.

    (1993)
  • Quigley C. Hydromorphone for acute and chronic pain. The Cochrane Database of Systematic Reviews 2002, Issue 1. Art....
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    Supervising editor: Robert K. Knopp, MD

    Author contributions: AKC, PEB, and EJG conceived the study and designed the trial. CS prepared all samples and helped with the design of the study. MKK assisted with quality control and analyzed the samples to confirm that the concentrations were correct after dilutions were performed. AKC and RM managed the data, including quality control. PB analyzed the data and provided all figures and tables. AKC drafted the manuscript, and all authors contributed substantially to its multiple revisions. AKC takes responsibility for the paper as a whole.

    Funding and support: The authors report this study did not receive any outside funding or support.

    Publication dates: Available online April 27, 2006.

    Reprints not available from the authors.

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