Postoperative Pain Management: Efficacy of Caudal Tramadol in Pediatric Lower Abdominal Surgery: A Randomized Clinical Study

AUTHORS

avatar Reza Farahmand Rad ORCID 1 , avatar Farnad Imani ORCID 1 , * , avatar Azadeh Emami ORCID 1 , avatar Reza Salehi ORCID 1 , avatar Ali Reza Ghavamy ORCID 1 , avatar Ali Nima Shariat 2

1 Pain Research Center, Department of Anesthesiology and Pain Medicine, Iran University of Medical Sciences, Tehran, Iran

2 Icahn School of Medicine of Mount Sinai, Mount Sinai Morningside Hospital Center, New York, USA

How to Cite: Farahmand Rad R, Imani F, Emami A, Salehi R, Ghavamy A R, et al. Postoperative Pain Management: Efficacy of Caudal Tramadol in Pediatric Lower Abdominal Surgery: A Randomized Clinical Study. Anesth Pain Med. 2021;11(4):e119346. doi: 10.5812/aapm.119346.

ARTICLE INFORMATION

Anesthesiology and Pain Medicine: 11 (4); e119346
Published Online: September 26, 2021
Article Type: Research Article
Received: September 6, 2021
Accepted: September 12, 2021
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Abstract

Background: One of the methods of pain control after pediatric surgical procedures is regional techniques, including caudal block, despite their limitations.

Objectives: In this study, the pain score and complications of caudal tramadol were evaluated in pediatrics following lower abdominal surgery.

Methods: In this study, 46 children aged 3 to 10 years were allocated into two equal groups (R and TR) for performing caudal analgesia after lower abdominal surgery. The injectate contained 0.2% ropivacaine 1 mL/kg in the R group (control group) and tramadol (2 mg/kg) and ropivacaine in the TR group. The pain score, duration of pain relief, amount of paracetamol consumption, hemodynamic alterations, and possible complications at specific times (1, 2, and 6 hours) were evaluated in both groups.

Results: No considerable difference was observed in the pain score between the groups in the first and second hours (P > 0.05). However, in the sixth hour, the TR group had a significantly lower pain score than the R group (P < 0.05). Compared to the R group, the TR group had a longer period of analgesia and lower consumption of analgesic drugs (P < 0.05). Heart rate and blood pressure differences were not significant between the two groups (P > 0.05). Similarly, the duration of operation and recovery time were not remarkably different between the two groups (P > 0.05). Complications had no apparent differences between these two groups, as well (P > 0.05).

Conclusions: In this study, the addition of tramadol to caudal ropivacaine in pediatric lower abdominal surgery promoted pain relief without complications.

1. Background

For pain management after pediatric lower abdominal surgery, various methods have been used so far, including the administration of opioid and non-opioid drugs, as well as performing central and peripheral nerve blocks (1-5). As a neuraxial procedure, caudal is one of the popular techniques for pain management in children after lower abdominal surgeries, particularly orchidopexy, hernia, etc., within peri-operative care (6). The main drug in these cases is usually local anesthetics, which are not commonly sufficient to induce prolonged analgesia if administered alone in caudal; thus, much research has been done to examine the efficacy of caudal analgesia in pediatric groups (7-10). Being similar to bupivacaine in structure, ropivacaine is one of the most common local anesthetics for postoperative pain management, but its duration of motor block is shorter and has better cardiovascular stability and less neurotoxicity, thus allowing for faster discharge from the recovery room (11-14).

Tramadol is a synthetic opioid analgesic with a moderate potency whose effects vary depending on the type of opioid-specific receptors and can cause differences in the physiological parameters obtained (15). Administration of tramadol as an adjuvant for pain management or adding it to local anesthetics in various methods has enhanced their analgesic potency without increasing the incidence of adverse effects (16-19).

Despite some available research in this field, the appropriate dose of tramadol to be added to ropivacaine in caudal epidural in children has not yet been defined.

2. Objectives

Our aim in this study was to investigate the pain score and complications of tramadol as an adjuvant to caudal ropivacaine in the pediatric population scheduled for lower abdominal operation.

3. Methods

Following the Ethics Committee approval (Ref: IR.IUMS.FMD.REC.1398.107) and receipt of the clinical trial registration code (Ref: IRCT20190929044924N1), written informed consent was obtained from the parents before the enrollment of children in this study. Forty-six pediatric patients (both sexes) aged 3 - 6 years, with ASA I-II, who were candidates for lower abdomen surgery, for 30 minutes to two hours under general anesthesia, were included in this double-blind, randomized clinical trial. The exclusion criteria for the study consisted of problematic surgeries (i.e., blood transfusion due to unacceptable bleeding), sacral deformities, hemorrhagic disorders, infections (local or systemic), history of drug hypersensitivity, and refusal of parents. The sample size of 46 patients was obtained using the following formula, who were randomly divided into two groups of 23:

n=2 z1- α2+Z1-b2δ2d2

To double-blind the study, the children’s parents and the researchers were kept unaware of the group classification.

The induction and maintenance of anesthesia were performed in the same manner for both groups (including propofol, fentanyl, and atracurium for induction and isoflurane for maintenance). After surgery and before extubation, a caudal epidural block was performed under an aseptic situation, by lateral decubitus position, using a 20 G needle (Pajunk, Germany) under ultrasonography with a high frequency (6 - 13 MHz) linear probe (Sonosite, USA). When the exact location of the needle tip was confirmed by the sonographic view, 2 - 4 mL was slowly administered. If there were not any blood pressure and heart rate alterations, the remainder of the injectable solution was administered slowly.

Patients were randomly divided into two equal groups, R and TR. The injectable solution was 0.2% ropivacaine 1 mL/kg (Ropivacaine, Molteni, Italy) up to the highest volume of 15 mL in the R group and 0.2% ropivacaine 1 mL/kg plus tramadol 2 mg/kg (Ultram; Vertical Pharmaceutical, USA) in the TR group. Following the caudal block, the neuromuscular blockade was reversed (by atropine and neostigmine) and tracheal extubation was performed. The patients were assessed at determined times (1, 2, and 6 hours after the operation), and if the pain score was more than 3, acetaminophen 15 mg/kg (Paracetamol Zolben, Switzerland) would be i.v. injected. Before and after the caudal injection, the pain scores were assessed using CHEOPS (Children’s Hospital of Eastern Ontario Pain Scale), and non-invasive blood pressure and heart rate monitoring were observed (Table 1). Moreover, the length of analgesia (pain score less than three), total acetaminophen used, post-anesthetic care unit stay (recovery time), and complications were evaluated.

Table 1. Modified CHEOPS (Children's Hospital of Eastern Ontario Pain Scale)
Score012
CryNo cryCrying, moaningScream
FacialSmilingComposedGrimace
VerbalPositiveNone or other complaintsPain complaint
TorsoNeutralShifting, tense, uprightRestrained
LegsNeutralKicks, squirm, drawn upRestrained

Data were analyzed by SPSS 25. The results were expressed as the mean ± standard deviation (SD) for parametric data (weight, age, pain score, length of pain relief, surgery duration, amount of acetaminophen consumption, blood pressure, and heart rate) and percentage for non-parametric data (sex, complications). Parametric data were compared using the independent t test if the data distribution was normal; alternatively, the comparison was carried out employing the Mann-Whitney U test if there was an abnormal distribution. Non-parametric data were also compared using the χ2 test or Fisher's exact test. A p value of less than 0.05 was considered statistically significant.

4. Results

Demographic data and other information considered in the study are given in Table 2. As can be seen, the mean pain score assessed in the first and second hours was not significantly different between the two groups (P > 0.05); however, it was significantly lower in the TR group than in the R group in the sixth hour (P < 0.05).

Table 2. Demographic Data, Pain Score, Analgesia, Acetaminophen Consumption, Heart Rate, Blood Pressure Alterations, and Complications
VariabesRTRP Value
Age (y)6.04 ± 1.86.26 ± 1.70.542
Sex (male: female) (n)12: 1114: 90.546
Operation time (min)45.6 ± 16.944.7 ± 15.80.664
Pain score
First hour2.61 ± 0.722.57 ± 0.660.832
Second hour3.0 ± 0.953.13 ± 0.920.639
Third hour6.87 ± 1.984.65 ± 1.470.001
Duration of analgesia (h)2.83 ± 0.784.13 ± 0.760.001
Acetaminophen (mg)80.13 ± 28.4361.87 ± 28.110.034
Blood pressure (mmHg)
Systolic94.5 ± 9.695.8 ± 5.60.604
Diastolic62.2 ± 3.863.2 ± 3.10.237
Heart rate (bpm)103.1 ± 8.3102.2 ± 9.20.844
Recovery time (min)126 ± 102138 ± 840.337
Complications
None19 (82.63)20 (86.8)0.778
Hypotension1 (4.3)2 (8.66)0.884
Tachycardia1 (4.3)1 (4.33)1.000
Nausea/vomiting1 (4.3)1 (4.33)1.000

a Values are expressed as mean ± SD or No. (%).

The TR group also proved to have prolonged analgesia and less analgesic consumption compared to the R group (P < 0.05). There was no significant difference in the heart rate and blood pressure (systolic and diastolic) between the two groups (P > 0.05). Regarding the adverse effects, the difference between these two groups was not significant (P > 0.05). Furthermore, the differences in the duration of surgery and recovery time between these groups were not significant (P > 0.05).

5. Discussion

This study showed that adding tramadol (2 mg/kg) to caudal epidural ropivacaine increased pain relief and reduced acetaminophen consumption without affecting the incidence of complications in pediatric patients following lower abdominal surgery under general anesthesia.

To date, several studies have been conducted on the addition of adjuvant drugs to local anesthetics in regional anesthesia in children and adults, which have produced different results in some cases, partly due to the dose of drugs, various concentrations of local anesthetics and adjuvants, and the type of surgery (20-24). Compared to ketamine, the addition of tramadol or fentanyl to local anesthetics in the axillary plexus block has accelerated the onset of sensory and motor blockade and reduced its duration and pain score, as well (25, 26).

To manage post-operative pain in pediatric lower abdominal surgery, tramadol and dexmedetomidine were separately added to caudal ropivacaine, and the results showed that the combination of caudal ropivacaine with dexmedetomidine had longer analgesia than its combination with tramadol, but the side effects were similar in the two groups (27). In our study, there existed no third group for further comparison, but it could be a good topic for future research. In a study, Jarineshin et al. conducted caudal block following anesthesia induction, and compared the addition of 2 µg/kg dexmedetomidine and 2 µg/kg fentanyl to caudal epidural bupivacaine 0.25% (28). The findings showed that dexmedetomidine was more effective than fentanyl in enhancing caudal analgesia for postoperative pain control without causing notable complications or hemodynamic alterations.

In some studies, non-opioid drugs such as ketamine and dexmedetomidine have been used to control pain in these cases, which have had considerable effects on postoperative pain management (29, 30), and its addition to caudal bupivacaine has also increased postoperative analgesia in children (31). In another study, the addition of tramadol, as compared with ketamine, to pediatric caudal ropivacaine was investigated, and the results indicated prolonged analgesia and reduced analgesic consumption in the tramadol group although it was associated with a high incidence of postoperative nausea and vomiting (32). In our study, on the contrary, the amount and the type of complications between the two groups were not different.

In a study conducted by Singh et al., adding tramadol (2 mg/kg) to ropivacaine increased the pain relief without hemodynamic side effects (33), which is consistent with the results of the present study. Furthermore, the addition of tramadol to bupivacaine, as compared with caudal levobupivacaine, did not make any change in the severity of pain, duration of analgesia, and side effects, which raises the question of whether the type of local anesthetic can influence the effects of adding tramadol (34).

In a study on pain management in infra-umbilical cord surgery in children, 2 mg/kg tramadol was added as an adjuvant to caudal ropivacaine 0.2% (1 mL/kg), which increased pain relief, though not associated with considerable effects on sedation and motor block (35), and thus is in line with the results obtained in our study.

5.1. Conclusion

Overall, although the addition of tramadol to caudal ropivacaine in children increased the effects of the caudal epidural blockade in children, such as increasing the duration of analgesia and reducing the dose of analgesics, it did not raise the adverse effects; thus, it could be recommended for administration with caudal ropivacaine. However, the most common problem in these patients was, of course, the dissatisfaction of some parents and their fear of performing a caudal blockade.

Footnotes

References

  • 1.

    Boric K, Dosenovic S, Jelicic Kadic A, Batinic M, Cavar M, Urlic M, et al. Interventions for postoperative pain in children: An overview of systematic reviews. Paediatr Anaesth. 2017;27(9):893-904. doi: 10.1111/pan.13203. [PubMed: 28707454].

  • 2.

    Malik KM, Imani F, Beckerly R, Chovatiya R. Risk of opioid use disorder from exposure to opioids in the perioperative period: A systematic review. Anesth Pain Med. 2020;10(1). e101339. doi: 10.5812/aapm.101339. [PubMed: 32337175]. [PubMed Central: PMC7158240].

  • 3.

    Suksompong S, von Bormann S, von Bormann B. Regional catheters for postoperative pain control: Review and observational data. Anesth Pain Med. 2020;10(1). e99745. doi: 10.5812/aapm.99745. [PubMed: 32337170]. [PubMed Central: PMC7158241].

  • 4.

    Pinto Filho WA, Silveira LHJ, Vale ML, Fernandes CR, Gomes JA. Gabapentin in Improvement of procedural sedation and analgesia in oncologic pediatric patients: A clinical trial. Anesth Pain Med. 2019;9(5). e91197. doi: 10.5812/aapm.91197. [PubMed: 31903327]. [PubMed Central: PMC6935294].

  • 5.

    Sirimontakan T, Artprom N, Anantasit N. Efficacy and safety of pediatric procedural sedation outside the operating room. Anesth Pain Med. 2020;10(4). e106493. doi: 10.5812/aapm.106493. [PubMed: 33134153]. [PubMed Central: PMC7539052].

  • 6.

    Wiegele M, Marhofer P, Lonnqvist PA. Caudal epidural blocks in paediatric patients: a review and practical considerations. Br J Anaesth. 2019;122(4):509-17. doi: 10.1016/j.bja.2018.11.030. [PubMed: 30857607]. [PubMed Central: PMC6435837].

  • 7.

    Ismail AA, Mohamed Hamza H, Ali Gado A. Efficacy of dexmedetomidine versus morphine as an adjunct to bupivacaine in caudal anesthesia for pediatric thoracic surgeries: A randomized controlled trial. Anesth Pain Med. 2021;11(2). e112296. doi: 10.5812/aapm.112296. [PubMed: 34336616]. [PubMed Central: PMC8314090].

  • 8.

    Imani F, Farahmand Rad R, Salehi R, Alimian M, Mirbolook Jalali Z, Mansouri A, et al. Evaluation of adding dexmedetomidine to ropivacaine in pediatric caudal epidural block: A randomized, double-blinded clinical trial. Anesth Pain Med. 2021;11(1). e112880. doi: 10.5812/aapm.112880. [PubMed: 34221950]. [PubMed Central: PMC8241816].

  • 9.

    Trifa M, Tumin D, Tobias JD. Dexmedetomidine as an adjunct for caudal anesthesia and analgesia in children. Minerva Anestesiol. 2018;84(7):836-47. doi: 10.23736/S0375-9393.18.12523-5. [PubMed: 29479931].

  • 10.

    Aliena SP, Lini C, Chirayath JJ. Comparison of postoperative analgesic effect of caudal bupivacaine with and without ketamine in Pediatric subumbilical surgeries. J Anaesthesiol Clin Pharmacol. 2018;34(3):324-7. doi: 10.4103/joacp.JOACP_60_17. [PubMed: 30386014]. [PubMed Central: PMC6194841].

  • 11.

    Gitman M, Barrington MJ. Local anesthetic systemic toxicity: A review of recent case reports and registries. Reg Anesth Pain Med. 2018;43(2):124-30. doi: 10.1097/AAP.0000000000000721. [PubMed: 29303925].

  • 12.

    Behnaz F, Soltanpoor P, Teymourian H, Tadayon N, Mohseni GR, Ghasemi M. Sympatholytic and anti-inflammatory effects of ropivacaine and bupivacaine after infraclavicular block in arterio venous fistula surgery. Anesth Pain Med. 2019;9(1). e85704. doi: 10.5812/aapm.85704. [PubMed: 30881912]. [PubMed Central: PMC6412917].

  • 13.

    Bishop B, Pearce B, Willshire L, Kilpin M, Howard W, Weinberg L, et al. High frequency, low background rate extrapleural programmed intermittent bolus ropivacaine provides superior analgesia compared with continuous infusion for acute pain management following thoracic surgery: A retrospective cohort study. Anesth Pain Med. 2019;9(5). e97052. doi: 10.5812/aapm.97052. [PubMed: 31903338]. [PubMed Central: PMC6925520].

  • 14.

    Olapour A, Akhondzadeh R, Rashidi M, Gousheh M, Homayoon R. Comparing the effect of bupivacaine and ropivacaine in Cesarean delivery with spinal anesthesia. Anesth Pain Med. 2020;10(1). e94155. doi: 10.5812/aapm.94155. [PubMed: 32337166]. [PubMed Central: PMC7144247].

  • 15.

    Barakat A. Revisiting tramadol: A multi-modal agent for pain management. CNS Drugs. 2019;33(5):481-501. doi: 10.1007/s40263-019-00623-5. [PubMed: 31004280].

  • 16.

    Imani F, Entezary SR, Alebouyeh MR, Parhizgar S. The maternal and neonatal effects of adding tramadol to 2% lidocaine in epidural anesthesia for Cesarean section. Anesth Pain Med. 2011;1(1):25-9. doi: 10.5812/kowsar.22287523.1271. [PubMed: 25729652]. [PubMed Central: PMC4335753].

  • 17.

    Sahmeddini MA, Khosravi MB, Seyedi M, Hematfar Z, Abbasi S, Farbood A. Comparison of magnesium sulfate and tramadol as an adjuvant to intravenous regional anesthesia for upper extremity surgeries. Anesth Pain Med. 2017;7(6). e57102. doi: 10.5812/aapm.57102. [PubMed: 29696122]. [PubMed Central: PMC5903376].

  • 18.

    Khajavi MR, Navardi M, Shariat Moharari R, Pourfakhr P, Khalili N, Etezadi F, et al. Combined ketamine-tramadol subcutaneous wound infiltration for multimodal postoperative analgesia: A double-blinded, randomized controlled trial after renal surgery. Anesth Pain Med. 2016;6(5). e37778. doi: 10.5812/aapm.37778. [PubMed: 27847695]. [PubMed Central: PMC5101596].

  • 19.

    Edinoff AN, Kaplan LA, Khan S, Petersen M, Sauce E, Causey CD, et al. Full Opioid Agonists and Tramadol: Pharmacological and Clinical Considerations. Anesth Pain Med. 2021;11(4). e119156. doi: 10.5812/aapm.119156.

  • 20.

    Abd-Elshafy SK, Yacoup AM, Abdalla EE, El-Melegy TT, Abd-Elsalam KA. A New Look on Adding Dexamethasone as an Adjuvant to Caudal Bupivacaine; Efficacy on Postoperative Pain and Vomiting in Pediatric Patients. Pain Physician. 2016;19(6):E841-52. [PubMed: 27454274].

  • 21.

    Edinoff AN, Fitz-Gerald JS, Holland KAA, Reed JG, Murnane SE, Minter SG, et al. Adjuvant drugs for peripheral nerve blocks: The role of nmda antagonists, neostigmine, epinephrine, and sodium bicarbonate. Anesth Pain Med. 2021;11(3). e117146. doi: 10.5812/aapm.117146. [PubMed: 34540646]. [PubMed Central: PMC8438710].

  • 22.

    Baduni N, Sanwal MK, Vajifdar H, Agarwala R. Postoperative analgesia in children: A comparison of three different doses of caudal epidural morphine. J Anaesthesiol Clin Pharmacol. 2016;32(2):220-3. doi: 10.4103/0970-9185.182106. [PubMed: 27275053]. [PubMed Central: PMC4874078].

  • 23.

    Edinoff AN, Houk GM, Patil S, Bangalore Siddaiah H, Kaye AJ, Iyengar PS, et al. Adjuvant drugs for peripheral nerve blocks: The role of alpha-2 agonists, dexamethasone, midazolam, and non-steroidal anti-inflammatory drugs. Anesth Pain Med. 2021;11(3). e117197. doi: 10.5812/aapm.117197. [PubMed: 34540647]. [PubMed Central: PMC8438706].

  • 24.

    Farrag WS, Ibrahim AS, Mostafa MG, Kurkar A, Elderwy AA. Ketamine versus magnesium sulfate with caudal bupivacaine block in pediatric inguinoscrotal surgery: A prospective randomized observer-blinded study. Urol Ann. 2015;7(3):325-9. doi: 10.4103/0974-7796.152039. [PubMed: 26229319]. [PubMed Central: PMC4518368].

  • 25.

    Senel AC, Ukinc O, Timurkaynak A. Does the addition of tramadol and ketamine to ropivacaine prolong the axillary brachial plexus block? Biomed Res Int. 2014;2014:686287. doi: 10.1155/2014/686287. [PubMed: 24883319]. [PubMed Central: PMC4032708].

  • 26.

    Akhondzadeh R, Rashidi M, Gousheh M, Olapour A, Tasbihi B. Comparison of the ketamine-lidocaine and fentanyl-lidocaine in postoperative analgesia in axillary block in upper limb fractures by ultrasound guidance. Anesth Pain Med. 2019;9(6). e92695. doi: 10.5812/aapm.92695. [PubMed: 32280613]. [PubMed Central: PMC7118445].

  • 27.

    Gupta S, Sharma R. Comparison of analgesic efficacy of caudal dexmedetomidine versus caudal tramadol with ropivacaine in paediatric infraumbilical surgeries: A prospective, randomised, double-blinded clinical study. Indian J Anaesth. 2017;61(6):499-504. doi: 10.4103/ija.IJA_712_16. [PubMed: 28655957]. [PubMed Central: PMC5474920].

  • 28.

    Jarineshin H, Fekrat F, Kargar Kermanshah A. Treatment of postoperative pain in pediatric operations: Comparing the efficiency of bupivacaine, bupivacaine-dexmedetomidine and bupivacaine-fentanyl for caudal block. Anesth Pain Med. 2016;6(5). e39495. doi: 10.5812/aapm.39495. [PubMed: 27847704]. [PubMed Central: PMC5101645].

  • 29.

    Imani F, Varrassi G. Ketamine as adjuvant for acute pain management. Anesth Pain Med. 2019;9(6). e100178. doi: 10.5812/aapm.100178. [PubMed: 32280623]. [PubMed Central: PMC7119219].

  • 30.

    Imani F, Zaman B, De Negri P. Postoperative pain management: Role of dexmedetomidine as an adjuvant. Anesth Pain Med. 2020;10(6). e112176. doi: 10.5812/aapm.112176. [PubMed: 34150582]. [PubMed Central: PMC8207883].

  • 31.

    Kaur D, Anand S. Comparison between caudal bupivacaine and bupivacaine with ketamine for postoperative analgesia in children: A prospective randomized clinical study. Anesth Essays Res. 2016;10(3):488-92. doi: 10.4103/0259-1162.179314. [PubMed: 27746538]. [PubMed Central: PMC5062222].

  • 32.

    Gunes Y, Secen M, Ozcengiz D, Gunduz M, Balcioglu O, Isik G. Comparison of caudal ropivacaine, ropivacaine plus ketamine and ropivacaine plus tramadol administration for postoperative analgesia in children. Paediatr Anaesth. 2004;14(7):557-63. doi: 10.1111/j.1460-9592.2004.01220.x. [PubMed: 15200652].

  • 33.

    Singh AP, Singh D, Singh Y, Jain G. Postoperative analgesic efficacy of epidural tramadol as adjutant to ropivacaine in adult upper abdominal surgeries. Anesth Essays Res. 2015;9(3):369-73. doi: 10.4103/0259-1162.161805. [PubMed: 26712976]. [PubMed Central: PMC4683493].

  • 34.

    Sezen G, Demiraran Y, Karagoz I, Kucuk A. The assessment of bupivacaine-tramadol and levobupivacaine-tramadol combinations for preemptive caudal anaesthesia in children: A randomized, double-blind, prospective study. Int J Clin Exp Med. 2014;7(5):1391-6. [PubMed: 24995101]. [PubMed Central: PMC4073762].

  • 35.

    Krishnadas A, Suvarna K, Hema VR, Taznim M. A comparison of ropivacaine, ropivacaine with tramadol and ropivacaine with midazolam for post-operative caudal epidural analgesia. Indian J Anaesth. 2016;60(11):827-32. doi: 10.4103/0019-5049.193672. [PubMed: 27942056]. [PubMed Central: PMC5125186].

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