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

• ClinicalTrials.gov Identifier: NCT00305110
• Recruitment Status: Completed
• First Posted: March 21, 2006
• Results First Posted: August 20, 2018
• Last Update Posted: August 20, 2018
• Sponsor: Montefiore Medical Center
• Information provided by (Responsible Party): Andrew Chang, MD, Montefiore Medical Center

Study Description

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

Condition or disease	Intervention/treatment	Phase
Acute Pain	Drug: 2 mg IV hydromorphone	Phase 2

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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 298 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: January 2006
• Actual Primary Completion Date: October 2006
• Actual Study Completion Date: October 2006

Arms and Interventions

Arm	Intervention/treatment
Experimental: 2 mg IV hydromorphone; 2 mg IV hydromorphone administered over 2-3 minutes	Drug: 2 mg IV hydromorphone; Other Name: Dilaudid

Outcome Measures

Primary Outcome Measures :

1. Number of Participants Requiring Naloxone [ Time Frame: immediately after infusion, up to 120 minutes post infusion ]
   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.

Secondary Outcome Measures :

1. Number of Participants Experiencing a Respiratory Rate Lower Than 12 Breaths Per Minute [ Time Frame: immediately after infusion, up to 120 minutes post infusion ]
   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.
2. Number of Participants Experiencing a Systolic Blood Pressure Less Than 90 mmHg [ Time Frame: Immediately after infusion, up to 120 minutes post infusion ]
   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.
3. Oxygen Desaturation Measured Over 2-hour Time Frame [ Time Frame: immediately after infusion, up to 120 minutes post infusion ]
   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.
4. Oxygen Saturation Measured Over 2-hour Time Frame [ Time Frame: baseline to 120 minutes post infusion ]
   blood oxygen saturation is measured periodically from 1 minute to 120 minutes after the medication was infused

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

United States, New York

Montefiore Medical Center

Bronx, New York, United States, 10467

Sponsors and Collaborators

Montefiore Medical Center

Investigators

• Principal Investigator: Andrew K Chang, MD; Montefiore Medical Center

More Information

• Responsible Party: Andrew Chang, MD, MD, Montefiore Medical Center
• ClinicalTrials.gov Identifier: NCT00305110
• Obsolete Identifiers: NCT01006850
• Other Study ID Numbers: MMC 0511307
• First Posted: March 21, 2006
• Results First Posted: August 20, 2018
• Last Update Posted: August 20, 2018
• Last Verified: August 2018

Keywords provided by Andrew Chang, MD, Montefiore Medical Center:

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

Additional relevant MeSH terms:

Emergencies; Acute Pain; Disease Attributes; Pathologic Processes; Pain; Neurologic Manifestations; Hydromorphone; Analgesics, Opioid; Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents