Safety Study of Intravenous Hydromorphone Using Incremental 1mg Doses up to 2mg for Adult ED Patients
Condition: Pain
Intervention: Hydromorphone
Intervention description: 1mg IV hydromorphone, followed by an optional dose of 1mg IV hydromorphone 15 minutes later if the patient answers "yes" to the question, "Do you want more pain medication?"
Intervention MeSH terms: Hydromorphone
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 230.0
Sex: All
Minimum age: 21 Years
Maximum age: 64 Years
Healthy volunteers: No
Keywords: Nonelderly patients with acute moderate to severe pain

Summary:

      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.
    

Eligibility criteria:

        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.