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Postoperative intravenous parecoxib sodium followed by oral celecoxib post total knee arthroplasty in osteoarthritis patients (PIPFORCE): a multicentre, double-blind, randomised, placebo-controlled trial.
Zhuang, Q, Tao, L, Lin, J, Jin, J, Qian, W, Bian, Y, Li, Y, Dong, Y, Peng, H, Li, Y, et al
BMJ open. 2020;(1):e030501
Abstract
OBJECTIVES To evaluate the morphine-sparing effects of the sequential treatment versus placebo in subjects undergoing total knee arthroplasty (TKA), the effects on pain relief, inflammation control and functional rehabilitation after TKA and safety. DESIGN Double-blind, pragmatic, randomised, placebo-controlled trial. SETTING Four tertiary hospitals in China. PARTICIPANTS 246 consecutive patients who underwent elective unilateral TKA because of osteoarthritis (OA). INTERVENTIONS Patients were randomised 1:1 to the parecoxib/celecoxib group or the control group. The patients in the parecoxib/celecoxib group were supplied sequential treatment with intravenous parecoxib 40 mg (every 12 hours) for the first 3 days after surgery, followed by oral celecoxib 200 mg (every 12 hours) for up to 6 weeks. The patients in the control group were supplied with the corresponding placebo under the same instructions. PRIMARY AND SECONDARY OUTCOME MEASURES The primary endpoint was the cumulative opioid consumption at 2 weeks post operation (intention-to-treat analysis). Secondary endpoints included the Knee Society Score, patient-reported outcomes and the cumulative opioid consumption. RESULTS The cumulative opioid consumption at 2 weeks was significantly smaller in the parecoxib/celecoxib group than in the control group (median difference, 57.31 (95% CI 34.66 to 110.33)). The parecoxib/celecoxib group achieving superior Knee Society Scores and EQ-5D scores and greater Visual Analogue Scale score reduction during 6 weeks. Interleukin 6, erythrocyte sedation rate and C-reactive protein levels were reduced at 72 hours, 2 weeks and 4 weeks and prostaglandin E2 levels were reduced at 48 hours and 72 hours in the parecoxib/celecoxib group compared with the placebo group. The occurrence of adverse events (AEs) was significantly lower in the parecoxib/celecoxib group. CONCLUSIONS The sequential intravenous parecoxib followed by oral celecoxib regimen reduces morphine consumption, achieves better pain control and functional recovery and leads to less AEs than placebo after TKA for OA. TRIAL REGISTRATION NUMBER ClinicalTrials.gov (ID: NCT02198924).
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Multimodal opioid-sparing postoperative pain regimen compared with the standard postoperative pain regimen in vaginal pelvic reconstructive surgery: a multicenter randomized controlled trial.
Petrikovets, A, Sheyn, D, Sun, HH, Chapman, GC, Mahajan, ST, Pollard, RR, El-Nashar, SA, Hijaz, AK, Mangel, J
American journal of obstetrics and gynecology. 2019;(5):511.e1-511.e10
Abstract
BACKGROUND Postoperative pain control after urogynecological surgery has traditionally been opioid centered with frequent narcotic administration. Few studies have addressed optimal pain control strategies for vaginal pelvic reconstructive surgery that limit opioid use. OBJECTIVE The objective of the study was to determine whether, ice packs, Tylenol, and Toradol, a novel opioid-sparing multimodal postoperative pain regimen has improved pain control compared with the standard postoperative pain regimen in patients undergoing inpatient vaginal pelvic reconstructive surgery. STUDY DESIGN This was a multicenter randomized controlled trial of women undergoing vaginal pelvic reconstructive surgery. Patients were randomized to the ice packs, Tylenol, and Toradol postoperative pain regimen or the standard regimen. The ice packs, Tylenol, and Toradol regimen consists of around-the-clock ice packs, around-the-clock oral acetaminophen, around-the-clock intravenous ketorolac, and intravenous hydromorphone for breakthrough pain. The standard regimen consists of as-needed ibuprofen, as-needed acetaminophen/oxycodone, and intravenous hydromorphone for breakthrough pain. The primary outcome was postoperative day 1 pain evaluated the morning after surgery using a visual analog scale. Secondary outcomes included the validated Quality of Recovery Questionnaire, satisfaction scores, inpatient narcotic consumption, outpatient pain medication consumption, and visual analog scale scores at other time intervals. In all, 27 patients in each arm were required to detect a mean difference of 25 mm on a 100 mm visual analog scale (90% power). RESULTS Thirty patients were randomized to ice packs, Tylenol, and Toradol and 33 to the standard therapy. Patient and surgical demographics were similar. The median morning visual analog scale pain score was lower in the ice packs, Tylenol, and Toradol group (20 mm vs 40 mm, P = .03). Numerical median pain scores were lower at the 96 hour phone call in the ice packs, Tylenol, and Toradol group (2 vs 3, P = .04). Patients randomized to the ICE-T regimen received fewer narcotics (expressed in oral morphine equivalents) from the postanesthesia care unit exit to discharge (2.9 vs 20.4, P < .001) and received fewer narcotics during the entire hospitalization (55.7 vs 91.2, P < .001). At 96 hour follow up, patients in the ice packs, Tylenol, and Toradol group used 4.9 ketorolac tablets compared with 4.6 oxycodone/acetaminophen tablets in the standard group (P = .81); however, ice packs, Tylenol, and Toradol patients required more acetaminophen than ibuprofen by patients in the standard arm (10.7 vs 6.2 tablets, P = .012). There were no differences in Quality of Recovery Questionnaire or satisfaction scores either in the morning after surgery or at 96 hour follow up. CONCLUSION The ice packs, Tylenol, and Toradol multimodal pain regimen offers improved pain control the morning after surgery and 96 hours postoperatively compared with the standard regimen with no differences in patient satisfaction and quality of recovery. Ice packs, Tylenol, and Toradol can significantly limit postoperative inpatient narcotic use and eliminate outpatient narcotic use in patients undergoing vaginal pelvic reconstructive surgery.
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Tramadol/dexketoprofen (TRAM/DKP) compared with tramadol/paracetamol in moderate to severe acute pain: results of a randomised, double-blind, placebo and active-controlled, parallel group trial in the impacted third molar extraction pain model (DAVID study).
Gay-Escoda, C, Hanna, M, Montero, A, Dietrich, T, Milleri, S, Giergiel, E, Zoltán, TB, Varrassi, G
BMJ open. 2019;(2):e023715
Abstract
OBJECTIVES To compare efficacy/safety of oral tramadol 75 mg/dexketoprofen 25 mg (TRAM/DKP) and TRAM 75 mg/paracetamol 650 mg (TRAM/paracetamol) in moderate to severe pain following surgical removal of impacted lower third molar. DESIGN Multicentre, randomised, double-blind, placebo-controlled, phase IIIb study. PARTICIPANTS Healthy adult patients scheduled for surgical extraction of at least one fully/partially impacted lower third molar requiring bone manipulation. 654 patients were randomised and 653 were eligible for analysis. INTERVENTIONS Surgery was performed under local anaesthetic. No sedation was permitted. Patients rated pain intensity (PI) using an 11-Numerical Rating Scale (NRS) (0 no pain; 10 worst pain). Participants experiencing moderate/severe pain (≥4) within 4 hours of surgery were randomised (2:2:1 ratio) to a single oral dose of TRAM/DKP 75/25 mg, TRAM/paracetamol 75/650 mg or placebo. MAIN OUTCOME MEASURES Efficacy was based patients' electronic diaries. Analgesia and pain were recorded as follows: pain relief (PAR) on a 5-point Verbal Rating Scale (0='no relief', 1='a little (perceptible) relief', 2='some (meaningful) relief', 3='lot of relief', 4='complete relief') at the predefined postdose time points t15 min, t30 min, t1 hour, t1.5 hour, t2 hour, t4 hour, t6 hour and t8 hour and PI on the 11-point NRS at t0 and at the same predefined postdose time points. Onset of analgesia documented using double stopwatch method over a 2-hour period. Primary endpoint was total pain relief over 6 hours (TOTPAR6). Rescue medication was available during the treatment period. RESULTS TRAM/DKP was superior to TRAM/paracetamol and placebo at the primary endpoint TOTPAR6 (p<0.0001). Mean (SD) TOTPAR6 in the TRAM/DKP group was 13 (6.97), while those in the active control and placebo groups were 9.2 (7.65) and 1.9 (3.89), respectively. Superiority of TRAM/DKP over active comparator and placebo was observed at all secondary endpoints. Incidence of adverse events was comparable between active groups. CONCLUSIONS TRAM/DKP (75/25 mg) is effective and superior to TRAM/paracetamol (75/650 mg) in relieving moderate to severe acute pain following surgical removal of impacted lower third molar, with a faster onset of action, greater and durable analgesia, together with a favourable safety profile. TRIAL REGISTRATION NUMBER EudraCT 2015-004152-22 and NCT02777970.
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No Difference in Early Analgesia Between Liposomal Bupivacaine Injection and Intrathecal Morphine After TKA.
Barrington, JW, Emerson, RH, Lovald, ST, Lombardi, AV, Berend, KR
Clinical orthopaedics and related research. 2017;(1):94-105
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BACKGROUND Opioid analgesics have been a standard modality for postoperative pain management after total knee arthroplasty (TKA) but are also associated with increased risk of nausea, pruritus, vomiting, respiratory depression, prolonged ileus, and cognitive dysfunction. There is still a need for a method of anesthesia that can deliver effective long-term postoperative pain relief without incurring the high cost and health burden of opioids and nerve blocks. QUESTIONS/PURPOSES (1) Is liposomal bupivacaine-based periarticular injection (PAI) more effective than morphine-based spinal anesthesia or ropivacaine-based PAI in controlling postoperative pain after TKA? (2) Do patients treated with liposomal bupivacaine-based PAI experience fewer opioid-related adverse events compared with patients treated with morphine-based spinal anesthesia or ropivacaine-based PAI in controlling postoperative pain after TKA? METHODS This multicenter, blind trial randomized 119 patients undergoing TKA with spinal anesthesia to receive spinal anesthesia plus periarticular injection with liposomal bupivacaine (40 patients), spinal anesthesia with bupivacaine plus intrathecal morphine (41 patients) but no liposomal bupivacaine injection, or spinal anesthesia with bupivacaine (38 patients) and no liposomal bupivacaine injection. The two groups that did not receive periarticular liposomal bupivacaine did receive periarticular injection with ropivacaine, and all three groups had ketorolac (30 mg) plus epinephrine (1:1000) in the periarticular injections. Patients in all three groups received identical perioperative multimodal analgesic and antiemetic drugs. All patients were analyzed in the group to which they were randomized and no patients were lost to followup. The primary study endpoints were visual analog score (VAS) for pain and narcotic use during postoperative day 1. Secondary endpoints included side effects associated with narcotic administration during the hospital stay. RESULTS Mean VAS pain in the liposomal bupivacaine PAI group was lower than that for the ropivacaine PAI group at 6 hours (1.8 ± 2.1 versus 3.3 ± 2.3, p = 0.005, mean difference: 1.5, 95% confidence interval [CI], 0.5-2.5) and 12 hours (1.5 ± 2.0 versus 3.3 ± 2.4, p < 0.001, mean difference: 1.8, 95% CI, 0.8-2.8) after surgery. The morphine spinal group had lower pain compared with the liposomal bupivacaine PAI group at 6 hours (0.9 ± 1.8 versus 1.8 ± 2.1, p = 0.035, mean difference: 1.0, 95% CI, 0.1-1.8), but there was no difference at 12 hours (0.8 ± 1.5 versus 1.5 ± 2.0, p = 0.086, mean difference: 0.7, 95% CI, -0.1 to 1.5). The magnitude of the differences at 6 and 12 hours are near the lower end of minimal clinically important differences reported in the literature, and thus the improvement shown in this study may only represent a small clinical improvement. Both the liposomal bupivacaine group (13% [five of 40]) and the ropivacaine group (5% [two of 38]) had fewer incidents of itching (pruritus) than the spinal morphine group (38% [15 of 41]) (p = 0.001). CONCLUSIONS This prospective multicenter three-arm blind randomized controlled trial showed potentially improved pain control at 6 and 12 hours in the liposomal bupivacaine and intrathecal morphine groups compared with the ropivacaine group at the cost of much higher incidences of pruritus (itching) in the intrathecal morphine group. Based on these results, we prefer the use of PAI with liposomal bupivacaine as an alternative to spinal anesthesia with intrathecal morphine as a result of similar postoperative pain control and the potential for reducing adverse events. LEVEL OF EVIDENCE Level I, therapeutic study.
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Use of prescribed opioids before and after bariatric surgery: prospective evidence from a U.S. multicenter cohort study.
King, WC, Chen, JY, Belle, SH, Courcoulas, AP, Dakin, GF, Flum, DR, Hinojosa, MW, Kalarchian, MA, Mitchell, JE, Pories, WJ, et al
Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery. 2017;(8):1337-1346
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BACKGROUND Limited evidence suggests bariatric surgery may not reduce opioid analgesic use, despite improvements in pain. OBJECTIVE To determine if use of prescribed opioid analgesics changes in the short and long term after bariatric surgery and to identify factors associated with continued and postsurgery initiated use. SETTING Ten U.S. hospitals. METHODS The Longitudinal Assessment of Bariatric Surgery-2 is an observational cohort study. Assessments were conducted presurgery, 6 months postsurgery, and annually postsurgery for up to 7 years until January 2015. Opioid use was defined as self-reported daily, weekly, or "as needed" use of a prescribed medication classified as an opioid analgesic. RESULTS Of 2258 participants with baseline data, 2218 completed follow-up assessment(s) (78.7% were female, median body mass index: 46; 70.6% underwent Roux-en-Y gastric bypass). Prevalence of opioid use decreased after surgery from 14.7% (95% CI: 13.3-16.2) at baseline to 12.9% (95% CI: 11.5-14.4) at month 6 but then increased to 20.3%, above baseline levels, as time progressed (95% CI: 18.2-22.5) at year 7. Among participants without baseline opioid use (n = 1892), opioid use prevalence increased from 5.8% (95% CI: 4.7-6.9) at month 6 to 14.2% (95% CI: 12.2-16.3) at year 7. Public versus private health insurance, more pain presurgery, undergoing subsequent surgeries, worsening or less improvement in pain, and starting or continuing nonopioid analgesics postsurgery were significantly associated with higher risk of postsurgery initiated opioid use. CONCLUSION After bariatric surgery, prevalence of prescribed opioid analgesic use initially decreased but then increased to surpass baseline prevalence, suggesting the need for alternative methods of pain management in this population.
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Efficacy and safety of Postoperative Intravenous Parecoxib sodium Followed by ORal CElecoxib (PIPFORCE) post-total knee arthroplasty in patients with osteoarthritis: a study protocol for a multicentre, double-blind, parallel-group trial.
Zhuang, Q, Bian, Y, Wang, W, Jiang, J, Feng, B, Sun, T, Lin, J, Zhang, M, Yan, S, Shen, B, et al
BMJ open. 2016;(9):e011732
Abstract
INTRODUCTION Total knee arthroplasty (TKA) has been regarded as a most painful orthopaedic surgery. Although many surgeons sequentially use parecoxib and celecoxib as a routine strategy for postoperative pain control after TKA, high quality evidence is still lacking to prove the effect of this sequential regimen, especially at the medium-term follow-up. The purpose of this study, therefore, is to evaluate efficacy and safety of postoperative intravenous parecoxib sodium followed by oral celecoxib in patients with osteoarthritis (OA) undergoing TKA. The hypothesis is that compared to placebo with opioids as rescue treatment, sequential use of parecoxib and celecoxib can achieve less morphine consumption over the postoperative 2 weeks, as well as better pain control, quicker functional recovery in the postoperative 6 weeks and less opioid-related adverse events during the 12-week recovery phase. METHODS AND ANALYSIS This study is designed as a multicentre, randomised, double-blind, parallel-group and placebo-controlled trial. The target sample size is 246. All participants who meet the study inclusion and exclusion criteria will be randomly assigned in a 1:1 ratio to either the parecoxib/celecoxib group or placebo group. The randomisation and allocation will be study site based. The study will consist of three phases: an initial screening phase; a 6-week double-blind treatment phase; and a 6-week follow-up phase. The primary end point is cumulative opioid consumption during 2 weeks postoperation. Secondary end points consist of the postoperative visual analogue scale score, knee joint function, quality of life, local skin temperature, erythrocyte sedimentation rate, C reactive protein, cytokines and blood coagulation parameters. Safety end points will be monitored too. ETHICS AND DISSEMINATION Ethics approval for this study has been obtained from the Ethics Committee, Peking Union Medical College Hospital, China (Protocol number: S-572) Study results will be available as published manuscripts and presentations at national and international meetings. TRIAL REGISTRATION NUMBER NCT02198924.
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Dose-response of intrathecal morphine when administered with intravenous ketorolac for post-cesarean analgesia: a two-center, prospective, randomized, blinded trial.
Berger, JS, Gonzalez, A, Hopkins, A, Alshaeri, T, Jeon, D, Wang, S, Amdur, RL, Smiley, R
International journal of obstetric anesthesia. 2016;:3-11
Abstract
BACKGROUND The appropriate dose of intrathecal morphine for post-cesarean analgesia is unclear. With the inclusion of routine non-steroidal anti-inflammatory drugs, the required dose of morphine may be significantly less than the 200-300μg common a decade ago. We performed a two-center, prospective, randomized, blinded trial comparing three doses of intrathecal morphine, combined with routine intravenous ketorolac, in 144 healthy women undergoing elective cesarean delivery. METHODS Patients received an intrathecal injection of hyperbaric bupivacaine 12mg, fentanyl 15μg and a randomized dose of 50, 100, or 150μg morphine in a volume of 2.2mL. Patients received intravenous ketorolac 30mg before leaving the operating room and 15mg intravenously every 6h for the duration of the study (24h). All received postoperative patient-controlled intravenous morphine. The primary endpoint was total intravenous morphine administered postoperatively over 24h, analyzed using mixed model regression. RESULTS There were no differences between dose groups (or institutions) in intravenous morphine use over 24h. Visual analog scale scores for pain and nausea did not differ. Pruritus was greater in the 100 and 150μg groups than the 50μg group at 6h and 12h, but there was no difference between groups in nausea or pruritus treatments. Respiratory depression or significant sedation did not occur. CONCLUSION The dose-response relationship of intrathecal morphine for multimodal post-cesarean analgesia suggests that 50μg produces analgesia similar to that produced by either 100μg or 150μg.
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Effect of postoperative analgesia on acute and persistent postherniotomy pain: a randomized study.
Bugada, D, Lavand'homme, P, Ambrosoli, AL, Klersy, C, Braschi, A, Fanelli, G, Saccani Jotti, GM, Allegri, M, ,
Journal of clinical anesthesia. 2015;(8):658-64
Abstract
STUDY OBJECTIVE The study objective is to identify differences in postoperative pain management according to different analgesic treatments, targeting 2 main pathways involved in pain perception. DESIGN The design is a randomized, parallel groups, open-label study. SETTING The setting is in an operating room, postoperative recovery area, and surgical ward. PATIENTS There are 200 patients undergoing open inguinal hernia repair (IHR) with tension-free technique (mesh repair). INTERVENTIONS The intervention is a randomization to receive ketorolac (group K) or tramadol (group T) for 3 days after surgery. MEASUREMENTS The measurements are differences in analgesic efficacy (numeric rating scale [NRS]) in the postoperative (up to 5 days) period, chronic pain incidence (1 and 3 months), side effects, and complications. MAIN RESULTS We found no differences in analgesic efficacy (NRS value ≥4 in the first 96 hours: 26% in group K vs 32% in group T, P = .43); the proportion of patients with NRS ≥4 was similar in both groups, and the time trajectories were not significantly different (P for interaction = .24). Side effects were higher (12% vs 6%) in the tramadol group, although not significantly (P = .14), with a case of bleeding in the ketorolac group and higher incidence of constipation in tramadol group. One patient in each group developed chronic pain. CONCLUSIONS Ketorolac or weak opioids are equally effective on acute pain and on persistent postsurgical pain development after IHR, and drug choice should be based on their potential side effects and patient's comorbidities. Further studies are needed to standardize the most rational approach to prevent persistent postsurgical pain after IHR.
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Intracameral phenylephrine and ketorolac during cataract surgery to maintain intraoperative mydriasis and reduce postoperative ocular pain: Integrated results from 2 pivotal phase 3 studies.
Hovanesian, JA, Sheppard, JD, Trattler, WB, Gayton, JL, Malhotra, RP, Schaaf, DT, Ng, E, Dunn, SH
Journal of cataract and refractive surgery. 2015;(10):2060-8
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PURPOSE To evaluate the efficacy and safety of phenylephrine 1.0%-ketorolac 0.3% (Omidria) for maintenance of mydriasis during, and reduction of ocular pain after, cataract surgery. SETTING Twenty centers in the United States and the Netherlands. DESIGN Prospective randomized clinical trials. METHODS Patients having cataract surgery or refractive lens exchange were enrolled in 2 clinical trials. Phenylephrine 1.0%-ketorolac 0.3% or placebo was added to irrigation solution and administered intracamerally during the procedure. Integrated analyses of primary and secondary endpoints were conducted. RESULTS The clinical trials comprised 808 patients (403 treatment and 405 placebo). Phenylephrine 1.0%-ketorolac 0.3% was superior to placebo for the maintenance of mydriasis during, and reduction of ocular pain following, cataract surgery. The mean area under the curve (AUC) change from baseline in pupil diameter was 0.08 mm for treatment compared with -0.50 mm for placebo (P < .0001). The mean AUC of ocular pain visual analog scale scores within 12 hours postoperatively was 4.16 mm for the treatment group and 9.06 mm for the placebo group (P < .001). Results of all secondary efficacy analyses demonstrated a significant treatment effect associated with phenylephrine 1.0%-ketorolac 0.3%. Treatment-emergent adverse events were as expected for a population having cataract surgery; no clinically significant differences in safety measures were observed between treatment groups. CONCLUSION In this integrated analysis, phenylephrine 1.0%-ketorolac 0.3% administered intracamerally with irrigation solution during cataract surgery was safe and effective for maintaining mydriasis during the procedure and reducing postoperative ocular pain. FINANCIAL DISCLOSURE Dr. Schaaf is an employee and holds an equity interest in Omeros Corporation. Drs. Hovanesian, Sheppard, Trattler, Gayton, and Ng are consultants to Omeros Corporation. No other author has a financial or proprietary interest in any material or method mentioned.
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A multicenter, randomized, double-blind placebo-controlled, single dose trial of the safety and efficacy of intravenous ibuprofen for treatment of pain in pediatric patients undergoing tonsillectomy.
Moss, JR, Watcha, MF, Bendel, LP, McCarthy, DL, Witham, SL, Glover, CD
Paediatric anaesthesia. 2014;(5):483-9
Abstract
BACKGROUND Tonsillectomy is one of the most common pediatric procedures in the United States. An optimal perioperative pain control regimen remains a challenge. Intravenous ibuprofen administered at induction of anesthesia may be a safe and efficacious option for postoperative tonsillectomy pain. OBJECTIVES To determine whether preoperative administration of intravenous ibuprofen (IV-ibuprofen) can significantly decrease the number of doses of postoperative fentanyl when compared with placebo in pediatric tonsillectomy surgical patients. METHODS This was a multicenter, randomized, double-blind placebo-controlled trial conducted at six hospitals in the United States. A total of 161 pediatric patients aged 6-17 years undergoing tonsillectomy were randomized to receive either a single preoperative dose of 10 mg·kg(-1) IV-ibuprofen or placebo (normal saline). Postoperative pain was managed with intravenous fentanyl (0.5 μg·kg(-1)) on an as needed basis when the visual analog scale (VAS) was >30 mm and deemed appropriate by recovery room nurse/physician. The primary endpoint was the number of doses and amount of postoperative fentanyl administered postoperatively for rescue analgesia. RESULTS There was a significant reduction in the number of postoperative doses and the amount of fentanyl administered after surgery in the IV-ibuprofen group compared with the placebo group (P = 0.021). There were no differences in the time to first analgesia request or the number of patients who required postoperative analgesia. There were no significant differences in the incidence of serious adverse events, surgical blood loss (P = 0.662), incidence of postoperative bleeding, or a need for surgical re-exploration between the treatment groups. CONCLUSION Administration of IV-ibuprofen, 10 mg·kg(-1) , significantly reduced fentanyl use in pediatric tonsillectomy patients.