Drug treatment varies widely in PAH patients presenting with shock
Study identified 25 initial vasoactive strategies across 2,347 adults
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A national database study found substantial variation in how clinicians manage people hospitalized with pulmonary arterial hypertension (PAH) who presented with shock, a life-threatening lack of blood flow to the body’s organs.
Researchers identified 25 different initial treatment strategies involving vasoactive medications, drugs that adjust blood pressure and heart function.
Researchers noted that the frequent use of phenylephrine, a blood pressure-boosting medication that may increase resistance in the lungs’ blood vessels and impair how the right side of the heart pumps blood into the lungs, “highlights an opportunity to improve education regarding its less favorable profile in PAH management.”
The study, “Patterns and Trends in Vasoactive Medication Use in Patients With Pulmonary Arterial Hypertension Presenting With Shock,” was published in Pulmonary Circulation.
Optimal vasoactive treatment remains unclear in PAH
PAH is marked by high blood pressure in the arteries that carry blood from the heart to the lungs, making the right side of the heart work harder to pump blood. In its advanced stages, severe PAH can trigger right heart failure.
About one in four people hospitalized with PAH are admitted to an intensive care unit, most often for heart failure or infection. Nearly half receive vasoactive medications to manage shock.
Because the optimal use of these medications in PAH has not been established, a team at the Boston University Chobanian & Avedisian School of Medicine sought to document how vasoactive medications are initially used in people with PAH and shock.
Their goal was to “inform the design of future comparative effectiveness studies seeking to optimize vasoactive regimens in patients with PAH.”
The team analyzed data from 2,347 adults admitted between May 2016 and December 2022 with PAH and shock present on admission. Patients who received invasive or noninvasive mechanical ventilation or underwent major surgery on the first hospital day were excluded. Data came from the Premier Inc. Healthcare Database, a claims database that includes about 25% of U.S. hospitalizations. The median age was 62 years, and 52.9% were women.
At hospital admission, more than half (54%) had kidney failure. After the first day, the majority (57.3%) received noninvasive or invasive mechanical ventilation. Septic shock, in which an infection causes dangerously low blood pressure, was diagnosed in 15.6%, while 18.4% had cardiogenic shock, which occurs when the heart cannot pump enough blood to the body. About one-fourth (28.5%) died during hospitalization.
On the first hospital day, norepinephrine, a drug that boosts blood pressure, was the most frequently used vasoactive medication, given to 45.8% of patients. This was followed by milrinone (32.1%), which helps the heart pump more strongly, and phenylephrine (29.3%) and vasopressin (24.1%), both of which increase blood pressure.
The most common single-medication approach was milrinone (16.6%), followed by norepinephrine (15.7%), phenylephrine (10.9%), and dobutamine (8.7%), which is used to strengthen the heartbeat.
Norepinephrine features in most common drug combinations
Among combinations, norepinephrine with vasopressin was the most frequent (3.4%), followed by norepinephrine with phenylephrine (2.8%), norepinephrine with dobutamine (1.9%), and norepinephrine with epinephrine (1.5%). A combination of norepinephrine, vasopressin, phenylephrine, and epinephrine (another blood pressure booster) was also used (1.5%).
The highest rates of septic shock were seen among patients treated with norepinephrine alone or with norepinephrine combined with vasopressin, dobutamine, or both. The lowest rates were seen with milrinone alone and two specific combinations: phenylephrine with milrinone, and norepinephrine with vasopressin, epinephrine, and milrinone.
The researchers noted that phenylephrine, the third most frequently used vasoactive medication in this study, may increase resistance in the lungs’ blood vessels and impair how the right side of the heart pumps blood into the lungs.
In a secondary analysis, 289 patients received phenylephrine for at least two days. After excluding those who ever required mechanical ventilation or underwent major surgery during hospitalization, 35 patients remained. In this group, the median duration of phenylephrine treatment was three days.
The researchers also saw similar use of milrinone and dobutamine, both medications that help the heart pump more strongly. They said this suggested clinical equipoise — genuine uncertainty about their relative effectiveness — and highlighted “the need for future comparative studies.”
The researchers noted that the study was limited by possible misclassification of PAH in the claims data and by medication records that showed use only by calendar day, making it unclear whether drugs listed together were given at the same time or one after another.
“In this multicenter retrospective cohort study of critically ill patients with PAH and shock, we observed a wide range of initial vasoactive strategies,” the authors wrote. “These results inform future studies seeking to identify optimal hemodynamic [blood flow] strategies in patients with PAH.”
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