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Objectives: This study aims to determine the usage pattern, effectiveness and safety of oral tramadol 75 mg and dexketoprofen trometamol 25 mg fixed-dose combination (TRAM/DKP FDC) in the short-term treatment of moderate-to-severe acute pain in real-world clinical practice in Asia., Design: Real-world, prospective, multicentre, observational, phase IV study., Setting: 13 tertiary-care hospital sites across the Philippines, Thailand, Malaysia and Singapore., Participants: Adult patients aged 18-80 years prescribed TRAM/DKP FDC for the short-term (up to 5 days) treatment of moderate-to-severe acute pain., Main Outcome Measures: Primary endpoints were the proportion of patients prescribed TRAM/DKP FDC with different types of postsurgical and non-surgical treatments, and the average dosing frequency and duration of TRAM/DKP FDC treatment. Secondary endpoints were the proportion of patients achieving ≥30% pain reduction at 8 hours post the first dose (pain severity was assessed using the 11-point Numeric Pain Rating Scale); patient satisfaction at the end of treatment (based on a 5-point Patient Global Evaluation Scale (PGE)) and safety including the incidence of adverse drug reactions (ADRs)., Results: Among 599 patients (median age 44 years, 61.3% female) enrolled in this study, 68.61% (n=411) were postsurgical and 31.39% (n=188) were non-surgical patients. TRAM/DKP FDC was prescribed in a diverse group of postsurgical patients (eg, orthopaedic, general and cancer surgery) as well as in non-surgical conditions (eg, lower back pain and musculoskeletal pain). In the majority of patients, TRAM/DKP FDC was prescribed every 8 hours (65.94%) and for 5 days (78.80%). There was a significant reduction in pain intensity throughout the study and 65% of patients achieved ≥30% pain reduction from baseline at 8 hours post the first dose of TRAM/DKP FDC on day 1. 95.69% of patients were satisfied with the treatment (rated good, very good and excellent on the PGE scale). Overall, 13.9% of patients reported ADRs; most were mild to moderate in severity. The most common ADRs were nausea, vomiting and dizziness., Conclusion: This study showed that TRAM/DKP FDC was used in diverse types of postsurgical and non-surgical patients in the real-world setting in Asia. It effectively reduced pain and was well tolerated with a high level of patient satisfaction., Competing Interests: Competing interests: BG, AG and DN are employees of A. Menarini Asia-Pacific Holdings Pte. Ltd., Singapore. All other authors report receiving investigator fees for this study from the sponsor., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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.

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., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., (© 2020 Société Française de Pharmacologie et de Thérapeutique.)

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., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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/ ).

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., (© 2019 Wiley Periodicals, Inc.)

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., (© 2018 Japan Society of Obstetrics and Gynecology.)

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., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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.

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.

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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., (Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.)

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.

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.

Background: Dexketoprofen has been shown to provide efficient analgesia and an opioid-sparing effect after orthopedic surgery. In this dose-finding study, we evaluated the analgesic efficacy and opioid-sparing effect of dexketoprofen administered intravenously (i.v.) after laparoscopic cholecystectomy (LCC)., Methods: Twenty-four patients undergoing LCC were randomized to receive dexketoprofen 10 or 50 mg i.v. 15 min before the end of the surgery. Subjects were provided with 0.2 mg/kg of oxycodone at anesthesia induction. In the recovery room, pain was assessed with an 11-point numerical rating scale (NRS; score of 0 = no pain, score of 10 = most severe pain) every 10 min. When the NRS score was ≥3/10 at rest or ≥5/10 at wound compression, a plasma sample was taken for analysis of oxycodone [to determine the minimum effective concentration (MEC)], its metabolites, and dexketoprofen. After that, subjects were titrated with oxycodone 2 or 3 mg i.v. every 10 min until the NRS score was <3/10 at rest and <5/10 at wound compression. At this point, a second plasma sample was taken for analysis of oxycodone [minimum effective analgesic concentration (MEAC)], its metabolites, and dexketoprofen., Results: At the onset of pain, the plasma oxycodone concentrations (MEC) were similar in the two groups: median 60 ng/mL (range 37-73) in the 10 mg group and median 52 ng/mL (range 24-79) in the 50 mg group. At the time of pain relief, the MEACs were 98 ng/mL (range 59-150) in the 10 mg group and 80 ng/mL (range 45-128) in the 50 mg group. The total doses of oxycodone needed to achieve pain relief were similar: 0.11 mg/kg (range 0-0.33) in the 10 mg group and 0.08 mg/kg (range 0-0.24) in the 50 mg group. Eleven subjects developed mild desaturation or a decreased respiratory rate after oxycodone titration., Conclusion: In the present double-blinded, randomized clinical trial, the need for a rescue opioid analgesic, oxycodone, was similar with the two dose levels of dexketoprofen-10 and 50 mg i.v.-after LCC.

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.

Introduction: Low tidal volume (VT) ventilation is recommended in patients with acute respiratory distress syndrome (ARDS). This may increase arterial carbon dioxide tension (PaCO2), decrease pH, and augment pulmonary vascular resistance (PVR). We hypothesized that Tris(hydroxymethyl)aminomethane (THAM), a pure proton acceptor, would dampen these effects, preventing the increase in PVR., Methods: A one-hit injury ARDS model was established by repeated lung lavages in 18 piglets. After ventilation with VT of 6 ml/kg to maintain normocapnia, VT was reduced to 3 ml/kg to induce hypercapnia. Six animals received THAM for 1 h, six for 3 h, and six serving as controls received no THAM. In all, the experiment continued for 6 h. The THAM dosage was calculated to normalize pH and exhibit a lasting effect. Gas exchange, pulmonary, and systemic hemodynamics were tracked. Inflammatory markers were obtained at the end of the experiment., Results: In the controls, the decrease in VT from 6 to 3 ml/kg increased PaCO2 from 6.0±0.5 to 13.8±1.5 kPa and lowered pH from 7.40±0.01 to 7.12±0.06, whereas base excess (BE) remained stable at 2.7±2.3 mEq/L to 3.4±3.2 mEq/L. In the THAM groups, PaCO2 decreased and pH increased above 7.4 during the infusions. After discontinuing the infusions, PaCO2 increased above the corresponding level of the controls (15.2±1.7 kPa and 22.6±3.3 kPa for 1-h and 3-h THAM infusions, respectively). Despite a marked increase in BE (13.8±3.5 and 31.2±2.2 for 1-h and 3-h THAM infusions, respectively), pH became similar to the corresponding levels of the controls. PVR was lower in the THAM groups (at 6 h, 329±77 dyn∙s/m(5) and 255±43 dyn∙s/m(5) in the 1-h and 3-h groups, respectively, compared with 450±141 dyn∙s/m(5) in the controls), as were pulmonary arterial pressures., Conclusions: The pH in the THAM groups was similar to pH in the controls at 6 h, despite a marked increase in BE. This was due to an increase in PaCO2 after stopping the THAM infusion, possibly by intracellular release of CO2. Pulmonary arterial pressure and PVR were lower in the THAM-treated animals, indicating that THAM may be an option to reduce PVR in acute hypercapnia.

What Is Known and Objective: Ketoprofen has high analgesic efficacy against inflammatory and nociceptive pain. Additionally, when ketoprofen is administered in conjunction with an opioid during pain management, it prevents the development of opioid-induced hyperalgesia. The main limitation for racemic ketoprofen IV administration is venous irritation. Dexketoprofen is the active enantiomer of racemic ketoprofen and has a similar analgesic efficacy in a dose proportion of 1 : 2, but it causes fewer adverse effects than racemic ketoprofen. It has been claimed that dexketoprofen may cause less frequent and less severe injection pain than racemic ketoprofen. In this study, we compared the injection pain of IV administered racemic ketoprofen and dexketoprofen in elective surgical patients., Methods: The ethics committee of our institution approved this randomized, double-blinded, two-treatment, two-period, crossover clinical comparison of ketoprofen and dexketoprofen. A total of 221 ASA I-III adult patients, aged 20-75 years, were initially IV administered either 0·5 mg/kg racemic ketoprofen followed 2 h later with 0·25 mg/kg dexketoprofen (group 1) or vice versa (group 2). Both compounds were diluted in 20 mL of normal saline and were injected over 6 min. Patients reported injection pain on an 11-point numerical rating scale (NRS) (0 = no pain, 10 = most pain)., Results and Discussion: Significantly less injection pain was reported after dexketoprofen administration. A total of 201 of 209 patients reported pain during racemic ketoprofen injection, and 157 of 210 patients reported pain during dexketoprofen injection, respectively. Moderate or severe pain was reported by 90 (41%) patients during racemic ketoprofen administration and by 43 (20%) during dexketoprofen injection (P = 0·001). The mean of injection pain during racemic ketoprofen injection was 4·2 (SD 2·5) and was 2·5 (2·4) during dexketoprofen injection (P = 0·001). No serious or unexpected adverse events were reported., What Is New and Conclusion: Dexketoprofen causes significantly less injection pain than racemic ketoprofen; therefore, it may be a more suitable IV non-steroidal anti-inflammatory than the racemate., (© 2015 John Wiley & Sons Ltd.)

Various drugs are known to cause pill esophagitis. Antimicrobial drugs and nonsteroidal anti-inflammatory drugs are the most common causes of pill-induced esophagitis. Most patients suffer only self-limiting pain, but serious complications can occur. A 21-year-old man was admitted to our outpatient clinic with retrosternal chest pain, dysphagia, and odynophagia complaints, which occurred within 2 weeks after starting dexketoprofen trometamol. An upper endoscopy system examination revealed three well-demarcated ulcers in the esophagus at 35 cm from the incisors. Dexketoprofen trometamol may cause esophageal lesions. This rare disorder should be considered in patients presenting with sudden-onset retrosternal pain in addition to dysphagia and odynophagia.

Mushroom poisoning is an important reason of plant toxicity. Wild mushrooms that gathered from pastures and forests can be dangerous for human health. The clinical outcomes and symptoms of mushroom toxicity vary from mild gastrointestinal symptoms to acute multiple organ failure. Toxic effects to kidney and liver of amatoxin are common but cardiotoxic effects are unusual. In this case, we reported the cardiotoxic effect of amatoxin with the elevated troponin-I without any additional finding in electrocardiography, echocardiography and angiography.

Background & Objectives: Effective pain control following outpatient surgical procedures is an important aspect of patient discharge. This study was carried out with an aim to investigate the histopathological effects of intra-articular dexketoprofen trometamol injection in knee joint on synovium and cartilage in an experimental rat model., Methods: In each of 40 rats, the right knee was designated as the study group and the left knee as the control group (NS group). Under aseptic conditions, 35 rats received an injection of 0.25 ml (6.25 mg) dexketoprofen trometamol into the right knee joint and an injection of 0.25 ml 0.9 per cent normal saline solution into the left knee joint. On the 1st, 2nd, 7th, 14th, and 21st days after intra-articular injection, rats in specified groups were sacrificed by intraperitoneal injection of 120 mg/kg sodium thiopental. Knee joints were separated and sectioned for histopathological examination. Inflammatory changes in the joints were recorded according to a grade scale., Results: No significant difference in terms of pathological changes both in synovium and cartilage was observed between the NS group and the study group on days 1, 2, 7, 14 and 21 after intra-articular injection of dexketoprofen or saline in the knee joint., Interpretation & Conclusions: The findings showed no evidence of significant histopathological damage to the cartilage and synovia for a period up to 21 days following intra-articular administration of dexketoprofen trometamol in the knee joints of rats.

In this study, the analgesic effects of dexketoprofen trometamol and meperidine hydrochloride were compared in patients diagnosed with renal colic. This study was a prospective, randomized, double-blind study. Fifty-two patients, between the ages of 18 and 70 years who were diagnosed with renal colic, were enrolled in the study after obtaining ethics committee approval. Before drug injection, dexketoprofen trometamol and meperidine hydrochloride were placed in closed envelopes, and the patients were randomly given a single dose of intravenous infusion for 20 minutes. Severity of pain and symptoms was evaluated with the numerical rating scale and renal colic symptom score for each patient immediately before administration of drugs and 30 minutes after the end of the application. At the same time, systolic arterial blood pressure, diastolic arterial pressure, respiratory rate, heart rate, nausea, vomiting, and reactions due to drug administration were recorded before and after drug administration. In statistical methods, t test, analysis of variance, and repeated measure analysis were used for the analysis of normally distributed continuous variables and the Mann-Whitney U, Kruskal-Wallis and Friedman tests were used for analysis of not-normally distributed continuous variables. In the analysis of discrete variables, the χ test was used. In both groups, a significant decrease was found in numerical rating scale values measured 30 minutes after drug administration, but the decline in dexketoprofen trometamol group (P = 0.02) was found to be more. Although a significant decrease was found in the renal colic symptom score (P < 0.001) values measured after drug administration in the dexketoprofen trometamol group, no significant decrease was found in the meperidine HCl (P = 0.058) group. After drug administration, a statistically significant decrease was found in the systolic arterial blood pressure, heart rate, and respiratory rate in both groups. Also, a statistically significant decrease was found in the diastolic arterial pressure in the meperidine group. But these changes in vital findings were not serious enough to disrupt patients' clinical status. With this study, we concluded that dexketoprofen trometamol, from the nonsteroidal anti-inflammatory drug group, can be within the primary treatment options for renal colic because of better analgesic efficacy, being well tolerated by patients compared with meperidine hydrochloride.

At least 50 % of female migraineurs experience migraine associated with the perimenstrual period, even though they may also suffer from attacks at other times of the cycle (menstrually related migraine, MRM). MRM attacks tend to be longer and more intense than those arising in other phases of the menstrual cycle, and are often aggravated by more pronounced vegetative phenomena. In this open preliminary trial, we tested the efficacy of associating frovatriptan and dexketoprofen for the treatment of an acute attack of MRM, diagnosed according to the criteria of the International Headache Society, in 24 patients between 19 and 45 years of age (mean 31.33 ± 7.33). Twenty-one of them completed the study. Pain relief was achieved by 76 % of patients at 2 h and by 86 % at 4 h. A pain-free state was achieved by 48 % at 2 h and by 62 % at 4 h from taking the product. A pain-free state at 24 h was present in 76 % of MRM sufferers, 33 % of whom showed a sustained pain-free state at 24 h. A rescue medication was needed by eight patients. While decidedly encouraging, the data of this study obviously need confirmation with double blind studies involving a greater number of patients.

A 70-year-old male patient was admitted complaining of weakness and pain in his arms and lower limbs. His serum creatine kinase and serum creatinine were markedly elevated (36,248 IU/L and 2.8 mg/dL, respectively). He had taken dexketoprofen trometamol because of a common cold, which had developed the previous night. Acute kidney injury caused by dexketoprofen-induced rhabdomyolysis was diagnosed by ruling out other possible causes, such as dermato/polymyositis, myxedema, brucellosis, and hepatitis. Dexketoprofen administration was stopped. As diuresis did not restore spontaneously, the patient was treated with I.V. alkaline solutions and mannitol. Hemodialysis was performed because of anuria and severe metabolic acidosis. The patient's renal function later recovered. In conclusion, dexketoprofen may be a potential risk factor for acute kidney injury and rhabdomyolysis.

The most common method of controlling acidemia during lung-protective ventilation is CO₂ removal with an extracorporeal lung assist (ECLA) system. Another possibility to prevent acidemia is based on intravenous (i.v.) application of tris-hydroxymethyl-aminomethane (3 mol/L, THAM) buffer, which can bind hydrogen protons and which can be removed from the body via renal replacement therapy (RRT). We investigated whether RRT combined with predilutional (prefilter) THAM-application provides an alternative to ECLA for a rescue situation. For this, anesthetized pigs, 40 kg of body weight, six animals per group, underwent 5 h of acidemia (pH 7.19-7.24) induced by acid infusion and permissive hypercapnia (low tidal volume ventilation, PaCO₂ 80-90 mmHg). Isovolemic, high-volume hemofiltration (HVHF) was operated with predilutional THAM-infusion for treatment. To evaluate adverse effects of this approach, we set up further groups: HVHF with postdilutional (post-filter) THAM-application; i.v.-THAM without HVHF; normal pH homeostasis with HVHF. Acid-base parameters, hemodynamics, renal function, and lung morphology were investigated. HVHF with predilutional THAM-infusion of 8 mmol/kg/h allowed fast pH normalization, significant reduction in PaCO₂ to 56 mmHg and tolerable hemodynamics. HVHF alone or lower dose i.v. THAM (2 mmol/kg/h) failed to produce a comparable result. A postdilutional THAM infusion reduced hemodynamic tolerability and increased lung edema formation. HVHF in pigs with normal acid-base status resulted in a decreased base excess and urine acidification. In conclusion, predilutional THAM-application and HVHF corrected the acid-base disorder and improved pulmonary hemodynamics. Further studies are necessary to optimize the protocol including the dosage., (© 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Recently, new concerns on the safety profile of nonsteroidal anti-inflammatory drugs (NSAIDs) have been raised by the European Medicines Agency (EMEA) and other regulatory authorities. The safety profile of oral dexketoprofen trometamol for the treatment of acute mild to moderate pain of different causes in actual conditions of use in the primary care setting was assessed. A prospective cohort study was designed to evaluate the tolerability of dexketoprofen compared with other commonly prescribed analgesics. Medications were given according to specifications in the summary of product characteristics. The intensity of pain was assessed at baseline and at days 1 and 7 of drug treatment using a 100-mm visual analog scale (VAS). Adverse events (AEs) were recorded. A total of 7,337 patients (median age [IQR] = 46 [33-61] years) were included in the study comparing dexketoprofen (n = 5,429), diclofenac (n = 485), ibuprofen (n = 479), paracetamol (n = 459), metamizole (n = 207), aceclofenac (n = 103), naproxen (n = 74), piroxicam (n = 69) and dexibuprofen (n = 32). The reasons for use were: musculoskeletal disorders, headache, dysmenorrhea and odontalgia. Treatment compliance was very high. Metamizole-paracetamol and dexketoprofen showed the lowest prevalence of AEs (2.7% and 3.6%, respectively), while aceclofenac-diclofenac showed the highest prevalence (8.2%) (P < 0.0001). AEs most frequently observed during NSAID treatment were those related to the gastrointestinal tract (3.5% of subjects, 84% of all AEs), followed by AEs related to the nervous system (0.4%) and skin (0.1%). Most of the reported AEs (91.3%) were of mild to moderate intensity (303 of 332) and only 3.3% of them were considered severe (11 of 332). Risks for gastrointestinal AEs were adjusted for age, gender, history of previous NSAID intake, gastroprotective drugs and reason for prescription. Taking metamizole-paracetamol as the reference group, the odds ratios (OR, 95%) were: 1.30 (0.77-2.19) for dexketoprofen, 1.57 (0.79-3.13) for ibuprofen and dexibuprofen, 2.31 (0.64-8.27) for naproxen, 2.63 (0.85-8.15) for piroxicam and 3.37 (1.87-6.06) for aceclofenac-diclofenac. These results confirm the safety of oral treatment with dexketoprofen in patients with acute pain of various etiologies observed in previous studies and support the use of dexketoprofen as a first-line drug for the approved therapeutic indications., (Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.)

This case report describes a previously healthy 35-year-old woman, with an episode of fever, neutropenia, thrombocytopenia and elevation of biochemical markers of liver injury, 10 days after beginning drug therapy with dexketoprofen trometamol. Infectious and autoimmune causes of neutropenia, and viral or autoimmune hepatitis were excluded. The resolution following withdrawal of dexketoprofen trometamol confirms the possibility of an adverse drug reaction.

Objective: The aim of this study was to assess the efficacy and safety of a single intravenous (i.v.) bolus of dexketoprofen trometamol compared with an i.v. infusion of dipyrone in patients with moderate to severe pain due to renal colic., Methods: A total of 308 patients with renal colic and visual analog scale (VAS) score >/=40 mm participated in a multicenter, randomized, double blind, double-dummy, parallel, and active-controlled study and were randomized to dexketoprofen 25 mg (n = 101), dexketoprofen 50 mg (n = 104), and dipyrone 2 g (n = 103)., Results: Mean [+/- standard deviation (SD)] total pain relief (TOTPAR) scores were similar in the dexketoprofen 50 mg (15.3 +/- 8.6) and dipyrone (15.5 +/- 8.6) and slighly higher than in dexketoprofen 25 mg (13.5 +/- 8.6), although significant differences were not achieved. In the same way, patients in the dexketoprofen 50 mg and dipyrone groups showed higher scores in the sum of pain intensity differences (SPID) and the sum of analogue pain intensity differences (SAPID) than patients in the dexketoprofen 25 mg group, reaching statistical significance in comparison with dexketoprofen 25 mg and dipyrone for SPID and SAPID (p < 0.05). The time-effect course for pain intensity differences and pain relief showed significantly higher values for both doses of dexketoprofen during the first 30 min after drug administration (p < 0.05). Dexketoprofen 50 mg and dipyrone groups had 66% and 70%, respectively, of patients with at least 50% of maximum obtainable TOTPAR in comparison with 56% in the dexketoprofen 25 mg group. The study medications were well tolerated., Conclusions: Dexketoprofen 50 mg administered as a single i.v. bolus was effective for the relief of moderate to severe pain in patients with renal colic, with a good safety profile and efficacy similar to i.v. dipyrone 2 g. Dexketoprofen produced analgesia that was faster in onset.

Objective: Diabetic endotheliopathy is the result of hyperglycemia and the production of oxygen-free radicals. In vitro and in vivo data have shown beneficial effects of dexlipotam (DEX), a tromethamine salt of R(+)-alpha-lipoic acid, on oxidative stress in hyperglycemic states, but no data are available on the effects of this agent on endothelial function. The purpose of this pilot study was to evaluate the impact of DEX on endothelial function in patients with type 2 diabetes (DM2) and to estimate the safety and tolerability of DEX., Material and Methods: DEX 960 mg and DEX 1,920 mg were investigated in DM2 patients over a period of 4 weeks using a randomized, placebo- (PLA) controlled, double-blinded study with 3 parallel groups. The marker of arterial function after 4-week therapy with DEX was the maximum percentage change versus baseline in the flow-mediated dilation of the brachial artery (FMD) after reperfusion., Results: A total of 114 diabetic patients were randomized to the three study groups. DEX was safe and well tolerated. Dyspepsia appeared to be the most relevant side effect of DEX treatment. Systolic (p = 0.078) and diastolic blood pressure (p = 0.059) tended to be lower in patients treated with DEX at a dose of 1,920 mg. There were no significant differences in FMD between the placebo- and the DEX-treated groups. In patients with poorer glucose control (HbA1c > 6.5% Hb), FMD increased significantly after 4-week treatment with DEX: PLA -1.51 +/- 2.98%, DEX 960 mg +1.22 +/- 3.22, p = 0.027, DEX 1,920 mg +1.47 +/- 3.78, p= 0.012. The magnitude of the mean change compared to placebo was 2.73% (DEX 920) and 2.98% (DEX 1,920) in patients with HbAlc > 7.5% Hb (DEX 960, p = 0.007, DEX 1,920, p = 0.032). The effects of treatment were usually statistically significant in subgroups with more severe vascular stress (longer duration of disease, pretreatment history, higher LDL-C, higher blood pressure)., Conclusion: DEX therapy appears to reduce endothelial dysfunction in DM2, especially in men with long history of DM2 and having poor glucose control. These findings will be useful in patient selection in future prospective clinical trials with drugs to treat vascular stress.

Dexketoprofen is the active isomer of ketoprofen and likewise belongs to the group of non-steroidal anti-inflammatory drugs (NSAIDs) derived from propionic acid. We have recently studied, using patch and photopatch tests, two women with a characteristic clinical picture of contact photodermatitis who had used topical dexketoprofen (Enangel) in the days before onset of the rash. In both cases we used the standard series of GEIDC, a series for NSAIDs, the product itself (Enalgel) and its excipients. On examination of the photopatches of both patients at 96 hours we found positive reactions to dexketoprofen and Enalgel. Furthermore, in one of the women we observed simultaneous photosensitivity to other NSAIDs and to several excipients of Enangel. Reviewing the literature we have found only three references on contact photodermatitis due to dexketoprofen. We describe two new cases, with multiple photosensitivities in one of them. We consider that such patients should be patch tested with dexketoprofen at 0.1-1 % petrolatum, concentrations that are notably inferior to those used in previous publications.

Objective: This study aimed to evaluate the analgesic efficacy and tolerability of dexketoprofen trometamol, a nonsteroidal anti-inflammatory drug, in comparison with that of racemic ketoprofen (both administered by intravenous infusion), in patients with postoperative pain., Methods: This was a multicentre, randomised, double-blind, parallel-group study. 252 patients with moderate to severe pain following hip or knee replacement surgery performed under general anaesthesia were randomly assigned to receive either dexketoprofen trometamol 50 mg or ketoprofen 100 mg, both administered by intravenous infusion every 8 hours over 2 days. A level of > or =40 mm on a 100 mm visual analogue scale (VAS) for pain was required for inclusion in the study. Pain intensity on the VAS at different time-points after the administration of the first dose was assessed and the sum of pain intensity differences (SAPID(0-8 h)) was calculated as the primary efficacy variable. The use of rescue medication, maximum pain intensity difference (PID(max)), time to PID(max) and safety were also evaluated., Results: The mean (+/- SE) adjusted SAPID(0-8 h) scores in the per-protocol population were 310.9 +/- 19.2 and 326.3 +/- 19.0 mm x h after dexketoprofen trometamol and ketoprofen treatment, respectively. The 95% CI for the difference between treatments (-59.1 to 28.3) was fully included within the range of equivalence of +/-65.3 mm x h. There were no significant differences with regard to secondary variables. The need for rescue analgesia was high in both groups; 81.3% of patients receiving dexketoprofen trometamol treatment and 87.1% receiving ketoprofen treatment required rescue analgesia. The time to achieve PID(max) was 284.7 and 308.5 min after dexketoprofen and ketoprofen, respectively. Treatment- related adverse events were experienced by 16% of patients in the dexketoprofen trometamol group compared with 21.3% in the ketoprofen group. Most patients were concomitantly treated with low-molecular-weight heparin (94.4%), and no haemorrhagic events related to the surgical procedure were reported. No adverse events related to renal function were detected during the study., Conclusion: The two medications were equivalent in terms of analgesic activity in the management of postoperative pain after orthopaedic surgery. The high use of rescue analgesics indicates a need for a multimodal approach to analgesia in this type of surgery. Dexketoprofen trometamol appeared to show a trend towards a better tolerability profile compared with the racemic compound.

The analgesic efficacy and safety of dexketoprofen trometamol (the active enantiomer of the racemic compound ketoprofen) (25mg q.i.d.) vs. ketorolac (10mg q.i.d.) was assessed in 115 patients with bone cancer pain included in a multicenter, randomized, double-blind, parallel group study. A level of >/=40 mm on the 100 mm visual analog scale (VAS) and >/=10 in the pain rating index were required for inclusion. At the end of treatment on day 7 (+1 day), mean values of VAS were 32+/-24 mm for dexketoprofen and 40+/-30 mm for ketorolac (P=0.12) but the pain rating index was significantly lower in patients given dexketoprofen (8.5+/-2.3 vs. 9.7+/-2.9, P=0.04). Moreover, most of the patients reached a pain intensity difference from baseline >/=20 mm (75% of patients for dexketoprofen and 65% of patients for ketorolac). Around half of patients in both treatments had a pain intensity <30 mm on VAS at the end of treatment (55% for dexketoprofen and 47% for ketorolac). In the overall assessment of efficacy, a higher percentage of both patients and physicians rated dexketoprofen as 'quite effective' or 'very effective' compared to ketorolac. The percentage of patients withdrawn from the study for any reason as well as for insufficient therapeutic effect or due to adverse events was lower in the dexketoprofen group than in the ketorolac group. Treatment-related adverse events occurred in 16% of patients given dexketoprofen and in 24% given ketorolac. Serious adverse events occurred in 3.5% of patients from both groups but only one case of gastrointestinal hemorrhage was considered related to ketorolac. We conclude that dexketoprofen trometamol 25 mg q.i.d. oral route is a good analgesic therapy in the treatment of bone cancer pain, comparable to ketorolac 10 mg q.i.d., with a good tolerability profile.