UBP 5.7 (Short Form): Hepatic – Liver Transplant & Alcoholism

Question 1

What is the MELD risk score?

(A 54-year-old, 5’10”, 62 kg gentleman is scheduled for orthotopic liver transplantation. The patient has a history of alcoholic cirrhosis with portal hypertension, jaundice, ascites, and bleeding esophageal varices. The abdominal exam reveals a tense and distended abdomen with a demonstrable fluid wave. He is a smoker and complains of dyspnea that worsens in the upright position. His medications include lactulose, neomycin, and vitamin K. Creatinine = 1.8 mg/dL.)

Answer 1

The model for end-stage liver disease, or MELD score, has replaced the Child-Turcotte-Pugh (CTP) as a tool for prioritizing organ allocation to adult patients (the pediatric end-stage liver disease model (PELD) is used to rank patients under 12 years old on the transplant list) in the hopes that it will prove superior to the CTP in allocating organs to those who are at the greatest risk of mortality.

The MELD score, which ranges from 6-40, is calculated using the patient’s –

• serum creatinine,
• bilirubin, and
• international normalized ratio (INR).

The higher the score, the higher the short-term mortality risk (most patients on the transplant list range from 11-20).

The MELD score is not utilized for patients with fulminant hepatic failure and/or a life expectancy of less than 7 days, as these individuals are designated as “Status 1” and given the highest priority.

Question 2

What do you think of this patient’s dyspnea?

(A 54-year-old, 5’10”, 62 kg gentleman is scheduled for orthotopic liver transplantation. The patient has a history of alcoholic cirrhosis with portal hypertension, jaundice, ascites, and bleeding esophageal varices. The abdominal exam reveals a tense and distended abdomen with a demonstrable fluid wave. He is a smoker and complains of dyspnea that worsens in the upright position. His medications include lactulose, neomycin, and vitamin K. Creatinine = 1.8 mg/dL.)

Answer 2

Given this patient’s history of smoking, alcohol abuse, and liver disease,

his dyspnea could be secondary to –

• smoking (COPD),
• alcoholic cardiomyopathy,
• cirrhotic cardiomyopathy,
• ascites (a tense, distended abdomen with a demonstrable fluid wave suggests significant ascites),
• pleural effusions,
• hepatopulmonary syndrome, or
• a combination of these.

Since the patient’s complaint of worsening dyspnea in the upright position (platypnea) is consistent with hepatopulmonary syndrome, I would – look for other signs and symptoms of this condition, such as –

• hypoxia (PaO2 < 70 mmHg on room air),
• fatigue,
• digital clubbing,
• spider angiomata, and
• arterial deoxygenation in the upright position (orthodeoxia).

Hepatopulmonary syndrome is defined by = the triad of liver disease, decreased oxygenation (an alveolar-arterial gradient > 20 mmHg and/or a PaO2 < 70 mmHg on room air), and intrapulmonary vascular dilation, which is diagnosed using contrast-enhanced echocardiography, perfusion lung scanning, or pulmonary arteriography.

Unless completely unresponsive to supplemental oxygen (indicating an unacceptable perioperative risk of graft hypoxia and failure),

• hepatopulmonary syndrome is an indication for liver transplantation.

Question 3

What do you think of the abdominal exam findings?

(A 54-year-old, 5’10”, 62 kg gentleman is scheduled for orthotopic liver transplantation. The patient has a history of alcoholic cirrhosis with portal hypertension, jaundice, ascites, and bleeding esophageal varices. The abdominal exam reveals a tense and distended abdomen with a demonstrable fluid wave. He is a smoker and complains of dyspnea that worsens in the upright position. His medications include lactulose, neomycin, and vitamin K. Creatinine = 1.8 mg/dL.)

Answer 3

The findings of a tense and distended abdomen with a fluid wave upon examination of this patient presenting for liver transplant is consistent with marked ascites, which may be contributing to his dyspnea.

The cause of ascites in cirrhosis is probably multifactorial, with portal hypertension and the renal retention of sodium and water (the cause of sodium retention is unclear) resulting in the transudation of fluid into the peritoneal cavity.

The accumulation of ascitic fluid in the peritoneum may exert pressure on the diaphragm and stomach that result in compromised pulmonary gas exchange and an increased risk of aspiration, respectively.

Question 4

Would you perform preoperative paracentesis?

(A 54-year-old, 5’10”, 62 kg gentleman is scheduled for orthotopic liver transplantation. The patient has a history of alcoholic cirrhosis with portal hypertension, jaundice, ascites, and bleeding esophageal varices. The abdominal exam reveals a tense and distended abdomen with a demonstrable fluid wave. He is a smoker and complains of dyspnea that worsens in the upright position. His medications include lactulose, neomycin, and vitamin K. Creatinine = 1.8 mg/dL.)

Answer 4

Assuming these exam findings represent significant ascites, I would consider preoperative therapeutic paracentesis due to the potential benefits of this procedure, such as –

• increased cardiac output
  
  • (relieves compression of inferior vena cava by ascitic fluid),
• improved pulmonary gas exchange
  
  • (increased pulmonary compliance and reduced V/Q mismatch with the reduction of ascitic fluid pressure on the diaphragm and/or pleural effusions), and
• decreased risk of gastric aspiration
  
  • (due to decreased ascitic fluid compression of the stomach).

In addition to these benefits, there is evidence that therapeutic paracentesis may –

• transiently reduce renin and aldosterone levels, serum creatinine and blood urea nitrogen, and portal pressures.

However, if I decided to perform the procedure, I would ensure adequate volume expansion with colloid solutions to prevent circulatory collapse with the progressive reaccumulation of ascitic fluid in the peritoneal space.

There is some evidence to support the practice of administering 50% of the plasma expander immediately following paracentesis, and reserving the other half for administration 6 hours later

• (when removing more than 5 L of ascitic fluid, some recommend administering albumin 6-8 g/dL of ascites drained, to prevent renal decompensation).

Question 5

Are you concerned about hepatorenal syndrome (HRS)?

(A 54-year-old, 5’10”, 62 kg gentleman is scheduled for orthotopic liver transplantation. The patient has a history of alcoholic cirrhosis with portal hypertension, jaundice, ascites, and bleeding esophageal varices. The abdominal exam reveals a tense and distended abdomen with a demonstrable fluid wave. He is a smoker and complains of dyspnea that worsens in the upright position. His medications include lactulose, neomycin, and vitamin K. Creatinine = 1.8 mg/dL.)

Answer 5

I am concerned given this patient’s elevated creatinine ( > 1.5 mg/dL), and

recognizing that up to 10% of patients with advanced liver disease and ascites develop this life-threatening functional renal failure characterized by – vasoconstriction of the renal vasculature, decreased glomerular filtration, preserved renal tubular function, hyperosmolar urine, urinary sodium excretion < 10 mEq/L, azotemia, and normal renal histology.

However, since there are many causes of renal failure in patients with end-stage liver disease, such as – pre-renal azotemia, acute tubular necrosis, and drug toxicity,

I would perform additonal laboratory testing to identify the cause of this patient’s elevated creatinine.

Question 6

How would you determine whether his elevated creatinine was due to hepatorenal syndrome?

(A 54-year-old, 5’10”, 62 kg gentleman is scheduled for orthotopic liver transplantation. The patient has a history of alcoholic cirrhosis with portal hypertension, jaundice, ascites, and bleeding esophageal varices. The abdominal exam reveals a tense and distended abdomen with a demonstrable fluid wave. He is a smoker and complains of dyspnea that worsens in the upright position. His medications include lactulose, neomycin, and vitamin K. Creatinine = 1.8 mg/dL.)

Answer 6

In determining the cause of this patient’s azotemia, I would –

• evaluate his response to a fluid challenge (1.5 liters);
• review the patient’s medications and history for the administration of nephrotoxic drugs or contrast agents; and
• check urine sodium levels, urinary osmolality, urine-to-plasma creatinine ratio, and a urinary sediment level.

If his renal function improved with a fluid challenge, this would be consistent with pre-renal azotemia rather than HRS.

If his urinary sodium was > 10 mEq/L and/or there were granular casts in the urine sediment, this would be consistent with ATN rather than HRS or pre-renal azotemia.

Moreover, I would consider the major and minor criteria that have been developed to assist in the diagnosis of HRS.

The major criteria are as follows:

1. the presence of advanced liver disease and portal hypertension;
2. a low GFR (serum creatinine > 1.5 mg/dL or creatinine clearance < 40 mL/min);
3. the absence of shock, infection, fluid losses, or treatment with nephrotoxic agents;
4. no sustained improvement in renal function in response to a 1.5 L fluid challenge;
5. the absence of proteinuria ( < 500 mg/day), urinary obstruction, or parenchymal renal disease (the latter two determined by ultrasonography).

The minor criteria include:

1. oliguria ( < 500 mL/24 hours);
2. a low urinary sodium concentration ( < 10 mEq/L);
3. a urine osmolality that exceeds plasma osmolality by at least 100 mOsm;
4. spontaneous dilutional hyponatremia (serum sodium < 130 mEq/L); and
5. the absence of red blood cells in the urine.

Question 7

Assuming this is hepatorenal syndrome, what is the pathophysiology of this condition?

(A 54-year-old, 5’10”, 62 kg gentleman is scheduled for orthotopic liver transplantation. The patient has a history of alcoholic cirrhosis with portal hypertension, jaundice, ascites, and bleeding esophageal varices. The abdominal exam reveals a tense and distended abdomen with a demonstrable fluid wave. He is a smoker and complains of dyspnea that worsens in the upright position. His medications include lactulose, neomycin, and vitamin K. Creatinine = 1.8 mg/dL.)

Answer 7

The increased levels of endothelial (prostacycline and nitric oxide) and nonendothelial (glucagon) vasodilators associated with severe liver disease lead to splanchnic arterial vasodilation.

Dilation of the splanchnic circulation leads to a reduction in “effective” blood volume sensed by the juxtaglomerular apparatus, which then leads to a compensatory activation of the renin-angiotensin-aldosterone system and sympathetic nervous system.

While activation of these systems leads to systemic and renal vasoconstriction, the effects are insufficient to counteract the vasodilation in the splanchnic circulation.

Persistent dilation of the splanchnic circulation and reduced perfusion of the kidneys results in profound intrarenal arterial vasoconstriction and, eventually, HRS.

Hepatorenal syndrome can be clinically classified as either Type 1 or Type 2 – depending on the severity and rapidity of the conditions onset.

• Type I HRS is characterized by –
  
  • rapidly progressive renal failure, with serum creatinine levels rising above 2.5 mg/dL and/or creatinine clearance decreasing to less than 20 mL per minute in less than two weeks.
• Type 2 HRS, on the other hand, is characterized by –
  
  • a slower onset, with serum creatinine levels rising above 1.5 mg/dL, but not meeting the criteria for Type 1 HRS.

Both types carry a poor prognosis (although Type 1 is worse),

with the definitive treatment being liver transplantation.

However, medical therapy with –

• albumin (volume expansion),
• midodrine (a vasoconstrictor), and
• octreotide (an inhibitor of splanchnic vasodilation)
  
  • – has been shown to significantly improve kidney function in some patients, and may serve as a bridge to transplantation.

Question 8

The patient’s platelets = 76 cells/µL, PT/PTT = 16/30 seconds, and INR = 1.4.

Would you give blood products prior to surgery?

(A 54-year-old, 5’10”, 62 kg gentleman is scheduled for orthotopic liver transplantation. The patient has a history of alcoholic cirrhosis with portal hypertension, jaundice, ascites, and bleeding esophageal varices. The abdominal exam reveals a tense and distended abdomen with a demonstrable fluid wave. He is a smoker and complains of dyspnea that worsens in the upright position. His medications include lactulose, neomycin, and vitamin K. Creatinine = 1.8 mg/dL.)

Answer 8

Given the urgency of the procedure, I would NOT attempt to normalize his coagulation status as long as his platelets were greater than 50,000-60,000 cells/µL, his INR was < 1.5, and there were no signs of active bleeding.

Hemostatic defects are common with end-stage liver disease due to –

• decreased production of coagulation and inhibitor factors
  
  • (the liver produces all the coagulation factors except factor VIII and von Willebrand’s factor),
• quantitative and qualitative platelet defects
  
  • (due primarily to portal hypertension-induced splenic sequestration),
• vitamin K deficiency
  
  • (although reduced synthesis and increased consumption play a greater role than vitamin K deficiency),
• hyperfibrinolysis
  
  • (from decreased hepatic clearance of plasminogen activator),
• decreased clearance of activated clotting factors, and
• disseminated intravascular coagulation.

The complete preoperative correction of coagulopathies associated with end-stage liver disease may prove difficult or even impossible, and the definitive treatment of liver transplantation should not be delayed unless absolutely necessary.

However, the patient’s coagulation status should be taken into account when placing invasive lines or monitors, especially when considering a pulmonary artery catheter, a TEE probe in a patient with esophageal varices, and/or an ICP monitor.

Question 9

Echocardiography estimates a pulmonary artery (PA) pressure of 46 mmHg.

Does this concern you?

(A 54-year-old, 5’10”, 62 kg gentleman is scheduled for orthotopic liver transplantation. The patient has a history of alcoholic cirrhosis with portal hypertension, jaundice, ascites, and bleeding esophageal varices. The abdominal exam reveals a tense and distended abdomen with a demonstrable fluid wave. He is a smoker and complains of dyspnea that worsens in the upright position. His medications include lactulose, neomycin, and vitamin K. Creatinine = 1.8 mg/dL.)

Answer 9

This does concern me since patients with PA pressures > 35 mmHg and pulmonary vascular resistance (PVR) > 250 dyne/sec/cm^-5 are at increased risk of perioperative death from right heart failure or hepatic failure.

In fact, since liver transplantation is contraindicated in patients with PA pressures > 50 mmHg, I would consider right heart catheterization for direct pressure measurement and confirmation of this estimated PA pressure

(echocardiographic estimates of PA pressure, determined using the maximum velocity of regurgitant flow across the tricuspid valve and the Bernoulli equation, have a poor positive predictive value).

If direct measurement indicated moderate pulmonary hypertension (mean PAP of 35-45 mmHg),

I would consider placing a pulmonary artery catheter prior to incision, recognizing that this may prove difficult in a patient with encephalopathy (patient is taking lactulose and neomycin).

Given this patient’s coagulation status, I would consider administering fresh frozen plasma and using ultrasound guidance to reduce the risk of significant bleeding during line placement

(while platelet administration could also be considered, there is some evidence that suggests platelet transfusion may prove detrimental to graft and patient survival).

Clinical Notes:

• Portopulmonary hypertension (PPH) is defined as a mean PAP > 25 mmHg or PVR > 120 dyne/sec/cm^-5 in the presence of a normal pulmonary capillary wedge pressure.
• Mild PPH = mean PAP of 25-35 mmHg
• Moderate PPH = mean PAP of 35-45 mmHg
• Severe PPH = mean PAP of > 45 mmHg

Question 10

Couldn’t you just utilize TEE and avoid placement of a pulmonary artery catheter?

(A 54-year-old, 5’10”, 62 kg gentleman is scheduled for orthotopic liver transplantation. The patient has a history of alcoholic cirrhosis with portal hypertension, jaundice, ascites, and bleeding esophageal varices. The abdominal exam reveals a tense and distended abdomen with a demonstrable fluid wave. He is a smoker and complains of dyspnea that worsens in the upright position. His medications include lactulose, neomycin, and vitamin K. Creatinine = 1.8 mg/dL.)

Answer 10

TEE could also be used during surgery to monitor cardiac function and fluid status of this patient with pulmonary hypertension.

However, I would be reluctant to utilize this monitor due to the increased risk of bleeding associated with placement in the presence of esophageal varices, a relative contraindication to TEE placement.

As always, this decision would have to be made after weighing all the associated risks and benefits.

Contraindications of TEE:
A. Absolute contraindications:

• Esophageal spasm.
• Esophageal stricture.
• Esophageal laceration.
• Esophageal perforation.
• Esophageal diverticula (e.g. Zenker?s diverticulum).

B. Relative contraindications:

• Large diaphragmatic hernia may significantly hinder TEE imaging because of lack of transducer mucosal approximation.
• Atlantoaxial disease and severe generalized cervical arthritis: TEE should never be performed if there is any question about stability of cervical spine.
• Patients who received extensive radiation to the mediastinum: this can cause significant difficulty in probe manipulation within the esophagus and is a relative contraindication if the anatomy of the esophagus is not known.
• Upper gastrointestinal bleeding, significant dysphagia and odynophagia are also relative contraindications (Khoury et al., 1994).

Question 11

The patient seems mildly confused.

Does this concern you?

(A 54-year-old, 5’10”, 62 kg gentleman is scheduled for orthotopic liver transplantation. The patient has a history of alcoholic cirrhosis with portal hypertension, jaundice, ascites, and bleeding esophageal varices. The abdominal exam reveals a tense and distended abdomen with a demonstrable fluid wave. He is a smoker and complains of dyspnea that worsens in the upright position. His medications include lactulose, neomycin, and vitamin K. Creatinine = 1.8 mg/dL.)

Answer 11

His treatment with neomycin and lactulose, drugs used to reduce the production of ammonia by intestinal bacteria, suggests previous problems with hepatic encephalopathy.

This mild confusion, therefore, does concern me because it may represent ongoing or worsening hepatic encephalopathy.

It is believed that hepatic encephalopathy results when – impaired liver function leads to the accumulation of circulating neurotoxins, such as – ammonia, GABA, mercaptans, short-chain fatty acids, and manganese.

Other potential contributing factors include – altered cerebral energy homeostasis, astrocyte swelling, and disruption of the blood brain barrier.

There are also several conditions that are associated with the precipitation of hepatic encephalopathy, such as – increased dietary protein, gastrointestinal bleeding, infection, hypovolemia, anemia, azotemia, paracentesis, recent creation of a portal-systemic shunt (TIPS procedure), diarrhea and vomiting, or diuretic therapy.

If after considering other potential causes of mild confusion (i.e. chronic subdural hematoma, psychoactive drugs, and Wernicke’s encephalopathy in this alcoholic patient) I believed this was hepatic encephalopathy, I woulld –

• attempt to identify and treat any potential inciting factors, giving special consideration to esophageal bleeding in this patient with a history of esophageal varices.
• In addition, I would evaluate the patient for signs of increased intracranial pressure, although increased ICP and cerebral edema are more likely in acute liver failure;
• AVOID HYPOkalemia, which can increase the renal production of ammonia;
• maintain a normal arterial pH, since alkalemia may lead to increased diffusion of ammonia across the blood brain barrier;
• correct any hypovolemia or anemia to optimize liver metabolism of circulating toxins; and
• use benzodiazepines and other psychoactive drugs cautiously, recognizing that further suppression of the central nervous system may exacerbate his condition.