Neurological Complications in Critically Ill Patients
Identifieur interne : 000267 ( Pmc/Corpus ); précédent : 000266; suivant : 000268Neurological Complications in Critically Ill Patients
Auteurs : Charles F. Bolton ; G. Bryan YoungSource :
- Neurology and General Medicine ; 2008.
Url:
DOI: 10.1016/B978-044306707-5.50055-9
PubMed: NONE
PubMed Central: 7152411
Links to Exploration step
PMC:7152411Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Neurological Complications in Critically Ill Patients</title><author><name sortKey="Bolton, Charles F" sort="Bolton, Charles F" uniqKey="Bolton C" first="Charles F." last="Bolton">Charles F. Bolton</name></author><author><name sortKey="Bryan Young, G" sort="Bryan Young, G" uniqKey="Bryan Young G" first="G." last="Bryan Young">G. Bryan Young</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmc">7152411</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7152411</idno><idno type="RBID">PMC:7152411</idno><idno type="doi">10.1016/B978-044306707-5.50055-9</idno><idno type="pmid">NONE</idno><date when="2008">2008</date><idno type="wicri:Area/Pmc/Corpus">000267</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000267</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Neurological Complications in Critically Ill Patients</title><author><name sortKey="Bolton, Charles F" sort="Bolton, Charles F" uniqKey="Bolton C" first="Charles F." last="Bolton">Charles F. Bolton</name></author><author><name sortKey="Bryan Young, G" sort="Bryan Young, G" uniqKey="Bryan Young G" first="G." last="Bryan Young">G. Bryan Young</name></author></analytic><series><title level="j">Neurology and General Medicine</title><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Tran, Dd" uniqKey="Tran D">DD Tran</name></author><author><name sortKey="Groeneveld, Aajb" uniqKey="Groeneveld A">AAJB Groeneveld</name></author><author><name sortKey="Van Der Meulen, J" uniqKey="Van Der Meulen J">J van der Meulen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Riedemann, Nc" uniqKey="Riedemann N">NC Riedemann</name></author><author><name sortKey="Guo, Rf" uniqKey="Guo R">RF Guo</name></author><author><name sortKey="Ward, Pa" uniqKey="Ward P">PA Ward</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bone, Rc" uniqKey="Bone R">RC Bone</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Glauser, Mp" uniqKey="Glauser M">MP Glauser</name></author><author><name sortKey="Zanetti, G" uniqKey="Zanetti G">G Zanetti</name></author><author><name sortKey="Baumgartner, Jd" uniqKey="Baumgartner J">JD Baumgartner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cowley, Hc" uniqKey="Cowley H">HC Cowley</name></author><author><name sortKey="Heney, D" uniqKey="Heney D">D Heney</name></author><author><name sortKey="Gearing, Aj" uniqKey="Gearing A">AJ Gearing</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Faust, Sn" uniqKey="Faust S">SN Faust</name></author><author><name sortKey="Levin, M" uniqKey="Levin M">M Levin</name></author><author><name sortKey="Harrison, Ob" uniqKey="Harrison O">OB Harrison</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Satran, R" uniqKey="Satran R">R Satran</name></author><author><name sortKey="Almog, Y" uniqKey="Almog Y">Y Almog</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bolton, Cf" uniqKey="Bolton C">CF Bolton</name></author><author><name sortKey="Young, Gb" uniqKey="Young G">GB Young</name></author><author><name sortKey="Zochodne, Dw" uniqKey="Zochodne D">DW Zochodne</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bolton, Cf" uniqKey="Bolton C">CF Bolton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jackson, Ac" uniqKey="Jackson A">AC Jackson</name></author><author><name sortKey="Gilbert, Jj" uniqKey="Gilbert J">JJ Gilbert</name></author><author><name sortKey="Young, Gb" uniqKey="Young G">GB Young</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Young, Gb" uniqKey="Young G">GB Young</name></author><author><name sortKey="Bolton, Cf" uniqKey="Bolton C">CF Bolton</name></author><author><name sortKey="Austin, Tw" uniqKey="Austin T">TW Austin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Young, Gb" uniqKey="Young G">GB Young</name></author><author><name sortKey="Bolton, Cf" uniqKey="Bolton C">CF Bolton</name></author><author><name sortKey="Archibald, Ym" uniqKey="Archibald Y">YM Archibald</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Straver, Js" uniqKey="Straver J">JS Straver</name></author><author><name sortKey="Keunen, Rwm" uniqKey="Keunen R">RWM Keunen</name></author><author><name sortKey="Stam, Cj" uniqKey="Stam C">CJ Stam</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Straver, Js" uniqKey="Straver J">JS Straver</name></author><author><name sortKey="Keunen, Wm" uniqKey="Keunen W">WM Keunen</name></author><author><name sortKey="Stam, Cj" uniqKey="Stam C">CJ Stam</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lorente, Je" uniqKey="Lorente J">JE Lorente</name></author><author><name sortKey="Landin, L" uniqKey="Landin L">L Landin</name></author><author><name sortKey="Renes, E" uniqKey="Renes E">E Renes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tanaka, K" uniqKey="Tanaka K">K Tanaka</name></author><author><name sortKey="Gotoh, F" uniqKey="Gotoh F">F Gotoh</name></author><author><name sortKey="Gomi, S" uniqKey="Gomi S">S Gomi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Anda, T" uniqKey="Anda T">T Anda</name></author><author><name sortKey="Yamashita, H" uniqKey="Yamashita H">H Yamashita</name></author><author><name sortKey="Khalid, H" uniqKey="Khalid H">H Khalid</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huynh, Kh" uniqKey="Huynh K">KH Huynh</name></author><author><name sortKey="Dorovini Zis, K" uniqKey="Dorovini Zis K">K Dorovini-Zis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Papadopoulos, Mc" uniqKey="Papadopoulos M">MC Papadopoulos</name></author><author><name sortKey="Moss, Rf" uniqKey="Moss R">RF Moss</name></author><author><name sortKey="Lamb, Fj" uniqKey="Lamb F">FJ Lamb</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Sarro, Gb" uniqKey="De Sarro G">GB De Sarro</name></author><author><name sortKey="Masuda, Y" uniqKey="Masuda Y">Y Masuda</name></author><author><name sortKey="Ascioti, C" uniqKey="Ascioti C">C Ascioti</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gautron, L" uniqKey="Gautron L">L Gautron</name></author><author><name sortKey="Lafon, P" uniqKey="Lafon P">P Lafon</name></author><author><name sortKey="Chaigniau, M" uniqKey="Chaigniau M">M Chaigniau</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Korcok, J" uniqKey="Korcok J">J Korcok</name></author><author><name sortKey="Wu, F" uniqKey="Wu F">F Wu</name></author><author><name sortKey="Tyml, K" uniqKey="Tyml K">K Tyml</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Soejima, Y" uniqKey="Soejima Y">Y Soejima</name></author><author><name sortKey="Fujii, Y" uniqKey="Fujii Y">Y Fujii</name></author><author><name sortKey="Ishikawa, T" uniqKey="Ishikawa T">T Ishikawa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Guerra Romero, L" uniqKey="Guerra Romero L">L Guerra-Romero</name></author><author><name sortKey="Tureen, Jh" uniqKey="Tureen J">JH Tureen</name></author><author><name sortKey="Fournier, Ma" uniqKey="Fournier M">MA Fournier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Olasmaa, M" uniqKey="Olasmaa M">M Olasmaa</name></author><author><name sortKey="Rothstein, Jd" uniqKey="Rothstein J">JD Rothstein</name></author><author><name sortKey="Guidotti, A" uniqKey="Guidotti A">A Guidotti</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Herkes, Gk" uniqKey="Herkes G">GK Herkes</name></author><author><name sortKey="Wszolek, Zk" uniqKey="Wszolek Z">ZK Wszolek</name></author><author><name sortKey="Westmoreland, Bf" uniqKey="Westmoreland B">BF Westmoreland</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kress, Jp" uniqKey="Kress J">JP Kress</name></author><author><name sortKey="Poheman, As" uniqKey="Poheman A">AS Poheman</name></author><author><name sortKey="O Connor, Mf" uniqKey="O Connor M">MF O'Connor</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Leo, Rj" uniqKey="Leo R">RJ Leo</name></author><author><name sortKey="Ballow, Ch" uniqKey="Ballow C">CH Ballow</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Jonghe, B" uniqKey="De Jonghe B">B De Jonghe</name></author><author><name sortKey="Sharshar, T" uniqKey="Sharshar T">T Sharshar</name></author><author><name sortKey="Lefaucheur, Jp" uniqKey="Lefaucheur J">JP Lefaucheur</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Maher, J" uniqKey="Maher J">J Maher</name></author><author><name sortKey="Bolton, C" uniqKey="Bolton C">C Bolton</name></author><author><name sortKey="Grand Maison, F" uniqKey="Grand Maison F">F Grand'Maison</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nicolle, Mw" uniqKey="Nicolle M">MW Nicolle</name></author><author><name sortKey="Stewart, Dj" uniqKey="Stewart D">DJ Stewart</name></author><author><name sortKey="Remtulla, H" uniqKey="Remtulla H">H Remtulla</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, R" uniqKey="Chen R">R Chen</name></author><author><name sortKey="Grand Maison, F" uniqKey="Grand Maison F">F Grand'Maison</name></author><author><name sortKey="Bolton, Cf" uniqKey="Bolton C">CF Bolton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bolton, Cf" uniqKey="Bolton C">CF Bolton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Leijten, Fss" uniqKey="Leijten F">FSS Leijten</name></author><author><name sortKey="De Weerd, Aw" uniqKey="De Weerd A">AW de Weerd</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Witt, Nj" uniqKey="Witt N">NJ Witt</name></author><author><name sortKey="Zochodne, Dw" uniqKey="Zochodne D">DW Zochodne</name></author><author><name sortKey="Bolton, Cf" uniqKey="Bolton C">CF Bolton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Berek, K" uniqKey="Berek K">K Berek</name></author><author><name sortKey="Margreiter, J" uniqKey="Margreiter J">J Margreiter</name></author><author><name sortKey="Willeit, J" uniqKey="Willeit J">J Willeit</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zifko, Ua" uniqKey="Zifko U">UA Zifko</name></author><author><name sortKey="Zipko, Ht" uniqKey="Zipko H">HT Zipko</name></author><author><name sortKey="Bolton, Cf" uniqKey="Bolton C">CF Bolton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lacomis, D" uniqKey="Lacomis D">D Lacomis</name></author><author><name sortKey="Petrella, Jt" uniqKey="Petrella J">JT Petrella</name></author><author><name sortKey="Giuliani, Mj" uniqKey="Giuliani M">MJ Giuliani</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Latronico, N" uniqKey="Latronico N">N Latronico</name></author><author><name sortKey="Fenzi, F" uniqKey="Fenzi F">F Fenzi</name></author><author><name sortKey="Recupero, D" uniqKey="Recupero D">D Recupero</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zochodne, Dw" uniqKey="Zochodne D">DW Zochodne</name></author><author><name sortKey="Bolton, Cf" uniqKey="Bolton C">CF Bolton</name></author><author><name sortKey="Wells, Ga" uniqKey="Wells G">GA Wells</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Leijten, Fss" uniqKey="Leijten F">FSS Leijten</name></author><author><name sortKey="Harinck De Weerd, Je" uniqKey="Harinck De Weerd J">JE Harinck-de Weerd</name></author><author><name sortKey="Poortvliet, Dcj" uniqKey="Poortvliet D">DCJ Poortvliet</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wijdicks, Ef" uniqKey="Wijdicks E">EF Wijdicks</name></author><author><name sortKey="Fulgham, Jr" uniqKey="Fulgham J">JR Fulgham</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mohr, M" uniqKey="Mohr M">M Mohr</name></author><author><name sortKey="Englisch, L" uniqKey="Englisch L">L Englisch</name></author><author><name sortKey="Roth, A" uniqKey="Roth A">A Roth</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Den Berghe, G" uniqKey="Van Den Berghe G">G Van den Berghe</name></author><author><name sortKey="Wouters, P" uniqKey="Wouters P">P Wouters</name></author><author><name sortKey="Weekers, F" uniqKey="Weekers F">F Weekers</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Leijten, Fss" uniqKey="Leijten F">FSS Leijten</name></author><author><name sortKey="De Weerd" uniqKey="De Weerd">de Weerd</name></author><author><name sortKey="Poortvliet, Dc" uniqKey="Poortvliet D">DC Poortvliet</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Segredo, V" uniqKey="Segredo V">V Segredo</name></author><author><name sortKey="Caldwell, Je" uniqKey="Caldwell J">JE Caldwell</name></author><author><name sortKey="Matthay, Ma" uniqKey="Matthay M">MA Matthay</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hirano, M" uniqKey="Hirano M">M Hirano</name></author><author><name sortKey="Ott, Br" uniqKey="Ott B">BR Ott</name></author><author><name sortKey="Raps, Ec" uniqKey="Raps E">EC Raps</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lacomis, D" uniqKey="Lacomis D">D Lacomis</name></author><author><name sortKey="Zochodne, Dw" uniqKey="Zochodne D">DW Zochodne</name></author><author><name sortKey="Bird, Sj" uniqKey="Bird S">SJ Bird</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Letter, Ma" uniqKey="De Letter M">MA De Letter</name></author><author><name sortKey="Schmitz, Pi" uniqKey="Schmitz P">PI Schmitz</name></author><author><name sortKey="Visser, Lh" uniqKey="Visser L">LH Visser</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Douglass, Ja" uniqKey="Douglass J">JA Douglass</name></author><author><name sortKey="Tuxen, Dv" uniqKey="Tuxen D">DV Tuxen</name></author><author><name sortKey="Horne, M" uniqKey="Horne M">M Horne</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Campellone, Jv" uniqKey="Campellone J">JV Campellone</name></author><author><name sortKey="Lacomis, D" uniqKey="Lacomis D">D Lacomis</name></author><author><name sortKey="Kramer, Dj" uniqKey="Kramer D">DJ Kramer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Perea, M" uniqKey="Perea M">M Perea</name></author><author><name sortKey="Picon, M" uniqKey="Picon M">M Picon</name></author><author><name sortKey="Miro, O" uniqKey="Miro O">O Miro</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Leung, Tw" uniqKey="Leung T">TW Leung</name></author><author><name sortKey="Wong, Ks" uniqKey="Wong K">KS Wong</name></author><author><name sortKey="Hui, Ac" uniqKey="Hui A">AC Hui</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Trojaborg, W" uniqKey="Trojaborg W">W Trojaborg</name></author><author><name sortKey="Weimer, Lh" uniqKey="Weimer L">LH Weimer</name></author><author><name sortKey="Hays, Ap" uniqKey="Hays A">AP Hays</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sitwell, Ld" uniqKey="Sitwell L">LD Sitwell</name></author><author><name sortKey="Weinshenker, Bg" uniqKey="Weinshenker B">BG Weinshenker</name></author><author><name sortKey="Monpetit, V" uniqKey="Monpetit V">V Monpetit</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Park, Ej" uniqKey="Park E">EJ Park</name></author><author><name sortKey="Nishida, T" uniqKey="Nishida T">T Nishida</name></author><author><name sortKey="Sufit, Rl" uniqKey="Sufit R">RL Sufit</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schwarz, J" uniqKey="Schwarz J">J Schwarz</name></author><author><name sortKey="Planck, J" uniqKey="Planck J">J Planck</name></author><author><name sortKey="Briegel, J" uniqKey="Briegel J">J Briegel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rich, Mm" uniqKey="Rich M">MM Rich</name></author><author><name sortKey="Bird, Sj" uniqKey="Bird S">SJ Bird</name></author><author><name sortKey="Raps, Ec" uniqKey="Raps E">EC Raps</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rich, Mm" uniqKey="Rich M">MM Rich</name></author><author><name sortKey="Teener, Jw" uniqKey="Teener J">JW Teener</name></author><author><name sortKey="Raps, Ec" uniqKey="Raps E">EC Raps</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bird, Sj" uniqKey="Bird S">SJ Bird</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lefaucher, Jp" uniqKey="Lefaucher J">JP Lefaucher</name></author><author><name sortKey="Nordine, T" uniqKey="Nordine T">T Nordine</name></author><author><name sortKey="Rodriguez, P" uniqKey="Rodriguez P">P Rodriguez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Trojaborg, W" uniqKey="Trojaborg W">W Trojaborg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ramsay, Da" uniqKey="Ramsay D">DA Ramsay</name></author><author><name sortKey="Zochodne, Dw" uniqKey="Zochodne D">DW Zochodne</name></author><author><name sortKey="Robertson, Dm" uniqKey="Robertson D">DM Robertson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zochodne, Dw" uniqKey="Zochodne D">DW Zochodne</name></author><author><name sortKey="Ramsay, Da" uniqKey="Ramsay D">DA Ramsay</name></author><author><name sortKey="Saly, V" uniqKey="Saly V">V Saly</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hanson, P" uniqKey="Hanson P">P Hanson</name></author><author><name sortKey="Dive, A" uniqKey="Dive A">A Dive</name></author><author><name sortKey="Brucher, Jm" uniqKey="Brucher J">JM Brucher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bolton, C" uniqKey="Bolton C">C Bolton</name></author><author><name sortKey="Chen, R" uniqKey="Chen R">R Chen</name></author><author><name sortKey="Wijdicks, E" uniqKey="Wijdicks E">E Wijdicks</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Banwell, Bl" uniqKey="Banwell B">BL Banwell</name></author><author><name sortKey="Mildner, Rj" uniqKey="Mildner R">RJ Mildner</name></author><author><name sortKey="Hassall, Ac" uniqKey="Hassall A">AC Hassall</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Danon, Mj" uniqKey="Danon M">MJ Danon</name></author><author><name sortKey="Carpenter, S" uniqKey="Carpenter S">S Carpenter</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bird, Sj" uniqKey="Bird S">SJ Bird</name></author><author><name sortKey="Rich, Mm" uniqKey="Rich M">MM Rich</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Al Jaberi, M" uniqKey="Al Jaberi M">M Al-Jaberi</name></author><author><name sortKey="Katirji, B" uniqKey="Katirji B">B Katirji</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hsia, Aw" uniqKey="Hsia A">AW Hsia</name></author><author><name sortKey="Hattab, Em" uniqKey="Hattab E">EM Hattab</name></author><author><name sortKey="Katz, Js" uniqKey="Katz J">JS Katz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcloughlin, Dm" uniqKey="Mcloughlin D">DM McLoughlin</name></author><author><name sortKey="Spargo, E" uniqKey="Spargo E">E Spargo</name></author><author><name sortKey="Wassif, Ws" uniqKey="Wassif W">WS Wassif</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Latronico, N" uniqKey="Latronico N">N Latronico</name></author><author><name sortKey="Shehu, I" uniqKey="Shehu I">I Shehu</name></author><author><name sortKey="Seghelini, E" uniqKey="Seghelini E">E Seghelini</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zifko, U" uniqKey="Zifko U">U Zifko</name></author><author><name sortKey="Chen, R" uniqKey="Chen R">R Chen</name></author><author><name sortKey="Remtulla, H" uniqKey="Remtulla H">H Remtulla</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Maher, J" uniqKey="Maher J">J Maher</name></author><author><name sortKey="Rutledge, F" uniqKey="Rutledge F">F Rutledge</name></author><author><name sortKey="Remtulla, H" uniqKey="Remtulla H">H Remtulla</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Spitzer, Ar" uniqKey="Spitzer A">AR Spitzer</name></author><author><name sortKey="Giancarlo, T" uniqKey="Giancarlo T">T Giancarlo</name></author><author><name sortKey="Maher, L" uniqKey="Maher L">L Maher</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="chapter-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Neurology and General Medicine</journal-id><journal-title-group><journal-title>Neurology and General Medicine</journal-title></journal-title-group></journal-meta><article-meta><article-id pub-id-type="pmc">7152411</article-id><article-id pub-id-type="publisher-id">B978-0-443-06707-5.50055-9</article-id><article-id pub-id-type="doi">10.1016/B978-044306707-5.50055-9</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Neurological Complications in Critically Ill Patients</article-title></title-group><contrib-group><contrib contrib-type="author" id="au1"><name><surname>Bolton</surname><given-names>Charles F.</given-names></name></contrib><contrib contrib-type="author" id="au2"><name><surname>Bryan Young</surname><given-names>G.</given-names></name></contrib></contrib-group><contrib-group><contrib contrib-type="editor"><name><surname>Aminoff</surname><given-names>Michael J.</given-names></name><degrees>MD, DSc, FRCP</degrees></contrib></contrib-group><aff>Professor, Department of Neurology, School of Medicine, University of California, San Francisco, California</aff><pub-date pub-type="pmc-release"><day>15</day><month>5</month><year>2009</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub"><year>2008</year></pub-date><pub-date pub-type="epub"><day>15</day><month>5</month><year>2009</year></pub-date><fpage>981</fpage><lpage>997</lpage><permissions><copyright-statement>Copyright © 2008 Elsevier Inc. All rights reserved.</copyright-statement><copyright-year>2008</copyright-year><copyright-holder>Elsevier Inc.</copyright-holder><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions></article-meta></front><body><p id="para94">The term <italic>critical illness</italic> has been widely used for many years to describe the condition of any patient with illness severe enough to be considered at risk for death. In modern general medical and surgical intensive care units (ICUs), where at least 25 percent of patients may have this condition,<xref rid="bib1" ref-type="bibr"><sup>1</sup></xref> it has become synonymous with the syndrome of sepsis and multiple organ failure. This syndrome has probably always been a component of preterminal illness, but before the advent of modern methods of treatment, the syndrome evolved so quickly that the nature of the preterminal events was not considered. However, with the use of intravenous transfusions, antibiotics, activated protein C, and improvements in assisted ventilation, patients are now kept alive for days, weeks, and even months in intensive or critical care units, and as many as 40 percent recover.<xref rid="bib1" ref-type="bibr">1</xref>, <xref rid="bib2" ref-type="bibr">2</xref> Thus, it is now possible to study the syndrome in detail, and its effects on the various major organ systems, including the central and peripheral nervous systems.</p><p id="para95">In the past, sepsis was defined as the systemic response to dividing and invading microorganisms of all types. However, in many instances the offending organism cannot be cultured. For example, blood cultures are negative in half of the patients suspected of being septic. Moreover, the criteria for diagnosing sepsis based on systemic responses are still unsettled. The term <italic>systemic inflammatory response syndrome</italic> (SIRS) should now be applied to a severe clinical insult that arises not only as the result of infection but also as the result of noninfectious processes such as trauma, burns, and pancreatitis.<xref rid="bib3" ref-type="bibr"><sup>3</sup></xref> The chief clinical features of this syndrome are two or more of the following: (1) temperature exceeding 38°C or less than 36°C, (2) heart rate greater than 90 beats/min, (3) respiratory rate greater than 20 breaths/min or arterial partial pressure of carbon dioxide (Paco<sub>2</sub>) less than 32 torr (4.3 kPa), and (4) white blood cell count (WBC) more than 12,000 cells/mm<sup>3</sup> or with more than 10 percent immature (band) forms.<xref rid="bib3" ref-type="bibr"><sup>3</sup></xref> SIRS may be accompanied by hypotension (blood pressure less than 90 mmHg or a reduction of more than 40 mmHg from baseline in the absence of other causes of hypotension).<xref rid="bib4" ref-type="bibr"><sup>4</sup></xref></p><p id="para96">In SIRS, cellular and humoral responses are activated<xref rid="bib2" ref-type="bibr">2</xref>, <xref rid="bib5" ref-type="bibr">5</xref> to produce changes in the microcirculation throughout the body (<xref rid="f1" ref-type="fig">Fig. 52-1</xref>). The cellular response involves epithelial and endothelial cells, macrophages, and neutrophils. These induce the humoral response; proinflammatory mediators are activated locally and include interleukins-1, -2, and -6, tumor necrosis factor (TNF)–α, arachidonic acid, coagulation factors, free oxygen radicals, and proteases. These cellular and humoral factors interact with themselves and with adhesion molecules, which are increased in the blood of septic patients.<xref rid="bib6" ref-type="bibr"><sup>6</sup></xref> Adhesion molecules adhere to leukocytes, platelets, and endothelial cells; they also induce “rolling neutrophils” and fibrin platelet aggregates that obstruct capillary flow. Endothelial damage increases capillary permeability, which induces local tissue edema. Levels of protein C are reduced in sepsis.<xref rid="bib2" ref-type="bibr"><sup>2</sup></xref> Endothelial damage impairs the endothelium-dependent activation of protein C, thus shifting the balance to thrombosis.<xref rid="bib7" ref-type="bibr">7</xref>, <xref rid="bib8" ref-type="bibr">8</xref> Activation of nitric oxide, now known to be the endovascular relaxing factor, causes arteriolar dilation, which may further slow capillary flow. Thus, essential nutrients fail to reach the organ parenchyma. For example, despite adequate oxygenation via mechanical ventilation, there is a severe oxygen debt at the parenchymal level contributing to multiple organ dysfunction.<xref rid="bib5" ref-type="bibr"><sup>5</sup></xref> Considering the profound disturbances of the microcirculation and the impaired delivery of substrates, especially oxygen and glucose, upon which the nervous system depends, it is not surprising that the nervous system is affected. There is no known specific treatment, but it is known that if the underlying sepsis can be brought under control by either medical or surgical means, the various manifestations of the syndrome disappear and full recovery is possible.<fig id="f1"><label>FIGURE 52-1</label><caption><p>Schematic, theoretical presentation of disturbances in the microcirculation to various organs, including brain, peripheral nerve, and muscle, in systemic inflammatory response syndrome (SIRS). The result is impaired perfusion due to excessive vasodilatation through overproduction of nitric oxide, and aggregation of cellular elements through activation of adhesion molecules and deactivation of protein C. Increased capillary permeability causes edema and the potential for entry of toxic substances.</p></caption><graphic xlink:href="gr1"></graphic><attrib>(Adapted with permission from Bolton CF: Neuromuscular manifestations of critical illness. Muscle Nerve 32:140, 2005.)</attrib><permissions><copyright-statement>© 2008 </copyright-statement><copyright-year>2008</copyright-year><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions></fig></p><p id="para97">The patients who are most susceptible are those suffering from multiple injuries or severe medical illness or who have just had major surgery, particularly if they are elderly or have serious underlying disease that may affect their resistance to infection. Early intubation and transfer to the critical care unit is usually necessary. In the course of time, various intravascular lines are inserted, either for treatment or to monitor vital function. There is little doubt that these invasive procedures induce the state of sepsis if it was not already present. Thus, it is generally recognized that patients who have been in the unit for more than 5 days almost invariably become septic and, if that is not controlled, soon develop the syndrome of multiple organ failure.</p><p id="para98">Either the central or peripheral nervous systems may be affected in 70 percent of patients with sepsis and multiple organ failure.<xref rid="bib9" ref-type="bibr"><sup>9</sup></xref> Within hours of the onset of sepsis, a mild encephalopathy develops, termed <italic>septic</italic> or <italic>sepsis-associated encephalopathy.</italic><xref rid="bib9" ref-type="bibr"><sup>9</sup></xref> When deterioration to a state of multiple organ failure occurs, this encephalopathy becomes severe, but it soon subsides if the sepsis is successfully treated. However, the clinician may then note that it is difficult to wean the patient from the mechanical ventilator. If lung and heart disease are excluded, <italic>critical illness polyneuropathy, critical illness myopathy,</italic> or a combination of both (<italic>critical illness neuromyopathy)</italic> is almost always the cause of this circumstance.<xref rid="bib10" ref-type="bibr"><sup>10</sup></xref> However, as with encephalopathy, the polyneuropathy or myopathy eventually disappears if the sepsis does not recur and the patient survives.</p><sec id="cesec1"><title>SEPTIC (SEPSIS-ASSOCIATED) ENCEPHALOPATHY</title><p id="para99">The term <italic>septic encephalopathy</italic> refers to altered brain function related to the presence of microorganisms or their toxins in the blood. This condition has been recognized by surgeons and internists as a component of multiple organ failure, but it has received little systematic study.</p><sec id="cesec2"><title>Clinical Features</title><p id="para100">The clinical diagnosis of septic encephalopathy is one of exclusion. Altered brain function in the febrile patient can be due to a number of conditions other than the sepsis itself (<xref rid="cetable1" ref-type="table">Table 52-1</xref>). Space does not allow a complete discussion of the differential diagnosis, butother entities can usually be ruled out by the history, physical examination, and laboratory tests. It is often necessary to perform a lumbar puncture to exclude bacterial meningitis.<table-wrap position="float" id="cetable1"><label>TABLE 52-1</label><caption><p>Causes of Encephalopathy in Febrile Patients</p></caption><table frame="hsides" rules="groups"><tbody><tr><td align="left"><list list-type="simple" id="celist1"><list-item id="celistitem1"><p id="para1"><bold><italic>Infections</italic></bold></p></list-item><list-item id="celistitem2"><p id="para2">Central nervous system<list list-type="simple" id="celist2"><list-item id="celistitem3"><p id="para3">Bacterial: meningitis, cerebritis, brain abscess, subdural/epidural empyema</p></list-item><list-item id="celistitem4"><p id="para4">Viral: encephalitis</p></list-item><list-item id="celistitem5"><p id="para5">Other: spirochetal, rickettsial, protozoal, helminthic</p></list-item></list></p></list-item><list-item id="celistitem6"><p id="para6">Intracranial thrombophlebitis</p></list-item><list-item id="celistitem7"><p id="para7">Bacterial endocarditis: may produce embolism, meningitis, mycotic aneurysm</p></list-item><list-item id="celistitem8"><p id="para8">Systemic infection</p></list-item><list-item id="celistitem9"><p id="para9">Direct organ damage, e.g., hepatitis</p></list-item><list-item id="celistitem10"><p id="para10">Septic encephalopathy</p></list-item><list-item id="celistitem11"><p id="para11"><bold><italic>Vascular Accidents</italic></bold></p></list-item><list-item id="celistitem12"><p id="para12">Pulmonary emboli</p></list-item><list-item id="celistitem13"><p id="para13">CNS: vertebrobasilar stroke, intracranial hemorrhage</p></list-item><list-item id="celistitem14"><p id="para14"><bold><italic>Mechanical Causes (Trauma)</italic></bold></p></list-item><list-item id="celistitem15"><p id="para15">Cerebral injury</p></list-item><list-item id="celistitem16"><p id="para16">Fat embolism (fractures of long bones)</p></list-item><list-item id="celistitem17"><p id="para17"><bold><italic>Immunological Conditions</italic></bold></p></list-item><list-item id="celistitem18"><p id="para18">Drug fever</p></list-item><list-item id="celistitem19"><p id="para19">Acetylsalicylic acid toxicity</p></list-item><list-item id="celistitem20"><p id="para20">Connective tissue disease</p></list-item><list-item id="celistitem21"><p id="para21"><bold><italic>Heat Stroke</italic></bold></p></list-item><list-item id="celistitem22"><p id="para22"><bold><italic>Metabolic Conditions</italic></bold></p></list-item><list-item id="celistitem23"><p id="para23">Acute adrenal failure</p></list-item><list-item id="celistitem24"><p id="para24">Thyroid storm (hyperthyroidism)</p></list-item><list-item id="celistitem25"><p id="para25">Porphyria</p></list-item><list-item id="celistitem26"><p id="para26"><bold><italic>Reye's Syndrome (Children)</italic></bold></p></list-item><list-item id="celistitem27"><p id="para27"><bold><italic>Neoplasms</italic></bold></p></list-item><list-item id="celistitem28"><p id="para28">Systemic malignancy with organ failure</p></list-item><list-item id="celistitem29"><p id="para29">Brain tumors, primary or secondary: affecting thermoregulation</p></list-item><list-item id="celistitem30"><p id="para30"><bold><italic>Hematological Causes</italic></bold></p></list-item><list-item id="celistitem31"><p id="para31">Hemolytic episodes, e.g., sickle cell disease</p></list-item><list-item id="celistitem32"><p id="para32">Leukemia</p></list-item><list-item id="celistitem33"><p id="para33"><bold><italic>Increased Muscular Activity</italic></bold></p></list-item><list-item id="celistitem34"><p id="para34">Convulsive seizures</p></list-item><list-item id="celistitem35"><p id="para35">Malignant neuroleptic syndrome</p></list-item></list></td></tr></tbody></table></table-wrap></p><p id="para101">We carried out a retrospective study on 12 autopsied patients<xref rid="bib11" ref-type="bibr"><sup>11</sup></xref> and a separate clinical, prospective study involving 69 patients, each with fever and either a positive blood culture or a localized bacterial or fungal infection as inclusion criteria.<xref rid="bib12" ref-type="bibr"><sup>12</sup></xref> Patients with a fever and either a positive blood culture or a localized bacterial or fungal infection were included for both studies. We excluded patients younger than 16 years and those with central nervous system (CNS) disorders unrelated to the febrile illness, preexisting metabolic disorders, and conditions that affect the brain other than by a septic mechanism. In the prospective study, we also excluded patients receiving heavy sedation or analgesics and those receiving skeletal muscle relaxants. For this study, using an arbitrary set of bedside criteria, we classified patients as nonencephalopathic, mildly encephalopathic, and severely encephalopathic. In our classification, nonencephalopathic patients cooperated with testing and passed a series of tests of attention, concentration, orientation, and short-term memory. The mildly encephalopathic patients completed testing but failed to “pass,” and the severely encephalopathic patients were too obtunded to test.</p><p id="para102">The clinical picture is similar to that of diffuse or multifocal encephalopathy in general. The level of consciousness varies from clouding of consciousness to coma. Delirium occurs infrequently, preceding stupor or coma. Mildly encephalopathic patients often show considerable fluctuation in their clinical state, and older individuals become especially confused at night. Attention, concentration, and memory are impaired. Writing disturbances occur, as in other acute confusional states. Paratonic rigidity, or <italic>gegenhalten</italic> (a rate-dependent resistance to passive movement), is almost universal in encephalopathic patients. Tremor, asterixis, and multifocal myoclonus occur in 10 to 25 percent of noncomatose encephalopathic patients. Alterations of pupillary size or reaction, abnormalities of individual cranial nerves, focal neurological signs, or convulsive seizures typically do not occur. Hemiparesis or gaze palsy was found in 6 and focal or generalized convulsive seizures occurred in 5 of the 12 patients in our retrospective (autopsy) series, but were rare in our prospective study. The difference may be accounted for, in part, by the duration of sepsis in the autopsy group and the pathological findings (discussed later).</p><p id="para103">As expected, the mortality rate in our prospective study was significantly greater among the severely encephalopathic patients than in the other groups.<xref rid="bib12" ref-type="bibr"><sup>12</sup></xref> Nearly half of the severely encephalopathic patients but none of the nonencephalopathic patients died. About 25 percent of the nonencephalopathic patients had clinical and electrophysiological evidence of mild peripheral neuropathy. Among the moderately and severely encephalopathic patients, 50 percent and 75 percent, respectively, had critical illness polyneuropathy; among the patients in the latter group, the polyneuropathy was usually severe.<xref rid="bib12" ref-type="bibr"><sup>12</sup></xref> The time courses of the encephalopathy and the polyneuropathy often differed. The encephalopathy peaked earlier and cleared long before the polyneuropathy in the course of the septic illness. Some severely encephalopathic patients were obtunded for a month or more, but CNS function improved soon after the infection and systemic metabolic problems were controlled or resolved.</p><p id="para104">There was a strong association of adult respiratory distress syndrome with severe encephalopathy. Transient hypotension was more common at the onset of sepsis in the severely encephalopathic patients, although there was no difference in blood pressure among the three groups at their initial neurological assessment. The degree of prior hypotension was not sufficient to account for the neurological findings. Interestingly, none of the following correlated with the severity of encephalopathy: age (a trend for correlation of age and degree of encephalopathy did not achieve statistical significance), gender, temperature, or type of organism (no difference between gram-positive and gram-negative organisms, but patients with <italic>Candida,</italic> although few in number, were more severely affected).</p></sec><sec id="cesec3"><title>Laboratory Features</title><p id="para105">The electroencephalogram (EEG) is a sensitive monitor of septic encephalopathy. We found it to be more sensitive than our arbitrary clinical assessment of mental status, in that some nonencephalopathic patients had mild EEG abnormalities that resolved on subsequent recordings. The mildest EEG change consisted of mild, generalized slowing (theta activity). More severe EEG abnormalities, which correlated with more profound depression of consciousness, consisted of greater slowing (delta activity), triphasic waves, or a burst-suppression pattern (<xref rid="f2" ref-type="fig">Fig. 52-2</xref>).<xref rid="bib13" ref-type="bibr"><sup>13</sup></xref> Using computational nonlinear analysis techniques, Straver and colleagues showed that EEG features correlated with the severity of illness and that the EEG became disorganized with greater severity of illness, suggesting a shift in the processing ability of the brain.<xref rid="bib14" ref-type="bibr"><sup>14</sup></xref> Although there is a direct relationship between the degree of EEG abnormality and mortality, some patients with even the most severe categories of abnormality recover. Thus, the EEG cannot be used to predict a hopeless prognosis in septic encephalopathy.<xref rid="bib13" ref-type="bibr">13</xref>, <xref rid="bib14" ref-type="bibr">14</xref><fig id="f2"><label>FIGURE 52-2</label><caption><p>Electroencephalograms (EEGs) from patients with septic encephalopathy. <bold>A,</bold> Patient with mild encephalopathy. The EEG shows a mild excess of low-voltage 6- to 7-Hz theta rhythms in both left (odd-numbered electrode placements) and right (even-numbered placements) hemispheres. <bold>B</bold> to <bold>D,</bold> Severely encephalopathic patients. <bold>B,</bold> Bilateral intermittent rhythmic delta (<3 Hz) waves on a background of mild slowing. <bold>C,</bold> Triphasic waves. <bold>D,</bold> Burst-suppression pattern.</p></caption><graphic xlink:href="gr2"></graphic></fig></p><p id="para106">Serum levels of creatinine and bilirubin showed a direct, linear correlation with the severity of the encephalopathy.<xref rid="bib13" ref-type="bibr"><sup>13</sup></xref> Although hyperventilation is a feature of sepsis, there were no significant differences in blood pH, bicarbonate, or Pco<sub>2</sub> among the three groups. In our retrospective study, a drop in platelet count was associated with the development of brain purpura and neurological signs.</p><p id="para107">We did not find any abnormalities in the cerebrospinal fluid (CSF) or on unenhanced computed tomography (CT) brain scans in any of our patients, including those who showed microabscesses at autopsy.<xref rid="bib13" ref-type="bibr"><sup>13</sup></xref></p><p id="para108">Using transcranial Doppler studies, Straver and colleagues have shown an increase in cerebral mean and end-diastolic flow velocities in the brains of patients with septic encephalopathy.<xref rid="bib15" ref-type="bibr"><sup>15</sup></xref> The severity of the systemic sepsis correlated with the increased flow velocity. This finding implies that patients with severe septic encephalopathy are at risk for ischemic cerebral damage. As a corollary, care should be taken to avoid hyperventilation in such patients. The drop in Paco<sub>2</sub> could lead to a further decrease in cerebral perfusion.</p></sec><sec id="cesec4"><title>Autopsy Findings</title><p id="para109">In our autopsy series, 8 of the 12 patients had disseminated microabscesses in the brain, chiefly in the cerebral cortex and subcortical white matter. Because there was some reaction in the brain around the microabscesses, these lesions did not appear to be just agonal phenomena.</p><p id="para110">Four patients had increased protoplasmic astrocytes in the cerebral cortex. They were unrelated to the microabscesses and probably reflected a metabolic encephalopathy. Three patients had central pontine myelinolysis, a condition that has been related to overcorrection of hyponatremia, as discussed in Chapter 19. Vascular lesions were found in six patients: five had multiple cerebral infarcts (one terminal), and one who had thrombocytopenia before death had brain purpura. We have had only two autopsies in our prospective series, and neither showed abnormalities in the brain.</p><p id="para111">The significance of the aforementioned pathological findings is not clear, mainly because these patients had been septic for weeks. There is no way of knowing with certainty when the lesions found at autopsy actually developed. It is possible that focal signs and seizures could have been produced by the lesions, but the microabscesses and vascular lesions were small and multifocal. Furthermore, occasionally focal signs and focal seizures can occur in metabolic encephalopathies.</p><p id="para112">In a literature search, we could not find a study of encephalopathy in septic humans comparable to ours. As we reported in this chapter in the third edition of this book, “watershed” cerebral infarctions have been described in patients who died of septic shock, but without clinical correlations. Such watershed infarcts are ischemic lesions at or near the terminal portions of the anterior, middle, and posterior cerebral arteries, and they are typically associated clinically with bibrachial paralysis, which we have never encountered in our patients. Other authors have chosen cases with microabscesses at postmortem examination, rather than starting with clinically septic patients. There is one report of a patient dying of sepsis due to a breast abscess who showed sagittal sinus thrombosis and thrombophlebitis of cerebral cortical veins.</p></sec><sec id="cesec5"><title>Pathogenesis</title><p id="para113">The pathogenesis of septic encephalopathy remains uncertain; however, there are a number of possible mechanisms that are not mutually exclusive. Since mild cases resolve without sequelae, it is likely that reversible, metabolic factors are operative. The cases with neurological deficits may have one or more of the structural lesions we have found at postmortem; for example, multifocal, microscopic ischemic lesions and microabscess of the brain.</p><p id="para114">The principal chemical mediators of the sepsis syndrome are cytokines, chemical messengers released from lymphocytes and macrophages. These play a key role in the alteration of the microcirculation of the brain (<xref rid="f1" ref-type="fig">Fig. 52-1</xref>), increased blood–brain barrier, altered metabolism of the body, and derangements of the brain's extracellular milieu and neurotransmitter balance.</p><p id="para115">Multifocal brain ischemia may relate to activation of “adhesion molecules,” the selectin and integrin group, causing leukocyte adherence or “rolling leukocytes,” which may be an early cause of endothelial cell damage.<xref rid="bib5" ref-type="bibr"><sup>5</sup></xref> This affects nitric oxide synthesis by the endothelium. Nitric oxide is the “vascular relaxing factor”; its synthesis is increased by endotoxin and cytokines in sepsis, leading to reduced peripheral vascular resistance and hypotension. Although this seems counterproductive, such multifocal vasodilatation helps ensure adequate organ perfusion in sepsis; inhibition of nitric oxide production can lead to decreased organ perfusion and a fall in oxygen extraction by tissues.<xref rid="bib16" ref-type="bibr"><sup>16</sup></xref> Nitric oxide plays an important role in regulating brain circulation and the permeability of the blood–brain barrier.<xref rid="bib17" ref-type="bibr"><sup>17</sup></xref> Endothelial damage in sepsis may then compromise regional cerebral blood-flow and account for the multifocal, dynamic increases in blood–brain (and possibly blood–nerve) permeability mentioned earlier. Uncommonly, brain lesions relate to focal brain or disseminated intravascular coagulation.</p><p id="para116">An increase in blood–brain barrier permeability in SIRS can produce multifocal vasogenic edema and alter the composition of the brain's extracellular fluid. Tumor necrosis factor–alpha and interferon-gamma increase the permeability of cerebral endothelial cells.<xref rid="bib18" ref-type="bibr">18</xref>, <xref rid="bib19" ref-type="bibr">19</xref> It has also been shown that the perivascular end-feet of astrocytes are disrupted in pigs with fecal peritonitis injected with endotoxin.<xref rid="bib20" ref-type="bibr"><sup>20</sup></xref> Alterations in the adrenergic system may also play a role: the β<sub>2</sub>-adenoreceptor agonist dopexamine inhibits brain edema in animal models of sepsis, while the α<sub>1</sub>-adenoreceptor blocker methoxamine prevents it. The combined effect increases tissue edema and alters the chemical milieu of the interstitial fluid of the brain. Cytokines themselves may directly affect brain function. Again, their access to the brain may be facilitated by alterations in blood–brain barrier function. When directly injected into the brain or ventricles of animals, interleukin-1 and interleukin-2 alter behavior and EEG frequencies.<xref rid="bib21" ref-type="bibr"><sup>21</sup></xref> Interleukin-1 facilitates sleep and induces fever by its effects on the hypothalamus. Some of these effects relate to activation of opiate receptors in the brain; the possibility of effects on other peptide systems in the brain remains to be explored. Proinflammatory cytokines may also activate STAT 3, a transcription molecule, in astrocytes.<xref rid="bib22" ref-type="bibr"><sup>22</sup></xref> The significance of this is not clear, but astrocytes play a key role in maintaining a homeostatic environment for CNS neurons. Lipopolysaccharides and proinflammatory cytokines, including interferon-gamma, upregulate inducible nitric oxide synthase (i-NOS) in astrocytes.<xref rid="bib23" ref-type="bibr"><sup>23</sup></xref> This leads to the production of reactive oxygen species such as nitric oxide and superoxide, causing oxidative stress for astrocytes and neurons of the brain.</p><p id="para117">Transport of amino acids across the blood–brain barrier is altered in sepsis; that is, there is an alteration in transcapillary transport systems. This could alter the chemical milieu of the brain cells; substances normally excluded from the brain may gain access to neuronal receptors. These include drugs as well as the relative amounts of certain endogenous substances. The latter include higher ratios of aromatic to branched-chain amino acids (increased in the plasma because of altered metabolism in liver and muscle) and increased exposure to other peptides and hormones. Such changes play a role in the documented alteration of certain putative neurotransmitters in sepsis, such as serotonin, norepinephrine, and dopamine. Additional neurotransmitter alterations include increased serotonin turnover and decreased noradrenergic transmission in the brain in sepsis.<xref rid="bib24" ref-type="bibr"><sup>24</sup></xref> A similar derangement in neurotransmitter balance occurs in hepatic and uremic encephalopathy. Astrocytic dysfunction, mentioned earlier, contributes to increases in extracellular glutamate, an excitotoxic neurotransmitter that can cause neuronal death or seizures through activation of <italic>N</italic>-methyl-d-aspartate (NMDA) receptors.<xref rid="bib25" ref-type="bibr"><sup>25</sup></xref></p><p id="para118">The brain may also be affected indirectly because of the failure or altered metabolism of other organ systems. Within 5 hours from the onset of sepsis, the liver shows impaired ability to clear indocyanine green. We have found an elevated serum bilirubin concentration in sepsis, with a direct relationship to the severity of the encephalopathy.<xref rid="bib12" ref-type="bibr"><sup>12</sup></xref> Endogenous benzodiazepine-like substance is also increased in hepatic failure.<xref rid="bib26" ref-type="bibr"><sup>26</sup></xref> Although this has not been explored in sepsis, we have found that some patients with septic encephalopathy may improve with flumazenil, a γ-aminobutyric acid–A antagonist, even in the absence of exogenous benzodiazepines (unpublished observations).</p><p id="para119">In advanced sepsis, the failure of other organs (e.g., kidneys, heart) may, in turn, affect brain function and lead to an encephalopathy.</p><p id="para120">In intensive care, iatrogenic factors should always be considered. Sedative drugs, particularly opiates and benzodiazepines, are commonly used to ease the use of assisted ventilation. If renal impairment occurs, opiate clearance is reduced, and this may lead to prolonged obtundation. Brain function of critically ill patients, as reflected by the EEG, is highly sensitive to midazolam; the same probably applies to other benzodiazepines.<xref rid="bib27" ref-type="bibr"><sup>27</sup></xref> On a clinical basis it is difficult to determine whether encephalopathy is due to sepsis, sedative drugs, or both. Daily interruption of sedative drugs may partially overcome this difficulty.<xref rid="bib28" ref-type="bibr"><sup>28</sup></xref> Continuous EEG monitoring may also be helpful.</p><p id="para121">Total parenteral nutrition is sometimes associated with hypophosphatemia or hyperosmolality, both of which may cause coma. High serum levels of penicillin, usually in association with renal impairment, may cause seizures, as may the newer antibiotic imipenem.<xref rid="bib29" ref-type="bibr"><sup>29</sup></xref> Central pontine myelinolysis may complicate the sudden increases of plasma osmolality in critically ill patients.</p><p id="para122">In summary, there are multiple, non–mutually exclusive mechanisms to explain septic encephalopathy. Many of these are reversible, but some mechanisms may lead to neuronal death, for example, oxidative stress, excitotoxicity, microinfarctions or osmotic demyelination. These are summarized in <xref rid="f3" ref-type="fig">Figure 52-3</xref>.<fig id="f3"><label>FIGURE 52-3</label><caption><p>This graphic represents the three principal cell types relevant to septic encephalopathy: the endothelial cell in brain capillaries, the astrocyte, and the neuron. Conceptually the encephalopathy can be divided into dysfunction that is reversible or irreversible, with structural changes in the brain. Further discussion is provided in the text. AA, amino acid; ARAS, ascending reticular activating system; BBB, blood–brain barrier; fx, function; rCBF, regional cerebral blood-flow.</p></caption><graphic xlink:href="gr3"></graphic><attrib>(From Wilson JX, Young GB: Progress in Neurosciences: Sepsis-associated encephalopathy—evolving concepts. Can J Neurol Sci 2003;30:98, with permission.)</attrib><permissions><copyright-statement>© 2008 </copyright-statement><copyright-year>2008</copyright-year><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions></fig></p></sec></sec><sec id="cesec6"><title>NEUROMUSCULAR PROBLEMS IN THE CRITICAL CARE UNIT</title><p id="para123">The list of conditions that can affect the neuromuscular system in patients in the critical care unit is remarkably long and potentially involves dysfunction of the entire nervous system (<xref rid="cetable2" ref-type="table">Table 52-2</xref>). To pinpoint the site of dysfunction may be extremely difficult, especially in the setting of the critical care unit. History taking is often impossible, as an endotracheal tube prevents speech, and the often associated encephalopathy prevents reliable communication of any type. The limbs are not easily assessed, owing to the presence of intravenous lines, splints, bandages, and so forth. Thus, although a neurological examination tailored to the comatose patient may provide some assessment of the nervous system, we have found that the presence and severity of either brain or peripheral nervous system dysfunction is often difficult to document by purely clinical methods.<table-wrap position="float" id="cetable2"><label>TABLE 52-2</label><caption><p>Differential Diagnosis of Neuromuscular Signs in Critically Ill Patients</p></caption><table frame="hsides" rules="groups"><tbody><tr><td align="left"><list list-type="simple" id="celist3"><list-item id="celistitem36"><p id="para36"><bold><italic>Encephalopathy</italic></bold></p></list-item><list-item id="celistitem37"><p id="para37">Septic</p></list-item><list-item id="celistitem38"><p id="para38">Anoxic-ischemic</p></list-item><list-item id="celistitem39"><p id="para39">Other</p></list-item><list-item id="celistitem40"><p id="para40"><bold><italic>Myelopathy</italic></bold></p></list-item><list-item id="celistitem41"><p id="para41">Anoxic-ischemic</p></list-item><list-item id="celistitem42"><p id="para42">Traumatic</p></list-item><list-item id="celistitem43"><p id="para43">Other</p></list-item><list-item id="celistitem44"><p id="para44"><bold><italic>Neuropathy</italic></bold></p></list-item><list-item id="celistitem45"><p id="para45">Critical illness polyneuropathy</p></list-item><list-item id="celistitem46"><p id="para46">Thiamine deficiency</p></list-item><list-item id="celistitem47"><p id="para47">Vitamin E deficiency</p></list-item><list-item id="celistitem48"><p id="para48">Nonspecific nutritional deficiency</p></list-item><list-item id="celistitem49"><p id="para49">Pyridoxine abuse</p></list-item><list-item id="celistitem50"><p id="para50">Hypophosphatemia</p></list-item><list-item id="celistitem51"><p id="para51">Aminoglycoside toxicity</p></list-item><list-item id="celistitem52"><p id="para52">Penicillin toxicity</p></list-item><list-item id="celistitem53"><p id="para53">Guillain–Barré syndrome</p></list-item><list-item id="celistitem54"><p id="para54">Motor neuron disease</p></list-item><list-item id="celistitem55"><p id="para55">Porphyria</p></list-item><list-item id="celistitem56"><p id="para56">Carcinomatous polyneuropathy</p></list-item><list-item id="celistitem57"><p id="para57">Compression neuropathy</p></list-item><list-item id="celistitem58"><p id="para58">Diphtheria</p></list-item><list-item id="celistitem59"><p id="para59"><bold><italic>Neuromuscular Transmission Defects</italic></bold></p></list-item><list-item id="celistitem60"><p id="para60">Neuromuscular blocking agents</p></list-item><list-item id="celistitem61"><p id="para61">Aminoglycoside toxicity</p></list-item><list-item id="celistitem62"><p id="para62">Myasthenia gravis</p></list-item><list-item id="celistitem63"><p id="para63">Lambert–Eaton myasthenic syndrome</p></list-item><list-item id="celistitem64"><p id="para64">Hypocalcemia</p></list-item><list-item id="celistitem65"><p id="para65">Hypomagnesemia</p></list-item><list-item id="celistitem66"><p id="para66">Organophosphate poisoning</p></list-item><list-item id="celistitem67"><p id="para67">Wound botulism</p></list-item><list-item id="celistitem68"><p id="para68">Tick-bite paralysis</p></list-item><list-item id="celistitem69"><p id="para69"><bold><italic>Myopathy</italic></bold></p></list-item><list-item id="celistitem70"><p id="para70">Critical illness (myosin-deficient) myopathy</p></list-item><list-item id="celistitem71"><p id="para71">Cachexia</p></list-item><list-item id="celistitem72"><p id="para72">Acute rhabdomyolysis</p></list-item><list-item id="celistitem73"><p id="para73">Acute necrotizing myopathy of intensive care</p></list-item><list-item id="celistitem74"><p id="para74">Electrolyte disturbances: potassium, phosphate, calcium, magnesium</p></list-item><list-item id="celistitem75"><p id="para75">Corticosteroid myopathy</p></list-item><list-item id="celistitem76"><p id="para76">Muscular dystrophy</p></list-item><list-item id="celistitem77"><p id="para77">Polymyositis</p></list-item><list-item id="celistitem78"><p id="para78">Acid maltase deficiency</p></list-item></list></td></tr></tbody></table></table-wrap></p><p id="para124">De Jonghe and co-workers in France tested muscle strength in critically ill patients when they became alert enough to voluntarily activate the muscles.<xref rid="bib30" ref-type="bibr"><sup>30</sup></xref> However, they found weakness in only 25 percent, less than half of those identified by electrophysiological methods.<xref rid="bib10" ref-type="bibr"><sup>10</sup></xref> Thus, we routinely use electrophysiology to assess such patients. Using electrophysiological tests, we have found that both septic encephalopathy and critical illness polyneuropathy are almost invariable manifestations of the sepsis and multiple organ failure syndrome, and the other conditions listed in the table are only rarely involved. In fact, these other conditions are usually evident before the patient has been admitted to the critical care unit and are the obvious reason for neuromuscular respiratory failure. Myasthenia gravis and Guillain–Barré syndrome are good examples, although in some instances it is necessary to exclude these conditions systematically. Repetitive nerve stimulation may be required to investigate for a defect in neuromuscular transmission. Such studies have revealed the presence of myasthenia gravis or the Lambert–Eaton myasthenic syndrome not previously suspected.<xref rid="bib31" ref-type="bibr">31</xref>, <xref rid="bib32" ref-type="bibr">32</xref> Electrophysiological studies may disclose motor neuron disease for the first time.<xref rid="bib33" ref-type="bibr"><sup>33</sup></xref> Muscle biopsy may be necessary to exclude primary myopathies such as polymyositis or a metabolic disturbance such as acid maltase deficiency. Except for critical illness polyneuropathy, the Guillain–Barré syndrome is, in our experience, the most common neuromuscular problem seen in the unit. It can almost invariably be recognized by clinical features occurring prior to admission to the critical care unit, by the pattern of abnormalities on electromyography (EMG) and nerve conduction studies, and by CSF examinations.</p><p id="para125">The following sections focus on the major neuromuscular conditions to be considered in critically ill patients being managed in critical care units.</p><sec id="cesec7"><title>Critical Illness Polyneuropathy</title><p id="para126">Critical illness polyneuropathy (<xref rid="cetable3" ref-type="table">Table 52-3</xref>) is a predominantly motor, axonal polyneuropathy occurring as a complication of the systemic inflammatory response (septic) syndrome in 50 to 70 percent of patients with that syndrome.<xref rid="bib34" ref-type="bibr">34</xref>, <xref rid="bib35" ref-type="bibr">35</xref>, <xref rid="bib36" ref-type="bibr">36</xref>, <xref rid="bib37" ref-type="bibr">37</xref>, <xref rid="bib38" ref-type="bibr">38</xref> Since as many as 50 percent of patients in major medical and surgical critical care units have the syndrome, critical illness polyneuropathy must now be regarded as a particularly common neuromuscular disorder. Critical illness myopathy may be common in units that frequently use neuromuscular blocking agents and steroids.<xref rid="bib39" ref-type="bibr"><sup>39</sup></xref><table-wrap position="float" id="cetable3"><label>TABLE 52-3</label><caption><p>Generalized Neuromuscular Conditions Associated With Critical Illness</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left">Condition</th><th align="left">Incidence</th><th align="left">Clinical Features</th><th align="left">Electrophysiological Findings</th><th align="left">Serum Creatine Kinase Level</th><th align="left">Muscle Biopsy</th><th align="left">Prognosis</th></tr></thead><tbody><tr><td colspan="7" align="left"><bold><italic>Polyneuropathy</italic></bold></td></tr><tr><td align="left">Critical illness polyneuropathy</td><td align="left">Common</td><td align="left">Flaccid limbs and respiratory weakness</td><td align="left">Axonal degeneration of motor and sensory fibers</td><td align="left">Nearly normal</td><td align="left">Denervation atrophy</td><td align="left">Variable</td></tr><tr><td colspan="7" align="left"><bold><italic>Neuromuscular Transmission Defect</italic></bold></td></tr><tr><td align="left">Transient neuromuscular blockade</td><td align="left">Common with neuromuscular blocking agents</td><td align="left">Flaccid limbs and respiratory weakness</td><td align="left">Abnormal repetitive nerve stimulation studies</td><td align="left">Normal</td><td align="left">Normal</td><td align="left">Good</td></tr><tr><td colspan="7" align="left"><bold><italic>Critical Illness Myopathy</italic></bold></td></tr><tr><td align="left">Thick-filament myosin loss</td><td align="left">Common with steroids, neuromuscular blocking agents, and sepsis</td><td align="left">Flaccid limbs and respiratory weakness</td><td align="left">Abnormal spontaneous activity</td><td align="left">Mildly elevated</td><td align="left">Loss of thick (myosin) filaments</td><td align="left">Good</td></tr><tr><td align="left">Rhabdomyolysis</td><td align="left">Rare</td><td align="left">Flaccid limbs</td><td align="left">Near normal</td><td align="left">Markedly elevated (myoglobinuria)</td><td align="left">Normal or mild necrosis</td><td align="left">Good</td></tr><tr><td align="left">Necrotizing myopathy of intensive care</td><td align="left">Rare</td><td align="left">Flaccid weakness and myoglobinuria</td><td align="left">Severe myopathy</td><td align="left">Markedly elevated, myoglobinuria</td><td align="left">Marked necrosis</td><td align="left">Poor</td></tr><tr><td align="left">Disuse (cachectic) myopathy</td><td align="left">Common?</td><td align="left">Muscle wasting</td><td align="left">Normal</td><td align="left">Normal</td><td align="left">Normal or type II fiber atrophy</td><td align="left">Good</td></tr><tr><td align="left">Combined polyneuropathy and myopathy</td><td align="left">Common</td><td align="left">Flaccid limbs and respiratory weakness</td><td align="left">Indicate combined polyneuropathy and myopathy</td><td align="left">Variable</td><td align="left">Denervation atrophy and myopathy</td><td align="left">Variable</td></tr></tbody></table></table-wrap></p><p id="para127">The first, and often the only, clinical sign of critical illness polyneuropathy is respiratory muscle weakness, manifested as a difficulty in weaning from the mechanical ventilator. Other neuromuscular causes of difficulty in weaning may be trauma to the phrenic nerve, neuromuscular transmission defect, primary myopathy, and disorders of central drive due to an associated encephalopathy.<xref rid="bib31" ref-type="bibr"><sup>31</sup></xref> In severe critical illness polyneuropathy there are weak or absent movements of the limbs, even when the limbs are stimulated distally by pressure over the nail beds. Tendon reflexes that were previously present cannot be elicited. By contrast, head, face, and jaw movements are relatively preserved. In two of our patients, this absence of movement in the extremities but preservation of movement of the head had erroneously been diagnosed as resulting from high cervical spinal cord disease. Patients with lesser degrees of polyneuropathy show more equivocal signs, with variably weak muscles, particularly distally, and reduced or absent tendon reflexes, notably at the ankles. However, many patients have no clinical signs of neuromuscular disease. The polyneuropathy tends to be more severe the longer that the patient is in the unit.</p><p id="para128">Electrophysiological studies clearly establish the presence of a peripheral neuropathy and document its severity.<xref rid="bib38" ref-type="bibr"><sup>38</sup></xref> Upper- and lower-limb motor and sensory conduction studies initially reveal only a reduction in the amplitude of compound muscle and sensory nerve action potentials, with no change in latency or conduction velocity. The duration of the compound muscle action potential (CMAP) may be prolonged, suggesting primary dysfunction of the muscle fiber membrane in addition to denervation (<xref rid="f4" ref-type="fig">Fig. 52-4</xref>).<xref rid="bib10" ref-type="bibr"><sup>10</sup></xref> Then, within a matter of 2 weeks, fibrillation potentials and positive sharp waves appear in muscle, and sensory and compound muscle action potentials are further reduced. Even in the more advanced stages of critical illness polyneuropathy, conduction velocity and distal latencies remain relatively normal, emphasizing the purely axonal, degenerative nature of the neuropathy.<fig id="f4"><label>FIGURE 52-4</label><caption><p>Measurement of compound thenar muscle action potentials at the onset of sepsis <bold>(A)</bold> and 3 weeks later <bold>(B).</bold> Note the marked decline in amplitude and increase in duration, without change in latency, on stimulation of the median nerve at the wrist and elbow. These changes suggest primary dysfunction of the muscle fiber membrane in addition to denervation.</p></caption><graphic xlink:href="gr4"></graphic><attrib>(From Bolton CF: Evidence of neuromuscular dysfunction in the early stages of the systemic inflammatory response syndrome. Intensive Care Med 19:1179, 2000, with permission.)</attrib><permissions><copyright-statement>© 2008 </copyright-statement><copyright-year>2008</copyright-year><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions></fig></p><p id="para129">Comprehensive examination of the entire nervous system at autopsy, plus nerve and muscle biopsy, has revealed that there is a primary axonal degeneration of motor and sensory fibers, particularly involving distal nerve fibers (<xref rid="f5" ref-type="fig">FIGURE 52-5</xref>, <xref rid="f6" ref-type="fig">FIGURE 52-6</xref>).<xref rid="bib36" ref-type="bibr">36</xref>, <xref rid="bib40" ref-type="bibr">40</xref> There is a resulting denervation atrophy of muscle; histopathological examination during the acute phase reveals scattered, angulated fibers and later shows grouped atrophy (<xref rid="f7" ref-type="fig">Fig. 52-7</xref>). Neither the nerve nor the muscle shows any inflammatory change. Aside from chromatolysis of the anterior horn cells secondary to the peripheral axonal injury, the CNS is spared. Axonal degeneration of intercostal and phrenic nerves and denervation atrophy of respiratory muscles explain the respiratory insufficiency. Latronico and associates found that some patients have abnormal electrophysiological but normal biopsy findings of nerve and muscle, suggesting that functional changes precede structural alterations.<xref rid="bib40" ref-type="bibr"><sup>40</sup></xref><fig id="f5"><label>FIGURE 52-5</label><caption><p>Transverse section of the superficial peroneal nerve showing severe axonal degeneration and loss of myelinated fibers. (Toluidine blue; original magnification 773×.)</p></caption><graphic xlink:href="gr5"></graphic><attrib>(From Zochodne DW, Bolton CF, Wells GA, et al: Critical illness polyneuropathy: a complication of sepsis and multiple organ failure. Brain 110:819, 1987, with permission.)</attrib><permissions><copyright-statement>© 2008 </copyright-statement><copyright-year>2008</copyright-year><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions></fig><fig id="f6"><label>FIGURE 52-6</label><caption><p>Longitudinal section of the deep peroneal nerve demonstrating axonal degeneration and loss of myelinated fibers. (Toluidine blue; original magnification 778×.)</p></caption><graphic xlink:href="gr6"></graphic><attrib>(From Zochodne DW, Bolton CF, Wells GA, et al: Critical illness polyneuropathy: a complication of sepsis and multiple organ failure. Brain 110:819, 1987, with permission.)</attrib><permissions><copyright-statement>© 2008 </copyright-statement><copyright-year>2008</copyright-year><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions></fig><fig id="f7"><label>FIGURE 52-7</label><caption><p>Transverse section of iliopsoas muscle showing scattered and grouped atrophic fibers consistent with denervation atrophy. (Hematoxylin and eosin; original magnification 195×.)</p></caption><graphic xlink:href="gr7"></graphic><attrib>(From Zochodne DW, Bolton CF, Wells GA, et al: Critical illness polyneuropathy: a complication of sepsis and multiple organ failure. Brain 110:819, 1987, with permission.)</attrib><permissions><copyright-statement>© 2008 </copyright-statement><copyright-year>2008</copyright-year><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions></fig></p><p id="para130">The mechanism of the polyneuropathy is not known. However, our investigations have excluded potential causes of polyneuropathy, including Guillain–Barré syndrome, various toxins, drugs (particularly antibiotics), and nutritional deficiency.<xref rid="bib41" ref-type="bibr"><sup>41</sup></xref> It is our belief that the polyneuropathy is probably caused by the same fundamental defect that affects all organ systems in the critical illness syndrome through involvement of the microcirculation (<xref rid="f1" ref-type="fig">Fig. 52-1</xref>). We speculate<xref rid="bib41" ref-type="bibr"><sup>41</sup></xref> that the primary axonal damage may be due to involvement of axonal transport systems, which are known to be energy-dependent; this fact may explain why predominantly distal nerve segments are involved. Moreover, it is known that the blood–nerve barrier, in contrast to the blood–brain barrier, shows increased permeability to histamine and serotonin. Several mediators of the septic syndrome are known to have histamine-like action. Circulating “toxins” could potentially gain access to the endoneurial space and directly damage the axon. It is also possible that disturbance of the microcirculation, as has been postulated to occur in sepsis and multiple organ failure, is the mechanism by which these events in peripheral nerve are initiated.</p><p id="para131">Our studies provide no evidence that the use of antibiotics causes the polyneuropathy. Indeed, because successful treatment of the sepsis results in improvement in the polyneuropathy, we advise that all medical and surgical means of improving the sepsis and multiple organ failure be instituted. Moreover, all critical care units should use whatever methods are necessary to avoid sepsis (e.g., use of sterile techniques and avoidance of invasive procedures unless absolutely necessary). Although we have no evidence that the polyneuropathy is due to nutritional deficiency, it seems prudent to administer total parenteral or enteral nutrition from the start of critical illness. Those individuals responsible for physical therapy and rehabilitation should be aware of the nature and severity of the polyneuropathy, so that they will take it into account as the patient gradually recovers.<xref rid="bib42" ref-type="bibr"><sup>42</sup></xref></p><p id="para132">Intravenous immune globulin has been widely used to treat sepsis but appears to have little effect on critical illness polyneuropathy.<xref rid="bib43" ref-type="bibr">43</xref>, <xref rid="bib44" ref-type="bibr">44</xref> Interventions to interrupt the septic cascade utilizing monoclonal and polyclonal antibodies directed against bacterial endotoxin, oxygen radical scavengers, platelet activating factor receptor antagonists, and hemofiltration techniques and plasma exchange have had little effect on the septic syndrome.<xref rid="bib10" ref-type="bibr"><sup>10</sup></xref> Administration of recombinant activator protein 1 to reduce intravascular thrombosis improved morbidity and mortality, but polyneuropathy was not evaluated.<xref rid="bib2" ref-type="bibr"><sup>2</sup></xref></p><p id="para133">The most interesting recent development was the well-designed study by van den Berghe and associates showing that better control of blood glucose levels utilizing insulin not only improves morbidity and mortality but also reduces the incidence of critical illness polyneuropathy.<xref rid="bib45" ref-type="bibr"><sup>45</sup></xref></p></sec><sec id="cesec8"><title>Motor Neuropathy and Neuromuscular Blocking Agents</title><p id="para134">Polyneuropathy may develop in patients who have been in the critical care unit for several days, or possibly weeks, and received competitive neuromuscular blocking agents, such as pancuronium bromide or the shorter-acting vecuronium, to ease mechanical ventilation.<xref rid="bib10" ref-type="bibr"><sup>10</sup></xref> These agents will have been used for longer than 48 hours, occasionally for days or weeks. When these agents are discontinued, difficulty in weaning the patient from the ventilator and limb paralysis are noted. The serum creatine kinase (CK) level is mildly or moderately elevated. Electrophysiological testing sometimes reveals a defect in neuromuscular transmission. If present, it will be demonstrated on slower rates of stimulation, as expected with a postsynaptic defect. There is evidence of severe primary axonal degeneration of predominantly motor fibers on nerve conduction and needle EMG studies. Muscle biopsy shows varying degrees of denervation atrophy and muscle necrosis.</p><p id="para135">Although the mechanism of this neuropathy is unknown, we believe that sepsis is an important underlying factor in the condition of most, if not all, of these patients.<xref rid="bib38" ref-type="bibr"><sup>38</sup></xref> Thus, if the various systemic complications can be treated successfully, the neuromuscular condition itself improves spontaneously and good recovery may occur, sometimes quite rapidly. We<xref rid="bib36" ref-type="bibr">36</xref>, <xref rid="bib38" ref-type="bibr">38</xref> and others<xref rid="bib37" ref-type="bibr">37</xref>, <xref rid="bib40" ref-type="bibr">40</xref>, <xref rid="bib46" ref-type="bibr">46</xref> have failed to implicate neuromuscular blocking agents as a cause of critical illness polyneuropathy. However, the neuromuscular blocking agent probably has an additional toxic effect on nerve and muscle, and its use should be avoided, if possible.</p></sec><sec id="cesec9"><title>Chronic Polyneuropathies</title><p id="para136">Occasionally, chronic polyneuropathies will evolve as rapidly developing respiratory insufficiency. Although rare, this may occur in chronic inflammatory demyelinating polyneuropathy and diabetic polyneuropathy. It is generally worthwhile to undertake phrenic nerve conduction studies and needle EMG of the diaphragm to show clearly that the respiratory insufficiency is due to the neuropathy. Such studies complement the conventional electrodiagnostic studies that document the presence of a polyneuropathy.</p></sec><sec id="cesec10"><title>Neuromuscular Transmission Disorders and Myopathies</title><p id="para137">As noted previously, neuromuscular transmission disorders and myopathies are more varied and complex and may be difficult to distinguish from critical illness polyneuropathy and especially from the motor axonal neuropathy or critical illness myopathy that may be associated with the SIRS and the use of competitive neuromuscular blocking agents and steroids. Electrophysiological studies, measurements of blood CK level, and at times muscle biopsy will usually further define the nature of the muscular weakness (<xref rid="cetable3" ref-type="table">Table 52-3</xref>).</p><sec id="cesec11"><title>Transient Neuromuscular Blockade</title><p id="para138">Competitive neuromuscular blocking agents, often used to ease mechanical ventilation, are metabolized or cleared by the liver and kidney. Hence, in the presence of failure of these organs, the effect of the neuromuscular blocking agent may be prolonged for a number of days after it has been discontinued.<xref rid="bib47" ref-type="bibr"><sup>47</sup></xref> Repetitive stimulation studies will correctly identify the defect in neuromuscular transmission. However, by the time of testing, many of these patients will already have developed an underlying critical illness polyneuropathy in addition to a neuromuscular transmission defect, each disclosed by electrophysiological studies. Recovery may be prolonged for several weeks or even months in severe cases.</p></sec><sec id="cesec12"><title>Critical Illness Myopathy</title><p id="para139">An acute myopathy often affects critically ill patients. Whereas acute quadriplegic myopathy<xref rid="bib48" ref-type="bibr"><sup>48</sup></xref> has been the most common designation, others include critical care myopathy, acute necrotizing myopathy of intensive care, thick filament myopathy, critical illness myopathy, acute corticosteroid myopathy, acute hydrocortisone myopathy, acute myopathy in severe asthma, and acute corticosteroid and pancuronium–associated myopathy. The term <italic>critical illness myopathy</italic> is now considered the most appropriate description for this syndrome.<xref rid="bib49" ref-type="bibr"><sup>49</sup></xref> By definition, patients are or were critically ill, and weakness should have started after the onset of critical illness.</p><p id="para140">Critical illness myopathy may occur independently of, or in association with, critical illness polyneuropathy. De Letter and co-workers showed a relationship between the early onset and severity of critical illness polyneuropathy and myopathy and Apache III scores, which measure the severity of critical illness and sepsis.<xref rid="bib50" ref-type="bibr"><sup>50</sup></xref> Critical illness myopathy develops in at least one third of ICU patients treated for status asthmaticus,<xref rid="bib51" ref-type="bibr"><sup>51</sup></xref> in 7 percent of patients after orthoptic liver transplantation,<xref rid="bib52" ref-type="bibr"><sup>52</sup></xref> and in patients after heart transplant.<xref rid="bib53" ref-type="bibr"><sup>53</sup></xref> It may occur in the severe acute respiratory syndrome (SARS), even though there is no evidence of virus on culture and electron microscopy.<xref rid="bib54" ref-type="bibr"><sup>54</sup></xref> In a prospective study by Trojaborg and colleagues,<xref rid="bib55" ref-type="bibr"><sup>55</sup></xref> all 22 critically ill patients showed clinical, electrophysiological, and muscle biopsy evidence of a primary myopathy.</p><p id="para141">The major feature is flaccid weakness, which tends to be diffuse, involving all limb muscles and the neck flexors and often the facial muscles and diaphragm. Thus, most patients are difficult to wean from mechanical ventilation. Ophthalmoplegia may be present.<xref rid="bib56" ref-type="bibr"><sup>56</sup></xref> Tendon reflexes are often depressed, but normal reflexes do not exclude the diagnosis. Myalgias are uncommon. Although the myopathy develops acutely, the time of onset is usually difficult to determine because of the commonly associated encephalopathy and administration of neuromuscular blocking agents.</p><p id="para142">Nerve conduction studies reveal low-amplitude CMAPs, some of which may be of long duration (<xref rid="f4" ref-type="fig">Fig. 52-4</xref>). Park and co-workers observed this prolongation in every muscle tested in patients with critical illness myopathy.<xref rid="bib57" ref-type="bibr"><sup>57</sup></xref> The sensory nerve action potentials (SNAPS) should be normal but may be reduced in amplitude owing to tissue edema. Near-nerve recordings overcome this difficulty. Examination of motor unit potentials may be impaired by the attendant septic encephalopathy and sedation. This difficulty may be partially overcome by recording from the tibialis anterior muscle and activating motor units by plantar stimulation. Fibrillation potentials and positive sharp waves will be present in both critical illness myopathy and neuropathy. In critical illness myopathy, motor unit potentials are of low amplitude and short duration, with high-frequency components. Quantitative studies of motor unit potentials confirm that their duration is decreased.<xref rid="bib55" ref-type="bibr"><sup>55</sup></xref> However, such units are also seen in critical illness polyneuropathy with predominantly distal motor axonopathy, as demonstrated in single-fiber studies.<xref rid="bib58" ref-type="bibr"><sup>58</sup></xref> Electrical inexcitability of the muscle membrane can be demonstrated by direct needle stimulation of the muscle<xref rid="bib59" ref-type="bibr"><sup>59</sup></xref> in patients with severe critical illness myopathy and markedly reduced or absent CMAPs.<xref rid="bib60" ref-type="bibr"><sup>60</sup></xref> In critical illness polyneuropathy, there is a response to direct muscle stimulation but not to stimulation of the nerve supplying the muscle. Direct muscle stimulation may therefore be helpful in the differentiation of these two disorders.<xref rid="bib61" ref-type="bibr">61</xref>, <xref rid="bib62" ref-type="bibr">62</xref> However, the results of direct muscle stimulation are only semiquantitative, and this, coupled with the coexistence of critical illness neuropathy and myopathy, may make interpretation difficult. Trojaborg has proposed an electrophysiological approach using the methods noted, plus motor unit estimate techniques.<xref rid="bib63" ref-type="bibr"><sup>63</sup></xref> A more consistent and easily measured response is the duration of the CMAP, which is increased in duration in a manner consistent with a primary myopathy (<xref rid="f4" ref-type="fig">Fig. 52-4</xref>).</p><p id="para143">Determination of serum CK level may be helpful in differential diagnosis (<xref rid="cetable3" ref-type="table">Table 52-3</xref>). Markedly elevated levels suggest a necrotizing myopathy,<xref rid="bib64" ref-type="bibr">64</xref>, <xref rid="bib65" ref-type="bibr">65</xref> whereas in other types of critical illness myopathy the serum CK elevations are not so severe and may be delayed for 10 days or more after administration of steroids.<xref rid="bib66" ref-type="bibr"><sup>66</sup></xref> By contrast, serum CK levels in critical illness polyneuropathy are normal or only mildly elevated.<xref rid="bib36" ref-type="bibr"><sup>36</sup></xref></p><p id="para144">Phrenic nerve conduction studies and needle EMG of the diaphragm and chest wall muscles are valuable in assessing patients with suspected critical illness myopathy.<xref rid="bib67" ref-type="bibr"><sup>67</sup></xref> Phrenic nerve conduction studies typically show normal latencies but diaphragm CMAP amplitudes may be reduced, with a return toward normal as recovery occurs. Needle EMG may reveal positive sharp waves and fibrillation potentials in respiratory muscles. Motor unit potentials may be difficult to interpret in the diaphragm because they normally have a “myopathic” appearance.</p><p id="para145">Identification of the subtypes of critical illness myopathy, as described here, may aid in prognostication (<xref rid="cetable3" ref-type="table">Table 52-3</xref>).<xref rid="bib10" ref-type="bibr"><sup>10</sup></xref></p><sec id="cesec13"><title>Thick-Filament Myosin Loss</title><p id="para146">This syndrome, frequently termed <italic>acute quadriplegic myopathy,</italic> occurs in the setting of sudden, severe asthma or in post-transplant patients requiring tracheal intubation and placement on a ventilator in combination with high-dose corticosteroids and neuromuscular blocking agents. It is a rare complication in critically ill children, post-transplant children being especially at risk.<xref rid="bib68" ref-type="bibr"><sup>68</sup></xref> Serum CK levels may be elevated only mildly. Muscle biopsy shows destruction of the thick myosin filaments, often seen on light microscopy but found more definitively on electron microscopy. The typical histopathological features are shown in <xref rid="f8" ref-type="fig">FIGURE 52-8</xref>, <xref rid="f9" ref-type="fig">FIGURE 52-9</xref>.<xref rid="bib69" ref-type="bibr"><sup>69</sup></xref> There is no specific treatment. The best approach is to avoid neuromuscular blocking agents and, especially, steroids, or to use these medications as sparingly as possible.<fig id="f8"><label>FIGURE 52-8</label><caption><p>Both histochemical type 1 and type 2 fibers show extensive central pallor. Myofibrillar ATPase (pH 9.4; 50×).</p></caption><graphic xlink:href="gr8"></graphic><attrib>(From Danon MJ, Carpenter S: Myopathy and thick filament [myosin] loss following prolonged paralysis with vecuronium during steroid treatment. Muscle Nerve 14:1131, 1991, with permission.)</attrib><permissions><copyright-statement>© 2008 </copyright-statement><copyright-year>2008</copyright-year><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions></fig><fig id="f9"><label>FIGURE 52-9</label><caption><p>At high magnification, central, sharply bounded A-band loss contrasts with its peripheral preservation. (Epoxy resin section, paraphenylene diamine, phase optics 1380×.)</p></caption><graphic xlink:href="gr9"></graphic><attrib>(From Danon MJ, Carpenter S: Myopathy and thick filament [myosin] loss following prolonged paralysis with vecuronium during steroid treatment. Muscle Nerve 14:1131, 1991, with permission.)</attrib><permissions><copyright-statement>© 2008 </copyright-statement><copyright-year>2008</copyright-year><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions></fig></p></sec><sec id="cesec14"><title>Rhabdomyolysis</title><p id="para147">Rhabdomyolysis occurs in the setting of critical illness and the use of neuromuscular blocking agents and corticosteroids.<xref rid="bib70" ref-type="bibr"><sup>70</sup></xref> It may be due to a variety of causes and presents with weakness, myalgia, and swelling in the affected muscles. Massive muscle necrosis results in the release of potassium and initially sequesters calcium. The resultant hyperkalemia and hypocalcemia may produce life-threatening cardiac arrhythmias and renal failure. Serum CK level is elevated, often to greater than 10,000 IU/L. Myoglobinuria occurs frequently. The electrophysiological findings are those of an acute myopathy. Motor and sensory nerve conduction studies are usually normal. On needle EMG, fibrillation potentials are usually sparse and transient and motor unit potentials often normal.<xref rid="bib71" ref-type="bibr"><sup>71</sup></xref> Muscle biopsy may be normal or show varying degrees of myofiber necrosis without inflammation, myosin loss, or other specific features. Thus, despite considerable weakness and elevated serum levels of CK, EMG and muscle biopsy are often unimpressive, consistent with rapid and complete recovery.</p><p id="para148">During bacteremia, microabscesses may be deposited throughout skeletal muscle and present the clinical picture of acute rhabdomyolysis. Blood culture will identify the offending organism, and muscle biopsy will identify the microabscesses. This is a variant of pyomyositis typically seen in tropical countries or in children.<xref rid="bib10" ref-type="bibr"><sup>10</sup></xref></p></sec><sec id="cesec15"><title>Acute Necrotizing Myopathy</title><p id="para149">Acute necrotizing myopathy of intensive care<xref rid="bib64" ref-type="bibr">64</xref>, <xref rid="bib65" ref-type="bibr">65</xref> may be simply an extension of acute rhabdomyolysis and is induced by the same variety of infective, chemical, and other insults. Serum CK levels are markedly elevated, myoglobulinuria is present, electrophysiological examinations suggest a severe myopathy, and pathological studies show widespread necrosis of muscle fibers. Recovery of muscle strength may not occur in severe cases.<xref rid="bib65" ref-type="bibr"><sup>65</sup></xref></p></sec><sec id="cesec16"><title>Cachectic Myopathy</title><p id="para150">Muscle weakness and wasting commonly occur in starvation and malnutrition, as in anorexia nervosa or following gastric bypass surgery for morbid obesity<xref rid="bib72" ref-type="bibr">72</xref>, <xref rid="bib73" ref-type="bibr">73</xref> and are termed <italic>cachectic myopathy</italic> or <italic>disuse atrophy</italic>. It is likely a common complication of critical illness and accounts for significant wasting and weakness of muscle. Electrophysiological findings and serum CK levels are normal. Muscle biopsy is normal or reveals type II fiber atrophy. The diagnosis of cachectic myopathy is made by exclusion of other neuromuscular complications of critical illness.</p></sec><sec id="cesec17"><title>Management of Critical Illness Myopathy</title><p id="para151">Whether a clinician should routinely pursue a muscle biopsy in order to distinguish critical illness myopathy from other myopathies or from critical illness polyneuropathy is questionable. Muscle biopsy should be considered if another myopathic process, such as an inflammatory myopathy, is suspected or if the histological findings may affect management. For example, a firm diagnosis of critical illness myopathy may lead to avoidance of intravenous corticosteroids or neuromuscular blocking agents. As indicated in <xref rid="cetable3" ref-type="table">Table 52-3</xref>, the various types of critical illness myopathy can be distinguished by clinical, electrophysiological, and histological features.<xref rid="bib10" ref-type="bibr"><sup>10</sup></xref> This is important for prognosis. Severe critical illness polyneuropathy and necrotizing myopathy of intensive care<xref rid="bib64" ref-type="bibr"><sup>64</sup></xref> may have a poor prognosis for recovery of strength, but the prognosis is much better for rhabdomyolysis, cachectic myopathy, and thick filament myosin loss.</p></sec></sec><sec id="cesec18"><title>Critical Illness Polyneuropathy and Myopathy</title><p id="para152">The predominance of either critical illness polyneuropathy or myopathy in individual patients probably varies depending on the use of neuromuscular blocking agents and corticosteroids. Thus, in an ICU where these medications were used in post-transplant patients, the incidence of critical illness myopathy was high<xref rid="bib39" ref-type="bibr"><sup>39</sup></xref>; by contrast, in another ICU where there were no post-transplant patients and neuromuscular blocking agents and steroids were rarely used, the incidence of myopathy was low.<xref rid="bib38" ref-type="bibr"><sup>38</sup></xref> Sepsis is likely the predominant underlying factor, with the additional factors of neuromuscular blocking agents and corticosteroids combining to account for the pathophysiology (<xref rid="f10" ref-type="fig">Fig. 52-10</xref>).<fig id="f10"><label>FIGURE 52-10</label><caption><p>A simplified depiction of theoretical mechanisms of dysfunction in critical illness polyneuropathy and myopathy. Sepsis with disturbance of microcirculation is a common underlying factor, neuromuscular (N-M) blocking agents enhance denervation, and corticosteroids subsequently induce a myopathy with thick-filament myosin loss. Varying pathological changes in muscle may result. In the early stages of sepsis, there may be a purely functional loss, with no structural change in nerve or muscle.</p></caption><graphic xlink:href="gr10"></graphic><attrib>(From Bolton CF: Neuromuscular complications of sepsis. Intensive Care Med 19:S58, 1993, with permission.)</attrib><permissions><copyright-statement>© 2008 </copyright-statement><copyright-year>2008</copyright-year><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions></fig></p><p id="para153">The range of severity of combined critical illness polyneuropathy and myopathy may be quite marked.<xref rid="bib10" ref-type="bibr"><sup>10</sup></xref> Despite severe respiratory and limb weakness with electrophysiological evidence of predominant involvement of muscle and marked elevations of serum CK, the patient may make a rapid recovery if the muscle biopsy is normal. Conversely, recovery may not occur in patients with clinical and electrophysiological evidence of severe involvement of both nerve and muscle, high levels of serum CK, myoglobin in the urine, and necrosis of muscle on morphological study. Latronico and associates reported that 74 of 263 patients (28%) with combined critical illness polyneuropathy (CIP) and critical illness myopathy (CIM) were left with severe disability.<xref rid="bib74" ref-type="bibr"><sup>74</sup></xref></p></sec></sec></sec><sec id="cesec19"><title>ELECTROPHYSIOLOGICAL STUDIES OF THE RESPIRATORY SYSTEM</title><p id="para154">The techniques of phrenic nerve conduction and needle EMG of the diaphragm have proved of great value in establishing that respiratory insufficiency is due to a neuromuscular disorder. The techniques can indicate impairment of “central drive” as a disturbance of the voluntary or automatic centers of respiration, or impairment of phrenic nerves, neuromuscular junction, or muscle. For example, in patients with Guillain–Barré syndrome, the degree of involvement of the phrenic nerves can be determined and will supplement measurements, including of vital capacity, in determining the need for respiratory assistance.<xref rid="bib75" ref-type="bibr"><sup>75</sup></xref></p><p id="para155">Documenting the degree of axonal degeneration or demyelination of phrenic nerves aids in long-term prognostication. In a study of 40 patients who had difficulty in weaning from the ventilator when a neuromuscular cause was suspected, 38 were shown to have such a disorder.<xref rid="bib76" ref-type="bibr"><sup>76</sup></xref> In an earlier study, Spitzer and associates also found a high incidence of both polyneuropathy and myopathy as causes of prolonged difficulty in weaning.<xref rid="bib77" ref-type="bibr"><sup>77</sup></xref> Most had critical illness polyneuropathy, but there were varying combinations of unilateral phrenic nerve damage, neuromuscular transmission defects, and primary myopathies. Combined electrophysiological studies of limbs and the respiratory system are therefore of assistance in identifying these conditions and rendering a prognosis.</p></sec><sec id="cesec20"><title>MONONEUROPATHIES</title><p id="para156">A variety of mononeuropathies may occur in patients being treated in the critical care unit. Lumbosacral or brachial plexopathies may be secondary to direct trauma, usually from motor vehicle accidents or surgery. Insertion of catheters into the iliac arteries or aorta may dislodge thrombi, and the resulting emboli impair vascular supply to nerves and, in this manner, induce focal ischemic plexopathy. Direct surgical trauma to vessels may also induce vascular insufficiency.</p><p id="para157">Motorcycle accidents commonly injure the brachial plexus. Proximal lesions are suggested by Horner's syndrome, winging of the scapula, and diaphragm paralysis. Electrophysiological studies, ideally performed after 3 weeks, further help to localize the lesion. Myelography, CT myelography, or magnetic resonance imaging (MRI) may provide more positive evidence of root avulsion, which would preclude attempts at operative nerve repair. Fractures of the pelvis may cause varying patterns of damage to the lumbosacral plexus.</p><p id="para158">Observations of focal weakness on reflex-induced voluntary movement, plus abnormalities of the tendon reflexes, may provide an initial clue to the presence of such damage. Thus, weakness of hip adduction and flexion and of knee extension and an absent patellar reflex suggest damage to the L2–L4 roots of the lumbosacral plexus.</p><p id="para159">Electrophysiological studies should successfully demonstrate abnormalities on motor and sensory nerve conduction studies and, in particular, needle EMG should localize the lesion to the brachial or lumbosacral plexus.</p><p id="para160">There are several types of mononeuropathies. If the patient's primary reason for admission to the unit was the postoperative state, the initial surgery may have induced a mononeuropathy when operating room equipment, or perhaps the surgery itself, directly damaged peripheral nerves, since a variety of limb nerves may be damaged by trauma. For example, weakness of dorsiflexion of the wrist and digits and an absent brachioradialis reflex suggest radial nerve damage in the spiral groove of the humerus by fracture or direct compression. Phrenic nerves may be damaged, either bilaterally or unilaterally, at the time of surgery by direct trauma or by the application of cold, as occurs with the hypothermia associated with cardiac surgery.</p><p id="para161">More distal nerves may be damaged as the result of impairment of nutrient blood supply through distal embolization. Thus, following cardiac or vascular surgery, patients may have varying combinations of involvement of femoral or sciatic nerves. Electrophysiological studies show a relatively pure axonal degeneration of motor and sensory fibers.</p><p id="para162">Patients who are being anticoagulated run the risk of hemorrhage. The sudden rise in tissue pressure produces a “compartment syndrome,” the severe compression resulting in ischemia to nerve, as well as muscle. The compartments most commonly involved are the iliopsoas and gluteal, producing acute femoral or sciatic neuropathies. Fractures and soft tissue trauma may also induce compartment syndromes. An immediate CT scan should be ordered, which will show the location of the hemorrhage. Then, surgical decompression may successfully decompress the nerve. The situation is so acute and urgent that electrophysiological studies are of little value.</p></sec></body><back><ref-list id="cebib1"><title>REFERENCES</title><ref id="bib1"><label>1</label><element-citation publication-type="journal" id="sbref1"><person-group person-group-type="author"><name><surname>Tran</surname><given-names>DD</given-names></name><name><surname>Groeneveld</surname><given-names>AAJB</given-names></name><name><surname>van der Meulen</surname><given-names>J</given-names></name></person-group><article-title>Age, chronic disease, sepsis, organ system failure, and mortality in a medical intensive care unit</article-title><source>Crit Care Med</source><volume>18</volume><year>1990</year><fpage>474</fpage><pub-id pub-id-type="pmid">2328591</pub-id></element-citation></ref><ref id="bib2"><label>2</label><element-citation publication-type="journal" id="sbref2"><person-group person-group-type="author"><name><surname>Riedemann</surname><given-names>NC</given-names></name><name><surname>Guo</surname><given-names>RF</given-names></name><name><surname>Ward</surname><given-names>PA</given-names></name></person-group><article-title>Novel strategies for the treatment of sepsis</article-title><source>Nat Med</source><volume>9</volume><year>2003</year><fpage>517</fpage><pub-id pub-id-type="pmid">12724763</pub-id></element-citation></ref><ref id="bib3"><label>3</label><element-citation publication-type="journal" id="sbref3"><person-group person-group-type="author"><name><surname>Bone</surname><given-names>RC</given-names></name></person-group><article-title>Let's agree on terminology: definitions of sepsis</article-title><source>Crit Care Med</source><volume>19</volume><year>1991</year><fpage>973</fpage><pub-id pub-id-type="pmid">1824030</pub-id></element-citation></ref><ref id="bib4"><label>4</label><element-citation publication-type="journal" id="sbref4"><article-title>American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis</article-title><source>Crit Care Med</source><volume>20</volume><year>1992</year><fpage>864</fpage><pub-id pub-id-type="pmid">1597042</pub-id></element-citation></ref><ref id="bib5"><label>5</label><element-citation publication-type="journal" id="sbref5"><person-group person-group-type="author"><name><surname>Glauser</surname><given-names>MP</given-names></name><name><surname>Zanetti</surname><given-names>G</given-names></name><name><surname>Baumgartner</surname><given-names>JD</given-names></name></person-group><article-title>Septic shock: pathogenesis</article-title><source>Lancet</source><volume>338</volume><year>1991</year><fpage>732</fpage><pub-id pub-id-type="pmid">1679876</pub-id></element-citation></ref><ref id="bib6"><label>6</label><element-citation publication-type="journal" id="sbref6"><person-group person-group-type="author"><name><surname>Cowley</surname><given-names>HC</given-names></name><name><surname>Heney</surname><given-names>D</given-names></name><name><surname>Gearing</surname><given-names>AJ</given-names></name></person-group><article-title>Increased circulating adhesion molecule concentrations in patients with the systemic inflammatory response syndrome: a prospective cohort study</article-title><source>Crit Care Med</source><volume>22</volume><year>1994</year><fpage>651</fpage><pub-id pub-id-type="pmid">7511496</pub-id></element-citation></ref><ref id="bib7"><label>7</label><element-citation publication-type="journal" id="sbref7"><person-group person-group-type="author"><name><surname>Faust</surname><given-names>SN</given-names></name><name><surname>Levin</surname><given-names>M</given-names></name><name><surname>Harrison</surname><given-names>OB</given-names></name></person-group><article-title>Dysfunction of endothelial protein C activation in severe meningococcal sepsis</article-title><source>N Engl J Med</source><volume>345</volume><year>2001</year><fpage>408</fpage><pub-id pub-id-type="pmid">11496851</pub-id></element-citation></ref><ref id="bib8"><label>8</label><element-citation publication-type="journal" id="sbref8"><person-group person-group-type="author"><name><surname>Satran</surname><given-names>R</given-names></name><name><surname>Almog</surname><given-names>Y</given-names></name></person-group><article-title>The coagulopathy of sepsis: pathophysiology and management</article-title><source>Isr Med Assoc J</source><volume>5</volume><year>2003</year><fpage>516</fpage><pub-id pub-id-type="pmid">12901250</pub-id></element-citation></ref><ref id="bib9"><label>9</label><element-citation publication-type="journal" id="sbref9"><person-group person-group-type="author"><name><surname>Bolton</surname><given-names>CF</given-names></name><name><surname>Young</surname><given-names>GB</given-names></name><name><surname>Zochodne</surname><given-names>DW</given-names></name></person-group><article-title>The neurological complications of sepsis</article-title><source>Ann Neurol</source><volume>33</volume><year>1993</year><fpage>94</fpage><comment></comment><pub-id pub-id-type="pmid">8388191</pub-id></element-citation></ref><ref id="bib10"><label>10</label><element-citation publication-type="journal" id="sbref10"><person-group person-group-type="author"><name><surname>Bolton</surname><given-names>CF</given-names></name></person-group><article-title>Neuromuscular manifestations of critical illness</article-title><source>Muscle Nerve</source><volume>32</volume><year>2005</year><fpage>140</fpage><pub-id pub-id-type="pmid">15825186</pub-id></element-citation></ref><ref id="bib11"><label>11</label><element-citation publication-type="journal" id="sbref11"><person-group person-group-type="author"><name><surname>Jackson</surname><given-names>AC</given-names></name><name><surname>Gilbert</surname><given-names>JJ</given-names></name><name><surname>Young</surname><given-names>GB</given-names></name></person-group><article-title>The encephalopathy of sepsis</article-title><source>Can J Neurol Sci</source><volume>12</volume><year>1985</year><fpage>303</fpage><pub-id pub-id-type="pmid">4084865</pub-id></element-citation></ref><ref id="bib12"><label>12</label><element-citation publication-type="journal" id="sbref12"><person-group person-group-type="author"><name><surname>Young</surname><given-names>GB</given-names></name><name><surname>Bolton</surname><given-names>CF</given-names></name><name><surname>Austin</surname><given-names>TW</given-names></name></person-group><article-title>The encephalopathy associated with septic illness</article-title><source>Clin Invest Med</source><volume>13</volume><year>1990</year><fpage>297</fpage><pub-id pub-id-type="pmid">2078909</pub-id></element-citation></ref><ref id="bib13"><label>13</label><element-citation publication-type="journal" id="sbref13"><person-group person-group-type="author"><name><surname>Young</surname><given-names>GB</given-names></name><name><surname>Bolton</surname><given-names>CF</given-names></name><name><surname>Archibald</surname><given-names>YM</given-names></name></person-group><article-title>The electroencephalogram in sepsis-associated encephalopathy</article-title><source>J Clin Neurophysiol</source><volume>9</volume><year>1992</year><fpage>145</fpage><pub-id pub-id-type="pmid">1552002</pub-id></element-citation></ref><ref id="bib14"><label>14</label><element-citation publication-type="journal" id="sbref14"><person-group person-group-type="author"><name><surname>Straver</surname><given-names>JS</given-names></name><name><surname>Keunen</surname><given-names>RWM</given-names></name><name><surname>Stam</surname><given-names>CJ</given-names></name></person-group><article-title>Nonlinear analysis of EEG in septic encephalopathy</article-title><source>Neurol Res</source><volume>20</volume><year>1998</year><fpage>100</fpage><pub-id pub-id-type="pmid">9522343</pub-id></element-citation></ref><ref id="bib15"><label>15</label><element-citation publication-type="journal" id="sbref15"><person-group person-group-type="author"><name><surname>Straver</surname><given-names>JS</given-names></name><name><surname>Keunen</surname><given-names>WM</given-names></name><name><surname>Stam</surname><given-names>CJ</given-names></name></person-group><article-title>Transcranial Doppler and systemic hemodynamic studies in septic shock</article-title><source>Neurol Res</source><volume>18</volume><year>1996</year><fpage>313</fpage><pub-id pub-id-type="pmid">8875447</pub-id></element-citation></ref><ref id="bib16"><label>16</label><element-citation publication-type="journal" id="sbref16"><person-group person-group-type="author"><name><surname>Lorente</surname><given-names>JE</given-names></name><name><surname>Landin</surname><given-names>L</given-names></name><name><surname>Renes</surname><given-names>E</given-names></name></person-group><article-title>Regulation of vascular tone in sepsis</article-title><source>Intensive Care World</source><volume>10</volume><year>1993</year><fpage>58</fpage></element-citation></ref><ref id="bib17"><label>17</label><element-citation publication-type="journal" id="sbref17"><person-group person-group-type="author"><name><surname>Tanaka</surname><given-names>K</given-names></name><name><surname>Gotoh</surname><given-names>F</given-names></name><name><surname>Gomi</surname><given-names>S</given-names></name></person-group><article-title>Inhibition of nitric oxide synthesis induces a significant reduction in local cerebral blood flow in the rat</article-title><source>Neurosci Lett</source><volume>127</volume><year>1991</year><fpage>129</fpage><pub-id pub-id-type="pmid">1881609</pub-id></element-citation></ref><ref id="bib18"><label>18</label><element-citation publication-type="journal" id="sbref18"><person-group person-group-type="author"><name><surname>Anda</surname><given-names>T</given-names></name><name><surname>Yamashita</surname><given-names>H</given-names></name><name><surname>Khalid</surname><given-names>H</given-names></name></person-group><article-title>Effect of tumor necrosis factor-alpha on the permeability of bovine brain microvessel endothelial cell monolayers</article-title><source>Neurol Res</source><volume>19</volume><year>1997</year><fpage>369</fpage><pub-id pub-id-type="pmid">9263215</pub-id></element-citation></ref><ref id="bib19"><label>19</label><element-citation publication-type="journal" id="sbref19"><person-group person-group-type="author"><name><surname>Huynh</surname><given-names>KH</given-names></name><name><surname>Dorovini-Zis</surname><given-names>K</given-names></name></person-group><article-title>Effects of interferon-gamma on primary cultures of human brain microvessel endothelial cells</article-title><source>Am J Pathol</source><volume>142</volume><year>1993</year><fpage>1265</fpage><pub-id pub-id-type="pmid">8475997</pub-id></element-citation></ref><ref id="bib20"><label>20</label><element-citation publication-type="journal" id="sbref20"><person-group person-group-type="author"><name><surname>Papadopoulos</surname><given-names>MC</given-names></name><name><surname>Moss</surname><given-names>RF</given-names></name><name><surname>Lamb</surname><given-names>FJ</given-names></name></person-group><article-title>Faecal peritonitis causes oedema and neuronal injury in pig cerebral cortex</article-title><source>Clin Sci</source><volume>96</volume><year>1999</year><fpage>461</fpage><pub-id pub-id-type="pmid">10209077</pub-id></element-citation></ref><ref id="bib21"><label>21</label><element-citation publication-type="journal" id="sbref21"><person-group person-group-type="author"><name><surname>De Sarro</surname><given-names>GB</given-names></name><name><surname>Masuda</surname><given-names>Y</given-names></name><name><surname>Ascioti</surname><given-names>C</given-names></name></person-group><article-title>Behavioural and ECoG spectrum changes induced by intracerebral infusion of interferons and interleukin 2 in rats are antagonized by naloxone</article-title><source>Neuropharmacology</source><volume>29</volume><year>1990</year><fpage>167</fpage><pub-id pub-id-type="pmid">1691831</pub-id></element-citation></ref><ref id="bib22"><label>22</label><element-citation publication-type="journal" id="sbref22"><person-group person-group-type="author"><name><surname>Gautron</surname><given-names>L</given-names></name><name><surname>Lafon</surname><given-names>P</given-names></name><name><surname>Chaigniau</surname><given-names>M</given-names></name></person-group><article-title>Spatiotemporal analysis of signal transducer and activator of transcription 3 activation in rat brain astrocytes and pituitary following peripheral immune challenge</article-title><source>Neuroscience</source><volume>112</volume><year>2002</year><fpage>717</fpage><pub-id pub-id-type="pmid">12074913</pub-id></element-citation></ref><ref id="bib23"><label>23</label><element-citation publication-type="journal" id="sbref23"><person-group person-group-type="author"><name><surname>Korcok</surname><given-names>J</given-names></name><name><surname>Wu</surname><given-names>F</given-names></name><name><surname>Tyml</surname><given-names>K</given-names></name></person-group><article-title>Sepsis inhibits uptake of ascorbate and redox cycling of dehydroascorbic acid: intracellular ascorbate depletion increases nitric oxide synthase induction and glutamate uptake inhibition</article-title><source>J Neurochem</source><volume>81</volume><year>2002</year><fpage>185</fpage><pub-id pub-id-type="pmid">12067232</pub-id></element-citation></ref><ref id="bib24"><label>24</label><element-citation publication-type="journal" id="sbref24"><person-group person-group-type="author"><name><surname>Soejima</surname><given-names>Y</given-names></name><name><surname>Fujii</surname><given-names>Y</given-names></name><name><surname>Ishikawa</surname><given-names>T</given-names></name></person-group><article-title>Local cerebral glucose utilization in septic rats</article-title><source>Crit Care Med</source><volume>18</volume><year>1990</year><fpage>423</fpage><pub-id pub-id-type="pmid">2318053</pub-id></element-citation></ref><ref id="bib25"><label>25</label><element-citation publication-type="journal" id="sbref25"><person-group person-group-type="author"><name><surname>Guerra-Romero</surname><given-names>L</given-names></name><name><surname>Tureen</surname><given-names>JH</given-names></name><name><surname>Fournier</surname><given-names>MA</given-names></name></person-group><article-title>Amino acids in cerebrospinal and brain interstitial fluid in experimental pneumococcal meningitis</article-title><source>Pediatr Res</source><volume>33</volume><year>1993</year><fpage>510</fpage><pub-id pub-id-type="pmid">8099728</pub-id></element-citation></ref><ref id="bib26"><label>26</label><element-citation publication-type="journal" id="sbref26"><person-group person-group-type="author"><name><surname>Olasmaa</surname><given-names>M</given-names></name><name><surname>Rothstein</surname><given-names>JD</given-names></name><name><surname>Guidotti</surname><given-names>A</given-names></name></person-group><article-title>Endoge-nous benzodiazepine receptor ligands in human and animal hepatic encephalopathy</article-title><source>J Neurochem</source><volume>55</volume><year>1990</year><fpage>2015</fpage><pub-id pub-id-type="pmid">2172467</pub-id></element-citation></ref><ref id="bib27"><label>27</label><element-citation publication-type="journal" id="sbref27"><person-group person-group-type="author"><name><surname>Herkes</surname><given-names>GK</given-names></name><name><surname>Wszolek</surname><given-names>ZK</given-names></name><name><surname>Westmoreland</surname><given-names>BF</given-names></name></person-group><article-title>Effects of midazolam on electroencephalograms of seriously ill patients</article-title><source>Mayo Clin Proc</source><volume>67</volume><year>1992</year><fpage>334</fpage><pub-id pub-id-type="pmid">1548948</pub-id></element-citation></ref><ref id="bib28"><label>28</label><element-citation publication-type="journal" id="sbref28"><person-group person-group-type="author"><name><surname>Kress</surname><given-names>JP</given-names></name><name><surname>Poheman</surname><given-names>AS</given-names></name><name><surname>O'Connor</surname><given-names>MF</given-names></name></person-group><article-title>Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation</article-title><source>N Engl J Med</source><volume>342</volume><year>2000</year><fpage>1471</fpage><pub-id pub-id-type="pmid">10816184</pub-id></element-citation></ref><ref id="bib29"><label>29</label><element-citation publication-type="journal" id="sbref29"><person-group person-group-type="author"><name><surname>Leo</surname><given-names>RJ</given-names></name><name><surname>Ballow</surname><given-names>CH</given-names></name></person-group><article-title>Seizure activity associated with imipenem use: clinical case reports and review of the literature</article-title><source>DICP</source><volume>25</volume><year>1991</year><fpage>351</fpage><pub-id pub-id-type="pmid">1926901</pub-id></element-citation></ref><ref id="bib30"><label>30</label><element-citation publication-type="journal" id="sbref30"><person-group person-group-type="author"><name><surname>De Jonghe</surname><given-names>B</given-names></name><name><surname>Sharshar</surname><given-names>T</given-names></name><name><surname>Lefaucheur</surname><given-names>JP</given-names></name></person-group><article-title>Paresis acquired in the intensive care unit: a prospective multi-center study</article-title><source>JAMA</source><volume>288</volume><year>2002</year><fpage>2859</fpage><pub-id pub-id-type="pmid">12472328</pub-id></element-citation></ref><ref id="bib31"><label>31</label><element-citation publication-type="journal" id="sbref31"><person-group person-group-type="author"><name><surname>Maher</surname><given-names>J</given-names></name><name><surname>Bolton</surname><given-names>C</given-names></name><name><surname>Grand'Maison</surname><given-names>F</given-names></name></person-group><article-title>Diagnostic difficulties in myasthenia gravis</article-title><source>Can J Neurol Sci</source><volume>22</volume><issue>1</issue><year>1995</year><fpage>S51</fpage></element-citation></ref><ref id="bib32"><label>32</label><element-citation publication-type="journal" id="sbref32"><person-group person-group-type="author"><name><surname>Nicolle</surname><given-names>MW</given-names></name><name><surname>Stewart</surname><given-names>DJ</given-names></name><name><surname>Remtulla</surname><given-names>H</given-names></name></person-group><article-title>Lambert–Eaton myasthenia gravis syndrome presenting with severe respiratory failure</article-title><source>Muscle Nerve</source><volume>19</volume><year>1996</year><fpage>1328</fpage><pub-id pub-id-type="pmid">8808659</pub-id></element-citation></ref><ref id="bib33"><label>33</label><element-citation publication-type="journal" id="sbref33"><person-group person-group-type="author"><name><surname>Chen</surname><given-names>R</given-names></name><name><surname>Grand'Maison</surname><given-names>F</given-names></name><name><surname>Bolton</surname><given-names>CF</given-names></name></person-group><article-title>Motor neuron disease presenting as acute respiratory failure: electrophysiological studies</article-title><source>Muscle Nerve</source><volume>20</volume><year>1997</year><fpage>517</fpage><pub-id pub-id-type="pmid">9121515</pub-id></element-citation></ref><ref id="bib34"><label>34</label><element-citation publication-type="book" id="sbref34"><person-group person-group-type="author"><name><surname>Bolton</surname><given-names>CF</given-names></name></person-group><chapter-title>Critical illness polyneuropathy</chapter-title><person-group person-group-type="editor"><name><surname>Thomas</surname><given-names>PK</given-names></name><name><surname>Asbury</surname><given-names>A</given-names></name></person-group><source>Peripheral Nerve Disorders II</source><year>1995</year><publisher-name>Butterworth-Heinemann</publisher-name><publisher-loc>Boston</publisher-loc><fpage>262</fpage></element-citation></ref><ref id="bib35"><label>35</label><element-citation publication-type="journal" id="sbref35"><person-group person-group-type="author"><name><surname>Leijten</surname><given-names>FSS</given-names></name><name><surname>de Weerd</surname><given-names>AW</given-names></name></person-group><article-title>Critical illness polyneuropathy: a review of the literature, definition and pathophysiology</article-title><source>Clin Neurol Neurosurg</source><volume>96</volume><year>1994</year><fpage>10</fpage><pub-id pub-id-type="pmid">8187376</pub-id></element-citation></ref><ref id="bib36"><label>36</label><element-citation publication-type="journal" id="sbref36"><person-group person-group-type="author"><name><surname>Witt</surname><given-names>NJ</given-names></name><name><surname>Zochodne</surname><given-names>DW</given-names></name><name><surname>Bolton</surname><given-names>CF</given-names></name></person-group><article-title>Peripheral nerve function in sepsis and multiple organ failure</article-title><source>Chest</source><volume>99</volume><year>1991</year><fpage>176</fpage><pub-id pub-id-type="pmid">1845860</pub-id></element-citation></ref><ref id="bib37"><label>37</label><element-citation publication-type="journal" id="sbref37"><person-group person-group-type="author"><name><surname>Berek</surname><given-names>K</given-names></name><name><surname>Margreiter</surname><given-names>J</given-names></name><name><surname>Willeit</surname><given-names>J</given-names></name></person-group><article-title>Polyneuropathies in critically ill patients: a prospective evaluation</article-title><source>Intensive Care Med</source><volume>22</volume><year>1996</year><fpage>849</fpage><pub-id pub-id-type="pmid">8905416</pub-id></element-citation></ref><ref id="bib38"><label>38</label><element-citation publication-type="journal" id="sbref38"><person-group person-group-type="author"><name><surname>Zifko</surname><given-names>UA</given-names></name><name><surname>Zipko</surname><given-names>HT</given-names></name><name><surname>Bolton</surname><given-names>CF</given-names></name></person-group><article-title>Clinical and electrophysiological findings in critical illness polyneuropathy</article-title><source>J Neurol Sci</source><volume>159</volume><year>1998</year><fpage>186</fpage><pub-id pub-id-type="pmid">9741406</pub-id></element-citation></ref><ref id="bib39"><label>39</label><element-citation publication-type="journal" id="sbref39"><person-group person-group-type="author"><name><surname>Lacomis</surname><given-names>D</given-names></name><name><surname>Petrella</surname><given-names>JT</given-names></name><name><surname>Giuliani</surname><given-names>MJ</given-names></name></person-group><article-title>Causes of neuromuscular weakness in the intensive care unit: a study of ninety-two patients</article-title><source>Muscle Nerve</source><volume>21</volume><year>1998</year><fpage>610</fpage><pub-id pub-id-type="pmid">9572240</pub-id></element-citation></ref><ref id="bib40"><label>40</label><element-citation publication-type="journal" id="sbref40"><person-group person-group-type="author"><name><surname>Latronico</surname><given-names>N</given-names></name><name><surname>Fenzi</surname><given-names>F</given-names></name><name><surname>Recupero</surname><given-names>D</given-names></name></person-group><article-title>Critical illness myopathy and neuropathy</article-title><source>Lancet</source><volume>347</volume><year>1996</year><fpage>1579</fpage><pub-id pub-id-type="pmid">8667865</pub-id></element-citation></ref><ref id="bib41"><label>41</label><element-citation publication-type="journal" id="sbref41"><person-group person-group-type="author"><name><surname>Zochodne</surname><given-names>DW</given-names></name><name><surname>Bolton</surname><given-names>CF</given-names></name><name><surname>Wells</surname><given-names>GA</given-names></name></person-group><article-title>Critical illness polyneuropathy: a complication of sepsis and multiple organ failure</article-title><source>Brain</source><volume>110</volume><year>1987</year><fpage>819</fpage><pub-id pub-id-type="pmid">3651796</pub-id></element-citation></ref><ref id="bib42"><label>42</label><element-citation publication-type="journal" id="sbref42"><person-group person-group-type="author"><name><surname>Leijten</surname><given-names>FSS</given-names></name><name><surname>Harinck-de Weerd</surname><given-names>JE</given-names></name><name><surname>Poortvliet</surname><given-names>DCJ</given-names></name></person-group><article-title>The role of polyneuropathy in motor convalescence after prolonged mechanical ventilation</article-title><source>JAMA</source><volume>274</volume><year>1995</year><fpage>1221</fpage><pub-id pub-id-type="pmid">7563512</pub-id></element-citation></ref><ref id="bib43"><label>43</label><element-citation publication-type="journal" id="sbref43"><person-group person-group-type="author"><name><surname>Wijdicks</surname><given-names>EF</given-names></name><name><surname>Fulgham</surname><given-names>JR</given-names></name></person-group><article-title>Failure of high dose intravenous immunoglobulins to alter the clinical course of critical illness polyneuropathy</article-title><source>Muscle Nerve</source><volume>17</volume><year>1994</year><fpage>1494</fpage><pub-id pub-id-type="pmid">7969261</pub-id></element-citation></ref><ref id="bib44"><label>44</label><element-citation publication-type="journal" id="sbref44"><person-group person-group-type="author"><name><surname>Mohr</surname><given-names>M</given-names></name><name><surname>Englisch</surname><given-names>L</given-names></name><name><surname>Roth</surname><given-names>A</given-names></name></person-group><article-title>Effects of early treatment with immunoglobulin on critical illness polyneuropathy following multiple organ failure and gram-negative sepsis</article-title><source>Intensive Care Med</source><volume>23</volume><year>1997</year><fpage>1144</fpage><pub-id pub-id-type="pmid">9434920</pub-id></element-citation></ref><ref id="bib45"><label>45</label><element-citation publication-type="journal" id="sbref45"><person-group person-group-type="author"><name><surname>Van den Berghe</surname><given-names>G</given-names></name><name><surname>Wouters</surname><given-names>P</given-names></name><name><surname>Weekers</surname><given-names>F</given-names></name></person-group><article-title>Inten-sive insulin therapy in the critically ill patients</article-title><source>N Engl J Med</source><volume>345</volume><year>2001</year><fpage>1359</fpage><pub-id pub-id-type="pmid">11794168</pub-id></element-citation></ref><ref id="bib46"><label>46</label><element-citation publication-type="journal" id="sbref46"><person-group person-group-type="author"><name><surname>Leijten</surname><given-names>FSS</given-names></name><name><surname>de Weerd</surname></name><name><surname>Poortvliet</surname><given-names>DC</given-names></name></person-group><article-title>Critical illness polyneuropathy in multiple organ dysfunction syndrome and weaning from the ventilator</article-title><source>Intensive Care Med</source><volume>22</volume><year>1996</year><fpage>856</fpage><comment></comment><pub-id pub-id-type="pmid">8905417</pub-id></element-citation></ref><ref id="bib47"><label>47</label><element-citation publication-type="journal" id="sbref47"><person-group person-group-type="author"><name><surname>Segredo</surname><given-names>V</given-names></name><name><surname>Caldwell</surname><given-names>JE</given-names></name><name><surname>Matthay</surname><given-names>MA</given-names></name></person-group><article-title>Persistent paralysis in critically ill patients after long-term administration of vecuronium</article-title><source>N Engl J Med</source><volume>327</volume><year>1992</year><fpage>524</fpage><pub-id pub-id-type="pmid">1353252</pub-id></element-citation></ref><ref id="bib48"><label>48</label><element-citation publication-type="journal" id="sbref48"><person-group person-group-type="author"><name><surname>Hirano</surname><given-names>M</given-names></name><name><surname>Ott</surname><given-names>BR</given-names></name><name><surname>Raps</surname><given-names>EC</given-names></name></person-group><article-title>Acute quadriplegic myopathy: complication of treatment with steroids, nondepolarizing blocking agents, or both</article-title><source>Neurology</source><volume>42</volume><year>1992</year><fpage>2082</fpage><pub-id pub-id-type="pmid">1436516</pub-id></element-citation></ref><ref id="bib49"><label>49</label><element-citation publication-type="journal" id="sbref49"><person-group person-group-type="author"><name><surname>Lacomis</surname><given-names>D</given-names></name><name><surname>Zochodne</surname><given-names>DW</given-names></name><name><surname>Bird</surname><given-names>SJ</given-names></name></person-group><article-title>Critical illness myopathy</article-title><source>Muscle Nerve</source><volume>23</volume><year>2000</year><fpage>1785</fpage><pub-id pub-id-type="pmid">11102901</pub-id></element-citation></ref><ref id="bib50"><label>50</label><element-citation publication-type="journal" id="sbref50"><person-group person-group-type="author"><name><surname>De Letter</surname><given-names>MA</given-names></name><name><surname>Schmitz</surname><given-names>PI</given-names></name><name><surname>Visser</surname><given-names>LH</given-names></name></person-group><article-title>Risk factors for the development of polyneuropathy and myopathy in critically ill patients</article-title><source>Crit Care Med</source><volume>29</volume><year>2001</year><fpage>2281</fpage><pub-id pub-id-type="pmid">11801825</pub-id></element-citation></ref><ref id="bib51"><label>51</label><element-citation publication-type="journal" id="sbref51"><person-group person-group-type="author"><name><surname>Douglass</surname><given-names>JA</given-names></name><name><surname>Tuxen</surname><given-names>DV</given-names></name><name><surname>Horne</surname><given-names>M</given-names></name></person-group><article-title>Myopathy in severe asthma</article-title><source>Am Rev Respir Dis</source><volume>146</volume><year>1992</year><fpage>517</fpage><pub-id pub-id-type="pmid">1362636</pub-id></element-citation></ref><ref id="bib52"><label>52</label><element-citation publication-type="journal" id="sbref52"><person-group person-group-type="author"><name><surname>Campellone</surname><given-names>JV</given-names></name><name><surname>Lacomis</surname><given-names>D</given-names></name><name><surname>Kramer</surname><given-names>DJ</given-names></name></person-group><article-title>Acute myopathy after liver transplantation</article-title><source>Neurology</source><volume>50</volume><year>1998</year><fpage>46</fpage><pub-id pub-id-type="pmid">9443456</pub-id></element-citation></ref><ref id="bib53"><label>53</label><element-citation publication-type="journal" id="sbref53"><person-group person-group-type="author"><name><surname>Perea</surname><given-names>M</given-names></name><name><surname>Picon</surname><given-names>M</given-names></name><name><surname>Miro</surname><given-names>O</given-names></name></person-group><article-title>Acute quadriplegic myopathy with loss of thick (myosin) filaments following heart transplantation</article-title><source>J Heart Lung Transplant</source><volume>20</volume><year>2001</year><fpage>1136</fpage><pub-id pub-id-type="pmid">11595571</pub-id></element-citation></ref><ref id="bib54"><label>54</label><element-citation publication-type="journal" id="sbref54"><person-group person-group-type="author"><name><surname>Leung</surname><given-names>TW</given-names></name><name><surname>Wong</surname><given-names>KS</given-names></name><name><surname>Hui</surname><given-names>AC</given-names></name></person-group><article-title>Myopathic changes associated with severe acute respiratory syndrome: a postmortem case series</article-title><source>Arch Neurol</source><volume>62</volume><year>2005</year><fpage>1113</fpage><pub-id pub-id-type="pmid">16009768</pub-id></element-citation></ref><ref id="bib55"><label>55</label><element-citation publication-type="journal" id="sbref55"><person-group person-group-type="author"><name><surname>Trojaborg</surname><given-names>W</given-names></name><name><surname>Weimer</surname><given-names>LH</given-names></name><name><surname>Hays</surname><given-names>AP</given-names></name></person-group><article-title>Electrophysiologic studies in critical illness associated weakness: myopathy or neuropathy—a reappraisal</article-title><source>Clin Neurophysiol</source><volume>112</volume><year>2001</year><fpage>1586</fpage><pub-id pub-id-type="pmid">11514240</pub-id></element-citation></ref><ref id="bib56"><label>56</label><element-citation publication-type="journal" id="sbref56"><person-group person-group-type="author"><name><surname>Sitwell</surname><given-names>LD</given-names></name><name><surname>Weinshenker</surname><given-names>BG</given-names></name><name><surname>Monpetit</surname><given-names>V</given-names></name></person-group><article-title>Complete ophthalmoplegia as a complication of acute corticosteroid- and pancuronium-associated myopathy</article-title><source>Neurology</source><volume>41</volume><year>1991</year><fpage>921</fpage><pub-id pub-id-type="pmid">2046941</pub-id></element-citation></ref><ref id="bib57"><label>57</label><element-citation publication-type="journal" id="sbref57"><person-group person-group-type="author"><name><surname>Park</surname><given-names>EJ</given-names></name><name><surname>Nishida</surname><given-names>T</given-names></name><name><surname>Sufit</surname><given-names>RL</given-names></name></person-group><article-title>Prolonged compound muscle action potential duration in critical illness myopathy</article-title><source>J Clin Neuromusc Dis</source><volume>5</volume><year>2004</year><fpage>176</fpage></element-citation></ref><ref id="bib58"><label>58</label><element-citation publication-type="journal" id="sbref58"><person-group person-group-type="author"><name><surname>Schwarz</surname><given-names>J</given-names></name><name><surname>Planck</surname><given-names>J</given-names></name><name><surname>Briegel</surname><given-names>J</given-names></name></person-group><article-title>Single-fiber electromyography, nerve conduction studies, and conventional electromyography in patients with critical-illness polyneuropathy: evidence for a lesion of terminal motor axons</article-title><source>Muscle Nerve</source><volume>20</volume><year>1997</year><fpage>696</fpage><pub-id pub-id-type="pmid">9149076</pub-id></element-citation></ref><ref id="bib59"><label>59</label><element-citation publication-type="journal" id="sbref59"><person-group person-group-type="author"><name><surname>Rich</surname><given-names>MM</given-names></name><name><surname>Bird</surname><given-names>SJ</given-names></name><name><surname>Raps</surname><given-names>EC</given-names></name></person-group><article-title>Direct muscle stimulation in acute quadriplegic myopathy</article-title><source>Muscle Nerve</source><volume>20</volume><year>1997</year><fpage>665</fpage><pub-id pub-id-type="pmid">9149072</pub-id></element-citation></ref><ref id="bib60"><label>60</label><element-citation publication-type="journal" id="sbref60"><person-group person-group-type="author"><name><surname>Rich</surname><given-names>MM</given-names></name><name><surname>Teener</surname><given-names>JW</given-names></name><name><surname>Raps</surname><given-names>EC</given-names></name></person-group><article-title>Muscle is electrically inexcitable in acute quadriplegic myopathy</article-title><source>Neurology</source><volume>46</volume><year>1996</year><fpage>731</fpage><pub-id pub-id-type="pmid">8618674</pub-id></element-citation></ref><ref id="bib61"><label>61</label><element-citation publication-type="book" id="sbref61"><person-group person-group-type="author"><name><surname>Bird</surname><given-names>SJ</given-names></name></person-group><chapter-title>Myopathies and disorders of neuromuscular transmission</chapter-title><person-group person-group-type="editor"><name><surname>Brown</surname><given-names>W</given-names></name><name><surname>Bolton</surname><given-names>C</given-names></name><name><surname>Aminoff</surname><given-names>MJ</given-names></name></person-group><source>Neuromuscular Function and Disease</source><year>2002</year><publisher-name>WB Saunders</publisher-name><publisher-loc>Philadelphia</publisher-loc><fpage>1507</fpage></element-citation></ref><ref id="bib62"><label>62</label><element-citation publication-type="journal" id="sbref62"><person-group person-group-type="author"><name><surname>Lefaucher</surname><given-names>JP</given-names></name><name><surname>Nordine</surname><given-names>T</given-names></name><name><surname>Rodriguez</surname><given-names>P</given-names></name></person-group><article-title>Origin of ICU acquired paresis determined by direct muscle stimulation</article-title><source>J Neurol Neurosurg Psychiatry</source><volume>77</volume><year>2006</year><fpage>500</fpage><pub-id pub-id-type="pmid">16306155</pub-id></element-citation></ref><ref id="bib63"><label>63</label><element-citation publication-type="journal" id="sbref63"><person-group person-group-type="author"><name><surname>Trojaborg</surname><given-names>W</given-names></name></person-group><article-title>Electrophysiological techniques in critical illness-associated weakness</article-title><source>J Neurol Sci</source><volume>242</volume><year>2006</year><fpage>83</fpage><pub-id pub-id-type="pmid">16412474</pub-id></element-citation></ref><ref id="bib64"><label>64</label><element-citation publication-type="journal" id="sbref64"><person-group person-group-type="author"><name><surname>Ramsay</surname><given-names>DA</given-names></name><name><surname>Zochodne</surname><given-names>DW</given-names></name><name><surname>Robertson</surname><given-names>DM</given-names></name></person-group><article-title>A syndrome of acute severe muscle necrosis in intensive care unit patients</article-title><source>J Neuropathol Exp Neurol</source><volume>52</volume><year>1993</year><fpage>387</fpage><pub-id pub-id-type="pmid">8355028</pub-id></element-citation></ref><ref id="bib65"><label>65</label><element-citation publication-type="journal" id="sbref65"><person-group person-group-type="author"><name><surname>Zochodne</surname><given-names>DW</given-names></name><name><surname>Ramsay</surname><given-names>DA</given-names></name><name><surname>Saly</surname><given-names>V</given-names></name></person-group><article-title>Acute necrotizing myopathy of intensive care: electrophysiological studies</article-title><source>Muscle Nerve</source><volume>17</volume><year>1994</year><fpage>285</fpage><pub-id pub-id-type="pmid">7906383</pub-id></element-citation></ref><ref id="bib66"><label>66</label><element-citation publication-type="journal" id="sbref66"><person-group person-group-type="author"><name><surname>Hanson</surname><given-names>P</given-names></name><name><surname>Dive</surname><given-names>A</given-names></name><name><surname>Brucher</surname><given-names>JM</given-names></name></person-group><article-title>Acute corticosteroid myopathy in intensive care patients</article-title><source>Muscle Nerve</source><volume>20</volume><year>1997</year><fpage>1371</fpage><pub-id pub-id-type="pmid">9342153</pub-id></element-citation></ref><ref id="bib67"><label>67</label><element-citation publication-type="book" id="sbref67"><person-group person-group-type="author"><name><surname>Bolton</surname><given-names>C</given-names></name><name><surname>Chen</surname><given-names>R</given-names></name><name><surname>Wijdicks</surname><given-names>E</given-names></name></person-group><chapter-title>Diseases of the peripheral nervous system</chapter-title><source>Neurology of Breathing</source><year>2004</year><publisher-name>Butterworth-Heinemann (Elsevier)</publisher-name><publisher-loc>Philadelphia</publisher-loc><fpage>165</fpage></element-citation></ref><ref id="bib68"><label>68</label><element-citation publication-type="journal" id="sbref68"><person-group person-group-type="author"><name><surname>Banwell</surname><given-names>BL</given-names></name><name><surname>Mildner</surname><given-names>RJ</given-names></name><name><surname>Hassall</surname><given-names>AC</given-names></name></person-group><article-title>Muscle weakness in critically ill children</article-title><source>Neurology</source><volume>61</volume><year>2003</year><fpage>1779</fpage><pub-id pub-id-type="pmid">14694046</pub-id></element-citation></ref><ref id="bib69"><label>69</label><element-citation publication-type="journal" id="sbref69"><person-group person-group-type="author"><name><surname>Danon</surname><given-names>MJ</given-names></name><name><surname>Carpenter</surname><given-names>S</given-names></name></person-group><article-title>Myopathy and thick filament (myosin) loss following prolonged paralysis with vecuronium during steroid treatment</article-title><source>Muscle Nerve</source><volume>14</volume><year>1991</year><fpage>1131</fpage><pub-id pub-id-type="pmid">1684024</pub-id></element-citation></ref><ref id="bib70"><label>70</label><element-citation publication-type="journal" id="sbref70"><person-group person-group-type="author"><name><surname>Bird</surname><given-names>SJ</given-names></name><name><surname>Rich</surname><given-names>MM</given-names></name></person-group><article-title>Critical illness myopathy and polyneuropathy</article-title><source>Curr Neurol Neurosci Rep</source><volume>2</volume><year>2002</year><fpage>527</fpage><pub-id pub-id-type="pmid">12359108</pub-id></element-citation></ref><ref id="bib71"><label>71</label><element-citation publication-type="journal" id="sbref71"><person-group person-group-type="author"><name><surname>Al-Jaberi</surname><given-names>M</given-names></name><name><surname>Katirji</surname><given-names>B</given-names></name></person-group><article-title>The value of EMG in rhabdomyolysis</article-title><source>Muscle Nerve</source><volume>18</volume><year>1995</year><fpage>1043</fpage></element-citation></ref><ref id="bib72"><label>72</label><element-citation publication-type="journal" id="sbref72"><person-group person-group-type="author"><name><surname>Hsia</surname><given-names>AW</given-names></name><name><surname>Hattab</surname><given-names>EM</given-names></name><name><surname>Katz</surname><given-names>JS</given-names></name></person-group><article-title>Malnutrition-induced myopathy following Roux-en-Y gastric bypass</article-title><source>Muscle Nerve 2001</source><volume>24</volume><year>2001</year><fpage>1692</fpage></element-citation></ref><ref id="bib73"><label>73</label><element-citation publication-type="journal" id="sbref73"><person-group person-group-type="author"><name><surname>McLoughlin</surname><given-names>DM</given-names></name><name><surname>Spargo</surname><given-names>E</given-names></name><name><surname>Wassif</surname><given-names>WS</given-names></name></person-group><article-title>Structural and functional changes in skeletal muscle in anorexia nervosa</article-title><source>Acta Neuropathol (Berl)</source><volume>95</volume><year>1998</year><fpage>632</fpage><pub-id pub-id-type="pmid">9650756</pub-id></element-citation></ref><ref id="bib74"><label>74</label><element-citation publication-type="journal" id="sbref74"><person-group person-group-type="author"><name><surname>Latronico</surname><given-names>N</given-names></name><name><surname>Shehu</surname><given-names>I</given-names></name><name><surname>Seghelini</surname><given-names>E</given-names></name></person-group><article-title>Neuromuscular sequelae of critical illness</article-title><source>Curr Opin Crit Care</source><volume>11</volume><year>2005</year><fpage>381</fpage><pub-id pub-id-type="pmid">16015120</pub-id></element-citation></ref><ref id="bib75"><label>75</label><element-citation publication-type="journal" id="sbref75"><person-group person-group-type="author"><name><surname>Zifko</surname><given-names>U</given-names></name><name><surname>Chen</surname><given-names>R</given-names></name><name><surname>Remtulla</surname><given-names>H</given-names></name></person-group><article-title>Respiratory electrophysiologic studies in Guillain–Barré syndrome</article-title><source>J Neurol Neurosurg Psychiatry</source><volume>60</volume><year>1996</year><fpage>191</fpage><pub-id pub-id-type="pmid">8708652</pub-id></element-citation></ref><ref id="bib76"><label>76</label><element-citation publication-type="journal" id="sbref76"><person-group person-group-type="author"><name><surname>Maher</surname><given-names>J</given-names></name><name><surname>Rutledge</surname><given-names>F</given-names></name><name><surname>Remtulla</surname><given-names>H</given-names></name></person-group><article-title>Neuromuscular disorders associated with failure to wean from the ventilator</article-title><source>Intensive Care Med</source><volume>21</volume><year>1995</year><fpage>737</fpage><pub-id pub-id-type="pmid">8847429</pub-id></element-citation></ref><ref id="bib77"><label>77</label><element-citation publication-type="journal" id="sbref77"><person-group person-group-type="author"><name><surname>Spitzer</surname><given-names>AR</given-names></name><name><surname>Giancarlo</surname><given-names>T</given-names></name><name><surname>Maher</surname><given-names>L</given-names></name></person-group><article-title>Neuromuscular causes of prolonged ventilator dependency</article-title><source>Muscle Nerve</source><volume>15</volume><year>1992</year><fpage>682</fpage><pub-id pub-id-type="pmid">1508233</pub-id></element-citation></ref></ref-list></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/StressCovidV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000267 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 000267 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= StressCovidV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé= PMC:7152411
|texte= Neurological Complications in Critically Ill Patients
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/RBID.i -Sk "pubmed:NONE" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd \
| NlmPubMed2Wicri -a StressCovidV1
| This area was generated with Dilib version V0.6.33. |  |