S3E2: Liver Cirrhosis - Hepatology

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This month, we're tackling one of the most complex medical conditions that can frequent the Emergency Department- liver cirrhosis.

Leah sat down with Liam Loughrey and Etimbuk Umana to go through our case of the undifferentiated septic patient and to talk all things SBP.

Kindly, Dr Iomhar O'Sullivan of CUH ED and EMed.ie, has corrected our homework as the AITR.

And finally, the Echo Chamber is back with Callum and Cian exploring the ways in which ultrasound can be used to help guide your management of patients who are simultaneously hypovolaemic and fluid overloaded.

Liver Cirrhosis

  • Late stage of progressive hepatic fibrosis with restructuring and remodelling of the hepatocytes and formation of regenerative nodules.

  • Acute Liver Failure: Acute deterioration in liver function (can be normal or abnormal) leading to encephalopathy

Decompensation

  • Sepsis can develop as an intercurrent event in decompensated cirrhosis but can also trigger a decompensation leading to multi-organ failure

  • Cirrhosis Associated Immune Dysfunction (CIAD): Increased and persistent systemic inflammation, liver disease severity and portal hypertension, leading to worsening of existing or new-onset decompensation of acute compensated liver failure.

  • Sepsis: State of profound immune dysfunction in which, during the early phase, a pro-inflammatory state, counterbalanced by an anti-inflammatory response, affects immune functions

  • In patients with dysregulated immune function such as cirrhosis- initial phase goes unchecked, progressing to sepsis-induced immunosuppression and a stage of immune paralysis


Pathophysiology

  • Cirrhotic patients- have low SVR, third space fluid accumulation, central hypovolaemia, hyperdynamic circulation with high cardiac output and subclinical cardiomyopathy


Causes

Trying to remember all the causes of both acute and chronic liver failure and causes of cirrhosis can be tricky at the best of times. We’re great advocates of a simple mnemonic. VINDICATE is a great one to recall aetiologies of disease and hits on all the main causes in no particular order.


VINDICATE

Vascular - Bud chiari

Infectious - Hepatitis, CMV, HIV, EBV

Neoplastic - Hepatocellular carcinoma

Degenerative -

Iatrogenic - Medications - amiodarone

Intoxication - Ethanol, paracetamol

Congenital - Cystic fibrosis

Autoimmune - Autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis

Traumatic - Rare

Endocrine - Fatty liver disease, Haemochromatosis

Metabolic - Wilson’s disease, a1 anti-tripsin


Analgesia

  • Avoid NSAIDs, opiates and anything that could precipitate a GI bleed or cause sedation in a patient that is vulnerable to encephalopathy

  • Avoid constipation

  • Paracetamol is generally well tolerated at a reduced dose of 2-3g/day

  • Fentanyl is considered a good choice for patients with CLD if opiate treatment is indicated

    • Reduce repeat doses by amount and frequency by 25-50%

  • Neuropathic pain

    • Gabapentin- initiate treatment at 300mg PO daily and titrate based on response and renal function

    • Pregabalin- 50mg BD PO and titrate

Dosing of pain medications can be tricky in cirrhotic patients. The key take home messages from our team are to avoid NSAIDs, opiates and anything that could precipitate a GI bleed or sedate a patient that is vulnerable to encephalopathy. The last thing we want is iatrogenic constipation.

Paracetamol can be given at reduced doses to a maximum of 2-3g/day, and fentanyl can be considered. As we learned from our Adult in the Room, it’s a good idea to consult the protocol in your ED and to follow evidence based practice for dosing regimes. Tramadol is often considered a good option (although, we never thought we’d use those words!)

For neuropathic pain, gabapentin and pregabalin are reasonable to consider in low doses. The most important thing is to try to reduce mixtures of analgesia.


Spontaneous Bacterial Peritonitis

Clinical Presentation

  • Fever

  • Abdominal pain

  • Altered mental status

  • Abdominal tenderness

  • Hypotension

Investigations

  • Laboratory

    • LFTs, coagulation screen, albumin, bilirubin

    • Electrolytes- hyponatraemia

    • FBC- multifactorial anaemia

      • Leukopaenia and neutropaenia

The Role for TAP

  • Indications

    • Clinical suspicion for SBP

    • Any patient with cirrhosis and ascites who is admitted to the hospital for clinical deterioration

  • Clinical evidence encourages abdominal paracentesis before giving antibiotics

  • In-hospital mortality has been shown to be reduced by 24% among patients who underwent early paracentesis

  • Send for

    • Aerobic and anaerobic cultures

    • Cell count and differential

    • Gram stain

    • Albumin, protein, LDH

    • Amylase, bilirubin

    • Glucose

  • No need to correct INR

  • Spontaneous bacterial peritonitis:

    • PMN (neutrophil count) >/ 250cells/mm

    • Positive ascitic fluid bacterial culture (most commonly E. coli and Klebsiella)

    • Absence of secondary causes of peritonitis

      • This would lead to secondary bacterial peritonitis- setting of a surgically treatable intra-abdominal source of infection

Treatment

  • Cover for gram-negative bacilli and also for gram-positive organisms

  • Ceftriaxone 2g BD IV or tazocin

  • Albumin has been proven to reduce the incidence of hepatorenal syndrome and mortality

    • 1.5g/kg of 20% albumin at the time of diagnosis followed by 1g/kg albumin 48h later

    • This is usually a decision made in tandem with gastroenterology

Other Considerations

Glucose

Hypoglycaemia is an important thing to watch out for. It can be a clear indication of further deterioration in your septic patient and can worsen encephalopathy and immune dysregulation.

5% or 10% dextrose is an option to help replace this.

Sepsis Eight?

Dr Íomhar O’Sullivan also makes the point that Pabrinex and N-acetylcysteine should be considered in all of these patients with decompensated liver cirrhosis. The benefits of giving them far out way any harm and are important tools in our kit to employ. Ultimately, they can be life saving.


Role of Vasopressors

  • Recent evidence in 2019 (CENSER Trial), has shown that early low-dose norepinephrine was significantly associated with increased shock control by 6 hours

King’s College Criteria

In considering discussing patients directly with an in-patient or local liver unit, you can consider the King’s College Criteria.

Paracetamol toxicity

  • Lactate > 3.5 4hrs after resuscitation

  • or

  • pH< 7.30 or lactate > 3.0 12hrs after resuscitation

  • or

  • INR > 6.5 (PT > 100 sec)

  • Creat > 3.4 mg/dl

  • Stage 3 or 4 encephalopathy

Non-paracetamol causes

  • Lactate > 3.5 4hrs after resuscitation

  • or

  • INR > 6.5 (PT > 100 sec)

  • or any 3 of the following:

  • INR > 3.5 (PT > 50 sec)

  • Age <10 or > 40 years

  • Serum bilirubin > 17.5 mg/dl

  • Duration of jaundice > 7 days

  • Aetiology: drug reaction




References

EMed.ie

UpToDate

Lewis JH, Stine JG. Review article: Prescribing medications in patients with cirrhosis – a practical guide. Aliment Pharmacol Ther 2013; 37:1132.

Permpikul et al.; Early Use of Norepinephrine in Septic Shock Resuscitation (CENSER): A Randomised Trial. 2019.

Sort P, Navasa M, Arroyo V, et al. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med. 1999 Aug 5;341(6):403-9. doi: 10.1056/NEJM199908053410603


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