ABSTRACT
Inflammation may contribute to postoperative cardiac complications and ketorolac, an anti-inflammatory agent inhibiting cyclooxygenase (COX), shows promise in enhancing cardiac graft patency by suppressing endothelial cell proliferation in animal studies. However, the safety of postoperative ketorolac use remains controversial. This study investigates the association between early ketorolac application and complications following cardiac surgery. Data from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database fueled this retrospective cohort study. The primary outcome is a composite of mortality, pulmonary insufficiency, severe acute kidney injury (AKI), hemorrhage or hematoma, infection, cardiogenic shock, and cerebrovascular infarction postcardiac surgery. Propensity score matching (PSM; 1:1 match, caliper 0.2), multivariate logistic regression, interaction stratification analysis, pairwise algorithmic, and overlap weight model analyses were employed. Following inclusion and exclusion criteria, 7143 patients who underwent valvular surgery or coronary artery bypass grafting (CABG) were included. PSM created a balanced cohort of 3270 individuals (1635 in the ketorolac group). The matched cohort exhibited an 8.1% overall rate of postoperative complications, with a lower composite outcome rate in patients receiving ketorolac within 48 h of surgery compared with those without (PSM, OR 0.70 [95% CI, 0.54-0.90]). Consistent associations were observed in total cohort analyses, sensitivity, and subgroup analyses. Early ketorolac use within 48 h post-CABG or valvular procedures in adults is independently associated with a lower incidence of composite postoperative adverse events. Prospective trials are warranted to assess causality.
Subject(s)
Cardiac Surgical Procedures , Databases, Factual , Ketorolac , Postoperative Complications , Humans , Ketorolac/administration & dosage , Ketorolac/adverse effects , Male , Female , Aged , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Postoperative Complications/etiology , Retrospective Studies , Middle Aged , Databases, Factual/statistics & numerical data , Cardiac Surgical Procedures/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Coronary Artery Bypass/adverse effects , Propensity ScoreABSTRACT
Ketorolac, a nonsteroidal anti-inflammatory drug, is used in combination with opioids to manage vaso-occlusive episodes (VOEs). The relationship between ketorolac use and kidney injury in pediatric patients with sickle cell disease (SCD) remains incompletely understood. We hypothesize that ketorolac is associated with acute kidney injury (AKI) in patients with SCD presenting with pain. All nonsurgical hospitalizations for VOEs treated with ketorolac between January 2014 and December 2022 were included. We used optimal matching methodology to identify control admissions (2:1 ratio) and used nonparametric tests to compare ketorolac administration between cases and controls. A total of 1319 encounters/253 patients were included in this study. AKI was noted in 1.1% of encounters and 5.5% of patients. Cases had significantly higher initial BUN than controls (9.0 vs. 6.0 mg/dL, P =0.012). In cases versus controls, there was significantly lower serum sodium (136.0 vs. 138.0 mmol/L, P =0.021). There was no association between ketorolac dose and development of AKI among children with SCD. Higher BUN and lower sodium in cases suggest that patients with AKI were more volume depleted on admission than controls. This highlights the need for strict assessment of fluid status upon admission for VOE.
Subject(s)
Acute Kidney Injury , Acute Pain , Anemia, Sickle Cell , Anti-Inflammatory Agents, Non-Steroidal , Ketorolac , Humans , Ketorolac/adverse effects , Ketorolac/therapeutic use , Anemia, Sickle Cell/complications , Anemia, Sickle Cell/drug therapy , Acute Kidney Injury/chemically induced , Acute Kidney Injury/etiology , Male , Female , Child , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Adolescent , Acute Pain/drug therapy , Acute Pain/etiology , Child, Preschool , Case-Control Studies , Retrospective Studies , Risk FactorsABSTRACT
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.
Subject(s)
Adenoidectomy , Anti-Inflammatory Agents, Non-Steroidal , Ketorolac , Postoperative Hemorrhage , Tonsillectomy , Humans , Tonsillectomy/adverse effects , Ketorolac/therapeutic use , Ketorolac/adverse effects , Female , Male , Postoperative Hemorrhage/chemically induced , Postoperative Hemorrhage/epidemiology , Child , Child, Preschool , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Adolescent , Adenoidectomy/adverse effects , Retrospective Studies , Propensity Score , Pain, Postoperative/drug therapy , InfantABSTRACT
BACKGROUND: Acute type A aortic dissection (aTAAD) is a critical and life-threatening condition. Previous research has demonstrated that the use of ketorolac not only reduces the progression, incidence, and severity of aortic aneurysms in animal models, but also decreases postoperative mortality and complications in patients undergoing open abdominal aortic aneurysm replacement. However, there is a lack of studies investigating the efficacy of ketorolac in treating aTAAD in humans. Therefore, we conducted a study to evaluate the safety and efficacy of ketorolac in patients with aTAAD. Our hypothesis was that ketorolac treatment for aTAAD patients would meet safety indicators and effectively improve patient prognosis. METHODS/DESIGN: This study is a single-center, randomized, double-blinded, and placebo-controlled study. A total of 120 patients with aTAAD will be recruited and will be randomized into the ketorolac group and placebo group with a ratio of 1:1. Ketorolac tromethamine 60 mg per 2 ml will be intramuscularly injected within 2 h before surgery, followed by intramuscular injections of 30 mg per 1 ml BID. on the first and second postoperative days in the Ketorolac group, while 0.9% saline will be administered at the same dose, dosage form, and time in the placebo group. This study aims to evaluate the safety and efficacy of ketorolac in improving the prognosis of aTAAD. The primary endpoint is the composite endpoint event concerning drug-related adverse events. Secondary endpoints include drug-related adverse events, laboratory examination of blood, diagnostic imaging tests, clinical biomarkers, etc. DISCUSSION: This study has been approved by the Medical Ethics Committee of Affiliated Nanjing Drum Tower Hospital, Nanjing University Medical College (approval number: 2023-197-02). This study is designed to evaluate the safety and efficacy of ketorolac in patients with aTAAD. All participating patients will sign an informed consent form, and the trial results will be published in international peer-reviewed journals. TRIAL REGISTRATION: The Chinese Clinical Trial Registry ( http://www.chictr.org.cn ) ChiCTR2300074394. Registered on 4 October 2023.
Subject(s)
Aortic Dissection , COVID-19 , Humans , SARS-CoV-2 , Ketorolac/adverse effects , Prognosis , Aortic Dissection/diagnostic imaging , Aortic Dissection/drug therapy , Aortic Dissection/surgery , Treatment Outcome , Randomized Controlled Trials as TopicABSTRACT
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.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Diclofenac , Ketorolac , Ophthalmic Solutions , Animals , Dogs , Female , Male , Administration, Topical , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Diclofenac/administration & dosage , Diclofenac/adverse effects , Diclofenac/toxicity , Dog Diseases/chemically induced , Dog Diseases/drug therapy , Gastrointestinal Diseases/veterinary , Gastrointestinal Diseases/chemically induced , Ketorolac/adverse effects , Ketorolac/administration & dosageABSTRACT
AIMS: Putative beneficial effects of neuropeptide W (NPW) in the early phase of gastric ulcer healing process and the involvement of cyclooxygenase (COX) enzymes were investigated in an acetic acid-induced gastric ulcer model. MAIN METHODS: In anesthetized male Sprague-Dawley rats, acetic acid was applied surgically on the serosa and then a COX-inhibitor (COX-2-selective NS-398, COX-1-selective ketorolac, or non-selective indomethacin; 2 mg/kg/day, 3 mg/kg/day or 5 mg/kg/day; respectively) or saline was injected intraperitoneally. One h after ulcer induction, omeprazole (20 mg/kg/day), NPW (0.1 µg/kg/day) or saline was intraperitoneally administered. Injections of NPW, COX-inhibitors, omeprazole or saline were continued for the following 2 days until rats were decapitated at the end of the third day. KEY FINDINGS: NPW treatment depressed gastric prostaglandin (PG) I2 level, but not PGE2 level. Similar to omeprazole, NPW treatment significantly reduced gastric and serum tumor necrosis factor-alpha and interleukin-1 beta levels and depressed the upregulation of nuclear factor kappa B (NF-κB) and COX-2 expressions due to ulcer. In parallel with the histopathological findings, treatment with NPW suppressed ulcer-induced increases in myeloperoxidase activity and malondialdehyde level and replenished glutathione level. However, the inhibitory effect of NPW on myeloperoxidase activity and NPW-induced increase in glutathione were not observed in the presence of COX-1 inhibitor ketorolac or the non-selective COX-inhibitor indomethacin. SIGNIFICANCE: In conclusion, NPW facilitated the healing of gastric injury in rats via the inhibition of pro-inflammatory cytokine production, oxidative stress and neutrophil infiltration as well as the downregulation of COX-2 protein and NF-κB gene expressions.
Subject(s)
Neuropeptides , Signal Transduction , Stomach Ulcer , Animals , Male , Rats , Acetates/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Cyclooxygenase 1/metabolism , Cyclooxygenase 2/metabolism , Cyclooxygenase Inhibitors/therapeutic use , Gastric Mucosa , Glutathione/metabolism , Indomethacin/therapeutic use , Ketorolac/adverse effects , Neuropeptides/therapeutic use , NF-kappa B/metabolism , Omeprazole/pharmacology , Omeprazole/therapeutic use , Peroxidase/metabolism , Rats, Sprague-Dawley , Stomach Ulcer/drug therapy , Ulcer/metabolism , Ulcer/pathologyABSTRACT
BACKGROUND: The most prevalent entrapment neuropathy is carpal tunnel syndrome (CTS). Although nonsteroidal antiinflammatory drugs (NSAIDs) are frequently prescribed for musculoskeletal disorders, oral NSAIDs do not provide any additional benefits for CTS. Nevertheless, the use of NSAID phonophoresis has shown significant improvement, possibly due to increased concentration in the target tissue. The effects of intracarpal injection of NSAIDs on CTS have not been studied. OBJECTIVE: We conducted a controlled trial to compare the efficacy of ketorolac and triamcinolone in treating CTS. METHODS: Mild to moderate CTS patients were randomly assigned to receive either a local injection of 30 mg ketorolac or 40 mg triamcinolone. Patients were evaluated using visual analog scale (VAS) for pain, severity, function, electrodiagnostic findings, patient satisfaction, and any complications at the injection site, at baseline and 12 weeks after the procedures. RESULTS: Fifty patients participated, and 43 completed the study. Both groups showed significant improvement in the VAS, severity, function, and electrodiagnostic scores at 3 months compared with the baseline. A comparison of the groups showed significant differences in VAS, severity, and function, with the improvement being significantly higher in the triamcinolone group. CONCLUSION AND RELEVANCE: The present study showed that injection of triamcinolone or ketorolac into the carpal tunnel relieved pain, increased function, and improved electrodiagnostic findings in patients with mild to moderate CTS. It also showed that triamcinolone was superior to ketorolac in terms of analgesic effect and resulted in greater improvement in symptom severity and function.
Subject(s)
Carpal Tunnel Syndrome , Triamcinolone , Humans , Triamcinolone/adverse effects , Ketorolac/adverse effects , Carpal Tunnel Syndrome/drug therapy , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Pain/drug therapy , Treatment OutcomeABSTRACT
Although the efficacy of ketorolac in pain management and the short duration of use align well with current clinical practice guidelines, few studies have specifically evaluated the impact of ketorolac on bony union after fracture or surgery. The purpose of this study was to review the current basic science and clinical literature on the use of ketorolac for pain management after fracture and surgery and the subsequent risk of delayed union or nonunion. Animal studies demonstrate a dose-dependent risk of delayed union in rodents treated with high doses of ketorolac for 4 weeks or greater; however, with treatment for 7 days or low doses, there is no evidence of risk of delayed union or nonunion. Current clinical evidence has also shown a dose-dependent increased risk of pseudoarthrosis and nonunion after post-operative ketorolac administration in orthopedic spine surgery. However, other orthopedic subspecialities have not demonstrated increased risk of delayed union or nonunion with the use of peri-operative ketorolac administration. While evidence exists that long-term ketorolac use may represent risks with regard to fracture healing, insufficient evidence currently exists to recommend against short-term ketorolac use that is limited to the peri-operative period. LEVEL OF EVIDENCE V: Narrative Review.
Subject(s)
Fractures, Bone , Ketorolac , Animals , Ketorolac/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Fracture Healing , Pain ManagementABSTRACT
OBJECTIVE: To determine if perioperative ketorolac is associated with an increased rate of reoperation for hemorrhage after pediatric tonsillectomy at 30 days and 48 hours. STUDY DESIGN: Single-center retrospective propensity-matched study. SETTING: Quaternary pediatric hospital and ambulatory surgery center. METHODS: Patients less than 18 years old undergoing tonsillectomy or adenotonsillectomy between January 1, 2015 and October 1, 2020 were included. Hemorrhage rates between exposed (K+) and unexposed (K-) patients were calculated for the total cohort and a 1:1 propensity-matched cohort. Additional analyses included: multivariable logistic regression, subgroup analysis of ASA 1 and 2 patients, subgroup analysis comparing children with teenagers. RESULTS: There were 5873 patients (42.1% K+) in the full cohort and 4694 patients in the propensity-matched cohort. Reoperation for hemorrhage within 30 days occurred in 1.9% of K+ patients and 1.6% of K- patients (P = 0.455) in the full cohort and 1.9% of K+ patients and 1.7% of K- patients (odds ratio [OR] 1.10, 95% confidence interval [CI] 0.72-1.69, P = 0.662) in the propensity-matched cohort. Reoperation within 48 hours occurred in 0.65% of K+ patients and 0.53% of K- patients (P = 0.679) in the full cohort and 0.68% of K+ patients and 0.51% of K- patients (OR 1.33, 95% CI 0.63-2.81, P = 0.451) in the propensity-matched cohort. There was no association between perioperative ketorolac administration and reoperation for hemorrhage in any of the other analyses. CONCLUSION: Ketorolac at end of surgery should be considered as part of the nonopioid analgesic regimen for pediatric tonsillectomy.
Subject(s)
Ketorolac , Tonsillectomy , Adolescent , Child , Humans , Ketorolac/adverse effects , Tonsillectomy/adverse effects , Retrospective Studies , Reoperation , Hemorrhage , Postoperative Hemorrhage/chemically inducedABSTRACT
BACKGROUND: Despite high satisfaction rates, reduction mammaplasty can have complications such as hematoma. Factors such as age, tobacco use, and comorbidities are known contributors, whereas the influence of race, BMI, certain medications, and blood pressure (BP) remain contentious. This study investigates hematoma risk factors in young women undergoing reduction mammaplasty. STUDY DESIGN: A retrospective review was conducted including all female patients who underwent bilateral reduction mammaplasty at a single institution between 2012 and 2022. Data on demographics, BMI, medical comorbidities, surgical techniques, medications, and perioperative BP were collected. Differences between patients who developed a hematoma and those who did not were assessed using chi-square, Fisher's exact, and t -tests. The relationship between perioperative BP and hematoma formation was assessed using logistic regression. RESULTS: Of 1,754 consecutive patients, 3% developed postoperative hematoma of any kind, with 1.8% returning to the operating room. Age (odds ratio [OR] 1.14, p = 0.01) and ketorolac use (OR 3.93, p = 0.01) were associated with hematoma development. Controlling for baseline BP, each 10 mmHg incremental increase in peak intraoperative BP (systolic BP [SBP]: OR 1.24, p = 0.03; mean arterial pressure: OR 1.24, p = 0.01) and postoperative BP (SBP: OR 1.41, p = 0.01; mean arterial pressure: OR 1.49, p = 0.01) escalated the odds of hematoma. Postoperative SBP variability also incrementally increased hematoma odds (OR 1.48, p < 0.01). Other factors, including race and surgical technique, were not significantly influential. CONCLUSIONS: Age, ketorolac use, and intra- and postoperative BP peaks and variability are risk factors for hematoma in reduction mammaplasty. This emphasizes the importance of perioperative BP management and optimizing pain management protocols.
Subject(s)
Ketorolac , Mammaplasty , Female , Humans , Ketorolac/adverse effects , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Hematoma/etiology , Hematoma/chemically induced , Mammaplasty/adverse effects , Mammaplasty/methods , Mastectomy/adverse effects , Risk Factors , Retrospective StudiesABSTRACT
INTRODUCTION: There is an urgent unmet medical need for a safe, effective, nonopioid analgesic agent for postoperative pain control. METHODS: This first-in-man study was designed to explore a data-informed, model-based candidate dosage regimen and safety of a novel formulation of ketorolac tromethamine (NTM-001) delivered as a 12.5-mg intravenous (IV) bolus followed immediately by 3.5 mg/h continuous infusion over 24 h compared versus IV bolus dosing of 30 mg generic ketorolac every 6 h. The study evaluated pharmacokinetic parameters and safety profiles based on a targeted product profile. A graphical overlay method and model-based comparisons were used to assess the concentration-time curve. RESULTS: Healthy adults (n = 28, 50% men) received NTM-001 and bolus dosing in an open-label crossover design. Observed plasma concentrations were tightly aligned with predicted values with no outliers. Graphical overlay comparisons showed low between-subject variability and agreed with forecasted concentration-time targets. The pharmacokinetic (PK) base models fit with preliminary PK data from both the NTM-001 and bolus groups with model fit median profiles within 95% prediction limits and no updating of the models. Consistent with serum concentration-time profiles, pain relief scores fell within predicted limits, with initial pain relief scores of NTM-001 slightly above the target profile, likely because the initial serum ketorolac concentrations were somewhat higher than predicted. The 24-h pain relief predicted for NTM-001 based on the area under the median ketorolac pain relief versus time curve was about 6% below that of the pain relief target. Both treatments were well tolerated and no subject withdrew because of adverse events. CONCLUSIONS: The PK parameters for NTM-001 and comparator bolus were similar to the modeling targets with no updating of the base model. There were no outliers and little intersubject variability. NTM-001 delivered as a bolus of 12.5 mg IV followed immediately by continuous infusion of 3.5 mg/h using a standard hospital infusion pump may offer an alternative to opioids for acute postoperative pain control.
Opioids are effective analgesics but the risk for opioid use disorder (OUD) and opioid-associated side effects limit their use even for postoperative pain. Ketorolac is an established nonopioid pain reliever that may be as efficacious as morphine in this setting. This study evaluated a new ketorolac product (NTM-001) compared to generic ketorolac. Both were delivered using a standard hospital intravenous (IV) drug pump. The new ketorolac product was administered first with a loading dose of 12.5 mg followed immediately by a continuous IV infusion of 3.5 mg/h. This was compared to IV generic ketorolac administered as a bolus dose of 30 mg every 6 h. The study enrolled 28 healthy adult volunteers. As a crossover study, subjects underwent both treatments: once with the continuous infusion (NTM-001) and once with the IV injection every 6 h (bolus group) with a "washout" period in between. Blood was collected from the volunteers at several time-determined points during the 48-h study to chart ketorolac concentrations in the blood, which can be correlated to predicted levels of pain control. In this study, blood concentrations of ketorolac were reliably predictable and side effects were generally mild with no unexpected adverse events. The continuous infusion group achieved analgesic benefit at a lower total dose than did the every-6-h group over 24 h.
Subject(s)
Ketorolac Tromethamine , Ketorolac , Adult , Male , Humans , Female , Ketorolac Tromethamine/adverse effects , Ketorolac/adverse effects , Healthy Volunteers , Analgesics, Opioid/therapeutic use , Pain, Postoperative/drug therapy , Double-Blind Method , Morphine/therapeutic useABSTRACT
BACKGROUND: A combination of opioids and adjunctive drugs can be used for intravenous patient-controlled analgesia (PCA) to minimize opioid-related side effects. We investigated whether two different analgesics administered separately via a dual-chamber PCA have fewer side effects with adequate analgesia than a single fentanyl PCA in gynecologic pelviscopic surgery. METHODS: This prospective, double-blind, randomized, and controlled study included 68 patients who underwent pelviscopic gynecological surgery. Patients were allocated to either the dual (ketorolac and fentanyl delivered by a dual-chamber PCA) or the single (fentanyl alone) group. Postoperative nausea and vomiting (PONV) and analgesic quality were compared between the two groups at 2, 6, 12, and 24 h postoperatively. RESULTS: The dual group showed a significantly lower incidence of PONV during postoperative 2-6 h (P = 0.011) and 6-12 h (P = 0.009). Finally, only two patients (5.7%) in the dual group and 18 (54.5%) in the single group experienced PONV during the entire postoperative 24 h and could not maintain intravenous PCA (odds ratio: 0.056, 95% CI [0.007, 0.229], P < 0.001). Despite the administration of less fentanyl via intravenous PCA during the postoperative 24 h in the dual group than in the single group (66.0 ± 77.8 vs. 383.6 ± 70.1 µg, P < 0.001), postoperative pain had no significant intergroup difference. CONCLUSIONS: Two different analgesics, continuous ketorolac and intermittent fentanyl bolus, administered via dual-chamber intravenous PCA, showed fewer side effects with adequate analgesia than conventional intravenous fentanyl PCA in gynecologic patients undergoing pelviscopic surgery.
Subject(s)
Fentanyl , Pain Management , Female , Humans , Analgesics, Opioid , Fentanyl/adverse effects , Gynecologic Surgical Procedures/adverse effects , Ketorolac/adverse effects , Pain, Postoperative/drug therapy , Pain, Postoperative/etiology , Pain, Postoperative/prevention & control , Postoperative Nausea and Vomiting/epidemiology , Postoperative Nausea and Vomiting/prevention & control , Prospective Studies , Double-Blind MethodABSTRACT
Because of the mutual relationship between neural inflammation and seizure, this study aimed to determine the effects of intracerebroventricular (ICV) injection of the steroidal and non-steroidal anti-inflammatory drugs on pentylenetetrazol (PTZ)-induced seizures during the estrous cycle in rats. A total of 105 adult female Wistar rats were selected and divided into seven groups, including the control (saline), ketorolac tris salt (7.5, 15, and 30 µg), and methylprednisolone acetate (0.15, 0.3, and 0.6 µg), each with four subgroups (proestrus, estrus, metestrus, and diestrus) and three replicates (n=5). After a week of acclimatization, the estrous phase determination and synchronization were performed. Acute epilepsy was inspired by the intraperitoneal injection of 80 mg/kg of PTZ 30 min after the ICV injection of ketorolac and methylprednisolone acetate. The initiation time of myoclonic seizures (ITMS), the initiation time of tonic-clonic seizures (ITTS), seizure duration (SD), and mortality rate (MR) were measured for 30 min. Data were shown as mean±SD and analyzed using One-way ANOVA followed by Tukey-Kramer multiple comparison post hoc test (P<0.05). According to the results, ketorolac (15 and 30 µg) and methylprednisolone acetate (0.3 and 0.6 µg) significantly increased the ITTS and ITMS but decreased SD during the estrous cycle, compared to the control (P<0.05). Moreover, MR and SD were significantly decreased by ketorolac (7.5, 15, and 30 µg) and methylprednisolone (0.3 and 0.6 µg), compared to the control during the estrous cycle (P<0.05). Therefore, it seems that both ketorolac and methylprednisolone possess dose-dependent anticonvulsant effects that may decrease neural inflammation.
Subject(s)
Ketorolac , Rats , Female , Animals , Rats, Wistar , Ketorolac/adverse effects , Methylprednisolone Acetate/adverse effects , Estrous Cycle , Seizures/chemically induced , Seizures/drug therapy , Inflammation , Anti-Inflammatory AgentsABSTRACT
Background Ketorolac, the non-steroidal anti-inflammatory drug, is thought to have less sedation as well as postoperative nausea and vomiting in comparison to opioids, but with higher risk of post-tonsillectomy hemorrhage as reported in some of the literatures. There is no consensus till date in the use of ketorolac in the management of pain following tonsil and adenoid related surgeries. Objective To find out the incidence of hemorrhage following tonsil and adenoid related surgeries in patients receiving ketorolac in postoperative period. Method This is a retrospective chart review of patients undergoing tonsil and adenoid related surgeries who had received ketorolac during April, 2013 to May, 2019 at department of ENT-HNS, Patan Academy of Health Sciences (PAHS), Lalitpur, Nepal. Post-tonsillectomy hemorrhage rate was calculated in pediatric and adult patients. Result During the study period, 103 patients (male - 50 and female - 53) received ketorolac in postoperative period. Tonsillectomy and adenotonsillectomy were performed in 71and 32 patients respectively. Forty-five patients were < 18 years whereas 58 were ≥ 18 years. Most common indication for surgery was recurrent tonsillitis (66/103) followed by adenotonsillar hypertrophy (31/103). Post-tonsillectomy hemorrhage was observed in 15 patients; among them, four out 45 were < 18 years and 11 out of 58 ≥ 18 years. All five patients out of 15, who required surgical intervention for post-tonsillectomy hemorrhage, were ≥ 18 years and were operated for recurrent tonsillitis. Rest of the patients (10/15) were managed conservatively. None of the patients required blood transfusion. Conclusion Ketorolac is not associated with increased risk of post-tonsillectomy hemorrhage in children and can safely be administered. Whereas in adults, recurrent tonsillitis being the most common indication for tonsillectomy, it should be used cautiously.
Subject(s)
Tonsillectomy , Tonsillitis , Adult , Humans , Child , Male , Female , Ketorolac/adverse effects , Tonsillectomy/adverse effects , Tonsillectomy/methods , Retrospective Studies , Hemorrhage/etiology , Analgesics , Tonsillitis/drug therapy , Tonsillitis/surgery , Tonsillitis/complications , Postoperative Hemorrhage/chemically induced , Postoperative Hemorrhage/epidemiology , Pain, Postoperative/drug therapy , Pain, Postoperative/etiologyABSTRACT
Ketorolac tromethamine (KT), is a widely used non-steroidal anti-inflammatory drug (NSAID) for treating moderate to severe pain. However, the use of KT has been restricted due to its highly toxic attributes that lead to severe gastric ulceration and bleeding. The protective effects of exogenous melatonin (MT) has been reported in conditions associated with gastro-intestinal disorders. This study aims at exploring the role of gastric endogenous MT level and it's metabolizing enzyme AANAT, at the onset of ketorolac mediated toxicities in the gastric mucosa. Gastric mucosal damage was induced in experimental rats by oral administration of graded doses of KT, where 50 mg/kg b.w. of KT was observed to incur maximum gastric lesions. However, gastric damages were found to be protected in rats, pre-treated with 60 mg/kg b.w. of MT. Post-sacrifice, mean ulcer index, oxidative status, total melatonin levels and enzyme activities associated with MT biosynthesis and catabolism were estimated. The results reveal that KT decreases AANAT activity with a concomitant decline in endogenous MT level which cumulatively aggravates gastric toxicity. Moreover, exogenous MT administration has been found to be protective in ameliorating this ulcerogenic process in rats, challenged with KT. Biochemical and histo-pathological observations revealed the reduction in oxidative stress level and replenishment of depleted gastric MT levels in MT pre-treated animals, which might be the causative factors in conferring protection to the gastric tissues and residing mitochondria. The results revealed a correlation between depleted gastric MT level and ulcer formation, which unveiled a novel ulcerogenic mechanism. This may bring forth future therapeutic relevance for treating patients suffering from KT mediated acute gastric toxicities.
Subject(s)
Melatonin , Stomach Ulcer , Rats , Animals , Melatonin/therapeutic use , Ketorolac/adverse effects , Ulcer/complications , Ulcer/drug therapy , Ulcer/pathology , Gastric Mucosa , Stomach/pathology , Stomach Ulcer/chemically induced , Stomach Ulcer/drug therapy , Stomach Ulcer/prevention & controlABSTRACT
BACKGROUND: There are conflicting data on the risk of postoperative pancreatic fistula (POPF) associated with postoperative NSAID use. The primary objective of this multi-center retrospective study was to assess the relationship between ketorolac use and POPF. The secondary objective was to assess for effect of ketorolac use on overall complication rate. METHODS: Retrospective chart review of patients undergoing pancreatectomy from January 1, 2005-January 1, 2016 was performed. Data on patient factors (age, sex, comorbidities, previous surgical history etc.), operative factors (surgical procedure, estimated blood loss, pathology etc.), and outcomes (morbidities, mortality, readmission, POPF) were collected. The cohort was compared based on ketorolac use. RESULTS: The study included 464 patients. Ninety-eight (21%) patients received ketorolac during the study period. Ninety-six (21%) patients were diagnosed with POPF within 30 days. There was a significant association between ketorolac use and clinically relevant POPF (21.4 vs. 12.7%) (p = 0.04, 95% CI [1.76, 1.04-2.97]). There was no significant difference in overall morbidity or mortality between the groups. DISCUSSION: Though there was no overall increase in morbidity, there was a significant association between POPF and ketorolac use. The use of ketorolac after pancreatectomy should be judicious.
Subject(s)
Pancreatectomy , Pancreatic Fistula , Humans , Ketorolac/adverse effects , Pancreas , Pancreatectomy/adverse effects , Pancreatectomy/methods , Pancreatic Fistula/etiology , Postoperative Complications/etiology , Retrospective Studies , Risk Factors , Male , FemaleABSTRACT
INTRODUCTION & OBJECTIVE: The opioid crisis has raised concerns for long-term sequela of routine administration of opioids to patients, particularly in the pediatric population. Nonsteroidal anti-inflammatory drug use is limited in hypospadias surgery due to concerns for post-operative bleeding, particularly with ketorolac. We hypothesize that ketorolac administration at the time of hypospadias repair is not associated with increased bleeding or immediate adverse events. METHODS: A retrospective single institution study included all patients undergoing hypospadias surgery from 2018 to 2021. Outcomes measured include peri-operative ketorolac administration, opioid prescriptions, and unplanned encounters (i.e., emergency department or office visits). Comparative statistics using non-parametric and binary/categorical tests and a logistic regression were performed. RESULTS: 1044 patients were included, among whom there were 562 distal, 278 proximal and 204 hypospadias complication repairs. Ketorolac was administered to 396 (37.9%) patients and its utilization increased during the study period [Summary Figure]. Patients receiving ketorolac were older (p = 0.002) and were prescribed opioids less often after surgery (2.0% vs 5.2%, p = 0.009). There was no difference in unplanned encounters across repair types (p = 0.1). Multivariate logistic regression showed ketorolac use was not associated with an increased likelihood of an unplanned encounter. DISCUSSION: The use of NSAIDs post-operatively has traditionally been limited due to concerns about bleeding risks, however the present study displayed no significant increases in unplanned patient encounters either in the ED or outpatient clinic after ketorolac administration. Our study has several limitations including its retrospective and single-institutional design, difficulties of pain assessment in pediatric population, and possibility of under estimation of unplanned encounters due to limited access to patients' records outside of our institution. CONCLUSIONS: The use of ketorolac is not associated with an increase in unplanned encounters in children undergoing hypospadias repair. It should be considered a safe agent for perioperative analgesia to decrease opioid utilization. Further studies will evaluate long-term surgical outcomes in children receiving ketorolac after hypospadias repair.
Subject(s)
Hypospadias , Ketorolac , Male , Humans , Child , Ketorolac/adverse effects , Hypospadias/surgery , Hypospadias/chemically induced , Analgesics, Opioid/therapeutic use , Retrospective Studies , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Pain, Postoperative/drug therapyABSTRACT
AIM: To evaluate the possible association of CYP2C8 gene polymorphisms with the clinical efficacy and safety of ketorolac in relation to postoperative pain. MATERIALS AND METHODS: The study included 107 patients after video laparoscopic cholecystectomy, who received ketorolac (30 mg 2.0 w/m 3 r/d) as postoperative pain relief. All patients were genotyped for CYP2C8. The pain syndrome was assessed using the visual analog scale, the McGill pain questionnaire. The profile of adverse reactions was assessed by the dynamics of red blood counts, as a possible trigger for the development of gastrointestinal bleeding according to the method of global assessment of triggers (Global Trigger Tool GTT). RESULTS: According to visual analog scale data: in carriers of the genotype CYP2C8*3 (rs10509681) and CYP2C8*3 (rs11572080) after 12, 24, 36, 48 hours the intensity of pain syndrome is lower than in carriers of the wild type (p0.05). According to the McGill pain questionnaire, there were no statistically significant differences in pain intensity between the two groups. CONCLUSION: In carriers of the genotype CYP2C8*3 (rs10509681) and CYP2C8*3 (rs11572080), the effectiveness of anesthesia with ketorolac is higher than in carriers of the wild type. Carriage of the genotype CYP2C8*3 (rs10509681) and CYP2C8*3 (rs10509681) does not affect the risk of developing adverse reactions after ketorolac anesthesia.
Subject(s)
Ketorolac , Pain, Postoperative , Humans , Ketorolac/adverse effects , Cytochrome P-450 CYP2C8/genetics , Pain, Postoperative/etiology , Pain, Postoperative/genetics , Pain Measurement , Polymorphism, Genetic , Double-Blind Method , Anti-Inflammatory Agents, Non-Steroidal/adverse effectsABSTRACT
BACKGROUND: Owing to the frequent perioperative use of ketorolac tromethamine and its ability to minimise postoperative opioid requirements, it is important to continually reassess harms associated with its use. Our primary objective was to investigate the extent of harms reporting in systematic reviews (SRs) on ketorolac for perioperative pain. METHODS: In May 2022, we conducted a search of major databases, MEDLINE (PubMed and Ovid), Embase, Epistemonikos, and the Cochrane Database of Systematic Reviews to identify eligible SRs on ketorolac for perioperative pain. Screening and data extraction were performed in masked, duplicate fashion. A MeaSurement Tool to Assess systematic Reviews-2 (AMSTAR-2) was used to appraise the methodological quality of included SRs. Corrected covered area (CCA) was calculated to determine overlap of primary studies between SR dyads. RESULTS: A total of 28 SRs evaluating 630 primary studies met the inclusion criteria. Seven SRs (7/28, 25%) reported no harms and 17 SRs (17/28, 60.7%) reported ≤50% of harms items. A significant association was found between completeness of harms reporting and whether harms were specified as a primary outcome (P<0.001). No other associations were statistically significant. Regarding methodological quality, 22 SRs were appraised as 'critically low' (22/28, 78.6%), 5 as 'low' (5/28, 17.9%), and 1 as 'high' (1/28, 3.6%). One SR dyad had a CCA >50% but neither reported harms. CONCLUSIONS: The extent of harms reporting in systematic reviews was inadequate. Given the importance that systematic reviews have on guiding perioperative decision-making, it is essential to improve the completeness of harms reporting.
Subject(s)
Ketorolac , Research Design , Humans , Ketorolac/adverse effects , Ketorolac Tromethamine , Analgesics, Opioid , Systematic Reviews as Topic , PainABSTRACT
BACKGROUND: Enhanced recovery after surgery (ERAS) protocols following mastectomy with or without implant-based breast reconstruction (IBBR) include ketorolac for multimodal perioperative analgesia. There are concerns that ketorolac could be associated with increased risk of postoperative hematoma formation. METHODS: Retrospective review of patients undergoing mastectomy with or without IBBR between January 2013 and December 2019 at a single institution. Patients received 15 mg, 30 mg, or no ketorolac depending on ERAS protocol adherence, patient characteristics, and surgeon preference. Clinically significant hematoma was defined as requiring surgical intervention on day of surgery or postoperative day 1. Patients were compared by demographics, surgical characteristics, ketorolac dose, and hematoma prevalence. Univariable and multivariable logistic regression evaluated hematoma formation odds. RESULTS: Eight hundred patients met inclusion criteria: 477 received ketorolac. Those who received ketorolac were younger, had lower ASA scores, were more likely to have bilateral procedures and undergo concomitant IBBR, had longer operative times, were less likely to take antiplatelet or anticoagulation medications, had higher PACU pain scores, and had higher incidence of hematomas requiring surgical intervention. Of the cohort, 4.4% had clinically significant hematomas. The 15 mg and 30 mg ketorolac groups had similar prevalence (6.0% vs 5.8%, p = 0.95). On univariable regression, there were increased odds of hematoma formation in patients who were younger, had bilateral procedures, had longer OR times, and who received ketorolac. On multivariable regression, none of the prior variables remained significant. CONCLUSION: After accounting for associations with longer operative times, concomitant IBBR, and bilateral procedures, ketorolac administration did not remain an independent risk factor for hematoma formation.