P Lemmers

Effect of the "InSurE" Procedure on Cerebral Oxygenation and Electrical Brain Activity of the Preterm Infant.

Background: In preterm infants with respiratory distress syndrome (RDS) nasal continuous positive airway pressure (nCPAP) with the “InSurE” procedure (intubation, surfactant, extubation) is increasingly used. However, its effect on cerebral oxygenation and brain function is not known. Objective: To evaluate the effects of the “InSurE” procedure in infants with RDS on regional cerebral oxygen saturation (rScO2) and relative cerebral fractional tissue oxygen extraction (cFTOE) using near infrared spectroscopy and on electrical brain activity using amplitude-integrated electroencephalography (aEEG). Methods: Sixteen infants with RDS, treated with the “InSurE” procedure, and 16 matched controls with nCPAP, were monitored for mean arterial blood pressure (MABP), arterial oxygen saturation (SaO2), rScO2, cFTOE and aEEG. Ten-minute periods were selected and averaged at 120 and 20 minutes before, during the procedure and at 30 minutes, 1, 2, 6, 12 and 24 h after the start of the “InSurE” procedure. aEEG was analysed by quantitative and qualitative (Burdjalov score) methods. Results: MABP was not different between groups on all time points. rScO2 and cFTOE were comparable between groups, but there was a trend towards lower rScO2 and higher cFTOE 30 minutes after opioid administration in the “InSurE” infants compared with controls (62% (SD 11) vs 68% (SD 10) and 0.30 (SD 0.10 ) vs 0.28 (SD 0.11), respectively). aEEG amplitudes and Burdjalov scores were significantly lower in “InSurE” infants from 30 minutes after opioid administration up to 24 h after the start of the procedure (p<0.05). Conclusion: In the present study, the “InSurE” procedure did not induce perturbation of cerebral oxygen delivery and extraction, whereas electrical brain activity decreased for a prolonged period of time.

Simultaneous quantitative assessment of cerebral physiology using respiratory-calibrated MRI and near-infrared spectroscopy in healthy adults☆

BACKGROUND Functional near-infrared spectroscopy (fNIRS) and functional MRI (fMRI) are non-invasive techniques used to relate activity in different brain regions to certain tasks. Respiratory calibration of the blood oxygen level dependent (BOLD) signal, and combined fNIRS-fMRI approaches have been used to quantify physiological subcomponents giving rise to the BOLD signal. A comparison of absolute oxygen metabolism parameters between MRI and NIRS, using spatially resolved (SRS) NIRS and respiratory calibrated MRI, could yield additional insight in the physiology underlying activation. MATERIALS AND METHODS Changes in the BOLD signal, cerebral blood flow (CBF), and oxygen saturation (SO2) were derived from a single MRI sequence during a respiratory challenge in healthy volunteers. These changes were compared to SO2 obtained by a single probe SRS NIRS setup. In addition, concentration changes in oxygenated (O2Hb), deoxygenated (HHb), and total haemoglobin (tHb), obtained by NIRS, were compared to the parameters obtained by MRI. RESULTS NIRS SO2 correlated with end-tidal CO2 (0.83, p<0.0001), the BOLD signal (0.82, p<0.0001), CBF (0.85, p<0.0001), and also MRI SO2 (0.82, p<0.0001). The BOLD signal correlated with NIRS HHb (-0.76, p<0.0001), O2Hb (0.41, p=0.001), and tHb (r=0.32, p=0.01). CONCLUSIONS Good correlations show that changes in cerebral physiology, following a respiratory challenge, go hand in hand with changes in the BOLD signal, CBF, O2Hb, HHb, NIRS SO2, and MRI SO2. Out of all NIRS derived parameters, the SO2 showed the best correlation with the BOLD signal.

A known and a novel mutation in the glycine decarboxylase gene in a newborn with classic nonketotic hyperglycinemia.

A term neonate displayed typical features of nonketotic hyperglycinemia (NKH). Conventional magnetic resonance imaging showed corpus callosum hypoplasia and increased signal intensity of the white matter. Magnetic resonance proton spectroscopy revealed high cerebral glycine levels. The liquor/plasma glycine ratio was increased. Genetic testing detected a known and a novel mutation in the glycine decarboxylase gene, leading to the classic form of glycine encephalopathy. Prenatal genetic testing in the subsequent pregnancy showed that this fetus was not affected. As features of neonatal NKH may not be very specific, recognition of the disease may be difficult. An overview of clinical, electroencephalography, and neuroimaging findings is given in this article.

PO-0475 The Effect Of Co2-insufflation On Cerebral Oxygenation In Thoracoscopic Repair Of Esophageal Atresia In Neonates

Aim of the study Infants undergoing neonatal surgery for thoracoscopic esophageal atresia repair are at high risk of adverse neurodevelopmental outcomes. Increasing concerns have been raised about the incidence of perioperative brain injury, this is suggested to be due to haemodynamic instability and hypoxia perioperatively. We evaluated the effects of CO2-insufflation on regional cerebral oxygen saturation (rScO2) during thoracoscopic esophageal atresia repair. Methods Observational study of 20 neonates undergoing thoracoscopic esophageal atresia repair. During surgery mean blood pressure (MABP), FiO2, arterial saturation and the cerebral oxygen saturation (rScO2) were continuously monitored. Four periods of 10 min were selected: (T=0) during anaesthesia, (T=1 and T=2) during CO2-insufflation and (T=3) after desufflation. Main results Complete registration was obtained in 14 neonates (median GA 36.9 [30.6–41.9], birth weight 2358 g [1395–4490]) and were included. After CO2-insufflation the FiO2 increased from 41% to 58%, whilst the saturation decreased from 96.3% to 92.5%(p < 0.05). The arterial pCO2 (mmHg) changed from 47 ± 6.9 to 56 ± 13(p < 0.05) after CO2-insufflation and remained stable at the end of insufflation and after desufflation. The rScO2 did not change after CO2-insufflation or desufflation. Conclusion Intrathoracic CO2-insufflation causes a decrease in arterial saturation and an increase in arterial pCO2. However, more importantly these changes did not result in significant fluctuations in cerebral oxygenation throughout the procedure. The insufflation of CO2 with 5 mmHg during thoracoscopy seems to be safe in neonates, since the cerebral oxygenation was preserved during the procedure.

Comparing Different NIRS Devices and their Sensors for Monitoring Regional Cerebral Oxygen Saturation in Neonates

Background and aim: Near-infrared spectroscopy (NIRS)-monitored regional cerebral oxygen saturation (rScO2) in neonates has been increasingly used to assess cerebral oxygen delivery and extraction. Consequently neonatal sensors were designed with their own algoritms to separate the signals of oxy- and deoxyhemoglobin. However,published reference values are mostly based on studies using adult (conventional) sensors with different algoritms.To compare rScO2 values between the conventional NIRS-sensors of 3 different brands and those especially designed for use on the neonatal head.Methods: 56 neonates admitted to our NICU were included. rScO2‘s were measured left and right fronto-parietally with a conventional and neonatal sensor on each side for at least one hour.Then the sensors were switched to the opposite side and measurements were continued for at least another hour.Results: We found a significant correlation between conventional and neonatal sensors (p< 0.01-p< 0.001). However, Bland-Altman analysis showed a consistent difference between sensors from 8-to-13%, showing higher values obtained with the neonatal sensors.Conclusions: Although a good correlation between conventional and neonatal NIRS sensors was detected, reference values should be re-established when using newly designed neonatal sensors.Moreover rScO2 values in the higher range measured with neonatal sensors appeared to be less reliable which may be a problem in case of hyperoxia, which is in particular a problem in the extremely preterm neonate whose brain is prone for hyperoxic-induced brain damage.

Predictive Role of F2-Isoprostanes as Biomarkers for Brain Damage after Neonatal Surgery

Objective Neonates have a high risk of oxidative stress during anesthetic procedures. The predictive role of oxidative stress biomarkers on the occurrence of brain injury in the perioperative period has not been reported before. Methods A prospective cohort study of patients requiring major surgery in the neonatal period was conducted. Biomarker levels of nonprotein-bound iron (NPBI) in plasma and F2-isoprostane in plasma and urine before and after surgical intervention were determined. Brain injury was assessed using postoperative MRI. Results In total, 61 neonates were included, median gestational age at 39 weeks (range 31–42) and weight at 3000 grams (1400–4400). Mild to moderate brain lesions were found in 66%. Logistic regression analysis showed a significant difference between plasma NPBI in patients with nonparenchymal injury versus no brain injury: 1.34 umol/L was identified as correlation threshold for nonparenchymal injury (sensitivity 67%, specificity 91%). In the multivariable analysis, correcting for GA, no other significant relation was found with the oxidative stress biomarkers and risk factors. Conclusion Oxidative stress seems to occur during anaesthesia in this cohort of neonates. Plasma nonprotein-bound iron showed to be associated with nonparenchymal injury after surgery, with values of 1.34 umol/L or higher. Risk factors should be elucidated in a more homogeneous patient group.

O-221 Safeboosc – A Phase Ii Randomised Clinical Trial On Cerebral Near-infrared Spectroscopy Oximetry In Extremely Preterm Infants

Background and aims Extremely preterm infants have a high risk of moderate to severe long-term neurodevelopmental impairment. Hypoxic or hyperoxic brain injury may be a contributing factor. The SafeBoosC trial investigated if it is possible to stabilise the cerebral oxygenation of extremely preterm infants. Methods This was a phase II randomised, single blinded, clinical trial. Infants born before 28 weeks of gestation were eligible. Within 3 h of birth, infants were randomly assigned to either cerebral near infrared spectroscopy (NIRS) oxygenation monitoring in combination with a treatment guideline (experimental) or blinded NIRS monitoring with standard care (control). The primary outcome was the area under the curve of the time series of absolute deviation from the cerebral oxygenation target range of 55% to 85%, expressed in % hours (the burden of hypoxia and hyperoxia). We hypothesised that there would be more than 50% reduction in this burden in the experimental group. Results 166 infants with a median postmenstrual age of 26.4 weeks were enrolled (Table 1). Two infants were withdrawn. 86 infants randomised to the NIRS group had a median burden of hypoxia and hyperoxia of 36.1% hours (IQR 9.2 to 79.5) compared with 81.3% hours (IQR 38.5 to 181.3) in the control group (Figure 1), a reduction of 58% (95% CI 35% to 73%) (p= <0.0001). We found no other statistically significant differences between the two groups to term corrected age. Conclusions Cerebral oxygenation was stabilised using a treatment guideline in combination with cerebral NIRS monitoring in extremely preterm infants. Abstract O-221 Table 1 Characteristics Experimental (n = 86) Control (n = 80) Birth weight, median (range), g. 806 (410 to 1286) 880 (490 to 1330) Gestational age at birth, median (IQR), wk. 26.6 (25.7 to 27.4) 26.8 (25.5 to 27.6) Male sex, n (%) 44 (51.2) 34 (42.5) Multiple births, n (%) 20 (23.3) 14 (17.5) Prenatal steroids, n (%) 58 (67.4) 56 (70.9) Prolonged rupture of membranes, n (%) 26 (30.6) 32 (40.5) Maternal clinical chorioamnionitis, n (%) 6 (7.1) 7 (9.0) Apgar score ≤ 5 at 5 min, n (%) 15 (17.6) 14 (17.7) Umbilical arterial pH, mean (SD) 7.33 (0.088) 7.31 (0.096)

PO-0710 Dosing Errors And Clinical Impact In Preterm Infants Due To Flow Rate Variability In Mult-infusion Therapy

Background and aims Almost all preterm infants on the NICU receive continuous intra-venous infusion therapy. Commonly, multiple pharmaceuticals are administered through one catheter (multi-infusion). Due to the mutual influence of infusion pumps, dosing errors can occur that may lead to adverse events. We designed an in vitro experiment to measure flow rate variability and dosing errors. Subsequently, possible clinical impact was investigated. Methods We conducted an n = 3 experiment with 3 syringe pumps and disposables as used in our NICU. A clinically relevant medication schedule was simulated using laser dyes as substitutes for pharmaceuticals. Real-time, inline, absorption spectrometry was used to measure dye concentrations and, subsequently, analyse flow rate variability. After changing the flow rate we registered temporary dosing errors in the parallel pumps, in addition, we registered start-up delays. A one-compartment pharmacological model was used to investigate the clinical impact of these errors. Results The significant temporary dosing errors were between 48.1% ± 12.9% and -32.5% ± 22.5% over- and under-dose respectively. Start-up delays were up to 0.71 ± 0.11 h. Our pharmacological model indicates that these dosing errors could lead to haemodynamic instability for commonly used inotropes. Conclusions Potential clinical impact includes hypertension, hypotension and intraventricular haemorrhages. We conclude that applying multi-infusion with currently used NICU infusion setups results in dosing errors with potential clinical impact. It is advised not to combine high-alert medication on a mutual lumen or line. In addition, it is advised to raise awareness about these phenomena. This study was co-funded by the EMRP.

PS-032 Perfusion Index In Preterm Infants During The First 3 Days Of Life

Background and aim The waveform amplitude produced by pulse oximeters can be expressed as an index of pulsatile vs. non-pulsatile signal. This perfusion index (PI) has been shown to correlate with cardiac output, stroke volume, and superior vena cava flow. The aim was to gather PI reference data in preterm infants and to explore if the PI is associated with common clinical parameters. Patients/methods The PI was recorded in 312 neonates <32 weeks GA during the first 72 h of life. Mixed-effects modelling was applied with PI as the dependent variable and the individual patient as a random factor. Subsequently the association with clinical parameters (i.e. GA, birth weight, IVH, PDA, inotropes) was explored. Results Mean GA was 28.5 weeks (SD ± 2.1). A quadratic model (0–24 h) combined with a linear model (24–72 h) provided the best fit. The lowest PI was reached 12–18 h after birth, thereafter gradually increasing until 72 h postnatal age. For the first 24 h PI was associated with gender (coefficient 0.05, p = 0.04), inotrope administration (-0.123, p < 0.0001), pulse pressure (0.014, p < 0.0001), SaO2 (-0.015, p < 0.0001), MABP (-0.013, p < 0.0001), and GA (0.014, p = 0.0168). After the first day, only associations with, inotrope administration (-0.17, p < 0.0001), pulse pressure (0.007, p < 0.0001), MABP (-0.014, p < 0.0001), and SaO2 (-0.01, p < 0.0001) remained. No association was found with, IVH, PDA, fluid boluses, or birth weight. Conclusions The evolution of PI values over time probably reflects transitional physiology. The associations with pulspressure, MABP, and inotrope administration suggest that the PI might have an application in blood pressure management.

EFFECT OF INDOMETHACINE INFUSION RATE FOR PATENT DUCTUS ARTERIOSUS ON CEREBRAL OXYGENATION IN PRETERM INFANTS

Background: Indomethacine treatment for patent ductus arteriosus (PDA), might lead to vasoconstriction of cerebral blood vessels and under-perfusion of the brain. A lower infusion rate might prevent this. We aimed to determine the effect of two indomethacine infusion rates on fractional cerebral oxygen extraction (FTOE), which is indicative for cerebral blood flow. Methods: In preterms with PDA, we compared the effect of indomethacine infusion (0.2 mg/kg) in 30 versus 60 minutes, on cerebral oxygenation. Patients in both groups were matched for GA, BW, PDA closure, and postnatal age. Near-infrared spectroscopy was used to measure regional cerebral oxygen saturation (rcSO2). Transcutaneous arterial oxygen saturation (tcSaO2) was measured simultaneously. FTOE was calculated: (tcSaO2- rcSO2)/tcSaO2. We analyzed 6 episodes of 1-h measurements: before, 1h-4h, and 12 hours after treatment, using Mann-Whitney-U-test. Results: Twenty infants (13 girls, median GA 27.0 weeks (range 25.3-28.7), BW 1007 gram (615- 1300), age 3.0 days (2-11)) were included, 10 in each group. No significant differences existed between the groups regarding GA, BW, age, effectiveness of indomethacine, need of surgery, and gender. The first hour after the start of treatment, we found an increase in FTOE of 0.04 in the 30 minutes-infusiongroup, compared to no change in FTOE in the 60-minutes-infusion group (p=.03). No significant differences were found at all other time-points. Conclusion: Higher infusion rate of indomethacine for PDA seems to decrease cerebral blood flow the first hour, compared to lower infusion rate, possibly due to indomethacine induced vasoconstriction. The clinical relevance of this difference needs to be Investigated.