Complement activation by in vivo neonatal and in vitro extracorporeal membrane oxygenation.

Johannes Graulich,Monika Marcinkowski,Karl Bauer,Michael Obladen,Christoph Bührer,Joseph Sonntag,Hans Kössel,Hans T Versmold

doi:10.1080/09629350220131908

Abstract

Complment activation during extracorporeal membrane oxygenation (ECMO) in newborns can be caused by both the underlying disease processes and by blood contact with the ECMO circuit. We investigated the relative importance of these mechanisms by measuring C3a, C5a and sC5b-9 before, during and after neonatal ECMO in six consecutive newborn patients using enzyme-linked immunoassay. In addition complement activation during in vitro ECMO with repeated flow of the same blood volume was measured using blood from healthy adult donors. C3a increased significantly in vivo after 1 h (from 1035+/-193 to 1865+/-419 microg/l) and in vitro ECMO (from 314+/-75 to 1962+/-1062 microg/l). C5a increased during ECMO without significant differences between in vivo and in vitro activation. In neonatal patients, sC5b-9 rose faster than in vitro, but the rapid increase was also significant for in vitro experiments (in vivo: from 328+/-63 to 1623+/-387 microg/l after 2 h; and in vitro: from 78+/-32 to 453+/-179 microg/l after 8 h). After this initial peak at 1-2 h, complement activation decreased gradually until 2-3 days after the initiation of ECMO. We conclude that in newborns the rapid activation of the complement system after the start of ECMO is predominantly caused by contact with artificial surfaces rather than the patient's underlying disease.

Highlights

Extracorporeal membrane oxygenation (ECMO) has become standard treatment for newborn infants with severe neonatal respiratory failure not responding to conventional pulmonary support.[1]
During ECMO, circulating plasma levels of inflammatory mediators and neutrophil activation increase.[4,5]. This generalized inflammatory reaction contributes to the capillary leak syndrome and pulmonary oedema observed during ECMO therapy.[6,7,8,9]
ECMO was started at a mean age of 147 h after birth and the mean duration of ECMO was 152 h

Summary

Introduction

Extracorporeal membrane oxygenation (ECMO) has become standard treatment for newborn infants with severe neonatal respiratory failure not responding to conventional pulmonary support.[1] Since the first successful ECMO treatment in 1971, more 10,000 babies have been treated world-wide with ECMO, with an improved survival and a favourable outcome compared with conventional treatment.[2] ECMO is used for temporary circulatory assist in children with heart failure awaiting transplantation.[3]. During ECMO, circulating plasma levels of inflammatory mediators and neutrophil activation increase.[4,5] This generalized inflammatory reaction contributes to the capillary leak syndrome and pulmonary oedema observed during ECMO therapy.[6,7,8,9] A major mechanism triggering this inflammatory reaction is the activation of complement by contact of blood with the surface of the synthetic tubing and the oxygenator. Complement activation has been described during cardiopulmonary bypass and the apheresis technique.[10,11,12] In contrast to cardiopulmonary bypass, which lasts only for a few hours and is combined with deep hypothermia, ECMO lasts for several days, is performed at normal temperature and the patient sometimes has systemic infection

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