Postoperative pain management in pediatric patients undergoing minimally invasive repair of pectus excavatum: The role of intercostal block,

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1 Journal of Pediatric Surgery (2013) 48, Postoperative pain management in pediatric patients undergoing minimally invasive repair of pectus excavatum: The role of intercostal block, Laura Lukosiene a,, Danguole Ceslava Rugyte a, Andrius Macas a, Lina Kalibatiene a, Dalius Malcius b, Vidmantas Barauskas b a Department of Anesthesiology, Hospital of Lithuanian University of Health Sciences Kaunas Clinics, Lithuania b Department of Pediatric Surgery, Hospital of Lithuanian University of Health Sciences Kaunas Clinics, Lithuania Received 17 August 2013; accepted 26 August 2013 Key words: Pectus excavatum; Intercostal block; Morphine; Children; Postoperative pain Abstract Purpose: There are no published data regarding value of intercostal block following pectus excavatum repair. Our aim was to evaluate the efficacy of intercostal block in children following minimally invasive repair of pectus excavatum (MIRPE). Methods: Forty-five patients given patient-controlled analgesia (PCA) with morphine postoperatively were studied. Twenty-six patients were given bilateral intercostal blocks after induction of anesthesia (PCA-IB group), and nineteen patients were retrospective controls without regional blockade (PCA group). All patients were followed up 24 h postoperatively. Results: A loading dose of morphine (0,1 ± 0,49 mg/kg) before starting PCA was used in seventeen patients in PCA group vs. no patient in PCA-IB group. Cumulative used morphine doses were lower up to 12 h after surgery in PCA-IB group (0,29 ± 0,08 μg/kg) than in the PCA group (0,46 ± 0,18 μg/kg), p b 0,01. There were no differences in pain scores, oxygen saturation values, sedation scores, and the incidence of pulmonary adverse events between the two groups. There was a tendency towards less morphine-related adverse effects in PCA-IB group compared to PCA group (p b 0,05). No complications related to the intercostal blocks were observed. Conclusion: Bilateral intercostal blocks following MIRPE are safe and easy to perform and can diminish postoperative opioid requirement. Double-blind randomized study is required to confirm the potential to diminish opioid related side effects Elsevier Inc. All rights reserved. Sponsoring Member: Walter J. Chwals, MD, FACS, FCCM, FAAP, Professor of Surgery and Pediatrics, Tufts Medical Center, Boston, MA. Conflict of Interest. The authors declare that is no conflict of interest. Corresponding author. Hospital of Lithuanian University of Health Sciences Kaunas Clinics Anesthesiology Kaunas Clinics, Lithuania. Tel.: address: lauralukos@gmail.com (L. Lukosiene). Pectus excavatum (PE) is a common chest wall deformity in children. The incidence is estimated to be from 1:300 to 1:1000, depending on race and country [1 3]. Male gender is at higher risk than female [1 3]. PE in older children is often associated not only with psychological stress, but also with reduced pulmonary and cardiovascular function, especially with exercise [4,5]. For over a decade a closed minimally /$ see front matter 2013 Elsevier Inc. All rights reserved.

2 2426 L. Lukosiene et al. invasive procedure introduced by Donald Nuss has performed instead of open Ravitch repair [6,7]. Nevertheless, pain following minimally invasive repair of pectus excavatum (MIRPE) is significant. Although epidural analgesia is effective and widely used after this kind of surgery, concerns have recently been raised over costs, invasiveness and safety of the epidural approach [8,9]. Furthermore, studies indicate that systemic analgesia with opioids can be as effective as epidural analgesia [10]. The advantages of systemic opioids are low cost, technical simplicity and safety. However, even with high doses, sufficient analgesia may be difficult to achieve, especially in the early postoperative period and during increased physical activity [9,11]. In turn, opioidrelated side effects may effect patient well-being and reduce overall quality of postoperative analgesia. Our previous experience with a multimodal approach combining systemic opioids and non-steroidal anti-inflammatory drugs (NSAIDs) for pain management following MIRPE indicated that acute postoperative period is extremely challenging and requires additional treatment [11]. An intercostal block is less invasive than epidural anesthesia, is relatively simple to perform and has been shown to be successfully used in children after thoracic and upper abdominal procedures [12 14]. The advantages of intercostal block include good analgesia, an opioid-sparing effect, improved pulmonary mechanics, reduced central nervous system depression, and avoidance of urinary retention [15]. There are no data regarding the value of intercostal block following the pectus excavatum repair. Therefore, the aim of the present study was to evaluate the efficacy of intercostal block in pediatric patients undergoing MIRPE. We prospectively studied 26 patients administered bilateral intercostal blocks and compared them with retrospective controls, treated using patient controlled analgesia (PCA) without regional anesthesia. 1. Methods Participants of study were children undergoing MIRPE in Hospital of Lithuanian University of Health Sciences Kaunas Clinics, Department of Pediatric Surgery from January 2008 to March After approval by local Regional Biomedical Research Ethics Committee (Protocol Nr. BE-2-26), 26 patients were prospectively examined. Consent was obtained from all the patients or their parents. They were given bilateral intercostal blocks after induction of anesthesia (PCA-IB group). The group of retrospective controls (PCA group) consisted of 19 patients without regional blockade. Patients in both groups were followed up 24 h postoperatively using the same follow-up documentation chart. In both groups patients underwent general anesthesia with tracheal intubation, following premedication with either oral or intravenous midazolam. Isoflurane (n = 8), sevoflurane (n = 37), fentanyl (n = 45), atracurium (n = 24), or rocuronium (n = 21) were used for maintenance of anesthesia. After induction of anesthesia, single shot intercostal blocks were performed in the PCA-IB group. Intercostal blocks were performed using technique first described by Moore [16], later by Kopatcz et al, Jagannathan et al [15,17]. The block was performed at the mid-axillary line with the patient lying in supine position. Using sterile technique, the block sites were identified and the lower rib margins were then located. The needle was inserted at an 80 angle with the skin and advanced until the rib was contacted. Afterwards the needle was gradually walked off the cauda edge of the rib. As soon as the needle lost contact with the rib, the needle was slowly inserted cm deeper than the lower border of the rib. After negative aspiration 4 to 5 ml of bupivacaine containing 5 μg/ml of adrenaline was injected. The procedure was repeated bilaterally into each intercostal space from Th4 to Th8. A short, beveled 22 gauge nerve stimulation needle was used in order to diminish the risk of pleural puncture. Ultrasound was not used. No regional blocks had been given to retrospective control patients. After surgery, all patients were extubated and PCA treatment was started. The PCA device settings for morphine were the same in both groups: bolus dose 20 μg/ kg, lock-out time 5 6 min, max 4 h dose 400 μg/kg, and a background infusion 5 6 μg/kg/h. The loading dose of morphine could be given before starting PCA at the discretion of the attending anesthesiologist. This decision was made on the basis of patient's pain level (restlessness, agitation or crying on emergence). All patients were given baseline analgesia of acetaminophen and ketoprofen by intravenous or oral/rectal routes. All patients were continuously monitored for respiratory function (oxygen saturation and respiratory rate), sedation and pain at rest until the discontinuation of PCA in the intensive care unit and surgical ward thereafter. The followup data were recorded at every 3 h, except for oxygen saturation, which was recorded hourly. For evaluating and quantifying the degree of sedation a 4- point sedation scale was used: 0 awake, 1 drowsy, 2 asleep, easy to arouse, 3 asleep, difficult to arouse. The children expressed their pain by a 10-point visual color analogue scale (VAS) from lower end of no pain to upper end of the worst possible pain. The backside of the scale was graded from 0 no pain to 10 worst possible pain [18]. The following adverse effects were scored as present or absent: nausea/vomiting retching or expulsion of gastric contents, urinary retention catheterization of the bladder. The need for oxygen therapy, any abnormal radiological findings and other pulmonary adverse effects were noted Statistics Continuous variables were checked for the normality of distribution. Normally distributed variables, such as patient's

3 The role of intercostal block Table 1 Patient's demographics, intraoperative fentanyl, postoperative doses of non-opioid analgesics, prophylactic ondansetron use and operating room time. age, weight, non-opioid analgesic doses, and oxygen saturation values, were compared using the Student's t-test. Non-normally distributed variables, such as cumulative opioid doses, were compared using the Mann Whitney U- test. A Bonferroni correction was used for multiple comparisons of cumulative morphine doses at different time intervals. Fisher's exact and z-test were used for proportions, such as gender and the incidence of adverse effects. For the comparison of overall VAS scores during 24 h, a general linear model for repeated measures was used. A p-value of less than 0,05 was considered statistically significant. Results are presented either as means ± SD, median (25 75 percentiles), or as a number of patients (%). 2. Results PCA-group N=19 PCA-IB group N=26 Age (years) 14,6 ± 3 14,3 ± 2,7 Weight (kg) 53,8 ± 13,4 52,2 ± 13,5 Gender: male/female 14/5 17/9 Intraoperative fentanyl (μg/kg) 4,7 ± 1,3 2,4 ± 0,9 24-h paracetamol dose (mg/kg) 28 ± 14,4 (N = 10) (N = 24) 19,4 ± 6,7 24-h ketoprofen dose (mg/kg) 3,5 ± 1,4 (N = 16) 3,0 ± 0,96 (N = 26) Prophylactic ondansetron 33% (N = 18) (N = 24) 79% Operating room time (min) 73,3 ± 14,1 70 ± 8,4 Data are mean ± SD. p b 0,05 compared to PCA group. Time between intubation and extubation. Demographic data, doses of analgesics used, prophylactic ondansetron use and operating room time (between intubation and extubation) are shown in Table 1. The two groups did not differ according to age, weight, gender, postoperative ketoprofen dose and operating room time, but less intraoperative fentanyl was required in the PCA-IB group. Oral or rectal acetaminophen was used in half of the patients in the PCA group, whereas intravenous acetaminophen was used in almost all patients in PCA-IB group. Prophylactic ondansetron usage was more frequent in the PCA-IB group. Seventeen patients in the PCA-group required a loading dose of morphine in the operating room before starting the PCA. Dosage ranged between 0.04 and 0.22 (mean ± SD 0.1 ± 0.49) mg/kg. No patient needed loading dose in the PCA-IB group. Cumulative used morphine doses (excluding the loading dose) 3, 6, 12 and 24 h after surgery are shown in Fig. 1. Significantly lower median (25 75 percentiles) doses Fig. 1 Median cumulative used morphine doses 3, 6, 12, and 24 h after surgery. Error bars are 75 percentiles. *p b 0,0125 (Mann-Whitney U-test with Bonferroni correction). up to 6 h after surgery were used in the PCA-IB group (0.15 ( ) mg/kg) than in the PCA-group (0.26 ( ) mg/kg), p b No differences were observed thereafter. Pain scores every 3 h up to 24 h after surgery are shown in Fig. 2. There were no differences in pain scores between patients in the PCA and PCA-IB groups. Postoperatively observed oxygen saturation values, sedation scores, pulmonary and opioid-related adverse effects are shown in Table 2. Oxygen saturation values, sedation scores and the incidence of pulmonary adverse events did not differ between the two groups. Patients given intercostal blocks suffered less morphine-related adverse effects compared to those not given regional blocks: 9/26 vs. 12/19, p b 0,05 (z-test), respectively. Postoperative oxygen therapy up to 8 h after surgery was required in 2 patients in the PCA-IB group: one with atelectasis and one with residual pneumothorax. No other treatment, except for physiotherapy was applied in these patients. Two patients required additional oxygen therapy up to 3 h postoperatively in the PCA group. 3. Discussion 2427 Several decades ago, D. Moore described the technique of intercostal block [19]. Studies in adults have shown that intercostal blocks improve analgesia, reduce opioid intake and have favorable effects on respiratory function, compared to opioids alone [20,21]. To our knowledge, this is the first study describing analgesia when bilateral intercostal blocks were used to manage early postoperative pain after the Nuss procedure. The main finding is that morphine use was significantly reduced with intercostal blocks. A second important finding is that the total number of morphine-related side effects were also decreased with the additional use of intercostal blocks. Reduced opioid doses were reported in children and adult

4 2428 L. Lukosiene et al. Fig. 2 Mean pain scores every 3 h after surgery in PCA and PCA IB group patients (error bars are standard deviations); p N 0,05 (general linear model for repeated measures). studies where parasternal intercostal blocks were used following heart surgery [14,20,22]. We found that opioid doses were significantly decreased up to 6 h postoperatively (Fig. 1). Similar findings have been reported in patients using a single shot parasternal block with bupivacaine [20]. Rothstein et al. investigated relationship of the dose of bupivacaine for an intercostal nerve block to the observed blood concentration. The elimination half-life in children from 3 months to 16 years old was reported to be 147 ± 80 min [23]. Thus, it is unlikely that analgesia would last longer than several hours after a single shot technique. A systematic review of adult studies following thoracotomies showed that repeated blocks or continuous infusions were more consistently associated with decreased opioid consumption than single shot techniques [24]. Reduced pain scores were reported to be decreased with parasternal blocks in children, and in a majority of adult studies exploring single shot, repeat or continuous intercostal or parasternal blocs [14,20,22,24]. Pain scores, though, were not significantly reduced in our study. PCA allows individual titration of analgesic. In addition, all of our patients received intravenous NSAIDs, which have been reported to effectively reduce postoperative pain in children [25]. Many patients in our study also received acetaminophen. Thus, it is not surprising that pain scores over 24 h were not different in the two study groups (Fig. 2). Reduced opioid doses are important as opioids cause side effects in a dose-dependent manner. Since oxygen desaturation is uncommon with thoracoplastic surgery when adequate analgesia is achieved [11], nausea/vomiting remains the most relevant side effect. It may prevent some patients from achieving effective analgesia postoperatively. In the present study, we had to discontinue treatment with morphine in two PCA group patients; one owing to protracted nausea/vomiting and one on the second postoperative day who complained of pain and shortness of breath. These findings further support the concept that the additional use of intercostal blocks can improve analgesia. Furthermore, we observed that overall opioid-related side effects, Table 2 Postoperative oxygen saturation, sedation scores, pulmonary and opioid-related adverse events in PCA and PCA-IB groups. Variable PCA group N=19 PCA-IB N=26 Spo2 96,6 ± 1,7 96,7 ± 1,0 Sedation 0,7 ± 0,4 0,9 ± 0,4 Pulmonary adverse events Pneumonia (infiltration) 1 (5.3%) - Upper respiratory infection 1 (5,3%) - Respiratory insufficiency 1 (5,3%) - owing to pain and bilateral pneumothorax Segmental atelectasis - 1(3,8%) Haemothorax - 1 (3,8%) Postoperative oxygen 2 (10,5%) 2 (7,7%) therapy required Total 5 (26%) 4 (15%) Opioid-related adverse effects Nausea/vomiting 8 (42,1%) 7 (26,9%) Urinary retention 3 (15,8%) 2 (7,7%) Respiratory rate b 10/min - - Discontinuation of PCA therapy 1(5,3%) - owing to persistent nausea/vomiting Total 12 (63,2%) 9 (34,6%) Data are mean ± SD and number of cases (%). p b 0,05, compared to PCA group (z-test). including nausea/vomiting, were reduced in patients additionally given intercostal blocks, likely because of the decreased opioid requirement. We cannot with certainty, however, attribute this decrease solely to the reduced morphine requirement in the PCA-IB group as intravenous, rather than oral, acetaminophen and more frequent prophylactic administration of ondansetron in this group versus the PCA group might have also contributed to this finding. Although we found intercostal blocks to be simple to perform, meticulous technique and safety are important. The incidence of pneumothorax is reported from less than 1% in adults [19] to 3,4% in children [12]. Residual pneumothorax following MIRPE was reported to occur in up to 30% of cases, however, most are subclinical and resume spontaneously [26]. According to the recent meta-analysis by A. Nasr et al., clinically significant pneumothorax occurs in less than 5% of cases [27]. The incidence of pneumothorax was 15% (4 patients) in the PCA-IB group vs. 11% (2 patients) in the PCA group, with only one patient in each group presenting with clinical symptoms. Thus we believe that the incidence of pneumothorax was not affected by the intercostal blockade. There was also one relevant clinical case of segmental atelectasis with desaturation, which could not be attributed to the method of analgesia but rather insufficient lung distension at the end of surgery. We had one case of clinically significant pleural effusion in the PCA-IB group. Pleural drainage confirmed the

5 The role of intercostal block diagnosis of hemothorax. The information regarding the incidence of bleeding following intercostal block is scarce. The intercostal artery courses along with the intercostal nerve within the costal groove and is covered by a rib laterally. Thus, a theoretical possibility of arterial damage exists, especially when the needle is advanced too cephalad beyond the lower edge of the rib. In addition, pleural injury could also occur in association with the vascular damage. However, only one case of hemothorax was reported in literature after intercostal catheterization [28]. We cannot know if this hemothorax occurred as a result of the blockade or the ensuing surgical procedure, but utilization of ultrasound while performing intercostal blocks would be helpful in preventing complications as pneumo- or hemothorax. While hemothorax may occur following MIRPE, the incidence has been reported to be less than 1% [27]. Regarding the use of NSAIDs for adjunctive pain control, the literature in the adult population suggests an associated increased the risk of bleeding [29] which has not been found to exist in children [25], so we continue to use NSAIDs with this kind of surgery. Because of an excellent vascular supply, systemic absorption after intercostal block is known to be faster than after other regional techniques. Furthermore, the rate of absorption in children has been reported to be higher compared to adults [23]. This may result in high plasma concentrations of local anesthetic and systemic toxic reactions. Bupivacaine can cause severe cardiac and/or neurologic side effects if toxic concentrations are reached. While neurologic manifestations may be masked during general anesthesia, cardiac complications should be kept in mind and appropriate measures to reduce absorption and the risk of toxicity applied. Johnson et al. found, that epinephrine added to bupivacaine for intercostal blockade decreased plasma concentrations up to 50% [30]. Rothstein et al. found that bupivacaine in doses of 2 4 mg/kg with epinephrine 1: was safe for intercostal nerve blockade in children under general anesthesia without demonstrable side effects [23]. We used 0,25% bupivacaine with 5 μg/ml (1: ) of epinephrine to reduce absorption and did not exceed 2 mg/ kg of total bupivacaine dose. Accidental intravascular injection can be another cause of systemic toxicity. We, therefore, always perform an aspiration test before and during injection. Safer local anesthetics, such as levobupivacaine or ropivacaine, can diminish the risk of toxicity and are used in children and adults [14,20]. It took on average 10 min to perform the bilateral intercostal blocks, but operating room time was not substantially prolonged. We think that lower doses of intraoperative opioid in the PCA-IB group allowed for faster extubation after procedure, which is consistent with the previous observations [14,20]. The results of our present study might have been biased by several methodological limitations: undefined strategies for the use of perioperative fentanyl and the loading dose of morphine, as well as different treatment patterns of prophylactic antiemetics and non-opioid analgesics between the two groups. Finally, the unblinded design of retrospective prospective study introduces potential bias. 4. Conclusion We found that multiple intercostal blocks following MIRPE are safe and easy to perform and can be applied in surgical settings to reduce the dose of PCA-administered opiates. We also found a decreased incidence of opioidrelated adverse effects in patients additionally given intercostal blocks. 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