Fluid in the Abdomen: What to Do Next?

Transcription

1 Fluid in the Abdomen: What to Do Next? Guadalupe García-Tsao, MD Professor of Medicine Yale University Chief, Digestive Diseases Section VA-CT Healthcare System Case # 1 Previously healthy 53-year old woman with new onset ascites that has developed slowly over the past 6 months. She does not drink alcohol and smokes 1 pack of cigarettes per day. She is obese, but has no other medical diagnoses and takes no medications. She reports that t she is also has easy fatigue over the past several months, dyspnea on exertion and decreased appetite with early satiety. Diagnostic paracentesis reveals: ascites albumin 1.5 g/dl, ascites total protein 2.6 g/dl, and ascites cell count 101 neutrophils/mm 3. Serum albumin is 2.9. Serum CA-125 is elevated at 1467 IU/mL (normal <35 IU/mL). Hepatic ultrasound is very limited due to body habitus but reveals patent portal and hepatic veins What is the next most appropriate diagnostic step? a) Exploratory laparotomy b) Echocardiogram c) Pelvic ultrasound d) Triple phase CT scan of the liver e) Cytologic analysis of the ascites fluid Copyright 2014 American College of Gastroenterology 1

2 CIRRHOSIS IS THE MOST COMMON CAUSE OF ASCITES Cirrhosis is the Most Common Cause of Ascites Peritoneal malignancy Cirrhosis Heart failure Peritoneal tuberculosis Others Pancreatic Budd-Chiari syndrome Nephrogenic ascites Portal vein obstruction almost never leads to ascites normal sinusoidal pressure Portal vein obstruction splanchnic capillary pressure Copyright 2014 American College of Gastroenterology 2

3 Hepatic vein obstruction leads to ascites formation Hepatic vein outflow block sinusoidal id pressure splanchnic capillary pressure Source of the main 3 causes of ascites Entity Source Pathophysiology Cirrhosis Heart failure Peritoneal malignancy/tb Hepatic sinusoid Hepatic sinusoid Fibrosis Patients and with nodules cirrhotic ascites causing have sinusoidal an HVPG and of at post-sinusoidal least 12 mmhg (nl 3-5) Morali et a. J Hepatol 2002 obstruction Congestion of liver due to right heart failure (post-hepatic block) Peritoneum Inflammation or infiltration of the peritoneum Copyright 2014 American College of Gastroenterology 3

4 Rationale Behind the Serum-Ascites Albumin Gradient (SAAG) (out of the sinusoid) (into the sinusoid) SIN hyd + PER onc = SIN onc + PER hyd SIN hyd = SIN onc - PER onc HVPG = Serum albumin - Ascites = SAAG albumin The Serum-Ascites Albumin Gradient (SAAG) Correlates With Sinusoidal Pressure HVPG (mmhg) Hoefs J, J Lab Clin Med 1983; 102:260 r = SAAG (g/dl) Copyright 2014 American College of Gastroenterology 4

5 SERUM-ASCITES ALBUMIN GRADIENT (SAAG) AND ASCITES PROTEIN LEVELS IN THE MOST COMMON CAUSES OF ASCITES Serum-Ascites Albumin Gradient and Ascites Protein Levels in the Most Common Causes of Ascites Serum ascites albumin gradient (g/dl) SAAG is an indicator of sinusoidal pressure. If >1.1 ascites is coming from the sinusoid Cirrhotic ascites Cardiac ascites Peritoneal malignancy THE PERMEABILITY OF THE HEPATIC SINUSOID VARIES IN HEALTH AND DISEASE The Permeability of the Hepatic Sinusoid Varies in Health and Disease no basement membrane Hepatocytes The normal sinusoid is leaky Sinusoid fibrous tissue deposition capillarization of sinusoid In cirrhosis, the hepatic sinusoid is less leaky Sinusoid Copyright 2014 American College of Gastroenterology 5

6 SERUM-ASCITES ALBUMIN GRADIENT (SAAG) AND ASCITES PROTEIN LEVELS IN THE MOST COMMON CAUSES OF ASCITES Serum-Ascites Albumin Gradient and Ascites Protein Levels in the Most Common Causes of Ascites Serum ascites albumin gradient (g/dl) Ascitic fluid total protein (g/dl) Cirrhotic ascites 0 Runyon, Ann Intern Med 1992; 117:215 SAAG is an indicator of sinusoidal pressure. If >1.1 ascites is coming from the sinusoid Cardiac ascites Peritoneal malignancy (75) Ascites protein is an indicator of leakiness of sinusoid, >2.5 the sinusoid is leaky (i.e. normal) SAAG and ascites total protein can establish the differential among the main causes of ascites CONDITION Cirrhosis Peritoneal malignancy SAAG high low ASCITES PROTEIN low high Heart failure high high Cutoff 1.1 g/dl 2.5 g/dl Copyright 2014 American College of Gastroenterology 6

7 Serum BNP has a higher diagnostic accuracy for cardiac ascites than SAAG/ascites protein Rules in Rules out Test LR (+) (rules in) SAAG >1.1; prot > Serum BNP >364 pg/ml LR(-) (rules out) SAAG <1.1; prot < Serum BNP < pg/ml Patients with new onset ascites Farias et al. Hepatology 2014; 59: New Onset Ascites* Diagnostic paracentesis SAAG 1.1 g/dl SAAG < 1.1 g/dl Asc Prot < 2.5 g/dl Asc Prot 2.5 g/dl Investigate cirrhosis Investigate posthepatic process Investigate peritoneal process CAT scan Endoscopy (varices) Cardiac echo Hepatic vein Doppler Cytology AFB/ ADA CAT scan If diagnosis still uncertain, values contradictory or borderline HVPG measurement ± TJLB Laparoscopy ± peritoneal biopsy Copyright 2014 American College of Gastroenterology 7

8 Case # 1 Previously healthy 53-year old woman with new onset ascites that has developed slowly over the past 6 months. She does not drink alcohol and smokes 1 pack of cigarettes per day. She is obese, but has no other medical diagnoses and takes no medications. She reports that t she is also has easy fatigue over the past several months, dyspnea on exertion and decreased appetite with early satiety. Diagnostic paracentesis reveals: ascites albumin 1.5 g/dl, ascites total protein 2.6 g/dl, and ascites cell count 101 neutrophils/mm 3. Serum albumin is 2.9. Serum CA-125 is elevated at 1467 IU/mL (normal <35 IU/mL). Hepatic ultrasound is very limited due to body habitus but reveals patent portal and hepatic veins What is the next most appropriate diagnostic step? a) Exploratory laparotomy b) Echocardiogram c) Pelvic ultrasound d) Triple phase CT scan of the liver e) Cytologic analysis of the ascites fluid Natural History of Chronic Liver Disease Chronic liver disease Compensated cirrhosis Decompensated cirrhosis Death Ascites VH Encephalopathy VH= variceal hemorrhage Copyright 2014 American College of Gastroenterology 8

9 In a cohort of patients with compensated cirrhosis, ascites was the most common decompensating event Decompensation Ascites VH HE Jaundice months D Amico G. Gastroenterology 2001; 120: A2 Cirrhosis Intrahepatic resistance Portal (sinusoidal) hypertension Splanchnic / systemic vasodilatation Effective arterial blood volume Diuretics Sodium retention Activation of neurohumoral systems Ascites Copyright 2014 American College of Gastroenterology 9

10 Case # 2 A 55-year old man with HCV cirrhosis complicated by ascites, lower extremity edema and hepatic encephalopathy is seen in clinic for scheduled follow-up. The patient complains of weight gain of at least 1-pound per day and increasing abdominal distension despite his diuretic regimen of furosemide 80 mg once daily and spironolactone 200 mg once daily. He says he is trying to adhere to a low sodium diet. Laboratory testing reveals: Creatinine 1.3 mg/dl, INR 1.8, total bilirubin 2.3 mg/dl, albumin 2.9 g/dl, sodium 130 meq/l potassium 3.8 meq/l. Urine output is 1.75 liters per day and his urinary sodium level is 90 meq/l. What is the next appropriate management step a) Begin IV albumin infusions b) Add metolazone c) Change furosemide dosing to 40 mg BID and continue spironolactone d) Refer to a dietitian for counseling e) Restrict fluid to 1.5 liters per day SPIRONOLACTONE IS MORE EFFECTIVE THAN FUROSEMIDE IN CIRRHOTIC PATIENTS WITH ASCITES Spironolactone is More Effective Than Furosemide in Uncomplicated Ascites Response No response Total Spironolactone ( mg/d) Furosemide ( mg/d) Perez-Ayuso et al. Gastroenterology 1983; 84:961 Copyright 2014 American College of Gastroenterology 10

11 Treatment of ascites Not an emergency, treat ascites in a stepwise unhurried manner Other complications (GI bleed AKI, infection) are absent or have resolved If patient uncomfortable large volume paracentesis Treatment aimed at achieving a negative sodium balance Less frequent dose reductions are needed when spironolactone is started alone Spironolactone Spironolactone alone* + Furosemide (n=50) (n=50) Response Rate 94% 98% Time to Response 12.8 days 12.3 days Dose reduction needed 34% 68% p=0.002 Santos et al., J Hepatol 2003; 39:187 * Followed by furosemide if necessary Copyright 2014 American College of Gastroenterology 11

12 In addition to spironolactone-based diuretics. Salt restriction (2g/day = ~90mEq/day) Do not compromise nutritional status Avoid non-steroidal anti-inflammatory drugs No water restriction unless serum Na <130 meq/l Low threshold to perform a diagnostic paracentesis to investigate SBP Management of Ascites Follow weight and labs (BUN, creatinine, lytes) Weight loss goals 2-3 lb a week; no more than 1 lb / day If no weight loss Make sure patient is not on NSAIDs Check urine Na. If any of the following, patient is eating too much salt: > 50 meq/l or greater than daily Na intake Spot UNa >UK (correlates with a 24-hour sodium excretion >78 meq/l) Copyright 2014 American College of Gastroenterology 12

13 Case # 2 A 55-year old man with HCV cirrhosis complicated by ascites, lower extremity edema and hepatic encephalopathy is seen in clinic for scheduled follow-up. The patient complains of weight gain of at least 1-pound per day and increasing abdominal distension despite his diuretic regimen of furosemide 80 mg once daily and spironolactone 200 mg once daily. He says he is trying to adhere to a low sodium diet. Laboratory testing reveals: Creatinine 1.3 mg/dl, INR 1.8, total bilirubin 2.3 mg/dl, albumin 2.9 g/dl, sodium 130 meq/l potassium 3.8 meq/l. Urine output is 1.75 liters per day and his urinary sodium level is 90 meq/l. What is the next appropriate management step a) Begin IV albumin infusions b) Add metolazone c) Change furosemide dosing to 40 mg BID and continue spironolactone d) Refer to a dietitian for counseling e) Restrict fluid to 1.5 liters per day Hepatic Hydrothorax Occurs in ~6% of patients with cirrhosis Krok KL, Cardenas A. Semin Respir Crit Care Med 2012; 33: Due to transdiaphragmatic movement of fluid from the peritoneum to the pleural space through h diaphragmatic defects Management same as for cirrhotic ascites Copyright 2014 American College of Gastroenterology 13

14 Patient with cirrhosis and new ascites Concomitant: GI hemorrhage Encephalopathy Renal dysfunction SBP/infection Yes No Yes Tense ascites Single LVP + albumin No Assess transplant candidacy Postpone specific treatment until complications improve/resolve Spironolactone 100 mg ± Furosemide 40 mg Wt loss 1 to 1.5 kg/week Continue same dose When ascites eliminated, downtitrate diuretics Wt loss Wt loss 0.5 kg <1 kg/week /day and/ or complications Increase dose (x2) q Decrease 1-2 wks dose or discontinue Cirrhosis Intrahepatic resistance Portal (sinusoidal) hypertension Splanchnic / systemic vasodilatation Effective arterial blood volume Activation of neurohumoral systems Sodium retention Ascites Refractory Ascites Copyright 2014 American College of Gastroenterology 14

15 Large volume-paracentesis (LVP): Local therapy Recurrence of ascites is the rule May be associated with postparacentesis circulatory dysfunction LVP WITHOUT ALBUMIN LEADS TO INCREASES INCIDENCE OF POST-PARACENTESIS CIRCULATORY DYSFUNCTION (PCD) LVP Without Albumin Leads to Increases in Renin, Renal Failure and Hyponatremia Plasma renin activity (ng/ml/h) 12 p<0.1 Postparacentesis circulatory dysfunction 8 ns (PCD) 4 % Renal failure / Hyponatremia p<0.1 0 Before After Albumin Before After No albumin 0 Albumin No albumin Gines et al., Gastroenterology 1988; 94:1493 Copyright 2014 American College of Gastroenterology 15

16 CONSEQUENCES OF POST-PARACENTESIS CIRCULATORY DYSFUNCTION (PCD) Consequences of post-paracentesis circulatory dysfunction (PCD) Shorter time to ascites recurrence Higher incidence of hyponatremia and renal dysfunction Higher mortality Gines et al., Gastroenterology 1996; 111:1002; Ruiz del Arbol et al., Gastroenterology 1997; 113:579 Post-paracentesis circulatory dysfunction (PCD) is lowest in patients receiving albumin after LVP % Development of PCD Overall Gines et al., Gastroenterology 1988; 94:1493; Gines et al., Gastroenterology 1996; 111:1002; Sola-Vera et al., Hepatology 2003; 37:1147 No expander Saline Synthetic expander Albumin* <5-6 L >5-6 L Ascites removed *6-8 g per liter of ascites removed Copyright 2014 American College of Gastroenterology 16

17 Cirrhosis Intrahepatic resistance Portal (sinusoidal) hypertension Other volume expanders? Vasoconstrictors? LVP Splanchnic / systemic vasodilatation Effective arterial blood volume ALBUMIN Activation of neurohumoral systems Sodium retention Water retention Renal vasoconstriction Ascites Refractory Ascites Hyponatremia Hepatorenal syndrome Compared to alternative treatment, albumin reduces the rate of PCD Favors albumin Favors control Bernardi et al. Hepatology 2012;55:1172. Copyright 2014 American College of Gastroenterology 17

18 Recurrence of ascites is no different in patients treated with LVP + albumin vs. octreotide/midodrine PCD : 18% (2/11) with Albumin 25% (2/8) with Octreotide/Midodrine (p=0.574) Bari et al. Accepted Clin Gastroenterol Hepatol. THE TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT Transjugular Intrahepatic Portosystemic Shunt Hepatic vein TIPS Portal vein Splenic vein Superior mesenteric vein Copyright 2014 American College of Gastroenterology 18

19 In Lebrec refractory (1996) 20 ascites, TIPS is more effective than LVP in preventing ascites recurrence Recurrence of ascites 0.14 ( ) Encephalopathy Death Death (excluding Lebrec) 2.34 ( ) 0.90 ( ) Heterogeneity χ 2 p= ( ) Better TIPS D Amico et al. Gastroenterology 2005; 129:1282 Better LVP Odds ratio In patients with refractory ascites, survival was better with TIPS than LVP* Survival Encephalopathy p=0.36 P=0.005 Greater survival benefit in patients treated with TIPS who had a MELD score <15 Salerno et al. Gastroenterology 2007;133: TIPS= transjugular intrahepatic portosystemic shunt LVP= large-volume paracentesis *individual data meta-analysis analysis Copyright 2014 American College of Gastroenterology 19

20 Case # 3 51 year-old woman with HCV cirrhosis hospitalized with ascites and severe shortness of breath. She is afebrile, HR 92 bpm, BP 99/61 mmhg, RR 24/minute, SaO 2 89% on room air. Exam notable for decreased breath sounds at the right base, moderately distended abdomen with shifting dullness and 1+ lower extremity edema. Laboratory evaluation reveals: Cr 1.2 mg/dl, total bilirubin 1.4 mg/dl, INR 1.7, albumin 1.9 g/dl, MELD 15. Chest-X-ray reveals a large right pleural effusion. Echocardiogram reveals EF 68% mild enlargement of the left and right atria, normal valves, and estimated PAP 24 mmhg. The patient is started on furosemide and spironolactone and low sodium diet with only mild improvement in her respiratory symptoms after two weeks of upward titration of diuretics. What do you recommend next for management of hepatic hydrothorax? a) Transjugular intrahepatic portosystemic shunt (TIPS) b) Serial thoracenteses with IV normal saline volume replacement c) Placement of small bore right-sided chest tube d) Surgical portosystemic shunt e) Weekly IV albumin infusions Refractory hepatic hydrothorax A trial of in-hospital diuretic therapy should be attempted Serial thoracenteses may be required too frequently Chest tube or indwelling catheter should not be placed ( infection, AKI) TIPS may need to be considered d earlier Clinical response (67%) and survival are also associated with pre-tips MELD <15 Dhanasekaran et al. Am J GE Copyright 2014 American College of Gastroenterology 20

21 Case # 3 51 year-old woman with HCV cirrhosis hospitalized with ascites and severe shortness of breath. She is afebrile, HR 92 bpm, BP 99/61 mmhg, RR 24/minute, SaO 2 89% on room air. Exam notable for decreased breath sounds at the right base, moderately distended abdomen with shifting dullness and 1+ lower extremity edema. Laboratory evaluation reveals: Cr 1.2 mg/dl, total bilirubin 1.4 mg/dl, INR 1.7, albumin 1.9 g/dl, MELD 15. Chest-X-ray reveals a large right pleural effusion. Echocardiogram reveals EF 68% mild enlargement of the left and right atria, normal valves, and estimated PAP 24 mmhg. The patient is started on furosemide and spironolactone and low sodium diet with only mild improvement in her respiratory symptoms after two weeks of upward titration of diuretics. What do you recommend next for management of hepatic hydrothorax? a) Transjugular intrahepatic portosystemic shunt (TIPS) b) Serial thoracenteses with IV normal saline volume replacement c) Placement of small bore right-sided chest tube d) Surgical portosystemic shunt e) Weekly IV albumin infusions Peritoneo-Venous Shunt (PVS) is Useful in the Treatment of Refractory Ascites Use of jugular vein will hinder TIPS placement Indicated in malignant ascites or patients who are not transplant or TIPS candidates One-way valve Intraabdominal adhesions may complicate liver transplant surgery Copyright 2014 American College of Gastroenterology 21

22 Pilot safety study of Automated Low-Flow pump for refractory Ascites (ALFA) (n=40) ALFA pump transfers ascites into the bladder Placed under general anesthesia 6-month followup LVP per month Infections antibiotic prophylaxis (76% 42%) Catheter dislodgement/problems (10/40=25%) Surgical complications (5/40) Progressive decrease in serum albumin 13 early termination, 8 died, 2 txp Bellot et al. J Hepatol 2013;58:922-7 Patients with refractory ascites on NSBB may have a poorer survival than those not on NSBB However, groups were unbalanced with patients in the NSBB group having a greater number of poor prognostic factors at baseline Serste et al. Hepatology 2010;52:1017 Copyright 2014 American College of Gastroenterology 22