Efficacy of Epidural Analgesia after Laparotomy in Children

Original Article Efficacy of Epidural Analgesia after Laparotomy in Children Klarieke Bravenboer-Monster 1 Claudia Keyzer-Dekker 1 Monique van Dijk 1 Lonneke Staals 2 Tom de Leeuw 2 Rene Wijnen 1 1 Department of Pediatric Surgery, ErasmusMC-Sophia Children s Hospital, Rotterdam, The Netherlands 2 Department of Anaesthesiology, ErasmusMC-Sophia Children s Hospital, Rotterdam, The Netherlands Address for correspondence Klarieke Bravenboer-Monster, MSc, Department of Pediatric Surgery, Erasmus MC-Sophia Children s Hospital, Wytemaweg 80, 3015 CN, Rotterdam 3000 CB, The Netherlands (e-mail: k.monster.1@erasmusmc.nl). Eur J Pediatr Surg Abstract Background Epidural analgesia (EDA) is used as postoperative pain treatment in children, but little is known about its efficacy after laparotomy in children. This retrospective study investigated the efficacy of postoperative EDA after laparotomy in children and the frequencies of adverse effects and complications. Materials and Methods Data of all children aged 0 to 18 years undergoing laparotomy and treated with EDA in our hospital from January 2014 to December 2015 were collected. EDA was classified as successful either if the catheter was removed when there was no further need, and the patient was comfortable with oral/rectal analgesics or when EDA was continued after intervention. Results Ninety children with a median age of 3.7 years were included in the study. In 65% (59/90), EDA was classified as successful. In 34% (20/59) of all successful cases, an additional intervention was needed. In 35% (31/90), the catheter was removed earlier than planned, in half of these cases after an intervention. The primary reason for earlier removal was inadequate analgesia and technical failure. Adverse effects occurred in 18% and complications in 1% of cases. The successful group was significantly younger Keywords abdominal surgery pediatric pain success rate adverse effects than the unsuccessful (p ¼ 0.003). Conclusion EDA after laparotomy positively contributed to postoperative pain treatment in two-thirds of children. Numbers of adverse effects and complications were low. It is important to optimize pain management after laparotomy in children; thus, further prospective studies should focus on optimizing EDA and comparing EDA with other techniques of analgesia. Introduction Postoperative pain in children after major surgical procedures, such as a laparotomy, can be treated in various ways. Worldwide, paracetamol and intravenous opioids are the most used analgesics given to children after laparotomy. Furthermore, as neuraxial blocks are relatively safe for children, epidural analgesia (EDA) is also commonly used. 1 EDA after open abdominal surgery in adults is associated with faster return of bowel function and reduced pain scores, but this does not translate into improved recovery. A systematic review and meta-analysis showed no significant difference in complication rate and length of stay in adults treated with EDA or alternative analgesic methods after open abdominal surgery. 2 Studies have shown several benefits of EDA in children over continuous intravenous opioids, such as less frequent received October 10, 2017 accepted after revision January 16, 2018 Georg Thieme Verlag KG Stuttgart New York DOI https://doi.org/ 10.1055/s-0038-1632372. ISSN 0939-7248.

and shorter postoperative ventilation, shorter intensive care unit stay, and earlier return of bowel function. 3,4 On the other hand; adverse effects and complications have been noted for EDA. The most common adverse effects are nausea and vomiting, pruritus, oversedation, and motor blockade. 5 With EDA, however, nausea, vomiting, and pruritus are seen less often than with intravenous opioids. 6 The incidence of EDA-related complications in children is 7.6:1,000, and most of these complications are infections and medication errors. 7,8 Complications are more common in neonates, and children aged under 1 year. 1,7,8 One in every 10,000 complications causes permanent neurological damage as the result of an epidural hematoma or abscess. 9 Ahigherlevelof success of EDA is found in younger children. 5,10 Unsuccessful EDA is related to the duration of surgery and technical failure of the epidural catheter. 5,10 13 Leakage is the major reason of early removal of the epidural catheter. 12 Previous studies have analyzed the efficacy and safety of EDA in children mainly after orthopedic and urologic procedures, which cannot be compared with such a surgical procedure as a laparotomy. Even studies including open abdominal surgery had only few patients undergoing a laparotomy. The aims of this study, therefore, were to evaluate the efficacy of EDA specifically after laparotomy in children, to determine the frequencies of adverse effects and complications, and to identify predictive factors for successful EDA. Materials and Methods Patients A retrospective study was performed of data of all patients aged 0 to 18 years treated with EDA after laparotomy from January 2014 to December 2015 in the Erasmus MC-Sophia Children s Hospital in Rotterdam, the Netherlands. When patients during this period underwent more than one laparotomy treated with EDA postoperatively, only the first laparotomy was included. Data Collection Individual patient data were obtained from electronic and paper medical records. Pre-operative data included gender, age, weight, and previous medical history. The operative data collected were type and duration of surgical procedure, part of procedure performed laparoscopically, surgical incision site, level, and moment (pre- or postoperatively) of epidural catheter insertion. The postoperative data obtained were pain scores, duration of epidural infusion, reasons for discontinuation of EDA, the need for an additional intervention, the number and type of adverse effects, the number, and type of complications. Postoperative Care The EDA consisted of a mixture of ropivacaine 0.2% and sufentanil 0.5 µg/ml, administered at 0.1 0.2 ml/kg/h. In addition, all children received paracetamol (oral/rectal/ intravenous) or a combination of paracetamol and diclofenac (oral/rectal/intravenous). A transurethral catheter was inserted in all cases. Assessment of Postoperative Pain During the course of epidural infusion, attending nurses assessed pain every 8 hours, using the validated COMFORT behavior scale, Faces Pain Scale, or the Numeric Rating Scale, depending on the child s age. The COMFORT behavior scale has been validated for postoperative pain in children aged 0 to 3 years. It is assigned by the attending nurse, in combination with the Numeric Rating Scale, and the total score range is 6 to 30. 14 16 The Faces Pain Scale (4 7 years) is a selfreported pain scale, which shows five drawn faces. The left face is smiling and reflects no pain at all (0); the right face reflects the most severe pain (4). The child points to the face that most closely resembles the level of pain. The Numeric Rating Scale is an 11-point numerical scale anchored with no pain (0) and most severe pain (10). 17 The Numeric Rating Scale was applied by nurses for children assessed in of all age, but children >7 years could also self-report pain with the Numeric Rating Scale. A COMFORT behavior score >17, a Faces Pain Scale > the second face or a Numeric Rating Scale > 4 were considered to reflect pain requiring intervention. 15,17 Members of the pain team (consisting of dedicated pain consultants and anesthesiologists) collected all data on pain scores, interventions, adverse effects, and complications on paper records during daily ward rounds. Definition of Successful EDA The reasons for early discontinuation of EDA were collected and categorized as follows: (1) no further need, satisfactory function, or need for mobilization; (2) unsatisfactory analgesia, suspected adverse effects, and complications; and (3) technical failure specified as leakage, occlusion, catheter fall out, and filter disconnection. EDA after laparotomy was classified as successful if the catheter could be removed, and the patient was comfortable by oral/rectal analgesia (paracetamol, diclofenac, tramadol, or oxycodone). An additional intervention consisted of a bolus/adjustment of epidural infusion or supplemental intravenous analgesia. EDA was still classified as successful if it was continued after the intervention. EDA was classified as unsuccessful if the epidural catheter was removed earlier than planned due to inadequate analgesia or technical failure. Statistical Methods Descriptive statistics were used for data of pain scores, adverse effects, complications, and reasons for removal of the EDA catheter. Not normally distributed variables are presented as median (range) or median (interquartile range [IQR]); normally distributed variables as mean with standard deviation including 95% confidence intervals (CIs). The successful and unsuccessful classified EDA groups were compared using Fisher s exact tests for categorical variables and Mann Whitney U-tests for continuous nonnormally distributed variables. Relative risks with 95% CI were presented where appropriate. The 95% CI for the difference between median values were calculated with the Hodges Lehman estimates. A P-value of < 0.05 was considered statistically significant. The statistical analyses were

performed using IBM SPSS Statistics 22.0 (SPSS, Chicago, Illinois, United States). Ethics The Medical Ethics Committee Erasmus Medical Centre has reviewed and approved the research protocol (MEC-2015 529). As only routinely collected data were used and analyzed anonymously, informed written consent from the parents was waived. Results Patients Data of 90 individual patients were included in the analyses. The median age was 3.7 years (range 0 17); the boy-girl ratio was 1.5:1 ( Table 1). Successful or Unsuccessful EDA EDA was classified as successful for 59 (65%) of the 90 children; in two-thirds (39/59) of cases without an intervention. In one of these latter cases, the epidural catheter was removed earlier than planned on the surgeon s request because the patient needed to be mobilized. In the remaining 20/59 children, EDA was successful after an intervention, and the epidural catheter was removed when there was no further need of EDA. EDA was classified as unsuccessful for 31 (35%) children, mostly because of technical failure (19/31; 61%), such as leakage (8), occlusion of the catheter (8), catheter dislodgment (1), and filter dislodgement (2). In 12 of the unsuccessful cases (12/31; 39%), unsatisfactory analgesia was the primary reason for earlier removal of the catheter. Unsatisfactory analgesia was the reason to apply EDA interventions in 28 (31%) of all children ( Fig. 1). Pain Scores Pain scores were available for all, but one children. Analysis revealed a significant difference (p ¼ 0.001) in the frequency of high pain scores between unsuccessfully and successfully treated patients, respectively, median 24% (IQR 4 50) versus 0% (IQR 0 20) (median difference 20%, 95% CI 5.7 30.0%) ( Fig. 2). High pain scores had been assigned to four patients whose EDA was classified as successful. AdverseEffectsandComplications Adverse effects had been documented for 16 (18%) of the 90 children. The most common adverse effect was pruritus, in 5/ 90 (6%) of the procedures. Erythema around the insertion site of the epidural catheter was seen in one patient when the catheter was removed, but other signs of infection were not seen. In one of the (1%) 90 patients, a complication was noted; this was a medication error in which the intravenous medication was given by the epidural catheter ( Table 2). Predictive Factors for Successful EDA Table 3 provides the results of the analysis of possible predictive factors for the efficacy of EDA after laparotomy. The median age of the successful group was 1.9 years (IQR 0.8 9.2) versus 9.3 years (IQR 3.9 14) of the unsuccessful group ( Fig. 3). Only younger age can be considered as a predictive factor (median difference between groups 4.38 years, 95% CI 1.15 7.29 years; p ¼ 0.003). Neither surgical incision site, level of epidural insertion, moment of epidural insertion, part of procedure laparoscopically, or duration of surgery was significant ( Table 3). Discussion EDA after laparotomy was successful in 65% of the children, which percentage compares well with other studies of postoperative EDA after different types of surgery in children. Jylli et al described a 63% success rate in a prospective study in children (age 0 20 years) receiving EDA postoperatively after urologic, orthopedic, or gastrointestinal surgery. 10 Strandness et al showed a success rate of 67% in a retrospective study of pediatric patients who received EDA after Table 1 Patient characteristics Patient characteristics Total population N ¼ 90 Male: female 54:36 Median age in years (range) 3.7 (0 17) Median weight in kg (range) 15 (3.2 74) Median duration of epidural infusion in hours (IQR) 66 (44 82) Median duration of surgery in minutes (IQR) a 113 (80 168) Type of surgery, N (%) Gastrointestinal 57 (63%) Abdominal wall 10 (11%) Diaphragm 8 (9%) Tumor resection 7 (8%) Nephrectomy 5 (6%) Liver 3 (3%) a In two patients, information regarding the duration of surgery could not be retrieved.

Fig. 1 Flowchart of patients with successful/unsuccessful EDA. EDA, epidural analgesia; IV, intravenous. N = 31 not successful N = 58 successful Postoperative epidural analgesia Fig. 2 Percentage high pain scores per patient in successful and unsuccessful EDA. EDA, epidural analgesia. thoracic surgery. 18 Unsatisfactory analgesia was a major reason for early epidural catheter removal in the present study (12/90; 13.3%) versus 21% and 13%, respectively, in the previous studies. 10,18 In the latter two studies, however, the definition of success differed from ours or was lacking. In the study of Jylli et al, EDA was considered not successful if intravenous opioids were needed in addition to a local anesthetic without opioids; and Strandness and et al did not provide a definition. 10,18 The definition of successful EDA in the present study is strict. If another definition would have been used, for example based on pain levels, the success rate might have been different. For that matter, the success rate associated with the use of a local anesthetic with opioids as in the present study is comparable with that of local anesthetic without opioids, although the latter is expected to have better analgesia compared with local. 10,18 In the present study, technical failure was the primary reason of catheter removal in 21% of all patients. A previous study reported that this was the case in 14% of patients. 18 Furthermore, in a multi-center cohort study one third of the adverse effects were found related to catheter failure. 13 Lastly, a review exploring the safety of pediatric EDA showed leakage of the epidural catheters in 10% of patients. 12 Such technical failures can lead to unsatisfactory analgesia and unnecessary pain. Future studies should focus on improving the technical aspects of EDA. Table 2 Types of adverse effects and complications Total population N ¼ 90 Adverse effects, N (%) Pruritus 5 (6%) Nausea 3 (3%) Motor blockade 1 (1%) Hypotension 1 (1%) Vomiting 1 (1%) Dizziness 1 (1%) Respiratory depression 1 (1%) Drowsiness 1 (1%) Redness insertion site catheter 1 (1%) Hematoma of the skin 1 (1%) Complications, N (%) Medication error 1 (1%)

Table 3 Analysis of possibly predictive factors for efficacy of EDA P-value Relative risk (95% CI) Unsuccessful N ¼ 31 (35%) Successful N ¼ 59 (65%) Factors Total N ¼ 90 Surgical incision site, N (%) Upper abdominal 58 (64%) 39 (66%) 19 (61%) 1.23 (0.50 3.03) 0.65 Lower abdominal 14 (16%) 7 (12%) 7 (23%) 0.46 (0.15 1.46) 0.23 Median 18 (20%) 13 (22%) 5 (16%) 1.47 (0.47 4.59) 0.59 Yes 20 (22%) 12 (20%) 8 (26%) 0.73 (0.26 2.04) 0.60 No 70 (78%) 47 (80%) 23 (74%) Part of procedure laparoscopically, N (%) Level of epidural insertion, N (%) Thoracic 41 (46%) 25 (43%) 16 (52%) 0.71 (0.30 1.70) 0.51 Thoracic/lumbar 9 (10%) 4 (7%) 5 (16%) 0.38 (0.09 1.55) 0.27 Lumbar 37 (42%) 27 (47%) 10 (32%) 1.83 (0.73 4.56) 0.26 Caudal 2 (2%) 2 (3%) 0 (0%) 0.64 (0.55 0.75) 0.54 Time of epidural insertion, N (%) Pre laparotomy 70 (80%) 24 (80%) 46 (79%) 1.04 (0.35 3.13) 0.59 Post laparotomy 18 (20%) 6 (20%) 12 (21%) Median difference (95% CI) Median age in years (IQR) 3.7 (0 17) 1.9 (0.8 9.2) 9.3 (3.9 14) 4.38 (1.15 7.29) 0.003 Median duration of surgery in minutes (IQR) 113(80 168) 114 (84 172) 109 (79 163) 4 ( 21 to 30) 0.66 Abbreviations: CI, confidence interval; EDA, epidural analgesia; IQR, interquartile range. Fig. 3 Age of the child versus success rate EDA. EDA, epidural analgesia. The possible explanations that must be considered in this study as a cause of unsuccesful EDA were the previous medical history of the patient (such as, previous surgical procedures or a chronical disease), which can lead to increased pain sensitivity as well as the degree of experience of the pediatric anesthesiologist to the epidural technique in children. Placement of an epidural catheter in children is performed under general anesthesia or deep sedation, whereas this is done in adults when they are awake. This has caused some debate in the field whether performing regional anesthesia in children is safe. However, a recent recommendation from the European and American Societies for Regional Anesthesia (ESRA and ASRA) states that the performance of regional anesthesia in children under general anesthesia or deep sedation is associated with acceptable safety and should be viewed as the standard of care. 19 The absolute risk of permanent neurological injury after EDA in children is unknown, but earlier studies suggested a low rate of serious complications associated with EDA in children. 9 In an investigation describing complications after 10,556 central nerve blocks in children, the incidence of complications was 0.29% (CI 95% 0.21 0.43). 1 The incidence of complications was significantly higher in central (epidural) blocks than for peripheral nerve blocks, but not one complication after epidural placement resulted in sequelae or harm 1 year later. In our study, neurological complications (such as, epidural hematoma or ischemic injuries to the spinal cord) were not seen. The number of patients in this study was too small to speculate about the incidence of possible neurological complications and the safety of EDA in children. In this study, pruritus and nausea were the most common adverse effects, like in previous studies. 5,10 As opposed to these studies, in our study, pruritus was somewhat more common than nausea, likely because we used a combination of local anesthetic and an opioid, in which the opioid is notorious for causing pruritus. In the other studies, the therapy of EDA consisted only of a local anesthetic. 5,10

Complications in the present study were seen in 1% of the total group and did not result in permanent injury. This result is comparable with other studies on the incidence and type of complications. In these studies, complications of EDA were more often seen in children younger than 1 year. 7,8 In the present study, numbers were too small to determine significant differences in complications between different age groups. In this study, younger age was associated with a higher success rate of EDA and fewer high pain scores. A possible explanation is the method by which pain was assessed: nurses assessed pain in younger children, whereas older children self-reported pain. Likewise, Jylli et al found a significantly higher level of success in younger children. 10 A study on EDA after major surgical procedures in 800 children demonstrated that the children older than 12 years old reported significantly higher pain scores than did the younger children. 5 A younger age thus seems to be a positive predictor of the efficacy of EDA in children. Still, the influence of the way in which pain is assessed should be further investigated. For example, assessing pain in motion and at rest in older children, as well as the role of parents in pain assessment of younger children. This will be more important in our clinic due to the recent introduction of the patient- and family-centered care. This study has several methodological limitations. First, inherent to the retrospective design, it is well possible that not all adverse effects and complications have been reported, and numbers are thus underestimated. Second, a limited number of pain scores was assessed and registered by pain team and nurses than prescribed by protocol. A possible explanation is lack of compliance with the pain management protocol (pain not assessed if a patient is thought to feel no pain). To improve postoperative pain treatment, better pain assessment is needed. Third, a multivariate analysis of several factors that may affect efficacy was not executed because numbers of patients in the subgroups (prematurity, mental or physical retardation, types of surgery, and diagnosis) were too small. Lastly, the influence of patient-controlled epidural analgesia (PCEA), which allows older children to self-administer a bolus epidural infusion, was not addressed. This might have improved the efficacy of EDA after laparotomy. Conclusion EDA after laparotomy was found successful in two-thirds of children in this study, although regularly an intervention was needed. In one-third of children the epidural catheter had to be removed earlier. This study shows the need of close monitoring of postoperative pain for timely recognition of unsatisfactory analgesia after laparotomy. The present study is unique because we analyzed a homogeneous patient group: children treated with EDA after laparotomy. Previous studies included various types of surgery. Future prospective studies should also focus on optimizing EDA, for example with PCEA, and on comparing EDA after laparotomy with other techniques of analgesia. Conflict of Interest None. Acknowledgments We thank Mr. J. Hagoort for editing the manuscript. References 1 Ecoffey C, Lacroix F, Giaufré E, Orliaguet G, Courrèges P; Association des Anesthésistes Réanimateurs Pédiatriques d Expression Française (ADARPEF). Epidemiology and morbidity of regional anesthesia in children: a follow-up one-year prospective survey of the French-Language Society of Paediatric Anaesthesiologists (ADARPEF). 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