Gerhard Pichler

Non-invasive versus invasive respiratory support in preterm infants at birth: systematic review and meta-analysis

Objective To assess the role of nasal continuous positive airway pressure (CPAP) initiated at birth for prevention of death and bronchopulmonary dysplasia in very preterm infants. Design Systematic review. Data sources PubMed, Embase, the Cochrane Central Register of Controlled Trials, and online Pediatric Academic Society abstracts from the year of inception to June 2013. Eligibility criteria for selecting studies Randomised controlled trials evaluating the effect of nasal CPAP compared with intubation in preterm infants born at less than 32 weeks’ gestation and presenting the outcomes of either death or bronchopulmonary dysplasia, or both (defined as the need for oxygen support or mechanical ventilation at 36 weeks corrected gestation), during hospital stay. Results Four randomised controlled trials (2782 participants) met the inclusion criteria, with 1296 infants in the nasal CPAP group and 1486 in the intubation group. All the trials reported bronchopulmonary dysplasia independently at 36 weeks corrected gestation, with borderline significance in favour of the nasal CPAP group (relative risk 0.91, 95% confidence interval 0.82 to 1.01, risk difference −0.03, 95% confidence interval −0.07 to 0.01). No difference in death was observed (relative risk 0.88, 0.68 to 1.14, risk difference −0.02, −0.04 to 0.01, respectively). Pooled analysis showed a significant benefit for the combined outcome of death or bronchopulmonary dysplasia, or both, at 36 weeks corrected gestation for babies treated with nasal CPAP (relative risk 0.91, 0.84 to 0.99, risk difference −0.04, -0.07 to 0.00), number needed to treat of 25). Conclusion One additional infant could survive to 36 weeks without bronchopulmonary dysplasia for every 25 babies treated with nasal CPAP in the delivery room rather than being intubated.

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 or ≥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 NCT01590316.

Reference Ranges for Regional Cerebral Tissue Oxygen Saturation and Fractional Oxygen Extraction in Neonates during Immediate Transition after Birth

OBJECTIVE To define reference ranges for regional cerebral tissue oxygen saturation (crSO2) and regional cerebral fractional tissue oxygen extraction (cFTOE) during the first 15 minutes after birth in neonates requiring no medical support. STUDY DESIGN The crSO2 was measured using near infrared spectroscopy (Invos 5100 cerebral/somatic oximeter monitor; Somanetics Corp, Troy, Michigan) during the first 15 minutes after birth for term and preterm neonates. The near infrared spectroscopy sensor was placed on the left forehead. Peripheral oxygen saturation and heart rate were continuously measured by pulse oximetry, and cFTOE was calculated. Neonates were excluded if they required any medical support. RESULTS A total of 381 neonates were included: 82 term neonates after vaginal delivery, 272 term neonates after cesarean delivery, and 27 preterm neonates after cesarean delivery. In all neonates, median (10th-90th percentiles) crSO2 was 41% (23-64) at 2 minutes, 68% (45-85) at 5 minutes, 79% (65-90) at 10 minutes, and 77% (63-89) at 15 minutes of age. In all neonates, median (10th-90th percentiles) cFTOE was 33% (11-70) at 2 minutes, 21% (6-45) at 5 minutes, 15% (5-31) at 10 minutes, and 18% (7-34) at 15 minutes of age. CONCLUSION We report reference ranges of crSO2 and cFTOE in neonates requiring no medical support during transition immediately after birth. The use of cerebral oxygenation monitoring and use of these reference ranges in neonates during transition may help to guide oxygen delivery and avoid cerebral hypo-oxygenation and hyperoxygenation.

Regional Oxygen Saturation of the Brain and Peripheral Tissue during Birth Transition of Term Infants

OBJECTIVE To evaluate regional tissue oxygenation of the brain and preductal and postductal peripheral (muscle) tissue during immediate transition after birth, and to correlate with peripheral preductal and postductal arterial oxygen saturation. STUDY DESIGN We conducted a prospective observational study. With near-infrared spectroscopy (NIRS), changes in regional oxygen saturation of the brain (rSO2brain), peripheral preductal tissue (rSO2pre), and peripheral postductal tissue (rSO2post) were measured during the first 10 minutes of life in 59 healthy term infants after elective caesarean delivery. Fractional tissue oxygen extraction was calculated for all 3 regions. RESULTS Mean rSO2brain increased rapidly from 44% (3 minutes) to 76% (7 minutes); thereafter no significant change occurred. Mean rSO2pre and rSO2post increased constantly from minute 3 to minute 10, from 36%(pre)/27%(post) to 66%(pre)/58%(post). Fractional tissue oxygen extraction decreased in all 3 regions during the first minutes of life. Fractional tissue oxygen extraction of the brain did not change significantly after 5 minutes, and preductal and postductal fractional tissue oxygen extraction did not change significantly after 8 minutes. CONCLUSIONS During transition, the brain had the highest saturation levels, indicating a preference of oxygen delivery to the brain. Fractional tissue oxygen extraction of the brain reached a plateau earlier compared with peripheral tissue.

Sustained inflation versus positive pressure ventilation at birth: a systematic review and meta-analysis

Context Sustained inflation (SI) has been advocated as an alternative to intermittent positive pressure ventilation (IPPV) during the resuscitation of neonates at birth, to facilitate the early development of an effective functional residual capacity, reduce atelectotrauma and improve oxygenation after the birth of preterm infants. Objective The primary aim was to review the available literature on the use of SI compared with IPPV at birth in preterm infants for major neonatal outcomes, including bronchopulmonary dysplasia (BPD) and death. Data source MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials, until 6 October 2014. Study selection Randomised clinical trials comparing the effects of SI with IPPV at birth in preterm infants for neonatal outcomes. Data extraction and synthesis Descriptive and quantitative information was extracted; data were pooled using a random effects model. Heterogeneity was assessed using the Q statistic and I2. Results Pooled analysis showed significant reduction in the need for mechanical ventilation within 72 h after birth (relative risk (RR) 0.87 (0.77 to 0.97), absolute risk reduction (ARR) −0.10 (−0.17 to −0.03), number needed to treat 10) in preterm infants treated with an initial SI compared with IPPV. However, significantly more infants treated with SI received treatment for patent ductus arteriosus (RR 1.27 (1.05 to 1.54), ARR 0.10 (0.03 to 0.16), number needed to harm 10). There were no differences in BPD, death at the latest follow-up and the combined outcome of death or BPD among survivors between the groups. Conclusions Compared with IPPV, preterm infants initially treated with SI at birth required less mechanical ventilation with no improvement in the rate of BPD and/or death. The use of SI should be restricted to randomised trials until future studies demonstrate the efficacy and safety of this lung aeration manoeuvre.

The SafeBoosC Phase II Randomised Clinical Trial: A Treatment Guideline for Targeted Near-Infrared-Derived Cerebral Tissue Oxygenation versus Standard Treatment in Extremely Preterm Infants

Near-infrared spectroscopy-derived regional tissue oxygen saturation of haemoglobin (rStO2) reflects venous oxygen saturation. If cerebral metabolism is stable, rStO2 can be used as an estimate of cerebral oxygen delivery. The SafeBoosC phase II randomised clinical trial hypothesises that the burden of hypo- and hyperoxia can be reduced by the combined use of close monitoring of the cerebral rStO2 and a treatment guideline to correct deviations in rStO2 outside a predefined target range. Aims: To describe the rationale for and content of this treatment guideline. Methods: Review of the literature and assessment of the quality of evidence and the grade of recommendation for each of the interventions. Results and Conclusions: A clinical intervention algorithm based on the main determinants of cerebral perfusion-oxygenation changes during the first hours after birth was generated. The treatment guideline is presented to assist neonatologists in making decisions in relation to cerebral oximetry readings in preterm infants within the SafeBoosC phase II randomised clinical trial. The evidence grades were relatively low and the guideline cannot be recommended outside a research setting.

Plasma Concentrations after Intravenous Administration of Phylloquinone (vitamin K1) in Preterm and Sick Neonates

Vitamin K prophylaxis usually is administered orally or intramuscularly, but in neonatal intensive care oral administration might not be feasible and intramuscular administration is not general practice in very small infants. No data are available about plasma levels after intravenous administration of vitamin K to neonates. Therefore, we investigated plasma levels in 18 infants: 14 preterms with a birthweight of 1785+/-648 g and 4 sick newborns with a birth-weight of 3167+/-510 g after administration of a single dose of 0.3+/-0.1 mg/kg phylloquinone (vitamin K(1)) (Konakion MM((R)), Roche) intravenously after birth. Blood was collected 22.9+/-18.4 hours after intravenous administration of vitamin K(1). In 10 neonates a second sample was obtained 111.8+/-49.1 hours after the first vitamin K(1) administration. Gas chromatography-mass spectrometry (GC-MS) was used as the method for determination of vitamin K(1). The measured plasma concentration after intravenous administration of vitamin K(1) was 191.3+/-102.6 ng vitamin K in the first sample /mL in the first sample and 98.7+/-75.2 ng vitamin K(1)/mL in the second samples. These results are similar to those described in newborns after oral administration of 3 mg vitamin K(1) and after intramuscular administration of 1.5 mg vitamin K(1). In conclusion, the recommendation of the producer to give 0.4 mg/kg of vitamin K intravenously to neonates, in whom oral or intramuscular administration is not feasible, seems to be rational.

How to Monitor the Brain during Immediate Neonatal Transition and Resuscitation: A Systematic Qualitative Review of the Literature

Background: The brain is vulnerable to injury and dysfunction during transition after birth in neonates. Clinical assessment of the neurological status immediately following birth is difficult, especially during resuscitation. Objective: Our aim was to review physiological monitoring of the brain during immediate postnatal transition - the first 15 min after birth. Methods: A systematic search of PubMed and EMBASE was performed using the following terms: newborn, neonate, neonates, transition, after-birth, delivery room, cerebral, brain, monitoring, neurology, oxygenation, saturation, activity, imaging, perfusion, Doppler, and blood flow. Additional articles were identified by manual search of cited references. Only human studies describing cerebral changes during the first 15 min after birth were included. Results: Six studies were identified, which described sequential measurements of cerebral perfusion using Doppler sonography, one of these in combination with continuous monitoring of cerebral tissue oxygenation with near-infrared spectroscopy (NIRS). A further 15 studies were identified that used NIRS to continuously monitor cerebral tissue oxygenation. In one study, cerebral activity was continuously monitored with an additional amplitude-integrated encephalogram. Conclusion: Monitoring the brain provides additional information during immediate transition and may help to guide resuscitation. Doppler sonography is technically challenging during resuscitation and is therefore of limited value. NIRS provides continuous monitoring and is feasible even in very-low-birth-weight infants. In the future, an amplitude-integrated encephalogram might give further information on the status of the brain, but before any of these modalities can routinely be recommended during neonatal resuscitation, clinical trials targeting stable brain function parameters are needed.

Cerebral and Peripheral Regional Oxygen Saturation during Postnatal Transition in Preterm Neonates

OBJECTIVE To evaluate peripheral regional oxygen saturation (rpSO₂) and cerebral regional oxygen saturation (rcSO₂) during the immediate postnatal transition in late preterm infants with and without the need for respiratory support. STUDY DESIGN This was a prospective observational study using near-infrared spectroscopy to evaluate changes in rpSO₂ and rcSO₂. These variables were measured during the first 15 minutes of life after elective cesarean delivery. Peripheral oxygen saturation (SpO₂) and heart rate were measured continuously by pulse oximetry, and cerebral fractional tissue oxygen extraction (cFTOE) was calculated. Two groups were compared based on their need for respiratory support: a respiratory support group and a normal transition group. Positive-pressure ventilation was delivered with a T-piece resuscitator, and oxygen was adjusted based on SpO₂ values. A Florian respiratory function monitor was used to record the ventilation variables. RESULTS There were 21 infants in the normal transition group and 21 infants in the respiratory support group. Changes in heart rate over time were similar in the 2 groups. SpO₂, rcSO₂, and rpSO₂ values were consistently higher in the normal transition group. In the respiratory support group, cFTOE values remained significantly elevated for a longer period. CONCLUSION This systematic analysis of rpSO₂, rcSO₂, and cFTOE in late preterm infants found significantly lower oxygen saturation values in infants who received respiratory support compared with a normal transition group. We hypothesize that the elevated cFTOE values in the respiratory support group represent compensation for lower oxygen delivery.

Recommendations to Increase the Validity and Comparability of Peripheral Measurements by Near Infrared Spectroscopy in Neonates 'Round Table', Section of Haematology, Oxygen Transport and Microcirculation, 48th Annual Meeting of ESPR, Prague 2007

Several studies of peripheral measurements with near infrared spectroscopy (NIRS) and venous or arterial occlusion have been performed in neonates. Results have been variable. Reasons include differences in patient populations, technical aspects of the devices used or the way measurements were made. It is therefore important that there should be common elements for measurement protocols. This statement proposes a standardised approach to allow comparison between different study populations and devices.