Šćepanović, Radisav

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  • Šćepanović, Radisav (3)
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Testing of newly synthesized propafenone derivatives antiarrhythmic activity in aconitic model of cardiac arrhythmia in rats

Ivković, Branka; Gojković-Bukarica, Ljiljana; Novaković, Radmila; Ćupić, Vitomir; Vladimirov, Sote; Živanović, Vladimir; Šćepanović, Radisav

(Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd, 2014)

TY  - JOUR
AU  - Ivković, Branka
AU  - Gojković-Bukarica, Ljiljana
AU  - Novaković, Radmila
AU  - Ćupić, Vitomir
AU  - Vladimirov, Sote
AU  - Živanović, Vladimir
AU  - Šćepanović, Radisav
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2297
AB  - By applying of aconitictest in in vivo experiments in rats under deep anesthesia, there was investigated the antiarrhythmic potential of newly synthetized fluorinated derivatives of propafenone. The animals were divided into four experimental groups. The first (aconitine group) was treated with aconitine at a dose of 60 μg/kg, which led to pronounced cardiac rhythm disorder in a short period of time. The appearance of ventricular extrasystole (VES) was taken as a parameter for ascertainment of cardiac rhytm disorder. The remaining three animal groups were taken for testing the potential of propafenone and propafenone fluorinated derivatives to stop the arrhythmia, and which was induced by i.v. aconitine injection (60 μg/kg). Propafenone, as well as 50F derivative, did not convert the disturbed cardiac rhythm (survival of animals was 0%). By applying 5PF derivative in a dose of 6 mg/kg, the animals survived with occasional establishment of sinus rhythm.
AB  - Primenom akonitinskog testa, u in vivo eksperimentima na pacovima u dubokoj anesteziji, ispitivan je antiaritmijski potencijal novosintetisanih fluoriranih derivata propafenona. Životinje su podeljene u četiri eksperimentalne grupe. Prva grupa (akonitinska grupa) je tretirana akonitinom u dozi od 60 μg/kg t.m., koja dovodi do vidnog poremećaja srčanog ritma u kratkom vremenskom periodu. Kao parameter za registrovanje poremećaja srčanog ritma uzetaje pojava ventrikularne ekstrasistole (VES). Ostale (tri) eksperimentalne grupe činile su životinje na kojima je ispitivan potencijal propafenona i fluoriranih derivata propafenona da zaustave aritmiju indukovanu i.v. injekcijom akonitina (60 μg/kg t.m.). Propafenon, kao i 50F derivat, nisu uspeli da konvertuju poremećen srčani ritam (preživljavanje životinja je 0 %). Prilikom aplikacije 5PF derivata u dozi od 6 mg/kg t.m. životinje su preživele, uz povremeno uspostavljanje sinusnog ritma.
PB  - Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd
T2  - Veterinarski glasnik
T1  - Testing of newly synthesized propafenone derivatives antiarrhythmic activity in aconitic model of cardiac arrhythmia in rats
T1  - Issledovanie antiaritmičeskoj aktivnosti vnov' sintezirovannyh proizvodnyh propafenona pri modelirovanii akonitovoi aritmii serdca u krys
T1  - Ispitivanje antiaritmijske aktivnosti novosintetisanih derivata propafenona u akonitinskom modelu srčane aritmije kod pacova
VL  - 68
IS  - 5-6
SP  - 281
EP  - 290
DO  - 10.2298/VETGL1406281I
ER  - 
@article{
author = "Ivković, Branka and Gojković-Bukarica, Ljiljana and Novaković, Radmila and Ćupić, Vitomir and Vladimirov, Sote and Živanović, Vladimir and Šćepanović, Radisav",
year = "2014",
abstract = "By applying of aconitictest in in vivo experiments in rats under deep anesthesia, there was investigated the antiarrhythmic potential of newly synthetized fluorinated derivatives of propafenone. The animals were divided into four experimental groups. The first (aconitine group) was treated with aconitine at a dose of 60 μg/kg, which led to pronounced cardiac rhythm disorder in a short period of time. The appearance of ventricular extrasystole (VES) was taken as a parameter for ascertainment of cardiac rhytm disorder. The remaining three animal groups were taken for testing the potential of propafenone and propafenone fluorinated derivatives to stop the arrhythmia, and which was induced by i.v. aconitine injection (60 μg/kg). Propafenone, as well as 50F derivative, did not convert the disturbed cardiac rhythm (survival of animals was 0%). By applying 5PF derivative in a dose of 6 mg/kg, the animals survived with occasional establishment of sinus rhythm., Primenom akonitinskog testa, u in vivo eksperimentima na pacovima u dubokoj anesteziji, ispitivan je antiaritmijski potencijal novosintetisanih fluoriranih derivata propafenona. Životinje su podeljene u četiri eksperimentalne grupe. Prva grupa (akonitinska grupa) je tretirana akonitinom u dozi od 60 μg/kg t.m., koja dovodi do vidnog poremećaja srčanog ritma u kratkom vremenskom periodu. Kao parameter za registrovanje poremećaja srčanog ritma uzetaje pojava ventrikularne ekstrasistole (VES). Ostale (tri) eksperimentalne grupe činile su životinje na kojima je ispitivan potencijal propafenona i fluoriranih derivata propafenona da zaustave aritmiju indukovanu i.v. injekcijom akonitina (60 μg/kg t.m.). Propafenon, kao i 50F derivat, nisu uspeli da konvertuju poremećen srčani ritam (preživljavanje životinja je 0 %). Prilikom aplikacije 5PF derivata u dozi od 6 mg/kg t.m. životinje su preživele, uz povremeno uspostavljanje sinusnog ritma.",
publisher = "Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd",
journal = "Veterinarski glasnik",
title = "Testing of newly synthesized propafenone derivatives antiarrhythmic activity in aconitic model of cardiac arrhythmia in rats, Issledovanie antiaritmičeskoj aktivnosti vnov' sintezirovannyh proizvodnyh propafenona pri modelirovanii akonitovoi aritmii serdca u krys, Ispitivanje antiaritmijske aktivnosti novosintetisanih derivata propafenona u akonitinskom modelu srčane aritmije kod pacova",
volume = "68",
number = "5-6",
pages = "281-290",
doi = "10.2298/VETGL1406281I"
}
Ivković, B., Gojković-Bukarica, L., Novaković, R., Ćupić, V., Vladimirov, S., Živanović, V.,& Šćepanović, R.. (2014). Testing of newly synthesized propafenone derivatives antiarrhythmic activity in aconitic model of cardiac arrhythmia in rats. in Veterinarski glasnik
Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd., 68(5-6), 281-290.
https://doi.org/10.2298/VETGL1406281I
Ivković B, Gojković-Bukarica L, Novaković R, Ćupić V, Vladimirov S, Živanović V, Šćepanović R. Testing of newly synthesized propafenone derivatives antiarrhythmic activity in aconitic model of cardiac arrhythmia in rats. in Veterinarski glasnik. 2014;68(5-6):281-290.
doi:10.2298/VETGL1406281I .
Ivković, Branka, Gojković-Bukarica, Ljiljana, Novaković, Radmila, Ćupić, Vitomir, Vladimirov, Sote, Živanović, Vladimir, Šćepanović, Radisav, "Testing of newly synthesized propafenone derivatives antiarrhythmic activity in aconitic model of cardiac arrhythmia in rats" in Veterinarski glasnik, 68, no. 5-6 (2014):281-290,
https://doi.org/10.2298/VETGL1406281I . .

The novel ortho-chloro derivate propafenone induced relaxation in isolated rat aorta

Ivković, Branka; Gojković-Bukarica, Ljiljana; Vladimirov, S.; Novaković, Radmila; Ćupić, Vitomir; Lešić, A.; Bumbaširević, M.; Šćepanović, Radisav

(Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd, 2013)

TY  - JOUR
AU  - Ivković, Branka
AU  - Gojković-Bukarica, Ljiljana
AU  - Vladimirov, S.
AU  - Novaković, Radmila
AU  - Ćupić, Vitomir
AU  - Lešić, A.
AU  - Bumbaširević, M.
AU  - Šćepanović, Radisav
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2063
AB  - The information on the inhibitory effect of propafenone in vascular smooth muscle is sparse. Propafenone acts through blockage of voltage-dependent cardiac Na+ channels, L-type Ca2+ channels, voltage-sensitive K+ (Kv) channels, as well as β-adrenergic receptors in the heart. The introduction of different chemical groups in the benzyl moiety of propafenone influences pharmacological properties of newly developed derivate of propafenone. Here we investigated the effect of new ortho-chloro derivate of propafenone (5OCl) on the vascular tone of precontracted rat aorta. 5OCl produced endothelium-independent relaxation of rat aorta. In order to test the involvement of different ion channels in 5OCl mechanism of action, antagonist of Na+, lidocaine, KV channels, 4-aminopyiridine (4-AP) and L-type Ca2+ channels, nifedipine were used. All tested antagonists of ion channels did not influence the relaxation of rat aorta induced by high a concentration of 5OCl (≥10 μM), but antagonized the relaxation induced by low concentrations of this propafenone derivate. Thus, 5OCl derivate has comparable potency and efficacy as propafenone. According to its interaction with lidocaine, 4-AP and nifedipine it seems that 5OCl partly shares the mechanism of action with propafenone. The mechanism of vasodilatation induced by high micromolar concentration of 5OCl is not defined and further investigations are necessary.
AB  - Informacije o efektima propafenona na vaskularne glatke mišiće su oskudne. Propafenon blokira voltažno-zavisne Na+ kanale, Ca2+ kanale L-tipa, voltažno-senzitivne K+ (Kv) kanale i β-adrenergičke receptore u srcu. Uvođenje različitih hemijskih grupa u benzilni deo molekula propafenona utiče na promenu njegovih farmakoloških osobina. U ovoj studiji je ispitivan uticaj novog orto-hloro derivata (5OCl) propafenona na vaskularni tonus prekontrahovane aorte pacova. Orto hlorni derivat (5OCl) je izazvao endotel-nezavisnu relaksaciju aortnih prstenova. Da bi se ispitala uloga različitih jonskih kanala u ovoj relaksaciji, korišćeni su lidokain, (antagonist Na+ kanala), 4-aminopiridin (antagonist Kv kanala) i nifedipin (antagonist Ca2+ kanala L-tipa). Testirani antagonisti jonskih kanala nisu uticali na relaksaciju aorte pacova izazvanu visokom koncentracijom 5OCl (≥10 μM), ali su zato antagonizovali relaksaciju aorte koncentracijama 5OCl koje su bile manje od 10 μM. Prema tome, 5OCl derivat ima sličnu jačinu i efikasnost kao propafenon. Prema njegovoj interakciji sa lidokainom, 4-AP i nifedipinom može se reći da je mehanizam dejstva 5OCl sličan propafenonu. Mehanizam vazodilatacije 5OCl derivata u koncentracijama većim od 10 μM nije definisan i za to su potrebna dalja istraživanja.
PB  - Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd
T2  - Acta veterinaria
T1  - The novel ortho-chloro derivate propafenone induced relaxation in isolated rat aorta
T1  - Relaksacija aorte pacova indukovana novosintetisanim orto-hlornim derivatom propafenona
VL  - 63
IS  - 4
SP  - 363
EP  - 371
DO  - 10.2298/AVB1304363I
ER  - 
@article{
author = "Ivković, Branka and Gojković-Bukarica, Ljiljana and Vladimirov, S. and Novaković, Radmila and Ćupić, Vitomir and Lešić, A. and Bumbaširević, M. and Šćepanović, Radisav",
year = "2013",
abstract = "The information on the inhibitory effect of propafenone in vascular smooth muscle is sparse. Propafenone acts through blockage of voltage-dependent cardiac Na+ channels, L-type Ca2+ channels, voltage-sensitive K+ (Kv) channels, as well as β-adrenergic receptors in the heart. The introduction of different chemical groups in the benzyl moiety of propafenone influences pharmacological properties of newly developed derivate of propafenone. Here we investigated the effect of new ortho-chloro derivate of propafenone (5OCl) on the vascular tone of precontracted rat aorta. 5OCl produced endothelium-independent relaxation of rat aorta. In order to test the involvement of different ion channels in 5OCl mechanism of action, antagonist of Na+, lidocaine, KV channels, 4-aminopyiridine (4-AP) and L-type Ca2+ channels, nifedipine were used. All tested antagonists of ion channels did not influence the relaxation of rat aorta induced by high a concentration of 5OCl (≥10 μM), but antagonized the relaxation induced by low concentrations of this propafenone derivate. Thus, 5OCl derivate has comparable potency and efficacy as propafenone. According to its interaction with lidocaine, 4-AP and nifedipine it seems that 5OCl partly shares the mechanism of action with propafenone. The mechanism of vasodilatation induced by high micromolar concentration of 5OCl is not defined and further investigations are necessary., Informacije o efektima propafenona na vaskularne glatke mišiće su oskudne. Propafenon blokira voltažno-zavisne Na+ kanale, Ca2+ kanale L-tipa, voltažno-senzitivne K+ (Kv) kanale i β-adrenergičke receptore u srcu. Uvođenje različitih hemijskih grupa u benzilni deo molekula propafenona utiče na promenu njegovih farmakoloških osobina. U ovoj studiji je ispitivan uticaj novog orto-hloro derivata (5OCl) propafenona na vaskularni tonus prekontrahovane aorte pacova. Orto hlorni derivat (5OCl) je izazvao endotel-nezavisnu relaksaciju aortnih prstenova. Da bi se ispitala uloga različitih jonskih kanala u ovoj relaksaciji, korišćeni su lidokain, (antagonist Na+ kanala), 4-aminopiridin (antagonist Kv kanala) i nifedipin (antagonist Ca2+ kanala L-tipa). Testirani antagonisti jonskih kanala nisu uticali na relaksaciju aorte pacova izazvanu visokom koncentracijom 5OCl (≥10 μM), ali su zato antagonizovali relaksaciju aorte koncentracijama 5OCl koje su bile manje od 10 μM. Prema tome, 5OCl derivat ima sličnu jačinu i efikasnost kao propafenon. Prema njegovoj interakciji sa lidokainom, 4-AP i nifedipinom može se reći da je mehanizam dejstva 5OCl sličan propafenonu. Mehanizam vazodilatacije 5OCl derivata u koncentracijama većim od 10 μM nije definisan i za to su potrebna dalja istraživanja.",
publisher = "Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd",
journal = "Acta veterinaria",
title = "The novel ortho-chloro derivate propafenone induced relaxation in isolated rat aorta, Relaksacija aorte pacova indukovana novosintetisanim orto-hlornim derivatom propafenona",
volume = "63",
number = "4",
pages = "363-371",
doi = "10.2298/AVB1304363I"
}
Ivković, B., Gojković-Bukarica, L., Vladimirov, S., Novaković, R., Ćupić, V., Lešić, A., Bumbaširević, M.,& Šćepanović, R.. (2013). The novel ortho-chloro derivate propafenone induced relaxation in isolated rat aorta. in Acta veterinaria
Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd., 63(4), 363-371.
https://doi.org/10.2298/AVB1304363I
Ivković B, Gojković-Bukarica L, Vladimirov S, Novaković R, Ćupić V, Lešić A, Bumbaširević M, Šćepanović R. The novel ortho-chloro derivate propafenone induced relaxation in isolated rat aorta. in Acta veterinaria. 2013;63(4):363-371.
doi:10.2298/AVB1304363I .
Ivković, Branka, Gojković-Bukarica, Ljiljana, Vladimirov, S., Novaković, Radmila, Ćupić, Vitomir, Lešić, A., Bumbaširević, M., Šćepanović, Radisav, "The novel ortho-chloro derivate propafenone induced relaxation in isolated rat aorta" in Acta veterinaria, 63, no. 4 (2013):363-371,
https://doi.org/10.2298/AVB1304363I . .

Low Fresh Gas Flow Balanced Anesthesia Versus Target Controlled Intravenous Infusion Anesthesia in Laparoscopic Cholecystectomy: A Cost-Minimization Analysis

Stevanović, Predrag; Petrova, Guenka; Miljković, Branislava; Šćepanović, Radisav; Perunović, Radoslav; Stojanović, Dragos; Dobrasinović, Janja

(Elsevier, Bridgewater, 2008)

TY  - JOUR
AU  - Stevanović, Predrag
AU  - Petrova, Guenka
AU  - Miljković, Branislava
AU  - Šćepanović, Radisav
AU  - Perunović, Radoslav
AU  - Stojanović, Dragos
AU  - Dobrasinović, Janja
PY  - 2008
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1033
AB  - Background: Laparoscopic surgery is widely recognized as a well-tolerated and effective method for cholecystectomy. It is also considered cost saving because it has been associated with a decreased hospital length of stay. Variables that might lead to increased costs in laparoscopic surgery are the technique and drugs used in anesthesia. Objective: The goal of this study was to compare the costs of 2 anesthetic techniques used in laparoscopic cholecystectomy (LC)-balanced versus IV anesthesia- from the standpoint of an outpatient surgical department, with a time horizon of 1 year. Methods: Patients scheduled to undergo elective LC were enrolled in this prospective case study. Patients were randomly allocated to receive balanced anesthesia, administered as low fresh gas flow (LFGF) with inhalational sevoflurane and IV sufentanil in a target controlled infusion (LFGF SS group), or IV anesthesia, administered as IV propofol/sufentanil in a target controlled infusion (TCI group). We used a microcosting procedure to measure health care resource utilization in individual patients to detect treatment differences. The costs of medications used for the induction and maintenance of anesthesia during surgery were considered for LFGF SS and TCI. Other end points included duration of anesthesia; mean times to early emergence, tracheal extubation, orientation, and postanesthesia discharge (PAD); pain intensity before first analgesia; number of analgesics required in the first 24 hours after surgery; and prevalences of nausea, vomiting, and agitation. Results: A total of 60 patients were included in this analysis (male/female ratios in the LFGF SS and TCI groups: 11/19 and 12/18, respectively; mean [SD] ages, 48 [7.9] and 47 [8.6] years; and mean [SD] body mass indexes, 26 [2.0] and 26 [3.0] kg/m(2)). The costs of anesthetics were significantly lower with LFGF SS compared with TCI (is an element of 17.40 [is an element of 2.66] vs is an element of 22.01 [is an element of 2.50] [2006 euros]). Times to early emergence and tracheal extubation were significantly shorter with LFGF SS than TCI (5.97 [1.16] vs 7.73 [1.48] minutes and 7.57 [1.07] vs 8.87 [1.45] minutes, respectively). There were no significant between-group differences in mean duration of anesthesia; times to orientation and PAD; pain intensity before first analgesia; number of analgesics required in the first 24 hours; or prevalences of nausea, vomiting, and agitation. Because no clinically significant differences in the anesthetic results were observed, a cost-minimization analysis was conducted and found that using LFGF SS, the outpatient surgical department could realize a budget savings of is an element of 454 per 100 patients. For the nearly 1000 expected patients per year, the savings for the department was calculated as is an element of 4540. Conclusion: The results from this cost analysis in these patients who underwent elective LC suggest that the use of sevoflurane through the LFGF technique would be cost saving in this outpatient surgical department. (Clin Ther. 2008;30:1714-1725)
PB  - Elsevier, Bridgewater
T2  - Clinical Therapeutics
T1  - Low Fresh Gas Flow Balanced Anesthesia Versus Target Controlled Intravenous Infusion Anesthesia in Laparoscopic Cholecystectomy: A Cost-Minimization Analysis
VL  - 30
IS  - 9
SP  - 1714
EP  - 1725
DO  - 10.1016/j.clinthera.2008.09.009
ER  - 
@article{
author = "Stevanović, Predrag and Petrova, Guenka and Miljković, Branislava and Šćepanović, Radisav and Perunović, Radoslav and Stojanović, Dragos and Dobrasinović, Janja",
year = "2008",
abstract = "Background: Laparoscopic surgery is widely recognized as a well-tolerated and effective method for cholecystectomy. It is also considered cost saving because it has been associated with a decreased hospital length of stay. Variables that might lead to increased costs in laparoscopic surgery are the technique and drugs used in anesthesia. Objective: The goal of this study was to compare the costs of 2 anesthetic techniques used in laparoscopic cholecystectomy (LC)-balanced versus IV anesthesia- from the standpoint of an outpatient surgical department, with a time horizon of 1 year. Methods: Patients scheduled to undergo elective LC were enrolled in this prospective case study. Patients were randomly allocated to receive balanced anesthesia, administered as low fresh gas flow (LFGF) with inhalational sevoflurane and IV sufentanil in a target controlled infusion (LFGF SS group), or IV anesthesia, administered as IV propofol/sufentanil in a target controlled infusion (TCI group). We used a microcosting procedure to measure health care resource utilization in individual patients to detect treatment differences. The costs of medications used for the induction and maintenance of anesthesia during surgery were considered for LFGF SS and TCI. Other end points included duration of anesthesia; mean times to early emergence, tracheal extubation, orientation, and postanesthesia discharge (PAD); pain intensity before first analgesia; number of analgesics required in the first 24 hours after surgery; and prevalences of nausea, vomiting, and agitation. Results: A total of 60 patients were included in this analysis (male/female ratios in the LFGF SS and TCI groups: 11/19 and 12/18, respectively; mean [SD] ages, 48 [7.9] and 47 [8.6] years; and mean [SD] body mass indexes, 26 [2.0] and 26 [3.0] kg/m(2)). The costs of anesthetics were significantly lower with LFGF SS compared with TCI (is an element of 17.40 [is an element of 2.66] vs is an element of 22.01 [is an element of 2.50] [2006 euros]). Times to early emergence and tracheal extubation were significantly shorter with LFGF SS than TCI (5.97 [1.16] vs 7.73 [1.48] minutes and 7.57 [1.07] vs 8.87 [1.45] minutes, respectively). There were no significant between-group differences in mean duration of anesthesia; times to orientation and PAD; pain intensity before first analgesia; number of analgesics required in the first 24 hours; or prevalences of nausea, vomiting, and agitation. Because no clinically significant differences in the anesthetic results were observed, a cost-minimization analysis was conducted and found that using LFGF SS, the outpatient surgical department could realize a budget savings of is an element of 454 per 100 patients. For the nearly 1000 expected patients per year, the savings for the department was calculated as is an element of 4540. Conclusion: The results from this cost analysis in these patients who underwent elective LC suggest that the use of sevoflurane through the LFGF technique would be cost saving in this outpatient surgical department. (Clin Ther. 2008;30:1714-1725)",
publisher = "Elsevier, Bridgewater",
journal = "Clinical Therapeutics",
title = "Low Fresh Gas Flow Balanced Anesthesia Versus Target Controlled Intravenous Infusion Anesthesia in Laparoscopic Cholecystectomy: A Cost-Minimization Analysis",
volume = "30",
number = "9",
pages = "1714-1725",
doi = "10.1016/j.clinthera.2008.09.009"
}
Stevanović, P., Petrova, G., Miljković, B., Šćepanović, R., Perunović, R., Stojanović, D.,& Dobrasinović, J.. (2008). Low Fresh Gas Flow Balanced Anesthesia Versus Target Controlled Intravenous Infusion Anesthesia in Laparoscopic Cholecystectomy: A Cost-Minimization Analysis. in Clinical Therapeutics
Elsevier, Bridgewater., 30(9), 1714-1725.
https://doi.org/10.1016/j.clinthera.2008.09.009
Stevanović P, Petrova G, Miljković B, Šćepanović R, Perunović R, Stojanović D, Dobrasinović J. Low Fresh Gas Flow Balanced Anesthesia Versus Target Controlled Intravenous Infusion Anesthesia in Laparoscopic Cholecystectomy: A Cost-Minimization Analysis. in Clinical Therapeutics. 2008;30(9):1714-1725.
doi:10.1016/j.clinthera.2008.09.009 .
Stevanović, Predrag, Petrova, Guenka, Miljković, Branislava, Šćepanović, Radisav, Perunović, Radoslav, Stojanović, Dragos, Dobrasinović, Janja, "Low Fresh Gas Flow Balanced Anesthesia Versus Target Controlled Intravenous Infusion Anesthesia in Laparoscopic Cholecystectomy: A Cost-Minimization Analysis" in Clinical Therapeutics, 30, no. 9 (2008):1714-1725,
https://doi.org/10.1016/j.clinthera.2008.09.009 . .
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