Comparative Study between Nalbuphine versus Tramadol on Postoperative Analgesia for Abdominal Surgery in Pediatric Cancer Patients: A Prospective, Randomized Clinical Trial

Comparative Study between Nalbuphine versus Tramadol on Postoperative Analgesia for Abdominal Surgery in Pediatric Cancer Patients: A Prospective, Randomized Clinical Trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Comparative Study between Nalbuphine versus Tramadol on Postoperative Analgesia for Abdominal Surgery in Pediatric Cancer Patients: A Prospective, Randomized Clinical Trial Fatma Hanafi Mahmoud Mostafa Elshamy, Ahmed Fahmy Ahmed, Norma Osama Abdallah Zayed, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7805933/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Effective postoperative pain management in pediatric patients is essential for recovery, though no single analgesic is considered superior. Nalbuphine and tramadol are common alternatives to traditional opioids, each with a distinct pharmacological profile. This study compares the efficacy and safety of nalbuphine versus tramadol in managing postoperative pain after abdominal surgery in pediatric cancer patients. Methods This prospective, randomized clinical trial involved 128 children with cancers (3–12 years) undergoing elective abdominal surgery. Patients were randomized into two groups: the Nalbuphine group (0.2 mg/kg IV every 8 hours) and the Tramadol group (2 mg/kg IV every 8 hours) for 72 hours postoperatively. Pain was assessed using the Wong-Baker FACES Pain Scale (WB), and rescue analgesia with paracetamol was provided as needed. The primary outcome measure was the time to first rescue analgesia, while secondary outcomes included pain scores, paracetamol consumption, and adverse effects. Results Nalbuphine provided superior pain relief during the first 24 hours postoperatively, with significantly lower WB scores compared to tramadol. However, tramadol demonstrated complete pain resolution by 48–72 hours, while some nalbuphine patients reported mild pain. The need for rescue analgesia was low and comparable between groups (9.4% vs. 7.8%, p = 0.752). Both drugs maintained hemodynamic stability and had similar safety profiles, with minimal adverse effects. Conclusion Nalbuphine offers better early postoperative pain control, while tramadol provides more sustained analgesia beyond 24 hours. Both drugs are effective and safe. Trial registration: this study was retrospectively registered at clinical trial gov. (ID: NCT07110051), URL: https://clinicaltrials.gov/study/NCT07110051?cond=NCT07110051&rank=1 , Date: 31/07/2025. Postoperative Pain Pediatric Patients Abdominal Surgery Rescue Analgesia Nalbuphine Tramadol Figures Figure 1 Introduction Postoperative pain in children is a critical aspect of perioperative care, as it can significantly affect their physical and emotional development. ​ It may result in complications such as sleep disturbances, wound reopening, bleeding, and delayed recovery. ​ Effective management of postoperative pain in children is essential to alleviate and control the discomfort they experience after surgery [ 1 ]. ​Postoperative pain in pediatric patients is generally managed using both pharmacologic and non-pharmacologic methods. Multimodal analgesia is often employed to achieve effective pain control while reducing the risk of side effects [ 2 ]. No single analgesic drug is universally superior for managing postoperative pain in children. Effective pain control relies on a multimodal approach that considers the individual child's requirements, the surgical procedure, and the risk of side effects [ 3 ]. Opioids are among the most frequently utilized analgesic agents. Morphine is a commonly used opioid for postoperative pain in children, used in patient-controlled analgesia and epidural regimens. It may provide better pain control than hydromorphone-containing solutions, but more research is needed for definitive conclusions [ 4 – 6 ]. Tramadol has been found to be as effective as morphine for managing postoperative pain in children, with studies indicating a lower risk of respiratory or hemodynamic depression compared to traditional opioids [ 6 , 7 ]. Nalbuphine is widely recognized for its effectiveness and safety in managing postoperative pain in children [ 8 ]. This compound functions as a mixed opioid agonist-antagonist, exhibiting agonistic activity at κ-receptors and antagonistic effects at µ-receptors. Its unique pharmacological profile provides effective analgesia while imposing a ceiling effect on respiratory depression, thereby enhancing its safety profile for pediatric applications relative to conventional opioids such as morphine [ 9 – 12 ]. Acetaminophen is the most commonly used non-opioid for managing mild to moderate postoperative pain. It is usually the first choice, but higher doses are required for pain relief than for fever reduction [ 13 – 15 ]. In the current study, we aim to compare nalbuphine versus tramadol for postoperative pain control in pediatric abdominal surgeries. Subjects and Methods This prospective randomized clinical trial included children scheduled for elective abdominal surgery. Under general anesthesia at the National Cancer Institute, Cairo University, in the period from April 2024 to April 2025. The study was approved by the Ethical Committee of the National Cancer Institute, Cairo University, Egypt (Approval No.: AP2403301015) and was retrospectively registered at clinical trial gov. (ID: NCT07110051), URL: https://clinicaltrials.gov/study/NCT07110051?cond=NCT07110051&rank=1 , Date: 31/07/2025. This study was done in accordance with Helsinki Declaration of 1975 (revised 2013). Informed written consent was obtained from the guardians of all participants. Inclusion criteria were children aged 3–12 years of American Society of Anesthesia (ASA) class I-III, scheduled for elective abdominal surgery under general anesthesia. Patients were excluded if they had an allergy to study drugs or previous chronic pain on opioids. Also, the child was excluded if their guardian’s refused participation. Randomization The study included 128 patients randomized into two equal groups using a computer-generated randomization table. The Nalbuphine Group (n = 64) received nalbuphine in 0.2 mg/kg doses after surgery. The Tramadol Group received tramadol in 2 mg/kg doses after surgery. Study Intervention In the operating room, a venous line was established, and monitoring probes (electrocardiography, noninvasive blood pressure, pulse oximeter, and Capnography) were applied. All patients were premedicated with midazolam 0.1mg/kg IV. The anesthetic protocol was standardized for all patients. General anesthesia was induced with propofol, 2 mg/kg, and fentanyl, 2 µg/kg, and maintained with sevoflurane. Endotracheal intubation was facilitated with rocuronium, 0.5 mg/kg. Additional intraoperative analgesia consisted of IV boluses of 1µg/Kg fentanyl to keep the heart rate (HR) and mean arterial blood pressure (MAP) within 20% of the preoperative baseline values. All patients will receive prophylactic antiemetic, ondansetron 0.1 mg/kg, at skin closure. After the end of the surgery, muscle relaxation was reversed using sugammadex 4 mg/kg After extubation, in the recovery room, the Nalbuphine group received a dose nalbuphine 0.2 mg/kg dose to be repeated every 8 hours for 72 hours. The Tramadol group received a dose of tramadol 2 mg/kg to be repeated every 8 hours for 72 hours. Wong-Barker's pain rating scale was used as a pain assessment tool every 8 hours for 72 hours. If the pain score is more than 4, patients were given a rescue dose of paracetamol 10mg/kg. If the pain score is more than 6, the frequency of narcotics was increased to every 6 hours. Frequency of rescue of paracetamol was recorded in the 1st 72 hours, as well as the postoperative nausea and vomiting (PONV). The Wong-Baker FACES Pain Rating Scale combines faces, numbers, and words to help individuals communicate their pain levels effectively. The scale ranges from 0 to 10, increasing in steps of 2. Each number corresponds to a face and a brief descriptive phrase. It is adaptable; users may choose to use just numbers without the faces or words. The descriptions for each number are: 0: no hurt or pain, 2: it hurts a little bit, 4: it hurts a little more, 6: it hurts even more, 8: it hurts a whole lot, 10: it hurts the worst. The primary measure was the time to first rescue analgesic requirement. The secondary objectives were the Wong-Barker (WB) pain score, frequency of paracetamol consumption, incidence of Itching, and PONV. Sample Size Calculation: Assuming a true difference in means between the test and the reference group of 1.5 units, and a pooled standard deviation of 4 units, the study would require a sample size of 17 for each group (i.e. a total sample size of 34) to achieve a power of 80% and a level of significance of 5%, for declaring that the test drug is superior to the active control drug at -2 units margin of superiority (assuming that a smaller mean is desirable). Statistical analysis Statistical analysis was done using IBM© SPSS© Statistics version 27 (IBM© Corp., Armonk, NY, USA). Quantitative data were expressed as mean and standard deviation or median as appropriate. Qualitative data were expressed as frequency and percentage. Independent-sample T-test or Mann-Whitney U test was used for the two-group comparison of numerical data according to data distribution. The Chi-square test was used to compare qualitative variables. All tests were two-tailed, and a p-value < 0.05 was considered significant. Results In this study, 135 patients were assessed for eligibility; 7 patients did not meet the criteria. The remaining patients were randomly allocated into two equal groups (64 patients in each). All allocated patients were followed up and analyzed statistically. Figure 1 There were no significant differences between the two groups in age (p = 0.239), sex (p = 0.288), or weight (p = 0.526). The most common surgical procedure in the two groups was nephrectomy, followed by abdominal exploration for different reasons, and adrenalectomy, with no difference between the two groups (Table 1 ). Table 1 Baseline characteristics and type of surgery in the two studied groups Nalbuphine Group (n = 64) Tramadol Group (n = 64) p-value Age (years) 7 (3–12) 9 (3–12) 0.239 Sex 0.288 Male 37 (57.8%) 31 (48.4%) Female 27 (42.2%) 33 (51.6%) Weight (kg) 29.8 ± 15.6 31.5 ± 15.5 0.526 Type of Surgery 0.683 Nephrectomy 20 (31.3%) 19 (29.7%) Exploration 15 (23.4%) 13 (20.3%) Adrenalectomy 12 (18.8%) 9 (14.1%) Others 17 (26.6%) 23 (35.9%) Data are presented as median (range), mean ± SD, or number (%) The nalbuphine group showed a lower WB score compared to the Tramadol group up to 24 hours postoperatively. However, after 48 and 72 hours, all patients in the Tramadol group reported no pain (WB score 0), while some patients in the nalbuphine group still experienced little pain (WB score 2), as shown in Table 2 . Few patients in each group required rescue analgesia (p = 0.752). The time to request rescue analgesia was apparently longer in the Tramadol group, but the difference only tended toward statistical significance (Table 3 ). There is no significant difference between the two groups regarding postoperative hemodynamic parameters and complications (Table 3 ). Table 2 Wong-Baker FACES Pain Scale score during the postoperative period in the two studied groups WB Score Nalbuphine Group (n = 64) Tramadol group (n = 64) p-value Immediate postoperative 0 7 (10.9%) 1 (1.6%) * 2 49 (76.6%) 60 (93.8%) 4 5 (7.8%) 3 (4.7%) 6 3 (4.7%) 0 (0.0%) After 1 hour 0 9 (14.1%) 4 (6.3%) 0.258 2 53 (82.8%) 56 (87.5%) 4 2 (3.1%) 2 (3.1%) 6 0 (0.0%) 2 (3.1%) After 2 hours 0 19 (29.7%) 5 (7.8%) 0.002 2 44 (68.8%) 58 (90.6%) 4 1 (1.6%) 0 (0.0%) 6 0 (0.0%) 1 (1.6%) After 4 hours 0 26 (40.6%) 9 (14.1%) 0.001 2 38 (59.4%) 55 (85.9%) After 8 hours 0 37 (57.8%) 11 (17.2%) < 0.001 2 27 (42.2%) 53 (82.8%) After 24 hours 0 46 (71.9%) 14 (21.9%) < 0.001 2 18 (28.1%) 50 (78.1%) After 48 hours 0 50 (78.1%) 64 (100.0%) < 0.001 2 14 (21.9%) 0 (0.0%) After 72 hours 0 55 (85.9%) 64 (100.0%) 0.003 2 9 (14.1%) 0 (0.0%) Data are presented as a number (%). * No p-value because of small numbers in subgroups. Table 3 Postoperative characteristics and complications in the two studied groups Nalbuphine Group (n = 64) Tramadol Group (n = 64) p-value Need for rescue analgesia 6 (9.4%) 5 (7.8%) 0.752 Time to rescue analgesia (hrs) 6 (5–8) 8 (6–16) 0.082 Mean arterial pressure (mmHg) 77 ± 6 77 ± 6 0.956 Systolic blood pressure (mmHg) 109 ± 8 107 ± 8 0.174 Diastolic blood pressure (mmHg) 68 ± 6 66 ± 7 0.135 Heart Rate (beats/min.) 104 ± 11 102 ± 10 0.295 Respiratory Rate/min. 22 ± 2 22 ± 2 0.922 SpO 2 99.2 ± .6 99.2 ± .5 0.862 Nausea and Vomiting 5 (7.8%) 5 (7.8%) 1.000 Itching 4 (6.3%) 1 (1.6%) 0.365 Constipation 2 (3.1%) 2 (3.1%) 1.000 Data are presented as number (%), median (range), or Mean ± SD. Discussion This study shows that nalbuphine provides better postoperative pain relief during the first 24 hours after abdominal pediatric surgery, while tramadol results in complete pain resolution within 48–72 hours. Both medications are safe and effective, with few side effects. The choice between them should depend on the clinical situation — especially the desired duration of pain control. During the initial postoperative period (0–24 hours), patients in the nalbuphine group consistently exhibited lower pain scores (with more individuals reporting WB scores of 0 or 2) compared to those in the tramadol group. Statistically significant differences favoring nalbuphine were observed as early as two hours post-surgery and continued through the 24-hour mark, indicating superior early analgesic efficacy for nalbuphine within this population. In contrast, in the subsequent period up to 72 hours, all patients receiving tramadol reported no pain (WB = 0) by 48 hours, whereas approximately 20% of those in the nalbuphine group continued to report mild pain (WB = 2). This trend reversal may indicate that tramadol offers more sustained pain control beyond 24 hours, potentially due to different pharmacokinetic characteristics. Until now, no single drug is best for pediatric postoperative pain; selection depends on each patient and surgical situation. Opioids like morphine and pethidine are commonly used for postoperative pain control in children with moderate to severe symptoms. Due to risks such as respiratory depression, vomiting, urinary retention, ileus, and dependence, dosing is often cautious, or other agents may be preferred [ 16 , 17 ]. In the current study, we compared two morphine alternatives in children subjected to abdominal surgery, tramadol and nalbuphine. Tramadol is reported to have a safety profile that differs from traditional opioids, especially in terms of respiratory and hemodynamic depression [ 7 ]. Nalbuphine provides pain relief mainly through κ-opioid agonism and µ-opioid antagonism, resulting in effective analgesia with a safer profile for respiratory depression in children [ 11 ]. Few studies have compared these two drugs for postoperative analgesia. In a double-blind study, tramadol infusion provided better postoperative analgesic efficacy than nalbuphine over 72 hours. Fewer children in the tramadol group required extra bolus doses within 12 hours post-surgery compared to the nalbuphine group. Both groups had a similar need for increased infusion rates over 72 hours, but overall, tramadol showed superior pain control in this regimen [ 18 ]. This finding is comparable to the current study, indicating more sustained pain relief with tramadol. In another randomized controlled trial using a single dose (0.2 mg/kg nalbuphine vs. 2 mg/kg tramadol), nalbuphine resulted in lower mean pain scores at 0- and 1-hour post-surgery, and fewer children required rescue analgesics compared to tramadol, though the difference was not statistically significant at later time points. The mean time to rescue analgesic was also slightly longer with nalbuphine [ 19 ]. A key difference exists in the type of surgery examined in this study compared to the current one. In the referenced research, the authors compared the two drugs in a day surgery setting, administering a single dose of each. The current work and previous studies indicate that tramadol may provide better overall pain control, but nalbuphine may offer superior early pain relief and longer duration with a single dose. Nalbuphine may suit single-dose use, while tramadol could be better for continuous infusion; however, more research is required to confirm this [ 18 – 21 ]. Nalbuphine and tramadol differ significantly in their mechanisms for pain relief in children. The former acts as a κ-opioid receptor agonist and a µ-opioid receptor antagonist. This mixed action provides analgesia and sedation, but with a ceiling effect for respiratory depression, making it safer for children compared to pure µ-opioid agonists like morphine or fentanyl [ 12 , 22 ]. The reduced effect of nalbuphine in the later postoperative period might be explained by its extensive first-pass metabolism, mainly via phase II glucuronidation (75%) and phase I oxidation-reduction (25%) [ 22 ]. On the other hand, tramadol exerts its effect via opioid and non-opioid mechanisms. It is a weak µ-opioid receptor agonist—less potent than traditional opioids. It inhibits the reuptake of norepinephrine and serotonin, enhancing endogenous pain inhibition pathways. Also, it inhibits α2-adrenoceptors, neurokinin 1, muscarinic, nicotinic acetylcholine, and NMDA receptors, contributing to its complex analgesic profile [ 21 , 23 – 25 ]. The extended duration of tramadol's efficacy over the 72-hour postoperative period may be attributed to its multiple mechanisms of action. Assessing pain in children after surgery is challenging due to the complexity involved in pain evaluation. Currently, there is no ideal assessment scale applicable to all types of pain or all age groups of children. In the current study, we used the Wong-Baker FACES Pain Scale for assessment of postoperative pain in the current series. The Wong-Baker FACES® Scale consists of six faces, each representing a different level of pain intensity. The visual representation of facial expressions allows patients, especially those with limited verbal skills or cognitive impairments, to communicate their pain levels intuitively. It suits children aged three years and older. It remains a cornerstone in pain assessment due to its simplicity, accessibility, and versatility [ 26 ]. In the current study, the need for rescue analgesia was very low and comparable between the two groups (9.4%, nalbuphine vs. 7.8%, tramadol, p = 0.752). In the limited number of patients, the time to rescue analgesia was longer in the tramadol group (median 8 vs. 6 hours), though not statistically significant (p = 0.082)—a trend that may become significant in a larger sample. However, the small number of patients questioned the strength of these results. Liaqat and Dar [ 19 ] reported comparable findings to the current study. The number of patients requiring rescue analgesics was greater in the tramadol group than in the nalbuphine group, and the mean time for the requirement of rescue analgesics was similar in both groups. In the current study, both drugs maintained hemodynamic stability, as blood pressure and heart rate readings remained within clinically accepted ranges, with no significant differences observed between the groups. Also, a few adverse effects were recorded in the two groups with no significant intergroup differences. Nausea/vomiting, constipation, and itching were reported, which aligns with known opioid-related side effects, though nalbuphine typically causes less pruritus than pure µ-agonists. Tramadol was associated with a higher incidence of vomiting compared to nalbuphine in the infusion study, but cardiovascular parameters remained stable in both groups. Nalbuphine, on the other hand, showed a slightly higher rate of sedation but fewer cases of vomiting compared to tramadol [ 18 ]. Both groups in the Liaqat and Dar study experienced side effects, with vomiting being the most common [ 19 ] Limitations While adequate to detect early differences, the study may be underpowered to confirm trends in rescue analgesia timing or rare side effects. Reliance on a categorical scale (Wong-Baker) limits hardness; continuous or composite pain scores might offer more sensitivity. We did not exhibit pharmacokinetic data of the two drugs, which is beyond the scope of this study. Understanding drug levels over time could clarify the observed temporal shift in efficacy. Conclusion Nalbuphine and tramadol are used to manage postoperative pain in pediatric patients following abdominal surgery. Both drugs have been found to provide analgesia and demonstrate a similar safety profile. Nalbuphine shows greater effect during the early postoperative period, while tramadol may offer benefits for extended analgesia beyond 24 hours, potentially reducing late pain or assisting with outpatient discharge. Both medications show comparable safety outcomes, with limited need for additional rescue medication and no reported serious complications. Declarations Ethics approval and consent to participate: The study was approved by the Ethical Committee of the National Cancer Institute, Cairo University, Egypt (Approval No.: AP2403301015) and was retrospectively registered at clinical trial gov. (ID: NCT07110051), URL: https://clinicaltrials.gov/study/NCT07110051?cond=NCT07110051&rank=1, Date: 31/07/2025. This study was done in accordance with Helsinki Declaration of 1975 (revised 2013). Informed written consent was obtained from the guardians of all participants. Consent for publication: Not applicable Availability of data and materials: Data is available on reasonable requests from corresponding author. Competing interests: The authors have no financial or proprietary interest in any material discussed in this article. Funding: No funding was received for conducting this study. Authors' contributions: All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by [F. H. M. M. E.], [A. F. A.], and [N. O. A. Z.]. The first draft of the manuscript was written by [F. H. M. M. E.], [A. F. A.], and [N. O. A. Z.]. All authors commented on previous versions of the manuscript. All authors read and approved of the final manuscript. Acknowledgements: Nill References Yang J-X, Zhang W-Y, Huang H-H, Jiang W-T, Zhou Y-F, Gu Y, et al. Parental involvement in postoperative pain management among children in a urology ward: A best practice implementation project. Nurs Open. 2023;10:3042–51. https://doi.org/10.1002/nop2.1551 Escalona-Espinosa A, Maldonado-Sánchez K, Pazos-Alvarado E, Castañeda P, Alcaraz-Ramos R, Aguilar-Romero D, et al. Postoperative Pain in Pediatrics. Topics in Postoperative Pain [Internet]. IntechOpen; 2023 [cited 2025 Sep 24]. https://doi.org/10.5772/intechopen.111788 Vittinghoff M, Lönnqvist PA, Mossetti V, Heschl S, Simic D, Colovic V, et al. Postoperative Pain Management in children: guidance from the Pain Committee of the European Society for Paediatric Anaesthesiology (ESPA Pain Management Ladder Initiative) Part II. Anaesthesia Critical Care & Pain Medicine. 2024;43:101427. https://doi.org/10.1016/j.accpm.2024.101427 Carney DE, Nicolette LA, Ratner MH, Minerd A, Baesl TJ. Ketorolac reduces postoperative narcotic requirements. J Pediatr Surg. 2001;36:76–9. https://doi.org/10.1053/jpsu.2001.20011 Cramer J. Comparison of Morphine- and Hydromorphone-Containing Patient-Controlled Epidural Analgesia Solutions in Pediatric Postoperative Patients. J Pediatr Pharmacol Ther. 2019;24:22–6. https://doi.org/10.5863/1551-6776-24.1.22 Li S, Xiong H, Jia Y, Li Z, Chen Y, Zhong L, et al. Oxycodone vs. tramadol in postoperative parent-controlled intravenous analgesia in children: a prospective, randomized, double-blinded, multiple-center clinical trial. BMC Anesthesiol. 2023;23:152. https://doi.org/10.1186/s12871-023-02054-8 Mahmoud AM, Hassanein EHM. Tramadol as an analgesic. Treatments, Mechanisms, and Adverse Reactions of Anesthetics and Analgesics [Internet]. Elsevier; 2022 [cited 2025 Sep 25]. p. 181–91. https://doi.org/10.1016/B978-0-12-820237-1.00018-1 Schnabel A, Reichl SU, Zahn PK, Pogatzki-Zahn E. Nalbuphine for postoperative pain treatment in children. Cochrane Database Syst Rev. 2014;2014:CD009583. https://doi.org/10.1002/14651858.CD009583.pub2 Schultz-Machata A-M, Becke K, Weiss M. [Nalbuphine in pediatric anesthesia]. Anaesthesist. 2014;63:135–43. https://doi.org/10.1007/s00101-014-2293-z Kubica-Cielińska A, Zielińska M. Zastosowanie nalbufiny w anestezjologii pediatrycznej. Anaesthesiol Intensive Ther. 2015;47:252–6. https://doi.org/10.5603/AIT.2015.0036 Torad FA, Hassan EA. Sedative, analgesic, and behavioral effects of nalbuphine-xylazine and nalbuphine-midazolam combinations in dogs. Journal of Veterinary Behavior. 2018;28:40–5. https://doi.org/10.1016/j.jveb.2018.07.002 Ng KT, Lim WE, Teoh WY, Zainal Abidin MFB. The effect of nalbuphine on prevention of emergence delirium in children: a systematic review with meta-analysis. Brazilian Journal of Anesthesiology (English Edition). 2024;74:844543. https://doi.org/10.1016/j.bjane.2024.844543 Kokinsky E, Thornberg E. Postoperative Pain Control in Children: A Guide to Drug Choice. Pediatric Drugs. 2003;5:751–62. https://doi.org/10.2165/00148581-200305110-00004 Beggs S. Paediatric analgesia. Aust Prescr. 2008;31:63–5. https://doi.org/10.18773/austprescr.2008.039 Caliskan E, Sener M, Kocum A, Ozyilkan NB, Ezer SS, Aribogan A. The efficacy of intravenous paracetamol versus dipyrone for postoperative analgesia after day-case lower abdominal surgery in children with spinal anesthesia: a prospective randomized double-blind placebo-controlled study. BMC Anesthesiol. 2013;13:34. https://doi.org/10.1186/1471-2253-13-34 Chan SH, Lara-Torre E. Surgical considerations and challenges in the pediatric and adolescent gynecologic patient. Best Pract Res Clin Obstet Gynaecol. 2018;48:128–36. https://doi.org/10.1016/j.bpobgyn.2017.10.007 Heydinger G, Kadado A, Elhamrawy A, Villalobos E, Tobias JD, Veneziano G. Dual Tunneled Epidural Wound Catheters for Postoperative Analgesia Following Posterior Spinal Fusion. J Med Cases. 2025;16:43–7. https://doi.org/10.14740/jmc4337 Moyao-García D, Hernández-Palacios JC, Ramírez-Mora JC, Nava-Ocampo AA. A pilot study of nalbuphine versus tramadol administered through continuous intravenous infusion for postoperative pain control in children. Acta Biomed. 2009;80:124–30. Liaqat N, Dar SH. Comparison of single-dose nalbuphine versus tramadol for postoperative pain management in children: a randomized, controlled trial. Korean J Anesthesiol. 2017;70:184. https://doi.org/10.4097/kjae.2017.70.2.184 Bedirli N, Akçabay M, Emik U. Tramadol vs dexmedetomidine for emergence agitation control in pediatric patients undergoing adenotonsillectomy with sevoflurane anesthesia: prospective randomized controlled clinical study. BMC Anesthesiol. 2017;17:41. https://doi.org/10.1186/s12871-017-0332-4 Walter CM, Abbasian N, Olbrecht VA. Trends in Pediatric Pain. Anesthesiology Clinics. 2020;38:663–78. https://doi.org/10.1016/j.anclin.2020.04.002 Pfiffner M, Berger-Olah E, Vonbach P, Pfister M, Gotta V. Pharmacometric Analysis of Intranasal and Intravenous Nalbuphine to Optimize Pain Management in Infants. Front Pediatr. 2022;10:837492. https://doi.org/10.3389/fped.2022.837492 Monteiro BP, Lambert C, Bianchi E, Genevois JP, Soldani G, Troncy E. Safety and efficacy of reduced dosage ketoprofen with or without tramadol for long-term treatment of osteoarthritis in dogs: a randomized clinical trial. BMC Vet Res. 2019;15:213. https://doi.org/10.1186/s12917-019-1960-3 Angasa D, Haddis L, Gashaw A, Zemedkun A, Gobena N. Postoperative analgesic efficacy of caudal tramadol added to bupivacaine compared to bupivacaine alone for pediatric elective infra umbilical surgery at Tikur Anbessa Specialized Hospital, Ethiopia, a prospective cohort study. International Journal of Surgery Open. 2020;27:32–8. https://doi.org/10.1016/j.ijso.2020.10.008 Yoo O, Tang EKY, Nguyen MN, Salman S, Hua AJ, Von Ungern Sternberg BS, et al. HPLC-UV assay of tramadol and O-desmethyltramadol in human plasma containing other drugs potentially co-administered to participants in a paediatric population pharmacokinetic study. Journal of Chromatography B. 2021;1184:122971. https://doi.org/10.1016/j.jchromb.2021.122971 Garra G, Singer AJ, Taira BR, Chohan J, Cardoz H, Chisena E, et al. Validation of the Wong-Baker FACES Pain Rating Scale in pediatric emergency department patients. Acad Emerg Med. 2010;17:50–4. https://doi.org/10.1111/j.1553-2712.2009.00620.x Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7805933","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":555997814,"identity":"f69b93ca-a50b-460e-96d6-a904e5c4524b","order_by":0,"name":"Fatma Hanafi Mahmoud Mostafa Elshamy","email":"","orcid":"","institution":"Cairo University, National Cancer Institute","correspondingAuthor":false,"prefix":"","firstName":"Fatma","middleName":"Hanafi Mahmoud Mostafa","lastName":"Elshamy","suffix":""},{"id":555997817,"identity":"f479d568-2a52-4857-ad5c-ba7cd5099771","order_by":1,"name":"Ahmed Fahmy Ahmed","email":"","orcid":"","institution":"Cairo University, National Cancer Institute","correspondingAuthor":false,"prefix":"","firstName":"Ahmed","middleName":"Fahmy","lastName":"Ahmed","suffix":""},{"id":555997819,"identity":"e90f511c-e001-4510-9aae-6b43546c8d93","order_by":2,"name":"Norma Osama Abdallah Zayed","email":"","orcid":"","institution":"Cairo University, National Cancer Institute","correspondingAuthor":false,"prefix":"","firstName":"Norma","middleName":"Osama Abdallah","lastName":"Zayed","suffix":""},{"id":555997820,"identity":"ab04195b-d6e3-45da-9c82-60f33a35929e","order_by":3,"name":"Reham M. Gamal","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCklEQVRIiWNgGAWjYFACHijNDiIMbBLAnIQCYrQwg7WkJTCwgbQYEK2F4TBECwMeLebtvQc/3fhlF83fzMD24EfB+Tx++e7EDw8MGOT5xQ5g1SJz5lyydG5fcu6Mwwzshj0Gt4sl23g3SwAdZjhzdgJWLRISOQbSuT3MuQ2HGdikGQxuJ244xrsBpCXB4DYOLfJvjH/n9tTnzodoOQfSsvkHXi0SPGbSOT8O526AaDkA0rINvy08OWbWuQ3HczcCtUj2GCQnzmzL3WaRYCCB2y/sZ4xv5/ypzp13vIFN4scfu8R+5rObb/6osJHnl8auBQwY20Ak/wcUs3ArB4M/BORHwSgYBaNgZAMAcMlarU23FfgAAAAASUVORK5CYII=","orcid":"","institution":"Cairo University, National Cancer Institute","correspondingAuthor":true,"prefix":"","firstName":"Reham","middleName":"M.","lastName":"Gamal","suffix":""}],"badges":[],"createdAt":"2025-10-08 08:53:30","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7805933/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7805933/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":97722247,"identity":"4cd3b2d8-27e3-4960-9e93-717f9730233f","added_by":"auto","created_at":"2025-12-08 15:39:19","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":111003,"visible":true,"origin":"","legend":"","description":"","filename":"FinalVersion6112025.docx","url":"https://assets-eu.researchsquare.com/files/rs-7805933/v1/826d5eaa382ad3b4a7c80fd4.docx"},{"id":97722249,"identity":"150be462-67b4-4c69-8805-eced8b0a0cf8","added_by":"auto","created_at":"2025-12-08 15:39:19","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":6375,"visible":true,"origin":"","legend":"","description":"","filename":"51c8bcf11d11415e954107aa63752a1d.json","url":"https://assets-eu.researchsquare.com/files/rs-7805933/v1/e8e6448414d6fac62d0943f0.json"},{"id":97895602,"identity":"cf591599-8918-4daf-85b2-5a5b3e89253b","added_by":"auto","created_at":"2025-12-10 15:34:33","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":89855,"visible":true,"origin":"","legend":"","description":"","filename":"51c8bcf11d11415e954107aa63752a1d1enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-7805933/v1/560cdf646b15506790a53adb.xml"},{"id":97722248,"identity":"0205fe1f-31b2-4a12-894c-0c7cb3f295f0","added_by":"auto","created_at":"2025-12-08 15:39:19","extension":"png","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":44154,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7805933/v1/c2a86f26e767b7b1f44c0a01.png"},{"id":97722251,"identity":"295233d1-550f-4890-8697-bc6623c27f1c","added_by":"auto","created_at":"2025-12-08 15:39:19","extension":"png","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":22315,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7805933/v1/8138518ea4392ec1e746500b.png"},{"id":97893866,"identity":"4e8ad247-3035-40c4-afd1-e67e90c77a50","added_by":"auto","created_at":"2025-12-10 15:31:23","extension":"xml","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":87532,"visible":true,"origin":"","legend":"","description":"","filename":"51c8bcf11d11415e954107aa63752a1d1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7805933/v1/3f845e48c3c464beb95b79bd.xml"},{"id":97722253,"identity":"7b96dc70-cb9c-4dff-a4ea-53bdc13e43e2","added_by":"auto","created_at":"2025-12-08 15:39:19","extension":"html","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":96375,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7805933/v1/3da25bd0ee59675f05733576.html"},{"id":97722245,"identity":"e85305be-fe31-4623-ac15-2fcdaa65f53d","added_by":"auto","created_at":"2025-12-08 15:39:19","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":44154,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eConsort flowchart\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7805933/v1/932d255c0ef06da2ab17c8fd.png"},{"id":108602580,"identity":"bf6b933f-da7b-405a-bbf9-36fc77aac77b","added_by":"auto","created_at":"2026-05-06 11:42:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":314742,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7805933/v1/f1c9a95b-759b-4643-9310-a38580bb5238.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparative Study between Nalbuphine versus Tramadol on Postoperative Analgesia for Abdominal Surgery in Pediatric Cancer Patients: A Prospective, Randomized Clinical Trial","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePostoperative pain in children is a critical aspect of perioperative care, as it can significantly affect their physical and emotional development. ​ It may result in complications such as sleep disturbances, wound reopening, bleeding, and delayed recovery. ​ Effective management of postoperative pain in children is essential to alleviate and control the discomfort they experience after surgery [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. ​Postoperative pain in pediatric patients is generally managed using both pharmacologic and non-pharmacologic methods. Multimodal analgesia is often employed to achieve effective pain control while reducing the risk of side effects [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eNo single analgesic drug is universally superior for managing postoperative pain in children. Effective pain control relies on a multimodal approach that considers the individual child's requirements, the surgical procedure, and the risk of side effects [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Opioids are among the most frequently utilized analgesic agents. Morphine is a commonly used opioid for postoperative pain in children, used in patient-controlled analgesia and epidural regimens. It may provide better pain control than hydromorphone-containing solutions, but more research is needed for definitive conclusions [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Tramadol has been found to be as effective as morphine for managing postoperative pain in children, with studies indicating a lower risk of respiratory or hemodynamic depression compared to traditional opioids [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eNalbuphine is widely recognized for its effectiveness and safety in managing postoperative pain in children [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. This compound functions as a mixed opioid agonist-antagonist, exhibiting agonistic activity at κ-receptors and antagonistic effects at \u0026micro;-receptors. Its unique pharmacological profile provides effective analgesia while imposing a ceiling effect on respiratory depression, thereby enhancing its safety profile for pediatric applications relative to conventional opioids such as morphine [\u003cspan additionalcitationids=\"CR10 CR11\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAcetaminophen is the most commonly used non-opioid for managing mild to moderate postoperative pain. It is usually the first choice, but higher doses are required for pain relief than for fever reduction [\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn the current study, we aim to compare nalbuphine versus tramadol for postoperative pain control in pediatric abdominal surgeries.\u003c/p\u003e"},{"header":"Subjects and Methods","content":"\u003cp\u003eThis prospective randomized clinical trial included children scheduled for elective abdominal surgery. Under general anesthesia at the National Cancer Institute, Cairo University, in the period from April 2024 to April 2025. The study was approved by the Ethical Committee of the National Cancer Institute, Cairo University, Egypt (Approval No.: AP2403301015) and was retrospectively registered at clinical trial gov. (ID: NCT07110051), URL: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://clinicaltrials.gov/study/NCT07110051?cond=NCT07110051\u0026amp;rank=1\u003c/span\u003e\u003cspan address=\"https://clinicaltrials.gov/study/NCT07110051?cond=NCT07110051\u0026amp;rank=1\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e, Date: 31/07/2025. This study was done in accordance with Helsinki Declaration of 1975 (revised 2013). Informed written consent was obtained from the guardians of all participants.\u003c/p\u003e\u003cp\u003eInclusion criteria were children aged 3\u0026ndash;12 years of American Society of Anesthesia (ASA) class I-III, scheduled for elective abdominal surgery under general anesthesia. Patients were excluded if they had an allergy to study drugs or previous chronic pain on opioids. Also, the child was excluded if their guardian\u0026rsquo;s refused participation.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eRandomization\u003c/h2\u003e\u003cp\u003eThe study included 128 patients randomized into two equal groups using a computer-generated randomization table. The Nalbuphine Group (n\u0026thinsp;=\u0026thinsp;64) received nalbuphine in 0.2 mg/kg doses after surgery. The Tramadol Group received tramadol in 2 mg/kg doses after surgery.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eStudy Intervention\u003c/h3\u003e\n\u003cp\u003eIn the operating room, a venous line was established, and monitoring probes (electrocardiography, noninvasive blood pressure, pulse oximeter, and Capnography) were applied. All patients were premedicated with midazolam 0.1mg/kg IV. The anesthetic protocol was standardized for all patients. General anesthesia was induced with propofol, 2 mg/kg, and fentanyl, 2 \u0026micro;g/kg, and maintained with sevoflurane. Endotracheal intubation was facilitated with rocuronium, 0.5 mg/kg. Additional intraoperative analgesia consisted of IV boluses of 1\u0026micro;g/Kg fentanyl to keep the heart rate (HR) and mean arterial blood pressure (MAP) within 20% of the preoperative baseline values. All patients will receive prophylactic antiemetic, ondansetron 0.1 mg/kg, at skin closure. After the end of the surgery, muscle relaxation was reversed using sugammadex 4 mg/kg\u003c/p\u003e\u003cp\u003eAfter extubation, in the recovery room, the Nalbuphine group received a dose nalbuphine 0.2 mg/kg dose to be repeated every 8 hours for 72 hours. The Tramadol group received a dose of tramadol 2 mg/kg to be repeated every 8 hours for 72 hours. Wong-Barker's pain rating scale was used as a pain assessment tool every 8 hours for 72 hours. If the pain score is more than 4, patients were given a rescue dose of paracetamol 10mg/kg. If the pain score is more than 6, the frequency of narcotics was increased to every 6 hours. Frequency of rescue of paracetamol was recorded in the 1st 72 hours, as well as the postoperative nausea and vomiting (PONV).\u003c/p\u003e\u003cp\u003eThe Wong-Baker FACES Pain Rating Scale combines faces, numbers, and words to help individuals communicate their pain levels effectively. The scale ranges from 0 to 10, increasing in steps of 2. Each number corresponds to a face and a brief descriptive phrase. It is adaptable; users may choose to use just numbers without the faces or words. The descriptions for each number are: 0: no hurt or pain, 2: it hurts a little bit, 4: it hurts a little more, 6: it hurts even more, 8: it hurts a whole lot, 10: it hurts the worst.\u003c/p\u003e\u003cp\u003eThe primary measure was the time to first rescue analgesic requirement. The secondary objectives were the Wong-Barker (WB) pain score, frequency of paracetamol consumption, incidence of Itching, and PONV.\u003c/p\u003e\n\u003ch3\u003eSample Size Calculation:\u003c/h3\u003e\n\u003cp\u003eAssuming a true difference in means between the test and the reference group of 1.5 units, and a pooled standard deviation of 4 units, the study would require a sample size of 17 for each group (i.e. a total sample size of 34) to achieve a power of 80% and a level of significance of 5%, for declaring that the test drug is superior to the active control drug at -2 units margin of superiority (assuming that a smaller mean is desirable).\u003c/p\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eStatistical analysis was done using IBM\u0026copy; SPSS\u0026copy; Statistics version 27 (IBM\u0026copy; Corp., Armonk, NY, USA). Quantitative data were expressed as mean and standard deviation or median as appropriate. Qualitative data were expressed as frequency and percentage. Independent-sample T-test or Mann-Whitney U test was used for the two-group comparison of numerical data according to data distribution. The Chi-square test was used to compare qualitative variables. All tests were two-tailed, and a p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eIn this study, 135 patients were assessed for eligibility; 7 patients did not meet the criteria. The remaining patients were randomly allocated into two equal groups (64 patients in each). All allocated patients were followed up and analyzed statistically. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThere were no significant differences between the two groups in age (p\u0026thinsp;=\u0026thinsp;0.239), sex (p\u0026thinsp;=\u0026thinsp;0.288), or weight (p\u0026thinsp;=\u0026thinsp;0.526). The most common surgical procedure in the two groups was nephrectomy, followed by abdominal exploration for different reasons, and adrenalectomy, with no difference between the two groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline characteristics and type of surgery in the two studied groups\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNalbuphine Group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;64)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTramadol Group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;64)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (3\u0026ndash;12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (3\u0026ndash;12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.239\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e0.288\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e37 (57.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31 (48.4%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e27 (42.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33 (51.6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWeight (kg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e29.8\u0026thinsp;\u0026plusmn;\u0026thinsp;15.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31.5\u0026thinsp;\u0026plusmn;\u0026thinsp;15.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.526\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eType of Surgery\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"4\" rowspan=\"5\"\u003e\u003cp\u003e0.683\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNephrectomy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20 (31.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19 (29.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExploration\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 (23.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (20.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAdrenalectomy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (18.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (14.1%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOthers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17 (26.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23 (35.9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are presented as median (range), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, or number (%)\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe nalbuphine group showed a lower WB score compared to the Tramadol group up to 24 hours postoperatively. However, after 48 and 72 hours, all patients in the Tramadol group reported no pain (WB score 0), while some patients in the nalbuphine group still experienced little pain (WB score 2), as shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Few patients in each group required rescue analgesia (p\u0026thinsp;=\u0026thinsp;0.752). The time to request rescue analgesia was apparently longer in the Tramadol group, but the difference only tended toward statistical significance (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). There is no significant difference between the two groups regarding postoperative hemodynamic parameters and complications (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eWong-Baker FACES Pain Scale score during the postoperative period in the two studied groups\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eWB Score\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNalbuphine Group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;64)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTramadol group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;64)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003eImmediate postoperative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7 (10.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1 (1.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e49 (76.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e60 (93.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5 (7.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3 (4.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3 (4.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003eAfter 1 hour\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e9 (14.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4 (6.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e0.258\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e53 (82.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e56 (87.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2 (3.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2 (3.1%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2 (3.1%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003eAfter 2 hours\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e19 (29.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5 (7.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e44 (68.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e58 (90.6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1 (1.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1 (1.6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eAfter 4 hours\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e26 (40.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9 (14.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e38 (59.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e55 (85.9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eAfter 8 hours\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e37 (57.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e11 (17.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e27 (42.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e53 (82.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eAfter 24 hours\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e46 (71.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e14 (21.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e18 (28.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e50 (78.1%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eAfter 48 hours\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e50 (78.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e64 (100.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e14 (21.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eAfter 72 hours\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e55 (85.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e64 (100.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e9 (14.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eData are presented as a number (%). * No p-value because of small numbers in subgroups.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePostoperative characteristics and complications in the two studied groups\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNalbuphine Group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;64)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTramadol Group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;64)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeed for rescue analgesia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (9.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (7.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.752\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTime to rescue analgesia (hrs)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (5\u0026ndash;8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (6\u0026ndash;16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.082\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMean arterial pressure (mmHg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e77\u0026thinsp;\u0026plusmn;\u0026thinsp;6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e77\u0026thinsp;\u0026plusmn;\u0026thinsp;6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.956\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSystolic blood pressure (mmHg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e109\u0026thinsp;\u0026plusmn;\u0026thinsp;8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e107\u0026thinsp;\u0026plusmn;\u0026thinsp;8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.174\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiastolic blood pressure (mmHg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e68\u0026thinsp;\u0026plusmn;\u0026thinsp;6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e66\u0026thinsp;\u0026plusmn;\u0026thinsp;7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.135\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeart Rate (beats/min.)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e104\u0026thinsp;\u0026plusmn;\u0026thinsp;11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e102\u0026thinsp;\u0026plusmn;\u0026thinsp;10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.295\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRespiratory Rate/min.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.922\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSpO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e99.2\u0026thinsp;\u0026plusmn;\u0026thinsp;.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e99.2\u0026thinsp;\u0026plusmn;\u0026thinsp;.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.862\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNausea and Vomiting\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (7.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (7.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eItching\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (6.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (1.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.365\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eConstipation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (3.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (3.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are presented as number (%), median (range), or Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study shows that nalbuphine provides better postoperative pain relief during the first 24 hours after abdominal pediatric surgery, while tramadol results in complete pain resolution within 48\u0026ndash;72 hours. Both medications are safe and effective, with few side effects. The choice between them should depend on the clinical situation \u0026mdash; especially the desired duration of pain control.\u003c/p\u003e\u003cp\u003eDuring the initial postoperative period (0\u0026ndash;24 hours), patients in the nalbuphine group consistently exhibited lower pain scores (with more individuals reporting WB scores of 0 or 2) compared to those in the tramadol group. Statistically significant differences favoring nalbuphine were observed as early as two hours post-surgery and continued through the 24-hour mark, indicating superior early analgesic efficacy for nalbuphine within this population. In contrast, in the subsequent period up to 72 hours, all patients receiving tramadol reported no pain (WB\u0026thinsp;=\u0026thinsp;0) by 48 hours, whereas approximately 20% of those in the nalbuphine group continued to report mild pain (WB\u0026thinsp;=\u0026thinsp;2). This trend reversal may indicate that tramadol offers more sustained pain control beyond 24 hours, potentially due to different pharmacokinetic characteristics.\u003c/p\u003e\u003cp\u003eUntil now, no single drug is best for pediatric postoperative pain; selection depends on each patient and surgical situation. Opioids like morphine and pethidine are commonly used for postoperative pain control in children with moderate to severe symptoms. Due to risks such as respiratory depression, vomiting, urinary retention, ileus, and dependence, dosing is often cautious, or other agents may be preferred [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In the current study, we compared two morphine alternatives in children subjected to abdominal surgery, tramadol and nalbuphine. Tramadol is reported to have a safety profile that differs from traditional opioids, especially in terms of respiratory and hemodynamic depression [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Nalbuphine provides pain relief mainly through κ-opioid agonism and \u0026micro;-opioid antagonism, resulting in effective analgesia with a safer profile for respiratory depression in children [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eFew studies have compared these two drugs for postoperative analgesia. In a double-blind study, tramadol infusion provided better postoperative analgesic efficacy than nalbuphine over 72 hours. Fewer children in the tramadol group required extra bolus doses within 12 hours post-surgery compared to the nalbuphine group. Both groups had a similar need for increased infusion rates over 72 hours, but overall, tramadol showed superior pain control in this regimen [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. This finding is comparable to the current study, indicating more sustained pain relief with tramadol.\u003c/p\u003e\u003cp\u003eIn another randomized controlled trial using a single dose (0.2 mg/kg nalbuphine vs. 2 mg/kg tramadol), nalbuphine resulted in lower mean pain scores at 0- and 1-hour post-surgery, and fewer children required rescue analgesics compared to tramadol, though the difference was not statistically significant at later time points. The mean time to rescue analgesic was also slightly longer with nalbuphine [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. A key difference exists in the type of surgery examined in this study compared to the current one. In the referenced research, the authors compared the two drugs in a day surgery setting, administering a single dose of each.\u003c/p\u003e\u003cp\u003eThe current work and previous studies indicate that tramadol may provide better overall pain control, but nalbuphine may offer superior early pain relief and longer duration with a single dose. Nalbuphine may suit single-dose use, while tramadol could be better for continuous infusion; however, more research is required to confirm this [\u003cspan additionalcitationids=\"CR19 CR20\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eNalbuphine and tramadol differ significantly in their mechanisms for pain relief in children. The former acts as a κ-opioid receptor agonist and a \u0026micro;-opioid receptor antagonist. This mixed action provides analgesia and sedation, but with a ceiling effect for respiratory depression, making it safer for children compared to pure \u0026micro;-opioid agonists like morphine or fentanyl [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The reduced effect of nalbuphine in the later postoperative period might be explained by its extensive first-pass metabolism, mainly via phase II glucuronidation (75%) and phase I oxidation-reduction (25%) [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOn the other hand, tramadol exerts its effect via opioid and non-opioid mechanisms. It is a weak \u0026micro;-opioid receptor agonist\u0026mdash;less potent than traditional opioids. It inhibits the reuptake of norepinephrine and serotonin, enhancing endogenous pain inhibition pathways. Also, it inhibits α2-adrenoceptors, neurokinin 1, muscarinic, nicotinic acetylcholine, and NMDA receptors, contributing to its complex analgesic profile [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. The extended duration of tramadol's efficacy over the 72-hour postoperative period may be attributed to its multiple mechanisms of action.\u003c/p\u003e\u003cp\u003eAssessing pain in children after surgery is challenging due to the complexity involved in pain evaluation. Currently, there is no ideal assessment scale applicable to all types of pain or all age groups of children. In the current study, we used the Wong-Baker FACES Pain Scale for assessment of postoperative pain in the current series. The Wong-Baker FACES\u0026reg; Scale consists of six faces, each representing a different level of pain intensity. The visual representation of facial expressions allows patients, especially those with limited verbal skills or cognitive impairments, to communicate their pain levels intuitively. It suits children aged three years and older. It remains a cornerstone in pain assessment due to its simplicity, accessibility, and versatility [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn the current study, the need for rescue analgesia was very low and comparable between the two groups (9.4%, nalbuphine vs. 7.8%, tramadol, p\u0026thinsp;=\u0026thinsp;0.752). In the limited number of patients, the time to rescue analgesia was longer in the tramadol group (median 8 vs. 6 hours), though not statistically significant (p\u0026thinsp;=\u0026thinsp;0.082)\u0026mdash;a trend that may become significant in a larger sample. However, the small number of patients questioned the strength of these results. Liaqat and Dar [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] reported comparable findings to the current study. The number of patients requiring rescue analgesics was greater in the tramadol group than in the nalbuphine group, and the mean time for the requirement of rescue analgesics was similar in both groups.\u003c/p\u003e\u003cp\u003eIn the current study, both drugs maintained hemodynamic stability, as blood pressure and heart rate readings remained within clinically accepted ranges, with no significant differences observed between the groups. Also, a few adverse effects were recorded in the two groups with no significant intergroup differences. Nausea/vomiting, constipation, and itching were reported, which aligns with known opioid-related side effects, though nalbuphine typically causes less pruritus than pure \u0026micro;-agonists.\u003c/p\u003e\u003cp\u003eTramadol was associated with a higher incidence of vomiting compared to nalbuphine in the infusion study, but cardiovascular parameters remained stable in both groups. Nalbuphine, on the other hand, showed a slightly higher rate of sedation but fewer cases of vomiting compared to tramadol [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Both groups in the Liaqat and Dar study experienced side effects, with vomiting being the most common [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/p\u003e"},{"header":"Limitations","content":"\u003cp\u003eWhile adequate to detect early differences, the study may be underpowered to confirm trends in rescue analgesia timing or rare side effects. Reliance on a categorical scale (Wong-Baker) limits hardness; continuous or composite pain scores might offer more sensitivity. We did not exhibit pharmacokinetic data of the two drugs, which is beyond the scope of this study. Understanding drug levels over time could clarify the observed temporal shift in efficacy.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eNalbuphine and tramadol are used to manage postoperative pain in pediatric patients following abdominal surgery. Both drugs have been found to provide analgesia and demonstrate a similar safety profile. Nalbuphine shows greater effect during the early postoperative period, while tramadol may offer benefits for extended analgesia beyond 24 hours, potentially reducing late pain or assisting with outpatient discharge. Both medications show comparable safety outcomes, with limited need for additional rescue medication and no reported serious complications.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethical Committee of the National Cancer Institute, Cairo University, Egypt (Approval No.: AP2403301015) and was retrospectively registered at clinical trial gov. (ID: NCT07110051), URL: https://clinicaltrials.gov/study/NCT07110051?cond=NCT07110051\u0026amp;rank=1, Date: 31/07/2025. \u0026nbsp;This study was done in accordance with Helsinki Declaration of 1975 (revised 2013). Informed written consent was obtained from the guardians of all participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData is available on reasonable requests from corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no financial or proprietary interest in any material discussed in this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was received for conducting this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by [F. H. M. M. E.], [A. F. A.], and [N. O. A. Z.]. The first draft of the manuscript was written by [F. H. M. M. E.], [A. F. A.], and [N. O. A. Z.]. All authors commented on previous versions of the manuscript. All authors read and approved of the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNill\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eYang J-X, Zhang W-Y, Huang H-H, Jiang W-T, Zhou Y-F, Gu Y, et al. Parental involvement in postoperative pain management among children in a urology ward: A best practice implementation project. Nurs Open. 2023;10:3042\u0026ndash;51. https://doi.org/10.1002/nop2.1551\u003c/li\u003e\n\u003cli\u003eEscalona-Espinosa A, Maldonado-S\u0026aacute;nchez K, Pazos-Alvarado E, Casta\u0026ntilde;eda P, Alcaraz-Ramos R, Aguilar-Romero D, et al. Postoperative Pain in Pediatrics. Topics in Postoperative Pain [Internet]. IntechOpen; 2023 [cited 2025 Sep 24]. https://doi.org/10.5772/intechopen.111788\u003c/li\u003e\n\u003cli\u003eVittinghoff M, L\u0026ouml;nnqvist PA, Mossetti V, Heschl S, Simic D, Colovic V, et al. Postoperative Pain Management in children: guidance from the Pain Committee of the European Society for Paediatric Anaesthesiology (ESPA Pain Management Ladder Initiative) Part II. Anaesthesia Critical Care \u0026amp; Pain Medicine. 2024;43:101427. https://doi.org/10.1016/j.accpm.2024.101427\u003c/li\u003e\n\u003cli\u003eCarney DE, Nicolette LA, Ratner MH, Minerd A, Baesl TJ. Ketorolac reduces postoperative narcotic requirements. J Pediatr Surg. 2001;36:76\u0026ndash;9. https://doi.org/10.1053/jpsu.2001.20011\u003c/li\u003e\n\u003cli\u003eCramer J. Comparison of Morphine- and Hydromorphone-Containing Patient-Controlled Epidural Analgesia Solutions in Pediatric Postoperative Patients. J Pediatr Pharmacol Ther. 2019;24:22\u0026ndash;6. https://doi.org/10.5863/1551-6776-24.1.22\u003c/li\u003e\n\u003cli\u003eLi S, Xiong H, Jia Y, Li Z, Chen Y, Zhong L, et al. Oxycodone vs. tramadol in postoperative parent-controlled intravenous analgesia in children: a prospective, randomized, double-blinded, multiple-center clinical trial. BMC Anesthesiol. 2023;23:152. https://doi.org/10.1186/s12871-023-02054-8\u003c/li\u003e\n\u003cli\u003eMahmoud AM, Hassanein EHM. Tramadol as an analgesic. Treatments, Mechanisms, and Adverse Reactions of Anesthetics and Analgesics [Internet]. Elsevier; 2022 [cited 2025 Sep 25]. p. 181\u0026ndash;91. https://doi.org/10.1016/B978-0-12-820237-1.00018-1\u003c/li\u003e\n\u003cli\u003eSchnabel A, Reichl SU, Zahn PK, Pogatzki-Zahn E. Nalbuphine for postoperative pain treatment in children. Cochrane Database Syst Rev. 2014;2014:CD009583. https://doi.org/10.1002/14651858.CD009583.pub2\u003c/li\u003e\n\u003cli\u003eSchultz-Machata A-M, Becke K, Weiss M. [Nalbuphine in pediatric anesthesia]. Anaesthesist. 2014;63:135\u0026ndash;43. https://doi.org/10.1007/s00101-014-2293-z\u003c/li\u003e\n\u003cli\u003eKubica-Cielińska A, Zielińska M. Zastosowanie nalbufiny w anestezjologii pediatrycznej. Anaesthesiol Intensive Ther. 2015;47:252\u0026ndash;6. https://doi.org/10.5603/AIT.2015.0036\u003c/li\u003e\n\u003cli\u003eTorad FA, Hassan EA. Sedative, analgesic, and behavioral effects of nalbuphine-xylazine and nalbuphine-midazolam combinations in dogs. Journal of Veterinary Behavior. 2018;28:40\u0026ndash;5. https://doi.org/10.1016/j.jveb.2018.07.002\u003c/li\u003e\n\u003cli\u003eNg KT, Lim WE, Teoh WY, Zainal Abidin MFB. The effect of nalbuphine on prevention of emergence delirium in children: a systematic review with meta-analysis. Brazilian Journal of Anesthesiology (English Edition). 2024;74:844543. https://doi.org/10.1016/j.bjane.2024.844543\u003c/li\u003e\n\u003cli\u003eKokinsky E, Thornberg E. Postoperative Pain Control in Children: A Guide to Drug Choice. Pediatric Drugs. 2003;5:751\u0026ndash;62. https://doi.org/10.2165/00148581-200305110-00004\u003c/li\u003e\n\u003cli\u003eBeggs S. Paediatric analgesia. Aust Prescr. 2008;31:63\u0026ndash;5. https://doi.org/10.18773/austprescr.2008.039\u003c/li\u003e\n\u003cli\u003eCaliskan E, Sener M, Kocum A, Ozyilkan NB, Ezer SS, Aribogan A. The efficacy of intravenous paracetamol versus dipyrone for postoperative analgesia after day-case lower abdominal surgery in children with spinal anesthesia: a prospective randomized double-blind placebo-controlled study. BMC Anesthesiol. 2013;13:34. https://doi.org/10.1186/1471-2253-13-34\u003c/li\u003e\n\u003cli\u003eChan SH, Lara-Torre E. Surgical considerations and challenges in the pediatric and adolescent gynecologic patient. Best Pract Res Clin Obstet Gynaecol. 2018;48:128\u0026ndash;36. https://doi.org/10.1016/j.bpobgyn.2017.10.007\u003c/li\u003e\n\u003cli\u003eHeydinger G, Kadado A, Elhamrawy A, Villalobos E, Tobias JD, Veneziano G. Dual Tunneled Epidural Wound Catheters for Postoperative Analgesia Following Posterior Spinal Fusion. J Med Cases. 2025;16:43\u0026ndash;7. https://doi.org/10.14740/jmc4337\u003c/li\u003e\n\u003cli\u003eMoyao-Garc\u0026iacute;a D, Hern\u0026aacute;ndez-Palacios JC, Ram\u0026iacute;rez-Mora JC, Nava-Ocampo AA. A pilot study of nalbuphine versus tramadol administered through continuous intravenous infusion for postoperative pain control in children. Acta Biomed. 2009;80:124\u0026ndash;30. \u003c/li\u003e\n\u003cli\u003eLiaqat N, Dar SH. Comparison of single-dose nalbuphine versus tramadol for postoperative pain management in children: a randomized, controlled trial. Korean J Anesthesiol. 2017;70:184. https://doi.org/10.4097/kjae.2017.70.2.184\u003c/li\u003e\n\u003cli\u003eBedirli N, Ak\u0026ccedil;abay M, Emik U. Tramadol vs dexmedetomidine for emergence agitation control in pediatric patients undergoing adenotonsillectomy with sevoflurane anesthesia: prospective randomized controlled clinical study. BMC Anesthesiol. 2017;17:41. https://doi.org/10.1186/s12871-017-0332-4\u003c/li\u003e\n\u003cli\u003eWalter CM, Abbasian N, Olbrecht VA. Trends in Pediatric Pain. Anesthesiology Clinics. 2020;38:663\u0026ndash;78. https://doi.org/10.1016/j.anclin.2020.04.002\u003c/li\u003e\n\u003cli\u003ePfiffner M, Berger-Olah E, Vonbach P, Pfister M, Gotta V. Pharmacometric Analysis of Intranasal and Intravenous Nalbuphine to Optimize Pain Management in Infants. Front Pediatr. 2022;10:837492. https://doi.org/10.3389/fped.2022.837492\u003c/li\u003e\n\u003cli\u003eMonteiro BP, Lambert C, Bianchi E, Genevois JP, Soldani G, Troncy E. Safety and efficacy of reduced dosage ketoprofen with or without tramadol for long-term treatment of osteoarthritis in dogs: a randomized clinical trial. BMC Vet Res. 2019;15:213. https://doi.org/10.1186/s12917-019-1960-3\u003c/li\u003e\n\u003cli\u003eAngasa D, Haddis L, Gashaw A, Zemedkun A, Gobena N. Postoperative analgesic efficacy of caudal tramadol added to bupivacaine compared to bupivacaine alone for pediatric elective infra umbilical surgery at Tikur Anbessa Specialized Hospital, Ethiopia, a prospective cohort study. International Journal of Surgery Open. 2020;27:32\u0026ndash;8. https://doi.org/10.1016/j.ijso.2020.10.008\u003c/li\u003e\n\u003cli\u003eYoo O, Tang EKY, Nguyen MN, Salman S, Hua AJ, Von Ungern Sternberg BS, et al. HPLC-UV assay of tramadol and O-desmethyltramadol in human plasma containing other drugs potentially co-administered to participants in a paediatric population pharmacokinetic study. Journal of Chromatography B. 2021;1184:122971. https://doi.org/10.1016/j.jchromb.2021.122971\u003c/li\u003e\n\u003cli\u003eGarra G, Singer AJ, Taira BR, Chohan J, Cardoz H, Chisena E, et al. Validation of the Wong-Baker FACES Pain Rating Scale in pediatric emergency department patients. Acad Emerg Med. 2010;17:50\u0026ndash;4. https://doi.org/10.1111/j.1553-2712.2009.00620.x \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Postoperative Pain, Pediatric Patients, Abdominal Surgery, Rescue Analgesia, Nalbuphine, Tramadol","lastPublishedDoi":"10.21203/rs.3.rs-7805933/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7805933/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eEffective postoperative pain management in pediatric patients is essential for recovery, though no single analgesic is considered superior. Nalbuphine and tramadol are common alternatives to traditional opioids, each with a distinct pharmacological profile. This study compares the efficacy and safety of nalbuphine versus tramadol in managing postoperative pain after abdominal surgery in pediatric cancer patients.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis prospective, randomized clinical trial involved 128 children with cancers (3\u0026ndash;12 years) undergoing elective abdominal surgery. Patients were randomized into two groups: the Nalbuphine group (0.2 mg/kg IV every 8 hours) and the Tramadol group (2 mg/kg IV every 8 hours) for 72 hours postoperatively. Pain was assessed using the Wong-Baker FACES Pain Scale (WB), and rescue analgesia with paracetamol was provided as needed. The primary outcome measure was the time to first rescue analgesia, while secondary outcomes included pain scores, paracetamol consumption, and adverse effects.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eNalbuphine provided superior pain relief during the first 24 hours postoperatively, with significantly lower WB scores compared to tramadol. However, tramadol demonstrated complete pain resolution by 48\u0026ndash;72 hours, while some nalbuphine patients reported mild pain. The need for rescue analgesia was low and comparable between groups (9.4% vs. 7.8%, p\u0026thinsp;=\u0026thinsp;0.752). Both drugs maintained hemodynamic stability and had similar safety profiles, with minimal adverse effects.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eNalbuphine offers better early postoperative pain control, while tramadol provides more sustained analgesia beyond 24 hours. Both drugs are effective and safe.\u003c/p\u003e\u003ch2\u003eTrial registration:\u003c/h2\u003e\u003cp\u003ethis study was retrospectively registered at clinical trial gov. (ID: NCT07110051), URL: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://clinicaltrials.gov/study/NCT07110051?cond=NCT07110051\u0026amp;rank=1\u003c/span\u003e\u003cspan address=\"https://clinicaltrials.gov/study/NCT07110051?cond=NCT07110051\u0026amp;rank=1\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e, Date: 31/07/2025.\u003c/p\u003e","manuscriptTitle":"Comparative Study between Nalbuphine versus Tramadol on Postoperative Analgesia for Abdominal Surgery in Pediatric Cancer Patients: A Prospective, Randomized Clinical Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-08 15:39:14","doi":"10.21203/rs.3.rs-7805933/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"40b43708-d059-4fce-8811-80abd90f0d8d","owner":[],"postedDate":"December 8th, 2025","published":true,"recentEditorialEvents":[{"type":"decision","content":"Withdrawn","date":"2026-05-06T11:24:34+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-06T11:40:02+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-08 15:39:14","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7805933","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7805933","identity":"rs-7805933","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}