3. Magnitud del problema
• Complicación frecuente (30-50%)
• Elevada mortalidad hospitalaria (20-50%)
• Riesgo elevado de resangrado
- 30% durante la primer semana
- 50% durante el primer año
Hemorragia aguda variceal
4. 44%
18%
16%
4%
7%
11%
Ulcus Péptico n:149
Várices Esofágicas n:61
Gastroduodenitis Erosiva n:53
Mallory Weiss n:13
Etiología Incierta n:22
Otras n:38
Páez M, Ferretti S, Bichara L, Armas V, Judchak S, Reggiardo M V, Bessone F, Vorobioff J, Ruffinengo O, Tanno H
Servicio de Gastroenterología y Hepatología del Hospital Provincial del Centenario
HEMORRAGIA DIGESTIVA ALTA AGUDA EN UNA UNIDAD DEHEMORRAGIA DIGESTIVA ALTA AGUDA EN UNA UNIDAD DE
ENDOSCOPIA DURANTE UN PERIODO DE 46 MESESENDOSCOPIA DURANTE UN PERIODO DE 46 MESES
Congreso Argentino de Gastroenterología 2003
n: 336 episodios
5. Magnitud del problema
• Complicación frecuente (30-50%)
• Elevada mortalidad hospitalaria (20-50%)
• Riesgo elevado de resangrado
- 30% durante la primer semana
- 50% durante el primer año
Hemorragia aguda variceal
6. Sobrevida en cirrosis hepática
0 4 8
0
20
40
60
80
100
Porcentajedesobrevidadesdesupresentación
110
102 6
Compensada
Ascitis
Encephalpatía
Sangrado variceal
Años desde la presentación
Saunders – Br Med J 1981
7. No ascitis
No várices
Compensada
Curso clínico de la cirrosis hepática
D`amico G - 2001
Várices
No ascitis
Ascitis ±
Várices
Sangrado ±
Ascitis
Muerte
Estadío 1
Estadío 2
Estadío 3
Estadío 4
Descompensada
7%
4,4%
1 %
3,4 %
4%
6,6%
7,6%
20 %
57 %
8. Prevalencia y tamaño variceal en pacientes
cirróticos al momento del diagnóstico
%
Pacientes
con várices
100
60
40
20
0
Global
n=494
Child A
n=346
Child B
n=114
80
Child C
n=34
Grandes
Medianas
Pequeñas
Pagliaro et al., In: Portal Hypertension: Pathophysiology and Management, 1994
PREVALENCE AND SIZE OF ESOPHAGEAL VARICES IN PATIENTS WITH NEWLY DIAGNOSED CIRRHOSIS
9. Riesgo de ruptura según tamaño variceal
%
Pacientes
sin
sangrado
100
50
25
0
0 12 24
75
3612 24 36
Várices grandes * *
p<0.01 *
Probabilidad de primer sangrado a 2 años:
• Várices pequeñas: 7%
• Várices grandes: 30%
Tiempo (meses)
No Varices
Várices pequeñas
*
Merli et al., Hepatol 2003; 38:266, **
Conn et al., Hepatology 1991; 13:902
LARGE VARICES ARE MORE LIKELY TO RUPTURE
11. Sospecha de sangrado variceal
Medidas generales
Manejo de complicaciones asociadas
Hemorragia aguda variceal
12. Medidas generales
• Reposición cuidadosa de la volemia (Hcto 21-27%)
• Prevención de las infecciones
• Tratamiento de la encefalopatía (Lactulosa)
• Monitoreo de la función renal (40 ml/hora)
• Intubación endotraqueal (encefalopatía)
• Corrección de la coagulopatía ????
Hemorragia aguda variceal
13. Medidas generales
• Reposición cuidadosa de la volemia (Hcto 21-27%)
• Prevención de las infecciones
• Tratamiento de la encefalopatía (Lactulosa)
• Monitoreo de la función renal (40 ml/hora)
• Intubación endotraqueal (encefalopatía)
• Corrección de la coagulopatía ????
Hemorragia aguda variceal
14. Reposición de la volemia
Riesgo de daño órgano
por disminución de la
oxigenación tisular
Riesgo de perpetuar el
sangrado por sobre-
expansión
16. Medidas generales
• Reposición cuidadosa de la volemia (Hcto 21-27%)
• Prevención de las infecciones
• Tratamiento de la encefalopatía (Lactulosa)
• Monitoreo de la función renal (40 ml/hora)
• Intubación endotraqueal (encefalopatía)
• Corrección de la coagulopatía ????
Hemorragia aguda variceal
17. Profilaxis ATB en pacientes cirróticos
con sangrado variceal
Bernard B et al.; Hepatology 1999
%
P<0.05
Metanálisis: 5 estudios, 530 pacientes
P<0.05
0
5
10
15
20
25
30
35
40
45
50
Infección Mortalidad
ATB
No ATB
19. Medidas generales
• Reposición cuidadosa de la volemia (Hcto 21-27%)
• Prevención de las infecciones
- Norfloxacina VO 400mg cada 12hs (7 días)
- Ceftriaxona EV 1g día (7 días) (Child C)
• Tratamiento de la encefalopatía (Lactulosa)
• Monitoreo de la función renal (40 ml/hora)
• Intubación endotraqueal (encefalopatía)
• Corrección de la coagulopatía ????
Hemorragia aguda variceal
25. Administración precoz de Terlipresina
en sangrado variceal agudo
Control de
hemorragia
Requerimiento
transfusional
Levacher et al., Lancet 1995
100
60
40
80
20
0
%
2.5
1.5
1
2
.5
0Unidades
Terlipresina
+ nitroglicerina
Placebo PlaceboTerlipresina
+ nitroglicerina
EARLY ADMINISTRATION OF TERLIPRESSIN IMPROVES CONTROL OF ACTIVE VARICEAL HEMORRHAGE
32. Escleroterapia
• Control del sangrado 62-100%
• Polidocanol (AET)
• Facilidad técnica
• Mayor tasa de complicaciones
• Eficaz para control del sangrado
y posterior erradicación con ligadura
endoscópica
Hemorragia aguda variceal
33. Bañares R et al., Hepatology 2002
Terapia endoscópica + farmacológica vs.
terapia endoscópica sola en sangrado variceal
Sclero + Octreotide Besson, 1995
Ligation + Octreotide Sung, 1995
Sclero + Octreotide / ST Signorelli, 1996
Sclero + Octreotide Ceriani, 1997
Sclero + Octreotide Signorelli, 1997
Sclero + ST Avgerinos, 1997
Sclero + Octreotide Zuberi, 2000
Sclero / ligation + Vapreotide Cales, 2001
TOTAL
En favor terapia
endoscópica sola
1 1.6 1.8 21.2 1.40.8
En favor terapia endoscópica
+ farmacológica
Relative
Risk
COMBINATION DRUG/ENDOSCOPIC THERAPY IS MORE EFFECTIVE THAN ENDOSCOPIC THERAPY ALONE
34. Sospecha de sangrado variceal
Resangrado
precoz
Falla para el control
del sangrado
Segundo tratamiento
endoscópico
Control del
sangrado
Sonda balón
Shunt
quirúrgico TIPS
Falla para el control
del sangrado
Child A/B Child C
Medidas generales
Manejo de complicaciones asociadas
Tratamiento farmacológico precoz
- Terlipresina
- Octreotide
Hemorragia aguda variceal
Control del
sangrado
Profilaxis
secundaria
80%
Aordaje endoscópico
(Diagnóstico – terapéutico)
35. Sonda balón de Sengstaken Blakemore
Indicaciones: • Terapia de rescate (falla del tratamiento)
• Sangrado masivo
Insuflación gástrica
Insuflación esofágica
Aspiración gástrica
Balón esofágico (40mmHg)
Balón gástrico (200ml)
36.
37. Sospecha de sangrado variceal
Tratamiento farmacológico precoz
- Terlipresina
- Octreotide
Medidas generales
Manejo de complicaciones asociadas
Tratamiento endoscópico
Control del
sangrado
Profilaxis
secundaria
Resangrado
precoz
Falla para el control
del sangrado
Segundo tratamiento
endoscópico
Shunt
quirúrgico TIPS
Falla para el control
del sangrado
Control del
sangrado
Sonda balón
Child A/B Child C
Hemorragia aguda variceal
40. Clasificación de las Várices Gástricas
GOV 1GOV 1
GOV 2GOV 2
IGV 1IGV 1
IGV 2IGV 2
Sarin et al, Am J Gastro 1989Sarin et al, Am J Gastro 1989; 84:1244; 84:1244
CLASSIFICATION OF GASTRIC VARICES
41. Várices Gástricas
• 10-15% de los episodios de sangrado variceal
• No se conoce aún la terapia óptima
• Inyección endoscópica de Cianoacrilato:
90% control del sangrado
• Hemostasia con Sonda balón
• TIPS: 90% control del sangrado
GASTRIC VARICES
49. Stents esofágicos en sangrado variceal
• Alta eficacia en la hemostasia
• Se puede dejar 7 días
• Baja incidencia de complicaciones
• Alternativa al tratamiento de rescate
(Balón SB)
50.
51. Early TIPS vs. terapia convencional en
sangrado variceal
García-Pagán et al - NEJM 2010
PTFE-TIPS (10mm)
(n=32)
(within 24h:19; 48h:10;
72h:3)
Continuar con terapia standard por 5 dias
seguida por profilaxis secundaria con EBL
+ BB + IsMn (n=31)
PTFE-TIPS as rescue treatment Early PTFE-TIPSTerapia standard
63 pacientes de alto riesgo con sangrado variceal
agudo
(Child B + sangrado activo ó Child C)
Randomización dentro 24h de admisión
Drogas vasoactivas + Tratamiento endoscópico + Antibióticos
52. Early TIPS vs. terapia convencional en
sangrado variceal
%
Falla para el control
del sangrado
45%
3%
28%
Mortalidad EPS
12%
100
75
50
25
0
García-Pagán et al - NEJM 20010
42%39%
p=0.001
p=NS
Early TIPS (n=32)
Terapia convencional (n=31)
p=0.001
53.
54. Profilaxis primaria del sangrado variceal
Endoscopía
No várices Várices pequeñas
sin signos rojos
Várices pequeñas
con signos rojos
Várices grandesRiesgo progresión
<10% a 3 años
Endoscopía de
control c/2-3 años
Riesgo progresión
10-15%/ año
Endoscopía de
control c/2 años
¿ß bloqueantes?
Riesgo aumentado
de sangrado
Profilaxis
primaria
55. Profilaxis primaria del sangrado variceal
Profilaxis primaria
ß-bloqueantes
Ligadura
endoscópica
• Experiencia
• Disponibilidad de recursos
• Preferencia y características del
paciente
• Efectos indeseables
• Contraindicaciones
• Sesiones c/2meses
hasta erradicación
• Control endoscópico
cada 6 meses
• 20mg cada 12hs VO
• FC: 55-60 lat/min
• Mayor dosis posible
• Dosis crecientes
56. Profilaxis secundaria del sangrado variceal
• Inicio al sexto día del sangrado
• ß bloqueantes + Ligadura endoscópica
• La disminución de HVPG es un importante predictor
de respuesta y de sobrevida
• No respondedores pueden beneficiarse con MNI
• En pacientes que sangran mientras reciben profilaxis
secundaria : - TIPS (Child C <13)
- Shunt quirúrgico (Child A y B)
- Trasplante hepático
57. Riesgo de resangrado en profilaxis
secundaria
(19 trials) (26 trials) (54 trials)
%
Resangrado
80
60
40
20
0
No tratados β-bloq Esclero-
terapia
(18 trials)
Ligadura
(6 trials)
HVPG
Resp*
(6 trials)
β -bloq
+ ISMN
(2 trials)
Ligadura
+
β-bloq
Bosch and García-Pagán, Lancet 2003
* ↓ HVPG <12 mmHg ó
>20% del basal
LOWEST REBLEEDING RATES ARE OBTAINED IN HVPG RESPONDERS AND IN PATIENTS TREATED WITH VARICEAL BAND LIGATION + BETA-BLOCKERS
58. Tension (T)
Wall thickness
(w)
Groszmann, Gastroenterology 1984; 80:1611
T = tp x r
w
Variceal Wall Tension (T) is a Major
Determinant of Variceal Rupture
Transmural
pressure (tp)
Radius
(r)
Esophagus
Varix
VARICEAL WALL TENSION IS A MAJOR DETERMINANT OF VARICEAL RUPTURE
Notas del editor
Slide 17
COMPLICATIONS OF CIRRHOSIS
Cirrhosis leads to two clinical syndromes: portal hypertension and liver insufficiency. Development of variceal hemorrhage and ascites are the direct consequence of portal hypertension, while jaundice occurs as a result of a compromised liver function. Encephalopathy is the result of both portal hypertension (portosystemic shunting) and liver dysfunction (decreased ammonia metabolism). Ascites in turn can become complicated by infection (spontaneous bacterial peritonitis) and by the development of a functional renal failure (hepatorenal syndrome).
Slide 84
PREVALENCE AND SIZE OF ESOPHAGEAL VARICES IN PATIENTS WITH NEWLY DIAGNOSED CIRRHOSIS
Esophageal varices are present in approximately half of the patients with cirrhosis. The prevalence correlates to the severity of liver disease with Child C cirrhotic patients being twice as likely to have varices as Child A patients. In addition, Child C patients are more likely to have large varices than patients with less severe liver disease.
Pagliaro et al., In: Portal Hypertension: Pathophysiology and Management, 1994; 72
Slide 98
LARGE VARICES ARE MORE LIKELY TO RUPTURE
The most important predictor of variceal hemorrhage is variceal size. The incidence of first variceal hemorrhage in patients with small varices is very small , at ~5% per year, while large varices bleed at a rate of ~15% per year.
Merli M, et al. J Hepatol 2003; 38: 266
Conn HO, et al. Hepatology 1991; 13: 902
Slide 140
PROPHYLACTIC ANTIBIOTICS PREVENT EARLY VARICEAL REBLEEDING
In a randomized controlled trial, patients randomized to prophylactic antibiotics had a significantly lower probability of developing early variceal rebleeding compared to patients who were randomized to on-demand antibiotics (that is, antibiotics given only in the presence of infection).
Hou MC, et al., Hepatology 2004; 39: 746
Slide 65
AN INCREASE IN PORTAL VENOUS INFLOW SUSTAINS PORTAL HYPERTENSION
The initial mechanism in the development of portal hypertension in cirrhosis is an increase in vascular resistance to portal flow mostly due to a distorted sinusoidal architecture. However, a subsequent increase in portal venous inflow secondary to splanchnic vasodilatation, maintains the portal hypertensive state.
Slide 65
AN INCREASE IN PORTAL VENOUS INFLOW SUSTAINS PORTAL HYPERTENSION
The initial mechanism in the development of portal hypertension in cirrhosis is an increase in vascular resistance to portal flow mostly due to a distorted sinusoidal architecture. However, a subsequent increase in portal venous inflow secondary to splanchnic vasodilatation, maintains the portal hypertensive state.
Slide 142
EARLY ADMINISTRATION OF TERLIPRESSIN IMPROVES CONTROL OF ACTIVE VARICEAL HEMORRHAGE
In a controlled trial in which cirrhotic patients with gastrointestinal hemorrhage were randomized to terlipressin + nitrates vs. placebo prior to hospitalization (at the patient’s home or in the ambulance), control of hemorrhage occurred in a larger proportion of patients randomized to active therapy who subsequently also required the transfusion of a significantly lower number of blood units.
Levacher et al., Lancet 1995; 346: 865
Slide 144
ENDOSCOPIC VARICEAL BAND LIGATION
Endoscopic variceal ligation consists of the placement of rubber rings on variceal columns with the objective of interrupting blood flow and subsequently developing necrosis of mucosa and submucosa and replacement of varices by scar tissue. Endoscopic therapy is a local therapy that has no effect on the pathophysiologic mechanisms that lead to portal hypertension and variceal rupture. Even though it achieves variceal obliteration, varices will eventually recur. Bleeding is controlled in 90% of cases of acute variceal hemorrhage with a rebleeding rate of 30%. Meta-analysis of trials comparing ligation with sclerotherapy has shown that ligation is associated with lower rebleeding rates, lower number of sessions to achieve variceal obliteration and lower mortality. Complications of endoscopic therapy are related mainly to the development of esophageal ulceration and strictures, significantly more frequent after sclerotherapy than after ligation.
Laine and Cook. Ann Intern Med 1995; 123:280
Slide 143
COMBINATION DRUG/ENDOSCOPIC THERAPY IS MORE EFFECTIVE THAN ENDOSCOPIC THERAPY ALONE
A meta-analysis of 8 trials comparing endoscopic therapy (sclerotherapy or band ligation) vs. endoscopic therapy + vasoactive drugs (somatostatin, octreotide, vapreotide) shows that combination therapy was better than endoscopic therapy alone in the initial control of bleeding and in achieving 5-day hemostasis. However, there were no differences in survival.
Bañares R, et al., Hepatology 2002; 35: 609
Slide 181
CLASSIFICATION OF GASTRIC VARICES
Gastric varices are those that extend from the esophagus into the stomach. They can be subclassified into 2 groups: gastroesophageal varices (GOV, gastric varices that are continuous with esophageal varices) and isolated gastric varices (IGV, gastric varices that occur in the absence of esophageal varices). GOV are in turn classified in GOV1 in which varices extend along the lesser curve for about 2–5 cm below the gastroesophageal junction; and GOV2 which are often long and tortuous and extending from the esophagus below the gastroesophageal junction toward the fundus. IGV are also subclassified into IGV1, varices located in the fundus that often are tortuous and complex in shape; and IGV2, ectopic varices in the antrum, corpus, and around the pylorus. For the purposes of some studies duodenal varices also have been included in this group.
Slide 182
GASTRIC VARICES
Gastric varices account for 10-15% of variceal bleeding episodes. Because of limited data from controlled trials, optimal therapy is not known. Vasoactive drugs have been used, but not studied. Endoscopic cyanoacrylate obturation of the varices can result in control of up to 90% of patients. A Linton Nachlas tube, which has a gastric balloon of volume 600 mL, may be used for variceal tamponade. TIPS can result in control of bleeding in over 90 percent of patients.
Uno de los cambios epideniológicos mas trascendentes de loa últimos años es la emergencia de gérmenes multiresistentes.
El grupo de Barcelona describe recientemente un elevado porcentaje de GMR en infecciones nosocomiales, la mayoria PBE
Uno de los cambios epideniológicos mas trascendentes de loa últimos años es la emergencia de gérmenes multiresistentes.
El grupo de Barcelona describe recientemente un elevado porcentaje de GMR en infecciones nosocomiales, la mayoria PBE
Uno de los cambios epideniológicos mas trascendentes de loa últimos años es la emergencia de gérmenes multiresistentes.
El grupo de Barcelona describe recientemente un elevado porcentaje de GMR en infecciones nosocomiales, la mayoria PBE
Uno de los cambios epideniológicos mas trascendentes de loa últimos años es la emergencia de gérmenes multiresistentes.
El grupo de Barcelona describe recientemente un elevado porcentaje de GMR en infecciones nosocomiales, la mayoria PBE
Slide 103
SURVIVAL IMPROVES IN PATIENTS IN WHOM HVPG DECREASES (HVPG RESPONDERS)
Patients who demonstrate a decrease in HVPG below 12 mmHg and/or a decrease &gt;20% from baseline not only have a lower risk of variceal bleeding but also have a lower mortality (graph) and a lower probability of developing other complications of portal hypertension such as ascites.
Abraldes et al. Hepatology 2003; 37:902
Slide 103
SURVIVAL IMPROVES IN PATIENTS IN WHOM HVPG DECREASES (HVPG RESPONDERS)
Patients who demonstrate a decrease in HVPG below 12 mmHg and/or a decrease &gt;20% from baseline not only have a lower risk of variceal bleeding but also have a lower mortality (graph) and a lower probability of developing other complications of portal hypertension such as ascites.
Abraldes et al. Hepatology 2003; 37:902
Slide 103
SURVIVAL IMPROVES IN PATIENTS IN WHOM HVPG DECREASES (HVPG RESPONDERS)
Patients who demonstrate a decrease in HVPG below 12 mmHg and/or a decrease &gt;20% from baseline not only have a lower risk of variceal bleeding but also have a lower mortality (graph) and a lower probability of developing other complications of portal hypertension such as ascites.
Abraldes et al. Hepatology 2003; 37:902
Slide 161
LOWEST REBLEEDING RATES ARE OBTAINED IN HVPG RESPONDERS AND IN PATIENTS TREATED WITH VARICEAL BAND LIGATION + BETA-BLOCKERS
In addition to HVPG responders (i.e. patients who achieve a reduction in hepatic venous pressure gradient below 12 mmHg or &gt;20% from baseline) in whom the rebleeding rate is around 10%, two trials comparing the combination of ligation + beta-blockers vs. ligation alone, show that combination therapy is more effective, with rebleeding rates of 14 and 23%, respectively. These therapies are placed in the context of no therapy (red bar) and other less effective therapies (orange bars).
Bosch J, and Garcia-Pagan JC, Lancet 2003; 361; 952
Lo GH, et al., Hepatology 2000; 32: 461
De la Pena J, et al., Hepatology 2005; 41: 572
Slide 99
VARICEAL WALL TENSION IS A MAJOR DETERMINANT OF VARICEAL RUPTURE
Rupture of a vessel occurs when the expanding force exceeds its maximal wall tension. The higher the tension, the greater the possibility of rupture. Tension in the varix (T) is directly proportional to transmural pressure (difference between the intravariceal and the intraluminal esophageal pressure) and to variceal radius (r) and is inversely proportional to variceal wall thickness. A large varix has a large radius and a thin wall and therefore a larger tension and a greater propensity to rupture.
Groszmann RJ. Gastroenterology 1984; 80:1611
