Oh the ways the liver can fail. As a new nurse practitioner this one was hard to get down. Cardiology is generally seen as the bee all end all when it comes to keeping our bodies running, but I’d like to talk about the under appreciated liver. Hepatology is fascinating because the normal function of the liver is supremely multi-faceted. Throw in a little pathology and any number of pathways can be deranged and within those any degree of severity can be seen. From acute to chronic to acute-on-chronic, severity can run the gamut. Decompensated cirrhosis is a common killer in most ICU’s. Given how poorly understood this disease state is, I’d like to talk about the complexity, progression, prognosis, and management of liver failure in the intensive care unit.

Liver failure is best understood by breaking it down to chronicity, severity, and sequelae.

Chronicity

Chronic Liver Failure

• > 6 months duration

• Fairly “stable”

• Most common causes: acute liver failure, ETOH, autoimmune hepatitis

• Other causes: HBV, HCV, NAFLD/NASH, Wilson’s disease, Primary Biliary Cirrhosis, Primary Sclerosing Cholangitis. PBC and PSC are diseases of the bile ducts.

• Only when this decompensates does it show up in the ICU

Acute Liver Failure

• < 26 weeks duration

• Abrupt damage that occurs in otherwise healthy liver

• Common causes: tylenol overdose, viral hepatitis, shock liver

• Healthy liver at baseline without cirrhosis so there will not be associated stigmata (ascites, varices, any complication of portal hypertension).

• The big problem is high ammonia levels which this patient is not accustomed to and this can create profound damage.

• High NH3 = cerebral edema, high ICP’s. Severity graded by westhaven criteria.

• Tylenol OD is 50% of the cases: LFT’s will rise 24-36h after ingestion, bilirubin may be nml/low initially. NH3 will be high (>150ish higher risk of cerebral edema). May see renal failure, lactic acidosis, death.

• Treatment:

  • Charcoal (only 1st 4h after ingestion), N-Acetlycysteine infusion

  • Transfer to a transplant center or one that offers MARS (look up Kings College Hospital Criteria for who should transfer).

    • MARS = Molecular Adsorbent Recirculating System aka liver dialysis. This removes albumin bound toxins (NH3 and bilirubin among them) from the body.

  • Permissive hypernatremia (145-155) if HE with high NH3, may need to give hypertonic saline

  • Keep MAP >75 for brain perfusion

Acute on Chronic Liver Failure

• > 26 weeks duration

• This is what we see the majority of the time in ICU.

• Any of the above causes are in place at baseline then something tips the scale.

  • The liver gets worse: ESLD advancing, med non-compliance, continued ETOH (most common).

  • A secondary insult occurs: sepsis, GIB are common.

• See below for grading of severity and treatment of sequelae.

• Typical symptoms seen: HE, Ascites, Jaundice, EV with bleeding

Severity

In all cases above the downstream effects of a failing liver are similar. With the exception of acute liver failure which will not see the associated problems caused by portal hypertension as outlined below. Severity is determined by the overall picture. There are a lot of classification scales, risk stratification scales, predictors of morbidity, surgical risk, etc, etc. The overwhelming majority of our patients will be acute on chronic failure (decompensated cirrhosis) and therefore that is the focus of this post. Decompensation is diagnosed when any of the below complications are present. The number and degree of complications adds to the picture of severity.

I use these calculations for inpatient ICU patients with decompensation:

• MELD-Na: Model for end stage liver failure. Predicts 90d mortality risk. Pretty good marker for how severe things are at this point in time. To be considered for transplant it must be >15. If >15 + other markers for acute illness they rise the ranks. Bear in mind this is a snapshot in time. The number varies constantly.

• Child-Pugh: To determine intra-operative mortality.

• Maddery’s Discriminant Function: to help determine if alcoholic hepatitis will respond to steroids. Contraindications: GI bleeding, infection, pancreatitis, renal failure, MDF score >54. If MDF >32 consider prednisolone daily with a taper.

I put this together with the overall picture - is there MSOF, are they in shock, is there sepsis and how treatable is the source, is HE bad enough they need to be intubated, are the kidneys failing to a point that dialysis is needed (not likely to help and most nephrologists won’t even offer it). This guides the GOC discussions.

Sequelae

1. Portal Hypertension

   Obstructed venous system in the liver can lead to any of the following. Will not see in acute cases.

   • Ascites: caused in part 2/2 vasodilation -> RAAS activation -> sodium + water retention. Consider paracentesis - diagnostic to find spontaneous bacterial peritonitis, therapeutic (caution if in shock, give back albumin), more often than not go ahead and treat empirically for SBP. In more stable conditions diuresis is warranted. Spironalactone daily will aid in this + address the sodium retention. Can add lasix for additional effect and to counteract the potassium retention.

   • Esophageal varices: essentially these are collateral veins that are compensating for the backflow. When things get severe they rupture causing a GIB. Should be on a BB at home, probably holding in ICU if shock. If GIB treat this appropriately. Consider TIPS.

   • Recurrent pleural effusions (hepatic hydrothorax): what can you do really? Diurese possibly, thora if really needed - do not put in chest tubes, they will just keep draining and likely drop BP. Paracentesis can help (in the absence of cardiac disease fluid originates in the pleural space 2/2 translocation across the diaphragm). Look for R>L effusions as a key.

   • Widespread vasodilation so MAPs are generally low at baseline. Midodrine. Early use of vasopressors if septic.

   • Consider getting a RUQ US with doppler flow to rule out a portal venous thrombosis or budd chiari syndrome (liver outflow tract problem) that could be causing the back flow

   • Hyponatremia: widespread vasodilation -> RAAS -> sodium (but in less quantity than) and water. Hypovolemic hypernatremia develops. The presence of hyponatremia increases mortality. Treat with 2g Na restricted diet. In ICU it’s hard to treat. Typically only if symptomatic and less than ~ 110. Then consider hypertonic saline.

   • Hepatic Encephalopathy

     • Westhaven criteria to grade. The Ammonia level alone does not diagnose HE. It is a clinical dx. Look for confusion, lethargy, coma, asterixis. Early signs of HE is diurnal sleep pattern.

     • Treat: Lactulose, Rifaximin, dialysis as last ditch. These patients rarely develop cerebral edema unless it is sustained/prolonged hyperammonemia. Unlike the acute patient they have developed adaptive patterns for handling the ammonia. MARS without a bridge to transplant is not a good plan so typically these patients are not considered a candidate.

   • Hepato-renal syndrome

     • This is a diagnosis of exclusion which is hard to do in ICU.

     • Splanchnic vasodilation -> RAAS activation -> renal vasoconstriction = kidney failure (without inherent kidney injury like ATN from sepsis or nephrotoxins).

     • If crt bumps in your pt give albumin, if no response and no other indication exists for the AKI you can consider HRS.

     • This is a bad sign and will move a patient up the transplant list.

     • Do not offer dialysis unless you have spoken with nephrology and made a group decision. This is another bridge to nowhere without transplant consideration. In general, if there is something reversible to treat we will consider it.

   • Hepato-pulmonary syndrome

     • Pulmonary vasodilation -> blood passes through pulmonary capillary beds without being oxygenated.

     • VQ mismatch with high Aa gradient creating an effective shunt.

     • Get an echo with a DELAYED bubble study. All caps for emphasis. Most places, when you order a bubble study are going to administer an O2 agitated flush of saline and look for immediate (1-2 cardiac cycles) shunt of R->L air. They are used to assessing for PFOs. They are not accustomed to looking for delayed return of air bubbles. Because the defect lies in the pulmonary capillary beds (not the cardiac septum itself) it will take longer (possibly >6 cardiac cycles) to appear.

     • Clinically you may see dyspnea, platypnea (this pt becomes short of breath when they sit upright and improved when laid flat) and orthodeoxia (SPO2 decrease with sitting upright and improved when laid flat), spider angiomas, clubbing of nails, cyanosis.

   • Hepatocellular Carcinoma: cirrhosis creates a high risk for development of HCC so they need surveillence. Not much to do about this in the decompensated state.

   • Vasoplegia: because of the widespread vasodilation these patients are effectively like walking distributive shock scenarios. Often they are on midodrine on a good day. Throw in a little infection and sepsis can be profound. They are exquisitely sensitive to sepsis because the pathophysiology is augmented.

     • Avoid sepsis like the plague.

     • Aggressive and early consideration for SBP and treatment.

     • Early initiation of pressors. MAP goal >60 unless you need augmented perfusion (cerebral edema, AKI). They are used to lower MAPs.

2. Thrombocytopenia

• 2/2 decreased production; increased destruction; spleen sequestration. Sepsis can worsen.

• Sets them up for bleeding risk

• My personal transfusion threshold is around 20. Unless there is clinical bleeding or a planned procedure.

• Remove any aggravating medications.

3. Coagulopathy

• 2/2 reduced production of clotting factors, inhibitors, and fibrinolytic proteins. Add this to thrombocytopenia = coagulopathy.

• Worsened by anticoagulants particularly if the patient has renal failure as well or they develop DIC.

• I monitor this with a TEG and replace appropriate products.

4. Hypoglycemia

• This is a late sign of failure, in fact can be one of the final signs so this should be considered an ominous sign.

• Treat the BG. Talk GOC.

5. Jaundice

• Bilirubin will rise. It is what it is.

• Check the bile ducts to ensure patent.

• Treat underlying condition.

• Consider cholestyramine for itching.