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      Metamizole versus placebo for panretinal photocoagulation pain control: a prospective double-masked randomized controlled study

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          Abstract

          Background

          Diabetic retinopathy is one of most common and threatening ocular diseases. Many of these patients need to be submitted to panretinal photocoagulation (PRP), experiencing a significant level of pain. The purpose of this study is to evaluate the effectiveness of oral metamizole in reducing pain during PRP in patients with proliferative diabetic retinopathy (PDR) and very severe non-proliferative diabetic retinopathy (VSNDR).

          Methods

          Patients from a single center with PDR or VSNDR and indication of bilateral PRP were recruited for a double-masked, controlled, prospective study. The treated eyes were randomly assigned in two groups, and each patient had one eye assigned per group. Group A received 1000 mg of metamizole and group B received a placebo pill 40 min before the laser treatment. The groups were switched for the treatment of the fellow eye. Each patient scored the pain sensation immediately after each PRP section using Scott’s visual analogue scale (VAS). The paired Student t test was used to measure the significance between the two groups VAS scores, with significance level adopted of p < 0.05.

          Results

          Twenty-one patients were recruited. The level of pain was significantly lower when submitted to PRP after oral metamizole treatment compared to placebo (p = 0.002). The mean pain scores for groups A and B were 4.72 ± 1.708 and 5.89 ± 1.967, respectively. The minimum/maximum scores within groups A and B were 1/8 and 1/10, respectively.

          Conclusions

          The use of 1000 mg of metamizole 40 min before PRP significantly reduces the pain associated with the procedure in patients with PDR or VSNDR.

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          Most cited references23

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          Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group.

          (1985)
          Data from the Early Treatment Diabetic Retinopathy Study (ETDRS) show that focal photocoagulation of "clinically significant" diabetic macular edema substantially reduces the risk of visual loss. Focal treatment also increases the chance of visual improvement, decreases the frequency of persistent macular edema, and causes only minor visual field losses. In this randomized clinical trial, which was supported by the National Eye Institute, 754 eyes that had macular edema and mild to moderate diabetic retinopathy were randomly assigned to focal argon laser photocoagulation, while 1,490 such eyes were randomly assigned to deferral of photocoagulation. The beneficial effects of treatment demonstrated in this trial suggest that all eyes with clinically significant diabetic macular edema should be considered for focal photocoagulation. Clinically significant macular edema is defined as retinal thickening that involves or threatens the center of the macula (even if visual acuity is not yet reduced) and is assessed by stereo contact lens biomicroscopy or stereo photography. Follow-up of all ETDRS patients continues without other modifications in the study protocol.
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            Metamizole-Associated Adverse Events: A Systematic Review and Meta-Analysis

            Background Metamizole is used to treat pain in many parts of the world. Information on the safety profile of metamizole is scarce; no conclusive summary of the literature exists. Objective To determine whether metamizole is clinically safe compared to placebo and other analgesics. Methods We searched CENTRAL, MEDLINE, EMBASE, CINAHL, and several clinical trial registries. We screened the reference lists of included trials and previous systematic reviews. We included randomized controlled trials that compared the effects of metamizole, administered to adults in any form and for any indication, to other analgesics or to placebo. Two authors extracted data regarding trial design and size, indications for pain medication, patient characteristics, treatment regimens, and methodological characteristics. Adverse events (AEs), serious adverse events (SAEs), and dropouts were assessed. We conducted separate meta-analyses for each metamizole comparator, using standard inverse-variance random effects meta-analysis to pool the estimates across trials, reported as risk ratios (RRs). We calculated the DerSimonian and Laird variance estimate T2 to measure heterogeneity between trials. The pre-specified primary end point was any AE during the trial period. Results Of the 696 potentially eligible trials, 79 trials including almost 4000 patients with short-term metamizole use of less than two weeks met our inclusion criteria. Fewer AEs were reported for metamizole compared to opioids, RR = 0.79 (confidence interval 0.79 to 0.96). We found no differences between metamizole and placebo, paracetamol and NSAIDs. Only a few SAEs were reported, with no difference between metamizole and other analgesics. No agranulocytosis or deaths were reported. Our results were limited by the mediocre overall quality of the reports. Conclusion For short-term use in the hospital setting, metamizole seems to be a safe choice when compared to other widely used analgesics. High-quality, adequately sized trials assessing the intermediate- and long-term safety of metamizole are needed.
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              Comparative safety evaluation of non-narcotic analgesics.

              Both spontaneous reports and single outcome studies may distort the overall safety evaluation of drugs. We identified epidemiologic studies, published from January 1970 to December 1995, that investigated the association of serious adverse effects with aspirin, diclofenac, acetaminophen, and dipyrone to determine and compare the excess mortality associated with short-term drug use. The estimated excess mortality due to community-acquired agranulocytosis, aplastic anemia, anaphylaxis, and serious upper gastrointestinal complications was 185 per 100 million for aspirin, 592 per 100 million for diclofenac, 20 per 100 million for acetaminophen, and 25 per 100 million for dipyrone. The estimates were largely influenced by the excess mortality associated with upper gastrointestinal complications. A relative risk estimate of 300 or more for the association of dipyrone with agranulocytosis would have been necessary for the excess mortality of dipyrone to be comparable to that of aspirin or diclofenac. Based on published epidemiologic evidence used to determine the excess mortality associated with short-term use of these four non-narcotic analgesics, the current regulatory ranking of the drugs appears inappropriate.
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                Author and article information

                Contributors
                +5511982633822 , barbosa.md@gmail.com
                lczacharias@gmail.com
                brenomsa@gmail.com
                beatrice.sgiusti@gmail.com
                rypreti@hotmail.com
                mlrmonteiro@terra.com.br
                mlrmonteiro@terra.com.br
                Journal
                Int J Retina Vitreous
                Int J Retina Vitreous
                International Journal of Retina and Vitreous
                BioMed Central (London )
                2056-9920
                12 November 2015
                12 November 2015
                2015
                : 1
                : 21
                Affiliations
                [1 ]Av. Dr. Enéas de Carvalho Aguiar, 255 Cerqueira César, São Paulo, 05403-000 Brazil
                [2 ]GRID grid.411074.7, ISNI 0000000122972036, , Hospital das Clínicas of University of Sao Paulo Medical School-HCFMUSP, ; São Paulo, Brazil
                Author information
                http://orcid.org/0000-0003-4607-1093
                Article
                21
                10.1186/s40942-015-0021-8
                5088477
                27847614
                a35ef8d8-0bb5-4a24-a2c1-12e9c4fd3710
                © de Araújo et al. 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 25 August 2015
                : 11 October 2015
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100005640, Faculdade de Medicina da Universidade de São Paulo;
                Categories
                Original Article
                Custom metadata
                © The Author(s) 2015

                diabetic retinopathy,panretinal photocoagulation,metamizole,analgesia,pain score

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