Article, Pediatrics

Prehospital pain management of injured children: a systematic review of current evidence

a b s t r a c t

Objectives: Injury is a common cause of acute pain in children. The objective of this study was to analyze the available evidence in prehospital pain management of injured children.

Methods: The Patient/Population, Intervention, Comparator, and Outcome question was as follows: “In pediatric patients requiring Prehospital analgesia for traumatic injuries, what is the Level of evidence (LOE) available for the safety and efficacy of pharmacologic interventions?” The electronic databases MEDLINE/PUBMED, EMBASE, and Google Scholar were searched to identify all the relevant articles published in electronic journals, books, and scientific Web sites over the last 20 years. Studies were included if they reported on Prehospital use of analgesics in injured children. Reviews, editorials, and surveys were excluded.

Results: Nineteen studies met the inclusion criteria. Thirteen were pediatric studies and 6 were studies of both adults and children. Nine were nonrandomized studies with concurrent controls (LOE-2), and 10 were retrospective case series and chart reviews (LOE-4). A measurable effect of analgesia was consistently found when analgesics were provided en route to the hospital; however, most studies reported a relatively low rate of analgesic use.

Conclusions: Only a few studies examined the efficacy of pediatric prehospital analgesia. Fentanyl at a dose of 1 to 3 ug/mg seems to have an accepted efficacy. The current level of evidence is insufficient to assess the safety profile of analgesics. The findings of this study suggest that the analgesic treatment of injured children in the prehospital setting is suboptimal.

(C) 2014

Introduction

Relief of acute pain in children is increasingly recognized as an im- portant and integral part of emergency care [1]. In prehospital settings, injuries are the most common cause of pain in children and should be treated appropriately [2]. Acute traumatic pain, when inadequately treated, has been found to have both immediate and long-lasting effects [3]. Emergency medical services (EMS) personnel report that the major challenges preventing or delaying the relief of acute pain during initial treatment include an inability to assess pain and fasting times, and a limited choice of agents and delivery routes. Variability in provider education and different beliefs have also been mentioned as barriers

? Disclosures: There was no specific funding source or dedicated financial support for this study. No author has any conflict of interest to declare. No honorarium, grant, or other form of payment was given to anyone to produce the article. The authors have not published or submitted any related papers from the same study. The corresponding author (NS) had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

* Corresponding author. Pediatric Emergency Department, Rambam Health Care Campus, 6 Ha’Aliya Street, Haifa 31096, Israel. Tel.: +972 4 8542522.

E-mail address: [email protected] (N. Samuel).

to providing this treatment, and they are potential areas of intervention [4,5]. These challenges, although present in the emergency department (ED), are even more pronounced in the prehospital setting and more marked in pediatric patients than in adults [6].

In recent years, a few initiatives sought to develop treatment guidelines for acute pediatric pain [1,7,8]. All mentioned a lack of high-level evidence and a need for further research in prehospital pain management [9]. Current guidelines and reviews of prehospital pediatric care refer to evidence found in adult studies or from studies performed in EDs. This extrapolation may be necessary, yet it carries inherent limitations, due to significant differences in setting and provider profiles.

The purpose of this review was to analyze the current level of evidence (LOE) in prehospital pain management of injured children, focusing on the safety and efficacy of prehospital analgesia.

Methods

This review was conducted in accordance with the International Liaison Committee on Resuscitation 2010 evidence evaluation process [10]. Review of the search strategy and findings was conducted by the three authors of the article.

http://dx.doi.org/10.1016/j.ajem.2014.12.012

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452 N. Samuel et al. / American Journal of Emergency Medicine 33 (2015) 451454

Patient/Population, Intervention, Comparator, and Outcome question

The review sought to identify evidence to answer the following Patient/Population, Intervention, Comparator, and Outcome (PICO) question: “In pediatric patients requiring prehospital analgesia for trau- matic injuries, what is the LOE available for the safety and efficacy of pharmacologic interventions?”

Search strategy

The electronic databases MEDLINE/PUBMED and EMBASE were searched for articles in the English language from 1995 to 2014. Search terms included (“pain management” or “pain” or “acute pain” or “analge*” or “morphine” or “fentanyl” or “ketamine” or “nitrous” or “opiate”) AND (“pre-hospital” or “emergency medical services” [MeSH Major Topic] or “emergency treatment” [MeSH Major Topic] or “emer- gency care” [MeSH Major Topic]). The Internet search engine Google Scholar was also searched, using the same search terms. The goal was to identify all relevant articles published in electronic journals, books, and scientific Web sites.

Studies were included only if they reported on injured children and the use of analgesic agents in the prehospital setting, and if they assessed safety and/or efficacy of analgesic agents in the prehospital setting. Studies examining medication administration rates, regarded as a parameter of efficacious treatment, were also included. Reviews, editorials, surveys, and case reports were excluded. Articles addressing management in the ED were also excluded. The references of the excluded articles were reviewed by two authors to ensure that relevant articles were not missed.

Evidence appraisal

Review process“>Studies were reviewed and classified by LOE for studies of therapeu- tic interventions (Table 1) [10].

Review process

The review process had three steps. First, all articles yielded by the search were reviewed by two authors. Studies that met criteria for further review were sent to all three authors who were asked to prepare independent drafts examining the PICO question. Once this step had been completed, the three authors met, and any disagreement was discussed. The final draft was agreed upon by all three authors.

Results

The search yielded 2404 articles. Nineteen studies met the inclusion criteria (Table 2). Of these, 13 were dedicated pediatric studies and 6 were studies of both adults and children. Of the 19 studies, 9 were LOE-2 (nonrandomized, concurrent controls) and 10 were LOE-4 (retrospective case series and chart reviews). (Figure)

Table 1

International Liaison Committee on Resuscitation LOE for therapeutic interventions [10]

LOE-1 Randomized controlled trials

(or meta-analyses of randomized clinical trials)

LOE-2 Studies using concurrent controls without true randomization (eg, pseudorandomized) or meta-analyses of such studies)

LOE-3 Studies using retrospective controls

LOE-4 Studies without a control group (eg, cases series)

LOE-5 Studies not directly related to the specific patient/population

(eg, different patient/population, animal models, mechanical models)

Efficacy

Five studies evaluated Analgesic efficacy [11-15]. Efficacy was defined as a measurable reduction in pain upon the administration of analgesics. Pain was measured using standard pain scales. Pain and reduction of pain were self-reported by verbal children and judged by the provider or parent for younger, nonverbal children. Three studies were pediatric, and 2 included mixed adult and Pediatric populations. One study was a prospective cohort, and the 4 others were retrospective case series. Two LOE-2 studies examined efficacy of analgesia. Opioids were included in both studies (Table 2) [13,15].

A combined adult and pediatric Helicopter EMS study found that a minimum dose of 2 ug/kg of fentanyl was associated with signif- icantly greater pain relief than lower doses [11]. This was the only study to evaluate incremental dose-dependent reduction of pain. Another HEMS study reported good response to Intravenous fentanyl at a dose of 1 to 3 ug/kg with a maximum dose of 5 ug/kg in non-intubated, in- jured children [12]. A study comparing Intranasal fentanyl in fixed, age-dependent doses, Intravenous morphine (0.1 mg/kg), and inhaled methoxyflurane found that morphine and fentanyl were equally effec- tive. Methoxyflurane was inferior in providing effective analgesia. Effec- tive analgesia was defined as a reduction in pain score of 30% or greater [13]. However, another study found that methoxyflurane had a signifi- cant effect on pain reduction as assessed by provider and parents [14]. A French cohort of a physician-staffed EMS examined the efficacy of paracetamol, morphine, nalbuphine, a 50:50 mixture of Nitrous oxide and oxygen, and a combination of drugs. Findings of this study revealed that, on arrival to the hospital, 67% of the children were still in pain, and 84% had experienced “some” pain relief. No significant differences were

found between agents [15].

Safety

Safety was defined as based on the rate of adverse cardiovascular or respiratory events requiring intervention upon the administration of analgesics. Additional adverse events included desaturation and hypo- tension occurring after administration of drugs, regardless of the need for intervention. Five LOE-4 studies, 3 exclusively pediatric, evaluated safety parameters. In a retrospective case series study of 164 children treated with ketamine intravenously or intramuscularly for traumatic injuries, there were no reported adverse cardiovascular or respiratory events [16]. The concomitant use of midazolam in 68% of cases main- tained a similar safety profile. Another small study reported no adverse events when ketamine was used during air transport. [17].

Two HEMS studies of fentanyl administration showed no significant differences in systolic blood pressure before and after administration. There were no cases of post-administration decline in blood pressure in any of the non-intubated patients, and only one case of a decline in blood pressure in an intubated 17-year-old with a severe head injury. Fentanyl administration did not significantly affect the oxygen satura- tion of non-intubated patients. There was a single case of a decline in saturation from 95% to 93% [12,18].

Inhaled methoxyflurane was used without any serious adverse events. Milder symptoms such as drowsiness, agitation, and deep seda- tion, especially in young children, were noted in up to 36% of cases [14].

Medication administration rates

Twelve studies, 8 of which were LOE-2, provided information on medication administration rates. It is important to note that appraisal of administration rates is dependent on the accuracy of pain documen- tation, which may sometimes be incomplete. Lerner et al [2] performed a retrospective analysis of the epidemiology and treatment of 55,642 children treated by the Pediatric Emergency Care Applied Research Network-affiliated EMS agencies. Twenty-six percent of children were transported due to traumatic injury, and an additional 16.1% cited

N. Samuel et al. / American Journal of Emergency Medicine 33 (2015) 451454 453

Table 2

Evidentiary table

Study (reference number)

Design (LOE)

Agents

Outcome measures

No. of pediatric patients

No. of patients younger than 5y

Studies of pediatric patients

Bendall et al [13] 2011

Retrospective comparative study [2]

Morphine, fentanyl, methoxyflurane

Efficacy

3312

Excluded

Johnson et al [26] 2014

Retrospective comparative study [2]

Mainly morphine and fentanyl

Administration rates

5057

NM

O’Donnell et al [25] 2013

Retrospective case control [2]

Fentanyl

Administration rates

946

218

Rogovik et al [21] 2007

Prospective cohort [2]

Acetaminophen, ibuprofen, opioids

Administration rates

310

48

Galinski et al [15] 2011

Prospective cohort [2]

Opiod/non-opiod

Administration rates, efficacy

258

155

Swor et al [20] 2005

Retrospective case controlled [2]

ND

Administration rates

73

4

Watkins [23] 2006

Prospective cohort [2]

Morphine, entonox

Administration rates

45

10

Lerner et al [2] 2014

Retrospective chart review [3]

ND

Administration rates

55642

18906

Izsak et al [19] 2008

Retrospective chart review [3]

ND

Administration rates

696

NM

Barker et al [27] 2014

Retrospective cohort [3]

Fentanyl, ketamine

Administration rates

349

NM

Bredmose et al [16] 2009

Retrospective cohort [3]

Ketamine, midazolam

Safety

164

50

Devellis et al [18] 1998

Retrospective chart review [3]

Fentanyl

Safety

131

NM

Babl et al [14] 2006

Prospective cohort [3]

Methoxyflurane

Efficacy, safety

105

15

Studies of combined adult and pediatric patients

Fullerton-Gleason et al [28] 2002

Retrospective case control [2]

Morphine

Administration rates

30

NM

Bendall et al [24] 2011

Retrospective comparative study [2]

Morphine, fentanyl, methoxyfluarne

Administration rates

NM

NM

White et al [22] 2000

Retrospective chart review [3]

Morphine, nitrous oxide

Administration rates

142

14

Svenson et al [17] 2007

Retrospective cohort [3]

Ketamine

Safety

NM

NM

Thomas et al [12] 2005

Retrospective cohort [3]

Fentanyl

Efficacy, safety

27

NM

Frakes et al [11] 2006

Retrospective cohort [3]

Fentanyl

Efficacy

NM

NM

Abbreviation: NM, not mentioned.

various painful conditions as their chief complaint. Analgesia was given to only 0.3% of children. This recent study is the largest to date on pediatric prehospital care. Another study reviewed the charts of 696 EMS cases and found that pain was noted in 446, yet analgesia was administered to only 15 (3.3%) [19]. A study of children with extremity fracture or burns found an administration rate of 21%, significantly lower than in adult matched controls [20]. A Canadian pediatric study that compared patients with extremity fractures to patients with soft tissue injuries reported that 37% of the children with fractures receivED analgesia, but only 3.2% of this group received opioids [21]. Time to medication was shorter for patients with suspected fractures. In a different cohort of 1000 adults and children with suspected extremity fractures, 2.1% of children received analgesia, a rate slightly higher than in adults. None of the children younger than 5 years received analgesia [22]. Another study with a similar patient population found a significant age bias disfavoring children younger than 5 years [23].

An Australian study comparing intravenous morphine, intranasal fentanyl, or inhaled methoxyflurane found children were less likely to receive opiate analgesia than adults [24]. Once administered, intranasal fentanyl was preferred to intravenous morphine. When fentanyl intra- nasal and intravenous administration rates were compared, a nonsignif- icant trend was shown to favor Intranasal administration [25]. A retrospective cross-sectional data analysis of 5057 children transported

by HEMS found an overall analgesia administration rate of only 14.6%. Younger age, lack of intravenous access, and transport from the scene as opposed to interfacility transport were all associated with an even lower administration rate of analgesia [26].

In another report of severely injured children transported by heli- copter, parenteral analgesia with ketamine or fentanyl was provided in 15% of cases. Peripheral nerve block was also selectively used [27]. Galinski et al [15] reported a strikingly higher administration rate of analgesia (92%). This could be attributable to the fact that EMS units participating in this study were mobile intensive care units staffed by physicians. Another study showed that a change in EMS protocol result- ed in higher morphine administration rates and a shorter time from arrival at the scene to the first dose of morphine [28]. This suggests the potential for protocol-driven interventions, similar to those in other areas of emergency and prehospital care.

Children younger than 5 years

The largest study to date of pediatric epidemiology encountered by prehospital EMS teams suggested that approximately a quarter of cases are small children [2]. Most studies defined small children as chil- dren younger than 5 years. Eleven studies provided information about this age group (Table 2). The study by Watkins [23] reported that 5

Figure. Flow chart of studies through Selection process.

454 N. Samuel et al. / American Journal of Emergency Medicine 33 (2015) 451454

years of age was a cutoff value for undertreatment of smaller children. It suggests that provider perception is a barrier to adequate analgesia.

Discussion

Efficacy

The current evidence (LOE-2) seems to show that fentanyl in a dose of 1 to 3 ug/kg has an accepted efficacy for the treatment of injured children in the prehospital setting. A potential for fentanyl using the nasal route has been recently highlighted in a Cochrane review [29]. Comparing the efficacy of other medications cannot be based on the current evidence; however, a measurable effect of analgesia has been consistently shown when analgesics were provided en route to the hospital (LOE-2 and LOE-4).

Safety

Studies evaluating the safety profile of pediatric prehospital analge- sia did not report any cases of adverse events requiring intervention (LOE-4). However, because of the retrospective nature of the evidence and the potential for underreporting biasing results, the current LOE is insufficient to assess the safety profile of analgesics provided to injured children in the prehospital setting.

Medication administration rates

Most studies reviewed above displayed a low rate of analgesic use in children, indicating that a substantial portion of children in moderate to severe pain are not treated with proper analgesia. This may be due to in- complete or inaccurate pain assessment, lack of provider training and exaggerated fears of adverse events (LOE-2 and LOE-4).

Children younger than 5 years

Evidence suggests an age bias disfavoring small children. The same factors biasing the treatment of children as compared to adults, men- tioned above, may be more pronounced in small children. An age bias may also affect research endeavors since, in combined adult and pediat- ric studies, small children are underrepresented or not identified and, in some cases, were excluded.

Conclusions

Only a few studies examined the efficacy of pediatric prehospital analgesia. Pediatric prehospital analgesia seems effective and has a measurable effect. Fentanyl in a dose of 1 to 3 ug/mg seems to have an accepted efficacy. The current LOE is insufficient to assess the safety pro- file of analgesics. The findings of this study suggest that the analgesic treatment of injured children in the prehospital setting is suboptimal.

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