ECMO in newborn infants: circulatory changes in relation to venovenous and venoarterial bypass. Implications for periferal organ circulation

Persistent pulmonary hypertension of the newborn (PPHN) is a life threatening
disease with a high mortality rate. Extracorporeal Membrane Oxygenation (ECMO)
with veno-arterial (V-A) or veno-venous (V-V) cannulation can provide a last
treatment option. Differences in circulatory changes between V-A and V-V ECMO
concerning the course of PPHN and organ perfusion are not known. Independent of
the underlying disease, courses of ECMO runs (with both systems) may differ a
lot. Impairment of renal function and oedema is frequently seen. Mechanisms
that may play a role are not well understood yet. A better understanding of
hemodynamic changes in systemic and pulmonary circulation during treatment of
PPHN with ECMO as well as consecutive changes in organ perfusion and function
will help to develop more rationalistic treatment strategies to accelerate the
recovery to a normal neonatal circulation and shorten ECMO treatment. This will
reveal positive effects for patients as well as favourable effects on economic
aspects for this very intensive treatment.

I. Evaluation of changes in pulmonary and systemic circulation during VV- ECMO
treatment and difference between V-V- and V-A ECMO
II. Evaluation of changes in cerebral, renal and mesenterial organ perfusion
during ECMO treatment and difference between V-V- and V-A ECMO
III. Evaluation of hemodynamic changes during ECMO treatment in relation to
renal function and difference between V-V- and V-A ECMO
IV. Evaluation of BNP as diagnostic parameter regarding fluid homeostasis
during ECMO treatment and difference between V-V- and V-A ECMO

The study will have an observational character including two cohorts. The first
cohort consists of a group of patients that have been evaluated in a former
study, exclusively treated with V-A ECMO. The second cohort of patients will
include prospectively patients receiving V-V as well as V-A ECMO. A study
period of 2 and a half years is aimed for inclusion of a sufficient number of
patients. All consecutively patients admitted for ECMO treatment to the
department of neonatology of the RUNMC will be evaluated for inclusion into the
study.

Intervention: All patients will receive the standard treatment following the
ECMO protocol of the department. According to the study protocol patients will
be evaluated at standard intervals starting directly before cannulation for
ECMO until 24 hours after decannulation. Evaluation will consist of
registration of hemodynamic variables and parameters for organ perfusion using
echocardiography and Doppler sonography, blood and urine sampling and
registration of physiological and patient data.

Adverse events that may be expected are discomfort for the patient during
echocardiography and Doppler sonography and anemia caused by blood losses
because of frequent determination of blood samples. Since all patients are
under continuous sedation and analgesia during ECMO treatment discomfort is
limited to a minimum during investigational procedures. Discomfort caused by
repetitive measurements has not been a problem during the previous study.

Anemia during ECMO procedure will be prevented by blood sampling in combination
with routine blood samples in order to control oxygenation and ventilation,
milieu interieur and concentration of haemoglobin and hematocrit. The
haemoglobin concentration is kept stable above eight mmol/l with transfusions
of packed cells according to standard ECMO protocol for all patients. All
patients are equipped with arterial lines and urine catheters which facilitates
blood and urine sampling without causing discomfort.

Newborn infants belong to the group of minor and incapacitated subjects
nevertheless it is necessary to perform this study in this specific patient
group because the pathology of PPHN is age related to the period of transition
from fetal to neonatal circulation. Organ function and circulatory changes in
an adult patient group are not comparable to the neonatal physiology.