ICU Management

Hypotension/shock:

• Both circulatory and cardiac abnormalities may develop in patients with cirrhosis
• In cirrhosis/acute on chronic liver failure (ACLF) patients presenting with shock, the approach should be guided by a systematic assessment of volume status and correction of hypotension in an effort to restore adequate end organ perfusion.
• Arterial catheters are recommended to guide resuscitative efforts. Central venous access is also recommended to aid the assessment of hemodynamic status (e.g. measurement of central venous pressure (CVP)) and as a route for vasoactive medications.
• Assessment of volume status in this patient population can be particularly challenging due to ascites and edema. Dynamic measures of volume and circulatory function such as echocardiography, changes in CVP in response to fluid challenge are preferable
• In ACLF/cirrhosis patients with additional organ failures aim for a MAP > 65 mmHg
• Volume expansion with ringer’s lactate, plasmalyte or concentrated albumin (25% 100 cc prn) is appropriate with fluid choice guided by the patient’s clinical status
• With upper GI bleeding, there is evidence to support a restrictive transfusion threshold of 70 g/L. This threshold is liberalized if bleeding is massive or if there is a history of ischemic heart disease etc.
• Norepinephrine is the recommended first-line agent as it is associated with fewer adverse events. Vasopressin may be used as a second-line agent.
• In patients where adrenal insufficiency is suspected, it is our practice to empirically administer hydrocortisone 200 mg IV in 4 divided doses. Continue until resolution of shock.

Respiratory failure:

• Pulmonary complications in cirrhosis can either be directly related to cirrhosis (portopulmonary hypertension, hepatopulmonary syndrome, hepatohydrothorax) or unrelated (e.g. pneumonia)
• Tense ascites and hepatic hydrothorax may complicate mechanical ventilation.
• Use typical lung protective ventilation strategies with low tidal volume ventilation and use of positive end expiratory pressure (PEEP) to maintain oxygenation.
• In patients with unexplained hypoxia, consider diagnostic studies to evaluate for hepatopulmonary syndrome and portopulmonary hypertension (e.g. contrast echocardiography).

Neurological Dysfunction

• See Hepatic Encephalopathy section for more on the topic
• Treat possible precipitating factors for hepatic encephalopathy (HE) and evaluate the response to ammonia lowering therapies (lactulatose, PEG, rifaximin).
• Consider CT head in patients do not respond to standard treatments or where HE onset is abrupt or severe
• Consider electroencephalogram (EEG) to exclude other causes of altered mental status in patients who fail to respond to standard therapy
• Consider intubation for airway protection in patients with a GCS of ≤ 8
• In patients who require intubation/mechanical ventilation for respiratory failure, the use of short acting agents such as fentanyl (25-200 ug/hour) or propofol (50-150 mcg/kg/min) should be considered. Avoid benzodiazepines as these agents precipitate more pronounced neurocognitive impairment

 Renal Dysfunction

• See Renal Dysfunction section for more on the topic
• Hepatorenal syndrome (HRS) and its physiology of renal vasoconstriction and splanchnic vasodilatation are one of several causes of Acute Kidney injury (AKI) in cirrhosis. Other causes of AKI include hypovolemia/prerenal azotemia, intrinsic renal/parenchymal disorders (acute tubular necrosis/ATN, nephrotoxicity, interstitial nephritis, glomerulonephritis/ nephropathy), and obstructive nephropathy. Consider urinalysis, renal ultrasound, blood pressure evaluation and medication history to rule out other causes of AKI.
• Albumin (1g/kg (20-25%) on day one, then 20-60 g/day thereafter) along with vasoconstrictor therapies have been relatively well studied in the treatment of HRS, in particular, vasopressin Consider Midodrine (maximum dose 15 mg TID) and octreotide (maximum dose 200 ug sc TID) if on the ward. If no effect, then a therapeutic trial of IV norepinephrine to maintain a MAP > 75 mm Hg in the ICU can be considered.
• Intermittent or continuous renal replacement therapy (RRT) may be used in HRS as a bridge to LT. The use of RRT in patients with HRS is likely only appropriate in the setting of a patient who is listed for LT or has another indication for RRT (i.e. uremia, acidosis, hyperkalemia)

Hemostatic Disorders:

• Patients with cirrhosis are in a fragile continuum between ineffective hemostasis and inappropriate thrombosis due to decreased production of procoagulant and anticoagulant factors
• INR (international normalized ratio) does not account for deficiencies of the anti-coagulation system (especially low protein C), which may result in a hypercoagulable state not reflected in prolongation of the INR.
• Consider maintaining platelets > 50 and a fibrinogen > 1.5 g/L as targets in cirrhosis patients requiring procedures or with active bleeding
• If available, consider viscoelastic tests of whole blood (thromboelastography (TEG), thromboelastometry (ROTEM)).

Variceal Bleeding

• See Varices section for more on the topic
• Consider early intubation in cirrhosis/ACLF patients with concomitant HE, respiratory distress or large volume hematemesis (> 500 ml blood) prior to performing endoscopy. Consider octreotide infusion to improve portal inflow with early endoscopy.
• In the event of failed endoscopy, a balloon tamponade device, such as the Sengstaken-Blakemore or Minnesota tube may be used as a bridge to more definitive therapy including repeat endoscopy or transjugular intrahepatic portosystemic shunting
• Administer prophylactic antibiotics (i.e. ceftriaxone 1g IV qd) given potential reduction in rates of rebleeding and bacterial infections

Sepsis

• See Spontaneous Bacterial Peritonitis and Pleuritis section for more on the topic
• Early antibiotics in cirrhosis/ACLF patients with septic shock improves mortality
• Increasing numbers of ACLF patients are presenting with septic shock bacteremia from gram negatives (50-60%) and multidrug resistant pathogens
• If severe sepsis is suspected, a thorough evaluation should promptly be followed by antibiotic administration, since each hour delay impairs outcome
• In patients with clinical improvement within 48-72 hours and a known pathogen, immediate tailoring of antibiotics is recommended. In patients without clinical improvement empiric antifungal therapy and CT scan is warranted.

Acute-on-chronic liver failure (ACLF) prognostication

• Consider the CLIF-C ACLF score or the NACSELD scores for evaluation of ACLF with organ failure
• See: NACSELD calculator
• See: CLIF-ACLF calculator 
• CLIF-C ACLF Score 

A CLIF-ACLF score of > 70 is associated with 90% mortality at Day 28. While predicting futility in ACLF is challenging, decisions regarding ICU admission should be based on factors including:

• Goals of Care
• Candidacy for liver transplant
• Age
• CLIF-C ACLF score
• Other comorbidities/sarcopenia