<?xml version="1.0" encoding="ISO-8859-1"?><cms:container xmlns:cms="http://edoc.hu-berlin.de/diml/module/cms"><cms:document><cms:meta><cms:entry id="front" part="front" ref="front" type="front"/><cms:entry id="N10009" part="front" ref="N10009" type="pagenumber">1</cms:entry><cms:entry type="title">Dosis - Wirkungs - Studie zum Einsatz von inhalativem Stickstoffmonoxid bei Patienten mit schwerem akutem Lungenversagen</cms:entry><cms:entry type="author">Matthias Bösel			</cms:entry><cms:entry id="N10035" part="front" ref="N10035" type="pagenumber">2</cms:entry><cms:entry id="N10081" part="front" ref="N10081" type="pagenumber">3</cms:entry><cms:entry id="N100E7" part="front" ref="N100E7" type="pagenumber">4</cms:entry><cms:entry id="chapter1" part="chapter1" ref="chapter1" type="chapter">1</cms:entry><cms:entry id="N10154" part="chapter1" ref="N10154" type="pagenumber">7</cms:entry><cms:entry id="N10159" part="chapter1" ref="N10159" type="section">1.1</cms:entry><cms:entry id="_Ref10556617" part="chapter1" ref="_Ref10556617" type="link"/><cms:entry id="N10190" part="chapter1" ref="N10190" type="pagenumber">8</cms:entry><cms:entry id="N10197" part="chapter1" ref="N10197" type="table"/><cms:entry id="N1020A" part="chapter1" ref="N1020A" type="pagenumber">9</cms:entry><cms:entry id="_Ref10556947" part="chapter1" ref="_Ref10556947" type="link"/><cms:entry id="_Ref10556987" part="chapter1" ref="_Ref10556987" type="link"/><cms:entry id="N10219" part="chapter1" ref="N10219" type="section">1.2</cms:entry><cms:entry id="N10226" part="chapter1" ref="N10226" type="pagenumber">10</cms:entry><cms:entry id="_Ref10556864" part="chapter1" ref="_Ref10556864" type="link"/><cms:entry id="N10232" part="chapter1" ref="N10232" type="section">1.3</cms:entry><cms:entry id="N1023C" part="chapter1" ref="N1023C" type="pagenumber">11</cms:entry><cms:entry id="_Ref10557325" part="chapter1" ref="_Ref10557325" type="link"/><cms:entry id="_Ref10557186" part="chapter1" ref="_Ref10557186" type="link"/><cms:entry id="N1024B" part="chapter1" ref="N1024B" type="section">1.4</cms:entry><cms:entry id="N1024F" part="chapter1" ref="N1024F" type="pagenumber">12</cms:entry><cms:entry id="chapter2" part="chapter2" ref="chapter2" type="chapter">2</cms:entry><cms:entry id="N10282" part="chapter2" ref="N10282" type="pagenumber">13</cms:entry><cms:entry id="N10287" part="chapter2" ref="N10287" type="section">2.1</cms:entry><cms:entry id="N102F7" part="chapter2" ref="N102F7" type="pagenumber">14</cms:entry><cms:entry id="N102FE" part="chapter2" ref="N102FE" type="table"/><cms:entry id="N10458" part="chapter2" ref="N10458" type="section">2.2</cms:entry><cms:entry id="N1045C" part="chapter2" ref="N1045C" type="pagenumber">15</cms:entry><cms:entry id="N10465" part="chapter2" ref="N10465" type="section">2.3</cms:entry><cms:entry id="N10475" part="chapter2" ref="N10475" type="pagenumber">16</cms:entry><cms:entry id="N104B5" part="chapter2" ref="N104B5" type="section">2.4</cms:entry><cms:entry id="N104BE" part="chapter2" ref="N104BE" type="section">2.5</cms:entry><cms:entry id="N104C5" part="chapter2" ref="N104C5" type="pagenumber">17</cms:entry><cms:entry id="N104CB" part="chapter2" ref="N104CB" type="section">2.6</cms:entry><cms:entry id="chapter3" part="chapter3" ref="chapter3" type="chapter">3</cms:entry><cms:entry id="N104E8" part="chapter3" ref="N104E8" type="pagenumber">18</cms:entry><cms:entry id="N104ED" part="chapter3" ref="N104ED" type="section">3.1</cms:entry><cms:entry id="N104F7" part="chapter3" ref="N104F7" type="table"/><cms:entry id="N106E4" part="chapter3" ref="N106E4" type="pagenumber">19</cms:entry><cms:entry id="N106EB" part="chapter3" ref="N106EB" type="table"/><cms:entry id="N10792" part="chapter3" ref="N10792" type="table"/><cms:entry id="N1088C" part="chapter3" ref="N1088C" type="pagenumber">20</cms:entry><cms:entry id="N10895" part="chapter3" ref="N10895" type="table"/><cms:entry id="N10949" part="chapter3" ref="N10949" type="section">3.2</cms:entry><cms:entry id="N1094D" part="chapter3" ref="N1094D" type="pagenumber">21</cms:entry><cms:entry id="N10957" part="chapter3" ref="N10957" type="mm">531#340</cms:entry><cms:entry id="N10966" part="chapter3" ref="N10966" type="pagenumber">22</cms:entry><cms:entry id="N1096D" part="chapter3" ref="N1096D" type="mm">530#307</cms:entry><cms:entry id="N10978" part="chapter3" ref="N10978" type="mm">532#297</cms:entry><cms:entry id="N10983" part="chapter3" ref="N10983" type="pagenumber">23</cms:entry><cms:entry id="N1098A" part="chapter3" ref="N1098A" type="pagenumber">24</cms:entry><cms:entry id="N1098E" part="chapter3" ref="N1098E" type="mm">585#415</cms:entry><cms:entry id="N10999" part="chapter3" ref="N10999" type="mm">605#384</cms:entry><cms:entry id="N109A3" part="chapter3" ref="N109A3" type="section">3.3</cms:entry><cms:entry id="N109A7" part="chapter3" ref="N109A7" type="pagenumber">25</cms:entry><cms:entry id="N109B4" part="chapter3" ref="N109B4" type="mm">564#218</cms:entry><cms:entry id="N109BF" part="chapter3" ref="N109BF" type="mm">563#201</cms:entry><cms:entry id="N109CA" part="chapter3" ref="N109CA" type="pagenumber">26</cms:entry><cms:entry id="N109D1" part="chapter3" ref="N109D1" type="mm">576#220</cms:entry><cms:entry id="N109DE" part="chapter3" ref="N109DE" type="mm">552#211</cms:entry><cms:entry id="N109EB" part="chapter3" ref="N109EB" type="pagenumber">27</cms:entry><cms:entry id="N109EF" part="chapter3" ref="N109EF" type="mm">563#232</cms:entry><cms:entry id="N109FC" part="chapter3" ref="N109FC" type="mm">564#217</cms:entry><cms:entry id="N10A0A" part="chapter3" ref="N10A0A" type="pagenumber">28</cms:entry><cms:entry id="N10A14" part="chapter3" ref="N10A14" type="mm">576#237</cms:entry><cms:entry id="N10A21" part="chapter3" ref="N10A21" type="mm">576#217</cms:entry><cms:entry id="N10A2E" part="chapter3" ref="N10A2E" type="pagenumber">29</cms:entry><cms:entry id="N10A3B" part="chapter3" ref="N10A3B" type="mm">586#291</cms:entry><cms:entry id="N10A48" part="chapter3" ref="N10A48" type="mm">587#292</cms:entry><cms:entry id="N10A52" part="chapter3" ref="N10A52" type="section">3.4</cms:entry><cms:entry id="N10A56" part="chapter3" ref="N10A56" type="pagenumber">30</cms:entry><cms:entry id="N10A63" part="chapter3" ref="N10A63" type="mm">563#232</cms:entry><cms:entry id="N10A70" part="chapter3" ref="N10A70" type="mm">563#235</cms:entry><cms:entry id="N10A7D" part="chapter3" ref="N10A7D" type="pagenumber">31</cms:entry><cms:entry id="N10A84" part="chapter3" ref="N10A84" type="mm">576#229</cms:entry><cms:entry id="N10A9A" part="chapter3" ref="N10A9A" type="pagenumber">32</cms:entry><cms:entry id="N10A9E" part="chapter3" ref="N10A9E" type="mm">576#253</cms:entry><cms:entry id="N10AA9" part="chapter3" ref="N10AA9" type="mm">563#223</cms:entry><cms:entry id="N10ABA" part="chapter3" ref="N10ABA" type="pagenumber">33</cms:entry><cms:entry id="N10ABE" part="chapter3" ref="N10ABE" type="mm">540#237</cms:entry><cms:entry id="N10AC9" part="chapter3" ref="N10AC9" type="mm">564#241</cms:entry><cms:entry id="N10ADA" part="chapter3" ref="N10ADA" type="pagenumber">34</cms:entry><cms:entry id="N10AE7" part="chapter3" ref="N10AE7" type="mm">576#262</cms:entry><cms:entry id="N10AF2" part="chapter3" ref="N10AF2" type="pagenumber">35</cms:entry><cms:entry id="N10AF6" part="chapter3" ref="N10AF6" type="mm">605#338</cms:entry><cms:entry id="N10B01" part="chapter3" ref="N10B01" type="mm">605#345</cms:entry><cms:entry id="chapter4" part="chapter4" ref="chapter4" type="chapter">4</cms:entry><cms:entry id="N10B10" part="chapter4" ref="N10B10" type="pagenumber">36</cms:entry><cms:entry id="N10B1E" part="chapter4" ref="N10B1E" type="section">4.1</cms:entry><cms:entry id="N10B25" part="chapter4" ref="N10B25" type="pagenumber">37</cms:entry><cms:entry id="_Ref10557257" part="chapter4" ref="_Ref10557257" type="link"/><cms:entry id="_Ref10557281" part="chapter4" ref="_Ref10557281" type="link"/><cms:entry id="_Ref58219179" part="chapter4" ref="_Ref58219179" type="link"/><cms:entry id="N10B32" part="chapter4" ref="N10B32" type="pagenumber">38</cms:entry><cms:entry id="N10B3C" part="chapter4" ref="N10B3C" type="pagenumber">39</cms:entry><cms:entry id="N10B45" part="chapter4" ref="N10B45" type="section">4.2</cms:entry><cms:entry id="N10B55" part="chapter4" ref="N10B55" type="pagenumber">40</cms:entry><cms:entry id="N10B5B" part="chapter4" ref="N10B5B" type="section">4.3</cms:entry><cms:entry id="N10B64" part="chapter4" ref="N10B64" type="section">4.4</cms:entry><cms:entry id="N10B6B" part="chapter4" ref="N10B6B" type="pagenumber">41</cms:entry><cms:entry ref="chapter5" type="chapter">5</cms:entry><cms:entry ref="N10B79" type="pagenumber">42</cms:entry><cms:entry ref="N10B8C" type="pagenumber">43</cms:entry><cms:entry ref="N10B96" type="back"/><cms:entry id="N10B98" part="N10B98" ref="N10B98" type="bibliography">
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				Danksagung</cms:entry><cms:entry id="N1125C" part="N11258" ref="N1125C" type="pagenumber">50</cms:entry><cms:entry id="N11277" part="N11277" ref="N11277" type="vita">
				Lebenslauf</cms:entry><cms:entry id="N1127B" part="N11277" ref="N1127B" type="pagenumber">51</cms:entry><cms:entry id="N11286" part="N11277" ref="N11286" type="table"/><cms:entry id="N1134E" part="N11277" ref="N1134E" type="table"/><cms:entry id="N11398" part="N11277" ref="N11398" type="table"/><cms:entry id="N11454" part="N11277" ref="N11454" type="table"/><cms:entry id="N114AE" part="N114AE" ref="N114AE" type="declaration">
				Erklärung an Eides Statt</cms:entry><cms:entry id="N114B2" part="N114AE" ref="N114B2" type="pagenumber">52</cms:entry><cms:entry part="chapter5" type=":current"/><cms:entry type=":lang">de</cms:entry><cms:entry id=":contents" part="front" ref=":contents" type=":contents">Inhaltsverzeichnis</cms:entry><cms:entry type=":help"><url href="http://...">Hilfe</url></cms:entry></cms:meta><cms:content><chapter id="chapter5" label="5">
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				<pagenumber id="N10B79" label="42" numbering="arabic" start="42"/>Zusammenfassung</head>
			<p>Durch die Applikation von inhalativem Stickstoffmonoxid (NO) kann bei Patienten mit schwerem akutem Lungenversagen (ARDS) selektiv der pulmonalarterielle Druck gesenkt, der durch das verschlechterte Ventilations-Perfusionverhältnis erhöhte Rechts-Links-Shunt vermindert und somit die arterielle Oxygenation verbessert werden.</p>
			<p>In der hier vorliegenden offenen, prospektiven Dosis-Wirkungs-Studie wurde der Einfluss von inhalativ appliziertem NO auf die Parameter des pulmonalen Gasaustausches und der Hämodynamik untersucht, und es sollte die für den Patienten unter Beachtung aller Untersuchungsergebnisse optimale NO-Dosis ermittelt werden. Zu diesem Zweck wurden 26 Patienten nach einem vorher festgelegten Protokoll NO in Konzentrationen von 0,01/ 0,1/ 1/ 10 und 100 ppm zur Beatmung zugesetzt. Es wurde der Einfluss folgender Faktoren auf die Wirkung von NO untersucht: das Alter, das Geschlecht, der Body-Mass-Index, die Ursache für Auftreten des ARDS, der Murray-Score und das Überleben des Patienten.</p>
			<p>Folgende Ergebnisse wurden festgestellt:</p>
			<p>Es kam durch die inhalative Applikation zu einer konzentrationsabhängigen Veränderung der Parameter des pulmonalen Gasaustausches und der Hämodynamik. Während der Druck im kleinen Kreislauf (PAP und PVR) signifikant gesenkt, die venöse Beimischung (Qs/Qt) verringert und somit die arterielle Oxygenierung verbessert (PaO2 und CaO2) werden konnte, änderten sich die Messwerte für die Parameter arterieller Kohlendioxidpartialdruck (PaCO2), systemischer arterieller Mitteldruck (AP), systemischer Widerstand (SVR), Cardiac Index (CI), Herzfrequenz (HF), zentraler Venendruck (ZVD) und pulmonalkapillärer Verschlussdruck (PCWP) nicht signifikant. Die rechtsventrikuläre Ejektionsfraktion änderte sich ebenfalls nicht signifikant.</p>
			<p>Als optimale Dosis konnte in dieser Studie eine NO-Konzentration zwischen 1 und 10 ppm gefunden werden. Eine weitere Dosiserhöhung führte zu keiner signifikanten Verbesserung der untersuchten Parameter. Auch wenn der Hämoglobinwert des Blutes und der Body-Mass-Index signifikant die zu einer Erhöhung des arteriellen Sauerstoffpartialdrucks um 20% (Responder) nötige Konzentration an NO beeinflusste, konnte kein anderer prädiktiver Wert für die Reaktion der Patienten auf NO gefunden werden. Die untersuchten biometrischen <pagenumber id="N10B8C" label="43" numbering="arabic" start="43"/>Daten Alter, Geschlecht, Body-Mass-Index, ARDS-Ursache, Murray-Score und Überleben des Patienten hatten keinen signifikanten Einfluss auf die NO-Wirkung. </p>
			<p>Die hier vorliegende Dosis-Wirkungs-Studie zum Einsatz von inhalativem NO bei Patienten mit ARDS bestätigt den therapeutischen Nutzen der NO-Applikation bis zu einer Konzentration von 10 ppm NO und somit weitgehend die Ergebnisse anderer Studien. Zur weiteren Untersuchung von Einflussgrößen auf die Wirkung von inhalativ verabreichtem NO bei ARDS-Patienten scheinen weiterführende, prospektive Studien mit größeren Patientenzahlen sinnvoll.</p>
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