1. PANCREATITIS AGUDA 09 Noviembre 2008 Julián Vega Adauy , Residente 1er año Medicina Interna Universidad de Concepción ASPECTOS DE MANEJO BASADOS EN LA EVIDENCIA ACTUALIZACION DE LOS SUPER LUNES
31. Índice de severidad de TC, Balthazar Suma: 0-3 BAJO; 4-6 MEDIO; 7-10 ALTO 6 >50 4 E 4 33-50 3 D 2 <33 2 C 0 0 1 B 0 A Puntuación % de necrosis Puntuación Balthazar
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36. Cuando existen muchos sistemas de puntaje para un mismo objetivo: A) Mucho interés B) Ninguno es bueno C) Todas las anteriores
37. ROC APACHE II, CTSI Balthazar F Ribeiro, Acta Cir. Bras 2008 G Gurleyik. J Pancreas 2006
38. ROC APACHE II, CTSI Balthazar F Ribeiro, Acta Cir. Bras 2008 G Gurleyik. J Pancreas 2006 APACHE II, Buena área bajo la curva Mejor ROC cercano a 8 ptos Indice de TAC mejor predictor, más tardio, menos práctico
39. ROC, PCR vs APACHE II como marcadores de mortalidad en UCI Prieto MF, Medicrit 2008
40. ROC, PCR vs APACHE II como marcadores de mortalidad en UCI Prieto MF, Medicrit 2008 APACHE II mejor ROC vs PCR PCR buen rendimiento
54. Utilidad de TAP urinario en predicción de severidad MAP: Mild acute pancreatitis, SAP: Severe acute pancreatitis Zhi-Su L. Hepatobiliary & Pancreatic diseases international, 2002
55. Utilidad de TAP urinario en predicción de severidad Zhi-Su L. Hepatobiliary & Pancreatic diseases international, 2002
56. Utilidad de TAP urinario en predicción de severidad TAP aparente mejor rendimiento que APACHE II para estratificar. Sin embargo poco protocolizado en cuanto a método y cut-off value Zhi-Su L. Hepatobiliary & Pancreatic diseases international, 2002
64. Algoritmo de decisiones en URG Pancreatitis aguda Criterios para estratificar gravedad Ranson, IMRIE, APACHE II PCR > 150mg/l ECO ABD (liq libre) IMC > 30 Elastasa PMN > 250mg/l, otros Ningún criterio de gravedad PAL >1 criterio UCI TAC cc: Balthazar + extensión necrosis <3 pts >4 pts PAL PAS
65.
66. fisiopatología y fases de la PA FASE TIEMPO EVENTOS MAYORES MUERTES F.O.M Infeccion Causas R. Pezzilli, et al. Ospedali Italiani Chirurgia 2004 horas INICIAL Alteración tráfico proteínas intra-acinares Acumulación TPS espacio intersticial ? ? ? 3-4ta sem TARDIA Bacterias GI Infección De necrosis 19% 37% 0 0 12% 28% 1era sem 2da sem TEMPRANA MEDIA Activación inapropiada proteasas Necrosis Alteración microcirculación Progresion de necrosis Activación Macrófagos 32% 12% 26% 0% 0% 5%
67. Modificado de Norman J. Am J Surg 1998 0 12 24 36 48 60 72 84 90 96 hs dolor Cascadas de citokinas Falla org ánica Ventana terapéutica y el magic bullet approach VENTANA TERAPÉUTICA
68.
69. Terapias y targets de intervención LEXIPAFANT INFLIXIMAB INFLIXIMAB GABEXATE
76. Limitaciones de los módelos experimentales Datos dificiles de EXTRAPOLAR Pastor CM, Frossard JL. FASEB J 2001
77. IL-10 en Pancreatitis Aguda New organ failure (%) Zou WG, et al. J Surg Res 2002 P NS Villoria A, et al. Pancreatology 2003 P<0.05 Eficacia en modelo experimental Sin efecto en estudios clínicos
78. PUFA (Polyunsaturated Fatty Acids) P<0.05 P<0.05 P NS Foitzik T, et al. JPEN 2002 Lasztity N, et al. Clin Nutr 2005; Eficacia en modelo experimental Sin efecto en estudios clínicos P<0.05 P<0.01 P<0.05
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82. Rendimiento de PAF para el dg de necrosis infectada 98 89 Rendimiento (%) 98 93 VPN (%) 100 83 VPP (%) 100 90 Especificidad (%) 97 88 Sensibilidad (%) > Sem 1 Total Parámetro
83. Infección pancreática es casi inexistente <7 mo dia Peack de incidencia es el dia 14 Dia 14 Dia 7 Dia 21 Tiempo de profilaxis?, 14 dias de profilaxis? Mantención? Beger et al. Gastroenterology 1986 99% 95% 68%
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85. UK guidelines for the management of acute pancreatitis UK Working Party on Acute Pancreatitis, Gut 2005
86. * Sin conflicto de interés ni royalties COMPRE IMIPENEM* UK Working Party on Acute Pancreatitis. Gut 2005
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91. Opciones de alimentación en PA TF Standard Rx (NPO, Do nothing) NPTC Severidad Tiempo de evolución Tolerancia S McClave. Nutritional Support in Acute Pancreatitis What are the Key Issues?. University of Louisville School of Medicine
92.
93. Prioridades en manejo nutricional ( ) = Protein/calorie Provision ( ) = Immune Modulation Tiempo (dias) Beneficio (%) 100 50 0 1 2 3 5 4 6 7 S McClave. Nutritional Support in Acute Pancreatitis What are the Key Issues?. University of Louisville School of Medicine
94. 0 12 24 36 48 60 72 84 90 96 hs dolor Cascadas de citokinas Falla org ánica Ventana terapéutica realimentación 48-72 hs (1) 1. S McClave. Nutritional Support in Acute Pancreatitis What are the Key Issues?. University of Louisville School of Medicine Modificado de Norman J. Am J Surg 1998
95. 0 12 24 36 48 60 72 84 90 96 hs dolor Cascadas de citokinas Falla org ánica Ventana terapéutica realimentación 48-72 hs (1) 1. S McClave. Nutritional Support in Acute Pancreatitis What are the Key Issues?. University of Louisville School of Medicine Modificado de Norman J. Am J Surg 1998
96. 0 12 24 36 48 60 72 84 90 96 hs dolor Cascadas de citokinas Falla org ánica Ventana terapéutica realimentación 48-72 hs (1) 1. S McClave. Nutritional Support in Acute Pancreatitis What are the Key Issues?. University of Louisville School of Medicine Modificado de Norman J. Am J Surg 1998
97. Marik, P. E et al. BMJ 2004 MA de RCT que comparan NE vs NP en Pancreatitis Aguda NE es superior a NP NP es riesgosa! PORFAVOR Alimente a sus pacientes por boca o por tubo
98. Marik, P. E et al. BMJ 2004 MA de RCT que comparan NE vs NP en Pancreatitis Aguda
99. Marik, P. E et al. BMJ 2004 Riesgo de infección en Pancreatits Aguda NE vs NP
100. Aumento stress con NE, Estimulación pancreática Disminuye stress, Integridad GI Realimentación precoz, espada de doble filo
101. NE Preservar integridad GI Disminución SIRS Inmunomodulación Aumento de Stress Estimulación pancreática Aumento de dolor Progresión de enfermedad Balance de objetivos realimentación precoz S McClave. Nutritional Support in Acute Pancreatitis What are the Key Issues?. University of Louisville School of Medicine
102. NE Preservar integridad GI Disminución SIRS Inmunomodulación Balance de objetivos realimentación precoz S McClave. Nutritional Support in Acute Pancreatitis What are the Key Issues?. University of Louisville School of Medicine Aumento de Stress Estimulación pancreática Aumento de dolor Progresión de enfermedad
103. N Balance de objetivos realimentación precoz <36 hs >36 hs
104. N Balance de objetivos realimentación precoz <36 hs Reducción Infección 55% (**) (1) Disminución estadía hosp 2.2 dias (**) (1) Tendencia a disminución mortalidad 48% (2) >36 hs Marik, CCM 2001 2. Heyland, JPEN 2003. 3 McClave, JPEN 2006.
105.
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107. Predicción de recaída de dolor en PA, implicancias para realimentar Logistic Score to Predict the Risk of Pain Relapse = 0.64 a + 1.11 b + 2.18 c - 9.06 a = Balthazar’s CT score (5 classes) b = Duration of painful period (5 classes) c = Serum lipase concentration on the day before refeeding <3xN (2 classes) 9.06 = Constant Levy P, et al. Gut 1997
109. Algoritmo de re-alimentación propuesto Avanzar a líquidos orales claros, volumen a tolerancia c/4-6 hs SNG en AP, Iniciar ¿ peptidos/MCT ? Evaluación a las 48hs, Ranson, APACHE II Leve a moderada Severa Tolera NE x SNG No tolera NE x SNG Switch a SNY NPTC si no tolera SNY >5to dia S McClave. Nutritional Support in Acute Pancreatitis What are the Key Issues?. University of Louisville School of Medicine
116. Congruencia de las guias de manejo publicadas Atlanta 1994 UK 1998 - 2005 SSAT 1998 Santorini 1999 AISP 1999 WCG 2002 JSAEM 2002 IAP 2003 Stratification of severity APACHE II BMI Chest X-ray N/a BMI Chest X-ray APACHE II APACHE-O CRP serum creatinine Chest X-ray + CRP CECT APACHE II APACHE II APACHE II CECT scanning Severe AP Severe AP N/a Severe AP Severe AP Severe AP Severe AP N/a Treatment of pain N/a N/a Yes N/a N/a Yes Yes N/a Treatment of nausea, vomiting, ileum N/a N/a N/a N/a Yes N/a N/a N/a Fluid replacement N/a Yes Yes N/a Yes Yes N/a N/a Early antibiotics Necrotizing pancreatitis Necrotizing pancreatitis Necrotizing pancreatitis Necrotizing pancreatitis Necrotizing pancreatitis Necrotizing pancreatitis Necrotizing pancreatitis Necrotizing pancreatitis ERCP+ES Cholangitis Jaundice Cholangitis Jaundice Severe AP Cholangitis Cholangitis Jaundice Severe AP Cholangitis Jaundice Severe AP Cholangitis Jaundice Severe AP Cholangitis Jaundice Severe AP Cholangitis Jaundice Surgery for sterile necrosis Rarely N/a N/a Rarely Rarely Rarely Rarely Rarely FNA to identify infected pancreatic necrosis Yes Yes N/a Yes Yes Yes Yes Yes Enteral nutrition N/a Yes N/a Yes N/a Yes Yes Yes Efficacy of antiproteases N/a No N/a No Severe AP No Yes N/a Pancreas Units Yes Yes Yes Yes Yes Yes Yes N/a Modificado de: Bradley EL. Pancreatology 2003 APACHE II CRP CECT
117. Congruencia de las guias de manejo publicadas Atlanta 1994 UK 1998 - 2005 SSAT 1998 Santorini 1999 AISP 1999 WCG 2002 JSAEM 2002 IAP 2003 Stratification of severity APACHE II BMI Chest X-ray N/a BMI Chest X-ray APACHE II APACHE-O CRP serum creatinine Chest X-ray + CRP CECT APACHE II APACHE II APACHE II CECT scanning Severe AP Severe AP N/a Severe AP Severe AP Severe AP Severe AP N/a Treatment of pain N/a N/a Yes N/a N/a Yes Yes N/a Treatment of nausea, vomiting, ileum N/a N/a N/a N/a Yes N/a N/a N/a Fluid replacement N/a Yes Yes N/a Yes Yes N/a N/a Early antibiotics Necrotizing pancreatitis Necrotizing pancreatitis Necrotizing pancreatitis Necrotizing pancreatitis Necrotizing pancreatitis Necrotizing pancreatitis Necrotizing pancreatitis Necrotizing pancreatitis ERCP+ES Cholangitis Jaundice Cholangitis Jaundice Severe AP Cholangitis Cholangitis Jaundice Severe AP Cholangitis Jaundice Severe AP Cholangitis Jaundice Severe AP Cholangitis Jaundice Severe AP Cholangitis Jaundice Surgery for sterile necrosis Rarely N/a N/a Rarely Rarely Rarely Rarely Rarely FNA to identify infected pancreatic necrosis Yes Yes N/a Yes Yes Yes Yes Yes Enteral nutrition N/a Yes N/a Yes N/a Yes Yes Yes Efficacy of antiproteases N/a No N/a No Severe AP No Yes N/a Pancreas Units Yes Yes Yes Yes Yes Yes Yes N/a Modificado de: Bradley EL. Pancreatology 2003 Múltiples guias clínicas y recomendaciones, reiteradas actualizaciones Variables niveles de congruencia entre guias APACHE II CRP CECT
118. Recomendaciones y nivel de evidencia de las guías publicadas A: RCT; B: No RCT; C: Opinión de expertos; N/a: not available Modificado de: Bradley EL. Pancreatology 2003 Atlanta 1994 UK 1998-2005 SSAT 1998 Santorini 1999 AISP 1999 WCG 2002 JSAEM 2002 IAP 2003 Estratificación severidad B B N/a B B N/a A N/a TAC B B N/a A A N/a B N/a Analgesia N/a N/a N/a N/a N/a N/a N/a N/a Rx Nauseas, vómitos, ileo N/a N/a N/a N/a C N/a N/a N/a Reemplazo fluidos N/a B B C C C N/a N/a AB precoz N/a B B A A B B A ERCP+ES N/a A B B A B B N/a Timing de Cole N/a B N/a N/a B B N/a B Cx para necrosis estéril N/a B N/a A B B B B PAF identificar necrosis infectada N/a B N/a B A N/a A B Nutri enteral N/a A N/a B N/a A B B Eficacia de antiproteasas N/a A N/a A A A A N/a Pancreas Units B B B C B N/a B N/a
120. TL. Bollen. British Journal of Surgery 2008. PA uno de los temas con más información disponible en internet
121. Fin de la presentación Muchas gracias por su atención Julián Vega Adauy, Residente 1er año Medicina Interna, Universidad de Concepción.
122.
Editor's Notes
Suma: 0-3 BAJO; 4-6 MEDIO; 7-10 ALTO= MORT DE 17% Y COMPLIC DE 92%. A: pancreas normal B: aumento de tamaño pancreatico focal o difuso, no evidencia de enfermedad peripancreatica C: alteraciones intrapancreaticas con afectacion de grasa pericpancreatica D: colección liquida unica mal definida E: 2 o mas colecciones liquidas mal definidas. Presencia de gas pancreatico o retroperitoneal.
Clinical and Imaging Prognostic Indices CT severity index >6, equivale a APACHE II >7
Clinical and Imaging Prognostic Indices CT severity index >6, equivale a APACHE II >7
We can distinguish three clinical phases regarding the pathophysiology of acute pancreatitis. There is not very much information on the initial phase of the disease in humans and, for the most part, it comes from experimental studies [1]. Of course, it is apparent that we can obtain good therapeutic results only if we treat the pancreatitis as soon as possible.
The time limit for efficacious medical treatment is of no more than 60 hours from the onset of symptoms of acute pancreatitis [2].
Lexipafant: Inhibidor del factor activador de plaquetas (inhibidor del factor activador de plaquetas), que ha demostrado mejorar la morbimortalidad en animales y humanos con pancreatitis aguda, al evitar el desarrollo de falla multiorgánica. En el Reino Unido, se llevó a cabo un estudio doble ciego placebo-controlado, con 290 pacientes a quienes se les administraba la medicación hasta 48 horas después de iniciados los síntomas, en el que se vio una reducción de la mortalidad de 20 a 10%. En Estados Unidos aún está en estudio esta sustancia Gabexate mesilate , a synthetic protease inhibitor
This slide outlines the key actions attributed to tumor necrosis factor (TNF). The effect of TNF on: - macrophages leads to an increase in proinflammatory cytokines and chemokines leading to increased inflammation - endothelium results in an increase in adhesion molecules and increased cell infiltrations and also in an acute phase response leads to an increase in C-reactive protein (CRP) in serum - fibroblasts leads to an increase in metalloproteinase synthesis and collagen production which contribute to tissue remodeling - epithelium results in increased ion transport and increased permeability, resulting in compromized barrier function.
The high incidence of organ failure within 72 hours after the onset of symptoms has undermined the primary hypothesis, and power calculations for future studies on severe acute pancreatitis will need to allow for this. Lexipafant had no effect on new organ failure during treatment. This study - performed with an adequately sized sample - has shown that antagonism of the PAF activity on its own is not sufficient to ameliorate SIRS in severe acute pancreatitis. However, if we look at the data reported, we cannot exclude that Lexipafant may have some effect, especially in patients treated within 48 hours from the onset of symptoms [34].
A paper published in 2001 highlighted the limitations of experimental models in acute pancreatitis [28].
Interleukin-10 represents a case of limitation of experimental research. In fact, this molecule was unable to prevent new organ failures in clinical practice
On the other hand, polyunsaturated fatty acids were able to decrease the length of hospitalization and the duration of jejunal feeding in humans, even if they were not able to decrease the number of new complications [31, 32].
The time limit for efficacious medical treatment is of no more than 60 hours from the onset of symptoms of acute pancreatitis [2].
The time limit for efficacious medical treatment is of no more than 60 hours from the onset of symptoms of acute pancreatitis [2].
The time limit for efficacious medical treatment is of no more than 60 hours from the onset of symptoms of acute pancreatitis [2].
Refeeding is crucial in patients who have recovered from an acute episode of pancreatitis but there are very few studies on this issue [46].
There is no congruence in the various guidelines regarding stratification of severity, diagnosis, treatment and presence of Pancreas Units [13].
There is no congruence in the various guidelines regarding stratification of severity, diagnosis, treatment and presence of Pancreas Units [13].
In the same way, there are no homogeneous evidence levels in the various guidelines [13].