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Background: Dipyrone (metamizole) is widely used for perioperative pain management in countries where it is marketed; however, uncertainty exists concerning the safe use of this drug, specifically considering the rare adverse event of an agranulocytosis., Methods: As evidence from published studies was lacking, an expert panel developed recommendations for the perioperative use of dipyrone. After a formal, structured consensus process, the recommendations were approved by the involved medical societies., Results: The panel agreed that blood cell counts shall not be standard for short-term perioperative use in patients unless they are at risk for neutropenia. The medical staff shall be aware of the symptoms and course of action when agranulocytosis is suspected. Patients shall be informed about the risks and benefits of dipyrone and about potential alternatives. The expert group concluded that dipyrone has a relatively positive risk-benefit ratio compared to other nonopioid analgesics. The group strongly recommended educating patients about the symptoms of agranulocytosis if they have received dipyrone over several days and/or treatment is to be continued after discharge, because agranulocytosis can occur several days after discontinuation of metamizole. Further recommendations refer to the information of the physician taking over the patient's care after discharge and the avoidance of re-exposure in patients having previously suffered from dipyrone-induced agranulocytosis., Conclusion: The group's recommendations shall be communicated in order to raise medical staff's and patients' awareness of the appropriate use of dipyrone in the perioperative period.

Objective: To provide further evidence of dependence on non-opioid analgesics (NOAs)., Methods: Post-hoc-analysis of a cross-sectional study of a ≥ -65-year-old non-demented German general hospital population. Four hundred in-patients (75 ± 6.4 years; 63% females) were included and screened for current and past dependence on NOAs using a structured interview (SKID-I) based on DSM-IV-TR. The addiction section of SKID-I was expanded to the following NOAs: gabapentinoids, acetaminophen, metamizole, flupirtine, and non-steroidal anti-inflammatory drugs (NSAIDs)., Results: We found twenty-eight seniors (7%) who fulfilled the criteria for a NOA-dependence. Of whom, twenty-four and four patients were currently dependent and in remission, respectively. According to SKID-I, twenty-one (75%) patients were mildly, five patients (17.9%) moderately, and two (7.1%) patients severely dependent on NOAs. All patients showed at least one sign of physical dependence (tolerance and/or withdrawal symptoms) and most of them reported additional behavioral dependence symptoms. Whereas there was one dependence on gabapentinoids or acetaminophen only, NSAIDs and metamizole were involved in the majority of cases (n = 25; 89.3%). Of note, ten (35.7%) seniors had a de-novo substance dependence exclusively on NOAs - including 2 females with signs of a de-novo dependence on metamizole, a NOA which yet has been not in the focus of addiction medicine., Conclusion: This cross-sectional study provides further evidence of the existence of a physical and behavioral dependence on NOAs including NSAIDs. Furthermore, preliminary evidence of a de-novo dependence on metamizole is provided which needs further verification., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Paracetamol is one of the most popular and widely used drugs for the treatment of pain and fever and provides safe and effective relief of these symptoms since decades. The mechanism of action is very complex and involves the inhibition of the peroxidase portion of the cyclooxygenase enzyme together with the modulation of the serotoninergic and cannabinoid system. Paracetamol is a safe drug, if used in accordance with the regulations and has demonstrated a superior side effect profile to many widely used NSAIDs.

Background & Aims: Among the potentially helpful indicators of poor prognosis in acute liver failure (ALF) are etiology, encephalopathy grade, blood lactate, and King's College Criteria (KCC). The accuracy of these parameters in predicting transplantation or death shows significant variation in different countries., Methods: We retrospectively analyzed 102 patients with ALF treated at our institution between 1996 and 2005. Baseline parameters, simplified acute physiology score III (SAPS-III), KCC, Model for End-Stage Liver Disease (MELD) score, and a novel score of bilirubin, lactate, and etiology (BiLE score) were compared between transplant-free survivors and patients who required liver transplantation or died, by using multivariate linear regression analysis and receiver operating characteristics (ROC)., Results: The most common causes of ALF were indeterminate liver failure (21%), acute hepatitis B (18%), acetaminophen ingestion (16%), and Budd-Chiari syndrome (9%). Transplantation-free survival was 38%, 44% of patients underwent liver transplantation, and 18% died without transplantation. Eight-week survival was 77%. The BiLE score was the best predictor of death or need of transplantation, with 79% sensitivity and 84% specificity. ROC analysis revealed a better performance of BiLE score when compared with bilirubin, lactate, MELD score, and SAPS-III (area under the curve: 0.87 +/- 0.04, 0.73 +/- 0.51, 0.73 +/- 0.52, 0.71 +/- 0.05, and 0.68 +/- 0.59, respectively)., Conclusions: The simple, combined BiLE score emerged as the best predictor of poor outcome in our patient cohort and should be prospectively evaluated in other populations.

Objective: Renal insufficiency is less common than liver failure in acetaminophen overdose but renal tubular damage occurs even in the absence of hepatotoxicity. Data published on this topic are rare consisting mostly of case reports or reports in a small number of patients. Presently, a larger number of patients with renal insufficiency associated with acetaminophen overdose should be analyzed using a multicenter approach., Study Design: Retrospective analysis of patients with acetaminophen-related nephrotoxicity reported to a poison center network from 1995 to 2003. Renal insufficiency was defined as elevated serum creatinine of more than double of the normal range (>2.4 mg/dL [212 micromol/L]). Patients were classified into 4 groups (A: creatinine 2.4-5.0 mg/dL, B: creatinine>5.0 mg/dL requiring no dialysis, C: creatinine>5.0 mg/dL requiring dialysis, D: creatinine>5.0 mg/dL with fatal outcome)., Results: Seventeen patients were included (8 female, 9 male, average age 31.7 +/- 21.1 yrs) with 6 patients in group A (B: 7, C: 2, D: 2). In 5 patients renal insufficiency occurred without elevation of liver enzymes. Regarding possible risk factors 5 patients concomitantly ingested nephrotoxic substances, 4 presented with dehydration due to vomiting, 4 with chronic excessive dosing (overdose) of acetaminophen, 3 showed pre-existing renal insufficiency, 2 pre-existing liver disease and 2 died with multiple organ failure., Conclusions: Renal insufficiency in acetaminophen overdose mostly resolved without dialysis and occurred isolated without hepatotoxicity in less than one-third of the investigated patients. Conditions which might play a role as influencing factors for renal complications included concomitant ingestion of nephrotoxic drugs, dehydration, chronic excessive dosing (overdose) of acetaminophen, pre-existing renal or liver disease and multiple organ failure. Renal function should be monitored in acetaminophen overdose particularly in patients showing the latter comorbidity.

We assessed the efficacy and safety of oral single doses of 0.5 and 1 g metamizol vs. 1 g acetylsalicylic acid (ASA) in 417 patients with moderate episodic tension-type headache included in a randomized, double-blind, placebo- and active-controlled, parallel, multicentre trial. Eligibility criteria included 18-65 years of age, history of at least two episodes of tension-type headache per month in the 3 months prior to enrollment, and successful previous pain relief with a non-opioid analgesic. Treatment arms were metamizol 0.5 g (n = 102), metamizol 1 g (n = 108), ASA 1 g (n = 102) and placebo (n = 105). The analgesic efficacy of 0.5 and 1 g metamizol vs. placebo was highly statistically significant (alpha: 0.025; one-sided) for sum of pain intensity differences, maximum pain intensity difference, number of patients with at least 50% pain reduction, time to 50% pain reduction, maximum pain relief and total pain relief. A trend towards an earlier onset of a more profound pain relief of 0.5 and 1 g metamizol over 1 g ASA was noticed. All medications including placebo were almost equally safe and well tolerated.

Drug-induced headache is well known to result from the abuse of compounds taken for the treatment of primary headache. The features of drug-induced headache depend on various features including the availability of drugs, the regional health system, and psychogenic factors of the patients. We performed a retrospective study on a series of 257 consecutive German patients presenting with drug-induced headache during the period 1983-1996. Our aim study was to evaluate the demographic features, the frequency of various drugs used, in particular of ergotamine derivates, and changes in these features during the study period. The frequency of drug-induced headache among all headache patients was 8%, with a female preponderance of 81%. Drug-induced headache occurred in all age groups, predominantly in migraine patients (35%). The mean number of substances used was 2.7, mainly, acetaminophen (47.9%), ergotamine tartrate (45%), and combined analgesics (56%). We did not find a significant difference between the associations with ergotamine tartrate and dihydroergotamine, although the latter was taken less frequently. Comparing the early and late years of our study period, there were no changes in the frequency of drug-induced headache (8% versus 7%), although changes in the frequency of some drugs changed (barbiturates, ergotamine tartrate, and codeine intake decreased whereas nonsteroidal anti-inflationary drugs, combined analgesics, and sumatriptan intake increased). Our data suggest that changes in drug availability and the introduction of classification criteria and treatment recommendations did not have a major impact on the frequency of drug-induced headache.

Thomapyrin has been on the German market as analgesic for the past 50 years. It is the prescription-free preparation with the highest sales there. This is an occasion to survey current state of scientific knowledge concerning combination analgesics with acetyl salicylic acid, paracetamol and caffeine. For the assessment and registration of fixed preparations authorities of different European countries and also USA have defined special criteria. Analgesic preparations must agree with these defined criteria. The importance of these combination analgesics in pain therapy is described with the respect to the latest scientific results. Combination analgesics represent an important area of self-medication by the patient. The properties of the active substances alone and in combination are set forth, with respect to pharmacokinetics and efficacy. The experimental and especially clinical results clearly show a broader spectrum of action in consequence of the different modes of action of the individual active substances. Analgesic action is 1.4 fold higher owing to added caffeine. The fixed combination of active substances does not change the profile of side effects. The conclusion is that combination analgesics such as Thomapyrine show a positive benefit/risk ratio. Furthermore such combination analgesics are appropriate for self-medications and suited to combat pain of different kinds.