A Randomized Controlled Trial Comparing a Fascia Iliaca Compartment Nerve Block to a Traditional Systemic Analgesic for Femur Fractures in a Pediatric Emergency Department

PAIN MANAGEMENT/ORIGINAL RESEARCH

A Randomized Controlled Trial Comparing a Fascia Iliaca Compartment Nerve Block to a Traditional Systemic Analgesic for Femur Fractures in a Pediatric Emergency Department Joe E. Wathen, MD Dexiang Gao, PhD Glenn Merritt, MD Gaia Georgopoulos, MD F. Keith Battan, MD

From the Department of Pediatrics, Division of Emergency Medicine (Wathen, Battan), the Research Institute (Gao), Division of Anesthesiology (Merritt), and Division of Orthopedics (Georgopoulos), University of Colorado at Denver and Health Science Center, The Children’s Hospital, Denver, CO.

Study objective: We determine whether a fascia iliaca compartment nerve block can provide superior pain management compared with intravenous morphine sulfate for the initial pain management of femur fracture patients presenting to a pediatric emergency department. The primary outcome measured is pain scores; a difference of 15% in scores assessed at 30 minutes from the study’s baseline pain management is considered clinically meaningful. Secondary outcomes include the duration of analgesia, the need for additional medications, adverse events, nerve block complications, and satisfaction scores. Methods: This was a prospective, randomized, unblinded, controlled trial conducted on children aged 15 months to 18 years with acute femur fractures, presenting to a free-standing, tertiary care children’s hospital. Patients were randomized to receive intravenous morphine sulfate or a fascia iliaca compartment nerve block using ropivacaine (Naropin). Pain scores (Children’s Hospital of Eastern Ontario Pain Scale [CHEOPS]; Face, Legs, Activity, Cry and Consolability Pain Scale; Faces Pain Scale) were recorded at initial analgesic administration (baseline), at 5, 10, 15, 30, and 60 minutes, and then hourly up to 6 hours from baseline by trained nursing observers and research assistants. Results: Fifty-five patients, 26 in the fascia iliaca compartment nerve block group and 29 in the morphine sulfate group, ranged in age from 16 months to 15 years (median 5.7 years). Baseline mean CHEOPS scores were similar: 9.4 fascia iliaca compartment nerve block and 9.5 morphine sulfate. Mean CHEOPS scores at 30 minutes after initial treatment were 5.87 for fascia iliaca compartment nerve block and 7.54 for morphine sulfate, with a difference of 1.67, which corresponds to an 18% (95% confidence interval [CI] 8% to 27%) difference in pain reduction between the 2 groups, according to the average baseline score of 9.45. Similar lower pain scores were observed in the fascia iliaca compartment nerve block group as early as 10 minutes from baseline and throughout the 6-hour duration of the study. In comparing the entire 6-hour CHEOPS pain scores, patients who received a fascia iliaca compartment nerve block showed lower scores by approximately 15% (95% CI 6% to 24%) compared to patients who received morphine sulfate. Median duration of analgesia was longer in the fascia iliaca compartment nerve block group compared with that in the morphine sulfate group (313 minutes [95% CI 154 to 360 minutes] versus 60 minutes [95% CI 10 to 255 minutes]). Fewer additional medications were given to patients who received the fascia iliaca compartment nerve block. No complications from the nerve block occurred. Satisfaction scores were higher with the fascia iliaca compartment nerve block among the medical staff. Conclusion: Fascia iliaca compartment nerve block provided clinically superior pain management compared with intravenous morphine sulfate at 30 minutes from baseline and throughout the initial 6 hours of medical treatment of children 16 months to 15 years who had isolated acute femur fractures. The results of this study, however, may be inflated by the nonblinding of the pain observers. Despite this potential bias, the fascia iliaca compartment nerve block should be considered as a valuable procedure in managing the pain commonly observed in these injured children. [Ann Emerg Med. 2007;50:162-171.] 0196-0644/$-see front matter Copyright © 2007 by the American College of Emergency Physicians. doi:10.1016/j.annemergmed.2006.09.006

162 Annals of Emergency Medicine

Volume , .  : August 

Wathen et al

Fascia Iliaca Compartment Nerve Block Editor’s Capsule Summary

What is already known on this topic Although the fascia iliaca compartment nerve block has been used for postoperative pain management in children, this is the first study to examine its use to manage acute femur fracture pain in children in the emergency department. What question this study addressed This 56-child randomized trial compared nerve block to morphine in the management of pain caused by femur fracture. What this study adds to our knowledge Nerve block administered by emergency physicians provided clinically superior pain management compared with intravenous morphine at 30 minutes and 6 hours from baseline. How this might change clinical practice Although these results may be inflated by the nonblinding of pain observers, the use of this relatively simple nerve block should be considered when pain from femur fracture is managed in children.

INTRODUCTION Background Managing the pain associated with the initial treatment of acute femur fractures can be challenging. Significant amounts of analgesics, sedatives, and muscle relaxants may be needed. In the pediatric and adult literature, femoral nerve blocks have been shown, primarily in the inpatient or operative setting, to be a safe, fast, and effective means of providing analgesia.1-5 There are a limited number of studies in the adult emergency department (ED) population that have described the successful use of a femoral nerve block or 3-in-1 femoral nerve block for acute pain femur fracture pain management.6-9 These nerve blocks, however, rely on either a peripheral nerve stimulator or the patient’s perception of paresthesia, both of which limit their use in the pediatric setting. In 1989, Dalens et al2 described a new single injection procedure, the fascia iliaca compartment nerve block, that effectively blocks the femoral, lateral femoral cutaneous, and obturator nerves without the use of either a nerve stimulator or the patient report of paresthesia. In this study evaluating postoperative analgesia in 120 pediatric patients, the fascia iliaca compartment nerve block provided safe and superior analgesia compared with the 3-in-1 femoral nerve block.2 The fascia iliaca compartment nerve block was therefore chosen in this study as a potential useful pediatric analgesic tool in the ED setting because it can be easily and quickly administered into a potential space that is lateral to the femoral nerve and vessels. Volume , .  : August 

Importance To our knowledge, no studies in the ED setting have been conducted using a nerve block to manage acute femur fracture pain in children. The use of a nerve block would be particularly useful in managing femur fracture pain in children who have the potential for multisystem injury. The ability to withhold systemic opiate analgesics and sedatives could allow for a more accurate assessment of other potential injuries. The use of the fascia iliaca compartment nerve block provides an option that has been shown to be safe and effective and can be administered without the use of a nerve stimulator, particularly important in the pediatric population.2 Goals of This Investigation To our knowledge, a fascia iliaca compartment nerve block and morphine sulfate have not been compared for the treatment of acute femur fracture pain management in children. The primary aim of this study is to compare these 2 methods of treatment with respect to pain scores (Children’s Hospital of Eastern Ontario Pain Scale [CHEOPS], Face, Legs, Activity, Cry and Consolability Pain Scale [FLACC], and Faces Pain Scale) during the initial 6 hours of medical management of acute femur fractures among children aged 15 months to 18 years. A difference of 15% between pain scores between fascia iliaca compartment nerve block and morphine sulfate treatment arms at 30 minutes after baseline was determined to be clinically important. Secondary aims included comparing the duration of analgesia, adverse events, the need for supplemental medications, and satisfaction scores. We hypothesized that the fascia iliaca compartment nerve block would provide clinically important lower pain scores compared with morphine sulfate for the initial treatment of pediatric femur fractures.

MATERIALS AND METHODS Study Design This was a prospective, randomized, unblinded, controlled, ED study conducted from February 2002 to May 2005, comparing pain scores for children with acute femur fractures by using either a fascia iliaca compartment nerve block or morphine sulfate. Blinding of this study was not attempted because it was believed that neither the patients nor the medical staff could be blinded to the interventions. Written informed consent was obtained from all parents or guardians for all patients. In addition, assent was obtained for patients aged 7 years or older. The study was approved by the state’s multiple institutional review board. Setting This study was conducted in a university-affiliated, freestanding, tertiary care children’s hospital and Level I trauma center with an annual ED patient census of 47,000. Selection of Participants Patients aged 15 months to 18 years and presenting to our pediatric ED with an acute femur fracture were eligible. Annals of Emergency Medicine 163

Fascia Iliaca Compartment Nerve Block Receiving narcotic pain medications before enrollment was not a reason for exclusion from the study. Patient selection was a convenience sampling based on availability of research assistants and physicians available to administer the fascia iliaca compartment nerve block. Research assistant availability ranged from 30 to 40 hours per week, with a self-made variable schedule that included all days of the week, as well as some evening hours. Excluded patients included children who were outside the specified age range, had an altered mental status, had a nerve or vascular injury in the affected limb, had abnormal bone structure (such as osteogenesis imperfecta), received fracture reduction, had a hypersensitivity to the study agents used, presented with significant multisystem distracting injuries (such as additional long bone fractures, moderate to severe abdominal pain, or extensive soft tissue injuries), or had social concerns including nonaccidental trauma. Interventions Informed consent or assent was obtained by the ED attending physician, fellow, or research assistant. Patients who gave consent were randomized with a computer-generated random-number table in blocks of 3 among 2 age groups (15 months to 5 years and 5 to 18 years) to receive either a fascia iliaca compartment nerve block or intravenous morphine sulfate. Morphine sulfate was dosed at 0.1 mg/kg. The rationale for randomizing among these 2 age groups was based on suggested age ranges for the different pain scoring tools used. The Faces Pain Score is a self-report tool recommended for children 5 years and older. The FLACC is a behavioral pain score applicable for children younger than 5 years. The CHEOPS, also a behavioral pain score, can be used for both age groups. The method for administering the fascia iliaca compartment nerve block was established in collaboration with our anesthesia department. Training on the technique of the fascia iliaca compartment nerve block consisted of initial instruction of the primary investigator in the operative room setting by an anesthesiologist. The primary investigator then gave group instruction to the ED physicians, both fellows (n⫽6) and attending physicians (n⫽11), at staff meetings, with yearly reminder sessions. In addition, there was a requirement of seeing and being instructed on the actual application of 1 block in the pediatric ED before actual administration of the first block. A list of on-call physicians with experience administering the block was available in the pediatric ED. The protocol did not preclude the application of a splint or traction during the study period. The application of either of these 2 was recorded. The protocol did preclude procedural sedation and analgesia for fracture reduction. Emergency physicians and orthopedic physicians treated all patients, which included routine patient evaluation, with the potential for minor manipulation of the fractured extremity. The fascia iliaca compartment nerve block was performed with the local anesthetic ropivacaine (Naropin). A 0.5% solution of ropivacaine (t½ of 4.2⫾1 hour, epidural) was drawn 164 Annals of Emergency Medicine

Wathen et al

Figure 1. Injection location for the fascia iliaca compartment nerve block.

up at a dose of 0.75 mL/kg for children less than 20 kg and 0.5 mL/kg for children greater than 20 kg, with a maximum dose of 30 mL.10 Surface landmarks were established by palpating the lateral aspect of the pubic bone and the adjacent anterior superior iliac spine. A point was then marked, using a surgical skin marker, along the inguinal ligament two thirds the distance laterally between these 2 landmarks (Figure 1). A 22gauge by 1-inch B-Plex short beveled needle (Plexufix brachial plexus anesthesia set; B. Braun Medical Inc., Bethlehem, PA) was inserted at a 90-degree angle going through the skin and then through 2 fascia planes, 2 “pops.” A negative aspiration test was performed. Pressure was applied caudally, approximately 1 inch inferior to the infusion site, before and during the infusion of the ropivacaine. This pressure was maintained for an additional 2 minutes after the infusion was completed to encourage upward or cephalad spread. All blocks were administered by either a pediatric ED fellow or attending physician after previous education and demonstration. The pediatric ED attending physicians were able to administer additional doses of narcotics, sedatives, or muscle relaxants to any patient at their discretion. All patients were monitored throughout the duration of the study, which included measurements of vital signs, continuous pulse oximetry, and cardiorespiratory monitoring. Data Collection and Processing Data were collected by trained nursing observers and research assistants during a 6-hour period, beginning with a baseline measurement. Baseline, or time zero, occurred when children received either the fascia iliaca compartment nerve block or the morphine sulfate. If patients left the ED before the 6-hour period was completed, then the research assistant would follow up and record final data measurements in the inpatient setting. Nursing observers and research assistants were not blinded to the previous pain scores. Research assistants were trained in assessing pain scores for pediatric patients in the ED before being involved in the study. Data were then entered by a Volume , .  : August 

Wathen et al separate professional research nurse through our hospital’s research institute, who entered the data onto a secured electronic data sheet. Additional data collected included age, sex, mechanism of injury, other associated injuries, location of fracture, type of fracture, and pain medications given before enrollment. Pediatric ED attending physicians, pediatric ED nurses, parents, and patients were asked at the end of the study period to rate their level of satisfaction with the degree of pain control provided using a Likertlike scale (an ordinal scale ranging from 1, least satisfied, to a 7, most satisfied). All adverse events data were recorded by either the ED physician or nurse treating the patient. In addition, all patients were treated by the orthopedic service during initial treatment of the femur fracture and for follow-up care. Patients were assessed for infection at the site of injection, as well as for abnormalities in their motor and sensory examinations, by the orthopedic service in the hospital and at follow-up clinic visits. These findings were classified as delayed complications. The first follow-up visit occurred 10 days to 2 weeks after the fracture. Patients were then followed up every 4 weeks until they healed. Final follow-up occurred 1 year postinjury. Standard evaluation forms were used in the orthopedic clinic to assess these patients. These data were collected and tabulated by one of the study investigators (G.G.). Outcome Measures The primary outcome was pain scores assessed at 30 minutes from baseline (study pain management). Three different pain scales were used. All patients were primarily assessed with the CHEOPS, which ranged from 4 to 13 with increasing pain. There were 4 CHEOPS repeated measures every 30 seconds at each point for each subject, and the average was used in analyses. Children younger than 5 years were additionally scored with a FLACC, ranging from 0 to 10 with increasing pain. Children 5 years and older reported an additional Faces Pain Scale, which ranged from 1 to 7 with increasing pain. Secondary outcome measures included the duration of analgesia, the need for additional medications, adverse events, and satisfaction scores. Adverse events that were recorded included respiratory complications (apnea, shallow breathing, oxygen desaturation less than 90% on room air at our elevation of 5,280 feet), central nervous system (perioral numbness, tinnitus, tremors/convulsions, drowsiness, altered mental status), peripheral nervous system–prolonged blockade (defined as either numbness or motor blockade present 12 hours after nerve block administration), cardiovascular (bradycardia, hypotension, chest palpations, chest pain), and other (vomiting, urticaria, pain or redness at the injection site). The use of supportive interventions such as airway positioning, supplemental oxygen, or assisted ventilation was documented. Respiratory complications were monitored by direct observation by trained personnel and with electronic patient monitoring equipment. Volume , .  : August 

Fascia Iliaca Compartment Nerve Block Primary Data Analysis Pain scores were each measured at baseline and at 5, 10, 15, 30, 60, 120, 180, 240, 300, and 360 minutes postmedication. Plots of the mean pain scores over time revealed linear relations between the scores and time, with a changing point of coefficients at 10 minutes postmedication for both groups. Thus, a piecewise linear mixed-effects regression model was applied to analyze the effects of the morphine sulfate and fascia iliaca compartment nerve block on the pain scores.11 In addition to the group indicator (morphine sulfate versus fascia iliaca compartment nerve block) in the model, the following risk variables were also considered: time (the first 10 minutes and after), interaction between group and time, additional medication, interaction between additional medication and group, interaction between additional medication and time, and associated injuries. The predicted difference in pain scores between the 2 groups at particular points, for example, at 30 minutes postmedication, could be easily estimated from the model. Details of statistical methods are given in Appendix E1 (available online at http://www.annemergmed.com)12-15 Time to the first additional medication (duration of analgesia) was analyzed using the Kaplan-Meier survival analysis method. Patients who did not receive additional medications were censored at 360 minutes. Median duration of analgesia and its 95% confidence intervals (CIs) are reported. Descriptive statistics were reported for the adverse events and satisfaction. SAS version 9 (SAS Institute Inc., Cary, NC) was used for all the analyses. Pⱕ.05 is considered statistically significant throughout. Sample size was estimated according to a previous study showing a 35% to 50% reduction of femur fracture pain with a nerve block compared to a 10% to 20% reduction with systemic analgesics alone.1 Estimating a pain score reduction of 35% in the fascia iliaca compartment nerve block group and 20% in the morphine sulfate group at 30 minutes postmedication, with initial CHEOPS pain score of 9.5 and an SD of 2 for both groups, a sample size of 26 in each group will provide 80% power to detect this 15% difference in pain reduction between the 2 groups, using a 1-sided t test at .05 significance level.

RESULTS Main Results There were a total of 55 patients enrolled, 26 into the nerve block group and 29 into the morphine group; see patient flow diagram (Figure 2). Twelve nerve blocks were performed by 5 pediatric emergency medicine attending physicians (median 2.5 blocks; range 1 to 4 blocks), 2 nerve blocks by 2 anesthesia attending physicians and 12 nerve blocks by 6 pediatric emergency medicine fellows (median 2 blocks; range 1 to 4 blocks). The age range of patients was 16 months to 15 years, with a median of 5.7 years. Male patients composed 80% of the patient cohort. Nearly all patients had received narcotic analgesic medications (morphine, fentanyl, Demerol, or codeine) before enrollment. The baseline pain scores were about the same between the 2 groups. Other patient characteristics Annals of Emergency Medicine 165

Fascia Iliaca Compartment Nerve Block Total Femur Fractures (n=329)

Wathen et al

Eligible Patients (n= 182) Eligible, Not Enrolled Patients: (n= 127) - No staff to administer FICNB (15) - Parental refusal (12) -ED too busy (5) -No research assistant (3) -Operating room ready (4) - No reason documented (88)*

Met Exclusion Criteria (n=147) -Outside age range (41) -Altered mental status (40) -Multi-system trauma (45) -Abnormal bone (5) -Cognitive delay (5) -NAT/social concerns (11)

Age 15months-5years Blocked randomized (n=24) FICNB(n=12) MS(n=12)

Enrolled Patients (n= 55)

Randomized to FICNB (n= 26)

Age 5 years-18years Blocked randomized (n=31) FICNB(n= 14) MS(n=17)

Randomized to IV Morphine (n= 29) 1 Patient at 2 Hours into Study Received FICNB in the Operating Room

Completed 6 Hour Study Period Randomized to FICNB (n= 26)

Completed 1 year follow-up Randomized to FICNB (n= 21)

Completed 6 Hour Study Period Randomized to IV Morphine (n= 28) Completed 1 year follow-up Randomized to IV Morphine (n= 24)

Figure 2. Patient flow algorithm. *Only patients who had a “reasons not enrolled sheet” filled out are reported; many of the patients in the “no reason given” would have been included in the categories listed but were not recorded. FICNB, Fascia iliaca compartment nerve block.

were similar between the groups, except for associated injuries, which occurred more commonly in the fascia iliaca compartment nerve block group (Table 1). A box and whisker plot (CHEOPS) and univariate plots (FLACC and Faces Pain Score) demonstrating the primary outcome, pain scores, were scored at each measured interval for both study groups (Figures 3 to 5). The distributions of the CHEOPS scores were substantially lower in both groups of the study during the first 10 minutes from baseline. The median scores in fascia iliaca compartment nerve block group, however, were lower compared with those in morphine sulfate group. Similar trends were shown for FLACC and Faces Pain Scores. At 30 minutes after initial pain management, the mean CHEOPS scores were 5.87 for fascia iliaca compartment nerve 166 Annals of Emergency Medicine

block and 7.54 for morphine sulfate, with a difference of 1.67, which corresponds to an 18% (95% CI 8% to 27%) difference in pain reduction between the 2 groups, according to the average baseline score of 9.45 for the 2 groups. At the same point, the reductions in Faces Pain Scale from baseline measures were 2.6 for fascia iliaca compartment nerve block and 1.7 for morphine sulfate, a difference of 0.9, corresponding to a 20% (95% CI ⫺16% to 56%) difference in pain reduction between the 2 groups. The reductions in FLACC at the same point were 5.6 for fascia iliaca compartment nerve block and 4.4 for morphine sulfate, a difference of 1.2, which corresponds to a 20% (95% CI ⫺26% to 66%) difference in pain reduction between the 2 groups. Because of the limited sample sizes for Faces Pain Scale and FLACC, the CIs are much wider. Volume , .  : August 

Wathen et al

Fascia Iliaca Compartment Nerve Block

Table 1. Comparison of patients between groups.

12 (41) 7 (24) 9 (31) 1 (4) 9.5 (1.8) 7.2 (2.5)

4.4 (1.7)

4.7 (2.1)

7 (27) 9 9

1 (4)

7

13 (50) 7 (27) 4 (15) 1 (4) 9.4 (1.9) 5.2 (2.3)

6

3 (10) 19 (66) 7 (24)

14

0

5

10

15

//

30

60

//

120 180 240 300 360

Time (minutes)

Figure 4. Faces Pain Scores (verbal patientsⱖ5 years). Small dots represent each subject’s score. Dots have been shifted slightly to throw superimposed points clear of one another. Larger rectangles indicate the median values at each time for each group. The x-axis has time breaks between 15 and 30 minutes and 60 and 120 minutes. FLACC pain score by time and treatment group N=12 for each group 10 8

Morphine

2

13

Morphine Nerve Block

9 14

MS, Morphine sulfate; MVC, motor vehicle crash. *Associated injuries included MS, 1 patient with a mild closed head injury, and in the FICNB group, 4 patients with mild closed-head injury, 1 with a clavicle fracture, and 2 with other small-bone fractures.

4

4 (15) 15 (58) 7 (27)

Faces Pain Score

7 (24) 11 (38) 2 (7) 2 (7) 7 (24) 28 (97)

2

9 (35) 3 (12) 5 (19) 2 (8) 7 (27) 26 (100)

0

23 (79) 5.8 (1.3, 13.2)

6

21 (80) 5.2 (1.5, 15.1)

Nerve Block N=14, Morphine N=17

4

Male (%) Age, y, median (min, max) Mechanism (%) Fall Jumping/tripped/running/sports MVC/auto-pedestrian Bicycle Other Received narcotic before study Location of femur fracture (%) Distal Middle Proximal Fracture type (%) Transverse Oblique Spiral Comminuted Baseline CHEOPS score, mean (SD) Baseline FLACC score, mean (SD) (n⫽23) Baseline Faces score, mean (SD) (n⫽31) Associated other injuries (%)* Traction applied during study Splinted during study

MS, Nⴝ29

FLACC Score

Patient Characteristics

Faces pain score by time and treatment group

FICNB, Nⴝ26

12 0

Nerve Block

CHEOPS Score

11

// 0

10

5

10

15

// 30

60

120 180 240 300 360

Time (minutes)

9 8

Figure 5. FLACC Pain Scores (15 months to 5 years). Small dots represent each subject’s score. Dots have been shifted slightly to throw superimposed points clear of one another. Larger rectangles indicate the median values at each time for each group. The x-axis has time breaks between 15 and 30 minutes and 60 and 120 minutes.

7 6 5 4 3 0

5

10

15

30

60 120 180 240 300 360

Time (minutes)

Figure 3. CHEOPS Pain Scale. Whiskers are inclusive of all patients. Box shows the 25th and 75th percentile, with additional horizontal lines indicating the medians and ⫹ indicating the means.

To model the pain scores, compound symmetric covariance structure for the repeated measures was selected according to Akaike information criteria values.13 This covariance structure assumes a common correlation among observations on a subject. Volume , .  : August 

The selected final model contained 5 fixed variables based on likelihood ratio testing: group indicator, time, time and group interaction, time and group interaction at the changing point, and additional medication. Predicted reductions in the CHEOPS scores at each point from baseline, for the FICNB and morphine sulfate groups, are reported (Table 2). Comparing combined pain scores for the duration of the 6-hour study, fascia iliaca compartment nerve block patients had approximately 15% (95% CI 6% to 34%) lower pain scores than the morphine sulfate group. Annals of Emergency Medicine 167

Fascia Iliaca Compartment Nerve Block

Wathen et al

Table 2. Predicted CHEOPS score reduction from baseline for FICNB and morphine sulfate groups.* FICNB Time Posttreatment, min 5 10 15 30 60 120 180 240 300 360

Reduction From Baseline 1.65 3.31 3.32 3.34 3.40 3.51 3.61 3.72 3.83 3.94

MS Reduction From Baseline

95% CI 1.35 2.71 2.72 2.75 2.82 2.95 3.05 3.14 3.21 3.26

1.96 3.91 3.92 3.93 3.97 4.06 4.17 4.30 4.45 4.61

0.95 1.91 1.92 1.95 2.01 2.14 2.26 2.39 2.51 2.64

FICNB-MS Difference in Reduction

95% CI 0.67 1.34 1.36 1.39 1.47 1.58 1.67 1.73 1.78 1.81

1.24 2.47 2.48 2.51 2.56 2.70 2.86 3.05 3.25 3.47

95% CI

0.70 1.40 1.40 1.39 1.38 1.37 1.35 1.33 1.31 1.30

0.29 0.57 0.57 0.58 0.59 0.59 0.55 0.49 0.40 0.30

1.11 2.23 2.22 2.20 2.18 2.15 2.14 2.17 2.23 2.30

*These data predicted based on the linear mixed-effects model with variables (group indicator, time, time and group interaction, time and group interaction at the changing point, and additional medication).

Table 3. Supplemental medications.

100

Interval, min, Post–Initial Medication

75 Percent without additional Analgesics 50

FICNB Morphine

25

0 0

100 200 300 Duration without additional Analgesia (min)

400

Figure 6. Percentage of patients over time who did not receive additional medications.

The median duration of analgesia was longer in the fascia iliaca compartment nerve block group compared with the morphine sulfate group (313 minutes [95% CI 154 to 360 minutes] versus 60 minutes [95% CI 10 to 255 minutes]). The percentage of patients who did not receive additional or supplemental medications (supplement free) was noticeably higher in the fascia iliaca compartment nerve block group compared with the morphine sulfate group (Figure 6). The types of supplemental medications, as well as the dosing used, are listed (Table 3). Adverse events that occurred during the study period, as well as long-term adverse events, are presented (Table 4). Respiratory adverse events included 1 patient in the nerve block and 6 patients in the morphine group who were hypoxic (pulse oximeter reading ⬍90% at elevation 5280 feet above sea level). The patient in the fascia iliaca compartment nerve block group who had hypoxia had a pulse oximetry reading of 86%, received oxygen only, and had complete resolution. This patient had received morphine sulfate 88 minutes before the nerve block. In the morphine sulfate group, there were 6 patients who became 168 Annals of Emergency Medicine

0–30 31–60 61–90 91–120 121–180 181–240 241–360 Total

FICNB (nⴝ26) D†

A‡

MS (nⴝ28)* M§

D

A

M

2 1

9 8 2 5 2 5 7 38

1 2

1

2 2

1 4 5 11

1 3 1 1

7

1 1 1 1 7

*One patient in the MS group was withdrawn from this analysis because the patient received supplemental FICNB in the operating room by the orthopedic service 2 hours after presentation. † D⫽diazepam (0.2 mg/kg). ‡ A⫽analgesic, morphine (0.1 mg/kg), fentanyl (1 ␮g/kg), Demerol (1 mg/kg), Toradol (0.5 mg/kg). § M⫽midazolam (0.1 mg/kg).

Table 4. Adverse events. Adverse Events Respiratory Central nervous system Cardiovascular Other* Delayed complications†

FICNB (Nⴝ26) No. (%)

MS (Nⴝ29) No. (%)

1 (3.8) 0 0 4 (15) 0

6 (20.7) 2 (6.9) 0 4 (13.8) 0

*Other included pain or redness at the injection site (FICNB), all vomiting (MS). † Delayed complications included infection, sensory abnormalities, motor blockade noted from 12 hours after administration through follow-up visits.

hypoxic: all received oxygen, and 3 of 6 received breathing cues. No patients received intubation or bag-valve-mask ventilation. Central nervous system adverse events included 2 patients in the morphine sulfate group who developed temporary altered mental status, ie, obtunded. They were noted to be difficult to arouse and had shallow breathing, and they received oxygen and were closely monitored. Neither developed apnea and both recovered. Other adverse events included 4 in each group. In Volume , .  : August 

Wathen et al the nerve block group, these were pain or redness at the injection site in all 4 patients, and in the morphine sulfate group, these were vomiting in all 4 patients. There were no cardiovascular adverse events or prolonged adverse events from the nerve blockade (numbness, motor paralysis, or infection). Satisfaction scores, based on efficacy of the provided analgesia, were recorded for physicians, nurses, parents, and patients. A Likertlike scale of satisfaction was used, with a range of 1 to 7; scores of 6 and 7 were determined to represent a high degree of satisfaction with the analgesia provided. The pediatric ED physician and nurse reported high satisfaction scores (6 and 7) more often with the fascia iliaca compartment nerve block compared with morphine sulfate: 20 patients (76.9%) with fascia iliaca compartment nerve block (physician) compared with 2 patients (7.7%) with morphine sulfate (physician); 19 patients (76%) fascia iliaca compartment nerve block (nurse) compared with 11 patients (40.7%) morphine sulfate (nurse). Parents and patients reported similar high satisfaction scores among both groups: 17 (65%) fascia iliaca compartment nerve block (parent) versus 11 (46%) morphine sulfate (parent); 5 (39%) fascia iliaca compartment nerve block (patient) versus 3 (21%) morphine sulfate (patient).

LIMITATIONS There was no attempt made to blind this study. This lack of blinding may have biased the behavioral pain scores but unlikely the self-reported pain scores. Lack of blinding to previous pain scores could have affected the treating physicians and the outcome assessors and led to a bias toward the study hypothesis. Although the use of supplemental medications may have been affected by the lack of blinding (less used in the nerve block group), we consider that the treatment of pain is a primary concern of our medical staff despite enrollment in a study. Finally, medical staff’s higher satisfaction scores in the nerve block group also may have been biased by the lack of blinding. It did not appear feasible that blinding the nurses or research assistants would succeed, especially given the fact that pain scores were obtained at time zero, as well as shortly after time zero. In addition, blinding was determined to be difficult because the majority of nerve blocks performed were by a member of the treatment team. The use of a separate on-call physician to provide a blinded nerve block resulted in an unacceptable delay in patient care. Finally, blinding was made difficult by the request by the anesthesiologist and the orthopedists to know which children were blocked before they went to the operating room. This knowledge was used by them to determine whether a nerve block could be provided in the operating room for children not already receiving one in the pediatric ED and who fell outside the 6-hour study period. This study has a sample size that was powered to show a difference in pain scores. This sample size was not large enough to make conclusions about the nerve block safety profile. There were, however, no significant adverse events that occurred immediately (respiratory, cardiovascular, central nervous system, or other) or after a delay (motor, sensory, or infection) in the Volume , .  : August 

Fascia Iliaca Compartment Nerve Block nerve block group. All nerve block patients were followed up during the hospitalization period and at later related visits by the orthopedic service for potential complications. The differences seen in the pain scores between the 2 treatment groups may also reflect the inherent pharmacodynamic differences between the 2 medications and the route of administration. Given the shorter duration of morphine, more aggressive monitoring and treatment of pain may have resulted in smaller differences in the pain scores. We, however, believed that our scores reflected accurately the pain commonly observed with such injuries in this setting. Initial enrollment into the study was hampered by the lack of providers available to perform the fascia iliaca compartment nerve block. No comparison between those enrolled into the study and those eligible but not enrolled was performed. We have reported reasons for missed enrollment in a sample of those eligible but not enrolled into the study (Figure 2). Finally, the fascia iliaca compartment nerve block was performed by physicians, all pediatric emergency medicine attending physicians, fellows, or anesthesiologists with various degrees of training. This variable (provider) was not accounted for in the regression analysis, because of the limited sample size. All physicians were provided with an instructional session, as well as a requirement of observing at least 1 fascia iliaca compartment nerve block administration. The overall success of the fascia iliaca compartment nerve block in this study supports this approach. The relative lack of experience in administering the fascia iliaca compartment nerve block would only serve to diminish the effectiveness scores in the fascia iliaca compartment nerve block study group.

DISCUSSION The use of nerve blocks to provide analgesia offers several advantages compared with traditional systemic medications. Primarily, this includes avoiding the systemic effects associated with parenteral analgesics, sedatives, and muscle relaxants. In addition, nerve blocks can provide a longer duration of relief compared to systemic medications. The use of nerve blocks to treat the pain associated with pediatric femur fractures has not been described in the ED setting. To our knowledge, our study represents the first randomized, controlled trial comparing the fascia iliaca compartment nerve block to morphine sulfate in the management of pain in children with acute femur fractures. Our study showed that both types of treatment can promptly reduce pain scores. However, the fascia iliaca compartment nerve block produced lower pain scores than morphine sulfate at 30 minutes from baseline and throughout the 6 hours of the study period. In addition, there was less need for supplemental analgesic medications for patients receiving the fascia iliaca compartment nerve block compared with those receiving IV morphine. We limited our study to 6 hours to focus on the initial treatment of patients with femur fractures. During this time, there is the potential for significant movement and attendant pain, including radiologic procedures, bed transfers, and application of traction and spica splints. In addition, during Annals of Emergency Medicine 169

Fascia Iliaca Compartment Nerve Block early management of femur fractures, muscle spasm can often be a contributing factor to pain. By providing early motor blockade with a fascia iliaca compartment nerve block, muscular spasm may be reduced or eliminated. Pain scores were measured with one of 3 tools in our study. These included the CHEOPS, FLACC, and Faces Pain Scale, all of which have been validated previously.16-18 The FLACC is a behavioral score validated in younger children (⬍7 years), whereas the Faces Pain Scale is a validated self-report score that can be used in the older, verbal child.19 CHEOPS offers the ability to score pain on a behavioral score on all ages of patients. Our results demonstrate clinically significant lower pain scores with the fascia iliaca compartment nerve block when measured with CHEOPS. Because of limited sample sizes, we do not have definite conclusions for Faces Pain Scores and FLACC, but similar trends hold. Fewer additional medications were needed in the fascia iliaca compartment nerve block group. One possible reason that nerve blocks are not frequently used in the ED may be the technical challenge thought to be associated with their administration. Another is the limited education to regional anesthesia that is provided during pediatric emergency medicine fellowship training. We found, however, that the fascia iliaca compartment nerve block was a simple block to administer with only a brief instructional review before its use. In the pediatric setting, the use of a peripheral nerve stimulator or obtaining patient feedback about paresthesia can be difficult. Neither of these components is needed with use of the fascia iliaca compartment nerve block. By administering the analgesic into a potential space with cephalad spread, the appropriate nerves can be affected without injecting analgesic in close proximity to these nerves. An additional advantage with this lateral site of injection is the reduction in potential complications associated with inadvertent intravascular or intraneural administration. Although numbers were small in this study, all patients were followed up in the hospital and at later related visits, with no reports of prolonged nerve blockade. The complication rate of femoral nerve blocks and fascia iliaca compartment nerve blocks are low and has been reported as zero in several studies.2,4,9 Although unusual, prolonged nerve block resulting from injection within the nerve has been reported.20,21 Intravascular injection has only rarely been reported and can be minimized with proper technique. Adverse effects associated with the fascia iliaca compartment nerve block in this study were minor and included pain and redness at the injection site, which resolved shortly. Adverse events in the morphine sulfate group were also minimal and not unexpected with this medication. Most previous nerve block studies have used bupivacaine as the analgesic agent.6,22 We, however, chose ropivacaine (Naropin) in this study, a relatively newer long-acting local anesthetic. Infusion studies have shown less depression of cardiac conductivity and contractility than bupivacaine, with similar efficacy.23,24 This cardiac complication would primarily be associated with inadvertent intravascular injection. It is likely, but unknown, that 170 Annals of Emergency Medicine

Wathen et al using bupivacaine for the fascia iliaca compartment nerve block would have provided results similar to ours. We conclude that for children presenting with an acute femur fracture, the use of a fascia iliaca compartment nerve block provides lower pain scores compared with IV morphine during the first 6 hours of medical management. Although the fascia iliaca compartment nerve block was safely administered in our small sample of young children, further study is needed to make formal safety recommendations. The nonblinding in the study, however, may limit the conclusions about the degree of pain score reduction reported. Despite this limitation, this technique of administrating analgesia should be considered in the ED management of pediatric femur fractures. Supervising editor: Kathy N. Shaw, MD, MSCE Author contributions: JEW conceived the study and designed the trial. GM provided training and instruction of the nerve block. GG provided orthopedic care and follow-up data. JEW supervised data collection. DG provided statistical analyses of the data. FKB assisted in study design and review of the manuscript. JEW drafted the article, and all authors contributed to its revision. JEW takes responsibility for the paper as a whole. Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article, that might create any potential conflict of interest. See the Manuscript Submission Agreement in this issue for examples of specific conflicts covered by this statement. Financial support was from The Children’s Hospital Research Institute. Publication dates: Received for publication December 14, 2005. Revisions received June 20, 2006, and August 24, 2006. Accepted for publication September 11, 2006. Available online January 8, 2007. This study was presented at the Pediatric Academic Societies meeting, May 2005, Washington, DC. Reprints not available from the authors. Address for correspondence: Joe E. Wathen, MD, The Children’s Hospital, Emergency Department B251, 1056 E 19th Ave, Denver, CO 80218; 303-837-5464, fax 303-7648694; E-mail [email protected]. REFERENCES 1. Haddad FS, Williams RL. Femoral nerve block in extracapsular femoral neck fractures. J Bone Joint Surg. 1995;77:922-923. 2. Dalens B, Vanneuville G, Tanguy A. Comparison of the fascia iliaca compartment block with the 3-in-1 block in children. Anesth Analg. 1989;69:705-713. 3. Tondare AS, Nadkarni AV. Femoral nerve block for fractured shaft of femur. Can Anaesth Soc J. 1982;29:270-271. 4. Grossbard GD, Love BR. Femoral nerve block: a simple and safe method of instant analgesia for femoral shaft fractures in children. Aust N Z J Surg. 1979;49:592-594. 5. Howard CB, Mackien IG, Fairclough J, et al. Femoral neck surgery using a local anesthetic technique. Anaesthesia. 1983;38:993-994. 6. Fletcher AK, Rigby AS, Heyes F. Three-in-one femoral nerve block as analgesia for fractured neck of femur in the emergency

Volume , .  : August 

Wathen et al

7. 8.

9.

10.

11. 12.

13. 14. 15.

department: a randomized, controlled trial. Ann Emerg Med. 2003;41:227-233. Finlayson BJ, Underhill TJ. Femoral nerve block for analgesia in fractures of the femoral neck. Arch Emerg Med. 1988;5:173-176. Van Leeuwen FL, Bronselaer K, Gilles M, et al. The “three in one” block as locoregional analgesia in the emergency department. Eur J Emerg Med. 2000;7:35-38. McGlone R, Sadhra K, Hamer DW, et al. Femoral nerve block in the initial management of femoral shaft fractures. Arch Emerg Med. 1987;4:163-168. Bosenberg AT, Thomas J, Cronje L, et al. Pharmacokinetics and efficacy of ropivacaine for continuous epidural infusion in neonates and infants. Pediatr Anesth. 2005;15:739-749. Neter J, Kutner M, Nachtsheim C, et al. Applied Linear Statistical Models. 4th ed. Chicago, IL; Irwin; 1996:474-478. Box GEP, Jenkins GM, Reinsel GC. Time Series Analysis: Forecasting and Control. 3rd ed. Upper Saddle River, NJ: Prentice Hall; 1994:200-201. Akaike H. A new look at the statistical model identification. IEEE Trans Automat Contr. 1974;19:716-723. Laird NM, Ware JH. Random-effects models for longitudinal data. Biometrics. 1982;38:963-974. SAS Institute Inc. SAS Manual 9.1. Cary, NC: SAS Institute Inc.; 2005.

Volume , .  : August 

Fascia Iliaca Compartment Nerve Block 16. Tyler D, Tu A, Douhit J, et al. Toward the validation of pain measurement tools for children: a pilot study. Pain. 1993;52:301309. 17. Bieri D, Reeve RA, Champion GD, et al. The Faces Pain Scale for the self-assessment of the severity of pain experienced by children: development, initial validation, and preliminary investigation for ratio scale properties. Pain. 1990;41:139-150. 18. Merkel S, Voepel-Lewis T, Shayevitz J, et al. The FLACC: a behavioral scale for scoring postoperative pain in young children. Pediatr Nurs. 1997;23:293-297. 19. Bullock B, Tennenbein M. Validation of 2 pain scales for use in the pediatric emergency department. Pediatrics. 2002;110:e33. 20. Lynch J. Prolonged motor weakness after femoral nerve block with bupivacaine 0.5%. Anesthesia. 1990;45:421. 21. Madej T, Ellis F, Halsall P. Prolonged femoral nerve block with 0.5% bupivacaine. Anaesthesia. 1988;43:607-608. 22. Ronchi L, Rosenbaum D, Athouel A, et al. Femoral nerve blockade in children using bupivacaine. Anesthesiology. 1989;70:622-624. 23. Scott DB, Lee A, Fagan D, et al. Acute toxicity of ropivacaine compared with that of bupivacaine. Anesth Analg. 1989;69:563569. 24. Inani G, Lampugnani E, Torre M, et al. Comparison of ropivacaine with bupivacaine for paediatric caudal block. Br J Anaesth. 1998; 81:247-248.

Annals of Emergency Medicine 171

APPENDIX E1 Mixed-effects models were used to assess the 2 pain management effects on the CHEOPS measures. The initial plot of means and SDs of CHEOPS over time suggested 2 linear pieces of CHEOPS for the 6-hour study time for each of the 2 groups, with a changing point around 10 minutes. Thus, a piecewise linear mixed-effects regression model was chosen for analyzing the data,11 in which the time variable in the model was treated as a continuous variable, with a changing point at 10 minutes to accommodate the 2 slopes before and after 10 minutes for each group. The correlation among repeated measures for a subject was taken into account. Akaike information criteria were used to determine which covariate structure fitted our data best by using a simple model in which the covariates included group indicator, time, and time and group indicator interaction.12,13 Several correlation structures were examined, including random subject effects, unstructured correlations between time and group indica-

171.e1 Annals of Emergency Medicine

tor, and time-series correlation among repeated measures, and both random subject effects and time-series correlation. The model with random subject effects as the correlation structure was found to have the smallest Akaike information criteria values and was chosen for analyzing our data. After determining the covariance structure for the repeated measures, we then examined the models in terms of the fixedeffect covariates. The risk variables initially put into the models included group indicator (morphine sulfate versus fascia iliaca compartment nerve block), time (the first 10 minutes and after), interaction between group and time, additional medication, interaction between additional medication and group, interaction between additional medication and time, and associated injuries. We do not expect that all the above parameters are significantly associated with the pain scores, and the likelihood ratio tests were used to determine which parsimony model fitted the data best. SAS Proc Mixed was used for the analyses, where the missing values (assuming missing at random) were accommodated in the analysis.14,15

Volume , .  : August 