Decompensated Dyspneic Dilemma

Abhi Shenoy

Case

A 57-year old male with a past medical history of hypertension, T2DM, and decompensated NASH cirrhosis presented to the hospital with lower extremity edema, abdominal distention and an 8-pound weight gain over the last few months and was subsequently admitted to the floor GI team. He reports improvement of his dyspnea when lying flat. He has been admitted 3-4 times in the last month due to various complications of cirrhosis, including hepatic encephalopathy, refractory ascites, and bleeding esophageal varices. He is currently listed for liver transplantation.

On examination, he is hemodynamically stable without hypotension or tachycardia, though over the last few weeks, has had a worsening oxygen requirement, now up to 3L from 1L two weeks ago. His BMI is 34 kg/m2. Physical exam is notable for abdominal distention, caput medusae, spider angiomata, + fluid wave, 2+ LE edema, AAOx3, no asterixis. Subtle cyanosis and digital clubbing is noted.

Which therapy is most likely to improve oxygenation in this patient?

Correct Answer:

Liver Transplantation

Answer: Liver Transplantation

Definition/Epidemiology of Hepatopulmonary Syndrome:

Hepatopulmonary syndrome (HPS), a term coined in 1977, has been increasingly recognized as an important clinical cause of dyspnea in decompensated cirrhosis, which can significantly impact mortality and influence liver transplant candidacy. It is a problem with the pulmonary vasculature, not the parenchyma, pleura, or diaphragm. It is now seen in up to 5-10% of patients who are undergoing evaluation for liver transplantation. Portal hypertension (including non-cirrhotic) is necessary for the manifestations associated with HPS. The presence of HPS may also influence the severity and frequency of portal hypertension-related complications.

The HPS symptom triad:

  1. Underlying Liver Disease with portal hypertension
  2. Pulmonary vascular dilatation (impairing gas exchange)
  3. Defect in Oxygenation

Practical Tips:

  1. If a patient has a PaO2 <70-80 mm Hg (preferably measured at rest, sitting) it is useful in helping identify clinically significant HPS. Severity of HPS significantly influences survival.
  2. Major cardiopulmonary abnormalities should be excluded to establish diagnosis, though HPS can coexist with primary cardiopulmonary abnormalities.

Figure 1. Diagnostic Criteria

**Adapted from Rodriguez-Roisin et al. N Engl J Med. 2008 May 29:358(22):2378-87.


Back to the case

As our patient became progressively hypoxemic, our patient was evaluated and accepted by the intensive care unit tam for further management.

Labs revealed: Na 128, Cr 1.2, Albumin 2.3, AST 90, ALT 136, INR 2.4, Platelets 97, Total Bilirubin 3.1. Hepatitis serologies, ANA, ASMA, AMA, LKM, A1AT, Iron Studies, Ceruloplasmin previously within normal limits.

He proceeded to desaturate and a STAT Arterial blood gas revealed: PaO2: 49 mmHg on high-flow nasal cannula oxygen. A Chest X-ray revealed a non-specific reticulonodular pattern bilaterally in the basal zones. CT Pulmonary angiography was performed which was negative for pulmonary embolism.

Review of prior records showed a recent EGD with Grade II varices (eradicated) and an ultrasound showing splenomegaly indicating a presence of portal hypertension.

Pathophysiology:

  • The pathophysiology remains unclear but many mechanistic hypotheses exist.
  • Portal hypertension is central to the development of HPS
  • HPS can develop in the setting portal hypertension secondary to cirrhosis or non-cirrhotic portal hypertension
  • Portal hypertension leads to micro-vascular dilatation of the pulmonary arterial circulation (due to angiogenesis, remodeling) leads to ineffective gas exchange à shunting of mixed venous blood à V/Q mismatch and decreased oxygenation (See figure 2)
  • There is also the absence of compensatory pulmonary vasoconstriction, which accentuates hypoxemia in patients with cirrhosis.

Why is there intrapulmonary vasodilatation? Short answer = Increased nitric oxide

Why is there increased nitric oxide in cirrhotics with HPS or in portal hypertension? Unknown.

Cool fact: Many studies have measured pulmonary production of exhaled NO in patients with cirrhosis. They are elevated with HPS and subsequently normalize post-OLT.

Figure 2. Pathophysiology of HPS

**Adapted from Rodriguez-Roisin et al. N Engl J Med. 2008 May 29:358(22):2378-87.

 

Clinical Manifestations: 

Respiratory symptoms with findings associated with cirrhosis and chronic liver disease are predominant.

  1. Dyspnea (on exertion more commonly) usually after years of liver disease
  2. Platypnea (dyspnea exacerbated when sitting up, improved by lying supine)
  3. Orthodeoxia (hypoxemia exacerbated by sitting up in upright position)
  4. Spider angiomata
  5. Digital clubbing
  6. Distal cyanosis

Important Trap: Do not mix up Porto-pulmonary hypertension with HPS

  • Obstruction of pulmonary arterial bed (due to portal vein mechanical obstruction) or hyper dynamic pulmonary circulation in the setting of cirrhosis leads to vasoconstriction, increased vascular resistance in the pulmonary vasculature, right heart failure and eventual death
  • Porto-pulmonary hypertension diagnosis is made by right heart catheterization

Treatment: Supportive care. No disease specific treatment modalities exist for HPS, aside from liver transplantation.

Survival without transplantation:

  • Overall survival in those not candidates for liver transplantation (due to comorbidities or age)
    • Median survival: 24 months
    • 5-year survival: 23%
  • Survival worse among those with PaO2 <50 mm Hg

Survival with transplantation:

  • 5-year overall survival of 76% after liver transplantation

Requirements for HPS MELD Exception for high priority liver transplantation: Must meet all 4 criteria

  1. Splenomegaly, varices, ascites, or thrombocytopenia
  2. Demonstrated shunt (either by ECHO or pulmonary scan)
  3. PaO2 of 60mmHg or less on room air within 30 days
  4. No underlying primary pulmonary disease

Back to the case

Our patient is now in the ICU on 100% FiO2 high-flow oxygen therapy. His PaO2 is now 60 mm Hg on room air. The transplant surgeons have evaluated the patient and find him to be a good candidate for transplantation. He is sent for a TTE with bubble study to rule out cardiopulmonary contributions to his dyspnea, and to confirm suspected hepatopulmonary syndrome.

His TTE with agitated saline revealed the following:

**Adapted from Rodriguez-Roisin et al. N Engl J Med. 2008 May 29:358(22):2378-87.

Understanding the Contrast-enhanced TTE with agitated saline:

  • Contrast is injected intravenously and TTE imaging is captured only after saline/bubbles are noted within the right atrium. Patient may be asked to cough or perform Valsalva maneuver to increase RA Pressure and creating a RA-to-LA pressure gradient
    • Negative study:
      • No bubbles visualized within the left heart after 2-10 cardiac cycles = No shunt
    • Positive study:
      • The presence of bubbles in 3-5 cardiac cycles (early) = Intracardiac shunt
      • The presence of bubbles in 4-8 cardiac cycles (delayed) = Intrapulmonary shunt
    • Figure A: Opacification of the right atrium and right ventricle with microbubbles shows the beginning of the study
    • Figure B: The opacification of the left atrium/left ventricle was after five cardiac cycles (delayed) confirming a intrapulmonary shunt, not an intracardiac shunt.

Back to the case

Our patient underwent a successful liver transplantation during this hospitalization and recovered well. He was able to be weaned off supplemental oxygen altogether over the following 6 months.

Take Home Points

  • HPS may present with dyspnea, cyanosis, spider angiomata, clubbing, platypnea, orthodeoxia
  • Definition: Wide (AaPO2) on room air = > 15 mm Hg (>20 mmHg if >64 years old)
  • Caused by pulmonary vascular dilatation and insufficient arterio-alveolar gas exchange which in-turn leads to hypoxemia
  • PaO2 of 60mm Hg or less
  • Treatment: Supportive care. No disease specific treatment modalities exist for HPS, aside from liver transplantation

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