[Oral dexketoprofen tromethamine for preemptive analgesia in extraction of impacted teeth: a randomized controlled double-blind trial].

PURPOSE: To study the preemptive analgesic effect of dexketoprofen tromethamine in extraction of impacted teeth. METHODS: Twenty patients with bilateral mandibular impacted teeth were selected, and were randomly divided into dexketoprofen tromethamine group(experimental group) and placebo group(control group). The pain scores of patients at 0.5, 2, 4, 8, 12, and 24 hours after tooth extraction were counted by numeric rating scale(NRS), and the total dosage of emergent analgesic drugs used in 24 hours was recorded. COX analysis method was used to compare the interval time and the number of cases of first application of emergent analgesic drugs after two operations, and the survival curve was drawn. SPSS 20.0 software package was used for data analysis. RESULTS: The NRS scores of postoperative pain in the experimental group were significantly lower than those in the control group at 2, 4, 8 and 12 hours after operation (P＜0.05). The dose of emergent analgesics used in the experimental group for 24 h was significantly lower than that in the control group (P＜0.05). Survival curve showed that the interval time between the first application of analgesics in the experimental group was significantly longer than that in the control group(P＜0.05). CONCLUSIONS: Dexketoprofen tromethamine can achieve obvious analgesic effect within 12 hours, but the analgesic effect is not obvious after 12 hours.

Bizarre Cutaneous Ulcers due to Self-Administered Intravenous Dexketoprofen Trometamol.

Systemic non-steroidal anti-inflammatory drug use may result in various cutaneous complications including maculopapular rash, fixed drug eruption, urticaria, and angioedema most frequently. However extensive cutaneous ulcers in relation to intravenous dexketoprofen trometamol use has not been identified before although cutaneous ulcers have been described in association with several opioids. Herein, we would like to present a 27-year-old male with a 1-year history of progressive deep cutaneous ulcers due to long term abusive intravenous use of dexketoprofen trometamol.

Intravenous lidocaine vs. NSAIDs for migraine attack in the ED: a prospective, randomized, double-blind study.

PURPOSE: Although different forms of lidocaine are used for migraine attack headaches, the effect of intravenous lidocaine is still limited. This study aimed to investigate the effects of intravenous lidocaine infusion for the treatment of migraine attack headaches. METHODS: A hundred patients with migraine attacks, aged between 18 and 65, were randomly divided into two groups. The lidocaine group (n = 50) received a 1.5 mg/kg lidocaine bolus and a 1 mg/kg infusion (first 30 min), followed by a 0.5 mg/kg infusion for a further 30 min intravenously. The non-steroidal anti-inflammatory drug (NSAID) group (n = 50) received 50 mg dexketoprofen trometamol and saline at the same volume as the lidocaine at the same time intervals intravenously. The Visual Analog Scale (VAS) pain scores, additional analgesia requirement, side effects, and revisits to the emergency department were recorded. RESULTS: The VAS score was significantly lower in the lidocaine group than in the NSAID group for the first 20th and 30th minutes (p = 0.014 and p = 0.024, respectively). There was no difference between the VAS scores for the remaining evaluation times (p > 0.05). In terms of secondary outcomes, rescue medication requirement was not different between the two groups at both the 60th and 90th minutes (p > 0.05). However, the number of patients revisiting ED within 48-72 h was statistically less in the lidocaine group than in the NSAID group (1/50 vs. 8/50; p = 0.031). CONCLUSION: Intravenous lidocaine may be an alternative treatment method for patients with migraine attack headaches in the emergency department.

The effectiveness of intradermal sterile water injection for low back pain in the emergency department: A prospective, randomized controlled study.

AIM: Low back pain (LBP) is a common musculoskeletal complaint among emergency department (ED) admissions. In this study, it was aimed to compare the effectiveness of systemic treatment with intradermal sterile water injection (ISWI) treatment protocol combined with systemic therapy in patients with LBP of unclear chronicity. METHODS: A prospective randomized, unblinded, controlled clinical study was conducted on patients admitted to the ED for LBP of unclear chronicity. One hundred twelve patients were randomly assigned to two groups; Group ISWI (n = 56) administered ISWI in the LBP region of patients along with systemic intravenous dexketoprofen therapy, while the other group (n = 56) received only systemic intravenous dexketoprofen therapy. The treatment methods' effectiveness was compared by measuring the pain intensity with the Visual Analog Scale (VAS) at admission, 10th minutes, 20th minutes, 30th minutes, and 24 h later. Also, opioid and analgesic consumptions in 24 h after treatment and patient satisfactions were compared. RESULTS: In the treatment of LBP, ISWI treatment was found to be more effective in relieving pain than systemic therapy alone (p < 0.001). Also, it was observed that opioid consumption in the ED and analgesic consumption within 24 h after treatments were decreased in the ISWI group (p < 0.001). The patient satisfaction in the ED was statistically increased (p < 0.001). DISCUSSION: In this unblinded study, ISWI with systemic therapy improved pain outcomes more than systemic therapy alone. Further research is needed to determine whether this was due entirely to placebo effect.

Antinociception and less gastric injury with the dexketoprofen-tapentadol combination in mice.

The purpose of this study was to evaluate the antinociceptive interaction between dexketoprofen and tapentadol in three different dose ratios, as well as the ulcerogenic activity of this combination. Dose-response curves were carried out for dexketoprofen, tapentadol, and dexketoprofen-tapentadol combinations in the acetic acid-induced writhing test in mice. On the other hand, the gastric damage of all treatments was assessed after the surgical extraction of the stomachs. Intraperitoneal administration of dexketoprofen and tapentadol induced a dose-dependent antinociceptive effect, reaching a maximal effect of about 58% and 99%, respectively. Isobolographic analysis and the interaction index showed that the three proportions produced an analgesic potentiation (synergistic interaction). Interestingly, the 1:1 and 1:3 ratios of the drugs combination produced minor gastric injury in comparison with the 3:1 proportion. Our data suggest that all proportions of the dexketoprofen-tapentadol combination produced a synergistic interaction in the acetic acid-induced visceral pain model in mice with a low incidence of gastric injury.

Pharmacokinetics, Safety, and Tolerability of Intravenous Felbinac Trometamol in Healthy Chinese Volunteers: A First-in-Human Single- and Multiple-Dose Escalation Phase I Study with a Randomized, Double-Blind, Placebo-Controlled Design.

BACKGROUND: Felbinac trometamol, an anti-inflammatory and analgesic drug, has been used to treat immediate postoperative pain. OBJECTIVE: The aim of this study was to evaluate the safety, tolerability, and pharmacokinetics of single or multiple intravenous infusions of felbinac trometamol in healthy Chinese volunteers. METHODS: A total of 56 healthy subjects were enrolled in a single-ascending dose study (11.78-377.00 mg), meanwhile 36 subjects were enrolled in a multiple-ascending dose study (47.13-188.50 mg). Safety endpoints included treatment-emergent adverse events, vital signs, electrocardiograms, and laboratory parameters. Pharmacokinetic endpoints included exposure of subjects to felblinac and metabolites of the drug in plasma, urine, and feces. RESULTS: Felblinac time to maximum plasma concentration was obtained at 0.5 h, corresponding to the end of the infusion. Maximum plasma concentration and area under the curve increased in a dose-dependent manner for felblinac and its metabolite, showing linear pharmacokinetic characteristics at single and multiple doses. After intravenous infusions of multiple doses three times (30 min each time) per day, the accumulation ratio of felblinac and its metabolite based on the area under the curve had a range of 1.34-1.45 and 1.60-1.87, respectively, across cohorts. After administration of the fourth dose, the plasma concentration of both felblinac and its metabolites was maintained at a steady state. Felbinac trometamol was well tolerated. Neither treatment-emergent adverse event frequency nor severity increased with increasing felbinac trometamol dose. CONCLUSIONS: Felbinac trometamol was well tolerated in our study. Based on the dose range in this study, 94.25 mg is the recommended target dose for a phase II study. CLINICAL TRIAL REGISTRATION: CTR20170496 and CTR20180896. The dates of registration are 2017-06-19 and 2018-07-02 ( https://www.chinadrugtrials.org.cn/ ).

A cleanser formulated with Tris (hydroxymethyl) aminomethane and l-arginine significantly improves facial acne in male Thai subjects.

BACKGROUND: Acne is one of the most common skin problems among human populations. A facial cleanser formulated with alkyl ether carboxylate (AEC) and alkyl carboxylate (AC) can improve acne by cleansing sebum on facial skin but cannot effectively remove keratotic plugs in the skin pores. Recently, we confirmed that Tris (hydroxymethyl) aminomethane and L-arginine (Tris/Arg) is able to reduce sebum levels, disrupt keratotic plugs in vitro and decrease pore size on facial skin. OBJECTIVE: To compare the efficacy of the Tris/Arg-formulated cleanser with the AEC/AC cleanser in Thai subjects with acne. METHODS: We designed a randomized, double-blind, controlled, parallel trial. Thirty-four male Thai subjects with mild to moderate acne were assigned to one of two groups: one group used the Tris/Arg cleanser while the other used the AEC/AC-based cleanser twice a day for 4 weeks. RESULTS: After 4 weeks, significant decreases in noninflammatory acne were observed in both groups, yet significant decreases in inflammatory acne were only observed in the Tris/Arg cleanser group. The sebum level prior to and 30 minutes after facial washing showed no change in either group. The average pore size with keratotic plugs on the cheeks was significantly decreased in the Tris/Arg group. More than half of subjects in both groups observed acne improvement but more subjects in the Tris/Arg group noted pore size improvement. CONCLUSION: The Tris/Arg formulated cleanser has a high efficacy for significantly reducing both noninflammatory and inflammatory acne accompanied by decreases in pore size with keratotic plugs in male Thai subjects.

Development of controlled release dexketoprofen tablets and prediction of drug release using Artificial Neural Network (ANN) modelling

Dexketoprofen trometamol (DT) is an active S (+) enantiomer of ketoprofen, and a non-steroidal anti-inflammatory agent. DT has a short biological half-life and the dosing interval is quite short when there is a need to maintain the desirable effect for longer time periods. Consequently, a controlled release DT tablet was designed for oral administration aiming to minimize the number of doses and the possible side effects. Calculations of the parameters for controlled release DT tablets were shown clearly. Controlled release matrix-type tablet formulations were prepared using hydroxypropyl methylcellulose (HPMC) (low and high viscosity), Eudragit RS and Carbopol, and the effects of different polymers on DT release from the tablet formulations were investigated. The dissolution rate profiles were compared and analyzed kinetically. An Artificial Neural Network (ANN) model was developed to predict drug release and a successful model was obtained. Subsequently, an optimum formulation was selected and evaluated in terms of its analgesic and anti-inflammatory activity. Although the developed controlled release tablets did not have an initial dose, they were found to be as effective as commercially available tablets on the market. Dissolution and in vivo studies have shown that the prepared tablets were able to release DT for longer time periods, making the tablets more effective, convenient and more tolerable.

Efficacy and safety of motherwort injection add-on therapy to carboprost tromethamine for prevention of post-partum blood loss: A meta-analysis of randomized controlled trials.

Motherwort (YiMuCao), a traditional Chinese herb, has been shown beneficial effects for women's diseases. This meta-analysis aimed to evaluate the efficacy and safety of motherwort injection add-on therapy to carboprost tromethamine for prevention of post-partum blood loss. A systematic literature search was conducted in PubMed, Embase, Cochrane Library, CNKI, VIP and Wanfang from their inception to December 2017. Randomized controlled trials that determined the add-on effects of motherwort injection to carboprost for prevention of post-partum blood loss were eligible. Pooled risk ratio (RR) and mean difference (MD) with 95% confidence interval (CI) were used to summarize the effect sizes. Eight trials including 1276 pregnant women fulfilled the inclusion criteria. Prophylactic use of motherwort injection add-on therapy significantly reduced the post-partum 2 h (MD -127.5 mL; 95% CI -149.13 to -105.88) and 24 h (MD -146.85 mL; 95% CI -179.77 to -113.94) blood loss and incidence of post-partum hemorrhage (RR 0.28; 95% CI 0.17-0.45) than carboprost. Moreover, adjunctive treatment with motherwort injection significantly decreased the length of the third stage of labor (MD -3.41 min; 95% CI -4.33 to -2.49) and duration of lochia (MD -7.13 days; 95% CI -8.49 to -5.76). There was no statistical significant difference in the incidence of adverse events (RR 0.76; 95% CI 0.50-1.16). Prophylactic use of motherwort injection add-on therapy to carboprost tromethamine could reduce post-partum blood loss. However, more well-designed trials are necessary to confirm the findings of this study due to the methodological flaws of the included trials.

European photopatch test baseline series: A 3-year experience.

BACKGROUND: In 2012, a consensus was reached regarding a baseline photopatch test series on the basis of the results of a European multicentre study. OBJECTIVES: To describe experience with the European photopatch test series. METHODS: A retrospective analysis of 116 patients tested with the European photopatch test series between 2014 and 2016 was performed. RESULTS: Fifty-five positive photopatch test reactions in 25 subjects were recorded, most commonly caused by the topical non-steroidal anti-inflammatory drugs ketoprofen, dexketoprofen, and etofenomate. Organic ultraviolet (UV) absorbers constituted the second main category of agents eliciting positive photopatch test reactions. Among UV absorbers, benozophenone-3 and octocrylene were the most frequent photoallergens. UV absorbers that have been introduced more recently rarely elicited positive photopatch test reactions. Positive patch test reactions were less commonly observed than positive photopatch test reactions, namely, 21 reactions in 14 patients. CONCLUSIONS: We present the largest clinical experience with the European photopatch test baseline series hitherto reported. The results are similar to those underlying the above consensus process, reaffirming the usefulness of this series.

Safety Assessment of Tromethamine, Aminomethyl Propanediol, and Aminoethyl Propanediol as Used in Cosmetics.

The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) reviewed the safety of tromethamine, aminomethyl propanediol, and aminoethyl propanediolas used in cosmetics. All 3 ingredients are reported to function in cosmetics as pH adjusters, and tromethamine and aminomethyl propanediol are also reported to function as fragrance ingredients. The Panel reviewed relevant animal and human data related to these ingredients, along with a previous safety assessment of aminomethyl propanediol. The Panel concluded that tromethamine, aminomethyl propanediol, and aminoethyl propanediol are safe in cosmetics in the practices of use and concentration as given in this safety assessment.

Comparison of IV dexketoprofen trometamol, fentanyl, and paracetamol in the treatment of renal colic in the ED: A randomized controlled trial.

OBJECTIVE: In this study, we aimed to compare the analgesic efficacy of intravenous dexketoprofen trometamol, fentanyl, and paracetamol in patients presenting to the emergency department with renal colic. MATERIALS AND METHOD: Data obtained from the emergency departments of Gaziantep University's Hospital for Research and Practice along with two other state hospitals in Gaziantep, Turkey between January 2016 and January 2017 was used for this study. A total of three hundred patients (n=300), who presented to the ER with complaints most common to renal colic whose diagnoses were subsequently confirmed with Computerized Tomography were included in the study. Patients' pain scores were recorded using the Visual Analogue Scale, at admission (immediately before drug administration), then at the 15th, and 30th minutes. SPSS 22.0 software package was used for analysis. p<0.05 was considered significant. RESULTS: At the 15th minute comparison, the efficacies of the three groups of drugs were not superior to one other, but at the 30th minute, dexketoprofen trometamol was statistically more effective than paracetamol and fentanyl. There was no statistically significant difference between fentanyl and paracetamol. The need for additional analgesia in the group receiving dexketoprofen trometamol was found to be lower. Dexketoprofen trometamol was statistically superior to the other two agents in achieving full analgesia at the end of the thirty-minute period. Fentanyl was found to be statistically significant in achieving moderate analgesia. CONCLUSION: As a Non-steroidal antiinflammatory drug dexketoprofen trometamol is superior to paracetamol and fentanyl in achieving analgesia and reducing the need for additional drugs for the treatment of renal colic.

The use of oral fosfomycin-trometamol in patients with catheter-associated urinary tract infections (CAUTI): new indications for an old antibiotic?

We present the results of a multicenter retrospective study of 35 difficult-to-treat patients with urinary tract infections associated with indwelling urinary catheters (CAUTIs). All patients received oral administration of 3 g fosfomycin trometamol once a day for two days and then with a dose of 3 g every 48 h for two weeks. The most commonly isolated strains were: Escherichia coli (65.7%) and Enterococcus spp. (25.7%); prevalence of Extended-Spectrum Beta-Lactamase strains was 48.5%. Six patients (17.1%) had a clinical response after a single dose of fosfomycin trometamol, 12 (34.2%) after two doses and 13 (37.1%) patients had a clinical response after three or more doses. Four patients (11.6%) failed prolonged antibiotic treatment with fosfomycin trometamol. During the follow-up period, 30 out of 35 (85.7%) patients were without symptomatic infections. No significant side effects were reported. In conclusion, fosfomycin trometamol seems to be a valid treatment option in patients with CAUTIs.

Effectiveness and safety of continuous ultrasound-guided femoral nerve block versus epidural analgesia after total knee arthroplasty. / Eficacia y seguridad del bloqueo femoral continuo guiado con ecografía frente a la analgesia epidural en el postoperatorio de artroplastia total de rodilla.

OBJECTIVES: Total knee arthroplasty is associated with severe postoperative pain. The aim of this study was to compare continuous ultrasound-guided femoral nerve block with continuous epidural analgesia, both with low concentrations of local anaesthetic after total knee arthroplasty. MATERIAL AND METHODS: A prospective, randomised, unblinded study of 60 patients undergoing total knee replacement, randomised into two groups. A total of 30 patients received continuous epidural block, while the other 30 received continuous ultrasound-guided femoral nerve block, as well as using 0.125% levobupivacaine infusion in both groups. Differences in pain control, undesirable effects, and complications between the two techniques were assessed, as well as the need for opioid rescue and the level of satisfaction with the treatment received during the first 48hours after surgery. RESULTS: No differences were found in demographic and surgical variables. The quality of analgesia was similar in both groups, although in the first six hours after surgery, patients in the epidural group had less pain both at rest and with movement (P=.007 and P=.011). This difference was not observed at 24hours (P=.084 and P=.942). Pain control at rest in the femoral block group was better at 48hours after surgery than in the epidural group (P=.009). The mean consumption of morphine and level of satisfaction were similar. Epidural analgesia showed the highest rate of side effects (P=.003). CONCLUSIONS: Continuous ultrasound-guided femoral nerve block provides analgesia and morphine consumption similar to epidural analgesia, with the same level of satisfaction, but with a lower rate of side effects after total knee arthroplasty.

Large doses of uterotonic drugs caused type II second degree sinoatrial block during cesarean section.

In China, it is a routine procedure to inject 250 µg of hemabate (sterile solution, an oxytocic, contains the tromethamine salt of the (I5S)-15 methyl analogue of naturally occurring prostaglandin F2α in a solution suitable for intramuscular injection) into the myometrium of patients experiencing uterine inertia after delivery, with an additional dose given in the event that the efficacy is not obvious. Although hemabate is prohibited from being used in patients with active liver disease, there are no restrictions regarding the application of hemabate in positive hepatitis B surface antigen (HbsAg)-positive subjects with normal liver function. Here we report adverse effects of hemabate in 1 HbsAg-positive subject with normal liver function. This subject experienced increased blood pressure, chest tightness, and type II second degree sinoatrial block 25 minutes after an additional injection of hemabate. Thus, special attention should be paid when applying hemabate in HbsAgpositive subjects with normal liver function.

REFRACTORY BRADYCARDIA--A RARE COMPLICATION OF CARBOPROST TROMETHAMINE FOR INDUCTION OF ABORTION

We report a first case of refractory several-hour sinus bradycardia, a rare but already described side effect of intramuscular administration of carboprost tromethamine to induce abortion for medical indication in a patient without cardiovascular and other diseases. After administration of atropine sulfate 3x0.5 mg intravenously without effect, the patient's sinus rhythm spontaneously normalized as carboprost was eliminated from the body (it has a 3-hour half-life). It is reasonable to believe that the specific prostaglandin underlay the etiology of bradycardia.

Acute dystonic reaction due to dexketoprofen trometamol.

Dexketoprofentrometamol (DKP), is a tromethamine salt of the water-soluble S-enantiomer of ketoprofen. As with all other non-steroidal anti-inflammatory agents, the most common side effect of DKP is gastric complications. In this paper, we report a case of dystonic reaction after intravenous DKP use. A 24-year-old man was admitted to our hospital after suffering a leg burn from boiling oil. He had no drug hypersensitivity. An intravenous preparation containing the active ingredient DKP was injected for analgesia, after which the patient experienced an involuntary flexion response in both upper extremities. With a suspected diagnosis of dystonia, biperiden lactate 5 mg/ml was administered via the intramuscular route and the contractions abated within 30 seconds of the injection.As non-steroidal anti-inflammatory agents are commonly used and prescribed in emergency departments, it should be kept in mind that an acute dystonic reaction can develop against one of these agents, DKP.