Post-liver Transplantation Management: A Detailed Review

Introduction

Liver transplantation aims to improve both life expectancy and quality of life for patients with advanced chronic liver disease (CLD) and to save lives in cases of acute liver failure (ALF). These patient groups differ significantly in age, prior health conditions, and organ dysfunction levels, requiring distinct supportive care approaches. Care focuses on monitoring and early detection of organ dysfunction, starting immunosuppression, and handling surgical complications. Close collaboration among specialists is important. Intensive care for liver transplant patients mainly involves stabilizing hemodynamics, correcting coagulation issues, weaning from ventilation, proper fluid management, preventing graft rejection, preserving kidney function, and prophylaxis against infections.

What Is Post-liver Transplantation?

Liver transplantation is widely used to treat various liver diseases, including cirrhosis, liver cancer, acute liver failure, and metabolic disorders. Advancements in anesthesia, surgery, transplant immunology, organ support, and critical care have led to longer survival for transplant recipients.

However, challenges like using marginal donors and graft recovery issues, along with postoperative complications, can limit success on an individual level. Given that liver transplantation is now performed on patients with multiple health issues, effective criteria, and care management are essential to support graft recovery and prevent complications.

CLD patients undergoing elective transplantation often return from the operating theater stable, without needing cardiovascular, oxygen, ventilatory, renal, or neurological support. Suppose the graft function is good, and there are no immediate surgical issues. In that case, these patients can quickly be taken off sedation and ventilation, extubated, and moved to the general ward within 48 hours. The system will organize treatment for ALF and complex CLD patients.

How to Manage Post-liver Transplantation Complications?

1. Cardiovascular Complications:

• Hypotension, often requiring vasopressor support like norepinephrine, can occur post-reperfusion but is usually temporary. Severe instability warrants investigation for underlying cardiac issues or new ischemic events. Right heart dysfunction from cirrhosis may need assessment, typically done through pulmonary artery catheterization to measure pressures and volumes.

• Mild to severe elevations in pulmonary arterial pressure (PAP) without intrinsic lung disease may indicate portopulmonary hypertension, sometimes managed preoperatively with pulmonary artery vasodilators.

• Acute increases in PAP during reperfusion may require Dobutamine or other inotropes to optimize cardiac output. Cardiac dysfunction in acute liver failure (ALF) may need onotropic support, with Dobutamine, Milrinone, or Levosimendan commonly used. Adrenal function assessment and hydrocortisone therapy may also be considered.

• Air embolism is a known risk during liver transplant surgery but typically presents with noticeable cardiovascular compromise in the operating room.

2. Respiratory Complications:

• High inspired oxygen levels after surgery may indicate either cardiac or primary respiratory problems. Respiratory examination and chest X-ray can reveal pneumothorax, lobar collapse, or pulmonary edema. If blood products were given, alveolar fluid build-up may result from volume overload or transfusion-related acute lung injury (TRALI).

• Re-expansion pulmonary edema can occur after draining long-standing hepatic hydrothorax. Acute lung injury (ALI) progressing to acute respiratory distress syndrome (ARDS) can develop during or after transplantation, especially in ALF cases. Chronic liver disease patients may also experience ALI or ARDS without a clear trigger, although rare. Pre-existing respiratory infections can worsen post-transplant, with pneumonia being a common complication, often caused by various bacteria and fungi.

• There is no specific ventilation strategy favored post-transplant, but high positive end-expiratory pressure (PEEP) may pose theoretical risks to liver blood flow by limiting venous return and causing congestion. However, recent research suggests that short-term PEEP up to 10 cmH20 does not impair systemic hemodynamics.

3. Renal Complications:

• Renal replacement therapy (RRT) is often started before transplant in ALF cases and should continue afterward.

• CLD patients with poor kidney function are at risk of further decline post-transplant, especially with cardiovascular instability and dehydration. Around 12 % of CLD patients may experience acute renal failure after surgery, but the majority recover renal function.

• Early initiation of RRT is recommended if there is a worsening trend in kidney function or persistently low urine output despite fluid resuscitation and optimal blood pressure. Intraoperative use of mannitol does not seem to protect renal function.

• Protective immunosuppression strategies may be considered for patients with significantly impaired pre-transplant kidney function.

4. Gastrointestinal Complications:

• All patients should initially receive ulcer prevention, typically with proton pump inhibitors. Enteral feeding can usually start unless there is a new hepaticojejunostomy or other surgical issue. In cases of abdominal swelling or when the graft is relatively large compared to the abdominal cavity, primary closure may not be possible, requiring a return to the ICU with a dressing over the incision. Closure typically occurs within two to ten days based on surgical elevation, and feeding is usually unaffected.

• Intraabdominal pressure should be monitored regularly, as increased pressure can lead to complications like renal failure, prolonged ventilation, and death. Further surgery may be necessary if pressure rises significantly.

• Pancreatitis may complicate acute liver failure (ALF) but is a relative contraindication to urgent transplantation due to high postoperative mortality. Clinical suspicion may arise from abdominal swelling, raised intraabdominal pressure, peritonitis, and elevated serum amylase levels. However, signs may be masked by sedation or paralysis due to the common systemic inflammatory response in both ALF and pancreatitis.

5. Neurological Complications:

• Fluctuations in cerebral perfusion pressure are common in the first 10 hours after surgery, posing a risk of intracranial hemorrhage (ICH) for patients with ALF immediately after transplantation.

• Close monitoring and aggressive care are necessary until graft function is confirmed and neurological stability is established. If elevated intracranial pressure is detected, deep sedation and other interventions may be needed until the graft has a positive effect.

• Neurological dysfunction usually improves within 48 hours, but any focal signs should be thoroughly investigated.

• Concerns about intracranial bleeding due to coagulopathy and/or reduced consciousness may prompt a CT scan. While hepatic encephalopathy in CLD patients can present with various signs, these are rarely observed post-transplant.

• Subclinical seizures may occur in ALF, warranting vigilance. Imaging may be necessary to rule out focal lesions causing epilepsy. Other early post-transplant neurological complications include central pontine myelinolyses (CPM) and paradoxical air embolism, especially in cirrhotic patients with hyponatremia, requiring an MRI for confirmation.

6. Hematological Complications:

• Patients often receive significant blood product transfusions during surgery, with further transfusions sometimes necessary upon returning to the ICU due to hemostatic issues.

• However, coagulation tests are crucial indicators of graft function, so additional palm transfusions should be avoided in the absence of bleeding to assess synthetic function early on accurately.

• Regular coagulation assessments should be conducted for those experiencing bleeding, including laboratory tests and thromboelastography.

• The decision to administer fresh, frozen plasma and cryoprecipitate should be made in consultation with the surgical team.

7. Antimicrobial Prophylaxis:

• Bacterial infections are common post-liver transplant (LT), with gram-negative organisms being predominant. Bacteremia may occur in up to 21 % of donors, potentially leading to transmission.

• Piperacillin-tazobactam has been found to be more effective in preventing infection compared to other antibiotics in randomized trials involving LT cases. Invasive fungal infections, like candidiasis or aspergillosis, affect 4 to 11 % of LT patients, usually diagnosed around 17 days post-LT.

• Interventions to reduce oral candidiasis risk are standard practice. Fluconazole interacts with tacrolimus, necessitating close monitoring if used concurrently. A recent study showed a significant reduction in post-LT infections (to 3 %) with a lactic acid bacteria and fiber enteral supplement.

8. Graft Failure and Dysfunction:

• Ischemic or anoxic insults during graft removal lead to hepatocellular dysfunction, with a reported incidence of clinically apparent graft dysfunction of up to 7 %. Donor factors like age, cardiovascular status, body mass index, hepatic steatosis, and cold ischemia time affect function.

• Predicting individual graft dysfunction is challenging, though steatosis and non-cranioencephalic trauma have been identified as predictive factors. Primary graft non-function (PNF) and primary graft dysfunction (PGD) have distinct definitions, but clinicians often rely on a combination of factors to suspect poor graft function.

• The management of PGD aims to reduce oxidative stress and improve microvascular perfusion. Prostaglandin E2 infusion improves morbidity, while evidence for N-acetylcysteine infusion is less established.

9. Immunosuppression:

• Tacrolimus-based immunosuppression is common post-LT but can cause neurotoxicity and nephrotoxicity. Renal-sparing induction agents like daclizumab, antithymocyte globulin (ATG), or monoclonal anti-T-cell antibodies sometimes delay calcineurin inhibitor initiation.

• Acute cellular rejection (ACR) occurs in around 30 % of recipients post-LT, typically five to ten days after surgery, requiring treatment with pulsed methylprednisolone. Liver biopsy confirmation may be challenging in patients with renal failure due to bleeding risk.

Conclusion:

Post-liver transplantation management requires a multidisciplinary approach to address complications and ensure optimal outcomes. Vigilant monitoring and prompt intervention are crucial in managing physiological challenges. Antimicrobial prophylaxis is key in preventing infections, while strategies to address graft failure and dysfunction are essential for long-term success. Despite the complexities involved, advancements in surgical techniques, critical care, and immunosuppressive therapies continue to improve for liver transplant recipients.