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Rizky Adriansyah

Efek parasetamol intravena dalam penutupan duktus arteriosus persisten pada bayi prematur = The effect of intravenous paracetamol on closure of patent ductus arteriosus in premature babies / Rizky Adriansyah

"ABSTRAK

Latar Belakang. Indometasin dan ibuprofen merupakan standar obat yang digunakan untuk menutup duktus arteriosus persisten dengan gangguan hemodinamik signifikan (hemodinamically significant patent ductus arteriosus, hs-PDA). Sediaan injeksi intravena dari kedua obat tersebut belum tersedia di Indonesia. Beberapa laporan kasus serial sebelumnya menunjukkan parasetamol intravena dapat menjadi alternatif pengobatan hs-PDA pada bayi prematur.

Tujuan. Untuk mengevaluasi efek parasetamol intravena dalam penutupan PDA pada bayi prematur.

Metode. Desain kuasi-eksperimental dilakukan mulai 15 Mei sampai 31 Agustus 2014 di Rumah Sakit Umum Pusat Dr. Cipto Mangunkusumo, Jakarta. Kriteria diagnosis hs-PDA berdasarkan ekokardiografi dan diameter duktus diukur dari pandangan parasternal sumbu pendek atau pandangan suprasternal sumbu panjang. Bayi prematur usia 2-7 hari diberikan parasetamol intravena dosis 15 mg/kg tiap 6 jam diberikan selama 3-6 hari dan dipantau sampai usia kronologis 14 hari. Uji Fischer exact digunakan untuk menilai hubungan antara kelompok bayi dengan penutupan PDA. Uji t berpasangan digunakan untuk menilai perubahan diameter duktus antara sebelum dan sesudah intervensi. Hasil penelitian dinyatakan bermakna jika P<0,05.

Hasil. Sebanyak 29 bayi diikutsertakan dalam penelitian. Rerata usia gestasi 30,8 minggu dan berat lahir 1347 gram. Sembilan belas berhasil menutup, 1 reopening, 9 gagal menutup, dan tidak ditemukan intoksikasi hati. Tidak ada perbedaan bermakna antara kelompok bayi berdasarkan usia gestasi dan berat lahir dalam penutupan PDA. Rerata diameter duktus sebelum intervensi 3,0 mm dan saat pemantauan usia empatbelas hari 0,6 mm. Diameter duktus berkurang sebelum dan sesudah intervensi (P<0,0001).

Kesimpulan. Parasetamol intravena efektif dalam penutupan PDA pada bayi prematur.

ABSTRACT

Introduction. Indomethacin and ibuprofen are standard drugs for closing hemodynamically significant patent ductus arteriosus (hs-PDA) in premature babies. Intravenous injection for both drugs is not yet available in Indonesia. Some previous case series shown intravenous paracetamol can be used as an alternative treatment of hs-PDA in premature babies.

Objective. To evaluate intravenous paracetamol effect on closure of PDA in premature babies.

Methods. Quasi-experimental design was conducted from May 15th to August 31th 2014 in the Dr. Ciptomangunkusumo General Hospital. Echocardiographic diagnosis of PDA was measured from parasternal-short-axis-view or suprasternal-long-axis-view. The premature babies aged 2 to 7 days were administered intravenous paracetamol of 15 mg/kg every six hours for a-3 day cycle and followed up to chronological age of 14 days. Fischer exact test was used to assess the association between babies group and closure of PDA. Pair t test was used to evaluate duct diameter between before, after intervention, and a-14 day follow up. P<0.05 was considered as statistically significant.

Results. Twenty-nine babies were included. Mean of gestational age was 30.8 weeks and birth weight was 1347 gram. Nineteen (65.5%) cases were successfully closed, 1 case reopening, 8 cases failed, and no hepatic intoxication seen. No significant differences between babies group on closure of PDA. The mean of duct diameter before, after intervention, and a-14 day follow up were 3.0 mm, 0.9 mm, and 0.6 mm, respectively (P<0.0001).

Conclusion. Intravenous paracetamol is quite effective on closure of PDA in premature babies."

Fakultas Kedokteran Universitas Indonesia, 2014

T-Pdf

UI - Tesis Membership Universitas Indonesia Library

Ni Putu Veny Kartika Yantie

Peran prostaglandin E2, vascular endothelial growth factor immature platelet fraction dan efek pemberian ibuprofen oral pada duktus arteriosus paten neonatus cukup bulan = The Role of prostaglandin vascular endothelial growth factor immature platelet fraction and efficacy of oral ibuprofen in patent ductus arteriosus of full term neonates

"Latar belakang: Morbiditas akibat duktus arteriosus paten (DAP) pada neonatus cukup bulan (NCB) cukup tinggi. Peran prostaglandin E2 (PGE2), trombosit (immature platelet fraction, IPF), dan vascular endothelial growth factor (VEGF) pada penutupan DA secara fungsional dan anatomis pada NCB belum banyak diteliti. Patofisiologi terjadinya DAP dapat memengaruhi tata laksana farmakologi dini yang belum terstandardisasi pada NCB. Penggunaan obat antiinflamasi nonsteroid seperti ibuprofen dimungkinkan dapat menghambat jalur sintesis prostaglandin dengan efek samping minimal.

Tujuan: Mengkaji peran prostaglandin E2, VEGF, IPF, dan efek pemberian ibuprofen oral dalam proses penutupan DA pada NCB.

Metode: Penelitian dilakukan di rumah sakit (RS) Sanglah Denpasar, RS Prima Medika Denpasar, dan RS Umum Daerah Wangaya Denpasar, dalam periode Maret sampai Agustus 2015. Penelitian terdiri dari 2 desain, pertama desain potong lintang pada pasien dengan DAP dan tanpa DAP secara consecutive sampling dan desain kedua uji klinis acak terkontrol ganda pada pasien DAP usia ≥ 48 jam. Pasien dengan DAP kemudian dimasukkan dalam uji klinis, dilakukan randomisasi untuk diberikan perlakuan ibuprofen oral dosis hari pertama 10 mg/kg, hari kedua dan ketiga 5 mg/kg atau plasebo. Pemantauan hemodinamik dan efek samping obat dilakukan selama pemberian perlakuan. Pemeriksaan ekokardiografi, PGE2, VEGF, IPF, dan kreatinin dilakukan pada hari pertama dan keempat pascapemberian perlakuan.

Hasil: Terdapat 64 subjek yang diteliti pada desain pertama dan 32 subjek pada desain kedua. Rerata kadar PGE2 lebih tinggi pada kelompok dengan DAP dibanding tanpa DAP, sedangkan rerata kadar VEGF dan IPF tidak berbeda. Ibuprofen oral tidak terbukti menurunkan diameter DA pascaperlakuan, tidak terdapat perbedaan rerata diameter pada kedua kelompok. Terdapat hubungan positif sedang terhadap perubahan kadar PGE2 dengan perubahan diameter DAP pascaperlakuan. Tidak terdapat perubahan hemodinamik atau efek samping akibat pemberian ibuprofen oral atau plasebo pada NCB dengan DAP.

Simpulan: Tingginya kadar PGE2 terbukti berperan dalam patensi DA pada NCB. Ibuprofen oral dosis 10 - 5 - 5 mg/kgBB tidak mengecilkan diameter DAP.

Background: Serious morbidity impact due to patent ductus arteriosus (PDA) in full-term neonates remains high. The functional role of prostaglandin E2 (PGE2), platelet (immature platelet fraction, IPF), and vascular endothelial growth factor (VEGF) has not been studied in the closure mechanism of ductus arteriosus (DA). Understanding of pathophysiology of PDA may influence early pharmacological treatments, which have not been standardized in full-term neonates. The use of non-steroidal anti-inflammatory drugs such as ibuprofen can be beneficial as a pharmacological agent in enhancing the closure of PDA with minimal adverse effects.
Objectives: To evaluate the role of prostaglandin E2, VEGF, IPF, and the effect of oral ibuprofen in the process of DA closure in full-term neonates.
Methods: This study was conducted in Sanglah General Hospital, Prima Medika Hospital, and Wangaya Hospital Denpasar. The study consisted of two designs, the first was cross-sectional design in subjects with and without PDA using consecutive sampling and the second was double blind randomized controlled trial in full-term infant aged ≥ 48 hours. Subjects with PDA were randomized to oral ibuprofen and placebo administration, in which ibuprofen was given consecutively 10 - 5 - 5 mg/kg. All subjects underwent echocardiography, PGE2, VEGF, and IPF assays. Hemodynamics monitoring was evaluated during trial and adverse effect due to ibuprofen was recorded by measuring urine volume and plasma creatinine level.
Results: From March to August 2015, there were 64 subjects recruited for the first design and 32 subjects in the second design. The mean level of PGE2 was higher significantly in the group with PDA than non PDA group, while the mean levels of VEGF and IPF showed no difference. In the second design, oral ibuprofen showed no effect in reducing DA diameter after treatment. There were no differences in mean diameter of DA in both groups before and after treatments. There was moderate positive relationship between levels of PGE2 and the change of PDA diameter. There were neither hemodynamic changes nor adverse effect due to the administration of oral ibuprofen or placebo.
Conclusions: A high level of PGE2 appears to play a pivotal role in DA patency of full-term neonates. Administration of oral ibuprofen in 10 - 5 - 5 mg/kg schedule could not induce PDA closure in full-term neonates."

Jakarta: Fakultas Kedokteran Universitas Indonesia, 2015

D-Pdf

UI - Disertasi Membership Universitas Indonesia Library

Jefferson

Efek Kombinasi Siklosporin dan Remote Ischemic Preconditioning terhadap Penurunan MDA, Konsentrasi Kalsium Sitosol, dan Edema Mitokondria pada Cedera Iskemia Reperfusi: Penelitian pada Pasien Tetralogi Fallot yang Menjalani Operasi Koreksi = Effect of Cyclosporine and Remote Ischemic Preconditioning Combination in lowering MDA, Cytosolic Calcium and Mithocondrial edema: A study of Ischemia Reperfusion Injury in Tetralogy of Fallot Patient Underwent Correction Surgery

"Latar Belakang: Low cardiac output syndrome (LCOS) pada operasi koreksi Tetralogy Fallot (TF) adalah komplikasi yang dapat meningkatkan angka kematian akibat cedera iskemia reperfusi. Terapi definitif cedera iskemia reperfusi belum ditemukan karena masalah translasi dari penelitian pada sel dan hewan coba ke penelitian pada manusia. Hatter Cardiovascular Institute merekomendasikan multitargeted therapy yang mengatasi obstruksi pembuluh darah (OPM), proteksi kardiomiosit, dan antiinflamasi. Penelitian ini menggunakan kombinasi siklosporin dan remote ischemic preconditioning (RIPC) untuk mencapai tujuan tersebut. Telah dilakukan pemeriksaan MDA dan edema mitokondria untuk membuktikan manfaat dari kombinasi siklosporin dan RIPC. Metodologi: Penelitian ini adalah uji acak tersamar ganda label terbuka yang dilakukan di RSCM dan JHC antara 2021 hingga 2022. Pasien TF usia 1-6 tahun diacak ke dalam kelompok kontrol yang mendapat terapi standar dan perlakuan yang mendapat siklosporin oral 3-5 mg/kgBB 2 jam sebelum operasi, dan RIPC sesaat setelah induksi. Limbah jaringan otot infundibulum dan sampel darah diambil di 3 fase: praiskemia, iskemia dan pascareperfusi. Ketiga jaringan yang diperoleh dilakukan isolasi mitokondria. Pemeriksaan JC-1 dan succinate dehydrogenase (SDH) dilakukan untuk mengukur kualitas isolat mitokondria. Pemeriksaan spektrofotometri terhadap isolat mitokondria dilakukan untuk mengukur edema mitokondria. Pemeriksaan MDA dilakukan untuk menilai stres oksidatif. Hasil: Terdapat 42 subyek yang mengikuti penelitian. Walaupun secara statistik tidak ada perbedaan bermakna kadar MDA, uji membran potensial, uji aktivitas enzim spesifik dan derajat edema mitokondria pada kelompok perlakuan dibandingkan kontrol namun terdapat kecenderungan penurunan MDA dan penurunan derajat edema mitokondria. Simpulan: Kombinasi siklosporin dan RIPC tidak bermakna secara statistik menurunkan kadar MDA dan derajat edema mitokondria pada pasien TF yang menjalani operasi koreksi. Terdapat kecenderungan penurunan MDA dan derajat edema mitokondria pada pasien TF yang mendapatkan siklosporin dan RIPC.

Background: Low cardiac output syndrome on Tetrallogy Fallot correction surgery is a complication caused by ischemic reperfusion Injury (IRI), which increases mortality rate. Definitive treatment of IRI has not been found until now. A multitargeted treatment that attenuates microvascular obstruction, cardiomyocyte protection, and antiinflammation in human is proposed by Hatter Cardiovascular Institute. Based on this recommendation, this study used combination of cyclosporine as an antiinflammation and treatment for microvascular obstruction and remote ischemic preconditioning (RIPC) as a cardiomyocyte protection measure. Outcome of this treatment will be analyzed mostly by evaluation of mitochondrial edema. Methods: This is an open label randomized controlled trial on patients with Tetralogy of Fallot (TF) underwent surgery in RSCM and JHC on 2021 until 2022. We recruited 1-6 year-old TF patient planned for surgical correction. Cyclosporine and RIPC were given as treatment. Chopped infundibular muscle prior to aortic cross clamping defined as preischemic sample, after aortic cross clamping defined as postischemic sample, and after aortic cross clamping off defined as postreperfusion sample. We performed isolation of mitochondria of each sample. JC-1 and succinate dehydrogenase (SDH) assays were performed to measure quality of mitochondrial isolation. Results: Forty two subjects were recruited in this research. Although there was no significant difference in MDA level and the severity of mitochondrial edema between control and treatment group, we found lower MDA post- reperfusion and lower trend of mitochondrial edema in treatment group. Conclusion: Treatment of TF patient with Cyclosporine-RIPC combination therapy tends to reduce MDA level and mitochondrial edema significantly."

Jakarta: Fakultas Kedokteran Universitas Indonesia, 2023

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UI - Disertasi Membership Universitas Indonesia Library

Dicky Fakhri

Peran polimorfisme toll like receptor 2 dan toll interacting protein terhadap kejadian sepsis dan respons imun pada anak di bawah 1 tahun yang menjalani operasi jantung terbuka = Role of toll like receptor 2 and toll interacting protein polymorphism in the development of sepsis and immunology response in children less than 1 year old undergoing open heart surgery

"[ABSTRAK

Latar Belakang: Pada anak dengan penyakit jantung bawaan (PJB) yang

menjalani operasi jantung terbuka, sepsis merupakan salah satu komplikasi

pascaoperasi. Lama prosedur pintas jantung paru, usia, status gizi, timektomi, dan

variasi genetik, seperti polimorfisme toll-like receptor (TLR) 2 dan tollinteracting

protein (TOLLIP) dapat memengaruhi respons imun. Informasi

mengenai peran faktor tersebut terhadap kejadian sepsis dan respons imun

pascaoperasi jantung terbuka masih terbatas.

Tujuan: Mengetahui peran polimorfisme TLR2, TOLLIP, dan faktor lainnya

terhadap kejadian sepsis dan respons imun pascaoperasi jantung terbuka untuk

memperoleh strategi paling tepat dalam penanganan kasus bedah jantung pada

anak.

Metodologi: Studi longitudinal dengan non-probability consecutive sampling

dilakukan pada anak <1 tahun yang menjalani operasi jantung terbuka.

Pemeriksaan polimorfisme TLR2 Arg677Trp, TLR2 N199N, TOLLIP rs5743867,

sel CD4 dan CD8 yang menyekresikan IFN-γ intraselular, sel Dendritik yang

mengekspresikan TLR2, dan sel NK. Pasien menjalani operasi jantung terbuka.

Setelah operasi, pasien dimonitor untuk menilai sepsis dan respons imun

pascaoperasi.

Hasil: Dari 108 subjek yang terlibat, 21,3% diantaranya mengalami sepsis.

Seluruh subjek adalah mutan TLR2 Arg677Trp, 92,6% pasien adalah mutan TLR2

N199N, dan 52,8% pasien adalah mutan TOLLIP rs5743867. Polimorfisme TLR2

N199N dan timektomi total tidak diikutkan dalam model analisis multivariat.

Polimorfisme TOLLIP rs5743867 (p = 0,358) menurunkan resiko sepsis, lama

prosedur pintas jantung paru ≥90 menit (p = 0,002), usia neonatus (p = 0,032), dan

gizi buruk (p = 0,558) meningkatkan risiko sepsis pascaoperasi. Jumlah respons

imun bervariasi antara kategori, namun secara umum komponen respons imun

lebih rendah pada pasien yang mengalami sepsis dibanding pada pasien yang tidak

mengalami sepsis.

Simpulan: Lama prosedur pintas jantung paru dan usia neonatus secara signifikan

memengaruhi risiko dan kecepatan sepsis pascaoperasi. Peran polimorfisme TLR2

N199N dan TOLLIP rs5743867 terhadap kejadian sepsis dan respons imun

pascaoperasi memerlukan studi komprehensif lebih lanjut.

ABSTRACT

Background: Sepsis is one of the complications in children with congenital heart

defect who underwent open heart surgery. Cardiopulmonary bypass (CPB) time,

age, nutritional status, thymectomy, and genetic variants, such as toll-like receptor

(TLR) 2 and toll-interacting protein (TOLLIP) polymorphism affect immune

response. Information regarding those factors in the development of sepsis and

immune response after open heart surgery is still limited.

Objectives: To understand the role of TLR 2 and TOLLIP polymorphism, as well

as other risk factors, in the development of sepsis and immune response following

open heart surgery to develop the best strategy in open heart surgery in children.

Methods: Longitudinal study with consecutive sampling were done in children <1

year old who underwent open heart surgery. Blood sample was obtained to check

for TLR2 Arg677Trp polymorphism, TLR2 N199N polymorphism, TOLLIP

rs5743867 polymorphism, the numbers of intracellular interferon γ CD4 and CD8,

TLR2 expression in Dendritic cells, and NK cells. Patient then underwent open

heart surgery. Thymectomy was done as indicated and CPB time was recorded.

After surgery, patient was monitored for signs of sepsis and immune response was

checked.

Results: Out of 108 patients involved in this study, 21.3% developed

postoperative sepsis. TLR2 Arg677Trp polymorphism was found in all patients,

TLR2 N199N polymorphism was found in 92.6% of the patients, and TOLLIP

rs5743867 polymorphism was found in 52.8% of the patients. TLR2 N199N

polymorphism and thymectomy were not included in multivariate analysis.

TOLLIP rs5743867 polymorphism (p = 0.358) reduced the risk of sepsis, CPB

time ≥90 menit (p = 0.002), neonates (p = 0.032), and severe malnutrition (p =

0.558) increased the risk of postoperative sepsis. Immune response?s counts vary

in each category, but were generally lower in patients who developed

postoperative sepsis.

Conclusion: Cardiopulmonary bypass time and neonates significantly influenced

the risk and hazard of postoperative sepsis. Further investigation on the role of

TLR2 N199N and TOLLIP rs5743867 polymorphism are necessary to provide

more comprehensive explanation on the development of postoperative sepsis and

the immune response after open heart surgery;Background: Sepsis is one of the complications in children with congenital heart