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Investigation of sumatriptan and ketorolac trometamol in the human experimental model of headache.
Ghanizada, H, Al-Karagholi, MA, Arngrim, N, Mørch-Rasmussen, M, Metcalf-Clausen, M, Larsson, HBW, Amin, FM, Ashina, M
The journal of headache and pain. 2020;(1):19
Abstract
BACKGROUND Pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) induces headache in healthy volunteers but the precise mechanisms by which PACAP38 leads to headache are unclear. We investigated the headache preventive effect of sumatriptan and ketorolac on PACAP38-induced headache in healthy volunteers. In addition, we explored contribution of vascular mechanisms to PACAP38-induced headache using high resolution magnetic resonance angiography. METHODS Thirty-four healthy volunteers were divided in two groups (A and B) and received infusion of PACAP38 (10 picomol/kg/min) over 20 min. Group A was pretreated with intravenous sumatriptan (4 mg) or ketorolac (30 mg) 20 min before infusion of PACAP38. Group B received infusion of sumatriptan or ketorolac as post-treatment 90 min after infusion of PACAP38. In both experiments, we used a randomized, double-blind, cross-over design. We recorded headache characteristics and circumference of extra-intracerebral arteries. RESULTS We found no difference in AUC (0-6 h) of PACAP38-induced headache in group A, pretreated with sumatriptan or ketorolac (p = 0.297). There was no difference between sumatriptan and ketorolac in PACAP38-induced circumference change (AUCBaseline-110 min) of MMA (p = 0.227), STA (p = 0.795) and MCA (p = 0.356). In group B, post-treatment with ketorolac reduced PACAP38-headache compared to sumatriptan (p < 0.001). Post-treatment with sumatriptan significantly reduced the circumference of STA (p = 0.039) and MMA (p = 0.015) but not of MCA (p = 0.981) compared to ketorolac. In an explorative analysis, we found that pre-treatment with sumatriptan reduced PACAP38-induced headache compared to no treatment (AUC0-90min). CONCLUSIONS Post-treatment with ketorolac was more effective in attenuating PACAP38-induced headache compared to sumatriptan. Ketorolac exerted its effect without affecting PACAP38-induced arterial dilation, whereas sumatriptan post-treatment attenuated PACAP38-induced dilation of MMA and STA. Pre-treatment with sumatriptan attenuated PACAP38-induced headache without affecting PACAP38-induced arterial dilation. Our findings suggest that ketorolac and sumatriptan attenuated PACAP38-induced headache in healthy volunteers without vascular effects. TRIAL REGISTRATION Clinicaltrials.gov (NCT03585894). Registered 13 July 2018.
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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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Comparing Ketorolac With Ibuprofen for Postoperative Pain: A Randomized Clinical Trial.
Dwarica, DS, Pickett, SD, Zhao, YD, Nihira, MA, Quiroz, LH
Female pelvic medicine & reconstructive surgery. 2020;(4):233-238
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Abstract
OBJECTIVES The objective of this study was to identify differences in pain perception and satisfaction with pain control in women receiving nonsteroidal anti-inflammatory drugs postoperatively. METHODS This was a prospective, randomized controlled trial including urogynecology surgical patients. After surgery, all patients were randomized to receive either intravenous (IV) ketorolac or ibuprofen. The patients completed 3 visual analog scales (VAS) assessing pain at rest, pain with ambulation, and satisfaction with pain control. Postoperative opioid use was also measured. RESULTS A total of 224 patients (112 in each arm) were included. Pain scores (SD) at rest in all patients who received ketorolac versus those who received ibuprofen was 2.30 (2.1) versus 2.68 (2.34) (P = 0.20). Pain scores (SD) with ambulation was 3.94 (2.57) versus 4.16 (2.73) (P = 0.57) in patients who received ketorolac and ibuprofen, respectively. Patients who received ketorolac rated their satisfaction with their pain regimen similarly to those who received ibuprofen (P = 0.50). The average amount (SD) of hydromorphone used in the ketorolac and ibuprofen arm was 3.68 (4.58) mg and 4.04 (4.97) mg, respectively (P = 0.58). A subgroup analysis based on type of surgery showed decreased pain at rest (VAS, 2.77 vs 4.88; P = 0.04) and increased satisfaction (VAS, 1.69 vs 4.67; P = 0.003) in patients who had laparotomy and received ketorolac. CONCLUSIONS There was no difference in pain and satisfaction with IV ketorolac compared with IV ibuprofen in patients who underwent all modalities of urogynecologic surgery. A subgroup of patients who underwent laparotomy had less pain with ketorolac.
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Atomized intranasal vs intravenous fentanyl in severe renal colic pain management: A randomized single-blinded clinical trial.
Nazemian, N, Torabi, M, Mirzaee, M
The American journal of emergency medicine. 2020;(8):1635-1640
Abstract
OBJECTIVES Renal colic is one of the most common painful disorders in patients referred to the emergency department. The main purpose of this study was to compare the efficiency of two methods of intravenous (IVF) and intranasal (INF) fentanyl administration in pain management in patients with severe renal colic. MATERIALS & METHODS This was a single-blind randomized clinical trial performed on patients with severe renal colic. The severity of pain was ≥8 based on the Numerical Rating Scale (NRS). The efficacy of pain management was compared within and between the IVF (intramuscular Ketorolac + intravenous fentanyl) and INF (intramuscular Ketorolac + intranasal fentanyl) groups at different times points. Oral consent was obtained from all the patients. RESULTS Of 220 individuals, 96 (43.60%) were women and 124 (56.40%) were men. There were no significant differences between the two groups regarding the baseline pain severity, age, sex, history of urolithiasis and body mass index (BMI). The pain severity showed a significant reducing trend in both groups (p < 0.0001). There was also a significant difference comparing the mean pain severity between groups at different times (p < 0.0001). In each group, the severity of pain showed significant reduction compared with its prior measurement (P < 0.0001). CONCLUSION Fentanyl is highly effective in controlling pain in patients with severe renal colic referring to the emergency department. Intranasal administration of fentanyl combination with ketorolac can be an appropriate, non-invasive, easy-to-use and fast alternative to the intravenous method to manage pain in these patients.
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Whole-Course Application of Dexmedetomidine Combined with Ketorolac in Nonnarcotic Postoperative Analgesia for Patients with Lung Cancer Undergoing Thoracoscopic Surgery: A Randomized Control Trial.
Miao, Z, Wu, P, Wang, J, Zhou, FC, Lin, Y, Lu, XY, Lv, R, Hou, QH, Wen, QP
Pain physician. 2020;(2):E185-E193
Abstract
BACKGROUND Opioid-based postoperative analgesia provides adequate analgesia with much adverse effects and immunosuppression. Dexmedetomidine and ketorolac have properties of opioid-sparing, antiinflammation, and immune protection. OBJECTIVES To investigate the efficacy and safety of whole-course application of dexmedetomidine combined with ketorolac in nonnarcotic postoperative analgesia and its effect on inflammatory response and immune function in thoracoscopic surgery of lung cancer. STUDY DESIGN Double-blind, randomized control trial. SETTING The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China. METHODS Sixty patients scheduled for thoracoscopic surgery were enrolled and randomly divided into 2 groups to receive a combination of intraoperative usage of dexmedetomidine and postoperative patient-controlled intravenous analgesia of dexmedetomidine 0.1 µg/kg/h and ketorolac 3 mg/kg (DEX group) or only postoperative patient-controlled intravenous analgesia of sufentanil 1.5 µg/kg and ketorolac 3 mg/kg (SUF group) for 48 hours. Vital signs, postoperative Visual Analog Scale (VAS) score, Ramsay sedation score, patient-controlled analgesia pressing times, consumption of sufentanil and rescue drug, and complications were compared between the 2 groups. The levels of inflammatory factors and immune function were also compared. RESULTS A significant reduction in median blood pressures and heart rates within 48 hours after surgery and perioperative consumption of sufentanil were observed in the DEX group compared with the SUF group (P < 0.05). No statistically significant difference was found in VAS scores, patient-controlled analgesia pressing times, and rescue drug consumption between the 2 groups (P > 0.05). The incidence of nausea was significantly lower in the DEX group compared with the SUF group (P < 0.05). A significant decrease of interleukin (IL)-1 beta, IL-6, tumor necrosis factor (TNF)-alpha, and increased CD4+ and CD4+/CD8+ were observed in the DEX group compared with the SUF group at 24 and 48 hours after surgery (P < 0.05). There was no difference in the levels of CD8+ and natural killer cells between the 2 groups (P > 0.05). LIMITATIONS This study was limited by its sample size. CONCLUSIONS Whole-course application of dexmedetomidine combined with ketorolac in nonnarcotic postoperative analgesia provided adequate and safe postoperative analgesia, reduced sufentanil consumption, analgesia-related complications, alleviated inflammatory response, and immunosuppression compared with sufentanil-based analgesia in thoracoscopic surgery. KEY WORDS Dexmedetomidine, ketorolac, sufentanil, thoracoscopic surgery, postoperative analgesic, patient-controlled analgesia, inflammatory response, immune function.
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A randomized controlled trial comparing the efficacies of ketorolac and parecoxib for early pain management after total knee arthroplasty.
Laoruengthana, A, Rattanaprichavej, P, Reosanguanwong, K, Chinwatanawongwan, B, Chompoonutprapa, P, Pongpirul, K
The Knee. 2020;(6):1708-1714
Abstract
BACKGROUND Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to reduce pain after orthopedic surgery. Currently, selective COX-2 inhibitors can provide effective pain reduction with less platelet inhibition compared with conventional NSAIDs. We aimed to compare the analgesic effect and perioperative blood loss (PBL) after total knee arthroplasty (TKA) between ketorolac and parecoxib administration. METHODS We conducted a prospective randomized controlled study of 100 unilateral TKAs. The ketorolac group of 50 patients received an intraoperative periarticular injection (PAI) with 100 mg of bupivacaine and 30 mg of ketorolac. Afterwards, 30 mg of ketorolac was intravenously injected every 12 h until 48 h. In the parecoxib group of 50 patients, 20 mg of parecoxib was added to PAI, and the first intravenous dose was 20 mg followed by 40 mg every 12 h. The primary outcomes were visual analog scales (VASs) of postoperative pain, amount of morphine consumption, PBL, and blood transfusion rate. RESULTS The ketorolac group had a significantly lower VAS pain score than the parecoxib group at 6 h after TKA (2.38 ± 2.52 vs. 4.12 ± 2.86, P < 0.01). Thereafter, the VAS of both groups and total morphine consumption at 24 and 48 h were comparable. The PBLs of the ketorolac and parecoxib groups were 529.72 ± 263.02 and 402.40 ± 191.47 ml, respectively (P = 0.01). However, the blood transfusion rates between groups were not different. CONCLUSION Parecoxib provides comparable analgesic effects to ketorolac. Additionally, perioperative use of parecoxib is safe and is associated with significantly less blood loss after TKA.
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Influence of Ketorolac Supplementation on Pain Control for Knee Arthroscopy: A Meta-Analysis of Randomized Controlled Trials.
Wan, RJ, Liu, SF, Kuang, ZP, Ran, Q, Zhao, C, Huang, W
Orthopaedic surgery. 2020;(1):31-37
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INTRODUCTION The efficacy of ketorolac supplementation on pain control for knee arthroscopy remains controversial. We conduct a systematic review and meta-analysis to explore the impact of ketorolac supplementation on pain intensity after knee arthroscopy. METHODS We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through September 2018 for randomized controlled trials (RCTs) assessing the effect of ketorolac supplementation vs placebo on pain management after knee arthroscopy. This meta-analysis is performed using the random-effect model. RESULTS Ten RCTs involving 402 patients are included in the meta-analysis. Overall, compared with control group for knee arthroscopy, ketorolac supplementation is associated with notably reduced pain scores at 1 h (MD = -0.66; 95% CI = -1.12 to -0.21; P = 0.004) and 2 h (MD = -0.90; 95% CI = -1.74 to -0.07; P = 0.03), prolonged time for first analgesic requirement (MD = 1.94; 95% CI = 0.33 to 3.55; P = 0.02) and decreased number of analgesic requirement (RR = 0.41; 95% CI = 0.23 to 0.75; P = 0.003), but has no obvious impact on analgesic consumption (MD = -0.56; 95% CI = -1.14 to 0.02; P = 0.06), as well as nausea and vomiting (RR = 0.44; 95% CI = 0.12 to 0.21; P = 0.21). CONCLUSIONS Ketorolac supplementation is effective to produce pain relief for knee arthroscopy.
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Comparing the effects of 3 oxygen delivery methods plus intravenous ketorolac on primary headaches: A randomized clinical trial.
Saeedi, M, Shahvaran, SM, Ramezani, M, Rafiemanesh, H, Karimialavijeh, E
The American journal of emergency medicine. 2020;(1):55-59
Abstract
OBJECTIVE To compare three different oxygen therapy methods in primary headaches. METHODS Design: A randomized placebo-controlled clinical trial was conducted between January 2016 and October 2017. SETTING The emergency department of a university-affiliated urban hospital in Tehran, Iran. PARTICIPANTS Adult patients (aged 18 years and above) with moderate and severe primary headaches (VAS score of 4 or more). INTERVENTIONS Participants were allocated to one of four groups. Group A (n = 34) received 30 mg of intravenous ketorolac plus oxygen at 15 l/min (min) through a non-rebreather mask (NRB), group B (n = 34) received 30 mg of intravenous ketorolac plus 7 l/min of oxygen through a 60% venturi mask, group C (n = 34) received 30 mg of intravenous ketorolac plus 4 l/min of oxygen through a nasal cannula and group D (n = 34) received 30 mg of intravenous ketorolac and room air. MAIN OUTCOMES MEASURED Pain was assessed using the visual analog scale (VAS) at 0, 15, 30 and 60 min after admission. RESULTS Altogether, 136 patients were included. The most significant VAS change occurred in the NRB group at 30 min (p-value = 0.001). At this point, pain reduction in the NRB group was clinically higher than for the venturi and nasal cannula groups, but this effect had disappeared at 60 min. CONCLUSION Although the non-rebreather mask was significantly more effective at 30 min, after 60 min, none of the groups met the endpoint criterion of a 1.3-cm difference on the VAS scale.
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Effect of the Combination of Ketorolac and Bupivacaine on Transversus Abdominis Plane Block for Postoperative Analgesia After Gynecological Laparoscopic Surgery.
Jiang, Q, Huang, SQ, Jiao, J, Zhou, XM
Medical science monitor : international medical journal of experimental and clinical research. 2020;:e925006
Abstract
BACKGROUND This study assessed the additional benefits of bupivacaine when combined with ketorolac for transversus abdominis plane (TAP) block after gynecological laparoscopic surgery. MATERIAL AND METHODS This randomized, observer-blind trial recruited 153 patients who underwent gynecological laparoscopic surgery. Patients were randomly assigned to receive bupivacaine combined with ketorolac 15 mg/side for TAP block (TK group), bupivacaine for TAP block and 30 mg postoperative intravenous ketorolac (T group), or 30 mg postoperative intravenous ketorolac alone (C group). The primary endpoints included consumption of sufentanil for 24 h postoperatively, actual press times of the patient-controlled analgesia (PCA) pump, and effective press times of the PCA pump, whereas the secondary endpoints included numerical rating scale (NRS) pain scores at rest and during activity, satisfaction with analgesia, episodes of nausea and vomiting and length of hospital stay. RESULTS Sufentanil consumption, actual press times of the PCA pump, and effective press times of the PCA pump were lower in the TK and T groups than in the C group. NRS scores at rest and during activity at 1, 2, 4, 6, and 24 hours were significantly lower in the TK and T groups than in the C group. The TK and T groups showed greater satisfaction with analgesia than the C group, while the TK group showed greater overall satisfaction than the C group. Lengths of stay, rates of nausea and vomiting, and venting times did not differ significantly among the three groups. CONCLUSIONS Combined ketorolac and bupivacaine as TAP block improved the effectiveness of analgesia without increasing adverse events. Trial registration number: ChiCTR1900022577.
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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.