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      CytoSorb removes MDMA in vitro, but is it an effective therapy in vivo?

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          Abstract

          Background

          3,4-Methylenedioxymethamphetamine intoxication can result in potentially lethal multi-organ failure, for which the current treatment is largely supportive. Recently, a report of the use of the CytoSorb device as a part of the successful treatment of a patient with 3,4-methylenedioxymethamphetamine intoxication and multi-organ failure has been described.

          Main body

          While 3,4-methylenedioxymethamphetamine was very effectively removed by CytoSorb in vitro, the degree of removal in the clinical setting described may have been minimal. Indeed, the therapy was started relatively late in this case, and, as the therapy is concentration dependent, the removal of 3,4-methylenedioxymethamphetamine is likely to have been limited. On the other hand, in this case, CytoSorb hemoadsorption was very effective to treat rhabdomyolysis and hyperinflammation.

          Conclusion

          The in vitro experimentation demonstrates that 3,4-methylenedioxymethamphetamine is effectively removed by CytoSorb. However, it is debatable whether the case report confirms the possibility of in vivo removal of 3,4-methylenedioxymethamphetamine by CytoSorb. Nevertheless, the potential of the CytoSorb device to contribute to the treatment of many critically ill patients has yet to be fully explored, and further studies are warranted.

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          Most cited references4

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          The pharmacology and toxicology of "ecstasy" (MDMA) and related drugs.

          H Kalant (2001)
          "Ecstasy" (MDMA) and related drugs are amphetamine derivatives that also have some of the pharmacological properties of mescaline. They have become popular with participants in "raves," because they enhance energy, endurance, sociability and sexual arousal. This vogue among teenagers and young adults, together with the widespread belief that "ecstasy" is a safe drug, has led to a thriving illicit traffic in it. But these drugs also have serious toxic effects, both acute and chronic, that resemble those previously seen with other amphetamines and are caused by an excess of the same sympathomimetic actions for which the drugs are valued by the users. Neurotoxicity to the serotonergic system in the brain can also cause permanent physical and psychiatric problems. A detailed review of the literature has revealed over 87 "ecstasy"-related fatalities, caused by hyperpyrexia, rhabdomyolysis, intravascular coagulopathy, hepatic necrosis, cardiac arrhythmias, cerebrovascular accidents, and drug-related accidents or suicide. The toxic or even fatal dose range overlaps the range of recreational dosage. The available evidence does not yet permit an accurate assessment of the size of the problem presented by the use of these drugs.
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            What Have We Learned about the Use of Cytosorb Adsorption Columns?

            Extracorporeal blood purification techniques have emerged and evolved in the recent years as a potential therapy for the purpose of immunomodulation in acute conditions like sepsis. Understanding the extent of immune system dysregulation involved in the pathophysiology of these conditions, resulted in the development of such treatment strategies aiming at restoring a balanced inflammatory response. Beyond conventional continuous renal replacement therapy, high volume hemofiltration, high cut-off membranes, adsorption alone and coupled plasma filtration adsorption are well-described techniques in the literature. The evidence to support their routine use, however, is conflicting and insufficient at this stage. Despite the low-quality level of evidence in favor of utilizing these techniques, studies to further explore their effectiveness, safety, and potential novel applications, continue to evolve. Our review aims at focusing on adsorption therapy, particularly using the adsorption columns Cystosorb.
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              In vitro Removal of Therapeutic Drugs with a Novel Adsorbent System

              Background/Aim: Substances in the middle molecular weight range have been shown to play a significant pathogenetic role in as diverse disorders as end-stage renal disease and multiple organ failure. To overcome the limitations in the amount removed by hemofilters, new sorbents with a high biocompatibility are actively being developed. Furthermore, biocompatible sorbents by their nonspecific adsorptive behavior could have great impact on detoxification treatment in exogenous intoxications. We performed an in vitro evaluation of a newly developed highly biocompatible sorbent cartridge (Betasorb ® ), examining its adsorptive capacity concerning therapeutic drugs. Methods: Uremic blood spiked with a range of therapeutic drugs was recirculated for 2 h in an in vitro hemoperfusion circuit containing a Betasorb device for hemoperfusion. The drug concentrations before and after the passage of the cartridge were measured, and the total amount removed was calculated. Results: The sorbent showed effective removal of glycopeptide antibiotics, digoxin, theophylline, phenobarbital, phenytoin, carbamazepine, and valproic acid. Moderate removal could be demonstrated for tacrolimus and cyclosporine A; aminoglycosides were removed to a small extent only. Conclusions: Betasorb hemoperfusion shows a potent adsorptive capacity concerning therapeutic drugs (except aminoglycosides) and could be of major value in the treatment of intoxications. On the other hand, drug monitoring and possible adjustments are necessary during Betasorb hemoperfusion to maintain the therapeutic ranges of the drugs in blood.
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                Author and article information

                Contributors
                patrick.honore@chu-brugmann.be
                Sebastien.Redant@CHU-Brugmann.be
                thomas.datzmann@uniklinik-ulm.de
                Journal
                Intensive Care Med Exp
                Intensive Care Med Exp
                Intensive Care Medicine Experimental
                Springer International Publishing (Cham )
                2197-425X
                29 July 2020
                29 July 2020
                December 2020
                : 8
                : 38
                Affiliations
                [1 ]GRID grid.411371.1, ISNI 0000 0004 0469 8354, ICU Department, Brugmann University Hospital, , Centre Hospitalier Universitaire Brugmann, ; Place Van Gehuchtenplein, 4, 1020 Brussels, Belgium
                [2 ]GRID grid.410712.1, Universitätsklinik Ulm, ; Ulm, Germany
                Article
                333
                10.1186/s40635-020-00333-z
                7391451
                32728974
                3f12293b-79f6-4a4d-84d7-194b04a65b5d
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 28 June 2020
                : 22 July 2020
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                © The Author(s) 2020

                3,4-methylenedioxymethamphetamine,intoxication,hemoperfusion,cytosorb

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