Comparing Intravenous Hydromorphone to Usual Care

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