Acute Liver failureWahid Altaf

Case…Thursday evening call from AnE registrar

Mr C.E. 56 Year old male.

Presenting complaint of

Jaundice

Confusion

Feeling unwell

Background history, liver transplant 8yrs ago with normal liver functions untill 20 days back.

Further questioning

Hypotension

Tachycardia

Vasodilatory shock

Severe Compensated Metabolic acidosis Ph 7.37 HCO3 14 lactate 8

Blood Glucose 2.5

Deranged Liver functions.( Bilirubin 116, ALP 357, GGT 103,AST 1241,ALT 873).

Definition of Liver failure

“The abrupt loss of hepatocellular function in a patient with previously normal liver function, the expression of which includes coagulopathy and encephalopathy.”

AASLD…“Evidence of a coagulation abnormality (INR>1.5) and mental alteration (encephalopathy) in a patient without pre-existing cirrhosis and with an illness of <26wks duration”

Encephalopathy

Classification

Parradox

Rapid onset ALF ----> higher risk of cerebral edema but better prognosis for recoveryClassic example: Paracetamol OD

Slow onset ALF -----> lower risk of cerebral edema, higher risk of portal hypertensive problems (e.g. ascites, variceal bleeding), and ultimately poorer prognosis (w/o transplant)Classic example: NANB hepatitis

Etiology

Common drugs causing ALF

Isoniazid

Sulfur Antibiotics

Nitrofurantoin

Azole antifungals

Antiepileptics- Phenytoin, sodium valproate.

Herbals-ex kava kava,ma huang,comfrey.

Ibuprofen

Statins

Prognosis…family

Poor prognosis

Phone a friend, call

Your consultant

Don’t hesitate to call

St. Vincent University Hospital.

Mortality

Hospital survival

Mid 1970”s ….. 17%

Mid 2000”s …... 62%

Pathophysiology

Death of a mass of hepatocytes.

Loss of vital synthetic and metabolic hepatic functions.

Sterile inflammatory condition leading to SIRS.

Aim of management is to halt progression from hepatic impairment to MODS.

Investigations

ALT, AST, ALP,GGT.

Bilirubin, Ammonia, Lactate.

Blood glucose, Coags: PT, aPTT, INR, Albumin.

Electrolytes, Mg, Phos.

Arterial blood gas

FBC with differential.

Drug screening, paracetamol levels

Investigations.

If under 35 years of age

Ceruloplasmin, Serum & urine copper

Anti HAV IgM

Anti HBc IgM/ Anti HBsAg

Anti-HCV

Pregnancy test

Autoimmune markers – ANA, ASMA, Ig levels

HIV status

Amylase & lipase

Invstg

Diagnostic imaging

Liver biopsy

Imaging

Microbiology : Strep parasanguinus and candida.

Ammonia levels

>75 mcg/l …Encephalopathy

>200 mcg/l…Cerebral oedema and raised ICP.

Cause-Specific therapy

Cause-specific therapy

N-Acetylcysetine

•May improve circulatory function and oxygen delivery

•No improvement in overall survival but significant improvement in transplant-free survival with encephalopathy grade 1-2.

Time to NAC administration important

Time in hrs Mortality (%)

<12 0.4

>12 6

>24 13

>48 19

•Now generally recommended for all patients with ALF

When to pick up the phone in paracetamol overdose

D2- pH <7.3 INR>3 Cr >200 Hypoglycaemia

D3- HE Cr>200 INR >4.5

D4- Any rise in INR Cr >250 HE

Good ICU housekeeping

Stress ulcer prophylaxis

No DVT prophylaxis

Feeding

Blood glucose management

Electrolytes like phosphate and magnesium.

Lines

Ultrasound guided

No correction of coagulopathy

Arterial line

Central line

Vascath

Severe Vasodilatory shock

Optimise cardiac filling pressures

–Haemodynamics can be challenging to determine given the disruptive effects of liver failure on the vasculature

Saline challenge, albumin.

Vasopressors

Vasopressors

Nor-Adrenaline

Terlipressin

Vasopressin..no evidence of splanchnic ischemia.

Sedation

Avoid if possible

Propofol/Remifentanyl is reasonable

Pulmonary considerations

Airway

–Elective intubation

–Elective intubation once in grade 3 encephalopathy

Rapid intubation technique

–Avoid spikes in ICP or decreased CPP

Pneumonia

–Commonest site of sepsis

Acute lung injury/ARDS

–In one third of patients

Renal failure

Renal failure in 50%

Particularly common with paracetamol overdose

–Liver and renal metabolites

Management

Volume control

Maintenance of blood pressure

Prevention/treatment of sepsis

Judicious selection of drugs

Early use of renal replacement therapy

–Before fluid problems aggravate cardiovascular status and ICP

–Sodium management

–Better ammonia level management

Complications of acute liver failure and management

Management of complications

Cerebral edema

Sepsis

Coagulopathy

Cerebral oedema

Predictors of cerebral edema

•Rapid onset ALF

―Rapid accumulation of glutamine overwhelms astrocytes' ability to exclude organic osmolytes

•Grade 3-4 encephalopathy

―High ammonia concentrations

•Infection and/or SIRS

―Case for prophylactic antibiotics

•Vasopressor therapy

•Renal replacement therapy

Invasive monitoring of ICP

Delaying the onset of raised ICP

Delaying the onset of raised ICP

Delaying the onset of raised ICP

Two principles in management of cerebral oedema

Raised ICP management

1st line Mannitol

2nd line Hyperventillation to PaCO2 25-35mmhg

3rd line Hypertonic saline, Hypothermia

4th line Barbiturates, Anticonvulsants

Other considerations Transplantation, total hepatectomy.

Infection

•Infection is near-universal

–Failing liver results in failed host defences

–Infection precipitates MOSF, cerebral oedema

–Frequent cause of death

•Organisms

–Bacterial and fungal

–Gram negative organisms (52%) more frequent than Gram-positive organisms (44%) and Candida Infection

Sites of sepsis

Recommendations

Minimize invasive procedures, strict asepsis

Daily chest radiograph and surveillance cultures

Empiric broad spectrum antibiotics for those patients at greatest risk:

–Grade 3-4 encephalopathy

–Renal failure

–Any component of SIRS

–Planned transplantation (includes antifungals)

Coagulopathy

Increased INR present by definition

Thrombocytopenia present in up to 70%

TEG is reassuring

Is there bleeding diathesis?

Significant bleeding is uncommon: 5%

–Anticoagulant proteins decrease in parallel with coagulation factors

–Spontaneous intracranial haemorrhage is rare

Less clinically-significant bleeding may occur from several sites

–Gastric mucosa

–PPIs

Invasive procedures offer the greatest risk

Correcting coagulopathy before invasive procedures

Correction itself carries risks

–Volume overload

–Aggravation of ICP

–Transfusion-related acute lung injury

–Thromboembolism (particularly with recombinant Factor VIIa)

Commonly used goal of INR <1.5 untested, lacks scientific basis

Correction obscures underlying trends in INR which are important prognostically.

Correcting coagulopathy before invasive procedures

FFP not encouraged except to correct coagulopathy before invasive procedure

–Effect modest, short-lived

–Does not improve survival

Platelet transfusions

–Rarely necessary

Recombinant activated Factor VII

–Is effective

–Cost

–Short-lived effect

–Prothrombotic

Other options

Liver transplant

MARS.. Extracorporeal support, dialysis against albumin.

CRRT against albumin.

Liver transplant

Accepted Indications Absolute contraindications

Acute Liver Failure Brainstem herniation

Decompensated cirrhosis with MELD>15

Severe intracranial hypertention (ICH>50)

Hepatocellular criteria with Milan criteria

Advanced cardiopulmonary disease.Haemodynamic unstability,requiring high dose pressors

Hilar cholangiocarcinoma Uncontrolled infection

Hepatopulmonary syndrome Multiorgan failure

Portopulmonary hypertention Current/Recent extrahepatic malignancy unless tumour free>2yrs

Primary hyperoxaluria Untrated alcoholism/Drug use

Cystic fibrosis with liver involvement

Severe uncontrolled mood disorders

Palliate

Declined by liver services

Refractory ICP

Blown pupils

Communication skills

Don’t forget morphine infusion.

In summary

•Causes

•Help

•Bloods

•NAC

•Early lines, don’t be afraid

•Drugs, dialysis

•Raised ICP

•Coagulation

•Manage Infections

•Transplant

•Palliate