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Title:Vpliv askorbinske kisline na pojav postoperativne ledvične okvare po operacijah na odprtem srcu : doktorska disertacija
Authors:ID Djordjević, Anže (Author)
ID Antonič, Miha (Mentor) More about this mentor... New window
ID Šušak, Stamenko (Comentor)
Files:.pdf DOK_Djordjevic_Anze_2022.pdf (1,65 MB)
MD5: 558FE7BE01A53A6ABF160476F4E7DBBF
 
Language:Slovenian
Work type:Doctoral dissertation
Typology:2.08 - Doctoral Dissertation
Organization:MF - Faculty of Medicine
Abstract:IZHODIŠČA Perioperativna ledvična okvara je pomemben dejavik smrtnosti, obolevnosti in stroškov v srčni kirurgiji, njena pojavnost v literaturi znaša od <1% in do 70%. Ledvična okvara, ki zahteva ledvično nadomestno zdravljenje, je povezana s posebej visoko smrtnostjo. Mnogo raziskav dokazuje, da tudi tista zmanjšanja ledvične funkcije, kjer ledvično nadomestno zdravjenje ni potrebno oziroma serumske vrednosti kreatinina porastejo le blago ali celo ne presežejo normalnih vrednosti, vplivajo na kratko- in dolgoročne rezultate kardiokirurškega zdravljenja. Obstaja več kot 30 definicij akutne ledvične okvare, zato je bil potreben splošno sprejet kompromis glede oblikovanja nove definicije v okviru delovne skupine Kidney Disease: Improving Global Outcomes (t.i. KDIGO klasifikacija akutne ledvične okvare) iz leta 2012. Nova KDIGO klasifikacija ima dobro napovedno vrednost obolevnosti in smrtnosti pri kritično bolnih, vključno s kardiokirurškimi bolniki. Veliko raziskav potrjuje uspešnost in varnost nadomeščanja askorbinske kisline pri visoko rizičnih bolnikih, kot so tudi tisti po operacijah na odprtem srcu, vendar smo do zdaj zasledili le nekaj manjših, ki so specifično primerjale skupine bolnikov z in brez suplementacije glede perioperativne ledvične okvare. Rezultati omenjenih raziskav kažejo, da nadomeščanje askorbinske kisline v njihovih subpopulacijah kardiokirurških bolnikov ni bilo povezano z manjšo okvaro ledvic. METODE V prospektivno raziskavo smo vključili odrasle kardiokirurške bolnike, operirane na Oddelku za kardiokirurgijo Univerzitetnega kliničnea centra Maribor in Kliniki za kardiovaskularno kirurgijo Inštituta za kardiovaskularne bolezni Vojvodine Sremska Kamenica v obdobju od decembra 2018 do maja 2019. Izključitveni kriteriji so bili starost pod 18 let, operacija brez uporabe zunajtelesnega krvnega obtoka, hiperoksalurija, anamneza ledvičnih kamnov, anamneza alergije na askorbinsko kislino, kritično predoperativno stanje (ventrikularna tahikardija ali ventrikularna fibrilacija, predoperativno kardiopulmonalno oživljanje, predoperativna inotropna podpora, vstavljena intra-aortna balonska črpalka), nujnost operacije, ki mora biti opravljena pred začetkom naslednjega delovnega dne, imunosupresivna ali antioksidativna terapija znotraj 30 dni pred operacijo, hipotermični cirkulatorni zastoj, predoperativna kronična ledvična bolezen z ocenjeno glomerulno filtracijo < 30 mL/min/1.73m2 in smrt bolnika pred zaključkom protokola študije (znotraj prvih petih postoperativnih dni). Bolnike smo razdelili na dve skupini, in sicer na testno in kontrolno. Kot kazalce ledvične funkcije smo uporabili serumsko koncentracijo kreatinina, ocenjeno glomerulno filtracijo in urno diurezo. Glede na predoperativne vrednosti smo izračunali absolutne in relativne spremembe. Vsakemu bolniku je bila med hospitalizacijo merjena urna diureza od intraoperativnega obdobja pa do petega dneva. Bolnike smo uvrstili v ustrezni razred po KDIGO klasifikaciji. Skupini smo primerjali tudi po nekaterih demografskih podatkih in tistih pred-, intra- in postoperativnih lastnostih, ki bi lahko vplivale na delovanje ledvic. V subpopulaciji bolnikov smo merili serumske vrednosti malondialdehida kot posrednega biomarkerja oksidativnega stresa. Za primerjavo skupin smo uporabili t-test za numerične in test χ-kvadrat za kategorične spremenljivke. Pri preizkušanju hipotez smo kot statistično pomembno upoštevali p < 0.05. REZULTATI Testno skupino, ki je prejela askorbinsko kislino, je sestavljalo 163 bolnikov, medtem ko je kontrolna skupina štela 169 bolnikov. Skupini sta se dobro ujemali glede na izhodiščno demografijo in so imele podobne intraoperativne značilnosti. Incidenci akutne ledvične okvare v testni in kontrolni skupini sta bili 20.9 % oziroma 28.4 % (p = 0.127). Ocenjena glomerulna filtracija se med študijskimi skupinami v celotnem pooperativnem obdobju ni razlikovala. V skupini, ki je prejela askorbinsko kislino, je bil trend višjih vrednosti malondialdehida s statistično značilnostjo prvi postoperativni dan in nižje bolnišnične umrljivosti (0.6 % proti 4.1 %, p = 0.067). Ob popustitvi aortne zažemke smo odkrili znatno povečanje koncentracije malondialdehida v serumu. Koncentracija malondialdehida v serumu se je še naprej povečevala in dosegla vrh 12 ur po operaciji. Nato je začela upadati, vendar je ostala pomembno višja v primerjavi s predoperativnimi vrednostmi 24 in 48 ur po operaciji. ZAKLJUČKI Po našem vedenju je pričujoče raziskovalno delo prva študija, ki: 1) je merila serumske vrednosti malondialdehida s pomočjo visoko specifične metode plinske kromatografije in masne spektrometrije, 2) je objavila podatke o največji skupini bolnikov po operaciji na odprtem srcu, katerim smo natančno merili perioperativne spremembe serumske koncentracije malondialdehida kot indikatorja oksidativnega stresa in 3) je objavila podatke o vplivu askorbinske kisline na pojav postoperativne akutne ledvične okvare pri največji randomizirani skupini bolnikov po operaciji na odprtem srcu. Askorbinska kislina ni pomembno znižala pojavnosti akutne ledvične okvare po operacijah na odprtem srcu z uporabo zunajtelesnega krvnega obtoka. Serumska koncentracija malodialdehida se pomembno poveča intraoperativno in narašča v zgodnjem pooperativnem obdobju do 12 ur po zaključku operacije. Pomembno povišana ostane do 48 ur po operaciji. Ključne besede: akutna ledvična okvara, askorbinska kislina, zunajtelesni krvni obtok, oksidativni stres, malondialdehid, plinska kromatografija in masna spektrometrija
Keywords:akutna ledvična okvara, askorbinska kislina, oksidativni stres, malondialdehid, plinska kromatografija in masna spektrometrija
Place of publishing:[S. l.
Place of performance:[S. l.
Publisher:A. Djordjević]
Year of publishing:2022
Number of pages:X f., 63 str.
PID:20.500.12556/DKUM-81511 New window
UDC:616.12-086-06:616.61+577.164.2:612.015.6(043.3)
COBISS.SI-ID:131348227 New window
Publication date in DKUM:29.11.2022
Views:870
Downloads:79
Metadata:XML DC-XML DC-RDF
Categories:MF
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Secondary language

Language:English
Title:Effect of Ascorbic Acid on Cardiac Surgery-Associated Acute Kidney Injury Incidence
Abstract:OBJECTIVES Cardiac surgery-associated acute kidney injury is a significant factor of morbidity and mortality after cardiac surgical procedures with an estimated incidence ranging up to 70%. Severe kidney failure requiring renal replacement therapy carries an exceptionally high mortality. Even subtle changes in kidney function can alter short- and long-term outcomes in this patient population. There are over 30 definitions of acute kidney injury with the most recent consensus been made to implement the KDIGO (Kidney Disease: Improving Global Outcomes) classification. There are multiple reports suggesting potentially beneficial effects of ascorbic acid in high risk or critically ill patient subgroups, which included also those after cardiac surgical procedures. However, only a handful of small non-randomized trials directly comparing groups with and without ascorbic acid supplementation were identified in the scientific literature. Their results show no reduction in cardiac surgery-associated acute kidney injury after ascorbic acid supplementation. METHODS All adult patients at the Department of Cardiac Surgery, University Medical Center Maribor, and Department of Cardiovascular Surgery, Institute of Cardiovascular Diseases Vojvodina, who required open heart surgery between December 2018 and May 2019, were enrolled in this prospective randomized study. Exclusion criteria were age under 18 years, off-pump surgery, hyperoxaluria, history of nephrolitiasis, critical preoperative state (ventricular tachycardia or ventricular fibrillation, presence of an intra-aortic balloon pump), emergent or salvage cases, immunosuppressive or antioxidative therapy less than 30 days prior to surgery, hypothermic circulatory arrest, preoperative chronic kidney disease with an estimated glomerular filtration rate < 30 mL/min/1.73m2 and death before the completion of the study protocol (< 5 postoperative days). All patients were randomized into either the control or test group. Kidney function was estimated depending on the serum concentration of creatinine, estimated glomerular filtration rate and urine output (measurements were performed from intraoperative period to fifth postoperative day). All patients were divided according to the KDIGO classification. Both groups were compared also regarding their demographic as well as pre-, intra- and postoperative characteristics, which could affect their kidney function. In a subpopulation of enrolled patients, serum concentrations of malondialdehyde were measured. Between-groups differences were appraised by t-test for normally distributed variables and proportions were compared using χ2 test. A 2-tailed p values equal or less than 0.05 were considered statistically significant. RESULTS 163 patients comprised the test group (ascorbic acid), whereas 169 patients were included in the control group. No siginiicant differences were observed between the groups regarding demographic and preoperative data. Acute kidney injury incidences were 20.9% and 28.4%, respectively (p = 0.127). Estimated glomerular filtration rate has not differed between groups during the entire study period. There was a trend towards higher malondialdehyde values in the ascorbic acid group with statistical significance on postoperative day 1. Additionaly, a trend towards lower mortality has been oberved in the test group (p = 0.067). After aortic cross-clamp removal, a significant increase in serum malondialdehyde levels was detected. They increased further up to 12 hours after surgery and decreased afterwards with statistical significance up to 48 hours after surgery. CONCLUSIONS The main findings of our study are that 1) it is the first trial measuring serum malondialdehyde values with the highly specific gas chromatography and mass spectrometry, 2) it published results of the largest patient group after open heart surgery with meticulous perioperative serum malondialdehyde measurements as an indicator of oxidative stress, and 3) it published data about the effect of ascorbic acid on postoperative acute kidney injury in the largest randomized group of cardiac surgical patients. Ascorbic acid did not significantly decrease the incidence of cardiac surgery-associated acute kidney injury. Serum concentrations of malondialdehyde significantly increases intraoperatively and continues to rise up to 12 hours after the surgery. It remaines significantly increased up to 48 hours after surgery. Keywords: acute kidney injury, ascorbic acid, cardiopulmonary bypass, oxidative stress, malondialdehyde, gas chromatography and mass spectrometry
Keywords:acute kidney injury, ascorbic acid, cardiopulmonary bypass, oxidative stress, malondialdehyde, gas chromatography and mass spectrometry


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