Dokument: Einfluss einer perioperativen α-adrenergen Rezeptorblockade auf die Komplikationsrate bei der Entfernung katecholaminproduzierender Tumoren
| Titel: | Einfluss einer perioperativen α-adrenergen Rezeptorblockade auf die Komplikationsrate bei der Entfernung katecholaminproduzierender Tumoren | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=53655 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20200708-111500-5 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Deutsch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Michael Miles Albin Stübs [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Kienbaum, Peter [Gutachter] Prof. Dr. Klenzner, Thomas [Gutachter] | |||||||
| Stichwörter: | Phäochromozytom | |||||||
| Dewey Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit | |||||||
| Beschreibungen: | Hintergrund: Patienten mit unbehandeltem Phäochromozytom oder Paragangliom entwickeln in bis zu 20 % der Fälle schwere langfristige kardiovaskuläre Komplikationen wie Arrhythmien und Myokardischämien. Die einzig kausale Therapie ist die operative Tumorentfernung, welche jedoch auf Grund schlecht kontrollierbarer Freisetzung endogener Katecholamine ein hohes Risiko für intraoperative hypertensive Krisen (IHK) und kardiale Arrhythmien birgt. Aus diesem Grund wird im Rahmen aktueller Leitlinien eine prophylaktische perioperative α-adrenerge Rezeptorblockade empfohlen, die jedoch hauptsächlich auf Expertenmeinung beruht. Allerdings treten selbst unter klinisch wirksamer α-adrenerger Rezeptorblockade intraoperative hypertensive Krisen auf. Ferner führt die mit der Tumorresektion einhergehende Elimination der aus dem Tumor freigesetzten Katecholamine zu lebensbedrohlichen Hypotensionen, die einer sorgfältigen Überwachung und Therapie bedürfen.
Methodik: Nach Prüfung durch die Ethikkommission der Ärztekammer Nordrhein (#13-2015) wurden weltweit 21 Zentren (Europa, USA, Australien) durch den Studienleiter aus dem Klinikum Essen-Mitte befragt. In der primären Analyse wurde die Assoziation zwischen einer α-adrenergen Rezeptorblockade und der Rate perioperativer Komplikationen (ein Zusammenschluss mehrerer kardialer und zentralnervöser Ereignisse) untersucht. Des Weiteren wurde der Zusammenhang zwischen einer perioperativen α-adrenergen Rezeptorblockade und den sekundären Endpunkten 1. Inzidenz von IHK über 250 mmHg, und 2. perioperative Letalität, erfasst. Zusätzlich untersuchten wir im Zentrum Düsseldorf die Assoziation zwischen einer strengeren Definition für IHK mit intraoperativen Blutdrücken über 180 mmHg, die postoperative Intensivstationsverweildauer (ICUVD) und die Krankenhausverweildauer (KHVD) mit einer perioperativen α-adrenergen Rezeptorblockade. Nachdem wir eine Assoziation der α-adrenergen Rezeptorblockade mit einer verlängerten KHVD fanden, führten wir eine multivariable lineare Regressionsanalyse durch, um den Einfluss potenzieller Störgrößen (Alter, hereditäre Erkrankung, Symptomatik, OP-Verfahren, Resektionsausmaß, Lateralität, Periduralanästhesie) zu kontrollieren. Ergebnisse: Es wurden 1860 Patienten, die sich der Resektion eines Phäochromozytoms oder Paraganglioms unterziehen mussten, retrospektiv ausgewertet. Bei diesen Patienten wurden 1517 Operationen unter perioperativer α-adrenerger Rezeptorblockade durchgeführt (82 %). 1467 Patienten wurden endoskopisch operiert (79 %), bei 393 Patienten wurde ein offener Zugang gewählt (21 %). Alle Patienten erhielten eine Allgemeinanästhesie, 133 Patienten erhielten perioperativ zusätzlich einen Periduralkatheter (7 %). Es zeigte sich eine positive Korrelation zwischen der Gabe einer intraoperativen α-adrenergen Rezeptorblockade und einer erhöhten Häufigkeit perioperativer Komplikationen (p < 0,01). Demgegenüber unterschied sich die Inzidenz intraoperativer Blutdrücke über 250 mmHg und die perioperative Letalität nicht zwischen den Gruppen mit und ohne α-adrenerger Rezeptorblockade. In der Untersuchung der Subgruppe am Zentrum Düsseldorf wurden die Daten von 58 Patienten ausgewertet. 45 Patienten erhielten eine α-adrenerge Rezeptorblockade mit Phenoxybenzamin, 13 Patienten erhielten keine α-adrenerge Rezeptorblockade. Es zeigte sich keine Assoziation zwischen einer α-adrenergen Rezeptorblockade mit IHK > 180 mmHg oder mit der ICUVD, jedoch zwischen einer α-adrenergen Rezeptorblockade und einer Verlängerung der KHVD (p = 0,03). In der multivariablen linearen Regressionsanalyse zeigte sich eine signifikante Verlängerung der KHVD um 8,1 Tage (2,6; 13,6, p < 0,01) in der Gruppe der Patienten mit α-adrenerger Rezeptorblockade, während ein endoskopisches OP-Verfahren die KHVD um 7,0 Tage (-11,6; -2,4, p < 0,01) verkürzte. Diese Einflussgrößen erwiesen sich als unabhängig (p < 0,01). Schlussfolgerung: Eine perioperative α-adrenerge Rezeptorblockade im Rahmen der operativen Entfernung katecholaminproduzierender Tumoren ist mit einer Erhöhung der perioperativen Komplikationen und einer Verlängerung der KHVD assoziiert. Auf der Basis dieser Ergebnisse sollten die Sicherheit und Effektivität einer perioperativen α-adrenergen Rezeptorblockade im Rahmen prospektiver Studien überprüft werden.Background: Patients with untreated pheochromocytoma or paraganglioma have an up to 20 % risk to develop severe long-term cardiovascular complications such as arrhythmia and myocardial ischemia. The only causal therapy is surgery to remove the tumor, which, however, bears a high risk of intraoperative hypertensive crisis (IHK) and cardiac arrhythmia due to the release of endogenous catecholamines which is difficult to control. For this reason, in line with current guidelines, a prophylactic perioperative α-adrenergic receptor blocker is recommended, although this is based mainly on expert opinion. However, intraoperative hypertensive crises occur, even under clinically effective α-adrenergic receptor blockers. Furthermore, the reduction of catecholamines following the tumor resection can lead to profound hypotensive crises requiring careful monitoring and therapy. Methodology: Following examination by the Ethical Review Committee of the Ärztekammer Nordrhein (13-2015), 21 international centers (Europe, USA, Australia) were surveyed by the Klinikum Essen-Mitte in the form of a retrospective questionnaire. In the primary analysis, the association between an alpha-adrenergic receptor blocker and the number of perioperative complications (a combination of several cardiac and central nervous system events) was investigated. In addition, the correlation between a perioperative α-adrenergic receptor blocker and the secondary endpoints 1. incidence of IHK over 250 mmHg and 2. perioperative mortality, was documented. In the Düsseldorf center we also examined the association between IHC over 180 mmHg, the length of postoperative time spent in the intensive care unit (ICUVD) and the length of time spent in hospital (KHVD) with a perioperative α-adrenergic receptor blocker. After an association of the α-adrenergic receptor blocker with an extended KHVD was identified, a multivariable linear regression analysis was carried out in order to monitor the influence of potential variables (age, hereditary disease, symptoms, surgery procedure, extent of resection, laterality, epidural anesthesia). Results: 1860 pheochromocytoma and paraganglioma operations were evaluated, 1517 of which were carried out using perioperative α-adrenergic receptor blockers (82%). 1467 patients had an endoscopic procedure (79%), while 393 underwent open surgery (21%). General anesthesia was used in all cases; 133 patients (7%) were also given an epidural catheter in the perioperative period. There was a positive correlation between the administration of intraoperative alpha-adrenergic receptor blockers and an increased frequency of perioperative complications (p < 0.01). The groups with and without alpha-adrenergic receptor blockers showed no difference in the incidence of intraoperative blood pressures of over 250 mmHg and perioperative lethality. In the Düsseldorf center sub-group study, 58 patients’ data were analyzed. 45 patients received α-adrenergic receptor blockers with phenoxybenzamine; 13 patients received no α-adrenergic receptor blockers. The study did not show any association between α-adrenergic receptor blockers and IHK > 180 mmHg or with ICUVD. There was a lengthened KHVD in the group of patients with α-adrenergic receptor blockers in the t-test (p = 0.03). Subsequent multivariable linear regression analysis showed the KHVD lengthened by 8,1 days (2,6; 13,6, p < 0,01) in the group of patients with α-adrenergic receptor blockers while an endoscopic surgical procedure was associated with a shortened KHVD by 7,0 days (-11,6; -2,4, p < 0,01). This association was confirmed to be the independent (p < 0,01). Conclusion: The use of perioperative α-adrenergic receptor blockers in the context of surgical removal of catecholamine-producing tumors is associated with an increase in perioperative complications and a longer KHVD. Based on these results, the safety and effectiveness of perioperative α-adrenergic receptor blockers should be reviewed in the course of prospective studies. | |||||||
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| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 08.07.2020 | |||||||
| Dateien geändert am: | 08.07.2020 | |||||||
| Promotionsantrag am: | 06.01.2020 | |||||||
| Datum der Promotion: | 01.07.2020 |
