Safety and Efficacy of Intravenous Hydromorphone in Elderly Emergency Department Patients With Acute Severe Pain

Safety and Efficacy of Intravenous Hydromorphone Using Incremental Doses of 0.5 mg in Elderly ED Patients With Acute Severe Pain

The hydromorphone protocol is more effective than usual care in Emergency Department (ED) patients age 65 years and older in terms of proportion who choose to forgo additional pain medication within 60 minutes post-baseline in the two groups.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: Hydromorphone; Drug: Usual care

• Study Type: Interventional
• Enrollment (Actual): 350
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Emergency Department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 120 years (Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age greater than or equal to 65 years: This is a study of elderly patients.
2. 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.
3. ED attending physician's judgment that patient's pain may warrant intravenous (IV) opioids: The factors that influence the decision to use parenteral opioids are complex and extensive. 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) or treatment (e.g., post-hysterectomy) 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 assess the role of opioids with the widest generalizability 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 a comprehensive 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 alternative.
4. Normal mental status: In order to provide measures of pain experienced the patient needs to have a normal mental status. The investigators will use a 6-item screener (Wilber 2008) 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. The investigators feel that the needs of patients on methadone may exceed the dosage ceiling of 1 mg that will be used for this study. Similar to sickle cell patients and chronic cancer patients, patients on methadone usually require significantly higher doses of opioids to control their pain. Thus, the investigators feel that it would be unethical to restrict the dose that this subset of patients can receive.
2. Use of other opioids or tramadol within past seven days: 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 opioids.
4. Chronic pain syndrome: frequently recurrent or daily pain for at least 3 months results 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. Alcohol intoxication: the presence of alcohol intoxication as judged by the treating physician may alter perception, report, and treatment of pain.
6. Systolic blood pressure <90 mm Hg: Opioids can produce peripheral vasodilation that may result in orthostatic hypotension.
7. Oxygen saturation <95% on room air: For this study, oxygen saturation must be 95% or above on room air in order to be enrolled.
8. 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.

9. C02 measurement greater than 46: In accordance with a similar study (04-12-360), 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Usual care	Drug: Usual care; Attending administers any IV opioid in any dose he chooses
Experimental: Hydromorphone; Hydromorphone protocol	Drug: Hydromorphone; 0.5 mg IV hydromorphone followed by an optional 0.5 mg IV dose; Other Names: Dilaudid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Successful Treatment	Number of patients with "successful treatment" is defined as the number of patients who declined additional pain medication within 1 hour of study entry when asked the question, "Do you want more pain medication?". This measure looks at declining pain medication at either 15 minutes or 60 minutes, whereas 4. Post-Hoc refers only to the answer to the question at the 60 minute mark post-baseline.	1 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in Pain Intensity From Baseline to 60 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 scores over time is calculated by subtracting the score at 60 minutes from the score at baseline (before treatment). These change values were then averaged.	60 minutes

Collaborators and Investigators

• Sponsor: Montefiore Medical Center

Publications and helpful links

General Publications

• Chang AK, Bijur PE, Davitt M, Gallagher EJ. Randomized clinical trial of an intravenous hydromorphone titration protocol versus usual care for management of acute pain in older emergency department patients. Drugs Aging. 2013 Sep;30(9):747-54. doi: 10.1007/s40266-013-0103-y.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2009
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: September 2, 2011
• First Submitted That Met QC Criteria: September 6, 2011
• First Posted (Estimate): September 7, 2011

Study Record Updates

• Last Update Posted (Actual): May 18, 2018
• Last Update Submitted That Met QC Criteria: April 20, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Pain; Emergency Department; Hydromorphone; Acute
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Hydromorphone
• Other Study ID Numbers: MMC 08-11-387