Petra Lemmers

Monitoring Neonatal Regional Cerebral Oxygen Saturation in Clinical Practice: Value and Pitfalls

This review focuses on the clinical use of near infrared spectroscopy (NIRS) to assess brain oxygenation by the tissue oxygenation index (TOI), and monitoring regional cerebral oxygen saturation (rScO2), cerebral fractional tissue oxygen extraction (cFTOE), which is derived from rScO2, and systemic oxygen saturation. Its precision and pitfalls are discussed. At this stage, it is clear that NIRS-monitored oxygenation of the brain by rScO2 or TOI lacks the precision required to be used as a robust quantitative variable to monitor cerebral oxygenation. Intra- and especially interpatient variability are too large for this aim. On the other hand, when used merely as a trend monitor in the individual patient, substantial changes in rScO2 or TOI and consequently of cFTOE, larger than the limits of agreement, can yield important clinical information that suggest an intervention. Since neonatal intensive care is for a substantial part ‘brain orientated’ this approach seems conceivable. This gives rise to the conclusion that NIRS-monitored TOI, rScO2 and cFTOE increasingly will have a role in clinical practice as semiquantitative indicators of changes in cerebral oxygenation and oxygen extraction. Combination with other (cerebral) parameters such as amplitude-integrated EEG and blood pressure seems promising for further optimization of monitoring the immature brain.

Impact of patent ductus arteriosus and subsequent therapy with indomethacin on cerebral oxygenation in preterm infants.

OBJECTIVES. A hemodynamically important patent ductus arteriosus is a common problem in the first week of life in the preterm infant. Although patent ductus arteriosus induces alterations in organ perfusion, scarce information is available of the impact of patent ductus arteriosus and its subsequent treatment on the oxygen supply and oxygen extraction of the brain. We investigated the impact of patent ductus arteriosus and its treatment with indomethacin on regional cerebral oxygen saturation and fractional tissue oxygen extraction by using near-infrared spectroscopy. PATIENTS AND METHODS. Twenty infants with patent ductus arteriosus (gestational age: <32 weeks), subsequently treated with indomethacin, were monitored for mean arterial blood pressure, arterial oxygen saturation, near-infrared spectroscopy–determined regional cerebral oxygen saturation, and fractional tissue oxygen extraction ([arterial oxygen saturation − regional cerebral oxygen saturation]/arterial oxygen saturation). Ten-minute periods were selected and averaged during patent ductus arteriosus, at 10, 20, 30, 60, and 120 minutes, and at 6,12, 24, and 36 hours after starting indomethacin treatment (to ductal closure) for mean arterial blood pressure, arterial oxygen saturation, regional cerebral oxygen saturation, and fractional tissue oxygen extraction. The patients with patent ductus arteriosus were matched for gestational age, birth weight, postnatal age, and severity of respiratory distress syndrome with infants without patent ductus arteriosus, who served as control subjects. RESULTS. Mean arterial blood pressure and regional cerebral oxygen saturation were significantly lower and fractional tissue oxygen extraction significantly higher compared with the control infants during patent ductus arteriosus (mean arterial blood pressure: 33 ± 5 vs 38 ± 6 mmHg; regional cerebral oxygen saturation: 62% ± 9% vs 72% ± 10%; fractional tissue oxygen extraction: 0.34 ± 0.1 vs 0.25 ± 0.1, respectively). Regional cerebral oxygen saturation and fractional tissue oxygen extraction were lower and higher, respectively, up to 24 hours after the start of indomethacin but normalized to control values afterward. Indomethacin had no additional negative effect on cerebral oxygenation. CONCLUSIONS. A hemodynamically significant patent ductus arteriosus has a negative effect on cerebral oxygenation in the premature infant. Subsequent and adequate treatment of a patent ductus arteriosus may prevent diminished cerebral perfusion and subsequent decreased oxygen delivery, which reduces the change of damage to the vulnerable immature brain.

Cerebral Oxygenation and Electrical Activity After Birth Asphyxia: Their Relation to Outcome

OBJECTIVE. To determine the value of regional cerebral oxygen saturation (rSo2), fractional cerebral tissue oxygen extraction (FTOE) measured by near-infrared spectroscopy (NIRS), and amplitude integrated electroencephalogram (aEEG) after birth asphyxia in relation to neurodevelopmental outcome. METHODS. NIRS measured rSo2, FTOE, and aEEG were monitored simultaneously, together with arterial oxygen saturation (Sao2) and blood pressure during the first 48 hours after severe birth asphyxia in 18 term infants. FTOE was calculated as [Sao2 − rSo2]/Sao2. Neurodevelopmental outcome was assessed at 3, 9, and 18 months and 3 and 5 years of age. At the time points 6, 12, 18, 24, 30, 36, 42, and 48 hours after birth, the mean values of Sao2, rSo2, FTOE, and mean arterial blood pressure were calculated over a 1-hour period. A stepwise-regression model was used to investigate the relative contribution of rSo2, FTOE, or aEEG to developmental outcome. RESULTS. Nine Infants died during the neonatal period as a result of neurologic deterioration, and 8 infants had a normal outcome at 5 years of age. One child developed learning disabilities and a mild diplegia. The rSo2 and FTOE remained stable in infants with a normal outcome. The rSo2 increased and the FTOE decreased after 24 hours in the infants with an adverse outcome. (rSo2: 65% vs 84% at 12 and 48 hours, respectively; FTOE: 0.32 vs 0.12 at 12 and 48 hours, respectively). aEEG showed the closest relationship with outcome, but also rSo2 showed a significant correlation 24 hours after birth. CONCLUSIONS. rSo2 and FTOE seem to reflect secondary energy failure. aEEG showed the closest relationship with outcome after severe birth asphyxia.

Comparing near-infrared spectroscopy devices and their sensors for monitoring regional cerebral oxygen saturation in the neonate

Background:Near-infrared spectroscopy (NIRS) is an upcoming clinical method for monitoring regional cerebral oxygen saturation (rScO2) in neonates. There is a growing market offering different devices and sensors. Even though this technique is increasingly clinically applied, little is known about the similarities and/or differences in rScO2 values between the different devices and sensors. The aim of this study was to compare the rScO2 values obtained in (preterm) neonates with all available sensors of three frequently used NIRS devices.Methods:Fifty-five neonates admitted to our neonatal intensive care unit (NICU) were included in this study. rScO2 was simultaneously monitored bilaterally with two different NIRS sensors (left and right frontoparietal) for at least 1 h. Then, the sensors were switched, and measurements were collected for at least another hour.Results:We detected a rather close correlation between all investigated sensors from the three different NIRS devices, but absolute rScO2 values showed substantial differences: Bland–Altman analysis showed average differences from 10 to 15%.Conclusion:Although the rScO2 values correlated well between different NIRS sensors, sometimes there were substantial differences between the absolute rScO2 values, which may complicate clinical application.

Is cerebral oxygen supply compromised in preterm infants undergoing surgical closure for patent ductus arteriosus

Background A haemodynamically important patent ductus arteriosus (PDA) is a risk factor for brain damage in preterm infants. The authors previously reported lower regional cerebral oxygen saturation (rScO2) in infants with PDA, which recovered after administration of indomethacin. However, PDA ligation has been reported to pose an even higher risk of neurodevelopmental impairment. Objective To investigate the impact of surgical closure of PDA on rScO2 and cerebral fractional tissue oxygen extraction (cFTOE), measured by near-infrared spectroscopy, and on amplitude-integrated electro-encephalography (aEEG) measured brain activity. Design/methods In 20 preterm infants (gestational age 24.7–30.4 weeks; birth weight 630–1540 g), blood pressure, arterial saturation, rScO2, cFTOE and aEEG were monitored before, during and up to 24 h after surgery. Results Before surgery, median (range) rScO2 was 53% (41–68%), and during surgery, but before ductal clipping, it was 46% (31–89%). Eleven infants showed a drop in blood pressure and 13 infants a drop in rScO2 during surgery (range 2–21%), accompanied by a decrease in aEEG amplitude. Twelve infants had rScO2 values below 50% during surgery, with five being below 40%. Only at 24 h after surgery was rScO2 higher (61% (36–85%), p<0.05) and cFTOE values lower (0.38 (0.09–0.61); p<0.05) compared with preclipping values. Conclusion Ductal ligation poses a risk for a further decrease in already compromised cerebral oxygenation in preterm infants.

Cerebral Tissue Oxygenation and Regional Oxygen Saturation Can Be Used to Study Cerebral Autoregulation in Prematurely Born Infants

The coupling of cerebral intravascular oxygenation (dHbD) with mean arterial blood pressure (MABP) was taken as a reflection of autoregulation assuming constant arterial oxygen content. However, this method is sensitive to movement artifacts. We examined whether the cerebral tissue oxygenation index (cTOI) and regional oxygen saturation (rScO2) may replace dHbD and changes in total Hb (dHbT), respectively. Correlation (COR) and coherence (COH) were used to measure the agreement of MABP with rScO2/dHbT and cTOI/dHbD. dHbD/cTOI and dHbT/rScO2 recordings of, respectively, 34 and 20 preterm infants in need for intensive care were studied during the first days of life. dHbD and cTOI were obtained with the NIRO300 and rScO2 and dHbT with the INVOS4100. Invasive MABP was measured continuously. COR and COH scores of MABP versus dHbD/dHbT were compared with the corresponding ones by replacing dHbD/dHbT by cTOI/rScO2, respectively. Generally, no significant score differences were found for dHbD/cTOI. Differences for dHbT/rScO2 were slightly larger but still within the normal variation of the parameters. Differences become insignificant when restricting calculations to epochs of larger variation in MABP (>10 mm Hg). Hence, we suggest that cTOI and rScO2 can be used to study cerebral autoregulation in newborns.

Reference values of regional cerebral oxygen saturation during the first 3 days of life in preterm neonates

Background:Currently, reliable reference values of regional cerebral oxygen saturation (rScO2) for different gestational age (GA) groups are lacking, which hampers the implementation of near-infrared spectroscopy (NIRS) alongside monitoring arterial oxygen saturation (SaO2) and blood pressure in neonatal intensive care. The aim of this study was to provide reference values for rScO2 and cerebral fractional tissue oxygen extraction (cFTOE; (SaO2 − rScO2)/SaO2) for small adult and neonatal NIRS sensors.Methods:In this study, 999 infants born preterm (GA <32 wk) were monitored with NIRS during the first 72 h of life. Mixed modeling was used to generate reference curves grouped per 2 wk of GA. In addition, the influence of a hemodynamically significant patent ductus arteriosus, gender, and birth weight were explored.Results:Average rScO2 was ~65% at admission, increased with GA (1% per week) and followed a parabolic curve in relation to postnatal age with a peak at ~36 h. The cFTOE showed similar but inverse effects. On average, the neonatal sensor measured 10% higher than the adult sensor.Conclusion:rScO2 and cFTOE reference curves are provided for the first 72 h of life in preterm infants, which might support the broader implementation of NIRS in neonatal intensive care.

Cerebral oxygenation and brain activity after perinatal asphyxia: does hypothermia change their prognostic value?

Background:Hypothermia is an established therapy in term neonates to reduce death and disability after perinatal asphyxia. Near-infrared spectroscopy-monitored regional cerebral oxygen saturation (rScO2) and amplitude-integrated electroencephalogram (aEEG)-monitored background pattern have been shown to be early predictors of long-term neurodevelopmental outcome. The aim of this study was to investigate the prognostic value of rScO2 and aEEG for neurodevelopmental outcome in neonates with hypoxic–ischemic encephalopathy (HIE) treated with hypothermia.Methods:In neonates with HIE who were subjected to hypothermia, the aEEG background pattern and rScO2 were studied prospectively from admission up to 84 h in relation to early magnetic resonance imaging and neurodevelopmental outcome at 18 mo of age.Results:Of 39 infants, 12 neonates died because of neurological deterioration. One had an adverse outcome and 26 had a favorable outcome. The rScO2 was higher in neonates with adverse outcome, although aEEG scores were lower. Positive predictive values at 12, 24, and 36 h of age for adverse outcome ranged from 50 to 67% for rScO2 and aEEG; negative predictive values ranged from 73 to 96% for rScO2 and 90 to 100% for aEEG. Combining rScO2 and aEEG increased positive predictive values (70–91%) and negative predictive values (90–100%).Conclusion:During hypothermia, rScO2 and aEEG measurements are early predictors of long-term outcome after HIE. Combining both parameters further improves early prediction.

Left-to-right differences of regional cerebral oxygen saturation and oxygen extraction in preterm infants during the first days of life.

In a prospective study, we monitored simultaneously left and right parieto-frontal-cerebral oxygen saturation (rScO2) and cerebral fractional tissue oxygen extraction (cFTOE) using near-infrared spectroscopy in 36 very preterm neonates during the first 3 d of life. Simple regression analysis showed a close correlation between left and right rScO2 (r = 0.89, p < 0.01) and cFTOE (r = 0.88, p < 0.01), respectively. The Bland and Altman-determined limits of agreement found overall limits of agreement of −8.5 to +9.5% and of −0.10 to +0.093% between left and right for rScO2 and for cFTOE, respectively. However, we found that during stable systemic oxygenation (i.e., arterial oxygen saturation [SaO2 between 85 and 97%]) the limits of agreement between left and right improved from −7.8 to +8.2% and −0.088 to +0.084 for rScO2 and cFTOE, respectively (all p < 0.05). We conclude that bilateral near-infrared spectroscopy–measured rScO2 and cFTOE can reveal differences up to 10% between left and right hemisphere, especially during unstable arterial saturations, which may indicate uneven cerebral oxygenation.

Cerebral Oxygenation and Oxygen Extraction in the Preterm Infant during Desaturation : Effects of Increasing FiO(2) to Assist Recovery

Background: In the clinical setting, episodes of desaturation in newborn infants are often treated by increasing the fraction of inspired oxygen (FiO2). Objectives: To study the effect of an increase in FiO2 on cerebral oxygenation during recovery from desaturation, as measured by near-infrared spectroscopy (NIRS). Methods: Peripheral arterial saturation (SaO2), NIRS-monitored cerebral saturation (rScO2), and fractional cerebral oxygen extraction (cFTOE) were analyzed in the first 3 days of life during 6 episodes of desaturation (SaO2 <75%, >30 s) in each of 24 otherwise stable spontaneously breathing preterm infants (gestational age 29.8 ± 1.5 weeks, birth weight 1,215 ± 280 g; mean ± SD), during 3 episodes without and 3 episodes with increased FiO2 during recovery from desaturation. Results: Post-recovery SaO2 with increased FiO2 was significantly higher than post-recovery SaO2 without increased FiO2. Post-recovery SaO2 and rScO2 were significantly increased over baseline saturations when FiO2 was increased. Post-recovery rScO2 was very high for several minutes in some cases, while cFTOE was highly suggestive of oxygen delivery that exceeded consumption. Conclusions: Assuming that NIRS-measured rScO2 is an indicator of cerebral oxygen content, an increase in FiO2 to assist recovery from desaturation may cause hyperoxygenation of the brain in relatively stable preterm infants. This procedure may be particularly harmful in the sick very preterm infant with limited regulation of brain circulation and poorly developed antioxidant defenses.