Liver Failure Patients - Ten Simple Tips for Complicated Patients

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The liver failure patient comes in two different flavors:

  • ACUTE: Defined as new onset hepatocellular dysfunction, coagulopathy with INR>1.5, and encephalopathy in the absence of preexisting liver disease.  In the US the majority of cases are caused by acetaminophen toxicity, as well as viral hepatitis, idiosyncratic drug reactions, toxins, and autoimmune/metabolic causes. 
  • CHRONIC: Underlying liver disease usually caused by alcohol or viral hepatitis punctuated by episodes of “decompensation” caused by a hepatic or extrahepatic precipitant (infection, bleeding, portal vein thrombosis, hepatic encephalopathy, trauma, etc.).
Liver failure acute vs chronic.jpg
 

Many principles are the same for these Two different populations, but some are different. Let's clarify when this is the case.

 

1.  Shoot first, ask questions later- have an extremely low threshold to give    N-Acetylcysteine in acute liver failure.

  • N-Acetylcysteine (NAC) is dramatically beneficial in acute liver failure (ALF) due to acetaminophen ingestion (the most common cause of ALF in the US) and has minimal drawbacks.  For this reason in the patient with liver failure where there is any possibility of acetaminophen toxicity, NAC should be given.  In a randomized clinical trial of 173 patients with non-acetaminophen related ALF, administration of NAC improved transplant free survival from 30% to 52% in patients with grade I/II hepatic encephalopathy [1].  There is also some evidence that NAC may improve out comes in patients with non-acetaminophen drug related liver failure [2].

 

2.  Phone a friend- consult a transplant capable facility early in acute liver failure

  • One of the most critical interventions in the acute liver failure patient is early discussion with a transplant-capable facility and early transfer.  90% of patients with acetaminophen-related liver failure will recover without requiring liver transplant; for most other causes of liver failure the rates of transplant free recovery are much lower.  Early consultation and transfer to a liver transplant capable facility is recommended, and absolutely indicated for:
    • INR > 2
    • Grade II or greater hepatic encephalopathy
    • Age < 10 or > 45
    • Etiology of liver failure that carries a poor prognosis (ie not acetaminophen) [2]

 

3.  Sicker patients are sicker- assess risk factors for progression to cerebral edema

  •  The most dreaded complication of acute and chronic liver failure is cerebral edema.  Two theories for the pathophysiology exist:
    • Increased ammonia is converted into glutamine by astrocytes, which results in cell swelling  
    • Inflammatory cytokines cause vasodilation and increased brain blood volume.  Patients with hyperacute liver failure, grade III/IV hepatic encephalopathy, need for vasopressors, and renal failure are at particularly high risk.
  • Absolute ammonia level does not correlate with degree of hepatic encephalopathy in chronic liver failure patients.  However, in the acute liver failure patient, a serum ammonia < 75ug/dL with grade I or II hepatic encephalopathy suggests a low risk of progression to cerebral edema while levels > 150 ug/dL represent very high risk [3].
 

4.  Keep your head- anticipate, prevent, and treat elevated ICP

 

5.  Manage the stress-  start stress dose steroids early in the hypotensive liver failure patient

  • Resuscitation of the hemodynamically unstable liver failure patient is generally similar to the non-liver failure patient and includes volume resuscitation with crystalloids followed by vasoactive medications, with norepinephrine being the vasopressor of choice (liver failure patients may have decreased response to pure alpha-agonists such as phenylephrine, and vasopressin may dangerously increase ICP).  However, a third of acute liver failure patients and up to 76% of those with chronic liver failure and septic shock have relative adrenal insufficiency [5].  Most intensivists I know tend to start stress dose steroids when the patient is thought to be volume repleted, the norepinephrine is up to 10-12 mcg/min (roughly 0.15 mcg/kg/min for a 70kg adult), and there are thoughts of adding a second vasopressor.  In the liver failure patient steroids should be started sooner.  Dose is hydrocortisone 50mg IV q6hours.  

 

6.  You’re not that good - don’t clinically exclude spontaneous bacterial peritonitis (SBP). 

  • SBP is tricky.  Only 68% of patients with SBP will have fever, and less than half will have abdominal tenderness [6].  Physician impression was only 76.5% sensitive to rule out SBP [7].  Presence of ascites + pretty much any complaint = diagnostic paracentesis.  >250k PMN’s is diagnostic.  The most common bugs are E. Coli, Klebsiella, Strep pneumo; treatment is with cefotaxime.

 

7.  Small fish, big pond - inoculate culture bottles at the bedside for better yield when doing a diagnostic paracentesis

  • Those little bacteria are floating around in an enormous ocean of ascites fluid, so they can be hard to find.  For every 5 patients who have immediate inoculation of the culture bottles at the bedside vs in the lab 4 hours later, one additional infection will be detected.[8]

 

8.  Don’t just do something, stand there - don’t try to correct coagulopathy in the nonbleeding liver failure patient

  • Liver patients are coagulopathic by definition; however they manage to be both bleedy and clotty at the same time.  This is called “rebalanced hemostasis” and probably due to decreased production of both pro- and anti-coagulant compounds.  Abnormal lab values don’t reflect bleeding risk, nor do they predict a need for transfusion during liver transplant; additionally thromboelastography studies show normal functional hemostasis in coagulopathic liver failure patients [9].  Spontaneous bleeding is rare. 

  • Empiric transfusion of FFP in the non-bleeding patient is not indicated; platelets should be transfused only if <10-20k.  There is NO evidence that correction of coagulopathy prior to procedures reduces complications.

 

9.  Take your vitamins - give vitamin K and GI prophylaxis in the coagulopathic liver failure patient

  • 25% of liver failure patients have vitamin K deficiency [10].   The degree to which their vitamin K deficiency vs hepatic dysfunction contributes to their coagulopathy is unclear, however administration of IV vitamin K is recommended.  These patients are at risk for GI bleeding and should receive H2 blocker or PPI.
 

10.  Common things are common - think infection in the liver failure patient

  • Infection is the most common underlying cause of decompensation of chronic liver disease, most commonly SBP and UTI.  Patients with acute liver failure are also at high risk for infection.  SIRS criteria are neither sensitive nor specific for the presence of infection in liver failure patients, cultures should be sent on any sick liver failure patient and there should be a low threshold to start empiric antibiotics.   Cirrhotic patients with upper GI bleed are at particularly increased risk of infection (45-66% develop bacterial infection within 5-7 days of their bleed), so antibiotics (ceftriaxone) should be administered to patients who present with upper GI bleeding.[11]
 

Tired of reading?  Watch Dr. Wood discuss her simple tips for Liver Failure Patients

Written by Samantha Wood, MD

Edited and Posted by Jeffrey A. Holmes, MD

 

References

1.  Lee WM, Hynan LS, Rossaro L, Fontana RJ, Stravitz RT, Larson AM, et al. Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure. Gastroenterology. 2009;137(3):856-64, 64 e1.

2.  Lee WM, Stravitz RT, Larson AM. Introduction to the revised American Association for the Study of Liver Diseases Position Paper on acute liver failure 2011. Hepatology. 2012;55(3):965-7.

3.  Bernal W, Hall C, Karvellas CJ, Auzinger G, Sizer E, Wendon J. Arterial ammonia and clinical risk factors for encephalopathy and intracranial hypertension in acute liver failure. Hepatology. 2007;46(6):1844-52.

4.  Murphy N, Auzinger G, Bernel W, Wendon J. The effect of hypertonic sodium chloride on intracranial pressure in patients with acute liver failure. Hepatology. 2004;39(2):464-70.

5.  O'Beirne J, Holmes M, Agarwal B, Bouloux P, Shaw S, Patch D, et al. Adrenal insufficiency in liver disease - what is the evidence? Journal of hepatology. 2007;47(3):418-23.

6.  Carey WD, Boayke A, Leatherman J. Spontaneous bacterial peritonitis: clinical and laboratory features with reference to hospital-acquired cases. The American journal of gastroenterology. 1986;81(12):1156-61.

7.  Chinnock B, Afarian H, Minnigan H, Butler J, Hendey GW. Physician clinical impression does not rule out spontaneous bacterial peritonitis in patients undergoing emergency department paracentesis. Annals of emergency medicine. 2008;52(3):268-73.

8.  Runyon BA, Antillon MR, Akriviadis EA, McHutchison JG. Bedside inoculation of blood culture bottles with ascitic fluid is superior to delayed inoculation in the detection of spontaneous bacterial peritonitis. Journal of clinical microbiology. 1990;28(12):2811-2.

9.  Lisman T, Porte RJ. Rebalanced hemostasis in patients with liver disease: evidence and clinical consequences. Blood. 2010;116(6):878-85.

10.  Pereira SP, Rowbotham D, Fitt S, Shearer MJ, Wendon J, Williams R. Pharmacokinetics and efficacy of oral versus intravenous mixed-micellar phylloquinone (vitamin K1) in severe acute liver disease. Journal of hepatology. 2005;42(3):365-70.

11.  Jalan R, Fernandez J, Wiest R, Schnabl B, Moreau R, Angeli P, et al. Bacterial infections in cirrhosis: a position statement based on the EASL Special Conference 2013. Journal of hepatology. 2014;60(6):1310-24.