Description of the condition
Femoral fracture (broken thigh bone) in children is an uncommon but serious injury (Rockwood 2006). Rewers 2005 found the majority (62.5%) of these fractures occur in the long central portion (or shaft) of the femur. Two studies conducted in the USA found an annual incidence of femoral shaft fractures of 19 per 100,000 children (Hinton 1999), and an annual incidence of all femoral fractures of 26 per 100,000 children (Rewers 2005). Male toddlers and teenagers are at highest risk of these injuries, while girls have a lower incidence than males for all age groups (Hinton 1999; Rewers 2005).
Children and adolescents with femoral fractures are almost always admitted to hospital for management of their injuries (Chu 2003; Hinton 1999; Rewers 2005). They invariably start their hospital experience in the Emergency Department (ED), often requiring transfer to a tertiary (specialist) children's hospital. Pain management is a crucial primary need of such children. They require analgesia or anaesthesia to facilitate obtaining radiographs as well as for the definitive management of their fractures. The initial care process involves from two to six transfers from stretcher to stretcher/ imaging/ operating suite table or hospital bed in the first few hours of care (Ronchi 1989).
Description of the intervention
Options for analgesia (pain relief) in the pre-hospital or Emergency Department setting include i) systemic oral or intravenous/intramuscular (parenteral) narcotics (such as morphine), ii) parenteral sedatives/anaesthetics (such as ketamine or propofol) or iii) local/regional anaesthetics (such as a femoral nerve or fascia iliaca compartment block with bupivacaine).
Femoral nerve block involves infiltration (injection) of local anaesthetic around the femoral nerve, which lies in a bundle next to the femoral artery and vein at the top of the thigh. Femoral nerve blocks are used both in the emergency setting and pre- or post-operatively for pain management of femoral fractures in all ages (Denton 1988; Johnson 1994; Mutty 2007; Schiferer 2007; Stewart 2007; Tobias 1994). Femoral nerve block was first described for pain management of paediatric femoral fractures several decades ago (Grossbard 1979).
Fascia iliaca compartment block involves injecting a large volume of local anaesthetic into an area beneath the connective tissue (fascia) at the top of the leg. This blocks three nerves - the femoral, obturator and lateral cutaneous nerves of the thigh - thus providing complete anaesthesia for the whole femur (Wathen 2007). The position of the injection site is such that nerve injury and accidental injection into blood vessels are theoretically avoided (Foss 2007).
How the intervention might work
In essence, nerve blocks prevent pain by blocking the passage of electrical impulses, that are prompted by a painful stimulus, along a nerve to the brain. Pain messages are transmitted to the brain through electrical impulses, arising from nerve endings, which pass along the nerves by the flow of charged ions (e.g. sodium) through channels in the nerve cell membranes. Local anaesthetics such as bupivicaine and ropivicaine work through the (reversible) inhibition of the voltage sensitive ion channels, such that sodium (an ion) no longer flows through the channel, preventing impulse generation (Cousins 1998; Foster 2000; Simpson 2005). At high enough levels of ion channel blockade, sensory information (pain) does not get to the central nervous system (the brain).
The theoretical advantages of regional anaesthesia for femoral fracture pain management include faster time to pain relief (McGlone 1987; Ronchi 1989), better pain relief, and avoidance of complications associated with systemic analgesics. The latter include respiratory depression, sedation and confusion (Bhatt 2009; Pena 1999), which can also interfere with the assessment of the patient's neurological status.
Potential complications associated with nerve blocks include accidental intravascular (into a blood vessel) injection, with the potential for medication-related effects such as cardiac depression and seizure, and neurological complications. In a large prospective series of regional anaesthetics, femoral nerve blocks were found to have a low rate of serious complications (2.9 episodes of peripheral neuropathy/10,000 blocks) with no cardio-respiratory complications or deaths (Auroy 2002). Delayed diagnosis of compartment syndrome is thought to be a potential complication of nerve blocks (Hyder 1996; Olsen 2005). Compartment syndrome occurs when the bleeding from a fracture causes too much pressure on the muscles and blood vessels in the area, cutting off delivery of oxygen to the muscles and causing damage. One of the symptoms of compartment syndrome is pain.
The efficacy of femoral nerve block is likely to be greater for children with mid-shaft fractures (compared with proximal third or distal third) because the femoral nerve provides the main sensory supply for this region (Tondare 1982).
Why it is important to do this review
Good pain management is one of the primary goals of paediatric injury care, especially with such a major injury as a femoral fracture. There is considerable variation in practice around the world in the early pain management for femoral fractures. While femoral nerve block is common in some countries (Australia (Chu 2003) and UK (Pennington 2011)), it is uncommon in the emergency setting in North America (Angelski 2010), where intravenous analgesia is generally used. There is a clear need for a systematic review of the evidence in order to inform the clinical practice in this area.
To assess the effects (benefits and harms) of femoral nerve or fascia iliaca compartment block for initial pain management of children with fractures of the femur. Nerve blocks can be provided in either the pre-hospital or in-hospital emergency setting, and with or without systemic analgesia.
Criteria for considering studies for this review
Types of studies
Randomized controlled trials and quasi-randomized (method of allocating participants to a treatment which is not strictly random; e.g. by date of birth, hospital record number, alternation) controlled trials assessing the effects of femoral nerve or fascia iliaca compartment block for initial pain management in children with fractures of the femur will be included.
Types of participants
Children aged 18 and under with an acute femoral fracture receiving pre-hospital or in hospital emergency care will be included. Diagnosis can be clinical with radiographic confirmation after enrolment.
Types of interventions
Femoral nerve or fascia iliaca compartment block by injection: this can be on its own or in combination with systemic (oral or intranasal or parenteral: intramuscular or intravenous) narcotic or non-narcotic (e.g. NSAID) analgesia and/or other non-medication methods of analgesia (e.g. sucrose, breast-feeding, distraction, hypnosis, and traction). The method of nerve location, such as ultrasound guidance or neurostimulation, will be recorded.
We aim to make two comparisons:
- Femoral nerve or fascia iliaca compartment block versus placebo (sham) or no injection, where all participants receive another method of analgesia (e.g. systemic analgesia).
- Femoral nerve or fascia iliaca compartment block versus systemic analgesia.
Types of outcome measures
- Failure of analgesia (for instance, failure to achieve a pain score of less than 4/10 on a Visual Analog Scale (VAS) or equivalent by 30 minutes). The CHEOPS (McGrath 1985), FLACC (Manworren 2003;Merkel 1997) and Faces (Bieri 1990) or FPS-R (Hicks 2001) pain scales are examples of other tools used in younger children.
- Pain level during procedures (e.g. imaging, reduction of fracture, application of traction or other immobilization) and transfers up to eight hours post intervention.
- Adverse outcomes related to method of analgesia (up to 48 hours after enrolment):
- Femoral nerve block
- Intravascular injection with medication related effects such as cardiac depression, arrhythmia or seizure
- Delayed diagnosis of compartment syndrome
- Injury to femoral nerve or artery
- Need for rescue medication related to complications
- Peripheral neuropathy/prolonged anaesthesia or paraesthesia
- Haematoma at injection site
- Infection at injection site
- Other unanticipated complications
- Comparison medications
- Respiratory depression
- Need for additional cardio-respiratory intervention
- Delayed diagnosis of neurologic deterioration in affected limb (i.e. loss of sensation or motor paralysis in the leg below the level of injury, compartment syndrome)
- Prolonged sedation
- Infection at IV site/phlebitis (inflammation of blood vessel)
- Other unanticipated complications
- Time to pain relief in minutes (clinically significant reduction in pain score (amount considered significant may vary depending on tool used - reduction in VAS score of > 13 mm (100 mm scale))
- Duration of pain control (assessed up to eight hours post presentation to health care facility);
- Need for additional pain control (systemic analgesia or repeated injection for nerve block) prior to immobilization or until eight hours after intervention
- Pain, discomfort and distress during application of analgesia (intravenous insertion, intramuscular injection, intranasal spray, nerve block injection)
- Patient and/or parental satisfaction
- Use of resources (time in emergency setting, costs associated with analgesia)
Search methods for identification of studies
We will search the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (to present), the Cochrane Central Register of Controlled Trials (The Cochrane Library current issue), MEDLINE (1950 to present), EMBASE (1974 to present) and Google Scholar. Registries of clinical trials (e.g. clinicaltrials.gov and the WHO International Clinical Trials Registry Platform) will be reviewed to identify ongoing and recently completed trials, with authors being contacted to determine relevance as necessary. All languages will be included.
In MEDLINE (Ovid Online), the subject-specific search will be combined with the sensitivity-maximizing version of the Cochrane Highly Sensitive Search Strategy for identifying randomized trials (Lefebvre 2011). Search strategies for The Cochrane Library and MEDLINE can be found in Appendix 1.
Searching other resources
We will handsearch potential high-yield journals to identify eligible reports of trials (e.g. emergency medicine, orthopaedic and anaesthesia journals). In addition, we will search reference lists of articles and authors of relevant papers will be contacted regarding any further published or unpublished work.
Data collection and analysis
Selection of studies
Reference management software will be used to merge and remove duplicates in search results. Two review authors (KB and NM) will independently screen all the citations identified by the search to identify potentially eligible studies. Full text reports will be sought for potentially eligible studies, before independent study selection by the above two authors. Disagreements will be resolved by discussion and involvement of a third author if necessary. Where necessary, we will attempt to contact trial authors for clarification of study methods and characteristics to establish eligibility.
Data extraction and management
Two authors (KB and JH) will independently extract information on study characteristics and results using a pre-piloted form. Missing or unclear trial details and data will be noted on the data extraction form. Any disagreements will be resolved by discussion between the two authors and if necessary, additional team members will be consulted.
Assessment of risk of bias in included studies
Two authors (KB and CB) will review the included studies for risk of bias in seven specific areas: sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessors, incomplete outcome data, selective outcome reporting and 'other issues' (including inappropriate administration of an intervention or co-intervention), as outlined in section 8.5 of the Cochrane Handbook (Higgins 2011). A consensus will be reached among the review team for any differences in risk of bias ratings between reviewers. Quality assessment will follow the Grade approach with four levels of quality (GRADE 2004).
Measures of treatment effect
Risk ratios with 95% confidence intervals will be calculated for dichotomous outcomes. Mean differences with 95% confidence intervals will be calculated for continuous outcomes. Standardised mean differences (SMD) and 95% confidence intervals will be calculated when combining results from studies using different measurement scales for the same outcome.
Unit of analysis issues
We anticipate that the unit of randomisation in trials testing nerve blocks will be the individual patient. Unit of analysis issues relating to multiple observations of the same outcome, in particular pain, are likely (Dexter 1995). We will extract data at clinically relevant time points and perform separate analyses for these (Philip 1990).
Dealing with missing data
Where necessary we will approach corresponding authors of trials for missing information and data. Where appropriate, we will perform intention-to-treat analyses to include all people randomised to the intervention groups. We will be alert to the potential mislabelling or non identification of standard errors and standard deviations. Unless missing standard deviations can be derived from confidence interval data, we will not assume values in order to present these in the analyses.
Assessment of heterogeneity
The chi² test and I² test (Higgins 2003) will be used to assess statistical heterogeneity together with visual inspection of the forest plot. Where there is statistically significant heterogeneity (chi² < 0.1), considerable or substantial heterogeneity (I² ≥ 75%), we will consider not pooling the data in a meta-analysis.
Assessment of reporting biases
Where there are sufficient numbers of trials (10 or more), we will generate funnel plots of the size of the treatment effect against the precision of the trial (1/standard error) to assess for publication bias. Should asymmetry exist, the "trim and fill" method described by Sutton 2000 will be used to calculate an adjusted overall confidence interval. Because there are other reasons for an asymmetric funnel plot, we will look for evidence of poor methodological quality of poor studies, true heterogeneity or chance as possible causes (Egger 1997).
Where appropriate from a clinical perspective, data from comparable trials will be pooled. Initially we will use the fixed-effect model and 95% confidence intervals. We will also consider using the random-effects model, especially where there is unexplained heterogeneity.
Subgroup analysis and investigation of heterogeneity
Subgroup analyses will be performed to explore potential sources of heterogeneity. Variables considered for subgroup analysis include:
Patient-related subgroup analyses
i) Age groups (0 to 3 years, 4 to 12 years and 13 to 18 years)
ii) Mid-shaft fracture versus non-mid-shaft fracture
iii) High energy fracture (e.g. comminuted fracture from a motor vehicle collision) versus low energy (e.g. from a simple fall)
Intervention-related subgroup analyses
iv) Ultrasound-guided versus nerve stimulation-guided versus landmark-guided block
v) Short acting versus long acting anaesthetic
v) Femoral nerve versus fascia iliaca compartment block
We will investigate whether the results of subgroups are significantly different by inspecting the overlap of confidence intervals, and performing the test for subgroup differences available in RevMan.
Where possible, we plan sensitivity analyses examining various aspects of trial and review methodology, including the effects of missing data, inclusion of trials at high risk of bias (specifically from lack of allocation concealment, assessor blinding), those using traction as a co-intervention, and inclusion of trials only reported in abstracts. We will look at including studies with and without narcotic comparator medications, a different time cut-off for the primary outcome (10 minutes) as well as a different pain score cut-off (< 3 or equivalent). We will examine the robustness of the fixed-effect results by checking these using the random-effects model.
'Summary of findings' tables
Where there are sufficient data, the results for the two main comparisons described in the Types of interventions will be summarised in 'Summary of findings' tables. We shall use the GRADE approach to assess the quality of evidence related to each of the primary outcomes listed in the Types of outcome measures (section 12.2, Higgins 2011).
Lindsey Elstub, Joanne Elliott, Vrisha Madhuri and Helen Handoll all provided constructive guidance and editing for which we are grateful.
We thank Darlene Chapman (Librarian) and Joanne Elliott (Trials Search Co-ordinator) for their assistance in designing the search strategies. We thank Jill Hayden, Janet Curran and Amy Plint for their advice on aspects of the protocol.
Appendix 1. Search strategies
The Cochrane Library (Wiley Online Library interface)
#1 MeSH descriptor Femur
#2 MeSH descriptor Nerve Block
#3 (#1 AND #2)
#4 MeSH descriptor Fractures, Bone explode all trees
#5 (#3 AND #4)
#6 (fem* near/2 fracture*):ti,ab
#7 (fem* near/2 Nerve Block*):ti,ab
#8 (#6 AND #7)
#9 (#5 OR #8)
MEDLINE (Ovid interface)
1 Femoral Fractures/
2 ((femur$ or femoral or thigh$) adj4 fracture$).tw.
3 1 or 2
4 Analgesia/ or exp Analgesics/
5 Anesthesia, Local/ or Nerve Block/
6 ((an?esthet$ or an?esthesia) adj4 (regional$ or local$)).tw.
7 ((nerv$ or femoral or fascia iliaca) adj1 block$).tw.
9 exp Pediatrics/
10 adolescent/ or exp child/ or exp infant/
11 (neonate$ or newborn or baby or babies or infant$ or child$ or teenage$ or teen$ or adolescen$ or schoolchild$ or school age or preschool$ or toddler$ or boy$ or girl$ or minors or pubert$ or pubescen$ or prepubescent$ or p?ediatric$ or youth$).tw.
14 randomized controlled trial.pt.
15 controlled clinical trial.pt.
18 drug therapy.fs.
23 exp animals/ not humans.sh.
24 22 not 23
Protocol first published: Issue 1, 2012
Contributions of authors
Karen Black conceived the review. Karen Black and Jason Howard designed the protocol with input at various stages from the other three authors. All authors approved the final version of the protocol.
Karen Black secured funding for the review and is the guarantor.
Declarations of interest
Sources of support
- IWK Health Centre Library, Librarian Darlene Chapman, Canada.Search strategy support
- Nova Scotia Health Research Foundation, Canada.Research Grant: the NSHRF has no vested interest in the outcome of this review.