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      Extracorporeal treatment for carbamazepine poisoning: Systematic review and recommendations from the EXTRIP workgroup

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          Abstract

          Context. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup was created to provide evidence and consensus-based recommendations on the use of extracorporeal treatments (ECTRs) in poisoning. Objectives. To perform a systematic review and provide clinical recommendations for ECTR in carbamazepine poisoning. Methods. After a systematic literature search, the subgroup extracted the data and summarized the findings following a pre-determined format. The entire workgroup voted via a two-round modified Delphi method to reach a consensus on voting statements, using a RAND/UCLA Appropriateness Method to quantify disagreement. Anonymous votes were compiled, returned, and discussed in person. A second vote determined the final recommendations. Results. Seventy-four articles met inclusion criteria. Articles included case reports, case series, descriptive cohorts, pharmacokinetic studies, and in-vitro studies; two poor-quality observational studies were identified, yielding a very low quality of evidence for all recommendations. Data on 173 patients, including 6 fatalities, were reviewed. The workgroup concluded that carbamazepine is moderately dialyzable and made the following recommendations: ECTR is suggested in severe carbamazepine poisoning (2D). ECTR is recommended if multiple seizures occur and are refractory to treatment (1D), or if life-threatening dysrhythmias occur (1D). ECTR is suggested if prolonged coma or respiratory depression requiring mechanical ventilation are present (2D) or if significant toxicity persists, particularly when carbamazepine concentrations rise or remain elevated, despite using multiple-dose activated charcoal (MDAC) and supportive measures (2D). ECTR should be continued until clinical improvement is apparent (1D) or the serum carbamazepine concentration is below 10 mg/L (42 the μ in μmol/L looks weird.) (2D). Intermittent hemodialysis is the preferred ECTR (1D), but both intermittent hemoperfusion (1D) or continuous renal replacement therapies (3D) are alternatives if hemodialysis is not available. MDAC therapy should be continued during ECTR (1D). Conclusion. Despite the low quality of the available clinical evidence and the high protein binding capacity of carbamazepine, the workgroup suggested extracorporeal removal in cases of severe carbamazepine poisoning.

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          Most cited references118

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          2012 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 30th Annual Report.

          This is the 30(th) Annual Report of the American Association of Poison Control Centers' (AAPCC) National Poison Data System (NPDS). As of July 1, 2012, 57 of the nation's poison centers (PCs) uploaded case data automatically to NPDS. The upload interval was 7.58 [6.30, 11.22] (median [25%, 75%]) min, creating a near real-time national exposure and information database and surveillance system. We analyzed the case data tabulating specific indices from NPDS. The methodology was similar to that of previous years. Where changes were introduced, the differences are identified. Poison center cases with medical outcomes of death were evaluated by a team of 34 medical and clinical toxicologist reviewers using an ordinal scale of 1-6 to assess the Relative Contribution to Fatality (RCF) of the exposure to the death. In 2012, 3,373,025 closed encounters were logged by NPDS: 2,275,141 human exposures, 66,440 animal exposures, 1,025,547 information calls, 5,679 human confirmed nonexposures, and 218 animal confirmed nonexposures. Total encounters showed a 6.9% decline from 2011, while healthcare facility (HCF) exposure calls increased by 1.2%. All information calls decreased by 14.8% and HCF information calls decreased by 1.7%, medication identification requests (Drug ID) decreased by 22.0%, and human exposures reported to US PCs decreased by 2.5%. Human exposures with less serious outcomes have decreased by 3.7% per year since 2008, while those with more serious outcomes (moderate, major, or death) have increased by 4.6% per year since 2000. The top five substance classes most frequently involved in all human exposures were analgesics (11.6%), cosmetics/personal care products (7.9%), household cleaning substances (7.2%), sedatives/hypnotics/antipsychotics (6.1%), and foreign bodies/toys/miscellaneous (4.1%). Analgesic exposures as a class increased the most rapidly (8,780 calls/year) over the last 12 years. The top five most common exposures in children aged 5 years or less were cosmetics/ personal care products (13.9%), analgesics (9.9%), household cleaning substances (9.7%), foreign bodies/toys/ miscellaneous (7.0%), and topical preparations (6.3%). Drug identification requests comprised 54.4% of all information calls. NPDS documented 2,937 human exposures resulting in death with 2,576 human fatalities judged related (RCF of 1-Undoubtedly responsible, 2-Probably responsible, or 3-Contributory). These data support the continued value of PC expertise and need for specialized medical toxicology information to manage the more severe exposures, despite a decrease in calls involving less severe exposures. Unintentional and intentional exposures continue to be a significant cause of morbidity and mortality in the US. The near real-time, always current status of NPDS represents a national public health resource to collect and monitor US exposure cases and information calls. The continuing mission of NPDS is to provide a nationwide infrastructure for public health surveillance for all types of exposures, public health event identification, resilience response, and situational awareness tracking. NPDS is a model system for the nation and global public health.
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            Extracorporeal treatment for acetaminophen poisoning: recommendations from the EXTRIP workgroup.

            The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup was created to provide evidence-based recommendations on the use of extracorporeal treatments (ECTR) in poisoning and the results are presented here for acetaminophen (APAP).
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              Position paper: Single-dose activated charcoal.

              Single-dose activated charcoal therapy involves the oral administration or instillation by nasogastric tube of an aqueous preparation of activated charcoal after the ingestion of a poison. Volunteer studies demonstrate that the effectiveness of activated charcoal decreases with time. Data using at least 50 g of activated charcoal, showed a mean reduction in absorption of 47.3%, 40.07%, 16.5% and 21.13%, when activated charcoal was administered at 30 minutes, 60 minutes, 120 minutes and 180 minutes, respectively, after dosing. There are no satisfactorily designed clinical studies assessing benefit from single-dose activated charcoal to guide the use of this therapy. Single-dose activated charcoal should not be administered routinely in the management of poisoned patients. Based on volunteer studies, the administration of activated charcoal may be considered if a patient has ingested a potentially toxic amount of a poison (which is known to be adsorbed to charcoal) up to one hour previously. Although volunteer studies demonstrate that the reduction of drug absorption decreases to values of questionable clinical importance when charcoal is administered at times greater than one hour, the potential for benefit after one hour cannot be excluded. There is no evidence that the administration of activated charcoal improves clinical outcome. Unless a patient has an intact or protected airway, the administration of charcoal is contraindicated. A review of the literature since the preparation of the 1997 Single-dose Activated Charcoal Position Statement revealed no new evidence that would require a revision of the conclusions of the Statement.
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                Author and article information

                Journal
                Clin Toxicol (Phila)
                Clin Toxicol (Phila)
                ICTX
                ictx20
                Clinical Toxicology (Philadelphia, Pa.)
                Taylor & Francis
                1556-3650
                1556-9519
                1 December 2014
                30 October 2014
                : 52
                : 10
                : 993-1004
                Affiliations
                [ a ]Division of Nephrology, Verdun Hospital, University of Montreal , Montreal, QC, Canada
                [ b ]Emergency Department and Clinical Toxicology Unit, Hospital Universitari Son Espases , Palma de Mallorca, Spain
                [ c ]Getulio Vargas University Hospital, Federal University of Amazonas , Manaus, AM, Brazil
                [ d ]Purdue University, College of Pharmacy, Department of Pharmacy Practice , Indianapolis and West Lafayette, IN
                [ e ]Department of Pharmacy and Therapeutics, Chinle Comprehensive Health Care Facility, Indian Health Services , Chinle, AZ, USA
                [ f ]Emergency Medicine and Medical Toxicology Service, McGill University Health Centre , Montréal, QC, Canada
                [ g ]Department of Biology, Hôpital Sacré-Cœur de Montréal, University of Montreal , QC, Canada
                [ h ]Department of Pharmacy and Therapeutics, and Department of Medicine Renal Electrolyte Division, University of Pittsburgh Schools of Pharmacy and Medicine , Pittsburgh, PA, USA
                [ i ]Departments of Medicine and Emergency Medicine New York University School of Medicine , New York, NY, USA
                Author notes

                *The EXTRIP workgroup also includes Kurt Anseeuw, Ashish Bhalla, Emmanuel A. Burdmann, Diane P. Calello, Paul I. Dargan, Brian S. Decker, David S. Goldfarb, Lotte C. Hoegberg, David N. Juurlink, Jan T. Kielstein, Martin Laliberté, Yi Li, Kathleen D. Liu, Robert MacLaren, Robert Mactier, Bruno Mégarbane, James B. Mowry, Véronique Phan, Darren M. Roberts, Timothy J. Wiegand, James F. Winchester.

                Address correspondence to Dr. Marc Ghannoum, MD, FRCPC, Verdun Hospital , 4000 Lasalle Boulevard, Verdun, QC H4G2A3 Canada. E-mail: marcghannoum@ 123456gmail.com
                Article
                973572
                10.3109/15563650.2014.973572
                4782683
                25355482
                4a95dfad-2eba-4b37-b199-fce63e74c1e6
                © 2014 The Author(s). Published by Taylor & Francis.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.

                History
                : 12 August 2014
                : 1 October 2014
                Page count
                Figures: 2, Tables: 8, References: 120, Pages: 12
                Categories
                Review Article

                Toxicology
                hemodialysis,hemoperfusion,overdose,anticonvulsant
                Toxicology
                hemodialysis, hemoperfusion, overdose, anticonvulsant

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