KC Transplant-Ygun bakimciini rolu
Transkript
KC Transplant-Ygun bakimciini rolu
27/04/16 EDITORIAL URRENT C OPINION The intensivist as nosocomial thanatologist Andrew K. Hilton a and Rinaldo Bellomo a,b Karaciğer Naklinde Yoğun Bakımcının Rolü Fuat H. Saner complex than the normal diagnosis of disease, in Intensivists are in a unique position to improve which the only immediately relevant dimension is nosocomial end-of-life care (EOLC). They undermedical. Diagnosing dying is a medically informed, stand the key aspects and limits of vital organ technology-mediated, social decision. support; they take into account the effect of specific The primary diagnosis of dying should be physiological derangements independent of the formally considered in the differential diagnostic underlying diagnosis; and they can explain to list of all patients who present with severe illness patients and families what the limits of the techand injury. This is especially important in patients nology of life support might be in a specific clinical with multiple co-morbidities, advanced age or poor situation. Thus, intensivists can guide colleagues, physical performance. However, the recognition of patients and their families toward an informed dying will be influenced by the social and cultural decision about EOLC. context. In some cultures, the primary diagnosis of In many countries, intensivists have also dying is sometimes perceived as helpful in preventincreased their involvement in managing acutely ing deteriorating ward patients though the AND rapid ICU ABDOMINAL AORTIC SURGERY S unnecessary, burdensome, painful, futile and undignified interventions. In other cultures, the response team (RRT) system. Consequently, they prevention of death itself is seen as more important. are now making frequent and often difficult deIn these different cultural and social environments, cisions about EOLC in the wards outside the ICU. ICU Days for differences patient characterisdoctors respond toindominant social attitudes.perform this relatively common surgery. As well as the traditional underlying physiological tics using multivariate logistic regresHowever, clinical characteristics can remain com-More importantly, our results indicate and medical diagnoses, analysis, the meta-diagnosis of In the bivariate the ICU charfamily differand physi-that ICU organizational characteristics ‘dying’ acteristics has to be associated formally considered. Unfortusion,despite there specific was nopatient, significant with increased ICU pelling cian factors. nately, the recognition that a patient is dying when ence in in-hospital mortality between are related to differences in in-hospital days included not daily rounds The concept of diagnostic uncertainty applies to organ support technology is having either available or in surgeons who performed fewer than 8 mortality, ICU days, and hospital length bybean ICU and physician (mean the primary diagnosis of dying as it does to any other place can difficult controversial, andincrease, characdiagnosis [6].performed There is, however, a uniqueof stay. Such information may provide terized by uncertainty discussed by Fisher the in this and those who 8 or more 65%; 95% CI,as35%-96%), having sur- medical dimension to this uncertainty [7]. Although the issue. Accordingly, a decision to withdraw or withcases per year. direction regarding ways to further imgeonorgan or both the surgeon ICU phy- diagnosis of pneumonia may or may not be correct, hold vital support is both and a medically Hospitals that had fewer than 36 cases sician manage patient act vs having the the risk that true pneumonia will develop is neverprovetheoutcomesforpatientswhohave informed decision and athe negotiated following by its diagnosis. In contrast, thehad risk ofhigh-risk operations such as abdominal discussion family and other the health providers of abdominal aortic surgery per year ICUwith physician manage patient in the increased dying is increased by the primary diagnosis of dying. [1–5]. a higher mean in-hospital mortality rate aortic surgery. Because the 5-year rela(mean increase, 95% CI, This self-fulfilling prophecy effect requires caution TheICU dying process can be 39%; interrupted at 18%any Curr. Opin. Crit Care Med, 2013: 19, 613-615 hospitals that had 36 or more cases and having an application ICU nurse-patient inthan making the diagnosis of dying. Objective prog-tive survival of aortic aneurysm patients, stage of55%), its development by the of techTitel models for vs hospitalized [8] shouldespecially octogenarians, is good and nology,ratio thus making primary diagper year (8% 5%; P = patients .005). When of lessthethan 1:2overarching during the day nostic be carefully applied, the limitations of these connosis that ‘the patient is dying’ more difficult. we adjusted for differences in patient supports surgery,27 strategies to reduce (mean increase, 29%; 95% CI, 1%-68%). sidered, and the consequences and degree of uncerConsider the following example: An 80-year-old characteristics using multivariate in-hospital mortality become increasIn dementia the multivariate as septic shown tainty of the diagnosis openly discussed [9]. lopatient with develops analysis, pneumonia, Respect for a patient’s wishesthat andhospia family’singly important. shock and renal failure surgery for a fractured regression, we found in Table 4, theafter ICU characteristics in- gistic wishes does not simply imply that the family alone neck of femur following a fall in a nursing home. Daily rounds by an ICU physician dependently associated with in- tals that had fewer than 36 cases per This patient could be considered to have sepsisdaysdysfunction for abdominal aortic year had a significantly higher in- were associated with a 3-fold reduction inducedcreased multipleICU organ syndrome, a Department of Intensive Care, Alfred Hospital and bhospitals Australian and Newin in-hospital mortality for abdominal necessitating vasoactive medications, replacehospital mortality rate than surgery cases included notrenal having daily Zealand Intensive Care Research Centre, School of Public Health and ment therapy and mechanical ventilation. Conthat had 36 Monash or more. As Melbourne, shown Victoria, in Table Medicine, University, Australia aortic surgery patients. This finding is rounds by an ICU physician (mean in- Preventive versely, this frail patient with advanced dementia Correspondence to Rinaldo Bellomo, and New Zealandconsistent with an emerging body of evi4, hospital volume alsoAustralian was inversely crease, 95% CI, 48%-126%), and Intensive could simply be83%; ‘dying’. Therapeutic intervention Care Research Centre, School of Public Health and Preventive may postpone not prevent ratio it. In of this associated in-hospital af- dence that suggests using full-time inhaving death, an ICUbut nurse-patient less Medicine, Monash with University, Alfred Hospitalmortality Campus, Commercial setting, the diagnosis of dying is made in the hierVictoria, Tel: +61 3in 9496 5992; fax: +61tensive care physicians can reduce interMelbourne, adjusting forAustralia. differences both ICU than 1:2 during the day (mean in- 3Road, 9496 3932; e-mail: Rinaldo.bellomo@austin.org.au archical preference to that of septic shock because and characteristics. hospital mortality.28,29 We found that crease, of 49%; 95%severe CI, 17%-91%). Curr Opinpatient Crit Care 2013, 19:613–615 of the presence chronic, and progressive daily rounds by an ICU physician were cognitive decline. Diagnosing dying is much more DOI:10.1097/MCC.0000000000000035 • Thantalogist: Ölüm üzerine araştırma yapan, interdisipliner bir girişim • Yoğun Bakım Hekimi: • Organ destek (KC, böbrek, akciğer) tedavisinin anahtar noktasını anlar • Teknik destek tedavinin kısıtlılıklarını bilir • End-of-life-care kararını tüm hekimler arasında en iyi bilir • Büyük sorumluluk Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Direktor: Prof. Dr. med. A. Paul Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Hospital and Surgeon Volume 1070-5295 ! 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Surgeons who performed fewer than 8 Yoğun Bakım Uzmanının Sağ kalım üzerine etkisi dominal aortic surgery patients andEtkisi sig- likely affect but were not associated with mortality rate than surgeonsSağ Yoğunhospital Bakım Uzmanının kalım Üzerine who performed 8 or more (10% vs 5%; nificant variation in ICU organizational reduced risk of surgical complications. P = .003). However, when we adjusted • Gözlem çalışması, Maryland eyaletinde 46 adet aortik anevrizma tedavisi uygulanan klinik katılmış • Tarih: 1994-1996 • Yapılan ankete YBÜ‘leri başkanlarının %85’i katılmış COMMENT associated with reduced risk of several This study demonstrateswww.co-criticalcare.com that there is sig- specific medical complications and in- Copyright © per Lippincott Williams & Wilkins. article isofprohibited. variation in of thethis outcomes ab- terventions that an intensivist would cases year had a higher meanUnauthorized in- nificantreproduction characteristics in Maryland hospitals that Table 3. Risk of Postoperative Complications With No Daily Rounds by an ICU Physician for Abdominal Aortic Surgery Patients in Maryland, 1994-1996* Complications Patients With Complication, % OR (95% CI) of Without vs (n = 2606) With Daily Rounds of ICU Physician Medical complications Pulmonary insufficiency after procedure Cardiac complications after procedure 11.8 10.8 1.9 (0.5-7.8) 1.4 (0.7-2.4) Acute renal failure 4.7 2.2 (1.3-3.9)† Septicemia 3.4 1.8 (1.2-2.6)† Acute myocardial infarction 2.6 1.4 (0.7-2.8) Daily rounds by an ICU physician may be a marker for team care, and this model can be widely applied because our results were not predicated on the presence of residents. Our study is unique because we evaluated mortality in a highrisk population, adjusted for differences in comorbidity and severity of illness, used multilevel modeling, and included data from 2606 patients from 39 hospitals, which provided us with the statistical power to detect clinically significant associations between organizational characteristics of ICUs and outcomes. Previous studies have had less power for detecting differences because they included many patients with a relatively low risk of in-hospital mortality and adjusted for differences in risk across patient populations, which may distort the relationship between ICU organizational characteristics and outcomes.1,3,30 We also found that variation in organizational characteristics of ICUs was associated with differences in resource use for patients undergoing ab- Yoğun bakım uzmanı olmayan YBÜ’de Mortalite riski üç kat artıyor (OR 3.0) Cardiac arrest Surgical complications Surgical complications after procedure‡ Surgical E codes§ Interventions Reintubation Reoperation for bleeding Platelet transfusion 1.2 2.9 (1.2-7.0)† 8.6 0.3 1.5 (0.8-2.0) 4.3 (0.9-20.0) 14.1 2.4 2.0 (1.1-4.1)† 1.1 (0.5-2.6) 2.0 6.4 (3.2-12.4)† *The complications associated with increased in-hospital mortality in abdominal aortic surgery patients were included in this analysis. For each complication, the multivariate model is adjusted for age, sex, race, ruptured/unruptured aneurysm, elective/urgent/emergent admission, comorbid diseases in Romano-Charlson index, hospital volume, and surgeon volume. ICU indicates intensive care unit; OR, odds ratio; and CI, confidence interval. †Data are statistically significant at P,.05. ‡Defined as hemorrhage during a procedure (ICD-9-CM code 9981), accidental laceration during a procedure (ICD9-CM code 9982), or disruption of operation wound (ICD-9-CM code 9983). §Surgical E codes are used to identify environmental events, circumstances, or conditions as the cause of an injury. 1314 JAMA, April 14, 1999—Vol 281, No. 14 Pronovost, JAMA, 1999: 281: 1310-1317 Titel Klinik für Allgemein-, Viszeral- und Transplantationschirurgie KC Transplantasyonu: YoğunSeminar Bakım Uzmanının Rolü – Fulminan Hepatik Yetmezlik Survival (%) ALF transplantation N-acetyl cysteine RRT 61 56 47 Hemodialysis 19 99 -2 00 3 20 04 -0 8 19 94 -9 8 19 89 -9 3 19 79 -8 3 Beds (n) 2 Intensivist Staffing (n) 19 84 -8 8 Years 19 73 -7 8 Transplantasyondan sonra FHY sağ kalım çeşitli dönemlere göre değerlendirme JOURNAL OForanı: HEPATOLOGY Operating as a high-volume centre for the care of patients etylcysteine, and intervention studies showed h liver disease, it has developed a multi-disciplinary approach 100 rovements in systemic and cerebral haemodynamics are of these patients as such has a unique opportunity to 106,107 oxygen uptake. Aand multicentre double-blind 108 uate the evolution of care andinchanges in the nature and outomised trial of N-acetylcysteine non-paracetamol thefailure illnesswas overcompleted time. In this we of analysed80data of77 ee of liver afterstudy, 8 years uitment. N-acetylcysteine wasliver welldisease tolerated and 3305 patients with acute admitted to the LITU74 with improved non-transplanted rciated the period 1973–2008, seeking to survival, evaluatebut and quantify the62 60 in patients treatedcare earlysupport in the course of disease and cts of intensive and the introduction and refinelow-grade encephalopathy. nt of ELT. We sought also to delineate the changes in disease eti-55 y and severity that had occurred over time, and how 40 these phalopathy and ammonia ted to the clinical complications and outcomes observed. 38 acute liver failure, hepatic encephalopathy Before December, 1984 (24) January, 1985 to December, 1989 (482) January, 1990 to December, 1994 (1259) January, 1995 to December, 1999 (1537) 5 2000 to 6 December, 102004 (1713) January, January, 2005 to December, 2008 (1158) 1 2 3 15 4 51 44 Continuous hemofiltration mpasses many neuropsychiatric disturbances, 25 25 20 ing from confusion and disorientation to ents and minor methods ICH therapy Mannitol 30% NaCl k coma and cerebral oedema, resulting in acranial hypertension. Although the frequency of nts and dataset 0 cally overt cerebral oedema has decreased over the Fig. 1. Schematic evolution of care for patients with ALI/ALF at the Liver 0 1 2 3 4 5 6 7 8 9 10 20 years, such hypertension still accounts for Intensive Therapy Unit, Kings College Hospital. ALF; acute liver failure, RRT; Years analysis is based on all patients aged P16 years admitted to the LITU renal replacement therapy, ICH; intracranial hypertension. 25% of deaths.8 Survival without transplantation for een 1973 and 2008, with a diagnosis of acute liver injury (ALI) or ALF. Incluents with acute liver failure is poor in those with Figure 3: Survival after liver transplantation for acute liver failure by date of surgery in Europe, 1984–2008 criteria for ALI included: (1) an INR of P1.5; (2) absence of a previous history Bernal, Lancet, 2010; 376, 190-201 from the European liver transplant registry. Numbers are completed 1, 5, and 10-year survival rates. re encephalopathy, and the risk of substantial Data linical/radiologic findings of liver disease; and (3) illness 626Numbers weeks in ofparentheses duraare surgeries done in each group. Bernal, J Hepatol, 2013: 59, 74-80 bral and intracranial hypertension (HE is grade P2) [11] at Thoseoedema who had or developed overt encephalopathy All patients developing ALF with overt HE with agitation or coma were intutest thosetheir withhospital hyperacute or acute presentations. In view of the closebated, relation between blood ammonia ime in during stay were classified as having ALF [12]. Transfer Titel sedated, and mechanically ventilated. Sedation was initially with moratients withconsidered subacute in disease, evenreferred the presence of andconcentrations cerebral complications of acute e LITU was all patients with ALF in those with and phine and midazolam and with routineund use of paralysing agents, with evolution Klinik für Allgemein-, ViszeralTransplantationschirurgie hepatic encepha lopathy suggests critically failure, treatments reduce con- with rare use of paralysis. In these cases, fest there were features raising prognostic concern, including liver hypoglycaemia, to usethat of fentanyl andammonia propofol infusions hepaticliver organfunction failure orthat, progressive coagulopathy with ancentra INR >2 or PT aired although infrequently tion could interrupt of regular hepaticclinical assessment and non-invasive techmonitoringprogression for ICH utilized . All patients with subacute disease and any or evidence of ciated with intracranial hypertension, is acoagulopathy sign of encephalopathy or niques, development intracranial with direct of ICP monitors first selectively used in 1977. In 2008, 13 of goutlook. liver volume were considered for transfer [13]. 42 (31%) concentrations patients ventilated with hypertension. Ammonia in overt the HE had ICP monitors inserted. atients were identified throughencephalopathy the admission diaries of the LITU which form a Treatment for ICH crises was initially with bolus intravenous mannitol and e pathogenesis of hepatic in acute circulation point to the complex interorgan metabolism nuous record since the unit first opened. Clinical data was derived from archived increased sedation with use of thiopentone in refractory cases. Continuous intrafailure is only partly understood, but clinical and that occurs in liver failure. Ammonia is primarily ds (1973–99) and after 1999 from the prospective LITU electronic database. venous infusion of hypertonic saline rimental evidence suggests an important role for produced in the small bowel from glutamine,(30%) was introduced for all ALF patients in he dataset collected comprised patient age, gender, contemporaneous etiol2001 and also used as bolus therapy for ICH, with mannitol and indomethacin for ed concentrations of circulating neurotoxins, metabolised by glutaminase to ammonia and and laboratory test results (INR, bilirubin, creatinine and sodium) on admissecond-line use. Active temperature management was introduced in patients 109 118,119 cially ammonia. Results is converted to urea by the to the LITU. Over the study period, from changeslaboratory in laboratoryglutamate. methods were Ammonia with severe HE in 1999, with a target of 36 !C and greater degrees of hypothermia 110–112 ies liver, but in reserved liver failure concentrations rise, to medical agents [8,14]. have shownupon ammonia-induced changes in healthy ely to have impacted these values. Etiology was classified into paracetfor those with ICH refractory an alternative pathway for detoxifi cationcysteine in muscle roand trans mitter synthesis and release, neuronal non-paracetamol, and the latter subclassified into viral,and non-paracetaIntravenous N-acetyl (NAC) was administered to all patients after drug-induced, pregnancy-related and ‘other’ etiologies. latter group becomes available, 1989. in which synthetase ative stress, impaired mitochondrial function, and The If theyglutamine had not received a loading bolus dose prior to LITU admission, 120 ded cases resulting from autoimmune Budd-Chiari syndrome, metabolises ammoniapatients back towere glutamine. otic disturbances resulting fromdisease, astrocytic initially administered 150 mg/kg over 15 min and all received an gnancy, Amantia to fungi, Wilson’s disease, and specific The hepatotoxins. infusion ofmight 100 mg/kg/24 for a maximum of 5 days or until the INR was <2. abolismischemia, of ammonia glutamine. The overall drug ornithine aspartate aid this hconversion sltwere as in indeterminate if none ofand theseastrocytic causative factors presInitially,agent intravenous antibiotics is aclassed change cerebral function and were represents an attractive for reduction of were administered to all patients after Patients with liver dysfunction from primary 113–115 or following admission, but useeff was reduced ling.109,111,112 circulating ammonia, and seems ective in over the time with current restriction to patients Findings from clinical studies systemic havesepsis tectomy were not included in this analysis. established HEin or chronic other organ dysfunction, those fulfilling or likely to fulfil encephalopathy liver gested a link between the development of high treatment of hepaticwith he presence or absence of overt encephalopathy and the requirement for intutransplant criteria and to those 122 without HE but with clinical signs of significant 121 es of hepatic encephalopathy and arterial ammonia disease. However, a large randomised trial of n and ventilation were documented as was placement of intracranial pressure systemic inflammation in the absence of confirmed sepsis [8,15]. entrations. However, althoughas intracranial hyperornithine aspartate in Indian patients with acute liver monitors. Patients were classified having ICH if in their clinical course they ion pupillary probablyabnormalities represents(dilated the (>6 most severe failure did tonot show improvements in ammonia loped mm) and sluggishly reactive Liver transplantation other than(in ammonia seem to be concentration, ),ifestation, a sustainedfactors ICP of P25 mmHg those with ICP monitoring), requirement hepatic encephalopathy, or survival ortant in hepatic encephalopathy pathogenesis. with placebo. Glutamine might be converted herapeutic intervention or at autopsy had evidence of gross CE.compared Clinical records first liver by transplant for ALFin was ot permit collection of comprehensive data in respect of infection incidence or vere hepatic encephalopathy and cerebral oedema back to glutamate andThe ammonia glutaminase theundertaken in 1984, and a total of 387 were 123 period. After 1990, all cases were selected using nationoverdisease. the study iotic those who fulfilled poorstates, prognostic KCC criteria but were to administration, arise in systemic inflammatory often gut, kidneys, liver, andperformed brain in this Alternative ©1999 American Medical Association. All rights reserved. Pronovost, JAMA, 1999: 281: 1310-1317 Titel Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Downloaded From: http://jama.jamanetwork.com/ by a UNIVERSITAET DUISBURG ESSEN User on 01/25/2016 Model for End-stage Liver Disease (MELD) Karaciğer yetmezliğini değerlendiren skor – Child-Pugh Skoru’nun yerine geçti Kolay hesaplanan bir skor 3 “objektif” Laboratuar değeriyle [ INR; Kreatinin; Bilirubin ] Ulusal bekleme listesinde 3 –ay sağ kalım oranıyla korelasyonu var 12/2006’dan beri Almanya’da karaciğer sunumu MELD skoruna göre uygulanıyor 129 Titel Klinik für Allgemein-, Viszeral- und Transplantationschirurgie 1 27/04/16 ET Bölgesinde Transplant Olan Hastaların Match MELD Değerleri 01/2007- 09/2013 MELD’e Bağlı Operasyon Riski % 3-Month Mortality as a Function of MELD Transplant sonrası en iyi sonuç veren MELD skoru 100 90 80 60 50 Almanay‘da organ kabul edildiğinde ortalama MELD 40 30 20 10 0 -20 -10 0 10 20 30 40 50 60 70 80 MELD Score MELD Eurotransplant Leiden 2013 Titel Titel Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Beyin Ölümü Olan Donörler/ Donor Risk Index: Eurotransplant ve UNOS Karşılaştırması UNOS ET DRI > 1.5 32% 63% DRI > 2 6% 23% Karaciğer Nakli ve Yüksek MELD Infeksiyon Diyaliz Originalarbeit 35 60 § Dialysis § No diaylsis 40 P = 0,001 30 20 Number of patients 60 Abb. 6 Donor-Risk-Index (DRI) von postmortalen Leber-Spendern im Eurotransplant-Bereich vs.50UNOS (nach Braat A et al. [20]). Number of patients 50 40 30 P=0,004 20 No infection Infection 10 10 0 <20 0 <20 21-30 21-30 31-40 MELD 31-40 MELD LTX Patients Essen 1/2011-12/2011 Schlitt, Z Gastroenerol 2011; 49:30-38 Titel Klinik für Allgemein-, Viszeral- und Transplantationschirurgie “Kronik-Üzerine Akut KC Yetmezliği” Titel Abb. 7 Entwicklung der Lebendspende zur Lebertransplantation im Eurotransplant-Bereich, und davon in Deutschland (1995 – 2009). Siroz Hastaları – Mekanik Ventilasyon ve Sağkalım Oranı Herhangi bir olay ACLF Karaciğer destek sistemleri ?? Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Heruntergeladen von: Universität Duisburg - Essen. Urheberrechtlich geschützt. % Mortality 70 Siroz İnflamasyon Mekanik ventilasyon gereken siroz hastaları N = 246 tigt werden, wobei hier die 1-Jahres-Überlebensrate sogar nur 75,8 % betrug. Hierbei konnte gezeigt werden, dass die VerYBÜ sağ olarak YBÜ‘de ölen hasta schlechterung des Überlebens fast ausschließlich durch die taburcu sayısı Transplantation von Patienten mit einem labMELD-Score von N = 84 (34.1%) N = 162 (65,9%) MOF Kısmen iyileşme über 30 zustande kam. Während das 1-Jahres-Überleben in den MELD-Score Gruppen < 10, 10 – 20 und 20 – 30 bei 84,5 %, Diskussion 83,4 % und 78,6 % lag, war es in der Gruppe > 30 bei nur 52,6 %. ! Damit stellen sich anhand dieser Studie die Ergebnisse sogar Während die Lebertransplantationszahlen in Deutschland über noch schlechter dar als in der Analyse der ET-Daten, die für 1-yıl transplant 1 yil içinde ölen LTX diese Gruppe (inkl. Retransplantation) ein 1-Jahres-Überleben die letzten 10Transplant – 15 Jahre leicht gestiegen sind, persistiert das olmadan sağ kalan hasta sayısı Ölüm ? n = 10 von knapp über 60 % dokumentiert. Ob diese Unterschiede Problem des gravierenden Mangels an postmortal gespendeten N = 17 N = 57 durch die Zentrumsauswahl oder durch inkomplette DokuOrganen. Mit der Einführung der MELD-basierten Leberallokamentation in den Analysen zustande kommen, bleibt letztlich tion im Dezember 2006 konnte zwar das geplante Ziel einer unklar. Eindeutig zeigt sich jedoch eine deutliche Verschlechteniedrigeren Mortalität auf der Warteliste zur LebertransplantaLevesque, J Hepatol 2014, 60: 570-578 Titel Titel Klinik für Allgemein-, ViszeralKlinik für Allgemein-, Viszeral- und Transplantationschirurgie rung der Ergebnisse der Lebertransplantation seit Einführung tion erreicht werden – de facto wurde sie und von Transplantationschirurgie 20 auf 10 % halder MELD-basierten Allokation. biert. Die Ergebnisse nach Lebertransplantation haben sich Während kurz nach MELD-Einführung die mittleren matchjedoch deutlich verschlechtert. Untersuchungen von WeismülMELD-Scores der transplantierten Patienten in Deutschland ler et al. konnten bereits 2009 zeigen – allerdings in einer bei 25 lagen – und aus diesem Zeitraum stammen die o. g. unizentrischen Evaluation –, dass das 1-Jahres-PatientenüberAnalysen –, hat sich der mittlere matchMELD-Score bei Allokaleben direkt nach Einführung der MELD-basierten Allokation tion inzwischen auf 34 erhöht. Dies bedeutet, dass damit nun von knapp 90% auf unter 80%, also rund um 10% abgenomvorwiegend Patienten in sehr schlechtem klinischem Zustand men hat [15]. Diese Ergebnisse konnten auch in einer multitransplantiert werden. Dies lässt befürchten, dass sich dadurch zentrischen Analyse basierend auf 7 deutschen Zentren bestä16,5 Mio. Einwohnern 3 Zentren (entsprechend 1,8 Zentren/10 Mio. Einwohner). Das Vereinigte Königreich verfügt über 8 Zentren bei ca. 61 Mio. Einwohnern (entsprechend 1,3 Zentren/10 Mio. Einwohner). Schlitt HJ et al. Aktuelle Entwicklungen der… Z Gastroenterol 2011; 49: 30 – 38 2 27/04/16 Olgu 1 • 64 yaşında hasta • NASH-Siroz, BMI: 33 kg/m2 • Hidropik dekompanse • HRS => diyaliz gerekiyor • Olgu 1 Intraop: 4 Eks, 10 g fibrinojen, 3000 I.E. PCC, 2 TK, 2000 ml Kristaloid Noradrenalin: 0,6 µg/kg/min Postop: diyaliz (CVVHD) postop 5. güne kadar Postop 4. gün : hasta ekstübe oluyor MELD 40 • 2 damar koroner yetmezliği => miyokard enfarktüsü geçirmiş => ACVB 2009 • PT 17% (INR 3.7), aPTT ≥ 170 sn., fibrinojen < 50 mg/dl, PLT 48/ nl • SCr 4,4 mg/dl, Bilirubin 22,4 mg/dl mekanik ventilasyon süresi: 125 saat Titel Titel Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Annals of Surgery ! Volume 259, Number 6, June 2014 Olgu 2 Yoğun Bakıma Kabul Olan Siroz Hastaları SD Complicated gastrointestinal bleeding 9% Prediction Model of Futile Outcome (encephalopathy, aspiration, or shock) utility are shown in Table 2. During MICU stay, vasopressors, mechanical ventilation, and RRT were required in 51%, 62%, and 19% of cases, respectively. Uncomplicated gastrointestinal bleeding 8% The multivariate analysis (Table 4)4% identified MELD score, Isolated acute renal failure Other 7% Finalrisk, diagnosisage-adjusted CCI 6 or more, and pre-OLT septic shock cardiac Complication of cirrhosis 40% Outcome and Causes of Death Gastrointestinalpredictors bleeding as independent for futility (Fig.23% 3), with greatest risk from Acute alcoholic hepatitis 4% Survival rates in the MICU, in the hosSpontaneous bacterial peritonitis 7% cardiac disorders (OR: 3.14) and age-adjusted CCI 6pital, or and more (OR: 6 months after MICU admission Isolated hepatic encephalopathy 5% were 59% (95% CI, 50%– 67%), 46% Hepatorenal syndrome 1% 3.95). Using 4 factors, of this model had a Acute diseaseall not related to cirrhosis the futility prediction 60% (95% CI, 38%–54%), and 38% (95% CI, Pneumonia 16% 30%– 47%), respectively (Fig. 1). Most c-statistic of 0.754. A futility score of 26 or more identified patients Other infection 14% deaths occurred in hospital, and the Status epilepticus 7% with a high futility risk defined by a 50% at 3survival months Cardiac failure 7% death rate 6-month of the patients disOther 16% charged alive from the hospital was 86%. after OLT, whereas patients with scores of 22 or less had an excellent Death in the MICU was attributable to Findlay, Liver 2011, 496-510 the persistence orTransplantation aggravation of the initial 3-month survival rate of 93% (Table 5). The model predicted futility disease in Care 79% ofMed cases2010, (multiple organ Crit 2108-2116 graphic variables (age, gender), comorbidities, ther individually if they were not used for SOFA Das, Titel 30%, and 50% for patients with scores of 20, 25, and 28 risk of 10%, functional status, admission (direct), variables calculation (degree of ascites, albuminemia, INR, failure, 60%; brain lesions, 10%; refractory shock, 9%) or to a secondary complication Klinik für Allgemein-, Viszeralund Transplantationschirurgie on diagnosis (direct complication of cirrhosis or natremia) or as components of the SOFA score. (Fig. 4). not, infection on admission), characteristics of To identify which score had the best discrim- in 21% of cases (bleeding, 11%; nosocomial 9 patients, 37 patients (22%) had a futile postll in-hospital, with 18 patients (49%) and 32 at 1 and 3 months. Patients with futile (n = = 132) outcomes were comparable in terms of d donor characteristics (Table 2), underlying ), and operative variables (Table 3). The donor for the futile and nonfutile groups (DRI 1.58 26%). Although the MELD scores were comps, recipients with futile outcomes had greater y, including a higher proportion with increased 14%), age-adjusted CCI 6 or more (43% vs atment (97% vs 87%), and pretransplant septic sofsurgery.com YBÜ süresi: 12 gün Klinikte kalma süresi: 45 gün shock (32% vs 18%). Allografts of patients with futile outcome had a analysis, 101 patients were alive and 68 paYBÜ kabul olan siroz hastalarının %40 kadarı sepsiste ve/veya septik şok tedavisinde higher degree of graft injury (alanine aminotransferase 1068 vs 562 wn causes of death included infection/sepsis in U/L) a higher fraction ofunit initial 30%) rdiovascular causes in 18 patients (26%), liver Table 1. and Characteristics of patients on intensive care admissionpoor function (49% had vs cirrhosis. Elevenand patients with previous transplantation and three patients nonfunction (16% vs 3%). At the timeValue of (Mean analysis, 31liver patients in the 24%), multiorgan failure in 5 patients (7.3%), " whose charts had been lost were excluded. Characteristics or Percentage) nonfutile group (23%) were dead. Hepatic failure was the138cause of included. Their atients (2.9%), and causes were unknown in 4 Finally, patients were characteristics are shown in Table 1. Male (%) 68% death Knaus in 22% of futile recipient Patients groups, with median follow-up time for living patients was 47 scale (autonomy): A/B/C/D and 26% of nonfutile 28%/48%/23%/1% were admitted directly from Charlson score (comorbidities) " 1.4 the emergencygroup department in 43% of recurrent C (89%) as the leading1.02 cause in the nonfutile -, 3-, 5-, and 8-year graft and patient survivals Cause ofhepatitis cirrhosis cases and from the ward or liver ICU in Alcohol with or without viral hepatitis 78% and nonviral failure (87%) in the futile (24% vs was present on %, and 53%, and 72%, 64%, 60%, and 56%, Pure viral B graft or C hepatitis 16% group. Cardiac 57% of cases. Infection Other 6% MICU admission in 56 patients (41% of Current alcohol abuse (in patients 6%) and infectious (38% vs 29%) causes of76%death werecases) more frequent . The posttransplant death rate was highest at and was microbiologically docuwith alcoholic cirrhosis) mented in 40 patients (71% of cases). Reason for intensive care unit admission in futile than in nonfutile groups. after OLT and 5% and 3% for the second and Isolated acute respiratory failure 27% Values for clinical and biological charIsolated coma 23% ars (Fig. 2B). acteristics defining severity on admission Shock " multiple organ failure 22% nsplantation in patients with MELD scores verall graft and patients’ survival for adult tory MELD scores of 40 or more (n = 169) ansplantation. B, The annual death rate for The death rate was 0 for the posttransplant a were analyzed for the period from the he MELD allocation system (February 27, er 31, 2010. Patients with acute liver failure splantation were not included. Postop 5. gün.: katekolaminler tamamen kesiliyor cirrhosis (cause of cirrhosis, severity as assessed with D’Amico’s classification, degree of ascites, albuminemia, INR, natremia), and organ failures. The SOFA score was computed because it exclusively assesses organ failures and thus has a clinical meaning. On the contrary, the ChildPugh and MELD/MELD-Na scores were not included in the analyses because their clinical meaning, when computed on ICU admission, is questionable in the ICU setting. For example, the Child-Pugh score is computed from variables linked with organ failures (bilirubinemia, degree of encephalopathy) and portal hypertension (degree of ascites) and from albuminemia, which, in the ICU setting, results not only from liver failure but also from hydration, capillary leak, and nutritional status. The Simplified Acute Physiology Score II score is also computed from variables linked with demographic characteristics, history, organ failures, and reason for admission. Including the Child-Pugh, MELD/MELD-Na, and Simplified Acute Physiology Score II scores in the analyses, because they share common components with the SOFA score (creatininemia, bilirubinemia), would have created unwanted correlations between the predictors. Instead, we included in the analyses the individual components used to compute these scores, ei- ination capacity to predict inhospital mortality, receiver operating characteristic curves were constructed and areas under receiver operating characteristic curves (AUROC) were compared (36). All available scores calculated on day 1 were tested for their capacity to predict death for the entire cohort. For patients still alive on day 3, AUROC values for the SOFA score and the number of organ failures were also calculated after 3 days. For the two scores with the best discrimination capacity, values associated with a very high probability of death (!80%) were determined (37). A p value !.05 was required for statistical significance. The study was approved by the Ethics Committee of the Société de Réanimation de Langue Française and received the required legal approval from the appropriate French data protection committees. According to the French regulation on research performed on data, usual informed consent was waived and replaced by information provided to patients. • 50 yaşında erkek hasta • MELD 28 • Primer sklerozan kolanjit (PSK) siroz • Tekrarlayıcı kolanjit geçiriyor (Candida alb ve VRE dahil) • Kliniğe kabul edildiğinde diüretikle kontrol edilemeyen asit=> 6 kez Prometheus tedavisi uygulanıyor • 4 MRGN (karbapeneme dirençli Enterbactereocea) rektal kolonizasyonlu • Pnömoni nedeniyle 1 hafta mekanik ventilasyon gerekiyor => iyileşiyor • 4 aydır Klinikte, bugüne kadar 2 defa YBÜ tedavisi görmüş Titel Klinik für Allgemein-, Viszeral- und Transplantationschirurgie infection, 5%; other, 5%). Death in the MICU was preceded by a written decision to limit or withdraw life-sustaining treatments in 65% of cases. Long-term Outcome of Nonfutile Patients The 132 patients in the nonfutile group had overall 1-, 3-, 5-, Inhospital and 8-year survivals of 89%, 79%, 75%, and 69%. TheRisk CoxFactors modelforfor Mortality Assessed on Day 1 graft failure/mortality-free survival identified recipient The age, postopresults of the univariate analysis are presented in Table 3. Of note is that erative grade 4 complications, hepatitis C, and metabolic syndrome the liver disease severity staged according as independent survival predictors (Table 4). The Harrells c-statistics to D’Amico’s classification did not correlate with inhospital mortality. of this model was 0.720. Patients with metabolic syndrome had poor Because hematologic failure was not associated with mortality, a modified SOFA long-term survival (Fig. 5D). LT in highest AcuityDISCUSSION Recipients • • • • score, excluding points for hematologic failure, was computed. The following factors were included in multivariate analysis: age, infection, secondary admission from a unit different from the emergency department, serum albumin, degree of ascites, INR, and modified SOFA score. After backward elimination, age older than 50 yrs, lower serum albumin, higher INR, and higher modified SOFA score remained independently associated with inhospital mortality (Table 4). This is one of the first studies to analyze outcome variables for liver transplant recipients with the highest MELD scores (≥40) at the RESULTS Ntime = 169 hasta ≥ 40 acuity of these extremely sick patients of OLT. TheMELD high medical Patient Characteristics was reflected by the severityDuring of theend-stage liver disease requiring study period, 2,728 patients Futile Score geliştiriliyor ay içindeki hasta kaybı olarak belirleniyor) were admitted to thetreatment MICU, of whom 152 ICU management and/or (3 life-support and by significant underlying comorbidities. The data indicate that excellent long-term 2110 Crit Care Med 2010 Vol. 38, No. 11 Futile outcome % 22 (37/169) outcome can be achieved for patients with MELD scores of 40 or more if theyskorda survive4the first yearrisk afterfaktörü OLT. tespit edilmiştir: Geliştirilen bağımsız LT in highest Acuity Recipients UCLA Futility risk score = 0,5 x MELD + 5 x (1= Charlson index ≥ 6, = 0, if Charlson index < 6 + 4 x (1= Cardiac risk, 0 = if no risk) + 3 x (1 = septic shock, 0 = no septic shock TABLE 4. Independent Risk Factors for Futility and Failure-Free Survival Risk Factors for Futility∗ OR 95% CI Futility score P MELD (per point) 1.14 0.98–1.32 0.091 Pre-OLT septic shock 2.38 0.96–5.56 0.059 Cardiac risk 3.14 1.25–7.92 0.015 Age-adjusted Charlson 3.95 1.18–13.2 0.026 Comorbidity Index ≥6 Risk Factors for HR 95%-CI P Failure-Free Survival† Recipient age (per year) 1.05 1.01–1.10 0.021 Petrowsky, Ann Surg 259, 2014, 1186-1194 Complication 2.23 1.17–4.29 0.015 Titel grade 4‡ Hepatitis C für Allgemein-, Viszeral2.82 1.40–5.70 0.004 Klinik und Transplantationschirurgie Metabolic syndrome 3.81 1.76–8.27 0.001 Skor low risk middle risk high risk ≤ 22 22.5-25.5 ≥ 26 Petrowsky, Ann Surg 259, 2014, 1186-1194 Titel Klinik für Allgemein-, Viszeral- und Transplantationschirurgie ∗ Logistic model (c-statistic 0.754). †Cox model (Harrells c-statistic 0.720). ‡Postoperative complications grade 4 were defined as life-threatening complications requiring ICU management for single- (grade 4a) or multiorgan dysfunction (grade 4b). CI indicates confidence interval; HR, hazard ratio. ⃝ C 2013 Lippincott Williams & Wilkins ght © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 3 27/04/16 En Acil Durumlarda KC Transplantasyonu Petrowsky et al Petrowsky, Ann Surg 259, 2014, 1186-1194 Titel Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Olgu 2 Annals of Surgery ! Volume 259, Number 6, June 2014 Olgu 2 • 50 yaşında erkek hasta • MELD 28 • Primer sklerozan kolanjit (PSK) siroz • Tekrarlayıcı kolanjit geciriyor ( Candida alb ve VRE dahil) • Kliniğe kabul edildiğinde diüretikle kontrol edilemeyen ascitt=> 6 kez FIGURE 4.tedavisi Posttransplant futility. Early postPrometheus uygulanıyor • 4toMRGN (karbapenem resistanli cumulative futility riskEnterbactereocea) score for therektal kolonizasyonlu transplant patient survival (A) stratified • low- (≤22 points), intermediate(22.5–25.5 Pnömoni nedeniyle 1 hafta mekanik ventilasyon gerekiyor => iyileşiyor • 4(log-rank aydir Klinikte, kadar 2 defa YBÜ tedavisi görmüş test,bugünr P < 0.0001). Points were as- points), and high-risk group (≥26 points) • signed to eachalındıktan futility risk factor according Bekleme listesine sonra Üst GIS Kanaması geçiriyor • Endoskopi girişimi basarili olamiyor/kanamayı engelleyen stent to the odds ratio. The cumulative futility risk score is calculated according to the following formula: score ==> 0.5 × (MELD score) + gerekyior • Akut solunum yetmezliği 3. kere mekanik ventilasyon Titel Charlson Comorbidity Index ≥6; 5 × (1 = Klinik für Allgemein-, Viszeral- und Transplantationschirurgie 0 = Charlson Comorbidity Index <6) + 4 × (1 = cardiac risk; 0 = no cardiac risk) + 3 × (1 = septic shock; 0 = no sepsis). The receiver operating characteristic curve of the logistic futility risk model had a c-statistic of 0.754 (B). C, The predictive futility risk according to the cumulative futility risk score. The intercept of this model was −7.9. D, Patients’ survival of the nonfutile and the entire group. Olgu 3 • 45 yaşında hasta • Hasta 1 hafta YBÜde kalıyor, kendi şartlarına göre iyileşiyor • NASH siroz, BMI 27 • 1 hafta sonra organ temin edilip transplante ediliyor • Diüretik ile kontrol edilemeyen ascitt • YBÜ Tx‘dan sonra 3 gün • Insüline bağımlı Diabetes mellitus • Toplam klinikte kalma süresi> 7 ay • Bili 21,4 mg/dl, SCr 6,9 mg/dl => CVVHD • Tx‘dan 7 hafta sonra klinikten taburcu oluyor • PT: %41, (INR 1,7), aPTT 39,7 sec., fibrinojen 148 mg/dl, PLT 39/nl • MELD: 37 Titel Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Titel Klinik für Allgemein-, Viszeral- und Transplantationschirurgie FIGURE 5. Posttransplant survival of nonfutile group stratified for independent predictors of graft-failure-free survival. KaplanMeier survival plots illustrate patients’ overall survival for nonfutile group (n=132) with (A) recipient age of 55 years or less Yoğun Bakımcının KCversus Naklindeki Rolü more than 55 years (P = 0.0015), (B) postoperative complications grade 4 versus less than grade 4 (P = 0.142), (C) hepatitis Olgu 3 Disiplinler Çalışma C versus no hepatitis C (P = 0.039), and (D) pretransplant MetS versus no pretransplant MetS (P = 0.0003).Arası P values for curveGerektiriyor comparison are computed using the log-rank (Mantel-Cox) test. HCV indicates hepatitis C virus; MetS, metabolic syndrome. Hepatolog/Nefrolog 1192 | www.annalsofsurgery.com ⃝ C 2013 Lippincott Williams & Wilkins Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Cerrah Hasta Anestezi Yoğun bakım Titel Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Titel Klinik für Allgemein-, Viszeral- und Transplantationschirurgie 4 Table 1 Baseline, donor, and outcome characteristics for 198 transplanted critically ill cirrhosis patients (first objective, five sites) and 106 nontransplanted critically ill cirrhosis patients (second objective, two sites) First objective (n = 198) Second objective (n = 106) Age (years) 53 (10) 54 (9.5) Female 67 (34%) 31 (29%) Hepatitis C 62 (31%) 30 (29%) Hepatitis B 17 (9%) 7 (7%) Alcohol PSC/PBC 30 (15%) 30 (15%) 24 (23%) 9 (9%) NASH/Cryptogenic 17 (9%) 18 (17%) Etiology 27/04/16 Comorbidities/Cirrhotic complications Charlson Score 1 (1) 0.7 (1) Ascites 100 (96%) 61 (71%) Variceal bleeding 53 (56%) 54 (64%) Hepatic encephalopathy Hepatorenal syndrome 107 (94%) 84 (63%) 67 (79%) 71 (69%) Spontaneous bacterial peritonitis 34 (41%) 37 (44%) Hemoglobin (g/L) 85 (23) 84 (22) White blood count (×109/L) 8.9 (5.2-14.5) 9.7 (6.5-15.4) Platelet count (×109/L) 64 (43-95) 70 (40-118) Hematology Biochemistry ET Bölgesinde 1-yıllık Sağ kalım Oranı (01/2014-12/2014) Olan Hastaların 2.2 (1.8-3.3) INRYB Bağlı Transplantasyon 2.1 (1.7-2.8) ALT (U/L) 46 (25-82) 53 (27-128) Nakil Sonrası Değerlendirilmesi Bilirubin (μM) 273 (95-575) 239 (95-469) Sodium (mM) 137 (130-143) 136 (130-143) Lactate (mM) 2.8 (1.6-4.6) 3.6 (2.4-7.8) pH 7.39 (7.32-7.46) 7.36 (7.25-7.44) Creatinine (μM) 197 (109-308) 207 (122-301) Physiology Mean arterial pressure (mm Hg) Glasgow Coma Scale score (admission) PO2/FiO2 ratio (mm Hg, admission) 67 (60-83) 52 (10) 10 (5) Transplant 227 (106)n= 198 9 (5) non-Transplant n= 106 195 (112) Organ support Vasopressors (admission) 84/186 (45%) 54/85 (64%) Vasopressors (any day) 95/108 (88%) 58/74 (78%) Mechanical ventilation (admission) MV (any day) 76/134 (57%) 100/114 (88%) 50/86 (58%) 61/74 (82%) RRT (admission) 49/187 (26%) 27/87 (31%) RRT (any day) 78/139 (56%) 42/76 (55%) Aggregate scores Child Turcotte Pugh (listing) 12.4 (1.6) MELD (listing) 24 (16-36) 23 (15-35) MELD (admit) 34 (26-39) 36 (27-40) MELD (transplant) SOFA (admit) 34 (27-40) 12.5 (4) 14 (4) SOFA (48 hours) 13 (5) 17 (4) SOFA (transplant) 14 (4) Titel Karvellas, Crit Care 2013, 17, R 28 Titel Klinik für Allgemein-, Viszeral- und Transplantationschirurgie p = 0.048 p = 0.001 Klinik für Allgemein-, Viszeral- und Transplantationschirurgie KC Yetmezliğinde mekanik ventilasyon ve vazopressör tedavisi gereken hastalar transplant olur mu? YB Bağlı Transplantasyon Olan Hastaların Nakil Sonrası Değerlendirilmesi Transplant ve ventilasyon YB ve mekanik ventilasyon YB ve nonventilasyon YB bağlı olmayan hasta N=40 N= 80 N = 120 Mekanik ventilasyondaki hastaların transplant‘a kabul edilme koşulları: FiO2 ≤ 40%, PEEP ≤10 mbar, NE: ≤ 0.1 µg/kg/min, infeksiyon belirtileri meçhul Titel Knaak, Liver Transpl., 21, 2015, 761-767 Karvellas, Crit Care 2013, 17, R 28 Titel Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Bulgular Örnek LIVER TRANSPLANTATION, Vol. 21, No. 6, 2015 KNAAK ET AL. 765 • 80 yaşında demanslı huzurevinde yaşayan hasta düşüp, femur boynunu kırıyor • Endoprotez ameliyatta uygulanıyor • Postoperatif dönemde: • Pnömoni • Sepsis • Akut böbrek hasari (AKIN III) Nasıl karar alınabilir? Knaak, Liver Transpl., 21, 2015, 761-767 Titel Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Titel Klinik für Allgemein-, Viszeral- und Transplantationschirurgie 5 Figure 1. (A) Patient survival after transplantation. (B) Graft survival after transplantation. vasopressors, mechanical ventilation, and the pres- patients because a similarly high mortality rate was 27/04/16 Karaciğer Naklinde Yoğun Bakımcının Rolü Olgu 3 Pubmed‘den cıkan sonuç • 45 yaşında hasta • NASH siroz, BMI 27 • Diüretik ile kontrol edilemeyen asit • İnsülin bağımlı diabetes mellitus • Bil 21,4 mg/dl, SCr 6,9 mg/dl => CVVHD • PT: %41, (INR 1,7), aPTT 39,7 sec., fibrinojen 148 mg/dl, PLT 39/nl • MELD: 37 Titel Titel Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Yoğun Bakım Uzmanının Sağkalım Üzerine Etkisi Meta-analiz Yoğun Bakım Uzmanının Sağ kalım Üzerine Etkisi Meta-analiz ICU Mortality Hospital Mortality Risk ratio (95% CI) Study % Weight Pollack et al 0.53 (0.17,1.64) Brown et al 0.48 (0.32,0.72) 8.4 Kuo et al 0.60 (0.49,0.73) 11.3 Al-Asadi et al 0.82 (0.61,1.10) 9.9 Manthous et al 0.71 (0.54,0.94) 10.1 Marini et al 0.54 (0.26,1.10) 4.7 DiCosmo et al 0.59 (0.44,0.79) 10.0 Ghorra et al 0.42 (0.20,0.90) 4.4 Baldock et al 0.69 (0.52,0.91) 10.0 Rosenfeld et al 0.15 (0.05,0.50) 2.3 Goh et al 0.38 (0.27,0.53) 9.3 Reich et al 0.61 (0.41,0.92) 8.2 Topeli et al 1.44 (1.00,2.07) 8.9 Overall (95% CI) 0.61 (0.50,0.75) .1 1 2.5 % Weight Li 0.93 (0.78,1.13) 11.0 Reynolds, et al 0.77 (0.63,0.94) 10.8 Brown, et al 0.69 (0.52,0.93) Multz et al retrospective 0.81 (0.62,1.07) Multz et al prospective 0.74 (0.53,1.05) 7.5 Manthous et al 0.72 (0.59,0.89) 10.6 Carson et al 1.39 (0.91,2.11) 6.2 Hanson et al 0.67 (0.19,2.29) 1.2 Pronovost et al 0.58 (0.43,0.79) 8.3 Dimick et al 0.26 (0.12,0.59) 2.5 Dimick et al 0.19 (0.07,0.55) 1.6 Baldock et al 0.65 (0.51,0.83) Rosenfeld et al 0.39 (0.19,0.81) 2.9 Blunt et al 0.69 (0.54,0.87) 10.0 Overall (95% CI) 0.71 (0.62,0.82) 8.6 9.0 9.7 10 Risk ratio .1 Titel Risk ratio (95% CI) Study Pronovost, JAMA: 288: 2151-2162 Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Titel 1 Risk ratio 10 Pronovost, JAMA: 288: 2151-2162 Klinik für Allgemein-, Viszeral- und Transplantationschirurgie 6