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Narrative review shows that the short-term use of ketorolac is safe and effective in the management of moderate-to-severe pain in children.
Marzuillo, P, Calligaris, L, Amoroso, S, Barbi, E
Acta paediatrica (Oslo, Norway : 1992). 2018;(4):560-567
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Abstract
UNLABELLED In June 2013, the European Medicine Agency recommended limiting codeine use in paediatric patients, creating a void in managing moderate pain. We reviewed the literature published in English (1985-June 2017) on the pharmacokinetic, pharmacodynamic and safety profile of ketorolac, a possible substitute for codeine and opioids, for treating moderate-to-severe pain. We found that gastrointestinal side effects were mainly reported with prolonged use, significant bleeding was reported in adenotonsillectomy, and adverse renal effects appeared to be limited to patients with specific coexisting risk factors. CONCLUSION The short-term use of ketorolac appears to be safe for children in many situations.
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Randomized controlled trial of intra-articular ketorolac on pain and inflammation after minor arthroscopic knee surgery.
Solheim, N, Gregersen, I, Halvorsen, B, Bjerkeli, V, Stubhaug, A, Gordh, T, Rosseland, LA
Acta anaesthesiologica Scandinavica. 2018;(6):829-838
Abstract
BACKGROUND Ketorolac is an effective non-steroidal anti-inflammatory drug, commonly used with local anaesthetics as part of local infiltration analgesia protocols following orthopaedic surgery. However, systemic uptake and drug action may be the major mechanism after local infiltration. The aims of this project were to study the effects of a small, systemically ineffective dose of ketorolac given intra-articularly for post-operative pain and also to study synovial inflammatory biomarkers. We investigated whether ketorolac affects pro-inflammatory biomarkers in an in vitro model, as well. METHODS In this placebo-controlled, blind, randomized study, we analysed intra-articular ketorolac (5 mg) in ambulatory minor knee surgery patients with moderate or severe pain (n = 44). We assessed post-operative pain intensity (n = 44) and analysed microdialysis samples taken from knee synovial tissue every 20 min (n = 34). We also tested cyclooxygenase-independent effects of ketorolac in synovial cells stimulated by prostaglandin E2 and chondroitin sulphate in vitro. RESULTS Intra-articular ketorolac (5 mg) administration did not reduce pain or synovial pro-inflammatory cytokines CXCL1, IL-8, and MCP-1, 0-120 min after knee arthroscopy. Female gender was a risk factor for moderate or severe pain (relative risk 1.45, 95% confidence interval 1.04-2.01). Paradoxically, ketorolac increased the release of CXCL1 and IL-8 in prostaglandin E2 and chondroitin sulphate-stimulated synovial cells in vitro. CONCLUSION Ketorolac prescribed at a low dose intra-articularly does not produce any detectable analgesic effect after minor knee surgery.
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Multi-Modal Pain Control in Ambulatory Hand Surgery.
Harrison, RK, DiMeo, T, Klinefelter, RD, Ruff, ME, Awan, HM
American journal of orthopedics (Belle Mead, N.J.). 2018;(6)
Abstract
We evaluated postoperative pain control and narcotic usage after thumb carpometacarpal (CMC) arthroplasty or open reduction and internal fixation (ORIF) of the distal radius in patients given opiates with or without other non-opiate medication using a specific dosing regimen. A prospective, randomized study of 79 patients undergoing elective CMC arthroplasty or ORIF of the distal radius evaluated postoperative pain in the first 5 postoperative days. Patients were divided into 4 groups: Group 1, oxycodone and acetaminophen PRN; Group 2, oxycodone and acetaminophen with specific dosing; Group 3, oxycodone, acetaminophen, and OxyContin with specific dosing; and Group 4, oxycodone, acetaminophen, and ketorolac with specific dosing. During the first 5 postoperative days, we recorded pain levels according to a numeric pain scale, opioid usage, and complications. Although differences in our data did not reach statistical significance, overall pain scores, opioid usage, and complication rates were less prevalent in the oxycodone, acetaminophen, and ketorolac group. Postoperative pain following ambulatory hand and wrist surgery under regional anesthesia was more effectively controlled with fewer complications using a combination of oxycodone, acetaminophen, and ketorolac with a specific dosing regimen.
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Efficacy of continuous in-wound infusion of levobupivacaine and ketorolac for post-caesarean section analgesia: a prospective, randomised, double-blind, placebo-controlled trial.
Wagner-Kovacec, J, Povalej-Brzan, P, Mekis, D
BMC anesthesiology. 2018;(1):165
Abstract
BACKGROUND In-wound catheters for infusion of local anaesthetic for post-caesarean section analgesia are well tolerated in parturients. Few studies have examined continuous in-wound infusion of a combination of local anaesthetic and non-steroidal anti-inflammatory drug for post-caesarean section analgesia. This single centre study evaluated post-operative analgesic efficacy and piritramide-sparing effects of continuous in-wound infusion of either local anaesthetic or non-steroidal anti-inflammatory agent, or the combination of both, versus saline placebo, when added to systemic analgesia with paracetamol. METHODS After National Ethical Board approval, 59 pregnant women scheduled for non-emergency caesarean section were included in this prospective, randomised, double-blind, placebo-controlled study. The parturients received spinal anaesthesia with levobupivacaine and fentanyl. Post-operative analgesia to 48 h included paracetamol 1000 mg intravenously every 6 h, with the studied agents as in-wound infusions. Rescue analgesia with piritramide was available as needed, titrated to 2 mg intravenously. Four groups were compared, using a subcutaneous multi-holed catheter connected to an elastomeric pump running at 5 mL/h over 48 h. The different in-wound infusions were: levobupivacaine 0.25% alone; ketorolac tromethamine 0.08% alone; levobupivacaine 0.25% plus ketorolac tromethamine 0.08%; or saline placebo. The primary outcome was total rescue piritramide used at 24 h and 48 h post-operatively, under maintained optimal post-caesarean section analgesia. RESULTS Compared to placebo in-wound infusions, ketorolac alone and levobupivacaine plus ketorolac in-wound infusions both significantly reduced post-operative piritramide consumption at 24 h (p = 0.003; p < 0.001, respectively) and 48 h (p = 0.001; p < 0.001). Compared to levobupivacaine, levobupivacaine plus ketorolac significantly reduced post-operative piritramide consumption at 24 h (p = 0.015) and 48 h (p = 0.021). For levobupivacaine versus ketorolac, no significant differences were seen for post-operative piritramide consumption at 24 h and 48 h (p = 0.141; p = 0.054). CONCLUSION Continuous in-wound infusion with levobupivacaine plus ketorolac provides greater opioid-sparing effects than continuous in-wound infusion with levobupivacaine alone. TRIAL REGISTRATION German Clinical Trials Register: retrospectively registered on 30 July, 2014, DRKS 00006559 .
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Antiplatelet Effect of Ketorolac in Children After Congenital Cardiac Surgery.
Kim, JS, Kaufman, J, Patel, SS, Manco-Johnson, M, Di Paola, J, da Cruz, EM
World journal for pediatric & congenital heart surgery. 2018;(6):651-658
Abstract
BACKGROUND Ketorolac is used for pediatric analgesia after surgery despite its known platelet inhibition via the arachidonic acid (AA) pathway. The degree of platelet inhibitory effect after cardiac surgery is not well characterized. Thromboelastography with platelet mapping (TEG-PM) is emerging as a frequently used test to evaluate platelet inhibition via the AA pathway. METHODS Post hoc analysis of a data set collected in a prospective observational cohort study evaluating platelet inhibition in children after congenital heart surgery with cardiopulmonary bypass (CPB). Categorization into two groups: (1) received ketorolac and (2) did not receive ketorolac for analgesia after surgery. The TEG-PM was evaluated at two time points (prior to surgery and 12-48 hours after CPB). RESULTS Fifty-three children were studied; mean age was 6.6 (range: 0.07-16.7) years and 45% (n = 24) were female. Participants were distributed into two groups by ketorolac use, 41 within the ketorolac group and 12 in the no ketorolac group. All 41 participants who received ketorolac had platelet inhibition and 11 (91.7%) of 12 participants who did not receive ketorolac had normal platelet function after surgery ( P < .0001). There was no difference in patient characteristics or clinical data between the two groups. CONCLUSIONS Ketorolac use in a cohort of children after congenital cardiac surgery was associated with platelet inhibition via the AA pathway when evaluated by TEG-PM.
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Use of Ketorolac After Outpatient Urogynecologic Surgery: A Randomized Control Trial.
Trowbridge, ER, Kim, D, Caldwell, L, Franko, D, Jackson, JN, Shilling, A, Hullfish, KL
Female pelvic medicine & reconstructive surgery. 2018;(4):281-286
Abstract
OBJECTIVE Patient surveys highlight a prevalence of moderate to severe pain in the postanesthesia care unit. Multimodal analgesia has been promoted to improve this with fewer opioid-induced adverse effects. The aim of this study was to evaluate the opioid sparing and analgesic effect of postoperative intravenous (IV) ketorolac after outpatient transvaginal surgery. METHODS Forty patients were enrolled in this institutional review board-approved, randomized, double-blind, placebo-controlled study, to receive either 30 mg of IV ketorolac or IV saline placebo postoperatively. Pain was assessed by visual analog scale at timed intervals. Narcotic pain medication was provided upon request. Narcotic use was reassessed by telephone 5 to 7 days postoperatively. Categorical characteristics were compared by χ. Continuous variables were evaluated by Mann-Whitney U test. RESULTS Twenty patients were randomized to each group. Groups were similar in age, health, and operative factors. There was no significant difference in mean pain scores at any interval. The ketorolac group had a total morphine equivalent consumption median of 7.5 mg versus 4.0 mg for placebo, which was not significant (P = 0.17). Total use of narcotic pills postoperatively was equivalent (median, 5). There was no difference in postoperative nausea. One Dindo grade II complication was reported in the ketorolac group of a postoperative pelvic hematoma requiring transfusion. DISCUSSION Intravenous ketorolac administered after outpatient transvaginal surgery did not result in a reduction of pain scores or total morphine consumption. There was one Dindo grade II complication in the ketorolac group. Larger randomized control trials are needed to validate these findings.
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Celecoxib versus ketorolac following robotic hysterectomy for the management of postoperative pain: An open-label randomized control trial.
Ulm, MA, ElNaggar, AC, Tillmanns, TD
Gynecologic oncology. 2018;(1):124-128
Abstract
OBJECTIVE Compare postoperative pain scores following hysterectomy in patients receiving perioperative celecoxib versus postoperative ketorolac as part of a multimodal pain regimen. METHODS Patients undergoing hysterectomy were randomized to receive scheduled intravenous ketorolac in the immediate postoperative period or oral celecoxib prior to surgery and continued for a total seven days. All patients received a common multimodal pain protocol consisting of scheduled acetaminophen, gabapentin, and opioids as needed. Inpatient pain scores and postoperative opioid use were analyzed. A questionnaire regarding outpatient opioid use and return to normal activities of daily living (ADLs) was returned two weeks postoperatively. RESULTS 192 patients were assessed for eligibility and 170 patients were randomized. Enrollment of patients undergoing open hysterectomy was closed prematurely for poor accruement (n = 32). 138 patients undergoing robotic hysterectomy were included were analyzed. There were no differences for inpatient pain scores (2.7 ± 1.9 v. 2.4 ± 1.6, p = 0.21). Average length of stay was similar between the two arms (11.6 ± 8.1 h v. 11.9 ± 7.6 h, p = 0.41). Patients in the celecoxib arm used less prescription opioids (6.0 ± 3.6 v. 8.1 ± 4.0, p = 0.001) and stopped using oral opioids earlier (3.8 ± 2.6 days v. 5.7 ± 2.8 days, p < 0.001). No differences were seen in inpatient opioid or anti-emetic usage, perioperative complications, or days to return to ADLs. CONCLUSIONS There was no difference in inpatient pain scores between patients who received celecoxib or ketorolac as part of multimodal pain control following robotic hysterectomy. Patients who received scheduled celecoxib for seven days after surgery used less prescription narcotics.
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Analgesic Effects of Locally Administered Ketorolac-based Analgesics After Breast Surgery: A Meta-Analysis of Randomized Controlled Trials.
Chen, JY, Feng, IJ, Loh, EW, Wang, LK, Lin, CC, Tam, KW
The Clinical journal of pain. 2018;(6):577-584
Abstract
OBJECTIVE Reducing postoperative pain following breast surgery is crucial for rapid recovery and shortening hospital stay. Ketorolac, a nonsteroidal anti-inflammatory drug, has been used as a postoperative analgesic in many surgical procedures. We conducted a systemic review and meta-analysis on the efficacy of locally administered ketorolac-based analgesics in managing pain after breast surgery. METHODS We searched the PubMed, Embase, Cochrane Library, Scopus, and ClinicalTrials.gov registry for randomized control trials (RCTs) published up to September 2016. The primary outcome was pain level assessed using a visual analog scale (VAS) at 1 and 6 hours following breast surgery. RESULTS We reviewed 4 RCTs with 255 patients. For meta-analysis, VAS at 1 and 6 hours of 3 similar RCTs were compared. At 1 hour, VAS scores were significantly lower in patients administered a ketorolac solution [weighted mean difference (WMD)=-2.04; 95% confidence interval (CI): -3.08 to -1.00] or ketorolac-bupivacaine solution (WMD=-2.30; 95% CI, -4.07 to -0.54) than in controls. At 6 hours, the ketorolac-bupivacaine solution reduced VAS scores significantly (WMD=-1.40; 95% CI, -2.48 to -0.32) compared with controls. However, at 1 hour, the ketorolac solution was significantly more effective than the bupivacaine solution was (WMD=-1.70; 95% CI, -2.81 to -0.59). DISCUSSION The effects of ketorolac-based analgesics vary as per the surgery and disease type. Locally administered ketorolac-based analgesics decreased postoperative pain in breast surgery patients, and the effect of local ketorolac was better than local bupivacaine. Therefore, ketorolac-based analgesics demonstrate considerable local infiltration during pain management after breast surgery.
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Effects of nefopam with fentanyl in intravenous patient-controlled analgesia after arthroscopic orthopedic surgery: a prospective double-blind randomized trial.
Oh, YN, Kim, KN, Jeong, MA, Kim, DW, Kim, JY, Ki, HS
Turkish journal of medical sciences. 2018;(1):142-149
Abstract
Background/aim: We performed this prospective randomized double-blind study to compare the effects of nefopam versus ketorolac in intravenous fentanyl-based patient-controlled analgesia (PCA) after shoulder arthroscopic orthopedic surgery. Materials and methods: Ninety-two patients were randomly divided into two groups to receive intravenous PCA. Patients were assigned to either the nefopam group (nefopam 120 mg and fentanyl 20 µg/kg) or the ketorolac group (ketorolac 2 mg/kg and fentanyl 20 µg/kg). Pain was assessed on a visual analogue scale (VAS) and a numeric rating scale (NRS). Additionally, patient satisfaction, adverse events, and vital signs were monitored. Results: There were no significant differences in VAS score (P = 0.48) or NRS score (P = 0.15) between the two groups. Similarly, patient satisfaction did not differ between the two groups [8.5(0.8) vs. 8.2(1.0), P = 0.14]. There were no statistically significant differences in the incidence of nausea (P = 0.72), vomiting (P = 0.46), urinary retention (P = 0.82), sweating (P = 0.49), or dizziness (P = 0.45) between the two groups. Likewise, there were no differences in heart rate [78.2(7.7) vs. 75.2(6.5), P = 0.18] or SpO2 [98.4(1.8) vs. 98.5(1.9), P = 0.83]. Conclusion: Nefopam is an appropriate alternative for co-administration with fentanyl-based PCA in patients who have difficulty using nonsteroidal antiinflammatory drugs.
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Effect of phenylephrine 1.0%-ketorolac 0.3% injection on tamsulosin-associated intraoperative floppy-iris syndrome.
Silverstein, SM, Rana, VK, Stephens, R, Segars, L, Pankratz, J, Rana, S, Juzych, MS, Nariman, N
Journal of cataract and refractive surgery. 2018;(9):1103-1108
Abstract
PURPOSE To determine the effect of phenylephrine 1.0%-ketorolac 0.3% injection (Omidria) on different components of intraoperative floppy-iris syndrome (IFIS). SETTING Silverstein Eye Centers, Kansas City, Missouri, USA. DESIGN Prospective case series. METHODS Men treated with tamsulosin having standard cataract extraction surgery were placed in a treatment group that received phenylephrine 1.0%-ketorolac 0.3% injection in the irrigation solution and a control group) that received basic saline solution. Every procedure was video recorded using an endocyclophotocoagulation (ECP) probe and microscopic view. Pupil dilation, iris billowing, and iris prolapse were measured using a micrometer, ECP recording grading scale, and microscopic recordings, respectively. RESULTS Each group (treatment and control) comprised 25 eyes of 25 patients. Although both groups had a decrease in pupil diameter before and after cataract extraction and before cataract extraction and after intraocular lens implantation, the changes were statistically significantly greater in the treatment group. Iris prolapse occurred in 3 patients (12.0%) in the treatment group and 14 patients (56.0%) in the control group (P < .001). Stage 3 (severe) pupil billowing occurred in 1 eye (4.0%) in the treatment group and 10 eyes (40.0%) in the control group (P < .001). CONCLUSIONS The use of the phenylephrine 1.0%-ketorolac 0.3% injection combination added to the irrigating solution during cataract surgery in patients at risk for IFIS led to significantly better prevention of miosis, less pupil billowing, and a reduced incidence of iris prolapse. A new grading scale for intraoperative iris abnormalities might be used for future evaluation.