Collagenase treatment decreases muscle stiffness in cerebral palsy: A preclinical ex vivo biomechanical analysis of hip adductor muscle fiber bundles.

AIM: To determine the dose-response relationship of collagenase Clostridium histolyticum (CCH) on collagen content and the change in muscle fiber bundle stiffness after ex vivo treatment of adductor longus biopsies with CCH in children with cerebral palsy (CP). METHOD: Biopsy samples of adductor longus from children with CP (classified in Gross Motor Function Classification System levels IV and V) were treated with 0 U/mL, 200 U/mL, 350 U/mL, or 500 U/mL CCH; percentage collagen reduction was measured to determine the dose-response. Peak and steady-state stresses were determined at 1%, 2.5%, 5%, and 7.5% strain increments; Young's modulus was calculated. RESULTS: Eleven patients were enrolled (nine males, two females, mean age at surgery 6 years 5 months; range: 2-16 years). A linear CCH dose-response relationship was determined. Peak and steady-state stress generation increased linearly at 5.9/2.3mN/mm2 , 12.4/5.3mN/mm2 , 22.2/9.7mN/mm2 , and 33.3/15.5mN/mm2 at each percentage strain increment respectively. After CCH treatment, peak and steady-state stress generation decreased to 3.2/1.2mN/mm2 , 6.5/2.9mN/mm2 , 12.2/5.7mN/mm2 , and 15.4/7.7mN/mm2 respectively (p < 0.004). Young's modulus decreased from 205 kPa to 100 kPa after CCH (p = 0.003). INTERPRETATION: This preclinical ex vivo study provides proof of concept for the use of collagenase to decrease muscle stiffness in individuals with CP.

The influence of tone on proximal femoral and acetabular geometry in neuromuscular hip displacement: A comparison of cerebral palsy and spinal muscular atrophy.

Purpose: The aim of this article was to compare longitudinal changes in hip morphology in cerebral palsy (hypertonic) and spinal muscular atrophy (hypotonic) to examine the influence of muscle tone on development of hip displacement. Methods: Children with spinal muscular atrophy (Types I and II) and cerebral palsy (Gross Motor Function Classification System IV and V) with hip displacement (migration percentage >30%) were included. Head shaft angle, migration percentage, and acetabular index were measured at T1 (1-2.5 years), T2 (3-5 years), and T3 (6-8 years). Analysis of variance testing and linear regression were utilized. Results: Sixty patients (cerebral palsy, N = 41; spinal muscular atrophy, N = 19) were included. Hip displacement occurred earlier in spinal muscular atrophy (34 months) than cerebral palsy (49 months) (p = 0.003). Head shaft angle was high and did not change between T1, T2, and T3, but significant changes in migration percentage were found (cerebral palsy: 23%, 36%, 45% (p < 0.01) and spinal muscular atrophy: 37%, 57%, 61% (p = 0.02)). Migration percentage increased by age in cerebral palsy (r = 0.41, p < 0.001), but not in spinal muscular atrophy (r = 0.18, p = 0.09). Acetabular index increased with migration percentage (cerebral palsy: r = 0.41, p < 0.001; spinal muscular atrophy: r = 0.48, p < 0.001). Conclusion: Persistent lateral physeal tilt by head shaft angle was found for both spinal muscular atrophy and cerebral palsy. Abnormal physeal alignment may be causally related to weakness of the hip abductor muscles rather than spasticity or muscle imbalance, resulting in coxa valga and secondary acetabular dysplasia. Level of evidence: III (case-control study).

Anterior distal femoral hemiepiphysiodesis in children with cerebral palsy: Establishing surgical indications and techniques using the modified Delphi method and literature review.

Purpose: The purpose of this study was to develop consensus for the surgical indications of anterior distal femur hemiepiphysiodesis in children with cerebral palsy using expert surgeon opinion through a modified Delphi technique. Methods: The panel used a 5-level Likert-type scale to record agreement or disagreement with 27 statements regarding anterior distal femur hemiepiphysiodesis. Consensus was defined as at least 80% of responses being in the highest or lowest 2 of the Likert-type ratings. General agreement was defined as 60%-79% falling into the highest or lowest 2 ratings. Results: For anterior distal femur hemiepiphysiodesis, 27 statements were surveyed: consensus or general agreement among the panelists was achieved for 22 of 27 statements (22/27, 82%) and 5 statements had no agreement (5/27, 18%). There was general consensus that anterior distal femur hemiepiphysiodesis is indicated for ambulatory children with cerebral palsy, with at least 2 years growth remaining, and smaller (<30 degrees) knee flexion contractures and for minimally ambulatory children to aid in standing/transfers. Consensus was achieved regarding the importance of close radiographic follow-up after screw insertion to identify or prevent secondary deformity. There was general agreement that percutaneous screws are preferred over anterior plates due to the pain and irritation associated with plates. Finally, it was agreed that anterior distal femur hemiepiphysiodesis was not indicated in the absence of a knee flexion contracture. Conclusion: Anterior distal femur hemiepiphysiodesis can be used to treat fixed knee flexion contractures in the setting of crouch gait, but other associated lever arm dysfunctions must be addressed by single-event multilevel surgery. Level of evidence: V.

Australian hip surveillance guidelines at 10 years: New evidence and implementation.

Optimum management of hip displacement in children with cerebral palsy (CP) is facilitated by an approach that focuses on anticipatory and preventive measures. Hip surveillance programs for children with CP were developed at the beginning of the new millennium, with the purpose of identifying hip displacement sufficiently early to permit a choice of effective management options. In the early years, hip surveillance was guided by epidemiological analysis of population-based studies of prevalence. In Australia, a National Hip Surveillance in CP Working Group was first convened in 2005. This resulted in a 2008 Consensus Statement of recommendations published and endorsed by Australasian Academy of Cerebral Palsy and Developmental Medicine (AusACPDM). The group undertook that the recommendations should be reviewed every 5 years to ensure currency and congruency with the emerging evidence base. As new evidence became available, hip surveillance guidelines developed, with the most recent 2020 Australian Hip Surveillance Guidelines endorsed by the AusACPDM. Implementing comprehensive hip surveillance programs has now been shown to improve the natural history of hip dislocations and improve quality of life. Standardised hip surveillance programs can also facilitate planning for multicentre research through harmonisation of data collection. This, in turn, can help with the identification of robust new evidence that is based on large cohort or population studies. Here a review of evidence informing the updated 2020 Hip Surveillance Guidelines is presented.

Ankle Dorsiflexor Function after Gastrocsoleus Lengthening in Children with Cerebral Palsy: A Literature Review.

Background and Objectives: Ambulant children with cerebral palsy can demonstrate persistent "foot drop" after successful gastrocsoleus lengthening (GSL) surgery for equinus deformity. This may be due to inadequate strength and/or selective motor control of the ankle dorsiflexor muscles. A procedure has been developed to reduce foot drop-Tibialis Anterior Tendon Shortening (TATS), to be performed in conjunction with GSL. However, it is currently unclear how ankle dorsiflexor function changes after surgery and which children could benefit from TATS. This review summarises changes in ankle dorsiflexor function after GSL for equinus, as reported in the literature. Methods: A search was performed of the Medline, Embase and PubMed databases from 1980 to 5 March 2021. Keywords included "cerebral palsy", "equinus deformity", "orthopedic procedures" and "gait analysis". The search identified 1974 studies. Thirty-three cohort studies met the inclusion criteria for this review. Results: Twenty-two studies reported improvement in swing phase ankle dorsiflexion kinematics, after GSL. There was also evidence that clinical measures of ankle dorsiflexor strength improved after surgery. Four studies reported changes in selective motor control, with mixed results across the studies. Conclusions: There is good evidence that swing phase ankle dorsiflexion improves after GSL surgery. Although, there is limited evidence that this correlates with reduced foot drop or diminished need for an ankle-foot orthosis. Future research should be prospective, randomised, include a large sample size, and should focus on identifying the optimal candidates for TATS.

Distal rectus femoris surgery in children with cerebral palsy: results of a Delphi consensus project.

PURPOSE: The purpose of this study was for an international panel of experts to establish consensus indications for distal rectus femoris surgery in children with cerebral palsy (CP) using a modified Delphi method. METHODS: The panel used a five-level Likert scale to record agreement or disagreement with 33 statements regarding distal rectus femoris surgery. The panel responded to statements regarding general characteristics, clinical indications, computerized gait data, intraoperative techniques and outcome measures. Consensus was defined as at least 80% of responses being in the highest or lowest two of the five Likert ratings, and general agreement as 60% to 79% falling into the highest or lowest two ratings. There was no agreement if neither threshold was reached. RESULTS: Consensus or general agreement was reached for 17 of 33 statements (52%). There was general consensus that distal rectus femoris surgery is better for stiff knee gait than is proximal rectus femoris release. There was no consensus about whether the results of distal rectus femoris release were comparable to those following distal rectus femoris transfer. Gross Motor Function Classification System (GMFCS) level was an important factor for the panel, with the best outcomes expected in children functioning at GMFCS levels I and II. The panel also reached consensus that they do distal rectus femoris surgery less frequently than earlier in their careers, in large part reflecting the narrowing of indications for this surgery over the last decade. CONCLUSION: This study can help paediatric orthopaedic surgeons optimize decision-making for, and outcomes of, distal rectus femoris surgery in children with CP. LEVEL OF EVIDENCE: V.

Split anterior tibialis tendon transfer to peroneus brevis for spastic equinovarus in children with hemiplegia.

PURPOSE: The aim of this study is to report the safety and eff-cacy of soft-tissue surgery incorporating split transfer of tibi-alis anterior to peroneus brevis (SPLATT-PB) for children with hemiplegic spastic equinovarus. METHODS: This was a retrospective case series of children and adolescents with spastic hemiplegia who had a novel combination of SPLATT-TB, intramuscular tenotomy of tibialis posterior and either spasticity management or gastrocsole-us lengthening as the index surgery. The principal outcome measures were changes in pain and difficulty with shoe wear and radiological parameters obtained from weight-bearing anteroposterior and lateral radiographs of the affected foot before and after surgery. RESULTS: A total of 63 patients with symptomatic spastic equinovarus met the inclusion criteria. Mean age at surgery was 9.8 years (6 to 18) and the mean follow-up was seven years (range 3 to 10 years). Foot pain and problems with shoe wear improved after surgery. Seven radiological criteria showed a clinically and statistically significant improvement at follow-up, the majority being in the normal range. There were 11 surgical adverse events, all classified as Modified Cla-vien-Dindo Grade II. Three patients required further surgery for recurrent equinus, eight patients required further surgery for valgus deformities and four patients required bony surgery for residual varus deformities. CONCLUSION: Soft-tissue surgery for spastic equinovarus was successful in the majority of children with spastic hemiplegia, particularly between ages eight and 12 years, resulting in a plantigrade, flexible foot with minimal pain or limitations in shoe-wear. Children younger than 8 years at index surgery were more prone to overcorrection into valgus. Children older than 12 years had persistent varus deformities requiring bony surgery. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Musculoskeletal Pathology in Cerebral Palsy: A Classification System and Reliability Study.

This article presents a classification of lower limb musculoskeletal pathology (MSP) for ambulant children with cerebral palsy (CP) to identify key features from infancy to adulthood. The classification aims to improve communication, and to guide referral for interventions, which if timed appropriately, may optimise long-term musculoskeletal health and function. Consensus was achieved by discussion between staff in a Motion Analysis Laboratory (MAL). A four-stage classification system was developed: Stage 1: Hypertonia: Abnormal postures are dynamic. Stage 2: Contracture: Fixed shortening of one or more muscle-tendon units. Stage 3: Bone and joint deformity: Torsional deformities and/or joint instability (e.g., hip displacement or pes valgus), usually accompanied by contractures. Stage 4: Decompensation: Severe pathology where restoration of optimal joint and muscle-tendon function is not possible. Reliability of the classification was tested using the presentation of 16 clinical cases to a group of experienced observers, on two occasions, two weeks apart. Reliability was found to be very good to excellent, with mean Fleiss' kappa ranging from 0.72 to 0.84. Four-stages are proposed to classify lower limb MSP in children with CP. The classification was reliable in a group of clinicians who work together. We emphasise the features of decompensated MSP in the lower limb, which may not always benefit from reconstructive surgery and which can be avoided by timely intervention.

Health professionals' experiences and barriers encountered when implementing hip surveillance for children with cerebral palsy.

AIM: This study aimed to explore health professionals' experiences of implementing hip surveillance for young people with cerebral palsy (CP) and to identify any barriers they encounter. METHODS: A cross-sectional web-based survey of health professionals supporting children with CP was conducted. Responses were analysed through mixed methods. Responses to items presented as ordinal scales were analysed using descriptive statistics, and open-ended responses through a qualitative approach to identify themes. RESULTS: A total of 32 paediatricians, 2 rehabilitation specialists and 50 physiotherapists completed the survey, with respondents working within both hospital- and community-based settings. Barriers most frequently reported were inconsistency in radiology practice and reporting (35%), parent engagement (32%), limited communication between clinicians (31%), lack of clarity in lines of responsibility (27%) and forgetting to undertake surveillance (26%). Four major themes were identified through qualitative analysis: (i) recognition of the importance of clinical guidelines to hip surveillance; (ii) the value of each role in the team around a child; (iii) the challenge of sharing responsibility; and (iv) the importance of communication in facilitating collaboration. CONCLUSIONS: Barriers can be encountered at each phase of the hip surveillance process, but there are also factors that act as facilitators. Locally, the results will inform the development of an enhanced state-wide approach to hip surveillance for all children with CP. The identified barriers do not appear unique to the local context, and the findings may be transferable to other settings. Awareness of the potential barriers and facilitators would be valuable to those implementing hip surveillance in other areas.

Classifying Adverse Events Following Lower Limb Orthopaedic Surgery in Children With Cerebral Palsy: Reliability of the Modified Clavien-Dindo System.

BACKGROUND: The modified Clavien-Dindo (MCD) system is a reliable tool for classifying adverse events (AEs) in hip preservation surgery and has since been utilized in studies involving lower limb surgery for ambulant and nonambulant children with cerebral palsy (CP). However, the profile of AEs recorded in children with CP compared with typically developing children is different, and the reliability of the MCD in CP is unknown. This study aimed to evaluate the interrater and intrarater reliability of the MCD system for classifying AEs following lower limb surgery in children with CP. METHODS: Eighteen raters were invited to participate, including clinicians from surgical, nursing, and physical therapy professions, and individuals with CP. Following a MCD familiarization session, participants rated 40 clinical scenarios on 2 occasions, 2 weeks apart. Fleiss' κ statistics were used to calculate interrater and intrarater reliability. RESULTS: The overall Fleiss' κ value for interrater reliability in the first rating was 0.70 (95% confidence interval, 0.61-0.80), and increased to 0.75 (95% confidence interval, 0.66-0.84) in the second rating. The average Fleiss' κ value for intrarater reliability was 0.78 (range, 0.48 to 1.00). Grading of more severe AEs (MCD III to V) achieved near perfect agreement (κ, 0.87 to 1.00). There was a lower level of agreement for minor AEs (MCD I-II) (κ, 0.53 to 0.55). A κ score of 0 to 0.2 was deemed as poor, 0.21 to 0.4 as fair, 0.41 to 0.6 as good, 0.61 to 0.8 as very good, and 0.81 to 1.0 as almost perfect agreement. CONCLUSIONS: The MCD System demonstrates a very good interrater and intrarater reliability following lower limb surgery in children with CP. The MCD can be used by clinicians from different health care professions with a high level of reliability. The MCD may improve standardization of AE recording with a view to accurate audits and improved clarity in outcome studies for CP. LEVEL OF EVIDENCE: Level II-diagnostic.

Symptomatic hallux valgus and dorsal bunion in adolescents with cerebral palsy: clinical and biomechanical factors.

AIM: The prevalence of severely symptomatic deformities of the first metatarsophalangeal (MTP) joint in adolescents with cerebral palsy (CP) requiring arthrodesis is unknown. Recent literature regarding these deformities is limited. We studied the presentation of severe, symptomatic deformities of the first ray in a large population of children and adolescents with CP and their association with gross motor function, CP subtype, and other musculoskeletal deformities. METHOD: We identified 41 patients with CP and a symptomatic deformity of the first MTP joint, managed by arthrodesis, from a large population based database over a 21-year period. Information recorded included demographics, CP subtype, Gross Motor Function Classification System (GMFCS), clinical presentation, and radiological features. RESULTS: Adolescents with spastic diplegia, at GMFCS levels II and III, were the most common group to develop symptomatic hallux valgus. In contrast, non-ambulant adolescents, at GMFCS levels IV and V, with dystonia or mixed tone, more commonly had dorsal bunions. INTERPRETATION: The type of first MTP joint deformity in patients with CP may be predicted by the type and distribution of movement disorder, and by GMFCS level. Specific patterns of associated musculoskeletal deformities may contribute to the development of these disorders and may provide a guide to surgical management. WHAT THIS PAPER ADDS: The prevalence of severe bunions requiring fusion surgery was 2%. The two types of bunion were hallux valgus and dorsal bunion. The type of bunion can be identified on both clinical and radiological grounds. The cerebral palsy subtype is predictive of the type of bunion.

Management of hypertonia in cerebral palsy.

PURPOSE OF REVIEW: The review provides an update on the treatment of hypertonia in cerebral palsy, including physical management, pharmacotherapy, neurosurgical, and orthopedic procedures. RECENT FINDINGS: Serial casting potentiates the effect of Botulinum neurotoxin A injections for spasticity. Deep brain stimulation, intraventricular baclofen, and ventral and dorsal rhizotomy are emerging tools for the treatment of dystonia and/or mixed tone. The long-term results of selective dorsal rhizotomy and the timing of orthopedic surgery represent recent advances in the surgical management of hypertonia. SUMMARY: Management of hypertonia in cerebral palsy targets the functional goals of the patient and caregiver. Treatment options are conceptualized as surgical or nonsurgical, focal or generalized, and reversible or irreversible. The role of pharmacologic therapies is to improve function and mitigate adverse effects. Further investigation, including clinical trials, is required to determine the role of deep brain stimulation, intraventricular baclofen, orthopedic procedures for dystonia, and rhizotomy.

Evidence-based Recommendations for Pediatric Orthopaedic Practice.

BACKGROUND: Evidence-based medicine has become the cornerstone to guide clinical practice decision-making. Evidence-based medicine integrates the strongest available evidence with clinical expertise to make decisions about clinical care. The quality of the evidence depends upon the soundness of the study methodology to allow for meaningful interpretation of the clinical results. The purpose of this review is to analyze the methodological design and clinical findings of published pediatric orthopaedic studies to determine their ability to change or influence clinical practice. METHODS: This is the first in a series of evidence-based reviews in pediatric orthopaedics. The pediatric orthopaedic literature was reviewed for randomized controlled trials (RCTs) published in 2013 to 2014. Two RCTs were selected from the Journal of Bone and Joint Surgery for in depth methodological review and analysis. Methodological reviews were performed by 2 orthopaedic surgeons with advanced research degrees. Following this, 2 clinical experts reviewed the articles to rate the clinical impact or value of each study. Methodological and clinical reviews were compiled, and a final recommendation on impact to change clinical practice was made based on both review components at the consensus of the panel. RESULTS: The first study reviewed investigated the impact of physical therapy on function following supracondylar humeral fractures in children. The reviewers deemed the superiority study to of sound design, and conclusions appropriate for the methodology used and clinical findings. The results do not compel a recommendation to change clinical practice. The second study investigated the impact of Botulinum Toxin A with casting for the treatment of idiopathic toe-walking in children. Although of relatively sound design, the sample size was too small to appropriately perform some statistical comparisons. No recommendation to change clinical practice could be made. CONCLUSION: Both RCTs reviewed were superiority studies with a negative result. No recommendation to change clinical practice could be made. SIGNIFICANCE: Interpretation of superiority studies with nonsignificant findings must be done with caution. The findings of both of these RCTs highlight the need for more noninferiority trials in the pediatric orthopaedic literature in order to appropriately demonstrate no difference between 2 treatment options.

Screening and referral for children with physical disabilities.

The clinical care of children with physical disabilities is a major priority for paediatricians and paediatric orthopaedic surgeons. Cerebral palsy (CP) is the prototypical condition and remains the most common cause of physical disability in developed countries. The incidence is approximately 2 per 1000 live births, translating to between 600 and 700 new children per annum in Australia, with approximately 34 000 children and adults currently living with CP. This figure is predicted to rise inexorably over the next 20 years. The care of children with physical disabilities, including those with CP, is usually coordinated by paediatricians, general practitioners and allied health teams including physiotherapists, with input from paediatric orthopaedic surgeons when appropriate. The emphasis in care for children with CP has moved from 'reactive' to 'proactive'. In the past, children are often referred when symptomatic, for example when a hip dislocation had occurred and became painful. The emphasis now is on coordinated, multidisciplinary care in which musculoskeletal manifestations of disability are identified by screening programmes. Systematic screening, especially when population-based and linked to a register, avoids children getting 'lost in the system'. Early and more effective interventions may be offered for the prevention of contractures, dislocation of the hip and spinal deformities. In this review, we will focus on the assessment of gait in children with physical disabilities, and monitoring for hip and spine deformity.

Hip Surveillance for Children With Cerebral Palsy: A Survey of the POSNA Membership.

BACKGROUND: Currently, hip surveillance programs for children with cerebral palsy exist in Europe, Australasia, and parts of Canada, but a neuromuscular hip surveillance program has yet to be adopted in the United States. The purpose of this study was to report the current orthopaedic practice of hip surveillance in children with cerebral palsy, identify areas of practice variation, and suggest steps moving forward to generate guidelines for national neuromuscular hip surveillance. METHODS: The entire membership of the Pediatric Orthopaedic Society of North America (POSNA) was surveyed in 2016 for information regarding their practice for hip surveillance in children with cerebral palsy. Detailed information regarding timing, frequency, and practice of hip surveillance was obtained in answers to 26 different questions. RESULTS: A survey response rate of 27% was obtained (350/1300 members) during the study period. The majority of respondents treated pediatric patients exclusively (97%), worked in an academic practice (70%), and was affiliated with a university (76%). In total, 18% (69/350) of respondents followed a regular cerebral palsy hip surveillance program, about half of whom (44%, 30/69) had adopted the Australian guidelines. Respondents agreed that a dislocated hip in a child with cerebral palsy was painful (90% agreement) and should be prevented by hip surveillance (93% agreement). Furthermore, 93% of respondents indicated they would follow a national surveillance program if one was in place. Age (79%), Gross Motor Function Classification System (81%), and migration percentage (MP) (78%) were all identified as critical elements to a hip surveillance program. The majority of respondents felt that a hip "at risk" for hip displacement had a MP between 20% and 30% (57% of respondents), whereas surgery should be utilized once the MP exceeded 40% (50% of respondents). CONCLUSIONS: Results from this survey demonstrate 90% of respondents agree that a dislocated hip could be painful and 93% would follow a national surveillance program if available. At a societal level, we have the ability to standardize cerebral palsy hip surveillance, thereby decreasing practice variation and improving quality of care delivery. LEVELS OF EVIDENCE: Level V.

Hip health at skeletal maturity: a population-based study of young adults with cerebral palsy.

AIM: We studied 'hip health' in a population-based cohort of adolescents and young adults with cerebral palsy to investigate associations between hip morphology, pain, and gross motor function. METHOD: Ninety-eight young adults (65 males, 33 females) from the birth cohort were identified as having developed hip displacement (migration percentage >30) and were reviewed at a mean age of 18 years 10 months (range 15-24y). Hip morphology was classified using the Melbourne Cerebral Palsy Hip Classification Scale (MCPHCS). Severity and frequency of pain were recorded using Likert scales. Gross motor function was classified by the Gross Motor Function Classification System (GMFCS). RESULTS: Hip pain was reported in 72% of participants. Associations were found between pain scores and both hip morphology and GMFCS. Median pain severity score for MCPHCS grades 1 to 4 was 2 (interquartile range [IQR] 1.0-3.0) compared to 7 (IQR 6.0-8.0) for grades 5 and 6 (severe subluxation or dislocation). Hip surveillance and access to surgery were associated with improved hip morphology and less pain. INTERPRETATION: Poor hip morphology at skeletal maturity was associated with high levels of pain. Limited hip surveillance and access to surgery, rather than GMFCS, was associated with poor hip morphology. The majority of young adults who had access to hip surveillance, and preventive and reconstructive surgery, had satisfactory hip morphology at skeletal maturity and less pain.

Comparison of lumbar epidural bupivacaine with fentanyl or clonidine for postoperative analgesia in children with cerebral palsy after single-event multilevel surgery.

AIM: To compare diazepam use, muscle spasm, analgesia, and side effects when clonidine or fentanyl are added to epidural bupivacaine in children with cerebral palsy after multilevel orthopaedic surgery. METHOD: Fifty children were prospectively randomized to receive clonidine (n=24, mean age 10y 10mo [SD 2y 11mo]) or fentanyl (n=26, mean age 10y 11mo [SD 2y 10mo]). RESULTS: There was no difference in primary outcome measures: median diazepam use (fentanyl 0, interquartile range [IQR] 0-0; clonidine 0, IQR 0-0; p=0.46), any muscle spasm (no muscle spasms in: fentanyl, 36%; clonidine, 62%; p=0.11), painful muscle spasm (fentanyl 40%; clonidine 25%; p=0.46), or pain score ≥6 (none: fentanyl 44%; clonidine 42%; p=0.29). There were differences in secondary outcome measures: no vomiting (clonidine 63%; fentanyl 20%); vomiting occurred more frequently with fentanyl (32% vomited more than three times; clonidine none; p=0.001). Fentanyl resulted in more oxygen desaturation (at least two episodes: fentanyl 20%; clonidine 0; p<0.001). Clonidine resulted in lower mean (SD) area under the curve for systolic blood pressure (fentanyl 106.5 [11.0]; clonidine 95.7mmHg [7.9]) and heart rate (fentanyl 104.9 beats per minute [13.6]; clonidine 85.3 [11.5]; p<0.001). INTERPRETATION: Clonidine and fentanyl provide adequate analgesia with low rates of muscle spasm, resulting in low diazepam use. The choice of epidural additive should be based upon the most tolerable side-effect profile.