Research ArticleResearch

Comparative efficacy of opioids for older adults presenting to the emergency department with acute pain

Systematic review

Maaike de Vries, Jonathan Gravel, Daphne Horn, Shelley McLeod and Catherine Varner
Canadian Family Physician December 2019, 65 (12) e538-e543;

Abstract

Objective To systematically review the literature for studies comparing the efficacy of opioid analgesics for older adults (≥ 65 years) presenting to the emergency department (ED) with acute pain.

Data sources The Cochrane Library, MEDLINE, EMBASE, Web of Science, and CINAHL were searched up to August or September 2017. Reference lists were searched for potential articles and ClinicalTrials.gov was searched for unpublished trials.

Study selection Randomized controlled trials (RCTs) were sought that compared the efficacy of 2 or more opioid analgesics for acute pain in older patients (≥ 65 years) in the ED. Two reviewers independently screened abstracts, assessed study quality, and extracted data.

Synthesis After screening titles and abstracts of 1315 citations, the full texts of 63 studies were reviewed and 1 RCT met the inclusion criteria. This study randomized older adult patients presenting to an urban academic ED with acute, severe pain to receive a single dose of either 0.0075 mg/kg intravenous hydromorphone or 0.05 mg/kg intravenous morphine. This study found no clinical or statistical difference between the 2 treatments.

Conclusion The lack of published research in this area demonstrates a considerable gap in knowledge of the comparative efficacy of opioid analgesics in the growing older adult patient population. Physicians are often uncertain in their choice of analgesia, potentially contributing to the undertreatment of pain. It is clear that well designed RCTs are urgently needed.

Currently, more than 20% of emergency department (ED) visits are made by adults 65 years of age and older.1 This proportion, as well as the absolute number of ED visits by older adults, will continue to increase as Canadians aged 65 and older make up a growing proportion of our population. The most common reason to seek care from the ED is for acute pain or acute exacerbations of chronic pain resulting from illness and injuries.2 Even though emergency care providers frequently treat pain in older adults, physicians often find choosing the best pain management approach challenging.

Mild-to-moderate acute pain is generally treated with acetaminophen and nonsteroidal anti-inflammatory drugs, with a short duration of immediate-release opioids prescribed if needed. Immediate-release opioids, such as hydromorphone, morphine, and oxycodone, are used to treat moderate-to-severe, acute pain in the ED, and patients might be given a prescription for opioids to manage their pain following discharge from hospital. Current guidance suggests use of multimodal pain control methods, which include nonpharmacologic treatments (eg, ice, heat, physical or massage therapy)3–5; however, there is very little evidence showing the efficacy of nonpharmacologic approaches to treating pain in the ED.3,4,6 Recommendations suggest that when opioids are prescribed for people with acute pain, the lowest effective dose of the least potent immediate-release opioid should be used.5,7,8

In the wake of the current North American opioid crisis, ED physicians might hesitate to prescribe opioids, even when other analgesics are contraindicated or insufficient, because of the increased awareness and attention around the overprescribing of opioids and the risks of dependence and addiction.9–12

Treatment of acute pain in older adults is also complicated by difficulties assessing pain owing to under-reporting by patients and atypical manifestations of pain; age-associated pharmacokinetic changes and enhanced pharmacodynamic sensitivity; potential differences in pain thresholds among older adults; and increased prevalence of persistent pain and pain-associated conditions such as osteoarthritis.13

Studies have shown older adults receive less analgesia than younger patients do,14–17 which has been interpreted as the undertreatment of pain in older adults by emergency care providers. However, other studies have demonstrated no difference in pain treatment by age.18,19 Regardless of whether there is an overall difference in pain treatment for older adults, older adults are particularly vulnerable to the adverse effects of undertreated acute pain. In the hospital setting, inadequate pain control in older adults has been associated with increased risk of delirium20 and longer hospital stays.21

No guidelines or best practices currently exist for the management of acute pain in older adults. Given the concerns of drug interactions, side effects, oversedation, and addiction, ED physicians often report uncertainty regarding the ideal choice of opioid analgesic in older adults.22 The objective of this systematic review was to summarize the findings from studies comparing the efficacy of opioids for treating acute pain in older adults in the ED.

METHODS

Data sources

A medical librarian (D.H.) implemented a systematic literature search to identify articles studying the efficacy of opioid analgesics for acute pain in older patients in the ED. Published studies were identified through searches in Ovid MEDLINE (1946 to September 2017), Ovid EMBASE (1947 to September 2017), Ovid Cochrane Central Register of Controlled Trials (to August 2017), Ovid Cochrane Database of Systematic Reviews (2005 to September 2017), Web of Science (1990 to September 2017), CINAHL (to September 2017), and the PubMed status subsets inprocess and pubmednotmedline (to September 2017). A combination of key words and subject headings was used to create search terms for opioids, older adults, emergency department, and pain. A full description of the search strategy is available on request from the corresponding author. Reference lists of relevant retrieved articles and reviews were also hand searched for other relevant citations, and the regulatory website ClinicalTrials.gov was searched to identify any unpublished trials. The searches were restricted to studies published in English.

Study selection

Two reviewers (J.G., M.D.) independently screened titles and abstracts to identify potential articles using Covidence systematic review software. The reviewers obtained full-text articles for studies they identified as potentially eligible and independently evaluated the articles against the inclusion criteria. Articles were eligible for inclusion if they described randomized controlled trials (RCTs) comparing the efficacy of 2 or more opioid analgesics for acute pain (onset of pain within 7 days) in older patients (≥ 65 years) in the ED. The main efficacy measures of interest for the systematic review were changes in pain intensity or in function. Studies that compared opioid analgesics to placebo or nonsteroidal anti-inflammatory drugs were excluded from this review. The 2 reviewers discussed and resolved any discrepancies. Reviewers were not blinded to author names, institutions, journals of publication, or results.

Data extraction and risk-of-bias assessment

Using a standardized data collection form, 2 reviewers (J.G., M.D.) independently extracted data on patient population (inclusion and exclusion criteria), participant characteristics (demographic characteristics and diagnoses), sample size, opioid treatment protocol, outcome measures, side effects and adverse events, and study design. Risk of bias was independently assessed using the Cochrane Collaboration’s tool23 and discrepancies in quality assessment scores were resolved by discussion.

SYNTHESIS

The search strategy yielded 1315 citations after duplicates were removed using the Covidence screening tool. Following the screening of titles and abstracts, 63 articles were identified for full-text review (Figure 1)24 and only 1 article met the inclusion criteria.

Figure 1.
Figure 1.

Flow diagram of inclusion process according to the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines24

*More than 1 exclusion criterion applied to some articles.

The included article by Chang et al presents the results of a prospective, randomized, double-blind clinical trial comparing the efficacy of weight-based intravenous (IV) hydromorphone and IV morphine in adults 65 years and older presenting with acute, severe pain to an urban academic ED in the Bronx, NY.25 Patients were excluded if they had taken opioids within the past 7 days or had chronic pain syndromes (eg, sickle cell disease, fibromyalgia). In this study, 194 eligible patients (70% female; mean age 75 years) were randomized to receive a single 0.0075 mg/kg dose of IV hydromorphone or a single 0.05 mg/kg dose of IV morphine. The primary outcome of this study was the difference between groups in mean decrease in pain measured using an 11-point numeric pain rating scale (NRS; where 0 = no pain and 10 = worst pain possible) at baseline and 30 minutes after medications were infused. The mean decrease in pain from baseline to 30 minutes was 3.8 NRS units among patients who received hydromorphone and 3.3 NRS units among patients who received morphine. This difference of 0.5 NRS units was not statistically significant (95% CI −0.2 to 1.3 NRS units) and was further attenuated after multivariable adjustment was performed that took into consideration age, weight, analgesics taken at home, and pain location. Furthermore, this difference was not considered clinically important based on a previous study by the same group, which defined a clinically significant difference as at least 1.3 NRS units.26,27 The mean decreases in NRS units at 10 minutes and at 2 hours were also not significantly different, and there was no difference in the incidence of adverse events (nausea, vomiting, systolic blood pressure < 90 mm Hg, pruritus, respiratory rate < 12 breaths/min, oxygen saturation < 95%). Neither hydromorphone nor morphine provided more than 50% pain relief to most of the included patients. Fourteen (15.1%) patients randomized to hydromorphone and 22 (24.4%) patients randomized to morphine were given additional analgesics over the study period (difference of −9.3%; 95% CI −20.8% to 2.2%).

Risk-of-bias assessment

The included RCT was judged to be at low risk of bias. The risk of selection bias was mitigated by randomization and allocation concealment, and risk of performance bias was mitigated by blinding participants, investigators, and physicians to the type of drug administered. Randomization was conducted using a computer-generated randomization list, and the encoded list was kept hidden from all study investigators, physicians, and research assistants. There was minimal risk of attrition bias in this study owing to the short study period, and the authors addressed incomplete outcome data by reporting the number and reason 11 randomized patients (4 patients in the hydromorphone group and 7 patients in the morphine group) were excluded from analysis.

DISCUSSION

The near-zero findings from this systematic review of studies comparing the efficacy of opioid analgesics in older adults in the ED demonstrates a persistent gap in knowledge that others have previously reported.14,28

It is widely recognized that metabolic pathways and pharmacologic properties vary among opioids.29 Comparative efficacy of immediate-release opioids has been studied in RCTs for several types of acute pain, including moderate-to-severe postoperative pain and pain associated with fractures.30–34 However, as demonstrated by this review, there is little evidence comparing opioids specifically in older adults. Therefore, health care providers often base care decisions on evidence from studies of younger adults, and simply use a smaller dose than what would be given to younger adults to account for age-related decline in the systemic clearance of analgesics, greater pharmacodynamic sensitivity to analgesic nervous system effects, and possible interactions with other drugs.8,13,35

Given that age-related pharmacodynamic and pharmacokinetic changes occur, it might not be reasonable to simply extrapolate evidence for treatment based on younger populations and assume it holds true in an older population. For instance, the authors of the one study included in this review found in an earlier study that in adults aged 18 to 64 years, there was a statistically and clinically significant decrease in pain among patients who received IV hydromorphone compared with those who received IV morphine.26 Their finding was not replicated in the study of older adults included in this review.25

In addition to potential differences in the efficacy of opioids for reducing severe, acute pain in older adults compared with younger adults, there might be differences in the comparative safety of opioids specific to the older adult population, given their overall increased vulnerability to adverse effects such as low blood pressure and low oxygen saturation.13,36

Although the authors in the included study did not find a statistically significant difference in mean decrease in pain between the 2 opioids (morphine and hydromorphone) in older adults, they speculate that this might have been because the initial dose of both drugs was too low.25 In both groups, approximately 60% of patients experienced a less than 50% decrease in pain after 30 minutes. Similarly, but among a younger adult population (21 to 65 years), researchers found 60% of patients who received IV morphine at 0.1 mg/kg (twice the amount given in the Chang et al study25) reported a less than 50% decrease in their severe, acute pain after 30 minutes.37

This systematic review did not find any studies comparing outcomes associated with opioids prescribed to older adults at discharge from the ED. The one study included in the review had a study period that lasted 2 hours during an ED visit. The consequences of inadequately treating acute pain reach beyond the hospital setting. Studies have shown pain to be associated with a decreased ability to conduct activities of daily living, poor self-rated health, depression, diminished quality of life, decreased cognition, and reduced mobility.38–42 Studies with longer follow-up time are needed to understand the effectiveness of opioids for controlling acute pain in older adults discharged from the ED.

Limitations

There are limitations to the systematic review that should be considered. To meet the research question, we limited the included studies to RCTs. However, the search strategy did not include a term for study design and we made note of any potentially relevant articles during the screening process. We did not come across any observational studies that compared treatment of acute pain with opioid analgesics among older adults. Also, the inclusion criteria required studies to have compared the effect of at least 2 opioids for the treatment of acute pain, so studies comparing opioids to other pharmacologic or nonpharmacologic treatments were not included in this review.

Conclusion

Despite pain being the most common reason older adults seek care from the ED and opioids being one of the most common interventions used for managing this pain, specifically when nonpharmacologic and nonopioid options are insufficient or contraindicated, ED physicians have little guidance for selecting the best opioid analgesic to treat older patients presenting with acute pain. Overall, there is little clinical evidence to support the systematic choice of one opioid over another, in terms of either efficacy or tolerability. The lack of evidence in this area highlights the need for research comparing the efficacy, side effects, and adverse events among types of opioid analgesics in older adults treated in the ED for acute pain.

Notes

Editor’s key points

  • ▸ Despite pain being the most common reason older adults seek care from the emergency department, and despite opioids being one of the most common interventions used for managing this pain, specifically when nonpharmacologic and nonopioid options are insufficient or contraindicated, emergency department physicians have little guidance for selecting the best opioid analgesic to treat older patients presenting with acute pain.

  • ▸ Given that age-related pharmacodynamic and pharmacokinetic changes occur, it might not be reasonable to simply extrapolate evidence for treatment based on younger populations and assume it holds true among an older population. In addition to potential differences in the efficacy of opioids for reducing severe, acute pain in older adults compared with younger adults, there might be differences in the comparative safety of opioids specific to the older adult population.

  • ▸ Overall, there is little clinical evidence to support the systematic choice of one opioid over another in older patients, in terms of either efficacy or tolerability. Although the authors in the only study that met the inclusion criteria for this review did not find a statistically significant difference in mean decrease in pain between 2 opioids (morphine and hydromorphone) in older adults, they speculate that this might have been because the initial dose of both drugs was too low.

Points de repère du rédacteur

  • ▸ Même si la douleur est la raison la plus fréquente pour laquelle les adultes plus âgés se présentent à l’urgence, et bien que les opioïdes soient l’une des interventions les plus courantes utilisées pour contrôler la douleur, surtout lorsque les options non pharmacologiques ou sans opioïdes sont insuffisantes ou contre-indiquées, les médecins des services d’urgence ont peu de sources d’information pour les guider dans le choix du meilleur analgésique opioïde pour traiter les patients plus âgés souffrant de douleur aiguë.

  • ▸ Étant donné qu’il se produit des changements pharmacodynamiques et pharmacocinétiques avec le vieillissement, il pourrait ne pas être avisé de simplement extrapoler les données probantes en faveur des traitements pour les populations plus jeunes et présumer qu’ils conviennent à la population plus âgée. En plus des différences possibles dans l’efficacité des opioïdes pour soulager la douleur sévère aiguë chez les adultes plus âgés par rapport aux adultes plus jeunes, il pourrait y avoir des distinctions dans l’innocuité comparative s’appliquant spécifiquement à la population adulte plus âgée.

  • ▸ Dans l’ensemble, très peu de données cliniques appuient systématiquement le choix d’un opioïde plutôt qu’un autre pour les patients plus âgés, que ce soit sur le plan de l’efficacité ou de la tolérabilité. Même si les auteurs de la seule étude qui répondait aux critères d’inclusion dans cette revue n’ont cerné aucune différence statistiquement significative dans la diminution moyenne de la douleur entre 2 opioïdes (morphine et hydromorphone) chez les adultes plus âgés, ils se sont demandé si cette constatation pourrait plutôt être attribuable à une dose initiale trop faible des 2 médicaments.

Footnotes

  • Contributors

    All authors contributed to the concept and design of the study; data gathering, analysis, and interpretation; and preparing the manuscript for submission.

  • Competing interests

    None declared

  • This article has been peer reviewed.

  • Cet article a fait l’objet d’une révision par des pairs.

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