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Clinical Investigations in Critical Care |

Dose-Response to Inhaled Aerosolized Prostacyclin for Hypoxemia Due to ARDS*

P. Vernon van Heerden, MD; Anne Barden, PhD; Nicholas Michalopoulos, BSc; Max K. Bulsara, MSc; Brigit L. Roberts, RN
Author and Funding Information

*From the Department of Pharmacology (Dr. van Heerden), University Department of Medicine (Dr. Barden), and Biostatistical Consulting Service (Mr. Bulsara), Department of Public Health, University of Western Australia, Nedlands, Australia; Department of Haematology (Mr. Michalopoulos), PathCentre, Perth, Australia; and Department of Intensive Care (Ms. Roberts), Sir Charles Gairdner Hospital, Perth, Australia.

Correspondence to: P.V. van Heerden, MD, Department of Intensive Care, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, WA 6009, Australia; e-mail: vernon@iinet.net.au



Chest. 2000;117(3):819-827. doi:10.1378/chest.117.3.819
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Study objectives: This study was carried out to determine the efficacy of and dose-response relationships to inhaled aerosolized prostacyclin (IAP), when used as a selective pulmonary vasodilator (SPV) in patients with severe hypoxemia due to ARDS.

Design: Unblinded, interventional, prospective clinical study.

Setting: A general ICU in a university-affiliated, tertiary referral center.

Patients: Nine adult patients with severe ARDS (lung injury score, ≥ 2.5).

Interventions: All patients received IAP over the dose range 0 to 50 ng/kg/min. The IAP was delivered via a jet nebulizer placed in the ventilator circuit. Dose increments were 10 ng/kg/min every 30 min.

Measurements and results: Cardiovascular parameters (cardiac index and mean pulmonary and systemic pressures), indexes of oxygenation (Pao2/fraction of inspired oxygen[ Fio2] ratio and alveolar-arterial oxygen partial pressure difference [P(A-a)O2]) and shunt fraction were measured or calculated at each dose interval, as were platelet aggregation and systemic levels of prostacyclin metabolite (6-keto prostaglandin F1α). A generalized linear regression model was used to determine a dose effect of IAP on these parameters. The Wilcoxon rank sum test for related measures was used to compare the effects of various doses of IAP. IAP acted as an SPV, with a statistically significant dose-related improvement in Pao2/Fio2 ratio (p = 0.003) and P(A-a)O2 (p = 0.01). Systemic prostacyclin metabolite levels increased significantly in response to delivered IAP (p = 0.001). There was no significant dose effect on systemic or pulmonary arterial pressures, or on platelet function, as determined by platelet aggregation in response to challenge with adenosine diphosphate.

Conclusions: IAP is an efficacious SPV, with marked dose-related improvement in oxygenation and with no demonstrable effect on systemic arterial pressures over the dose range 0 to 50 ng/kg/min. Despite significant systemic levels of prostacyclin metabolite, there was no demonstrable platelet function defect.

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