Early red cell transfusion favourably alters cerebral oxygen extraction in very preterm newborns.

BACKGROUND: Elevated cerebral fractional tissue oxygen extraction (cFTOE; ≥0.4) predicts early brain injury in very preterm infants. While blood transfusion increases oxygen-carrying capacity, its ability to improve cerebral oxygen kinetics in the immediate newborn period remains unknown. OBJECTIVE: To investigate the effect of red blood cell (RBC) transfusion in the first 24 h of life on cFTOE in infants ≤29 weeks gestation. METHODS: cFTOE was calculated from cerebral tissue oxygenation index (TOI) and cutaneous oximetry measured over a 30 min epoch before and after transfusion. Infants were dichotomised according to pre-transfusion cFTOE (low <0.4 vs high ≥0.4). RESULTS: 24 babies were included, 12 in each group. Pre- and post-transfusion Hb were similar between the groups. cFTOE significantly reduced after transfusion in the high but not low-extraction group (p<0.01). CONCLUSIONS: Early RBC transfusion favourably alters cerebral oxygen kinetics in infants with elevated cFTOE, showing potential for modification of the risk of hypoxic (brain) injury.

Haemoglobin transfusion threshold in very preterm newborns: a theoretical framework derived from prevailing oxygen physiology.

The overwhelming majority of very preterm newborns receive at least one transfusion during their in hospital stay. However, despite two recent randomised trials, the appropriate haemoglobin transfusion threshold in these high risk infants remains unclear. Typically, clinicians consider gestation, chronologic age and illness severity in order to determine the need for transfusion. There is, however, no simple way to balance these heterogeneous variables in order to arrive at a transfusion threshold without considering the prevailing oxygen physiology. This is particularly important during the transition to extra-uterine life, a time when the risk of brain injury is highest. We hypothesise that dysregulated cerebral oxygen handling, characterised by restricted oxygen consumption from suboptimal oxygen delivery increases the risk of hypoxic ischaemic brain injury in very preterm newborns and is the single common patho-physiologic process underlying early acquired brain injury in the preterm newborn. Our proposed framework, based on the physiology of oxygen handling, considers the prevailing oxygen kinetics in the very preterm newborn as a means of deriving the appropriate Hb transfusion threshold thereby balancing oxygen delivery and consumption and avoiding hypoxic ischaemic early brain injury. Manipulation of the oxygen delivery equation, with consideration of the likely chronologic changes to cardiac output in particular, permit derivation of a transfusion threshold in the first week of life and represents a novel therapeutic intervention aimed solely at prevention of early acquired brain injury and its associated long term neuro-developmental burden.

The cerebral critical oxygen threshold of ventilated preterm lambs and the influence of antenatal inflammation.

Perinatal inflammation is associated with adverse neurodevelopmental outcomes, which may be partly due to changes in the cerebral oxygen delivery/consumption relationship. We aimed to determine the critical oxygen delivery threshold of the brain of preterm, ventilated lambs and to determine whether the critical threshold is affected by exposure to inflammation in utero. Pregnant ewes received intra-amniotic injection of lipopolysaccharide or saline at 125 or 127 days of gestation. Pulmonary and systemic flow probes and catheters were surgically positioned in the fetus immediately before delivery at 129 days of gestation. After delivery, lambs were ventilated for 90 min using a positive end-expiratory pressure recruitment strategy. Cardio-respiratory variables and blood gases were measured regularly. Systemic and cerebral oxygen delivery, consumption (Fick), and extraction were calculated, and the relationship between cerebral delivery and consumption analyzed. Linear regression was used to define the transition or "critical" oxygen threshold as the point at which the slope of the oxygen delivery/consumption curve changed to be > 10°. Four subgroups were defined according to the calculated critical threshold. A total of 150 measurements were recorded in 18 lambs. Fetal cerebral oxygen consumption was increased by antenatal lipopolysaccharide (P < 0.05). The postnatal critical oxygen threshold was 3.6 ml·kg⁻¹·min⁻¹, corresponding to cerebral oxygen consumption of 0.73 ml·kg⁻¹·min⁻¹. High oxygen delivery and consumption were associated with increased pulmonary and carotid blood flow and systemic extraction compared with low oxygen delivery and consumption. No postnatal effect of antenatal inflammation was observed. Inflammation in utero increases fetal, but not postnatal, cerebral oxygen consumption. Adverse alterations to pulmonary blood flow can result in reduced cerebral blood flow, oxygen delivery, and consumption. Regardless of exposure to inflammation, there is a consistent postnatal relationship between cerebral oxygen delivery and consumption.

Pharyngeal pressure with high-flow nasal cannulae in premature infants.

OBJECTIVE: The aim of this study was to measure pharyngeal pressures in preterm infants receiving high-flow nasal cannulae. STUDY DESIGN: A total of 18 infants were studied (median gestational age 34 weeks, weight 1.619 kg). A catheter-tip pressure transducer was introduced into the nasopharynx. Flow was sequentially increased to a maximum of 8 l min(-1) and decreased to a minimum of 2 l min(-1). RESULT: There was a strong association between pharyngeal pressure and both flow rate and infant weight (P<0.001, r (2)=0.61), but not mouth closure. This relationship could be expressed as pharyngeal pressure (cm H(2)O)=0.7+1.1 F (F=flow per kg in l min(-1) kg(-1)). CONCLUSION: High-flow nasal cannulae at flow rates of 2 to 8 l min(-1) can lead to clinically significant elevations in pharyngeal pressure in preterm infants. Flow rate and weight but not mouth closure are important determinants of the pressure transmitted.

Influenza in the neonatal intensive care unit.

Influenza has historically been an uncommon illness in the newborn period, although epidemic outbreaks in neonatal intensive care units have been described. There is currently significant concern about the possibility of a new pandemic of influenza in the near future. During a pandemic neonates are likely to be exposed, with significant illness more likely in pre-term newborns due to reduced levels of passively transferred protective maternal antibodies. While newer therapies have been shown to be effective in reducing the severity of illness in adults and children, such therapies are untried in neonates. Supportive care and measures to contain and prevent spread of infection may well be the most important measures in the event of a neonate acquiring influenza, including the avian variety.

Exhaled breath measures of inflammation: are they useful in neonatal chronic lung disease?

Neonatal chronic lung disease is a common problem for surviving infants of extreme prematurity. Although the precise pathophysiology is still not known, it is clear that inflammation provides a common link that amplifies the injury to the premature lung. Current invasive measures of pulmonary inflammation include markers in blood and airway effluent, with the cellular composition of tracheal fluid being the "gold standard". In this article available exhaled breath measures, particularly nitric oxide, carbon monoxide, volatile hydrocarbons, and exhaled breath condensate, are reviewed with particular reference to sample collection, analysis, and common pitfalls as they apply to the ventilated premature newborn at risk of chronic lung disease. Although they have great potential, all measures require thorough validation before being used clinically.

Peripheral retinal ablation for threshold retinopathy of prematurity in preterm infants.

BACKGROUND: This section is under preparation and will be included in the next issue. OBJECTIVES: In premature infants with threshold retinopathy of prematurity (ROP) does peripheral retinal ablation, by any means, reduce the incidence of adverse ophthalmic outcome? SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used. This included a search of the Cochrane Neonatal Group Register of Clinical Trials, MEDLINE, EMBASE, previous reviews including cross references, abstracts from pediatric and ophthalmologic meetings, letters and expert informants. Search terms included "Retinopathy of Prematurity" [MeSH Terms], "Retrolental Fibroplasia" [All Fields] and "Lightcoagulation" [All Fields] or "Cryosurgery" [All Fields]. In addition, a personal bibliographic database was used as a cross-reference. SELECTION CRITERIA: All trials in human premature infants with threshold ROP utilizing random or quasi random allocation to either peripheral retinal ablation of the avascular retina, by any means, or concurrent control group with independent outcome assessment were initially selected for review. Following methodologic review, only studies using random allocation were selected for data extraction. DATA COLLECTION AND ANALYSIS: Relevance and validity were assessed by the two authors and consensus reached. Each author extracted clinical outcomes from valid reports independently. Data analysis was conducted according to the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: Two randomised trials were identified. Data from these studies show that peripheral retinal ablation reduces the risk of (1) early unfavorable retinal structure from 47. 9% to 28.1% (absolute risk reduction 19.8% [95% CI 27.9 - 11.8%]), (2) unfavorable retinal structure in early childhood from 44.3% to 26.3% (absolute risk reduction 18% [95% CI 27.0 - 9.1%]) and (3) unfavorable visual acuity in early childhood from 63% to 50.6% (absolute risk reduction 12.2% [95% CI 21.2 - 3.1]). In addition, visual fields in sighted eyes were slightly smaller in the treated (51.3 degrees +/- 11.8 degrees ) group as compared to the control (58.2 degrees +/- 14.5 degrees ) group. REVIEWER'S CONCLUSIONS: Peripheral retinal ablation reduces the incidence of adverse ophthalmic outcome in premature infants with threshold ROP. In sighted eyes, peripheral retinal ablation may reduce the size of the visual field. At this stage, long term outcomes remain unknown.