Safety and Efficacy of Ketorolac After Craniotomy for Tumor Resection.

OBJECTIVE: Postoperative pain is the most common undesirable outcome after neurosurgery. Ketorolac is a non-steroidal anti-inflammatory drug (NSAID) which is administered parenterally and carries a theoretical increased risk of bleeding. Our study aims to determine whether ketorolac after craniotomy for tumor resection significantly changes the rate of postoperative adverse events, adequately controls pain, and decreases concurrent narcotic usage. METHODS: We performed a retrospective chart review of all adult patients who underwent craniotomy for brain tumor resection from 2013 to 2022. Analysis of patients who received ketorolac and those who did not in the post-operative period were compared for adverse events associated with ketorolac use. Secondary outcomes included patient-reported pain scores and postoperative opioid usage. RESULTS: 1,114 patients were included, of which 70 received ketorolac in the postoperative period. Patients who received ketorolac often received it after narcotics failed to provide adequate pain control. Patients receiving ketorolac were younger (p=0.001) and had a lower comorbidity index (p=0.041) compared to the non-ketorolac group. Patients receiving ketorolac did not experience a significantly increased rate of bleeding events (p=0.850). Patients recieving ketorolac had significantly higher baseline levels of pain (p=0.018) and opioid usage (p=0.047). When matched for chronic comorbidities including pain disorders, the ketorolac group only displayed higher levels of pain early in the postoperative course (POD 0-1) but not in latter part of the initial postoperative period. CONCLUSIONS: Ketorolac is a safe and effective option for pain control after craniotomy for tumor resection. Prospective data is needed to better validate these retrospective observations.

Comparison of ketorolac intravenous versus acetaminophen intravenous in treating headache following head trauma: a semi-experimental study.

BACKGROUND: Post-traumatic headache is a disabling secondary headache disorder often attributed to traumatic brain injury and affects millions of individuals worldwide. Few studies have been done on the treatment needs of these patients in emergency departments. The purpose was to compare the effectiveness of ketorolac intravenous versus acetaminophen intravenous in reducing headaches in patients following head trauma. METHODS: This was a semi-experimental study in which the participants were assigned two groups. In the acetaminophen intravenous group, 1 g acetaminophen and in the ketorolac intravenous group, 60 mg of this drug was injected. Statistical analysis was done with IBM SPSS statistical software version 21, and a P-value less than 0.05 was considered statistically significant. RESULTS: Among samples after 6 h from the injection, the pain score in the ketorolac intravenous group was less than the acetaminophen intravenous group (P = 0.006). Also, the pain reduction rate in the ketorolac intravenous group was more than the acetaminophen intravenous group from before the injection until 2 h after it (P = 0.01) and before injection until 6 h after it (P = 0.001). The frequency of drowsiness in 2 and 6 h after drug administration in the ketorolac intravenous group was lower than the acetaminophen intravenous group, which is significant in 2 h after drug administration (P = 0.038). The verbal analog scale score comparison for two groups 2 h before medicine administration with pain control score (P = 0.03) and 6 h with pethidine use control (P = 0.003) is significant. CONCLUSIONS: According to this study, ketorolac's intravenous effect on pain control is better than that of acetaminophen intravenous. With more samples, we can express the survey results more decisively in the future.

Enhancing analgesia in acute renal colic pain: a randomized controlled trial of gabapentin adjunct to ketorolac-based regimen.

Background: Renal colic is characterized by severe pain that is highly disabling. Gabapentin, an antiepileptic medication, is often recommended as a first-line therapy for neuropathic pain. However, its effectiveness in managing somatic pain, which is defined as the result of activity by pain receptors in the deep tissues, such as renal colic pain, is not as well-established. Method: A phase 3 randomized clinical trial was conducted to evaluate the adjuvant analgesic effects of gabapentin on acute renal colic pain. Eligible patients participated in the study via random allocation to the control or gabapentin groups using the block randomization method. All patients received a shared regimen of ketorolac and rescue morphine as the conventional analgesic treatment for renal colic pain. Gabapentin was added as an adjuvant analgesic for the gabapentin group. Result: A total of 63 individuals with an average age of 41.35 ± 13.08, were enrolled and completed the study. At the time of admission, there were no significant differences between the baseline characteristics of two groups, with exception of weight. The gabapentin group showed a significantly higher percentage of patients with pain severity of less than 5 after 60 and 90 min, as well as a significantly lower percentage of morphine rescue requirement and total morphine intake (mg) and mg/kg. Conclusion: In cases of acute renal colic, gabapentin significantly decreases both the amount of morphine required and the degree of pain, indicating that it may be a useful adjutant to standard analgesic regimens. Treatment regimens that include gabapentin may help individuals manage their pain and become less reliant on opioids. Clinical Trial Registration: https://irct.behdasht.gov.ir/trial/56066, identifier: IRCT20200322046833N2.

Troxerutin effect on gastric ulcers induced by ketorolac in rats: Relation with oxidative stress.

Gastric ulcers are an essential side effect associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs). Free radicals are one of the important mechanisms contributing to the development of gastric ulcers caused by NSAIDs. This prompted us to choose troxerutin, which has antioxidant and anti-inflammatory effects, especially with a lack of studies investigating the preventive effect of troxerutin on gastric ulcers. Twenty-nine rats were divided into five groups: A Vehicle group, a Keto group (30 mg/kg of ketorolac), and two troxerutin groups (150 mg/kg or 200 mg/kg of troxerutin, respectively). A Miso group was used as a reference with (100 µg/kg of misoprostol). Troxerutin and misoprostol were administered orally 1 h before ketorolac. The ulcer index was determined considering the numbers and severity of ulcerations. Gastric tissue inflammation was evaluation microscopically. Both thiobarbituric acid reactive substance levels and catalase activity were measured as markers of oxidative stress in gastric tissue. Our data showed an improvement in ulcer indices with troxerutin and misoprostol compared with ketorolac, with improvement in gastric inflammation observed with misoprostol but not with troxerutin. These results were accompanied by a reduction in gastric oxidative stress induced by ketorolac with both troxerutin and misoprostol. This study highlights, for the first time, the antioxidant effect of troxerutin on gastric ulcers. This effect may contribute to the good prevention of ketorolac-induced gastric ulcers.

Comparing postoperative pain relief: ketorolac and Nasocalcin spray versus lidocaine and Nasocalcin spray in abdominal surgery patients.

Objectives: Postoperative pain management is critical for patient recovery after abdominal surgery. This study compared intravenous lidocaine and ketorolac for reducing postoperative pain and opioid use, along with Nasocalcin nasal spray. Methods: In this randomized controlled trial, 58 abdominal surgery patients were allocated to receive either intravenous lidocaine plus Nasocalcin spray (n=29) or intravenous ketorolac plus Nasocalcin spray (n=29) before surgery. Pain intensity (visual analog scale) and postoperative opioid consumption were assessed at 1, 6, 12, and 24 h after surgery. Results: Patients receiving ketorolac plus Nasocalcin spray reported significantly lower pain scores at all time points compared to lidocaine plus Nasocalcin (P<0.001). Average 24-h pain scores were 4.5 with ketorolac versus 5.1 with lidocaine. Mean opioid consumption was also lower in the ketorolac group (31.9 mg) versus the lidocaine group (43.9 mg, P<0.001). Conclusion: Preoperative ketorolac plus Nasocalcin nasal spray resulted in superior pain relief and less opioid use compared to lidocaine plus Nasocalcin after abdominal surgery. Ketorolac may be a more effective analgesic option, while Nasocalcin spray is a safe adjunct. These findings can inform clinical practice for optimizing postoperative analgesia.

Ketorolac Dose Ceiling Effect for Pediatric Headache in the Emergency Department.

OBJECTIVE: This study sought to demonstrate a non-inferiority analgesic ceiling effect previously -demonstrated within adults for pediatric patients receiving a maximum ketorolac dose of 15 mg. METHODS: We conducted a retrospective cohort study of pediatric ED patients weighing at least 60 kg treated with 30 mg (pre-intervention) or 15 mg (post-intervention) intravenous (IV) ketorolac for headache. The primary outcome included patient-reported pain scores. Additional outcomes included demographic variables, adjunct medication use and adverse effects. Categorical data were evaluated using a χ2 test, and numerical data were evaluated using an ANOVA F test and Welch 2-sample t test. RESULTS: The pre- and post-intervention groups included 216 and 62 patients, respectively. Overall demographics were similar between the groups (72.3% female, 49.3% White/Caucasian, mean age 15.5 years, mean weight 79.2 kg, and mean baseline 10-point pain score 7.5). Twelve (5.6%) in the pre-intervention group required rescue analgesic compared with 2 patients (3.2%) in the post-intervention group (p = 0.416). In the pre-intervention group, 198 patients (91.7%) received nausea medication compared with 52 patients (83.9%) in the post-intervention group (p = 0.087). Mean 10-point pain scores following ketorolac administration decreased by 3.9 in the pre-intervention group compared with 5.1 in the post-intervention group (p = < 0.001). Common (0.9%) or rare (0.9%) side effects were infrequent and only seen in the pre-intervention group patients. CONCLUSIONS: Truncating the maximum intravenous ketorolac dose in pediatric patients at least 60 kg in weight to 15 mg compared with 30 mg results in effective analgesia in pediatric patients with headache. Future research could explore differences in admission rates, treatment of other indications, or treatment with multiple-dose regimens.

Pain relief during intrauterine device placement in nulligravid women with both oral ketorolac and an analgesic: a double-blinded randomised trial.

OBJECTIVE: We assessed whether the administration of oral ketorolac with an analgesic provides effective pain relief during placement of an intrauterine device (IUD) in nulligravid women. METHODS: We conducted a double-blinded randomised trial in the Department of Obstetrics and Gynaecology, University of Campinas Faculty of Medical Sciences, Campinas, SP, Brazil. We randomised participants who voluntarily agreed to participate to receive either one pill containing ketorolac 20 mg together with one pill containing dipyrone 300 mg, scopolamine 6.5 µg, hyoscyamine 104 µg, and homatropine 1 mg or placebo 60 min before IUD placement. The participants and providers were blinded to the randomisation group. The primary outcome was pain assessment (measured on a 0-10 visual analogue scale) during IUD placement. RESULTS: We enrolled participants and randomised them 1:1 between November 7, 2023, and January 31, 2024. We analysed 60 women in each group. There were no differences between the groups in the pain score during tenaculum placement, uterine sounding, and IUD placement, and in the overall perception of pain. However, the pain score was significantly lower 10 min after the procedure in women who received the treatment compared with women who received the placebo. CONCLUSION: Oral ketorolac associated with an analgesic administered 60 min before IUD placement was not significantly better than placebo during tenaculum placement, uterine sounding, and IUD insertion, and did not significantly reduce the overall pain perception. However, this treatment did significantly reduce pain 10 min after the procedure. TRIAL REGISTRATION: The trial was registered at Registro Brasileiro de Ensaios Clínicos (REBEC; in English: The Brazilian Registry of Clinical Trials) under number RBR-7phn8yv on November 6, 2023. https://ensaiosclinicos.gov.br/rg/RBR-7phn8yv.

Pain at IUD placement after one pill containing ketorolac 20 mg together with one analgesic pill given 60 min before placement were similar than placebo.

Efficacy of Ketorolac Tromethamine Diluted Saline Irrigant on Postoperative Sequelae in Patients Undergoing Lower Third Molar Impaction Surgery: A Prospective Clinical Study.

Background Lower third molar surgery is very commonly performed for minor oral surgery by an oral and maxillofacial surgeon. One of the main chief complaints that patients report back to the clinic after getting their lower third molar impaction surgery is immediate postoperative pain. In our study, we have compared the efficacy of ketorolac tromethamine diluted saline solution over plain saline solution used as an irrigant in reducing postoperative swelling and pain. Aim The aim of the current study is to analyse the efficiency of ketorolac tromethamine diluted saline solution over normal saline without any drug dilution in reducing postoperative sequelae like pain and swelling after surgical removal of the lower third molar. Materials and methods This study was carried out at the Department of Oral and Maxillofacial Surgery, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, from April 2023 to July 2023. The study included 50 individuals who wanted to prophylactically get the lower third molar removed surgically. These participants were divided into two groups. One group received ketorolac diluted saline irrigant while the other group received plain saline (0.9% NaCl) as irrigant. Postoperatively, pain and swelling were evaluated in both groups. Both pain and swelling were measured preoperatively, postoperatively after 48 hours, and postoperatively after seven days. The swelling was measured using a 4-point measuring scale, and pain measurement was done using a 10-point visual analogue scale. Statistical analysis was done using Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 23.0, Armonk, NY). For the comparison of continuous variables between the two groups, an unpaired t-test was used. The normality of the results obtained was checked using the Shapiro-Wilk test. The results were considered statistically significant if the P-value was less than 0.05. Results Based on the results obtained it was found that participants who were included in the ketorolac saline group had comparatively lower postoperative pain scores than participants in the plain saline group and this was statistically significant (P=0.001). Postoperative swelling was also comparatively lower in the ketorolac tromethamine saline group but the results were not statistically significant at the end of day 7 (P=0.09). Conclusion Upon observing the cumulative results obtained, we conclude that ketorolac saline (10mg/100mL) was more efficacious in terms of pain reduction than the regular saline solution in impacted lower third molar surgery.

Comparative Analysis of Ketorolac and Parecoxib for Postoperative Pain Management in Uvulopalatopharyngoplasty.

Background/Objectives: Uvulopalatopharyngoplasty (UPPP) is a prevalent surgical procedure for treating obstructive sleep apnea. Effective postoperative pain management is crucial for patient comfort and recovery. This study aimed to compare the analgesic efficacies of parecoxib and ketorolac in patients undergoing UPPP. Methods: A prospective, randomized, double-blind study was conducted on 83 patients who received either parecoxib (40 mg intravenously every 12 h) or ketorolac (30 mg intravenously every 8 h) for 2 days following UPPP. Postoperative pain and swallowing discomfort were assessed using visual analog scales (VASs) at 4, 24, 48, and 72 h. The time to resume eating and adverse reactions were also recorded. Results: At 24 and 48 h postoperatively, the mean VAS score was significantly higher in the ketorolac group compared to the parecoxib group (5.0 ± 2.3 vs. 3.6 ± 2.2, p = 0.005 and 3.9 ± 2.2 vs. 2.5 ± 1.7, p < 0.001, respectively). However, no significant difference in the mean VAS scores was observed between the two groups at 72 h postoperatively. With regards to postoperative swallowing pain, the ketorolac group exhibited significantly higher mean VAS scores than the parecoxib group at 4, 24, 48, and 72 h postoperatively. Conclusions: Intravenous parecoxib may offer superior analgesic benefits in the early postoperative period, particularly in alleviating swallowing pain, compared to ketorolac in UPPP procedures.

Nonsteroidal anti-inflammatory drugs for analgesia in intensive care units: a survey of Canadian critical care physicians.

PURPOSE: Opioids remain the mainstay of analgesia for critically ill patients, but its exposure is associated with negative effects including persistent use after discharge. Nonsteroidal anti-inflammatory drugs (NSAIDs) may be an effective alternative to opioids with fewer adverse effects. We aimed to describe beliefs and attitudes towards the use of NSAIDs in adult intensive care units (ICUs). METHODS: Our survey of Canadian ICU physicians was conducted using a web-based platform and distributed through the Canadian Critical Care Society (CCCS) email distribution list. We used previously described survey development methodology including question generation and reduction, pretesting, and clinical sensibility and pilot testing. RESULTS: We received 115 completed surveys from 321 CCCS members (36%). Nonsteroidal anti-inflammatory drugs use was most described as "rarely" (59 respondents, 51%) with the primary concern being adverse events (acute kidney injury [108 respondents, 94%] and gastrointestinal bleeding [92 respondents, 80%]). The primary preferred analgesic was acetaminophen (75 respondents, 65%) followed by opioids (40 respondents, 35%). Most respondents (91 respondents, 80%) would be willing to participate in a randomized controlled trial examining NSAID use in critical care. CONCLUSIONS: In our survey, Canadian critical care physicians did not mention commonly using NSAIDs primarily because of concerns about adverse events. Nevertheless, respondents were interested in further studying ketorolac, a commonly used NSAID outside of the ICU, in critically ill patients.

RéSUMé: OBJECTIF: Les opioïdes restent le pilier de l'analgésie pour les patient·es gravement malades, mais l'exposition à ces agents est associée à des effets négatifs, notamment à leur utilisation persistante après le congé de l'hôpital. Les anti-inflammatoires non stéroïdiens (AINS) pourraient constituer une alternative efficace aux opioïdes avec moins d'effets indésirables. Nous avons cherché à décrire les croyances et les attitudes à l'égard de l'utilisation des AINS dans les unités de soins intensifs (USI) pour adultes. MéTHODE: Notre sondage auprès des médecins intensivistes au Canada a été mené à l'aide d'une plateforme Web et distribué aux personnes sur la liste de distribution électronique de la Société canadienne de soins intensifs (SCSI). Nous avons utilisé une méthodologie d'élaboration d'enquêtes décrite précédemment, y compris la génération et la réduction de questions, les tests préalables, la sensibilité clinique et les tests pilotes. RéSULTATS: Nous avons reçu 115 sondages remplis par 321 membres de la SCSI (36 %). L'utilisation d'anti-inflammatoires non stéroïdiens a été décrite comme « rare ¼ (59 répondant·es, 51 %), la principale préoccupation étant les événements indésirables (insuffisance rénale aiguë [108 répondant·es, 94 %] et saignements gastro-intestinaux [92 répondant·es, 80 %]). Le principal analgésique préféré était l'acétaminophène (75 répondant·es, 65 %), suivi des opioïdes (40 répondant·es, 35 %). La plupart des répondant·es (91 répondant·es, 80 %) seraient prêt·es à participer à une étude randomisée contrôlée examinant l'utilisation des AINS en soins intensifs. CONCLUSION: Dans notre sondage, les médecins intensivistes au Canada n'ont pas mentionné l'utilisation courante d'AINS, principalement en raison de préoccupations concernant leurs effets indésirables. Néanmoins, les répondant·es étaient intéressé·es à étudier plus avant le kétorolac, un AINS couramment utilisé en dehors des soins intensifs, chez les patient·es gravement malades.

Dropless Cataract Surgery: The Effect of Intracameral Phenylephrine/Ketorolac Infusion as a Single Agent on Postoperative Outcomes.

Objective The objective of this study was to assess the feasibility of using an intracameral phenylephrine/ketorolac infusion during cataract surgery as a single agent to prevent postoperative pain, inflammation, and other complications. Methods A prospective, single-group feasibility study was conducted in which phenylephrine/ketorolac infusion was administered during cataract surgery and no perioperative topical drops were initially prescribed. Patients underwent optical coherence tomography, corrected distance visual acuity testing, and slit lamp biomicroscopy examination at perioperative visits, during which they also reported symptoms of pain, irritation, and/or photophobia. A goal adverse event (AE) rate was set at ≤5.0%. Results A total of 94 eyes (60 patients) were included in this study. The AE rate was 13.8% (13/94 eyes) with pain/irritation in eight eyes, cystoid macular edema (CME) in three eyes, and corneal edema in three eyes. Conclusions Based on an AE rate goal of ≤5.0%, using intraoperative, intracameral phenylephrine/ketorolac alone was not deemed a feasible alternative to current postoperative eye drop regimens in our clinical setting. However, a 13.8% AE rate is comparable to the rates of postoperative CME, corneal edema, pain, and irritation in the published literature. Thus, more research is needed to truly define this approach as inferior or non-inferior to the current standard of care.

A Novel Formulation of Ketorolac Tromethamine (NTM-001) in Continuous Infusion in Adults with and without Renal Impairment: A Randomized Controlled Pharmacologic Study.

INTRODUCTION: There is a medical need for a safe, effective nonopioid postoperative analgesic for older subjects, including those with mild to moderate renal impairment. METHODS: Participants (≥ 65 years) were stratified by no, mild, or moderate renal impairment defined as creatinine clearance 60-89 mL/min for mild and 30-59 mL/min for moderate. Subjects were randomized to receive a loading dose of 6.25 mg of ketorolac tromethamine drug candidate NTM-001 followed by a 1.75 mg/h continuous intravenous (IV) infusion over 24 h or an IV bolus injection of ketorolac tromethamine (KETO-BOLUS) of 15 mg every 6 h. There were four treatment periods of 24 h for each subject with a minimum 7-day washout between them. This was a crossover study so subjects served as their own controls. Blood drawn from the subjects was used to plot concentration-time profiles against target profiles. Adverse events were monitored. RESULTS: Thirty-nine subjects enrolled. Concentration-time profiles showed low intersubject variability. Model-predicted curves for those with renal impairment closely matched observed plasma concentrations. Continuous infusion maintained higher mean plasma concentrations than the bolus regimen. No serious or unexpected adverse events were observed. No deaths occurred. CONCLUSIONS: NTM-001 was considered safe and well tolerated in this population of participants ≥ 65 years, including in those with mild or moderate renal impairment. There were fewer adverse events in the continuous infusion group. The predictable pharmacologic properties and blood concentration levels suggest that continuous IV infusion of ketorolac can be used as an effective postoperative pain reliever in older subjects.

Controlling postoperative pain can lead to faster recovery. Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug (NSAID), like ibuprofen and naproxen, that can be as effective as morphine without the same risks. In hospitals, ketorolac is usually administered intravenously (IV) either continuously or as a bolus injection. A bolus of ketorolac may result in adverse gastrointestinal side effects. In this study, a new formulation of ketorolac tromethamine, NTM-001, was administered IV as a continuous 24 h infusion compared to IV boluses of ketorolac tromethamine every 6 h in volunteers. Volunteers were older (≥ 65 years) and had no, mild, or moderate kidney dysfunction. One randomized group received a starting IV dose of 6.26 mg followed by a continuous IV infusion of 1.75 mg/h of over 24 h. The other group received single NTM-001 IV bolus injections of ketorolac tromethamine 15 mg every 6 h over 24 h (4 doses, 60 mg) over the 24 h. After completing the first study, subjects waited at least a week and then switched groups, giving the study a crossover design so it could be observed how each subject responded to both regimens. Blood drawn from the subjects was tested for standard pharmacokinetic (PK) parameters. The data show that blood concentrations of NTM-001 can be reliably predicted. Side effects were mild and the continuous infusion reduced side effects. No unexpected adverse events occurred. These data show that NTM-001 can be used safely in older individuals, including those with mild or moderate kidney impairment.

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.

Comparaison of Efficacy and Safety of Fentanyl Transdermal Patch with Oral Ketorolac for Pain Management in Dry Socket: A Randomized Clinical Trial.

Objectives: The aim of this study was to compare the efficacy and safety of transdermal Fentanyl patch with oral Ketorolac for pain management in dry socket patients. Study design: Sixty patients who were diagnosed with dry socket (VAS > 40 mm) were recruited in this prospective randomized controlled trial. Patients were divided into two groups. Group1 (n = 30) Transdermal Fentanyl patch (25mcg/hr) was given and in Group 2 (n = 30) Ketorolac 10 mg Oral tablet was prescribed for pain management. The primary endpoint was the mean pain scores within 72 h evaluated by visual analog scale (VAS). Secondary measures included the safety and tolerability, amount of rescue medication (analgesic and antiemetic) and effectiveness of treatment interventions by Brief Pain Inventory Questionnaire (BPI). Results: The mean VAS pain scores were significantly less in group 1 (Fentanyl) as compared to group 2 (ketorolac) on all follow-up days. Significant difference was noted in the mean amount of rescue analgesic medication. It was 2.16 + 1.53 in group 1 and 8.50 + 3.98 in group 2. Side effects were seen in both the groups. Nausea (46%) and vomiting (43%) were reported in group 1 while headache (36.6%) and epigastric pain (53.3%) in group 2. Conclusions: Thus, transdermal Fentanyl was better in pain control than Ketorolac with less need for rescue analgesic medication in dry socket.

Effects of dexmedetomidine and ketorolac applied for patient­controlled analgesia on the balance of Th1/Th2 and level of VEGF in patients undergoing laparoscopic surgery for cervical cancer: A randomized controlled trial.

The aim of the present study was to explore the effects of dexmedetomidine (DEX) combined with ketorolac on postoperative patient-controlled analgesia (PCA), the balance of Th1/Th2 and the level of vascular endothelial growth factor (VEGF) in patients with cervical cancer following laparoscopic radical surgery. A total of 70 women with cervical cancer undergoing laparoscopic radical hysterectomy were enrolled in the study to randomly receive postoperative dexmedetomidine combined with ketorolac analgesia (DK group) and postoperative sufentanil analgesia (SUF group). The primary outcomes were the serum levels of interleukin-4 (IL-4), interferon-γ (IFN-γ) and VEGF, and the IFN-γ/IL-4 ratio 30 min before induction (T0), and 24 and 48 h after surgery. Secondary outcomes included numerical rating scale scores at 0 h (T0), 4 h (T1), 12 h (T2), 24 h (T3) and 48 h (T4) postoperatively, cumulative times of rescue analgesia, as well as the incidence of postoperative side effects within 48 h from surgery. Patients in the DK group reported similar analgesic effects as patients in the SUF group at T2, T3 and T4, and the incidence of postoperative nausea and vomiting was significantly lower in the DK group. In the DK group, the serum concentration of IFN-γ and IFN-γ/IL-4 ratio at 24 and 48 h after surgery were higher compared with those in the SUF group. Conversely, the serum concentrations of IL-4 at 24 h after surgery and VEGF at 24 and 48 h after surgery were significantly lower. The results indicated that the combination of DEX and ketorolac for PCA significantly improved postoperative pain and decreased the serum level of VEGF, which are associated with tumor angiogenesis. In addition, it maintained the homeostasis of postoperative immune dysfunction of patients with cervical cancer by shifting the balance between type 1 T helper cells and type 2 T helper cell (Th1/Th2 balance) to Th1 (registration no. ChiCTR1900027979; December 7, 2019).

A sequential, multiple-assignment, randomized trial of analgesic strategies for acute musculoskeletal Pain.

BACKGROUND: Most methodologically rigorous, ED-based, comparative effectiveness analgesic studies completed in the last two decades failed to find a clinically important difference between the comparators. We believe that many of these comparative effectiveness studies were biased towards the null hypothesis because some ED patients with intense pain will respond to relatively mild interventions. We hypothesized that including a run-in period would alter the results of an acute pain RCT. METHODS: We conducted a sequential, multiple-assignment, randomized study. Adults with acute moderate/severe musculoskeletal pain were randomized (3:1 ratio) to run-in period or no run-in. We administered 650 mg acetaminophen to run-in participants. Those run-in patients who reported insufficient relief one-hour later were randomized (1:1 ratio) to ibuprofen 800mg PO or ketorolac 20mg PO as were all participants randomized to no run-in. The primary outcome was achieving a clinically important improvement, defined as improvement ≥1.3 on a 0-10 scale. We built a logistic regression model including run-in/no run-in, ketorolac/ibuprofen, age and sex. RESULTS: Of 307 participants who received acetaminophen, 100 (32.6%) reported inadequate relief and were randomized to an NSAID. Of the 100 patients randomized to no run-in, 84/100 (84%) achieved the primary outcome versus 246/287 (86%) run-in participants (95% CI for difference = 2%:-7,10%). Among run-in participants who received an NSAID, 82/99(83%) achieved the primary outcome versus 84/100(84%) no run-in participants (p = 0.82). Among all ibuprofen participants, 44/49(90%) randomized to run-in and 42/50(84%) randomized to no run-in achieved the primary outcome. Among all ketorolac participants, 38/50(76%) randomized to run-in and 42/50 (84%) randomized to no run-in achieved the primary outcome. We observed the following results in a multivariable analysis: OR for ketorolac versus ibuprofen:0.60 (95% CI: 0.28, 1.28); OR for run-in versus no run-in:0.91(95% CI: 0.43, 1.93). CONCLUSIONS: Among patients with acute musculoskeletal pain, using an acetaminophen first strategy did not alter pain outcomes.

A Comparative Analysis of the Efficacy and Safety of Nimesulide/Paracetamol Fixed-Dose Combination With Other NSAIDs in Acute Pain Management: A Randomized, Prospective, Multicenter, Active-Controlled Study (the SAFE-2 Study).

Objective In this study, we aimed to compare the efficacy and safety of the fixed-dose combination (FDC) of nimesulide (100 mg) + paracetamol (325 mg) [NP], ketorolac (10 mg) [Kt] alone, diclofenac (50 mg) + paracetamol (325 mg) [DP], and aceclofenac (100 mg) + paracetamol (325 mg) [AP] in patients with acute painful conditions. Methods This was a randomized, prospective, open-label, multicentre, active-controlled study involving patients aged ≥18 years, with acute painful conditions like low back pain, acute musculoskeletal disorders, and trauma such as tendinitis, tenosynovitis, bursitis, sprains and strains, migraine, dental pain, painful dental procedures, and post-surgical pain. Reduction in pain intensity and liver, renal, gastrointestinal, and cardiovascular safety were assessed on days seven and 14. Results A total of 600 patients were randomized into NP, Kt, DP, and AP groups in a 1:1:1:1 ratio. NP, DP, and AP were administered twice a day while Kt was given three times a day. The reduction of pain as measured by the numerical rating scale (NRS) scores at the end of day seven was 3.75 ± 1.58 in the NP group, 2.96 ± 1.18 in the Kt group, 3.42 ± 1.42 in the DP group, and 3.47 ± 1.30 in the AP group. The pain reduction in the NP group was significantly greater (p<0.001) as compared to the Kt group and non-inferior to the DP and AP groups on days seven and 14. Non-inferiority was concluded between the NP, DP, and AP groups as the lower limit of 95% CI of the difference in the change of pain intensity on both days seven and 14 was above the predefined margin of -1.0. All the drugs were well tolerated, but a significantly greater number of adverse events were reported in the DP group (32) as compared to the NP group (14) (p<0.05). The most common adverse events reported during the study were nausea, gastritis, and abdominal pain in all four groups. There was no significant alteration in liver and renal function tests except a rise in serum creatinine in the DP group. Conclusions The FDC of nimesulide with paracetamol is superior to ketorolac and non-inferior to the FDC of diclofenac with paracetamol and aceclofenac with paracetamol in the management of pain in patients with acute painful conditions. The tolerability profile of the FDC of nimesulide with paracetamol is similar to that of ketorolac but better than diclofenac with paracetamol and aceclofenac with paracetamol combinations.

Early Utilization of Ketorolac in Cleft Palate Repair.

OBJECTIVE: To determine the effect of ketorolac on opiate requirement and hospital length of stay after palatoplasty. DESIGN: This was a retrospective chart review. SETTING: This study was completed at an urban tertiary medical center. PATIENTS: Those who underwent palatoplasty with a pediatric otolaryngologist between 2010-2020. INTERVENTIONS: Incorporation of standing Ketorolac into the immediate post-operative pain regimen. MAIN OUTCOME MEASURES: T-test analysis was performed to determine whether initiation of ketorolac within 24 h post-palatoplasty was correlated with shorter length hospitalization or reduced opiate requirement. RESULTS: A total of 55 pediatric subjects (49.1% female) were included in this study. Average age at time of surgery was 13 months (range 9.9-33.9 months). On two tailed t-test, use of ketorolac within the first 24 h after palatoplasty was associated with shorter length of stay (mean of 1.68 vs 2.57 days, t = 2.58, P = .01) and lower total opiate dosage during hospitalization (mean of 2.8 vs 9.16 morphine milligram equivalents, t = 3.37, P = .001). CONCLUSIONS: Among patients undergoing palatoplasty, there is a significant relationship between the early utilization of ketorolac and decreased length of hospitalization as well as decreased opiate requirement. This has important consequences to help improve pain control with reduced opiates requirement as well as length of stay. Future prospective studies can help elicit the causative effect of Ketorolac on these parameters and can investigate whether use of Ketorolac has an effect on long term recovery and post-discharge opiate requirements as well.

Effect of perioperative ketorolac on postoperative bleeding after pediatric tonsillectomy.

INTRODUCTION: Ketorolac is a frequently used anesthetic pain agent which is traditionally avoided during tonsillectomy due to concern for postoperative hemorrhage. Our goal was to assess the degree of risk associated with the use of Ketorolac following pediatric tonsillectomy. METHODS: The TriNetX electronic health records research database was queried in January 2024 for patients undergoing tonsillectomy with or without adenoidectomy under the age of 18 years and without a diagnosed bleeding disorder. Patients were separated into two cohorts either having received or not having received ketorolac the same day as surgery. Propensity score matching was performed for age at the time of surgery, sex, race, ethnicity, and preoperative diagnoses. The outcomes assessed were postoperative hemorrhage requiring operative control within the first day (primary hemorrhage) and within the first month after surgery (secondary hemorrhage). RESULTS: 17,434 patients were identified who had undergone pediatric tonsillectomy with or without adenoidectomy and had received ketorolac the same day as surgery. 290,373 patients were identified who had undergone pediatric tonsillectomy with or without adenoidectomy and had not received ketorolac the same day as surgery. 1:1 propensity score matching resulted in 17,434 patients within each cohort. Receipt of ketorolac the same day as surgery resulted in an increased risk of primary hemorrhage OR 2.158 (95 % CI 1.354, 3.437) and secondary hemorrhage OR 1.374 (95 % CI 1.057, 1.787) requiring operative control. CONCLUSION: Ketorolac use during pediatric tonsillectomy with or without adenoidectomy was associated with an increased risk of postoperative primary and secondary bleeding requiring surgery.