Efficacy and safety profile of a single dose of hydromorphone compared with morphine in older adults with acute, severe pain: A prospective, randomized, double-blind clinical trial

doi:10.1016/j.amjopharm.2009.02.002

The American Journal of Geriatric Pharmacotherapy

Volume 7, Issue 1, February 2009, Pages 1-10

https://doi.org/10.1016/j.amjopharm.2009.02.002 Get rights and content

Abstract

Background: Older adults (ie, those aged ≥65 years) are the fastest growing segment of the US population, with an estimated ~71 million expected by 2030. Over the past 10 years, there has been an 11% increase in the number of emergency department (ED) visits by older adults, and pain is their most common chief complaint.

Objective: The goal of this study was to compare weight-based IV hydromorphone and IV morphine in adults aged ≥65 years presenting to the ED with acute, severe pain.

Methods: This was a prospective, randomized, double-blind clinical trial of older adults with acute, severe pain at an adult, urban academic ED. Patients were randomly allocated to receive a single dose of 0.0075-mg/kg IV hydromorphone or 0.05-mg/kg IV morphine. The primary outcome was the between-group difference in decrease in pain from baseline to 30 minutes after the medications were infused. Patients' degree of pain was measured on a numerical rating scale (NRS) where “0” was defined as “no pain” and “10” was defined as “the worst pain possible.” Adverse effects, pain reduction at 10 minutes and 2 hours postbaseline, patient evaluations of satisfaction and pain relief at 30 minutes postbaseline, and use of additional analgesics and antiemetics were tracked as secondary outcomes.

Results: A total of 194 patients were randomized to treatment; 183 patients (hydromorphone group, n = 93; morphine group, n = 90 [overall mean (SD) age, 75 (8) years]) had sufficient data for analysis at the primary end point of 30 minutes postbaseline. The mean decrease in pain from baseline to 30 minutes in patients allocated to IV hydromorphone was 3.8 versus 3.3 NRS units in patients allocated to IV morphine. This difference of 0.5 NRS unit (95% CI, −0.2 to 1.3) was neither clinically nor statistically significant. A majority of patients in both groups (57.0% randomized to hydromorphone and 58.9% randomized to morphine) failed to achieve a ≥50% reduction in pain within 30 minutes of treatment. The incidence of adverse effects from baseline to 30 minutes was not statistically different in the 2 groups.

Conclusions: A single dose of IV hydromorphone at 0.0075 mg/kg was neither clinically nor statistically different from IV morphine at 0.05 mg/kg for the treatment of acute, severe pain at 30 minutes postbaseline in these older adults in the ED. The incidence of adverse effects was not statistically different. Our data suggest that hydromorphone and morphine in the doses given had similar efficacy and safety profiles in these older adults. Neither regimen provided ≥50% pain relief for the majority of patients. Future investigations of acute pain management in older adults should examine the efficacy and safety of higher initial (loading) doses of opioids titrated at frequent intervals until adequate analgesia is achieved.

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A Randomized Study of Intravenous Hydromorphone Versus Intravenous Acetaminophen for Older Adult Patients with Acute Severe Pain
2022, Annals of Emergency Medicine
Citation Excerpt :
Intravenous opioids are the mainstay of treating acute severe pain in the ED setting.7 Among older patients, intravenous hydromorphone is effective and safe using both weight-based dosing (0.0075 mg/kg) and fixed 0.5 mg doses.8,9 However, because of the fear of adverse medication reactions, such as respiratory depression or hypotension; medication interactions; and long-term sequelae, such as opioid use disorder and chronic pain syndromes, some have called for minimizing the use of opioids in the ED.
We conducted a randomized study to compare the efficacy and adverse event profile of 1,000 mg of intravenous acetaminophen to that of 0.5 mg of intravenous hydromorphone among patients aged 65 years or more with acute pain of severity that was sufficient enough to warrant intravenous opioids.
This randomized comparative effectiveness study with 162 participants was conducted in 2 urban emergency departments (EDs). The primary outcome was an improvement in a 0 to 10 pain scale from baseline to 60 minutes later. Secondary outcomes included the need for additional analgesic medication and adverse events that were attributable to the investigational medication. The minimum clinically important difference was an improvement of 1.3 on the 0 to 10 pain scale.
The median baseline pain score was 10 (interquartile range 8 to 10) in both the groups. By 60 minutes, patients taking acetaminophen improved by 3.6 (standard deviation 2.9) on the 0 to 10 pain scale, whereas patients taking hydromorphone improved by 4.6 (standard deviation 3.3) (95% confidence interval [CI] for the difference of 1.0 was 0.1 to 2.0). Additional analgesic medications were required for 37 (46%) of 81 patients taking acetaminophen and 31 (38%) of 81 patients taking hydromorphone (95% CI for the rounded difference of 7% was −8% to 23%). Adverse events were reported by 6 (7%) of 81 patients taking acetaminophen and 10 (12%) of 81 patients taking hydromorphone (95% CI for the difference of 5% was −4% to 14%) and included dizziness, drowsiness, headache, and nausea.
Although 0.5 mg of the intravenously administered hydromorphone was statistically superior to 1,000 mg of intravenous acetaminophen administered in older patients with acute severe pain in the ED, this difference was not clinically significant. Regardless of the medication received, many participants experienced minimal or incomplete pain relief.
American Society for Pain Management Nursing Guidelines on Monitoring for Opioid-Induced Advancing Sedation and Respiratory Depression: Revisions
2020, Pain Management Nursing
This report presents up-to-date evidence and expert consensus-based revisions to the ASPMN 2011 guidelines that inform interprofessional clinical decision-making for hospitalized adults receiving opioid analgesics.
Systematic review of the literature.
A 14-member expert panel was charged with reviewing and grading the strength of scientific evidence published in peer reviewed journals and revising the ASPMN 2011 existing guidelines. Panel members formulated recommendations based on the strength of evidence and reached consensus through discussion, reappraisal of evidence, and voting by majority when necessary. The American Society of Anesthesiologists evidence categories for grading and classifying the strength of the evidence were used. Recommendations were subjected to a critical review by ASPMN members as well as external reviews.
The 2011 guidelines were found to still be relevant to clinical practice, but new evidence substantiated refinement and more specific recommendations for electronic monitoring. The revised guidelines present risk factors divided into three categories: patient-specific, treatment-related, and environment of care. Specific recommendations for the use of electronic monitoring are delineated.
All hospitalized patients that are administered opioids for acute pain are at risk of opioid induced advancing sedation and respiratory depression, but some patients are at high risk and require extra vigilance to prevent adverse events. All patients must be assessed for level of risk. Adaptations to the plan of care and monitoring strategies should be driven by iterative re-assessments according to level of risk.
Opioid medications continue to be a major component in the management of acute pain. Clinicians have the primary responsibility for safe and effective pain management. Evidence based monitoring strategies can improve patient safety with opioids.
Low-dose ketamine vs morphine for acute pain in the ED: A randomized controlled trial
2015, American Journal of Emergency Medicine
To compare the maximum change in numeric rating scale (NRS) pain scores, in patients receiving low-dose ketamine (LDK) or morphine (MOR) for acute pain in the emergency department.
We performed an institutional review board–approved, randomized, prospective, double-blinded trial at a tertiary, level 1 trauma center. A convenience sample of patients aged 18 to 59 years with acute abdominal, flank, low back, or extremity pain were enrolled. Subjects were consented and randomized to intravenous LDK (0.3 mg/kg) or intravenous MOR (0.1 mg/kg). Our primary outcome was the maximum change in NRS scores. A sample size of 20 subjects per group was calculated based on an 80% power to detect a 2-point change in NRS scores between treatment groups with estimated SDs of 2 and an α of .05, using a repeated-measures linear model.
Forty-five subjects were enrolled (MOR 21, LDK 24). Demographic variables and baseline NRS scores (7.1 vs 7.1) were similar. Ketamine was not superior to MOR in the maximum change of NRS pain scores, MOR = 5 (confidence interval, 6.6-3.5) and LDK = 4.9 (confidence interval, 5.8-4). The time to achieve maximum reduction in NRS pain scores was at 5 minutes for LDK and 100 minutes for MOR. Vital signs, adverse events, provider, and nurse satisfaction scores were similar between groups.
Low-dose ketamine did not produce a greater reduction in NRS pain scores compared with MOR for acute pain in the emergency department. However, LDK induced a significant analgesic effect within 5 minutes and provided a moderate reduction in pain for 2 hours.
Pain management in the emergency department: A review
2014, Journal Europeen des Urgences et de Reanimation
Les données récentes de la littérature montrent que la douleur reste insuffisamment prise en charge dans nos services d’urgence, quel que soit l’âge des consultants. Chez la personne âgée, la difficulté est accrue en raison du manque d’études prospectives, ce qui complique l’évaluation de leurs besoins spécifiques. L’utilisation des morphiniques est toujours aussi faible, malgré de nouvelles molécules disponibles, les anciennes idées reçues persistent, de nouvelles réticences ont surgi. Le spectre de la toxicomanie est réapparu outre Atlantique, la titration morphinique intraveineuse déçoit, l’hyperalgésie effraie, les douleurs chroniques et neuropathiques tiennent les urgentistes en échec… De nouvelles voies d’administrations des morphiniques sont testées mais ne sont pas encore fiables, les traitements étiologiques ciblés évoluent peu. Mais les réponses organisationnelles tiennent leurs promesses, les infirmiers d’accueil et d’orientation sont devenus les nouveaux piliers de la prise en charge antalgique aux urgences, de nouveaux scores d’évaluation chez le pauci-communiquant se sont développés et sont utiles. En matière de douleurs provoquées, la situation évolue également dans le bon sens, les modalités de sédation procédurale se précisent. Enfin, on assiste à l’émergence de nouveaux médicaments polyvalents comme la kétamine, qui apportent des solutions à diverses problématiques (hyperalgésie, douleurs rebelles, sédation consciente…). Les nouveaux enjeux de la prise en charge « qualitative » de la douleur viennent s’ajouter aux anciens objectifs « quantitatifs », les urgentistes sont devenus des « spécialistes » de la douleur aiguë, dans leurs services, et de plus en plus dans la littérature.
Recent data from the literature show that pain is inadequately supported in our emergency rooms, whatever the age of the consultants. In the elderly, the difficulty is increased due to the lack of prospective studies, which complicates assessment of their specific needs. The use of opioids is still weak, despite new molecules available, the old ideas persist, new reluctance arose. The spectrum of addiction reappeared across the Atlantic, intravenous morphine titration disappoints, hyperalgesia scares, chronic and neuropathic pain hold the emergency hits. New routes of administration of opioids are tested but are not yet reliable, the targeted etiological treatments have changed little. But the organizational responses to their promises, nursing home and guidance have become the new pillar of taking analgesic care for emergencies, new assessment in the pauci-communicating scores have been developed and are useful. In terms of pain caused, the situation is evolving in the right direction, modality of procedural sedation is becoming clear-cut. Finally, we are witnessing the emergence of new drugs versatile as ketamine, which provide solutions to various problems (hyperalgesia, intractable pain, conscious sedation). The new challenges of “qualitative” management of pain in addition to old “quantitative” goals, emergency have become “experts” in the acute pain management in their services, and increasingly in the literature.
Hydromorphone: Evolving to Meet the Challenges of Today's Health Care Environment
2013, Clinical Therapeutics
Citation Excerpt :
Taken together, these characteristics make hydromorphone attractive therapeutically when a continuous subcutaneous infusion is indicated. In randomized, double-blind trials in patients with acute, severe pain, intravenous hydromorphone (0.0075–0.015 mg/kg) was shown to be an equally effective and well-tolerated alternative to intravenous morphine (0.05–0.1 mg/kg).36,37 A prospective, noncomparative cohort study in 269 adults with acute, severe pain found that a 2-mg intravenous dose of hydromorphone was efficacious.38
Hydromorphone, a potent analogue of morphine, has long had an important role in pain management and is included in several international guidelines for managing pain. Advances in hydromorphone formulations and the ways in which hydromorphone is being used clinically today warrant a review of the drug’s pharmacotherapeutic utility.
The history and recent advances in hydromorphone pharmacotherapy are reviewed. Areas covered include the pharmacologic and metabolic profile of hydromorphone, the role of hydromorphone in pain management, formulations and routes of administration, and issues related to relative opioid potencies, equianalgesic ratios, and opioid rotation. Because hydromorphone, like all opioids, carries a risk of misuse, abuse, and illicit diversion, the related issues of tamper-resistant formulations and “dose-dumping” of extended-release formulations are discussed.
Due to the epidemic of prescription opioid overdoses associated with prescription opioid abuse in the United States, development of tamper-resistant opioid formulations that avoid dose-dumping issues has become a significant goal of pharmaceutical manufacturers. The current formulation of hydromorphone extended-release potentially provides the benefits of long-acting hydromorphone (ie, continuous pain control, increased quality of life, freedom to perform daily activities) to appropriate patients, while reducing the risks of abuse and without compromising safety.
Randomized clinical trial of the 2 mg hydromorphone bolus protocol versus the "1+1" hydromorphone titration protocol in treatment of acute, severe pain in the first hour of emergency department presentation
2013, Annals of Emergency Medicine
Citation Excerpt :
Taking into consideration the heightened risk of adverse effects associated with administration of too large or too rapid a dose of intravenous opioid, we wished to develop a modified titration strategy appropriate to the constraints of the ED. After conducting a series of prospective interventional efficacy and safety studies examining different intravenous opioids administered in a range of doses during systematically varying intervals,20-27 we have reached a point at which we have selected 1 mg intravenous hydromorphone as our preferred incremental dose of opioid.22-24 The central question of this investigation is to determine the optimal dose of intravenous hydromorphone with which to initiate an ED pain protocol targeted at attainment of satisfactory analgesia within a reasonable timeframe.
We compare a high initial dose of 2 mg intravenous hydromorphone against titration of 1 mg intravenous hydromorphone followed by an optional second dose.
Patients aged 21 to 64 years with severe pain were randomly allocated to 2 mg intravenous hydromorphone in a single bolus or the “1+1” hydromorphone titration protocol. 1+1 Patients received 1 mg intravenous hydromorphone followed by a second 1 mg dose 15 minutes later if they answered yes when asked, Do you want more pain medication? The primary outcome was the between-group difference in proportion of patients who declined additional analgesia at 60 minutes.
Of the 350 enrolled patients, 334 had sufficient data for analysis. The proportion who declined additional analgesics was 67.5% in the 2 mg bolus arm and 67.3% in the 1+1 titration arm (difference 0.2%; 95% confidence interval −9.7% to 10.2%). The between-group difference in numeric rating scale pain scores was 0.4 numeric rating scale units (95% confidence interval −0.3 to 1.1). The incidence of adverse effects was similar; 42.3% of 1+1 patients achieved satisfactory analgesia at 1 hour with only 1 mg hydromorphone.
A hydromorphone 1+1 titration protocol provides similar pain relief to an initial 2 mg bolus dose, with no apparent clinical advantage to the latter. The 1+1 titration protocol had an opioid-sparing effect because 50% less opioid was needed to achieve satisfactory analgesia for 42.3% of patients allocated to this protocol.

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Efficacy and safety profile of a single dose of hydromorphone compared with morphine in older adults with acute, severe pain: A prospective, randomized, double-blind clinical trial

Abstract

Emerg Med Clin North Am

Ann Emerg Med

Am J Geriatr Pharmacother

Am J Emerg Med

Ann Emerg Med

Clin Geriatr Med

Ann Emerg Med

J Pain Symptom Manage

National Hospital Ambulatory Medical Care Survey: 2005 Emergency department summary

Adv Data

Geriatrics

A review of predictive factors

Anesthesiology

Postoperative analgesia: Economics, resource use, and patient satisfaction in an urban teaching hospital

Anesth Analg

Systematic Assessment of Geriatric Drug Use via Epidemiology [published correction appears in JAMA. 1999;281:136]

JAMA

Pain management in frail, community-living elderly patients

Arch Intern Med

The effect of emergency department crowding on the management of pain in older adults with hip fracture

J Am Geriatr Soc