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Presence and predictors of pain after orthopedic surgery and associated orthopedic outcomes in children with cerebral palsy

Abstract While children with cerebral palsy (CP) may undergo 8‐22 orthopedic surgeries in their lifetime, little is known about the associated pain. We aimed to assess the pain presence before and one year after lower extremity orthopedic surgery, predictors of pain presence at follow‐up, and the association between pain and orthopedic outcomes related to surgery. This retrospective study included 86 children with CP (M age = 10.0 years, SD = 3.2; range = 4.1‐17.3 years, Gross Motor Functional Classification System (GMFCS) level I‐III) who underwent orthopedic surgery and had completed questionnaires at gait analyses before (M = 2.7 months; range = 0.0‐5.7) and after surgery (M = 11.8 months; range = 9.0‐14.9). Pain presence, location, and Pediatric Outcomes Data Collection Instrument (PODCI) scores were documented before and after surgery at gait analyses. Pain prevalence was 60% at baseline and 56% at follow‐up. Significant predictors of pain presence at follow‐up included (1) pain presence at baseline (range of odds ratios [OR] across any/all locations = 3.22 to 15.54), (2) older age (range of OR for any pain, back, knee, and foot pain = 1.24‐1.26), (3) female sex (decreased OR for males for ankle pain = 0.12), (4) having hip surgery (decreased OR for foot pain = 0.20), and (5) lower GMFCS level (OR for foot pain = 0.41). Changes in PODCI Sports and Physical Function scores were associated with changes in hip and knee pain (P < .03); PODCI scores worsened for patients who had pain at both time points and improved for patients who had pain at baseline but not follow‐up. Pain was present for over half of the participants before and after orthopedic surgery. Pain presence at follow‐up was predicted by pain presence at baseline. Pain and functional outcomes were correlated at follow‐up. Prospective studies examining perioperative pain experience and factors predicting pain outcomes are warranted.


| INTRODUC TI ON
Cerebral palsy (CP) is the most common cause of physical disability in children, affecting 1.5-2.5 out of every 1000 live births and resulting in impaired postural and motor development and a sequela of musculoskeletal impairments and often co-occurring with impairments in sensation, cognition, and communication. 1,2 Prevalence estimates of orthopedic surgery in children with CP vary based on differences in CP severity sampled and different treatment practices across institutions and countries. In the United States individuals with CP may undergo 8-22 orthopedic surgeries in their lifetime. [3][4][5][6] Population estimates in Denmark suggest approximately 41%, 54%, and 62% of the children aged 8-15 years with CP in Gross Motor Function Classification System (GMFCS) levels I, II, and III-V, respectively, undergo orthopedic surgery. 7 Orthopedic surgeries continue to be frequent into adulthood; Horstmann et al reported 94% of adult participants with CP (n = 105) had experienced at least one lower extremity orthopedic surgery over a 5-year span. 8 Orthopedic surgeries aim to improve posture and limb alignment, normalize range of motion, or transfer muscle attachments to make muscles more functional-with intent to have a positive impact on function and pain, with greater emphasis placed on mobility for those in GMFCS level I-III and hip preservation and comfort in GMFCS levels IV-V.
While pain reduction may be a goal of orthopedic surgery in CP, 9 there is a dearth of research specific to pain outcomes from this treatment, possibly due to the challenges of obtaining self-reported pain among the approximate 25%-50% of individuals with cognitive or communication impairments (Novak 2012).
Surprisingly, only 5% of 229 orthopedic outcome studies assessed pain prevalence. 10 The quality and level of evidence for these studies was low, predictive factors were not explored, and about half of the available studies were conducted with sample sizes of less than 25 participants. In several cases, preoperative pain was not quantified limiting the opportunity to understand pain outcomes following surgery. [11][12][13] Of the studies with larger sample sizes (n ≥ 25) and with pain assessments conducted before and after surgery, the majority found pain reduced following surgery or trended in that direction. [14][15][16] Pelrine et al 17 found that pain did not change significantly and Lauder et al 18  Given the invasive nature of orthopedic surgeries and the frequency at which they typically occur in CP, it is reasonable to be concerned about the development of chronic postsurgical pain (CPSP) as an especially troubling outcome. 9,17,18 CPSP is defined as pain that develops or increases in intensity after a surgical procedure and persists beyond the healing process (≥3 months 19 ). In typically developing children and adolescents, CPSP affects approximately 13-42% of those undergoing predominantly orthopedic procedures 20,21 ; up to 69% experience some level of chronic pain after spinal fusions. 22 There is no reason to expect that individuals with CP would be spared incurring CPSP at similar rates, especially considering children with CP are typically exposed to repeated surgeries, including multilevel surgeries (SEMLS) involving multiple procedures performed during a single operation. 3 It is also problematic when preexisting pain does not resolve as intended following orthopedic surgery. For individuals without disabilities, preoperative pain persists after surgery (persistent pain) approximately 26%-30% of the time in adult samples undergoing a variety of orthopedic and nonorthopedic surgeries. 23 to the important finding that pain is common, long-lasting, and can be debilitating in individuals with CP. Specifically, chronic pain is estimated to affect 40%-60% of children or adolescents with CP [29][30][31][32][33][34][35][36][37] compared with 10%-37% of typically developing peers. 34,[38][39][40][41][42] Chronic pain has repeatedly been associated with decreased life satisfaction, physical function, self-care, sleep, involvement in social activities, and academics. 33,[43][44][45] Factors predictive of nonsurgical chronic pain in CP include increased gross motor impairment, 46,47 bilateral involvement, 48 older age, 48 and female sex. 49 As preexisting pain is arguably the strongest predictor of CPSP in populations without physical disability and given the high estimates of chronic pain in CP, it is imperative that preoperative pain be assessed in children with CP as a potential risk factor for development of CPSP.
To address the need for more information regarding pain before and after lower extremity orthopedic surgery in CP, we undertook a preliminary, retrospective approach. We aimed to (1) quantify the prevalence of back and lower extremity pain before and after orthopedic surgery, (2) identify preoperative factors associated with pain presence after orthopedic surgery (ie, presence of pain before surgery, CP severity, age, sex, type of surgery), and (3) examine relationships between pain presence before and after surgery and functional/mobility outcomes following surgery.

| ME THODS
This was a retrospective study for which the Institutional Review Board granted waiver of consent. Patient data from Gillette Children's Specialty Healthcare gait laboratory database were queried from January 1st, 2008 to November 30, 2020 to identify children who met the following inclusion criteria: (1) diagnosis of bilateral CP, (2) Gross Motor Functional Classification System (GMFCS 50 ) level I-III, (3) spastic or mixed tone, (4) <18 years old, (5) two gait analyses (termed baseline and follow-up) at which a proxyreported pain questionnaire was completed (standard of care at our institution), (6) not receiving intrathecal baclofen, and (7) lower extremity orthopedic surgery performed between the two gait analyses. If a child had bilateral surgery, only the right side was analyzed to ensure independence of observations. The baseline gait analysis occurred within 6 months prior to surgery; the follow-up gait analysis occurred 9-15 months after surgery.
Pain was assessed using a questionnaire provided to clinical patients at the time of gait analysis starting in 2008 ( Figure S1).
Retrospective pain findings using this questionnaire have been previously published. 17,51,52 The questionnaire only assessed pain presence by location (ie, back, hip, knee, ankle, foot, or other) and when pain was experienced (beginning/end of day, walking short distances, walking long distances, standing, navigating stairs or uneven terrain, constant/not activity related) at both the baseline and follow-up gait analyses. Pain described as "other" was included if it was described as back or lower extremity pain. We provided summary level pain information (termed "any pain") when patients had pain at one or more of the six locations.
Demographic information included age, sex, and CP severity.
CP severity was defined using GMFCS levels (ranging from I-V) where higher GMFCS levels indicate greater motor impairment.
Participants included in this study were GMFCS level I (ambulant without assistance), level II (ambulant without assistive devices, limitations in mobility outside the home), and level III (ambulant with assistive devices, wheelchair required outside the home). The location of orthopedic surgery was assigned (hip: psoas lengthening, adductor lengthening, femoral derotation osteotomy; knee: hamstring lengthening, patellar tendon advancement, rectus femoris transfer, distal femoral extension osteotomy, epiphysiodesis; ankle/foot: tibial derotation osteotomy, gastrocnemius or soleus lengthening, ankle/ foot soft and bony procedures).
Functional outcomes were collected at both the baseline and follow-up gait analyses using the Pediatric Outcomes Data Collection Instrument (PODCI; parent proxy due to patient age). 53 In particular, we were interested in performance on the Transfers and Basic Mobility and the Sports and Physical Function scales, which inquire about difficulty or ability to perform various mobility-related activities of daily living (eg, short distance walking, getting on or off chairs, toilets, vehicles) or more challenging skills (eg, running, biking, sports, prolonged walking, and prolonged stair climbing), respectively. Higher scores indicate greater mobility and functioning.

| RE SULTS
There were 86 participants who met the inclusion criteria (participant characteristics described in Table 1). Participants had various soft tissue or bony surgeries ( Figure S2). The majority of children (87% at baseline, 93% at follow-up) reported participation in physical therapy and/or home exercise programs.

| Pain prevalence
Pain prevalence at any location was 60% at baseline and 56% at follow-up ( Figure 1). Pain at individual locations ranged from 10% (hip) to 34% (foot) at baseline and 12% (ankle) to 33% (foot) at follow-up  Figure 1). Pain at individual locations was experienced most often during prolonged walking for each pain except back pain, which was most often experienced at the beginning or end of the day (Table S1).

| Predictors of pain presence at follow-up
In the full models with all five predictors, the location of orthopedic surgery and GMFCS level were not statistically significant predictors for all but foot pain, so the reduced model (which excluded these two predictors) was used (

| DISCUSS ION
The prevalence of pain before and after orthopedic surgery has rarely been reported for children with CP. In our sample, back or lower extremity pain prevalence remained unchanged from before to approximately 1 year after orthopedic surgery. Pain was reported in over half of the children. This is similar to the approximate 40%-60% reported by several other cross-sectional studies reporting pain prevalence in CP. 29 In this preliminary retrospective study, we found that the strongest predictor of pain presence at follow-up was the existence of pain at baseline. This is consistent with other studies assessing surgical outcomes in both children and adult populations with or without CP. 17,[60][61][62][63] The odds of each pain presence at follow-up either trended toward an increase (hip, ankle; both of which had the smallest sample sizes) or significantly increased (any, back, knee, foot) as age increased. This is consistent with previous findings that pain prevalence increases with age among those with CP. 48  CP severity and hip surgery were associated with foot pain outcomes. Those with lower GMFCS levels (ie, less severe CP, greater mobility/function) had an increased odds of foot pain at follow-up.
As others have found, this is likely due to greater weightbearing and mobility activities by those in lower GMFCS levels who have greater motor abilities. 65 Accordingly, 72% of participants in the current sample reported that their foot pain occurred during prolonged walking. These activities might be something participants in higher GMFCS levels may not be able to do or they may be protected from because of using upper extremity assistive devices to offload lower extremity stresses. Also, in alignment with previous studies, greater GMFCS level appeared to be associated with increases in other types of pain (eg, hip pain 65 ), but those analyses were likely underpowered given smaller sample sizes. Having hip surgery was associated with decreased foot pain at follow-up. We do not have a plausible explanation for why having hip surgery was associated with decreased ipsilateral foot pain at follow-up; it may be a spurious finding.
We assessed proxy-reported functional outcomes in relation  This is partially explained by provider referral practice, but some patients who do are being seen because of some concern of the family, limiting generalizability to the broader ambulatory CP population. Relatedly, results may not generalize outside our institution based on our general treatment philosophy and inclusion criteria, especially individuals with hemiplegia, in GMFCS levels IV-V, or on neuropathic pain and/or tone medications (eg, intrathecal baclofen).
Future studies are needed to explore pre-and postoperative pain in these subpopulations. Fourth, the average baseline pain assessment occurred 2.7 months prior to surgery at the baseline gait analysis, so we cannot be sure if that pain still existed at the time of surgery.
Fifth, sample sizes for those with location-specific pain ranged from 9 to 29 children. Therefore, this study was underpowered to analyze location-specific outcomes. Sixth, we cannot attribute change in pain or functional outcomes to orthopedic surgery because we lack a control group. Seventh, pain was assessed via proxy-report, which is not without issue, as parents/caregivers may over or underestimate pain prevalence. 66 However, proxy-report is the established method for pain research in young children and in samples where cognitive impairment may impede the ability to self-report. Finally, we cannot isolate the effects of one group of surgeries (eg, knee surgeries) on a given joint pain (eg, knee pain) because concomitant surgeries were often performed. This, however, represents standard of care.
Further research is needed to explore the trajectory of perioperative pain to include thorough assessments of intensity, duration, interference, and quality of the pain. Such studies should include opioid use and factors that are associated with extended opioid use.
It will be important to assess different classifications of perioperative pain, specifically preexisting chronic pain, incident pain (acute surgical pain), persistent chronic pain (present before surgery), and CPSP. Further work is needed to prospectively test the predictive factors identified in the current study, as well as additional factors, to confirm validity in predicting pain outcomes. It will be important to directly test the hypothesis that intervening on identified modifiable predictive factors will lead to improved pain outcomes.
The ability to presurgically identify those with CP at greater risk for postoperative pain would provide the rationale to deploy the currently available clinical perioperative pain management strategies, preoperative mental health assessments/treatment, and facilitate informed decision-making around treatment options.

| CON CLUS IONS
This study documented that back or lower extremity pain was present in over half of ambulatory children with CP both before and after lower extremity orthopedic surgery. Having baseline pain increased the odds of having pain at follow-up by approximately 2-15 times, depending on the location of the pain. Clinicians should be aware of this risk factor in their patients, be diligent in longitudinally tracking those patients' pain, and consider involving a multidisciplinary pain management team preoperatively. Future prospective study is warranted to thoroughly assess pain experience, typical pain trajectories, and variables predictive of pain outcomes.

ACK N OWLED G M ENTS
The authors would like to thank Cole Hagen for his help with data extraction. This study was funded, in part, by Eunice Kennedy Healthcare. Data are available upon reasonable request from the corresponding author.

CO N FLI C T O F I NTE R E S T
None of the authors has a conflict of interest to declare.