Clinical Pearls: Pulmonary Hypertension
August 16, 2022
By Jessica Sheard
This article is part of a series appearing in
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Pulmonary hypertension (PH) is an uncommon, yet serious disease that significantly impacts those who are diagnosed. Once an individual is diagnosed with pulmonary hypertension, their mortality rate increases seven-fold, regardless of the classification or severity of PH at diagnosis1
. The prevalence of PH globally is 1% but increases to 10% in those over the age of 651
. The Pulmonary Hypertension Association estimates that there are between 5,000 and 10,000 patients, of all ages, genders, and backgrounds, living with PH in Canada2
. Although there has been significant progress to the diagnosis and management of PH in Canada, the prognosis in these patients remains poor, and patients affected still face significant morbidity and mortality1
. Pharmacists can play a key role in pulmonary hypertension management by ensuring medication safety, patient adherence, patient and provider education, side effect management, and transitions of care support3
There are five classes of PH that are recognized by the World Health Organization (WHO), the Canadian Cardiovascular Society, and the Canadian Thoracic Society1
It is important for pharmacists in acute care centres to be aware of the differences between the classifications of pulmonary hypertension, as they will guide both chronic medication management in acute pulmonary hypertension, as well as the treatment of acute pulmonary hypertension itself.
Available Targeted Therapies in Canada
There are 10 Health Canada approved targeted therapies for use in pulmonary arterial hypertension. These medications target three mechanisms that are known to cause PAH and its symptoms. Patients diagnosed with PAH often have deficient levels of prostacyclin1
. Prostacyclin pathway agents are used in PAH to open blood vessels and improve symptoms of PAH, such as chest pain and shortness of breath4
. Pulmonary arterial hypertension is also associated with elevations in endothelin-1, a potent vasoconstrictor1
. Endothelin receptor antagonists will reverse the effects of endothelin-1 and help to prevent blood vessels from narrowing1,4
. PAH patients will also be deficient in endogenous nitric oxide (NO)1
. Two families of medications are used as nitric oxide pathway agents, phosphodiesterase type 5 inhibitors (PDE-5i) and soluble guanylate-cyclase stimulators (sGCs)1
Patients hospitalized with acute pulmonary hypertension often experience concomitant right ventricular (RV) failure. RV failure in PH patients can lead to rapid decompensation and cardiogenic shock, that may be irreversible and lead to death5. Patients may present to hospital with either acute onset of chronic PAH, or acute PAH6. Patients with pre-existing PAH are vulnerable to serious illness and death from acute onset PAH6. These patients may have predisposing factors such as COPD, sleep disordered breathing, portopulmonary hypertension, and right heart failure that will exacerbate to acute PAH6. Acute PAH may also occur in patients without prior PAH, due to massive pulmonary embolism (PE), sepsis, or acute lung injury (ALI)6.
Acute management of pulmonary hypertension is first focused on treating triggering factors such as presence of infection, anemia, arrhythmia, PE, or other comorbidities, and administering supportive therapy5,7. Right ventricular dysfunction or failure must be prioritized in PH management through fluid status, managing RV afterload, and by optimizing cardiac output5,6,7. Most cases of RV failure are associated with fluid overload7,8. In these patients, fluid overload should be treated using IV diuretics5,7. However, in some cases hypovolemic patients may require fluid administration7. Reducing RV afterload is one of the most important interventions to reverse RV failure in PH patients7. Therapies used to reduce RV afterload in the acute setting include prostacyclins and other PAH-targeted therapies, as well as inhaled nitric oxide5,7. Epoprostenol, a prostacyclin, is often the drug of choice in PAH with RV failure5. This agent is used initially due to its rapid onset, shorter half-life, titratability, and pronounced reduction in afterload and mortality8. Treprostinil may also be used in place of epoprostenol, however, it is less often used due to its longer half-life5. Once the patient has been stabilized, there may be addition of oral endothelin receptor antagonists or PDE-5 inhibitors with or without withdrawal of the prostacyclin, depending if the patient is experiencing acute PAH or acute on chronic PAH7. Sildenafil’s short half-life and minimal side effects make it useful in critically ill PAH patients5. Nonspecific vasodilators such as calcium channel blockers should not be used in these patients due to profound systemic hypotension7. PAH patients who are critically ill with RV failure must also have cardiac output and systemic blood pressure optimized, while reducing pulmonary vascular resistance. Patients with low cardiac output and hypotension may need treatment with inotropes such as the β1-agonist dobutamine5,7. Vasopressors such as norepinephrine (NE) and vasopressin can be used to optimize systemic blood pressure and perfusion5,7.
Hypoxemia is common in critically ill patients with pulmonary hypertension. Hypoxemia in these patients may lead to added pulmonary vasoconstriction, and treatment with supplemental oxygen should be initiated with an oxygen saturation of over 90% recommended5. Due to the complex nature of pulmonary hypertension, it is highly recommended to contact a centre of expertise as soon as possible, and to obtain a referral to a pulmonary hypertension centre if possible5,7.
Initiation of new PAH medications in critically ill patients is complex and should be managed with the help of an experienced PH team, including pharmacists5
. It is important not to initiate medications indicated for Group 1 PH, in patients diagnosed with Groups 2-5 PH, as they may worsen symptoms, including precipitation of pulmonary edema in Group 2 PH patients5
. However, in most patients admitted to hospital with pre-existing pulmonary hypertension, home treatment should be continued5
. Abrupt discontinuation or dose reductions of PAH therapies may result in rapid decompensation and death in hospitalized patients5
. PAH medications are considered high-risk and are prone to potentially fatal medication errors9
. There are important clinical considerations for when patients are hospitalized while receiving PAH targeted therapy.
Transitions of Care
Pharmacists can play a key role the transitions of care for critically ill PH patients, including at hospital discharge. A recent report explored the role of critical care and ambulatory care pharmacists within a multidisciplinary team to improve the transitions of care for pulmonary hypertension patients10. In this program, the critical care pharmacist collected a PAH medication history, information on their home medication specialty pharmacy, and initiated medication access steps for new medications in hospital10. When the patient’s care was transferred to the ambulatory care pharmacist prior to discharge, the ambulatory care pharmacist provided adherence and medication counselling, adverse effect management, contacted the patient’s specialty pharmacy to ensure medication is continued, followed up on medication coverage, and followed up with the patient within 14 days after their discharge to ensure adherence and provide education when needed10.
While the complex and progressive nature of pulmonary hypertension results in significant morbidity and mortality for patients, pharmacists can play an important role in ensuring safe medication management while patients are in hospital. Pharmacists can aid in continuity of care for important PAH targeted therapy medications in hospitalized PAH patients and help to manage medications in both acute PAH and acute on chronic PAH. Pharmacists can also ensure that PAH target therapies are not used in inappropriate patient populations such as Group 2 and 3 PH, where the underlying heart or lung disease should be the focus of management. Finally, pharmacists can provide important education and ensure medication coverage to improve the transitions of care for their PH patients from their hospital admission to their discharge.
- Hirani, N., Brunner, N. W., Kapasi, A., Chandy, G., Rudski, L., Paterson, I., Langleben, D., Mehta, S., & Mielniczuk, L. (2020). Canadian Cardiovascular Society/Canadian Thoracic Society Position Statement on pulmonary hypertension. Canadian Journal of Cardiology, 36(7), 977–992. https://doi.org/10.1016/j.cjca.2019.11.041
- About Pulmonary Hypertension. Pulmonary Hypertension Association. 2021. Retrieved June 23, 2022, from https://phassociation.org/AboutPHA/
- Macaulay, T. E., Covell, M. B., & Pogue, K. T. 2015. An update on the management of Pulmonary Arterial Hypertension and the pharmacist’s role. Journal of Pharmacy Practice, 29(1), 67–76. https://doi.org/10.1177/0897190015615902
- Treatment Options. Pulmonary Hypertension Association of Canada. 2021. Retrieved June 23, 2022, from https://phacanada.ca/For-Physicians/Treatment-Options
- Barnett, C. F., O’Brien, C., & De Marco, T. 2022. Critical Care Management of the patient with pulmonary hypertension. European Heart Journal. Acute Cardiovascular Care, 11(1), 77–83. https://doi.org/10.1093/ehjacc/zuab113
- Hui-li, G. 2011. The Management of Acute Pulmonary Arterial Hypertension. Cardiovascular Therapeutics, 29: 153-175. https://doi-org.cyber.usask.ca/10.1111/j.1755-5922.2009.00095.x
- Hoeper, M. M., & Granton, J. 2011. Intensive Care Unit management of patients with severe pulmonary hypertension and right heart failure. American Journal of Respiratory and Critical Care Medicine, 184(10), 1114–1124. https://doi.org/10.1164/rccm.201104-0662ci
- Tilea, I., Varga, A., Georgescu, A.-M., & Grigorescu, B.-L. 2021. Critical Care Management of decompensated right heart failure in Pulmonary Arterial Hypertension Patients – an ongoing approach. The Journal of Critical Care Medicine, 7(3), 170–183. https://doi.org/10.2478/jccm-2021-0020
- Barlow, A., Barlow, B., Koyfman, A., Long, B., & Bissell, B. 2021. Pulmonary arterial hypertension in the emergency department: A focus on medication management. The American Journal of Emergency Medicine, 47, 101–108. https://doi.org/10.1016/j.ajem.2021.03.072
- Martirosov, A. L., Smith, Z. R., Hencken, L., MacDonald, N. C., Griebe, K., Fantuz, P., Grafton, G., Hegab, S., Ismail, R., Jackson, B., Kelly, B., Miller, M., & Awdish, R. 2020. Improving transitions of care for critically ill adult patients on pulmonary arterial hypertension medications. American Journal of Health-System Pharmacy, 77(12), 958–965. https://doi.org/10.1093/ajhp/zxaa079