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PATIENT EDUCATION
This process is important and should proceed in an orderly
and compulsive fashion. Information for the patient must
include the following components:
- Introduction to the concept of long-term drug infusion
- Discussion of realistic expectations
- Education about technical aspects of epoprostenol
use
- Potential adverse effects of epoprostenol
Providers should also consider the available resources
in their own facility to provide the comprehensive and
intensive management that these patients require. Importantly,
although epoprostenol therapy can be life-saving when
used appropri-ately, it can potentially complicate, and
in some cases worsen, symptoms with catastrophic results
if it is incorrectly initiated, administered, or managed
over the long term. Careful atten-tion to four aspects
of treatment is required when consider-ing long-term use
of epoprostenol: (1) patient eligibility, (2) patient
education, (3) drug initiation, and (4) treatment maintenance
and follow-up.
PATIENT ELIGIBILITY
The decision about whether a patient should be treated
with epoprostenol requires consideration of a number of
issues:
- Does the patient have appropriate clinical indications?
- Are there clinical contraindications?
- Are alternative medications more suitable?
- Have issues of medical coverage been defined?
- Is the patient able and willing to learn and comply
with
the regimen?
- Can adequate follow-up be assured?
Introduction to therapy
Prior to making the decision to proceed with epoprostenol
therapy, patients should be shown the actual delivery
system, have all procedures demonstrated, and ideally
have an opportunity to meet another epoprostenol patient.
This may dramat-ically reduce the anxiety associated with
starting long-term intravenous therapy. Patients may be
more likely to benefit if they have the opportunity to
meet someone of the same sex, disease substrate, and age
range. Patients can be given information about the Pulmonary
Hypertension Association (PHA), which may assist them
in locating another patient in their area.
With the advent of new drug therapy, it is feasible that
some patients may ultimately be weaned from epoprostenol,
but they should understand that it is very likely going
to be part of their daily routine forever, unless they
undergo lung or heart-lung transplantation. In our experience,
patients must have control over the decision-making process
to learn and properly care for the delivery system. To
ensure success, written and visual (videotape or compact
disc) material to review at home can be offered to supplement
face-to-face teaching prior to making a final decision
regarding epoprostenol therapy.
Realistic outlook
Patients should have realistic perceptions about the drug.
Although epoprostenol has the potential for making a signifi-cant
difference in quality of life and for improving survival,
it has not proved to be a cure for PAH. It is inconvenient,
has side effects, and has associated risks. Patients must
realize that there may not be immediate improvement in
symptoms.
Although the majority of patients improve, it is impossible
to predict the magnitude or duration of the therapeutic
response. Patients have to understand that initial improvement
in symptoms does not guarantee continued improvement or
preclude eventual decline. While it is essential to hear
this information from the pulmonary hypertension center
providers, patients also may benefit from discussion with
other patients and caregivers through support groups.
They should not, however, base their expectations on results
of therapy in other patients.
Technical education
Although the approach to education and drug initiation
differs among large centers based on experience and resources,
there are some common practices. Patients should be taught
by experienced health care providers and ideally by the
same people who will be following their care over the
long term. At the Mayo Clinic, patients are provided with
preprinted step-by- step directions in a manual that covers
pump operation, drug reconstitution, and cassette and
tubing change. They are encouraged to share a copy of
this information with their local physician. Teaching
should occur in intensive blocks before and during the
actual initiation of the drug. Whether the infusion is
initiated on an inpatient or an outpatient basis, it must
be done in a monitored setting with immediate access to
emergency equipment and care. Long-term epoprostenol infusion
should be initiated using CADD I or Legacy pumps.
The process of reconstituting epoprostenol and all facets
of pump operation and catheter care must be fully explained
and demonstrated. Patients and support persons should
be able to demonstrate their proficiency in all phases
of epoprostenol administration before they can be considered
adequately trained. This ensures that the patient always
has a back-up person trained, which reduces patient stress.
Adverse effects
Patients should also be aware of common potential
side effects, including jaw pain, headache, hypotension,
nausea, diarrhea, and flushing. More long-term side effects
may include leg and foot pain, and skin rash. Others,
such as high cardiac output failure, anemia, thrombocytopenia,
pancytope-nia, or weight loss, may be recognized by the
clinician with careful follow-up over time. Some of the
latter effects may also, however, be due to other underlying
disease. Finally, certain adverse effects may be related
to the delivery system, including catheter-related infection
or sepsis, catheter-related thrombosis, pump failure,
and rebound symptoms or death due to sudden discontinuation
of epoprostenol.
DRUG INITIATION
A 6 or 9 French single-lumen tunneled central venous catheter
in the subclavian or internal jugular vein is the preferred
approach for long-term epoprostenol therapy. The central
venous catheter should be tunneled to an exit site that
will allow the patient to see the site in order to care
for it independently. Sutures should be removed after
4 weeks. Catheters are changed only when they become dysfunctional
or infected. Many patients maintain the same catheter
for many years. If a tunneled catheter must be removed
for a period of time (for example, because of infection)
a short-term dedicated catheter, such as a percutaneous
intravenous cen-tral catheter (PICC) or midline catheter,
is appropriate for short-term use. Such catheters have
limited stability and are difficult to care for using
only one hand.
Epoprostenol infusion through the catheter is typically
started in a monitored setting at an infusion rate of
2 to 3 ng/kg/min. Vital signs are obtained before and
at least every half hour for at least 2 to 3 hours after
drug initiation. Teaching sessions occur on a daily basis
until patients and support persons demonstrate proficiency
in the techniques of sterile preparation of the medication,
operation of the infusion pump, and care of the central
venous catheter. At the time of discharge, patients are
provided with detailed contact infor-mation. Patients
are instructed to see their local physicians within the
first month of returning home, offering them the opportunity
to become familiar with their current status, and to assist
with their assessment and monitoring, including anticoagulation.
A proactive approach has been successful with this pa-tient
population. Once the patient is fairly comfortable with
the procedures and has minimal jaw pain, mild diarrhea,
or headache, the epoprostenol dosage is increased by 1
to 2 ng/kg/min. The patient is called or instructed to
call within the next week or sooner if dyspnea decreases
or the side effects cause discomfort.
TREATMENT MAINTENANCE AND FOLLOW-UP
Important issues in long-term management include:
- Communication
- Dose modification
- Interaction with the referring physician
- Follow-up at the clinic
- Emergencies
Communication
While large pulmonary hypertension centers have different
communication protocols, virtually all include telephone
contact as part of management. At the Mayo Clinic, patients
are instructed to call at least every two weeks. The following
information is always obtained:
- Verification of current pump rate
- Number and type of vials that are being mixed
- Current weight
- Interim change in symptoms (including functional status)
or side effects, and relationship to dose changes
- Verification of prothrombin time monitoring, including
recent international normalized ratio (INR)
Dose adjustment
When epoprostenol was FDA-approved, experienced clinicians
felt that frequent and consistent dose escalations were
advisable in order to “stay ahead” of symptoms, rather
than to try to catch up once they recurred or worsened.
As a conse-quence of this dosing strategy and because
of extended patient survival, substantial numbers of patients
began to receive epoprostenol infusion rates of 100 ng/kg/min
and higher. Over time, it became apparent that the consequences
of high epoprostenol doses in some patients included high
output states and fatigue.5
Epoprostenol dosing should be individualized to the patient,
taking into consideration severity of symptoms, side effects,
and underlying disease. Some patients who experience improvement
in symptoms during initiation of epoprostenol in the hospital
or monitored outpatient setting will report increased
symptoms on returning home to a more physically challenging
environment. Thus, close regular contact with these patients
is imperative.
Role of referring physicians
Local medical providers, including primary care physicians,
specialists, and emergency personnel, should be informed
about patients’ need for epoprostenol and its implications.
Patients’ current symptoms, medications and doses, the
target range for the INR, potential complications, and
plan for the future should be provided to primary care
and other local practitioners. Local providers should
also know how and when to contact the pulmonary hypertension
center, particu-larly for problems that occur after clinic
hours. Laminated instruction cards inserted into the pump
pack are useful in emergency situations.
Clinic follow-up
Patients are generally seen for follow-up examination
in the clinic 1 month after initiation and then every
3 to 6 months, depending on response to treatment. They
are called or advised to call every 2 to 4 weeks to report
symptoms and side effects, or sooner if problems arise.
The frequency of contact depends on the stability of the
patient, side effects, and overall comfort level.
During follow-up telephone surveillance, new or worsening
symptoms should prompt a visit to the clinic for evaluation.
Many centers repeat hemodynamic assessment after 1 year
of therapy. Right-heart catheterization is the gold standard
for assessment of pulmonary hemodynamics. The expectation
at 1 year should be improvement in pulmonary hemodynamics
but not normalization of them. Echocardiographic evaluation
after approximately 3 to 6 months of treatment can provide
useful interim estimation of pulmonary hemodynamics.
Emergencies
All potential emergency situations and proper responses
should be discussed and “role-played” with patients during
initial teaching. Ideally, local emergency rooms or emergency
medical staff should be informed about PAH and its treatment
and emergency requirements. Patients sometimes take on
this responsibility themselves. If necessary, a letter
can be provided to emergency services about the importance
of maintaining the infusion at all times and even via
a peripheral vein if necessary. Stickers located on the
infusion pump show the current dose of epoprostenol as
well as warn that the pump cannot be turned off for any
reason. Patients are also encour-aged to wear a medic
alert bracelet or carry a laminated card listing their
health problems as well as pump warnings. Urgent situations
include central catheters being inadvertently pulled out,
a torn or leaking catheter, pump malfunction, and central
line infection (particularly tunnel infection or sepsis).
Patients need to call 911 or proceed to an emergency room
and be certain that the ambulance or emergency personnel
are aware that interrupted epoprostenol delivery constitutes
an emergency and that intravenous access must be estab-lished
immediately. The pulmonary hypertension center should
be contacted for further instructions if at all possible.
A back-up medication cassette and supplies should be brought
to the hospital. Infections related to long-term indwelling
central lines can be minimized by strict attention to
aseptic care.
References
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WB, et
al. Treatment of primary pulmonary hypertension with continuous
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