A forty-two (42) year old man has been well, apart  from a history of alcohol induced liver dysfunction and portal hypertension.  He has abstained from alcohol for the past 8 months after being told that  it would kill him.   After  a  large  haematemesis he presents  drowsy, clinically shocked, with a blood pressure of 80 systolic, heart rate of 124 beats/minute, cold and clammy peripheries.  He is also clinically jaundiced.

Variceal bleeding is diagnosed and it initially responds to therapy.  48 hours post admission he remains on invasive respiratory support, with weak withdrawal response to pain despite minimal sedation, a persistent coagulopathy, and is inotrope dependent.  Serum bilirubin concentration is elevated (100 micromol/L [N 3-20]).  He develops a further acute variceal bleed associated with hypotension.

(c) At 6 days there has been no further haematemeses. However he has a Glasgow Coma Score (GCS) of 5, despite no sedation.  His serum bilirubin concentration is now 350 micromol/L. Prothrombin time and serum creatinine concentration are twice normal.  A CT of the head shows no focal abnormality.  What supportive therapies and strategies would you have in place at this stage and why?

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College Answer

Specific strategies to minimise hepatic encephalopathy should have been described if not already done so (including the use of lactulose). Precipitants must be minimised (treatment of infections, avoidance  of  sedatives,  correction  of  electrolyte  abnormalities/hypoxia, avoid  alkalosis,  limit dietary protein, consider unproven dietary supplements including BCAA etc.). Cautious volume expansion should be considered. Other reversible causes for renal dysfunction and coma should be sought and excluded. Management of ICP  may be necessary (and the CT does not exclude cerebral oedema). General supportive care should be considered (eg. physiotherapy, avoidance of line- related problems, family support etc.). Specific treatment may be required for ascites and its effects (drainage, colloid replacement etc).

Discussion

The college has given us a patient with a combination of several reasons to be encephalopathic; of these, the major one is liver failure -but we are also reminded that the creatinine has doubled.

Management of hepatic encephalopathy:

Specific management of hepatic encephalopathy

  • Lactulose
  • Rifaximin
  • Avoidance of hyponatremia
  • Nutritional management:
    • Branched-chain amino acids (BCAAs) and a reduced amount of aromatic amino acids
    • High fiber diet
    • Pro-biotics (though their benefit is unclear)

Management of the precipitating cause

  • Stop GI bleeding (endoscopy, banding, etc)
  • Antibiotics for SBP
  • Correct dehydration
  • Withdraw hepatotoxins

Supportive management of the encephalopathic patient

  1. Support the airway.  If the patient is comatose or uncooperative, they may require intubation in order to correct disorders of gas exchange (as they may not be compliant with NIV and chest physiotherapy)
  2. Wean ventilation to spontaneous mode as tolerated.​ Hypoxia and hpercapnea can be readily corrected if the patient is mechanically ventilated; otherwise, posture with chest physiotherapy and deep breathing exercises are crucial
    Avoid NIV; abdominal distension and a fluctuating level of consciousness will likely result in aspiration. HFNP is ok. 
  3. Support haemodynamically;
    noradrenaline +/- terlipressin may be appropriate if hepatorenal syndrome is suspected
    Albumin (20%) is a reasonable resuscitation fluid
    Hepatic flow should be optimised by monitoring for abdominal compartment syndrome
  4. Avoid sedation. As needed, use drugs which do not depend on hepatic metabolism (eg. remifentanyl).
    Cerebral oedema and the potential for intracranial catastrophe should be investigated with a CT brain
  5. Correct electrolyte derangement
  6. Monitor renal function (hepatorenal syndrome)
  7. Ensure BSL is monitored and supplemental glucose is made available
    Ensure thiamine is co-administerd with glucose!
  8. Correct clinically significant anaemia. 
    Address haematinic factor deficiencies.
  9. Antibiotics as appropriate: ceftriaxone may be required if SBP is a real possibility.
    Blood cultures and inflammatory markers should be collected.

Pursuit of other explanations for decreased level of consciousness:

  • Minimise sedation
  • Optimise oxygenation and ventilation
  • Screen for sepsis
  • Observe for physical signs suggestive of raised intracranial pressure
  • Manage uremia, and consider dialysis

References

References

Wendon, Julia, et al. "Critical care and cirrhosis: outcome and benefit." Current opinion in critical care 17.5 (2011): 533-537.

Riggio, Oliviero, et al. "Management of hepatic encephalopathy as an inpatient." Clinical Liver Disease 5.3 (2015): 79-82.

Bajaj, J. S. "Review article: the modern management of hepatic encephalopathy." Alimentary pharmacology & therapeutics 31.5 (2010): 537-547.

 

Amodio, Piero, et al. "The nutritional management of hepatic encephalopathy in patients with cirrhosis: International Society for Hepatic Encephalopathy and Nitrogen Metabolism Consensus." Hepatology 58.1 (2013): 325-336.

 

Als-Nielsen, Bodil, Lise Lotte Gluud, and Christian Gluud. "Nonabsorbable disaccharides for hepatic encephalopathy." Cochrane Database Syst Rev 2 (2004).

 

Bass, Nathan M., et al. "Rifaximin treatment in hepatic encephalopathy." New England Journal of Medicine 362.12 (2010): 1071-1081.