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.

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

8 patients excluded from initial 215 for protocol violations: 1 from missing data, 7 for failure to receive intravenous hydromorphone after requesting it

120 minutes