Cardiovascular

MARS®: The new frontier in treating acute liver failure

After an unintentional acetaminophen overdose, 26-year-old Emma Paulson (not her real name), is transferred from the emergency department to the intensive care unit (ICU). On admission, her blood acetaminophen level is above 200 mcg/mL, her bilirubin level is 4.2 mg/dL, and her International Normalized Ratio (INR) is 3.6 and rising. She is diagnosed with grade 2 encephalopathy, but is physiologically stable with adequate respiratory function.

Within 4 hours, she progresses to grade 3 encephalopathy with worsening hemodynamics. The physician decides to initiate molecular adsorbent recirculating system (MARS®) therapy. He orders intubation for airway protection, a computed tomography (CT) scan to check for cerebral edema, a dual-lumen hemodialysis catheter of at least 13 Fr diameter to obtain I.V. access for MARS, an arterial line, and a central venous line. Before the nurse inserts these lines, she administers fresh-frozen plasma and platelets to stabilize Ms. Paulson’s coagulation and minimize bleeding.

The liver synthesizes clotting factors, detoxifies toxins, breaks down hormones and medications, metabolizes essential nutrients, and promotes biotransformation. When this crucial organ fails, toxins build up—with life-threatening effects. Acute liver failure (ALF) is defined as severe acute liver injury with hepatic encephalopathy and an elevated INR or prothrombin time (indicating impaired synthetic function) in a patient without cirrhosis or preexisting liver disease, when the illness is of less than 26 weeks’ duration.

ALF carries high morbidity and mortality. An estimated 2,000 to 3,000 cases occur yearly in the United States. Without liver transplantation, patient outcome is unpredictable and mortality can reach 80%. Multisystemic failure is the most common cause of death (greater than 50%). This makes early evaluation for possible liver transplantation and management of clinical changes imperative.

ALF most commonly affects young adults. In the United States, the most common causes are toxicity and idiosyncratic drug reactions. Early recognition and prompt intervention are critical to survival. (See Causes of acute liver failure by clicking the PDF icon above.)

In ALF, encephalopathy arises from inability to clear increased circulating amounts of ammonia, bilirubin, and other neurotoxins. These toxins contribute to an altered level of consciousness (LOC) and worsening cerebral edema. Cerebral edema results from changes in the blood-brain barrier caused by excess ammonia and its breakdown to glutamine. (See What happens in encephalopathy by clicking the PDF icon above.)


Understanding MARS

Over the past 10 years, new technology, collaborative medical management, and liver transplantation have improved outcomes for patients with ALF. But not all patients are eligible for liver transplantation. Those who aren’t may benefit from MARS, a two-part dialysis system that replaces the liver’s lost excretory and detoxification functions.

A useful adjunct until normal liver function resumes, MARS combines traditional continuous renal replacement therapy (CRRT) technology with large protein-bound particle removal via albumin dialysis. It removes ammonia, bilirubin, bile acids, aromatic amino acids, nitric oxide, tryptophan, copper, creatinine, protoporphyrin, urea, and diazepam. Human albumin cleans protein-bound toxins, while the bicarbonate-based dialysate binds other water-soluble elements. By supporting the injured liver and decreasing the encephalopathy risk, MARS gives the liver time to regain normal function. The technology is approved by the Food and Drug Administration for use in ALF caused by drug overdose, as well as in hepatic encephalopathy due to decompensation of chronic liver disease.

Patient selection and timing are crucial. Standard indications for MARS include ALF caused by drugs or toxins, grade 1 or higher encephalopathy, INR above 2.0, and pH below 7.3 in the absence of acute kidney failure. The MARS protocol is developed in collaboration with a hepatologist, a ne­phrologist, critical care specialists, and nursing staff.

MARS requires central venous access for dialysis—preferably, internal jugular or subclavian access. The patient may require fresh-frozen plasma or platelets before catheter placement to reverse existing coagulopathy; however, the effect is only short-term. Once these products are given and catheter placement is verified, at least 2 hours should elapse before MARS begins, to prevent the system from clotting. System setup and priming take 1 to 2 hours. Because of the complexity of this therapy, one nurse cares for the patient throughout MARS therapy while a second manages the system.

Antibiotics and vasopressors may need to be titrated to maintain effective therapeutic blood levels. Systemic anticoagulation with heparin or trisodium citrate may be required. If used, citrate must be titrated to the patient’s ionized calcium level; based on results, calcium must be supplemented to prevent severe hypocalcemia.
The recommended treatment mode is intermittent, with treatment lasting 8 hours daily for 3 consecutive days. CRRT may be used between MARS sessions to support renal function and continue filtration of smaller and mid-range molecular substances (particularly ammonia).

Potential adverse events of MARS include mild thrombocytopenia, catheter-related fever or sepsis,
hemodynamic instability, bleeding, risks associated with line disconnection, and blood loss from insufficient anticoagulation and filter clotting.

Caring for ALF patients

Nursing care for patients with ALF requires a multidisciplinary approach to address the many aspects of assessment, monitoring, and intervention required. Management goals focus on supporting the patient until the liver begins to recover or the patient is transitioned to transplantation. These goals include:

  • early identification of the cause of ALF
  • rapid interventions for increased intracranial pressure (ICP), coagulopathy, and encephalopathy
  • management of multisystemic failure.

ICP monitoring may be initiated based on CT results and mental status changes. ICP should be kept below 20 mm Hg.

Managing encephalopathy

Acetylcysteine improves survival for patients with grade 1 or 2 encephalopathy and benefits patients with non-acetaminophen toxicities. Lactulose and rifaximin offer additional toxin clearance and are given by nasogastric or rectal tube to bind and excrete toxins in the gut. In patients who aren’t getting MARS, CRRT can improve encephalopathy and cerebral edema by removing ammonia and other small-molecular–size particles. Patients with decreased LOC require intubation to protect the airway.

Hemodynamic support and monitoring

Vascular changes from circulating toxins lead to vasodilation, contributing to the need for hemodynamic support. Vasopressors may be used to maintain mean arterial pressure (MAP) above 80 mm Hg to support cerebral perfusion pressure (CPP). MAP should be kept above 70 or 80 mm Hg and CPP above 60 mm Hg. To reduce brain swelling, give hypertonic saline solution as ordered to maintain a serum sodium level of 145 to 155 mEq/L.

Other interventions

To help prevent increased ICP and brain herniation, position the patient with the head upright to help prevent coughing and gagging. As ordered, minimize high positive end-expiratory pressure and use low-tidal–volume ventilation. Be aware that mild hypothermia (32° to 34° F [0° to 1.1° C]) cools the brain, decreasing oxygen demand. Avoid sedation, if possible; if it’s needed, expect the physician to order short-acting propofol.
Keeping the patient stable requires fluid management, monitoring of infection and metabolic parameters, nutrition maintenance, and prompt recognition of GI bleeding. Perform regular neurologic checks, focusing on pupillary changes, LOC, and encephalopathy.

Scenario continued

Ms. Paulson’s CT scan shows early cerebral edema, so she’s placed on hourly monitoring of ICP, which ranges from 12 to 25 mm Hg. Because of her increasing encepha­lopathy, she’s receiving vasopressors to maintain MAP above 70 mm Hg, with CPP above 60 mm Hg to preserve effective brain perfusion. She receives hypertonic saline solution every 6 hours to maintain a serum sodium level of 145 to 155 mEq/L.

After her first MARS treatment, Ms. Paulson becomes more responsive to voice and command. The resin filter quickly changes color from a light amber to bronze, reflecting toxin removal and decreasing encephalopathy. As the remaining 8-hour MARS treatments are completed, she shows continued improvement. It’s amazing to see her progress from grade 3 encephalopathy to exclaiming “Oh! Hi. Where am I?” in response to stimuli 72 hours later, indicating improvement to grade 0 encephalopathy. She is discharged home 14 days after admission. She continues to do well and doesn’t require a liver transplant.

Of course, ALF doesn’t always resolve as quickly as this. Further study, time, and experience will determine the role of MARS in managing ALF. Although it effectively removes toxins and improves encephalopathy, it hasn’t been shown to significantly reduce mortality. Nonetheless, many studies show a significant morbidity benefit. Ongoing research is needed to validate its benefits and risks.

Selected references

Bernal W, Auzinger G, Dhawan A, Wendon J. Acute liver failure. Lancet. 2010;376(9736):
190-201.

Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, Blei AT. Hepatic encepha­lopathy—definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology. 2002;35(3):716-21.

Kramer L, Kodras K. Detoxification as a treatment goal in hepatic failure. Liver Int. 2011;31(suppl 3):1-4.

Lee WM, Larson AM, Stravitz T. AASLD position paper: the management of acute liver failure: update 2011. Baltimore, MD: American Association for the Study of Liver Diseases; 2011. www.guideline.gov/content.aspx?id=36894. Accessed December 26, 2013.

Mitzner SR, Stange J, Klammt S, Koball S, Hickstein H, Reisinger EC. Albumin dialysis MARS: knowledge from 10 years of clinical investigation. ASAIO J. 2009;55(5):498-502.

Pathikonda M, Munoz SJ. Acute liver failure. Ann Hepatol. 2010;9(1):7-14.

Rademacher S, Oppert M, Jörres A. Artificial extracorporeal liver support therapy in patients with severe liver failure. Expert Rev Gastroenterol Hepatol. 2011;5(5):591-9.

Stange J. Extracorporeal liver support. Organogenesis. 2011;7(1):64-73.

Trotter JF. Practical management of acute liver failure in the Intensive Care Unit. Curr Opin Crit Care. 2009;15(2):163-7.

Vaid A, Chweich H, Balk EM, Jaber BL. Molecular adsorbent recirculating system as artificial support therapy for liver failure: a meta-analysis. ASAIO J. 2012;58(1):51-9.

Mary D. Still is a clinical nurse specialist in surgery and transplant critical care at Emory University Hospital in Atlanta, Georgia.

Related Articles:

Leave a Reply

You have to agree to the comment policy.

 

Newsletter Subscribe

  • This field is for validation purposes and should be left unchanged.

Test Your Nursing Knowledge

Answer this interactive quiz to be entered to win a gift card.

  • This field is for validation purposes and should be left unchanged.

Insights Blog

Shares