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This article is part of the series Selected articles from the Annual Update in Intensive Care and Emergency Medicine 2013.

Highly Accessed Open Badges Review

Analgesia in the emergency department: a GRADE-based evaluation of research evidence and recommendations for practice

Chris Lipp*, Raj Dhaliwal and Eddy Lang

Author Affiliations

University of Calgary, Faculty of Medicine, Alberta Health Services, Calgary, Canada

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Critical Care 2013, 17:212  doi:10.1186/cc12521

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2013 and co-published as a series in Critical Care. Other articles in the series can be found online at Further information about the Annual Update in Intensive Care and Emergency Medicine is available from

The electronic version of this article is the complete one and can be found online at:

Published:19 March 2013

© 2013 Springer-Verlag Berlin Heidelberg and BioMed Central


Emergency physicians care for patients with pain on an extremely frequent basis [1-20]. The prevalence of pain as the presenting complaint of patients seeking emergency department (ED) care ranges from 38% [3] to as high as 78% [1]. As a result, evidence-based use of analgesics should be a foundational skill of emergency physicians. However, the literature consistently reports that emergency physicians are often poor at treating pain [1,2,8,13,14,16,19,20]. Notwithstanding the prevalence of pain in the ED, many patients often report that their pain was not properly treated [3,7,20]. In addition to a compromised patient experience, sub-optimal treatment of pain will result in decreased department flow, increased wait times, more return visits to the ED, and increased hospitalization rates.

Very few evidence-based resources and guidelines exist to inform emergency physicians on how to treat pain. One recent guideline on acute pain management compiled by the college of Anaesthetists of Australia and New Zealand [21] was focused primarily on treating pain perioperatively and did not include stratified or graded recommendations based on the literature, highlighting the paucity of emergency medicine-specific guidance. Emergency physicians need an effective, evidenced-based approach to analyze and apply the options available for acute pain management.

The objective of this article is to synthesize and evaluate the quality of medical literature surrounding analgesia delivery in the adult ED using the Grading Assessment, Development and Evaluation (GRADE) framework. We further strived to provide emergency physicians with graded recommendations upon which analgesics should be used to treat adults with acute pain in the ED.

Question formulation

Prior to searching the literature we developed seven clinically-oriented questions based on a scoping of the literature and a review of locally utilized ED analgesic order sets. This initial surveying of medical literature and our local practice environment allowed us to identify the most commonly prescribed intravenous and oral analgesics used in adult EDs in our health care region.

We then used the patient-intervention-comparison-outcome (PICO) approach to develop our seven research questions (Table 1). This approach has been adopted by many authors of systematic reviews and guideline panels, including the International Liaison Committee on Resuscitation (ILCOR) and the American College of Chest Physicians (ACCP) [22-24]. It involves identifying a specific population or setting to which recommendations may be applied. Subsequently each question compares two specific management strategies (intervention and comparison). Finally, we defined important patient oriented outcomes (e.g., change in pain) as well as any adverse effects of the medication or other safety concerns. All seven draft questions were reviewed and revised through an iterative process involving all authors. These seven clinically-based PICO questions compared analgesics (morphine, fentanyl, hydromorphone, non-steroidal anti-inflammatory drugs [NSAIDs], codeine, oxycodone) commonly used in the management of adult acute pain in the ED. The primary critical outcome across all PICO questions was a clinically significant change in pain using validated instruments, such as a visual analog (VAS) or numeric rating scale (NRS). The time frame used to assess change in pain varied from 30 minutes to two hours, depending on the medication route of administration. Secondary patient-oriented outcomes included serious adverse events, patient satisfaction, and side effects. Serious adverse events were defined as respiratory depression (less than 12 breaths per minute), decline in pulse oximetry oxygen saturation to less than 92%, decline in systolic blood pressure below 90 mmHg, or the need for administration of naloxone after opioid administration.

Table 1. The seven questions developed for analysis

Search strategy

After developing the seven PICO questions we conducted searches for each question using PubMed, Ovid MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, and the TRIPdatabase. These databases were systematically searched following consultation with a professional health sciences librarian who assisted us in our search methodology and use of specific keywords including Medical Subject Headings (MeSH) terms (Table 2). Our search took place over a six-month period of time, from January to June 2011. We conducted seven unique searches using the same search keywords as well as the various names of the intervention and comparison drugs in each question. When possible, we used MeSH terms for searching the U.S. National Library of Medicine. Prior to searching the databases we also developed inclusion and exclusion criteria (Table 2) to assist us in focusing each literature search.

Table 2. Search keywords, inclusion and exclusion criteria for literature searches

The results of each literature search were saved and a single reviewer screened titles, flagging articles that met the inclusion criteria based on the search keywords and terms.

Articles flagged as relevant in the initial screen were selected for abstract review. Abstracts for each PICO question were screened by the same reviewer and when abstracts met the inclusion criteria, a full text copy of the article was retrieved.

Use of GRADE

In our analysis of the situation we decided to use the GRADE framework, which is becoming the benchmark for communicating evidence-based medicine throughout the world [25]. Numerous prominent health organizations, including the World Health Organization (WHO), the ACCP, the Society of Critical Care Medicine (SCCM), the National Institute for Clinical Excellence (NICE, UK), and the European Respiratory Society (ERS) have endorsed or adopted the GRADE approach as a means of analyzing medical evidence and developing guidelines.

We used the GRADE system and its quality of evidence criteria as well as GRADE-Pro software to analyze the articles for each PICO question. This software-supported approach is used in the GRADE methodology and enables clinician-researchers to succinctly analyze structured clinical questions using the GRADE methodology [26,27]. GRADE classifies evidence into four categories (high, moderate, low and very low) based on a body of evidence related to a specific outcome. This classification is based on an assessment of the research studies in question, including assessing for bias, indirectness, imprecision, inconsistency, and publication bias. Subsequently, the software assists the researcher through a multifactorial process of compiling the results of each study for the outcomes studied in the research question. The software then summarizes all the pertinent details of the research question and each outcome in a summary of findings (SoF) table. Each SoF table outlines the level of evidence for each question (high, moderate, low, or very low) and serves as the basis for making recommendations on each clinical question.

Following the grading of the evidence for each of the seven PICO questions, seven separate SoF tables were developed by the first author using the GRADE-Pro software. Subsequently the first author drafted recommendations for each of the seven PICO question using the data in the SoF tables. Once these drafts were complete, the second and third authors reviewed the SoF tables and reviewed the recommendations in an iterative process. These recommendations were then compiled into a succinct table.


A total of 153 abstracts were screened for eligibility and 26 articles met eligibility criteria. Three articles compared fentanyl and morphine (PICO #1); five articles assessed hydromorphone (PICO #2), two of which analyzed the 1 + 1 hydromorphone protocol (PICO #3); three articles compared oral hydromorphone and oxycodone (PICO #4); eight articles compared non-specific NSAIDs and codeine-acetaminophen (PICO #5); two articles compared specific NSAIDs and codeine-acetaminophen (PICO #6); and five articles compared oxycodone and codeine (PICO #7).

The same reviewer assessed the full text articles and determined that 14 of the 26 offered quantitative results that could be analyzed using the GRADE-pro software [28-41]. The remaining 12 articles were excluded because they did not compare both drugs assessed in a PICO question [42-47], compared analgesics not addressed in the seven PICO questions (such as acetaminophen alone) [48,49], used unconventional medication dosing [50,51], used non-validated pain measurement scales [52,53], and/or unusual study designs [50].

The 14 articles evaluated using the GRADE approach included eight randomized clinical trials, four systematic reviews, one retrospective cohort study, and one prospective clinical trial. An example of a SoF table developed for PICO number two is included (Table 3). Similar SoF tables were developed for each PICO question. Overall, the grading process supported the use of intravenous hydromorphone and fentanyl as superior to intravenous morphine for rapid and effective pain relief (weak recommendation, moderate quality evidence). Oral NSAIDs, oxycodone, and hydromorphone are generally superior to codeine-acetaminophen combinations (weak recommendations, very-low quality evidence; due to bias, indirectness, and imprecision).

Table 3. The summary of findings table for PICO #2: Hydromorphone (i.v.) vs. morphine (i.v.) for acute severe pain in the emergency department


Using the GRADE framework, we have synthesized and evaluated the medical literature surrounding analgesia delivery in the adult ED and developed clear and actionable recommendations for analgesic use based on graded recommendations. Despite using a thorough, systematic approach to reviewing the literature on each PICO question we identified only 14 articles that met our inclusion criteria. However, although the number of studies used to make our recommendations may seem low, our recommendations take into consideration the quality of evidence of the studies. Pragmatic derivations of the seven PICO questions, their recommendations, and the rationale for these recommendations are listed in Table 4[28-41]. Furthermore, we also developed a flow-chart as a suggested approach to analgesia in the ED (Figure 1).

Table 4. The intravenous and oral analgesics analyzed in this study: Associated recommendations and rationale

thumbnailFigure 1. Suggested approach to acute pain in the emergency department. NSAID: non-steroidal anti-inflammatory drug; IV: intravenous.

Despite the synthesis of information in this study there are also some limitations to consider. First, there is a limited body of literature analyzing the use and efficacy of analgesics in the ED setting. Even after searching multiple databases there were few studies conducted in the ED setting that compared one oral analgesic with another oral analgesic. As a result, many of our recommendations were limited by the fact that some studies were conducted in postoperative settings and subsequently downgraded due to indirectness. Second, there were difficulties making comparisons between different studies that compared the various oral agents. In particular, it was difficult to properly compare studies in which codeine-acetaminophen combinations were used as there is a significant amount of variability in the codeine to acetaminophen ratio in the various combinations of this oral analgesic. As a result, we were unable to clearly compare two studies if they differed in their codeine to acetaminophen ratios. Third, while the authors collaborated extensively throughout this project, only one author was responsible for analyzing the article titles and abstracts. Finally, this review did not include the pediatric population in the literature search, and our recommendations do not extend to treating acute pain in children.

Despite these limitations this study also has a number of strengths. First, this study is extremely relevant to emergency physicians and health care workers who must treat acute pain, and to our knowledge it is the first GRADE-based evaluation of ED analgesia. Furthermore, this study serves as a model for clinician-researchers and administrators who want to promote evidence-based medicine in their clinical context. By conducting similar PICO question based analyses, successful knowledge translation from medical literature into clinical practice may be accomplished and, thereby, insure that treatments at the bedside remain current.


Despite the frequent occurrence of pain in ED patients, there are no ED-based syntheses and guidelines that compare analgesics commonly used in the ED. We have developed the first GRADE based recommendations for improving analgesia in the ED. Going forward, these findings can be used by ED clinicians and guideline panels to evaluate and develop analgesic order sets based on specific clinical presentations as well as drive the research agenda in ED analgesia.

These evidence-based guidelines have the potential to not only impact on patient morbidity, but also on health care costs and ED efficiency. As health care professionals with the role of treating emergent health problems, it is crucial that all emergency physicians have up-to-date, evidence-based knowledge to adequately treat acute pain.

Competing interests

The authors declare that they have no competing interests.

List of abbreviations used

ACCP: American College of Chest Physicians; CI: Confidence interval; COX: cyclooxygenase; ED: emergency department; ERS: European Respiratory Society; GRADE: Grading Assessment, Development and Evaluation; ILCOR: International Liaison Committee on Resuscitation (ILCOR); IV: intravenous; MeSH: Medical Subject Headings; MMSE: mini mental state examination; NICE: National Institute for Clinical Excellence; NRS: numeric rating scale; NSAID: non-steroidal anti-inflammatory drug; PICO: Population-Intervention Comparison-Outcome; RR: risk ratio; SCCM: Society of Critical Care Medicine; SoF: summary of findings; VAS: visual analogue; WHO: World Health Organization.


We thank Dr Helen Lee-Robertson, librarian at the University of Calgary Health Sciences Center, for her contributions to this study.


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