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Chronic postsurgical pain in children: prevalence and risk factors. A prospective observational study
British Journal of Anaesthesia, 117 (4): 489–96 (2016) doi: 10.1093/bja/aew260 Paediatrics
PAEDIATRICS
Chronic postsurgical pain in children: prevalence and risk factors. A prospective observational study
1
CHU de Bordeaux, Service d’Anesthésie Pédiatrique, Hôpital Pellegrin, Place Amélie Raba Léon, F-33076 Bordeaux, France, 2USMR, Université de Bordeaux, 176 Rue Léo Saignat, F-33076 Bordeaux, France, and 3INSERM U 12-11, Laboratoire Maladies Rares: Génétique et Métabolisme (MRGM) Université de Bordeaux, 176 Rue Léo Saignat, F-33076 Bordeaux, France *Corresponding author. E-mail: [email protected]
Abstract Background: Chronic postsurgical pain (CPSP) is well known in adults, with prevalence rates ranging from 10 to 50%. Little is known about the epidemiology of CPSP in children. The aim of this prospective observational study was to evaluate the prevalence of CPSP after surgery in children. Methods: After informed consent, children aged six to18 yr were included. Characteristics and risk factors for CPSP were recorded. Exclusion criteria included ambulatory surgery, refusal, inability to understand and change of address. All eligible children completed a preoperative questionnaire the day before surgery about pain, anxiety and their medical history. All data concerning anaesthetic and surgical procedures, such as acute pain scores (VAS) during the first 24 h were recorded. Three months after surgery all included children were sent a postoperative questionnaire about pain at the surgical site. Results: Altogether, 291 children were enrolled; the mean age was 12 yr, most subjects were male (60%). The most common type of surgery was orthopaedic (63%). In the 258 patients who completed the study, the prevalence of CPSP was 10.9%, most often with a neuropathic origin (64.3%). The two main risk factors were the existence of recent pain before surgery (<1 month) and the severity of acute postoperative pain (VAS >30 mm) in the first 24 h after orthopaedic and thoracic surgeries. Six months after surgery, only five children needed a visit with a chronic pain practitioner. Conclusions: These results highlight the necessity of evaluating and treating perioperative pain in order to prevent CPSP in children. Key words: children; chronic pain; postoperative pain
Chronic postsurgical pain (CPSP), defined as pain persisting 3 months after surgery,1 is well known in adults.1–3 Its incidence depends on the type of surgery, with rates of up to 60% after amputations, 30 to 50% after thoracotomies or breast surgeries,4 and approximately 10% after inguinal hernia repairs. Among patients experiencing CPSP, neuropathic syndromes5 are more frequent.4 6 7
The causes of CPSP in adults are not fully known, but several risks factors have been established. The main predictive risks factors are preoperative pain, many surgeries, psychological factors, surgical risks of nerve damage,8 9 and the severity of acute postoperative pain.10 In children, chronic medical pain is frequent,11 occurring most commonly in children with chronic diseases. The prevalence of
Accepted: May 26, 2016 © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: [email protected]
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H. Batoz1, *, F. Semjen1, M. Bordes-Demolis1, A. Bénard2 and K. Nouette-Gaulain1,3
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Editor’s key points • Little is known about the epidemiology of chronic post-surgical pain (CPSP) in children. • The authors performed a prospective study of the prevalence and risk factors for CPSP in children. • The prevalence of CPSP was found to be 10.9%. • Risk factors for CPSP were pain before surgery and severe acute postoperative pain.
Methods Patients Following approval from the hospital Ethics Committee of CHU de Bordeaux, France (Comité de Protection des Personnes SudOuest et Outre-Mer III, Chairperson Pr JP Duprat) and informed consent of the children and their parents, all children aged six to 18 yr undergoing elective surgery in our institution between March 2010 and April 2011 were included in this prospective observational study. The study was reviewed and approved by the French committee for personal data protection (CNIL ref. 1415799). A coordinating clinical research assistant (CRA) was designated to assist the main investigator with subject recruitment and follow-up. Children undergoing day case surgery, who were unwilling to participate, who had an insufficient understanding of the questionnaires or who moved away from their current address during the study period, were not included.
Procedure Information on the study was first given at the preanaesthetic visit in the month before surgery. Parents and children read an information sheet at home and gave us their verbal consent. The day before the intervention, eligible children with the help of their parents, completed the preoperative questionnaire.
Measure In the preoperative questionnaire, patient characteristics information including age, sex, weight, height, medical or surgical history, and history of chemotherapy or radiotherapy were collected. For pre-existent pain (>1 month) and recent pain (<1 month), the following parameters were gathered: history, location (site of later surgery or elsewhere), frequency and intensity of the pain (the pain score on the VAS was transformed into a 3-modality outcome: VAS <30 = mild pain, 30–59 = moderate pain, ≥60 = severe pain) and neuropathic component (self-report DN4 scale ≥4). The DN4 is a validated tool to screen for a
Statistical analysis Sample size estimation According to the literature, the expected prevalence of persisting pain (CPSP) at three months after surgery in adults is 20%.3 To
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pain such as headaches, abdominal pain12 and back pain13 varies from 25 to 46%.14 15 The prevalence of severe chronic pain and multi-site pain is especially high in girls.16 While the severity of acute postoperative pain in children has been extensively studied, only few, mostly retrospective studies focused on CPSP in this population.17 The aim of this epidemiologic prospective study was to determine the prevalence of CPSP, defined as persisting pain 3 months after surgery and rated ≥30 on a 100-point visual analogue scale (VAS), in children aged six to 18 yr. We also intended to determine the intensity of CPSP, the prevalence of neuropathic syndrome and the risk factors for CPSP.
neuropathic origin of chronic pain in adults.5 The DN4 has been used in paediatric patients aged more than six yr with burn sequelae because patients and their parents easily understand it.18 It includes three items about the type of pain (burning/painful and cold/electric shock), four items about the associated symptoms (tingling/pins and needles/numbness/itching), two about the existence of numbness in the painful area (on contact/on pinching), and one on the initiation or enhancement of pain by rubbing. It was initially designed to be completed with the help of a physician, but for the purposes of this study, the questions were adapted for completion by the patient.19 Four questions were asked regarding the impact of the pre-existing pain on current functioning, including attending school, eating, sleeping and playing. The impact of the pain was defined as severe if it impaired either eating or sleeping and was defined as moderate if it impaired educational or recreational activities without interfering with sleeping or eating. We considered there to be no impact on daily activities if the answers to all four questions were ‘no.’ Parents and children reported if they had taken any medication. Finally, they had to fill in a Visual Analogue Scale of anxiety (VAS anxiety 0–100 mm).20 The anxiety score on the VAS was transformed into a three-modality outcome: VAS <30 = mild anxiety, 30–59 = moderate anxiety and ≥60 = severe anxiety. The ‘preoperative’ questionnaire was kept in the study file. On the day of the surgery, we collected data about the anaesthetic (general anaesthesia±regional anaesthesia) and surgical procedures (type of surgery, duration, and scar size). An evaluation of the child’s pain was conducted in the first 24 h after the surgery using a VAS score (0–100 mm). The pain score on the VAS was transformed into a three-modality ordinal outcome (<30 = mild pain; 30–59 = moderate pain; ≥60 = severe pain). Children were asked about their worst pain at rest in times slots (H0; H1; H2; H4; H8; H12). Evaluations of pain began just after extubation (H0). Ten to twelve weeks after surgery, a questionnaire with a prestamped return envelope was sent to all eligible children included in the study. Response was required for three months after surgery. If they failed to reply by the four months mark, we called them to complete the questionnaire by phone. In the postoperative questionnaire, they were asked about the status of their pain in the operated area three months after the surgery using a VAS score (0–100 mm). In patients with CPSP (VAS ≥30 mm), they also completed the DN4 questionnaire to determine if there was a neuropathic component. They were also asked four questions regarding the impact of CPSP on daily activities such as going to school, playing, eating or sleeping, as in the preoperative questionnaire. They were asked if they had received any medications or analgesic treatments, and if they had pain in another location, and if so, what the intensity was (using a VAS score). Those experiencing pain were asked if they had been given any treatment for it, and if so, what type. Finally, we asked if children could participate in athletic activities and if they had experienced anxiety since the surgery (VAS anxiety 0–100 mm). When we received questionnaires by mail, a pain doctor contacted all children who reported a VAS score ≥30 mm in any location to suggest they visit a practitioner for analgesic treatment. This telephone contact was done at least five months after surgery.
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estimate the prevalence with a precision of plus or minus 5% (95% confidence interval (CI): 15%–25%), 250 patients were required (NQUERY® Advisor 6.0, Statistical Solutions Ltd, Cork, Ireland). With a sample size of 250 patients and a 20% prevalence of CPSP, 50 patients were expected to report CPSP in our study. With such a number of events, at least five factors could be included in our final multivariate logistic regression model.
Results Participants Of the 1141 medical assessed for eligibility, 850 patients (73%) were ineligible for the study. The main causes for ineligibility were being discharged from the hospital on the day of the surgery, interventions without surgical sections (such as endoscopy), refusals or patients unable to understand the study. Of the 291 participants, 258 (88%) returned the questionnaire. Of the 33 patients who did not complete the study, 15 (5%) were lost to follow-up, 17 (6%) did not return the questionnaire and one (0.3%) declined participation after initial approval (Fig. 1).
Patient characteristics data The mean [min-max] age at the time of inclusion was 12 [6–18] yr, with 46% from six to 11 yr and 54% from 12 to 18 yr, and the majority of the children were males (60%). The main type of surgery was orthopaedic (Table 1). In table 1, the patient characteristics data of the 291 recruited patients sample and the 258 patients contributing data at three months, were similar. In this population of 291 children, 13.6% had a medical history of chronic disease, 4.9% had received chemotherapy before and 2.1% had received radiotherapy. Half of them had a surgical history (49.8%), mainly for orthopaedic surgeries. The majority of the children were not anxious the day before surgery (57% reported no anxiety) (Table 2). One hundred and sixty-eight children (61.6%) experienced moderate to severe pre-existent pain (>1 month) before surgery (Table 2). The pain was mostly (120/168) because of the pathology motivating the surgery. A history of neuropathic pain (DN4 ≥4) was found in 34/168 children. One hundred and eleven children (39.9%) reported recent pain (<1 month) at the time of surgery. In most patients, the pain was because of the pathology motivating the surgery (77.6%). Sixtyfive patients (23.4%) experienced severe pain (VAS score ≥60/
Not eligible (n=850)
Patients included (n=291)
Patients excluded (n=33) Loss of contact (n=15) Didn’t return the questionnaire (n=17) Declined participation (n=1) Patients completed the study (n=258)
Fig 1 Flow chart of the cohort.
Table 1 Patient characteristics Variable
All patients n=291
Age at inclusion Mean (range) 12.04 (6–18) Distribution according to age (%) 6–11 yr 134 (46) 12–18 yr 157 (54) Sex n (% male) 175 (60.1) Type of surgery n (%) Orthopaedics 180 (61.8) Thoracic surgery 25 (8.6) Laparotomy/ 40 (13.8) scopic Uro/inguinal 25 (8.6) surgery All surgeries 21 (7.2) pooled
Patients who completed the study n=258
P
12.07 (6–18)
0.670
116 (45) 142 (55) 156 (60.5)
0.298
164 (63.6) 22 (8.5) 33 (12.8)
0.750 0.572
22 (8.5) 17 (6.6)
100) (Table 2). A neuropathic component was found in 14/107 (12.8%) children. As shown in Table 2, the data from patients who completed the study were not significantly different from those who did not.
Prevalence and characteristics of CPSP at three months Of the 258 participants who completed the study, 28 (10.9%, [95% CI: 7.3–15.3]) reported pain (VAS ≥30/100) in the operated area (Table 3). Severe pain (VAS ≥60/100) was reported by 10/28 children reported CPSP, (i.e. 3.9%, [95% CI: 1.9–7.0] of the 258 patients who completed the study). A neuropathic component (DN4 ≥4) was found in 18 of the 28 (64.3%) children with CPSP (Table 3).
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Statistical method The prevalence of CPSP and its binomial 95% confidence interval were estimated. Factors associated with the presence of CPSP (in the whole sample and in the subgroup of patients with orthopaedic or thoracic surgery), were investigated using a logistic regression model. Factors associated with CPSP in the univariate analysis with statistical significance <0.20 were included in the multivariate model and other factors that we wanted the multivariate analysis to be adjusted for: (i) regional anaesthesia, and acute pain within the first 24 h post-surgery for the analysis conducted in the whole sample; (ii) age, major type of surgery, and regional anaesthesia for the analysis restricted to patients with orthopaedic or thoracic surgery. The final multivariate models were checked for interactions. Analyses were performed using SAS® software (version 9.2 or later).
Assessed for eligibility (n=1141)
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Table 2 Preoperative data on medical or surgical histories, preoperative pain, and anxiety before surgery. *m.d for missing data Variable
Patients who completed the study (n=258) n (%)
P
284 (7) 162 (57.0) 65 (22.9) 57 (20.1)
254 (4) 150 (59.0) 55 (21.7) 49 (19.3)
0.133
273 (18) 105 (38.4) 66 (24.2) 102 (37.4) 168 (0) 107 (63.7) 13 (7.7) 48 (28.6)
244 (14) 91 (37.3) 58 (23.8) 95 (38.9) 148 (5) 99 (66.9) 12 (8.1) 37 (25.0)
0.251 0.288
278 (13) 167 (60.1%) 46 (16.5%) 65 (23.4%) 107 (4) 83 (77.6)
248 (10) 149 (60.1%) 40 (16.1%) 59 (23.8%) 95 (4) 73 (76.8)
7 (6.5) 17 (15.9)
6 (6.3) 16 (16.9)
Table 3 Intensity of CPSP (VAS mm) at three months, neuropathic component, impact on activity and treatment Variable
n
Intensity of CPSP (VAS) Mild (<30) 230 Moderate (30–59) 18 Severe (≥60) 10 In children moderate to severe CPSP (n=28) Neuropathic pain 18 Impact of pain on activities Moderate 22 Severe 6 Analgesic treatment No analgesics 3 Only first class 15 First and second class 7 Three classes 3 Antineuropathic treatment 0
% 89.1 7.0 3.9 64.3 78.5 21.5 10.7 53.6 25.0 10.7 0.0
Twenty-five (89.3%) children were given analgesics because of CPSP, usually acetaminophen or/and an NSAID. Regardless of the intensity of the reported pain, the impact of the pain was severe for six children (22.2%) (Table 3).
Surgical and anaesthetic procedures in children with and without CPSP The main type of surgery in this study was orthopaedic (63.6%). Of those 164 children, 22 (13.4%) presented with CPSP. Among
0.611
0.737
children who underwent thoracotomy (22 children), 5 (23%) reported CPSP. In the population of children with CPSP (28), 23 (85.2%) had significant acute postoperative pain (VAS ≥ 30) during the first 24 h (Supplementary material, Fig. S1). Regional anaesthesia was not associated with CPSP in this sample. As far as the anaesthetic and surgical procedures were concerned ( premedication agents, hypnotic or opioid agents, scar size), no risk factors were associated with CPSP. All 28 children with CPSP were called back after receipt of the questionnaire, five to six months after the surgery. None of them needed to be admitted to the hospital because of pain. A visit with a chronic pain practitioner was suggested to five of them. The other 23 children had pain resolved entirely when we called them.
Risk factors of CPSP Among the 13 potential risk factors investigated in the univariate analysis, five were associated with CPSP with a statistical significance (P<0.2): age at inclusion, pre-existent pain (>1 month), intensity of recent pain, type of surgery, and scar size (Table 4). They all were included in the multivariate analysis together with two other factors that we wanted the multivariate analysis to be adjusted for: regional anaesthesia and acute pain within the first 24 h post-surgery. In the multivariate model, only recent pain (<1 month) was independently associated with CPSP (P=0.007). Children reporting a recent pain had a higher risk of developing CPSP, would the recent pain be moderate (OR=5.6; [95% CI: 1.8–17.8]) or severe (OR=3.3; [95% CI: 1.1–10.1]) (Table 4). No interaction was retrieved in this final multivariate model. When we restricted our analysis to patients with thoracotomies or orthopaedic procedures (n=171 in the multivariate
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Anxiety (VAS) Total n (md*) Mild (<30) Moderate (30–59) Severe (≥60) Pre-existent pain (>1 month) (VAS) Total n (md*) Mild (<30) Moderate (30–59) Severe (≥60) Location of pain (≥30) Site of later surgery Site of later surgery and elsewhere Pain elsewhere Recent pain (<1 month) (VAS) Total n (md*) Mild (<30) Moderate (30–59) Severe (≥60) Location of recent pain (≥30) Site of later surgery Site of later surgery and elsewhere Pain elsewhere
All patients (n=291) n (%)
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Table 4 Univariate and multivariate analysis of CPSP risk factors. CI, Confidence Interval; OR, Odds Ratio Variable
Comparison
n
n CPSP
Univariate analysis OR
Sex Age at inclusion in two classes Pre-existent pain (>1 month, VAS ≥30) Recent pain (<1 month, VAS ≥30)
Scar size >3 cm Regional anaesthesia Acute pain within the first 24 h post-surgery (VAS score ≥30) History of chronic diseases Chemotherapy History of surgery
Planning of surgery Premedication
156 102 115 143 153 91 149 40 59 71 17 142 151 107 163 95 184 65 35 222 13 244 130 69 59 29 225 223 35
16 12 7 21 19 5 9 8 8 1 5 22 20 8 19 9 23 4 3 24 1 26 16 8 4 4 24 24 4
analysis), the presence of recent pain (<1 month) before surgery and severe acute postoperative pain in the first 24 h were associated with a higher risk of CPSP (Table 5).
Discussion This prospective observational study highlights that the prevalence of CPSP is lower in children than in adults.3 4 10 21 We found that chronic postsurgical pain is an important issue in children undergoing surgery, occurring in 11% (CI: 7–15) of patients. Severe chronic postsurgical pain occurred in 4% (CI: 2–7) of children and was mostly of neuropathic origin (64.3%). However, 23/28 of patients were pain-free when we called them upon receipt of the questionnaire, and impairments of pain were mild for 22/28 of them. These results are similar to the previous data. In retrospective studies, authors found CPSP in 13% of children, and after thoracotomies,22 CPSP was found in 16% of children.23 Neuropathic components and anaesthetic procedure details were not recorded. In our study, 2/3 of the procedures were orthopaedic surgeries (63.5%), similar to other studies,22 because of the ages included. CPSP after orthopaedic procedures was found in 13% of children, and of those patients, a neuropathic origin was found in 63%. In our study, thoracotomies were the second most common type of surgery associated with a high rate of CPSP (22.7%), mostly with a neuropathic component. Our results are comparable with those of Kristensen and colleagues23 who examined chronic pain
ref 1.167 ref 2.66 2.44 ref ref 3.89 2.44 ref 20.88 11.00 1.89 ref 1.26 ref 2.18 ref 0.77 ref 0.70 ref ref 0.93 0.52 1.15 ref 0.93 ref
95% CI
P
OR
IC 95%
P
[0.517–2.57]
0.689
[1.13–6.96] [0.94–7.57]
0.028 0.118
1.84 0.82
[0.64–6.16] [0.23–3.07]
0.282 0.765
0.017
[1.82–17.77] [1.094–10.15]
0.007 . . 0.087
[1.69–341.31] [1.57–159.36] [0.92–8.43]
0.091
[3.11–4.14] [2.24–198.86] [0.83–4.72]
0.160
. 5.62 3.31 . 15.14 8.53 2.56
[0.56–3.04]
0.681
1.36
[0.50–4.11]
0.561
[0.80–7.65]
0.244
22.10
[0.67–8.11]
0.232
[0.18–2.38]
1.00
[0.04–3.77]
1.00
[1.36–10.96] [0.87–6.72] 0.001
0.56 [0.36–2.25] [0.14–1.49] [0.32–3.26]
0.766
[0.33–3.34]
1.00
after thoracotomies in children and youths. They found a prevalence of chronic pain of 19% in children aged seven to 12 yr, and 28% in those aged 13 to 25 yr. After adjusting for confounding variables, younger ages did not appear to protect against CPSP in our study (younger ages were a significant protective factor against CPSP in the univariate but not in the multivariate analysis). This can be explained by the high incidence of orthopaedic surgeries in the group of older children in our study. Moreover, in adults, several studies found that the risk of chronic pain decreased with age: from 39–58% in patients >40 yr of age to 14–17% in patients more than 65 yr.24 Therefore, it is difficult to make conclusions about the influence of age on the onset of CPSP. A major finding of this study is the predominance of neuropathic components in severe CPSP (64.3%, 18/28 children), as seen in adult literature.25 The explanation for this discrepancy could be that authors failed to seek out neuropathic pain in CPSP in children. The only study that addressed this question was retrospective and included few patients.26 In paediatrics studies about chronic medical pain, a neuropathic component is rare. In our study, most of children had a surgical history (49.8%) and that can explain the high rate of neuropathic pain. The underdiagnosis is the most probable explanation for the lack of specific treatments for children who suffer from severe pain. To us, this result is a very important finding as specific treatments do exist and neuropathic pain should be a therapeutic target in the management of CPSP.
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Major type of surgery
Male Female 6–11 yr 12–18 yr Yes No Mild Moderate Severe Others Thoracic Orthopaedic Yes No Yes No Yes No Yes No Yes No No Minor Major Emergency Planned Yes No
Multivariate model (248 patients)
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Table 5 Univariate and multivariate analysis of CPSP risk factors after orthopaedic or thoracic surgery. CI, Confidence Interval; OR, Odds Ratio Comparison
n
n CPSP
Univariate analysis
Sex
Male Female 6–11 yr 12–18 yr Yes No Mild Moderate Severe Thoracic Orthopaedic Yes No Yes No Yes No Yes No Yes No No Simplex Complex Emergency Planned Yes No
111 75 61 125 118 54 114 28 36 22 164 116 70 116 70 127 51 26 159 8 177 84 52 50 12 174 172 14
15 12 6 21 19 4 8 8 8 5 22 19 8 18 9 23 3 3 23 1 25 15 8 4 3 24 23 4
ref 1.22 ref 1.85 2.40 ref ref 5.30 3.79 ref 0.53 1.52 ref 1.24 ref 3.54 ref 0.77 ref 0.87 ref ref 0.84 0.40 2.08 ref 0.39 ref
OR
Age at inclusion in two classes Pre-existent pain (>1 month, VAS ≥30) Recent pain (<1 month, VAS ≥30)
Major type of surgery Scar size >3 cm Regional anaesthesia Acute pain within the first 24 h post-surgery (VAS score ≥30) History of chronic diseases Chemotherapy History of surgery
Planning of surgery Premedication
It would be better to develop an interdisciplinary paediatric pain rehabilitation program for all children at risk of developing CPSP, as is done for chronic medical pain.27 Until now, children with CPSP were not identified, so post-surgical pain was not supported properly. Second, we tried to determine the main risk factors associated with CPSP. We found that recent preoperative pain and acute pain after orthopaedic and thoracic surgeries were associated with an increased risk of developing CPSP. These data are similar to results in the adult population.3 24 28 When compared with existing literature,29 30 regional anaesthesia associated with general anaesthesia did not decrease the risk of CPSP. There may be two explanations for this result. The first is the fact that regional anaesthesia was used in the vast majority of surgeries carrying a risk of postoperative pain, for example in thoracotomies and orthopaedic procedures. Indeed, our study was not designed to show the benefits of regional anaesthesia on the onset of CPSP. The second way to explain this result is to consider the severity of acute postoperative pain, a significant outcome after orthopaedic and thoracic surgeries, as a sign of failed regional anaesthesia. A limitation of our study was the exclusion of ambulatory surgeries. It is possible that the prevalence of CPSP after ambulatory surgeries is lower because interventions are less painful. For instance, inguinal herniorraphy is almost always performed as an ambulatory surgery. Nevertheless, chronic pain after inguinal herniorraphy is reported in approximately 12% of adults5 and is
Multivariate model (171 patients)
95% CI
P
[0.53–2.77]
0.675
[0.74–5.28] [0.85–8.61]
0.269 0.150 0.002
[1.76–16.08] [1.29–11.18] [0.19–1.73] [0.64–3.87]
0.328 0.397
[0.54–3.07]
0.673
[1.16–15.42]
0.037
[0.17–2.45]
1.000
[0.05–5.18]
1.000
OR
ref 2.81 0.82 ref ref 6.62 3.85 ref 0.40
1.26 ref 4.04 ref
IC 95%
P
[0.85–11.89] [0.23–3.07]
0.116 0.765
[0.10–1.75]
0.005 . . . 0.197
[0.44–4.04]
0.674
[1.19–19.14]
0.042
[0.057–1.54]
0.114
[2.02–22.79] [1.19–12.90]
0.285 [0.31–2.09] [0.11–1.18] [0.44–7.57]
0.387
[0.12–1.50]
0.126
0.27
observed in children as well,9 so it is unlikely that our results would have changed dramatically. We included only children more than six yr of age because self-report with VAS scale can be used for postoperative pain evaluation. In order to explore neuropathic postoperative pain, we have chosen the DN4 questionnaire for use as self-report instrument, because this questionnaire was yet used in children aged >six yr.18 Even if the prevalence of CPSP is less than in adults, detecting CPSP may prevent fear of pain in children and adolescents with neuropathic pain and complex regional pain syndrome.31 The heterogeneity of our study sample with regard of the type of surgery makes our results difficult to interpret, (i.e. the type of surgery seems to be confounded with site of scar). In future studies, the prevalence of CPSP in scoliosis or thoracic surgeries could be evaluated separately. In our study, we have only included children without polyhandicap even if this population is probably at high-risk to develop CPSP with a neuropathic origin, because of difficulties of evaluation. Despite these limitations, this study represents an important assessment of chronic pain after paediatric surgery. We must improve preoperative and acute postoperative analgesia to decrease the proportion of CPSP seen after surgeries in children as in adults,32 primarily after orthopaedic and thoracic procedures. Moreover, as nerve lesions and central sensitization are involved in CPSP development, we probably should diagnose neuropathic pain before the child leaves hospital.33 Finally, during surgery
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Variable
Chronic postsurgical pain in children
Authors’ contributions Study design/planning: A.B., H.B. Study conduct: H.B., M.B-D. Data analysis: A.B. Writing paper: H.B., F.S., K.N-G. Revising paper: all authors
Supplementary material Supplementary material is available at British Journal of Anaesthesia online.
Acknowledgements Data monitoring: Sandrine Desjardins (DRCI, CHU de Bordeaux). Scientific collaboration for the design of the study: Paul Perez (USMR, CHU de Bordeaux). Assistance for subject recruitment and data collection: Lorena Sanchez (clinical research assistant, CHU de Bordeaux and Louise Baschet (data manager, CHU Bordeaux).
Declaration of interests None declared.
Funding CHU de Bordeaux, Place Amélie Raba Léon, F-33076 Bordeaux, France.
References 1. Macrae WA. Chronic post-surgical pain: 10 years on. Br J Anaesth 2008; 101: 77–86 2. Bruce J, Drury N, Poobalan AS, Jeffrey RR, Smith WC, Chambers WA. The prevalence of chronic chest and leg pain following cardiac surgery: a historical cohort study. Pain 2003; 104: 265–73 3. Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet 2006; 367: 1618–25
4. Duale C, Ouchchane L, Schoeffler P, Dubray C. Neuropathic aspects of persistent postsurgical pain: a French multicenter survey with a 6-month prospective follow-up. The Journal of Pain: Official Journal of the American Pain Society 2014; 15: 24 e1-e0 5. Bouhassira D, Attal N, Alchaar H, et al. Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain 2005; 114: 29–36 6. Martinez V, Baudic S, Fletcher D. [Chronic postsurgical pain]. Ann Fr Anesth Reanim 2013; 32: 422–35 7. Wilkins KL, McGrath PJ, Finley GA, Katz J. Phantom limb sensations and phantom limb pain in child and adolescent amputees. Pain 1998; 78: 7–12 8. Maguire MF, Ravenscroft A, Beggs D, Duffy JP. A questionnaire study investigating the prevalence of the neuropathic component of chronic pain after thoracic surgery. Eur J Cardiothorac Surg 2006; 29: 800–5 9. Wildgaard K, Ravn J, Kehlet H. Chronic post-thoracotomy pain: a critical review of pathogenic mechanisms and strategies for prevention. Eur J Cardiothorac Surg 2009; 36: 170–80 10. Bonnet A, Lavand’homme P, France MN, Reding R, De Kock M. [Postoperative pain trajectories to identify risk of chronic postsurgical pain in living donors for liver transplantation]. Ann Fr Anesth Reanim 2012; 31: 945–9 11. Zernikow B, Wager J, Hechler T, et al. Characteristics of highly impaired children with severe chronic pain: a 5-year retrospective study on 2249 pediatric pain patients. BMC Pediatr 2012; 12: 54 12. Schurman JV, Friesen CA. Chronic abdominal pain in children: an update. Mo Med 2006; 103: 69–75 13. Sato T, Ito T, Hirano T, et al. Low back pain in childhood and adolescence: a cross-sectional study in Niigata City. Eur Spine J 2008; 17: 1441–7 14. Hermann C, Hohmeister J, Zohsel K, Tuttas ML, Flor H. The impact of chronic pain in children and adolescents: Development and initial validation of a child and parent version of the Pain Experience Questionnaire. Pain 2008; 135: 251–61 15. Roth-Isigkeit A, Thyen U, Raspe HH, Stoven H, Schmucker P. Reports of pain among German children and adolescents: an epidemiological study. Acta Paediatr 2004; 93: 258–63 16. Perquin CW, Hazebroek-Kampschreur AA, Hunfeld JA, et al. Pain in children and adolescents: a common experience. Pain 2000; 87: 51–8 17. Kristensen AD, Ahlburg P, Lauridsen MC, Jensen TS, Nikolajsen L. Chronic pain after inguinal hernia repair in children. Br J Anaesth 2012; 109: 603–8 18. Orellana Silva M, Yanez V, Hidalgo G, Valenzuela F, Saavedra R. 5% lidocaine medicated plaster use in children with neuropathic pain from burn sequelae. Pain Med 2013; 14: 422–9 19. Bouhassira D, Lanteri-Minet M, Attal N, Laurent B, Touboul C. Prevalence of chronic pain with neuropathic characteristics in the general population. Pain 2008; 136: 380–7 20. Crandall M, Lammers C, Senders C, Savedra M, Braun JV. Initial validation of a numeric zero to ten scale to measure children’s state anxiety. Anesth Analg 2007; 105: 1250–3 21. Brandsborg B, Nikolajsen L, Hansen CT, Kehlet H, Jensen TS. Risk factors for chronic pain after hysterectomy: a nationwide questionnaire and database study. Anesthesiology 2007; 106: 1003–12 22. Fortier MA, Chou J, Maurer EL, Kain ZN. Acute to chronic postoperative pain in children: preliminary findings. J Pediatr Surg 2011; 46: 1700–5
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and/or face to patient considered at risk for CPSP, prophylactic antineuropathic treatment could be given.34 35 In the future, it would be interesting to create an interdisciplinary preventive paediatric pain treatment program designed for children at risk of CPSP. In conclusion, this study suggests that three months after surgery, the prevalence of CPSP after paediatric surgery (10.9%) is an important issue, in particular the high proportion of it with a neuropathic origin (64%). However, only five children needed a visit with a chronic pain practitioner six months after surgery. These findings are very important because CPSP is not accounted for and, therefore, is not treated despite its intensity. The two main risk factors for CPSP are the existence of pain shortly before surgery and the severity of acute postoperative pain in the first 24h after orthopaedic and thoracic surgeries. In the future, it would be interesting to evaluate the prevalence of chronic postoperative pain in younger children (
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30. Weber T, Matzl J, Rokitansky A, et al. Superior postoperative pain relief with thoracic epidural analgesia versus intravenous patient-controlled analgesia after minimally invasive pectus excavatum repair. J Thorac Cardiovasc Surg 2007; 134: 865–70 31. Simons LE. Fear of pain in children and adolescents with neuropathic pain and complex regional pain syndrome. Pain 2016; 157(Suppl 1): S90–7 32. Brennan TJ, Kehlet H. Preventive analgesia to reduce wound hyperalgesia and persistent postsurgical pain: not an easy path. Anesthesiology 2005; 103: 681–3 33. Martinez V, Ben Ammar S, Judet T, Bouhassira D, Chauvin M, Fletcher D. Risk factors predictive of chronic postsurgical neuropathic pain: the value of the iliac crest bone harvest model. Pain 2012; 153: 1478–83 34. Sun Y, Li T, Wang N, Yun Y, Gan TJ. Perioperative systemic lidocaine for postoperative analgesia and recovery after abdominal surgery: a meta-analysis of randomized controlled trials. Dis Colon Rectum 2012; 55: 1183–94 35. Chaparro LE, Smith SA, Moore RA, Wiffen PJ, Gilron I. Pharmacotherapy for the prevention of chronic pain after surgery in adults. Cochrane Database Syst Rev 2013; 7: CD008307 Handling editor: A. R. Absalom
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23. Kristensen AD, Pedersen TA, Hjortdal VE, Jensen TS, Nikolajsen L. Chronic pain in adults after thoracotomy in childhood or youth. Br J Anaesth 2010; 104: 75–9 24. Aasvang E, Kehlet H. Chronic postoperative pain: the case of inguinal herniorrhaphy. Br J Anaesth 2005; 95: 69–76 25. Batoz H, Verdonck O, Pellerin C, Roux G, Maurette P. The analgesic properties of scalp infiltrations with ropivacaine after intracranial tumoral resection. Anesth Analg 2009; 109: 240–4 26. Ouaki J, Dadure C, Bringuier S, et al. Continuous infusion of ropivacaine: an optimal postoperative analgesia regimen for iliac crest bone graft in children. Paediatr Anaesth 2009; 19: 887–91 27. Logan DE, Conroy C, Sieberg CB, Simons LE. Changes in willingness to self-manage pain among children and adolescents and their parents enrolled in an intensive interdisciplinary pediatric pain treatment program. Pain 2012; 153: 1863–70 28. Gottschalk A, Ochroch EA. Clinical and demographic characteristics of patients with chronic pain after major thoracotomy. Clin J Pain 2008; 24: 708–16 29. Richardson J. Chronic pain after thoracic surgery. Acta Anaesthesiol Scand 2000; 44: 220
PAEDIATRICS
Chronic postsurgical pain in children: prevalence and risk factors. A prospective observational study
1
CHU de Bordeaux, Service d’Anesthésie Pédiatrique, Hôpital Pellegrin, Place Amélie Raba Léon, F-33076 Bordeaux, France, 2USMR, Université de Bordeaux, 176 Rue Léo Saignat, F-33076 Bordeaux, France, and 3INSERM U 12-11, Laboratoire Maladies Rares: Génétique et Métabolisme (MRGM) Université de Bordeaux, 176 Rue Léo Saignat, F-33076 Bordeaux, France *Corresponding author. E-mail: [email protected]
Abstract Background: Chronic postsurgical pain (CPSP) is well known in adults, with prevalence rates ranging from 10 to 50%. Little is known about the epidemiology of CPSP in children. The aim of this prospective observational study was to evaluate the prevalence of CPSP after surgery in children. Methods: After informed consent, children aged six to18 yr were included. Characteristics and risk factors for CPSP were recorded. Exclusion criteria included ambulatory surgery, refusal, inability to understand and change of address. All eligible children completed a preoperative questionnaire the day before surgery about pain, anxiety and their medical history. All data concerning anaesthetic and surgical procedures, such as acute pain scores (VAS) during the first 24 h were recorded. Three months after surgery all included children were sent a postoperative questionnaire about pain at the surgical site. Results: Altogether, 291 children were enrolled; the mean age was 12 yr, most subjects were male (60%). The most common type of surgery was orthopaedic (63%). In the 258 patients who completed the study, the prevalence of CPSP was 10.9%, most often with a neuropathic origin (64.3%). The two main risk factors were the existence of recent pain before surgery (<1 month) and the severity of acute postoperative pain (VAS >30 mm) in the first 24 h after orthopaedic and thoracic surgeries. Six months after surgery, only five children needed a visit with a chronic pain practitioner. Conclusions: These results highlight the necessity of evaluating and treating perioperative pain in order to prevent CPSP in children. Key words: children; chronic pain; postoperative pain
Chronic postsurgical pain (CPSP), defined as pain persisting 3 months after surgery,1 is well known in adults.1–3 Its incidence depends on the type of surgery, with rates of up to 60% after amputations, 30 to 50% after thoracotomies or breast surgeries,4 and approximately 10% after inguinal hernia repairs. Among patients experiencing CPSP, neuropathic syndromes5 are more frequent.4 6 7
The causes of CPSP in adults are not fully known, but several risks factors have been established. The main predictive risks factors are preoperative pain, many surgeries, psychological factors, surgical risks of nerve damage,8 9 and the severity of acute postoperative pain.10 In children, chronic medical pain is frequent,11 occurring most commonly in children with chronic diseases. The prevalence of
Accepted: May 26, 2016 © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: [email protected]
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H. Batoz1, *, F. Semjen1, M. Bordes-Demolis1, A. Bénard2 and K. Nouette-Gaulain1,3
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Editor’s key points • Little is known about the epidemiology of chronic post-surgical pain (CPSP) in children. • The authors performed a prospective study of the prevalence and risk factors for CPSP in children. • The prevalence of CPSP was found to be 10.9%. • Risk factors for CPSP were pain before surgery and severe acute postoperative pain.
Methods Patients Following approval from the hospital Ethics Committee of CHU de Bordeaux, France (Comité de Protection des Personnes SudOuest et Outre-Mer III, Chairperson Pr JP Duprat) and informed consent of the children and their parents, all children aged six to 18 yr undergoing elective surgery in our institution between March 2010 and April 2011 were included in this prospective observational study. The study was reviewed and approved by the French committee for personal data protection (CNIL ref. 1415799). A coordinating clinical research assistant (CRA) was designated to assist the main investigator with subject recruitment and follow-up. Children undergoing day case surgery, who were unwilling to participate, who had an insufficient understanding of the questionnaires or who moved away from their current address during the study period, were not included.
Procedure Information on the study was first given at the preanaesthetic visit in the month before surgery. Parents and children read an information sheet at home and gave us their verbal consent. The day before the intervention, eligible children with the help of their parents, completed the preoperative questionnaire.
Measure In the preoperative questionnaire, patient characteristics information including age, sex, weight, height, medical or surgical history, and history of chemotherapy or radiotherapy were collected. For pre-existent pain (>1 month) and recent pain (<1 month), the following parameters were gathered: history, location (site of later surgery or elsewhere), frequency and intensity of the pain (the pain score on the VAS was transformed into a 3-modality outcome: VAS <30 = mild pain, 30–59 = moderate pain, ≥60 = severe pain) and neuropathic component (self-report DN4 scale ≥4). The DN4 is a validated tool to screen for a
Statistical analysis Sample size estimation According to the literature, the expected prevalence of persisting pain (CPSP) at three months after surgery in adults is 20%.3 To
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pain such as headaches, abdominal pain12 and back pain13 varies from 25 to 46%.14 15 The prevalence of severe chronic pain and multi-site pain is especially high in girls.16 While the severity of acute postoperative pain in children has been extensively studied, only few, mostly retrospective studies focused on CPSP in this population.17 The aim of this epidemiologic prospective study was to determine the prevalence of CPSP, defined as persisting pain 3 months after surgery and rated ≥30 on a 100-point visual analogue scale (VAS), in children aged six to 18 yr. We also intended to determine the intensity of CPSP, the prevalence of neuropathic syndrome and the risk factors for CPSP.
neuropathic origin of chronic pain in adults.5 The DN4 has been used in paediatric patients aged more than six yr with burn sequelae because patients and their parents easily understand it.18 It includes three items about the type of pain (burning/painful and cold/electric shock), four items about the associated symptoms (tingling/pins and needles/numbness/itching), two about the existence of numbness in the painful area (on contact/on pinching), and one on the initiation or enhancement of pain by rubbing. It was initially designed to be completed with the help of a physician, but for the purposes of this study, the questions were adapted for completion by the patient.19 Four questions were asked regarding the impact of the pre-existing pain on current functioning, including attending school, eating, sleeping and playing. The impact of the pain was defined as severe if it impaired either eating or sleeping and was defined as moderate if it impaired educational or recreational activities without interfering with sleeping or eating. We considered there to be no impact on daily activities if the answers to all four questions were ‘no.’ Parents and children reported if they had taken any medication. Finally, they had to fill in a Visual Analogue Scale of anxiety (VAS anxiety 0–100 mm).20 The anxiety score on the VAS was transformed into a three-modality outcome: VAS <30 = mild anxiety, 30–59 = moderate anxiety and ≥60 = severe anxiety. The ‘preoperative’ questionnaire was kept in the study file. On the day of the surgery, we collected data about the anaesthetic (general anaesthesia±regional anaesthesia) and surgical procedures (type of surgery, duration, and scar size). An evaluation of the child’s pain was conducted in the first 24 h after the surgery using a VAS score (0–100 mm). The pain score on the VAS was transformed into a three-modality ordinal outcome (<30 = mild pain; 30–59 = moderate pain; ≥60 = severe pain). Children were asked about their worst pain at rest in times slots (H0; H1; H2; H4; H8; H12). Evaluations of pain began just after extubation (H0). Ten to twelve weeks after surgery, a questionnaire with a prestamped return envelope was sent to all eligible children included in the study. Response was required for three months after surgery. If they failed to reply by the four months mark, we called them to complete the questionnaire by phone. In the postoperative questionnaire, they were asked about the status of their pain in the operated area three months after the surgery using a VAS score (0–100 mm). In patients with CPSP (VAS ≥30 mm), they also completed the DN4 questionnaire to determine if there was a neuropathic component. They were also asked four questions regarding the impact of CPSP on daily activities such as going to school, playing, eating or sleeping, as in the preoperative questionnaire. They were asked if they had received any medications or analgesic treatments, and if they had pain in another location, and if so, what the intensity was (using a VAS score). Those experiencing pain were asked if they had been given any treatment for it, and if so, what type. Finally, we asked if children could participate in athletic activities and if they had experienced anxiety since the surgery (VAS anxiety 0–100 mm). When we received questionnaires by mail, a pain doctor contacted all children who reported a VAS score ≥30 mm in any location to suggest they visit a practitioner for analgesic treatment. This telephone contact was done at least five months after surgery.
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estimate the prevalence with a precision of plus or minus 5% (95% confidence interval (CI): 15%–25%), 250 patients were required (NQUERY® Advisor 6.0, Statistical Solutions Ltd, Cork, Ireland). With a sample size of 250 patients and a 20% prevalence of CPSP, 50 patients were expected to report CPSP in our study. With such a number of events, at least five factors could be included in our final multivariate logistic regression model.
Results Participants Of the 1141 medical assessed for eligibility, 850 patients (73%) were ineligible for the study. The main causes for ineligibility were being discharged from the hospital on the day of the surgery, interventions without surgical sections (such as endoscopy), refusals or patients unable to understand the study. Of the 291 participants, 258 (88%) returned the questionnaire. Of the 33 patients who did not complete the study, 15 (5%) were lost to follow-up, 17 (6%) did not return the questionnaire and one (0.3%) declined participation after initial approval (Fig. 1).
Patient characteristics data The mean [min-max] age at the time of inclusion was 12 [6–18] yr, with 46% from six to 11 yr and 54% from 12 to 18 yr, and the majority of the children were males (60%). The main type of surgery was orthopaedic (Table 1). In table 1, the patient characteristics data of the 291 recruited patients sample and the 258 patients contributing data at three months, were similar. In this population of 291 children, 13.6% had a medical history of chronic disease, 4.9% had received chemotherapy before and 2.1% had received radiotherapy. Half of them had a surgical history (49.8%), mainly for orthopaedic surgeries. The majority of the children were not anxious the day before surgery (57% reported no anxiety) (Table 2). One hundred and sixty-eight children (61.6%) experienced moderate to severe pre-existent pain (>1 month) before surgery (Table 2). The pain was mostly (120/168) because of the pathology motivating the surgery. A history of neuropathic pain (DN4 ≥4) was found in 34/168 children. One hundred and eleven children (39.9%) reported recent pain (<1 month) at the time of surgery. In most patients, the pain was because of the pathology motivating the surgery (77.6%). Sixtyfive patients (23.4%) experienced severe pain (VAS score ≥60/
Not eligible (n=850)
Patients included (n=291)
Patients excluded (n=33) Loss of contact (n=15) Didn’t return the questionnaire (n=17) Declined participation (n=1) Patients completed the study (n=258)
Fig 1 Flow chart of the cohort.
Table 1 Patient characteristics Variable
All patients n=291
Age at inclusion Mean (range) 12.04 (6–18) Distribution according to age (%) 6–11 yr 134 (46) 12–18 yr 157 (54) Sex n (% male) 175 (60.1) Type of surgery n (%) Orthopaedics 180 (61.8) Thoracic surgery 25 (8.6) Laparotomy/ 40 (13.8) scopic Uro/inguinal 25 (8.6) surgery All surgeries 21 (7.2) pooled
Patients who completed the study n=258
P
12.07 (6–18)
0.670
116 (45) 142 (55) 156 (60.5)
0.298
164 (63.6) 22 (8.5) 33 (12.8)
0.750 0.572
22 (8.5) 17 (6.6)
100) (Table 2). A neuropathic component was found in 14/107 (12.8%) children. As shown in Table 2, the data from patients who completed the study were not significantly different from those who did not.
Prevalence and characteristics of CPSP at three months Of the 258 participants who completed the study, 28 (10.9%, [95% CI: 7.3–15.3]) reported pain (VAS ≥30/100) in the operated area (Table 3). Severe pain (VAS ≥60/100) was reported by 10/28 children reported CPSP, (i.e. 3.9%, [95% CI: 1.9–7.0] of the 258 patients who completed the study). A neuropathic component (DN4 ≥4) was found in 18 of the 28 (64.3%) children with CPSP (Table 3).
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Statistical method The prevalence of CPSP and its binomial 95% confidence interval were estimated. Factors associated with the presence of CPSP (in the whole sample and in the subgroup of patients with orthopaedic or thoracic surgery), were investigated using a logistic regression model. Factors associated with CPSP in the univariate analysis with statistical significance <0.20 were included in the multivariate model and other factors that we wanted the multivariate analysis to be adjusted for: (i) regional anaesthesia, and acute pain within the first 24 h post-surgery for the analysis conducted in the whole sample; (ii) age, major type of surgery, and regional anaesthesia for the analysis restricted to patients with orthopaedic or thoracic surgery. The final multivariate models were checked for interactions. Analyses were performed using SAS® software (version 9.2 or later).
Assessed for eligibility (n=1141)
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Table 2 Preoperative data on medical or surgical histories, preoperative pain, and anxiety before surgery. *m.d for missing data Variable
Patients who completed the study (n=258) n (%)
P
284 (7) 162 (57.0) 65 (22.9) 57 (20.1)
254 (4) 150 (59.0) 55 (21.7) 49 (19.3)
0.133
273 (18) 105 (38.4) 66 (24.2) 102 (37.4) 168 (0) 107 (63.7) 13 (7.7) 48 (28.6)
244 (14) 91 (37.3) 58 (23.8) 95 (38.9) 148 (5) 99 (66.9) 12 (8.1) 37 (25.0)
0.251 0.288
278 (13) 167 (60.1%) 46 (16.5%) 65 (23.4%) 107 (4) 83 (77.6)
248 (10) 149 (60.1%) 40 (16.1%) 59 (23.8%) 95 (4) 73 (76.8)
7 (6.5) 17 (15.9)
6 (6.3) 16 (16.9)
Table 3 Intensity of CPSP (VAS mm) at three months, neuropathic component, impact on activity and treatment Variable
n
Intensity of CPSP (VAS) Mild (<30) 230 Moderate (30–59) 18 Severe (≥60) 10 In children moderate to severe CPSP (n=28) Neuropathic pain 18 Impact of pain on activities Moderate 22 Severe 6 Analgesic treatment No analgesics 3 Only first class 15 First and second class 7 Three classes 3 Antineuropathic treatment 0
% 89.1 7.0 3.9 64.3 78.5 21.5 10.7 53.6 25.0 10.7 0.0
Twenty-five (89.3%) children were given analgesics because of CPSP, usually acetaminophen or/and an NSAID. Regardless of the intensity of the reported pain, the impact of the pain was severe for six children (22.2%) (Table 3).
Surgical and anaesthetic procedures in children with and without CPSP The main type of surgery in this study was orthopaedic (63.6%). Of those 164 children, 22 (13.4%) presented with CPSP. Among
0.611
0.737
children who underwent thoracotomy (22 children), 5 (23%) reported CPSP. In the population of children with CPSP (28), 23 (85.2%) had significant acute postoperative pain (VAS ≥ 30) during the first 24 h (Supplementary material, Fig. S1). Regional anaesthesia was not associated with CPSP in this sample. As far as the anaesthetic and surgical procedures were concerned ( premedication agents, hypnotic or opioid agents, scar size), no risk factors were associated with CPSP. All 28 children with CPSP were called back after receipt of the questionnaire, five to six months after the surgery. None of them needed to be admitted to the hospital because of pain. A visit with a chronic pain practitioner was suggested to five of them. The other 23 children had pain resolved entirely when we called them.
Risk factors of CPSP Among the 13 potential risk factors investigated in the univariate analysis, five were associated with CPSP with a statistical significance (P<0.2): age at inclusion, pre-existent pain (>1 month), intensity of recent pain, type of surgery, and scar size (Table 4). They all were included in the multivariate analysis together with two other factors that we wanted the multivariate analysis to be adjusted for: regional anaesthesia and acute pain within the first 24 h post-surgery. In the multivariate model, only recent pain (<1 month) was independently associated with CPSP (P=0.007). Children reporting a recent pain had a higher risk of developing CPSP, would the recent pain be moderate (OR=5.6; [95% CI: 1.8–17.8]) or severe (OR=3.3; [95% CI: 1.1–10.1]) (Table 4). No interaction was retrieved in this final multivariate model. When we restricted our analysis to patients with thoracotomies or orthopaedic procedures (n=171 in the multivariate
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Anxiety (VAS) Total n (md*) Mild (<30) Moderate (30–59) Severe (≥60) Pre-existent pain (>1 month) (VAS) Total n (md*) Mild (<30) Moderate (30–59) Severe (≥60) Location of pain (≥30) Site of later surgery Site of later surgery and elsewhere Pain elsewhere Recent pain (<1 month) (VAS) Total n (md*) Mild (<30) Moderate (30–59) Severe (≥60) Location of recent pain (≥30) Site of later surgery Site of later surgery and elsewhere Pain elsewhere
All patients (n=291) n (%)
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Table 4 Univariate and multivariate analysis of CPSP risk factors. CI, Confidence Interval; OR, Odds Ratio Variable
Comparison
n
n CPSP
Univariate analysis OR
Sex Age at inclusion in two classes Pre-existent pain (>1 month, VAS ≥30) Recent pain (<1 month, VAS ≥30)
Scar size >3 cm Regional anaesthesia Acute pain within the first 24 h post-surgery (VAS score ≥30) History of chronic diseases Chemotherapy History of surgery
Planning of surgery Premedication
156 102 115 143 153 91 149 40 59 71 17 142 151 107 163 95 184 65 35 222 13 244 130 69 59 29 225 223 35
16 12 7 21 19 5 9 8 8 1 5 22 20 8 19 9 23 4 3 24 1 26 16 8 4 4 24 24 4
analysis), the presence of recent pain (<1 month) before surgery and severe acute postoperative pain in the first 24 h were associated with a higher risk of CPSP (Table 5).
Discussion This prospective observational study highlights that the prevalence of CPSP is lower in children than in adults.3 4 10 21 We found that chronic postsurgical pain is an important issue in children undergoing surgery, occurring in 11% (CI: 7–15) of patients. Severe chronic postsurgical pain occurred in 4% (CI: 2–7) of children and was mostly of neuropathic origin (64.3%). However, 23/28 of patients were pain-free when we called them upon receipt of the questionnaire, and impairments of pain were mild for 22/28 of them. These results are similar to the previous data. In retrospective studies, authors found CPSP in 13% of children, and after thoracotomies,22 CPSP was found in 16% of children.23 Neuropathic components and anaesthetic procedure details were not recorded. In our study, 2/3 of the procedures were orthopaedic surgeries (63.5%), similar to other studies,22 because of the ages included. CPSP after orthopaedic procedures was found in 13% of children, and of those patients, a neuropathic origin was found in 63%. In our study, thoracotomies were the second most common type of surgery associated with a high rate of CPSP (22.7%), mostly with a neuropathic component. Our results are comparable with those of Kristensen and colleagues23 who examined chronic pain
ref 1.167 ref 2.66 2.44 ref ref 3.89 2.44 ref 20.88 11.00 1.89 ref 1.26 ref 2.18 ref 0.77 ref 0.70 ref ref 0.93 0.52 1.15 ref 0.93 ref
95% CI
P
OR
IC 95%
P
[0.517–2.57]
0.689
[1.13–6.96] [0.94–7.57]
0.028 0.118
1.84 0.82
[0.64–6.16] [0.23–3.07]
0.282 0.765
0.017
[1.82–17.77] [1.094–10.15]
0.007 . . 0.087
[1.69–341.31] [1.57–159.36] [0.92–8.43]
0.091
[3.11–4.14] [2.24–198.86] [0.83–4.72]
0.160
. 5.62 3.31 . 15.14 8.53 2.56
[0.56–3.04]
0.681
1.36
[0.50–4.11]
0.561
[0.80–7.65]
0.244
22.10
[0.67–8.11]
0.232
[0.18–2.38]
1.00
[0.04–3.77]
1.00
[1.36–10.96] [0.87–6.72] 0.001
0.56 [0.36–2.25] [0.14–1.49] [0.32–3.26]
0.766
[0.33–3.34]
1.00
after thoracotomies in children and youths. They found a prevalence of chronic pain of 19% in children aged seven to 12 yr, and 28% in those aged 13 to 25 yr. After adjusting for confounding variables, younger ages did not appear to protect against CPSP in our study (younger ages were a significant protective factor against CPSP in the univariate but not in the multivariate analysis). This can be explained by the high incidence of orthopaedic surgeries in the group of older children in our study. Moreover, in adults, several studies found that the risk of chronic pain decreased with age: from 39–58% in patients >40 yr of age to 14–17% in patients more than 65 yr.24 Therefore, it is difficult to make conclusions about the influence of age on the onset of CPSP. A major finding of this study is the predominance of neuropathic components in severe CPSP (64.3%, 18/28 children), as seen in adult literature.25 The explanation for this discrepancy could be that authors failed to seek out neuropathic pain in CPSP in children. The only study that addressed this question was retrospective and included few patients.26 In paediatrics studies about chronic medical pain, a neuropathic component is rare. In our study, most of children had a surgical history (49.8%) and that can explain the high rate of neuropathic pain. The underdiagnosis is the most probable explanation for the lack of specific treatments for children who suffer from severe pain. To us, this result is a very important finding as specific treatments do exist and neuropathic pain should be a therapeutic target in the management of CPSP.
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Major type of surgery
Male Female 6–11 yr 12–18 yr Yes No Mild Moderate Severe Others Thoracic Orthopaedic Yes No Yes No Yes No Yes No Yes No No Minor Major Emergency Planned Yes No
Multivariate model (248 patients)
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Table 5 Univariate and multivariate analysis of CPSP risk factors after orthopaedic or thoracic surgery. CI, Confidence Interval; OR, Odds Ratio Comparison
n
n CPSP
Univariate analysis
Sex
Male Female 6–11 yr 12–18 yr Yes No Mild Moderate Severe Thoracic Orthopaedic Yes No Yes No Yes No Yes No Yes No No Simplex Complex Emergency Planned Yes No
111 75 61 125 118 54 114 28 36 22 164 116 70 116 70 127 51 26 159 8 177 84 52 50 12 174 172 14
15 12 6 21 19 4 8 8 8 5 22 19 8 18 9 23 3 3 23 1 25 15 8 4 3 24 23 4
ref 1.22 ref 1.85 2.40 ref ref 5.30 3.79 ref 0.53 1.52 ref 1.24 ref 3.54 ref 0.77 ref 0.87 ref ref 0.84 0.40 2.08 ref 0.39 ref
OR
Age at inclusion in two classes Pre-existent pain (>1 month, VAS ≥30) Recent pain (<1 month, VAS ≥30)
Major type of surgery Scar size >3 cm Regional anaesthesia Acute pain within the first 24 h post-surgery (VAS score ≥30) History of chronic diseases Chemotherapy History of surgery
Planning of surgery Premedication
It would be better to develop an interdisciplinary paediatric pain rehabilitation program for all children at risk of developing CPSP, as is done for chronic medical pain.27 Until now, children with CPSP were not identified, so post-surgical pain was not supported properly. Second, we tried to determine the main risk factors associated with CPSP. We found that recent preoperative pain and acute pain after orthopaedic and thoracic surgeries were associated with an increased risk of developing CPSP. These data are similar to results in the adult population.3 24 28 When compared with existing literature,29 30 regional anaesthesia associated with general anaesthesia did not decrease the risk of CPSP. There may be two explanations for this result. The first is the fact that regional anaesthesia was used in the vast majority of surgeries carrying a risk of postoperative pain, for example in thoracotomies and orthopaedic procedures. Indeed, our study was not designed to show the benefits of regional anaesthesia on the onset of CPSP. The second way to explain this result is to consider the severity of acute postoperative pain, a significant outcome after orthopaedic and thoracic surgeries, as a sign of failed regional anaesthesia. A limitation of our study was the exclusion of ambulatory surgeries. It is possible that the prevalence of CPSP after ambulatory surgeries is lower because interventions are less painful. For instance, inguinal herniorraphy is almost always performed as an ambulatory surgery. Nevertheless, chronic pain after inguinal herniorraphy is reported in approximately 12% of adults5 and is
Multivariate model (171 patients)
95% CI
P
[0.53–2.77]
0.675
[0.74–5.28] [0.85–8.61]
0.269 0.150 0.002
[1.76–16.08] [1.29–11.18] [0.19–1.73] [0.64–3.87]
0.328 0.397
[0.54–3.07]
0.673
[1.16–15.42]
0.037
[0.17–2.45]
1.000
[0.05–5.18]
1.000
OR
ref 2.81 0.82 ref ref 6.62 3.85 ref 0.40
1.26 ref 4.04 ref
IC 95%
P
[0.85–11.89] [0.23–3.07]
0.116 0.765
[0.10–1.75]
0.005 . . . 0.197
[0.44–4.04]
0.674
[1.19–19.14]
0.042
[0.057–1.54]
0.114
[2.02–22.79] [1.19–12.90]
0.285 [0.31–2.09] [0.11–1.18] [0.44–7.57]
0.387
[0.12–1.50]
0.126
0.27
observed in children as well,9 so it is unlikely that our results would have changed dramatically. We included only children more than six yr of age because self-report with VAS scale can be used for postoperative pain evaluation. In order to explore neuropathic postoperative pain, we have chosen the DN4 questionnaire for use as self-report instrument, because this questionnaire was yet used in children aged >six yr.18 Even if the prevalence of CPSP is less than in adults, detecting CPSP may prevent fear of pain in children and adolescents with neuropathic pain and complex regional pain syndrome.31 The heterogeneity of our study sample with regard of the type of surgery makes our results difficult to interpret, (i.e. the type of surgery seems to be confounded with site of scar). In future studies, the prevalence of CPSP in scoliosis or thoracic surgeries could be evaluated separately. In our study, we have only included children without polyhandicap even if this population is probably at high-risk to develop CPSP with a neuropathic origin, because of difficulties of evaluation. Despite these limitations, this study represents an important assessment of chronic pain after paediatric surgery. We must improve preoperative and acute postoperative analgesia to decrease the proportion of CPSP seen after surgeries in children as in adults,32 primarily after orthopaedic and thoracic procedures. Moreover, as nerve lesions and central sensitization are involved in CPSP development, we probably should diagnose neuropathic pain before the child leaves hospital.33 Finally, during surgery
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Variable
Chronic postsurgical pain in children
Authors’ contributions Study design/planning: A.B., H.B. Study conduct: H.B., M.B-D. Data analysis: A.B. Writing paper: H.B., F.S., K.N-G. Revising paper: all authors
Supplementary material Supplementary material is available at British Journal of Anaesthesia online.
Acknowledgements Data monitoring: Sandrine Desjardins (DRCI, CHU de Bordeaux). Scientific collaboration for the design of the study: Paul Perez (USMR, CHU de Bordeaux). Assistance for subject recruitment and data collection: Lorena Sanchez (clinical research assistant, CHU de Bordeaux and Louise Baschet (data manager, CHU Bordeaux).
Declaration of interests None declared.
Funding CHU de Bordeaux, Place Amélie Raba Léon, F-33076 Bordeaux, France.
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