Patients with PAH Who Get Sepsis Experience Care Differences

Patients with pulmonary arterial hypertension (PAH) who develop sepsis are treated differently from patients without PAH, in part because it takes physicians longer to identify sepsis, according to a new review.

The findings are based on a decade’s worth of data from two academic hospitals. The study was published in BMC Pulmonary Medicine.

Alexander Sherman, MD, of the University of California Los Angeles David Geffen School of Medicine, explained along with colleagues that sepsis is the second most common cause of in-hospital death among people with PAH.

A 2020 study found that while mortality among people with PAH who were admitted to the hospital for a non-cardiac primary cause, the overall mortality rate was 6.9% (P < 0.001). However, among patients with PAH hospitalized due to sepsis, the mortality rate was 25.0%.

Sherman and colleagues said several cardiac and pulmonary implications of sepsis, including decreased right ventricular preload, increased right ventricular afterload, and reduced contractility, are already exacerbated in people with PAH. Yet, they said current management guidelines for PAH are based on expert opinion rather than clinical data. That lack of data can be particularly challenging with regard to fluid management, they said. Fluid resuscitation is typically a first step toward restoring preload in patients with sepsis. Yet, doing so risks worsening a patient’s cardiac function.

“[R]ight ventricular volume overload can lead to impaired cardiac output, with catastrophic implications for the pulmonary and systemic circulations,” they said.

In an effort to build the database of available information, Sherman and colleagues decided to look back at the cases of 30 patients with pre-existing PAH who were admitted to either of two academic hospitals for sepsis between the years 2013 and 2022. They constructed a cohort of 96 matched controls with which to compare the PAH group.

They found that concerns about fluid management appeared to impact patient care. The control group received significantly more fluids during the first 24 hours of care compared to people with PAH (median 0 mL v. 1216 mL, P < 0.001). People with PAH, on the other hand, were more likely to receive vasoactive medications (23.3% vs. 8.3%; P = 0.037).

“The 2021 Surviving Sepsis Guidelines recommend fluid resuscitation as first-line in patients with sepsis and organ hypoperfusion or septic shock, yet PAH patients with hypotension in this study frequently received pressors as the first treatment rather than IV fluid,” Sherman and colleagues noted.

They said their results, along with other recent evidence, suggest that systematic fluid restriction may be harmful, though they said it is also important that hemodynamic evaluations be made on an individualized basis.

When patients with PAH waited longer to receive fluids, they also waited longer to receive antibiotics, the investigators said, suggesting clinicians may have been slow to identify sepsis. People with PAH also tended to stay in the hospital longer (mean ± SD, 31.6 ± 48.5 days vs. 17.5 ± 30.7 days, P = 0.127).

Moreover, 30-day mortality was notably higher among people with PAH (23.3% v. 13.5%, P = 0.376). Patients with PAH who died tended to be older and have higher Charlson comorbidity indices compared to those who served, the investigators found. Those who died were also more likely to need high flow nasal cannula within 24 hours, and to have lower heart rates and temperatures upon admission.

Sherman and colleagues said they believe theirs is the first study to look at PAH and sepsis alongside right heart catheterization data that could validate PAH diagnosis. Prior research, they said, relied on large administrative databases that lacked objective confirmation of PAH. They said their findings make clear that the existing research gap is leading to differential care.

“Further research is needed to help guide decision-making around early fluid management in patients with PAH presenting with sepsis,” they concluded.