Transcript Nursing Considerations For Prostacyclin Therapy

Johnell Diwan, RN, BSN
Pulmonary Hypertension Clinic Coordinator
Legacy Medical Group, Pulmonary & Sleep Medicine

Background and definition

Clinical classification

Pathophysiology/Natural history

Signs and symptoms/diagnosis

Treatment of PAH

Emergency Considerations
Rare disease (orphan designation) of the pulmonary
microvasculature affecting 15 to 50 people per million
inhabitants in the Western world1
Affects all races
Affects all ages; however, most prevalent in 4th and 5th decades of
life
Higher prevalence in females
Global burden of PAH may be underestimated because
of:1,2
Underdiagnosis (eg, nondescript symptoms)
Misdiagnosis (eg, asthma, left-heart disease)
Increasing risk factors (eg, HIV infection, schistosomiasis)
HIV, human immunodeficiency virus.
1. Humbert. Eur Respir J. 2007;30:1-2. 2. Humbert et al. Chest. 2007;132:365-367.
1.
McLaughlin. J Am Coll Cardiol. 2009. 2. Humbert. Am J Resp Crit Care Med. 2006.
2.
3. Humbert. Eur Resp Rev. 2012. 4. Armstrong. bmjopen.bmj.com. 2012. 5. Champion. Circulation. 2009.
3.
6. Badesch. Chest. 2010
Seven-year survival from time of diagnostic right-sided heart catheterization for full REVEAL Registry cohort,
using left truncation methods. ■ = estimated survival estimate ± SE at each particular time point
REVEAL, Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management
Benza et al Chest 2012;142 (2):448-456
3
1
PVR >3 WU
PVR >3 WU
≤15
mPAP,
mm Hg
≥25
mm Hg
mPAP ≥25 mm Hg
2
PAWP ≤15 mm Hg
CO, cardiac output; mPAP, mean pulmonary arterial pressure; PAWP, pulmonary arterial wedge pressure; PVR, pulmonary
vascular resistance; WU, Wood units.
1. Kaluski et al. Heart Drug. 2003;2:225-235. 2. Rubin. Chest. 1993;104:236-250. 3. McLaughlin and McGoon.
Circulation. 2006;114:1417-1431. 4. McLaughlin et al. Circulation. 2009;119:2250-2294.
PAH
Mean PAP ≥25 mm Hg
+
PAWP/LVEDP ≤15 mm
Hg
+
PVR > 3 Woods units
PH
Mean PAP ≥25 mm Hg
LVEDP, left ventricular end-diastolic pressure; PAP, pulmonary arterial pressure; PAWP, pulmonary artery wedge
pressure; PH, pulmonary hypertension.
Hoeper M, et al. J Am Coll Cardiol. 2013;62(25):42-50.
Pulmonary
Hypertension
WHO
GROUP 1
WHO
GROUP 2
PAH
Left-heart
related
● Idiopathic (IPAH)
● Heritable
● Drug- and toxininduced
● Associated with
other conditions
(APAH)
– Connective tissue
disease
– HIV infection
– Portal
hypertension
– Congenital heart
disease (repaired)
– Schistosomiasis
WHO Group 1′
● Pulmonary venoocclusive disease
● Pulmonary
capillary
hemangiomatosis
● WHO Group 1″
Persistent PH of
the
newborn
● Systolic
dysfunction
● Diastolic
dysfunction
● Valvular
disease
• Congenital/
acquired left
heart
inflow/outflow
tract
obstruction
and
congenital
cardiomyopat
hies
WHO
GROUP 3
WHO
GROUP 4
WHO
GROUP 5
Lung/hypoxia
CTEPH
Other
Chronic
thromboembolic
pulmonary
hypertension
Unclear
multifactorial
mechanisms
● COPD
related
● ILD
● Other pulmonary
diseases with
mixed restrictive
and
obstructive
pattern
● Sleepdisordered
breathing
● Alveolar
hypoventilation
disorders
● Chronic
exposure
to high altitude
● Developmental
lung diseases
• Hematologic
•
•
•
disorders
Systemic
disorders
Metabolic
disorders
Others
CTEPH, chronic thromboembolic pulmonary hypertension; COPD, chronic obstructive pulmonary disease; ILD,
interstitial lung disease; HIV, human immunodeficiency virus; PH, pulmonary hypertension; WHO, World Health
Organization. Simonneau G et al. J Am Coll Cardiol. 2013;62:D34-D41.
Progression of Pulmonary Vascular Disease
Right
Pulmonary
Right
Ventricle
Pulmonary
Arteries
Progression
of Pulmonary
Vascular
Disease
Ventricle
Arteries
Right Ventricle
Pulmonary Arteries
Normal
wall
ThinThin
RV RV
wall
Progression of Pulmonary Vascular Disease
Healthy PA Endothelium
Right Ventricle
Pulmonary Arteries
Healthy
PA
endothelium
Thin
walled
relaxed PAs
Thin
RV wall
Thin-walled
relaxed
PAs
LargePA
capillary
network
Healthy
Endothelium
Normal
CO/PVR
andPAs
perfusion
Thincapillary
walled
relaxed
Large
network
Thincapillary
RV wall network
Large
Normal
CO/PVR
and perfusion
Healthy PA Endothelium
Failure
Compensation
Normal CO/PVR and perfusion
Thin walled relaxed PAs
Hypertrophied
Large capillary
network RV
Abnormal
endothelium
Normal
CO/PVR
andPA
perfusion
Hypertrophied
RV
Hypertrophied
RV PAs
Constricted stiff
Abnormal
PA endothelium
Abnormal
endothelium
Loss PA
of microvessels
Constricted
stiff
PAs in PVR,
Constricted
stiff
PAs
Normal
CO,
mild
increase
Hypertrophied
RV
Loss
of
microvessels
Loss
of PA
microvessels
moderate
decrease
in perfusion
Abnormal
endothelium
Normal CO, mild increase in PVR,
Constricted
stiff
PAs
Normal
mildin↑perfusion
PVR,
moderateCO,
decrease
Loss of microvessels
moderate
↓
in
perfusion
Dilated
Normal CO, mild increase
in RV
PVR,
moderate
decrease
in perfusion
Cell
proliferation
in
the PA wall
Dilated RV
Obliterative
PA
remodeling
Cell proliferation
in the PA wall
Dilated
RV
Severe
decrease
in CO and perfusion
Obliterative
Dilated PA
RV remodeling
Cell
proliferation
in and
PA perfusion
wall
with
severe
increase
in PVR
Severe
decrease
in the
CO
Cell proliferation
in
PA wall
Obliterative
PA
remodeling
with severe
in PVR
Obliterative
PA increase
remodeling
Champion H, et al. Comprehensive invasive and noninvasive approach to the RV. Circulation.
2009;120:992-1007
Severe
decrease
in CO perfusion,
and perfusion
Severe
↓ CO and
with severe increase in PVR
Champion H, et al. Comprehensive invasive and noninvasive approach to the RV. Circulation. 2009;120:992-1007
with severe ↑ PVR
Champion H, et al. Comprehensive invasive and noninvasive approach to the RV. Circulation. 2009;120:992-1007
14
CO, cardiac output; LV, left ventricle; PA, pulmonary artery; PVR, pulmonary vascular resistance;
RV right
14
ventricle.
14
Figure adapted from Champion et al. Circulation. 2009;120:992-1007. With permission.
Dizziness
Shortness of breath (dyspnea)
Rapid or irregular heart
beats (Tachycardia)
Feeling tired or
worn out (fatigue)
Swollen ankles and legs
(edema)
McLaughlin et al. J Am Coll Cardiol. 2009;53:1573-1619.
Fainting (syncope)
Jugular Venous
Distention
Low blood pressure
Hepatomegaly
Shortness of breath (dyspnea)
Chest pain
(angina)
Swollen abdomen
(ascites)
McLaughlin et al. J Am Coll Cardiol. 2009;53:1573-1619.
Diagnostic
Outcomes
History and physicalb

Chest x-rayb

Echocardiogram

Assess for RV and RA enlargement, RV dysfunction, TR
velocity to measure RVSP
Electrocardiogram

Evaluate for right heart enlargement and strain, cardiac
rhythm
Cardiac
catheterizationb

Evaluate for CHD; measure wedge pressure or LVEDP;
establish severity and prognosis; test vasodilator therapy
PFTs with DLCO

Assess obstructive and restrictive airway disease
VQ scan

Rule out thromboembolic disease
Evaluate signs and symptoms, family history, associated
diseases, ANA
Assess for RV enlargement, peripheral hypovascularity
(pruning), and prominent pulmonary arteries
ANA, antinuclear antibody; CHD, congenital heart disease; DLCO, diffusing capacity of the lung for carbon monoxide; HIV, human immunodeficiency
virus; LVEDP, left ventricular end-diastolic pressure; PFT, pulmonary function test; RA, right atrial; RV, right ventricular; RVSP, right ventricular systolic
pressure; TR, tricuspid regurgitation; VQ, ventilation-perfusion.
a Additional tests may be ordered to rule out possible causes of PAH (pulmonary arteriography, blood tests [HIV, hepatic disease, scleroderma],
polysomnography [sleep-disordered breathing]). b Required for referral.
McLaughlin and McGoon. Circulation. 2006;114:1417-1431.
WHO
Definition
Class I

Patients with PAH but without resulting limitation of physical
activity. Ordinary physical activity does not cause undue dyspnea
or fatigue, chest pain, or near syncope
Class II

Patients with PAH 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 PAH resulting in marked limitation of physical activity.
They are comfortable at rest. Less than ordinary physical activity
causes undue dyspnea or fatigue, chest pain, or near syncope
Class IV

Patients with PAH with inability to carry out any physical activity
without symptoms. These patients manifest signs of right heart
failure. Dyspnea or fatigue may even be present at rest.
Discomfort is increased by any physical activity
WHO, World Health Organization.
Rubin. Chest. 2004;126(suppl 1):7S-10S.
Early stage PAH
LV
RV

US/DS/MAR11/001
Moderate severity PAH
RV
LV
Severe PAH
RV
LV
Echocardiography provides estimated RV systolic pressure and
morphologic cardiac abnormalities
Images and video courtesy of Paul Forfia, MD, Hospital of the University of Pennsylvania
Heart and Vascular Center.
Triad of right heart findings1,2
RV enlargement (98% of patients)2
Septal flattening (systolic [interventricular]; 90% of patients)2
RV systolic dysfunction (qualitative; 76% of patients)2
Other features2
RA enlargement (92% of patients)
“Grade I” diastolic dysfunction (peak E < peak A; 70% of patients)
Normal LV function (all patients)
>Mild mitral regurgitation (<2% of patients)
IPAH, idiopathic pulmonary arterial hypertension; LV, left ventricular; RA, right atrial; RV, right ventricular .
1. Forfia and Vachiéry. Am J Cardiol. 2012;110(6)(suppl):16S-24S. 2. Bossone et al. J Am Soc Echocardiogr. 1999;12(8):655-662.

Confirm diagnosisa
◦ Gold standard

Evaluate severity of PAH

Assess congenital heart
defects

Exclude left-sided heart
disease

Assess response to
vasodilator challenge

Assess key hemodynamic
parameters
Required for every patient with suspected pulmonary
hypertension
1. McLaughlin et al. Circulation. 2009;119:2250-2294. 2. Tolle et al. Circulation. 2008;118:2183-2189.
Measurement of pulmonary vasoreactivity is important in PAH
diagnosis and treatment selection
Must be done cautiously in patients with PAH, especially in
those with signs of overt right heart failurea or hemodynamic
instability
Positive response defined by ≥10 mm Hg  in mPAP, with mPAP ≤40 mm
Hg and without  CO
Approximately 13% of patients with IPAH have a positive response
Only 6.8% had a favorable clinical response to chronic CCB therapy at 1
year
Other PAH treatments should be evaluated if patient does not
improve to FC I or II
Acute right heart failure with shock is considered a contraindication to
vasodilator testing.
CCB, calcium channel blocker; IPAH, idiopathic pulmonary arterial hypertension; RHC, right heart catheterization.
1. McLaughlin et al. J Am Coll Cardiol. 2009;53:1573-619.
2. Oudiz and Langleben. Adv Pulmonary Hypertension. 2005;4:15-25.
Pre-symptomatic/
Compensated
Symptomatic/
Decompensating
Declining/
Decompensated
CO
Symptom Threshold
PAP
PVR
RAP
Right Heart
Dysfunction
Time
CO, cardiac output; PAP, pulmonary arterial pressure; PVR, pulmonary
vascular resistance; RAP, right atrial pressure.
Protect the Right Side of the Heart, Improve Right
Ventricular Function
♥ Digoxin
♥ Oxygen
♥ Control Volume status with
diuretics and fluid restriction
♥ DRY IS GOOD!!!
♥ Anti-coagulants

◦
Responsiveness to acute vasodilators
◦
Functional class
◦
Rate of progression
◦
Prior or concomitant drug therapy (therapeutic
pathway)
◦
Pulmonary hemodynamics, RV function
◦
Comorbidities (liver, heart disease, immunity)
◦
Psychosocial/financial
◦
Patient/clinician preference
Determinants of risk
Lower risk
Higher risk
No
Yes
Gradual
Rapid
II, III
IV
6MWD
Longer (>400 m)
Shorter (<300 m)
CPET
Peak VO2 >10.4 mL/kg/min
Peak VO2 <10.4 mL/kg/min
Minimal RV dysfunction
Pericardial effusion, significant
RV enlargement/dysfunction,
right atrial enlargement
RAP <10 mm Hg
CI >2.5 L/min/m2
RAP >20 mm Hg
CI <2.0 L/min/m2
Minimally elevated
Significantly elevated
Clinical evidence of RV
failure
Progression
WHO functional class
Echocardiographic
findings
Hemodynamics
BNP
BNP, B-type natriuretic peptide; CI, cardiac index; CPET, cardiopulmonary exercise test; 6MWD, 6-minute
walk distance; RAP, right atrial pressure; RV, right ventricular; VO2, volume of oxygen consumption; WHO,
World Health Organization.
McLaughlin et al. J Am Coll Cardiol. 2009;53:1573-1619.
Functional class I or II
Echocardiography/CMR
Normal/near-normal RV size and function
Hemodynamics
Normalization of RV function (RAP <8 mm Hg and CI >2.5 to 3.0
l/min/m2)
6-min walk distance
>380 to 440 m; may not be aggressive enough in young individuals
Cardiopulmonary exercise testing
Peak VO2 >15 ml/min/kg and EqCO2 <45 l/min/l/min
B-type natriuretic peptide level
Normal
FC, functional class; CMR, cardiac Magnetic resonance; RV, right ventricle; RAP, right atrial pressure;
CI, cardiac index; 6MWD, 6-minute walk distance.
McLaughlin V, et al. JACC. 2013;62(25) Supp D.
ABNORMALITIES
Nitric oxide
deficiency
Prostacyclin
deficiency
Endothelin
overexpression
THERAPIES
PDE-5 inhibitors
Block the activity of PDE-5,
restoring vasodilation
through an increase in
cGMP1
Prostacyclin
Supplement the deficiency in
PGI2, resulting in vasodilation
and inhibition of platelet
aggregation2
ERAs
Block the binding of ET-1 to its
receptors, preventing
vasoconstrictor effects of ET-13
cGMP, cyclic guanosine monophosphate; ERA, endothelin receptor antagonist; ET-1, endothelin; PDE-5, phosphodiesterase
type 5; PGI2, prostacyclin.
1. Humbert et al. J Am Coll Cardiol. 2004;43(suppl S):13S-24S. 2. Humbert et al. N Engl J Med. 2004;351:1425-1436.
3. Galiè et al. Eur Heart J. 2004;25:2243-2278.
Prostacyclins act to:
• Relax smooth muscle by increasing
intracellular cAMP
• Inhibit platelet aggregation
• Inhibit smooth muscle cell proliferation
• Inhibit pulmonary vascular remodeling
Flolan®  Remodulin®  Ventavis®
Epoprostenol sodium  Tyvaso®
Veletri ®
Humbert M, Sitbon O, Simonneau G. Drug Therapy: Treatment of Pulmonary Arterial
Hypertension. New England Journal of Medicine. 2004;351:1425-36.
Attributes
•
•
•
•
Half-life 3-5 minutes
Requires continuous IV administration
Potential rebound effect
Requires dedicated central tunneled catheter for chronic use, can
use peripheral or PICC for acute use
Stable for 24 hours on pump with icepacks, stable for 48 hours
refrigerated, stable for 8 hours at room temperature
Ice packs required
Generic equivalent is AP rated (final formulation only)
•
•
•
Clinical considerations
•
•
•
•
•
Must be initiated in a hospital or controlled setting
Dosed in ng per kg per minute
Usually initiated at 2ng per kg per minute
Increased by 2ng per kg per minute until dose-limiting
effects warrant reduction
Other considerations:
DO NOT stop pump under any circumstances
DO NOT draw blood or flush (dedicated line)
• Not compatible with any medications or fluids
• Risk of central line infection and sepsis
• Insert peripheral IV for central line complications
Goal: to improve exercise capacity in patients with WHO group I PAH
Flolan® (epoprostenol sodium) [package insert]. Research Triangle Park, NC:
GlaxoSmithKline; 2011.
Epoprostenol sodium for injection [package insert]. Irvine, CA: TEVA; 2009.
Dose-limiting considerations:
Expected/Excess
•
Flushing
•
Hypotension
•
Jaw pain
•
Rash
•
Diarrhea
•
Headache
•
Nausea
•
Foot pain
•
Vomiting
•
Warm
extremities
Insufficient
•
Short of
breath at rest
•
Pallor
•
Cough
•
Cool
extremities
•
Chest pain
•
Cyanosis
Flolan® (epoprostenol sodium) [package insert]. Research Triangle
Park, NC: GlaxoSmithKline; 2008.
Epoprostenol sodium for injection [package insert]. Irvine, CA: TEVA;
2009.
Flolan®
Epoprostenol sodium
Veletri®
Photo Source: Internal Accredo Photo
Attributes
• Half-life = 4.5 hours
• Dosed in ng per kg per min
• Dose is increased based on clinical response
(increments of 1.25 ng/kg/min for 4 weeks and
later at 2.5 ng/kg/min per week)
Clinical Considerations
• Remodulin IV—initiated in a hospital setting
• No reconstitution necessary – dilute to volume
appropriate for pump being used (normal saline,
sterile water, sterile glycine diluent for Flolan)
• Stable at room temperature, no ice packs needed
• Risk of central line infection and sepsis
•DO NOT stop Remodulin IV under any
circumstance
Goal: to diminish symptoms associated with
exercise in patients with WHO group I PAH
Remodulin ® (treprostinil) Injection [package insert]. Research
Triangle Park, NC: United Therapeutics Corp.; 2014.
Dose-limiting considerations:
Expected/excess
•
Flushing
•
Nausea/vomiting
•
Insufficient
•
Short of breath at
rest
Foot/leg pain
•
Fatigue
•
Diarrhea
•
•
Hypotension
Lower extremity
edema
•
Rash
•
Syncope
•
Warm extremities
•
Cough
•
Cool extremities
•
Pallor
•
Cyanosis
•
Chest pain
Remodulin ® (treprostinil) Injection [package insert]. Research Triangle Park, NC:
United Therapeutics Corp.; 2014.
CADD-Legacy® (IV)
Crono Five (IV)
(subcutaneous)
CADD-MS® 3 (IV)
CADD-MS® 3
Photo Source: Internal Accredo
Photo
Central Venous Catheter (CVC)





Single Lumen CVC ONLY for
prostacyclin administration.
CVC should be placed by
interventional radiology or
vascular surgery
If possible, anesthesia should
be avoided during placemat
CVC should be tunneled under
the skin
Examples of CVC’s include:
◦ Broviacs
◦ Hickmans
◦ Groshongs
CVC= Central Venous Catheter
Adverse effects of prostacyclin
Indications of pulmonary arterial
hypertension
Headache
Dyspnea
Jaw pain
Fatigue
Nausea/Vomiting
Chest pain
Diarrhea
Palpitations
Extremity Pain
Lower extremity edema
Flushing
Ascites
Thrombocytopenia
Syncope
Kingman, M et al. Safety Recommendations for Administering Intravenous Prostacyclins in the Hospital. Crit
Care Nurse 2013;33:32-39.

Signs and symptoms
◦
◦
◦
◦
◦
Acute respiratory decompensation
Tachycardia
Hypoxemia
Angina
Dizziness



If a patient is on a home infusion pump, don’t stop the pump until
the Specialty Pharmacy (SP) or MD’s office has been contacted
If possible, utilize the patient as a resource for needed information
such as concentration, dose, pump rate, etc
Reach out to the SP FIRST if there are questions related to dosing
or the pump. They have a 24/7/365 Call Center to help with any
questions or concerns you may have
◦ Their number can be found on the side of the pump
Specialty pharmacies can make initiating Remodulin therapy easier for you
by providing continuous patient support with ongoing services and
resources for long-term success
• All third-party reimbursement management
– New patients
– Patients transitioning from other PAH therapies
• Patient assessment and evaluation
• Teaching
– Pre-teaching and ongoing support
– In-home, hospital, or clinic
• Discharge planning support
• 24/7 patient hotline access




When a patient comes to the hospital, he/she should bring
his/her back up pump along
If he/she does not have the back up pump, have a family
member bring it from home unless you use hospital
pumps for prostacyclin infusion
It is good practice to check with the hospitals’ Biomedical
or Risk Management Department in advance to
understand any rules or barriers to patient provided
pumps in the hospital
Remodulin can be given on hospital pumps if the patient
is unable to manage his/her own pump

When switching to a hospital pump from a home
infusion pump, consider what actions should be
taken if the new concentration for Remodulin is
different than the patient’s home concentration
◦ Withdraw the drug from the central line before starting
the newly mixed drug (different concentration/different
pump rate)
◦ Consider re-priming the line with the new concentration
of drug (avoid disruption in therapy)



If patient has a central line NEVER flush the line – flushing could
result in prostacyclin bolus
Do NOT interrupt the infusion
A single lumen catheter (ie. Hickman) is the preferred route for
prostacyclin delivery
◦ If you must give Remodulin in a double or triple lumen catheter, use the
most distal port

If the patient’s central line is occluded, it is essential to place
peripheral access and utilize the peripheral line until new central
access can be established
◦ Due to the risks associated with sudden infusion disruption, the patient
should have two peripheral lines placed to ensure that there is back up
access if the initial peripheral access is lost

A cracked or leaking catheter is an emergency.
The patient will need to have the prostacyclin run
through a peripheral line and Interventional
Radiology will need to be contacted to repair the
line
◦ Peripheral line is only a TEMPORARY measure

Other emergencies:

Urgent considerations:
◦ Catheter becomes occluded, falls out or is pulled out
◦ Any interruption in the delivery of a prostanoid (IV or SC)
◦ Oozing or draining at the site
◦ Fever of unknown origin
IV, intravenous; SC, subcutaneous