PBE Manejo en Urgencias

Cristina Gago Bellido

Residente 3 año MFyC

Hospital Sagunto

Índice

  Caso clínico

  Introducción

  PBE

Caso clínico

  Mujer de 57 años que acude a Urgencias por aumento del perímetro abdominal, dolor abdominal generalizado y disnea a mínimos esfuerzos, progresiva, de dos semanas de evolución. Aumento de 2-3 Kg. No refiere disminución de la diuresis ni aumento de edemas en MMII. No fiebre, ni sensación distérmica. No otros síntomas.

  EXPLORACIÓN FÍSICA.

Caso clínico

ANTECEDENTES:

-  No RAM.

-  No HTA. No DM. No DL.

-  Hipotiroidismo

-  Hepatopatía crónica por infección VHC genotipo 1b. Biopsia 1999. En 2000 recibió tto con INF y Rivabirina en 2 ocasiones sin obtener respuesta viral. Episodio de HDA secundaria a úlcera duodenal que requirió hemostasia endoscópica con adrenalina.

-  Último ingreso en enero 2014 por descompensación hidrópica y PBE

-  No hábitos tóxicos. Independiente ABVD.

-  Tratamiento habitual: Enalapril 20 mg 1-0-0, Seguril 1-1-0, Aldactone 100 mg 0,5-1-0, Aldoleo 50/50, Parapres 16 mg, Besitran 100 mg, Acfol, Omeprazol 20 mg, Eutirox 75 mg.

Introducción

  CIRROSIS HEPÁTICA

Constituye el estadio tardío de la hepatopatía crónica, en el que se observa el grado más avanzado de fibrosis. Se caracteriza por la distorsión de la arquitectura hepática y la formación de nódulos de regeneración.

En nuestro medio más del 90% de los casos de cirrosis hepática se deben al alcohol y a virus (VHC y VHB).

Introducción

  Diagnóstico: Signos clínicos + analíticos + pruebas de imagen (eco/TC/ RM/elastografía de transición)

  Fases de la cirrosis:

COMPENSADA DESCOMPENSADA -  Asintomático-oligosintomático -  Duración variable -  Síntomas inespecíficos (astenia, anorexia,

pérdida peso) pueden tener HTP-varices esofágicas

-  A la exploración: estigmas hepatopatía, hepatoesplenomegalia

-  Seguimiento cada 6 m (dco precoz hepatocarcinoma-descompensaciones-HTP)

-  A medida que evoluciona la enfermedad, se desarrollan complicaciones relacionadas con la HTP (ascitis, HDA varices, EH), con la insuficiencia hepatocelular (ictericia)

-  Peor pronóstico -  Evaluados como posibles candidatos al

trasplante hepático

Introducción

  PRONÓSTICO: variable, depende de múltiples factores, como la etiología, la gravedad, la presencia de complicaciones y las enfermedades asociadas.

Introducción

  COMPLICACIONES DE LA CIRROSIS HEPÁTICA:

-  Ascitis Peritonitis bacteriana espontánea

-  HDA secundaria a HTP

-  Encefalopatía hepática

-  Síndrome hepatopulmonar

-  Síndrome hepatorrenal

-  Hidrotórax hepático

-  Carcinoma hepatocelular

PBE Concepto

 Es la infección del líquido ascítico en pacientes cirróticos sin fuente aparente de infección intraabdominal.

  Monomicrobiana (>92%) BGN Escherichia coli . En ocasiones por cocos gram positivos.

  Prevalencia:1,5-3,5% ambulatorios y 10-30% en hospitalizados

  Factores de riesgo: situaciones que deprimen la actividad del sistema mononuclearfagocítico: hipovolemia, hemorragia digestiva, fármacos vasoconstrictores esplácnicos, cirugía, alcoholismo, inmunosupresión, etc.

PBE Clínica

Depende del grado de evolución del cuadro pudiendo ser:

PBE Diagnóstico

  Se establece mediante paracentesis, por un recuento en el líquido ascítico de PMN:

En pacientes con ascitis hemorrágica (>10.000hematíes/µl), hay que restar 1 PMN por cada 250 hematíes.

  Cultivo de líquido ascítico: no es necesario para dco (30-50% son negativos)

  Cyturtest 55% falsos negativos

PBE Diagnóstico

Paracentesis diagnóstica

PBE Diagnóstico diferencial

  PERITONITIS BACTERIANA SECUNDARIA

Infección del líquido ascítico debida a una perforación visceral o bien a un absceso de un órgano abdominal. Se debe sospechar en aquellos casos de ausencia de respuesta al tratamiento de la PBE, mayor aumento de PMN en el líquido ascítico (habitualmente>10.000/µl) y un cultivo de líquido ascítico polimicrobiano.

Habitualmente requiere tratamiento quirúrgico y antibioterapia de amplio espectro.

PBE Tratamiento

  MEDIDAS GENERALES:

1.  Vigilar parámetros hemodinámicos.

2.  Fluidoterapia de mantenimiento 500-1000 glucosalino/24h

3.  Deben evitarse causas que favorezcan la aparición de EH y maniobras que puedan deteriorar la función renal, como la administración de fármacos nefrotóxicos (AINE, aminoglucósidos, etc.) o diuréticos

4.  Reducción ingesta Na a 2 g/día.

5.  Paracentesis evacuadora: se debe evitar en caso de infección activa (nunca si PBE)

PBE Tratamiento   TRATAMIENTO ANTIBIÓTICO EMPÍRICO: iniciar inmediatamente tras el diagnóstico de PBE, sin esperar a los

resultados del cultivo de líquido ascítico.

1.  Ceftriaxona 2 g/24 horas iv durante 5 días

2.  Cefotaxima 2 g/12 horas iv durante 5 días

3.  Amoxicilina/clavulánico (1 g/6-8 horas iv 2 días 500 mg/8 h vo 6-12 días)

4.  Ciprofloxacino 400 mg/12 horas iv durante 5 días (indicado en alérgicos a betalactámicos).No, si el paciente ha realizado profilaxis previa con quinolonas, en áreas con alta prevalencia de resistencia a quinolonas ni en PBE nosocomial

5.  Ofloxacino oral (400mg/12 horas) durante 8 días en el caso de una PBE extrahospitalaria no complicada y siempre que no se haya realizado profilaxis previa con quinolonas

6.  Si la PBE es de adquisición intra-hospitalaria, se valorará como tratamiento inicial los carbapenems o glucopéptidos

Nueva paracentesis diagnóstica a las 48h: ante sospecha de respuesta inadecuada. Si los PMN no han descendido un 25%: cambiar la ATB/descartar PBE secundaria

PBE Tratamiento

PBE Tratamiento

  PROFILAXIS DEL SÍNDROME HEPATORRENAL:

El principal predictor de supervivencia en pacientes con PBE es el desarrollo de fallo renal durante la infección (como consecuencia de una disminución en el volumen vascular efectivo, que incide sobre un estado circulatorio previamente alterado)

  La administración de albúmina a dosis de 1,5 g/kg en las seis primeras horas tras el diagnóstico y 1 g/kg a las 48-72 horas previene el SHR y reduce la mortalidad de un 30 a un 10%. Restringir el uso de albúmina a:

Caso clínico

  RX tórax. Sin hallazgos

  Hemograma: Anemia NN Hb 9.2, trombopenia 97.000

  Coagulación: Quick 87% INR 1.1

  Bioquímica: I renal Cr 1.7 Urea 102, Br 2

  Orina: Bacteriuria

  Líquido ascítico: Recuento células 225/mm3 Polinucleares 52% Mononucleares 48% Hematíes 2000/mm3 Proteínas, glucosa, albúmina pte

Caso clínico   Tratamiento al ingreso:

-  Control de constantes y diuresis por turno

-  Dieta hiposódica/de protección hepática

-  Cefotaxima 2 g/12h iv

-  Enalapril 20 mg 1-0-0

-  Valsartán 40 mg 1-0-0

-  Seguril 1-1-1

-  Aldactone 100 mg 0.5-1-0

-  Sertralina 100 mg 0-0-1

-  Acfol 5 mg 1-0-0

-  Omeprazol 20 mg 1-0-0

-  Eutirox 75 mg 1-0-0

Se diagnostica erróneamente de PBE. Se realiza paracentesis diagnóstica/evacuadora obteniendo 4 litros de líquido ascítico transparente. Administramos 2U albúmina y Cefotaxima 1 g iv

Obliga a control estrecho de la PA

No aumentar diuréticos!

PBE Profilaxis

  El mecanismo principal para el desarrollo de la infección es la traslocación bacteriana (ATB para lograr la descontaminación intestinal selectiva)

PROFILAXIS PRIMARIA PROFILAXIS SECUNDARIA 1.  Hemorragia gastrointestinal: Norfloxacino 400 mg/12 horas o Ceftriaxona 1 g/24 horas durante 7 días (mayor eficacia en cirróticos con al menos 2 de los siguientes criterios: ascitis, malnutrición grave, EH o bilirrubina >3 mg/dl)

2. Pacientes con proteínas totales en líquido ascítico <1,5 g/dl y al menos uno de los siguientes criterios: creatinina ≥1,2 mg/dl, Child ≥9, sodio sérico ≤130mEq/l, bilirrubina ≥3 mg/dl y BUN≥25 mg/d

La probabilidad de desarrollar un nuevo episodio de PBE tras un primero es de un 70%, por lo que la profilaxis secundaria está recomendada en estos pacientes. Norfloxacino (400 mg/día) permanente. Sulfametoxazol-trimetoprim (800-160 mg/24 horas). En pacientes que permanezcan sin ascitis durante un largo periodo de tiempo por mejoría en su función hepática se puede valorar suspender la profilaxis.

PBE Pronóstico

  Actualmente la mortalidad de la PBE oscila alrededor del 20%, mientras que la supervivencia al año tras el primer episodio es muy baja (30-50%), por lo que todo paciente que se recupere de una PBE debe de ser considerado como potencial candidato a trasplante hepático.

PBE Conclusiones

© 2009 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY

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Management and treatment of patients with cirrhosis and portal hypertension

tion (122) and theoretically can contribute to precipitating renal dysfunction in patients with SBP (who are already predisposed because of the presence of a bacterial infection), the perform-ance of LVP should be delayed until a! er the resolution of SBP. Similarly, medications that can potentially decrease e" ective intravascular volume, such as diuretics, should be avoided dur-ing acute infection.

# e strategy in the diagnosis and management of SBP is summarized in Table 4 .

Prevention of recurrent SBP . In patients who survive an epi-sode of SBP, the 1-year cumulative recurrence rate is high, at ~ 70 % . # erefore, it is essential that patients who have recovered from an episode of SBP be started on antibiotic prophylaxis to prevent recurrence before they are discharged from the hospi-tal. # erapies are summarized in Supplementary Table 6.

Accepted therapies . In a double-blind, placebo-controlled study, continuous oral norfloxacin was shown to signifi-cantly decrease the 1-year probability of developing recur-rent SBP from 68 % (in the placebo group) to 20 % (in the norfloxacin group) (123) . The reduction in SBP caused by gram-negative organisms was even more dramatic, from 60 % to 3 % . Prophylactic therapy was discontinued after 6 months of therapy and therefore, the effect on survival was not evaluable. As the median survival of patients who develop SBP is ~ 9 months (124) , antibiotic prophylaxis in this setting does not imply an inordinately prolonged period of administration.

Dose and duration . # e dose of nor$ oxacin used in studies of secondary prophylaxis of SBP is 400 mg by mouth (po) q.d. (123,125) . Prophylaxis should be continued until liver trans-plantation or until the disappearance of ascites (likely to occur in alcoholics who stop alcohol ingestion).

Contraindications / side e! ects . # e development of infec-tions by quinolone-resistant organisms is the main complica-tion of long-term nor$ oxacin prophylaxis. In a study carried out in a large number of cirrhotic patients hospitalized with an infection, gram-negative bacteria isolated from patients on long-term quinolone prophylaxis were signi% cantly more likely to be not only quinolone-resistant but also trimethoprim / sulfamethoxazole-resistant compared with those of patients not on prophylaxis (100) .

Alternative therapies . Nor$ oxacin is not on the VA National Formulary; however, other quinolones with a similar spectrum, such as cipro$ oxacin or levo$ oxacin, could theoretically be used instead; the latter with the added advantage of gram-posi-tive coverage.

Although a study has described that cipro$ oxacin admin-istered weekly (750 mg / week) can prevent SBP (126) , it had methodological problems and, additionally, the use of inter-mittent cipro$ oxacin has been related to a higher occur-rence of quinolone-resistant organisms in stool specimens (127) . In a more recent RCT, daily nor$ oxacin (400 mg / day) was more e" ective than weekly ru$ oxacin (400 mg / week) in preventing recurrent SBP due to Enterobacteriaceae (125) . # erefore, quinolones administered weekly cannot be recom-mended (Supplementary Table 6 ). Another trial using oral trimethoprim / sulfamethoxazole (one double-strength tablet daily, 5 days per week) (128) also showed e& cacy in preventing SBP. However, this trial included patients with an earlier history of SBP and those who had never experienced an episode of SBP, hindering the interpretation of these results. Nevertheless, in patients who are unable to take quinolones, this alternative is reasonable.

# e strategy in the prevention of recurrent SBP is summa-rized in Table 5 .

Table 4 . Diagnosis and management strategy in spontaneous bacterial peritonitis (SBP)

Diagnosis Consider SBP and perform diagnostic paracentesis if: Symptoms / signs (abdominal pain, fever, chills)

Patient is in emergency room or admitted Worsening renal function or encephalopathy

SBP present if ascites PMN count > 250 cells / ! l (if fl uid bloody, subtract 1 PMN per 250 RBC / ! l)

General management Avoid therapeutic paracenteses during active infection Intravenous albumin (1 g / kg of body weight) if BUN > 30 mg / dl, creatinine > 1 mg / dl, bilirubin > 4 mg / dl; repeat at day 3 if renal dysfunction persists Avoid aminoglycosides

Specifi c management Cefotaxime (2 g i.v. every 12 h) or

Ceftriaxone (2 g every 24 h) or

Ampicillin / sulbactam (2g / 1 g i.v. every 6 h)

Follow-up Continue therapy for 7 days Repeat diagnostic paracentesis at day 2

If ascites PMN count decreases by at least 25 % at day 2, intravenous therapy can be switched to oral therapy (quinolone such as ciprofl oxacin or levofl oxacin 250 mg p.o. b.i.d.) to complete 7 days of therapy

b.i.d., twice a day; BUN, blood urea nitrogen; i.v., intravenous; PMN, polymorphonuclear (neutrophil) cell count; p.o., orally; RBC, red blood cell count.

The American Journal of GASTROENTEROLOGY VOLUME 104 | JULY 2009 www.amjgastro.com

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Garcia-Tsao et al.

decrease in renal function (135) and therefore, cyclooxygenase-2 inhibitor use should also be avoided until more clinical data become available.

Long-term antibiotic prophylaxis in the prevention of the ! rst episode of SBP (i.e., primary prophylaxis) in patients with cir-rhosis and ascites is controversial. Given the risk of developing antibiotic-resistant organisms (100,136) , the long-term use of prophylactic antibiotics should be restricted to the sub-popula-tion of patients at the highest risk of developing SBP. Low ( < 1 – 1.5 g / dl) total protein levels in ascites are useful for determining the susceptibility of developing SBP (137) ; however, the prob-ability of developing SBP in unselected patients with low ascites protein level is still low (9 – 14 % ) in control groups of prospec-tive RCTs (138,139) and does not justify prophylaxis in all of them. In a recent placebo-controlled study that selected patients with low ( < 1.5 g / l) ascites protein who also had advanced liver failure (CTP score " 9 and serum bilirubin " 3 mg / dl) or renal dysfunction (serum creatinine ! 1.2 mg / dl, blood urea nitrogen level ! 25 mg / dl, or serum sodium level " 130 mEq / l) nor# oxacin at a dose of 400 mg p.o. q.d. was associated with a reduction in the 1-year probability of SBP (7 vs. 61 % ), HRS (28 vs. 41 % ), and 3-month mortality rate (140) . It must be noted that all patients included in the study were initially hospitalized, less than half of the patients with low ascites protein met entry criteria, and the survival bene! t did not extend to 1 year. However, it is in this selected sub-population of patients with cirrhosis and ascites, that prophylaxis with nor# oxacin (400 mg po q.d.) should be undertaken. Another placebo-controlled study that targeted patients with low ascites protein and low risk of developing SBP (serum bilirubin < 3.2, platelet count < 98,000) showed a tendency for lower SBP rate (4 vs. 14 % , P = 0.16) and lower mortality (12 vs. 28 % , P = 0.08) in patients treated with oral cip-ro# oxacin compared with placebo (139); however, the study is underpowered and no ! rm conclusions can be drawn from it.

Management of uncomplicated ascites . Candidates . Candi-dates are cirrhotic patients with ascites not associated with infection or renal dysfunction (141) . Recommendations for uncomplicated cirrhotic ascites apply to patients with uncom-plicated hepatic hydrothorax (Supplementary Table 7 ). Diu-retics can lead to a reduction in intravascular volume and to renal dysfunction and should not be initiated in patients with rising creatinine. In addition, diuretics should not be initiated in patients with concomitant complications of cirrhosis known to be associated with decreased e$ ective arterial blood volume, such as variceal hemorrhage or SBP.

Accepted therapies . Sodium restriction is recommended for all cirrhotic patients with ascites. Although dietary sodium should be restricted to levels lower than urinary sodium excretion, sodium restriction to 88 mEq / day (i.e., 2 g of sodium per day or 5.2 g of dietary salt per day, considering that 1 mEq of sodium = 23 mg of sodium = 58.5 mg of dietary salt) is a real-istic goal, particularly in an outpatient setting. Patients with a baseline urinary sodium excretion >50 mEq / day may respond to salt restriction alone. Most patients will require the addition

Treatment of ascites Ascites is one of the most frequent complications of cirrhosis. In compensated cirrhotic patients, ascites develops at a 5-year cumulative rate of ~ 30 % (3) . Once ascites develops, the 1-year survival rate is ~ 50 % compared with the 1-year survival rate of >90 % in patients with compensated cirrhosis (3,129 – 131) . Prognosis is particularly poor in patients who develop refrac-tory ascites (132) or HRS (133) .

Treatment of ascites has not resulted in signi! cant improve-ments in survival. However, treating ascites is important, not only because it improves the quality of life of the cirrhotic patient but also because SBP, a lethal complication of cir-rhosis, does not occur in the absence of ascites. Patients go through a sequence of diuretic-responsive ascites, followed by refractory ascites, and then HRS.

General measures . Contrary to the treatment of heart failure, in which achieving a negative sodium and water balance im-plies a certain urgency given the risk / presence of pulmonary edema, cirrhotic ascites therapy is not an emergency as the risk of death is not implicit unless the # uid becomes infected. % erefore, treatment of patients with cirrhosis and ascites is based on oral (not i.v.) diuretics in a stepwise slow manner and should only be initiated in a “ stable ” cirrhotic patient, i.e., in a patient for whom complications, such as GI hemorrhage, bacterial infection, and renal dysfunction are absent or have resolved. In a patient with tense ascites who experiences ab-dominal discomfort and / or respiratory distress, a single LVP can be performed before or concomitant to starting diuretic therapy.

As mentioned above, NSAIDs, including aspirin, blunt the natriuretic e$ ect of diuretics and should be avoided in cirrhotic patients with ascites (47,48) . Although selective cyclooxygen-ase-2 inhibitors have not been shown to impair natriuresis or to induce renal dysfunction in cirrhotic rats (134) , preliminary data in patients indicate that celecoxib may be related to a

Table 5 . Management strategy in the prevention of recurrent SBP

Recommended therapy Oral norfl oxacin 400 mg p.o. q.d. (preferred) or

Oral ciprofl oxacin 250 – 500 mg q.d. a or

Oral levofl oxacin 250 mg q.d. a

Alternative therapy TMP-SMX 1 double-strength tablet p.o. q.d. (Patients who develop quinolone-resistant organisms may also have resistance to TMP-SMX)

Duration Prophylaxis should be continued until the disappearance of ascites or until liver transplantation

p.o., orally; SBP, spontaneous bacterial peritonitis; TMP-SMX, trimethoprim-sulfamethoxazole; q.d., once daily. a Empirical doses.

Bibliografía

  Management and treatment of patients with cirrhosis and portal hypertension: Recommendations from the Department of Veterans Affairs Hepatitis C Resource Center Program and the National Hepatitis C Program. AM J Gastroenterol 2009.

  Manual de Diagnóstico y Terapéutica Médica. Hospital Universitario 12 Octubre.

  Medicina de Urgencias y Emergencias. Guía diangóstica y protocolos de actuación. L. Jiménez Murillo.

  Ascitis y síndrome hepatorrenal. Medicine, 2012.

  Profilaxis y tratamiento de la peritonitis bacteriana espontánea en el paciente cirrótico. Medicine, 2012.

  Manual de Urgencias. Carlos Bibiano.

  Guía de actuación en Urgencias. Vázquez Lima.

  Manual de protocolos y Actuación en Urgencias. Complejo Hospitalario de Toledo.

¡¡¡Muchas gracias!!!