A 42-year-old male is admitted to ICU following a cadaveric orthotopic liver transplant for end-stage liver disease secondary to alcohol-induced cirrhosis.

  • List the important management principles for the first 24 hours specific to this patient.
  • Despite weaning sedation he remains unresponsive 12 hours after ICU admission. What are the possible causes?
 

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College Answer

a)

Haemodynamic stabilization – optimize cardiac output and tissue perfusion and avoid fluid overload as ventricular function may be impaired. Close haemodynamic monitoring. Vaso-active agents as indicated.

Correction of anaemia and coagulopathy – maintain haemocrit 0.25 – 0.3 to keep blood viscosity low. INR £2, APTT £50 secs, Fibrinogen above 0.5 g/L and Platelets above 30 x 109/L.

Fluid and electrolyte management – appropriate negative fluid balance day 1 decreases risk of pulmonary complications. Fluid overload may aggravate graft congestion and oedema caused by ischaemic-reperfusion. Electrolyte imbalances are common and need to be corrected.

Correction of metabolic abnormalities – hypoglycaemia is an ominous sign of compromised liver recovery, hyperglycaemia also may occur, acid-base abnormalities also occur

Early weaning from mechanical ventilation – associated with better outcome but not feasible in patients with respiratory failure, haemodynamic instability, pulmonary oedema, primary graft dysfunction, encephalopathy etc. Unsucessful early extubation may result in impaired oxygen delivery to transplanted liver

Monitoring of graft function LFTs, lactate, BSL, coagulation, hepatic artery doppler

Early detection of surgical complications - bleeding

Immunosuppressants

Infection prophylaxis

Housekeeping including analgesia (PCA) and appropriate nutrition plan

Other – ICP monitoring if decompensated CLD pre-op

b)

Delayed metabolism of sedative / anaesthetic drugs

Metabolic derangements – hypoglycaemia, hyponatraemia, hyperosmolar syndrome

Hepatic encephalopathy

Hypoxic-ischaemic cerebral injury

Seizures

Intracerebral haemorrhage

Discussion

This is a delicate topic for anybody who has not had the privilege of working in one of the sandstone centres of excellence, where liver transplants for the rich and famous serve as a constant source of private funding and media attention.

Thus, let there be a brief digression into the specifics of managing a post-op orthotopic liver transplant patient in the ICU.

(Incidentally, for those like me who were unsure precisely what the long words mean, "orthotopic" transplantation is the total removal of the old diseased liver, and the implantation of the donated organ into the same anatomical position).

The above link points to a scanned document from the Atlas of Organ Transplantation, which deals extensively with the pre-operative and peri-operative management of liver transplantation, detailing such interesting time intervals as "the Anhepatic stage". It however, is more aimed at the surgeons. Because the quality of the scanner leaves much to be desired, the gory pictures of open livers are just black-and-white blurs.

However, there is plenty of literature regarding the critical care management of liver transplant recipients.

Let us approach this answer systematically.

  • Airway:
    • Historically these patients tend to remain intubated for the first 12-24 hours, although there is good evidence that early extubation (eg. in theatre) has no adverse effects.
  • Breathing:
    • In order for the graft to survive normoxia must be established
    • The general "word of mouth" advice in these situations is to minimise the PEEP. In order for the anastomoses to remain intact, PEEP should be minimised, as it will increase the CVP and thus compromise the venous vascular anastomotic sites. However, some studies have reported no significant change to the hepatic venous flow even with PEEP as high as 15cm H2O.
    • Positive pressure ventilation in general is a bad idea, as organ perfusion is decreased by positive pressure, and perfusion of the donated liver is very important in the early stages.
    • Thus, early weaning from invasive ventilation is one of the major goals
  • Circulation
    • There is likely to be a degree of shock. Given that fluid management must remain relatively conservative, vasopressors and inotropes must be deployed liberally. After all, the graft needs to remain perfused.
    • Hepatic oedema due to over-resuscitation should be avoided.
    • Arbitrarily, the CVP should remain within the range of 6-10.
    • Observe for reactive vasoconstriction
      • These patients, with heir dead livers, have been in a vasodilated state, associated with nitric oxide synthase hyperactivity.
      • Now, with their new livers, normal vascular tone will return.
      • This might mean a sudden massive increase in the afterload.
      • Thus, their left ventricles, which are chronically deconditioned, might decompensate when faced with such demands.
      • Thus, GTN or nitroprusside infusions should be used liberally in these people.
    • The need for RF and LV functional assessment as well as pulmonary arterial pressure measurements and
  • Neurology and sedation
    • No specific recommendations can be made, rather than to say that both hepatic and renal dysfunction in the post-operative period is to be anticipated, and thus drugs which do not rely on organ metabolism should be used. Remifentanyl and propofol spring to mind.
  • Fluids and electrolytes
    • There is some "magical" preload at which the CVP is reasonable, preload adequate, and cardiac output satisfactory. Finding this magic preload is something of an art.
    • Initially, fluid resuscitation should take place, but the fluid of choice should not be Hartmanns because the new liver will probably not be able to metabolise the lactate.
    • After the initial post-operative resuscitation phase is over, a negative fluid balance should be pursued; generating a lower pressure in the right side of the thoracic circulation will serve to draw blood from the graft, and thus theoretically should improve graft perfusion.
    • Renal function needs to be watched closely - renal failure is associated with poor graft survival.
  • Graft function
    • There is a phase of "preservation injury" with very high LFTs but this tends to disappear over the first 3-4 days. Thereafter, synthetic function should be restored.
    • Monitoring of the graft consist of several sequential assessments:
      • Hepatic arterial Doppler
      • BSL
      • Lactate
      • Bilirubin
    • Typically, 1-9% of liver transplants fail within hours of surgery.
  • Surveillance for abdominal compartment syndrome
    • Due to the extensive nature of the procedure and due to the preexisting portal venous pathology, this issue (with pressure over 25mmHg) is fairly common.
    • Abdominal girth values are required as sequential measurements.
  • Nutritional support
    • There is no string reason to recommend TPN here. Like in most other situation, nasogastric enteral feeding is probably best. A degree of ileus is to be expected, and usually resolves
  • Hematological support
    • This consists of the replacement of missing blood products and blood cells.
    • Essentially, there is no specific hemoglobin goal, and what you are trying to do is prevent bleeding from the anastomotic sites.
    • Its probably OK to be slightly coagulopathic, because you don't want to develop a hepatic arterial thrombus.
  • Immune suppression
    • I will not litter this summary with discussion of the relative merits of each class of antirejection drug. Suffice to say, cyclosporin tacrolimus and mycophenolate are gradually giving way to monoclonal antibodies and other immunomodulator drugs which have slightly less devastating organ system effects.
  • Antibiotics and sepsis surveillance
    • Many of these patients die from postoperative infectious complications
    • 48 hrs of IV antibiotics are typically administered
    • The Sanford Guide recommends linezolid, ciprofloxacin and fluconazole.
    • The belowlinked article from 2011 also suggests 14 days of aciclovir, given the propensity for embarrassing HSV reactivation.

The second part of this question is far less interesting, and refers mainly to the candidate's ability to generate differentials for a decreased level of consciousness.

Using a usual template, one can arrive at a series of differential easily:

  • Vascular causes, eg. stroke or hypoxic brain injury
  • Infectious causes, eg. reactivated HSV or CMV encephalitis
  • Drug-related causes, eg. slow metabolism of anaesthetic drugs reliant on hepatic clearance
  • Hepatic encephalopathy
  • Haematological, eg. intracranial bleeding due to coagulopathy
  • Electrolyte disturbances, for instance cerebral oedema due to hyponatremia
  • Endocrine disturbance eg. hypoglycaemia

References

References

The best, most comprehensive source is this article:

Feltracco, Paolo, et al. "Intensive care management of liver transplanted patients." World journal of hepatology 3.3 (2011): 61.

The rest are also helpful.

Stieber, Andrei C., R. D. Gordon, and J. R. Galloway. "Orthotopic liver transplantation." Hepatology. A text book of liver disease. WB Saunders, Philadelphia (1996): 1759-1780.

Mazariegos, George V., Ernesto P. Molmenti, and David J. Kramer. "Early complications after orthotopic liver transplantation." Surgical Clinics of North America 79.1 (1999): 109-129.

Razonable, Raymund R., et al. "Critical care issues in patients after liver transplantation." Liver Transplantation 17.5 (2011): 511.

Mandell, M. Susan, et al. "Reduced use of intensive care after liver transplantation: influence of early extubation." Liver Transplantation 8.8 (2002): 676-681.