Background: Despite recent advances in surgical procedures and immunosuppressive regimes, early pancreatic graft dysfunction, mainly specified as ischemia–reperfusion injury (IRI)— Remains a common cause of pancreas graft failure with potentially worse outcomes in simultaneous pancreas-kidney transplantation (SPKT). Anesthetic conditioning is a widely described strategy to attenuate IRI and facilitate graft protection. Here, we investigate the effects of different volatile anesthetics (VAs) on early IRI-associated posttransplant clinical outcomes as well as graft function and outcome in SPKT recipients. Methods: Medical data of 105 patients undergoing SPKT between 1998–2018 were retrospectively analyzed and stratified according to the used VAs. The primary study endpoint was the association and effect of VAs on pancreas allograft failure following SPKT; secondary endpoint analyses included “IRI- associated posttransplant clinical outcome” as well as long-term graft function and outcome. Additionally, peak serum levels of C-reactive protein (CRP) and lipase during the first 72 h after SPKT were determined and used as further markers for “pancreatic IRI” and graft injury. Typical clinicopathological characteristics and postoperative outcomes such as early graft outcome and long-term function were analyzed. Results: Of the 105 included patients in this study three VAs were used: isoflurane (n = 58 patients; 55%), sevoflurane (n = 22 patients; 21%), and desflurane (n = 25 patients, 24%). Donor and recipient characteristics were comparable between both groups. Early graft loss within 3 months (24% versus 5% versus 8%, p = 0.04) as well as IRI-associated postoperative clinical complications (pancreatitis: 21% versus 5% versus 5%, p = 0.04; vascular thrombosis: 13% versus 0% versus 5%; p = 0.09) occurred more frequently in the Isoflurane group compared with the sevoflurane and desflurane groups. Anesthesia with sevoflurane resulted in the lowest serum peak levels of lipase and CRP during the first 3 days after transplantation, followed by desflurane and isoflurane (p = 0.039 and p = 0.001, respectively). There was no difference with regard to 10-year pancreas graft survival as well as endocrine/metabolic function among all three VA groups. Multivariate analysis revealed the choice of VAs as an independent prognostic factor for graft failure three months after SPKT (HR 0.38, 95%CI: 0.17–0.84; p = 0.029). Conclusions: In our study, sevoflurane and desflurane were associated with significantly increased early graft survival as well as decreased IRI-associated post-transplant clinical outcomes when compared with the isoflurane group and should be the focus of future clinical studies evaluating the positive effects of different VA agents in patients receiving SPKT.

<p>UVOD. Bilijarna kalkuloza je najče&scaron;će oboljenje hepatobilijarnog sistema, a holecistektomija predstavlja jedan od najče&scaron;će izvođenih operativnih zahvata. Laparoskopska holecistektomija je danas zlatni standard lečenja holelitijaze. Laparoskopska holecistektomija je pokazala pobolj&scaron;anje u klinički značajnim ishodima kao &scaron;to su skraćenje operativnog vremena, kraća hospitalizacija, smanjenje jačine i trajanja postoperativnog bola i brži povratak dnevnim i radnim aktivnostima. Postoperativna bol i vreme potpunog oporavka ostaju dva glavna problema posle nekomplikovane laparoskopske holecistektomije koje bi trebalo pobolj&scaron;ati. Bol koji je povezan sa laparoskopskom holecistektomijom je kompleksan i multifaktorijalan. On nastaje o&scaron;tećenjem tkiva, disekcijom i uklanjanjem žučne kesice iz svoje lože, stimulacijom periportalnih nerava, iritacijom dijafragme, mehaničkim i hemijskim interakcijama gasa i pneumoperitoneuma, incizijama portova. Istraživanja su označila parijetalni i visceralni bol kao dva glavna mehanizma nastanka bola kod laparoskopske holecistektomije. Bol se ne može meriti nego proceniti jer je subjektivni osećaj. Pokazalo se potrebnim da se na čvr&scaron;ćim naučnim osnovama da odgovor na pitanje da li je moguće blokirati parijetalni i visceralni bol posle laparoskopske holecistektomije u akutnoj fazi. CILJEVI. Cilj studije je da uporedi standardnu analgeziju (ne-opioidnu) (grupa O) sa davanjem parijetalne blokade (grupa P), ili davanjem visceralne blokade (grupa V), ili sa obe date blokade (grupa P+V). Primarni ishodi studije su bolesnikov procenjeni bol pre operacije i posle operacije na 1, 2, 4, 6, 12, 24, 48 sati i 7. dana. Sekundarni ishodi studije su bolesnikova procenjena mučnina na 1,2,4,6,12 sati i bolesnikova procenjena mobilnost 1. 2. i 7. dan. HIPOTEZA. Blokada postoperativnog visceralnog bola i blokada postoperativnog parijetalnog bola posle laparoskopske holecistektomije putem intraperitonealne lokalne infiltracije anestetikom i putem lokalne infiltracije anestetikom pristupnih laparoskopskih portova može značajno smanjiti rani postoperativni bol. MATERIJAL I METODE. Ova prospektivna, randomizirana jednostruko slepa studija je započela septembra 2014. godine i trajala je do januara 2016. godine. Istraživanje je sprovedeno na Klinici za abdominalnu, endokrinu i transplantacionu hirurgiju i Urgentnom centru Kliničkog centra Vojvodine u Novom Sadu kod bolesnika operisanih metodom laparoskopske holecistektomije. Rad je podeljen u nekoliko celina. 1. Procena veličine uzorka; 2. Procena podobnosti za studiju; 3. Anketiranje i uključivanje u studiju; 4. Razvrstavanje u grupe i operativni rad; 5. Period postoperativnog praćenja; 6. Statistička obrada i pisanje rada.<br />1. Procena veličine uzorka. Studija je realizovana podelom bolesnika u 4 grupe. Neophodni broj bolesnika je izračunat uzimajući podatke iz pilot istraživanja slične studije iz 2012. godine. Veličina uzorka je računata za primarni ishod studije&nbsp; (bolesnikov procenjen bol sa NAS) na pretpostavci da treba biti 20% smanjenja bola u prvom postoperativnom satu, uz verovatnoću Tip 1 gre&scaron;ke &alpha;=0.05 i Tipa 2 gre&scaron;ke &beta;=0.10 da postigne adekvatnu statističku snagu oko 80% i da otkrije 20% razlike u srednjoj vrednosti procenjenog bola jedan sat nakon laparoskopske&nbsp; holecistektomije. Procenjeni broj ispitanika po grupama prema zadatim kriterijumima je bio (P+V=65; P=68; V=68; O=65). Studija je započela uključivanjem prvog bolesnika u studiju a zavr&scaron;ena ispunjenim periodom praćenja sve dok poslednji bolesnik nije doneo upitnike o bolu, mučnini i kretanju. 2. Procena podobnosti za studiju. U periodu studije ukupan broj holecistektomiranih bolesnika je bio 1024 (440 klasično i 584 laparoskopski). Samo pogodni bolesnici su anketirani (584) i pročitali su informacioni list o istraživanju. Uključivanje ili procena podobnosti bolesnika za studiju sprovedena je na osnovu uključnih i isključnih kriterijuma. U studiju nije uključeno ukupno 226 bolesnika. Od tog broja 82 bolesnika je odbilo učestvovati u studiji a 144 bolesnika nije ispunilo uključne postavljene kriterijume. Svojim potpisom potvrdilo je uče&scaron;će u studiji 358 bolesnika. 3. Anketiranje i uključivanje u studiju. Nakon prijema bolesnika u bolnicu ispitivači su uzimali anamnezu i bolesnicima je ponuđen informacioni list i informisani pristanak. Nakon čitanja informacije, potpisivanja informisanog pristanka i zadovoljavanja&nbsp; uključnih i isključnih kriterijuma 358 bolesnika je uključeno u studiju. Obavljena je preoperativna priprema i ispitivači su popunili deo podataka u individualnom listu. 4. Razvrstavanje u grupe i operativni rad. Neposredno preoperativno od strane nezavisne osobe neuključene u studiju napravljena je randomizacija izabranih (n=358) u studijske grupe tablicama slučajnog izbora, tako da bolesnici nisu znali kojoj grupi pripadaju, dok su operater i osoblje to znali na početku operacije (jednostruko slepa studija). Nakon randomizacije i operacije bolesnici pripadaju jednoj od sledeće 4 grupe: Kontrolna grupa O=89, u kojoj su bolesnici sa urađenom laparoskopskom&nbsp; holecistektomijom bez visceralne blokade anestetikom i bez parijetalne blokade anestetikom. Eksperimentalna grupa P=88, u kojoj su bolesnici sa urađenom laparoskopskom holecistektomijom bez visceralne blokade anestetikom i sa parijetalnom blokadom anestetikom. Eksperimentalna grupa V=92, u kojoj su bolesnici sa urađenom laparoskopskom holecistektomijom sa visceralnom blokadom anestetikom i bez parijetalne blokade anestetikom. Eksperimentalna grupa P+V=89, u kojoj će biti bolesnici sa urađenom laparoskopskom holecistektomijom sa visceralnom blokadom anestetikom i sa parijetalnom blokadom anestetikom. Primenjivan je uobičajni, standardni protokol anestezije za laparoskopske operacije kod svih ispitanika. Svim bolesnicima plasirana je orogastrična sonda koja se nakon operacije odstranjivala. Kod&nbsp; bolesnika kod kojih je primenjivan lokalni anestetik neposredno pre početka operacije pravio se rastvor lokalnog anestetika (Marcaine&reg; 0,25%). Bolesnici su otpu&scaron;teni sa bolničkog lečenja prvog postoperativnog dana, pod uslovom da nisu imali komplikacija. 5. Postoperativno praćenje i ispunjavanje upitnika. Po dolasku na odeljenje&nbsp; bolesnicima je odmah uključivana ista analgezija. Tokom ispunjavanja informisanog pristanka, bolesnici su dobili upitnik na kojoj će sami procenjivati nivo bola, mučnine i kretanja tokom ležanja u bolnici i vremena praćenja od 7 dana kući. Bolesnici su dolazili na unapred zakazane postoperativne kontrole 7 do 10 dana posle operacije i donosili ispunjene upitnike. Otpu&scaron;teno je i za praćenje ostalo n=302 laparoskopski operisanih bolesnika a isključeno iz studije n=20 bolesnika. 6. Statistička obrada i pisanje rada. Ukupno je analizirano 274 listića operisanih bolesnika: u Grupi P+V =67; u Grupi P =70; u Grupi V =70 i u Grupi O =67. Od osnovnih deskriptivnih statističkih parametara za kvalitativnu i kvantitativnu procenu dobijenih rezultata su kori&scaron;ćeni apsolutni brojevi, relativni brojevi, mediana, mod, aritmetička sredina i standardna devijacija (SD). Obrada podataka se vr&scaron;ila&nbsp; osnovnim i naprednim statističkim metodama i programima. Rezultati su prikazani tabelarno i grafički. REZULTATI. Demografski podaci. Ukupno je bilo 188 žena i 86 mu&scaron;karaca, u odnosu 2,2 : 1. Prosečna starost cele grupe je bila 52,1 &plusmn; 15,72 godine. Ukupno je bilo 179 zaposlenih i 95 nezaposlenih. Ukupno je bilo 45 ispitanika sa osnovnim obrazovanjem, 153 ispitanika sa srednjim obrazovanjem i 76 ispitanika sa visokim obrazovanjem. Ukupno je bilo 186 nepu&scaron;ača i 88 pu&scaron;ača. Prosečna vrednost BMI cele grupe je bila 27,24 &plusmn; 4,21 kg/m2. Prosečna vrednost ASA u celoj grupi je bila 2,03 (mediana=2, mod=2). Ne postoji statistički značajna razlika između posmatranih grupa u odnosu na posmatrane parametre. Laboratorijski podaci. Postoji statistički značajna razlika u vrednosti leukocita između posmatranih grupa (p=0,039), u vrednosti uree između posmatranih grupa (p=0,040). Ne postoji statistički značajna razlika u vrednosti eritrocita, trombocita, hemoglobina, &Scaron;UK-a, kreatinina i bilirubina posmatranih grupa. Operativni i postoperativni podaci. Ne postoji statistički značajna razlika u količini upotrebljenog Fentanila između posmatranih grupa. Postoji statistički značajna razlika u dužini trajanja operacije između posmatranih grupa (p=0,003), u trajanju postavljenog abdominalnog drena između posmatranih grupa (p=0,024), u trajanju hospitalizacije između posmatranih grupa (p=0,027), u broju dana do povratka uobičajenim aktivnostima između posmatranih grupa (p=0,000), u broju uzetih tableta između posmatranih grupa (p=0,000). Prosečna ocena zadovoljstva bolesnika posle operacije u celoj grupi je bila 8,80 (mediana=9; mod=10). Najbolju ocenu zadovoljstva bolesnika posle operacije je imala grupa P+V. Procena bola, mučnine i kretanja. Postoji statistički značajna razlika između posmatranih grupa u proceni jačine bola pre operacije (p=0,003). Postoji statistički značajna razlika između posmatranih grupa u proceni jačine bola 1h posle operacije (najbolju procenu bola je imala grupa P+V); u proceni jačine bola 2h posle operacije (najbolju procenu bola je imala grupa P+V); u proceni jačine bola 4h posle operacije (najbolju procenu bola je imala grupa P); u proceni jačine bola 6h posle operacije (najbolju procenu bola je imala grupa P+V); u proceni jačine bola 12h posle operacije (najbolju procenu bola je imala grupa P+V); u proceni jačine bola 24h posle operacije (najbolju procenu bola je imala grupa P+V); u proceni jačine bola 48h posle operacije (najbolju procenu bola je imala grupa P) i u proceni jačine bola 7 dana posle operacije (najbolju procenu bola je imala grupa P). Procenjena bol se pojačava otprilike 2,5 sata posle operacije sa vrhom 3 sata posle operacije, a smanjuje se na istu vrednost kao 2. sata posle operacije, otprilike 5. sata posle operacije. U vremenskim intervalima 1, 2. i 7. postoperativni dan postoji značajno pobolj&scaron;anje u postoperativnoj mobilnosti bolesnika. U vremenskim intervalima 1, 2, 4, 6 i 12 sati postoji značajno pobolj&scaron;anje u procenjenoj vrednosti mučnine bolesnika. Korelacije. Statistički značajna pozitivna korelacija ocene bola posle 1. sata, posle 2. sata, posle 6. sata, posle 12. sata je utvrđena sa brojem uzetih tableta (p=0,000), kao i procene mučnine (p=0,000). Statistički značajna pozitivna korelacija procene bola posle 4. sata je utvrđena sa brojem uzetih tableta (p=0,006), kao i aktivnosti (p=0,014). Statistički značajna korelacija procene bola posle 24. sata je utvrđena sa brojem uzetih tableta (p=0,000; pozitivna) i trajanjem operacije (p=0,028; negativna). Statistički značajna pozitivna korelacija procene bola posle 48. sata i posle 7 dana je utvrđena sa brojem uzetih tableta (p=0,000). ZAKLJUČCI: Primena lokalnog anestetika datog na bilo koji način značajno smanjuje bol posle laparoskopske holecistektomije. Primena lokalnog anestetika datog i&nbsp; portalno i visceralno (P+V) značajno smanjuje bol u odnosu na samo portalnu (P) ili visceralnu (V) primenu u vremenskim intervalima 2, 6, 12 sat posle laparoskopske holecistektomije. Portalna (P) primena sa ili bez visceralne (V) primene lokalnog anestetika značajno smanjuje bol u vremenskim intervalima 1, 4, 24, 48 sati i 7 dana posle laparoskopske holecistektomije. Najbolje kretanje je bilo u grupi P+V posle laparoskopske holecistektomije. Najbolje smanjenje procenjene mučnine je bilo u grupi P posle laparoskopske holecistektomije. Najraniji povratak uobičajenim aktivnostima zabeležen je u grupi P+V. Najbolja ocena zadovoljstva bolesnika hirur&scaron;kim lečenjem bila je u grupi P+V. Postoperativna bol ima najznačajniju pozitivnu korelaciju sa procenjenom mučninom i brojem tableta uzetih od momenta otpusta do prve kontrole bolesnika.</p> / <p>INTRODUCTION: Biliary calculosis is the most frequent disease of the hepatobiliary system, and cholecystectomy is one of the most frequently performed surgical procedures. Today laparoscopic cholecystectomy represents the golden standard in treating cholelithiasis. Laparoscopic cholecystectomy showed improvement in the clinically significant outcomes, such as: reducing the duration of the surgery, shorter hospital stay, reducing the intensity and duration of postoperative pain and faster return to normal daily and working activities. Postoperative pain and the time of full recovery remain the two major problems after a non-complicated laparoscopic cholecystectomy and they should be improved. The pain related to laparoscopic cholecystectomy is complex and multi-factorial in origin. The pain occurs due to damaged tissues, dissection and removal of gallbladder from its cavity, stimulation of periportal nerves, irritation of the diaphragm, mechanical and chemical interaction of gases and pneumoperitoneum and port incisions. Researches have denoted parietal and visceral pains as two major mechanisms in occurrence of pain in laparoscopic cholecystectomy. Pain cannot be measured, but estimated, as it is a subjective feeling. It was considered necessary to find the answer, based on solid scientific evidence, if it was possible to block parietal and visceral pain after laparoscopic cholecystectomy in its acute phase. OBJECTIVES: The aim of this study is to compare standard, non-opioid, analgesia (group O) with applying parietal blockade (group P), or visceral blockade (group V), or compare with both applied blockades (group P+V). The primary outcomes of the study are the patient&acute;s estimated pain before surgery and 1, 2, 4, 6, 12, 24, 48 hours and 7th day after the surgery. The secondary outcomes of this study are the patient&acute;s estimated nausea level during 1, 2, 4, 6, 12 hours, along with the patient&acute;s estimated mobility 1st, 2nd and 7th day, postoperatively. HYPOTHESIS. Blockade of postoperative visceral pain and blockade of postoperative parietal pain following laparoscopic cholecystectomy, applying intraperitoneal local infiltration with anesthetic and also by local infiltration with anesthetic through accessible laparoscopic ports, can significantly reduce early postoperative pain. MATERIAL AND METHODS: This prospectively randomized single-blinded study started in September 2014 and lasted up to January 2016. The research was carried out at the Clinic for Abdominal, Endocrine and Transplantation Surgery and Emergency Center, Clinical Center of Vojvodina in Novi Sad and it involved patients who underwent laparoscopic cholecystectomy. This study has been divided into several units. 1. Assessment of sample size; 2. Assessment of eligibility for the study; 3. Survey and inclusion in the study; 4. Group formation and operational work; 5. Period of postoperative follow-up; 6. Statistical processing and writing the paper.1. Assessment of sample size. The study was realized by dividing the patients into 4 groups. The number of patients necessary was determined based on the data taken as pilot study from a similar study from 2012. Sample size was calculated for the primary outcome of the study (patient&acute;s estimated pain with NAS) based on the assumption that a pain reduction of 20% should occur during the first postoperative hour, with the probability of Type 1 error &alpha;=0.05 and Type 2 error &beta;=0.10 to reach the adequate statistical power of about 80%, and to reveal 20% difference in the average value of the estimated pain one hour after the laparoscopic cholecystectomy. The assessed number of respondents in groups according to the set criteria was (P+V =65;P =68;V =68; O =65). The study started when the first patient was included and it ended with the complete follow-up period when the last patient handed in the survey about pain, nausea and mobility. 2. Assessment of eligibility for the study. During the study the number of patients undergoing surgery applying the method of cholecystectomy was 1024 (440 classical and 584 laparoscopic). Only the suitable patients were surveyed (584) and given to read the information leaflet about the study. Inclusion and assessment of patients&acute; eligibility was performed on the basis of inclusion and exclusion criteria. A total of 226 patients was not included in the study. Out of that number 82 patients refused to participate in the study and 144 did not fulfill the inclusive criteria set. By signing 358 patients confirmed their participation in the study. 3. Survey and inclusion in the study. After admitting the patients to hospital the surveyors took their anamnesis and the patients were offered an information leaflet and informed consent. Following the reading of the information leaflet, signing the informed consent and satisfying the criteria for inclusion and exclusion, 358 patients were included in the study. Preoperative preparations were performed and the surveyors filled in some of the data on the individual list. 4. Group formation and operational work. Prior to the surgery an independent person not included in the study carried out the randomisation of the patients chosen (n=358) into study groups by random selection tables. The patients did not know which group they belonged to, while it became known to the surgeon and the operation stuff at the beginning of the surgery (singleblinded study). After randomization and surgery the patients belonged to one of the following groups: Control group O=89 of patients with performed laparoscopic cholecystectomy without visceral blockade by anesthetic and without parietal blockade by anesthetic. Experimental group P=88 of patients with performed laparoscopic cholecystectomy without visceral blockade by anesthetic but with parietal blockade by anesthetic. Experimental group V=92 of patients with performed laparoscopic cholecystectomy with visceral blockade by anesthetic but without parietal blockade by anesthetic. Experimental group P+V=89 of patients with performed laparoscopic cholecystectomy with visceral blockade by anesthetic and with parietal blockade by anesthetic. The standard protocol of anesthesia for laparoscopic cholecystectomy was applied to all patients. An orogastric tube used during the surgery, was removed after it. In patients with applied local anesthetic immediately before surgery a solution of local anesthetic was made (Marcaine&reg; 0,25%). The patients were discharged from hospital the first postoperative day, provided that no complications occurred. 5. Postoperative follow-up and completing the questionnaire. When admitted to the ward the patients were given the same kind of analgesia. While completing the informed consent the patients were given a questionnaire for estimating their pain level, nausea and mobility during their stay in hospital and during the 7-day follow-up period at home. The patients were required to come for 7 and 10-day postoperative check-ups by appointment and then they handed in the questionnaires. n=302 patients with performed laparoscopic cholecystectomy were released and designated for follow-up, and n=20 patients were excluded from the study. 6. Statistical processing and writing the paper. In total 274 operated patients&acute; slips were analysed, by groups as follows: in Group P+V =67; in Group P =70; in Group V =70 and in Group O =67. From the basic descriptive statistical parametres for qualitative and quantitative assessment of results obtained, absolute numbers, relative numbers, the median, mode, arithmetic mean and standard deviation (SD) were used. Data processing was carried out using basic and advanced statistical methods and programmes. The results are presented in tabular and graphical manner. RESULTS. Demographic data. In total there were 188 women and 86 men, in proportion 2,2 : 1. The average age of the whole group was 52,1 &plusmn; 15,72 years. In total there were 179 employed and 95 unemployed persons. In total there were 45 surveyed patients with primary education, 153 surveyed patients with secondary education and 76 surveyed patients with higher education. In total there were 186 nonsmokers and 88 smokers. The mean BMI value of the whole group was 27,24 &plusmn; 4,21 kg/m2. The mean value of ASA of the whole group was 2,03 (the median=2, mode=2). There is no significant difference among the groups observed considering the observed parametres. Laboratory data. There is a statistically significant difference in the value of leukocytes among the observed groups (p=0,039), and in the value of urea among the observed groups (p=0,040). There is no statistically significant difference in the value of the erythrocyte, platelets, hemoglobin, blood glucose, creatinine and bilirubin of the&nbsp; observed groups. Operative and postoperative data. There is no statistically significant difference in the amount of Fentanyl&reg; applied among the observed groups. There is statistically significant difference in the length of the surgery among the observed groups (p=0,003), in the duration of the positioning of abdominal drainage among the observed groups (p=0,024), in the duration of hospital stay among the observed groups (p=0,027), in the number of days until getting back to regular activities among the observed groups&nbsp; (p=0,000), in the number of taken pills among the observed groups (p=0,000). The patients&acute; average satisfaction grade after surgery in the whole group was 8,80 (the median=9; mode=10). Group P+V had the best patient&lsquo;s satisfaction grade after the surgery. Assessment of pain, nausea and mobility. There is statistically significant difference in the estimation of pain intensity before surgery among the observed groups (p=0,003). There is statistically significant difference in the estimation of pain intensity 1 hour after surgery among the observed groups (P+V having the best estimated pain); in the estimation of pain intensity 2 hours after&nbsp; surgery (P+V having the best estimated pain); in the estimation of pain intensity 4 hours after surgery (P having the best estimated pain); in the estimation of pain intensity 6 hours after surgery (P+V having the best estimated pain); in the estimation of pain intensity 12 hours after surgery (P+V having the best estimated pain); in the estimation of pain intensity 24 hours after surgery (P+V having the best estimated pain); in the estimation of pain intensity 48 hours after surgery (P having the best estimated pain) also in the estimation of pain intensity 7 days after surgery (P having the best estimated pain). The estimated pain intensifies at about 2,5 hours after surgery and peaks 3 hours after surgery, and decreases to the same level as it was during 2nd hour after surgery approximately during 5th hour after surgery. There is considerable improvement in mobility of patients in the time interval 1st, 2nd and 7th postoperative days. There is considerable improvement in estimated nausea level of patients in the time interval 1, 2, 4, 6 and 12 hours. Correlations. Statistically significant positive correlation in estimated pain after 1st hour, after 2nd hour, after 6th hour and after 12th hour was determined by the number of tablets taken (p=0,000), just like the estimated nausea level (p=0,000). Statistically significant positive correlation in estimated pain after 4th hour was determined by the number of tablets taken (p=0,006), just like the activities (p=0,014). Statistically significant positive correlation in estimated pain after 24th hour was determined by the number of tablets taken (p=0,000; positive), and by the duration of the surgery (p=0,028; negative). Statistically significant positive correlation in estimated pain after 48th hour and after 7 days was determined by the number of tablets taken (p=0,000). CONCLUSIONS: The application of local anesthetic, regardless of how it was applied, considerably reduces pain after laparoscopic cholecystectomy. The application of local anesthetic by port or viscerally (P+V) considerably reduces pain compared to only by port (P) or only visceral (V) application in the time intervals of 2, 6, and 12 hours after laparoscopic cholecystectomy. The application of local anesthetic by port (P), with or without visceral (V), considerably reduces pain in the time intervals of 1, 4, 24, and 48 hours and 7 days after laparoscopic cholecystectomy. The best mobility was shown by group P+V after laparoscopic cholecystectomy. Estimated nausea was most reduced in group P after laparoscopic cholecystectomy. Group P+V presented the earliest return to regular activities. The best patients&acute; satisfaction grade with surgical treatment was shown by group P+V. Postoperative pain is most considerably positively correlated with the estimated nausea and pills taken, from the moment of patient&acute;s release from hospital to the first check-up.<br />&nbsp;</p>

Proposta: O hospital é parte integrante de um sistema coordenado de saúde, cuja função é a prestação de serviços. Os administradores hospitalares preocupam-se em obter o menor custo possível e maximizar a qualidade. Como o custo hospitalar tem uma parcela importante representada pelo consumo de materiais e medicamentos, sendo a farmácia o setor responsável pelo controle, estoque e dispensação, o profissional farmacêutico tem-se aprimorado profissionalmente e desenvolvido pesquisas e estudos, para reformular suas atividades básicas e retomar algumas funções primárias como a farmacoeconomia, a fim de adequar-se as novas exigências. É relevante neste contexto o sistema de distribuição de medicamentos, que se iniciou com a dose coletiva, cujos principais problemas era o aumento do potencial de erros de medicação, as perdas econômicas decorrentes da falta de controles, e o tempo excessivo gasto pela enfermagem para separar a medicação, em vez de dar assistência aos pacientes. Depois avançou para dose individualizada, que além de minimizar e/ou extinguir todas as desvantagens da dose coletiva, apresentava um controle mais efetivo do consumo dos medicamentos, aumentando a integração do farmacêutico com a equipe de saúde, sendo sua principal desvantagem, o aumento das necessidades de recursos humanos e infra-estrutura da Farmácia Hospitalar. E por último a dose unitária, originada da dose individualizada, que tem como principais objetivos racionalizar a terapêutica, diminuir custos sem reduzir a qualidade da dispensação; e garantir que os medicamentos prescritos cheguem ao paciente de forma segura e higiênica, assegurando a eficácia do esquema terapêutico prescrito. Após associar os conceitos descritos acima, a farmácia do Centro Cirúrgico do Instituto Central do Hospital das Clínicas da Faculdade de Medicina da USP propôs-se a identificar o elenco representativo de produtos, e utilizar estes grupos de medicamentos, na elaboração, ampliação, e experimentação do sistema de dispensação de kit. Esta nova alternativa pretende atingir como os dois principais benefícios a melhor utilização de recursos econômicos e a elevação da qualidade de assistência prestada ao paciente e equipe multiprofissional. Método: O método de pesquisa utilizado foi um estudo de caso qualitativo/quantitativo, sendo o mesmo realizado no Centro Cirúrgico do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, no período de 12/05/2002 a 22/07/2002. Foram escolhidas como amostra as dez salas do bloco III, onde pudemos acompanhar procedimentos de médio e grande porte de determinadas especialidades médicocirúrgicas. O estudo foi dividido em três etapas, sendo as duas primeiras experimentais, e a terceira apenas de análise e interpretação dos achados. Foi realizado o mapeamento do elenco de medicamentos disponibilizado (seja nos carrinhos de drogas, nos kits e nas solicitações extra) e o levantamento do consumo de três dias de funcionamento de cada sala cirúrgica do Bloco III, nas duas etapas experimentais. Na primeira etapa - pré kit - o levantamento foi realizado através da verificação do elenco e das quantidades contidas nos carros de parada e anestesia de cada uma das salas, às 06h30min da manhã antes do início das cirurgias e no final da tarde após o término da última, assim, delimitando o consumo/dia/sala. Estes levantamentos eram feitos em dias aleatórios para não induzir a equipe médica ou a enfermagem em modificar seu consumo. Na segunda etapa - pós kit - realizou-se o levantamento dentro da unidade farmacêutica através da análise dos documentos de dispensação do kit e notas de débito, onde estavam relacionadas as quantidades de medicamentos utilizadas e solicitadas pela auxiliar de enfermagem durante a cirurgia. A confirmação desta documentação era feita através da conferencia do kit e devolução de medicamentos extra. Os carros de medicamentos não estavam mais sendo utilizados, apenas os kits e os medicamentos extra, que pela rotina estabelecida deviam ser devolvidos após o término de cada cirurgia, não permanecendo nada em sala entre uma cirurgia e outra. Após o fechamento dos dois levantamentos pré e pósimplantação do kit procedeu-se às seguintes análises dos resultados: Comparação do consumo de medicamentos por sala/dia; Relação de preço de cada medicamento utilizado; Cálculo do valor total gasto por sala/dia; Comparação do valor gasto por sala/dia. Vale assinalar que: Os anestésicos inalatórios não entraram no levantamento dos medicamentos utilizados nas cirurgias, pois comportam frações diferentes para cada paciente; No primeiro dia de mapeamento (pré e pós) das salas cirúrgicas, os medicamentos vencidos encontrados foram recolhidos e considerados como consumidos. Resultados: Não houve críticas nem reclamações em relação ao novo sistema implantado. Quantitativamente, houve uma redução de aproximadamente 47% no estoque inicial, 54% nas solicitações extras e 30,4% no consumo de medicamentos, com impacto muito relevante sobre os custos. Conclusões: Foi viável e benéfica a prática de implantação dos kits, pois houve redução de aproximadamente 60% nos gastos, estimados pelo preço de medicamentos, traduzindo menores perdas e desperdícios. / Purpose: The hospital a integrant of a health coordinated system, which duty is offer services. The hospital administrators\' worry is get the lowest cost as possible and increasing the quality. As the hospital cost has an important installment represented by the medicine and materials consumed, and the pharmacy being the control responsible section, storage and dispensation, the pharmacist has improving professionally and developing researches and studies, in order to reformulate ones basics activities and recover some primary functions such as pharmaco economy, in order to adequate the new demands. The medicine distribution system is relevant in this context, which has started with a collective dose, which the main problems were the medicine error increased, the economic losses because of the lack of control, and the excessive expenses by the nurse ring in order to sort out the medicine, instead of patient care. Then it upgrade to the individual dose, which has not only decrease and /or extinguishes all the disadvantage of collective dose, presented a more effective control of the medicine consume, increasing the pharmacist integration along with health group, being the main disadvantage, the increase of Hospital Pharmacy infrastructure and human recourse need. And the one dose being the last one, being a derivation from the individual dose, which has as the main targets rationalize the therapy, decrease the costs without reducing the dispensation quality; and guaranty that the prescribed medicine reach the patient in a hygienic and safe fashion, guarantying the efficacy of the prescribed therapeutic scheme. After having connect the above described concepts, the Surgery Room of Instituto Central do Hospital das Clínicas da Faculdade de Medicina da USP purpose identify a representative product group, and use these medicine group, on the kit dispensation system elaboration, increase , and experiment. This new alternative intend to hit as the two main benefits which are the better use of economic resources and increasing the assistance quality giving to the patient and to the multi professional team. Method: The used research method applied was a qualitative/quantitative study case, where it was applied at the Centro Cirúrgico do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, from 12/05/2002 to 22/07/2002. Were chosen as samples the ten surgey rooms of Block III, where we could follow big and medium port procedures of specific medical surgery specialties. The study was divided into three steps, where the first two experiments, and the third one was only analyses and comprehension of found. From the available medicine group mapping was taken (which means ones in the drug trolleys, at the kits and the extra solicitations) and the inventory of three day consumptions of each surgery room at the Block III, at the two experimental steps. At the first step - pre kit - the inventory was taken through a verification of the group the quantities which were in the drug emergency trolley and anesthesia of each room, at 06:30 min a.m. before the surgeries starting and at the late afternoon after the last surgery happened, so, determining the consumption/ day/room. These inventories were chosen in random days way in order not to prompt the medical or the nursing group to modify their consumption. At the second step - post kit - the inventory was taken in the pharmacy unit through out of a kit dispensation documents analyses and debit note, which were listed the medicine amount used and from the nurse asked for during the surgery. This document confirmation was done through out of the kit checking and the extra medicine return. The medicine trolley were not use any more, only the kits and the extra medicine, which through the established routine should be returned after each surgery ended, and nothing was left in the surgery room between surgeries. The analyses of the results were taken right after the closing of the two research pre and post kit implementation: Medicine consume comparison by room/day; Listing the price of each medicine used; Total expenses calculated by room/day; Comparison of expenses by room/day. Is worthwhile note that: The inhale ting anesthetic are not considered on the used medicine inventory used at the surgery, because it holds different fractions for each patient; At the first surgery room mapping day (pre and post) the out of day medicine were took away and considered as used. Results: There were no criticism nor complaints related to implemented new system. Quantitatively, there was a decrease of 47% on the initial stock, 54% at the extra solicitations and 30,4% at the medicine consumption, with a very related impact on the costs. Conclusions: The implementation of the kits was totally viable because there was about 60% costs reduction, estimated by the medicine price, presenting less losses and wastings.

INTRODUÇÃO: A segurança da administração de anestésicos locais com vasoconstritor em pacientes diabéticos submetidos à cirurgia oral não está bem fundamentada na literatura. OBJETIVO: Investigar a ocorrência de variação da glicemia nos períodos pré, trans e pós-operatório de exodontia de dentes superiores, sob anestesia local com lidocaína 2% sem e com adrenalina 1:100.000, em portadores de diabetes mellitus tipo 2. Secundariamente, avaliar os efeitos hemodinâmicos e o grau de ansiedade. MÉTODOS: Estudo prospectivo e randomizado com pacientes portadores de diabetes acompanhados na Unidade Clinica de Coronariopatia Crônica do Instituto do Coração do Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo. A monitorização contínua da glicemia durante 24 horas foi realizada através do MiniMed Continuous Glucose Monitoring System (CGMS, Medtronic). Os pacientes foram divididos em dois grupos: LSA - que recebeu 5,4 mL lidocaína 2% sem adrenalina e LCA - que recebeu 5,4 mL de lidocaína 2% com adrenalina 1:100.000. Os níveis de glicemia foram avaliados nas 24 horas (período basal) e nos tempos determinados: uma hora antes, durantes e até uma hora após a exodontia (período de procedimento). Os parâmetros hemodinâmicos foram avaliados por meio de um medidor de pressão arterial digital automático e o nível de ansiedade através de uma escala. RESULTADOS: Dos 400 pacientes avaliados, 70 foram incluídos no estudo, sendo 35 randomizados no grupo LSA e 35 no grupo LCA. A análise das médias da glicemia nos grupos LSA e LCA durante os períodos (basal e procedimento) não demonstrou diferença estatisticamente significativa (p=0,229 e p=0,811, respectivamente). Também não houve diferença significativa (p=0,748) na glicemia entre os grupos em cada tempo avaliado. Entretanto, nos dois grupos houve decréscimo significativo da glicemia (p < 0,001) ao longo dos tempos avaliados. Os grupos LSA e LCA não apresentaram diferenças significativas em relação à PAS (p=0,176), à PAD (p=0,913), à FC (p=0,570) e ao nível de ansiedade. CONCLUSÃO: A administração de 5,4mL de lidocaína 2% com adrenalina 1:100.000 não provocou alteração significativa da glicemia, parâmetros hemodinâmicos e nível de ansiedade em relação ao grupo sem vasoconstritor / INTRODUCTION: The safety of administration of local anesthetics with epinephrine for diabetic patients undergoing oral surgery is not well grounded in the literature. OBJECTIVE: To investigate the occurrence of variation of glucose in the pre, intra and postoperative extraction of upper teeth under local anesthesia with lidocaine 2% with and without 1:100.000 epinephrine in patients with type 2 diabetes mellitus. Secondly, to evaluate the hemodynamic effects and degree of anxiety. METHODS: A prospective randomized study of patients with diabetes attended in Coronary Chronic Clinics Unit, Heart Institute, Hospital das Clinicas in University of São Paulo Medical School. Continuous monitoring of blood glucose for 24 hours was performed using MiniMed Continuous Glucose Monitoring System (CGMS, Medtronic) and the patients were divided into two groups: LSA - which received 5.4 mL of 2% lidocaine without epinephrine and LCA - which received 5.4 mL of 2% lidocaine with 1:100,000 epinephrine. Blood glucose levels were assessed at 24 hours (baseline period) and at certain times: one hour before, during, and up to one hour after oral surgery (procedure period). We evaluated the hemodynamic parameters through a digital automatic pressure meter and anxiety level was measured by the scale. RESULTS: Of 400 patients evaluated, 70 were included in these study, 35 were randomized in the LSA group and 35 in the group LCA. The analysis of mean glicemia in groups LSA and LCA during the baseline period and procedure showed no statistically significant difference (p = 0.229 and p = 0.811, respectively). There was no difference in blood glucose (p = 0.748) between the groups at each time evaluated. However, in both groups there was a significant decrease in blood glucose (p < 0.001) over the time periods studied. The groups showed no significant differences regarding SBP (p = 0.176), DBP (p = 0.913), HR (p = 0.570) and anxiety level. CONCLUSION: The administration of 5.4 mL of 2% lidocaine with epinephrine 1:100.000 caused no significant change in blood glucose, hemodynamic parameters and level of anxiety compared to the group without vasoconstrictor

Introdução: Em pacientes sob intubação endotraqueal os mecanismos fisiológicos de climatização do ar inspirado são anulados. Durante anestesia geral, quando os gases inspiratórios são ofertados secos e frios, a manutenção da umidade das vias aéreas é condição importante para prevenção de lesões da mucosa respiratória e ressecamento das secreções. Os sistemas de anestesia possuem propriedades de umidicação inerentes, decorrentes do sistema respiratório circular e a presença do absorvedor de CO2. Entretanto, os níveis de umidificação, durante a anestesia, dependem de vários fatores incluindo o tipo de ventilador anestésico, montagem do sistema respiratório e o fluxo de gás fresco utilizado. Porém não há dados na literatura que tenham investigado o efeito nos níveis de umidade do gás inspirado nas propriedades físicas e de transportabilidade do muco respiratório. Objetivo: Avaliar os níveis de Temperatura (T), umidade absoluta (UA) e umidade relativa (UR) do ar inspirado durante anestesia geral oferecidos pelo sistema circular valvular com absorção de CO2 e com a adição do HME em dois tipos de ventiladores (Dräger e Takaoka). Avaliar os efeitos do HME sobre os níveis de Temperatura e Umidade dos gases inspirados ofertados pelos dois equipamentos. Avaliar o impacto da umidade sobre as propriedades físicas e de transportabilidade do muco respiratório. Método: Foram selecionados 44 pacientes da Clínica Cirúrgica II do Departamento de Gastroenterologia do HCFMUSP com indicação de cirurgia abdominal eletiva e anestesia geral com duração superior a 4 horas. Os pacientes foram alocados em 4 grupos conforme o tipo do ventilador utilizado (Dräger ou Takaoka) e a presença ou ausência do HME. O muco respiratório e os dados de temperatura, UR e UA do gás ofertado foram coletados logo após a intubação endotraqueal, e a cada duas horas até o final da cirurgia. A análise do muco respiratório foi realizada através dos seguintes métodos: Transportabilidade mucociliar (MCT), em palato de rã; Transportabilidade pela tosse (TT), através da máquina simuladora da tosse e as propriedades de superfície, através do Ângulo de contato (AC). Resultado: O ventilador Dräger foi significantemente mais efetivo em ofertar níveis mais altos de T, UA e UR comparado ao ventilador Takaoka. A adição do HME aumentou a T e UA nos dois equipamentos. A UR aumentou somente no ventilador Takaoka. Houve um aumento do TMC e da TT no grupo que apresentou níveis mais altos de umidade (i.e. Dräger + HME). O AC não mostrou diferenças entre os quatro grupos. A análise longitudinal mostrou que o TMC foi positivamente afetado com o aumento da UA e UR. A TT foi positivamente afetada com a adição do HME. Conclusão: Nossos resultados mostram que o ventilador Dräger produziu níveis significantemente mais altos de umidade comparados ao ventilador Takaoka e que a adição do HME aumentou os níveis de umidade nos dois equipamentos estudados. Os equipamentos anestésicos e a adição do HME afetaram os níveis de umidade ofertados ao paciente durante a anestesia geral, e essas mudanças influenciaram a transportabilidade do muco respiratório / Background: In patients who are intubated, the natural mechanism of gas climatization by the nose and the upper airway is bypassed. During anesthesia, when the inspiratory gases are cold and dry, humidification of gases is recommended to prevent drying of the mucosal epithelium and respiratory secretions. The anesthesia systems have inherent humidifying properties as a result of the valvular rebreathing of some of the expired humidity and of the production of water in the CO2 absorber. However, the level of moisture in anesthetic ventilation is critically dependent on several factors that include the equipment, the arrangement of the circle breathing system and the fresh gas flow. To date the effect of humidity on respiratory mucus properties and transportability was not investigated. Objectives: The objective of this study was to measure the humidity and temperature of the inspired gas from a circle absorber system in two different ventilators (Dräger and Takaoka) and the effect of a heat and moisture exchanger (HME) on the inspired gas. Furthermore, we also evaluated the impact of humidity on in vitro mucus transportability and physical properties. Methods: We studied 44 patients with no pulmonary disease scheduled for elective surgery that were randomly allocated in four groups according to the anesthetic equipment (Dräger or Takaoka) and the absence or presence of HME. Respiratory mucus was collected and Temperature (T), absolute humidity (AH), relative humidity (RH) of inspired gases were recorded immediately after intubation (T0) and every 2 hours. In vitro respiratory mucus was studied by mucociliary transportability (MCT) by the frog palate method; cough clearance (CC) by the cough equipment, and contact angle (CA) by direct observation. Results: Dräger equipment delivered significantly higher levels of RH and AH when compared to Takaoka. The addition of HME increased AH and T in both equipments. RH was improved only in the Takaoka equipment. MCT, CC showed a non-significant trend to be higher in the group that provided the highest humidity (i.e Dräger + HME). CA did not change among groups. Longitudinal analysis showed that MCT was positively affected by an increase in AH and RH. CC was positively affected by the addition of HME. Conclusion: Our results showed that Dräger equipment was more effective in humidifying anesthetic gas than Takaoka. The performance of both equipments was improved when HME was added. The anesthetic equipment and the addition of HME affect the humidity delivered to the patient that in turn influences in vitro respiratory mucus transportability

O objetivo deste estudo foi investigar o comportamento da pressão arterial e o papel da ansiedade durante tratamento odontológico em hipertensos. Foram avaliados 65 hipertensos sob tratamento anti-hipertensivo (pressão arterial = 140/90 mm Hg) com teste de ansiedade IDATE (n=34), medidas de pressão arterial de 2/2 minutos (aparelho oscilométrico automático) e pela MAPA (n=42) com medidas de 15/15 minutos durante 8 horas nos dias dos experimentos odontológicos Verificou-se elevação da pressão arterial sistólica de curta duração e pequena magnitude ( < 10 mm Hg) independentemente do uso de prilocaína com ou sem felipressina. Os pacientes com ansiedade apresentaram pressão arterial maior do que os sem ansiedade em alguns procedimentos sugerindo que a ansiedade pode ter papel na elevação da pressão arterial / The objective of this study was to investigate the behavior of blood pressure and the role of anxiety during dental treatment of hypertensive patients. An evaluation was made of sixty-five hypertensive patients (blood pressure = 140/90 mm Hg) under anti-hypertensive treatment were evaluated by the IDATE anxiety test (n = 34), blood pressure measurements 2/2 minutes (automatic oscillometric device), and ABPM (n = 42) with 15/15 minutes measurements, during 8 hours on the days of the two dental experiments. Evaluation an increase in systolic pressure of short duration and little magnitude ( < 10 mm Hg) was found, regardless of using prilocaine with or without felypressin. During some procedures, the patients presenting anxiety had higher blood pressure than those without anxiety, suggesting that anxiety may play a role in the increase of blood pressure

O objetivo deste estudo foi investigar o comportamento da pressão arterial e o papel da ansiedade durante tratamento odontológico em hipertensos. Foram avaliados 65 hipertensos sob tratamento anti-hipertensivo (pressão arterial = 140/90 mm Hg) com teste de ansiedade IDATE (n=34), medidas de pressão arterial de 2/2 minutos (aparelho oscilométrico automático) e pela MAPA (n=42) com medidas de 15/15 minutos durante 8 horas nos dias dos experimentos odontológicos Verificou-se elevação da pressão arterial sistólica de curta duração e pequena magnitude ( < 10 mm Hg) independentemente do uso de prilocaína com ou sem felipressina. Os pacientes com ansiedade apresentaram pressão arterial maior do que os sem ansiedade em alguns procedimentos sugerindo que a ansiedade pode ter papel na elevação da pressão arterial / The objective of this study was to investigate the behavior of blood pressure and the role of anxiety during dental treatment of hypertensive patients. An evaluation was made of sixty-five hypertensive patients (blood pressure = 140/90 mm Hg) under anti-hypertensive treatment were evaluated by the IDATE anxiety test (n = 34), blood pressure measurements 2/2 minutes (automatic oscillometric device), and ABPM (n = 42) with 15/15 minutes measurements, during 8 hours on the days of the two dental experiments. Evaluation an increase in systolic pressure of short duration and little magnitude ( < 10 mm Hg) was found, regardless of using prilocaine with or without felypressin. During some procedures, the patients presenting anxiety had higher blood pressure than those without anxiety, suggesting that anxiety may play a role in the increase of blood pressure

Macromolecular interactions play very important roles in regulation of all levels of biological processes. Aberrant macromolecular interactions often result in diseases. By applying a combination of spectroscopy, calorimetry, computation and other techniques, the protein-protein interactions in the system of the Shaw2 Kv channel and the protein-RNA interactions in West Nile virus RNA-cellular protein TIAR complex were explored. In the former system, the results shed light on the local structures of the key channel components and their potential interaction mediated by butanol, a general anesthetic. In the later studies, the binding modes of TIAR RRM2 to oligoU RNAs and West Nile virus RNAs were investigated. These findings provided insights into the basis of the specific cellular protein–viral RNA interaction and preliminary data for the development of strategies on how to interfere with virus replication

Diss. (sammanfattning) Umeå : Umeå universitet, 2009. / Härtill 5 uppsatser. Även tryckt utgåva.

Thesis (M.A.)--University of South Florida, 2006. / Title from PDF of title page. Document formatted into pages; contains 52 pages. Includes bibliographical references.