From evidence to clinical practice: Effective implementation of therapeutic hypothermia to improve patient outcome after cardiac arrest*

Abstract

Objective-The coagulation and inflammatory cascades may be linked in the pathogenesis of acute lung injury and acute respiratory distress syndrome. However, direct evidence for the contribution of abnormalities in coagulation and fibrinolysis proteins to outcomes in patients with acute lung injury/acute respiratory distress syndrome is lacking.Design-Retrospective measurement of plasma levels of protein C and plasminogen activator inhibitor-1 in plasma samples that were collected prospectively as part of a large multicenter clinical trial. The primary outcome was hospital mortality. To evaluate the potential additive value of abnormalities of these biomarkers, the excess relative risk of death was calculated for each combination of quartiles of protein-C and plasminogen activator inhibitor-1 levels. Setting-Ten university medical centers.Patients-The study included 779 patients from a multicenter clinical trial of a protective ventilatory strategy in acute lung injury/acute respiratory distress syndrome and 99 patients with acute cardiogenic pulmonary edema, as well as ten normal controls. Measurements and MainResults-Compared with plasma from controls and patients with acute cardiogenic pulmonary edema, baseline protein-C levels were low and baseline plasminogen activator inhibitor-1 levels were elevated in acute lung injury/acute respiratory distress syndrome. By multivariate analysis, lower protein C and higher plasminogen activator inhibitor-1 were strong independent predictors of mortality, and ventilator-free and organ-failure-free days. Plasminogen activator inhibitor-1 and protein C had a synergistic interaction for the risk of death. Conclusions-Early acute lung injury/acute respiratory distress syndrome is characterized by decreased plasma levels of protein C and increased plasma levels of plasminogen activator inhibitor-1 that are independent risk factors for mortality and adverse clinical outcomes. Measurement of plasminogen activator inhibitor-1 and protein-C levels may be useful to identify those at highest risk of adverse clinical outcomes for the development of new therapies. NIH Public Access Keywordsacute respiratory distress syndrome; protein C; plasminogen activator inhibitor-1; coagulation; fibrinolysis Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening disorders characterized by severe inflammation in the lungs and frequent occurrence of multiple organ failure (1). Despite numerous randomized controlled trials of therapies aimed at modulating the inflammatory response in ALI/ARDS (2), the only therapy that has been proven to reduce mortality is a protective ventilatory strategy (3). Although mortality from ALI/ARDS has declined in clinical trials, epidemiologic studies that include all patients with ALI/ARDS still report mortality rates >50% (4). Insight into the pathophysiological derangements that characterize early clinical ALI/ARDS may help to guide the development of new therapies for this devastating disorder.The degree of alterations ...

Scandinavian Clinical practice guidelines for therapeutic hypothermia and post‐resuscitation care after cardiac arrest

“…There have also been several previous studies with historical controls [25][26][27] considered as GOE IV, and experimental studies. [28][29][30][31] Recently, several observational studies, with historical controls [32][33][34][35] (GOE IV), uncontrolled studies 36,37 (GOE V) and a European registry 39 (GOE V), all show that MTH is feasible, safe, has few side effects and seems to contribute toward improved survival.…”

“…20 Recently, observational studies 32,34 (GOE IV) and two registry reports 39,40 (GOE V) have reported the feasibility of treating patients with non-VF cardiac arrest. Although the prognosis for this group of cardiac-arrested patients is worse, 39 recent survival data on non-VF patients are promising 38 (GOE V).…”

Erweiterte Reanimationsmaßnahmen für Erwachsene („advanced life support“)

“…In einer Registerarbeit mit mehr als 6000 Patienten nach Kreislaufstillstand war eine Hypotonie (SBD <90 mmHg) zum Zeitpunkt der Aufnahme auf die ICU mit einem schlechteren Outcome vergesellschaftet [855]. Ein gutes Outcome konnte in Studien mit Patienten erreicht werden, die nach präklinischem Kreislaufstillstand in eine Klinik aufgenommen wurden, wenn der MAP zwischen mindestens 65-75 mmHg [630] und höchs-tens 90-100 mmHg [633,670] lag. Aufgrund fehlender definitiver Daten soll der Ziel-MAP so eingestellt werden, dass eine ausreichende Urinproduktion (1 ml/kgKG und /h) sowie eine normale oder fallende Plasmalaktatkonzentration erreicht werden können.…”

“…In den ersten 48 h nach Kreislaufstillstand ist eine hypertherme Phase typisch (Hyperpyrexie; [696,697,698] [709]. Sechs Studien mit historischen Kontrollgruppen wiesen den Nutzen der therapeutischen Hypothermie bei komatösen Überlebenden eines präklinischen Kreislaufstillstands aufgrund aller EKG-Rhythmen nach [630,633,710,711,712,713]. Zwei nichtrandomisierte Studien mit gleichzeitig durchgeführten Kontrollen deuten auf einen möglichen Nutzen der Hypothermie nach einem präklinischen und innerklinischen Kreislaufstillstand infolge anderer initialer Herzrhythmen hin [714,715].…”

From Door to Recovery: A Collaborative Approach to the Development of a Post–Cardiac Arrest Center

“…12,23 The goals of care after cardiac arrest are described in Table 1. 14 Post-cardiac arrest patients have varied clinical manifestations of altered neurologic, cardiovascular, and metabolic function.…”