The effects of cerebral oximetry in mechanically ventilated newborns: a protocol for the SafeBoosC-IIIv randomised clinical trial.

BACKGROUND: The SafeBoosC project aims to test the clinical value of non-invasive cerebral oximetry by near-infrared spectroscopy in newborn infants. The purpose is to establish whether cerebral oximetry can be used to save newborn infants' lives and brains or not. Newborns contribute heavily to total childhood mortality and neonatal brain damage is the cause of a large part of handicaps such as cerebral palsy. The objective of the SafeBoosC-IIIv trial is to evaluate the benefits and harms of cerebral oximetry added to usual care versus usual care in mechanically ventilated newborns. METHODS/DESIGN: SafeBoosC-IIIv is an investigator-initiated, multinational, randomised, pragmatic phase-III clinical trial. The inclusion criteria will be newborns with a gestational age more than 28 + 0 weeks, postnatal age less than 28 days, predicted to require mechanical ventilation for at least 24 h, and prior informed consent from the parents or deferred consent or absence of opt-out. The exclusion criteria will be no available cerebral oximeter, suspicion of or confirmed brain injury or disorder, or congenital heart disease likely to require surgery. A total of 3000 participants will be randomised in 60 neonatal intensive care units from 16 countries, in a 1:1 allocation ratio to cerebral oximetry versus usual care. Participants in the cerebral oximetry group will undergo cerebral oximetry monitoring during mechanical ventilation in the neonatal intensive care unit for as long as deemed useful by the treating physician or until 28 days of life. The participants in the cerebral oximetry group will be treated according to the SafeBoosC treatment guideline. Participants in the usual care group will not receive cerebral oximetry and will receive usual care. We use two co-primary outcomes: (1) a composite of death from any cause or moderate to severe neurodevelopmental disability at 2 years of corrected age and (2) the non-verbal cognitive score of the Parent Report of Children's Abilities-Revised (PARCA-R) at 2 years of corrected age. DISCUSSION: There is need for a randomised clinical trial to evaluate cerebral oximetry added to usual care versus usual care in mechanically ventilated newborns. TRIAL REGISTRATION: The protocol is registered at www. CLINICALTRIALS: gov (NCT05907317; registered 18 June 2023).

Cerebral Oximetry Monitoring in Extremely Preterm Infants.

BACKGROUND: The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking. METHODS: In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we assigned extremely preterm infants (gestational age, <28 weeks), within 6 hours after birth, to receive treatment guided by cerebral oximetry monitoring for the first 72 hours after birth or to receive usual care. The primary outcome was a composite of death or severe brain injury on cerebral ultrasonography at 36 weeks' postmenstrual age. Serious adverse events that were assessed were death, severe brain injury, bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and late-onset sepsis. RESULTS: A total of 1601 infants underwent randomization and 1579 (98.6%) were evaluated for the primary outcome. At 36 weeks' postmenstrual age, death or severe brain injury had occurred in 272 of 772 infants (35.2%) in the cerebral oximetry group, as compared with 274 of 807 infants (34.0%) in the usual-care group (relative risk with cerebral oximetry, 1.03; 95% confidence interval, 0.90 to 1.18; P = 0.64). The incidence of serious adverse events did not differ between the two groups. CONCLUSIONS: In extremely preterm infants, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth was not associated with a lower incidence of death or severe brain injury at 36 weeks' postmenstrual age than usual care. (Funded by the Elsass Foundation and others; SafeBoosC-III ClinicalTrials.gov number, NCT03770741.).

Cerebral near-infrared spectroscopy monitoring (NIRS) in children and adults: a systematic review with meta-analysis.

BACKGROUND: Cerebral oxygenation monitoring utilising near-infrared spectroscopy (NIRS) is increasingly used to guide interventions in clinical care. The objective of this systematic review with meta-analysis and Trial Sequential Analysis is to evaluate the effects of clinical care with access to cerebral NIRS monitoring in children and adults versus care without. METHODS: This review conforms to PRISMA guidelines and was registered in PROSPERO (CRD42020202986). Methods are outlined in our protocol (doi: 10.1186/s13643-021-01660-2). RESULTS: Twenty-five randomised clinical trials were included (2606 participants). All trials were at a high risk of bias. Two trials assessed the effects of NIRS during neonatal intensive care, 13 during cardiac surgery, 9 during non-cardiac surgery and 1 during neurocritical care. Meta-analyses showed no significant difference for all-cause mortality (RR 0.75, 95% CI 0.51-1.10; 1489 participants; I2 = 0; 11 trials; very low certainty of evidence); moderate or severe, persistent cognitive or neurological deficit (RR 0.74, 95% CI 0.42-1.32; 1135 participants; I2 = 39.6; 9 trials; very low certainty of evidence); and serious adverse events (RR 0.82; 95% CI 0.67-1.01; 2132 participants; I2 = 68.4; 17 trials; very low certainty of evidence). CONCLUSION: The evidence on the effects of clinical care with access to cerebral NIRS monitoring is very uncertain. IMPACT: The evidence of the effects of cerebral NIRS versus no NIRS monitoring are very uncertain for mortality, neuroprotection, and serious adverse events. Additional trials to obtain sufficient information size, focusing on lowering bias risk, are required. The first attempt to systematically review randomised clinical trials with meta-analysis to evaluate the effects of cerebral NIRS monitoring by pooling data across various clinical settings. Despite pooling data across clinical settings, study interpretation was not substantially impacted by heterogeneity. We have insufficient evidence to support or reject the clinical use of cerebral NIRS monitoring.

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.

BACKGROUND: Multiple clinical conditions are associated with cerebral hypoxia/ischaemia and thereby an increased risk of hypoxic-ischaemic brain injury. Cerebral near-infrared spectroscopy monitoring (NIRS) is a tool to monitor brain oxygenation and perfusion, and the clinical uptake of NIRS has expanded over recent years. Specifically, NIRS is used in the neonatal, paediatric, and adult perioperative and intensive care settings. However, the available literature suggests that clinical benefits and harms of cerebral NIRS monitoring are uncertain. As rates of clinically significant hypoxic-ischaemic brain injuries are typically low, it is difficult for randomised clinical trials to capture a sufficiently large number of events to evaluate the clinical effect of cerebral NIRS monitoring, when focusing on specific clinical settings. The aim of this systematic review will be to evaluate the benefits and harms of clinical care with access to cerebral NIRS monitoring versus clinical care without cerebral NIRS monitoring in children and adults across all clinical settings. METHODS: We will conduct a systematic review with meta-analysis and trial sequential analysis. We will only include randomised clinical trials. The primary outcomes are all-cause mortality, moderate or severe persistent cognitive or neurological deficit, and proportion of participants with one or more serious adverse events. We will search CENTRAL, EMBASE, MEDLINE, and the Science Citation Index Expanded from their inception and onwards. Two reviewers will independently screen all citations, full-text articles, and extract data. The risk of bias will be appraised using the Cochrane risk of bias tool version 2.0. If feasible, we will conduct both random-effects meta-analysis and fixed-effect meta-analysis of outcome data. Additional analysis will be conducted to explore the potential sources of heterogeneity (e.g. risk of bias, clinical setting). DISCUSSION: As we include trials across multiple clinical settings, there is an increased probability of reaching a sufficient information size. However, heterogeneity between the included trials may impair our ability to interpret results to specific clinical settings. In this situation, we may have to depend on subgroup analyses with inherent increased risks of type I and II errors. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020202986 . This systematic review protocol has been submitted for registration in the International Prospective Register of Systematic Reviews (PROSPERO) (http://www.crd.york.ac.uk/prospero) on the 12th of October 2020 and published on the 12th of November 2020 (registration ID CRD42020202986 ).

Cerebral near-infrared spectroscopy monitoring for prevention of brain injury in very preterm infants.

BACKGROUND: Cerebral injury and long-term neurodevelopmental impairment is common in extremely preterm infants. Cerebral near-infrared spectroscopy (NIRS) enables continuous estimation of cerebral oxygenation. This diagnostic method coupled with appropriate interventions if NIRS is out of normal range (that is cerebral oxygenation within the 55% to 85% range) may offer benefits without causing more harms. Therefore, NIRS coupled with appropriate responses to abnormal findings on NIRS needs assessment in a systematic review of randomised clinical trials and quasi-randomised studies. OBJECTIVES: To evaluate the benefits and harms of interventions that attempt to alter cerebral oxygenation guided by cerebral NIRS monitoring in order to prevent cerebral injury, improve neurological outcome, and increase survival in preterm infants born more than 8 weeks preterm. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 8), MEDLINE via PubMed (1966 to 10 September 2016), Embase (1980 to 10 September 2016), and CINAHL (1982 to 10 September 2016). We also searched clinical trial databases, conference proceedings, and the reference lists of retrieved articles for randomised clinical trials and quasi-randomised studies. SELECTION CRITERIA: Randomised clinical trials and quasi-randomised clinical studies comparing continuous cerebral NIRS monitoring for at least 24 hours versus blinded NIRS or versus no NIRS monitoring. DATA COLLECTION AND ANALYSIS: Two review authors independently selected, assessed the quality of, and extracted data from the included trials and studies. If necessary, we contacted authors for further information. We conducted assessments of risks of bias; risks of design errors; and controlled the risks of random errors with Trial Sequential Analysis. We assessed the quality of the evidence with GRADE. MAIN RESULTS: One randomised clinical trial met inclusion criteria, including infants born more than 12 weeks preterm. The trial employed adequate methodologies and was assessed at low risk of bias. One hundred and sixty-six infants were randomised to start continuous cerebral NIRS monitoring less than 3 hours after birth until 72 hours after birth plus appropriate interventions if NIRS was out of normal range according to a guideline versus conventional monitoring with blinded NIRS. There was no effect of NIRS plus guideline of mortality until term-equivalent age (RR 0.50, 95% CI 0.29 to 1.00; one trial; 166 participants). There were no effects of NIRS plus guideline on intraventricular haemorrhages: all grades (RR 0.93, 95% CI 0.65 to 1.34; one trial; 166 participants); grade III/IV (RR 0.57, 95% CI 0.25 to 1.31; one trial; 166 participants); and cystic periventricular leukomalacia (which did not occur in either group). Likewise, there was no effect of NIRS plus guideline on the occurrence of a patent ductus arteriosus (RR 1.96, 95% CI 0.94 to 4.08; one trial; 166 participants); chronic lung disease (RR 1.27, 95% CI 0.94 to 1.50; one trial; 166 participants); necrotising enterocolitis (RR 0.83, 95% CI 0.33 to 1.94; one trial; 166 participants); and retinopathy of prematurity (RR 1.64, 95% CI 0.75 to 3.00; one trial; 166 participants). There were no serious adverse events in any of the intervention groups. NIRS plus guideline caused more skin marks from the NIRS sensor in the control group than in the experimental group (unadjusted RR 0.31, 95% CI 0.10 to 0.92; one trial; 166 participants). There are no data regarding neurodevelopmental outcome, renal impairment or air leaks.The quality of evidence for all comparisons discussed above was assessed as very low apart from all-cause mortality and adverse events: these were assessed as low and moderate, respectively. The validity of all comparisons is hampered by a small sample of randomised infants, risk of bias due to lack of blinding, and indirectness of outcomes. AUTHORS' CONCLUSIONS: The only eligible randomised clinical trial did not demonstrate any consistent effects of NIRS plus a guideline on the assessed clinical outcomes. The trial was, however, only powered to detect difference in cerebral oxygenation, not morbidities or mortality. Our systematic review did not reach sufficient power to prove or disprove effects on clinical outcomes. Further randomised clinical trials with low risks of bias and low risks of random errors are needed.