Successful Management of Valproate Overdose by a Combination of Extracorporeal Therapies
Identifieur interne : 000950 ( Istex/Corpus ); précédent : 000949; suivant : 000951Successful Management of Valproate Overdose by a Combination of Extracorporeal Therapies
Auteurs : P. Yalamanchili ; Z. Al Aly ; E. GonzalezSource :
- Hemodialysis International [ 1492-7535 ] ; 2004-01.
Abstract
Valproic acid toxicity is not infrequent and is difficult to treat, as there is no specific antidote. In the past, this drug was considered unremovable by extracorporeal methods because of the highly protein bound state (90–95%). However, recent reports suggest that the toxicokinetics of valproate vary considerably from the pharmacokinetics at therapeutic levels, and at higher concentrations protein‐binding sites become saturated. The drug's relatively low molecular weight (144 Da), small volume of distribution (0.13–0.23 L/kg), and saturable protein binding render it potentially amenable to extracorporeal removal, but published experience is scant and there are only a few reported instances in which patients were successfully treated with extracorporeal methods. Here we report the case of a patient with serious valproate toxicity treated with simultaneous “in series” hemodialysis and hemoperfusion followed by continuous veno‐venous hemodiafiltration. A 35‐year‐old homeless male presented to the emergency department after ingesting 120 pills of valproic acid. Initial valproic acid level was 59 µg/mL. Urine drug screen was negative and serum chemistries including LFTs were normal. He was treated with activated charcoal and admitted to the intensive care unit. 4 h later, he developed respiratory failure and became hemodynamically unstable. He was intubated and successfully resuscitated. Subsequently, the valproic acid level was found to be 553 µg/mL and a decision was made to employ extracorporeal methods for drug removal. “In series” hemodialysis and hemoperfusion were done for 4 h and simultaneous blood samples for measurement of valproic acid levels were obtained as blood entered the hemoperfusion column (arterial) and as it exited the hemodialysis membrane (venous). Extraction ratio, whole blood, and plasma clearances were calculated and they compared substantially with the published data. The above measures decreased valproate levels from 572.6 (pre‐dialysis level) to 203.2 µg/mL. This was followed by continuous veno‐venous hemodiafiltration for 18 h, which sustained the drug removal and prevented significant post‐dialytic rebound. This is the first reported instance in which these three methods were administered together successfully in the management of valproic acid toxicity.
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DOI: 10.1111/j.1492-7535.2004.0085as.x
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<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Successful Management of Valproate Overdose by a Combination of Extracorporeal Therapies</title><author><name sortKey="Yalamanchili, P" sort="Yalamanchili, P" uniqKey="Yalamanchili P" first="P." last="Yalamanchili">P. Yalamanchili</name><affiliation><mods:affiliation>St. Luke's Hospital, Chesterfield</mods:affiliation></affiliation></author><author><name sortKey="Al Aly, Z" sort="Al Aly, Z" uniqKey="Al Aly Z" first="Z." last="Al Aly">Z. Al Aly</name><affiliation><mods:affiliation>St. Louis University Hospital, St. Louis, MO, U.S.A.</mods:affiliation></affiliation></author><author><name sortKey="Gonzalez, E" sort="Gonzalez, E" uniqKey="Gonzalez E" first="E." last="Gonzalez">E. Gonzalez</name><affiliation><mods:affiliation>St. Louis University Hospital, St. Louis, MO, U.S.A.</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:5224C0523F45C564603136DB982361168093B06B</idno><date when="2004" year="2004">2004</date><idno type="doi">10.1111/j.1492-7535.2004.0085as.x</idno><idno type="url">https://api.istex.fr/ark:/67375/WNG-GLRWSS6H-K/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">000950</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000950</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main">Successful Management of Valproate Overdose by a Combination of Extracorporeal Therapies</title><author><name sortKey="Yalamanchili, P" sort="Yalamanchili, P" uniqKey="Yalamanchili P" first="P." last="Yalamanchili">P. Yalamanchili</name><affiliation><mods:affiliation>St. Luke's Hospital, Chesterfield</mods:affiliation></affiliation></author><author><name sortKey="Al Aly, Z" sort="Al Aly, Z" uniqKey="Al Aly Z" first="Z." last="Al Aly">Z. Al Aly</name><affiliation><mods:affiliation>St. Louis University Hospital, St. Louis, MO, U.S.A.</mods:affiliation></affiliation></author><author><name sortKey="Gonzalez, E" sort="Gonzalez, E" uniqKey="Gonzalez E" first="E." last="Gonzalez">E. Gonzalez</name><affiliation><mods:affiliation>St. Louis University Hospital, St. Louis, MO, U.S.A.</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Hemodialysis International</title><title level="j" type="alt">HEMODIALYSIS INTERNATIONAL</title><idno type="ISSN">1492-7535</idno><idno type="eISSN">1542-4758</idno><imprint><biblScope unit="vol">8</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="95">95</biblScope><biblScope unit="page" to="96">96</biblScope><biblScope unit="page-count">100</biblScope><publisher>Blackwell Science Inc</publisher><pubPlace>Oxford, UK; Malden, USA</pubPlace><date type="published" when="2004-01">2004-01</date></imprint><idno type="ISSN">1492-7535</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1492-7535</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Valproic acid toxicity is not infrequent and is difficult to treat, as there is no specific antidote. In the past, this drug was considered unremovable by extracorporeal methods because of the highly protein bound state (90–95%). However, recent reports suggest that the toxicokinetics of valproate vary considerably from the pharmacokinetics at therapeutic levels, and at higher concentrations protein‐binding sites become saturated. The drug's relatively low molecular weight (144 Da), small volume of distribution (0.13–0.23 L/kg), and saturable protein binding render it potentially amenable to extracorporeal removal, but published experience is scant and there are only a few reported instances in which patients were successfully treated with extracorporeal methods. Here we report the case of a patient with serious valproate toxicity treated with simultaneous “in series” hemodialysis and hemoperfusion followed by continuous veno‐venous hemodiafiltration. A 35‐year‐old homeless male presented to the emergency department after ingesting 120 pills of valproic acid. Initial valproic acid level was 59 µg/mL. Urine drug screen was negative and serum chemistries including LFTs were normal. He was treated with activated charcoal and admitted to the intensive care unit. 4 h later, he developed respiratory failure and became hemodynamically unstable. He was intubated and successfully resuscitated. Subsequently, the valproic acid level was found to be 553 µg/mL and a decision was made to employ extracorporeal methods for drug removal. “In series” hemodialysis and hemoperfusion were done for 4 h and simultaneous blood samples for measurement of valproic acid levels were obtained as blood entered the hemoperfusion column (arterial) and as it exited the hemodialysis membrane (venous). Extraction ratio, whole blood, and plasma clearances were calculated and they compared substantially with the published data. The above measures decreased valproate levels from 572.6 (pre‐dialysis level) to 203.2 µg/mL. This was followed by continuous veno‐venous hemodiafiltration for 18 h, which sustained the drug removal and prevented significant post‐dialytic rebound. This is the first reported instance in which these three methods were administered together successfully in the management of valproic acid toxicity.</div></front></TEI><istex><corpusName>wiley</corpusName><keywords><teeft><json:string>hemodialysis</json:string><json:string>international society</json:string><json:string>annual dialysis conference</json:string><json:string>renal</json:string><json:string>nephrology</json:string><json:string>fistula</json:string><json:string>hemodialysis patient</json:string><json:string>dialyzer</json:string><json:string>heparin</json:string><json:string>dialysate</json:string><json:string>datum</json:string><json:string>urea</json:string><json:string>online</json:string><json:string>venous</json:string><json:string>esrd</json:string><json:string>creatinine</json:string><json:string>hemodialysis hemodialysis 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size</json:string><json:string>urea mass</json:string><json:string>dialysis modality</json:string><json:string>initial flow</json:string><json:string>vascular surgeon</json:string><json:string>causative agent</json:string><json:string>precautionary measure</json:string><json:string>peer pressure</json:string><json:string>syndrome</json:string><json:string>ontario</json:string><json:string>albumin</json:string><json:string>clearance</json:string><json:string>mortality</json:string><json:string>complication</json:string><json:string>hemoglobin</json:string><json:string>diabetes</json:string><json:string>infection</json:string></teeft></keywords><author><json:item><name>P. Yalamanchili</name><affiliations><json:string>St. Luke's Hospital, Chesterfield</json:string></affiliations></json:item><json:item><name>Z. Al Aly</name><affiliations><json:string>St. Louis University Hospital, St. Louis, MO, U.S.A.</json:string></affiliations></json:item><json:item><name>E. Gonzalez</name><affiliations><json:string>St. Louis University Hospital, St. Louis, MO, U.S.A.</json:string></affiliations></json:item></author><articleId><json:string>HDI085AS</json:string></articleId><arkIstex>ark:/67375/WNG-GLRWSS6H-K</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>abstract</json:string></originalGenre><abstract>Valproic acid toxicity is not infrequent and is difficult to treat, as there is no specific antidote. In the past, this drug was considered unremovable by extracorporeal methods because of the highly protein bound state (90–95%). However, recent reports suggest that the toxicokinetics of valproate vary considerably from the pharmacokinetics at therapeutic levels, and at higher concentrations protein‐binding sites become saturated. The drug's relatively low molecular weight (144 Da), small volume of distribution (0.13–0.23 L/kg), and saturable protein binding render it potentially amenable to extracorporeal removal, but published experience is scant and there are only a few reported instances in which patients were successfully treated with extracorporeal methods. Here we report the case of a patient with serious valproate toxicity treated with simultaneous “in series” hemodialysis and hemoperfusion followed by continuous veno‐venous hemodiafiltration. A 35‐year‐old homeless male presented to the emergency department after ingesting 120 pills of valproic acid. Initial valproic acid level was 59 µg/mL. Urine drug screen was negative and serum chemistries including LFTs were normal. He was treated with activated charcoal and admitted to the intensive care unit. 4 h later, he developed respiratory failure and became hemodynamically unstable. He was intubated and successfully resuscitated. Subsequently, the valproic acid level was found to be 553 µg/mL and a decision was made to employ extracorporeal methods for drug removal. “In series” hemodialysis and hemoperfusion were done for 4 h and simultaneous blood samples for measurement of valproic acid levels were obtained as blood entered the hemoperfusion column (arterial) and as it exited the hemodialysis membrane (venous). Extraction ratio, whole blood, and plasma clearances were calculated and they compared substantially with the published data. The above measures decreased valproate levels from 572.6 (pre‐dialysis level) to 203.2 µg/mL. This was followed by continuous veno‐venous hemodiafiltration for 18 h, which sustained the drug removal and prevented significant post‐dialytic rebound. This is the first reported instance in which these three methods were administered together successfully in the management of valproic acid toxicity.</abstract><qualityIndicators><score>10</score><pdfWordCount>24342</pdfWordCount><pdfCharCount>151874</pdfCharCount><pdfVersion>1.4</pdfVersion><pdfPageCount>33</pdfPageCount><pdfPageSize>595 x 782 pts</pdfPageSize><pdfWordsPerPage>738</pdfWordsPerPage><pdfText>true</pdfText><refBibsNative>false</refBibsNative><abstractWordCount>323</abstractWordCount><abstractCharCount>2322</abstractCharCount><keywordCount>0</keywordCount></qualityIndicators><title>Successful Management of Valproate Overdose by a Combination of Extracorporeal Therapies</title><genre><json:string>abstract</json:string></genre><host><title>Hemodialysis International</title><language><json:string>unknown</json:string></language><doi><json:string>10.1111/(ISSN)1542-4758</json:string></doi><issn><json:string>1492-7535</json:string></issn><eissn><json:string>1542-4758</json:string></eissn><publisherId><json:string>HDI</json:string></publisherId><volume>8</volume><issue>1</issue><pages><first>95</first><last>96</last><total>100</total></pages><genre><json:string>journal</json:string></genre></host><namedEntities><unitex><date><json:string>8/1/03</json:string><json:string>2/8/03</json:string><json:string>between May 2002 and September 2003</json:string><json:string>2001</json:string><json:string>1993</json:string><json:string>1971</json:string><json:string>1998</json:string><json:string>6050</json:string><json:string>1203</json:string><json:string>1999</json:string><json:string>4445</json:string><json:string>1990</json:string><json:string>2/10/03</json:string><json:string>2003</json:string><json:string>1995</json:string><json:string>2/3/03</json:string><json:string>2001 and 6/2003</json:string><json:string>1087</json:string><json:string>1117</json:string><json:string>2004</json:string><json:string>3706</json:string></date><geogName></geogName><orgName><json:string>University of Toronto</json:string><json:string>Loyola University</json:string><json:string>Department of Internal Medicine</json:string><json:string>Genpharm</json:string><json:string>Saint Michael’s Hospital, Toronto, Ontario, Canada</json:string><json:string>Michael’s Hospital, Toronto, Ontario, Canada</json:string><json:string>Department of Internal Medicine, Yonsei University College of Medicine, Seoul</json:string><json:string>Air Force</json:string><json:string>Spokane Kidney Center</json:string><json:string>Kidney Center</json:string><json:string>Washington University</json:string><json:string>Amiens University Hospital, Amiens, France</json:string><json:string>Hospital ID</json:string><json:string>Department of Nephrology, Hippokratio General Hospital, Thessaloniki, Greece</json:string><json:string>Children’s Hospital, Vancouver, BC, Canada</json:string><json:string>University of Mississippi</json:string><json:string>University Hospital of Ioannina, Greece</json:string><json:string>University of Texas Medical Branch</json:string><json:string>Kalamazoo Center for Medical Studies</json:string><json:string>Health Sciences Center</json:string><json:string>US Vascular Access Protocol</json:string><json:string>China, Hong Kong, and Canada</json:string><json:string>The Catholic University</json:string><json:string>Medical Center</json:string><json:string>Barsoum Cairo Kidney Center, Cairo, Egypt</json:string><json:string>Department of General Surgery</json:string><json:string>Lynchburg Nephrology Dialysis Inc.</json:string><json:string>Louis University</json:string><json:string>US HD</json:string><json:string>Department of Internal Medicine, National Taiwan University Hospital</json:string><json:string>Department of Orthopaedic Surgery, Osaka Police Hospital, Osaka, Japan</json:string><json:string>Division of Nephrology</json:string><json:string>Minneapolis Medical Research Foundation, Minneapolis, MN</json:string><json:string>Department of Microbiology, Cukurova University, Adana, Turkey</json:string><json:string>Society for Hemodialysis Short Daily Hemodialysis</json:string><json:string>Renal Care Center, Yokohama</json:string><json:string>University of Missouri</json:string><json:string>InCube, Inc.</json:string><json:string>Shonan Institute of Technology, Fujisawa, Kanagawa</json:string><json:string>Clinical Laboratory, Medical University Hospital</json:string><json:string>Department of Nephrology, Hippokration General Hospital, Thessaloniki, Greece</json:string><json:string>Department of Internal Medicine, The Catholic University of Korea, Seoul, South Korea</json:string><json:string>Tuchiya General Hospital, Hiroshima, Hiroshima, Japan</json:string><json:string>University of California San Francisco Medical Center, San Francisco</json:string><json:string>En Chu Kong Hospital, Taipei, Taiwan</json:string><json:string>Society for Hemodialysis Daily Online Hemodia</json:string><json:string>Jos University Teaching Hospital, Jos, Nigeria, and University of New Mexico, Albuquerque, NM</json:string><json:string>Ministry of Health</json:string><json:string>Department of Clinical Pathology, The Catholic University of Korea, Seoul, South Korea</json:string><json:string>Department of Nephrology, Papageorgiou General Hospital</json:string><json:string>Louis University Hospital, St</json:string><json:string>Renal Research Institute, New Haven, CT</json:string><json:string>Department of Nephrology</json:string><json:string>Department of Medicine, Semmelweis University, Budapest, Hungary</json:string><json:string>Dialysis Center</json:string><json:string>Department of Blood Puri</json:string><json:string>Division of Rheumatology</json:string><json:string>Department of Nephrology, Kobe General Hospital, Kobe, Japan</json:string><json:string>and US HD</json:string><json:string>Childrens Hospital, University of Texas Medical Branch, Galveston, TX</json:string><json:string>Abstracts Hemodialysis International</json:string><json:string>VA Hospital/Loyola University Medical Center, Chicago, IL</json:string><json:string>Department of Nephrology H</json:string><json:string>Division of Pediatric Nephrology</json:string><json:string>Baskent University</json:string><json:string>General Hospital, Athens, Greece</json:string><json:string>Consiglio</json:string><json:string>The Jos University</json:string><json:string>University of Texas Health Science Center, San Antonio</json:string><json:string>Department of Clinical Science, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden</json:string><json:string>University Faculty of Medicine</json:string><json:string>Virginia Commonwealth University</json:string><json:string>Medical University</json:string><json:string>Society for Hemodialysis</json:string><json:string>Shonan Institute of Technology, Fujisawa</json:string><json:string>Department of Chemical Pathology</json:string><json:string>Louisiana State University</json:string><json:string>Department of Pediatric Nephrology, University Children</json:string><json:string>Department of Nephrology, Hospital Universitario</json:string><json:string>University Hospitals of Cleveland</json:string><json:string>Division of Molecular Medicine</json:string><json:string>Department of Internal Medicine, University of Turin, Turin, Italy</json:string><json:string>Luke’s Hospital, Chester</json:string><json:string>Hospital for Sick Children, Toronto, Ontario, Canada</json:string><json:string>Department of Internal Medicine, NHIC Ilsan Hospital, Goyang, Gyeonggi, Korea</json:string><json:string>Aksys Ltd.</json:string><json:string>Kingston General Hospital, Kingston, Ontario, Canada</json:string><json:string>Department of Biochemistry</json:string><json:string>Turkey Vascular</json:string><json:string>Mercy Hospital, Kansas City, MO</json:string><json:string>Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea</json:string><json:string>Hemodialysis Hemodialysis International</json:string><json:string>Lamentin Hospital, Martinique</json:string><json:string>Taiwan HD</json:string><json:string>Institute of Medical Science, Tokai University, Isehara, Japan</json:string><json:string>Department of Nephrology, SSMC</json:string><json:string>Department of Internal Medicine and General Surgery</json:string><json:string>Department of Biostatistics, Cukurova University, Adana, Turkey</json:string><json:string>Department of Internal Medicine, Medical Research Institute, Alexandria University, Alexandria, Egypt</json:string><json:string>Michael’s Hospital Infection Control Department and Health, Canada</json:string><json:string>Central Laboratory of Immunology and Microbiology</json:string><json:string>University of Washington</json:string><json:string>Aksys Ltd</json:string><json:string>Department of Nephrology, Overton Brooks Veterans Affairs Medical Center, and Nephrology, Louisiana State University Health Sciences Center, Shreveport, LA</json:string></orgName><orgName_funder></orgName_funder><orgName_provider></orgName_provider><persName><json:string>J. Mislang</json:string><json:string>M.M. Iqbal</json:string><json:string>D.C. Jin</json:string><json:string>Kong Wu</json:string><json:string>G. Sakellariou</json:string><json:string>D. Banik</json:string><json:string>G. Piccoli</json:string><json:string>V. Laugel</json:string><json:string>R. Diamond</json:string><json:string>N. Seyrek</json:string><json:string>M. Kasahara</json:string><json:string>R. Pecoits-Filho</json:string><json:string>S.Y. Hayashi</json:string><json:string>M. Utley</json:string><json:string>R.C. Manfro</json:string><json:string>S.K. Shin</json:string><json:string>R. Garsia</json:string><json:string>C. George</json:string><json:string>J.P. Ebben</json:string><json:string>S. Sugahara</json:string><json:string>M. Sharaf-El-Din</json:string><json:string>GI Sx</json:string><json:string>T. Sakai</json:string><json:string>J. Bower</json:string><json:string>J.S. Floras</json:string><json:string>A.M. Zaki</json:string><json:string>E. Kulah</json:string><json:string>J. Torrente</json:string><json:string>Y.J. Choi</json:string><json:string>K.E. Yeates</json:string><json:string>A. Arbeiter</json:string><json:string>Research</json:string><json:string>K. Schiro-Harvey</json:string><json:string>Q. Fan</json:string><json:string>K. Weigel</json:string><json:string>J.A. Traver</json:string><json:string>F.O. Finkelstein</json:string><json:string>M.M. Nascimento</json:string><json:string>A. Petropoulou</json:string><json:string>N. Azam</json:string><json:string>L. Nagy</json:string><json:string>H. Kawanishi</json:string><json:string>I. Stanchev</json:string><json:string>U.S.A. Objective</json:string><json:string>I. Ma</json:string><json:string>C. Liaskos</json:string><json:string>S. Christopoulou</json:string><json:string>I. Kulcsar</json:string><json:string>S. White</json:string><json:string>M. Sevilla</json:string><json:string>U.S.A. Bacteremia</json:string><json:string>R.S. Lockridge</json:string><json:string>J.C.D. Baylon</json:string><json:string>D.R. Ryu</json:string><json:string>S. Paydas</json:string><json:string>J. Samik</json:string><json:string>V.U. Dreizin</json:string><json:string>C.W. Yang</json:string><json:string>D.S. Han</json:string><json:string>S. Ferenczi</json:string><json:string>D. Hobbs</json:string><json:string>L. Flynn</json:string><json:string>J. Hynes</json:string><json:string>J. Terzic</json:string><json:string>M.F. Weiss</json:string><json:string>D.S. Lirenman</json:string><json:string>E.J. Choi</json:string><json:string>V. Methods</json:string><json:string>A. Jeantet</json:string><json:string>R. Halker</json:string><json:string>S. Yang</json:string><json:string>R. Carson</json:string><json:string>S. Cetiner</json:string><json:string>V. Liakopoulos</json:string><json:string>S.J. Oh</json:string><json:string>M. Velizatova</json:string><json:string>B.A. Warady</json:string><json:string>T. Gehr</json:string><json:string>C. Bainey</json:string><json:string>Y.S. Chang</json:string><json:string>Y.O. Kim</json:string><json:string>P. Karabatakis</json:string><json:string>Y.S. Kim</json:string><json:string>L.L. Jones</json:string><json:string>D.L. Campbell</json:string><json:string>R.H. Glew</json:string><json:string>A. Takesawa</json:string><json:string>S.H. Lee</json:string><json:string>C.T. Chan</json:string><json:string>T. Drossert</json:string><json:string>E.I. Agaba</json:string><json:string>K. Sakurai</json:string><json:string>S. Blankshaen</json:string><json:string>R.A. Tzamaloukas</json:string><json:string>S. Zarogiannis</json:string><json:string>K. McPhail</json:string><json:string>S. Hadjiev</json:string><json:string>E. Weinhandl</json:string><json:string>L. Paille</json:string><json:string>A.M. Belechri</json:string><json:string>P.F. Hoyer</json:string><json:string>T.S. Ing</json:string><json:string>L. Cantey</json:string><json:string>A.J. Collins</json:string><json:string>T. Fuji</json:string><json:string>M. Kreuzer</json:string><json:string>R. Nemec</json:string><json:string>M. Philipneri</json:string><json:string>J. Szegedi</json:string><json:string>B. Young</json:string><json:string>Z.J. Twardowski</json:string><json:string>A. Papagianni</json:string><json:string>N.K. Atray</json:string><json:string>G. Barril</json:string><json:string>V. Papazov</json:string><json:string>M. Burdese</json:string><json:string>M.S. Jackson</json:string><json:string>M.Y. Hassan</json:string><json:string>M. Gellens</json:string><json:string>I. El-Esper</json:string><json:string>U.S.A. Nephrogenic</json:string><json:string>M. Jayoma</json:string><json:string>E.A. Iliescu</json:string><json:string>E. Mitsopoulos</json:string><json:string>J. Traeger</json:string><json:string>L.A. Douglas</json:string><json:string>H.A. Maiza</json:string><json:string>B. Lindholm</json:string><json:string>U.S.A. Background</json:string><json:string>M.O. Spencer</json:string><json:string>A. Kroeker</json:string><json:string>N. Herian</json:string><json:string>A.C. Yamashita</json:string><json:string>A. Livolsi</json:string><json:string>C.M. Kjellstrand</json:string><json:string>C. Li</json:string><json:string>V. Carreno</json:string><json:string>P. Hann</json:string><json:string>T. Masuda</json:string><json:string>Hemodialysis</json:string><json:string>T. Eisen</json:string><json:string>G. Maranon</json:string><json:string>The</json:string><json:string>E.W. Kang</json:string><json:string>Have</json:string><json:string>I. Quality</json:string><json:string>U. Vester</json:string><json:string>J. Tsai</json:string><json:string>F.B. Atac</json:string><json:string>P. Caro</json:string><json:string>M. Ragab</json:string><json:string>R. Galland</json:string><json:string>E. Delawari</json:string><json:string>Anecdotal</json:string><json:string>P. Erhard</json:string><json:string>I. Kiss</json:string><json:string>J.A. Miller</json:string><json:string>Y. Sato</json:string><json:string>S. Sezer</json:string><json:string>L. Haglund</json:string><json:string>C. Carmicheal</json:string><json:string>E.K. Zervou</json:string><json:string>D. Hines</json:string><json:string>A. Jones</json:string><json:string>R.Z. Ismagilov</json:string><json:string>H. Vos</json:string><json:string>F. Boitte</json:string><json:string>T. Ing</json:string><json:string>S. Chaudhury</json:string><json:string>U.S.A. Central</json:string><json:string>G. Zabioglou</json:string><json:string>S.K. Banerjee</json:string><json:string>J. Bartolome</json:string><json:string>Any Relationship</json:string><json:string>E. Gonzalez</json:string><json:string>G.B. Piccoli</json:string><json:string>O.M. Cairoli</json:string><json:string>Nephrology</json:string><json:string>M. Shenouda</json:string><json:string>R.M. Hossain</json:string><json:string>M. Fischbach</json:string><json:string>K. Larson</json:string><json:string>A. Bruchfeld</json:string><json:string>A. Yoshimoto</json:string><json:string>V. Sreenarasimhaiah</json:string><json:string>F. Tio</json:string><json:string>P. Stenvinkel</json:string><json:string>M. Imran</json:string><json:string>Y. Chen</json:string><json:string>G. Wagner</json:string><json:string>H.M. Cho</json:string><json:string>Z. Arat</json:string><json:string>S. Yamasaki</json:string><json:string>H. Okada</json:string><json:string>H.S. Chae</json:string><json:string>N. Kojcheva</json:string><json:string>G. Kyriakopoulos</json:string><json:string>M. Yoshikawa</json:string><json:string>M.D. Lee</json:string><json:string>A. Verhallen</json:string><json:string>N. Islam</json:string><json:string>M.P. Kooistra</json:string><json:string>A. Grundy</json:string><json:string>K. Ako</json:string><json:string>L. Troidle</json:string><json:string>S.L. Johnson</json:string><json:string>A. Joseph</json:string><json:string>To</json:string><json:string>J.I. Kim</json:string><json:string>U.S.A. Introduction</json:string><json:string>A.S. Azhitaeva</json:string><json:string>S.J.A.M. Stokvis</json:string><json:string>L. Extracorporeal</json:string><json:string>S.A. Yoon</json:string><json:string>Day Length</json:string><json:string>S. Gorogh</json:string><json:string>D. Kirmizis</json:string><json:string>M.A. Pachaly</json:string><json:string>T. Nakai</json:string><json:string>S. Chiang</json:string><json:string>W.S. Andrews</json:string><json:string>P. Kiriklidou</json:string><json:string>A. Stein</json:string><json:string>K.H. Choi</json:string><json:string>H. Nemoto</json:string><json:string>D.J. Vanderjagt</json:string><json:string>G.N. Dalekos</json:string><json:string>S.S. Haqqie</json:string><json:string>F. Dapena</json:string><json:string>G. Soragna</json:string><json:string>F. Coronel</json:string><json:string>P. Helms</json:string><json:string>L. Wales</json:string><json:string>C. Adams</json:string><json:string>Blood Bank</json:string><json:string>J.E. Carter</json:string><json:string>S.W. Kang</json:string><json:string>P. Sanz</json:string><json:string>E. Hryciw</json:string><json:string>R.N. Foley</json:string><json:string>Y.M. Ku</json:string><json:string>S. Peng</json:string><json:string>M. Gai</json:string><json:string>T.J. Vachharajani</json:string><json:string>M.C. Riella</json:string><json:string>S.B. Chebrolu</json:string><json:string>J. Campbell</json:string><json:string>M.J. Thomas</json:string><json:string>A.M. Verhallen</json:string><json:string>R. Martinez</json:string><json:string>Doppler</json:string><json:string>Y.S. Shin</json:string><json:string>C. Holloman</json:string><json:string>C.A. Solid</json:string><json:string>H.C. Song</json:string><json:string>R. Selgas</json:string><json:string>I. Sakaji</json:string><json:string>M. Agraharkar</json:string><json:string>A. Rico</json:string><json:string>A. Rahman</json:string><json:string>J. Buss</json:string><json:string>S. Islam</json:string><json:string>A. Saito</json:string><json:string>B. Borbas</json:string><json:string>J. Valente</json:string><json:string>D. Shore</json:string><json:string>A. Bidani</json:string><json:string>Ht</json:string><json:string>E. Tutal</json:string><json:string>N. Kanbara</json:string><json:string>T. Suzuki</json:string><json:string>L. Renner</json:string><json:string>T. McComb</json:string><json:string>A. Zolota</json:string><json:string>S.W. McConnell</json:string><json:string>C. Rizos</json:string><json:string>Y. Kanno</json:string><json:string>G. Seydaoglu</json:string><json:string>M. Oadri</json:string><json:string>D. Motta</json:string><json:string>M. Salomone</json:string><json:string>D.C. Holland</json:string><json:string>Val Val</json:string><json:string>Elevation</json:string><json:string>K. Masuhara</json:string><json:string>M.P. Ruiz</json:string><json:string>A. Pierratos</json:string><json:string>S. Dobrev</json:string><json:string>M.F. Pipkin</json:string><json:string>El Pilar</json:string><json:string>H.Y. Choi</json:string><json:string>C.R. Blagg</json:string><json:string>D.T. Gilbertson</json:string><json:string>U. Princesa</json:string><json:string>R.M. Lindsay</json:string><json:string>E. Alexopoulos</json:string><json:string>U.S.A. Methods</json:string><json:string>C. Siegel</json:string><json:string>K. Chiang</json:string><json:string>Factor</json:string></persName><placeName><json:string>TX</json:string><json:string>U.S.</json:string><json:string>Menlo Park</json:string><json:string>Leiden</json:string><json:string>IL</json:string><json:string>MS</json:string><json:string>Utrecht</json:string><json:string>Terashima</json:string><json:string>Ankara</json:string><json:string>Columbia</json:string><json:string>Germany</json:string><json:string>Greece</json:string><json:string>Shreveport</json:string><json:string>Mineshima</json:string><json:string>Edmonton</json:string><json:string>NY</json:string><json:string>Dallas</json:string><json:string>Bangladesh</json:string><json:string>Korea</json:string><json:string>Seoul</json:string><json:string>Brazil</json:string><json:string>Spokane</json:string><json:string>Albany</json:string><json:string>Dhaka</json:string><json:string>Turkey</json:string><json:string>Richmond</json:string><json:string>Matsushima</json:string><json:string>Taiwan</json:string><json:string>Canada</json:string><json:string>LA</json:string><json:string>VA</json:string><json:string>Lynchburg</json:string><json:string>American</json:string><json:string>Madrid</json:string><json:string>HEL</json:string><json:string>Lincolnshire</json:string><json:string>U.S.</json:string><json:string>Kazakhstan</json:string><json:string>Seattle</json:string><json:string>MO</json:string><json:string>Jackson</json:string><json:string>China</json:string><json:string>Bulgaria</json:string><json:string>Toronto</json:string><json:string>Galveston</json:string><json:string>Japan</json:string><json:string>Strasbourg</json:string><json:string>America</json:string><json:string>Nigeria</json:string><json:string>Brussels</json:string><json:string>EPS</json:string><json:string>Tokyo</json:string><json:string>Chicago</json:string><json:string>CA</json:string><json:string>Palm Beach</json:string><json:string>U.S.</json:string><json:string>Saint Michael</json:string><json:string>France</json:string><json:string>Essen</json:string><json:string>WA</json:string><json:string>Cleveland</json:string><json:string>Spain</json:string><json:string>Lyon</json:string><json:string>Belgium</json:string><json:string>OH</json:string><json:string>Netherlands</json:string><json:string>Osaka</json:string></placeName><ref_url></ref_url><ref_bibl><json:string>second session, 4390</json:string><json:string>April 2001</json:string><json:string>second session, 6167</json:string><json:string>third session, 4775</json:string><json:string>Devereaux et al.</json:string><json:string>first session, 4477</json:string><json:string>third session, 5178</json:string><json:string>second session, 4167</json:string><json:string>first session, 5443</json:string><json:string>first session, 4633</json:string><json:string>third session, 5078</json:string><json:string>March 2003</json:string><json:string>September 1997</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/WNG-GLRWSS6H-K</json:string></ark><categories><wos><json:string>1 - science</json:string><json:string>2 - urology & nephrology</json:string></wos><scienceMetrix><json:string>1 - health sciences</json:string><json:string>2 - clinical medicine</json:string><json:string>3 - urology & nephrology</json:string></scienceMetrix><scopus><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - Nephrology</json:string><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - Hematology</json:string></scopus><inist><json:string>1 - sciences appliquees, technologies et medecines</json:string><json:string>2 - sciences biologiques et medicales</json:string><json:string>3 - sciences medicales</json:string></inist></categories><publicationDate>2004</publicationDate><copyrightDate>2004</copyrightDate><doi><json:string>10.1111/j.1492-7535.2004.0085as.x</json:string></doi><id>5224C0523F45C564603136DB982361168093B06B</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/ark:/67375/WNG-GLRWSS6H-K/fulltext.pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/ark:/67375/WNG-GLRWSS6H-K/bundle.zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/ark:/67375/WNG-GLRWSS6H-K/fulltext.tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main">Successful Management of Valproate Overdose by a Combination of Extracorporeal Therapies</title><title level="a" type="short">24th Annual Dialysis Conference: Abstracts</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Blackwell Science Inc</publisher><pubPlace>Oxford, UK; 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Here we report the case of a patient with serious valproate toxicity treated with simultaneous “in series” hemodialysis and hemoperfusion followed by continuous veno‐venous hemodiafiltration. A 35‐year‐old homeless male presented to the emergency department after ingesting 120 pills of valproic acid. Initial valproic acid level was 59 µg/mL. Urine drug screen was negative and serum chemistries including LFTs were normal. He was treated with activated charcoal and admitted to the intensive care unit. 4 h later, he developed respiratory failure and became hemodynamically unstable. He was intubated and successfully resuscitated. Subsequently, the valproic acid level was found to be 553 µg/mL and a decision was made to employ extracorporeal methods for drug removal. “In series” hemodialysis and hemoperfusion were done for 4 h and simultaneous blood samples for measurement of valproic acid levels were obtained as blood entered the hemoperfusion column (arterial) and as it exited the hemodialysis membrane (venous). Extraction ratio, whole blood, and plasma clearances were calculated and they compared substantially with the published data. The above measures decreased valproate levels from 572.6 (pre‐dialysis level) to 203.2 µg/mL. This was followed by continuous veno‐venous hemodiafiltration for 18 h, which sustained the drug removal and prevented significant post‐dialytic rebound. This is the first reported instance in which these three methods were administered together successfully in the management of valproic acid toxicity.</p></abstract><textClass><keywords rend="tocHeading1"><term>Hemodialysis Abstracts from the 24th Annual Dialysis Conference</term></keywords></textClass><langUsage><language ident="en"></language></langUsage></profileDesc><revisionDesc><change when="2019-12-20" who="#istex" xml:id="pub2tei">formatting</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/WNG-GLRWSS6H-K/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley component found"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Blackwell Science Inc</publisherName><publisherLoc>Oxford, UK; Malden, USA</publisherLoc></publisherInfo><doi origin="wiley" registered="yes">10.1111/(ISSN)1542-4758</doi><issn type="print">1492-7535</issn><issn type="electronic">1542-4758</issn><idGroup><id type="product" value="HDI"></id><id type="publisherDivision" value="ST"></id></idGroup><titleGroup><title type="main" sort="HEMODIALYSIS INTERNATIONAL">Hemodialysis International</title></titleGroup></publicationMeta><publicationMeta level="part" position="01001"><doi origin="wiley">10.1111/hdi.2004.8.issue-1</doi><numberingGroup><numbering type="journalVolume" number="8">8</numbering><numbering type="journalIssue" number="1">1</numbering></numberingGroup><coverDate startDate="2004-01">January 2004</coverDate></publicationMeta><publicationMeta level="unit" type="abstract" position="0009500" status="forIssue"><doi origin="wiley">10.1111/j.1492-7535.2004.0085as.x</doi><idGroup><id type="unit" value="HDI085AS"></id></idGroup><countGroup><count type="pageTotal" number="100"></count></countGroup><titleGroup><title type="tocHeading1">Hemodialysis Abstracts from the 24th Annual Dialysis Conference</title></titleGroup><eventGroup><event type="firstOnline" date="2004-01-23"></event><event type="publishedOnlineFinalForm" date="2004-01-23"></event><event type="xmlConverted" agent="Converter:BPG_TO_WML3G version:2.3.15 mode:FullText source:Header result:Header" date="2010-07-19"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-01-26"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-24"></event></eventGroup><numberingGroup><numbering type="pageFirst" number="95">95</numbering><numbering type="pageLast" number="96">96</numbering></numberingGroup><linkGroup><link type="toTypesetVersion" href="file:HDI.HDI085AS.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="0"></count><count type="tableTotal" number="0"></count><count type="formulaTotal" number="0"></count><count type="referenceTotal" number="0"></count><count type="wordTotal" number="0"></count><count type="linksPubMed" number="0"></count><count type="linksCrossRef" number="0"></count></countGroup><titleGroup><title type="main">Successful Management of Valproate Overdose by a Combination of Extracorporeal Therapies</title><title type="shortAuthors">24th Annual Dialysis Conference: Abstracts</title><title type="short">24th Annual Dialysis Conference: Abstracts</title></titleGroup><creators><creator creatorRole="author" xml:id="cr1" affiliationRef="#a256-1"><personName><givenNames>P.</givenNames><familyName>Yalamanchili</familyName></personName></creator><creator creatorRole="author" xml:id="cr2" affiliationRef="#a256-2"><personName><givenNames>Z.</givenNames><familyName>Al Aly</familyName></personName></creator><creator creatorRole="author" xml:id="cr3" affiliationRef="#a256-2"><personName><givenNames>E.</givenNames><familyName>Gonzalez</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="a256-1"><unparsedAffiliation>St. Luke's Hospital, Chesterfield</unparsedAffiliation></affiliation><affiliation xml:id="a256-2"><unparsedAffiliation>St. Louis University Hospital, St. Louis, MO, U.S.A.</unparsedAffiliation></affiliation></affiliationGroup><abstractGroup><abstract type="main" xml:lang="en"><p>Valproic acid toxicity is not infrequent and is difficult to treat, as there is no specific antidote. In the past, this drug was considered unremovable by extracorporeal methods because of the highly protein bound state (90–95%). However, recent reports suggest that the toxicokinetics of valproate vary considerably from the pharmacokinetics at therapeutic levels, and at higher concentrations protein‐binding sites become saturated. The drug's relatively low molecular weight (144 Da), small volume of distribution (0.13–0.23 L/kg), and saturable protein binding render it potentially amenable to extracorporeal removal, but published experience is scant and there are only a few reported instances in which patients were successfully treated with extracorporeal methods. Here we report the case of a patient with serious valproate toxicity treated with simultaneous “in series” hemodialysis and hemoperfusion followed by continuous veno‐venous hemodiafiltration. A 35‐year‐old homeless male presented to the emergency department after ingesting 120 pills of valproic acid. Initial valproic acid level was 59 µg/mL. Urine drug screen was negative and serum chemistries including LFTs were normal. He was treated with activated charcoal and admitted to the intensive care unit. 4 h later, he developed respiratory failure and became hemodynamically unstable. He was intubated and successfully resuscitated. Subsequently, the valproic acid level was found to be 553 µg/mL and a decision was made to employ extracorporeal methods for drug removal. “In series” hemodialysis and hemoperfusion were done for 4 h and simultaneous blood samples for measurement of valproic acid levels were obtained as blood entered the hemoperfusion column (arterial) and as it exited the hemodialysis membrane (venous). Extraction ratio, whole blood, and plasma clearances were calculated and they compared substantially with the published data. The above measures decreased valproate levels from 572.6 (pre‐dialysis level) to 203.2 µg/mL. This was followed by continuous veno‐venous hemodiafiltration for 18 h, which sustained the drug removal and prevented significant post‐dialytic rebound. 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In the past, this drug was considered unremovable by extracorporeal methods because of the highly protein bound state (90–95%). However, recent reports suggest that the toxicokinetics of valproate vary considerably from the pharmacokinetics at therapeutic levels, and at higher concentrations protein‐binding sites become saturated. The drug's relatively low molecular weight (144 Da), small volume of distribution (0.13–0.23 L/kg), and saturable protein binding render it potentially amenable to extracorporeal removal, but published experience is scant and there are only a few reported instances in which patients were successfully treated with extracorporeal methods. Here we report the case of a patient with serious valproate toxicity treated with simultaneous “in series” hemodialysis and hemoperfusion followed by continuous veno‐venous hemodiafiltration. A 35‐year‐old homeless male presented to the emergency department after ingesting 120 pills of valproic acid. Initial valproic acid level was 59 µg/mL. Urine drug screen was negative and serum chemistries including LFTs were normal. He was treated with activated charcoal and admitted to the intensive care unit. 4 h later, he developed respiratory failure and became hemodynamically unstable. He was intubated and successfully resuscitated. Subsequently, the valproic acid level was found to be 553 µg/mL and a decision was made to employ extracorporeal methods for drug removal. “In series” hemodialysis and hemoperfusion were done for 4 h and simultaneous blood samples for measurement of valproic acid levels were obtained as blood entered the hemoperfusion column (arterial) and as it exited the hemodialysis membrane (venous). Extraction ratio, whole blood, and plasma clearances were calculated and they compared substantially with the published data. The above measures decreased valproate levels from 572.6 (pre‐dialysis level) to 203.2 µg/mL. This was followed by continuous veno‐venous hemodiafiltration for 18 h, which sustained the drug removal and prevented significant post‐dialytic rebound. This is the first reported instance in which these three methods were administered together successfully in the management of valproic acid toxicity.</abstract><relatedItem type="host"><titleInfo><title>Hemodialysis International</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><identifier type="ISSN">1492-7535</identifier><identifier type="eISSN">1542-4758</identifier><identifier type="DOI">10.1111/(ISSN)1542-4758</identifier><identifier type="PublisherID">HDI</identifier><part><date>2004</date><detail type="volume"><caption>vol.</caption><number>8</number></detail><detail type="issue"><caption>no.</caption><number>1</number></detail><extent unit="pages"><start>95</start><end>96</end><total>100</total></extent></part></relatedItem><identifier type="istex">5224C0523F45C564603136DB982361168093B06B</identifier><identifier type="ark">ark:/67375/WNG-GLRWSS6H-K</identifier><identifier type="DOI">10.1111/j.1492-7535.2004.0085as.x</identifier><identifier type="ArticleID">HDI085AS</identifier><accessCondition type="use and reproduction" contentType="copyright">© Wiley. 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