Hidratación con Ringer Lactato combinado con diclofenaco rectal en la prevención de pancreatitis poscolangiopancreatografía retrógrada endoscópica

ObjectiveDifferent measures are recommended to reduce pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). We conducted a study in patients with ERCP treated with rectal diclofenac or lactated Ringer's solution, or both interventions, to assess whether there is a decrease in the number of cases of post-ERCP pancreatitis.Material and methodsA mixed cohort study involving 1,896 patients from 2009 to 2018. Up to June 2012 without treatment (Group I). Subsequently, 100 mg of rectal diclofenac (Group II). Since 2016, lactated Ringer's solution 200 ml/hour during the procedure and 4 hours after it, in addition to 500 ml over 30 minutes when the pancreas was cannulated (Group III). Since 2017, lactated Ringer's solution plus Diclofenac (Group IV). There were 725 patients in group I, and 530, 227 and 414 patients in groups II, III and IV, respectively. Factors predisposing to post-ERCP pancreatitis and post-ERCP pancreatitis cases that were defined by consensus criteria have been collected.ResultsThere were 65 cases of post-ERCP pancreatitis (3.4%); 2.9%, 3.4%, 3.1% and 4.3% in groups I, II, III and IV, respectively (P = .640). In group I, there was 4.2% of post-ERCP pancreatitis in naïve papillae and 4%, 4.9% and 6.3% in groups II, III and IV, respectively (P = .585). The severity of post-ERCP pancreatitis and adverse effects were similar in all groups. 38.4% were high-risk patients. There were also no differences in post-ERCP pancreatitis in this group (P = .501).ConclusionIn this work, no benefit was obtained with diclofenac plus hydration in reducing the number and severity of cases of post-ERCP pancreatitis nor with the other prophylactic measures.     

Pharmacological approach to acute pancreatitis

The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis （AP） based on experimental animal models and clinical trials. Somatostatin （SS） and octreotide inhibit the exocrine production of pancreatic enzymes and may be useful as prophylaxis against Post Endoscopic retrograde cholangiopancreatography Pancreatitis （PEP）. The protease inhibitor Gabexate mesilate （GM） is used routinely as treatment to AP in some countries, but randomized clinical trials and a meta-analysis do not support this practice. Nitroglycerin （NGL） is a nitrogen oxide （NO） donor, which relaxes the sphincter of Oddi. Studies show conflicting results when applied prior to ERCP and a large multicenter randomized study is warranted. Steroids administered as prophylaxis against PEP has been validated without effect in several randomized trials. The non-steroidal anti-inflammatory drugs （NSAID） indomethacin and diclofenac have in randomized studies showed potential as prophylaxis against PEP. Interleukin 10 （IL-10） is a cytokine with anti-inflammatory properties but two trials testing IL-10 as prophylaxis to PEP have returned conflicting results. Antibodies against tumor necrosis factor-alpha （TNF-α） have a potential as rescue therapy but no clinical trials are currently being conducted. The antibiotics beta- lactams and quinolones reduce mortality when necrosis is present in pancreas and may also reduce incidence of infected necrosis. Evidence based pharmacological treatment of AP is limited and studies on the effect of potent anti-inflammatory drugs are warranted.     

Reversible oligohydramnios in the second trimester of pregnancy in two patients with long-term diclofenac exposure

The use of non-steroidal anti-inflammatory drugs like diclofenac in the third trimester of pregnancy can cause severe side effects, in particular oligohydramnios, premature closure of ductus arteriosus, and fetal kidney damage. However, the treatment with non-steroidal anti-inflammatory drugs until gestational week 28 is accepted as relatively safe. Here we describe two retrospectively reported cases of early-onset oligohydramnios associated with long-term diclofenac exposure of at least 150 mg per day. The pathological findings were detected at gestational weeks 22 and 23, respectively. Amniotic fluid turned to normal after discontinuation of diclofenac in both cases, suggesting causality. Although early-onset oligohydramnios is a rare complication, caution for long-term diclofenac use in high doses is recommended even before gestational week 28.     

Low-dose SoluMatrix diclofenac in the treatment of osteoarthritis: A 1-year,open-label,Phase III safety study

Introduction. Diclofenac is used for the treatment of osteoarthritis (OA); however, like other nonsteroidal anti-inflammatory drugs (NSAIDs) it can be associated with serious dose-related adverse events (AEs). Low-dose SoluMatrix® diclofenac has been developed to provide efficacy at lower diclofenac doses. A recently published Phase III study evaluated the efficacy and safety of SoluMatrix diclofenac 35 mg twice daily (b.i.d.) and thrice daily (t.i.d.) in patients with OA pain treated for 12 weeks. Methods. This Phase III multicenter, open-label study assessed the safety of SoluMatrix diclofenac in patients with OA dosed up to 52 weeks (ClinicalTrials.gov: NCT01510912). The study enrolled 602 chronic NSAID/acetaminophen users, aged ≥40 years with OA of the knee or hip. Patients received SoluMatrix diclofenac 35 mg b.i.d., which could be increased to t.i.d. and subsequently reduced to b.i.d. as needed. Safety assessments included AEs, vital signs, physical examination findings, 12-lead electrocardiogram, and clinical laboratory test results. Patient-reported outcomes were evaluated by the Short Form-36 (SF-36). Results. A total of 601 patients received SoluMatrix diclofenac; 373 of 601 patients (62.1%) received treatment for ≥11 months. The most frequent AEs included upper respiratory tract infection, headache, urinary tract infection, diarrhea, nasopharyngitis, and nausea. Serious gastrointestinal, cardiovascular, renal, and hepatic AEs were uncommon. A small proportion (99 patients, 16.5%) of patients discontinued participation in the study due to AEs. Clinically meaningful improvements from baseline in Physical Component Summary Scores of the SF-36 were noted at week 12 and were sustained through week 52. Improvements in six of the eight individual physical and mental SF-36 domains were also noted. Conclusion. SoluMatrix diclofenac treatment for up to 1 year was generally well tolerated in patients with OA pain and associated with improvement in quality of life measures. Trial Registration: www.clinicaltrials.gov identifier: NCT01510912.     

Klinischer Stellenwert von Monointoxikationen mit Ibuprofen, Diclofenac und Metamizol

Zusammenfassung Fragestellung Aufgrund der steigenden Anzahl suizidaler und parasuizidaler Intoxikationen mit Schmerzmitteln, soll die Häufigkeit und der klinische Stellenwert von Monointoxikationen der drei häufigsten Generika der Gruppe der nichtsteroidalen und steroidalen Antirheumatika/Analgetika (ohne Berücksichtigung der Acetylsalicylsäure), Diclofenac, Ibuprofen und Metamizol, untersucht werden und eruiert werden, ab welcher Dosierung eine intensivmedizinische Überwachung nötig erscheint. Patienten und Methodik Im Untersuchungszeitraum vom 1. Januar 1995 bis 31. Dezember 2001 wurden alle beim Giftinformationszentrum Mainz dokumentierten Monointoxikationen o. g. Generika mittels des Datenverarbeitungsprogramms ADAM-Dok/-Aus (basierend auf Microsoft^®Access^®) ausgewertet. Die Feststellung des Schweregrades erfolgte mittels des Poison Severity Scores. Zur speziellen Betrachtung gelangten nur die nichtsteroidalen Antirheumatika/Analgetika. Ergebnisse Im o. g. Zeitraum kam es zu 1281 Monointoxikationen mit NSAR und SAR, davon 40% Ibuprofen, 31% Diclofenac und 13% Metamizol. Bei Monointoxikationen mit Ibuprofen kam es erst ab einer Dosierung von 300 mg/kg KG zu schwerwiegenden, lebensbedrohlichen Vergiftungserscheinungen. Bei Diclofenac und Metamizol zeigten sich komplett unterschiedliche klinische Verläufe (Hypotonie, Herzrhythmusstörung und Niereninsuffizienz bei niedriger Dosierung, Symptomfreiheit bei hoher Dosierung). Zusammenfassung Bei Monointoxikationen mit Ibuprofen sollte erst ab einer Dosierung von 300 mg/ kg KG eine intensivmedizinische Überwachung angestrebt werden. Aufgrund komplett unterschiedlicher klinischer Verläufe (schwere Symptome bei niedriger Dosierung und keine Symptome bei hoher Dosierung) ist bezüglich der Festlegung einer kritischen Dosierung bei Monointoxikationen mit Diclofenac und Metamizol zur Zeit keine klare Aussage möglich. Hierzu sollten weitere Untersuchungen folgen. Bei jeder Art von Intoxikation empfehlen wir die Rücksprache mit einem Giftinformationszentrum, z. B. 06131/19240.     

双氯芬酸钠联合间苯三酚治疗肾绞痛80例疗效分析

目的：：比较曲马多、双氯芬酸钠联合间苯三酚治疗急性肾绞痛的疗效。方法：160例肾绞痛患者随机分为2组,每组80例患者,曲马多组采用曲马多肌注和间苯三酚静脉滴注治疗,双氯芬酸钠组采用双氯芬酸钠肌注和间苯三酚静脉滴注治疗。观察两组的疗效,疼痛开始缓解时间、完全缓解时间和不良反应情况。结果：双氯芬酸钠组显效率为92.5%(58/80）,明显高于曲马多组(P<0.05）。双氯芬酸钠组疼痛开始缓解时间、疼痛完全缓解时间明显短于曲马多组(P<0.05）。双氯芬酸钠组不良反应发生率明显低于曲马多组(P<0.05）。结论：双氯芬酸钠联合间苯三酚治疗急性肾绞痛疗效确切,值得临床推广应用。     

Precision cut intestinal slices are an appropriate ex vivo model to study NSAID-induced intestinal toxicity in rats

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used therapeutic agents, however, they are associated with a high prevalence of intestinal side effects. In this investigation, rat precision cut intestinal slices (PCIS) were evaluated as an ex vivo model to study NSAID-induced intestinal toxicity.Firstly, PCIS were incubated with 0–200 μM diclofenac (DCF), one of the most intensively studied NSAIDs, to investigate whether they could correctly reflect the toxic mechanisms. DCF induced intestinal toxicity in PCIS was shown by morphological damage and ATP depletion. DCF induced endoplasmic-reticulum (ER) stress, mitochondrial injury and oxidative stress were reflected by up-regulated HSP-70 (heat shock protein 70) and BiP (binding immunoglobulin protein) gene expression, caspase 9 activation, GSH (glutathione) depletion and HO-1 (heme oxygenase 1) gene up-regulation respectively. Furthermore, DCF intestinal metabolites, which gave rise to protein adduct but not toxicity, were detected in PCIS.Secondly, PCIS were incubated with various concentrations of five NSAIDs. Typical NSAID-induced morphological changes were observed in PCIS. The ex vivo toxicity ranking (diflunisal > diclofenac = indomethacin > naproxen ≫ aspirin) showed good correlation with published in vitro and in vivo data, with diflunisal being the only exception.In conclusion, PCIS correctly reflect the various mechanisms of DCF-induced intestinal toxicity, and can serve as an ex vivo model for the prediction of NSAID-induced intestinal toxicity.