Comparing Intravenous Hydromorphone to Usual Care
Comparing Intravenous Hydromorphone to Usual Care
In this randomized controlled trial, 2 mg intravenous (IV) hydromorphone will be more
 efficacious than usual care (usual care is analgesic management according to the judgment of
 the attending physician caring for that patient) in emergency department (ED) patients aged
 21-64 years. The primary efficacy outcomes are the proportion of patients in each arm who
 choose to forgo additional pain medication in 30 minutes of entry into the study and the
 change in numerical rating scale (NRS) pain scores from baseline to 30 minutes post baseline.
Patients were randomized to the 2 mg IV hydromorphone group or usual care; allocation was
 generated with www.randomization.com, using sealed opaque envelopes opened in sequential
 order by the research assistants (RAs) immediately following enrollment. Patients randomly
 allocated to usual care received an initial dose of IV opioid; the type and dose of which was
 determined by the treating emergency physician (EP). Patients in the 2 mg hydromorphone group
 were allocated to receive 2 mg IV hydromorphone, administered slowly over 2 to 3 minutes. All
 patients were placed on 2 L O2 by nasal cannula. Subjects were blinded to the treatment they
 were assigned. At 30 minutes, both groups were asked the following scripted question: "Do you
 want more pain medication?" Patients in either group who answered or otherwise indicated
 "yes" had their treating attending physician notified, who then decided on further pain
 management. Those who answered or otherwise indicated "no" did not receive additional
 analgesic at that time. Attending physicians were thus able to treat patients' pain in any
 manner they deemed fit once this primary study endpoint was reached. In addition to
 acquisition of the primary endpoint, patients were also asked to rate their pain on a
 previously validated and reproducible standard verbal NRS ranging from 0 ("no pain") through
 10 ("worst pain possible") at 15, 30, 45, 60, 90, and 120 minutes following administration of
 the initial opioid dose at time 0. For safety reasons, patients were monitored for a total of
 120 minutes (i.e., 90 minutes past the primary study endpoint) to determine adverse effects.
 Systolic blood pressure, heart rate, oxygen saturation, nausea, vomiting, and pruritus were
 assessed at baseline and at 15, 30, 45, 60, 90, and 120 minutes after initial administration
 of opioid. Patients who experienced oxygen desaturation (defined as < 95%) were gently
 aroused if sleeping, asked to take several deep breaths, and repositioned into a sitting
 position if they had been in a reclined position. Nasal cannula oxygen was also increased to
 4 L, and the treating attending physician was notified. Subsequent management, including the
 use of naloxone, was per the treating attending physician's discretion.
Inclusion Criteria:

 1. Age greater than 21 years and less than 65 years: This is a study of non-elderly adult
 patients.

 2. Pain with onset within 7 days: Pain within seven days is the definition of acute pain
 that has been used in ED literature.

 3. ED attending physician's judgment that patient's pain warrants IV opioids: The factors
 that influence the decision to use parenteral opioids are complex. An approach that is
 commonly taken to address the issue of patient selection in drug trials is to use a
 specific condition (e.g., renal colic) that would generally be thought to be
 appropriately treated with an opioid analgesic, thereby eliminating individual
 judgment about eligibility for the study. However in order to maximize the external
 validity of the role of opioids in the ED setting, the investigators decided to enroll
 patients with a variety of diagnoses, all with a complaint of acute pain. Opioids are
 not an appropriate treatment for all patients who present with a complaint of pain
 (e.g., gastroenteritis, migraine). Therefore, unless there is a restriction to
 patients with a specific diagnosis, either an extensive list of diagnoses and
 situations in which opioids are indicated must be specified, or clinical judgment
 needs to be used. The investigators have opted for the latter, since it most closely
 approximates the circumstances of clinical practice.

 Exclusion Criteria:

 1. Use of other opioids or tramadol within past 24 hours: to avoid introducing assembly
 bias related to recent opioid use, since this may affect baseline levels of pain and
 need for analgesics.

 2. Prior adverse reaction to opioids.

 3. Chronic pain syndrome: frequently recurrent or daily pain for at least 3 months
 results in modulation of pain perception which is thought to be due to down-regulation
 of pain receptors. Examples of chronic pain syndromes include sickle cell anemia,
 osteoarthritis, fibromyalgia, and peripheral neuropathies.

 4. Alcohol intoxication: the presence of alcohol intoxication as judged by the treating
 physician may alter pain perception.

 5. Systolic Blood Pressure <90 mm Hg: Opioids can produce peripheral vasodilation that
 may result in orthostatic hypotension.

 6. Oxygen saturation < 95% on room air: For this study, oxygen saturation must be 95% or
 above on room air in order to be enrolled.

 7. Use of monoamine oxidase (MAO) inhibitors in past 30 days: MAO inhibitors have been
 reported to intensify the effects of at least one opioid drug causing anxiety,
 confusion and significant respiratory depression or coma.

 8. C02 measurement greater than 46: In accordance with standard protocol, three subsets
 of patients will have their CO2 measured using a handheld capnometer prior to
 enrollment in the study. If the CO2 measurement is greater than 46 then the patient
 will be excluded from the study. The 3 subsets are as follows:

 -  All patients who have a history of chronic obstructive pulmonary disease (COPD)

 -  All patients who report a history of asthma together with greater than a 20
 pack-year smoking history

 -  All patients reporting less than a 20 pack-year smoking history who are having an
 asthma exacerbation