Icu management of acute liver failure

1. MANAGEMENT OF
ACUTE LIVER
FAILURE IN CRITICAL
CARE
Dr.Nida Shafqat
Supervisor: Dr.Vijay Valecha

2. Introduction
• ALF can be defined as a severe liver injury, clinically characterized by
coagulopathy and hepatic encephalopathy within 26 weeks of symptom onset in
previously healthy subjects
• Owing to loss of hepatic function, ALF results in hepatic encephalopathy,
coagulopathy, and multiorgan failure within a short period of time.
• The hallmark of acute liver failure (ALF) is encephalopathy.
• The presence of a liver injury is suggested by raised transaminase levels (in the thousands
indicating hepatocellular necrosis),
• impairment of synthetic function manifested by coagulopathy (INR>1.5),
• and metabolic derangements such as hypoglycaemia and lactic acidosis.

3. • The speed of onset of encephalopathy after the onset of symptoms (usually
jaundice) is important in both categorisation and prognosis.
• If this is than seven days the term ‘hyperacute’ liver failure is used
• 8-28 days indicates ‘acute’ liver failure
• 5 to 26 weeks, is termed ‘subacute’ liver failure.

6. Major causes of acute liver failure Examples
Drugs Dose related:
– Paracetamol
Idiosyncratic:
– Isoniazid
– Beta-lactams
– NSAIDS
– Herbal remedies
Toxins Amanita mushroom
Viral HAV, HBV, HEV, HSV, CMV, EBV
Vascular thrombosis Budd-Chiari syndrome
Inherited metabolic disorders Wilson’s disease
Pregnancy-related Acute fatty liver of pregnancy
Other Autoimmune hepatitis
Reye Syndrome

8. • In the developed world paracetamoloverdose is the most common
cause of ALF
• However worldwide, viral aetiologies(Hepatitis A, B and E) and
seronegative hepatitis predominate.

9. Management
Patients with acute liver failure exhibiting any combination of encephalopathy,
acute renal failure, hypotension, lactic acidemia or hypoglycemia should be
admitted to the ICU as fulminant deterioration is likely.

10. Initial Evaluation and Investigations
• Critically ill patients with acute liver failure with airway compromise or
respiratory failure should be urgently intubated and appropriately
ventilated.
• Shocked patients must be resuscitated with intravenous fluid and
vasoactive infusions.
• Hypoglycemia should be checked for and reversed with prompt parenteral
glucose administration.
• A careful history, clinical examination and series of investigations should
follow.

14. Prevention and Management of Neurological
Complications in Acute Liver Failure
• The risk of death from cerebral edema and associated refractory
intracranial hypertension from acute liver failure is considerable
• The combination of mild hyperventilation, high dose hemodiafiltration,
hypernatremia and mild hypothermia has been termed quadruple-H therapy
and may be readily delivered in most ICUs.

15. Summary of quadruple-H interventions and therapeutic
targets for acute liver failure patients with severe
encephalopathy.
Neuroprotective
Intervention
Therapeutic Target Method of Therapy Mechanism
Hyperventilation PaCO2 = 35 mmHg or
that achieved by the
patient prior to
intubation (whichever
is lower)
Set mechanical
ventilation to achieve
sufficient minute
ventilation
Attenuates cerebral
hyperemia
Lowers ICP
Hemodiafiltration Blood ammonia < 60
µmol/l and even daily
fluid balance
High volume CRRT
utilizing dialysis and
filtration
Reduces blood
ammonia
concentration
Allows precise
metabolic, electrolyte
and fluid management
Cooling effect.

16. Summary of quadruple-H interventions and therapeutic
targets for acute liver failure patients with severe
encephalopathy.
Hypernatremia Serum sodium 145–155 mmol/l Continuous infusion of
concentrated saline via central
venous catheter
Increased serum tonicity and
reduces cerebral edema
Hypothermia Core temperature 33–35 °C CRRT circuit and external
cooling blanket
Reduces ammonia production
and CNS uptake
Attenuates cerebral hyperemia
and reduces cerebral metabolic
rate
Reduces neuro-excitation
Anti-inflammatory effects

17. Management
• Acute management is focussed on –
• Global organ support
• Cerebral protection
• Identification of patients likely to benefit from liver transplantation (LT), and liason
with a specialist liver unit
• Ensuring safe inter-hospital transfer

18. Global organ support

19. Circulation
• Vasodilatory shock is common.
• Invasive monitoring (eg. with ‘pulse-induced contour cardiac output’ – PiCCO) will aid assessment
of volume and identify co-existing cardiac dysfunction.
• Aggressive fluid resuscitation is almost always required, with the fluid volume required often
exceeding 3 litres.
• As in head injury, salt-containing fluids are appropriate, since hyponatraemia may exacerbate
cerebral oedema.
• Vasopressor therapy should be instituted if mean arterial blood pressure does not respond to filling.
• Patients requiring inotropes may have relative adrenal deficiency and should have a short
synacthen (ACTH stimulation) test and hydrocortisone 50mg 6 hourly commenced.

20. Renal acid base balance
• Whether as a result of the primary pathology that also affects the liver (e.g., paracetamol
overdose) or as a consequence of systemic inflammatory response with shock, renal failure is a
common problem in patients with acute liver failure.
• Consequences of renal failure include electrolyte derangement and fluid balance problems,
both of which contribute significantly to the complex pathophysiology of acute liver failure.
• Continous veno-venous haemofiltration (CVVHF) will be required if the patient is anuric or acidotic.
• CVVHF is favoured since it is better tolerated by patients with haemodynamic compromise.
• A bicarbonate buffered replacement solution should be used (lactate will not be handled well by the liver),
and epoprostanol (Flolan!) used to anticoagulate the circuit.
• High volume (90mls/kg/hr) can be used if the acid-base status is extremely deranged.

21. Respiratory function
• Although ARDS can develop in ALF, specific ventilatory strategies are not usually
recommended in the early phase.

22. Coagulation
• The extent of coagulopathy is critical in deciding if the patient will benefit from LT, and administration
of FFP is not recommended unless there is clinically significant bleeding.
• Platelets can be supported freely.
• Coagulopathy should not necessarily preclude central line insertion (especially femoral) by an
experienced operator.
• Dissemninated intravascular coagulation and fibrinogen defects can further complicate the
coagulopathy.
• Gastric ulcer protection with iv or enteral proton pump inhibitors reduces the risk of gastrointestinal
bleeding.
• Sometimes, despite severe derangement of measured clotting parameters, a
hypercoaguable state develops and may result in thrombotic complications, such as digital
ischemia, portal vein thrombosis or lower limb deep venous thrombosis.

23. Protection against sepsis
• Bacterial and fungal sepsis complicated a high proportion of ALF patients before
antibacterial prophylaxis became standard.
• Recommended agents are TazobactamPiperacillin (Tazocin®) 4.5g/iv/tds and
Fluconazole 200mg/iv daily.

24. Gastrointestinal tract and nutrition
• Gastric ulcer protection with IV or enteral proton pump inhibitors reduces the risk of
gastrointestinal bleeding.
• There are no contraindications to early enteral feeding, and standard amounts of
nitrogen and carbohydrate can be administered.

25. Fluid and electrolyte Management
• Patients with acute liver failure will tend to accumulate a positive fluid
balance and electrolyte abnormalities due to the administration of fluid
boluses for circulatory support, clotting factors and various other
intravenous therapies, such as antimicrobials.
• This can have several undesirable consequences including a predisposition
to cerebral edema.

26. Cerebral protection

28. Cerebral Edema and Intracranial Hypertension
• Cerebral edema occurs in many patients with high-grade encephalopathy.
• Brainstem herniation is a common cause of death in acute liver failure and
occurs because of severe cerebral swelling causing refractory intracranial
hypertension.
• The accumulation of ammonia, and the loss of cerebral autoregulation
resulting in hyperemia are two key drivers in the development of cerebral
edema.

30. • Cerebral blood flow is normally tightly regulated across a wide range of
systemic arterial pressures.
• Autoregulation is lost in patients with severe acute liver failure due to
abnormal regulation of vasoactive mediators within the CNS.
• This leads to cerebral hyperemia and vasogenic edema in severely
encephalopathic patients.

31. • Cerebral oedema complicates severe encephalopathy, and may occur in 80% of patients in grade IV.
• Those most at risk are the young, the septic, the hyponatraemic and patients with significant elevations in blood ammonia (which
appears to have an important role in both encephalopathy and oedema).
• Arterial ammonia concentration correlates with the degree of encephalopathy, and is useful in assessing the risk of developing
intracranial hypertension.
• Venous ammonia levels are significantly lower than arterial levels due to the ability of skeletal muscle to metabolise ammonia.
• Clinical signs of rising intracranial pressure (ICP) are hypertonia, clonus, pupillary abnormalities (dilatation, reduced responsiveness
to light) and in the latter stages hypertension (bursts to > 200 mmHg, or sustained above 150 mmHg), bradycardia and cerebral
posturing.
• Such patients will have been intubated for airway protection. Recommended sedation is propofol (possible beneficial cerebral
metabolic effects) and fentanyl. Additionally the following prophylactic measures are advised.

32. Posture
• Positioning the head in the midline, with the angle of the body 20° from horizontal
will aid cerebral venous outflow.

33. Normocapnia
• Hypercapnia should be avoided, however the ‘traditional’ approach of
hyperventilation and low PaCO2, although effective in short term reduction of
cerebral blood flow and ICP, can lead to cerebral vasospasm and increased risk of
brain injury.

34. Body temperature
• Fever should be managed with cooling blankets, or if on CVVHF reduced thermal
compensation.

35. Avoidance of stimulation
• Surges in ICP are seen in monitored patients who are exposed to stimuli such as
loud noise, suctioning and excessive movement.
• Specific treatments if raised ICP is suspected include the following. These would
normally be undertaken only after discussion with a specialist centre.

36. Mannitol
• 0.5g/kg boluses over 10 minutes may be administered and repeated, but serum
osmolarity should be monitored so that 320 mosm/L is not exceeded.
• To prevent fluid overload a 500ml diuresis (or negative balance if being
haemofilitered) should be obtained after each bolus.

37. Hypothermia
• Small case series have demonstrated that reducing the core temperature to 32°-
34°C (‘moderate hypothermia’) can safely bring about significant and prolonged
reductions in ICP in patients with raised ICP that has not responded to medical
therapy.
• However, there are concerns about increased susceptibility to infection,
cardiovascular instability and bleeding with hypothermia of this degree.

38. Hypernatremia
• Serum sodium in the range 145-155 mmol/L has been shown to have a beneficial
effect on ICP. This target can be achieved with continuous central infusion of 30%
NaCl, with regular monitoring.
• A slow bolus of 20ml 30% sodium chloride may also be administered for possible
surges in ICP.
• Indomethacin and thiopentone are also used in cases resistant to these measures,
but will usually only be administered after insertion of an intra-cranial pressure
monitor.

39. King’s College Hospital criteria used by
the United Kingdom Transplant (UKT)
service for liver transplant

41. nsuring safe inter-hospital transfer

42. • If the patient requires transfer to a liver unit, remember that deterioration can occur
swiftly, especially in terms of conscious level, cerebral perfusion and
cardiovascular stability.
• Where available, air transfer is often advised if the disease process appears to be
advanced.

44. Thankyou