Acute Severe Pain
Conditions
Keywords
acute, pain, emergency department, hydromorphone, in ER
Brief 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.
Interventions
DRUGHydromorphone
Sponsors
Montefiore Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 64 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Requesting Pain Medication in Different Patterns Over Time | 4 hours | This is a descriptive hypothesis-generating trial, which is why it is not being compared in a randomized fashion to a comparison group. We are examining extended titration by expanding our 1+1 protocol to a 1+1+1+1 protocol and the various patterns of opioid request. For example, some may state no every time they are asked Do you want more pain medication? Some will state yes each time, and others will answer yes and no at different time periods. We will report these various patterns (i.e. X participants answered no everytime they were asked, Y answered yes everytime they were asked, Z answered no twice, etc). Time points 2, 3, and 4 are dependent on patient response to Do you want more pain medication? Time 1 is 30 min post-baseline. For those who answer no, Time 2 is 30 minutes later (at 1 hour), and for yes, Time 2 is 30 minutes after additional pain medication is given. This pattern follows for Time 3 and 4, with a total study time of 4 hours |
Secondary
| Measure | Time frame |
|---|---|
| Adverse Events and Side Effects by Total Amount of Hydromorphone Received | 120 min |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hydromorphone All eligible patients will receive 1 mg IV hydromorphone. Thereafter, they will be repeatedly asked the question, Do you want more pain medicine? This question will be asked 30 minutes after they answered no or 30 minutes after the completion of the next dose of 1 mg IV hydromorphone, which occurs when the patients answers yes. Patients will receive a maximum of 4 mg IV hydromorphone over a 4 hour period.
Hydromorphone | 207 |
| Total | 207 |
Baseline characteristics
| Characteristic | Hydromorphone |
|---|---|
| Age, Continuous | 41 years STANDARD_DEVIATION 12 |
| Initial NRS pain intensity NRS = 10 | 118 Participants |
| Initial NRS pain intensity NRS = 5-7 | 21 Participants |
| Initial NRS pain intensity NRS = 8 | 27 Participants |
| Initial NRS pain intensity NRS = 9 | 41 Participants |
| Location of pain Abdomen/pelvis | 153 Participants |
| Location of pain Back | 15 Participants |
| Location of pain Extremities | 8 Participants |
| Location of pain Flank | 22 Participants |
| Location of pain Other | 9 Participants |
| Nauseated or vomited before receiving first dose of opioid | 134 Participants |
| Race/Ethnicity, Customized Black | 44 Participants |
| Race/Ethnicity, Customized Hispanic | 143 Participants |
| Race/Ethnicity, Customized White/Other | 20 Participants |
| Region of Enrollment United States | 207 Participants |
| Sex: Female, Male Female | 122 Participants |
| Sex: Female, Male Male | 85 Participants |
| Weight | 177 lbs STANDARD_DEVIATION 34 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 207 |
| other Total, other adverse events | 68 / 207 |
| serious Total, serious adverse events | 0 / 207 |
Outcome results
Primary
Number of Participants Requesting Pain Medication in Different Patterns Over Time
This is a descriptive hypothesis-generating trial, which is why it is not being compared in a randomized fashion to a comparison group. We are examining extended titration by expanding our 1+1 protocol to a 1+1+1+1 protocol and the various patterns of opioid request. For example, some may state no every time they are asked Do you want more pain medication? Some will state yes each time, and others will answer yes and no at different time periods. We will report these various patterns (i.e. X participants answered no everytime they were asked, Y answered yes everytime they were asked, Z answered no twice, etc). Time points 2, 3, and 4 are dependent on patient response to Do you want more pain medication? Time 1 is 30 min post-baseline. For those who answer no, Time 2 is 30 minutes later (at 1 hour), and for yes, Time 2 is 30 minutes after additional pain medication is given. This pattern follows for Time 3 and 4, with a total study time of 4 hours
Time frame: 4 hours
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydromorphone | Number of Participants Requesting Pain Medication in Different Patterns Over Time | No requests for additional pain medication | 94 Participants |
| Hydromorphone | Number of Participants Requesting Pain Medication in Different Patterns Over Time | Requested additional pain medication, Time 1 only | 20 Participants |
| Hydromorphone | Number of Participants Requesting Pain Medication in Different Patterns Over Time | Requested additional pain medication, Time 2 only | 22 Participants |
| Hydromorphone | Number of Participants Requesting Pain Medication in Different Patterns Over Time | Requested additional pain medication, Time 3 only | 19 Participants |
| Hydromorphone | Number of Participants Requesting Pain Medication in Different Patterns Over Time | Requested additional pain medication, Time 4 only | 18 Participants |
| Hydromorphone | Number of Participants Requesting Pain Medication in Different Patterns Over Time | Requested add'l pain medication at >1 time point | 2 Participants |
Secondary
Adverse Events and Side Effects by Total Amount of Hydromorphone Received
Time frame: 120 min
Population: Nausea and vomiting were only assessed as adverse events among patients who did not have nausea and vomiting before the study began
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydromorphone | Adverse Events and Side Effects by Total Amount of Hydromorphone Received | Oxygen saturation <95% | 3 Participants |
| Hydromorphone | Adverse Events and Side Effects by Total Amount of Hydromorphone Received | Systolic blood pressure <90 mmHg | 1 Participants |
| Hydromorphone | Adverse Events and Side Effects by Total Amount of Hydromorphone Received | Pulse rate <50 beats/min | 1 Participants |
| Hydromorphone | Adverse Events and Side Effects by Total Amount of Hydromorphone Received | Vomiting | 4 Participants |
| Hydromorphone | Adverse Events and Side Effects by Total Amount of Hydromorphone Received | Nausea | 6 Participants |
| Hydromorphone | Adverse Events and Side Effects by Total Amount of Hydromorphone Received | Respiratory Rate <10 breaths/min | 1 Participants |
| Hydromorphone | Adverse Events and Side Effects by Total Amount of Hydromorphone Received | Pruritus | 8 Participants |
| 2 mg Hydromorphone | Adverse Events and Side Effects by Total Amount of Hydromorphone Received | Systolic blood pressure <90 mmHg | 0 Participants |
| 2 mg Hydromorphone | Adverse Events and Side Effects by Total Amount of Hydromorphone Received | Oxygen saturation <95% | 5 Participants |
| 2 mg Hydromorphone | Adverse Events and Side Effects by Total Amount of Hydromorphone Received | Respiratory Rate <10 breaths/min | 0 Participants |
| 2 mg Hydromorphone | Adverse Events and Side Effects by Total Amount of Hydromorphone Received | Pulse rate <50 beats/min | 1 Participants |
| 2 mg Hydromorphone | Adverse Events and Side Effects by Total Amount of Hydromorphone Received | Pruritus | 8 Participants |
| 2 mg Hydromorphone | Adverse Events and Side Effects by Total Amount of Hydromorphone Received | Nausea | 14 Participants |
| 2 mg Hydromorphone | Adverse Events and Side Effects by Total Amount of Hydromorphone Received | Vomiting | 5 Participants |
| 3 mg Hydromorphone | Adverse Events and Side Effects by Total Amount of Hydromorphone Received | Respiratory Rate <10 breaths/min | 1 Participants |
| 3 mg Hydromorphone | Adverse Events and Side Effects by Total Amount of Hydromorphone Received | Systolic blood pressure <90 mmHg | 0 Participants |
| 3 mg Hydromorphone | Adverse Events and Side Effects by Total Amount of Hydromorphone Received | Pruritus | 2 Participants |
| 3 mg Hydromorphone | Adverse Events and Side Effects by Total Amount of Hydromorphone Received | Vomiting | 0 Participants |
| 3 mg Hydromorphone | Adverse Events and Side Effects by Total Amount of Hydromorphone Received | Nausea | 2 Participants |
| 3 mg Hydromorphone | Adverse Events and Side Effects by Total Amount of Hydromorphone Received | Oxygen saturation <95% | 1 Participants |
| 3 mg Hydromorphone | Adverse Events and Side Effects by Total Amount of Hydromorphone Received | Pulse rate <50 beats/min | 0 Participants |
| 4 mg Hydromorphone | Adverse Events and Side Effects by Total Amount of Hydromorphone Received | Pulse rate <50 beats/min | 0 Participants |
| 4 mg Hydromorphone | Adverse Events and Side Effects by Total Amount of Hydromorphone Received | Respiratory Rate <10 breaths/min | 0 Participants |
| 4 mg Hydromorphone | Adverse Events and Side Effects by Total Amount of Hydromorphone Received | Systolic blood pressure <90 mmHg | 0 Participants |
| 4 mg Hydromorphone | Adverse Events and Side Effects by Total Amount of Hydromorphone Received | Vomiting | 0 Participants |
| 4 mg Hydromorphone | Adverse Events and Side Effects by Total Amount of Hydromorphone Received | Nausea | 3 Participants |
| 4 mg Hydromorphone | Adverse Events and Side Effects by Total Amount of Hydromorphone Received | Pruritus | 2 Participants |
| 4 mg Hydromorphone | Adverse Events and Side Effects by Total Amount of Hydromorphone Received | Oxygen saturation <95% | 0 Participants |
Post Hoc
Mean Pain Intensity Score in Numerical Rating Scale (NRS) Units at Each Time Point, Based on Response to the Question, Do You Want More Pain Medication?
Pain intensity is measured on the numerical rating scale (NRS) with scores from 0 (no pain) to 10 (worst pain imaginable). Time points 2, 3, and 4 are dependent on patient response to Do you want more pain medication? Time 1 is 30 min post-baseline. For those who answer no at Time 1, Time 2 is 30 minutes later (at 1 hour), and for those who answer yes, Time 2 is 30 minutes after additional pain medication is given. This pattern follows for Time 3 and 4, with a total study time of 4 hours
Time frame: 4 hours
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Hydromorphone | Mean Pain Intensity Score in Numerical Rating Scale (NRS) Units at Each Time Point, Based on Response to the Question, Do You Want More Pain Medication? | Time 1, Yes | 7.4 units on a scale |
| Hydromorphone | Mean Pain Intensity Score in Numerical Rating Scale (NRS) Units at Each Time Point, Based on Response to the Question, Do You Want More Pain Medication? | Time 1, No | 3.8 units on a scale |
| Hydromorphone | Mean Pain Intensity Score in Numerical Rating Scale (NRS) Units at Each Time Point, Based on Response to the Question, Do You Want More Pain Medication? | Time 2, Yes | 7.2 units on a scale |
| Hydromorphone | Mean Pain Intensity Score in Numerical Rating Scale (NRS) Units at Each Time Point, Based on Response to the Question, Do You Want More Pain Medication? | Time 2, No | 2.9 units on a scale |
| Hydromorphone | Mean Pain Intensity Score in Numerical Rating Scale (NRS) Units at Each Time Point, Based on Response to the Question, Do You Want More Pain Medication? | Time 3, Yes | 7.1 units on a scale |
| Hydromorphone | Mean Pain Intensity Score in Numerical Rating Scale (NRS) Units at Each Time Point, Based on Response to the Question, Do You Want More Pain Medication? | Time 3, No | 3.1 units on a scale |
| Hydromorphone | Mean Pain Intensity Score in Numerical Rating Scale (NRS) Units at Each Time Point, Based on Response to the Question, Do You Want More Pain Medication? | Time 4, Yes | 6.8 units on a scale |
| Hydromorphone | Mean Pain Intensity Score in Numerical Rating Scale (NRS) Units at Each Time Point, Based on Response to the Question, Do You Want More Pain Medication? | Time 4, No | 2.4 units on a scale |
Post Hoc
Number of Patients Responding to the Question, Do You Want More Pain Medication? at Each Time Point
Time points 2, 3, and 4 are dependent on patient response to Do you want more pain medication? Time 1 is 30 min post-baseline. For those who answer no at Time 1, Time 2 is 30 minutes later (at 1 hour), and for those who answer yes, Time 2 is 30 minutes after additional pain medication is given. This pattern follows for Time 3 and 4, with a total study time of 4 hours
Time frame: 4 hours
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Hydromorphone | Number of Patients Responding to the Question, Do You Want More Pain Medication? at Each Time Point | Time 1 | Yes | 42 Participants |
| Hydromorphone | Number of Patients Responding to the Question, Do You Want More Pain Medication? at Each Time Point | Time 1 | No | 165 Participants |
| Hydromorphone | Number of Patients Responding to the Question, Do You Want More Pain Medication? at Each Time Point | Time 2 | Yes | 41 Participants |
| Hydromorphone | Number of Patients Responding to the Question, Do You Want More Pain Medication? at Each Time Point | Time 2 | No | 166 Participants |
| Hydromorphone | Number of Patients Responding to the Question, Do You Want More Pain Medication? at Each Time Point | Time 3 | Yes | 31 Participants |
| Hydromorphone | Number of Patients Responding to the Question, Do You Want More Pain Medication? at Each Time Point | Time 3 | No | 176 Participants |
| Hydromorphone | Number of Patients Responding to the Question, Do You Want More Pain Medication? at Each Time Point | Time 4 | Yes | 39 Participants |
| Hydromorphone | Number of Patients Responding to the Question, Do You Want More Pain Medication? at Each Time Point | Time 4 | No | 168 Participants |