Transcript Pulmonary CPC - Scott & White Memorial Hospital

Pulmonary CPC
Taylor Pruett, MD
January 11, 2008
CC: Weakness
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HPI: 54 year old Caucasian female with chief complaint of
weakness. She has a history of cirrhosis secondary to
Hepatitis C. Extensive rheumatologic evaluation at the
time of diagnosis was negative.
The patient was referred to the pulmonary department 2
years prior to the current presentation for dyspnea. Several
tests were performed in evaluation of this. Spirometry was
normal; the DLco was 49% predicted. Shunt study X 2
was 11%. Oxygen requirements to maintain oxygen
saturations over 92% was 4-6 LPM. Echocardiogram with
agitated saline was normal except for the late appearance of
bubbles in the pulmonary veins suggestive of
intrapulmonary shunting. Pulmonary arteriograms and CT
of the chest were normal.
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Due to the persistent hypoxemia, the patient was listed high
for transplant.
Liver transplant was performed eight months prior to this
admission. The patient reported that she no longer
required oxygen by two months post-transplant.
Four months prior to this admission the patient had a mild
course of rejection, and one month prior to admission she
was diagnosed with hepatic encephalopathy. Liver biopsy
was performed at that time and revealed Grade 3, stage 2
Hepatitis C without rejection. Lactulose was initiated, but
since then the patient has had increasing weakness,
dyspnea, and mild lower extremity edema.
Her BP post-transplant was in the 120s/70s and her
creatinine ranged from 1.4-1.9. Her transaminases were 2X
the upper limit of normal.
History
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Past Medical History: as above, plus iron deficiency anemia and allergic
rhinitis
Past Surgical History: liver transplant, cesarean section 20 years ago,
tonsillectomy remotely
Social: The patient currently stays at home. She denies alcohol,
tobacco, or illicit drug use. She and her husband live in Waco
Allergies: Erythromycin, Zosyn, Vicodin
Medications
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Prograf 1 mg po daily
Myfortic 360 mg po nightly
Prevacid 30 mg po BID
Bumex 1 mg po daily
Centrum daily
Caltrate-D daily
Actigall 300 mg po QID
Reglan 10 mg po TID
Physical Exam
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Vital Signs: Afebrile, BP 115/77, P 84, O2 sat 93% on RA
General: Fatigued, Oriented X3
HEENT: PERRLA, mild icterus, oral mucosa moist
Neck: no adenopathy; JVP with a variable degree of
elevation by multiple examiners
Lungs: no rales
Cardiovascular: regular rhythm with questionable murmur
and ventricular lift
Abdomen: soft, no rebound tenderness, no hepatomegaly
or evidence of ascites
Extremities: edema to the lower calves that is symmetric
Laboratory Data
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WBC 4.9, normal diff
Hb 17.1
Platelets 106
Troponin 0.14
CK 48
CKMB 7.5
Na 140
K 5.5
Cl 107
carbon dioxide 22
BUN 21
Cr 1.9
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TBili 4.7
Alk phos 119
AST 88
ALT 32
TP 6.0
Alb 3.7
INR 1.5
PT 17.4
PTT 43
BNP 1792
Studies
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EKG revealed normal sinus rhythm with right axis deviation,
right ventricular hypertrophy, and an incomplete right bundle
branch block. There was evidence of left atrial enlargement
and anteroseptal infarction, age undetermined.
Chest Xray: hazy opacification at the loft lower thorax with
blunting of the costophrenic angles bilaterally consistent with
pleural fluid or thickening. Cardiac silhouette remains
prominent and there is slight fullness at the hilar region.
Limited echocardiogram at the bedside in the Emergency
room revealed a large pericardial effusion.
Hospital Course
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The patient was admitted for further evaluation
She underwent pericardiocentesis with removal of 175 ml of serous
fluid
Blood pressure subsequently declined with fall in urine output
EKG was unchanged
Creatinine increased from 1.9 on admission to 2.7 then 3.8 the
following day
A diagnostic procedure was performed, and the patient ultimately
expired
Objectives
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Discussion of pre-transplant diagnosis
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Discussion of post-transplant diagnosis
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Desired diagnostic testing
Problem List (Pre-transplant)
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Dyspnea
Hepatitis C with cirrhosis
Pulmonary function abnormalities (decreased DLCO)
Severe hypoxemia
Intrapulmonary shunt
Hepatopulmonary Syndrome
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Hepatopulmonary syndrome consists of a triad of
advanced chronic liver disease, arterial oxygenation defect,
and widespread intrapulmonary vascular dilations (IPVDs)
Estimated to occur in 4 – 47% of patients with chronic
liver disease
Mild to moderate hypoxemia is common in chronic liver
disease
Severe hypoxemia with PaO2 <60 mmHg should suggest
HPS (in the absence of other cardiopulmonary disease)
Can be associated with any form of chronic liver disease as
well as some forms of acute liver disease
Clinical Manifestations
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80% of patients have signs of chronic liver disease as their
initial presentation. 20% present with dyspnea.
The presence of abundant spider angiomata has been
suggested as a marker for the severity of HPS
Frequently associated with hyperdynamic circulation
manifested as elevated cardiac output (>7 L/min),
decreased systemic and pulmonary vascular resistance, and
narrowed arterial – mixed venous oxygen content
difference
Pulmonary findings include platypnea (increase in dyspnea
in the upright position) and orthodexia (decrease O2 sat in
the upright position)
Intrapulmonary Vascular Dilations
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IPVDs are the hallmark of hepatopulmonary syndrome
They are widespread vascular dilations which result in
decreased resistance and increased blood flow through
the pulmonary vasculature.
Unclear what causes IPVDs. Suggested causes include
failure of the damaged liver to metabolize circulating
vasodilators, production of a vasodilator by the liver, and
inhibition of circulating vasoconstrictor by the damaged
liver
Nitric oxide and the persistent induction of nitric oxide
synthase are presumed to play a role in the development
of IPVDs
IPVDs
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Diffuse dilatation of the pulmonary circulation results
in a right-to-left shunt, orthodexia, loss of hypoxia
induced vasoconstriction, and over-perfusion of low
ventilation areas
Orthodexia thought to be secondary to perfusion of
IPVDs in the lung bases in the upright position
Hypoxemia in HPS
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Three components to gas exchange abnormalities:
-ventilation - perfusion mismatch
-intrapulmonary shunting
-impaired oxygen diffusion
All of these mechanisms are a direct result of IPVDs
When HPS is mild, the predominant mechanism of
hypoxemia is V/Q mismatch. This is due to the
presence of areas in which ventilation is preserved,
but perfusion is profoundly increased due to massive
dilation of the vessels
When HPS is severe, the primary mechanism of
hypoxemia is intrapulmonary right-to-left shunting
Right-to-Left Shunting
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Anatomic shunt exists when the alveoli are bypassed. This
occurs in intracardiac shunts, pulmonary AVMs, and
hepatopulmonary syndrome
Physiologic shunts occur when there is perfusion of nonventilated areas such as in atelectasis, pneumonia, and
ARDS
IPVDs do not function as true anatomic shunts
Oxygen molecules are unable to diffuse to the center of the
blood vessel due to the degree of dilation and the large
diameter of the vessel.
Oxygenation typically improves as supplemental oxygen is
provided
IPVDs
Diagnosis
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Echocardiogram (contrast-enhanced) – gold standard for diagnosis
Nuclear Scanning (Scans show uptake over the kidneys of
Technetium-labeled macroaggregated albumin which should normally
be trapped by the pulmonary bed)
Pulmonary angiography (used to exclude other causes of hypoxemia)
Chest Xray (usually relatively normal)
Pulmonary function tests
-Spirometry (usually normal unless there is coexisting obstructive or
restrictive lung disease)
-Diffusion capacity (mildly to severely impaired)
-Shunt fraction
-ABG (PaO2 <80 mmHG and A-a gradient >20 mmHG)
Echocardiogram
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Contrast-enhanced echo is the preferred diagnostic modality
for detecting IPVDs
Intravenous indocyanine dye or agitated saline can
differentiate between intracardiac and intrapulmonary shunts.
These are normally filtered by the pulmonary bed and do not
enter the left heart.
In an intracardiac shunt, dye will appear in the left heart
within 3 heartbeats
In an intrapulmonary shunt, dye will appear in the left heart
later, within 3-6 heartbeats
TEE can directly visualize microbubbles in the pulmonary
veins as they enter the left atrium
Treatment
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Multiple attempts have been made to improve oxygenation in
HPS. There has been no improvement associated with
attempts to physically occlude IPVDs, oppose vasodilators,
and treatment of the underlying liver disease.
A few case reports have documented improvement with
transjugular intrahepatic portosystemic shunt placement
(TIPS), but this has been inconsistent and its use is not
recommended.
One report on a single patient successfully treated with
inhaled N(G)-nitro-L-arginine methyl ester (L-NAME) which
is an inhibitor of nitric oxide synthesis. Treatment resulted in
an increase of PaO2 from 52 to 70 mmHg and an increase in
the 6 minute walk distance.
Liver Transplant
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To date, liver transplant offers the most benefit for patients with severe
and refractory hypoxemia.
Significant improvements in oxygenation and reversal of shunting have
been documented after transplantation.
No randomized trials have been performed in this area, however,
multiple observational studies show significant survival benefit
Back to our patient…
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Met criteria for HPS (severe hypoxemia, chronic liver disease, IPVDs)
Underwent liver transplant 8 months ago. Significant improvement in
oxygenation (she no longer required supplemental O2 after 2 months)
Unfortunately, the patient has now developed signs of chronic liver
disease including hepatic encephalopathy.
Biopsy of the transplanted liver reveals advanced hepatitis C
Current Problem List
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Weakness, Dyspnea, Edema
Active hepatitis C in transplanted liver
Immunocompromised
Evidence of right-sided heart failure (demonstrated by EKG, elevated
BNP, and physical exam)
Pericardial effusion
Pulmonary Hypertension
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Pathologic state characterized by consistently elevated
pulmonary arterial pressure and secondary right ventricular
failure.
Defined as a mean pulmonary artery pressure greater than
25 mmHg at rest or 30 mmHg with exercise (as measured
with right heart cath)
Elevation of the pressure inside the normally low pressure
pulmonary vascular bed results in increased vascular
resistance and decreased cardiac output.
Results from reduction in the caliber of the pulmonary
vessels, an increase in pulmonary blood flow, or both.
Classification
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Pulmonary hypertension was previously classified as either Idiopathic
pulmonary arterial hypertension (IPAH – also called Primary
pulmonary hypertension) or secondary pulmonary hypertension
Some forms of secondary PH very closely resemble IPAH in their
histopathologic features, history, and response to treatment.
The World Health Organization has now reclassified pulmonary
hypertension into five groups
WHO Classifications
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Group 1 PH – “Pulmonary Arterial Hypertension”
Group 2 PH – “Pulmonary venous hypertension” – PH
due to left-sided heart disease (atrial, ventricular, or
valvular)
Group 3 PH – “PH associated with disorders or the
respiratory system or hypoxemia” – includes interstitial lung
disease, COPD, obstructive sleep apnea, alveolar
hypoventilation disorders, and other causes of hypoxemia
Group 4 PH – “PH caused by chronic thromboembolic
disease” – includes chronic thrombotic occlusion of the
vasculature as well as non thrombotic PE (eg,
schistosomiasis)
Group 5 PH – caused by inflammation, mechanical
obstruction, or extrinsic compression of the pulmonary
vasculature (sarcoidosis, histiocytosis, fibrosing
mediastinitis)
Group 1 PAH
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Referred to as Pulmonary Arterial Hypertension (PAH)
Includes sporadic and familial IPAH, as well as PAH
secondary to diseases which localize to the small pulmonary
arterioles (Collagen vascular diseases, congenital heart disease
with systemic-to-pulmonary shunts, portal hypertension, HIV,
and anorexigens)
Hemodynamic parameters of PAH:
-mean PAP >25 mmHg at rest or 30 mmHg with exercise
-Pulmonary capillary wedge pressure PCWP <15 mmHG
-Pulmonary vascular resistance >120 dynes/sec/cm5
-Transpulmonary gradient >10 mmHg (difference between
mean PAP and PCWP
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Idiopathic pulmonary arterial hypertension exists when
another cause cannot be identified. There may be a role of
an abnormal bone morphogenic protein receptor type II
(up to 25% of sporadic IPAH have abnormal BMPR2)
Possibly autosomal dominant with incomplete penetrance
of BMPR2 in familial IPAH
Collagen vascular diseases such as scleroderma cause
obliteration of alveolar capillaries and narrowing of small
arteries and arterioles due to pulmonary vascular disease
and interstitial fibrosis. There is an association with the
presence of Raynaud phenomenon and those who develop
PAH.
Intracardiac shunts result in pulmonary blood volume
overload, resulting in PAH
Anorexigens, stimulants, HIV can all result in PAH
Portopulmonary Hypertension
Portopulmonary Hypertension
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PPHTN refers to pulmonary arterial hypertension which is
associated with portal hypertension and there is no other
identifiable cause of the PAH.
PPHTN is demonstrated by right heart cath. The
parameters for diagnosis are the same as PAH.
The prevalence of PPHTN is highest in patients
undergoing evaluation for liver transplant (3.5 to 16.1%)
Chronic liver disease without portal hypertension does not
cause PPHTN.
Causes of portal hypertension which have been associated
with PPHTN include cirrhosis, portal vein thrombosis,
hepatic vein sclerosis, congenital portal circulation
abnormalities, and periportal fibrosis
Pathogenesis of PPHTN
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The cause of PPHTN is not known.
The most accepted theory is that a humoral substance which
would normally be metabolized by the liver is able to reach the
pulmonary circulation. Proposed substances include
serotonin, IL-1, endothelin-1, glucagon, secretin,
thromboxane B2, and vasoactive intestinal peptide.
Increased levels of all of these substances have been detected
in patients with portal hypertension
May be a genetic predisposition (abnormal BMPR2)
Thromboembolism from the portal system
Hyperdynamic circulation in patients with liver disease may
cause PPHTN due to increased blood flow and increased
sheer stress on the pulmonary vasculature
Pathology
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The findings in PPHTN are identical to those seen in IPAH.
Findings include vasoconstriction, remodeling of the muscular
pulmonary arterial walls, and in situ thrombosis
2 subtypes of pulmonary arteriopathy in PPHTN:
-Plexogenic pulmonary arteriopathy – medial hypertrophy, intimal
fibrosis, and lesions which involve the entire wall of the vessel.
-Thrombotic pulmonary arteriopathy – characterized by medial
hypertrophy, thrombosis, and eccentric, nonlaminar intimal fibrosis.
Plexogenic lesions generally indicate that PH is irreversible.
Medial hypertrophy is an early and potentially reversible form of the
disease
Clinical Presentation
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Patients typically present with exertional dyspnea, lethargy, and
fatigue. These symptoms are due to inability of the cardiac
output to increase with exercise.
Exertional chest pain, syncope, and edema may develop as
right ventricular failure develops.
Anorexia and abdominal pain may result from passive hepatic
congestion
Cough, hemoptysis, and hoarseness (Ortner’s syndrome) may
develop due to compression of the laryngeal nerve by a
dilated pulmonary artery.
In PPHTN, manifestations of portal hypertension typically
precede those of PAH. These symptoms typically appear
from 2-15 years before PAH is documented
Physical exam
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Increased intensity of the pulmonic component of the second heart
sound (may be palpable). Splitting of the second heart sound widens
with right ventricular failure or right bundle branch block
Systolic ejection murmur, increased with inspiration
Right ventricular failure results in systemic venous hypertension, which
can lead to elevated jugular venous pressure, RV third heart sound,
tricuspid murmur if regurgitation is present, hepatomegaly, pulsatile
liver, peripheral edema, and ascites
Diagnostic Evaluation
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Chest Xray – classic findings include enlargement of
pulmonary arteries with distal pruning. This may not be seen
until late in the course of the disease
Electrocardiogram – evidence of right ventricular
hypertrophy, right axis deviation, right bundle branch block,
right atrial enlargement
Pulmonary function tests – look for evidence of underlying
lung disease
Echocardiogram – estimate pulmonary artery systolic pressure
and assess right ventricular size and function; may show Dshaped septum with paradoxical bulging during diastole;
tricuspid regurgitation secondary to right ventricular dilatation
Diagnostic Evaluation
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Chest Xray – classic findings include enlargement of
pulmonary arteries with distal pruning. This may not be seen
until late in the course of the disease
Electrocardiogram – evidence of right ventricular
hypertrophy, right axis deviation, right bundle branch block,
right atrial enlargement
Pulmonary function tests – look for evidence of underlying
lung disease
Echocardiogram – estimate pulmonary artery systolic pressure
and assess right ventricular size and function; may show Dshaped septum with paradoxical bulging during diastole;
tricuspid regurgitation secondary to right ventricular dilatation
Electrocardiogram demonstrating the changes of right ventricular hypertrophy (long arrow)
with strain in a patient with primary pulmonary hypertension. Right axis deviation (short
arrow), increased P-wave amplitude in lead II (black arrowhead), and incomplete right
bundle branch block (white arrowhead) are highly specific but lack sensitivity for the
detection of right ventricular hypertrophy.12
Diagnostic Evaluation
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Chest Xray – classic findings include enlargement of
pulmonary arteries with distal pruning. This may not be seen
until late in the course of the disease
Electrocardiogram – evidence of right ventricular
hypertrophy, right axis deviation, right bundle branch block,
right atrial enlargement
Pulmonary function tests – look for evidence of underlying
lung disease
Echocardiogram – estimate pulmonary artery systolic pressure
and assess right ventricular size and function; may show Dshaped septum with paradoxical bulging during diastole;
tricuspid regurgitation secondary to right ventricular dilatation
The four chamber view shows severe dilation of the right ventricle (RV) and right atrium
(RA) with evidence of high right sided filling pressure; the interventricular septum (red
arrow) and the interatrial septum (white arrows) bulge into the left ventricle (LV) and left
atrium (LA) respectively.
Diagnosis
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Overnight oximetry – nocturnal desaturation is
common in PH. However, polysomnography is the
gold standard for diagnosis of obstructive sleep
apnea
V/Q scan – evaluate for thromboembolic disease
Labs – HIV, LFTs, ANA, RF, ANCA, BNP
Exercise testing – determine NYHA class and
establish a baseline for determining response to
treatment
Right heart catheterization - needed to confirm the
diagnosis by measuring PA pressures
Patients with pulmonary hypertension but without resulting
Class I limitation of physical activity. Ordinary physical activity does not
cause undue dyspnea or fatigue, chest pain, or near syncope.
Class II
Patients with pulmonary hypertension resulting in slight
limitation of physical activity. They are comfortable at rest.
Ordinary physical activity causes undue dyspnea or fatigue,
chest pain, or near syncope.
Class III Patients with pulmonary hypertension resulting in marked
limitation of physical activity. They are comfortable at rest. Less
than ordinary activity causes undue dyspnea or fatigue, chest
pain, or near syncope.
Class IV Patients with pulmonary hypertension with inability to carry
out any physical activity without symptoms. These patients
manifest signs of right heart failure. Dyspnea or fatigue may be
present even at rest. Discomfort is increased by any physical
activity.
Primary Therapy
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For secondary forms of pulmonary hypertension, the
primary therapy is aimed at the underlying cause.
There is no primary therapy for Group 1 PAH, and
advanced therapy is often required.
There are several therapies which should be considered for
all groups including:
-Diuretics to decrease hepatic congestion and peripheral
edema
-Oxygen therapy for anyone with hypoxemia
-Anticoagulation due to the risk of intrapulmonary
thrombosis and thromboembolism from sluggish
pulmonary flow, dilated right heart, and venous stasis
-Digoxin to improve left ventricular function and control
heart rate in patients with SVT associated with right heart
dysfunction
Advanced Therapy
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Refers to the administration of agents with complex mechanisms of
action including vasodilation, vascular growth, and remodeling
Most well established in patients with Group 1 PAH
May be applicable in all groups if they remain NYHA class III or IV
after primary therapy
Patients should undergo vasoreactivity testing prior to initiation of
advanced therapy
Vasoreactivity test
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Involves administration of a short-acting vasodilator
and then measurement of hemodynamic response
with right heart catheterization.
Commonly used vasodilators include epoprostenol,
adenosine, and inhaled nitric oxide
The vasoreactivity test is positive if the mean
pulmonary artery pressure decreases by at least 10
mmHg or to a level less than 40 mmHg, with an
increased or unchanged cardiac output and minimally
reduced or unchanged systemic blood pressure
Calcium Channel Blockers
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Patients with a positive vasoreactivity test should be tried on a
calcium channel blocker. Those with a negative test have not
been shown to benefit from CCB therapy
The goal of CCB therapy is to decrease pulmonary artery
pressure and decrease the right ventricular afterload
A positive response to treatment is referred to as patients being
in functional class I or II with near normal hemodynamics after
several months of therapy
Patients with PPHTN should not undergo vasoreactivity testing
because they are rarely vasoreactive and they have high risk of
adverse effects from pure vasodilator therapy
Advanced Therapy
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Patients with a negative vasoreactivity test, those who failed a
6 month CCB trial, and patients with PPHTN should be
considered for alternative therapy
Advanced therapy includes Prostanoids, Endothelin receptor
antagonists, or Phosphodiesterase inhibitors
Prostanoids – Epoprostenol (Flolan), Treprostinol
(Remodulin), and Iloprost (Ventavis)
Endothelin receptor antagonists – Bosentan (Tracleer)
Phosphodiesterase inhibitors – Sildenafil (Viagra, Revatio)
Refractory Pulmonary Hypertension
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Atrial septostomy – creates a right-to-left shunt in order to
increase systemic blood flow and bypass the pulmonary vascular
obstruction. In some patients this increases cardiac output and
improves systemic oxygen delivery. There is a high procedurerelated mortality risk.
Transplantation – both lung and heart-lung transplant have been
successful in IPAH
Liver transplant has been successful in patients with PPHTN
Prognosis
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Survival in untreated IPAH is approximately 3 years. If
there is severe PAH or right ventricular failure, survival is
usually less than one year.
Prognosis in PPHTN is extremely poor with high six
month mortality (50%). Death is usually from infection or
right heart failure
Poor prognostic factors
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Age greater than 35 at presentation
NYHA class III or IV with failure to improve to a lower
class during treatment
Pericardial effusion
large right atrial size
elevated right atrial pressure
septal shift during diastole
increased BNP
hypocapnea
Summary
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Pre-transplant diagnosis: Hepatopulmonary
Syndrome
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Post-transplant diagnosis: Pulmonary
Hypertension
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Diagnostic procedure needed: Right heart
catheterization
Thanks!
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Dr. William Petersen
Dr. Karen Brust
Dr. Esther Fields
Dr. Geoff Fillmore
Dr. Heather Henderson
Dr. Jonathan Mock
References
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Murray and Nadel’s Textbook of Respiratory Medicine, 4th ed. (2005)
Current Diagnosis and Treatment in Cardiology, 2nd ed. (2003)
UpToDate
Prognosis of Pulmonary Arterial Hypertension. Chest 2004; 126:1
Diagnosis and Treatment of Pulmonary Hypertension. American Family
Physician 2001; 63:9
www.lib.mcg.edu
www.rfumsphysiology.pbwiki.com