Risk factors for low back pain after iliac vein stenting for non-thrombotic iliac vein lesions.

OBJECTIVE: Iliac vein stenting is an option being explored to treat chronic venous insufficiency. We have noted that our most common postoperative complication is low back pain after stent placement, which is occasionally quite severe. We wanted to investigate risk factors that are involved in this phenomenon and identify potentially modifiable factors. METHODS: Patients who failed 3 months of conservative therapy had iliac vein interrogation performed. We limited the scope of this database to non-thrombotic iliac vein lesions treated in the office in which Wallstents were placed. Data were collected from September 2012 to August 2020 for 2308 consecutive outpatients who underwent 3747 procedures. Before August 2016, patients received pre-procedure oral valium (n = 2679) and thereafter, patients received intravenous (IV) sedation (n = 1068). A pain score, on a Likert scale ranging from 0 to 10, was assessed within 1 hour postoperatively. We analyzed the medications administered and correlated them with pain scores. RESULTS: The average of all the pain scores was 0.86 (range, 0-10; standard deviation [SD], 2.00). Age had a slight inverse effect on pain scores (r = -0.12; P < .00001). Presenting signs (based upon CEAP) (P = .11) and body mass index (P = .88) did not have a significant effect on pain scores. Average pain score for females (0.96) was slightly higher than for males (0.70), with P < .0001. Average pain score for procedures on the right side (0.67) was lower than for procedures on the left side (1.01), with P < .0001. Average pain score for patients who received IV sedation (mean, 0.68; SD, 1.58) was lower than that for those who did not (mean, 0.93; SD, 2.15), with P = .0004. When using a single agent, propofol was associated with the lowest pain scores (P < .0001). Toradol displayed a dose-dependent effect on pain score (P < .0001). The best combination of agents for pain control was propofol and toradol together. CONCLUSIONS: Overall, the vast majority of pain scores were low. Factors that were associated with lower pain scores were older age, male sex, procedures on the right side, and IV sedation, in particular with the use of propofol. These data may help us better target patients anticipated to have high pain scores and suggest the preferential use of propofol and toradol.

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

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

Preparation of polycaprolactone and polymethacrylate nanofibers for controlled ocular delivery of ketorolac tromethamine: Pharmacokinetic study in Rabbit's Eye.

Ophthalmitis is an inflammation of the eye triggered by various conditions including diseases, allergy, trauma, or surgery. Management of this condition usually includes administration of topical anti-inflammatory eye drops such as nonsteroidal anti-inflammatory drugs. To overcome the challenges of conventional eye drops such as frequent administration and low intraocular bioavailability, nanofibrous inserts of Ketorolac tromethamine (KET) were developed in this study. Polycaprolactone and polymethacrylate containing KET were electrospun to prepare biocompatible and biodegradable nanofibers. The inserts were studied for morphology, drug-polymer interaction, physicochemical properties, cell viability, in vitro drug release study and pharmacokinetic study in rabbit's eye. Uniform nanofibers with mean diameters < 350 nm were developed. Suitable mechanical properties with tensile strength up to 2.8 MPa indicated high strength and flexibility of inserts. Nanofibers exhibited controlled drug release for up to 140 h at a concentration more than 50 µg/ml in tears without causing any damage or irritation to the eye. Formulations indicated enhanced pharmacokinetics with 6- to 8-times higher Area Under the Curve (AUC0-144) compared to KET eye drop. Acceptable cell viability confirmed the safety of inserts. Due to the fact that this preservative-free polymer insert can obtain therapeutic concentration in the tear film without fluctuation, it can be a suitable alternative for the treatment of intraocular inflammations with less complications, easier use, and even higher intraocular penetration.

Effects of topical ketorolac tromethamine on tear parameters, meibography, goblet cell density, and conjunctival oxidative stress in healthy dogs.

OBJECTIVES: The objective of the study was to evaluate whether a twice-daily instillation of 0.45% preservative-free ketorolac tromethamine (FKT) or 0.4% benzalkonium chloride-preserved ketorolac tromethamine (BACKT), every 12 h for 30 days may affect tear film parameters and the meibography in healthy dogs. Additionally, we assessed whether the same treatments irritated the ocular surface, affected goblet cell density (GCD), and the levels of oxidative stress biomarkers (OSB) in the conjunctiva of the same dogs. PROCEDURES: Experimental and masked comparison study. In 11 healthy dogs baseline values of the lipid layer thickness, tear meniscus height, non-invasive tear breakup time (NI-TFBT), and the meibomian gland (MG) loss were assessed by OSAvet®. For each dog, one eye received 40 µL of BACKT, while the other received 40 µL FKT, every 12 h for 30 consecutive days. Tear parameters and meibography were repeated 15, 30, and 60 days post-treatments. Conjunctival hyperemia and blepharospasm were monitored at the same time points. At baseline and Day 30, a conjunctival biopsy was collected for GCD and OSB determination. RESULTS: Conjunctival hyperemia and blepharospasm were not observed. At Day 15, the MG loss increased only in FKT-treated eyes (p < .001). On Day 30, both treatment groups showed increased MG loss, shortened NI-TFBT, and reduced GCD and catalase (p < .05). At Day 30, BACKT-treated eyes showed lower levels of superoxide dismutase (SOD) (p = .006) and higher levels of malondialdehyde (MDA) (p = .02). Differences between treatments were not observed for any parameter at any time point (p > .05). 60 days after treatment, OSAvet® parameters tended to return to values assessed at baseline; however, significant differences remained for MG loss (p < .05). CONCLUSIONS: Twice-daily instillation of KT, containing or not BAC, for 30 consecutive days shortened NI-TFBT, decreased GCD, and increased the MG loss in healthy dogs. KT should be used with caution when prescribed for long periods, particularly in patients with tear film abnormalities. However, future controlled studies using KT, BAC, and other topical NSAIDs are indicated to further support this finding.

Efficacy of Oral Toradol (Ketorolac) Compared to Oral Tramadol as a Preemptive Analgesic in Impacted Third Molar Surgery.

OBJECTIVE: To compare ketorolac with Tramadol as a preemptive analgesic in impacted third molar surgery in terms of mean pain score, mean time of first analgesic and mean total analgesic consumption postoperatively. STUDY DESIGN: Experimental study. Place and Duration of the Study: Department of Oral and Maxillofacial Surgery, Islamic International Dental Hospital, (IIDH) Riphah International University, Islamabad, from March 2018 to March 2020. METHODOLOGY: Ninety-four patients, aged 18-45 years with impacted third molars were divided into two groups. Preoperatively oral tramadol 50 mg was given in group A and oral ketorolac 10 mg was given in group B. Pain score was measured 3 hours postoperatively, using the visual analogue scale (VAS), the time was noted for first analgesic consumption in hours and total consumption of analgesics. RESULTS: The mean postoperative pain was measured for both groups. Pain was significantly less in Group B. The mean pain score was 4.02+1.20 in group A and 3.42+1.08 in group B measured at 3 hours postoperatively (p=0.02). The mean time interval for 1st postoperative analgesic was 2.90+1.24 hours in group A and 3.61+1.02 in group B (p=0.007). The mean total analgesic consumption was 3.75+1.27 grams in Group A and 2.27+1.74 grams min Group B (p=0.006). CONCLUSION: Preemptive Ketorolac has a more prolonged analgesic effect as compared to tramadol. KEY WORDS: Preemptive analgesia, Tramadol, Ketorolac, Pain score, Third molar surgery.

The effect of topical ketorolac tromethamine on macular thickening after phacoemulsification in diabetic patients.

BACKGROUND: To determine the effect of ketorolac tromethamine 0.5% in preventing post-phacoemulsification macular thickening. This randomized clinical trial. patients randomized 1:1 to receive either topical ketorolac three times a day or a placebo. METHODS: A total of 101 eyes of 101 diabetic patients who were scheduled for phacoemulsification and had normal macular contour and thickness enrolled consecutively. The topical ketorolac and placebo were prescribed on the day before surgery and continued up to 4 weeks after surgery. Patients with proliferative diabetic retinopathy, a history of intravitreal injection in less than three months, a history of macular photocoagulation in less than 6 months, and any other concomitant ocular pathologies were excluded. Central macular thickness (CMT) and best corrected visual acuity (BCVA) was recorded in the follow-ups of 6, 12, and 24 weeks after the surgery and compared with the controls. RESULTS: 49 eyes in the case group and 52 eyes in the control group were analyzed. Mean BCVA was significantly improved in both groups at all follow-ups (P < 0.001 for all). There was no statistically significant difference regarding the BCVA in different time points except week 12 (P = 0.028) among the study group. In the case and control groups, CMT was increased at all follow-ups (P < 0.05). There was no statistically significant difference when comparing the two groups regarding the mean of CMT at any time point postoperatively (P > 0.05 for all). CONCLUSION: Based on our findings, topical ketorolac tromethamine 0.5% is not effective in the prevention of post-phacoemulsification macular thickening in diabetic patients. TRAIL REGISTRATION: The study protocol was registered into www. CLINICALTRIAL: gov with the RCT registration number NCT03551808. (2018/06/11 ) CLINICAL TRIAL REGISTRATION NUMBER: NCT03551808.

Effect of Ketorolac Tromethamine Combined With Remifentanil on Reducing Complications During the General Anesthesia Emergence.

PURPOSE: To observe the effect of ketorolac tromethamine combined with remifentanil in sedation and analgesia during general anesthesia emergence and reducing general anesthesia complications. DESIGN: This is an experimental design. METHODS: A total of 90 patients who underwent partial or total thyroidectomy in our hospital were selected and randomly divided into three groups with 30 cases in each group. Routine general anesthesia combined with endotracheal intubation was given for general anesthesia, and different treatments were administered when the skin was sutured. Group K: intravenous injection of ketorolac tromethamine 0.9 mg/kg, intravenous injection of normal saline 10 mL/h by micropump until awakening and extubation; R group: intravenous injection of normal saline 2 mL, micropump intravenous injection of remifentanil 0.1 mcg/kg/min until awakening and extubation; KR group: intravenous injection of ketorolac tromethamine 0.5 mg/kg, micropump intravenous injection remifentanil 0.05 mcg/kg/min until awakening and extubation. After the operation, all patients entered the postanesthesia care unit (PACU) for recovery, extubation, scoring. The incidence and condition of various complications were counted. FINDINGS: There was no significant difference in the general information or operation duration of the patients (P > .05). The types of general anesthesia induction drugs in each group were the same, and there was no significant difference in drug measurement (P > .05). The visual analogue scales of KR group were: 2.2 ± 0.6(T0) and 2.4 ± 0.9(T1), the Self-Rating Anxiety Scale scores of the KR groups were: 4.1 ± 0.6(T0), 3.7 ± 0.4(T1). Compared with the KR group, the visual analogue scale and Self-Rating Anxiety Scale scores of the K and R groups at T0 and T1 were increased (P < .05); the visual analogue scale and Self-Rating Anxiety Scale scores of the K and R groups at T0 and T1 were not significantly different (P > .05); at T2, there was no significant difference in visual analogue scale and Self-Rating Anxiety Scale scores among the three groups (P > .05). There was no significant difference in extubation time or PACU transfer time among the three groups (P > .05). The incidence of adverse reactions in KR group were: 3.3% (nausea), 3.3% (vomit), 0 (coughing and drowsiness). Compared with the KR group, the incidence of adverse reactions was higher in the K and R groups. CONCLUSIONS: Ketorolac tromethamine combined with remifentanil can effectively relieve pain and sedation during general anesthesia recovery and reduce the incidence of complications related to general anesthesia recovery. At the same time, the application of ketorolac tromethamine can reduce the dosage of remifentanil and inhibit the occurrence of adverse reactions when used alone.

Ketorolac Tromethamine Loaded Nano-Spray Dried Nanoparticles: Preparation, Characterization, Cell Viability, COL1A1 Gene Simulation and Determination of Anti-inflammatory Activity by In vivo HET-CAM Assay.

BACKGROUND: Ketorolac tromethamine (KT) is a non-steroidal anti-inflammatory drug from the heteroaryl acetic acid derivatives family. The most widely used new nanotechnological approaches for topical drug delivery are polymeric nanoparticles (NPs). OBJECTIVE: Successful results have been obtained with low doses in many treatments, such as cancer, antimicrobial, pain, made with nanoparticle formulations of drug active ingredients. METHODS: NPs were prepared using Nano Spray-Dryer. The cytotoxicity of the optimum formulation in BJ (ATCC® CRL-2522™) human fibroblast cells was determined by the WST- 1 method and the gene activity was elucidated by mRNA isolation and real-time polymerase chain reaction (RT-PCR). The in vivo HET- CAM assay was performed for anti-inflammatory activity. RESULTS: NPs presented PDI values lower than 0.5, and therefore particle size distribution was decided to be monodisperse. Positive zeta potential values of NPs highlighted the presence of the cationic ammonium group of Eudragit® RS 100. The release rates observed from KT-NP coded formulations after 24 hours were 78.4% ± 2.9, demonstrating extended release from all formulations, relative to pure KT. The lowest concentration of KT-NP increased fibroblast cell proliferation higher than the highest concentration of KT. The 5-fold increased effect of KT-NP formulation on collagen gene expression compared to KT is also related to the enhanced anti-inflammatory effect in line with the in vivo HET-CAM assay results. CONCLUSION: With the obtained cell viability, gene expression, and HET-CAM results, it has the hope of a successful nano-topical formulation, especially in both wound healing and anti-inflammatory treatment.

Effect of ketorolac tromethamine combined with dezocine prior administration on hemodynamics and postoperative analgesia in patients undergoing laparoscopic hernia repair.

OBJECTIVE: To observe the effect of Ketorolac tromethamine combined with dezocine prior administration on hemodynamics and postoperative sedation in patients undergoing laparoscopic hernia repair. METHODS: 100 male patients aged 60 to 80 years old, a line to elective laparoscopic inguinal hernia repair, were randomly divided into four groups: control group (Group A) and dezocine group (Group B), ketorolac tromethamine group (Group C), ketorolac tromethamine combined with dezocine group (Group D). Patients were administrated with 0.1 mg/kg dezocine in Group B, 0.5 mg/kg ketorolac in Group C, 0.1 mg/kg dezocine, and 0.5 mg/kg ketorolac in Group D, and with an equal dose of normal saline in group A. The heart rate (HR) and mean arterial pressure (MAP) of patients in 4 groups were recorded at each time point as follows, T0 (enter the operating room), T1 (before skin resection), 10 min after pneumoperitoneum (T2), mesh placement (T3), and laryngeal mask extraction (T4). Operation time, awakening time (time from drug withdrawal to consciousness recovery), the dosage of propofol, sufentanil, remifentanil, and intraoperative vasoactive drug dosage were recorded to compare. Visual analog scale score and sedation Ramsay score were evaluated 1, 6, 12, and 24 hours after extubation. RESULTS: There was no significant difference in operation time, anesthesia recovery time, sufentanil dosage, and vasoactive drugs among all groups. The amount of propofol in Group B and D was less than that in Group A and C (P < .05), and there was no difference between Group B and D, A and C (P > .05). The amount of remifentanil in Group B, C, and D was less than that in Group A (P < .05), and Group D was less than B and C (P < .05). After extubation, HR and MAP were significantly higher than before (P < .05). Compared with T0, HR and MAP increased in each group at T4, but MAP and HR in Group D increased the least (P < .05). There were significant differences between Group B, C, D, and A, MAP and HR fluctuated little during extubation (P < .05), but there was a significant difference between Group D and B, C (P < .05). Visual analog scale scores of Group B, C, and D were lower than those of A at 1, 6, and 12 hours after surgery (P < .05), and there was a significant difference between Group D, and B, C (P < .05). Ramsay scores in Group B and D were higher than those in A and C at 1 and 6 hours after the operation (P < .05). There was no difference in the incidence of adverse reactions among groups. CONCLUSION: The prophylactic use of ketorolac tromethamine and dezocine before laparoscopic inguinal hernia repair can reduce hemodynamic disorder during anesthesia recovery, increase postoperative sedative and analgesic effects.

Ketorolac tromethamine represses senescence in aging articular chondrocytes.

The present study aims to explore the potential function of ketorolac tromethamine in treating osteoarthritis by examining its effects on interleukin-1ß (IL-1ß)-triggered cellular senescence in chondrocytes. More ß-galactosidase (SA-ß-Gal) positively stained cells, promoted cell fraction in the G0/G1 phase, increased release of matrix metalloproteinase (MMP)-3 and MMP-13, and upregulated cellular senescence-related genes (p21 and p53) were observed in IL-1ß-challenged HC-A cells, all of which were significantly reversed by 25 and 50 mg/mL ketorolac tromethamine. Furthermore, the upregulated cyclooxygenase-2 (COX-2) and elevated release of prostaglandin E2 in IL-1ß- challenged HC-A cells were dramatically repressed by ketorolac tromethamine. Lastly, the inhibitory effects of ketorolac tromethamine on the activation of SA-ß-Gal and the upregulation of p21 and p53 were greatly abolished by the overexpression of COX-2. Collectively, ketorolac tromethamine repressed cellular senescence in aging articular chondrocytes by inhibiting COX-2.

In situ gelling system for sustained intraarticular delivery of bupivacaine and ketorolac in sheep.

Suboptimal control of postoperative pain following knee arthroplasty can slow recovery and reduce patient satisfaction. Intraarticular (IA) administration of bupivacaine and ketorolac offers efficient pain control and minimizes opioid consumption. However, the clinical benefits of this approach are short lived due to rapid clearance of drugs from the joint cavity. Here, we describe a poloxamer based thermoresponsive in situ gelling system for the sustained IA delivery of bupivacaine hydrochloride (BH) and ketorolac tromethamine (KT) following knee surgery in an ovine model. Drug loaded formulations were prepared using poloxamer 407, poloxamer 188 and sodium chloride. In vitro characterization was conducted, followed by in vivo evaluation of sustained drug release and safety in an ovine model of knee joint surgery. Rheological studies revealed a Newtonian-like flow of the developed formulation at room temperature, confirming its injectability, followed by a transition to a viscous gel as temperature approached body temperature. The developed formulation successfully sustained the in vivo release of BH for 72 h and KT for 48 h, as determined by circulating drug levels, compared to 24 and 8 h for marketed drug solutions. The concentrations of BH and KT in the synovial fluids at 72 h were 11.5 and 1.8 times that of marketed products, suggesting a significant increase in the IA residence time. The developed formulation induced a comparable inflammatory response compared to the marketed drug solutions, however a significantly higher chondrotoxicity was observed following administration of the gel formulations. Poloxamers based in situ gelling systems are promising delivery platforms for the sustained and localised IA delivery of BH and KT, with potential clinical benefits in managing the postoperative pain following knee arthroplasty.

Toradol to Reduce Ureteroscopy Symptoms Trial (TRUST).

OBJECTIVE: To assess the use of intraoperative IV ketorolac (Toradol) on the peri-operative total morphine milligram equivalent (MME) requirements of patients undergoing ureteroscopy for nephrolithiasis. METHODS: Patients undergoing ambulatory ureteroscopy for nephrolithiasis were randomized to receive ketorolac at time of anesthesia induction. Patients and surgeons were blinded to treatment. Intraoperative, postoperative and combined MME were calculated. Multivariable regression was used to identify independent predictors of MME requirement. Complications were recorded. RESULTS: A total of 94 patients were analyzed following randomization. There were 46 patients in the treatment arm and 48 patients in the control arm. There were no statistically significant differences in gender, age, BMI, operative length or baseline pain medication use between groups (P >.05). Patients in the treatment arm required lower intraoperative MME when compared to the control arm (17.1 vs 24, P< .01). There were no statistically significant differences in the postoperative MME requirements between groups. The combined peri-operative MME was lower in the treatment arm compared to the control arm (22.2 vs 30.4, P< .02). Ketorolac use was an independent predictor of lower MME use on multivariable analysis (beta coefficient -5.1, P< .01). There was no statistically significant difference with regards to complication numbers between the treatment arms. CONCLUSION: Ketorolac during ureteroscopy is associated with a 37% reduction in narcotic requirement and is an independent predictor of decreased peri-operative narcotic needs. These findings show that intra-operative use of ketorolac effectively reduces narcotic requirements and should be considered independently or as part of a multimodal pain control protocol, unless otherwise contraindicated.

HPV Lesions and Other Issues in the Oral Cavity Treatment and Removal without Pain.

Due to different oral and dental conditions, oral mucosa lesions such as those caused by the human papilloma virus and temporomandibular joint pathologies often have to be treated by surgical, ablative or extractive procedures. The treatment and control of pain and inflammation during these procedures is essential to guarantee the patient's well-being. For the foregoing reason, a hydrogel based on sodium alginate and hyaluronic acid containing 2% of ketorolac tromethamine has been developed. We characterized it physically, mechanically and morphologically. The rheological results suggest that the formulation can be easily and gently applied. Ex vivo permeation studies show that Ketorolac Tromethamine is able to penetrate through the buccal and sublingual mucosae, in addition to being retained in the mucosae's structure. Through an in vitro test, we were able to evaluate the role that saliva plays in the bioavailability of the drug, observing that more than half of the applied dose is eliminated in an hour. The histological and cytotoxic studies performed on pigs in vivo showed the excellent safety profile of the formulation, as well as its high tolerability. In parallel, a biomimetic artificial membrane (PermeaPad®) was evaluated, and it showed a high degree of correlation with the oral and sublingual mucosa.

Intravenous Ketorolac Infusion for Intractable Pleuritic Pain Secondary to Metastatic Epithelioid Hemangioendothelioma.

Background: Epithelioid hemangioendothelioma (EHE) patients can experience severe pain. Nonsteroidal anti-inflammatory drugs, including ketorolac tromethamine, can effectively treat cancer-related pain, provide an opioid-sparing effect, and may be particularly effective for EHE pain. There are limited data describing prolonged (>5 days) continuous intravenous (IV) ketorolac infusion for cancer-related pain and no data on its use in EHE. Case Description: A 67-year-old woman with metastatic hepatic EHE suffered from chronic intractable pleuritic pain unresponsive to trials of nonopioid, opioid, adjuvant medications, and nonpharmacological interventions. In the hospital, continuous IV ketorolac infusion at 3.8 mg/hour (91.2 mg/day) effectively managed pain. With thorough monitoring, the patient was discharged on continuous IV ketorolac infusion at 3 mg/hour (72 mg/day). Infusion continued for 79 days without clinical or laboratory evidence of ketorolac toxicity. Conclusion: Ketorolac tromethamine as a long-term infusion is a potentially viable analgesic for patients with intractable EHE-related pain unresponsive to standard therapies.

Ketorolac tromethamine pretreatment suppresses sufentanil-induced cough during general anesthesia induction: a prospective randomized controlled trial.

BACKGROUND: To observe the effect of pretreatment with ketorolac tromethamine on sufentanil-induced cough in general anesthesia patients. METHODS: A total of 102 patients were screened, and 90 patients were scheduled for elective surgery under general anesthesia. The 90 patients were randomly divided into two groups: the control group (C group) and the observation group (KT group). Five minutes before anesthesia induction, the observation group was given ketorolac tromethamine 0.5 mg/kg intravenously within 3 s, while the control group was given the same amount of normal saline intravenously. All patients were given a sufentanil bolus of 0.5 µg/kg (within 3 s) intravenously. One minute later, propofol 2.5 mg/kg and vecuronium 0.15 mg/kg were injected intravenously, and endotracheal intubation was guided by laryngoscopy. The number of coughs that occurred within 1 min after sufentanil injection was recorded. The mean arterial pressure (MAP), heart rate (HR) and pulse oxygen saturation (SpO2) were recorded at T0 (immediately before pretreatment), T1 (5 min after pretreatment), T2 (before intubation), T3 (1 min after intubation) and T4 (5 min after intubation). The incidence of adverse reactions, including nausea and vomiting, dizziness, drowsiness, delay of recovery, restlessness in the recovery period, respiratory depression and postoperative incision pain, was analyzed. RESULTS: Within 1 min after sufentanil injection, the incidence and severity of cough in the KT group was significantly lower than that in the C group (P <  0.05). At T0, T1, T2, T3 and T4, there were no significant differences in MAP, HR and SpO2 between the two groups (P >  0.05). There was no significant difference in the dosage of sufentanil, propofol, remifentanil and vecuronium, the incidence of nausea and vomiting, the delay of recovery, dizziness, drowsiness or respiratory depression between the two groups (P >  0.05). However, the incidence of restlessness and the number of patients with VAS scores > 3 in the KT group were significantly lower than those in the C group (P <  0.05). CONCLUSION: Pretreatment with intravenous ketorolac tromethamine can significantly reduce the incidence of sufentanil-induced cough during induction of general anesthesia, which can also significantly reduce postoperative incision pain and restlessness during the recovery period. TRIAL REGISTRATION: Chinese Clinical Trial Registry (registration number# ChiCTR2000030287 ; date of registration: 27/02/2020).

DDX3 modulates cisplatin resistance in OSCC through ALKBH5-mediated m6A-demethylation of FOXM1 and NANOG.

Platinum based drugs alone or in combination with 5FU and docetaxel are common regimen chemotherapeutics for the treatment of advanced OSCC. Chemoresistance is one of the major factors of treatment failure in OSCC. Human RNA helicase DDX3 plays an important role in cell proliferation, invasion, and metastasis in several neoplasms. The potential role of DDX3 in chemoresistance is yet to be explored. Enhanced cancer stem cells (CSCs) population significantly contributes to chemoresistance and recurrence. A recent study showed that m6A RNA regulates self-renewal and tumorigenesis property in cancer. In this study we found genetic (shRNA) or pharmacological (ketorolac salt) inhibition of DDX3 reduced CSC population by suppressing the expression of FOXM1 and NANOG. We also found that m6A demethylase ALKBH5 is directly regulated by DDX3 which leads to decreased m6A methylation in FOXM1 and NANOG nascent transcript that contribute to chemoresistance. Here, we found DDX3 expression was upregulated in both cisplatin-resistant OSCC lines and chemoresistant tumors when compared with their respective sensitive counterparts. In a patient-derived cell xenograft model of chemoresistant OSCC, ketorolac salt restores cisplatin-mediated cell death and facilitates a significant reduction of tumor burdens. Our work uncovers a critical function of DDX3 and provides a new role in m6 demethylation of RNA. A combination regimen of ketorolac salt with cisplatin deserves further clinical investigation in advanced OSCC.

Systemic absortion and adverse effects of topical ocular use of ketorolac tromethamine and sodium diclofenac in New Zealand rabbits for 90 days / Absorção sistêmica e efeitos adversos do uso tópico ocular por 90 dias de cetorolaco de trometamina e diclofenacode sódio em coelhos da raça Nova Zelândia

The effect of the systemic absorption of 0.1% diclofenac sodium (DS) eyedrop was compared to that of 0.5% ketorolac tromethamine (KT) in female New Zealand white rabbits treated on both eyes three times a day for 90 days. The rabbits were divided in three groups of six animals (n= 18): KT group, DS group, and control (Co) group, in which saline (0.9% NaCl) solution was instilled. Water and food consumption were measured daily, clinical examination was performed weekly, and blood samples were collected every 30 days for laboratory examination. The plasma was analyzed for the presence of KT and DS by solid-phase extraction (SPE) associated with mass spectrometry (MS). Systemic absorption of these drugs was confirmed by SPE-MS, allowing their separation and identification in the plasma. At the end of the treatment, the animals were euthanized and necropsied, and no macroscopic or microscopic changes were found. This observation confirmed the laboratory results, which were within normal reference standards for the species. According to the results obtained, it can be concluded that treatment with eyedrops containing KT and DS for 90 days in healthy rabbits does not cause adverse systemic effects.(AU)

Comparou-se o efeito da absorção sistêmica do colírio de diclofenaco de sódio 0,1% (DS) em relação ao de cetorolaco de trometamina 0,5% (CT) em coelhas da raça Nova Zelândia, tratadas nos dois olhos, três vezes ao dia, por 90 dias. As coelhas foram separadas em três grupos de seis animais (n=18): grupo CT, grupo DS e grupo controle (Co), no qual foi instilada solução fisiológica (NaCl 0,9%). Os consumos de água e ração foram mensurados diariamente, os exames clínicos foram realizados semanalmente e o sangue foi coletado a cada 30 dias para realização de exames laboratoriais. O plasma foi analisado para detectar a presença de CT e DS por extração em fase sólida (SPE) associada à espectrometria de massas (MS). A absorção sistêmica desses fármacos foi confirmada por SPE-MS, permitindo sua separação e identificação no plasma. Ao final do tratamento, os animais foram eutanasiados e necropsiados, e não foram encontradas alterações macroscópicas ou microscópicas. Essa observação confirmou os resultados laboratoriais, que estavam dentro dos padrões de referência para a espécie. De acordo com os resultados obtidos, pode-se concluir que o tratamento com colírio contendo KT e DS, por 90 dias, em coelhos saudáveis, não causa efeitos adversos sistêmicos.(AU)

Multimodal opioid-sparing postoperative pain regimen compared with the standard postoperative pain regimen in vaginal pelvic reconstructive surgery: a multicenter randomized controlled trial.

BACKGROUND: Postoperative pain control after urogynecological surgery has traditionally been opioid centered with frequent narcotic administration. Few studies have addressed optimal pain control strategies for vaginal pelvic reconstructive surgery that limit opioid use. OBJECTIVE: The objective of the study was to determine whether, ice packs, Tylenol, and Toradol, a novel opioid-sparing multimodal postoperative pain regimen has improved pain control compared with the standard postoperative pain regimen in patients undergoing inpatient vaginal pelvic reconstructive surgery. STUDY DESIGN: This was a multicenter randomized controlled trial of women undergoing vaginal pelvic reconstructive surgery. Patients were randomized to the ice packs, Tylenol, and Toradol postoperative pain regimen or the standard regimen. The ice packs, Tylenol, and Toradol regimen consists of around-the-clock ice packs, around-the-clock oral acetaminophen, around-the-clock intravenous ketorolac, and intravenous hydromorphone for breakthrough pain. The standard regimen consists of as-needed ibuprofen, as-needed acetaminophen/oxycodone, and intravenous hydromorphone for breakthrough pain. The primary outcome was postoperative day 1 pain evaluated the morning after surgery using a visual analog scale. Secondary outcomes included the validated Quality of Recovery Questionnaire, satisfaction scores, inpatient narcotic consumption, outpatient pain medication consumption, and visual analog scale scores at other time intervals. In all, 27 patients in each arm were required to detect a mean difference of 25 mm on a 100 mm visual analog scale (90% power). RESULTS: Thirty patients were randomized to ice packs, Tylenol, and Toradol and 33 to the standard therapy. Patient and surgical demographics were similar. The median morning visual analog scale pain score was lower in the ice packs, Tylenol, and Toradol group (20 mm vs 40 mm, P = .03). Numerical median pain scores were lower at the 96 hour phone call in the ice packs, Tylenol, and Toradol group (2 vs 3, P = .04). Patients randomized to the ICE-T regimen received fewer narcotics (expressed in oral morphine equivalents) from the postanesthesia care unit exit to discharge (2.9 vs 20.4, P < .001) and received fewer narcotics during the entire hospitalization (55.7 vs 91.2, P < .001). At 96 hour follow up, patients in the ice packs, Tylenol, and Toradol group used 4.9 ketorolac tablets compared with 4.6 oxycodone/acetaminophen tablets in the standard group (P = .81); however, ice packs, Tylenol, and Toradol patients required more acetaminophen than ibuprofen by patients in the standard arm (10.7 vs 6.2 tablets, P = .012). There were no differences in Quality of Recovery Questionnaire or satisfaction scores either in the morning after surgery or at 96 hour follow up. CONCLUSION: The ice packs, Tylenol, and Toradol multimodal pain regimen offers improved pain control the morning after surgery and 96 hours postoperatively compared with the standard regimen with no differences in patient satisfaction and quality of recovery. Ice packs, Tylenol, and Toradol can significantly limit postoperative inpatient narcotic use and eliminate outpatient narcotic use in patients undergoing vaginal pelvic reconstructive surgery.

Efficacy of Liposomal Bupivacaine Compared with Multimodal Periarticular Injections for Postoperative Pain Control following Total Knee Arthroplasty.

Single-dose long-acting periarticular anesthetics have been shown to be an effective method of postoperative analgesia in total knee arthroplasty (TKA). This study retrospectively compares the efficacy of multimodal periarticular injection consisting of a combination of ropivacaine, duramorph, epinephrine, and toradol (HC) with liposomal bupivacaine (LB) periarticular injection in TKA. This study was a retrospective matched comparative chart review of two cohorts of patients who underwent TKA within a single health care system and cared for by one provider. We compared 22 patients who were treated with LB intraoperatively (LBG) with 41 matched controls who were treated with HC periarticular injection (HCG). These cases were retrospectively reviewed at 0 to 6, 6 to 12, 12 to 24, 24 to 48, and 48 to 72 hours. We reviewed pain scores and opioid use per the preceding time period, total opioid use, length of stay (LOS), and wound complications between the two groups. The two groups showed no statistical difference in total opioids used. In both the 6- to 12-hour and 12- to 24-hour intervals, the LBG required significantly more opioids than the HCG, with p-values of 0.0039 and 0.0061, respectively. Pain scores were not significantly different for any time period. We found no difference in LOS. The LBG tended to have lower doses of antiemetics than the HCG. No significant difference was found in postoperative pain scores and total opioid use between LB and multimodal periarticular intraoperative injections in TKA. Our data demonstrated decreased opioid consumption in the HC group compared with the LB group in both the 6- to 12-hour and 12- to 24-hour time intervals postoperatively. At our institution, LB costs US$314.99, whereas HC costs US$95.