Pulmonary arterial hypertension is a relatively rare but serious condition – in fact, 60 percent of patients don’t live more than 5 years after diagnosis. Most treatment of the disease involves dilating the arteries to lower pressure. But increasingly, research suggests inflammation may be behind the condition – and newer therapies are on the horizon.
A review of pulmonary arterial hypertension from this immunological perspective -- including specialized information for anesthesiologists -- is now available from the journal Anesthesiology.
Pulmonary hypertension is defined as a resting mean pulmonary artery pressure of 25 millimeters of mercury or higher. Pulmonary arterial hypertension is a type of pulmonary hypertension that mainly affects the blood vessels in the lung. Cases can be idiopathic, hereditary, or associated with infections or a variety of autoimmune or other systemic conditions.
The disease is progressive and cannot be cured. More awareness and better management has meant more patients are undergoing non-cardiac surgery, but operations are high-risk. About 40 percent of patients have serious complications, and up to 8 percent die, usually within 48 hours due to right heart failure.
Whenever possible, patients should delay surgery until consulting with a multidisciplinary team to optimize therapy in advance.
All 14 FDA-approved therapies work by dilating the pulmonary vasculature. They target four major pathways, including calcium channels and endothelin receptors. Nitric oxide, a potent vasodilator, can be inhaled, rebalancing the mix of constricting and dilating substances. And prostanoids have direct dilation effects.
Some drugs may need to be continued during surgery and may affect anesthetics, so great care should be taken when planning operations with these patients.
While existing drugs may be moderately effective, they don’t address the underlying inflammatory mechanisms that have been implicated in the disease. These include increased levels of cytokines or other mediators, as well as infiltration of a variety of immune cells and even autoantibodies, especially later in the disease.
Given these findings, there is considerable interest in developing new therapies. The authors identified 70 registered clinical trials since 2015, 14 of which are focused on inflammation, including targeting B cells with the antibody rituximab; inhibiting interleukin-1 beta and N-F-kappa-B; and blocking the neutrophil molecule elastase, which contributes to harmful remodeling of lung vessels.
As new immunology-based drugs come online, anesthesiologists will have to be vigilant in considering interactions with anesthetics, evaluating patients for infection, and in identifying other conditions that may result when susceptible patients have surgery.
Find out more about how anesthesiologists can take on pulmonary artery hypertension by reading the full review today.