title: A Three-phase Approach for the Early Identification of Acute Lung Injury Induced by Severe Sepsis.
abstract: A number of studies have reported that acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are independent risk factors for organ dysfunction and mortality in patients with sepsis. Although ALI/ARDS might be an essential therapeutic target during the management of sepsis, severe sepsis should be treated effectively and as soon as identified. We have classified three phases, ranging from sepsis to organ dysfunction, characterizing the interaction between neutrophils and platelets. The first phase is neutrophil extracellular trap (NET) formation and intravasated platelet aggregation. The next phase is extravasated platelet aggregation (EPA), promoted by NET-facilitated detachment of endothelial cells. The final phase is organ dysfunction, caused by pulmonary veno-occlusive disease (VOD), fibrosis, and immunoparalysis induced by EPA. Severe sepsis is characterized by a continuum of coagulopathy, with coagulation abnormalities often developing before the onset of clinical symptoms. The initial medical treatment for ALI/ARDS is inhibition of NET formation and intravasated platelet aggregation to prevent endothelial cell damage (Phase 1). Beraprost and silvestat, phosphodiesterase 3 (PDE3) inhibitors, are often administered in clinical practice. To determine hypercoagulopathy, plasma levels of thrombin-antithrombin complex and plasmin-plasmin inhibitor complex are continuously monitored in patients with suspected sepsis. Furthermore, the implementation of quality indicators for the early management of severe sepsis and septic shock is strongly associated with a reduced mortality. We conclude that pathophysiology of organ dysfunction from severe sepsis is caused by pulmonary VOD, fibrosis, and EPA-facilitated immunoparalysis. In order to prevent ALI/ARDS in patients with sepsis, countermeasures for NET and platelet aggregation should be pre-emptively employed and confirmed by several trials.
authors.affiliation: Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan tomoharumiya@gmail.com.
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Miyashita
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, U.S.A.
authors.forename: Ali Karim
authors.initials: AK
authors.lastname: Ahmed
authors.affiliation: Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nakanuma
authors.affiliation: Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.
authors.forename: Seisho
authors.initials: S
authors.lastname: Sakai
authors.affiliation: Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kinoshita
authors.affiliation: Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.
authors.forename: Isamu
authors.initials: I
authors.lastname: Makino
authors.affiliation: Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.
authors.forename: Keishi
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.
authors.forename: Katsunobu
authors.initials: K
authors.lastname: Oyama
authors.affiliation: Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Tajima
authors.affiliation: Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takamura
authors.affiliation: Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.
authors.forename: Itasu
authors.initials: I
authors.lastname: Ninomiya
authors.affiliation: Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.
authors.forename: Sachio
authors.initials: S
authors.lastname: Fushida
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, U.S.A.
authors.forename: John W
authors.initials: JW
authors.lastname: Harmon
authors.affiliation: Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ohta
mesh_terms: D055371:Acute Lung Injury / Q000175:diagnosis* / Q000209:etiology; D006801:Humans; D018805:Sepsis / Q000150:complications* / Q000503:physiopathology
keywords: Sepsis; acute lung injury (ALI); acute respiratory distress syndrome (ARDS); extravasated platelet aggregation (EPA); neutrophil extracellular trap (NET); review; veno-occlusive disease