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Innovative approaches to the management of ascites in cirrhosis

A better understanding of the pathogenetic mechanisms leading to ascites formation has helped guide therapeutic strategies, i.e. the pre-emptive use of NSBBs to reduce portal pressure and hence delay the appearance of ascites, the use of albumin to increase the effective arterial blood volume and to reduce the extent of inflammation, or SGLT2 inhibitors to block renal sodium excretion. Refinements in the application of TIPS and the use of alfapump for the treatment of refractory ascites are measures that could improve patients’ quality of life and potentially survival. New omics techniques will add further tools to individualise ascites treatment and ultimately improve patient outcomes, though…

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 Management of Refractory Ascites Due to Portal Hypertension: Current Status

Although dietary sodium restriction and diuretic administration are effective initial steps to control fluid accumulation, refractory ascites develops in 11% of patients with cirrhosis after 5 years. Large-volume paracentesis and creation of transjugular intrahepatic portosystemic shunts (TIPS) are the two most common percutaneous approaches used to treat refractory ascites, with some evidence suggesting the latter provides improved survival, quality of life, and cost-effectiveness. Implanted drainage devices, including tunneled peritoneal catheters and peritoneovenous shunts, represent alternative treatment options in patients who are not candidates for TIPS creation and who do not wish to undergo serial large-volume paracentesis.

Articles of Interest

Abdominal Pain and Ascites: Not Always Related to Portal Hypertension

Eosinophilic gastroenteritis is a rare inflammatory disorder of the gastrointestinal tract with an estimated prevalence of one in 100,000. The typical presentation consists of vague gastrointestinal symptoms with the mucosal involvement of the digestive system. Rarely, it presents as eosinophilic ascites.

Albumin for Patients with SBP or Large-Volume Paracentesis

Both therapeutic and diagnostic paracentesis are common procedures in emergency medicine, and the diagnosis and initial management of SBP fall well within our practice parameters. Given the increased boarding times observed in many EDs, it is prudent that the emergency physician be aware of treatment modalities that require initiation within the first several hours of patient care. As a result, it seems reasonable to begin the administration of albumin to patients with SBP concomitantly with antibiotics while the patient is still in the ED, as this has been shown to decrease the risk of both renal impairment and mortality. It is also reasonable to consider albumin infusion in patients undergoing large volume paracentesis (more than 5 liters of ascitic fluid removed), though the evidence in support of this is much less compelling.

Approach to the Sick Cirrhotic Patient

Author: Brit Long, MD (@long_brit, EM Chief Resident at SAUSHEC, USAF) // Edited by: Jennifer Robertson, MD and Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UT Southwestern Medical Center / Parkland Memorial Hospital) Case It is 1am, and emergency medical services (EMS) calls and states that a 45-year-old male with massive hematemesis is being transported to the emergency department (ED). He is unstable per report. EMS has achieved peripheral intravenous (IV) access. Since the patient is reported to be unstable, you begin to prepare the resuscitation room. The patient arrives and he appears very ill. You immediately assess the patient’s airway, breathing and circulation (ABCs). A nurse establishes a second IV line as soon as the patient is transferred to the ED bed. The patient appears cachectic with a protuberant abdomen. Streaks of red are present around his oropharynx. Initial vital signs (VS) include a respiratory rate (RR) of 32, blood pressure (BP) of 72/48, heart rate (HR) of 115, temperature (T) of 37.8 Celsius, and oxygen saturation (SpO2) of 90% on 2 liters (L) nasal cannula (NC). The patient has an altered mental status and is weakly attempting to swat the nurses and paramedics away. Pic1 Pic2 How will you approach this sick, unstable cirrhotic patient? What are some of the complications of patients with cirrhosis and chronic liver disease? Background Cirrhosis is the late stage of progressive hepatic fibrosis and is considered irreversible. In 2010, cirrhosis was the 8th leading cause of death in the U.S., and it most commonly due to Hepatitis C, followed by alcohol.1,2 Acute liver failure can also be due to drugs (most commonly acetaminophen), viral hepatitis, autoimmune, ischemia (shock liver), Wilson’s disease, and idiopathic (up to 14% of causes). Due to the many complications of cirrhosis, patient life expectancy is drastically reduced.1-3 Major complications of cirrhosis include variceal hemorrhage, ascites, spontaneous bacterial peritonitis (SBP), hepatic encephalopathy, hepatorenal syndrome, and hepatopulmonary syndrome. If one of these develops, the patient is considered to have decompensated cirrhosis. Bleeding, infection, increased alcohol intake, dehydration, electrolyte abnormalities (hypokalemia specifically), and constipation can all ultimately contribute to the development of decompensated cirrhosis.2,3 Pathologic changes in the liver lead to the above complications. These pathologic changes include fibrosis and the formation of regenerative nodules that replace normal hepatic tissue. This decreases hepatic venous flow and elevates portal pressures. This in turn causes splenomegaly, resulting in anemia, hypoalbuminemia, thrombocytopenia, and often ascites.1-4 Approach to Initial Resuscitation: Once you walk into the room of the sick cirrhotic patient, always start with the ABCs. If you are alone, you will need to systematically go through the ABCs yourself. If you have a team of EMTs, techs, and nurses, then you can lead the resuscitation and the ABCs can be obtained simultaneously. Ensure that the patient is responsive. If the patient is unresponsive and has no pulse, begin Advanced Cardiac Life Support (ACLS) measures. Ensure that the patient is protecting his or her airway. If the patient has massive hematemesis or shows poor mentation, have a low threshold to initiate advanced airway measures (see below). Check the lungs and breath sounds for equal chest rise and to evaluate for other abnormal breath sounds. Intravenous access is critically important in these patients, and ensuring bilateral large bore IV access is essential. If you cannot obtain IV access, then acquire an intraosseous (IO) line. In the initial resuscitation stages, IV and IO access are better than central access. For circulation, repeat VS and BP readings liberally. If the patient is hypotensive and not bleeding, an IV fluid bolus may help. Adequate perfusion should be measured by clinical factors such as mental status, capillary refill, pulse pressure, HR, pulse strength, urine output and mean arterial pressure (MAP). Using more than one clinical factor is best. If the patient is bleeding, start a transfusion with 1:1:1 ratio of pRBC:FFP:platelets. These patients often are coagulopathic. Replacing fibrinogen (if less than 100mg/dL) with cryoprecipitate can also be helpful. Tranexamic acid (TXA) may also be useful. Ensure you adequately expose the patient and look for signs of infection. Complete a quick neurologic exam (gross cranial nerve, motor, sensory, and cerebellar exams). Always check an initial blood glucose, as these patients are often hypoglycemic. Laboratory work should be drawn. A type and cross should be obtained immediately, as these patients may require a significant amount of blood products. A complete blood count (CBC), lactate, venous blood gas (VBG), liver function tests (LFTs), basic metabolic panel (BMP) ammonia level, coagulation panel, fibrinogen level, and electrocardiogram (ECG) (ischemia can occur with shock and bleeding in these patients) should also be ordered. With bleeding or any instability, administer ceftriaxone 1 gram (g) IV or cefotaxime 2g IV. If bleeding, an IV octreotide bolus of at 50mcg followed by 50mcg/hour can decrease transfusion needs. If outside of the U.S., one should administer terlipressin 2mg IV instead of octreotide. Please see a prior post on the approach to the unstable gastrointestinal (GI) bleeder by emDocs.net for further information: http://www.emdocs.net/unstable-patient-gi-bleed/ Airway Intubating these patients can be difficult. The concepts of no desaturation (NO DESAT) and delayed sequence intubation (DSI) can be beneficial in decreasing morbidity and mortality. Pre-oxygenating and de-nitrogenating the lungs prior to intubation will provide an oxygen reservoir prior to intubation. This is particularly helpful in patients like the cirrhotic patient, who may desaturate more quickly during intubation. To perform DSI, place the patient on supplemental oxygen by NC. If needed, add a facemask with 15 liters (L) O2. If the patient continues to demonstrate low oxygen levels, non-invasive positive pressure ventilation (NIPPV) may be considered. However, use caution and avoid NIPPV in patients with active hematemesis. Ketamine is a useful medication to administer during DSI as it helps reduce patient discomfort and agitation, allowing for adequate pre-oxygenation and intubation. Using ketamine will also allow you to place a nasogastric tube, which will decrease aspiration risk and clear the stomach of any present blood. A NG tube should only be used to clear the stomach of potential aspiration material and not to diagnose an upper gastrointestinal (GI) bleed. EMCrit (www.emcrit.org) provides an excellent summary on intubating patients with GI bleeding. This can work with any sick cirrhotic patient. The steps include: (1) Empty the stomach using a NG tube, and administer metoclopramide 10mg IV. (2) Intubate the patient with the head of the bed elevated to 45 degrees. Have suction ready. (3) Ensure adequate pre-oxygenation. Without pre-oxygenation, these patients may rapidly desaturate once medications are provided. (4) Use smaller doses of the induction and sedation medications. Many of these patients will already be hypotensive and/or altered and thus, will require lower doses of sedation medication (s). (5) On the other hand, use higher doses of the paralytic medication given during induction and intubation. Paralytic medications such as rocuronium will also augment lower esophageal tone. (6) Maximize your equipment and have backup techniques and tools ready. These include a videoscope, direct laryngoscope, bougie, laryngeal mask airway (LMA), suction set up, and a meconium aspirator. (7) If you fail the first attempt, bag slowly and gently, and consider placing an LMA. (8) If the patient vomits, place him or her in Trendelenburg position to keep emesis contents out of the lungs. (9) The meconium aspirator can be attached to the endotracheal tube (ETT) for improved suction if your baseline suction device is weaker. (10) Expect the patient to aspirate with the intubation and be prepared for massive systemic inflammatory response (SIRS).5 History and Exam If possible, assess the patient’s full medical history including his or her normal weight, chronic medications, follow up visits, prior complications of cirrhosis and endoscopic records. Other important questions to ask include any anorexia, fever, abdominal pain, pruritis, melena, and hematemesis. After a primary survey and full vital signs have been assessed, a full exam should be conducted. Look for any signs of cerebral edema and herniation (Cushing’s reflex and/or posturing). Volume status can be difficult to ascertain in these patients due to abnormal volume distribution. Test for asterixis (raising both arms with wrists hyperextended) and jaundice (best found under the tongue and sclera). Ascites can be difficult to diagnosis based on exam alone, but ultrasound can be helpful in this setting. Signs of chronic liver failure include ascites, caput medusa (superficial periumbilical veins), muscular atrophy, gynecomastia, testicular atrophy, spider angiomas, palmar erythema, and parotid gland enlargement.3,6 Ascites Ascites, or the accumulation of fluid in the abdomen, is the most common complication of cirrhosis. Close to 60% of cirrhotic patients will have ascites within 10 years of diagnosis. Portal hypertension is the first step in fluid accumulation.6,7 When a patient presents with concerning signs for ascites, one should question him or her regarding weight gain and abdominal girth. These both have positive likelihood ratios (LR) of 3.2 and 4.16, respectively.8 A Shifting dullness on exam also has a positive LR of 5.76, while a fluid wave has the highest LR of 9.6.8 No ankle swelling has a negative LR of 0.10 and no change in abdominal girth has a LR of 0.17. However, 1500 mL of ascitic fluid is required for several of these findings. Ultrasound, as demonstrated below, can also assist in diagnosing ascites.8 Pic3 Chronic management of ascites includes diuresis and sodium restriction. Usually, spironolactone and furosemide are prescribed in a 100:40 ratio. Abstaining from alcohol should be encouraged, as this will drastically improve ascites. These patients ultimately require GI/primary care for medical management Indications for paracentesis in the ED setting include new-onset ascites, suspected spontaneous bacterial peritonitis (SBP) and/or relief of cardiorespiratory or GI manifestations of tense ascites. Specifically, removal of more than 5 L can assist in improving dyspnea and early satiety. Paracentesis may also be associated with collateral advantages, such as a reduction in hepatic venous pressure gradients, intravariceal pressure, and variceal wall tension, which can in turn decrease risk of GI bleeding. It is important to note that there is no level of international normalized ratio (INR) or platelets that serves as a contraindication for paracentesis.

Diagnosis and Management of Ascites

A transjugular intrahepatic portosystemic shunt (TIPS), which is placed by Interventional Radiology, has been shown in multiple multicenter, randomized, controlled trials to be superior to serial large-volume paracenteses in the control of ascites, but with varying results on the impact on overall transplant-free survival and the risk of inducing or worsening hepatic encephalopathy.

Guidelines on the management of ascites in cirrhosis

In patients with untreatable ascites, alternatives to repeated hospital drainage include placing a small tube (stent) in the liver. This specialised procedure is known as a transjugular intrahepatic portosystemic shunt (TIPSS). The TIPSS procedure is effective in reducing the need for repeated fluid drainage. Because of potential side effects, patients should be selected carefully for this procedure. This is particularly true for patients with more advanced liver disease, where the insertion of a TIPSS can potentially be harmful.

Management of Ascites in Patients with Cirrhosis: An Update

Ascites represents a critical event in the natural history of liver cirrhosis. From a prognostic perspective, its occurrence marks the transition from the compensated to the decompensated stage of the disease, leading to an abrupt worsening of patients’ life expectancy. Moreover, ascites heralds a turbulent clinical course, characterized by acute events and further complications, frequent hospitalizations, and eventually death.

Management of cirrhotic ascites

The most common complication to chronic liver failure is ascites. The formation of ascites in the cirrhotic patient is caused by a complex chain of pathophysiological events involving portal hypertension and progressive vascular dysfunction. Since ascites formation represents a hallmark in the natural history of chronic liver failure it predicts a poor outcome with a 50% mortality rate within 3 years.

Optimal management of cirrhotic ascites: A review for internal medicine physicians

According to the amount of fluid in the abdominal cavity, uncomplicated ascites is graded from 1 to 3, and the cornerstone of its management consists of restriction of salt intake, diuretics and large-volume paracentesis (LVP); in recent years, long-term administration of human albumin has acquired a new interesting role. Refractory ascites is primarily managed with LVP and transjugular intrahepatic portosystemic shunt (TIPS) placement in selected patients.

Paracentesis: A Step by Step Procedure Guide

Indications: New onset ascites or ascites of unknown origin. Patient with a known ascites who has fever, abdominal pain, hypotension or encephalopathy. Symptomatic treatment of large ascites

Paucis Verbis card: Ascites assessment with paracentesis

This installment of the Paucis Verbis (In a Few Words) e-card series provides an evidence-based review of the literature on topics related to the paracentesis procedure. Especially helpful is the pooled data of likelihood ratios. Like most everything in medicine, a lab test should be used in conjunction with your pretest probability in clinical decision making, and LR’s help with with this.

Routine Diagnostic Paracentesis for Ascites

Given the high mortality rate observed with SBP and the poor test characteristics associated with physician assessment, guidelines recommend routine diagnostic paracentesis in all patients admitted to the hospital with cirrhosis and ascites. Considering the strong association between delayed diagnosis and mortality, strong consideration should be given toward early diagnostic paracentesis in the ED for these patients.

Should All Admitted Patients with Ascites Get a Paracentesis?

In this large, retrospective chart review of patients with cirrhosis and ascites who were admitted to the hospital for any reason, performance of diagnostic paracentesis was associated with decreased in-hospital mortality. Although this has been part of “standard care” for some time, in this current study, it occurred in only 51% of patients. As emergency providers we are uniquely capable to perform these procedures, and our choices in the ER will affect clinical course throughout our patient’s admissions.

Resources

AlfaPump

The alfapump is a subcutaneously implanted battery-operated pump, which automatically and continually moves ascites from the abdominal cavity to the bladder, where it is excreted naturally from the body. Now, with new DirectLink technology, patients and physicians are offered an unprecendented level of comfort and convenience.