The clinical effects of cerebral near-infrared spectroscopy monitoring (NIRS) versus no monitoring:a protocol for a systematic review with meta-analysis and trial sequential analysis

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No neurodevelopmental benefit of cerebral oximetry in the first randomised trial (SafeBoosC II) in preterm infants during the first days of life

Aim: Cerebral hypoxia has been associated with neurodevelopmental impairment. We studied whether reducing cerebral hypoxia in extremely preterm infants during the first 72 hours of life affected neurological outcomes at two years of corrected age. Methods: In 2012‐2013, the phase II randomised Safeguarding the Brains of our smallest Children trial compared visible cerebral near‐infrared spectroscopy (NIRS) monitoring in an intervention group and blinded NIRS monitoring in a control group. Cerebral hy oxia was significantly reduced in the intervention group. We followed up 115 survivors from eight European centres at two years of corrected age, by conducting a medical examination and assessing their neurodevelopment with the Bayley Scales of Infant and Toddler Development, Second or Third Edition, and the parental Ages and Stages Questionnaire (ASQ). Results: There were no differences between the intervention (n = 65) and control (n = 50) groups with regard to the mean mental developmental index (89.6 ± 19.5 versus 88.4 ± 14.7, p = 0.77), ASQ score (215 ± 58 versus 213 ± 58, p = 0.88) and the number of children with moderate‐to‐severe neurodevelopmental impairment (10 versus six, p = 0.58). Conclusions: Cerebral NIRS monitoring was not associated with long‐term benefits or harm with regard to neurodevelopmental outcome at two years of corrected age

Clinical use of cerebral oximetry in extremely preterm infants is feasible

Introduction: The research programme Safeguarding the Brains of our smallest Children (SafeBoosC) aims to test the benefits and harms of cerebral near-infrared spectroscopy (NIRS) oximetry in infants born before 28 weeks of gestation. In a phase II trial, infants will be randomised to visible cerebral NIRS oximetry with pre-specified treatment guidelines compared to standard care with blinded NIRS-monitoring. The primary outcome is duration multiplied with the extent outside the normal range of regional tissue oxygen saturation of haemoglobin (rStO2) of 55 to 85% in percentage hours (burden). This study was a pilot of the Visible ­Oximetry Group. Material and methods: This was an observational study including ten infants. Results: The median gestational age was 26 weeks + three days, and the median start-up time was 133 minutes after delivery. The median recording time was 69.7 hours, mean rStO2 was 64.2 ± 4.5%, median burden of hyper- and hy­poxia was 30.3% hours (range 2.8-112.3). Clinical staff responded to an out of range value 29 times – only once to values above 85%. In comparison, there were 83 periods of more than ten minutes with an rStO2 below 55% and four episodes with an rStO2 above 85%. These periods accounted for 72% of the total hypoxia burden. A total of 18 of the 29 interventions were adjustments of FiO2 which in 13 of the 18 times resulted in an out-of-range SpO2. Two infants suffered second-degree burns from the sensor. Five infants died. In all cases, this was unrelated to NIRS monitoring and treatment. Conclusion: The intervention of early cerebral NIRS monitoring proved feasible, but prolonged periods of hypoxia went untreated. Thus, a revision of the treatment guideline and an alarm system is required

Cerebral near infrared spectroscopy oximetry in extremely preterm infants: phase II randomised clinical trial

Objective To determine if it is possible to stabilise the cerebral oxygenation of extremely preterm infants monitored by cerebral near infrared spectroscopy (NIRS) oximetry. Design Phase II randomised, single blinded, parallel clinical trial. Setting Eight tertiary neonatal intensive care units in eight European countries. Participants 166 extremely preterm infants born before 28 weeks of gestation: 86 were randomised to cerebral NIRS monitoring and 80 to blinded NIRS monitoring. The only exclusion criterion was a decision not to provide life support. Interventions Monitoring of cerebral oxygenation using NIRS in combination with a dedicated treatment guideline during the first 72 hours of life (experimental) compared with blinded NIRS oxygenation monitoring with standard care (control).Main outcome measures The primary outcome measure was the time spent outside the target range of 55-85% for cerebral oxygenation multiplied by the mean absolute deviation, expressed in %hours (burden of hypoxia and hyperoxia). One hour with an oxygenation of 50% gives 5%hours of hypoxia. Secondary outcomes were all cause mortality at term equivalent age and a brain injury score assessed by cerebral ultrasonography. Randomisation Allocation sequence 1:1 with block sizes 4 and 6 in random order concealed for the investigators. The allocation was stratified for gestational age (26 weeks).Blinding Cerebral oxygenation measurements were blinded in the control group. All outcome assessors were blinded to group allocation. Results The 86 infants randomised to the NIRS group had a median burden of hypoxia and hyperoxia of 36.1%hours (interquartile range 9.2-79.5%hours) compared with 81.3 (38.5-181.3) %hours in the control group, a reduction of 58% (95% confidence interval 35% to 73%, P<0.001). In the experimental group the median burden of hypoxia was 16.6 (interquartile range 5.4-68.1) %hours, compared with 53.6 (17.4-171.3) %hours in the control group (P=0.0012). The median burden of hyperoxia was similar between the groups: 1.2 (interquartile range 0.3-9.6) %hours in the experimental group compared with 1.1 (0.1-23.4) %hours in the control group (P=0.98). We found no statistically significant differences between the two groups at term corrected age. No severe adverse reactions were associated with the device. Conclusions Cerebral oxygenation was stabilised in extremely preterm infants using a dedicated treatment guideline in combination with cerebral NIRS monitoring.Trial registration ClinicalTrial.gov NCT0159031

A phase II randomized clinical trial on cerebral near-infrared spectroscopy plus a treatment guideline versus treatment as usual for extremely preterm infants during the first three days of life (SafeBoosC): study protocol for a randomized controlled trial

Background: Every year in Europe about 25,000 infants are born extremely preterm. These infants have a 20% mortality rate, and 25% of survivors have severe long-term cerebral impairment. Preventative measures are key to reduce mortality and morbidity in an extremely preterm population. The primary objective of the SafeBoosC phase II trial is to examine if it is possible to stabilize the cerebral oxygenation of extremely preterm infants during the first 72 hours of life through the application of cerebral near-infrared spectroscopy (NIRS) oximetry and implementation of an clinical treatment guideline based on intervention thresholds of cerebral regional tissue saturation rStO2. Methods/Design: SafeBoosC is a randomized, blinded, multinational, phase II clinical trial. The inclusion criteria are: neonates born more than 12 weeks preterm; decision to conduct full life support; parental informed consent; and possibility to place the cerebral NIRS oximeter within 3 hours after birth. The infants will be randomized into one of two groups. Both groups will have a cerebral oximeter monitoring device placed within three hours of birth. In the experimental group, the cerebral oxygenation reading will supplement the standard treatment using a predefined treatment guideline. In the control group, the cerebral oxygenation reading will not be visible and the infant will be treated according to the local standards. The primary outcome is the multiplication of the duration and magnitude of rStO2 values outside the target ranges of 55% to 85%, that is, the ‘burden of hypoxia and hyperoxia’ expressed in ‘%hours’. To detect a 50% difference between the experimental and control group in %hours, 166 infants in total must be randomized. Secondary outcomes are mortality at term date, cerebral ultrasound score, and interburst intervals on an amplitude-integrated electroencephalogram at 64 hours of life and explorative outcomes include neurodevelopmental outcome at 2 years corrected age, magnetic resonance imaging at term, blood biomarkers at 6 and 64 hours after birth, and adverse events. Discussion: Cerebral oximetry guided interventions have the potential to improve neurodevelopmental outcome in extremely preterm infants. It is a logical first step to test if it is possible to reduce the burden of hypoxia and hyperoxia. Trial registration: ClinicalTrial.gov, NCT0159031

A phase II randomized clinical trial on cerebral near-infrared spectroscopy plus a treatment guideline versus treatment as usual for extremely preterm infants during the first three days of life (SafeBoosC): study protocol for a randomized controlled trial.

BACKGROUND: Every year in Europe about 25,000 infants are born extremely preterm. These infants have a 20% mortality rate, and 25% of survivors have severe long-term cerebral impairment. Preventative measures are key to reduce mortality and morbidity in an extremely preterm population. The primary objective of the SafeBoosC phase II trial is to examine if it is possible to stabilize the cerebral oxygenation of extremely preterm infants during the first 72 hours of life through the application of cerebral near-infrared spectroscopy (NIRS) oximetry and implementation of an clinical treatment guideline based on intervention thresholds of cerebral regional tissue saturation rStO2. METHODS/DESIGN: SafeBoosC is a randomized, blinded, multinational, phase II clinical trial. The inclusion criteria are: neonates born more than 12 weeks preterm; decision to conduct full life support; parental informed consent; and possibility to place the cerebral NIRS oximeter within 3 hours after birth. The infants will be randomized into one of two groups. Both groups will have a cerebral oximeter monitoring device placed within three hours of birth. In the experimental group, the cerebral oxygenation reading will supplement the standard treatment using a predefined treatment guideline. In the control group, the cerebral oxygenation reading will not be visible and the infant will be treated according to the local standards. The primary outcome is the multiplication of the duration and magnitude of rStO2 values outside the target ranges of 55% to 85%, that is, the 'burden of hypoxia and hyperoxia' expressed in '%hours'. To detect a 50% difference between the experimental and control group in %hours, 166 infants in total must be randomized. Secondary outcomes are mortality at term date, cerebral ultrasound score, and interburst intervals on an amplitude-integrated electroencephalogram at 64 hours of life and explorative outcomes include neurodevelopmental outcome at 2 years corrected age, magnetic resonance imaging at term, blood biomarkers at 6 and 64 hours after birth, and adverse events. DISCUSSION: Cerebral oximetry guided interventions have the potential to improve neurodevelopmental outcome in extremely preterm infants. It is a logical first step to test if it is possible to reduce the burden of hypoxia and hyperoxia. TRIAL REGISTRATION: ClinicalTrial.gov, NCT01590316.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Peripheral tissue oximetry:comparing three commercial near-infrared spectroscopy oximeters on the forearm

Estimation of regional tissue oxygenation (rStO(2)) by near infrared spectroscopy enables non-invasive end-organ oxygen balance monitoring and could be a valuable tool in intensive care. However, the diverse absolute values and dynamics of different devices, and overall poor repeatability of measurements are a problem. The aim of the present study is to test the hypothesis that INVOS 5100C, FORE-SIGHT and NONIN EQUANOX 7600 have similar properties concerning absolute values, repeatability, and sensitivity to changes in rStO(2). To test repeatability the sensors were repositioned 20 times during hemodynamic steady state on the adult forearm. Afterwards six vascular occlusions by inflation of an upper arm cuff were done to achieve low oxygenation in the forearm. Absolute values were compared by repeated-measures ANOVA, repeatability was estimated by the within-subject standard deviation, S(w), and response to changing oxygenation by the down slope of rStO(2) during vascular occlusion in the respective arm. 10 healthy adults, 21–29 years old, with double skinfolds on the forearm less than 10 mm participated. The median rStO(2) was 70.7 % (interquartile range (IQR) 7.7 %), 68.4 % (IQR 8.4 %), and 64.6 % (IQR 4.8) with INVOS, NONIN, and FORE-SIGHT, respectively, the median rate of decline was 13.2 %/min (IQR 9.6), 22.8 %/min (IQR 18.0), and 10.8 %/min (IQR 6.0), and the same-site repeatability was 2.9 % (95 % CI 2.4–3.3), 4.6 % (CI 3.9–5.3), and 2.0 % (CI 1.7–2.3). INVOS gave significantly higher steady state values than FORE-SIGHT, and NONIN had the steepest decline in rStO(2), but the poorest repeatability. Two measures of signal-to-noise were similar among devices. This suggests that good repeatability comes at the expense of low sensitivity to changes in oxygenation. Values of rStO(2) on the forearm from INVOS, NONIN and FORE-SIGTH cannot be used interchangeably

Calibration of a prototype NIRS oximeter against two commercial devices on a blood-lipid phantom

In a blood-lipid liquid phantom the prototype near-infrared spectroscopy oximeter OxyPrem was calibrated against the INVOS® 5100c adult sensor in respect to values of regional tissue oxygen haemoglobin saturation (rStO2) for possible inclusion in the randomised clinical trial - SafeBoosC. In addition different commercial NIRS oximeters were compared on changing haemoglobin oxygen saturation and compared against co-oximetry. The best calibration was achieved with a simple offset and a linear scaling of the OxyPrem rStO2 values. The INVOS adult and pediatric sensor gave systematically different values, while the difference between the NIRO® 300 and the two INVOS sensors were magnitude dependent. The co-oximetry proved unreliable on such low haemoglobin and high Intralipid levels