Multisite Near-infrared spectroscopy monitoring in newborn infants at risk of circulatory failure

Circulatory failure is an important cause of mortality and morbidity in
seriously ill newborn infants admitted to the neonatal intensive care unit
(NICU). Because clinical and biochemical parameters which are currently used to
estimate systemic blood flow are often poor predictors of low systemic blood
flow and impaired tissue oxygenation, there is a risk of over- and
undertreatment of these infants with the risk of adverse outcome and iatrogenic
damage. Near-infrared spectroscopy (NIRS) is a non-invasive method which can be
used to measure tissue oxygenation continuously as a bedside monitoring device.
By means of NIRS, regional tissue oxygen saturation (rSO2) can be measured
which reflects the venous-weighted oxygen saturation of the underlying tissue.
Fractional tissue oxygen extraction (FTOE) is thought to reflect the balance
between tissue oxygen supply, dependent on tissue perfusion, and tissue oxygen
consumption, and can be calculated when rcSO2 and arterial oxygenation (tcSaO2)
are measured simultaneously by the following equation: FTOE = (tcSaO2 -
rSO2)/tcSaO2. There is some evidence that the combination of somatic and
cerebral (multi-site) NIRS monitoring could help to assess systemic blood flow
and organ perfusion. If so, multi-site NIRS monitoring could help to diagnose
and monitor newborns with impaired organ perfusion at risk of brain injury and
organ damage in need of treatment. However, before multi-site NIRS-monitoring
can be implemented in clinical care, more information is needed about the value
of multi-site NIRS-monitoring as diagnostic tool in newborn infants with
circulatory failure. By lack of a golden standard for organ perfusion in
neonates, we therefore want to investigate the relation between somatic and
cerebral oxygenation on one hand and current hemodynamic parameters and somatic
and neurologic outcome on the other hand.

The primary goal of this study is to determine if the use of multi-site
NIRS-monitoring in newborn infants at risk of circulatory failure could lead to
a better diagnosis, treatment and outcome in these infants compared to the use
of conventional used hemodynamic parameters alone. As there is no golden
standard for tissue perfusion in newborn infants available, we will relate
somatic and cerebral tissue oxygenation to conventional used hemodynamic
parameters on one hand and short- and long-term neurologic and somatic outcome
on the other hand. Furthermore, we will investigate the effect of currently
used interventions on cerebral and somatic tissue oxygenation and hemodynamic
parameters

Primary objective:
- to determine the relation between blood pressure and cerebral tissue
oxygenation in newborns with circulatory failure due to
variable causes

Secondary objectives:
- to determine the relation between blood pressure and somatic (abdominal and
kidney) tissue oxygenation in newborns with circulatory failure
due to variable causes
- to determine the relation between other hemodynamic parameters (heart rate,
capillary refill, urinary output, base excess and serum lactate)
and cardiac output as measured with doppler echocardiography on one hand and
cerebral and somatic (abdominal and kidney) tissue
oxygenation on the other hand in newborns with circulatory failure due to
variable causes
- to determine the relation between somatic (abdominal and kidney) and cerebral
tissue oxygenation on one hand and somatic and neurologic
outcome on the other hand in newborns with circulatory failure due to
variable causes
- to determine the effect of various forms of treatment of circulatory failure
(e.g. volume expansion, dopamine, dobutamine, hydrocortisone) on
somatic (abdominal and kidney) and cerebral tissue oxygenation on one hand
and hemodynamic parameters on the other hand in newborns
with circulatory failure due to variable causes

Prospective observational cohort study in which 66 newborn infants at risk of
circulatory failure due to patent ductus arteriosus, clinical sepsis or
acyanotic congenital heart disease will be included. As soon as the risk of
circulatory failure is recognized by the attending neonatologist, newborns will
be considered for inclusion. When parental informed consent has been obtained
previously, newborns will be included in the study. For cerebral and somatic
regional tissue oxygenation monitoring, we will use an INVOS 5100C
near-infrared spectrometer (Somanetics Corporation, Troy, MI) and pediatric and
neonatal SomaSensors (Somanetics Corporation). The SomaSensors will be placed
on three locations: on the left frontoparietal side of the neonate's head
(cerebral), 1 cm below the umbilicus (abdominal/splanchnic), and on the left
posterior flank (kidney). We will use an elastic bandage to keep the
SomaSensors in place to avoid skin irritation. NIRS-monitoring will be
continued for the duration of circulatory failure as decided by the attending
neonatologist, but at least for 72 hours. Simultaneous to the NIRS-recordings,
pre- and postductal transcutaneous arterial oxygen saturation (tcSaO2) will be
measured by pulse-oximetry on the right arm and the leg and FTOE, which is
thought to reflect the balance between oxygen supply and oxygen extraction,
will be calculated with the following equation: FTOE = (tcSaO2 - rSO2)/tcSaO2.

During the study period, additional clinical and biochemical parameters which
give an impression of systemic blood flow, which can influence somatic or
cerebral tissue oxygenation or which will give an impression of kidney or liver
function will be prospectively gathered during the study period, as part of
clinical routine. These data consist of heart rate, blood pressure, urinary
output, capillary refill, blood gas values (pO2, pCO2, pH, base excess), serum
lactate, glucose concentration, hemoglobin concentration, ASAT, ALAT, LDH,
bilirubine, creatinine and ureum. In addition, cardiac output (superior vena
cava flow, left ventricular output, right ventricular output) will be assessed
once within 48 hours of inclusion by means of doppler echocardiography.

The multi-site NIRS measurements are non-invasive and do not interfere with
routine clinical care. As cerebral oxygenation monitoring is already part of
routine clinical care, only two extra sensors will be applied. Because sensors
are held in place by elastic bandages, and are not sticked to the skin, skin
irritation is avoided. Hemodynamic parameters will only be collected as part of
clinical routine, and do therefore not pose an extra burden on the child. Data
from this study can not be obtained in another population, as the intention of
this study is to use multi-site NIRS monitoring in neonatal intensive care. In
addition, only newborn infants often suffer from circulatory failure as a
result of prematurity, patent ductus arteriosus or uncorrected congenital heart
disease. The results from this study offer more knowledge about a new
monitoring device which could help to identify neonates at risk of brain injury
or organ damage earlier and more adequate, and which could help to guide
adequate therapy, thereby improving outcome.