Inhalation of activated protein C: A possible new adjunctive intervention in acute respiratory distress syndrome

Lars Heslet¹, Jakob Steen Andersen¹, Henrik Sengeløv², Björn Dahlbäck³, Jorgen Dalsgaard-Nielsen⁴

¹Department of Intensive Care ITA 4131; ²Department of Hematology L, University Hospital of Copenhagen, Rigshospitalet, Denmark; ³Department of Laboratory Medicin, Clinical Chemistry, Lund University, University Hospital, Malmö, Sweden; ⁴Department of Clinical Biochemistry, Gentofte University Hospital, Hellerup, Denmark

Abstract: Acute respiratory distress syndrome (ARDS) is a potential lethal disease. At present time no evidence based intervention reduces mortality. The pathophysiology of ARDS include intraalveolar fibrin deposition, hyperinflammation and reduced cellular host defense in the airspace. The normal lung activates protein C (PC) to activated protein C (APC), in contrast to the ARDS lung where the PC-APC axis is disrupted. The lungs have targets for inhaled APC as illustrated by a patient case with ARDS, unresponsive to conventional therapy. After inhalation of 190 µg/kg of APC (Drotrecogin alpha activated) three times a day for seven days, a clear reduction in infiltrates on chest X-ray and a 138% increase in oxygenation capacity as reflected by the PaO₂/FiO₂ ratio was brought about. The patient, however, died later after cardiac arrest after suspected recurrence of the T-cell lymphoma. No local or systemic adverse effects was found related to the iAPC, during, after or at the time of death. It is suggested based on existing studies and the presented case that inhaled APC is a new treatment option in patients with ARDS – a hypothesis which should be substantiated in a larger series of ARDS patients.

Keywords: ARDS, activated protein C inhalation, pulmonary hemostasis, pulmonary host defense