Titration of Intravenous Hydromorphone
Condition: Acute Severe Pain
Intervention: Hydromorphone
Intervention MeSH terms: Hydromorphone
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 215.0
Sex: All
Minimum age: 21 Years
Maximum age: 64 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: acute; pain; emergency department; hydromorphone; in ER

Summary:

      This is an exploratory, hypothesis-generating safety and efficacy study for patients who come
      to the ER in acute (less than 7 days in duration) severe pain. Patients with chronic pain
      will not be enrolled. Eligible patients will receive up to a maximum of 4 mg IV hydromorphone
      over a 4 hour period. Hydromorphone will be given as 1 mg increments based on how the patient
      responds to the question, "Do you want more pain medicine?". This question will be asked
      repeatedly 30 minutes after the patient answers "no" or 30 minutes after the most recent dose
      of IV hydromorphone (which occurs if the patient answers "yes"). Up to 10% (approximately 30
      patients) will serve as a pilot at the start of the study.
    

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: Patients age 65 and over will be excluded from 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 Emergency Department (ED) literature.

             4. ED attending physician's judgment that patient's pain warrants use of morphine

             5. 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. Similar to sickle cell patients and chronic
             cancer patients, patients on methadone usually require significantly higher doses of
             opioids to control their pain.

             2. Use of other opioids or tramadol within past 24 hours: 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: patients will be excluded if they state
             that they have an allergy 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. Patients for whom the attending physician suspects is addicted to opioids: patients
             will be excluded if the attending suspects the patient may be addicted to opioids or
             seeking to obtain them for diversionary reasons, such as for monetary profit or other
             illicit use.

             6. Alcohol intoxication: the presence of alcohol intoxication as judged by the
             treating physician may alter perception, report, and treatment of pain.

             7. Systolic Blood Pressure <100 mm Hg: Hydromorphone can produce peripheral
             vasodilation that may result in orthostatic hypotension or syncope.

             8. Respiratory rate < 12/minute: Hydromorphone can cause respiratory depression.

             9. Oxygen saturation <95% on room air: For this study, oxygen saturation must be 95%
             or above on room air in order to be enrolled.

             10. Heart rate < 60 beats/minute: Hydromorphone can cause bradycardia.

             11. 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.

             12. Carbon dioxide measurement greater than 46: three subsets of patients will have
             their carbon dioxide measured using a handheld capnometer prior to enrollment in the
             study. If the carbon dioxide 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