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The effectiveness and safety of paediatric prehospital pain management: a systematic review

Abstract

Background

Clinically meaningful pain reduction with respect to severity and the adverse events of drugs used in prehospital pain management for children are areas that have not received sufficient attention. The present systematic review therefore aims to perform a comprehensive search of databases to examine the preferable drugs for prehospital pain relief in paediatric patients with acute pain, irrespective of aetiology.

Methods

The systematic review includes studies from 2000 and up to 2020 that focus on children’s prehospital pain management. The study protocol is registered in PROSPERO with registration no. CRD42019126699. Pharmacological pain management using any type of analgesic drug and in all routes of administration was included. The main outcomes were (1) measurable pain reduction (effectiveness) and (2) no occurrence of any serious adverse events. Searches were conducted in PubMed, Medline, Embase, CINAHL, Epistemonikos and Cochrane library. Finally, the risk of bias was assessed using the Joanna Briggs Institute (JBI) checklist and a textual narrative analysis was performed due to the heterogeneity of the results.

Results

The present systematic review on the effectiveness and safety of analgesic drugs in prehospital pain relief in children identified a total of eight articles. Most of the articles reviewed identified analgesic drugs such as fentanyl (intranasal/IV), morphine (IV), methoxyflurane (inhalational) and ketamine (IV/IM). The effects of fentanyl, morphine and methoxyflurane were examined and all of the included analgesic drugs were evaluated as effective. Adverse events of fentanyl, methoxyflurane and ketamine were also reported, although none of these were considered serious.

Conclusion

The systematic review revealed that fentanyl, morphine, methoxyflurane and combination drugs are effective analgesic drugs for children in prehospital settings. No serious adverse events were reported following the administration of fentanyl, methoxyflurane and ketamine. Intranasal fentanyl and inhalational methoxyflurane seem to be the preferred drugs for children in pre-hospital settings due to their ease of administration, similar effect and safety profile when compared to other analgesic drugs. However, the level of evidence (LOE) in the included studies was only three or four, and further studies are therefore necessary.

Background

Prehospital care providers have traditionally focused on time-sensitive acute illness and major traumas, which represent only a small number of patients. However, in the prehospital setting, large groups of patients experience a variety of illnesses and injuries with frequent symptoms and signs, including pain [1]. It is thought that effective analgesia is one of the top outcome measures of prehospital care [2]. It is also considered among the top factors in the satisfaction of the patients’ family [3]. The prevalence of acute pain in prehospital settings ranges from 42 to 53% [4,5,6].

Previous studies of children in prehospital care show that although the pain was documented in the ambulance records, the level of pain was not assessed in 66–96% of cases [5, 7]. Previous findings also show that 52–88% of children in prehospital setups did not receive pain medication despite having moderate to severe pain [5, 8]. The most common reasons for not providing adequate pain medication to children in prehospital settings include fearing side effects, difficulties with intravenous (IV) line access, being under five years of age, the lack of a pain assessment and the assumption that children need less analgesia than adults [9,10,11,12].

The evidence, however, indicates that adequate prehospital pain management in children relieves suffering, contributes to timely emergency department (ED) analgesia, prevents chronic pain and improves recovery [13, 14]. Conversely, inadequate pain management harms children’s development and increases morbidity and mortality [15, 16]. The negative effect of inadequate pain management could also extend to fear of medical care or medical/medication over-use in adulthood [17].

In prehospital pain medication for children, clinically meaningful reductions of pain severity and evaluations of adverse events of drugs for different age groups are areas that lack sufficient investigation. A few small-scale and systematic reviews of prehospital pain management have been conducted, but these either concerned the adult age group, trauma aetiologies or were specific to one analgesic agent only [18,19,20]. Because of the lack of high-level evidence, there are no clear guidelines regarding the choice of drug, recommended dose or which route of administration is preferable for prehospital pain management of children, irrespective of aetiology [12, 21]. The current original systematic review aims to examine the effectiveness and safety of analgesic drugs for prehospital pain relief in paediatric patients with acute pain of any cause.

Methods

This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines [22]. The review question, outcomes, inclusion criteria and methods of analysis were predefined, and the protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO), with registration no. CRD42019126699 [23].

Review question and types of participants

The main research question for this systematic review was, ‘What are the preferred drugs for prehospital pain relief in paediatric patients with acute pain?’. The study participants were children under the age of eighteen with acute pain (i.e. a sudden pain lasting less than 3 months) in the prehospital setting. A prehospital setting is defined here as a place where any acute medical care is provided by ambulance care providers before the patient arrives at the hospital. In this review, preferable analgesic drugs were determined by the effectiveness and safety of the drugs. The primary outcome of this review concerned the effectiveness of the analgesic drugs employed. The drugs’ effectiveness was defined as a clinically meaningful pain reduction as measured by a reduction of two or more points from the initial pain severity score after the administration of analgesic drugs based on standardised clinical pain assessment tools [24]. The secondary outcome concerned safety as defined by no occurrence of any serious adverse events in the prehospital setting after analgesic administration. The U.S. Food and Drug Administration (FDA) defines a serious adverse event as any serious undesirable experiences such as death, substantial risk of dying (life-threatening), hospitalisation, disability or permanent damage, congenital anomaly, required intervention to prevent permanent impairment and other serious medical events associated with the use of a medical product in a patient [25].

Eligibility criteria

The current review included all studies that focus on children’s prehospital pain management in low-, middle- and high-income countries. We included any mixed age group studies if there was a separate analysis for children under eighteen years of age. Since knowing the standalone effect of other non-pharmacological pain managements is difficult, only studies that addressed pharmacological pain management with any type of analgesic drugs in all routes of administration were included. Pain evaluation papers were included if pharmacological pain interventions were integrated. To examine all types of analgesic drugs that are used, we included all qualifications of prehospital care providers despite variation in their training, scope and expertise in the different prehospital setups. The publications included in this review comprised randomised control trials, non-randomised control studies, a cohort with control groups, interrupted time series, cross-sectional and case series studies.

Studies that examined chronic pain were excluded because the patient’s response to chronic pain management is different when compared to acute pain management [26]. As with the medical setup, the patients’ characteristics and the level of the responders’ training varied, studies that report on any sort of out-of-hospital pain treatments given by non-ambulance service providers, ambulance care while in medical transfers and in-hospital transfers were excluded. Pain management given in fixed healthcare facilities and/or by any other non-healthcare professionals was also excluded. As the primary and secondary outcomes of this review concerned the effectiveness and safety of analgesic drugs, studies that did not produce findings on either of these outcomes were excluded. In addition, qualitative studies, case reports, guidelines, continuing professional development (CPDs), letters to editors, service evaluation, conference abstracts and abstracts that did not have full text were also excluded.

Search strategy

The search strategy was developed by the four authors (YA, TS, FH and KS) who are the subject specialists and was peer-reviewed by another author (MH) who is a research librarian. Studies were identified through electronic database searches including PubMed, Ovid Medline (1946 to 15 December 2020), Ovid Embase (1974 to 15 December 2000), CINAHL (Ebsco), Epistemonikos and Cochrane library. The relevant medical subject headings (MeSH terms) and keywords used for the systematic search strategy are presented in Table 1. The searches were limited as regards publication year (the past 20 years from 2000 to 2020) and language (English, Danish, Norwegian or Swedish). The search strategy for each database is presented in Tables 2, 3, 4, 5, 6,  7. All independent reviewers performed the literature searches from all included databases and imported these to the Covidence software. The last searches were rerun by the research librarian (MH) on 16 December 2020. In addition, a hand search was conducted of the reference lists of the studies included in the current systematic review and systematic review reports concerning a similar topic, which resulted in the identification of one additional article.

Table 1 The MeSH terms and keywords according to the modified PICO
Table 2 Medline Search Strategy
Table 3 Embase Search Strategy
Table 4 PubMed Search Strategy
Table 5 CINAHL Search Strategy
Table 6 Cochrane Library Search Strategy
Table 7 Epistemonikos Search Strategy

Study selection

The results of the conducted search were combined, and duplicate studies were eliminated using the Covidence software. Titles and/or abstracts of studies were screened and carefully read by the four review authors (YA, TS, FH and KS) to identify potentially eligible studies. The full text of these articles was then retrieved and independently reviewed by the same four authors. The articles were included if the two authors agreed on that specific article. Discrepancies were resolved through discussion with a third reviewer (one of the four authors who had not reviewed that specific article).

Data extraction

We modified a data extraction template from Covidence version 2.0 [27]. One randomly selected article among the included studies was used as a pilot test. Two review authors performed the extraction (YA and TS) and resolved any disagreements through discussion. The general characteristics of the included studies, the name of the administered analgesic drug, the route of administration and the dose were extracted. In addition, the two outcome variables of the review and any age-specific results for small children (< 5 years old) were extracted. An email was forwarded to the respective corresponding authors of the included studies to obtain any additional information and confirm the correctness of the extracted data.

Assessment of the risk of bias

The Joanna Briggs Institute (JBI) checklist was used to assess the risk of bias for each of the study designs employed in the included articles [28]. The JBI checklists for analytical cross-sectional, prevalence, case series and cohort study designs were used. The level of evidence (LOE) was also classified according to the evidence evaluation worksheet by the International Liaison Committee on Resuscitation for therapeutic interventions (Table 8) [29]. Two authors (YA and KS) independently conducted a risk of bias assessment and a third author (FH) resolved any disagreements. No article was excluded on the basis of these assessments.

Table 8 Levels of Evidence (LOE) for Studies of Therapeutic Interventions

Data synthesis

Due to the heterogeneity of outcome variables, we performed a textual narrative analysis of the findings from each of the included studies. We structured our synthesis based on the characteristics of the studies and the types of drugs they included.

Results

We imported a total of 10,844 studies from six electronic databases. After removing duplicates (n = 3696), 7,148 titles/abstracts were screened. Of these, we reviewed 311 full-text studies. We also reviewed an additional 17 full-text studies identified from hand-searched reference lists. In all, 328 full-text articles comprising 320 studies were excluded, and eight studies [30,31,32,33,34,35,36,37] that met the eligibility criteria were included in the review. The selection process and grounds for exclusion are presented in a PRISMA flowchart below (Fig. 1).

Fig. 1
figure 1

PRISMA flow chart indicating the number of identified and included articles

Characteristics of the included studies

According to the evidence evaluation worksheet developed by the International Liaison Committee on Resuscitation for therapeutic interventions, the current review found level three and four evidence only, despite using a broad search strategy. Among the eight included studies, six were cross-sectional studies while the remaining two were case series and cohort studies, respectively. All studies were conducted in high-income countries; five in Australia [30, 31, 33, 34, 36] and three in Europe [32, 35, 37]. The publication year ranges from 2006 to 2017. The studies involved a total of 71,674 study participants. Six studies examined the paediatrics age group only. The other two [32, 34] included both adults and paediatrics (both had a separate report for the paediatric age group). The overall characteristics of the included studies are presented in Table 9.

Table 9 Characteristics of the included studies

Types of drugs

Six studies [30,31,32,33, 36, 37] examined the effectiveness of the reported analgesic drugs while two did not address this outcome [34, 35]. Furthermore, five studies [30, 32, 34, 35, 37] assessed the safety of the drugs, while the other three focused solely on their effectiveness [31, 33, 36].

Effectiveness and safety of intranasal Fentanyl as a single analgesic drug

Five of the studies [31,32,33, 36, 37] evaluated fentanyl as a single analgesic drug in children. Jennings describes fentanyl administration via both intranasal and IV routes (the results were not specified separately for each route of administration) [33], while the other studies addressed fentanyl administration via the intranasal route only. Each of the five studies identified fentanyl as an effective analgesic drug. Of these, two studies [32, 37] found that Intranasal Fentanyl (INF) given at a dose of 50 µg as a single dose (mean cumulative dose of 114 µg) [32] and a total of 1.5 µg/kg (initial mean (SD) dose of 50 (± 10)µg) [37] had no serious adverse events. The most common minor adverse events reported due to the administration of fentanyl are presented in Table 9. The dosage and any adverse events of fentanyl were not described in the other three studies [31, 33, 36]

Effectiveness and safety of Morphine as a single analgesic drug

Among the eight included studies, three investigated the use of morphine [31, 33, 36], all of which described the effectiveness of morphine administration in pain reduction. None of these studies stated the drug dosages or any adverse events.

In the study by Lord [31], 65% of morphine administration was via the IV route while other routes of administration were not described. The other two studies [33, 36] examined morphine administration via the IV route only. These two studies also compared the effect of morphine and fentanyl on pain reduction, and both found that morphine had an equivalent effect to fentanyl in pain reduction.

Effectiveness and safety of inhalational Methoxyflurane as a single analgesic drug

A total of five studies [30, 31, 33, 34, 36] addressed the use of inhalational Methoxyflurane (IHM). Of these, three studies [31, 33, 36] examined the effectiveness of the drug, while the other two [30, 34] focused on adverse events related to IHM.

A case series conducted over a time span of eight months in Australia identified a mean pain reduction from the initial pain score of 7.9–3.2 after 10 min of IHM administration [30]. In this study, about 91.4% of children received a single dose of 3 ml IHM while the others received two doses. In addition, only ten (9.5%) patients received additional IV morphine after the IHM administration had commenced. No serious adverse events had been caused by the IHM administration. About 33.3% and 8% of children under and over five years, respectively, developed deep sedation after receiving IHM. None of these deeply sedated patients had received additional IV morphine. They had immediately regained full consciousness within minutes as methoxyflurane administration was discontinued, and no further measures were needed. In addition, no renal impairment was reported from methoxyflurane administration. The most common minor adverse events found in this study are presented in Table 9.

One cohort study [34] conducted a separate analysis of 594 patients under the age of 12 years who received methoxyflurane, all of whom received a single IHM dose of 3 ml (0.3%). This study did not address the effectiveness of the drug. However, it found no observed increased risk of disease occurrence following methoxyflurane administration when compared to a similar group of patients who did not receive methoxyflurane. The investigated outcome variables among the exposed and control group were the presence of ischemic heart disease, diabetes, renal disease, cancer and hepatic diseases.

The other three retrospective cross-sectional studies conveyed the effectiveness of methoxyflurane in pain reduction [31, 33, 36]. In addition, Bendall found that IHM had less analgesic effect when compared to morphine, fentanyl and combined agents (AOR 0.52; 95% CI 0.36–0.74) [36]. In contrast, another study [33] reported that methoxyflurane had the greatest odds of achieving clinically meaningful pain reduction when compared to morphine and fentanyl (AOR 5.3; 95% CI 4.8–5.9). The drug doses and/or any adverse events were not described in any of the three retrospective cross-sectional studies.

Effectiveness and safety of Ketamine as a single analgesic drug

Only one retrospective database review examined the use of ketamine in children below the age of 16 [35]. The mean administered drug dose was 1.0 mg/kg (ranges from 0.1 to 5.8 mg/kg). The route of administration was IV (86%) and intramuscular (IM) (14%). A majority (68%) of patients also received a mean dose of 0.1 mg/kg midazolam as a co-drug. The study did not look at the effectiveness of the drug. No deaths or any implementation of basic airway manoeuvres had occurred due to ketamine administration. In all, only one adverse event had been recorded, which was desaturation (desaturation < 4%) in only four (2.4%) patients. Furthermore, the study did not find desaturation in children younger than three years of age after receiving an analgesic dose of ketamine.

Effectiveness and safety of combination analgesic drugs

Three studies examined the effectiveness of combination analgesic drugs [31, 36, 37]. All three identified the effectiveness of the use of combination drugs. None of these studies examined adverse events from the use of combination drugs.

The first study reported that intranasal fentanyl in combination with paracetamol ± ibuprofen ± inhaled nitrous oxide had a 79% effectiveness in pain reduction [37]. The second study showed that a combination of the three drugs (morphine, fentanyl and methoxyflurane) had a median pain score change of 4 (IQR 3–6) [31]. The third study identified that the use of a combination of more than one drug from the three analgesics (morphine, fentanyl and methoxyflurane) had a statistically significant higher median pain score difference (median pain score difference of 6 (IQR 4–7)) compared to use of the drugs independently. However, there was no statistical evidence suggesting that combination drugs were more effective than morphine or fentanyl alone after controlling for factors such as age and gender [36].

Risk of bias

The JBI critical appraisal checklist was used to assess the risk of bias. The JBI checklists for analytical cross-sectional, prevalence, case series and cohort study designs were used. Nine questions were assessed using the prevalence study design checklist, eight in the analytical, ten in the case series and eleven in the cohort study design. The findings of the assessment are provided in Table 10.

Table 10 Risk of bias assessment findings based on the respective research designs checklist of the JBI tool

Discussion

The present systematic review on the effectiveness and safety of analgesic drugs used in prehospital pain relief in children identified a total of eight articles. Most of these articles concerned analgesic drugs such as fentanyl (intranasal/IV), morphine (IV), methoxyflurane (inhalational) and ketamine (IV/IM). The studies examine the effects of fentanyl (intranasal/IV), morphine (IV) and methoxyflurane (inhalational), and all of the analgesic drugs were found to be effective. Adverse events of intranasal fentanyl, inhalational methoxyflurane and IV/IM ketamine were also described. However, none of these drugs were found to have serious adverse events.

The Italian Intersociety Recommendations on pain management in emergency settings stated that ‘the ideal prehospital analgesic should be easy to use, safe, effective, and have a predictable dose–response relationship with rapid onset and a short duration of action’ [38]. Our results show that both intranasal fentanyl and inhalational methoxyflurane are effective and safe to administer both as single drugs and/or in combination with other examined analgesic drugs. Similarly, several studies conducted in different acute care settings support that intranasal fentanyl and inhalational methoxyflurane are effective analgesic drugs with no serious adverse events [19, 39,40,41,42,43]. It has been suggested that these drugs are easy to administer and have a rapid onset and short duration of action [42, 44, 45]. Moreover, the present review found that fentanyl has an equivalent effect to morphine. A randomised control trial conducted in Australian emergency departments also found similar results [39]. Therefore, intranasal fentanyl and inhalational methoxyflurane seem to be the drugs of choice due to their ease of administration, rapid onset, short duration of action, effect and safety profile for children's pain relief in prehospital settings. However, it can be difficult to administer inhalational methoxyflurane in non-cooperative children and in cases involving facial trauma. Similarly, contraindications for nasal drug administrations could be a limitation to administering intranasal fentanyl.

Morphine (IV) was identified in the present systematic analysis as an effective analgesic drug, but the safety of the drug was not evaluated in any of the studies included in this review. This is supported by previous results, and IV morphine has traditionally been reported as the gold standard drug for acute pain relief in acute care settings [40, 46, 47]. Furthermore, the findings support that analgesic doses of ketamine (IV/IM) are safe to use in acute care settings [48,49,50]. Although we could not find any studies that address the effectiveness of ketamine for the purpose of this review, previous studies have identified ketamine as an effective analgesic drug in acute care settings [48,49,50]. However, difficulties concerning IV access, anxiety related to painful IM injection and prolonged prehospital time are obvious limitations in IV/IM morphine and ketamine administration in the prehospital pain management of children [13, 40, 41].

The current review did not identify any serious adverse events from the analgesic drugs included in the studies. However, previous studies have demonstrated that opioids (morphine and fentanyl) have adverse events such as respiratory depression, apnoea, sedation, bradycardia and gastrointestinal dysmotility [51, 52]. There is also a fear of sedation, respiratory depression, renal and hepatic failure related to methoxyflurane use [53, 54]. In addition, Ketamine has dose-dependent adverse events such as sedation, hypoxia, laryngospasm, hypersalivation, nausea and vomiting [55, 56]. Hence, to minimise the potential risk due to these adverse events, opioids, methoxyflurane and ketamine should always be administered with caution. Naloxone for an opioid antagonist and/or airway opening and ventilatory devices should always be ready on hand [57].

Limitations of the included studies and the current review

Most of the studies included in this review were based on retrospective chart reviews. Poor data recording, underreport biases and selection biases are the major challenges of such designs. The training level, scope, and expertise of the care providers could also vary accordingly. It is unclear whether such variations would affect the effectiveness and safety of the included drugs. It would be good to study this in the future research.

Our systematic review has some limitations. Firstly, the systematic literature searches were limited by publication year (the past 20 years from 2000 to 2020) and language (English, Danish, Norwegian or Swedish). This was due to the purpose of having current pharmacological prehospital pain management modalities and due to the authors’ language capabilities and expenses. Secondly, the corresponding authors of four of the included studies [32, 34, 36, 37] did not respond to requests for further information when contacted.

Except in combination with opioids, the authors were not able to find studies that examine the effectiveness and safety of any other common analgesic drugs such as acetaminophen and Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), which could be given for mild to moderate pain [43, 51, 52]. We were also unable to find studies related to the effects and safety of prehospital use of nitrous oxide (Entonox) and nerve block drugs in children.

Conclusions

Our systematic review revealed that fentanyl (intranasal/IV), morphine (IV), methoxyflurane (inhalational) and combination drugs are effective analgesic drugs for children in prehospital settings. No serious adverse events were reported in the administration of intranasal fentanyl, inhalational methoxyflurane or IV/IM ketamine. Intranasal fentanyl and inhalational methoxyflurane seem to be the preferred drugs for children in pre-hospital settings due to their ease of administration, similar effect and safety profile when compared to other analgesic drugs. However, caution must be shown in reaching this conclusion since the included studies’ level of evidence (LOE) was level three and four only.

This systematic review found that there is a paucity of high-level evidence on children’s prehospital pain management. Furthermore, all of the studies included were conducted solely from the perspectives of high-income countries. Well-designed comprehensive studies that include the context of low- and middle-income countries should also be conducted. In addition to single analgesic drugs, multimodal analgesia also needs further analysis in future studies of prehospital pain management in children.

Availability of data and materials

All data generated or analysed during this study are included in this published article.

Abbreviations

CINAHL:

Cumulative Index of Nursing and Allied Health Literature

CPDs:

Continuing Professional Developments

DIKU:

Norwegian Agency for International Cooperation and Quality Enhancement in Higher Education

ED:

Emergency Department

Embase:

Excerpta Medica Database

FDA:

Food and Drug Administration

IHM:

Inhalational Methoxyflurane

IM:

Intramuscular

INF:

Intranasal Fentanyl

IV:

Intravenous

JBI:

Joanna Briggs Institute

LOE:

Level of Evidence

Medline:

Medical Literature Analysis and Retrieval System Online

MeSH:

Medical Subject Headings

NORPART:

Norwegian Partnership Programme for Global Academic Cooperation

NSAIDs:

Non-steroidal Anti-inflammatory Drugs

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-analyses

PROSPERO:

International Prospective Register of Systematic Review

References

  1. KD Friesgaard 2018 Acute pain in the prehospital setting: a register-based study of 41.241 patients Scandinavian J Trauma Resuscit Emergency Med 26 1 53

    Google Scholar 

  2. J Turner 2013 What outcome measures should be developed for pre-hospital care? Results of a consensus event Prehospital Disaster Med 28 Supp. 1 S89 S89

    Google Scholar 

  3. R Pagnamenta JR Benger 2008 Factors influencing parent satisfaction in a children’s emergency department: prospective questionnaire-based study Emerg Med J 25 7 417

    PubMed  CAS  Google Scholar 

  4. M Galinski 2010 Prevalence and management of acute pain in prehospital emergency medicine Prehospital Emerg Care 14 3 334 339

    Google Scholar 

  5. A Murphy 2016 A prevalence and management study of acute pain in children attending emergency departments by ambulance Prehosp Emerg Care 20 1 52 58

    PubMed  Google Scholar 

  6. B Lord M Woollard 2011 The reliability of vital signs in estimating pain severity among adult patients treated by paramedics Emerg Med J 28 2 147

    PubMed  Google Scholar 

  7. H Hennes MK Kim RG Pirrallo 2005 PREHOSPITAL PAIN MANAGEMENT Prehosp Emerg Care 9 1 32 39

    PubMed  Google Scholar 

  8. R Pilbery J Miles F Bell 2019 A service evaluation of paediatric pain management in an English ambulance service Bt Paramedic J 4 2 37

    Google Scholar 

  9. N Watkins 2006 Paediatric prehospital analgesia in Auckland Emerg Med Austral 18 1 51 6

    Google Scholar 

  10. B DeBruyne 2014 Emergency medical services provider comfort with pre-hospital analgesia administration to children Can J Emerg Med 16 S52 S53

    Google Scholar 

  11. DM Williams 2012 Barriers to and enablers for prehospital analgesia for pediatric patients Prehosp Emerg Care 16 4 519 526

    PubMed  Google Scholar 

  12. KM Adelgais K Brown 2014 Pediatric prehospital pain management: impact of advocacy and research Clin Pediatric Emerg Med 15 1 49 58

    Google Scholar 

  13. SH Thomas S Shewakramani 2008 Prehospital trauma analgesia J Emerg Med 35 1 47 57

    PubMed  Google Scholar 

  14. R Sinatra 2010 Causes and consequences of inadequate management of acute pain Pain Med 11 12 1859 1871

    PubMed  Google Scholar 

  15. WT Zempsky NL Schechter 2003 What's new in the management of pain in children Pediatrics Rev 24 10 337 347

    Google Scholar 

  16. SJ Weisman B Bernstein NL Schechter 1998 Consequences of inadequate analgesia during painful procedures in children Arch Pediatrics Adolescent Med 152 2 147 149

    CAS  Google Scholar 

  17. JT Pate 1996 Childhood medical experience and temperament as predictors of adult functioning in medical situations Children's Health Care 25 4 281 298

    Google Scholar 

  18. C Park 2010 Prehospital analgesia: systematic review of evidence BMJ Milit Health 156 Suppl 4 S295 300

    Google Scholar 

  19. N Samuel IP Steiner I Shavit 2015 Prehospital pain management of injured children: a systematic review of current evidence Am J Emerg Med 33 3 451 454

    PubMed  Google Scholar 

  20. GA Whitley R Pilbery 2019 Pre-hospital intranasal analgesia for children suffering pain: a rapid evidence review Bt Paramedic J 4 3 24

    Google Scholar 

  21. M Gausche-Hill 2014 An evidence-based guideline for prehospital analgesia in trauma Prehosp Emerg Care 18 sup1 25 34

    PubMed  Google Scholar 

  22. MJ Page 2021 PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews BMJ 372 160

    Google Scholar 

  23. Fredrik Hetmann TS, Kacper Sumera, Matt Holland, Yonas Abebe Tessema. Pediatric prehospital pain management; a systematic review. 2019 [cited 2021 May 11]; Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019126699.

  24. B Bulloch M Tenenbein 2002 Assessment of clinically significant changes in acute pain in children Acad Emerg Med 9 3 199 202

    PubMed  Google Scholar 

  25. (FDA), T.U.S.f.a.d.a. What is a Serious Adverse Event? 2016 [cited 2021 June 26]; Available from: https://www.fda.gov/safety/reporting-serious-problems-fda/what-serious-adverse-event.

  26. KP Grichnik FM Ferrante 1991 The difference between acute and chronic pain Mt Sinai J Med 58 3 217 20

    PubMed  CAS  Google Scholar 

  27. Covidence. Create and publish a data extraction template 2021 February 3, 2021 [cited 2021 May 28]; Available from: https://support.covidence.org/help/create-and-publish-a-data-extraction-template.

  28. Adelaide, T.U.o. JBI, critical appriasal tools 2020 [cited 2021 May 11]; Available from: https://jbi.global/critical-appraisal-tools.

  29. PT Morley 2009 Evidence evaluation worksheets: the systematic reviews for the evidence evaluation process for the 2010 International Consensus on Resuscitation Science Resuscitation 80 7 719 721

    PubMed  Google Scholar 

  30. FE Babl 2006 Inhaled methoxyflurane as a prehospital analgesic in children Emerg Med Austral 18 4 404 10

    Google Scholar 

  31. B Lord PA Jennings K Smith 2016 The epidemiology of pain in children treated by paramedics Emerg Med Austral 28 3 319 24

    Google Scholar 

  32. APH Karlsen 2014 Safety of intranasal fentanyl in the out-of-hospital setting: a prospective observational study Ann Emerg Med 63 6 699 703

    PubMed  Google Scholar 

  33. PA Jennings B Lord K Smith 2015 Clinically meaningful reduction in pain severity in children treated by paramedics: a retrospective cohort study Am J Emerg Med 33 11 1587 90

    PubMed  Google Scholar 

  34. IG Jacobs 2010 Health effects of patients given methoxyflurane in the pre-hospital setting: a data linkage study Open Emerg Med J 3 7 13

    Google Scholar 

  35. PP Bredmose 2009 Pre-hospital use of ketamine in paediatric trauma Acta Anaesthesiologica Scandinavica 53 4 543 545

    PubMed  CAS  Google Scholar 

  36. JC Bendall PM Simpson PM Middleton 2011 Effectiveness of prehospital morphine, fentanyl, and methoxyflurane in pediatric patients Prehosp Emerg Care 15 2 158 165

    PubMed  Google Scholar 

  37. AP Murphy 2017 Intranasal fentanyl for the prehospital management of acute pain in children Eur J Emerg Med 24 6 450 454

    PubMed  Google Scholar 

  38. G Savoia 2015 Italian Intersociety Recommendations on pain management in the emergency setting (SIAARTI, SIMEU, SIS 118, AISD, SIARED, SICUT, IRC) Minerva Anestesiol 81 2 205 225

    PubMed  CAS  Google Scholar 

  39. M Borland 2007 A randomized controlled trial comparing intranasal fentanyl to intravenous morphine for managing acute pain in children in the emergency department Ann Emerg Med 49 3 335 340

    PubMed  Google Scholar 

  40. Murphy A, et al. Intranasal fentanyl for the management of acute pain in children. Cochrane Database Syst Rev. 2014(10).

  41. ML Borland I Jacobs G Geelhoed 2002 Intranasal fentanyl reduces acute pain in children in the emergency department: a safety and efficacy study Emerg Med 14 3 275 280

    Google Scholar 

  42. F Coffey 2014 STOP!: a randomised, double-blind, placebo-controlled study of the efficacy and safety of methoxyflurane for the treatment of acute pain Emerg Med J 31 8 613 618

    PubMed  Google Scholar 

  43. Yousefifard M, et al. Pre-hospital pain management; a systematic review of proposed guidelines. Arch Acad Emerg Med. 2019;7(1).

  44. D Braude M Richards 2004 Appeal for fentanyl prehospital use Prehosp Emerg Care 8 4 441

    PubMed  Google Scholar 

  45. A Fabbri 2020 Role of inhaled methoxyflurane in the management of acute trauma pain J Pain Res 13 1547

    PubMed  PubMed Central  CAS  Google Scholar 

  46. C Rickard 2007 A randomized controlled trial of intranasal fentanyl vs intravenous morphine for analgesia in the prehospital setting Am J Emerg Med 25 8 911 917

    PubMed  Google Scholar 

  47. V Bounes 2008 Is there an ideal morphine dose for prehospital treatment of severe acute pain? A randomized, double-blind comparison of 2 doses Am J Emerg Med 26 2 148 154

    PubMed  Google Scholar 

  48. JE Svenson MK Abernathy 2007 Ketamine for prehospital use: new look at an old drug Am J Emerg Med 25 8 977 980

    PubMed  Google Scholar 

  49. K Porter 2004 Ketamine in prehospital care Emerg Med J 21 3 351 354

    PubMed  PubMed Central  CAS  Google Scholar 

  50. P Jennings P Cameron S Bernard 2011 Ketamine as an analgesic in the pre-hospital setting: a systematic review Acta anaesthesiologica scandinavica 55 6 638 643

    PubMed  CAS  Google Scholar 

  51. ST Verghese RS Hannallah 2010 Acute pain management in children J Pain Res 3 105

    PubMed  PubMed Central  CAS  Google Scholar 

  52. RD Blondell M Azadfard AM Wisniewski 2013 Pharmacologic therapy for acute pain Am Family Physic 87 11 766 772

    Google Scholar 

  53. WB Crandell SG Pappas A Macdonald 1966 Nephrotoxicity associated with methoxyflurane anesthesia J Am Soc Anesthesiol 27 591

    CAS  Google Scholar 

  54. P Tomlin 1965 Methoxyflurane Bt J Anaesthesia 37 9 706 709

    CAS  Google Scholar 

  55. N Vadivelu 2016 Role of ketamine for analgesia in adults and children J Anaesthesiol Clin Pharmacol 32 3 298

    PubMed  PubMed Central  CAS  Google Scholar 

  56. AM Burnett 2012 The emergency department experience with prehospital ketamine: a case series of 13 patients Prehosp Emerg Care 16 4 553 559

    PubMed  Google Scholar 

  57. PM Lago 2003 Analgesia and sedation in emergency situations and in the pediatric intensive care unit Jornal de pediatria 79 S223 S230

    PubMed  Google Scholar 

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Acknowledgements

The authors would like to thank Associate Professor Hilde Tinderholt Myrhaug and University Librarian Malene Wøhlk Gundersen, both of whom work at OsloMet, for their methodological advice and valuable suggestions on the search strategy.

Funding

The first author has received full funding from Oslo Metropolitan University (Norwegian Agency for International Cooperation and Quality Enhancement in Higher Education (DIKU/NORPART) project 2018/10182), Faculty of Health Sciences.

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The search strategy was developed by the four authors (YA, TS, FH and KS) who are the subject specialists, and was peer-reviewed by another author (MH) who is a research librarian. The last searches were rerun by the research librarian (MH). The study selection was conducted by the four authors (YA, TS, FH and KS), respectively. The risk of bias was assessed by FH, KS and YA. Data extraction was conducted by YA and TS. All authors were involved in the data synthesis. YA wrote the draft manuscript and TS, FH and KS revised it accordingly. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yonas Abebe.

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Abebe, Y., Hetmann, F., Sumera, K. et al. The effectiveness and safety of paediatric prehospital pain management: a systematic review. Scand J Trauma Resusc Emerg Med 29, 170 (2021). https://doi.org/10.1186/s13049-021-00974-3

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Keywords

  • Children
  • Paediatrics
  • Prehospital
  • Ambulance
  • Analgesia
  • Pain management
  • Fentanyl
  • Morphine
  • Methoxyflurane
  • Ketamine