Association Between Body Size and Response to Hydromorphone in ED

Pain is the most common complaint for patients presenting to the emergency department (ED).
Morphine and hydromorphone are the two most commonly administrated intravenous opioid
analgesics. However, a large inter-individual variation in the response to morphine or
hydromorphone has been observed and a significant number of patients do not have
satisfactory pain relief after receiving commonly administered doses of these two
medications. Current studies have focused on investigating optimal strategies of intravenous
opioid use for moderate and severe pain in the ED.

Contrary to the commonly recommended total body weight (TBW) based dosing strategy, a recent
publication did not demonstrate a linear relationship between TBW and clinical response to
morphine.

The ultimate goal of the research is to identify optimal methods of dosing opioids to
alleviate pain in ED patients. The objective of this study is to examine the association
between two measures of body size/body composition and response to a standard dose of
hydromorphone. The null hypothesis is that there is no association between the measures of
body size/composition and response to 1 mg hydromorphone, and thus no difference between the
associations. If a strong association exists between TBW or BMI and pain response, it will
lend support for the importance of taking body size or composition into account when making
decisions about hydromorphone dosing in the ED. It will lay the groundwork for future
studies of analgesic dosing. This is of particular importance given the increasing
prevalence of obesity in the US and other developed nations.

Specific Aims:

1. To test the association between analgesic response to a standard dose of hydromorphone
and total body weight in ED patients with acute pain requiring intravenous opioid
analgesia.

2. To test the association between analgesic response to a standard dose of hydromorphone
and BMI.

3. To compare the associations between analgesic response to a standard dose of
hydromorphone and the two measures of body size/composition, BMI and TBW.

4. To assess whether the associations between response to hydromorphone and these measures
of body size/composition are confounded or modified by gender, age, ethnicity and
certain genetic polymorphisms.

The results of the current study will suggest whether body size or composition play a role
in the clinical response to hydromorphone and may lay the groundwork for further studies to
determine whether dosing should be modified to take these characteristics into account
either continuously, e.g. 0.015 mg/kg hydromorphone or categorically (increasing doses by
category of BMI).

Inclusion Criteria:

- English or Spanish speaking

- Age 18 - 65 years old

- Acute pain (less than 7 days in duration)

- Pain with sufficient severity to warrant use of intravenous opioids in the judgment
of ED attending physician

Exclusion Criteria:

- Allergy to hydromorphone

- Systolic blood pressure < 90 mm Hg

- Room air oxygen saturation by pulse oximetry < 95% at baseline without supplemental
oxygen

- Alcohol or other drug intoxication as judged by the attending physician

- Suspicion of drug seeking by ED physician

- Use of opioids within the past 24 hours

- Use of a monoamine oxidase inhibitor

- Concurrent use of benzodiazepines

- Presence of a chronic pain syndrome (such as sickle cell disease, peripheral
neuropathy, diabetic neuropathy, or fibromyalgia)

- History of COPD, sleep apnea, renal failure, liver disease

- Pregnancy or breast feeding

- Prior entry of patient in the study

- Inability or unwillingness to provide informed consent