Learning About PPH
Inside your lungs are millions of very small blood vessels called
capillaries. Each one is about as wide as a hair, large enough for
blood cells to barely pass through. The inside of the vessel is lined
with endothelial cells. The outside is lined with smooth muscle cells.
The endothelial cells keep blood from leaking out. The smooth muscle
cells allow the capillary to get a bit narrower or wider, depending on
how much blood is surging back and forth between the heart and lungs.
With PPH, for unknown reasons, some of the endothelial cell lining of
the lung's capillaries get peeled off. As blood leaks into the smooth
muscle cells they continuously constrict as a reaction. Multiplied
thousands of times this chokes off the flow of blood between the heart
and lungs, causing dizziness exhaustion, fainting and finally heart
failure.
What is Pulmonary Hypertension?
Pulmonary hypertension is a rare blood vessel disorder of the lung in
which the pressure in the pulmonary artery (the blood vessel that
leads from the heart to the lungs) rises above normal levels and may
become life threatening.
Symptoms of pulmonary hypertension include shortness of breath with
minimal exertion, fatigue, chest pain, dizzy spells and fainting. When
pulmonary hypertension occurs in the absence of a known cause, it is
referred to as primary pulmonary hypertension (PPH). This term should
not be construed to mean that because it has a single name it is a
single disease. There are likely many unknown causes of PPH. PPH is
extremely rare, occurring in about two persons per million population
per year.
Secondary pulmonary hypertension (SPH) means the cause is known. A
common cause of SPH are the breathing disorders emphysema and
bronchitis. Other less frequent causes are the inflammatory or
collagen vascular diseases such as scleroderma, CREST syndrome or
systemic lupus erythematosus (SLE). Congenital heart diseases that
cause shunting of extra blood through the lungs like ventricular and
atrial septal defects, chronic pulmonary thromboembolism (old blood
clots in the pulmonary artery), HIV infection, liver disease and
diet drugs like fenfluramine and dexfenfluramine are also causes
of pulmonary hypertension.
Pulmonary hypertension is frequently misdiagnosed and has often
progressed to late stage by the time it is accurately diagnosed.
Pulmonary hypertension has been historically chronic and incurable
with a poor survival rate. However, new treatments are available
which have significantly improved prognosis.
Recent data indicate that the length of survival is continuing to
improve, with some patients able to manage the disorder for
15 to 20 years or longer.
TREATMENT
Today there is treatment to help almost every PH patient.
Doctors might begin by trying to lower lung pressures with calcium-
channel blockers. The next step is usually to try epoprostenol.
Then a transplant is considered.
Secondary PH
As long as the underlying disease exists, it will continue to cause PH.
Once you have PH, especially if you have had it for some time, curing
the disease that caused it may not make it go away, so the PH itself
will usually need separate treatment. Sometimes curing the underlying
problem does cure the PH.
Pulmonary Thromboendarterectomy
When PH is caused by a blood clot (or clots) in a pulmonary artery, a
surgical procedure called a pulmonary thromboendartectomy may restore
almost normal blood flow to the lungs. Most clots form in a leg, break
off, and travel to a lung. If they do not dissolve (most do), and if
they lodge in the lung, they age and become almost like scar tissue.
When the clot grows into the wall of the vessel, it may take a decade
or longer before the overloaded vasculature that remains becomes
damaged from the extra load it is carrying, and PH symptoms may appear.
Not all chronic clots cause PH.
An EKG or MRI can reveal the existence of clots, but only an angiogram
can tell doctors where the clot is, so they can determine whether it can
be removed by surgery. During the thromboendartectomy, the body is
cooled way down and blood flow may be stopped for up to 20 minutes. The
mortality rate for the operation has fallen to about six percent at the
University of California at San Diego, where doctors pioneered this
procedure. Most survivors are essentially cured of PH.
Oxygen
Just as a lack of oxygen can cause PH, PH sometimes causes reduced oxygen
in the bloodstream. Low levels of bloodstream oxygen make PH worse, so
often PH patients need supplemental oxygen.
Important for Oxygen Users:
¨ Oxygen is highly flammable so you must keep yourself, your tank
and your tubing a safe distance from any open flame or lit cigarette.
Your oxygen company will provide you with an “Oxygen in Use” sign to
post and more guidance on oxygen safety.
¨ Carbon monoxide poisoning is especially dangerous for people with
PH. It is a good idea to get a CO detector, which can be plugged into an
electrical outlet in your house. Aviation shops for private pilots sell
simple “dots” that change color when carbon monoxide is present.
Diuretics
PH causes fluid retention. Helpful hints to combat fluid retention
include removing salt from your diet, which also helps prevent systemic
hypertension, and may reduce the risk of osteoporosis and kidney stones.
If cutting back on salt does not satisfactorily address the problem,
your doctor can prescribe a diuretic to help your kidneys eliminate water.
Two commonly used diuretics include furosemide (Lasix) and spironolactone
(Aldactone).
Important:
¨ When using diuretics, keep your potassium levels up by eating
bananas, cantaloupe, honeydew melon, potatoes and orange juice. Do not
eat licorice.
¨ Be cautious of salt substitutes that contain potassium chloride
and avoid potassium pills. This can be too much potassium for those
with kidney problems or taking certain blood pressure or heart
medications.
Anticoagulants
Anticoagulants, also known as “blood thinners,” make blood less likely to
clot. Clots (thrombi) in the lungs can cause or worsen PH. Two studies
have found that PH patients who use anticoagulants live longer than those
who do not use them. Doctors usually prescribe warfarin (Coumadin or
Panwarfin). Yes, warfarin is the chemical used in rat poison, but the
carefully manufactured brand name pills are the preferred method. Aspirin
is also an anticoagulant, but it acts on the platelets instead of the
little fiber-like agents in the blood that are more likely to contribute
to PH. Aspirin has not been tested as a treatment for PH, and there is no
evidence that platelets clog pulmonary arteries.
Important:
¨ Pro-time Checks: It is important to not be over- or under-
anticoagulated. To keep your dosage right, you need regular pro-time
(prothrombin time) checks to measure the amount of time it takes for your
blood to clot. The warfarin dosage will vary by individual, depending on
metabolism, diet, and other medications.
¨ Home Testing: The FDA has approved two home testing systems,
available only by prescription, called Pro Time and CoaguChek. They cost
approximately $1,300 to $2,000. Ask your doctor and your insurance
company for information on this possibility.
¨ Pre-surgery Precautions: It is usually necessary to stop taking
warfarin for five to 10 days before an operation or serious dental
procedure. While you are off warfarin, your doctor might prescribe
injections of heparin.
¨ Side Effects of Anticoagulant Therapy: Blue or purplish toes or
fingers; prolonged or unusual bleeding, including increased menstrual
flow, red or dark brown urine, red or tarry-black stools, coughing up
blood or stuff that looks like coffee grounds, bleeding gums when
brushing teeth, hard-to-stop nosebleeds or bleeding from cuts; unusual
bruising for unknown reasons; fevers, diarrhea, vomiting; signs of
internal bleeding like a swollen or painful abdomen, back pain,
dizziness, joint pain, stiffness, a severe or long-lasting headache.
¨ Common Drug Interactions with Warfarin: Do not use aspirin
(acetylsalicylic acid), or aspirin-containing drugs, unless your doctor
prescribes them. Pepto-Bismol contains salicylate and can also increase
bleeding. Avoid ibuprofin-containing drugs. Tylenol is okay for pain
relief. Antibiotics like Bactrim, Cotrim, Septra, SMZ-TMP, Sulfatrim,
Uroplus, Flagyl and Protostat all can greatly increase the effect of
warfarin. Use them only with your doctor’s consent.
¨ Diet and Warfarin: Vitamin K (phylloquinone) plays a role in the
synthesis of four clotting factors and therefore makes warfarin less
effective. It is found in large amounts mostly in leafy green vegetables,
in canola oil and soybean oil. Veggies are good for you, so don’t stop
eating them, but do not suddenly change your diet to include more things
high in Vitamin K without getting your warfarin dose adjusted.
Ø Common foods very high in Vitamin K: mint, parsley, spinach, green
tea, swiss chard, cucumber peel, kale, brussels sprouts.
Ø Foods high in Vitamin K: broccoli, collard greens, endive, green
scallions, watercress.
Vitamin E, on the other hand, boosts the effects of warfarin. Let your
doctor know if you take it, and don’t change your use of it without
informing your doctor.
TRANSPLANTATION ISSUES
As recent years have proved, pulmonary hypertension is treated
successfully in many patients, eliminating the need for lung
transplantation. But there are still too many out there with end
stage pulmonary hypertension who have exhausted all treatment options
and are in need of transplant.
For most patients and families, the prospect of undergoing a lung
transplant produces feelings of anxiety and uncertainty. Knowledge
is the best defense in dealing with these feelings.
Medical treatment of primary pulmonary hypertension is directed toward
reduction of symptoms and prolongation of life. Modalities for which
benefit has been demonstrated convincingly include: calcium channel
blockers, long-term intravenous epoprostenol anticoagulation, inotropic
support, diuretic therapy, and oxygen supplementation. A variety of
vasodilators have been reported in small observational studies to have
salutary effects, but in broad experience the benefits have been
inconsistent, nonexistent or complicated by adverse effects. These agents
have included: acetycholine, alpha-adrenergic antagonists, direct-acting
vasodilators, beta-adrenergic antagonists, angiotensin-converting enzyme
inhibitors, and serotonergic blockers.
Calcium channel blockers
After the generally poor experience with vasodilators and the marginally
better early experience with conventional doses of calcium channel
blockers. Rich and Brundage reported that the use of high doses of
nifedipine or diltiazem in patients with primary pulmonary hypertension
resulted in substantial pulmonary hemodynamic benefit in a significant
proportion of patients. Eight of thirteen patients who received a
cumulative loading dose of nifedipine or diltiazem were classified as
responders, in which a positive response was defined as a 50% decline
in pulmonary vascular resistance and a 33% decline in mean pulmonary
arterial pressure. These patients were treated chronically with
nifedipine 120 to 240 mg daily or diltiazem 240 to 720 mg daily; all
experienced symptomatic improvement. One patient died after the dose
of nifedipine was lowered due to apparent viral gastroenteritis. Five
patients underwent hemodynamic restudy after one year, and four
demonstrated sustained hemodynamic improvement.
Further investigation showed that when patients who responded with a
decrease of pressure and resistance were treated chronically with
high-dose calcium channel blockers, their long-term hemodynamic
status, symptoms and survival were significantly better than
nonresponders who were not treated. Whether treatment with high doses
of calcium channel blockers produce the salutary effects or whether
an acute favorable response to calcium channel blocker administration
identifies a group of patients with a better prognosis is unclear.
Epoprostenol
Epoprostenol sodium (prostacyclin, PGI2) is one of 90 prostaglandins
synthesized from arachadonic acid, is predominantly produced in
endothelial cells, and is a powerful endogenous vascular smooth muscle
relaxer and inhibitor of platelet aggregation.
Evidence suggests that a component of pulmonary hypertension is a low
ratio of epoprostenol in relation to thromboxane A2. The response to
acute infusion of epoprostenol has been observed to correlate with
the response to other vasodilators, including nifedipine. The capacity
of responding hemodynamically to acute or short-term vasodilator
administration correlates with the survival of the patient with
primary pulmonary hypertension regardless of long-term treatment.
Thus, the capability of the pulmonary vascular bed to acutely
vasodilate has been considered a predictor of therapeutic efficacy
of pulmonary antihypertensive medications.
In addition to its reported role as an acute vasodilation testing agent,
epoprostenol administered chronically by portable intravenous infusion
pump was found to be feasible and produced sustained hemodynamic
benefit, simptomatic improvement and enhanced oxygenation in a patient
followed for thirteen months and in ten severely disabled primary
pulmonary hypertension patients treated up to 25 months.
Anticoagulation
Several observations suggest that anticoagulation is warranted. The
thromboembolic form of primary pulmonary hypertension accounts for over
half of pathologically examined cases; the interruption of a continuing
thrombotic process is of presumed importance. Patients treated with
anticoagulants appear to have longer survival than untreated patients.
Finally, right ventricular failure may predispose to deep venous or
intracardiac thrombus formation, possibly complicating the illness.
Oxygen, digoxin, and diuretics
Although no clear-cut survival or hemodynamic benefit has been shown to
result from the use of oxygen in the patient with primary pulmonary
hypertension, portable oxygen is an important adjunct to the symptomatic
care of the hypoxemic patient.
Despite the lack of directed investigation, experience suggests that at
least some patients with clinical right ventricular failure experience
symptomatic improvement with chronic administration of digoxin. Clearly,
patients with peripheral edema and ascites require diuresis as
aggressively as possible within the constraints of maintaining adequate
right ventricular preload in the face of pulmonary hypertension.
Approach to management
Assess vasodilator capacity
Screening for pulmonary vascular responsiveness permits prediction of
response to long-term vasodilator treatment and selection of a
vasodilating agent. Short-acting drugs which have been used as acute
vasodilating test drugs include: epoprostenol, adenosine, nitric oxide,
and acetylcholine.
Testing is performed by administering incremental doses of the
short-acting vasodilator until a positive hemodynamic response or
negative endpoint is observed:
Negative endpoints for acute vasodilator testing (epoprostenol) in
approximate order of frequency
Hypotension
Headache
Severe flushing
Nausea, emesis
Restlessness, anxiety
Chest pressure, tightness, pain
Bradycardia
Severe lightheadedness
Pulmonary edema
Protocols for acute vasodilator assessment:
High-dose calcium channel blockade
The use of calcium channel blockers should be limited to patient subset
populations of relatively high expectation of success (judging from the
acute vasodilator study) and low risk. Patients with a mean right atrial
pressure of >15 or cardiac output or cardiac output < 2.0 liters are advised
not to undergo testing or treatment with calcium channel blockers because of
the likelihood that the negative inotropic effect will precipitate or
exacerbate right ventricular failure.
All patients should be hemodynamically monitored during the initiation
of calcium channel blockers. This is necessary not only to document any
hemodynamic benefit and titrate the dose to optimal effect, but also to
detect early any evidence of worsening pulmonary hypertension or right
ventricular dysfunction. An established protocol for initiating calcium
channel blockers has been advocated by Rich: nifedipine 20 mg or
diltiazem 60 mg (for patients with a resting heart rate > 100 beats/min)
is given by mouth hourly, with hemodynamic measurements made immediately
before each dose. Dosing was continued until a positive response occurred
, adverse effects intervened, or a total of 10 doses was given. An
alternative protocol used at the Mayo Clinic combines the use of smaller
"test" doses and an accelerated loading dose: nifedipine (nonextended
release) 10 mg hourly for three hours, then 20 mg hourly for three hours,
then one dose of 30 mg, followed in 4 hours by 40 mg, followed in 4 hours
by 50 mg. The procedure is terminated when an endpoint is reached, and a
maintenance dose is initiated: in the Mayo protocol, the highest tolerated
effective single dose is given every 6 hours, and the patient is ambulated.
The dose is adjusted if necessary. The occurrence or worsening of pedal
edema may be managed by diuretics, or by substitution of an equipotent dose
of diltiazem in place of nifedipine. The maintenance dose preferred by Rich
is half the cumulative dose given every 6 to 8 hours.
Epoprostenol
Consideration should be given to referring patients to experienced
referral centers for initiation of epoprostenol. Initiation of the drug
has usually been done during hemodynamic monitoring, incrementing drug
dosage following the protocol summarized in the above table. As experience
has accrued, the medication has increasingly been initiated during
inpatient admission, but without hemodynamic monitoring. In this situation,
the optimal dose is defined as the highest dose which does not produce
unacceptable side effects.
Once the optimal tolerated dose is identified, a chronic central venous
catheter may be placed and the infusion transferred from peripheral to
central line. At this point, dedicated nursing instruction about aseptic
home management of the central catheter, use of the pump and
reconstitution of the medication should be undertaken. Most patients
require 2 to 4 days of in- and outpatient instruction, perhaps assisted
by written and video or multimedia instruction, before they and the
medical personnel can be confident of appropriate learning. Long-term
cooperation between the referral center and the primary physician is
necessary for proper management of primary pulmonary hypertension
patients treated with epoprostenol. All members of the medical team
must realize the absolute necessity of maintaining an uninterrupted
infusion, since cessation of the drug has been associated with severe
rebound pulmonary hypertension, marked dyspnea, syncope, and death. The
central catheter should never be used for blood drawing or infusion of
other medications. Patients should have a backup pump in the event of
mechanical failure. Patients and their families are trained to identify
catheter defects and methods of attempting to clear an occluded line.
Local medical personnel are reminded that if the central catheter fails,
the infusion at the same rate should be transferred immediately to a
peripheral line after priming.
Most investigators have found that patients tend to do best if the
maintenance dose is gradually increased on a regular basis in the
absence of side effects."Prophylactic" increments of 1-2 ng/kg/min
every 1 to 4 weeks have been employed, and some patients are currently
on doses in excess of 100 ng/kg/min. The absence of expected side
effects has been used as an indicator for increasing the dose.
Expected side effects include jaw/parotid pain (especially at the
commencing of chewing), diarrhea, musculoskeletal discomfort, mild
flushing or limb warmth, and photosensitivity. Other side effects may
occur but do not necessarily reflect either excess or insufficient
medication, such as ascites, depression, rash, or thrombocytopenia.
These outcomes may be idiosyncratic drug reactions or sequelae of the
underlying disease. Signals of potentially excessive drug doses include
severe flushing, bradycardia, back pain, hypotension, headache,
nausea, and vomiting.
The majority of patients treated with epoprostenol feel improved with
enhanced exercise tolerance. Supplemental oxygen may be discontinued
in some cases, if comfort is maintained without it. Adjustment of
other medications, such as previously initiated vasodilators, may be
necessary. Occasionally, patients may need to be reminded to avoid
overexertion if their symptomatic improvement exceeds objective
hemodynamic improvement.
Epoprostenol may effectively stabilize progressively ill individuals,
allowing them to be viable transplant candidates ("pharmacological bridge
to transplant"). Occasionally, patients on a transplant waiting list may
show sufficient evidence of improvement to raise the question of whether
transplant should be deferred or is still advisable at all. Sufficient
comparative evidence is not available to permit clear recommendations in
such situations, though in the absence of survival results comparable to
heart transplantation, and in an environment of inadequate numbers of
donor organs, it may be reasonable to reconsider lung transplantation in
some patients who have stabilized.
Additional treatment
Patients with pulmonary hypertension should be anticoagulated (unless
specific contraindications exist) because of retrospectively demonstrated
survival benefit and the possible role of in situ thrombosis complicating
the course of the disease. Patients receiving epoprostenol warrant
anticoagulation to prevent catheter tip thrombosis, and possible
embolization through a patent foramen ovale into the systemic circulation.
An international normalized ratio of 2-2.5 has been considered appropriate
anticoagulation.
Oxygen should be administered to hypoxemic patients, and those with
clinical evidence of right heart failure may require digoxin and
diuretics.Long-term treatment with inhaled nitric oxide or aerosolized
epoprostenol has been reported but cannot yet be recommended for general
use.
Learning About PPH
The followings links are to other web sites that concentrate on PPH and PPH
related medicine.
National Insitute's of Health (NIH) Web Page on PPH
Pulmonary Hypertension Association
United Therapeuics Corporation
William Harvey Medical Research Foundation
William Harvey Press
Primary Pulmonary Hypertension: Medical Treatment
Michael D. McGoon, M.D.
The purpose of this artical and my sending it to you is two fold; one
to educate people to an illness that may end up killing my wife; one that
started out and she thought was just a cold. If you get a cold and it seems
that you cannot shake it, get to a doctor.
My other reason for this is that my wife and I need the help of the public.
We live in welland and must travel to Toronto we have been relying on
friends to get us back and forth to Toronto as we do not have a vehicle
that will make the trip.
Everyone has heard the storys on the news of how the public pulls together
to help someone that is sick. Well that is what we are asking for you to
do.
We need to raise enough money to buy a reliable vehicle, have money for a room
in Toronto, and for meals; also we would like to raise enough to prepay
for my wifes funeral expences, as even with a transplant the odds are not good
65% that she survives the surgery and 45% that she will survive 5 years.
Once she has the surgery we will have to spend 3 days a week in Toronto
for the first 3 to 6 months and gradually it tapers off to 1 day every 3 months.
So we will also need to raise enough money to be able to keep up with or day to
day expences here. We had raised aproximatly $2200.00 but that has been used
during the last 3 trips to toronto as 1 trip was 5 days long, 1 trip 3 days
long and the last only a day. Each of these trips is very expencive, a hotel
room costs $75.00 a day,so we tried the hostel and that cost us $90.00 a
day. As well the last time we went up we where driven one way but took the bus
back home that cost us almost $50.00. By getting our own vehicle we could
eliminate some of these expences.
A trust acct has been set up with the TD Bank branch #3824 acct #3157670.
Please YOUR help is needed in this quest to save a life. Or you can send
donations to 78 DOVER ROAD
WELLAND ONTARIO
L3B 2V2
YOURS SINCERLY
JIM BOTTRILL
