Safety Study of Intravenous Hydromorphone Using Incremental 1mg Doses up to 2mg for Adult ED Patients
Safety Study of Intravenous Hydromorphone Using Incremental 1mg Doses up to 2mg for Adult ED Patients
We wish to examine the safety and speed of onset of giving a dose of 1mg hydromorphone
 followed by an additional 1mg. Eligible patients will be given 1 mg intravenous (IV)
 hydromorphone. At 15 minutes, these patients will be asked the question, "Do you need more
 pain medication?" Those that answer "yes" will receive an additional 1mg IV hydromorphone.
 Those that answer "no" will not receive additional pain medications at that time period (15
 minutes). Thus, we wish to give up to 2 mg IV hydromorphone titrated to patients' pain, which
 we believe will result in less incidence of oxygen desaturation.

 If our study shows that this regimen is safe, its efficacy can be assessed in future trials.
 Positive results of those trials may lead to the use of this regimen to improve pain
 management in the emergency department.
Prospective interventional study at an urban academic emergency department (ED). One
 milligram of IV hydromorphone was administered to adults 21 to 64 years of age who had acute
 severe pain. Fifteen minutes later, patients were asked whether they wanted more pain
 medication. If they answered yes, they received another 1 mg of IV hydromorphone and were
 again asked 15 minutes later whether they wanted more pain medication. The primary efficacy
 outcome was the proportion of patients who had adequate analgesia, defined as declining
 additional hydromorphone within 1 hour of entering the protocol. The primary safety outcome
 was incidence of oxygen desaturation less than 95%. Secondary outcomes included numeric
 rating scale pain scores and adverse events.
Inclusion Criteria:

 1. Age greater than 21 years: Patients under the age of 21 are automatically triaged to
 the Children's Hospital at Montefiore Emergency Department, and hence cannot be
 enrolled in this study.

 2. Age less than 65 years of age: Patients age 65 and over will be excluded in this study
 as the effects on opioids on the elderly may be different than in the non-elderly.

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

 4. ED attending physician's judgment that patient's pain warrants use of morphine: The
 factors that influence the decision to use parenteral opioids are complex and
 extensive. 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) or
 treatment (e.g., post-hysterectomy) 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 assess the role of
 hydromorphone with the widest generalizability in the ED setting, we 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 a comprehensive list of diagnoses and
 situations in which opioids are indicated must be specified, or clinical judgment
 needs to be used. We have opted for the latter alternative.

 5. The use of patients with a variety of diagnoses, and therefore heterogeneous painful
 stimuli, risks masking a treatment effect because of large inter-individual
 variability. There are several design and analytic factors (detailed below) that
 attenuate this risk: 1) a sufficiently large number of patients will be randomly
 assigned to each group so that the variety of painful stimuli will be equally
 distributed between treatment groups; 2) change in pain intensity and pain relief will
 be analyzed rather than absolute pain intensity or pain relief therefore reducing
 variability.

 6. Normal mental status: In order to provide measures of pain experienced the patient
 needs to have a normal mental status. Orientation to person, place and time will be
 used as an indicator of sufficiently normal mental status to participate in the study.

 Exclusion Criteria:

 1. Prior use of methadone: the effect of methadone use on the perception of acute pain is
 unknown and suspected to be altered. We feel that the needs of patients on methadone
 may exceed the dosage ceiling of 2mg that will be used for this study. Similar to
 sickle cell patients and chronic cancer patients, patients on methadone usually
 require significantly higher doses of opioids to control their pain. Thus, we feel
 that it would be unethical to restrict the dose that this subset of patients can
 receive.

 2. Use of other opioids or tramadol within past seven days: to avoid introducing bias
 related to opioid tolerance that may alter the response to the study medication
 thereby masking the medication's effect.

 3. Prior adverse reaction to hydromorphone.

 4. Chronic pain syndrome: frequently recurrent or daily pain for at least 3 months result
 in alteration in 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, migraine, and peripheral neuropathies.

 5. Alcohol intoxication: the presence of alcohol intoxication as judged by the treating
 physician may alter perception, report, and treatment of pain.

 6. Systolic Blood Pressure <90 mm Hg: Hydromorphone can produce peripheral vasodilation
 that may result in orthostatic hypotension or syncope.

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

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

 9. C02 measurement greater than 46: In accordance with a similar study (04-12-360), 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:

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

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

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

 10. Pregnancy: this will be determined by asking the female of reproductive age about her
 pregnancy status and/or through the results of urine or serum pregnancy test.