Vera Dietz

The Influence of the Timing of Cord Clamping on Postnatal Cerebral Oxygenation in Preterm Neonates: A Randomized, Controlled Trial

OBJECTIVE. Our goal was to investigate the effect of placentofetal transfusion on cerebral oxygenation in preterm infants by near-infrared spectroscopy. SUBJECTS. A total of 39 preterm infants with a median gestational age of 30.4 weeks were randomly assigned to an experiment group (n = 15) and a control group (n = 24). INTERVENTIONS. The delivery of the infants in the experiment group was immediately followed by maternal administration of syntocinon, the infant was placed 15 cm below the placenta, and cord clamping was delayed by 60 to 90 seconds. The infants in the control group were delivered conventionally. At the ages of 4 and 24 hours, cerebral hemoglobin concentrations, cerebral blood volume, and regional tissue oxygenation were measured by near-infrared spectroscopy. RESULTS. Cerebral blood volume was not different between the 2 groups at the age of 4 hours (6.1 vs 5.8 mL/100 g of tissue) nor at the age of 24 hours (6.2 vs 6.2 mL/100 g of tissue). Mean regional tissue oxygenation of the experiment group was higher at the ages of 4 hours (69.9% vs 65.5%) and of 24 hours (71.3% vs 68.1%). CONCLUSION. Delayed clamping of the umbilical cord improves cerebral oxygenation in preterm infants in the first 24 hours.

The influence of a clear layer on near-infrared spectrophotometry measurements using a liquid neonatal head phantom

It is difficult to test near-infrared spectrophotometry instruments in vivo. Therefore we constructed a liquid phantom which mimics the neonatal head. It consists of a spherical 3.5 mm thick layer of silicone rubber simulating skin and bone and a 0.5 mm thick clear layer of polypropylene imitating cerebrospinal fluid. It acts as container for a liquid solution with Intralipid, 60 micromol l(-1) haemoglobin and yeast. The solution was oxygenated using oxygen and then deoxygenated by the yeast. From the instrumental (Critikon 2020) algorithm, we found that with increasing scattering (0.5%, 1%, 1.5% and 2% Intralipid concentration) the reading was increasingly offset from the expected value of 0 micromol l(-1) by 55.7, 68.6, 76.5 and 80.4 micromol l(-1) (oxyhaemoglobin) and 16.0, 24.4, 29.6 and 31.7 micromol l(-1) (deoxyhaemoglobin). This reduced the range of the oxygen saturation reading from the expected 100% to 31.5, 21.1, 14.3 and 11.5%. Haemoglobin concentration changes were increasingly underestimated by a factor of two to four. For a second algorithm based on the diffusion approximation the offsets were smaller: oxyhaemoglobin 11.4, 17.8, 22.5 and 25.1 micromol l(-1) and deoxyhaemoglobin 1.3, 3.4, 5.2 and 6.0 micromol l(-1). The range of the oxygen saturation reading was higher: 41.3, 29.2, 23.4 and 16.6%. Concentration changes were underestimated by a factor of six to ten. This study demonstrates the need to develop algorithms which take into consideration anatomical structures.

Cyclical fluctuations in blood pressure, heart rate and cerebral blood volume in preterm infants

Many recently published papers describe cyclical changes of cerebral circulatory variables, mainly in cerebral blood flow velocity (CBFV) performed with Doppler sonography. In this paper we focus on another important variable of cerebral circulation: on cerebral blood volume (CBV) measured by near infrared spectrophotometry (NIRS). In a retrospective analysis of NIRS measurements in 20 preterm infants (median 27 3/7 weeks of gestation), the dominating frequencies and prevalence of cyclical changes of CBV and its possible correlation with peripheral circulatory variables (mean arterial pressure and heart rate) was examined. In 19 out of the 20 infants cyclical changes of CBV were found within a frequency range of 2-4.7 cycles/min which is comparable to the results of the Doppler studies describing fluctuations in CBFV. A dominating frequency of heart rate (HR), was found only in 12 out of 20 infants, and it was with 2.1-3.8 cycles/min in a similar range compared to CBV. In mean arterial blood pressure (MABP), however we detected cycles with longer periods every 1-2.5 min in 14 out of 20 infants. There was a significant coherence between MABP/CBV and HR/CBV. The area under the coherence curve, however, was significantly larger between MABP and CBV as compared to HR and CBV (P = 0.0007, Wilcoxon signed-rank test).

MEASUREMENT OF ABSOLUTE CEREBRAL HAEMOGLOBIN CONCENTRATION IN ADULTS AND NEONATES

The concentration and saturation of the main oxygen carrier of the blood—the haemoglobin—may be an important clinical factor to judge the oxygenation of tissue. The brain is very sensitive to under-oxygenation. So far, the measurement of absolute cerebral haemoglobin concentration by near infrared spectrophotometry (NIRS) has not taken into account the contribution of skull and skin, which causes an underestimation by a factor of 3 [Owen-Reece, 1996] in adults.

Comparison of three methods to measure absolute cerebral hemoglobin concentration in neonates by near-infrared spectrophotometry.

Three methods by which to determine absolute total cerebral hemoglobin concentration (tHb in micromol/L) by near-infrared spectrophotometry (NIRS) have evolved: (1) tHbo, requiring oxygenation changes and arterial oxygen saturation measurements as a reference using a relative NIRS algorithm, (2) tHbg, using a geometrical multidistance principle and (3) tHbgo, a combination of both. The aim of this study was to compare the three methods quantitatively. Sixteen clinically stable preterm infants with a mean gestational age of 29.6 (range of 25.1-36.4) weeks, birthweight of 1386 (680-2820) g and a postnatal age of 2.5 (0.5-6) days, who needed supplemental oxygen, were enrolled. The mean+/-standard deviation tHbg was 150.2+/-41.8 micromol/L (range of 61.6-228.9 micromol/L), the tHbo was 62.1+/-27.2 micromol/L (26.0-110.8 micromol/L) and the tHbgo was 89.3+/-45.6 micromol/L (26.5-195.9 micromol/L). The correlation coefficient among the three methods were tHbg and tHbgo r=0.736; tHbo and tHbgo r=0.938; tHbg and tHbo r=0.598. A multiple regression with variable selection by Mellows C(p) showed, that tHbg was correlated to the birthweight, the postnatal age, the heart rate and the pCO2 (r(2)=0.588), tHbo and tHbgo were associated with the hemoglobin concentration in the blood, the mean arterial blood pressure and the pCO2 (r(2)=0.493 and 0.406, respectively). The three methods (tHbg, tHbo, and tHbgo) give systematically different tHb readings and large intersubject variability.

Tissue oxygen saturation measured by near infrared spectrophotometry correlates with arterial oxygen saturation during induced oxygenation changes in neonates.

The aim of this study was to compare quantitatively the changes in tissue oxygen saturation (TOS), determined by two algorithms (TOSc and TOSa) based on near-infrared spectrophotometry, to the changes in arterial oxygen saturation (SaO2) measured by pulse oximetry. TOSc is an algorithm derived by the manufacturer (Critikon) based on a modified Beer-Lambert law; TOSa, our own algorithm, uses the diffusion approximation of light transport for the semi-infinite boundary condition. Slow changes of more than 3% in SaO2 were carried out in 20 mechanically ventilated neonates by altering the inspired oxygen fraction. For each change the regression lines of TOSc versus SaO2, TOSa versus SaO2 and TOSc versus TOSa were calculatcd. For each infant the mcan slope, intercept and r2 of these lines were determined. In 18 preterm infants we obtained median 9.5 (range one to 13) measurements corresponding to a total of 166 measurements. The mean SaO2 was 91.6 (SD 2.3)%, TOSc was 64.7 (SD 7.2)% and TOSa was 71.4 (SD 11.0)%. Changes in TOSc and TOSa were strongly correlated to changes in SaO2 (r2 = 0.86 and r2 = 0.87). TOSc considerably but systematically underestimated the size of the change: delta TOSc = 0.49 delta SaO2. TOSa quantified changes reasonably correctly: delta TOSa = 0.90 delta SaO2. Changes in TOSc and TOSa were highly correlated (r2 = 0.98). These results are promising, but the large inter-individual variation requires further work.

CO2 Reactivity of the Cerebral Hemoglobin Concentration in Healthy Term Newborns Measured by Near Infrared Spectrophotometry

CO2 reactivity of cerebral hemoglobin concentration was studied in 16 healthy term neonates on days 1 and 4 after birth using the near infrared spectrophotometry (NIRS) technique. The aim was to establish data on the physiological range of CO2 reactivity in healthy newborns and to investigate the influence of postnatal age on it. The CO2 reactivity measured by NIRS is expressed as the change of the total cerebral hemoglobin concentration (tHbR) per change of CO2 tension in µmol/l/kPa. We evaluated CO2 reactivity during increases and decreases of transcutaneous CO2 partial pressure and found in our methodological setting the data of the increases more reliable. In all infants but 1 we found a tHbR on day 1 with a mean value of 8.19 µmol/l/kPa (–1.39 to 18.87), in all infants on day 4 with a mean value of 9.54 µmol/l/kPa (2.76–25.88). There is a trend to higher values between day 1 and day 4 (difference = 2.25 µmol/l/kPa; p = 0.08). The noninvasive NIRS technique enabled us to test the cerebrovascular CO2 reactivity of the tHbR for the first time in healthy term newborns. Data on its physiologic range and variability are presented and compared to findings from ventilated infants and other age groups. As the CO2 reactivity might be an indicator for infants at risk of cerebral damage, it is necessary to have data on the physiological range of this parameter.

How to Evaluate Slow Oxygenation Changes to Estimate Absolute Cerebral Haemoglobin Concentration by Near Infrared Spectrophotometry in Neonates

Brain injury is a major cause of long-term disability in newborn infants. Disturbed cerebral haemodynamics and oxygen supply may be important etiological factors, and these are currently investigated. Near infrared spectrophotometry (NIRS) in combination with pulse oxymetry is widely used to determine cerebral blood volume (CBV) in neonates. In a similar, but simpler way cerebral haemoglobin concentration (CHC), which is more relevant for cerebral oxygenation, can be obtained from the same measurements.

Testing near-infrared spectrophotometry using a liquid neonatal head phantom

We constructed a liquid phantom, which mimics the neonatal head for testing near infrared spectrophotometry instruments. It consists of a spherical, 3.5 mm thick layer of silicone rubber simulating skin and bone and acts as container for a liquid solution with IntralipidTM, 60 micrometers ol/l haemoglobin and yeast. The IntralipidTM concentration was varied to test the influence of scattering on haemoglobin concentrations and tissue oxygenation determined by the Critikon 2020. The solution was oxygenated using pure oxygen and then deoxygenated by the yeast. For the instruments algorithm, we found with increasing scattering (0.5%, 1%, 1.5% and 2% IntralipidTM concentration) an increasing offset added to the oxy- (56.7, 90.8, 112.5, 145.2 micrometers ol/l respectively) and deoxyhaemoglobin (25.4, 44.3, 58.5, 65.9 micrometers ol/l) concentration causing a decreasing range (41.3, 31.3, 25.0, 22.2%) of the tissue oxygen saturation reading. However, concentration changes were quantified correctly independently of the scattering level. For an other algorithm based on the analytical solution the offsets were smaller: oxyhaemoglobin 12.2, 34.0, 53.2, 88.8 micrometers ol/l and deoxyhaemoglobin 1.6, 11.2, 22.2, 28.1 micrometers ol/l. The range of the tissue oxygen saturation reading was higher: 71.3, 55.5, 45.7, 39.4%. However, concentration changes were not quantified correctly and depended on scattering. This study demonstrates the need to develop algorithms, which take into consideration the anatomical structures.

Variability of Cerebral Hemoglobin Concentration in Very Preterm Infants During the First 6 Hours of Life

Cerebral hemoglobin concentration (cHbc), a major determinant of oxygen transport capacity in the brain, shows a considerable variability due to physiological and methodological factors. In order to determine the (relative) contribution of these factors, the cHbc variability within the first 6 hours of life was studied in 28 very preterm infants using near infrared spectrophotometry (NIRS). Mean cHbc values were 46.4 +/- 14.1 micromol/l (2.75 +/- 0.84 ml/100 g). Is the variability in cHbc related to the methodology of cHbc measurements or to physiological variables? A statistical model of stepwise regression (backward selection) with 13 independent variables and with cHbc as a dependent variable showed that, from the total variability of +/- 14.1 micromol/l, only 3.7 micromol/l (26%) were of methodological origin, while the major portion, 9.3 micromol/l (66%) were related to four physiological variables: birth weight, gestational age, blood glucose and transcutaneous carbon dioxide tension. The remaining 1.1 micromol/l (7.8%) were unexplained. We conclude that NIRS, which allows continuous monitoring of cerebral oxygenation and metabolism even in the first hours of postnatal life, is a valid technique to measure cHbc in very preterm infants. The major portion of the large variability of early cHbc registrations can be attributed to physiological factors.