Intravenous ibuprofen versus ketorolac for perioperative pain control in open abdominal hysterectomy: a randomized controlled trial.

BACKGROUND: We aimed to compare the analgesic effects of intravenous ibuprofen to ketorolac after open abdominal hysterectomy. METHODS: This randomized double-blinded controlled trial included adult women scheduled for elective open abdominal hysterectomy. Participants were randomized to receive either 30 mg ketorolac (n = 50) or 800 mg ibuprofen (n = 50) preoperatively, then every 8 h postoperatively for 24 h. All participants received paracetamol 1 gm/6 h. Rescue analgesic was given if the visual analogue scale (VAS) for pain assessment was > 3. The primary outcome was the mean postoperative dynamic VAS during the first 24 h. Secondary outcomes were static VAS, intraoperative fentanyl consumption, postoperative morphine consumption, time to independent movement, and patient's satisfaction. RESULTS: Forty-six patients in the ibuprofen group and fifty patients in the ketorolac group were analyzed. The 24-h dynamic and static VAS were similar in the two groups. The median (quartiles) dynamic VAS was 1.1 (0.9, 1.9) in the ibuprofen group versus 1.0 (0.7, 1.3) in the ketorolac group, P-value = 0.116; and the median (quartiles) static VAS was 0.9 (0.6, 1.3) in the ibuprofen group versus 0.7 (0.4, 1.1) in the ketorolac group, P-value = 0.113. The intra- and postoperative analgesic requirements were also similar in the two groups. However, patient satisfaction was slightly higher in the ketorolac group than that in the ibuprofen group (median [quartiles]: 6 [5, 7] versus 5 [4, 7], respectively), P-value: 0.009. CONCLUSION: The two drugs, intravenous ibuprofen and ketorolac produced similar analgesic profile in patients undergoing open abdominal hysterectomy receiving multimodal analgesic regimen. NCT05610384, Date of registration: 09/11/2022 CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05610384. https://clinicaltrials.gov/ct2/show/NCT05610384.

Opioid-Sparing Nonsteroid Anti-inflammatory Drugs Protocol in Patients Undergoing Intramedullary Nailing of Tibial Shaft Fractures: A Randomized Control Trial.

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective analgesics commonly used in fracture management. Although previously associated with delayed fracture healing, multiple studies have demonstrated their safety, with minimal risks of fracture healing. Given the current opioid crisis in the United States, alternate pain control modalities are essential to reduce opioid consumption. This study aims to determine whether the combination of oral acetaminophen and intravenous ketorolac is a viable alternative to opioid-based pain management in closed tibial shaft fractures treated with intramedullary nailing. METHODS: We conducted a randomized controlled trial evaluating postoperative pain control and opioid consumption in patients with closed tibial shaft fractures who underwent intramedullary nailing. Patients were randomized into an NSAID-based pain control group (52 patients) and an opioid-based pain control group (44 patients). Visual analog scale (VAS) scores and morphine milligram equivalents (MMEs) were evaluated at 12-hour postoperative intervals during the first 48 hours after surgery. Nonunion and delayed healing rates were recorded for both groups. RESULTS: A statistically significant decrease in MMEs was noted at every measured interval (12, 24, 36, and 48 hours) in the NSAID group compared with the opioid group ( P -value 0.001, 0.001, 0.040, 0.024, respectively). No significant change in visual analog scale scores was observed at 12, 36, and 48 hours between both groups ( P -value 0.215, 0.12, and 0.083, respectively). A significant decrease in VAS scores was observed at the 24-hour interval in the NSAID group compared with the opioid group ( P -value 0.041). No significant differences in union rates were observed between groups ( P -value 0.820). DISCUSSION: Using an NSAID-based postoperative pain protocol led to a decrease in opioid consumption without affecting pain scores or union rates. Owing to the minimal risk of short-term NSAID use, their role in the perioperative management of tibia shaft fractures is justified, especially when they reduce opioid consumption markedly. LEVEL OF EVIDENCE: Therapeutic Level I.

Systemic absorption and gastrointestinal adverse effects from topical ketorolac and diclofenac ophthalmic solutions in healthy dogs.

OBJECTIVE: To investigate systemic absorption and gastrointestinal (GI) adverse effects of topical ketorolac 0.5% and diclofenac 0.1% ophthalmic solutions. ANIMALS: 11 healthy purpose-bred Beagles. METHODS: Dogs were randomly assigned to receive either ketorolac (n = 6) or diclofenac (5), 1 drop in both eyes 4 times daily for 28 days. Upper GI endoscopy was performed on days 0 and 29 with mucosal lesion scores (0 to 7) assigned to each region evaluated. Plasma samples were collected on days 14, 21, and 28 for measurement of diclofenac and ketorolac using high-performance liquid chromatography-mass spectrometry. RESULTS: GI erosions and/or ulcers developed in all ketorolac-treated dogs and 1 of 5 diclofenac-treated dogs. Post-treatment mucosal lesion score for the antrum was higher in the ketorolac group than in the diclofenac group (P = .006) but not significantly different for any other region. Post-treatment antral mucosal lesion scores were significantly related to plasma ketorolac concentrations (P < .001). Ketorolac and diclofenac were detected in the plasma at all time points (median ketorolac day 14, 191 ng/mL; day 21, 173.5 ng/mL; and day 28, 179.5 ng/mL; and median diclofenac day 14, 21.1 ng/mL; day 21, 20.6 ng/mL; day 28, 27.5 ng/mL). Vomiting and decreased appetite events were observed uncommonly and were not significantly different between treatment groups. CLINICAL RELEVANCE: GI ulceration and erosion developed after ophthalmic administration of ketorolac and diclofenac, with higher plasma concentrations and more severe GI lesions associated with ketorolac. Clients should be alerted to this potential risk with ophthalmic use and informed to watch for systemic clinical signs that would warrant veterinary reevaluation.

Does Scheduled Low-Dose Short-Term NSAID (Ketorolac) Modulate Cytokine Levels After Orthopaedic Polytrauma? A Secondary Analysis of a Randomized Clinical Trial.

OBJECTIVES: To determine whether scheduled low-dose, short-term ketorolac modulates cytokine concentrations in orthopaedic polytrauma patients. DESIGN: Secondary analysis of a double-blinded, randomized controlled trial. SETTING: Single Level I trauma center from August 2018 to October 2022. PATIENT SELECTION CRITERIA: Orthopaedic polytrauma patients between 18 and 75 years with a New Injury Severity Score greater than 9 were enrolled. Participants were randomized to receive 15 mg of intravenous ketorolac every 6 hours for up to 5 inpatient days or 2 mL of intravenous saline similarly. OUTCOME MEASURES AND COMPARISONS: Daily concentrations of prostaglandin E2 and interleukin (IL)-1a, IL-1b, IL-6, and IL-10. Clinical outcomes included hospital and intensive care unit length of stay, pulmonary complications, and acute kidney injury. RESULTS: Seventy orthopaedic polytrauma patients were enrolled, with 35 participants randomized to the ketorolac group and 35 to the placebo group. The overall IL-10 trend over time was significantly different in the ketorolac group ( P = 0.043). IL-6 was 65.8% higher at enrollment compared to day 3 ( P < 0.001) when aggregated over both groups. There was no significant treatment effect for prostaglandin E2, IL-1a, or IL-1b ( P > 0.05). There were no significant differences in clinical outcomes between groups ( P > 0.05). CONCLUSIONS: Scheduled low-dose, short-term, intravenous ketorolac was associated with significantly different mean trends in IL-10 concentration in orthopaedic polytrauma patients with no significant differences in prostaglandin E2, IL-1a, IL-1b, or IL-6 levels between groups. The treatment did not have an impact on clinical outcomes of hospital or intensive care unit length of stay, pulmonary complications, or acute kidney injury. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Neurotrophic Keratopathy after wide retinal endolaser and postoperative Ketorolac eye drops: A case series.

PURPOSE: We report a series of 5 cases, happened in a period of 5 months, who developed neurotrophic keratopathy (NK) following pars plana vitrectomy (PPV) and retinal endolaser for rhegmatogenous retinal detachment (RRD). In our several decennary experience of surgical center predominantly based on vitreoretinal surgery, we had rare cases of postoperative NK. These recent cases of post-surgical NK happened contextually to our change of postoperative non-steroidal anti-inflammatory drugs (NSAIDs) drops, based on Ketorolac Tromethamine 0.5% eye drops. CASES PRESENTATION: Five patients with a mean age of 61 ± 7.3 years were treated with one or more PPV with intraoperative peripheral endolaser for RRD. Nobody had previous herpetic keratitis, systemic disease like diabetes mellitus or other predisposing factors for NK. In the postoperative period, all patients received Ketorolac Tromethamine 0.5% eye drops for a mean period of 54 ± 25 days. During follow-up visits they developed NK and they were successfully treated with suspension of Ketorolac eye drops, application of therapeutic contact lens or amniotic membrane patch and topical lubricant therapy. CONCLUSIONS: Postoperative Ketorolac eye drops, in patients who underwent PPV with endolaser, may reduce the corneal sensitivity, predispose to epithelial disruption and NK development. Studies are needed to explore the effect of NSAIDs on corneal sensitivity reduction in patient who will undergo PPV and extensive endolaser.

Comparison of Preemptive Effect of Intravenous Ketorolac Versus Nalbuphine on Postoperative Shivering and Pain in Patients Undergoing Surgery Under Spinal Anesthesia: A Prospective, Randomized, Double-Blind Study.

BACKGROUND: Postoperative pain and postanesthesia shivering are the two common problems in patients undergoing surgery under spinal anesthesia (SA). The present study aimed to compare the preemptive prescription of the single dose of intravenous (IV) ketorolac versus nalbuphine on postoperative shivering and pain in patients undergoing surgery under SA. METHODS: Present study was a prospective, randomized double-blind study, conducted on patients of either gender, with American Society of Anesthesiologists physical status class I or II, aged 21-60 years, posted for elective lower abdominal surgeries under SA. Patients were randomized by computer-generated random numbers into two groups of 50 patients each: group N (received 0.2 mg/kg nalbuphine IV) and group K (received 0.5 mg/kg ketorolac IV). RESULTS: The incidence of postoperative shivering was 22 % and 36 % in groups N and K respectively and the difference was statistically significant. The first request for analgesia (minutes) was later in group N (295.17 ± 54.62) than in group K (223.80 ± 15.34) and the difference was statistically significant. Increased total analgesic consumption was noted more in group K (131.34 ± 43.27) than in group N (79.23 ± 21.34), and the difference was statistically significant (P < 0.0001). The incidence of side effects was comparable among both groups. CONCLUSION: Preemptive nalbuphine had less incidence of postoperative shivering, delayed first request for analgesia, and less total analgesic consumption than ketorolac in patients undergoing surgery under SA.

Comparación de ibuprofeno y ketorolaco intravenosos para analgesia postoperatoria en niños tratados mediante cirugía de la zona inferior del abdomen: estudio aleatorizado, controlado y de no inferioridad / Comparison of intravenous ibuprofen versus ketorolac for postoperative analgesia in children undergoing lower abdominal surgery: A randomized, controlled, non-inferiority study

Antecedentes: A menudo se utilizan antiinflamatorios no esteroideos para analgesia multimodal, para controlar el dolor postoperatorio. El objetivo de este estudio aleatorizado, controlado, doble ciego y de no inferioridad fue comparar los efectos analgésicos postoperatorios de ibuprofeno y ketorolaco intravenosos en niños tratados mediante cirugía unilateral abierta de la zona inferior del abdomen. Los autores supusieron que la analgesia postoperatoria producida por ibuprofeno intravenoso no sería inferior a la de ketorolaco intravenoso. Métodos: Sesenta y seisniños de 2 a 8 años de edad fueron programados para cirugía unilateral de la zona inferior del abdomen. Los pacientes del grupo ibuprofeno recibieron 10mg/kg/6h de ibuprofeno intravenoso y los pacientes del grupo ketorolaco recibieron 0,5mg/kg/6h de ketorolaco por vía intravenosa. La medida del objetivo primario fue el consumo morfina postoperatoria durante 24h. Las medidas del resultado secundario fueron la puntuación del dolor postoperatorio, la incidencia de fiebre postoperatoria temprana y la incidencia de efectos adversos relativos a ibuprofeno y ketorolaco incluyendo dolor durante la infusión del fármaco, vómitos, dolor epigástrico y reacción alérgica. Resultados: Cincuenta y nuevepacientes completaron el estudio (30 de ibuprofeno y 29 de ketorolaco). No se produjo diferencia significativa (p=0,305) en cuanto a consumo medio (desviación estándar) de morfina postoperatoria durante 24h (μ/kg) entre el grupo ibuprofeno, 160 (5,31), y el grupo ketorolaco, 14,65 (4,61). Las puntuaciones de dolor reportadas fueron similares en ambos grupos. La incidencia de fiebre postoperatoria fue significativamente menor (p=0,039) en el grupo ibuprofeno (3%) que en el grupo ketorolaco (20%). La incidencia de efectos adversos fue similar en ambos grupos.(AU)

Background: Non-steroidal anti-inflammatory drugs are often used as part of multimodal analgesia to control postoperative pain. This randomized, controlled, double-blinded, non-inferiority study aimed to compare the postoperative analgesic effects of intravenous ibuprofen versus ketorolac in children undergoing open unilateral lower abdominal surgery. The authors hypothesized that postoperative analgesia produced by intravenous ibuprofen would be non-inferior to that of intravenous ketorolac. Methods: Sixty-six children aged 2 to 8 years who were scheduled to undergo unilateral lower abdominal surgery, were recruited. Patients in the ibuprofen group received 10mg/kg/6h intravenous ibuprofen. Patients in the ketorolac group were given 0.5mg/kg/6h intravenous ketorolac. The primary outcome measure was 24-h postoperative morphine consumption. The secondary outcome measures were postoperative pain score, the incidence of early postoperative fever and the incidence of ibuprofen and ketorolac adverse effects including pain during drug infusion, vomiting, epigastric pain and allergic reaction. Results: Fifty-nine patients completed the study (30 ibuprofen, 29 ketorolac). There was no significant difference (P=.305) in the mean (SD) 24-h postoperative morphine consumption (μ/kg) between intravenous ibuprofen, 16.00 (5.31), and ketorolac, 14.65 (4.61). The reported pain scores were similar in both groups. The incidence of postoperative fever was significantly lower (p=0.039) in the ibuprofen group (3%) than the ketorolac group (20%). The incidence of adverse effects was similar in both ibuprofen and ketorolac groups. Conclusions: Intravenous ibuprofen can be used as an alternative to ketorolac for postoperative analgesia in children undergoing unilateral lower abdominal surgery because both drugs similarly provide safe and effective postoperative analgesia.(AU)

The Effect of Perianal Tramadol Infiltration on Postoperative Pain Following Hemorrhoidectomy.

INTRODUCTION: The present study was attempted to evaluate the effect of perianal infiltration of tramadol on postoperative pain in patients undergoing hemorrhoidectomy. METHOD: This double-blind clinical trial study was carried out on 90 patients with grade 3 and 4 hemorrhoids undergoing hemorrhoidectomy. Patients were randomly assigned into 3 groups of control or bupivacaine or tramadol. Before the surgery, perianal infiltration of .25% bupivacaine or tramadol or normal saline was prescribed to each group, respectively. Data on pain severity (based on the visual analog scale (VAS), the duration of surgery, sedation score, pain at the first defecation, first request time for additional analgesia, nausea and vomiting, and analgesic intakes) were evaluated and analyzed. RESULTS: Duration of surgery was almost similar in all 3 groups (P = .974). The results showed a significant difference in pain score between 3 groups (P ≤.05) at all times after the surgery. In addition, the means of sedation scores (P = .03), pain score at the first defecation (P = .001), the time to first analgesic request (P = .001), and ketorolac administration times (P = .01) were significantly different between 3 groups. Finally, no complication was reported regarding postoperative nausea and vomiting. CONCLUSION: Given the notable efficacy of tramadol in reducing pain after hemorrhoidectomy and its minor side effects, this medication is suggested as an effective topical anesthetic to decrease pain after hemorrhoidectomy.

Randomised trial of IV metoclopramide vs IV ketorolac in treatment of acute primary headaches.

INTRODUCTION: Headache is one of the most common neurological conditions among emergency department visits (ED), although the best therapy has not been identified yet. Therefore, in the current study, we aimed to compare the pain-relieving effect of metoclopramide and ketorolac in acute primary headaches patients. METHODS: This double-blind, randomised clinical trial was conducted at Golestan Hospital, Ahvaz, Iran. This research involved all adult patients with acute primary (migraine or tension-type) headaches presented to the ED. Pain intensity was assessed with 0 to 10 verbal Numeric Rating Scales (NRS). The subjects were randomised into 10 mg intravenous (IV) metoclopramide or 30 mg IV ketorolac groups. Pain score and drug adverse reactions were compared between the two groups at baseline, 15, 30, and 60 min after baseline. RESULTS: 108 patients completed this trial and were equally divided into two groups (mean age of 34 ± 8.54 years; 57.4% female). Before treatment, the mean pain score was 6.9 and 6.8 in metoclopramide and ketorolac groups, respectively (p > 0.05). Metoclopramide failed to provide more improvement in pain score at 30 min (p = 0.55) and 60 min (p = 0.15) from baseline. There were no serious adverse events in this study. Only five patients required rescue medication which four of them were in ketorolac group. CONCLUSION: We were unable to reject the null hypothesis that there would be no difference in pain outcomes between metoclopramide and ketorolac.

Comparing two doses of intramuscular ketorolac for treatment of acute musculoskeletal pain in a military emergency department.

STUDY OBJECTIVE: The goal of the study was to assess a low-dose versus a high-dose of intramuscular (IM) ketorolac for non-inferiority in adults with acute MSK pain in an emergency department (ED). METHODS: This was a single-blinded, randomized controlled, non-inferiority trial of adults presenting to an ED with a chief complaint of acute MSK pain. Patients were randomized to either a 15 mg or a 60 mg IM ketorolac dose. The primary outcome was the mean difference of change in pain from baseline to 60-min between the two groups as reported on a 100-mm (mm) visual analog scale (VAS). Secondary outcomes included the mean difference of change in VAS scores at 30-min and the incidence of reported adverse effects associated with the administration of ketorolac. RESULTS: One hundred ten patients were randomized with 55 in each group. The mean difference in pain between groups at 60-min (0.2 mm [95% CI -8.5-8.7]; p = .98) and 30 min (-1.7 mm [95% CI -8.5-5.1; p = .63) was less than the predetermined non-inferiority margin of 13 mm. There were no major adverse effects reported. Minor adverse effects were more frequent in the 60 mg group (n = 9; 16.4% vs. n = 1; 1.8%; p = .016) with burning at the injection site being the most commonly reported. CONCLUSIONS: A 15 mg dose of IM ketorolac was found to be non-inferior to a 60 mg dose for acute MSK pain in adults presenting to the ED. Discontinuing the practice of ordering 60 mg doses of IM ketorolac in place of a lower dose for acute MSK pain should be considered.

The Analgesic Benefits of Ketorolac to Local Anesthetic Wound Infiltration Is Statistically Significant But Clinically Unimportant: A Comprehensive Systematic Review and Meta-Analysis.

Objective: Even though ketorolac-infiltration is said to provide superior postoperative analgesic benefits in different surgical procedures, its safety and efficacy remain to be validated because of the lack of high-quality evidence. We aimed to summarize the efficacy and safety of ketorolac-infiltration based on published randomized-controlled trials (RCTs). Approach: This work followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, assessing the methodological quality of systematic reviews and the Cochrane Collaboration recommendations. We searched for RCTs evaluating the efficacy of ketorolac-infiltration in adults in the PubMed, Web of Science, Embase, Cochrane Library, Chinese databases, and Google Scholar. The two co-primary outcomes of this meta-analysis were rescue analgesic consumption in the 24-h postoperative period and rest pain scores. Results: Twelve trials (761 patients) were analyzed. Ketorolac-infiltration provided a clinically unimportant benefit in morphine consumption (mean difference, -2.81 mg; 95% confidence interval [CI], -5.11 to -0.50; p = 0.02; moderate-quality evidence). Low-to-moderate quality evidence supported a brief (2-6 h), clinically subtle, but statistically consistent effect of surgical site ketorolac-infiltration in reducing wound pain at rest. High-quality evidence supported shorter hospital stays for surgical patients receiving local ketorolac-infiltration when compared to controls (mean difference, -0.12 days; 95% CI, -0.17 to -0.08; p < 0.00001). Further, ketorolac-infiltration does not improve any opioid-related side effects. Innovation: Ketorolac-infiltration provides statistically significant but clinically unimportant benefits for improving postoperative wound pain. Conclusion: Overall, despite the fact that current moderate-to-high quality of evidence does not support routine using of ketorolac as an adjuvant to local anesthetic for wound infiltration, these findings underscore the importance of optimizing agents and sustained delivery parameters in postoperative local anesthetic practice. Clinical Trials.gov ID: CRD42021229095.

Single-dose intravenous ketorolac for acute postoperative pain in adults.

BACKGROUND: Postoperative pain is common and may be severe. Postoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) reduces patient opioid requirements and, in turn, may reduce the incidence and severity of opioid-induced adverse events (AEs). OBJECTIVES: To assess the analgesic efficacy and adverse effects of single-dose intravenous ketorolac, compared with placebo or an active comparator, for moderate to severe postoperative pain in adults. SEARCH METHODS: We searched the following databases without language restrictions: CENTRAL, MEDLINE, Embase and LILACS on 20 April 2020. We checked clinical trials registers and reference lists of retrieved articles for additional studies. SELECTION CRITERIA: Randomized double-blind trials that compared a single postoperative dose of intravenous ketorolac with placebo or another active treatment, for treating acute postoperative pain in adults following any surgery. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane.  Our primary outcome was the number of participants in each arm achieving at least 50% pain relief over a four- and six-hour period. Our secondary outcomes were time to and number of participants using rescue medication; withdrawals due to lack of efficacy, adverse events (AEs), and for any other cause; and number of participants experiencing any AE, serious AEs (SAEs), and NSAID-related or opioid-related AEs. For subgroup analysis, we planned to analyze different doses of parenteral ketorolac separately and to analyze results based on the type of surgery performed. We assessed the certainty of evidence using GRADE. MAIN RESULTS: We included 12 studies, involving 1905 participants undergoing various surgeries (pelvic/abdominal, dental, and orthopedic), with 17 to 83 participants receiving intravenous ketorolac in each study. Mean study population ages ranged from 22.5 years to 67.4 years. Most studies administered a dose of ketorolac of 30 mg; one study assessed 15 mg, and another administered 60 mg. Most studies had an unclear risk of bias for some domains, particularly allocation concealment and blinding, and a high risk of bias due to small sample size. The overall certainty of evidence for each outcome ranged from very low to moderate. Reasons for downgrading certainty included serious study limitations, inconsistency and imprecision. Ketorolac versus placebo Very low-certainty evidence from eight studies (658 participants) suggests that ketorolac results in a large increase in the number of participants achieving at least 50% pain relief over four hours compared to placebo, but the evidence is very uncertain (risk ratio (RR) 2.81, 95% confidence interval (CI) 1.80 to 4.37). The number needed to treat for one additional participant to benefit (NNTB) was 2.4 (95% CI 1.8 to 3.7). Low-certainty evidence from 10 studies (914 participants) demonstrates that ketorolac may result in a large increase in the number of participants achieving at least 50% pain relief over six hours compared to placebo (RR 3.26, 95% CI 1.93 to 5.51). The NNTB was 2.5 (95% CI 1.9 to 3.7). Among secondary outcomes, for time to rescue medication, moderate-certainty evidence comparing intravenous ketorolac versus placebo demonstrated a mean median of 271 minutes for ketorolac versus 104 minutes for placebo (6 studies, 633 participants). For the number of participants using rescue medication, very low-certainty evidence from five studies (417 participants) compared ketorolac with placebo. The RR was 0.60 (95% CI 0.36 to 1.00), that is, it did not demonstrate a difference between groups. Ketorolac probably results in a slight increase in total adverse event rates compared with placebo (74% versus 65%; 8 studies, 810 participants; RR 1.09, 95% CI 1.00 to 1.19; number needed to treat for an additional harmful event (NNTH) 16.7, 95% CI 8.3 to infinite, moderate-certainty evidence). Serious AEs were rare. Low-certainty evidence from eight studies (703 participants) did not demonstrate a difference in rates between ketorolac and placebo (RR 0.62, 95% CI 0.13 to 3.03). Ketorolac versus NSAIDs  Ketorolac was compared to parecoxib in four studies and diclofenac in two studies. For our primary outcome, over both four and six hours there was no evidence of a difference between intravenous ketorolac and another NSAID (low-certainty and moderate-certainty evidence, respectively). Over four hours, four studies (337 participants) produced an RR of 1.04 (95% CI 0.89 to 1.21) and over six hours, six studies (603 participants) produced an RR of 1.06 (95% CI 0.95 to 1.19). For time to rescue medication, low-certainty evidence from four studies (427 participants) suggested that participants receiving ketorolac waited an extra 35 minutes (mean median 331 minutes versus 296 minutes). For the number of participants using rescue medication, very low-certainty evidence from three studies (260 participants) compared ketorolac with another NSAID. The RR was 0.90 (95% CI 0.58 to 1.40), that is, there may be little or no difference between groups.   Ketorolac probably results in a slight increase in total adverse event rates compared with another NSAID (76% versus 68%, 5 studies, 516 participants; RR 1.11, 95% CI 1.00 to 1.23; NNTH 12.5, 95% CI 6.7 to infinite, moderate-certainty evidence). Serious AEs were rare. Low-certainty evidence from five studies (530 participants) did not demonstrate a difference in rates between ketorolac and another NSAID (RR 3.18, 95% CI 0.13 to 76.99). Only one of the five studies reported a single serious AE. AUTHORS' CONCLUSIONS: The amount and certainty of evidence for the use of intravenous ketorolac as a treatment for postoperative pain varies across efficacy and safety outcomes and amongst comparators, from very low to moderate. The available evidence indicates that postoperative intravenous ketorolac administration may offer substantial pain relief for most patients, but further research may impact this estimate. Adverse events appear to occur at a slightly higher rate in comparison to placebo and to other NSAIDs. Insufficient information is available to assess whether intravenous ketorolac has a different rate of gastrointestinal or surgical-site bleeding, renal dysfunction, or cardiovascular events versus other NSAIDs. There was a lack of studies in cardiovascular surgeries and in elderly populations who may be at increased risk for adverse events.

The efficacy of periarticular injection intraoperatively for mini-open rotator cuff repair: A comparative study.

BACKGROUND: The optimal postoperative analgesia after open rotator cuff repair surgery remains unclear. This study compared the use of a multimodal pain regimen including periarticular injection (PAI), with a control condition. We hypothesized that PAI leads to decreased opioid consumption and lower pain scores. METHODS: The perioperative analgesic regimen was standardized and implemented from January 1, 2017 to December 31, 2017. The PAI was administered from July 1, 2017 to December 31, 2017. The historical control group was enrolled from January 1, 2017 to June 30, 2017. The evaluation items included assessments of pain using a 10-point visual analog scale (VAS) before and after the mini-open rotator cuff repair and on postoperative days 1, 2, and 3. The dose of ketorolac suppository and its side effects were also evaluated. RESULTS: The VAS score on the day of the operation was significantly low in the PAI group and less incidence of night pain. The time point of the rescue drug was longer in the PAI group than the control group (12.7 hours vs. 0.62 hours; p < 0.01). No cardiac or central nervous system toxicity was observed. DISCUSSION: In our study, PAI in the shoulder after mini-open rotator cuff repair showed effective pain control on the day of the surgery, postponed the time of the first dosage of intravenous pain medication, and reduced the total dosage of the intravenous pain medication.

Prospective randomized trial of continuous femoral nerve block with posterior capsular injection versus periarticular injection for analgesia in primary total knee arthroplasty.

Background: Femoral nerve block (NB) and periarticular injection (PI) are 2 common options for pain control after total knee arthroplasty (TKA). We performed a prospective triple-blinded randomized trial comparing continuous femoral NB to PI, with follow-up to 1 year. Methods: Patients younger than 70 years of age who were scheduled to undergo elective primary TKA under spinal anesthesia between 2009 and 2010 were randomly allocated to receive either continuous femoral NB or PI. Patients in the NB group received ropivacaine through an NB catheter and a sham saline PI. The PI group received a PI of ropivacaine, morphine, ketorolac and epinephrine, and a sham saline infusion via an NB catheter. Both groups had standardized oral analgesia preoperatively, spinal anesthesia and sedation, and postoperative analgesia. Surgeons, anesthesiologists, patients and assessors were blinded to group assignment. Pain was measured twice daily on postoperative days 1 and 2, at rest and with motion, with a numeric rating scale. Patient satisfaction, pain (Oxford Knee Score) and range of motion were assessed at 1 year. Results: There were 39 participants in the NB group and 35 participants in the PI group. There were no statistically significant differences between the groups at baseline. Statistically but nonclinically significant reductions in pain scores on postoperative day 2 and in narcotic need on the day of surgery were found in the PI group. Patient-reported satisfaction did not differ at any time point. At 1 year, knee flexion was significantly greater in the NB group than in the PI group (mean range of motion 120° v. 110°, p = 0.03). Conclusion: There was no demonstrated improvement in pain control with the use of an NB versus PI when used with multimodal analgesia. Clinicians should opt for the modality that has the best efficiency for their surgical environment. ClinicalTrials.gov # NCT00869037

Contexte: Le bloc nerveux (BN) fémoral et l'infiltration périarticulaire (IP) sont 2 options d'usage courant pour maîtriser la douleur après l'arthroplastie totale du genou (ATG). Nous avons procédé à un essai prospectif randomisé à triple insu afin de comparer le BN fémoral et l'IP, avec un suivi allant jusqu'à 1 an. Méthodes: Les patients de moins de 70 ans qui devaient subir une ATG élective sous épidurale entre 2009 et 2010 ont été assignés aléatoirement à un BN fémoral continu ou à une IP. Les patients du groupe soumis au BN recevaient de la ropivacaïne par un cathéter de BN et une IF simulée (solution saline). Le groupe soumis à l'IP recevait de la ropivacaïne, de la morphine, du kétorolac et de l'épinéphrine et une perfusion simulée (solution saline) par un cathéter de BN. Les 2 groupes avaient reçu une analgésie orale standard avant l'intervention, une anesthésie rachidienne avec sédatifs et une analgésie postopératoire. Les chirurgiens, les anesthésiologistes, les patients et les évaluateurs ne connaissaient pas l'assignation des agents aux différents groupes. La douleur a été mesurée 2 fois par jour aux jours 1 et 2 postopératoires, au repos et à la mobilisation, au moyen d'une échelle numérique. La satisfaction des patients, la douleur (questionnaire d'Oxford pour le genou) et l'amplitude de mouvement ont toutes été évaluées après 1 an. Résultats: Le groupe soumis au BN comptait 39 participants et le groupe soumis à l'IP en comptait 35. Il n'y avait aucune différence statistiquement significative entre les groupes au départ. Des réductions statistiquement (et non cliniquement) significatives des scores de douleur au deuxième jour postopératoire et du recours aux narcotiques le jour de la chirurgie ont été notées dans le groupe soumis à l'IP. La satisfaction autodéclarée des patients n'a différé à aucun moment. Au bout de 1 an, la flexion du genou était significativement plus marquée dans le groupe soumis au BN que dans le groupe soumis à l'IP (amplitude de mouvement moyenne 120° c. 110°, p = 0,03) Conclusion: On n'a démontré aucune amélioration de la maîtrise de la douleur avec l'utilisation du BN c. IP avec analgésie multimodale. Les médecins devraient opter pour la modalité qui offre le meilleur degré d'efficience en fonction de leur environnement chirurgical. ClinicalTrials.gov # NCT00869037

Non-steroidal anti-inflammatory drugs (NSAIDs) for trigger finger.

BACKGROUND: Trigger finger is a common hand condition that occurs when movement of a finger flexor tendon through the first annular (A1) pulley is impaired by degeneration, inflammation, and swelling. This causes pain and restricted movement of the affected finger. Non-surgical treatment options include activity modification, oral and topical non-steroidal anti-inflammatory drugs (NSAIDs), splinting, and local injections with anti-inflammatory drugs. OBJECTIVES: To review the benefits and harms of non-steroidal anti-inflammatory drugs (NSAIDs) versus placebo, glucocorticoids, or different NSAIDs administered by the same route for trigger finger. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, CNKI (China National Knowledge Infrastructure), ProQuest Dissertations and Theses, www.ClinicalTrials.gov, and the WHO trials portal until 30 September 2020. We applied no language or publication status restrictions. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) and quasi-randomised trials of adult participants with trigger finger that compared NSAIDs administered topically, orally, or by injection versus placebo, glucocorticoid, or different NSAIDs administered by the same route. DATA COLLECTION AND ANALYSIS: Two or more review authors independently screened the reports, extracted data, and assessed risk of bias and GRADE certainty of evidence. The seven major outcomes were resolution of trigger finger symptoms, persistent moderate or severe symptoms, recurrence of symptoms, total active range of finger motion, residual pain, patient satisfaction, and adverse events. Treatment effects were reported as risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). MAIN RESULTS: Two RCTs conducted in an outpatient hospital setting were included (231 adult participants, mean age 58.6 years, 60% female, 95% to 100% moderate to severe disease). Both studies compared a single injection of a non-selective NSAID (12.5 mg diclofenac or 15.0 mg ketorolac) given at lower than normal doses with a single injection of a glucocorticoid (triamcinolone 20 mg or 5 mg), with maximum follow-up duration of 12 weeks or 24 weeks. In both studies, we detected risk of attrition and performance bias. One study also had risk of selection bias. The effects of treatment were sensitive to assumptions about missing outcomes. All seven outcomes were reported in one study, and five in the other. NSAID injection may offer little to no benefit over glucocorticoid injection, based on low- to very low-certainty evidence from two trials. Evidence was downgraded for bias and imprecision. There may be little to no difference between groups in resolution of symptoms at 12 to 24 weeks (34% with NSAIDs, 41% with glucocorticoids; absolute effect 7% lower, 95% confidence interval (CI) 16% lower to 5% higher; 2 studies, 231 participants; RR 0.83, 95% CI 0.62 to 1.11; low-certainty evidence). The rate of persistent moderate to severe symptoms may be higher at 12 to 24 weeks in the NSAIDs group (28%) compared to the glucocorticoid group (14%) (absolute effect 14% higher, 95% CI 2% to 33% higher; 2 studies, 231 participants; RR 2.03, 95% CI 1.19 to 3.46; low-certainty evidence). We are uncertain whether NSAIDs result in fewer recurrences at 12 to 24 weeks (1%) compared to glucocorticoid (21%) (absolute effect 20% lower, 95% CI 21% to 13% lower; 2 studies, 231 participants; RR 0.07, 95% CI 0.01 to 0.38; very low-certainty evidence). There may be little to no difference between groups in mean total active motion at 24 weeks (235 degrees with NSAIDs, 240 degrees with glucocorticoid) (absolute effect 5% lower, 95% CI 34.54% lower to 24.54% higher; 1 study, 99 participants; MD -5.00, 95% CI -34.54 to 24.54; low-certainty evidence). There may be little to no difference between groups in residual pain at 12 to 24 weeks (20% with NSAIDs, 24% with glucocorticoid) (absolute effect 4% lower, 95% CI 11% lower to 7% higher; 2 studies, 231 participants; RR 0.84, 95% CI 0.54 to 1.31; low-certainty evidence). There may be little to no difference between groups in participant-reported treatment success at 24 weeks (64% with NSAIDs, 68% with glucocorticoid) (absolute effect 4% lower, 95% CI 18% lower to 15% higher; 1 study, 121 participants; RR 0.95, 95% CI 0.74 to 1.23; low-certainty evidence). We are uncertain whether NSAID injection has an effect on adverse events at 12 to 24 weeks (1% with NSAIDs, 1% with glucocorticoid) (absolute effect 0% difference, 95% CI 2% lower to 3% higher; 2 studies, 231 participants; RR 2.00, 95% CI 0.19 to 21.42; very low-certainty evidence). AUTHORS' CONCLUSIONS: For adults with trigger finger, by 24 weeks' follow-up, results from two trials show that compared to glucocorticoid injection, NSAID injection offered little to no benefit in the treatment of trigger finger. Specifically, there was no difference in resolution, symptoms, recurrence, total active motion, residual pain, participant-reported treatment success, or adverse events.

Ketorolac plus Lidocaine vs Lidocaine for pain relief following core needle soft tissue biopsy: A CONSORT-compliant double-blind randomized controlled study.

BACKGROUNDS: The main objective of this study was to compare the pain control efficacy of local administration of Lidocaine with or without the nonsteroidal anti-inflammatory drug, Ketorolac, and local conventional Lidocaine injection in core needle biopsy of the musculoskeletal tumor. METHODS: The current study was a randomized, double-blind controlled clinical trial that included 128 patients with suspected musculoskeletal tumors. Patients were randomly assigned to either the Ketorolac plus Lidocaine (n = 64) or Lidocaine group (n = 64). The Ketorolac - Lidocaine combination syringe contained 30 mg Ketorolac and 2% Lidocaine - adrenaline dosage, and the Lidocaine syringe contained 2% Lidocaine - adrenaline dosage. The level of pain after core needle biopsy was evaluated for each patient at 1, 6, 12, 24, 48, and >48 hours by a Visual Analog Scale (VAS). The mean VAS changes over time were compared between the Ketorolac plus Lidocaine and Lidocaine groups using a linear mixed model. RESULTS: baseline information including mean age of patients in Lidocaine group (51.5 ±â€Š19.4 years) and in Lidocaine - Ketorolac combination group (50.1 ±â€Š18 years), diagnosis (malignant, benign, metastatic, infection), tumor location (upper and lower extremities, back), VAS score 1-hour post-operation (mild and moderate pain) were noted. The VAS score ratings were significantly lower in Lidocaine - Ketorolac combination group when compared to the Lidocaine group during the 1 to 24 hours post-operation time period. CONCLUSION: Patients receiving Lidocaine - Ketorolac combination dosage had significantly lower VAS scores, and these results confirm that local injection of Lidocaine - Ketorolac combination had a superior pain-controlling effect during the first 24 hours after the biopsy procedure in comparison to Lidocaine injection alone, as measured by VAS score scale.

Intranasal ketorolac, diagnosis, and desensitization for aspirin-exacerbated respiratory disease.

BACKGROUND: Intranasal ketorolac has been proposed as a diagnostic test for aspirin-exacerbated respiratory disease (AERD) and a faster, safer, and reliable addition to facilitating aspirin (ASA) desensitization. OBJECTIVE: We conducted the first prospective study to dissect the impact of intranasal ketorolac incorporation during ASA desensitization vs standard oral protocols in concert with evaluating its diagnostic use for AERD. METHODS: Patients with AERD were enrolled in a prospective open-label observational study between November 2006 and August 2013. Participants selected either one of the following desensitization protocols: intranasal ketorolac 1 day before oral ASA (group 1, combined) or ketorolac challenge with greater than 2 weeks elapsing until oral ASA (group 2, washout). All patients were on a leukotriene-modifying drug (montelukast) for at least 1 week before the challenge. RESULTS: A total of 20 patients were enrolled: 13 in group 1 and 7 in group 2. No significant differences were seen for baseline symptom scores or forced expiratory volume in 1 second. Group 1 exhibited significant increases for the threshold dose of ASA (P = .009), the likelihood of having silent ASA desensitization (P = .01), and decreased reaction severity to oral ASA (P = .04). There were no significant differences in reaction forced expiratory volume in 1 second, the incidence of extrapulmonary symptoms, limited nasoocular reactions, rescue treatment requirements, or time to symptom resolution. There was 100% concordance between reactions to intranasal ketorolac and oral ASA for group 2, supporting its use as a diagnostic test for AERD. CONCLUSION: Intranasal ketorolac is a useful diagnostic test and adjunct within the combined ketorolac/ASA protocol to achieve effective, efficient, and perhaps safer desensitization to ASA for patients with AERD.

The analgesic effect of ketorolac addition for renal colic pain: A meta-analysis of randomized controlled studies.

INTRODUCTION: The effect of ketorolac addition for the pain control of renal colic remains controversial. We conduct a systematic review and meta-analysis to explore the analgesic efficacy of ketorolac addition for renal colic. METHODS: We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through September 2020 for randomized controlled trials (RCTs) assessing the analgesic efficacy of ketorolac addition for renal colic. This meta-analysis is performed using the random-effect model. RESULTS: Four RCTs are included in the meta-analysis. In patients with renal colic pain, ketorolac addition is associated with significantly lower pain scores at 10-20 min (SMD=-2.50; 95% CI=-4.31 to -0.68; P=0.007) and analgesic rescue (RR=0.68; 95% CI=0.52 to 0.89; P=0.006), but reveals no notable effect on nausea (RR=0.36; 95% CI=0.12 to 1.12; P=0.08), vomiting (RR=0.50; 95% CI=0.13 to 1.95; P=0.31), or dizziness (RR=0.68; 95% CI=0.05 to 0.60; P=0.007). CONCLUSIONS: Ketorolac addition may improve the analgesic efficacy for renal colic pain.

Effectiveness of Standard Combination Therapy in Pediatric Migraine.

BACKGROUND: A combination of parenteral medications (often referred to as standard combination therapy) is frequently used in the treatment of acute migraine in the pediatric emergency department (PED). The primary aim of this study was to evaluate the two-hour, 24-hour, and seven-day impact of one such regimen on pain in children who present to the PED. Standard combination therapy for purposes of our study is defined as a bolus of intravenous saline, and a combination of intravenous ketorolac, prochlorperazine, and diphenhydramine. METHODS: This prospective observational study included 120 children between the ages seven and 18 years who presented to the PED with migraine, whose parents could read and understand the consent form in English, and who were treated with standard combination therapy. The primary outcome measure for this study was the change in severity of pain as noted by the child using the Faces Pain Scale-Revised. We analyzed normally distributed continuous variables by mean and standard deviation, whereas non-normally distributed continuous variables are reported by median and interquartile range. RESULTS: Nonparametric Friedman testing on the entire cohort (n = 120) noted that there was a statistically significant change in the Faces pain scale from before administration of standard combination therapy to the two-hour, 24-hour, and one-week time point with a reduction in pain score of 87.5%, 100%, and 50%, respectively, at the three time points. CONCLUSIONS: This study noted moderate relief of pain after administration of standard combination therapy, which persisted at one-week after administration.