Dunbar Ivy, MD
Assistant Professor of Pediatrics
Director of Pediatric Pulmonary Hypertension Program
Pediatric Heart Lung Center
University of Colorado Health Sciences Center
The Children's Hospital
Trish Eells, RN, MS, CPNP
Pediatric Heart Lung Center
The Children's Hospital
Pulmonary hypertension (PH) occurs when there is high blood pressure in the lungs. Pulmonary hypertension is a disease that involves both the heart and the lungs. Without treatment, the blood pressure in the lungs continues to rise over time, and it eventually may result in heart failure.
There are two types of pulmonary hypertension: primary and secondary. Primary pulmonary hypertension (PPH) means that there is no known cause for the pulmonary hypertension. It is a disease that is still not well understood. It may be associated with certain conditions, such as HIV, diet pill use, drug abuse, or exposure to various toxins. Secondary pulmonary hypertension (SPH) means that there is a disease or a condition that caused the pulmonary hypertension to develop. The pulmonary hypertension developed after, or secondary to, the other disease. Conditions or diseases that may lead to pulmonary hypertension include congenital heart defects, persistent pulmonary hypertension of the newborn, chronic lung diseases, autoimmune diseases, and liver disease.
Pulmonary hypertension may be diagnosed in infancy or later in life. Pulmonary hypertension affects people of all races and backgrounds.
In pulmonary hypertension, the blood vessels in the lungs constrict, i.e., they become smaller than normal. This constriction causes the pressure to build up in the vessels. The heart must work harder to try and push through the blood.
Because the heart must work harder to push through the blood, people with pulmonary hypertension often feel tired and may be short of breath, especially after activity. Other complaints may include dizziness, chest pain, fainting spells, and palpitations. People with pulmonary hypertension have a wide variety of symptoms; no two patients are the same. Sometimes, the complaints seem to come and go, with certain days being better than other days.
Pulmonary hypertension is a disease that worsens over time. As the pressure in the lungs gets higher, the heart must continue to work harder. Over time, the heart may not be able to pump as well. Some patients may notice swelling of their legs and their feet. They may develop tenderness over their liver. Some people may have trouble sleeping at night, requiring two or more pillows to get comfortable. The extra fluid in their lungs may cause this discomfort. Oxygen levels in the blood may become lower than normal, causing the lips and the nails to have a bluish tint to them. The fingertips may begin to bulge in appearance. Often, there are changes in appetite, and weight loss.
Most patients with pulmonary hypertension have had symptoms for about two years before they are diagnosed with the condition. This is because many of the symptoms are so subtle in the beginning, and they are similar to other conditions. It is important that a patient with pulmonary hypertension selects a physician and a center with experience in treating it. To diagnose pulmonary hypertension, a doctor conducts a variety of tests. The doctor performs a complete physical exam, with careful attention to a cardiac exam. A physician checks for unusual heart sounds that may indicate higher pressure in the lungs. The doctor also looks for certain physical findings, such as enlarged neck veins or swelling, which are associated with pulmonary hypertension.
A variety of blood tests are used to check blood counts and to assess liver and kidney function. It is important to look for the presence of other diseases, such as congenital heart disease. An electrocardiogram, or an EKG, is performed to look for evidence of a thickened heart, or abnormal heartbeats. Pulmonary function tests are done to look for any underlying lung disease that may be causing the symptoms. A ventilation perfusion scan looks for clots or blockages in the blood vessels of the lungs. A six-minute walk may be performed to determine the amount of distance that can be walked in this time period. This measurement is useful to follow once treatment begins for pulmonary hypertension.
An echocardiogram, which is an ultrasound of the heart, is very important. The echocardiogram allows a doctor to look at the heart and to find any structural problems that may exist. It also allows a doctor to look at the overall heart function and size, and to estimate pulmonary artery pressures.
A right-heart catheterization is the most important test used to diagnose pulmonary hypertension and to decide treatment options. This procedure involves placing a catheter in the groin and threading it up to the right side of the heart and into the pulmonary artery. In this position, it is possible to measure directly the pulmonary artery pressures, the filling pressures of the heart, and the cardiac output. The heart catheterization also allows a doctor to exclude any type of structural abnormality. During the procedure, a variety of medications are administered. These medications may include oxygen, nitric oxide, and prostacyclin. After each medication is given, the above measures are repeated. Future treatment options are determined based on the pulmonary artery pressures that are obtained after these medications.
There are a variety of treatments available for pulmonary hypertension. Treatment is specific to each patient, and is based on the information obtained during the heart catheterization. When secondary pulmonary hypertension is present, it is important to identify and treat the underlying cause, whenever possible. Sometimes, despite treatment of the cause, the pulmonary hypertension may continue. At times, treatment of the condition may cause an improvement in the pulmonary hypertension.
Medical treatment options include a variety of medications taken by mouth. Drugs may be used to remove the extra fluid that sometimes is retained with pulmonary hypertension. Such medications are called diuretics, and include lasix or aldacatone. To help the right heart squeeze better, a medicine called digoxin may be used. Patients with pulmonary hypertension are at risk for clot formation in the small vessels of their lungs. Warfarin is used in patients with pulmonary hypertension to help keep their blood thin and to reduce the risk of clot formation. Oxygen may be prescribed for patients who have low levels of oxygen in their blood. Other patients may use it while sleeping, and often feel less tired upon awakening.
Calcium channel blockers, such as Nifedipine, work to lower the pulmonary pressures in approximately 40% of children with primary pulmonary hypertension. These medications work by dilating the arteries in the lungs, causing the pulmonary pressure to fall. Sometimes, if the arteries have become rigid over time, they will not relax with the calcium channel blockers.
Epoprostenol sodium-also called prostacyclin, Flolan, or PGI2-is an intravenous medication that was approved for the treatment of primary pulmonary hypertension in 1995. This medication is similar in structure and in function to a substance made in the body called prostaglandin. It works by dilating blood vessels, by reducing clot formation, by improving cardiac output, and by slowing the growth of smooth muscle cells.
The dose of prostacyclin is increased over time to achieve maximal benefit and minimal side effects. Side effects to the medication include jaw pain, rash, flushing, stomachache, diarrhea, headache, musculoskeletal pain, and depression.
Prostacyclin is not a very stable drug; therefore, it cannot be given by mouth. Currently, prostacyclin is given intravenously through a permanent catheter placed in the large veins of the body. The catheter, called a Broviac or a Hickman, must be placed in the operating room. The medication is given 24 hours a day on a portable infusion pump. The caregivers must learn to mix the medication daily and to administer it using the pump. Interruptions in the drug delivery, even if brief, may cause a sudden rise in the pulmonary pressures, resulting in a reappearance of the symptoms, or even death.
Prostacyclin therapy is considered life long. However, the long-term result with it is good, with the survival rate predicted to be over 80% in a 5-year time period.
The surgical treatment for pulmonary hypertension is a lung transplant, which permanently will rid a patient of the disease.
Complications to therapy with prostacyclin include infection in the blood or at the site of the catheter, catheter fracture or displacement, and/or pump malfunction. Despite the current delivery method and the possible complications, children who are receiving intravenous prostacyclin tolerate it well. The vast majority of children attend school and participates in age-appropriate activities. Once treatment begins, their level of energy greatly increases.
Some patients with pulmonary hypertension undergo lung transplantation. There are complications related to a lung transplant that include rejection of the transplanted organ, and side effects to the transplant medications. Often, timing of the transplant is difficult to predict.
The major complication of pulmonary hypertension is right-heart failure. As the pressure in the lungs continues to build over time, the heart becomes a less effective pump. The right heart increases in size, and it eventually compromises the left heart function. Additional complications may include low platelet counts and severe bleeding in the lungs (called pulmonary hemorrhage). Without treatment, primary pulmonary hypertension is a fatal disease.
Currently, primary pulmonary hypertension cannot be prevented. Research is being conducted to identify genetic markers of this disease, which would allow early screening of those individuals at risk for it based on their family history. Presently, it is recommended that immediate family members be followed by an echocardiogram every five years, or as needed, to assist with early diagnosis and treatment.
In secondary pulmonary hypertension, treatment of the underlying condition is vital. For a child with a congenital heart defect, it is necessary to stay in close contact with a cardiologist. The surgical repair of the heart defect must be considered based on the child's condition.
Routine recommendations for children with pulmonary hypertension include annual flu vaccines, the use of antibiotics for significant upper respiratory tract infections, the treatment of a fever of 101 degrees or greater, a high fiber diet to prevent constipation and straining with bowel movements, and oxygen for airline travel.
In recent years, a great deal of research has been devoted to pulmonary hypertension. Newer therapies include treatment with a more stable form of prostacyclin, called UT-15. This medication is injected beneath the skin in the abdomen, and it does not require a central line. The half-life of the medication is longer; therefore, the risk of complications with an abrupt halt in delivery is lower. Clinical trials of this medication are currently underway in the United States and in Europe.
An investigational gas, called nitric oxide, is being examined for its role in the treatment of pulmonary hypertension. This gas is a powerful dilator of the blood vessels in the lungs. It also works to prevent the platelets from clumping together. Many patients with pulmonary hypertension have received this gas in the hospital, and some patients have shown a lowering of their pressures and an improvement in their symptoms. A small number of patients have gone home with nitric oxide. Though the gas remains investigational, in the future, it may be more common to treat patients at home with it.
Endothelin blockers and thromboxane inhibitors are investigational medicines that would block the narrowing of the blood vessels (vasoconstriction) that occurs in pulmonary hypertension. If the vasoconstriction is blocked, it is thought that the resultant opening (vasodilation) of the blood vessels would lower the pulmonary artery pressure.
An oral form of prostacyclin is being tested for its use in treating pulmonary hypertension. This drug is similar to intravenous prostacyclin. It is a more stable form of prostacyclin, and can therefore be given as a pill taken several times a day.
For more information on pulmonary hypertension, log on to: http://www.phassociation.org/AboutPH
Barst RJ. Recent advances in the treatment of pediatric pulmonary artery hypertension. Pediatric Clinics of North America 1999;46(2):331-45.
Ivy DD, Wolfe RR, Abman SH. Congenital heart disease. In Peacock AJ, ed. Pulmonary circulation: a handbook for clinicians. New York: Chapman and Hall Medical, 1996:449-66.
Ivy DD, Neish SR, Abman SH. Regulation of the pulmonary circulation. In Garson A, Bricker JT, Fisher DJ, Neish SR, eds. The science and practice of pediatric cardiology. Baltimore: Williams and Wilkins, 1998:329-47.
About the Author
Dr. Ivy is an assistant professor of pediatrics at the University of Colorado Health Sciences Center in Denver, Colorado, where he also serves as co-director of the pediatric cardiology fellowship program. Additionally, Dr. Ivy is director of the pediatric pulmonary hypertension program at the Pediatric Heart Lung Center. Board certified in both pediatrics and pediatric cardiology, his major scientific interests include pulmonary hypertension, pulmonary vascular biology, fetal circulation, cardiac intensive care, cardiac transplantation, and cardiac catheterization. Dr. Ivy has been instrumental in procuring grant monies for pulmonary and cardiac research. He is an accomplished clinician and investigator, authoring numerous papers, book chapters, presentations, scholarly reviews, and abstracts, for which he has been recognized with awards. Dr. Ivy is active in professional societies and institutional committees, in addition to participating on various journal review boards and partaking in visiting professorships.
Trish Eells, RN, MS, CPNP, is the coordinator for the Pediatric Heart Lung Center at The Children's Hospital, and a nurse practitioner in the Pulmonary Hypertension Program. The Pulmonary Hypertension Program treats children with both primary and secondary pulmonary hypertension, and offers a variety of approved and experimental therapies.