Cardiac Considerations During Orthotopic Liver Transplantation

Pulmonary Hypertension

Because liver transplant patients are five times more likely to have pulmonary hypertension, an echocardiogram before surgery is strongly suggested. Although liver transplant recipients are more likely to have pulmonary hypertension, the severity of pulmonary hypertension does not correlate with the severity of the liver disease.

There are no definitive recommendations on the time frame within which an echocardiogram should be obtained, but because the underlying disease can change quickly, it is best to have one done close to surgery. If the preoperative echocardiogram was not completed in a time frame that encompasses the patient's current disease state, it should be repeated.

Although the pathophysiology of pulmonary hypertension in liver disease is not fully understood, the contributing factors include neurohumoral activation, vasoconstriction within the pulmonary arteries, genetic predisposition, a hyperdynamic arterial circulatory system, and increased pressure within the venous system ( Box 17.1 ). A patient is considered to have pulmonary hypertension when the pulmonary artery systolic pressure (PASP) by echocardiography is greater than 30 mm Hg. Severity is based on the PASP with mild pulmonary hypertension being 31 to 44 mm Hg, moderate 45 to 59 mm Hg, and severe greater than 60 mm Hg. It is well documented that there is a decrease in survival for patients displaying severe pulmonary hypertension. Therefore a widely accepted absolute contraindication to liver transplantation is a PASP greater than 50 mm Hg.

Box 17.1

Proposed Etiologies of Pulmonary Hypertension in Liver Disease

• Humoral substances: serotonin, interleukin-1, glucagon, or endothelin-1 enter through portosystemic collaterals, increasing pressure in the pulmonary arteries.

• Genetic predisposition: the gene for familial pulmonary hypertension has been localized to chromosome 2.

• Thromboembolism: thromboemboli from the portal venous system to the pulmonary circulation producing pulmonary arterial hypertension.

• Hyperdynamic circulation: increased blood flow causes sheer stress on the vascular wall, producing pulmonary hypertension.

It is strongly recommended that any patient with moderate to severe pulmonary hypertension by echocardiography undergo a right heart catheterization. If the right heart catheterization shows a mean pulmonary artery pressure (PAP) greater than 25 mm Hg and a pulmonary capillary wedge pressure 15 mm Hg or less, then the liver transplant can proceed. If the mean PAP is 35 to 45 mm Hg, the patient should be referred to a pulmonologist for management. If the patient has a good response to vasodilatory therapy, then the outcome after liver transplant is comparable to that of other candidates. Any patient who has a mean PAP greater than 45 mm Hg will require initial medical management and should not receive an immediate transplant ( Table 17.2 ).

Hepatopulmonary Syndrome

Hepatopulmonary syndrome is defined by arterial hypoxemia that is attributable to pulmonary vasculature changes in the setting of advanced hepatic disease ( Box 17.2 ). The pathogenesis is unclear. It has been proposed that the damaged liver's inability to clear mediators of pulmonary vasodilation such as nitric oxide, tumor necrosis factor-α, and heme-oxygenase–derived carbon monoxide all contribute to pulmonary capillary dilation with occasional direct arteriovenous (AV) connections.

Box 17.2

Diagnostic Criteria for Hepatopulmonary Syndrome ^a

a All three criteria are required.

• Presence of liver disease (with or without portal hypertension)

• Arterial hypoxemia

• Pulmonary vascular changes

Irrespective of the pathogenesis, there are three principal mechanisms of arterial hypoxemia in HPS: ventilation/perfusion (V/Q) mismatch, diffusion limitation, and less frequently, anatomic shunt. V/Q mismatch leads to the transit of deoxygenated mixed venous blood straight into the systemic circulation, which depresses arterial saturation (i.e., high venous admixture). Diffusion limitation is the result of enlarged alveolar capillaries, which leads to a reduction in alveolar surface area relative to capillary cross-sectional area. The driving pressure (i.e., partial pressure of oxygen from alveoli to blood) is inadequate to equilibrate with the blood in the center of the enlarged capillary. Unlike a true shunt, this form of hypoxemia responds to increasing fraction of inspired oxygen (F _I O ₂ ) because this will increase the driving pressure of oxygen from the alveoli to the capillary. The severity of HPS is based on the arterial partial pressure of oxygen. Finally, direct anatomic shunt from pulmonary artery (PA) capillaries to pulmonary venous capillaries is rare and like most forms of pure shunt is refractory to increasing F _I O ₂ ( Box 17.3 ).

Box 17.3

Grading System for Hepatopulmonary Syndrome

• Mild: PaO ₂ >80 mm Hg on room air

• Moderate: PaO ₂ <80 mm Hg on room air

• Severe: PaO ₂ between 50 and 60 mm Hg on room air

• Very severe: PaO ₂ <50 mm Hg on room air or PaO ₂ <300 mm Hg on F _I O ₂ of 1.0

F _I O ₂ , Fraction of inspired oxygen; PaO ₂ , arterial partial pressure of oxygen.

The diagnosis of HPS is made via both clinical examination and diagnostic testing. Aside from dyspnea and hypoxemia in the setting of advanced hepatic disease, there are two unusual markers of HPS on clinical examination: platypnea and orthodeoxia. These are worsening dyspnea and arterial hypoxemia in the upright position, which improve by transitioning to the recumbent position. Clinically, this contrasts with most other causes of hypoxemia and dyspnea, which improve in the upright position. Mechanistically, this occurs because the majority of HPS-related vascular changes occur in the base of the lungs. Moving to the upright position forces a higher proportion of the cardiac output into these pathologic regions and worsens gas exchange.

Diagnostic testing for intrapulmonary AV shunt is done, in part, via echocardiography, again assuming this is completed in an appropriate time frame. During the echocardiogram, a bubble study can be completed to detect an intrapulmonary AV shunt, patent foramen ovale, or atrial septal defect ( Fig. 17.1 ). The late appearance of bubbles in the left atrium (e.g., 6–10 beats) is consistent with HPS and an AV shunt. In contrast, the early appearance of bubbles in the left atrium (e.g., within 2–3 beats) or a defect in the interatrial septum appreciated on two-dimensional imaging may be indicative of a patent foramen ovale or atrial septal defect.

Hepatorenal Syndrome

Hepatorenal syndrome is acute renal failure secondary to the physiologic sequelae of hepatic dysfunction. It is a diagnosis of exclusion defined by acutely worsening renal function in the setting of advanced hepatic disease once other causes of acute kidney injury have been excluded ( Box 17.4 ). The disease is categorized into severe (type 1) and less severe (type 2), which are largely defined by the rate of rise in creatinine.

Box 17.4

Diagnostic Criteria for Hepatorenal Syndrome

• Cirrhosis with ascites + AKI

  • KDIGO criteria for AKI commonly used: creatinine increase >0.3 mg/dL in <48 hours or increase in serum creatinine >50% in <7 days

• Absence of shock state

  • Confounded by the fact that spontaneous bacterial peritonitis or another infection is often a precipitant of HRS

• Absence of hypovolemia

  • Often defined as off diuretics or given a volume challenge

• Absence of precipitating or nephrotoxic medications

• Absence of parenchymal renal disease

  • Minimal hematuria or minimal proteinuria

AKI, Acute kidney injury; HRS, hepatorenal syndrome; KDIGO, Kidney Disease: Improving Global Outcomes.

The pathogenesis of HRS is secondary to cardiovascular and humoral changes associated with end-stage liver disease. As liver function declines, there is a global drop in systemic vascular resistance (SVR) secondary to increases in vasoactive mediators such as nitric oxide. The drop in SVR leads to increases in cardiac output, but a drop in systemic blood pressure. Paradoxically, the renal vascular beds often display localized increases in vascular resistance brought on by hypotension-induced increases in circulating catecholamines and activation of the renin-angiotensin-aldosterone pathway. Combined with sequestration of large volumes of fluid within the splanchnic vasculature, as well as intravascular fluid losses due to ascites and edema, this leads to profound decreases in renal blood flow and progressive renal failure. In other words, it shares pathophysiologic mechanisms similar to prerenal-type renal failure.

Hepatorenal syndrome, especially type 1, is associated with a very high mortality rate if the underlying hepatic disease is not reversed or the patient is not transplanted. Temporizing therapies are directed at improving renal perfusion. Common treatment modalities include intravascular volume expansion with exogenous albumin, while concurrently increasing perfusion pressures with vasoactive medications such as norepinephrine, vasopressin, or terlipressin. In addition, it is common for these patients presenting for liver transplantation to require continuous renal replacement therapy. This has practical implications for the transplant anesthesiologist, including vascular access limitations, hemodynamic perturbations with fluid shifts, electrolyte imbalances, and the need for support staff to manage the dialysis machine intraoperatively.