A PLACEBO-CONTROLLED TRIAL OF PROSTACYCLIN IN ACUTE RESPIRATORY-FAILURE IN COPD

Although patients with COPD often have elevated pulmonary artery press ures (PAP) and pulmonary vascular resistance (PVR), it is uncertain wh ether treatment of this pulmonary hypertension is beneficial. We evalu ated the extent of pulmonary hypertension in 16 patients with severe C OPD complicated by acute respiratory failure and pulmonary hypertensio n. We assessed the hypothesis that the vasodilator prostacyclin (PGI(2 )) would reduce PVR and improve systemic O-2 transport. Patients with a COPD exacerbation requiring mechanical ventilation, and mean PAP gre ater than 30 mm Hg, were randomized to receive PGI(2) or placebo, in a ddition to conventional therapy. Randomization to PGI(2) or placebo th erapy occurred 1 to 12 h after intubation, while the patient was mecha nically ventilated. An optimal PGI(2) dose (2 to 12 ng/kg/min, IV) was established in an initial dose-ranging study and then this dose was i nfused continuously for 48 h, PGI(2) initially reduced PVR, but this e ffect dissipated within 24 h, indicating the development of tachyphyla xis. Tolerance to the adverse effects of PGI(2) (tachycardia, hypotens ion, flushing, and headache) also developed over time. PGI(2) treatmen t was associated with a significant fall in PaO2 but no increase in sy stemic oxygen transport. PGI(2) proved to be a nonselective vasodilato r that caused mild hypoxemia. Despite acute respiratory failure, pulmo nary hypertension is mild in patients with severe COPD receiving mecha nical ventilation and IV PGI(2) is not beneficial in such patients.