Pulmonary Disorders II

Approved dose is 200 mcg twice daily; increase at weekly intervals to the highest tolerated dose

(maximum dose 1600 mcg twice daily); adjustment necessary for moderate hepatic impairment

Dosing should be reduced to once daily in patients receiving moderate CYP2C8 inhibitors whereas

selexipag is contraindicated in patients receiving strong CYP2C8 inhibitors (e.g., gemfibrozil);

dose increase necessary with CYP2C8 inducers

Adverse effects include headache, diarrhea, nausea and jaw pain.

Activin-signaling inhibitor

Sotatercept is a recombinant activin receptor type IIA-Fc (ActRIIA-Fc) fusion protein that binds

to activin A to improve the balance between pro-proliferative and antiproliferative signaling to

modulate vascular proliferation (J Heart Lung Transplant. 2024:S1053-2498(24)01874-6).

The 7th World PH Symposium recommendations for use of sotatercept include using it as

add-on therapy for those receiving ERA/PDE5i combination therapy at intermediate-low,

intermediate-high, and high risk (in those already receiving parenteral prostacyclin) (Eur Respir J.

2024;64(4):2401325).

Sotatercept is a subcutaneous injection that is administered every 3 weeks. The initial dose is 0.3

mg/kg subcutaneously × 1 dose, followed by 0.7 mg/kg subcutaneously every 3 weeks.

The half-life is around 24 days.

ii.

Unlike other PAH medications, sotatercept does not provide an acute pulmonary vasodilatory

activity, thus potentially limiting its role in the critically ill population (J Cardiovasc Pharmacol

Ther. 2024;29:10742484231225310).

thrombocytopenia, increased hemoglobin, and hypertension.

Baseline hemoglobin and platelets are required before initiating therapy. Repeat hemoglobin

and platelets are required before the first 5 doses. If the platelets decrease to less than 50 × 103/

μL or the hemoglobin increases to greater than 2 g/dL from the previous dose and is above the

upper limit of normal (ULN), increases greater than 4 g/dL from baseline, or is greater than

2 g/dL above the ULN, it is recommended to delay treatment by 3 weeks. Hemoglobin and/

or platelets should be reassessed before resuming sotatercept. If treatment is delayed greater

than 9 weeks, the sotatercept dose should be modified to 0.3 mg/kg subcutaneously × 1 dose,

followed by 0.7 mg/kg subcutaneously every 3 weeks.

Managing Decompensated PAH

Decompensated PAH generally presents with worsening symptoms of right heart failure such as

shortness of breath, syncope, fluid retention, or even multiorgan failure due to poor perfusion (Eur

Respir J. 2019;53:1801906).

venous oxygen saturation, lactic acidosis, and decreased urine output.

Manage contributing factors such as infections, anemia, arrhythmias, rebound PH (nonadherence or

ineffective dosing), hypoxemia, acidosis, and metabolic abnormalities. Because of the hemodynamic

effects of MV, both invasive and noninvasive, it is recommended to correct hypoxia using high-flow

nasal cannula. Application of MV and PEEP increases PVR. It is recommended to use MV only if high-

Supportive therapies include optimizing RV preload through fluid optimization (diuretics or dialysis),

maintaining aortic root pressure, improving RV contractility, and reducing RV afterload.

Temporary discontinuation of CCBs and β-blockers to eliminate negative inotropic effects

Hemodynamic support (Table 9)

Maintaining aortic root pressure and minimizing RV ischemia can be accomplished using

vasopressors, which increase the systemic vascular resistance (SVR) and ultimately improve RV