Comparative analgesic efficacy of oxycodone/acetaminophen versus hydrocodone/acetaminophen for short-term pain management in adults following ED discharge
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Clinical Question
In adult patients, how effective is oxycodone/acetaminophen compared to hydrocodone/acetaminophen for acute extremity pain?
Bottom Line
Both opioids reduced pain scores almost equally (4.4 numerical rating scale (NRS) units in oxycodone/acetaminophen group, 4.0 NRS units in hydrocodone/acetaminophen group). No statistically significant difference in analgesic efficacy was observed between oxycodone/acetaminophen (5 mg/325 mg) and hydrocodone/acetaminophen (5 mg/325 mg) for treatment of acute musculoskeletal extremity pain in adults following Emergency Department (ED) discharge.
Major Points
Oxycodone/acetaminophen and hydrocodone/acetaminophen are among the most commonly prescribed oral opioid discharge medications in EDs across the country. Very few studies have been conducted to compare the efficacy of one versus the other and the results obtained have varied. Because of this, a group of doctors working at a busy ED in New York designed a study to compile data supporting increased efficacy of one intervention versus the other.
The study was a prospective, randomized, double-blind clinical trial that included non-elderly adult ED patients randomly allocated at discharge to receive oxycodone/acetaminophen (5 mg/325 mg) or hydrocodone/acetaminophen (5 mg/325 mg) as treatment for acute musculoskeletal extremity pain. A numerical rating scale for pain was used to measure scores over a 2-hour period following the most recent dose of the drug, obtained by telephone 24 hours after ED discharge. Both opioids reduced pain scores by approximately 50% and there were no clinically or statistically significant differences in analgesic efficacy between the two agents for treating acute musculoskeletal extremity pain in adults following ED charge.
Guidelines
As of May 2016, no guidelines have been published that reflect the results of this trial.
Design
- CONSORT-compliant, prospective, randomized, double-blinded controlled clinical trial
- N = 240
- Hydrocodone/Acetaminophen (n=113)
- Oxycodone/Acetaminophen (n=107)
- Setting: Department of Emergency Medicine, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY.
- Enrollment: 24 hours
- Mean Follow-Up: 26.5 hours
- Analysis: per-protocol
- Primary Outcome: The between-group difference in improvement in mean NRS pain scores at approximately 24 hours post discharge, measured at 2 hours following the most recent ingestion of the study drug relative to the time of phone contact.
Population
Inclusion Criteria
- Seen at ED of Albert Einstein College of Medicine
- Presented with acute musculoskeletal extremity pain and attending physician planned to discharge them with short course oral opioids for outpatient pain management
- Acute pain defined as less than 7 days’ duration
- Extremity defined as distal to and including the shoulder or hip joints
Exclusion Criteria
- History of prior or current methadone use
- Chronic condition requiring frequent or continuous pain management (eg. sickle cell fibromyalgia, chronic neuropathy).
- Allergy to oxycodone, hydrocodone or acetaminophen
- History of prior or current recreational opioid use
- Ingestion of an oral opioid in the past 24 hours
- Medications that may affect opioid or acetaminophen metabolism (e.g., hepatitis, renal insufficiency, hypothyroidism hyperthyroidism, adrenal disease) or use of medications known to interact with opioids or acetaminophen.
Baseline Characteristics
- 220 patients met inclusion criteria, signed informed consent, were randomized and analyzed
- 20 additional patients were in trial but could not be followed up with or didn’t take medication
- Baseline characteristics reported for each group were nearly the same
- Both groups had more females than males but the percent of the group that was female was higher in the oxycodone/acetaminophen group (56.1%)
- Latino was the most represented ethnicity for each group (62.6% in oxycodone/acetaminophen), African American the second highest (29.9%) and “other” the lowest (7.5%). These percentages were almost equal between groups
- Median pain intensity on discharge was the same for each group (8)
- Median age was nearly the same (39.4 for oxycodone/acetaminophen)
- Time to follow up was an hour earlier for oxycodone/acetaminophen (27 hours)
- The diagnoses represented were nearly the same percentage within in each group (36.4% sprains, 58.9% extremity fracture and 4.7% other for oxycodone/acetaminophen)
- The number of patients who took an analgesic before presenting to the ED was slightly lower in the oxycodone/acetaminophen group (27.6%)
Interventions
The interventions employed in this trial were oxycodone/acetaminophen 5mg/325mg (brand name Percocet) and hydrocodone/acetaminophen 5mg/325mg (brand name Vicodin) for 3 days.
Outcomes
Primary Outcomes
The between-group difference in improvement in mean NRS pain scores at approximately 24 hours post discharge, measured at 2 hours following the most recent ingestion of the study drug relative to the time of phone contact. The outcome was that both opioids reduced pain scores almost equally. Mean change in NRS pain scores 2 hours after the most recent dose of study medication was 4.4 NRS units in the oxycodone/acetaminophen group versus 4.0 NRS units in the hydrocodone/acetaminophen group, for a difference of 0.4 NRS units that was found to not be not statistically significant (95% CI = -0.2 to 1.1).
Secondary Outcomes
The secondary outcomes were for 50% or greater decrease in pain score, satisfaction with analgesic and if the patients would want the same analgesic again. None of these outcomes had a statistically significant difference between groups.
Subgroup Analysis
It is common in some EDs that physicians will prescribe opioids with instructions to take a second dose if the patient feels the pain is uncontrolled. A clinically relevant subgroup that was taken into account after the study was done was the population of patients who took additional doses of opioids optionally at varying points in time. This study was unable to design a methodologically valid means of analyzing the data under conditions where varying doses of analgesics would be taken by different patients across a range of time intervals within the same comparison group. This could potentially be considered when designing a further study.
Adverse Events
Adverse events reported were (from most common to least common) nausea, vomiting, constipation, diarrhea, pruritus, rash, dizziness, drowsiness and confusion. Nausea and dizziness were significantly more common with oxycodone/acetaminophen than with hydrocodone/acetaminophen but only nausea was statistically significant (95% CI = 1.1-18.6).
Criticisms
Internal
- It is common in some ED’s that physicians will prescribe opioids with instructions to take a second dose if the patient feels the pain is uncontrolled. This study did not incorporate data under conditions where varying doses of analgesics would be taken by different patients across a range to time intervals within the same comparison group. Therefore, this study may not be relevant to EDs in which additional doses of study medication were optionally taken at varying points in time by individual subjects.
External
- Although the study utilized a pain scale, people have varying tolerances to pain which could result in lower quality data.
- Based on the age of the population included in the study (21-64), it could be questioned whether or not the information would be relevant to children and the elderly > age 65.
- This study’s participants were mostly Latino or African American (90.9%) so results might not be applicable to different ethnicities.
- The study only looked at the efficacy of the opioids for a specific condition (acute extremity pain being discharged from the ED) so its findings might not be relevant for other conditions.
- The study only followed patients being discharged from one ED so it might not apply to other geographic areas.
Funding
- This study received grant support from the Harold and Muriel Block Institute for Clinical and Translational Research at Einstein and Montefiore.