doktorska disertacija
Ivan Kneževič (Author), Bojan Vrtovec (Mentor), Anton Crnjac (Co-mentor)

Abstract

Odpovedovanje presadka (OP) je poguben zaplet, ki se pojavi v zgodnjem pooperativnem obdobju po presaditvi srca. Pokaže se kot huda prekatna disfunkcija presajenega srca, posledica pa je zelo visoko umrljivost in obolevnost. Kljub velikemu napredku v preprečevanju in zdravljenju OP, je to še vedno vodilni vzrok smrti v prvih 30. dneh po presaditvi. V današnjem času je hudo nesorazmerje med številom čakajočih na presaditev srca in številom dajalcev pripeljalo do tega, da velikokrat uporabimo organe slabših dajalcev in/ali iz bolj oddaljenih donorskih bolnic, kar ima za posledico daljše čase hladne ishemije. Obenem se prejemniki zaradi dolgih čakalnih list slabšajo in največji delež prejemnikov je pred presaditvijo na urgentni listi za presaditev, kar kaže na njihovo slabo splošno stanje. Za preprečevanje in zdravljenje OP po presaditvi se najpogosteje uporabljajo inotropna zdravila. Levosimendan je predstavnik nove generacije inotropnih zdravil, ki poveča kontraktilnost miokarda brez bistvenega povečanja porabe kisika v primerjavi s klasičnimi inotropnimi zdravili. Levosimendan nima izraženega proaritmogenega učinka, sočasno znižuje periferno vaskularno rezistenco in povzroči vazodilatacijo v sistemskem in pljučnem obtoku, izboljša oskrbo srčne mišice s kisikom, jo razbremeni in izboljša pretok skozi venčne arterije. Levosimendan ima tudi kardioprotektivni učinek, tako da zmanjša ishemično-reperfuzijsko poškodbo, ima protivnetne in protiapoptotične lastnosti ter ščiti miokard pred oksidativnim stresom. Cilj raziskave je ugotoviti kratkoročne in dolgoročne vplive perioperativne aplikacije levosimendana pri bolnikih po presaditvi srca. V študijo smo vključili 103 bolnike, ki so imeli opravljeno presaditev srca v UKC Ljubljana. V študijsko skupino smo vključil 56 zaporednih bolnikov. Vsi so prejeli infuzijo levosimendana po priporočeni shemi (0,1 mcg/kg/tt). V kontrolno skupino smo vključili 47 bolnikov, ki v perioperativnem obdobju niso prejeli levosimendana, zdravljeni so bili s klasično inotropno terapijo. Bolnike smo sledili 1 leto po presaditvi. Primarna zasledovana dogodka sta bila 30 dnevno in 1-letno preživetje po presaditvi. Sekundarni zasledovani dogodki so bili trajanje vazoaktivne in inotropne podpore ter njihova količino v neposrednem pooperativnem obdobju po presaditvi srca, spremembe hemodinamike v pljučni cirkulaciji v perioperativnem obdobju, čas do ekstubacije in čas do odpusta iz enote intenzivne terapije. Po presaditvi srca smo ugotovili statistično značilno razliko v umrljivosti zaradi odpovedi presadka tako v prvih 30. dneh (2,9 % v študijski skupini proti 12 % v kontrolni skupini; p=0,04), kakor tudi v enem letu (2,9 % proti 13,3%; p=0,02). Kljub napovedno bolj tvegani skupini za slabše delovanje ledvic po presaditvi, smo ugotovili, da so v študijski skupini bolniki po presaditvi srca imeli statistično pomembno nižje vrednosti serumskega kreatinina (79,83±37,20 µmol/L proti 106,71±50,20 µmol/L; p=0,03) in višje vrednosti očistka kreatinina (110,26±47,65 mL/min proti 83,52±40,00 mL/min; p=0,005) kot v kontrolni skupini. V študijski skupini je prišlo tudi do večjega znižanja pljučne hipertenzije (srednji pljučni pritisk: -14±5 mmHg) kot v kontrolni skupini (-7±4 mmHg; p=0,03). Statistično pomembno več bolnikov iz študijske skupine je potrebovalo vazoaktivno podporo z noradrenalinom (87 % proti 31 %; p=0,0002); trajanje podpore pa je bilo statistično mejno pomembno daljše (90,63±80,21 ur proti 49,47±39,91 ur; p=0,06) kot v kontrolni skupini. Bolniki v študijski skupini so bili intubirani dlje časa (4,65±6,92 dni proti 1,03±0,86 dni v kontrolni skupini; p=0,001). Zaključki Perioperativna uporaba levosimendana pomembno izboljša kratkoročno in dolgoročno preživetje po presaditvi srca, izboljša delovanje ledvic in je povezana z znižanjem pljučne hipertenzije. Bolniki, ki prejmejo levosimendan, potrebujejo več vazoaktivne podpore, kar je povezano z daljšo hospitalizacijo v enoti intezivne terap

Keywords

levosimendan;presaditev srca;intraoperativna aplikacija;ledvična funkcija;Bolezni krvožilja;Disertacije;Transplantacija srca;Kirurško zdravljenje;Komplikacije;Levosimendan;

Data

Language: Slovenian
Year of publishing:
Typology: 2.08 - Doctoral Dissertation
Organization: UM MF - Faculty of Medicine
Publisher: I. Kneževič]
UDC: 616.12-089.844:615.22(043.3)
COBISS: 512531768 Link will open in a new window
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Other data

Secondary language: English
Secondary title: Influence of perioperative levosimendan application on outcome after heart transplantation
Secondary abstract: Primary graft failure (PGF) is a devastating complication that occurs in the early postoperative period after heart transplantation. PGF appears as severe ventricular dysfunction of the transplanted heart and results in a very high mortality and morbidity. Despite significant progress in the prevention and treatment of PGF, it still represents the leading cause of death in the first 30 days after transplantation. Due to serious disproportion between the number of patients waiting for a heart transplant and the number of suitable donors, more marginal donors are used and due to an increasing distance from the donor hospitals there is a clear trend towards prolonged cold ischemia times. At the same time, the recipients are deteriorating due to long waiting lists and majority of the recipients are placed on a priority list (HU) before transplantation which indicates their general condition is worsening. For the prevention and treatment of PGF after transplantation inotropes are most commonly used. Levosimendan is representative of a new generation of inotropic drugs that increase myocardial contractility without a significant increase in myocardial oxygen consumption compared with conventional inotropic agents. Levosimendan has no proarryhithmic effects and at the same time reduces peripheral vascular resistance with the vasodilatation in the systemic and pulmonary circulation. Levosimendan improves supply of the heart muscle with oxygen, and improves the flow through the coronary arteries. Levosimendan has a cardioprotective effect by reducing ischemia-reperfusion injury, has anti-inflammatory and anti-apoptotic properties, and protects the myocardium from oxidative stress. The aim of the study is to determine the short-term and long-term effects of perioperative application of levosimendan in patients undergoing heart transplantation. In the study we included 103 patients who had a heart transplant performed in the University Medical Centre Ljubljana. The study group included 56 consecutive patients. All have received an infusion of levosimendan the recommended regimen (0.1 mg / kg / bw). In the control group, we included 47 patients who have not received levosimendan, and were treated with conventional inotropic therapy. Patients were followed for 1 year after heart transplantation. Primary end-points were 30-day and 1-year survival after transplantation. Secondary end-points were duration of vasoactive and inotropic support and their quantity in the immediate postoperative period after heart transplantation, haemodynamic changes in the pulmonary circulation in the perioperative period, time of mechanical ventilation, and time to discharge from the intensive care unit. After heart transplantation, we found a statistically significant difference in mortality rates due to graft failure, both in the first 30 days (2.9% in the study group and 12% in the control group; p = 0.04), as well as in one year (2, 9% vs. 13.3%; p = 0.02). Although the study group had a higher risk of impaired renal function, we found that after transplantation patients in the study group had significantly lower serum creatinine levels (79.83 ± 37.20 μmol / L to 106.71 ± 50.20 μmol / L; p = 0.03) and higher creatinine clearance values (110.26 ± 47.65 mL / min vs 83.52 ± 40.00 mL / min; p = 0.005) than in the control group. The study group also had a greater reduction in pulmonary hypertension (mean pulmonary pressure: -14 ± 5 mmHg) than in the control group (-7 ± 4 mmHg; p = 0.03). Significantly more patients in the study group needed a vasoactive support with norepinephrine (87% vs. 31%; p = 0.0002), and there was a trend towards longer duration of vasoactive support in the study group (90.63 ± 80.21 hours to 49.47 ± 39.91 hours; p = 0.06). Patients in the study group also required longer mechanical ventilation (4.65 ± 6.92 days versus 1.03 ± 0.86 days in the control group; p = 0.001).
Secondary keywords: levosimendan;heart transplantation;intraoperative application;renal function;
URN: URN:SI:UM:
Type (COBISS): Dissertation
Thesis comment: Univ. v Mariboru, Medicinska fak.
Pages: 87 f.
ID: 8760990