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Comparing the effects of ketorolac and Paracetamol on postoperative pain relief after coronary artery bypass graft surgery. A randomized clinical trial.
Javaherforooshzadeh, F, Abdalbeygi, H, Janatmakan, F, Gholizadeh, B
Journal of cardiothoracic surgery. 2020;(1):80
Abstract
INTRODUCTION Pain management after coronary artery bypass graft (CABG) surgery remains challenging. OBJECTIVE This study aimed to compare the effects of Ketorolac and Paracetamol on postoperative CABG pain relief. METHOD This double-blind randomized clinical trial study was conducted in Ahvaz, Iran, from September 2018-December 2019. Two consecutive groups of 60 patients undergoing elective on-pump coronary artery bypass graft surgery. INTERVENTION The patients were divided into 0.5 mg/kg of ketorolac mg/dl and 10 mg/kg of Paracetamol after surgery for pain management. Primary outcomes were: visual analog pain scale (VAS) at the time point immediately after extubation (baseline) and at 6, 12, 24 and 48 h and the total dose of morphine consumption. Secondary outcomes included the hemodynamic variables, weaning time, chest tube derange, in-hospital mortality and myocardial infarction. STATISTICAL ANALYSIS The data were analyzed using SPSS version 22(SPSS, Chicago, IL). The Mann-Whitney U-test was used to compare demographic data, VAS scores, vital signs, and side effects. Repeated measurements were tested within groups using Friedman's ANOVA and the Wilcoxon rank-sum test. Values were expressed as means ± standard deviations. Statistical significance was defined as a p-value < 0.05. RESULTS Compared with baseline scores, there were significant declines in VAS scores in both groups throughout the time sequence (P< 0.05). The statistical VAS score was slightly higher in the Paracetamol group at most time points, except for the time of 6 h. However, at 24 and 48 h, the VAS score in group Paracetamol was significantly higher than in group Ketorolac. There were no significant differences between groups about hemodynamic variables. CONCLUSION The efficacy of ketorolac is comparable to that of Paracetamol in postoperative CABG pain relief. TRIAL REGISTRY IRCT20150216021098N5. Registered at 2019-09-12.
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Analgesic efficacy of ketorolac associated with a tramadol/acetaminophen combination after third molar surgery - a randomized, triple-blind clinical trial.
Martins, LD, Rezende, M, Loguercio, AD, Bortoluzzi, MC, Reis, A
Medicina oral, patologia oral y cirugia bucal. 2019;(1):e96-e102
Abstract
BACKGROUND This study compared the efficacy of ketorolac alone versus its combination with tramadol/acetaminophen for pain control after mandibular third molar surgery. MATERIAL AND METHODS A randomized, triple-blind clinical trial was carried out with 52 patients divided into 2 groups: Group K+T+A (1 tablet of Ketorolac 10 mg plus and 1 capsule of Tramadol 37.5 mg/acetaminophen 325 mg) and Group K (1 tablet of Ketorolac 10 mg plus and 1 placebo capsule). The treatments were given 1 h before the surgery and was repeated 4 times per day, for 48 h. The difference in postoperative pain was assessed by 4 primary end-points: pain intensity (VAS 100mm, for 48 h), rescue medication, overall assessment and adverse effects. RESULTS Significant differences in pain intensity were observed in the different times (p < 0.05). The comparison of groups in each time showed significant differences only of 9 h, with lower level of pain intensity for group K+T+A (p = 0.005). The need of analgesics was higher in Group K (p < 0.001), the need of antiemetic were greater in Group K+T+A (p < 0.0001). No significant difference between groups were observed in overall assessment. The adverse effects was higher in Group K+T+A. CONCLUSIONS The current study showed that both ketorolac and the combination of ketorolac plus tramadol/acetaminophen showed good control of pain after the extraction of the lower third molars. Although the combination group showed lower pain at 9 h, the difference is small and not clinically relevant.
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Postoperative pain and bleeding after adenotonsillectomy versus adenotonsillotomy in pediatric obstructive sleep apnea: an RCT.
Borgström, A, Nerfeldt, P, Friberg, D
European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. 2019;(11):3231-3238
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PURPOSE Our previous randomized controlled trial (RCT) of children with obstructive sleep apnea (OSA) showed no significant differences between adenotonsillectomy (ATE) and adenotonsillomy (ATE) in improving nocturnal respiration and symptoms after one year. This is the continuous report with the evaluation of postoperative morbidity concerning bleeding and pain. METHODS A double-blinded RCT including 79 children, aged 2-6 years, with moderate to severe OSA, randomized to either ATE (n = 40) or ATT (n = 39). From one to ten days postoperatively, parents filled in a logbook with six pain-related outcomes (parent and child grading pain at different levels, days of analgesic use and return to normal diet). Peri- and postoperative bleeding were also registered. RESULTS 63 patients (80%) returned the logbook. There were significant differences between groups in only two of the six pain-related outcomes in favor of the ATT group; first day when the children graded themselves as pain free (p = 0.021, Log Rank Test), and first day the caregiver estimated pain VAS ≤ 5 (p = 0.007, Log Rank Test). Two (5%) cases of postoperative bleeding occurred in the ATE group, one of which needed a return to theatre. No case of postoperative bleeding was seen in the ATT group. CONCLUSIONS The results from this RCT are in line with previous comparative studies between ATT and ATE. Children operated with ATT had significantly less postoperative pain in one-third of the outcomes, and less bleeding than ATE. However, as the differences in morbidity between the surgical methods were minor the clinical significance is uncertain. TRIAL REGISTRATION This study was approved by the Swedish Regional Ethics Board in Stockholm, Sweden (Dnr 2011/925-32 and 2013/2274-32) and registered at ClinicalTrials.gov (Trial registration number NCT01676181).
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Administering analgesia sublingually is a suitable option for children with acute abdominal pain in the emergency department.
Cozzi, G, Zanchi, C, Chiaretti, A, Tipo, V, Cernich, M, D'Anna, C, Fantacci, C, Conversano, E, Zanon, D, Ronfani, L, et al
Acta paediatrica (Oslo, Norway : 1992). 2019;(1):143-148
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AIM: Acute abdominal pain is a frequent complaint in children attending emergency departments. The aim of this study was to investigate the pain score reductions when children with acute abdominal pain received medication sublingually. METHODS We carried out a multicentre randomised controlled trial in three children's hospitals in Italy between March 2015 and June 2017. Children from four to 18 years of age with acute abdominal pain were recruited if their self-reported pain was at least six on a scale from 0-10. The children were randomised to receive ketorolac 0.5 mg/kg (n = 70) or tramadol 2 mg/kg (n = 70) sublingually or a melt in the mouth powder of 20 mg/kg paracetamol (n = 70). The main study outcome was the pain scores for the three drugs after two hours. RESULTS The 210 children (58.6% girls) had a median age of 12 years with an interquartile range of 9-14.3. The median pain scores at two hours were not significantly different between ketorolac 2.0 (interquartile ranges, IQR 0.0-4.3) and tramadol 3.0 (IQR 1.0-5.0) vs paracetamol 3.0 (IQR 0.8-5.0). The median pain reductions were all 5.0 points. CONCLUSION Delivering analgesia sublingually was a suitable option for pain relief in children with acute abdominal pain in the emergency department.
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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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PDA-TOLERATE Trial: An Exploratory Randomized Controlled Trial of Treatment of Moderate-to-Large Patent Ductus Arteriosus at 1 Week of Age.
Clyman, RI, Liebowitz, M, Kaempf, J, Erdeve, O, Bulbul, A, Håkansson, S, Lindqvist, J, Farooqi, A, Katheria, A, Sauberan, J, et al
The Journal of pediatrics. 2019;:41-48.e6
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OBJECTIVE To compare early routine pharmacologic treatment of moderate-to-large patent ductus arteriosus (PDA) at the end of week 1 with a conservative approach that requires prespecified respiratory and hemodynamic criteria before treatment can be given. STUDY DESIGN A total of 202 neonates of <28 weeks of gestation age (mean, 25.8 ± 1.1 weeks) with moderate-to-large PDA shunts were enrolled between age 6 and 14 days (mean, 8.1 ± 2.2 days) into an exploratory randomized controlled trial. RESULTS At enrollment, 49% of the patients were intubated and 48% required nasal ventilation or continuous positive airway pressure. There were no differences between the groups in either our primary outcome of ligation or presence of a PDA at discharge (early routine treatment [ERT], 32%; conservative treatment [CT], 39%) or any of our prespecified secondary outcomes of necrotizing enterocolitis (ERT, 16%; CT, 19%), bronchopulmonary dysplasia (BPD) (ERT, 49%; CT, 53%), BPD/death (ERT, 58%; CT, 57%), death (ERT,19%; CT, 10%), and weekly need for respiratory support. Fewer infants in the ERT group met the rescue criteria (ERT, 31%; CT, 62%). In secondary exploratory analyses, infants receiving ERT had significantly less need for inotropic support (ERT, 13%; CT, 25%). However, among infants who were ≥26 weeks gestational age, those receiving ERT took significantly longer to achieve enteral feeding of 120 mL/kg/day (median: ERT, 14 days [range, 4.5-19 days]; CT, 6 days [range, 3-14 days]), and had significantly higher incidences of late-onset non-coagulase-negative Staphylococcus bacteremia (ERT, 24%; CT,6%) and death (ERT, 16%; CT, 2%). CONCLUSIONS In preterm infants age <28 weeks with moderate-to-large PDAs who were receiving respiratory support after the first week, ERT did not reduce PDA ligations or the presence of a PDA at discharge and did not improve any of the prespecified secondary outcomes, but delayed full feeding and was associated with higher rates of late-onset sepsis and death in infants born at ≥26 weeks of gestation. TRIAL REGISTRATION ClinicalTrials.gov: NCT01958320.
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Pain Management After Surgical Tonsillectomy: Is There a Favorable Analgesic?
Jotić, A, Savić Vujović, K, Milovanović, J, Vujović, A, Radin, Z, Milić, N, Vučković, S, Medić, B, Prostran, M
Ear, nose, & throat journal. 2019;(6):356-361
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The aim of this study was to examine how ibuprofen and paracetamol prevent pain after cold-steel extracapsular tonsillectomy in children. Also, we examined the relation between age, gender, nausea, postoperative bleeding, antibiotic use, type of diet, and postoperative pain intensity and the type of administered analgesic. A prospective study was conducted on 147 children (95 males and 52 females, aged 7-17 years) who underwent tonsillectomy in the Clinical-Hospital Center "Dragiša Mišović" from January 1 to June 30, 2016. The degree of pain was measured using a visual analog scale (VAS). We did not observe any significant differences in postoperative nausea, hospitalization rate postoperative bleeding, and antibiotic use between the paracetamol and ibuprofen groups. A test of within-patient effects showed that VAS scores changed significantly during the postoperative follow-up period (P = .00), but there were no significant differences between the groups (P = .778). After 12 hours, 29.3% of the patients on paracetamol and 21.8% on ibuprofen were transferred to a soft diet; after 24 hours, 84.8% of the paracetamol group and 85.5% of the ibuprofen group were on a soft diet (χ2 test, P < .05). There was a statistically significant correlation between VAS scores measured 4 hours after the surgery and the time of transference to the soft diet (Spearman ρ test, P < .001). The transfer to soft and normal diets was not significantly different between the 2 groups as assessed by the VAS scores (Pearson χ2 test, P = .565).There is still no consensus on the most effective postoperative pain-control regiment after tonsillectomy. This study showed that satisfactory pain management was achieved equally with both paracetamol and ibuprofen.
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An open-label, randomized, four-treatment crossover study evaluating the effects of salt form, acetaminophen, and food on the pharmacokinetics of phenylephrine.
Gelotte, CK
Regulatory toxicology and pharmacology : RTP. 2018;:333-338
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Phenylephrine hydrochloride (HCl) is a decongestant available in over-the-counter (OTC) medicines. Previously marketed prescription products contained phenylephrine tannate, an extended-release salt, which allowed dosing every 8-12 h. Given the regulatory history that cold medicines marketed before 1962 had limited supporting clinical data, and with widespread replacement of pseudoephedrine by phenylephrine in OTC products over the last ten years, the need for contemporary studies grew. This exploratory crossover study evaluated effects of salt form, acetaminophen, and food on phenylephrine pharmacokinetics and metabolites in healthy adults. Test treatments were 25 mg phenylephrine tannate (equivalent to 10 mg phenylephrine HCl) combined with 200 mg guaifenesin, fasted; 10 mg phenylephrine HCl combined with 650 mg acetaminophen, fasted; and 10 mg phenylephrine HCl, fed. The reference treatment was 10 mg phenylephrine HCl, fasted. Plasma phenylephrine pharmacokinetics and urine metabolites were determined. Although the tannate salt slowed phenylephrine absorption compared with the HCl salt, terminal concentrations were similar, suggesting that products containing the tannate salt should not be dosed less frequently than those containing the HCl salt. The premise that acetaminophen increases phenylephrine bioavailability by competition for presystemic sulfation was corroborated by increased phenylephrine sulfate in urine. Food delayed phenylephrine absorption, but not the total amount absorbed.
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Prior acetaminophen consumption impacts the early adaptive cellular response of human skeletal muscle to resistance exercise.
D'Lugos, AC, Patel, SH, Ormsby, JC, Curtis, DP, Fry, CS, Carroll, CC, Dickinson, JM
Journal of applied physiology (Bethesda, Md. : 1985). 2018;(4):1012-1024
Abstract
Resistance exercise (RE) is a powerful stimulus for skeletal muscle adaptation. Previous data demonstrate that cyclooxygenase (COX)-inhibiting drugs alter the cellular mechanisms regulating the adaptive response of skeletal muscle. The purpose of this study was to determine whether prior consumption of the COX inhibitor acetaminophen (APAP) alters the immediate adaptive cellular response in human skeletal muscle after RE. In a double-blinded, randomized, crossover design, healthy young men ( n = 8, 25 ± 1 yr) performed two trials of unilateral knee extension RE (8 sets, 10 reps, 65% max strength). Subjects ingested either APAP (1,000 mg/6 h) or placebo (PLA) for 24 h before RE (final dose consumed immediately after RE). Muscle biopsies (vastus lateralis) were collected at rest and 1 h and 3 h after exercise. Mammalian target of rapamycin (mTOR) complex 1 signaling was assessed through immunoblot and immunohistochemistry, and mRNA expression of myogenic genes was examined via RT-qPCR. At 1 h p-rpS6Ser240/244 was increased in both groups but to a greater extent in PLA. At 3 h p-S6K1Thr389 was elevated only in PLA. Furthermore, localization of mTOR to the lysosome (LAMP2) in myosin heavy chain (MHC) II fibers increased 3 h after exercise only in PLA. mTOR-LAMP2 colocalization in MHC I fibers was greater in PLA vs. APAP 1 h after exercise. Myostatin mRNA expression was reduced 1 h after exercise only in PLA. MYF6 mRNA expression was increased 1 h and 3 h after exercise only in APAP. APAP consumption appears to alter the early adaptive cellular response of skeletal muscle to RE. These findings further highlight the mechanisms through which COX-inhibiting drugs impact the adaptive response of skeletal muscle to exercise. NEW & NOTEWORTHY The extent to which the cellular reaction to acetaminophen impacts the mechanisms regulating the adaptive response of human skeletal muscle to resistance exercise is not well understood. Consumption of acetaminophen before resistance exercise appears to suppress the early response of mTORC1 activity to acute resistance exercise. These data also demonstrate, for the first time, that resistance exercise elicits fiber type-specific changes in the intracellular colocalization of mTOR with the lysosome in human skeletal muscle.
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Intravenous Dexketoprofen versus Intravenous Paracetamol for Dysmenorrhea: A Randomized Controlled Trial.
Serinken, M, Eken, C, Karcıoğlu, Ö
Balkan medical journal. 2018;(4):301-305
Abstract
BACKGROUND Dysmenorrhea is one of the most common acute pain disorders among women of reproductive age. AIMS To compare the effects of IV paracetamol with dexketoprofen in patients presenting with primary dysmenorrhea to the emergency department. STUDY DESIGN Randomized controlled trial. METHODS Patients over 18 years old presenting with pelvic pain related to menstruation were eligible for the study. Study patients received 1 g paracetamol or 50 mg dexketoprofen in 100 mL normal saline with a 4-5 minute infusion via the intravenous route. Pain intensity was measured by a visual analog scale at 15 and 30 minutes. Patients were randomized and assigned to either of two study arms via sealed envelopes. Study drugs were identical in color, and thus both personnel and patients were blinded to the study drug. The dexketoprofen group comprised 49 patients, and the paracetamol group had 50 patients in the final analysis. RESULTS The mean age of the study subjects was 20.9±2.5 and the mean duration of the pain was 1.9±1.7 (median: 1, interquartile range: 1 to 2) hours. Both dexketoprofen (median change: 33, 95% CI: 24 to 38) and paracetamol (median change: 21, 95% CI: 12 to 32) effectively reduced the pain at 15 minutes, which was repeated at 30 minutes (median change: 63, 95% CI: 57 to 65 vs 55.5, 95% CI: 50 to 59, respectively). Pain improvement in the dexketoprofen group was better than in the paracetamol group at 15 (median difference: 8, 95% CI: 0 to 16, p=0.048) and 30 (median difference: 6, 95% CI: 1 to 12, p=0.028) minutes, which was statistically significant but not clinically significant. CONCLUSION Dexketotoprofen has a better visual analogue scale score that is not clinically relevant compared to paracetamol.