Pain
Conditions
Keywords
Acute, Pain, Emergency Department, Hydromorphone, Protocol
Brief summary
In this randomized controlled trial, 2 mg intravenous (IV) hydromorphone will be more efficacious than usual care (usual care is analgesic management according to the judgment of the attending physician caring for that patient) in emergency department (ED) patients aged 21-64 years. The primary efficacy outcomes are the proportion of patients in each arm who choose to forgo additional pain medication in 30 minutes of entry into the study and the change in numerical rating scale (NRS) pain scores from baseline to 30 minutes post baseline.
Detailed description
Patients were randomized to the 2 mg IV hydromorphone group or usual care; allocation was generated with www.randomization.com, using sealed opaque envelopes opened in sequential order by the research assistants (RAs) immediately following enrollment. Patients randomly allocated to usual care received an initial dose of IV opioid; the type and dose of which was determined by the treating emergency physician (EP). Patients in the 2 mg hydromorphone group were allocated to receive 2 mg IV hydromorphone, administered slowly over 2 to 3 minutes. All patients were placed on 2 L O2 by nasal cannula. Subjects were blinded to the treatment they were assigned. At 30 minutes, both groups were asked the following scripted question: Do you want more pain medication? Patients in either group who answered or otherwise indicated yes had their treating attending physician notified, who then decided on further pain management. Those who answered or otherwise indicated no did not receive additional analgesic at that time. Attending physicians were thus able to treat patients' pain in any manner they deemed fit once this primary study endpoint was reached. In addition to acquisition of the primary endpoint, patients were also asked to rate their pain on a previously validated and reproducible standard verbal NRS ranging from 0 (no pain) through 10 (worst pain possible) at 15, 30, 45, 60, 90, and 120 minutes following administration of the initial opioid dose at time 0. For safety reasons, patients were monitored for a total of 120 minutes (i.e., 90 minutes past the primary study endpoint) to determine adverse effects. Systolic blood pressure, heart rate, oxygen saturation, nausea, vomiting, and pruritus were assessed at baseline and at 15, 30, 45, 60, 90, and 120 minutes after initial administration of opioid. Patients who experienced oxygen desaturation (defined as \< 95%) were gently aroused if sleeping, asked to take several deep breaths, and repositioned into a sitting position if they had been in a reclined position. Nasal cannula oxygen was also increased to 4 L, and the treating attending physician was notified. Subsequent management, including the use of naloxone, was per the treating attending physician's discretion.
Interventions
DRUGHydromorphone
2 mg IV hydromorphone over to 2-3 minutes
DRUGUsual care
Attending administers IV opioid of his choosing
Sponsors
Montefiore Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age greater than 21 years and less than 65 years: This is a study of non-elderly adult patients. 2. Pain with onset within 7 days: Pain within seven days is the definition of acute pain that has been used in ED literature. 3. ED attending physician's judgment that patient's pain warrants IV opioids: The factors that influence the decision to use parenteral opioids are complex. 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) 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 maximize the external validity of the role of opioids in the ED setting, the investigators 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 an extensive list of diagnoses and situations in which opioids are indicated must be specified, or clinical judgment needs to be used. The investigators have opted for the latter, since it most closely approximates the circumstances of clinical practice.
Exclusion criteria
1. Use of other opioids or tramadol within past 24 hours: to avoid introducing assembly bias related to recent opioid use, since this may affect baseline levels of pain and need for analgesics. 2. Prior adverse reaction to opioids. 3. Chronic pain syndrome: frequently recurrent or daily pain for at least 3 months results in modulation of 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, and peripheral neuropathies. 4. Alcohol intoxication: the presence of alcohol intoxication as judged by the treating physician may alter pain perception. 5. Systolic Blood Pressure \<90 mm Hg: Opioids can produce peripheral vasodilation that may result in orthostatic hypotension. 6. Oxygen saturation \< 95% on room air: For this study, oxygen saturation must be 95% or above on room air in order to be enrolled. 7. Use of monoamine oxidase (MAO) inhibitors in past 30 days: MAO inhibitors have been reported to intensify the effects of at least one opioid drug causing anxiety, confusion and significant respiratory depression or coma. 8. C02 measurement greater than 46: In accordance with standard protocol, 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: * All patients who have a history of chronic obstructive pulmonary disease (COPD) * All patients who report a history of asthma together with greater than a 20 pack-year smoking history * All patients reporting less than a 20 pack-year smoking history who are having an asthma exacerbation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Declined Additional Medication at 30 Minutes | 30 minutes | Amount of patients who choose to forgo additional pain medication at 30 minutes post-baseline when asked the question, Do you want more pain medication? |
| Mean Change in Pain Intensity Score From Baseline to 30 Minutes | 30 minutes | Pain intensity is measured on the numerical rating scale (NRS) with scores ranging from 0 (no pain) to 10 (worst pain imaginable). The change in NRS score is calculated by subtracting the score at 30 minutes post treatment from the score at baseline, before treatment. The average of these values was calculated. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hydromorphone 2 mg of IV dilaudid will be administered over 2-3 minutes as initial dose.
2 mg IV hydromorphone: 2 mg IV hydromorphone over to 2-3 minutes | 164 |
| Usual Care The attending physician administers whatever IV opioid he/she deems appropriate in whatever dose he/she chooses for initial dosing
Usual care: Attending administers IV opioid of his choosing | 161 |
| Total | 325 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 4 | 6 |
Baseline characteristics
| Characteristic | Hydromorphone | Usual Care | Total |
|---|---|---|---|
| Age, Continuous | 41.4 years STANDARD_DEVIATION 12.2 | 41.2 years STANDARD_DEVIATION 12.3 | 41.3 years STANDARD_DEVIATION 12.3 |
| Location of Pain Abdomen | 101 Participants | 110 Participants | 211 Participants |
| Location of Pain Other | 63 Participants | 51 Participants | 114 Participants |
| Nauseated or vomited before receiving opioids in the ED No | 67 Participants | 62 Participants | 129 Participants |
| Nauseated or vomited before receiving opioids in the ED Unknown | 1 Participants | 0 Participants | 1 Participants |
| Nauseated or vomited before receiving opioids in the ED Yes | 96 Participants | 99 Participants | 195 Participants |
| Pain Intensity Score of 10 | 103 Participants | 103 Participants | 206 Participants |
| Pain Intensity Score of 3-7 | 19 Participants | 21 Participants | 40 Participants |
| Pain Intensity Score of 8 | 22 Participants | 22 Participants | 44 Participants |
| Pain Intensity Score of 9 | 20 Participants | 15 Participants | 35 Participants |
| Race/Ethnicity, Customized African American | 38 Participants | 41 Participants | 79 Participants |
| Race/Ethnicity, Customized Hispanic | 113 Participants | 103 Participants | 216 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 5 Participants | 8 Participants |
| Race/Ethnicity, Customized White | 10 Participants | 12 Participants | 22 Participants |
| Region of Enrollment United States | 164 Participants | 161 Participants | 325 Participants |
| Sex: Female, Male Female | 101 Participants | 91 Participants | 192 Participants |
| Sex: Female, Male Male | 63 Participants | 70 Participants | 133 Participants |
| Weight | 195.4 lbs STANDARD_DEVIATION 39 | 201.4 lbs STANDARD_DEVIATION 42.8 | 198.4 lbs STANDARD_DEVIATION 41 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 164 | 0 / 161 |
| other Total, other adverse events | 61 / 164 | 33 / 161 |
| serious Total, serious adverse events | 0 / 164 | 0 / 161 |
Outcome results
Primary
Mean Change in Pain Intensity Score From Baseline to 30 Minutes
Pain intensity is measured on the numerical rating scale (NRS) with scores ranging from 0 (no pain) to 10 (worst pain imaginable). The change in NRS score is calculated by subtracting the score at 30 minutes post treatment from the score at baseline, before treatment. The average of these values was calculated.
Time frame: 30 minutes
Population: The discrepancy between the number of patients enrolled and randomized and the number of patients analyzed is due to: never given IV opioids (10), missing primary outcome data (4), enrolled twice (2), and received IV ketorolac prior to enrollment (9)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydromorphone | Mean Change in Pain Intensity Score From Baseline to 30 Minutes | 6.7 units on a scale | Standard Deviation 2.9 |
| Usual Care | Mean Change in Pain Intensity Score From Baseline to 30 Minutes | 5.6 units on a scale | Standard Deviation 3.2 |
Primary
Number of Participants Who Declined Additional Medication at 30 Minutes
Amount of patients who choose to forgo additional pain medication at 30 minutes post-baseline when asked the question, Do you want more pain medication?
Time frame: 30 minutes
Population: The discrepancy between the number of patients enrolled and randomized and the number of patients analyzed is due to: never given IV opioids (10), missing primary outcome data (4), enrolled twice (2), and received IV ketorolac prior to enrollment (9)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hydromorphone | Number of Participants Who Declined Additional Medication at 30 Minutes | 127 Participants |
| Usual Care | Number of Participants Who Declined Additional Medication at 30 Minutes | 106 Participants |
Post Hoc
Number of Participants Who Achieved at Least 50% Decline in NRS Pain Score at 30 Minutes
Time frame: 30 minutes
Population: The discrepancy between the number of patients enrolled and randomized and the number of patients analyzed is due to: never given IV opioids (10), missing primary outcome data (4), enrolled twice (2), and received IV ketorolac prior to enrollment (9)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hydromorphone | Number of Participants Who Achieved at Least 50% Decline in NRS Pain Score at 30 Minutes | 136 Participants |
| Usual Care | Number of Participants Who Achieved at Least 50% Decline in NRS Pain Score at 30 Minutes | 111 Participants |
Post Hoc
Number of Participants Who Reported no Pain or Mild Pain at 30 Minutes
Time frame: 30 minutes
Population: The discrepancy between the number of patients enrolled and randomized and the number of patients analyzed is due to: never given IV opioids (10), missing primary outcome data (4), enrolled twice (2), and received IV ketorolac prior to enrollment (9)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hydromorphone | Number of Participants Who Reported no Pain or Mild Pain at 30 Minutes | 122 Participants |
| Usual Care | Number of Participants Who Reported no Pain or Mild Pain at 30 Minutes | 95 Participants |
Post Hoc
Number of Patients Who Achieved Absolute Pain Intensity Score of 3 or Less at 30 Minutes
Pain intensity is measured on the numerical rating scale (NRS) with scores ranging from 0 (no pain) to 10 (worst pain imaginable)
Time frame: 30 minutes
Population: The discrepancy between the number of patients enrolled and randomized and the number of patients analyzed is due to: never given IV opioids (10), missing primary outcome data (4), enrolled twice (2), and received IV ketorolac prior to enrollment (9)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hydromorphone | Number of Patients Who Achieved Absolute Pain Intensity Score of 3 or Less at 30 Minutes | 114 Participants |
| Usual Care | Number of Patients Who Achieved Absolute Pain Intensity Score of 3 or Less at 30 Minutes | 90 Participants |