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2.
J Transl Med ; 22(1): 102, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38273276

RESUMO

BACKGROUND: While antibiotics remain our primary tools against microbial infection, increasing antibiotic resistance (inherent and acquired) is a major detriment to their efficacy. A practical approach to maintaining or reversing the efficacy of antibiotics is the use of other commonly used therapeutics, which show synergistic antibacterial action with antibiotics. Here, we investigated the extent of antibacterial synergy between the antibiotic gentamicin and the anti-inflammatory ketorolac regarding the dynamics of biofilm growth, the rate of acquired resistance, and the possible mechanism of synergy. METHODS: Control (ATCC 12600, ATCC 35984) and clinical strains (L1101, L1116) of Staphylococcus aureus and Staphylococcus epidermidis with varying antibiotic susceptibility profiles were used in this study to simulate implant-material associated low-risk and high-risk biofilms in vitro. The synergistic action of gentamicin sulfate (GS) and ketorolac tromethamine (KT), against planktonic staphylococcal strains were determined using the fractional inhibitory concentration measurement assay. Nascent (6 h) and established (24 h) biofilms were grown on 316L stainless steel plates and the synergistic biofilm eradication activity was determined and characterized using adherent bacteria count, minimum biofilm eradication concentration (MBEC) measurement for GS, visualization by live/dead imaging, scanning electron microscopy, gene expression of biofilm-associated genes, and bacterial membrane fluidity assessment. RESULTS: Gentamicin-ketorolac (GS-KT) combination demonstrated synergistic antibacterial action against planktonic Staphylococci. Control and clinical strains showed distinct biofilm growth dynamics and an increase in biofilm maturity was shown to confer further resistance to gentamicin for both 'low-risk' and 'high-risk' biofilms. The addition of ketorolac enhanced the antibiofilm activity of gentamicin against acquired resistance in staphylococcal biofilms. Mechanistic studies revealed that the synergistic action of gentamicin-ketorolac interferes with biofilm morphology and subverts bacterial stress response altering bacterial physiology, membrane dynamics, and biofilm properties. CONCLUSION: The results of this study have a significant impact on the local administration of antibiotics and other therapeutic agents commonly used in the prevention and treatment of orthopaedic infections. Further, these results warrant the study of synergy for the concurrent or sequential administration of non-antibiotic drugs for antimicrobial effect.


Assuntos
Gentamicinas , Infecções Estafilocócicas , Humanos , Gentamicinas/farmacologia , Gentamicinas/uso terapêutico , Cetorolaco/farmacologia , Cetorolaco/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Staphylococcus aureus , Biofilmes , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/prevenção & controle , Testes de Sensibilidade Microbiana
3.
Orphanet J Rare Dis ; 19(1): 22, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38254184

RESUMO

Pain is an hallmark of sickle-cell-related acute clinical manifestations as part of acute vaso-occlusive crisis (VOC). In SCD pain has different origins such as vascular or neuropathic pain, which requires multimodal analgesia. This is based on the administration of drugs with different pharmacological mechanisms of action, maximizing analgesia and minimizing their adverse events and the risk of drug-addition in patients experiencing acute-recurrent pain events as in SCD. Ketorolac is a potent non-narcotic analgesic, being relatively safe and effective during pain-management in children and adults. Up to now, there is a lack of safety information on continuous infusion ketorolac as used to control acute pain in patients with SCD, and the benefits/risks ratio needs to be investigated. Here, we report for the first time the safety profile of ketorolac in the special population of patients with SCD. We confirmed that ketorolac in combination with tramadol, an opioid like molecule, is effective in pain control of adult patients with SCD experiencing acute severe VOCs defined by pain visual analog scale. Our study shows that short term (72 h) continuous infusion of ketorolac plus tramadol is not associated with adverse events such as liver or kidney acute disfunction or abnormalities in coagulation parameters during patients' hospitalization and within 30 days after patients discharge. This is extremely important for patients with SCD, who should have access to multimodal therapy to control recurrent acute pain crisis in order to limit central sensitization a fearsome issue of undertreated recurrent acute pain and of chronic pain.


Assuntos
Dor Aguda , Analgesia , Anemia Falciforme , Hemoglobinopatias , Tramadol , Adulto , Criança , Humanos , Cetorolaco/uso terapêutico , Dor Aguda/tratamento farmacológico , Anemia Falciforme/complicações , Anemia Falciforme/tratamento farmacológico
4.
Int Wound J ; 21(1): e14661, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38272819

RESUMO

This meta-analysis evaluates the impact of topical ketorolac on surgical site wound healing and scar formation after cataract surgery. A thorough literature search, adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, identified eight relevant studies from 2348 articles. The selected studies were analysed for wound healing efficacy, using the redness, edema, ecchymosis, discharge and approximation (REEDA) scale, and scar formation, assessed by the Manchester scar scale (MSS). Results indicated that ketorolac significantly improved wound healing, with lower REEDA scores 1 week post-surgery (I2 = 97%; Random: standardised mean difference (SMD): -10.93, 95% CI: -13.85 to -8.00, p < 0.01), and reduced scar formation, evidenced by lower MSS scores 3 months post-surgery (I2 = 74%; Random: SMD: -9.67, 95% CI: -11.03 to -8.30, p < 0.01). The findings suggest that topical ketorolac is beneficial in post-cataract surgery care, enhancing wound healing and reducing scarring.


Assuntos
Extração de Catarata , Catarata , Humanos , Cetorolaco/uso terapêutico , Cicatriz , Extração de Catarata/métodos , Cicatrização , Edema
5.
Cochrane Database Syst Rev ; 1: CD015432, 2024 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-38180091

RESUMO

BACKGROUND: Children often require pain management following surgery to avoid suffering. Effective pain management has consequences for healing time and quality of life. Ibuprofen, a frequently used non-steroidal anti-inflammatory drug (NSAID) administered to children, is used to treat pain and inflammation in the postoperative period. OBJECTIVES: 1) To assess the efficacy and safety of ibuprofen (any dose) for acute postoperative pain management in children compared with placebo or other active comparators. 2) To compare ibuprofen administered at different doses, routes (e.g. oral, intravenous, etc.), or strategies (e.g. as needed versus as scheduled). SEARCH METHODS: We used standard Cochrane search methods. We searched CENTRAL, MEDLINE, Embase, CINAHL and trials registries in August 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in children aged 17 years and younger, treated for acute postoperative or postprocedural pain, that compared ibuprofen to placebo or any active comparator. We included RCTs that compared different administration routes, doses of ibuprofen and schedules. DATA COLLECTION AND ANALYSIS: We adhered to standard Cochrane methods for data collection and analysis. Our primary outcomes were pain relief reported by the child, pain intensity reported by the child, adverse events, and serious adverse events. We present results using risk ratios (RR) and standardised mean differences (SMD), with the associated confidence intervals (CI). We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included 43 RCTs that enroled 4265 children (3935 children included in this review). We rated the overall risk of bias at the study level as high or unclear for 37 studies that had one or several unclear or high risk of bias judgements across the domains. We judged six studies as having a low risk of bias across all domains. Ibuprofen versus placebo (35 RCTs) No studies reported pain relief reported by the child or a third party, or serious adverse events. Ibuprofen probably reduces child-reported pain intensity less than two hours postintervention compared to placebo (SMD -1.12, 95% CI -1.39 to -0.86; 3 studies, 259 children; moderate-certainty evidence). Ibuprofen may reduce child-reported pain intensity, two hours to less than 24 hours postintervention (SMD -1.01, 95% CI -1.24 to -0.78; 5 studies, 345 children; low-certainty evidence). Ibuprofen may result in little to no difference in adverse events compared to placebo (RR 0.79, 95% CI 0.51 to 1.23; 5 studies, 384 children; low-certainty evidence). Ibuprofen versus paracetamol (21 RCTs) No studies reported pain relief reported by the child or a third party, or serious adverse events. Ibuprofen likely reduces child-reported pain intensity less than two hours postintervention compared to paracetamol (SMD -0.42, 95% CI -0.82 to -0.02; 2 studies, 100 children; moderate-certainty evidence). Ibuprofen may slightly reduce child-reported pain intensity two hours to 24 hours postintervention (SMD -0.21, 95% CI -0.40 to -0.02; 6 studies, 422 children; low-certainty evidence). Ibuprofen may result in little to no difference in adverse events (0 events in each group; 1 study, 44 children; low-certainty evidence). Ibuprofen versus morphine (1 RCT) No studies reported pain relief or pain intensity reported by the child or a third party, or serious adverse events. Ibuprofen likely results in a reduction in adverse events compared to morphine (RR 0.58, 95% CI 0.40 to 0.83; risk difference (RD) -0.25, 95% CI -0.40 to -0.09; number needed to treat for an additional beneficial outcome (NNTB) 4; 1 study, 154 children; moderate-certainty evidence). Ibuprofen versus ketorolac (1 RCT) No studies reported pain relief or pain intensity reported by the child, or serious adverse events. Ibuprofen may result in a reduction in adverse events compared to ketorolac (RR 0.51, 95% CI 0.27 to 0.96; RD -0.29, 95% CI -0.53 to -0.04; NNTB 4; 1 study, 59 children; low-certainty evidence). AUTHORS' CONCLUSIONS: Despite identifying 43 RCTs, we remain uncertain about the effect of ibuprofen compared to placebo or active comparators for some critical outcomes and in the comparisons between different doses, schedules and routes for ibuprofen administration. This is largely due to poor reporting on important outcomes such as serious adverse events, and poor study conduct or reporting that reduced our confidence in the results, along with small underpowered studies. Compared to placebo, ibuprofen likely results in pain reduction less than two hours postintervention, however, the efficacy might be lower at two hours to 24 hours. Compared to paracetamol, ibuprofen likely results in pain reduction up to 24 hours postintervention. We could not explore if there was a different effect in different kinds of surgeries or procedures. Ibuprofen likely results in a reduction in adverse events compared to morphine, and in little to no difference in bleeding when compared to paracetamol. We remain mostly uncertain about the safety of ibuprofen compared to other drugs.


Assuntos
Ibuprofeno , Dor Pós-Operatória , Humanos , Acetaminofen , Ibuprofeno/uso terapêutico , Cetorolaco , Morfina , Dor Pós-Operatória/tratamento farmacológico , Criança
6.
J Orthop Surg (Hong Kong) ; 32(1): 10225536231225758, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38182131

RESUMO

BACKGROUND: Total knee arthroplasty (TKA) is a routine orthopedic procedure often associated with significant postoperative pain. Efficient pain management is paramount for patient recovery, with nonsteroidal anti-inflammatory drugs (NSAIDs) being a common choice. Nevertheless, the specific NSAID and its dosing regimen can have varying impacts on outcomes. METHODS: In this retrospective cohort study spanning from January 2016 to December 2020, we analyzed patients who underwent TKA. These patients were divided into two groups: one receiving preemptive low-dose ketorolac (15 mg) followed by 15 mg every 6 h for 48 h, and the other receiving parecoxib (40 mg) every 12 h for the same duration. We assessed pain scores, opioid consumption, and monitored adverse events. RESULTS: Our findings reveal that ketorolac yielded superior results compared to parecoxib. Specifically, patients receiving ketorolac reported significantly lower Visual Numeric Rating Scale (VNRS) scores at 8- and 20-h post-surgery. This trend was further confirmed by linear mixed models (p = .0084). Additionally, ketorolac was associated with reduced opioid consumption during the initial 24 h. Importantly, the rates of adverse events were comparable between the two groups. CONCLUSION: The utilization of preemptive low-dose ketorolac demonstrates promising potential in bolstering pain control within the initial 24 h post-TKA, potentially reducing the need for opioids. However, further exploration is required to thoroughly assess its prolonged analgesic effects and safety across various surgical contexts. These investigations could provide invaluable insights for optimizing pain management protocols.


Assuntos
Artroplastia do Joelho , Cetorolaco , Humanos , Cetorolaco/uso terapêutico , Analgésicos Opioides/uso terapêutico , Estudos Retrospectivos , Pontuação de Propensão , Analgésicos , Anti-Inflamatórios não Esteroides/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle
7.
Ann Pharmacother ; 58(3): 205-213, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37278013

RESUMO

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.


Assuntos
Síndrome do Túnel Carpal , Triancinolona , Humanos , Triancinolona/efeitos adversos , Cetorolaco/efeitos adversos , Síndrome do Túnel Carpal/tratamento farmacológico , Anti-Inflamatórios não Esteroides/efeitos adversos , Dor/tratamento farmacológico , Resultado do Tratamento
8.
Korean J Anesthesiol ; 77(1): 77-84, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37312413

RESUMO

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.


Assuntos
Fentanila , Manejo da Dor , Feminino , Humanos , Analgésicos Opioides , Fentanila/efeitos adversos , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Cetorolaco/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Náusea e Vômito Pós-Operatórios/epidemiologia , Náusea e Vômito Pós-Operatórios/prevenção & controle , Estudos Prospectivos , Método Duplo-Cego
10.
Otolaryngol Head Neck Surg ; 170(3): 928-936, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37925621

RESUMO

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.


Assuntos
Cetorolaco , Tonsilectomia , Adolescente , Criança , Humanos , Cetorolaco/efeitos adversos , Tonsilectomia/efeitos adversos , Estudos Retrospectivos , Reoperação , Hemorragia , Hemorragia Pós-Operatória/induzido quimicamente
11.
Adv Ther ; 41(2): 659-671, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38070041

RESUMO

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.


Assuntos
Cetorolaco de Trometamina , Cetorolaco , Adulto , Masculino , Humanos , Feminino , Cetorolaco de Trometamina/efeitos adversos , Cetorolaco/efeitos adversos , Voluntários Saudáveis , Analgésicos Opioides/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Método Duplo-Cego , Morfina/uso terapêutico
12.
Eur J Orthop Surg Traumatol ; 34(1): 673-681, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37688640

RESUMO

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.


Assuntos
Fraturas Ósseas , Cetorolaco , Animais , Cetorolaco/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Consolidação da Fratura , Manejo da Dor
13.
Spine (Phila Pa 1976) ; 49(2): 73-80, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37737686

RESUMO

STUDY DESIGN: A randomized, double-blinded, placebo-controlled trial. OBJECTIVE: To examine the effect of intravenous ketorolac (IV-K) on hospital opioid use compared with IV-placebo (IV-P) and IV acetaminophen (IV-A). SUMMARY OF BACKGROUND DATA: Controlling postoperative pain while minimizing opioid use after lumbar spinal fusion is an important area of study. PATIENTS AND METHODS: Patients aged 18 to 75 years undergoing 1 to 2 level lumbar fusions between April 2016 and December 2019 were included. Patients with chronic opioid use, smokers, and those on systemic glucocorticoids or contraindications to study medications were excluded. A block randomization scheme was used, and study personnel, hospital staff, and subjects were blinded to the assignment. Patients were randomized postoperatively. The IV-K group received 15 mg (age > 65) or 30 mg (age < 65) every six hours (q6h) for 48 hours, IV-A received 1000 mg q6h, and IV-P received normal saline q6h for 48 hours. Demographic and surgical details, opioid use in morphine milliequivalents, opioid-related adverse events, and length of stay (LOS) were recorded. The primary outcome was in-hospital opioid use up to 72 hours. RESULTS: A total of 171 patients were included (58 IV-K, 55 IV-A, and 58 IV-P) in the intent-to-treat (ITT) analysis, with a mean age of 57.1 years. The IV-K group had lower opioid use at 72 hours (173 ± 157 mg) versus IV-A (255 ± 179 mg) and IV-P (299 ± 179 mg; P = 0.000). In terms of opiate use, IV-K was superior to IV-A ( P = 0.025) and IV-P ( P = 0.000) on ITT analysis, although on per-protocol analysis, the difference with IV-A did not reach significance ( P = 0.063). When compared with IV-P, IV-K patients reported significantly lower worst ( P = 0.004), best ( P = 0.001), average ( P = 0.001), and current pain ( P = 0.002) on postoperative day 1, and significantly shorter LOS ( P = 0.009) on ITT analysis. There were no differences in opioid-related adverse events, drain output, clinical outcomes, transfusion rates, or fusion rates. CONCLUSIONS: By reducing opioid use, improving pain control on postoperative day 1, and decreasing LOS without increases in complications or pseudarthrosis, IV-K may be an important component of "enhanced recovery after surgery" protocols.


Assuntos
Cetorolaco , Transtornos Relacionados ao Uso de Opioides , Humanos , Pessoa de Meia-Idade , Cetorolaco/uso terapêutico , Analgésicos Opioides/uso terapêutico , Tempo de Internação , Método Duplo-Cego , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia
14.
Ann Emerg Med ; 83(3): 217-224, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37999652

RESUMO

STUDY OBJECTIVE: Atomized intranasal (IN) drug administration offers an alternative to the intravenous (IV) route. We aimed to evaluate the analgesic efficacy of IN versus IV ketorolac in emergency department patients with acute renal colic. METHODS: We conducted a double-blind, randomized controlled trial on adult patients (aged 18 to 64 years) with severe renal colic and numerical rating scale pain ratings ≥7.0. They were randomly assigned (1:1) to receive single doses of either IN or IV ketorolac. Our main outcomes were differences in numerical rating scale reduction at 30 and 60 minutes. A 95% confidence interval (CI) was calculated for each mean difference, with a minimum clinically important difference set at 1.3 points. Secondary outcomes included treatment response, adverse events, rescue medications, and emergency department revisits. We analyzed using intention-to-treat. RESULTS: A total of 86 and 85 patients with similar baseline characteristics were allocated to the IV and IN groups, respectively. Mean numerical rating scale scores were 8.52 and 8.65 at baseline, 3.85 and 4.67 at 30 minutes, and 2.80 and 3.04 at 90 minutes, respectively. The mean numerical rating scale reduction differences between the IV and IN groups were 0.69 (95% CI -0.08 to 1.48) at 30 minutes and 0.10 (95% CI -0.85 to 1.04) at 60 minutes. There were no differences in secondary outcomes. CONCLUSION: Neither IN or IV ketorolac was superior to the other for the treatment of acute renal colic, and both provided clinically meaningful reductions in pain scores at 30 to 60 minutes.


Assuntos
Cólica , Cólica Renal , Adulto , Humanos , Cetorolaco/uso terapêutico , Cólica Renal/tratamento farmacológico , Administração Intravenosa , Dor/tratamento farmacológico , Método Duplo-Cego , Serviço Hospitalar de Emergência , Anti-Inflamatórios não Esteroides/uso terapêutico , Cólica/tratamento farmacológico
15.
Drug Des Devel Ther ; 17: 3757-3766, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38144418

RESUMO

Purpose: We investigate the efficacy and safety of butorphanol in multimodal analgesia combined with dexmedetomidine and ketorolac via patient-controlled intravenous analgesia (PCIA) after hepatobiliary surgery, as compared with sufentanil. Patients and Methods: Postoperative follow-up data of hepatobiliary surgery patients in Henan Provincial People's Hospital from March 2018 to June 2021 were collected retrospectively and divided into butorphanol group (group B) or sufentanil group (group S) according to the postoperative intravenous controlled analgesia scheme. The baseline characteristics and surgical information of the two groups were matched through propensity score matching (PSM). Results: A total of 3437 patients were screened, and PSM yielded 1816 patients after matching, including 908 in the butorphanol group and 908 in the sufentanil group. Compared with group S, the incidence of moderate-to-severe pain on the first postoperative day and the second postoperative day was lower in group B during rest (3.2% vs 10.9%, P<0.001; 1.2% vs 4.6%, P<0.001), and during movement (7.0% vs 18.9%, P<0.001; 2.6% vs 8.7%, P<0.001). Patients receiving butorphanol had a lower morphine consumption (50mg vs 120mg, P<0.001). The bolus attempts of an analgesic pump in group B were significantly lower than in group S (1 vs 2, P<0.001). Postoperative hospital length of stay was shortened in group B (11d vs 12d, P=0.017). The occurrence of postoperative vomiting was lower in group B (1.4% vs 3.0%, P=0.025) than in group S. However, more patients in group B experienced dizziness (0.9% vs 0.1%, P=0.019). Conclusion: Compared with sufentanil, the application of butorphanol in multimodal analgesia combined with dexmedetomidine and ketorolac via PCIA ameliorated postoperative pain after hepatobiliary surgery, with reduced opioid consumption and shorter postoperative hospital length of stay.


Assuntos
Dexmedetomidina , Sufentanil , Humanos , Sufentanil/uso terapêutico , Butorfanol/uso terapêutico , Estudos Retrospectivos , Cetorolaco , Analgésicos Opioides/uso terapêutico , Analgesia Controlada pelo Paciente , Dor Pós-Operatória/tratamento farmacológico
16.
PLoS One ; 18(12): e0296158, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38127958

RESUMO

OBJECTIVE: Anesthesia is correlated with the prognosis of cancer surgery. However, evidence from prospective studies focusing on breast cancer is currently limited. This systematic review aimed to investigate the effect of anesthesia-related interventions on oncological outcomes following breast cancer surgery in prospective studies. METHODS: Literature searches were performed from inception to June. 2023 in the Pubmed, Web of Science, Embase, and ClinicalTrials databases. The main inclusion criteria comprised a minimum of one-year follow-up duration, with oncological outcomes as endpoints. Anesthesia-related interventions encompassed, but were not limited to, type of anesthesia, anesthetics, and analgesics. The risk of bias was assessed using the Cochrane Risk of Bias Tool. RESULTS: A total of 9 studies were included. Anesthesia-related interventions included paravertebral nerve block (3), pectoral nerve block (1), sevoflurane (2), ketorolac (2), and infiltration of lidocaine (1). Cancer recurrence, metastasis, disease-free survival, or (and) overall survival were assessed. Among all included studies, only infiltration of lidocaine was found to prolong disease-free survival and overall survival. CONCLUSION: Regional anesthesia and propofol did not improve oncological outcomes following breast cancer surgery. The anti-tumorigenic effect of ketorolac warrants future studies with larger sample sizes. Perioperative infiltration of lidocaine around the tumor may be a promising anti-tumorigenic intervention that can prolong overall survival in patients with early breast cancer.


Assuntos
Anestesia por Condução , Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Estudos Prospectivos , Cetorolaco , Recidiva Local de Neoplasia , Lidocaína
17.
Urologiia ; (6): 108-112, 2023 Dec.
Artigo em Russo | MEDLINE | ID: mdl-38156692

RESUMO

INTRODUCTION: Urinary tract disorders are one of the most common pathologies in children, regardless of age, and every year their prevalence is growing. Our study is dedicated to improvement of postoperative pain management after pediatric urologic procedures and to implementation of modern approaches for enhanced recovery. AIM: To develop optimal methods of postoperative pain relief for moderate and severe intensity of pain syndrome in children undergoing urological procedures. MATERIALS AND METHODS: The study involved 34 patients who were undergone to urological procedures. For an objective assessment of the quality of anesthesia, the following research methods were used: clinical study with the determination of the pain intensity on a visual analogue scale (VAS) and the determination of systolic and diastolic blood pressure, pulse oximetry and echocardiographic study. RESULTS: The analysis of the postoperative period with monitoring of blood pressure, oxygen saturation, pulse oximetry, subjective assessment of the pain intensity on the VAS and the echocardiographic study showed that the relative stability of the condition was associated with an adequate pain relief. The use of a combination of infulgan, which caused an early analgesic effect, with tramadol realizing its action later, provides a prolongation of analgesia. A combination of tramadol with infulgan was several times more efficient than ketorolac. CONCLUSIONS: The use of a combined analgesia after urological procedures, including ketorolac, provides a hemodynamically stability in the entire postoperative period.


Assuntos
Tramadol , Criança , Humanos , Cetorolaco , Analgésicos Opioides , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Período Pós-Operatório , Método Duplo-Cego
18.
Arch Razi Inst ; 78(3): 807-813, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-38028823

RESUMO

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.


Assuntos
Cetorolaco , Ratos , Feminino , Animais , Ratos Wistar , Cetorolaco/efeitos adversos , Acetato de Metilprednisolona/efeitos adversos , Ciclo Estral , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Inflamação , Anti-Inflamatórios
19.
Environ Sci Pollut Res Int ; 30(56): 118536-118544, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37917255

RESUMO

Ketorolac, a highly persistent NSAID of environmental concern, was significantly removed from water (80% removal) through photoelectrocatalysis where titanium dioxide nanotubes prepared by Ti foil electrochemical anodization at 30 V were used as photoanodes. Fifteen milligrams per liter of ketorolac solutions in a 0.05 M Na2SO4 aqueous medium was subjected to irradiation from a 365-nm light with an intensity of 1 mWcm-2 and under an applied potential of 1.3 V (vs. Hg/Hg2SO4/sat.K2SO4) at pH 6.0. When each process (photo and electrocatalysis) was carried out separately, less than 20% drug removal was achieved as monitored through UV-vis spectrophotometry. Through scavenging experiments, direct oxidation on the photogenerated holes and oxidation by hydroxyl radical formation were found to play a key role on ketorolac's degradation. Chemical oxygen demand (COD) analyses also showed a significant COD decreased (68%) since the initial COD value was 31.3 mg O2/L and the final COD value was 10.1 mg O2/L. A 48% mineralization was also achieved, as shown by total organic carbon (TOC) analyses. These results showed that electrodes based on titania nanotubes are a promising alternative material for simultaneous photocatalytic and electrocatalytic processes in water remediation.


Assuntos
Mercúrio , Nanotubos , Poluentes Químicos da Água , Água , Cetorolaco , Titânio , Oxirredução , Eletrodos , Catálise
20.
Kathmandu Univ Med J (KUMJ) ; 21(81): 3-6, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37800417

RESUMO

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.


Assuntos
Tonsilectomia , Tonsilite , Adulto , Humanos , Criança , Masculino , Feminino , Cetorolaco/efeitos adversos , Tonsilectomia/efeitos adversos , Tonsilectomia/métodos , Estudos Retrospectivos , Hemorragia/etiologia , Analgésicos , Tonsilite/tratamento farmacológico , Tonsilite/cirurgia , Tonsilite/complicações , Hemorragia Pós-Operatória/induzido quimicamente , Hemorragia Pós-Operatória/epidemiologia , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia
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