Elise A. Verhagen

Cerebral tissue oxygen saturation and extraction in preterm infants before and after blood transfusion

Objective Preterm infants often need red blood cell (RBC) transfusions. The aim of this study was to determine whether haemoglobin levels before transfusion were associated with regional cerebral tissue oxygen saturation (rcSO2) and fractional tissue oxygen extraction (FTOE) and whether RBC transfusions were associated with rcSO2 and FTOE during the 24-h period thereafter. Design Prospective observational cohort study. Setting Third level neonatal intensive care unit. Patients Thirty-three preterm infants (gestational age 25–34 weeks, birth weight 605–2080 g) were included. Interventions None. Main Outcome Measures RcSO2 was measured during a 1-h period, before, 1 h after and 24 h after a 15 ml/kg RBC transfusion in 3 h. Using rcSO2 and transcutaneous arterial oxygen saturation (tcSaO2) values, FTOE was calculated: FTOE=(tcSaO2−rcSO2)/tcSaO2. Results Forty-seven RBC transfusions were given. RcSO2 and FTOE correlated strongly with haemoglobin before transfusion (r=0.414 and r=−0.462, respectively, p<0.005). TcSaO2 did not correlate with haemoglobin before transfusion. 24 h after transfusion, rcSO2 increased from a weighted mean of 61% to 72% and FTOE decreased from a weighted mean of 0.34 to 0.23. The decrease in FTOE was strongest in the group with haemoglobin below 6.0 mmol/l (97 g/l). The decrease in FTOE was already present 1 h after transfusion and remained unchanged at 24 h after transfusion. Conclusion Following RBC transfusion, cerebral tissue oxygen saturation increases and FTOE decreases. The data suggest that cerebral oxygenation in preterm infants may be at risk when haemoglobin decreases under 6 mmol/l (97 g/l).

Cerebral Oxygenation in Preterm Infants With Germinal Matrix-Intraventricular Hemorrhages

Background and Purpose— Preterm infants are at risk of developing germinal matrix hemorrhages–intraventricular hemorrhages (GMH-IVH). Disturbances in cerebral perfusion are associated with GMH-IVH. Regional cerebral tissue oxygen saturation (rcSO2), measured with near-infrared spectroscopy, and fractional tissue oxygen extraction (FTOE) were calculated to obtain an indication of cerebral perfusion. Our objective was to determine whether rcSO2 and FTOE were associated with GMH-IVH in preterm infants. Methods— This case–control study included 17 preterm infants with Grade I to III GMH-IVH or periventricular hemorrhagic infarction (median gestational age, 29.4 weeks; range, 25.4 to 31.9 weeks; birth weight, 1260 g; range, 850 to 1840 g). Seventeen preterm infants without GMH-IVH, matched for gestational age and birth weight, served as control subjects (gestational age, 29.9 weeks; range, 26.0 to 31.6 weeks; birth weight, 1310 g; range, 730 to 1975 g). RcSO2 and transcutaneous arterial oxygen saturation were measured during 2 hours on Days 1 to 5, 8, and 15 after birth. FTOE was calculated as FTOE=(transcutaneous arterial oxygen saturation−rcSO2)/transcutaneous arterial oxygen saturation. Results— Multilevel analyses showed that rcSO2 was lower and FTOE higher in infants with GMH-IVH on Days 1, 2, 3, 4, 5, 8, and 15. The largest difference occurred on Day 5 with rcSO2 median 64% in infants with GMH-IVH versus 77% in control subjects and FTOE median 0.30 versus 0.17. RcSO2 and FTOE were not affected by the grade of GMH-IVH. Conclusions— Preterm infants with GMH-IVH had lower rcSO2 and higher FTOE during the first 2 weeks after birth irrespective of the grade of GMH-IVH. This suggests that cerebral perfusion is decreased persistently for 2 weeks in infants with GMH-IVH, even in the presence of mild hemorrhages.

Cerebral oxygen saturation and extraction in preterm infants with transient periventricular echodensities.

OBJECTIVE: Our aim was to determine regional cerebral tissue oxygen saturation and fractional tissue oxygen extraction in preterm infants with transient periventricular echodensities. We hypothesized that as a result of reduced cerebral perfusion, regional cerebral tissue oxygen saturation will be lower and fractional tissue oxygen extraction will be higher during the first days after birth. PATIENTS AND METHODS: This was a prospective, observational study of 49 preterm infants (gestational age median: 30.1 weeks [26.0–31.8 weeks]; birth weight median: 1220 g [615–2250 g]). We defined transient periventricular echodensities as echodensities that persisted for >7 days. Regional cerebral tissue oxygen saturation was measured on days 1–5, 8, and 15 after birth. Fractional tissue oxygen extraction was calculated as (transcutaneous arterial oxygen saturation − regional cerebral tissue oxygen saturation)/transcutaneous arterial oxygen saturation. RESULTS: Transient periventricular echodensities were found in 25 of 49 infants. During the first week we found no difference between the 2 groups for cerebral tissue oxygen saturation and fractional tissue oxygen extraction values. On day 15 after birth, cerebral tissue oxygen saturation was lower in preterm infants with transient periventricular echodensities (66%) compared with infants without echodensities (76%) (P = .003). Fractional tissue oxygen extraction in infants with transient periventricular echodensities (0.30) was higher than fractional tissue oxygen extraction in infants without transient periventricular echodensities (0.20) (P < .001). The differences could not be explained by confounding variables. CONCLUSIONS: Persistent transient periventricular echodensities may be associated with increased cerebral oxygen demand after the first week after birth, which is contrary to our hypothesis. Cerebral oxygenation may be involved in the recovery of perinatal white matter damage.

Cerebral oxygenation is associated with neurodevelopmental outcome of preterm children at age 2 to 3 years

The aim of the study was to determine whether regional cerebral tissue oxygen saturation (rcSO2) and fractional tissue oxygen extraction (FTOE), using near‐infrared spectroscopy, are associated with neurodevelopmental outcome of preterm infants.

Effect of Indomethacin Infused over 30 Minutes on Cerebral Fractional Tissue Oxygen Extraction in Preterm Newborns with a Patent Ductus Arteriosus

Background: A significant patent ductus arteriosus (PDA) is a common finding in the first days of life and, if persistent, is associated with an increased morbidity and mortality in the preterm newborn. Objectives: Our aim was to investigate, using near-infrared spectroscopy, the effect of indomethacin on the fractional tissue (cerebral) oxygen extraction (FTcOE) in a group of preterm newborns undergoing medical treatment for a PDA. Methods: This is a prospective, observational study. A cohort of 18 preterm newborns (<32 weeks) undergoing treatment for a PDA with indomethacin were monitored continuously for mean arterial blood pressure, arterial oxygen saturation (SpO2) and regional cerebral oxygen saturation (rcSO2). Measurements were started 1 h before and continued for 4 h after the first indomethacin dose. A final measurement (1 h) was made within 24 h of completing the full course. FTcOE = [SpO2 – rcSO2]/SpO2 was then calculated. To analyze the data, we chose to average the measurements over 1-hour periods. Results: There was a significant increase in the FTcOE (0.06, 95% CI 0.04–0.09, p < 0.001) noticeable within the 1st hour after the start of indomethacin administration, which peaked in the 2nd hour (FTcOE increased by 0.08, 95% CI 0.04–0.11, p < 0.001) and lasted for the full 4-hour period measured. Conclusion: Indomethacin, infused over 30 min, significantly increased the FTcOE in the preterm newborn, the effect lasting at least 4 h. This may represent a protective response to the indomethacin-induced reduction in cerebral blood flow demonstrated by others and warrants further investigation.

The relationship between electrocerebral activity and cerebral fractional tissue oxygen extraction in preterm infants.

Impaired cerebral oxygen delivery may cause cerebral damage in preterm infants. At lower levels of cerebral perfusion and oxygen concentration, electrocerebral activity is disturbed. The balance between cerebral oxygen delivery and oxygen use can be measured by near-infrared spectroscopy (NIRS), and electrocerebral activity can be measured by amplitude-integrated EEG (aEEG). Our aim was to determine the relationship between regional cerebral tissue oxygen saturation (rcSO2), fractional tissue oxygen extraction (FTOE), and aEEG. We recorded longitudinal digital aEEG and rcSO2 prospectively in 46 preterm infants (mean GA 29.5 wk, SD 1.7) for 2 hr on the 1st to 5th, 8th, and 15th d after birth. We excluded infants with germinal matrix hemorrhage exceeding grade I and recordings of infants receiving inotropes. FTOE was calculated using transcutaneous arterial oxygen saturation (tcSaO2) and rcSO2 values: (tcSaO2 − rcSO2)/tcSaO2. aEEG was assessed by calculating the mean values of the 5th, 50th, and 95th centiles of the aEEG amplitudes. The aEEG amplitude centiles changed with increasing GA. FTOE and aEEG amplitude centiles increased significantly with postnatal age. More mature electrocerebral activity was accompanied by increased FTOE. FTOE also increased with increasing postnatal age and decreasing Hb levels.

Measuring cerebrovascular autoregulation in preterm infants using near-infrared spectroscopy: An overview of the literature

ABSTRACT Introduction: The preterm born infant’s ability to regulate its cerebral blood flow (CBF) is crucial in preventing secondary ischemic and hemorrhagic damage in the developing brain. The relationship between arterial blood pressure (ABP) and CBF estimates, such as regional cerebral oxygenation as measured by near-infrared spectroscopy (NIRS), is an attractive option for continuous non-invasive assessment of cerebrovascular autoregulation. Areas covered: The authors performed a literature search to provide an overview of the current literature on various current clinical practices and methods to measure cerebrovascular autoregulation in the preterm infant by NIRS. The authors focused on various aspects: Characteristics of patient cohorts, surrogate measures for cerebral perfusion pressure, NIRS devices and their accompanying parameters, definitions for impaired cerebrovascular autoregulation, methods of measurements and clinical implications. Expert commentary: Autoregulation research in preterm infants has reported many methods for measuring autoregulation using different mathematical models, signal processing and data requirements. At present, it remains unclear which NIRS signals and algorithms should be used that result in the most accurate and clinically relevant assessment of cerebrovascular autoregulation. Future studies should focus on optimizing strategies for cerebrovascular autoregulation assessment in preterm infants in order to develop autoregulation-based cerebral perfusion treatment strategies.

Effect of balloon atrial septostomy on cerebral oxygenation in neonates with transposition of the great arteries.

Background:The aim of this study was to determine the effect of balloon atrial septostomy (BAS) on cerebral oxygenation in neonates with transposition of the great arteries (TGA).Methods:In term neonates with TGA, regional cerebral tissue oxygen saturation (rcSO2) was measured using near-infrared spectroscopy (NIRS) for a period of 2 h, before BAS, after BAS, and 24 h after BAS. In neonates who did not require BAS on clinical grounds, rcSO2 was measured within 24 h of admission and 24 h later.Results:BAS was performed in 12 of 21 neonates. rcSO2 increased from a median of 42% (before) to 48% at 2 h after BAS (P < 0.05), as did transcutaneous arterial oxygen saturation (spO2) (from 72% to 85%, P < 0.01). rcSO2 increased further during the next 24 h (from 48% to 64%, P < 0.05), whereas spO2 remained stable. Although beginning from a lower baseline (42 vs. 51%, P < 0.01), rcSO2 was higher in neonates treated with BAS, as compared with neonates not treated with BAS, 24 h after the procedure (64 vs. 58%, P < 0.05); spO2 was, however, similar between the two groups.Conclusion:BAS improves cerebral oxygen saturation in neonates with TGA. Complete recovery of cerebral oxygen saturation occurred only 24 h after BAS.

Volume Expansion Does Not Alter Cerebral Tissue Oxygen Extraction in Preterm Infants with Clinical Signs of Poor Perfusion

Background: Preterm infants with signs of poor perfusion are often treated with volume expansion, although evidence regarding its effect on cerebral perfusion is lacking. Moreover, the effect is questionable in preterm infants with an adequate cerebrovascular autoregulation (CAR). A useful measure to assess perfusion is cerebral fractional tissue oxygen extraction (cFTOE). Objectives: To assess the effect of volume expansion on cFTOE in preterm infants with signs of poor perfusion. Methods: In this observational study, we assessed cFTOE using near-infrared spectroscopy in preterm infants with signs of poor perfusion before, during and 1 h after volume expansion treatment. Simultaneously, we measured mean arterial blood pressure (MABP). We tested the effect of volume expansion on both cFTOE and MABP, using multi-level analyses. We intended to define a subgroup that responded to volume expansion with an increase in blood pressure and a decrease in cFTOE, suggesting absent CAR. Results: In 14 preterm infants, with a median gestational age of 26.7 weeks (25.0-28.7 weeks) and a median birth weight of 836 g (615-1,290 g), we found a small increase in MABP during (1.4 ± 1.4 mm Hg, p = 0.003) and after (1.8 ± 1.7 mm Hg, p = 0.001) volume expansion, but no change in cFTOE during (-0.19 ± 0.1% p = 0.44) or after (-0.53 ± 0.1% p = 0.34) volume expansion. We were unable to define a subgroup lacking CAR. Conclusions: Cerebral perfusion, as assessed by cFTOE, does not improve in preterm infants with signs of poor perfusion following volume expansion. In these infants, either CAR is present or volume expansion is inadequate to affect cFTOE.

Maternal antihypertensive drugs may influence cerebral oxygen extraction in preterm infants during the first days after birth.

Abstract Objective: To determine whether maternal antihypertensive drugs influenced cerebral oxygenation in preterm infants during the first days after birth. Methods: We included 49 preterm infants (median gestational age 30.3 weeks, (range 26.0–31.9), birth weight 1250 g (560–2250)). Regional cerebral oxygen saturation (rcSO2) was measured by near-infrared spectroscopy on postnatal days 1, 2, 3, 4 and 5. Fractional tissue oxygen extraction (FTOE) was calculated using rcSO2 and arterial oxygen saturation (SpO2) values:(SpO2 − rcSO2)/SpO2. Results: Nine mothers were treated with labetalol and/or MgSO4 during pregnancy, three mothers with labetalol, MgSO4 and nifedipine, and 19 mothers with nifedipine only. Eighteen infants served as controls. Multivariate linear regression analysis showed that exposure to labetalol and/or MgSO4 during pregnancy decreased FTOE on day 1 after birth, while nifedipine did not. Conclusions: Treating pregnant women with labetalol and/or MgSO4 may influence cerebral oxygen extraction in their offspring shortly after birth.