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Safety of Hydromorphone in Adult Patients Presenting to the Emergency Department With Acute Severe Pain

Safety and Speed of Onset of a Fixed Dose of Intravenous Hydromorphone in the Treatment of Adult Patients Presenting to the Emergency Department With Acute Severe Pain

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00305110
Enrollment
298
Registered
2006-03-21
Start date
2006-01-31
Completion date
2006-10-31
Last updated
2018-08-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acute Pain

Keywords

Pain, Acute, Emergency Department, Severe, Hydromorphone, Dilaudid, Adult

Brief summary

The purpose of this study is to determine the safety and speed of onset of 2mg intravenous hydromorphone (Dilaudid) in patients weighing at least 150 lbs presenting to the emergency department with acute severe pain

Detailed description

Introduction and Background: Pain is cited as the most frequent reason for visits to emergency departments (EDs) (McCaig, 2001). It can be estimated from the National Hospital Ambulatory Medical Care Survey, an annual survey of a representative sample of visits to US EDs, that there are 17 million visits per year to US EDs for specific complaints of pain, 29 million visits including back symptoms and injuries not otherwise specified as well as specific mentions of pain. However it is widely acknowledged that pain is seriously under-treated in the ED as well as in other health care settings (Ducharme, 1996; Selbst, 1990; Wilson, 1989). The concern regarding under-treatment is reflected in new standards for pain management developed by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) requiring assessment of pain at triage in the ED and referring to pain measurement as the fifth vital sign (Philips, 2000). Proper pain management is a tremendous challenge to ED physicians as pain is not only a noxious experience but also a symptom of injury and disease that needs to be understood and appropriately treated. Further complicating pain management is the large interpersonal variability in pain perception and expression reflecting cultural, contextual, and individual differences between people. Reasons for under-treating pain include concern over side effects of opioids, perception of pain complaints as possible drug-seeking behavior, under-staffing, concern that analgesics will mask symptoms or delay early diagnosis and treatment, and contribute to risks of tolerance and dependence in vulnerable patients. Morphine has long been considered the gold standard in pain control. Hydromorphone is another powerful opioid that has been used extensively for the management of post-operative pain and morphine-resistant cancer-related pain. A recent Cochrane review on the use of hydromorphone found 32 studies that focused on acute pain (Quigley, 2003). Of these 32 studies, only 9 involved intravenous forms of hydromorphone (Coda, 1997; Collins, 1996; Deutsch, 1968; Jasani, 1994; Liu, 1995; Mahler, 1975; Rapp, 1996; Searle, 1994; Urquhart, 1988). Of these 8 studies, 5 involved patient controlled analgesia, and only 1 study compared IV hydromorphone to IV morphine (Mahler, 1975). The Cochrane review concludes that there are substantial gaps in the understanding of the efficacy and potency of hydromorphone. We have recently completed a study in non-elderly adult patients (IRB 04-08-225) that showed that weight-based IV hydromorphone provides better pain relief than weight-based IV morphine. This result was both statistically and clinically significant. We also demonstrated in this same study that IV hydromorphone has a faster onset and also provided statistically significant improvement in pain relief at 5 minutes as compared to IV morphine. Although weight-based dosing of medications is common in pediatrics, most emergency physicians use whole integer amounts of pain medications. IV hydromorphone is more potent than IV morphine, so the dosages given are much smaller. We therefore wish to give a standard 2 mg dose of IV hydromorphone to all non-elderly adult patients weighing at least 150 lbs presenting to the ED with acute severe pain. We wish to examine the safety and speed of onset of hydromorphone using such a protocol. Our general thought is that to develop more evidence based practice, we need to generate more practice based evidence. This study attempts to do this as it is practiced based and very practical. We wish to take the drug as it comes (2mg Dilaudid in an ampule) and use all of it, thus alleviating the need to waste the excess opioid (and alleviating the need to find a second person to witness the wasting). We also wish to use a weight cutoff that everyone can remember (150 lbs). We believe that this protocol will provide greater pain relief and help address the issue of inadequate pain treatment, or oligoanalgesia, that is prominent in the literature (Sobel 2002, Wilson, 1989, Goldfrank 2000). Finally, in our multiple studies of pain conducted in the ED, we have found a relatively high rate of refusal to receive pain medication. We think this may represent a component to the problem of oligoanalgesia that is widespread in the ED. We wish to investigate the reasons for patient refusal to receiving parental opioid medications (fear of addiction, side effects, etc).

Interventions

DRUG2 mg IV hydromorphone

Sponsors

Montefiore Medical Center
Lead SponsorOTHER

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
Yes

Inclusion criteria

1. Age greater than 21 years 2. Age less than 65 years of age 3. Pain with onset within 7 days 4. ED attending physician's judgment that patient's pain warrants use of morphine 5. Normal mental status

Exclusion criteria

1. Prior use of methadone 2. Use of other opioids or tramadol within past seven days 3. Prior adverse reaction to hydromorphone. 4. Chronic pain syndrome 5. Alcohol intoxication 6. SBP \<90 mm Hg 7. Use of MAO inhibitors in past 30 days 8. C02 measurement greater than 46

Design outcomes

Primary

MeasureTime frameDescription
Number of Participants Requiring Naloxoneimmediately after infusion, up to 120 minutes post infusionNaloxone is a reversal agent - a medication that reverses the effects of another. Hydromorphone is an opiate pain medication that acts as a depressant to the body, thereby slowing it down. A large slow down is dangerous, as it can cause the breathing rate to slow down too much and prevent enough oxygen from entering the body and reaching the brain, resulting in death. Naloxone is a medication that blocks the receptors binding opiate pain medication and reversing the body's reaction to the hydromorphone, allowing body processes to return to normal speeds, including the breathing rate. The use of naloxone in the study indicates that the participant received too much pain medication or reacted more strongly than the average person, requiring the rescue medication to reverse the negative effects. The number of participants who required naloxone is assessed.

Secondary

MeasureTime frameDescription
Oxygen Saturation Measured Over 2-hour Time Framebaseline to 120 minutes post infusionblood oxygen saturation is measured periodically from 1 minute to 120 minutes after the medication was infused
Number of Participants Experiencing a Respiratory Rate Lower Than 12 Breaths Per Minuteimmediately after infusion, up to 120 minutes post infusionNormal respiratory rate ranges from 12 to 20 breaths per minute. The decreased respiration results in a decreased amount of oxygen entering the body and therefore low amount of oxygen supplied to the brain. Prolonged oxygen deprivation can result in injury or death. Respiratory rates lower than 12 breaths per minute is a sign of distress. Number of participants experiencing a respiratory rate lower than 12 breaths per minute is measured.
Number of Participants Experiencing a Systolic Blood Pressure Less Than 90 mmHgImmediately after infusion, up to 120 minutes post infusionNormal systolic blood pressure is approximately 120 mmHg. A low systolic blood pressure indicates blood, and therefore oxygen, are not being distributed around the body properly. This leads to a decreased amount of oxygen for the body to use and can result in injury or death if prolonged or severe.
Oxygen Desaturation Measured Over 2-hour Time Frameimmediately after infusion, up to 120 minutes post infusionblood oxygen saturation less than 95% is considered oxygen desaturation. Blood oxygen saturation is normally above 95%. Oxygen desaturation of less than 90% is dangerous because there is less oxygen throughout the body for cellular energy. Prolonged or severe blood oxygen desaturation can result in injury or death.

Countries

United States

Participant flow

Participants by arm

ArmCount
2 mg IV Hydromorphone
2 mg IV hydromorphone administered over 2-3 minutes 2 mg IV hydromorphone
269
Total269

Withdrawals & dropouts

PeriodReasonFG000
Overall StudyMissing data29

Baseline characteristics

Characteristic2 mg IV Hydromorphone
Age, Continuous41 years
STANDARD_DEVIATION 11
Baseline Pain intensity
10
158 Participants
Baseline Pain intensity
7
22 Participants
Baseline Pain intensity
8
45 Participants
Baseline Pain intensity
9
33 Participants
Baseline Pain intensity
less than 7
10 Participants
Disposition
Admitted
122 Participants
Disposition
Against medical advice
3 Participants
Disposition
Discharged
144 Participants
Final diagnosis
Abcess
7 Participants
Final diagnosis
Appendicitis
18 Participants
Final diagnosis
Biliary colic/cholecystitis
21 Participants
Final diagnosis
Diverticulitis
14 Participants
Final diagnosis
Gastritis
8 Participants
Final diagnosis
Kidney Stone
38 Participants
Final diagnosis
Low back pain
7 Participants
Final diagnosis
Nonspecific abdominal pain
65 Participants
Final diagnosis
Other
68 Participants
Final diagnosis
Pancreatitis
9 Participants
Final diagnosis
Pyelonephritis
6 Participants
Final diagnosis
Small bowel obstruction
8 Participants
Pain Location
Abdomen
205 Participants
Pain Location
Other
64 Participants
Race/Ethnicity, Customized
African-American
85 Participants
Race/Ethnicity, Customized
Hispanic
163 Participants
Race/Ethnicity, Customized
Other
5 Participants
Race/Ethnicity, Customized
White
16 Participants
Region of Enrollment
United States
269 Participants
Sex: Female, Male
Female
166 Participants
Sex: Female, Male
Male
103 Participants
Weight198 pounds
STANDARD_DEVIATION 38

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
0 / 269
other
Total, other adverse events
100 / 269
serious
Total, serious adverse events
0 / 269

Outcome results

Primary

Number of Participants Requiring Naloxone

Naloxone is a reversal agent - a medication that reverses the effects of another. Hydromorphone is an opiate pain medication that acts as a depressant to the body, thereby slowing it down. A large slow down is dangerous, as it can cause the breathing rate to slow down too much and prevent enough oxygen from entering the body and reaching the brain, resulting in death. Naloxone is a medication that blocks the receptors binding opiate pain medication and reversing the body's reaction to the hydromorphone, allowing body processes to return to normal speeds, including the breathing rate. The use of naloxone in the study indicates that the participant received too much pain medication or reacted more strongly than the average person, requiring the rescue medication to reverse the negative effects. The number of participants who required naloxone is assessed.

Time frame: immediately after infusion, up to 120 minutes post infusion

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
2 mg IV HydromorphoneNumber of Participants Requiring Naloxone0 Participants
Secondary

Number of Participants Experiencing a Respiratory Rate Lower Than 12 Breaths Per Minute

Normal respiratory rate ranges from 12 to 20 breaths per minute. The decreased respiration results in a decreased amount of oxygen entering the body and therefore low amount of oxygen supplied to the brain. Prolonged oxygen deprivation can result in injury or death. Respiratory rates lower than 12 breaths per minute is a sign of distress. Number of participants experiencing a respiratory rate lower than 12 breaths per minute is measured.

Time frame: immediately after infusion, up to 120 minutes post infusion

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
2 mg IV HydromorphoneNumber of Participants Experiencing a Respiratory Rate Lower Than 12 Breaths Per Minute12 Participants
Secondary

Number of Participants Experiencing a Systolic Blood Pressure Less Than 90 mmHg

Normal systolic blood pressure is approximately 120 mmHg. A low systolic blood pressure indicates blood, and therefore oxygen, are not being distributed around the body properly. This leads to a decreased amount of oxygen for the body to use and can result in injury or death if prolonged or severe.

Time frame: Immediately after infusion, up to 120 minutes post infusion

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
2 mg IV HydromorphoneNumber of Participants Experiencing a Systolic Blood Pressure Less Than 90 mmHg2 Participants
Secondary

Oxygen Desaturation Measured Over 2-hour Time Frame

blood oxygen saturation less than 95% is considered oxygen desaturation. Blood oxygen saturation is normally above 95%. Oxygen desaturation of less than 90% is dangerous because there is less oxygen throughout the body for cellular energy. Prolonged or severe blood oxygen desaturation can result in injury or death.

Time frame: immediately after infusion, up to 120 minutes post infusion

ArmMeasureGroupValue (NUMBER)
2 mg IV HydromorphoneOxygen Desaturation Measured Over 2-hour Time Frameat least 95% oxygen saturation, all time points68 participants
2 mg IV HydromorphoneOxygen Desaturation Measured Over 2-hour Time Frame90-94% oxygen saturation, one or more times26 participants
2 mg IV HydromorphoneOxygen Desaturation Measured Over 2-hour Time Framebelow 90% oxygen saturation, one or more times6 participants
Secondary

Oxygen Saturation Measured Over 2-hour Time Frame

blood oxygen saturation is measured periodically from 1 minute to 120 minutes after the medication was infused

Time frame: baseline to 120 minutes post infusion

ArmMeasureGroupValue (MEDIAN)
2 mg IV HydromorphoneOxygen Saturation Measured Over 2-hour Time Frame5 minutes post infusion97 % oxygen saturation
2 mg IV HydromorphoneOxygen Saturation Measured Over 2-hour Time FrameBaseline99 % oxygen saturation
2 mg IV HydromorphoneOxygen Saturation Measured Over 2-hour Time Frame1 minute post infusion98 % oxygen saturation
2 mg IV HydromorphoneOxygen Saturation Measured Over 2-hour Time Frame2 minutes post infusion98 % oxygen saturation
2 mg IV HydromorphoneOxygen Saturation Measured Over 2-hour Time Frame3 minutes post infusion98 % oxygen saturation
2 mg IV HydromorphoneOxygen Saturation Measured Over 2-hour Time Frame4 minutes post infusion98 % oxygen saturation
2 mg IV HydromorphoneOxygen Saturation Measured Over 2-hour Time Frame15 minutes post infusion97 % oxygen saturation
2 mg IV HydromorphoneOxygen Saturation Measured Over 2-hour Time Frame30 minutes post infusion98 % oxygen saturation
2 mg IV HydromorphoneOxygen Saturation Measured Over 2-hour Time Frame120 minutes post infusion98 % oxygen saturation
Post Hoc

Pain Intensity Assessed Over 2-hour Time Frame

Pain intensity is measured on the numerical rating scale (NRS), from 0 (no pain) to 10 (worst pain possible). Participants are asked to rate their pain periodically over a 2 hour time period following infusion of the medication.

Time frame: baseline up to 120 minutes after post infusion

ArmMeasureGroupValue (MEDIAN)
2 mg IV HydromorphonePain Intensity Assessed Over 2-hour Time FrameBaseline10 units on a scale
2 mg IV HydromorphonePain Intensity Assessed Over 2-hour Time Frame1 minute post infusion4 units on a scale
2 mg IV HydromorphonePain Intensity Assessed Over 2-hour Time Frame2 minutes post infusion3 units on a scale
2 mg IV HydromorphonePain Intensity Assessed Over 2-hour Time Frame3 minutes post infustion3 units on a scale
2 mg IV HydromorphonePain Intensity Assessed Over 2-hour Time Frame4 minutes post infusion2 units on a scale
2 mg IV HydromorphonePain Intensity Assessed Over 2-hour Time Frame5 minutes post infusion1 units on a scale
2 mg IV HydromorphonePain Intensity Assessed Over 2-hour Time Frame15 minutes post infusion1 units on a scale
2 mg IV HydromorphonePain Intensity Assessed Over 2-hour Time Frame30 minutes post infusion0 units on a scale
2 mg IV HydromorphonePain Intensity Assessed Over 2-hour Time Frame120 minutes post infusion1 units on a scale

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026