A Review of the Burden of Trauma Pain in Emergency Settings in Europe

A Review of the Burden of Trauma Pain in Emergency Settings in Europe Pain Ther https://doi.org/10.1007/s40122-018-0101-1 REVIEW A Review of the Burden of Trauma Pain in Emergency Settings in Europe . . . Patrick D. Dißmann Maxime Maignan Paul D. Cloves . . Blanca Gutierrez Parres Sara Dickerson Alice Eberhardt Received: October 5, 2017 The Author(s) 2018 review aims to explore these unmet needs and ABSTRACT describe barriers to the delivery of effective analgesia for trauma pain in emergency set- Trauma pain represents a large proportion of tings. A comprehensive, qualitative review of admissions to emergency departments across the literature was conducted using a structured Europe. There is currently an unmet need in the search strategy (Medline, Embase and Evidence treatment of trauma pain extending throughout Based Medicine Reviews) along with additional the patient journey in emergency settings. This Internet-based sources to identify relevant human studies published in the prior 11 years Enhanced digital features To view enhanced digital (January 2006–December 2017). From a total of features for this article go to https://doi.org/10.6084/ 4325 publications identified, 31 were selected m9.figshare.6340571. for inclusion based on defined criteria. Numer- Electronic supplementary material The online ous barriers to the effective treatment of trauma version of this article (https://doi.org/10.1007/s40122- pain in emergency settings were identified, 018-0101-1) contains supplementary material, which is available to authorized users. which may be broadly defined as arising from a lack of effective pain management pan-Euro- P. D. Dißmann pean and national guidelines, delayed or absent Emergency Department, Klinikum Lippe GmbH, pain assessment, an aversion to opioid analgesia Detmold, Germany and a delay in the administration of analgesia. Several commonly used analgesics also present M. Maignan Emergency Department, Grenoble Alpes University limitations in the treatment of trauma pain due Hospital, CHUGA, Grenoble, France to the routes of administration, adverse side effect profiles, pharmacokinetic properties and P. D. Cloves South East Coast Ambulance Service, Brighton, UK suitability for use in pre-hospital settings. These combined barriers lead to the inadequate and B. Gutierrez Parres ineffective treatment of trauma pain for Emergency Department, Puerta de Hierro University patients. An unmet need therefore exists for Hospital, Madrid, Spain novel forms of analgesia, wider spread use of S. Dickerson (&) available analgesic agents which overcome Mundipharma International Limited, Cambridge, some limitations associated with several treat- UK e-mail: sara.dickerson@mundipharma.com ment options, and the development of proto- cols for pain management which include A. Eberhardt patient assessment of pain. Mundipharma GmbH, Limburg, Germany Pain Ther We conducted a qualitative review of pub- Funding: Mundipharma International Ltd. lished literature with the aim of identifying current barriers to the effective management of trauma pain in Europe. Based on these findings, Keywords: Ambulance; Analgesia; Emergency; we sought to identify potential areas for Pain; Trauma improvement in the management of trauma pain in emergency settings. INTRODUCTION METHODS Management of trauma pain by healthcare professionals (HCPs) in the emergency depart- A literature search was conducted to identify ment (ED) and prehospital settings is a crucial publications reporting current treatment element of care. Approximately 38 million approaches for trauma pain in emergency set- people across Europe visit the hospital ED each tings in Europe (including both pre-hospital year due to injuries, with 5.3 million of these and EDs), the limitations of these therapies and patients admitted for further treatment [1]. Pain other barriers to effective pain control. An is often the main complaint of trauma patients integrative review framework was used. This and is reported by up to 70% of patients in pre- approach enables evaluation of heterogeneous hospital settings and 91% in EDs [2–4]. studies, thereby providing comprehensive However, inadequate relief of trauma pain is methodology to assess a particular healthcare commonly reported by patients in the EU and phenomenon [13]. The following computerized beyond [5]. For example, in a large, multicenter bibliographic databases were searched using the study conducted in the US and Canada, 74% of OVID search engine: Medline, Embase, and the patients were discharged from the ED in mod- Evidence-Based Medicine Reviews. The search erate or severe pain [6]. Moderate-to-severe pain was limited to human studies published in is also commonly reported by patients dis- English language in the past 11 years (January charged from European EDs [7]. In Europe, the 01, 2006–December 31, 2017). Combinations of treatment for trauma pain is largely similar terms were utilized such as (analgesia or acute between the pre-hospital setting and the ED, pain or injury or trauma pain) and (emergency mainly consisting of paracetamol, non-steroidal services or emergency department or pre-hos- anti-inflammatory drugs (NSAIDs), nitrous pital) OR (treatment pathway or standard of oxide (N O), and opioids [3, 8–10]. Current use care) OR (cost or economic or financial) OR of these analgesics may be considered inade- (quality of life or treatment satisfaction or social quate. Indeed, prospective data from Norwegian cost). Retrieved abstracts were assessed for rele- and Italian EDs indicated only 14 and 32% of vance against a pre-defined inclusion and patients with moderate-to-severe pain received exclusions criteria, agreed by the co-authors analgesia, respectively [10, 11]. Suboptimal prior in order to establish the objectives of this assessment and management of trauma pain literature analysis (Table 1). The search strategy has also been reported by emergency medical was agreed by all co-authors, and all co-authors services in prehospital settings [3, 12]. The were involved in the final selection and impact associated with lack of effective pain appraisal of the papers. All types of studies were control also extends beyond the patient’s per- captured in this qualitative review, including spective to the wider emergency setting as HCPs randomized controlled trials (RCTs), observa- are, in turn required to manage increased levels tional studies, review articles, and treatment of pain which impacts resources [4]. Conse- guidelines. quently, there appears to be an unmet need for An additional search of Internet-based a safe, timely, and efficacious treatment for sources (websites of the World Health Organi- trauma pain in emergency settings. zation, NHS Choices, and College of Pain Ther Table 1 Inclusion and exclusion criteria used in the literature review Inclusion criteria Exclusion criteria Publications were included which: Publications were excluded which: 1. Discussed the prevalence or incidence of pain in 1. Did not report on pain or treatments for pain emergency settings 2. Focused on long-term chronic pain 2. Discussed pain in relation to time and duration of pain 3. Related solely to the treatment of trauma pain in specific before relief in emergency settings patient groups, including: pediatrics, elderly, pregnant, or 3. Reported treatment pathways for mild, moderate, and patients with reduced consciousness (papers that included severe trauma pain in emergencies. This could be recorded subgroups of populations [e.g., elderly or pediatric also as ‘‘pain induced by trauma’’, ‘‘trauma-induced pain’’, or patients] within a range of individuals were not excluded) ‘‘acute pain from fractures’’ 4. Focused on the treatment of pain from major trauma 4. Captured treatment patterns and pain management of 5. Did not have a European focus patients with moderate-to-severe trauma pain 5. Described the limitations of current treatments for trauma pain in emergency settings 6. Discussed the burden of trauma pain in an emergency setting on healthcare providers Emergency Medicine) was conducted to iden- RESULTS tify relevant gray literature, i.e., research pro- duced by organizations outside of traditional Search Results publishing channels. This search was con- ducted using no pre-defined search criteria and Our searches revealed a sparsity of relevant included both publicly available information European literature on trauma pain manage- and peer-reviewed publications that may not ment. From 4325 publications identified in the yet be indexed in databases such as PubMed or literature search, 31 were selected for inclusion Embase because of their recent publication in this analysis based on the inclusion and date or because they were published in journals exclusion criteria described in Table 1 (Fig. 1). that are not indexed within these databases. The publications identified by the primary lit- Additional references were identified by tar- erature search included eight observational geted searching for information to corroborate patient assessments, eight literature reviews, expert knowledge shared by authors of work- eight patient chart reviews, three RCTs (and ing practices in their respective countries. associated subanalyses), one pain management Investigative questions regarding the standard guideline, and one HCP questionnaire. Thirteen of care in the treatment of trauma pain and additional publications were identified through barriers to effective management of trauma a grey literature search of freely available sour- pain were developed and addressed using evi- ces, including six literature reviews, three dence collated from the identified studies. This observational patient assessments, one RCT, article is based on previously conducted studies one pain management guideline and two and does not contain any studies with human patient information Web pages. Details of these participants or animals performed by any of 44 publications are summarized in the supple- the authors. mentary material (Supplementary Table 1 and Supplementary Table 2). Pain Ther Fig. 1 Schematic of publications included in the literature review for trauma pain What is the Standard of Care What are the Pharmacological Treatment in the Treatment of Trauma Pain? Options for Mild to Moderate Pain? Paracetamol and/or NSAIDs are often used in first-line treatment of mild to moderate pain Common analgesics used in the pre-hospital with the route of administration, usually orally and ED settings in Europe include paracetamol, or intravenous (IV), depending on the setting NSAIDs, N O, and opioids [3, 8, 9]. The type of and patient needs [8, 18–20]. Commonly pre- analgesic used can depend on trauma type, pain scribed NSAIDs in Europe include ibuprofen, severity or triage system in the ED [8, 9, 14]. diclofenac, and naproxen [8, 21]. In a recent Regional blocks, for example local anesthesia double-blind study, paracetamol was found to and peripheral nerve blocks, may also be be non-inferior to diclofenac as an analgesic for administered in the treatment of trauma pain acute, minor musculoskeletal trauma [22]. [8, 15, 16]. These treatments may reduce the However, paracetamol does not have the anti- need for rescue/additional analgesic treatment inflammatory properties of NSAIDs. [17]. Although not a common theme in the N O is an inhaled, rapid-onset, short-acting literature identified in this search, non-phar- analgesic commonly used in emergency settings macological approaches also play an important [8, 23]. N O has been used as an analgesic in role in ameliorating trauma pain, for example pre-hospital settings and EDs for many years, immobilizing limbs and applying dressings or where its short duration of action (B 5 min of ice packs, and may be used in conjunction with analgesia) is well suited for the treatment of drug therapy [3, 8]. Some treatment options acute trauma pain [24]. have limitations which may hinder effective Metamizole (dipyrone) is a non-opioid anal- pain relief in emergency settings, and are dis- gesic and its use in emergency settings varies cussed below. considerably across Europe. Metamizole is ban- ned in some countries (e.g., the UK, Sweden, Pain Ther and some countries outside of Europe including associated with nephrotoxicity [33]. Low-dose the US) due to concern over myelotoxicity, but methoxyflurane has been used extensively in its use is widespread across others (e.g., Spain emergency settings in Australia and New Zeal- and Germany, based on authors discussions) and for over 30 years and was recently approved [25–27]. A recent systematic review indicated in some European countries (including Bel- more large-scale studies are required to better gium, France, Ireland, and the UK) for the understand the risks and benefit of metamizole emergency relief of moderate-to-severe pain in relative to other analgesics [27]. conscious adults with trauma and associated Weak opioids such as codeine and tramadol pain [34, 35]. In a double-blind trial (STOP!) of are also used to treat moderate trauma pain adults and adolescents presenting at the ED [8, 28]. Tramadol acts at l-opioid receptors and with moderate pain arising from minor trauma, inhibits the reuptake of serotonin and nore- methoxyflurane provided greater improve- pinephrine [29]. This provides an atypical ments in pain versus placebo at timepoints from analgesic effect to that usually experienced with 5 to 20 min and was well tolerated (adverse this class of pain relief products along with less events were mild and transient) [36]. Subgroup severe side effect profile. Typical opioid side analysis of the STOP! trial in adults and those effects are uncommon with tramadol use, with contusions and lacerations confirmed making this analgesic a useful analgesic option these findings [37–39]. [24, 29]. Multimodal pain management using two or more drugs with differing modes of action has an important role alleviating trauma pain. For What are the Pharmacological Treatment example, paracetamol, NSAIDs, or ketamine Options for Severe Pain may be used in combination with opioids Opioids provide effective analgesia for severe [8, 12, 19, 29]. Evidence outside the setting of trauma pain and are available by several routes trauma pain suggests this approach can reduce of administration, including IV, or intranasal the dose of opioids required (opioid-sparing (IN), intraosseous (IO), subcutaneous (SC), and effect) [40]. per os (PO). While morphine is most commonly used in emergency settings across Europe for severe pain, use of other opioids including fen- What are the Barriers to Effective tanyl and oxycodone is also common Management of Trauma Pain? [3, 28, 30, 31]. Ketamine can also provide effective analgesia The journey of a patient with trauma pain, for severe trauma pain [12, 28, 31]. Although including ambulance care, triage, and physician the exact mechanism of action is largely assessments in the ED, presents several stages unknown, its wide therapeutic index, cardio- where barriers to effective management may vascular stability, and lack of respiratory exist (Fig. 2). The barriers identified in this lit- depression make ketamine attractive for use in erature analysis are discussed in detail below, the pre-hospital setting [28]. The dissociative including limitations of currently available effect associated with ketamine also makes it an therapies, HCP perceptions regarding opioids, effective treatment for trauma pain, although lack of national emergency pain treatment safety concerns over psychological manifesta- guidelines in most European countries, and tions and long-term psychotomimetic effects inadequate pain assessment in emergency set- have been raised [32]. tings. These findings highlight that significant Low-dose methoxyflurane, a non-opioid, cultural changes are needed in emergency volatile fluorinated hydrocarbon, is adminis- medicine to improve trauma pain management tered via the hand-held Penthrox inhaler. and incorporate a more patient-centric While use of methoxyflurane for general anes- approach. thesia was discontinued due to renal safety concerns, administration of sub-anesthetic concentrations for short periods is not Pain Ther Fig. 2 Treatment pathway and barriers to effective man- IV intravenous. Barriers to effective management of agement of trauma pain in Europe. ED emergency trauma pain are detailed in boxes department, HCP healthcare professional, IN intranasal, What are the Limitations of Current common route of administration in emergency Treatment Options for Trauma Pain? settings and provides fast-onset pain relief [19]. The type of analgesic recommended for use in However, IV analgesics can be difficult to the treatment of pain in emergency settings can administer in some circumstances, such as on depend on trauma type, pain severity, and the scene of accidents. Problems can also occur triage system in the ED [8, 14, 19]. Limitations in attempting to gain IV access in cold weather associated with commonly used analgesics were in pre-hospital settings, or in patients with dif- identified, which underscore the need for ficult vein access, causing further discomfort to alternate analgesics to address trauma pain distressed individuals and delaying onset of (Fig. 2). analgesia. Furthermore, in some countries, including Denmark, many paramedics are not authorized to administer IV medication [41]. Difficulties Associated with Routes Studies outside of this Europe-focused literature of Administration search have also reported associations between The route of administration of analgesics in the IV access difficulties and increased on-scene treatment of trauma pain may present several time for ambulance crews, and consequent ED limitations. IV analgesia is often the most Pain Ther crowding as attention of HCPs is diverted The widespread availability of paracetamol [42–44]. and some NSAIDs without prescription in Eur- IV and other methods of administering ope means that many patients may have self- medications by injection can be painful and medicated with these drugs prior to presenting may not be suitable for use in patients with at the ED [47]. As overdosing is associated with ‘needle-phobia’. In addition, while SC admin- serious side effects, inquiry should be made istration of analgesics can provide rapid and regarding recent use of over-the-counter parac- titratable pain relief, it is unsuitable for ede- etamol-containing preparations before pre- matous or hypovolemic patients. IM adminis- scribing [8, 47]. Of note, a recent review of tration does not allow for dose titration or observational studies (which was not focused adjustment, potentially resulting in ineffective on emergency trauma pain) revealed consider- and indeterminate levels of analgesia. Further- able toxicity with paracetamol at the upper end more, IO administration of analgesia requires of standard analgesic doses [48]. Limitations of prior placement of IO access, which causes the metamizole analgesia are largely associated with patient further pain and is not used in common its uncertain safety profile, resulting in a ban in practice. Many trauma patients eligible for local countries such as Sweden and the UK [26, 27]. anesthesia or regional nerve blocks fail to A US-based review of pain management in ED receive such treatment, which has been attrib- also discussed how patients may become frus- uted in part to inadequate training of HCPs in trated if the same analgesia they have already these procedures [15, 16]. taken is offered again in the ED [24]. The use of IN analgesia in emergency settings is less invasive compared to IV administration. Practicalities of N O However, IN analgesia can cause administration N O analgesia may be unsuitable for some issues in patients with facial trauma such as patients, for example individuals with pneu- epistaxis, blocked nose, and accidental swal- mothorax or facial/head trauma [8, 23]. The lowing [45]. In such individuals, this may result varied efficacy experienced by patients receiving in a suboptimal dose of analgesia and therefore N O also means there are a limited number of ineffective treatment of trauma pain. non-responders to this treatment [23]. Despite its proven analgesic effect, opera- Opioid Safety Profile tional issues can hinder the use of N Oas Opioids are considered the benchmark for treatment involves large amounts of equipment analgesia of severe pain in emergency settings. (such as cylinders and breathing apparatus) and However, opioids are associated with a chal- transport of bulky cylinders of premixed N O lenging safety profile, including risks of respi- and oxygen [34]. The mix of oxygen and N O ratory depression, cardiovascular events, can separate at cold temperatures and must be nausea, and vomiting [28, 46]. As a result of stored at temperatures above 10 C for at least associated adverse events (particularly respira- 24 h prior to use to avoid potentially hypoxic tory depression), patients require prolonged concentrations being delivered as the cylinder monitoring and observation following opioid empties [34]. The equipment required for N O administration, therefore increasing the HCP treatment can also limit the accessibility of workload and patient length of stay [14]. analgesia in some situations (for example to patients in remote locations) and also impacts the volume of equipment available in an Limited Efficacy of Weak Analgesics ambulance. It has been proposed that Weaker analgesics such as metamizole, parac- methoxyflurane, which is delivered in the etamol, and NSAIDs are limited in their ability handheld Penthrox inhaler, can overcome to treat moderate-to-severe pain. Pain as a result some of the limitations associated with N O of trauma can quickly escalate in severity, and treatment as portability is particularly desirable therefore the use of weaker analgesics may for emergency care in remote locations or provide ineffective analgesia. Pain Ther rescue helicopter missions, as well for urban for pain management [9, 11, 14, 19]. However, paramedics who carry heavy backpacks [34, 35]. while details of institution-specific protocols are not widely published, these guidelines are likely to be inconsistent, which is supported by vari- Lack of Effective Pain Management Guidelines ations in the most common types of analgesia Pain management guidelines are important for administered to treatment trauma pain across the effective management of trauma pain as this European countries [7, 19, 23, 30]. There are guidance is intended to ensure all patients also numerous reports that adherence to pain receive appropriate pain relief. This literature management protocols in Europe is lacking review identified no pan-European guidelines (Fig. 2)[3, 11, 14, 30, 53]. Consequently, the for the treatment of trauma pain in prehospital development and implementation of effective or hospital settings, and also a lack of consistent pan-European and/or national guidelines is guidelines at a national level. Indeed, only two required to provide a clear process for the published guidelines were identified by our lit- management of trauma pain and reduce dis- erature analysis: institution clinical practice crepancies in treatment which may lead to dif- guideline (Switzerland) and College of Emer- fering levels of pain relief in patients gency Medicine (UK) [8, 19]. These guidelines [14, 18, 53]. broadly reflect US evidence-based guidance for prehospital trauma analgesia [49]. In 1986, the World Health Organization Inadequate Assessment of Trauma Pain (WHO) issued a ‘pain relief ladder’ outlining Evaluation of patient pain is vital for the analgesics recommended for relief from cancer implementation of effective pain management pain in adults (Fig. 3)[50]. This format may protocols [5, 8]. A number of instruments have provide a basis for the recommendation of been developed to aid the evaluation of pain, opioids in the treatment of moderate-to-severe such as the visual analogue scale (VAS) and trauma pain in both the pre-hospital setting numerical rating scale (NRS), which are com- and ED [19, 49]. However, it must be noted that monly used in emergency settings [54]. Most of despite its clear and simple guidance, the WHO the studies which evaluated pain in this litera- ladder does not consider newer medications ture analysis utilized a NRS [3, 9–11, 20, 23, 41]. and was developed to address cancer-related It should be noted that pain assessment scales pain rather than being specific for emergency are associated with limitations, measurements trauma pain [51, 52]. Indeed, a meeting of are not interchangeable and some are better experts in 2007 urged the WHO to develop suited to research rather than clinical practice guidelines specific for trauma pain in emer- settings [54]. However, when used in conjunc- gency settings [52]. tion with clinical observations relating to pain It was noted in some studies identified in this intensity, these instruments provide HCPs with literature analysis that individual countries and an objective measure of patient pain and in institutions have developed their own protocols assist them to select the most appropriate analgesic. Our literature search indicated that inade- quate assessment of pain in emergency settings is common in Europe, which has, in part, been attributed to time constraints and ambiguity in protocols [3, 11, 31, 53]. If pain is not assessed frequently it cannot be comprehensively trea- ted; consequently under evaluation of pain will result in undertreatment of some patients [4]. Guidance on the use of pain assessment tools is often specified to the local level, although may be based on national or international recom- Fig. 3 Pathway for the treatment of pain (adapted from the WHO cancer pain ladder) [50] mendations [8, 11, 19]. Pain Ther Aversion to Opioid Analgesia suffering [5]. Reports that patients in pain upon The limitations associated with opioid analgesia arrival at ED experience more pain during discussed previously result in an aversion to examinations and procedures than other indi- opioid use by some patients and HCPs [14]. For viduals, which may in part by attributed to example, in an Italian hospital emergency hyperalgesia, also underscores the need for department, despite 77% of patients reporting prompt administration of effective analgesia [4]. severe pain which warranted opioid therapy per Data from real-world studies included in this the center’s pain management protocol, this literature analysis indicate that many patients was administered to only 3% of patients [20]. with moderate-to-severe trauma pain do not HCP aversion to administering opioid analgesia receive analgesia within the 15 to 20-min has been attributed to regulatory barriers in timeframe suggested in the two local European prescription, concern over patient drug-seeking guidelines identified [8, 19]. For example, in a behavior or addiction, increased demands due French observational study, 35% of patients to patient monitoring, and fear of masking waited for more than 60 min before examina- other symptoms of trauma [14, 30, 41, 53]. The tion, and average waiting times in excess of phenomenon of ‘opioid aversion’ is also widely 40 min were reported in other audits conducted documented in studies conducted in other in hospitals in France and Portugal [4, 18, 59]. regions [6, 55]. Opioids can provide potent Similarly, in a prehospital setting, an average of analgesia when appropriately prescribed for 38 min was reported between paramedic arrival moderate-to-severe pain, and consequently and administration of analgesia in a pan-Euro- aversion to opioid use can result in the pean audit of patients with emergency trauma undertreatment of trauma pain. HCPs’ reluc- pain [60]. A critical area for improvement in tance to prescribe and administer opioids time to analgesia in the ED is in triage time. directly hinders pain management in both pre- Patients’ first demonstration of pain in the ED hospital and ED settings. Across a range of set- presents an opportunity to provide appropriate tings, some patients also express concerns analgesia, so a delay in this process presents a regarding opioid treatment and desire to be barrier to timely pain relief [59]. Triage systems offered non-opioid pain relief [56]. used in EDs typically include an assessment of When used appropriately, opioids present an patients’ pain to guide analgesia use and prior- effective treatment for severe trauma pain. itize patients for treatment [4, 8, 20, 61]. The Overcoming physician and patient aversion to Manchester Triage System has been utilized and opioid use may therefore reduce the burden of adapted by many European countries (for trauma pain by providing an effective treat- example, Germany and Switzerland), where ment. This could potentially be achieved by the patients are assigned a triage category and cor- development of evidence-based national treat- responding target time to assessment [61]. ment guidelines which clearly document Triage assessment of pain in European hospital appropriate use of opioid analgesics for short- EDs has been shown to result in rapid and term administration to address acute trauma effective analgesia, although some studies indi- pain, including patient selection. Readily avail- cate failings in implementation of triage proto- able information on the risks of opioid-related cols as patients continue to receive suboptimal side effects, overdose, diversion, and depen- analgesia [4, 9, 20, 62]. dency associated with acute use could also be Attitudes of some HCPs towards pain in useful to assist HCPs to make informed deci- emergency settings can also delay administra- sions in emergency trauma settings, since much tion of analgesia, for example that pain is a of the published literature on these issues per- minor priority in trauma care as it is not life- tains to chronic opioid therapy [57, 58]. threatening [53]. Studies conducted in the US indicate that overcrowding in the ED con- tributes to a prolonged time to analgesia as Delay to Administration of Analgesia HCPs experience increased time pressures. Time to analgesia is critical in the treatment of Increased patient numbers in the ED can result trauma pain as delays result in undue patient Pain Ther in increased time to patient assessment, time to Barriers to the effective management of analgesic ordering, and time to administration trauma pain in emergency settings outside of of analgesia [63–65]. Time to analgesia also the analgesic products used were also identified. presents a barrier to effective pain relief in pre- These included failure to use validated pain hospital emergency settings. For example, short scales to aid triage assessment as well as low time at the scene and secondary missions were prioritization of trauma pain by some HCPs associated with untreated persistent pain in [11, 53]. Furthermore, our literature search patients with moderate-to-severe pain attended identified no pan-European clinical guidelines by a helicopter emergency medical service [12]. addressing management of trauma pain in The form of analgesia administered in ambu- emergency settings and only two local guideli- lances can also influence the burden of trauma nes [8, 19]. However, several publications pain, as IV analgesia can increase on-scene time referred to institution-specific protocols due to administration, resulting in longer mis- [9, 11, 14]. Consequently, development of sion times [42]. Furthermore, in some European national and regional European guidelines countries, ambulance personnel are not per- detailing analgesic use and the wider manage- mitted to administer opioid analgesics, ment of trauma pain in Europe would be key in although a recent study in Germany supported reducing the burden of pain to HCPs [52, 55]. prehospital fentanyl and morphine adminis- Such guidelines should also include methods to tered by specially trained paramedics [66]. accurately assess patient pain. Therefore, we When pain cannot be managed effectively in recommend that relevant professional organi- pre-hospital settings, this also results in a zations across Europe who represent HCPs greater burden for HCPs when patients arrive at treating patients with trauma pain convene to the ED. The metabolism of analgesics can also develop clinical practice guidelines. Indeed, influence the time taken to achieve pain relief, input from global experts should also be con- an important factor in emergency settings, and sidered for best-practice recommendations. The consequently sources of variability that may findings from this European-focused literature influence pharmacokinetics and pharmacody- analysis on trauma pain are supported by US- namics should be considered (Fig. 2)[67]. focused and global literature reviews, which call for timely assessment of pain at presentation and following administration of analgesia using DISCUSSION age-appropriate, validated scales, and wider implementation of pain management protocols Pain imposes a substantial burden on emer- [24, 55, 68]. gency care, as this is often the primary com- Some barriers to the effective management plaint of patients presenting to EDs [59]. We of trauma pain in emergency settings could be have identified a variety of limitations associ- addressed by use of easily portable, IN, non- ated with many analgesics, including difficulties opioid analgesia such as methoxyflurane associated with IV administration necessary for [34, 35]. Furthermore, by multimodal analgesia, some drugs and bulky equipment requirements i.e., multiple complementary analgesic agents for N O, particularly in pre-hospital settings used in combination, physicians can ensure [34, 43, 44]. Other treatment-associated limita- that patients achieve adequate pain relief tions identified include aversion to opioid throughout their journey in emergency settings analgesics due to perceptions associated with and possibly reduce the side effects associated this class of agents, safety concerns, and regu- with strong analgesics such as opioids [69]. The latory barriers [14, 41, 53]. Consequently, for use of multimodal analgesia also allows the the treatment of moderate-to-severe trauma physician to tailor pain relief to an individual pain in emergency settings, there remains an patient [69]. Patient-controlled analgesia may unmet need for analgesic agents to be widely provide a solution to dosage and frequency used that have a fast onset of action, limited limitations of current methods of pain relief contraindications, and are easy to administer. [70, 71]. Pain Ther The literature review was limited by only Editorial Assistance. The authors would like searching for articles in the English language, to acknowledge Hannah Collings and Ashley which may have discounted local language Enstone (Adelphi Values PROVE) for their con- publications and guidelines. This review also tribution to developing the literature search focused solely on the treatment of adult strategy, conducting the literature review, and patients with trauma pain and so does not dis- drafting the manuscript, funded by Mundi- cuss the separate challenges faced when treating pharma International Ltd. Editorial assistance elderly or pediatric patients (such as the likeli- in the preparation of this article was also pro- hood of comorbidities and analgesic dosing vided by Sia ˆn Marshall of SIANTIFIX Ltd, considerations). Some publications identified Cambridgeshire, UK, funded by Mundipharma from the literature review also included discus- International Ltd. sion of acute pain, not always as a result of Authorship. All named authors meet the trauma. These publications were captured as International Committee of Medical Journal they provide a valuable insight into the barriers Editors (ICMJE) criteria for authorship for this to effective management of acute pain in article, take complete responsibility for the emergency settings. Furthermore, while this integrity and accuracy of this work as a whole, publication discusses the burden of trauma pain and have given their approval for this version to in Europe as a whole, due to the limited results be published. of the literature search, information from all European countries could not be included. Disclosures. Patrick D. Dißmann received a consultancy fee and travel expenses from CONCLUSIONS Mundipharma International Ltd. Maxime Maignan received a consultancy fee and travel In conclusion, based on evidence in published expenses from Mundipharma International Ltd. literature, the management of trauma pain in Paul D. Cloves received a consultancy fee and emergency settings across Europe could be travel expenses from Mundipharma Interna- improved by the development of novel anal- tional Ltd. Blanca Gutierrez Parres received a gesics and greater uptake of available agents, consultancy fee and travel expenses from which overcome several of the practical and Mundipharma International Ltd. Sara Dicker- safety limitations associated with widely used son is an employee of Mundipharma Interna- products. Improved measures of assessing tional Limited. Alice Eberhardt is an employee patient pain and the development and imple- of Mundipharma GmbH. mentation of effective protocols for pain man- Compliance with Ethics Guidelines. This agement will also be important steps in article is based on previously conducted studies reducing the burden of trauma pain in emer- and does not contain any studies with human gency settings in Europe. participants or animals performed by any of the authors. ACKNOWLEDGEMENTS Open Access. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International Funding. Article processing charges for this License (http://creativecommons.org/licenses/ review paper were funded by Mundipharma by-nc/4.0/), which permits any noncommer- International Ltd. All authors had full access to cial use, distribution, and reproduction in any all of the data in this study and take complete medium, provided you give appropriate credit responsibility for the integrity of the data and to the original author(s) and the source, provide accuracy of the data analysis. a link to the Creative Commons license, and indicate if changes were made. Pain Ther physician-staffed helicopter emergency medical REFERENCES service. Anesth Analg. 2017;125(1):200–9. 13. Whittemore R, Knafl K. The integrative review: 1. EuroSafe. Injuries in the European Union: Summary updated methodology. 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A Review of the Burden of Trauma Pain in Emergency Settings in Europe

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Medicine & Public Health; Internal Medicine; Pain Medicine
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Abstract

Pain Ther https://doi.org/10.1007/s40122-018-0101-1 REVIEW A Review of the Burden of Trauma Pain in Emergency Settings in Europe . . . Patrick D. Dißmann Maxime Maignan Paul D. Cloves . . Blanca Gutierrez Parres Sara Dickerson Alice Eberhardt Received: October 5, 2017 The Author(s) 2018 review aims to explore these unmet needs and ABSTRACT describe barriers to the delivery of effective analgesia for trauma pain in emergency set- Trauma pain represents a large proportion of tings. A comprehensive, qualitative review of admissions to emergency departments across the literature was conducted using a structured Europe. There is currently an unmet need in the search strategy (Medline, Embase and Evidence treatment of trauma pain extending throughout Based Medicine Reviews) along with additional the patient journey in emergency settings. This Internet-based sources to identify relevant human studies published in the prior 11 years Enhanced digital features To view enhanced digital (January 2006–December 2017). From a total of features for this article go to https://doi.org/10.6084/ 4325 publications identified, 31 were selected m9.figshare.6340571. for inclusion based on defined criteria. Numer- Electronic supplementary material The online ous barriers to the effective treatment of trauma version of this article (https://doi.org/10.1007/s40122- pain in emergency settings were identified, 018-0101-1) contains supplementary material, which is available to authorized users. which may be broadly defined as arising from a lack of effective pain management pan-Euro- P. D. Dißmann pean and national guidelines, delayed or absent Emergency Department, Klinikum Lippe GmbH, pain assessment, an aversion to opioid analgesia Detmold, Germany and a delay in the administration of analgesia. Several commonly used analgesics also present M. Maignan Emergency Department, Grenoble Alpes University limitations in the treatment of trauma pain due Hospital, CHUGA, Grenoble, France to the routes of administration, adverse side effect profiles, pharmacokinetic properties and P. D. Cloves South East Coast Ambulance Service, Brighton, UK suitability for use in pre-hospital settings. These combined barriers lead to the inadequate and B. Gutierrez Parres ineffective treatment of trauma pain for Emergency Department, Puerta de Hierro University patients. An unmet need therefore exists for Hospital, Madrid, Spain novel forms of analgesia, wider spread use of S. Dickerson (&) available analgesic agents which overcome Mundipharma International Limited, Cambridge, some limitations associated with several treat- UK e-mail: sara.dickerson@mundipharma.com ment options, and the development of proto- cols for pain management which include A. Eberhardt patient assessment of pain. Mundipharma GmbH, Limburg, Germany Pain Ther We conducted a qualitative review of pub- Funding: Mundipharma International Ltd. lished literature with the aim of identifying current barriers to the effective management of trauma pain in Europe. Based on these findings, Keywords: Ambulance; Analgesia; Emergency; we sought to identify potential areas for Pain; Trauma improvement in the management of trauma pain in emergency settings. INTRODUCTION METHODS Management of trauma pain by healthcare professionals (HCPs) in the emergency depart- A literature search was conducted to identify ment (ED) and prehospital settings is a crucial publications reporting current treatment element of care. Approximately 38 million approaches for trauma pain in emergency set- people across Europe visit the hospital ED each tings in Europe (including both pre-hospital year due to injuries, with 5.3 million of these and EDs), the limitations of these therapies and patients admitted for further treatment [1]. Pain other barriers to effective pain control. An is often the main complaint of trauma patients integrative review framework was used. This and is reported by up to 70% of patients in pre- approach enables evaluation of heterogeneous hospital settings and 91% in EDs [2–4]. studies, thereby providing comprehensive However, inadequate relief of trauma pain is methodology to assess a particular healthcare commonly reported by patients in the EU and phenomenon [13]. The following computerized beyond [5]. For example, in a large, multicenter bibliographic databases were searched using the study conducted in the US and Canada, 74% of OVID search engine: Medline, Embase, and the patients were discharged from the ED in mod- Evidence-Based Medicine Reviews. The search erate or severe pain [6]. Moderate-to-severe pain was limited to human studies published in is also commonly reported by patients dis- English language in the past 11 years (January charged from European EDs [7]. In Europe, the 01, 2006–December 31, 2017). Combinations of treatment for trauma pain is largely similar terms were utilized such as (analgesia or acute between the pre-hospital setting and the ED, pain or injury or trauma pain) and (emergency mainly consisting of paracetamol, non-steroidal services or emergency department or pre-hos- anti-inflammatory drugs (NSAIDs), nitrous pital) OR (treatment pathway or standard of oxide (N O), and opioids [3, 8–10]. Current use care) OR (cost or economic or financial) OR of these analgesics may be considered inade- (quality of life or treatment satisfaction or social quate. Indeed, prospective data from Norwegian cost). Retrieved abstracts were assessed for rele- and Italian EDs indicated only 14 and 32% of vance against a pre-defined inclusion and patients with moderate-to-severe pain received exclusions criteria, agreed by the co-authors analgesia, respectively [10, 11]. Suboptimal prior in order to establish the objectives of this assessment and management of trauma pain literature analysis (Table 1). The search strategy has also been reported by emergency medical was agreed by all co-authors, and all co-authors services in prehospital settings [3, 12]. The were involved in the final selection and impact associated with lack of effective pain appraisal of the papers. All types of studies were control also extends beyond the patient’s per- captured in this qualitative review, including spective to the wider emergency setting as HCPs randomized controlled trials (RCTs), observa- are, in turn required to manage increased levels tional studies, review articles, and treatment of pain which impacts resources [4]. Conse- guidelines. quently, there appears to be an unmet need for An additional search of Internet-based a safe, timely, and efficacious treatment for sources (websites of the World Health Organi- trauma pain in emergency settings. zation, NHS Choices, and College of Pain Ther Table 1 Inclusion and exclusion criteria used in the literature review Inclusion criteria Exclusion criteria Publications were included which: Publications were excluded which: 1. Discussed the prevalence or incidence of pain in 1. Did not report on pain or treatments for pain emergency settings 2. Focused on long-term chronic pain 2. Discussed pain in relation to time and duration of pain 3. Related solely to the treatment of trauma pain in specific before relief in emergency settings patient groups, including: pediatrics, elderly, pregnant, or 3. Reported treatment pathways for mild, moderate, and patients with reduced consciousness (papers that included severe trauma pain in emergencies. This could be recorded subgroups of populations [e.g., elderly or pediatric also as ‘‘pain induced by trauma’’, ‘‘trauma-induced pain’’, or patients] within a range of individuals were not excluded) ‘‘acute pain from fractures’’ 4. Focused on the treatment of pain from major trauma 4. Captured treatment patterns and pain management of 5. Did not have a European focus patients with moderate-to-severe trauma pain 5. Described the limitations of current treatments for trauma pain in emergency settings 6. Discussed the burden of trauma pain in an emergency setting on healthcare providers Emergency Medicine) was conducted to iden- RESULTS tify relevant gray literature, i.e., research pro- duced by organizations outside of traditional Search Results publishing channels. This search was con- ducted using no pre-defined search criteria and Our searches revealed a sparsity of relevant included both publicly available information European literature on trauma pain manage- and peer-reviewed publications that may not ment. From 4325 publications identified in the yet be indexed in databases such as PubMed or literature search, 31 were selected for inclusion Embase because of their recent publication in this analysis based on the inclusion and date or because they were published in journals exclusion criteria described in Table 1 (Fig. 1). that are not indexed within these databases. The publications identified by the primary lit- Additional references were identified by tar- erature search included eight observational geted searching for information to corroborate patient assessments, eight literature reviews, expert knowledge shared by authors of work- eight patient chart reviews, three RCTs (and ing practices in their respective countries. associated subanalyses), one pain management Investigative questions regarding the standard guideline, and one HCP questionnaire. Thirteen of care in the treatment of trauma pain and additional publications were identified through barriers to effective management of trauma a grey literature search of freely available sour- pain were developed and addressed using evi- ces, including six literature reviews, three dence collated from the identified studies. This observational patient assessments, one RCT, article is based on previously conducted studies one pain management guideline and two and does not contain any studies with human patient information Web pages. Details of these participants or animals performed by any of 44 publications are summarized in the supple- the authors. mentary material (Supplementary Table 1 and Supplementary Table 2). Pain Ther Fig. 1 Schematic of publications included in the literature review for trauma pain What is the Standard of Care What are the Pharmacological Treatment in the Treatment of Trauma Pain? Options for Mild to Moderate Pain? Paracetamol and/or NSAIDs are often used in first-line treatment of mild to moderate pain Common analgesics used in the pre-hospital with the route of administration, usually orally and ED settings in Europe include paracetamol, or intravenous (IV), depending on the setting NSAIDs, N O, and opioids [3, 8, 9]. The type of and patient needs [8, 18–20]. Commonly pre- analgesic used can depend on trauma type, pain scribed NSAIDs in Europe include ibuprofen, severity or triage system in the ED [8, 9, 14]. diclofenac, and naproxen [8, 21]. In a recent Regional blocks, for example local anesthesia double-blind study, paracetamol was found to and peripheral nerve blocks, may also be be non-inferior to diclofenac as an analgesic for administered in the treatment of trauma pain acute, minor musculoskeletal trauma [22]. [8, 15, 16]. These treatments may reduce the However, paracetamol does not have the anti- need for rescue/additional analgesic treatment inflammatory properties of NSAIDs. [17]. Although not a common theme in the N O is an inhaled, rapid-onset, short-acting literature identified in this search, non-phar- analgesic commonly used in emergency settings macological approaches also play an important [8, 23]. N O has been used as an analgesic in role in ameliorating trauma pain, for example pre-hospital settings and EDs for many years, immobilizing limbs and applying dressings or where its short duration of action (B 5 min of ice packs, and may be used in conjunction with analgesia) is well suited for the treatment of drug therapy [3, 8]. Some treatment options acute trauma pain [24]. have limitations which may hinder effective Metamizole (dipyrone) is a non-opioid anal- pain relief in emergency settings, and are dis- gesic and its use in emergency settings varies cussed below. considerably across Europe. Metamizole is ban- ned in some countries (e.g., the UK, Sweden, Pain Ther and some countries outside of Europe including associated with nephrotoxicity [33]. Low-dose the US) due to concern over myelotoxicity, but methoxyflurane has been used extensively in its use is widespread across others (e.g., Spain emergency settings in Australia and New Zeal- and Germany, based on authors discussions) and for over 30 years and was recently approved [25–27]. A recent systematic review indicated in some European countries (including Bel- more large-scale studies are required to better gium, France, Ireland, and the UK) for the understand the risks and benefit of metamizole emergency relief of moderate-to-severe pain in relative to other analgesics [27]. conscious adults with trauma and associated Weak opioids such as codeine and tramadol pain [34, 35]. In a double-blind trial (STOP!) of are also used to treat moderate trauma pain adults and adolescents presenting at the ED [8, 28]. Tramadol acts at l-opioid receptors and with moderate pain arising from minor trauma, inhibits the reuptake of serotonin and nore- methoxyflurane provided greater improve- pinephrine [29]. This provides an atypical ments in pain versus placebo at timepoints from analgesic effect to that usually experienced with 5 to 20 min and was well tolerated (adverse this class of pain relief products along with less events were mild and transient) [36]. Subgroup severe side effect profile. Typical opioid side analysis of the STOP! trial in adults and those effects are uncommon with tramadol use, with contusions and lacerations confirmed making this analgesic a useful analgesic option these findings [37–39]. [24, 29]. Multimodal pain management using two or more drugs with differing modes of action has an important role alleviating trauma pain. For What are the Pharmacological Treatment example, paracetamol, NSAIDs, or ketamine Options for Severe Pain may be used in combination with opioids Opioids provide effective analgesia for severe [8, 12, 19, 29]. Evidence outside the setting of trauma pain and are available by several routes trauma pain suggests this approach can reduce of administration, including IV, or intranasal the dose of opioids required (opioid-sparing (IN), intraosseous (IO), subcutaneous (SC), and effect) [40]. per os (PO). While morphine is most commonly used in emergency settings across Europe for severe pain, use of other opioids including fen- What are the Barriers to Effective tanyl and oxycodone is also common Management of Trauma Pain? [3, 28, 30, 31]. Ketamine can also provide effective analgesia The journey of a patient with trauma pain, for severe trauma pain [12, 28, 31]. Although including ambulance care, triage, and physician the exact mechanism of action is largely assessments in the ED, presents several stages unknown, its wide therapeutic index, cardio- where barriers to effective management may vascular stability, and lack of respiratory exist (Fig. 2). The barriers identified in this lit- depression make ketamine attractive for use in erature analysis are discussed in detail below, the pre-hospital setting [28]. The dissociative including limitations of currently available effect associated with ketamine also makes it an therapies, HCP perceptions regarding opioids, effective treatment for trauma pain, although lack of national emergency pain treatment safety concerns over psychological manifesta- guidelines in most European countries, and tions and long-term psychotomimetic effects inadequate pain assessment in emergency set- have been raised [32]. tings. These findings highlight that significant Low-dose methoxyflurane, a non-opioid, cultural changes are needed in emergency volatile fluorinated hydrocarbon, is adminis- medicine to improve trauma pain management tered via the hand-held Penthrox inhaler. and incorporate a more patient-centric While use of methoxyflurane for general anes- approach. thesia was discontinued due to renal safety concerns, administration of sub-anesthetic concentrations for short periods is not Pain Ther Fig. 2 Treatment pathway and barriers to effective man- IV intravenous. Barriers to effective management of agement of trauma pain in Europe. ED emergency trauma pain are detailed in boxes department, HCP healthcare professional, IN intranasal, What are the Limitations of Current common route of administration in emergency Treatment Options for Trauma Pain? settings and provides fast-onset pain relief [19]. The type of analgesic recommended for use in However, IV analgesics can be difficult to the treatment of pain in emergency settings can administer in some circumstances, such as on depend on trauma type, pain severity, and the scene of accidents. Problems can also occur triage system in the ED [8, 14, 19]. Limitations in attempting to gain IV access in cold weather associated with commonly used analgesics were in pre-hospital settings, or in patients with dif- identified, which underscore the need for ficult vein access, causing further discomfort to alternate analgesics to address trauma pain distressed individuals and delaying onset of (Fig. 2). analgesia. Furthermore, in some countries, including Denmark, many paramedics are not authorized to administer IV medication [41]. Difficulties Associated with Routes Studies outside of this Europe-focused literature of Administration search have also reported associations between The route of administration of analgesics in the IV access difficulties and increased on-scene treatment of trauma pain may present several time for ambulance crews, and consequent ED limitations. IV analgesia is often the most Pain Ther crowding as attention of HCPs is diverted The widespread availability of paracetamol [42–44]. and some NSAIDs without prescription in Eur- IV and other methods of administering ope means that many patients may have self- medications by injection can be painful and medicated with these drugs prior to presenting may not be suitable for use in patients with at the ED [47]. As overdosing is associated with ‘needle-phobia’. In addition, while SC admin- serious side effects, inquiry should be made istration of analgesics can provide rapid and regarding recent use of over-the-counter parac- titratable pain relief, it is unsuitable for ede- etamol-containing preparations before pre- matous or hypovolemic patients. IM adminis- scribing [8, 47]. Of note, a recent review of tration does not allow for dose titration or observational studies (which was not focused adjustment, potentially resulting in ineffective on emergency trauma pain) revealed consider- and indeterminate levels of analgesia. Further- able toxicity with paracetamol at the upper end more, IO administration of analgesia requires of standard analgesic doses [48]. Limitations of prior placement of IO access, which causes the metamizole analgesia are largely associated with patient further pain and is not used in common its uncertain safety profile, resulting in a ban in practice. Many trauma patients eligible for local countries such as Sweden and the UK [26, 27]. anesthesia or regional nerve blocks fail to A US-based review of pain management in ED receive such treatment, which has been attrib- also discussed how patients may become frus- uted in part to inadequate training of HCPs in trated if the same analgesia they have already these procedures [15, 16]. taken is offered again in the ED [24]. The use of IN analgesia in emergency settings is less invasive compared to IV administration. Practicalities of N O However, IN analgesia can cause administration N O analgesia may be unsuitable for some issues in patients with facial trauma such as patients, for example individuals with pneu- epistaxis, blocked nose, and accidental swal- mothorax or facial/head trauma [8, 23]. The lowing [45]. In such individuals, this may result varied efficacy experienced by patients receiving in a suboptimal dose of analgesia and therefore N O also means there are a limited number of ineffective treatment of trauma pain. non-responders to this treatment [23]. Despite its proven analgesic effect, opera- Opioid Safety Profile tional issues can hinder the use of N Oas Opioids are considered the benchmark for treatment involves large amounts of equipment analgesia of severe pain in emergency settings. (such as cylinders and breathing apparatus) and However, opioids are associated with a chal- transport of bulky cylinders of premixed N O lenging safety profile, including risks of respi- and oxygen [34]. The mix of oxygen and N O ratory depression, cardiovascular events, can separate at cold temperatures and must be nausea, and vomiting [28, 46]. As a result of stored at temperatures above 10 C for at least associated adverse events (particularly respira- 24 h prior to use to avoid potentially hypoxic tory depression), patients require prolonged concentrations being delivered as the cylinder monitoring and observation following opioid empties [34]. The equipment required for N O administration, therefore increasing the HCP treatment can also limit the accessibility of workload and patient length of stay [14]. analgesia in some situations (for example to patients in remote locations) and also impacts the volume of equipment available in an Limited Efficacy of Weak Analgesics ambulance. It has been proposed that Weaker analgesics such as metamizole, parac- methoxyflurane, which is delivered in the etamol, and NSAIDs are limited in their ability handheld Penthrox inhaler, can overcome to treat moderate-to-severe pain. Pain as a result some of the limitations associated with N O of trauma can quickly escalate in severity, and treatment as portability is particularly desirable therefore the use of weaker analgesics may for emergency care in remote locations or provide ineffective analgesia. Pain Ther rescue helicopter missions, as well for urban for pain management [9, 11, 14, 19]. However, paramedics who carry heavy backpacks [34, 35]. while details of institution-specific protocols are not widely published, these guidelines are likely to be inconsistent, which is supported by vari- Lack of Effective Pain Management Guidelines ations in the most common types of analgesia Pain management guidelines are important for administered to treatment trauma pain across the effective management of trauma pain as this European countries [7, 19, 23, 30]. There are guidance is intended to ensure all patients also numerous reports that adherence to pain receive appropriate pain relief. This literature management protocols in Europe is lacking review identified no pan-European guidelines (Fig. 2)[3, 11, 14, 30, 53]. Consequently, the for the treatment of trauma pain in prehospital development and implementation of effective or hospital settings, and also a lack of consistent pan-European and/or national guidelines is guidelines at a national level. Indeed, only two required to provide a clear process for the published guidelines were identified by our lit- management of trauma pain and reduce dis- erature analysis: institution clinical practice crepancies in treatment which may lead to dif- guideline (Switzerland) and College of Emer- fering levels of pain relief in patients gency Medicine (UK) [8, 19]. These guidelines [14, 18, 53]. broadly reflect US evidence-based guidance for prehospital trauma analgesia [49]. In 1986, the World Health Organization Inadequate Assessment of Trauma Pain (WHO) issued a ‘pain relief ladder’ outlining Evaluation of patient pain is vital for the analgesics recommended for relief from cancer implementation of effective pain management pain in adults (Fig. 3)[50]. This format may protocols [5, 8]. A number of instruments have provide a basis for the recommendation of been developed to aid the evaluation of pain, opioids in the treatment of moderate-to-severe such as the visual analogue scale (VAS) and trauma pain in both the pre-hospital setting numerical rating scale (NRS), which are com- and ED [19, 49]. However, it must be noted that monly used in emergency settings [54]. Most of despite its clear and simple guidance, the WHO the studies which evaluated pain in this litera- ladder does not consider newer medications ture analysis utilized a NRS [3, 9–11, 20, 23, 41]. and was developed to address cancer-related It should be noted that pain assessment scales pain rather than being specific for emergency are associated with limitations, measurements trauma pain [51, 52]. Indeed, a meeting of are not interchangeable and some are better experts in 2007 urged the WHO to develop suited to research rather than clinical practice guidelines specific for trauma pain in emer- settings [54]. However, when used in conjunc- gency settings [52]. tion with clinical observations relating to pain It was noted in some studies identified in this intensity, these instruments provide HCPs with literature analysis that individual countries and an objective measure of patient pain and in institutions have developed their own protocols assist them to select the most appropriate analgesic. Our literature search indicated that inade- quate assessment of pain in emergency settings is common in Europe, which has, in part, been attributed to time constraints and ambiguity in protocols [3, 11, 31, 53]. If pain is not assessed frequently it cannot be comprehensively trea- ted; consequently under evaluation of pain will result in undertreatment of some patients [4]. Guidance on the use of pain assessment tools is often specified to the local level, although may be based on national or international recom- Fig. 3 Pathway for the treatment of pain (adapted from the WHO cancer pain ladder) [50] mendations [8, 11, 19]. Pain Ther Aversion to Opioid Analgesia suffering [5]. Reports that patients in pain upon The limitations associated with opioid analgesia arrival at ED experience more pain during discussed previously result in an aversion to examinations and procedures than other indi- opioid use by some patients and HCPs [14]. For viduals, which may in part by attributed to example, in an Italian hospital emergency hyperalgesia, also underscores the need for department, despite 77% of patients reporting prompt administration of effective analgesia [4]. severe pain which warranted opioid therapy per Data from real-world studies included in this the center’s pain management protocol, this literature analysis indicate that many patients was administered to only 3% of patients [20]. with moderate-to-severe trauma pain do not HCP aversion to administering opioid analgesia receive analgesia within the 15 to 20-min has been attributed to regulatory barriers in timeframe suggested in the two local European prescription, concern over patient drug-seeking guidelines identified [8, 19]. For example, in a behavior or addiction, increased demands due French observational study, 35% of patients to patient monitoring, and fear of masking waited for more than 60 min before examina- other symptoms of trauma [14, 30, 41, 53]. The tion, and average waiting times in excess of phenomenon of ‘opioid aversion’ is also widely 40 min were reported in other audits conducted documented in studies conducted in other in hospitals in France and Portugal [4, 18, 59]. regions [6, 55]. Opioids can provide potent Similarly, in a prehospital setting, an average of analgesia when appropriately prescribed for 38 min was reported between paramedic arrival moderate-to-severe pain, and consequently and administration of analgesia in a pan-Euro- aversion to opioid use can result in the pean audit of patients with emergency trauma undertreatment of trauma pain. HCPs’ reluc- pain [60]. A critical area for improvement in tance to prescribe and administer opioids time to analgesia in the ED is in triage time. directly hinders pain management in both pre- Patients’ first demonstration of pain in the ED hospital and ED settings. Across a range of set- presents an opportunity to provide appropriate tings, some patients also express concerns analgesia, so a delay in this process presents a regarding opioid treatment and desire to be barrier to timely pain relief [59]. Triage systems offered non-opioid pain relief [56]. used in EDs typically include an assessment of When used appropriately, opioids present an patients’ pain to guide analgesia use and prior- effective treatment for severe trauma pain. itize patients for treatment [4, 8, 20, 61]. The Overcoming physician and patient aversion to Manchester Triage System has been utilized and opioid use may therefore reduce the burden of adapted by many European countries (for trauma pain by providing an effective treat- example, Germany and Switzerland), where ment. This could potentially be achieved by the patients are assigned a triage category and cor- development of evidence-based national treat- responding target time to assessment [61]. ment guidelines which clearly document Triage assessment of pain in European hospital appropriate use of opioid analgesics for short- EDs has been shown to result in rapid and term administration to address acute trauma effective analgesia, although some studies indi- pain, including patient selection. Readily avail- cate failings in implementation of triage proto- able information on the risks of opioid-related cols as patients continue to receive suboptimal side effects, overdose, diversion, and depen- analgesia [4, 9, 20, 62]. dency associated with acute use could also be Attitudes of some HCPs towards pain in useful to assist HCPs to make informed deci- emergency settings can also delay administra- sions in emergency trauma settings, since much tion of analgesia, for example that pain is a of the published literature on these issues per- minor priority in trauma care as it is not life- tains to chronic opioid therapy [57, 58]. threatening [53]. Studies conducted in the US indicate that overcrowding in the ED con- tributes to a prolonged time to analgesia as Delay to Administration of Analgesia HCPs experience increased time pressures. Time to analgesia is critical in the treatment of Increased patient numbers in the ED can result trauma pain as delays result in undue patient Pain Ther in increased time to patient assessment, time to Barriers to the effective management of analgesic ordering, and time to administration trauma pain in emergency settings outside of of analgesia [63–65]. Time to analgesia also the analgesic products used were also identified. presents a barrier to effective pain relief in pre- These included failure to use validated pain hospital emergency settings. For example, short scales to aid triage assessment as well as low time at the scene and secondary missions were prioritization of trauma pain by some HCPs associated with untreated persistent pain in [11, 53]. Furthermore, our literature search patients with moderate-to-severe pain attended identified no pan-European clinical guidelines by a helicopter emergency medical service [12]. addressing management of trauma pain in The form of analgesia administered in ambu- emergency settings and only two local guideli- lances can also influence the burden of trauma nes [8, 19]. However, several publications pain, as IV analgesia can increase on-scene time referred to institution-specific protocols due to administration, resulting in longer mis- [9, 11, 14]. Consequently, development of sion times [42]. Furthermore, in some European national and regional European guidelines countries, ambulance personnel are not per- detailing analgesic use and the wider manage- mitted to administer opioid analgesics, ment of trauma pain in Europe would be key in although a recent study in Germany supported reducing the burden of pain to HCPs [52, 55]. prehospital fentanyl and morphine adminis- Such guidelines should also include methods to tered by specially trained paramedics [66]. accurately assess patient pain. Therefore, we When pain cannot be managed effectively in recommend that relevant professional organi- pre-hospital settings, this also results in a zations across Europe who represent HCPs greater burden for HCPs when patients arrive at treating patients with trauma pain convene to the ED. The metabolism of analgesics can also develop clinical practice guidelines. Indeed, influence the time taken to achieve pain relief, input from global experts should also be con- an important factor in emergency settings, and sidered for best-practice recommendations. The consequently sources of variability that may findings from this European-focused literature influence pharmacokinetics and pharmacody- analysis on trauma pain are supported by US- namics should be considered (Fig. 2)[67]. focused and global literature reviews, which call for timely assessment of pain at presentation and following administration of analgesia using DISCUSSION age-appropriate, validated scales, and wider implementation of pain management protocols Pain imposes a substantial burden on emer- [24, 55, 68]. gency care, as this is often the primary com- Some barriers to the effective management plaint of patients presenting to EDs [59]. We of trauma pain in emergency settings could be have identified a variety of limitations associ- addressed by use of easily portable, IN, non- ated with many analgesics, including difficulties opioid analgesia such as methoxyflurane associated with IV administration necessary for [34, 35]. Furthermore, by multimodal analgesia, some drugs and bulky equipment requirements i.e., multiple complementary analgesic agents for N O, particularly in pre-hospital settings used in combination, physicians can ensure [34, 43, 44]. Other treatment-associated limita- that patients achieve adequate pain relief tions identified include aversion to opioid throughout their journey in emergency settings analgesics due to perceptions associated with and possibly reduce the side effects associated this class of agents, safety concerns, and regu- with strong analgesics such as opioids [69]. The latory barriers [14, 41, 53]. Consequently, for use of multimodal analgesia also allows the the treatment of moderate-to-severe trauma physician to tailor pain relief to an individual pain in emergency settings, there remains an patient [69]. Patient-controlled analgesia may unmet need for analgesic agents to be widely provide a solution to dosage and frequency used that have a fast onset of action, limited limitations of current methods of pain relief contraindications, and are easy to administer. [70, 71]. Pain Ther The literature review was limited by only Editorial Assistance. The authors would like searching for articles in the English language, to acknowledge Hannah Collings and Ashley which may have discounted local language Enstone (Adelphi Values PROVE) for their con- publications and guidelines. This review also tribution to developing the literature search focused solely on the treatment of adult strategy, conducting the literature review, and patients with trauma pain and so does not dis- drafting the manuscript, funded by Mundi- cuss the separate challenges faced when treating pharma International Ltd. Editorial assistance elderly or pediatric patients (such as the likeli- in the preparation of this article was also pro- hood of comorbidities and analgesic dosing vided by Sia ˆn Marshall of SIANTIFIX Ltd, considerations). Some publications identified Cambridgeshire, UK, funded by Mundipharma from the literature review also included discus- International Ltd. sion of acute pain, not always as a result of Authorship. All named authors meet the trauma. These publications were captured as International Committee of Medical Journal they provide a valuable insight into the barriers Editors (ICMJE) criteria for authorship for this to effective management of acute pain in article, take complete responsibility for the emergency settings. Furthermore, while this integrity and accuracy of this work as a whole, publication discusses the burden of trauma pain and have given their approval for this version to in Europe as a whole, due to the limited results be published. of the literature search, information from all European countries could not be included. Disclosures. Patrick D. Dißmann received a consultancy fee and travel expenses from CONCLUSIONS Mundipharma International Ltd. Maxime Maignan received a consultancy fee and travel In conclusion, based on evidence in published expenses from Mundipharma International Ltd. literature, the management of trauma pain in Paul D. Cloves received a consultancy fee and emergency settings across Europe could be travel expenses from Mundipharma Interna- improved by the development of novel anal- tional Ltd. Blanca Gutierrez Parres received a gesics and greater uptake of available agents, consultancy fee and travel expenses from which overcome several of the practical and Mundipharma International Ltd. Sara Dicker- safety limitations associated with widely used son is an employee of Mundipharma Interna- products. Improved measures of assessing tional Limited. Alice Eberhardt is an employee patient pain and the development and imple- of Mundipharma GmbH. mentation of effective protocols for pain man- Compliance with Ethics Guidelines. This agement will also be important steps in article is based on previously conducted studies reducing the burden of trauma pain in emer- and does not contain any studies with human gency settings in Europe. participants or animals performed by any of the authors. ACKNOWLEDGEMENTS Open Access. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International Funding. Article processing charges for this License (http://creativecommons.org/licenses/ review paper were funded by Mundipharma by-nc/4.0/), which permits any noncommer- International Ltd. All authors had full access to cial use, distribution, and reproduction in any all of the data in this study and take complete medium, provided you give appropriate credit responsibility for the integrity of the data and to the original author(s) and the source, provide accuracy of the data analysis. a link to the Creative Commons license, and indicate if changes were made. Pain Ther physician-staffed helicopter emergency medical REFERENCES service. Anesth Analg. 2017;125(1):200–9. 13. Whittemore R, Knafl K. The integrative review: 1. EuroSafe. Injuries in the European Union: Summary updated methodology. 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Journal

Pain and TherapySpringer Journals

Published: Jun 2, 2018

References

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