A 49-year-old lady with a background of alcoholism and Child-Pugh C cirrhosis has presented to hospital with melaena and haematemesis. She required a massive transfusion and gastroscopy. Multiple varices were banded and she was transferred to the ICU following this procedure. She is now Day 3 in ICU and has remained intubated.
Salient findings on examination include:
- Intubated
- GCS E2 VT M5
- Agitated, restrained; appears to be moving all 4 limbs
- Urine output 20ml/hr
- Ventilator settings:
- FiO2 25%
- Spontaneous mode of ventilation (PSV)
- PEEP 6 cm H2O
- PS 10 cmH2O
- Infusions: fentanyl 20mcg/hr; normal saline 60ml/hr
- ABG and biochemistry:
- pH 7.49
- PaO2 75 mmHg
- PaCO2 31 mmHg
- Na+ 130
- K+ 4.1
- HCO3- 25
- Urea 17.0 mmol/L
- Creatinine 250 µmol/L
- Bilirubin 65 µmol/L
- INR 2.5
What are the most likely causes of her decreased level of consciousness?
(This is not a real CICM viva)
Why is this alcoholic now comatose? The possibilities are endless:
- Vascular causes, eg. stroke
- Infectious causes, eg. sepsis, septic encephalopathy, or even a CNS infection
- Neoplasm of the CNS, which was previously unknown
- Drug-related decreased level of consciousness, from intoxication of some sort (including iatrogenic, like the overzealous administration of diazepam for alcohol withdrawal) to a drug withdrawal syndrome (eg. a non-convulsive status epilepticus)
- Something nonmedical, like a psychiatric syndrome involving catatonia
- Trauma, eg. subdural haematoma from an unreported fall
- Endocrine causes, eg.
- hypoglycaemia due to liver disease
- hypothyroidism
- hypoadrenalism
- hyponatremia
- uraemia
- Wernicke's encephalopathy
Hepatic encephalopathy should be in this list.
What clinical signs would help distinguish hepatic encephalopathy from other differentials?
- Tremor
- Muscular incoordination
- Impaired handwriting
- Slurred speech
- Asterixis
- Hypoactive or hyperactive reflexes
- Ataxia
- Nystagmus
- Clonus and myoclonus
- Dilated pupils (and, if you're lucky, pupillary hippus)
- Jactitations (restless tossing and muscle or limb twitching)
- Opisthotonus
How would you stage this condition? Are you aware of any staging systems?
Stage I
|
- Metabolic tremor
- Muscular incoordination
- Impaired handwriting
|
Stage II
|
- Slurred speech
- Asterixis
- Hypoactive reflexes
- Ataxia
|
Stage III
|
- Hyperactive reflexes
- Nystagmus
- Babinski’s sign
- Clonus
- Rigidity
|
Stage IV
|
- Dilated pupils
- Opisthotonus
- Coma
|
What causes hepatic encephalopathy?
- Hyperammonaemia and cerebral oedema
- Cerebral inflammation
- Changes in neurotransmisssion
- GABA-ergic or benzodiazepine pathway abnormalities
- Manganese neurotoxicity
- Impaired cerebral mitochondrial function
- Dysfunction of the blood brain barrier due to ammonia
What is the value of serum ammonia measurements in this setting?
- Not diagnostic of hepatic encephalopathy
- Not correlated to the severity
- Can be elevated for a host of other reasons
- Has prognostic value
- Is related to mortality in cirrhosis
- Can predict encephalopathy when higher than 100
- Can lead to cerebral oedema when acutely and severely elevated
- May lead to the over-prescription of lactulose
What are your management strategies for hepatic encephalopathy?
- Treat the cause
- Reduce intestinal nitrogen load
- Reduce ammonia levels in other ways
- Branched-chain amino acids (BCAAs) and a reduced amount of aromatic amino acids
- High fiber diet
- Pro-biotics (though their benefit is unclear)
- Ammonia scavengers
- Prevent exacerbation
- Stop GI bleeding (endoscopy, banding, etc)
- Avoidance of hyponatremia
- Antibiotics for SBP
- Correct dehydration
- Withdraw hepatotoxins
How does lactulose exert the desired effect?
- Cathartic (increases gut transit time)
- Decrease ammonia production by changing colonic pH
- Increase ionisation of ammonia to ammonium (to some minimal degree)
- Changing the proportion of urease-deficient organisms in the gut (to some minimal degree)
Does this patient need an ICP monitor?
- Grade 3-4 by the Parsons-Smith scale deserves an ICP monitor, IF:
- the patient is young
- the presentation is "hyperacute"
- the serum ammonia is over 150mmol/L (anything over 200 is associated with cerebellar herniation)
- ICP monitoring should be performed with a parenchymal device, such as a Codman catheter (as the risk of bleeding with these is much less than with an EVD). Some authors recommend covering the coagulopathy with some Factor VIIa just before inserting the monitor.
Does this patient have hepatorenal syndrome? How do you define this?
- Cirrhosis
- Ascites
- Creatinine level over 150mmol/L
- failure of this to improve after fluid replacement, diuretic withdrawal and albumin (1g/kg of body weight)
- Absence of shock
- No current or recent nephorotoxic drugs
- No parenchymal kidney disease, eg. proteinuria > 500 mg/day, microhematuria (> 50 red blood cells per high power field),
and/or abnormal renal ultrasonography
What are the two types of hepatorenal syndrome?
- There are two imaginatively title subtypes, Type 1 and Type 2.
- The distinction between them seems to be basically the speed of decline: Type 1 deteriorates faster than Type 2.
- Type 1 is defined as a doubling of creatinine over 2 weeks, whereas Type 2 is anything slower than that.
What is the mechanism of hepatorenal syndrome?
- Worsening hepatic function leads to worsening splanchnic arterial and venous vasodilation, mainly due to an excess of nitric oxide synthesis in this part of the circulatory system.
- As the result, more and more of the blood volume ends up sequestered in the splanchnic circulation
- The apparent loss of circulating volume leads to a series of predictable neurohumoural responses, such as renin-angiotensin-aldosterone overactivity and sympathetic overactivity
- The splanchnic circulation remains immune to this, as the vastly excessive amount of nitric oxide produced there tends to override the systemic vasoconstrictor release.
- As a result, renal arterial vascular resistance increases in proportion to splanchnic and systemic arterial vasodilation
- This, there is progressive renal vasoconstriction and thus decreased glomerular filtration
- In addition to this, worsening hepatic failure results in increasing ascites pressure (and thus decreasing renal perfusion pressure).
What are some common precipitants of hepatorenal syndrome?
- Large volume paracentesis without albumin replacement
- Spontaneous bacterial peritonitis (SBP)
- Sepsis of any origin (but especially SBP)
- Nephrotoxic drugs in a patient with cirrhosis, particularly NSAIDs
- Rapid diuresis
- GI bleeding
What are the management options for hepatorenal syndrome?
- Albumin and fluid resuscitation:
- On its own, the effect from this is minimal; mortality is ~ 70%
- Terlipressin
- Improves mortality from 70% to 50%
- Thought to improve renal perfusion by decreasing the tension within the ascites compartment.
- Noradrenaline
- The idea is to increase renal perfusion by increasing the MAP by about 10mmHg
- Octreotide
- potent agent of splanchnic vasoconstriction
- Mortality perhaps 60%
- If all else fails, TIPS procedure may be appropriate.
- As this disorder has an abysmal survival rate, those who qualify for transplant should be worked up for one.
- this is the only definitive management for hepatorenal syndrome.
- It takes about 1 year for the renal function to recover, and apparently in 25% of patients it never recovers completely.