Hemorrhage under veno-venous extracorporeal membrane oxygenation in acute respiratory distress syndrome patients: a retrospective data analysis

Abstract

Background: Despite being still invasive and challenging, technical improvement has resulted in broader and more frequent application of extracorporeal membrane oxygenation (ECMO), to prevent hypoxemia and to reduce invasiveness of mechanical ventilation (MV). Heparin-coated ECMO-circuits are currently standard of care, in addition to heparin based anticoagulation (AC) regimen guided by activated clotting time (ACT) or activated partial thromboplastin time (aPTT). Despite these advances, a reliable prediction of hemorrhage is difficult and the risk of hemorrhagic complication remains unfortunately high. We hypothesized, that there are coagulation parameters that are indices for a higher risk of hemorrhage under veno-venous (VV)-ECMO therapy.

Methods: Data from 36 patients with severe respiratory failure treated with VV-ECMO at a University Hospital intensive care unit (ICU) were analyzed retrospectively. Patients were separated into two groups based on severity of hemorrhagic complications and transfusion requirements. The following data were collected: demographics, hemodynamic data, coagulation samples, transfusion requirements, change of ECMO-circuit during treatment and adverse effects, including hemorrhage and thrombosis.

Results: In this study 74 hemorrhagic events were observed, one third of which were severe. Patients suffering from severe hemorrhage had a lower survival rate on VV-ECMO (43% vs. 91%; P=0.002) and in ICU (36% vs. 86%; P=0.002). SAPS II, factor VII and X were different between mild and severe hemorrhage group.

Conclusions: Severe hemorrhage under VV-ECMO is associated with higher mortality. Only factor VII and X differed between groups. Further clinical studies are required to determine the timing of initiation and targets for AC therapies during VV-ECMO.

Keywords: Acute respiratory distress syndrome (ARDS); anticoagulation (AC); extracorporeal membrane oxygenation (ECMO); heparin.

Conflict of interest statement

Conflicts of Interest: Part of these data has been presented in form of abstracts at the American Thoracic Society international conference 2010 (New Orleans) and at the European Society of Intensive Care Medicine annual congress 2010 (Barcelona).

Figures

Figure 1

Coagulation parameters I. Data are presented as Box-Plot and Whiskers: Box is median, 1st and 3rd quartile, whiskers are drawn to the furthest point within 1.5× IQR from the box. Blank boxes are mild hemorrhage group, filled boxes are severe hemorrhage group. Abscissa is day of ECMO-treatment. Values are presented as mean ± SEM. Fibrinogen: *P=0.038; Factor II: *P#P=0.0029; Factor VIII: *P=0.0006; Factor X: *P<0.0001, #P=0.0193, $P=0.0234. #, group-time effect; $, group effect; *, time effect; INR, international normalized ratio; SEM, standard error of the mean.

Figure 2

Coagulation parameters II and heparin dose. Data are presented as Box-Plot and Whiskers: Box is median, 1st and 3rd quartile, whiskers are drawn to the furthest point within 1.5× IQR from the box. Blank boxes are mild hemorrhage group, filled boxes are severe hemorrhage group. Abscissa is day of ECMO-treatment. Values are presented as mean ± SEM. INR, *P

Figure 3

Blood count and pH. Data are presented as Box-Plot and Whiskers: Box is median, 1st and 3rd quartile, whiskers are drawn to the furthest point within 1.5× QR from the box. Blank boxes are mild hemorrhage group, filled boxes are severe hemorrhage group. Abscissa is day of ECMO-treatment. Values are presented as mean ± SEM. Leukocytes: *P

Figure 4

Transfused units of erythrocytes, fresh frozen plasma FFP, platelets, temperature and SAPS II. Data are presented as Box-Plot and Whiskers: Box is median, 1st and 3rd quartile, whiskers are drawn to the furthest point within 1.5× IQR from the box. Blank boxes are mild hemorrhage group, filled boxes are severe hemorrhage group. Abscissa is day of ECMO-treatment. Values are presented as mean ± SEM. Transfused units of packed red blood cells: $P=0.0032 (log transformed); Transfused units fresh frozen plasma: *P=0.0221 (log transformed); Transfused units of platelets: *P=0.0373 (log transformed); Temperature: *P<0.0001; SAPS II: $P=0.0194; Heparin dose/kg: *P<0.0001. $, group effect; *, time effect; FFP, fresh frozen plasma; SEM, standard error of the mean.

Figure 5

ROTEG-parameters. Data are presented as Box-Plot and Whiskers: Box is median, 1st and 3rd quartile, whiskers are drawn to the furthest point within 1.5× IQR from the box. Blank boxes are mild hemorrhage group, filled boxes are severe hemorrhage group. Abscissa is day of ECMO-treatment. Values are presented as mean ± SEM. ROTEG-R: *P=0.0004; ROTEG-K: *P=0.0004 (log transformed). *, time effect; SEM, standard error of the mean; ECMO, extracorporeal membrane oxygenation.