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Crit Care Nurse 2004 Apr; 24(2): 42-54
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Clinical Article

Advances in Prostacyclin Therapy for Pulmonary Arterial Hypertension

Patricia L. Eells, RN, MS, CPNP

Patricia L. Eells is a pediatric nurse practitioner with an extensive background in the treatment of children with pulmonary hypertension. She has 15 years of experience in critical care nursing.

To purchase reprints, contact The InnoVision Group, 101 Columbia, Aliso Viejo, CA 92656. Phone, (800) 809-2273 or (949) 362-2050 (ext 532); fax, (949) 362-2049; e-mail, reprints{at}aacn.org.

Pulmonary arterial hypertension (PAH) is a progressive, life-threatening, incurable disease. It is characterized by mean pulmonary artery pressure greater than 25 mm Hg at rest or 30 mm Hg with activity.1,2 Pulmonary hypertension was once differentiated into primary and secondary forms but was reclassified in 1998 after the World Health Organization symposium on pulmonary hypertension. This reclassification was designed to reflect clinical patterns of disease. The current classification is based on differences between primary pulmonary hypertension (PPH) and pulmonary hypertension of certain known causes.1,3 These types of hypertension differ with respect to patients’ clinical manifestations and pulmonary histopathologic findings.1,2,4 The reclassification allows categorization by common clinical features (Table 1Go).


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  		Table 1 Classification of pulmonary arterial hypertension according to the World Health Organization1

 
A diagnosis of PPH indicates PAH with no identifiable cause and includes the familial or the genetic form of the disease.5 Although most cases of PPH are sporadic, the prevalence of familial disease is at least 6%.1,2,6 Other forms of pulmonary hypertension as described in the World Health Organization proposals include pulmonary venous hypertension, pulmonary hypertension associated with disorders of the respiratory system and/or hypoxemia, pulmonary hypertension caused by chronic thrombotic and/or embolic disease, and pulmonary hypertension resulting from disorders that affect the pulmonary vasculature.1,2 Before the World Health Organization reclassification, the aforementioned categories were referred to as secondary pulmonary hypertension.

Patients with PAH are further classified according to their level of functional ability. This classification is determined by patients’ exercise performance. The functional assessment grading scale shown in Table 2Go has been modified according to the functional classification system of the New York Heart Association.1,2 Patients with class I disease have PAH but are symptom-free. Patients with class IV disease may have signs or symptoms of PAH while at rest and cannot undertake physical activity without having signs and symptoms of PAH.1,2


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  		Table 2 Functional classification of pulmonary hypertension according to the World Health Organization (modified after the New York Heart Association functional classification)1,2

 
The incidence of PPH is 1 to 2 cases per 1 million per year. PPH is rapidly progressive and fatal when left untreated.1,2 Other causes of PAH may account for an additional 1 to 2 cases per million each year.1,2 Histological changes take place sequentially and include smooth muscle hypertrophy of the arterial wall, intimal proliferation, in situ thrombosis, occlusion of small vessels, and the formation of plexiform lesions that are unevenly distributed throughout the pulmonary vasculature.3,7,8 The cross-sectional area of the pulmonary vascular bed is severely diminished by the obliteration of small vessels (Figure 1Go).9



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  		Figure 1 Pathogenesis of pulmonary arterial hypertension. Reprinted from Gaine,9 with permission.

 
Altered function of the pulmonary vascular endothelium may also be an important consideration in patients with PAH.8,10,11 An imbalance in the ratio of prostacyclin, which causes vasodilatation, and thromboxane, which causes vasoconstriction, may occur. This finding suggests that either enhanced activity of thromboxane or diminished production of prostacyclin may contribute to the pathogenesis of PAH.10,11 Additionally, impaired synthesis of the endothelium-derived vasodilator nitric oxide and increased production of the endothelium-derived vasoconstrictor endothelin have been associated with PAH.5,10–12

Progressive and sustained elevations in pulmonary artery pressure and pulmonary vascular resistance ultimately lead to right ventricular failure.3 According to data from a US national registry of patients started in 1981, without treatment, the median survival of patients with PPH is 2.8 years after diagnosis, with survival rates of 68%, 48%, and 34% after 1, 3, and 5 years, respectively.13,14 Variables associated with poor prognosis include New York Heart Association functional class III or IV, the presence of Raynaud phenomenon, increased right atrial pressure, increased mean pulmonary artery pressure, reduced cardiac index, and decreased carbon monoxide diffusion capacity.14


   Evaluation of Patients With PAH
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The diagnosis of PAH remains difficult and is often elusive, particularly early in the course of the disease. Initial signs and symptoms are typically subtle and nonspecific, and the onset of the disease is gradual.1 In addition, the incidence of the disease is relatively low, and caregivers most likely are not familiar with the potential signs and symptoms. As a result, the diagnosis of PAH is commonly delayed, sometimes for more than 2 years after the onset of signs and symptoms.2,5

In general, the signs and symptoms of PAH reflect the inability of the pulmonary vascular bed to accommodate increases in cardiac output. Initial signs and symptoms may include pallor, shortness of breath, dyspnea on exertion, syncope, and chest pain related to right ventricular ischemia.2,5 Physical findings depend on the severity of the disease and may include a loud S2 in the pulmonary region, a right ventricular heave, and a pulmonary flow murmur. Progression of right-sided heart failure is signaled by jugular venous distention, edema, and an S3 gallop.5,6 Of note, however, no signs and symptoms are specific to PAH, and additional clinical tests are required to confirm the diagnosis.

The algorithm presented in Figure 2Go shows appropriate diagnostic testing for patients being evaluated for PAH.5,15 Radiographs may show enlarged central pulmonary arteries and right ventricular enlargement.6 An echocardiogram is obtained to determine the presence or absence of left ventricular dysfunction and valvular disease. Estimated pressure readings from the right ventricle may be helpful in predicting disease severity. The right atrium or right ventricle may be enlarged.2 Evaluation of the right side of the heart can assist in building of a more complete picture of the degree of heart failure. An echocardiogram is used to detect any congenital heart disease and to assess any shunts present.6 Serial echocardiograms are helpful in long-term follow-up to monitor disease progression and the patient’s response to treatment.1 Electrocardiograms may be used to detect evidence of right atrial and right ventricular hypertrophy.2,6



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  		Figure 2 Algorithm for diagnostic testing and classification of pulmonary hypertension. Abbreviation: HIV-1, human immunodeficiency virus type 1. *Antinuclear antibody, antineutrophic cytoplasmic antibody, rheumatoid factor. Reprinted from Gaine and Rubin,5,15 with permission of Elsevier and the Pulmonary Hypertension Association.

 
A ventilation-perfusion lung scan is required to exclude chronic thromboembolic disease.5 Pulmonary angiography can be performed if the ventilation-perfusion scan indicates intermediate probability of thromboembolic disease. Other diagnostic studies may include computed tomography to detect interstitial lung disease or high-resolution computed tomography in place of ventilation-perfusion studies. Pulmonary function tests may also be used to detect any common respiratory ailments that might be causing shortness of breath.6 A sleep study should be done to screen for sleep apnea, which may contribute to pulmonary hypertension.5 A standardized exercise test known as the 6-minute walk is also used to give an estimate of a patient’s exercise tolerance.6 This test should be repeated over time in patients with PAH. Results from the 6-minute walk are useful in assessing a patient’s response to therapy and/or disease progression. In addition, serological tests are done to detect collagen vascular disease, hepatitis, or infection with human immunodeficiency virus.5

Right heart catheterization is the most important and useful diagnostic tool in the evaluation of patients with PAH. This procedure is the only way in which pulmonary artery pressure, cardiac output, and pulmonary vascular resistance can be specifically determined.5 Catheterization is also important in excluding left-sided cardiac dysfunction. During catheterization, vasoreactivity must be evaluated to determine the appropriate treatment pathway (Figure 3Go).16 Patients who are in heart failure or whose hemodynamic status is unstable are not suitable candidates for vasoreactivity testing, because this may cause further deterioration in their hemodynamics.



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  		Figure 3 Treatment pathway for pulmonary arterial hypertension, with options available after classification and vasoreactivity testing. Functional assessment gradings are those of the modified New York Heart Association functional classification system. *IIIa (early stage III) and IIIb (advanced stage III) classifications. Modified from Tapson et al.16 with permission of the Pulmonary Hypertension Association.

 
Vasoreactivity testing involves assessing a patient’s response to the short-term administration of a selected vasodilator. Accepted vasodilators for this type of testing include inhaled nitric oxide, intravenous adenosine, and intravenous epoprostenol.1,5 A patient’s acute response may correlate with his or her response to oral vasodilator therapy. Although not uniformly defined, a positive or favorable response may be indicated by a reduction in baseline mean pulmonary artery pressure of at least 20%, with either no change or an increase in cardiac output, and minimal effect on systemic blood pressure.17,18 Patients who have a positive response are generally appropriate candidates for therapy with oral calcium channel blockers. However, such responses typically occur in only 20% to 30% of patients.1,2,5,11 A negative response is indicated by no significant improvement or by a deterioration in pulmonary hemodynamics.2 Patients who have a negative response are unlikely to benefit from therapy with oral calcium channel blockers.1


   Medical Treatment
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 Medical Treatment
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 Conclusion
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Historically, conventional therapy of patients with PAH involved treatment with oral calcium channel blockers, diuretics, and anticoagulants and the restriction of physical activity. Recent advances in therapeutics and in the understanding of the pathophysiology of pulmonary hypertension have led to new medical treatment options with prostacyclin therapies. Surgical treatment options, which are not discussed here, include lung or heart-lung transplantation for patients who are unresponsive to conventional therapy and atrial septostomy, which also typically is reserved for patients in whom medical management is unsuccessful.

Anticoagulants
Most patients with PAH are started on anticoagulant therapy at the time of diagnosis, unless they have any known contraindications.6 Patients with PAH experience a decrease in cardiac output due to the left ventricular compression that occurs with right ventricular hypertrophy. As a result, they are at risk for pulmonary embolism. The decrease in cardiac output is also associated with injury to the pulmonary vascular bed.5 In studies19,20 in adults with PPH, use of anticoagulants was associated with improved survival. Treatment guidelines1,2 recommend a target international normalized ratio of 1.5 to 2.0, although individual clinical circumstances may require adjustment of this range.

Oral Vasodilators
In patients with PAH, the decision to use oral vasodilators is based on the occurrence of pulmonary vasoconstriction.13,19,21 Determination of the suitability of these agents for any given patient is based on the results of acute vasoreactivity testing performed during cardiac catheterization. Data22 obtained in children with PPH indicated 1-, 3-, and 5-year survival rates of 97% in those who responded positively to vasoreactive agents. Nonresponders had poor survival when treated with calcium channel blockers, with 1-, 3-, and 5-year survivals of 66%, 52%, and 35%, respectively. As stated previously, approximately only a quarter of patients respond to therapy with oral calcium channel blockers.1,2,5,11 Nifedipine and diltiazem are used most commonly. The major limitation of these agents is their nonselectivity for the pulmonary vasculature. Adverse effects include systemic hypotension, edema, and hypoxemia.6 Inappropriate use of vasodilators can result in rapid clinical deterioration, with worsening heart failure and hemodynamic measures. Oral vasodilators should not be used in patients with a cardiac index of 2.1 or less, and/or a pulmonary arterial saturation of 63% or less, and/or a right atrial pressure of 10 mm Hg or greater.2

Adjunctive Therapies
Inotropic agents are used to improve contractility and maintain cardiac output.1 Diuretics, such as furosemide, are used as needed to prevent volume overload, thereby reducing ventricular overload.5 Oxygen is used to maintain adequate arterial saturation, thereby preventing the vasoconstriction and increases in pulmonary pressure often associated with hypoxemia.2

Prostacyclin Therapies
The prostaglandins are potent endogenous vasodilators with antiproliferative and cytoprotective properties. Their action is associated with remodeling of the pulmonary vascular bed and with reductions in endothelial cell injury and hyperco-agulability.2 Notably, imbalances in the ratio of thromboxane to prostacyclin metabolites have been detected in patients with pulmonary hypertension, with reduced pulmonary arterial levels of prostacyclin synthase.1 A comparison of current prostacyclin therapies highlights their unique differences and indications (Table 3Go).


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  		Table 3 Comparison of therapy with treprostinil and epoprostenol

 

   Treatment With Epoprostenol Pharmacological Properties
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The naturally occurring prostaglandin epoprostenol (prostacyclin) is produced by the vascular endothelium. Epoprostenol is a potent, short-acting vasodilator of both the systemic and the pulmonary arterial vascular beds and is an inhibitor of platelet aggregation.23 In addition, epoprostenol may provide benefit through effects on vascular growth and remodeling of the vascular bed.11 As the agent is unstable at pH values less than 10.5, it cannot be given orally. Because of its short half-life in the circulation, epoprostenol must be given via continuous intravenous infusion.23

Intravenous therapy with epoprostenol sodium (Flolan) was approved by the Food and Drug Administration in 1995 as a long-term treatment for patients with PPH and New York Heart Association class III or class IV disease. In an open, prospective, randomized 12-week clinical trial in 81 patients with class III or class IV PPH, continuous intravenous epoprostenol significantly improved hemodynamics, exercise capacity, quality of life, and survival.24 Since the approval of epoprostenol, patients with pulmonary hypertension associated with other conditions have also been treated with this agent. Intravenous epoprostenol has been administered as long-term therapy to patients with PAH associated with connective tissue disease, congenital heart disease, and infection with human immunodeficiency virus. Approval for long-term treatment of patients with pulmonary hypertension associated with the scleroderma spectrum of diseases was granted in 1999.

Long-term therapy with intravenous epoprostenol was effective in the treatment of pulmonary hypertension in patients deemed to be nonresponders to conventional vasodilator therapy.21,22 In one study,22 a group of 24 children noted as nonresponders to vasoactive agents and subsequently treated with intravenous epoprostenol had 100% survival after 1 and 2 years, and 92% survival after 3 and 4 years. In contrast, 22 nonresponders treated with conventional therapy alone had survival rates of 43%, 34%, 29%, and 29% after 1, 2, 3, and 4 years, respectively.22 Intravenous therapy with epoprostenol was either declined or unavailable for the second group of children.

Complications
Although successful in the treatment of pulmonary hypertension, intravenous epoprostenol therapy is both costly and complex. Therapy requires the insertion of a central venous catheter for continuous administration. This requirement predisposes patients to the complications of catheter infection, sepsis, thrombosis, paradoxical embolus, catheter fracture or displacement, and difficulties associated with pump malfunction.5,24,25 Because the elimination half-life of intravenous epoprostenol is only 2 to 3 minutes, any abrupt cessation in administration may cause a rebound episode of pulmonary hypertension and possibly sudden death.5,24 Conversely, inadvertent administration of a bolus of epoprostenol can cause abrupt, profound systemic hypotension and loss of consciousness. Adverse effects of the drug include headache, jaw pain, diarrhea, rash, flushing, stomachache, muscle pain, and arthralgia.2

Another disadvantage of epoprostenol is the need to carry a bulky intravenous pump at all times. Patients must also have a backup pump, intravenous tubing, and medication with them at all times for use in the event of mechanical failure. The medication must be kept cold with ice packs during infusion to maintain its stability during a 24-hour period. The drug can be administered at room temperature, but infusions must be changed every 8 hours. Patients and their caregivers must reconstitute the drug, in many instances reconstituting multiple vials, every 24 hours. Education of patients and their families is critical. Caregivers must remain vigilant at all times to protect patients from the life-threatening complications that may occur.

Moreover, therapy remains costly; the mean annual cost for the medication is US $60000.8 Estimations of cost for a drug of this type typically do not reflect additional costs for infusion pumps, tubing, and syringes. Estimates also do not include the cost of inpatient days for placement or replacement of the central catheter or for the treatment of catheter-related complications such as infection. Prostacyclin therapy is not curative, and therefore lifelong treatment and education are required.


   Treatment With Treprostinil Sodium Pharmacological Properties
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Conclusion
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Treprostinil sodium (Remodulin) is a synthetic, stable form of prostacyclin.25 The major pharmacological actions are the same as those of epoprostenol: direct vasodilation of the pulmonary and systemic vascular beds and inhibition of platelet aggregation.25,26 Unlike epoprostenol, treprostinil is chemically stable, with a neutral pH at room temperature.25,26 In addition, treprostinil has a longer elimination half-life of approximately 3 hours.26 These differences are of considerable importance, because the physical properties of treprostinil allow the drug to be administered as a subcutaneous infusion and at room temperature.26

Treprostinil was approved by the Food and Drug Administration in May 2002 for the treatment of PAH in patients with New York Heart Association class II to class IV disease.27,28 Approval was granted after the results of a 12-week, double-blind, placebo-controlled multicenter trial involving 470 patients with PAH who were not responsive to conventional therapy.29 Treprostinil produced clinically significant improvements in exercise tolerance (6-minute walking distance and Borg dyspnea score), signs and symptoms of PAH, and hemodynamics. The acute hemodynamic effects of treprostinil are similar to those of epoprostenol.30,31

Because treprostinil was introduced into clinical practice so recently, reports of experience with its use are currently limited. The following discussion, therefore, reflects my own experience in the management of patients with PAH with this innovative new agent.

Patients’ Education
Education of patients about the role of treprostinil in their treatment and its delivery is critical. Some centers have patients hospitalized when treatment is initiated, with medication and delivery instruction provided by experienced nurses. The length of stay required for this purpose is typically less than 3 days. Other centers instruct patients before therapy is started. After this initial teaching, therapy may be started in the outpatient clinic or in a short-stay setting, with the patient being admitted for less than a day.

The choice of the most appropriate setting for the initiation of treatment varies among practitioners and centers and is influenced by several factors. These factors include patients’ comfort and skill, the presence or absence of support systems for patients, patients’ overall clinical condition, the stability of patients’ clinical condition, and the comfort level of the prescribing practitioner. Thus, initiation of treprostinil therapy differs markedly from that epoprostenol therapy, which always requires hospital admission for surgical placement of a central venous catheter for drug administration. Additional days in the hospital are then required to achieve appropriate dosage levels and to instruct patients on care of the central venous catheter, drug administration, and management.

Patients and caregivers must receive extensive training in pump operation before treatment begins. All parties must show that they can program the pump accurately for drug delivery and can recognize and respond to basic pump alarms. The pumps must never be immersed in water, but patients may shower with the devices in place if the pumps are protected with shower bags. Pump batteries are changed once each month, and each patient must have 2 devices readily available at all times in case of pump failure. Pumps must be shielded with lead during radiography and must never be exposed to magnetic fields, such as those used during magnetic resonance imaging. If a patient must undergo such imaging, special extension tubing must be used to keep his or her pump out of the room during the procedure.

Administration and Dosing
Treprostinil is available in 4 concentrations: 1, 2.5, 5, and 10 mg/mL.26 Patients are supplied with their prescribed concentration of the drug and withdraw a specified quantity from a 20-mL multidose vial every 72 hours. No reconstitution is needed, and the drug is ready for infusion via a microinfusion pump immediately after withdrawal from the vial. The device currently in use is the MiniMed 407C (Medtronic MiniMed, Northridge, Calif ), an extremely small and lightweight pump that resembles a pager (Figure 4Go). Because treprostinil is stable at room temperature, no cooling of the drug is required during infusion.



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  		Figure 4 Subcutaneous infusion of treprostinil sodium.

 
Treprostinil is administered via the self-insertion of a subcutaneous catheter. It is helpful if patients have the opportunity to practice subcutaneous injections with isotonic sodium chloride solution during teaching sessions so that they are familiar with this technique before treatment starts. Caregivers, particularly parents, often appreciate the opportunity to practice this skill before therapy begins. This practice allows patients to feel the injection and enhances their insight into the experience. The injections are relatively painless and are well tolerated by patients of all ages. After the injection is completed, the needle is withdrawn, and a soft, flexible catheter is left in place. The site is then covered with an occlusive dressing. Critical care nurses often can validate that proper technique is being used, increasing the caregivers’ confidence.

The primary site for treprostinil delivery is the subcutaneous tissue of the abdomen. Patients are instructed to divide their abdomen into 4 quadrants. Injection sites are then rotated clockwise, moving from one quadrant to the next. Injection sites should be at least 2.54 cm (1 in) apart. Patients are taught to avoid areas immediately above and below the umbilicus, because these areas tend to be more sensitive than other abdominal areas. Alternative sites for injection include the posterior parts of the arms, above the elbow, and the outer parts of the thighs, although comfort with these areas varies substantially among patients. Injection sites are typically changed every 3 days. The syringe containing treprostinil and the infusion delivery system are changed at the same time as the site of injection.

Infusion tubing must be clamped if the syringe containing treprostinil is removed from the pump during drug delivery. This clamping is vital to avoid inadvertent bolus injection. The signs and symptoms of overdosage are consistent with reported adverse effects and include flushing, headache, hypotension, nausea, vomiting, and diarrhea. Most events are self-limiting and resolve with a reduction in dose or cessation of treatment.

Treprostinil dosages vary among patients and are increased over time. Therapy is typically started at a dosage of 1.25 ng/kg per minute. If this initial dosage is not tolerated, the infusion rate is decreased to 0.625 ng/kg per minute.26 The goal of long-term dosage adjustments is to establish a dose at which the signs and symptoms of PAH are improved and adverse effects of treprostinil are minimized.26 There is no set rate of increase or predetermined maximum dosage. Critical care nurses should emphasize this important variability in dosing during teaching. Patients must learn to accurately report their signs and symptoms of PAH, as well as adverse effects of treprostinil. Patients must maintain close contact with their prescribing practitioner, and dosage adjustments are made accordingly.

Adverse Effects
Adverse effects of treprostinil therapy include headache, flushing, stomachache, diarrhea, jaw pain, and pain and reactions at the infusion site.26 Reactions at the infusion site include erythema, induration, and rash. In my experience, most adverse effects associated with treprostinil therapy are less severe than those associated with epoprostenol therapy.

Pain at the injection site may be a problem. The intensity of the pain differs from patient to patient; some patients have moderate to severe pain at low doses, whereas others have no pain or only very mild pain with larger doses. The pain may lead some patients to consider cessation of therapy, despite the promise of clinical benefit. Therefore, patients should be aware of the potential for such pain before they start therapy. Patients should receive instruction in appropriate pain management strategies. Indeed, many centers provide patients with handouts on pain management. Such measures should not be viewed as a substitute for close communication between patients and prescribing practitioners or pulmonary hypertension nurses.

Several therapies are available to reduce the level of pain at the injection site, although the response to them varies between patients. A stepwise approach is therefore often used in an effort to find the most effective treatment with the fewest complications. Topical agents include aloe vera gel, vitamin E cream, local anesthetic preparations such as lidocaine patches, hydrocortisone cream, arnica oil, and various proprietary topical preparations containing anti-inflammatory or soothing ingredients. Treatment with pluronic lecithin organogel is an exciting development in the management of pain and reactions at the injection site. The gel is a transdermal delivery vehicle that enhances penetration of various topical pain medications. In a recent 12-week pilot study,32 referred to as the Wisconsin Protocol, the safety and effectiveness of 4 formulations of pluronic lecithin organogel in treating pain and reactions at the infusion site were examined. The results indicated that these gels provide symptomatic pain relief and significant reductions in healing time.32

Oral therapies for pain include nonsteroidal anti-inflammatory agents, acetaminophen, diphenhydramine, and low-dosage antidepressants such as amitriptyline or paroxetine (Table 4Go). Acute narcotic treatment may be prescribed for severe pain.


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  		Table 4 Therapies for relief of pain at the infusion site

 
Additional recommendations for relieving pain include alternating application of cold compresses and heat, acupuncture, and the use of relaxation techniques. Patients may gain additional relief by changing injection sites more or less frequently than usual or by changing to a shorter catheter. Decreasing the rate of increases in dosage may also be beneficial but should be undertaken only in direct consultation with a pulmonary hypertension specialist.

Patients and caregivers must be prepared to respond to disease- and infusion-related emergencies. Patients are encouraged to obtain and wear medical identification bracelets that state that the wearer has pulmonary hypertension and emphasize that the infusion of medication should not be stopped. It is also important to indicate whether the patient is taking an anticoagulant. Patients and caregivers should uhave contact numbers with them at all times in case of emergency. Consultation with a healthcare practitioner should be sought immediately if any unusual, persistent, or severe signs or symptoms occur.

Psychosocial Aspects
Patients must adapt to wearing the treprostinil infusion pump for continuous drug delivery. Although the pump is quite compact, its presence is constant. Issues of body image and intimacy must be explored openly with patients, both at the start of therapy and on an ongoing basis. This aspect of therapy may be especially important in children and adolescents, because concerns with body image and intimacy may change considerably over time as these patients grow older. Nurses and other care providers must be sensitive to these issues and must provide opportunities for open, honest discussion. Patients may find great value in discussing their experiences with others who are receiving the same treatment. Formal or informal support groups offer valuable benefits.


   Conclusion
Top
 Evaluation of Patients With...
 Medical Treatment
 Treatment With Epoprostenol...
 Treatment With Treprostinil...
 Conclusion
References
 Bibliography
 
The introduction of treprostinil offers new hope for patients with PAH. However, treatment is not curative and therefore must be continued indefinitely. To date, several patients in the United States have successfully made the transition from intravenous epoprostenol therapy to subcutaneous treatment with treprostinil.25 Most of these patients have subsequently been able to carry on with efficacious maintenance therapy. The advantages of a subcutaneous delivery system are clear: use of a central venous catheter is obviated, and the risks of thrombosis, catheter fracture, and infection are eliminated or reduced substantially. Inpatient days needed for the initiation of treatment and for delivery-related complications would be expected to be fewer with subcutaneous delivery of drug than with intravenous delivery. The substantially longer half-life of treprostinil relative to epoprostenol is likely to protect patients from sudden rebound pulmonary hypertensive crises and the risk of sudden death upon abrupt discontinuation of the drug. Finally, the infusion system for treprostinil is much smaller and lighter than the delivery system for epoprostenol and does not require constant cooling. These benefits should translate into improvements in quality of life for patients and more effective utilization of healthcare resources.

Regardless of the chosen treatment pathway, patients with pulmonary hypertension must undergo lifelong therapy. Comprehensive support for patients is an integral part of the treatment plan. Critical care nurses play a pivotal role in addressing the needs of patients who have pulmonary hypertension. This role includes the continual evaluation of each patient’s response to therapy and the reinforcement of previous education about the therapy. Determining which PAH treatment protocol is best for a patient requires consideration of the patient’s overall functional status, support system, and desire for autonomy. These factors must be examined at the outset of therapy and reexamined periodically. A close collaborative relationship between patient, nurse, and physician will ensure the best possible care and outcomes.


   Acknowledgment
 
The author would like to acknowledge financial support for this original, independent work from United Therapeutics Corporation. This support was utilized for the purpose of medical editing by an independent third party.


   References
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 Evaluation of Patients With...
 Medical Treatment
 Treatment With Epoprostenol...
 Treatment With Treprostinil...
 Conclusion
 References
Bibliography
 

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   Bibliography
Top
 Evaluation of Patients With...
 Medical Treatment
 Treatment With Epoprostenol...
 Treatment With Treprostinil...
 Conclusion
 References
 Bibliography
 
PH Neighborhood: http://www.phneighborhood.com.

Pulmonary Hypertension Association: http://www.phassociation.org.

United Therapeutics Corporation: http://www.unither.com.





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