Determinants of cerebral fractional oxygen extraction using near infrared spectroscopy in preterm neonates.

Cerebral fractional oxygen extraction (FOE) represents the balance between cerebral oxygen delivery and consumption. This study aimed to determine cerebral FOE in preterm infants during hypotension, during moderate anemia, and with changes in the PaCO2. Three groups of neonates were studied: stable control neonates (n = 43), anemic neonates (n = 46), and hypotensive neonates (n = 19). Cerebral FOE was calculated from the arterial oxygen saturation measured by pulse oximetry, and cerebral venous oxygen saturation was measured using near infrared spectroscopy with partial jugular venous occlusion. Mean +/- SD cerebral FOE was similar in control (0.292+/-0.06), anemic (0.310+/-0.08; P = 0.26), and hypotensive (0.278+/-0.06; P = 0.41) neonates. After anemic neonates were transfused, mean +/- SD cerebral FOE decreased to 0.274+/-0.05 (P = 0.02). There was a weak negative correlation with the hemoglobin concentration (n = 89, r = -0.24, P = 0.04) but not with the hemoglobin F fraction (n = 56, r = 0.24, P = 0.09). In the hypotensive neonates, there was no relationship between cerebral FOE and blood pressure (n = 19, r = 0.34, P = 0.15). There was a significant negative correlation between cerebral FOE and PaCO2 within individuals (n = 14, r = -0.63, P = 0.01), but there was no relationship between individuals (n = 14, r = 0, P = 1). Cerebral FOE was not significantly altered in neonates with either mild anemia or hypotension. There were, however, changes in cerebral FOE when physiological changes occurred over a relatively short period: Cerebral FOE decreased after blood transfusion and increased with decreasing PaCO2. As no change in cerebral FOE was seen during hypotension, it was speculated that cerebral oxygen delivery may have been maintained by cerebral blood flow autoregulation.

Peripheral fractional oxygen extraction and other measures of tissue oxygenation to guide blood transfusions in preterm infants.

The physiological effects of anemia in the preterm infant are complex and the indications for transfusions in preterm infants are controversial. A measure of the adequacy of tissue oxygenation may be a better guide to the need for transfusions than currently used criteria. This article considers 2 measures of tissue oxygenation of preterm infants: 1) The whole blood lactate concentration, and 2) Peripheral fractional oxygen extraction (FOE) by using near infrared spectroscopy. Several studies have shown falls in blood lactate concentration after blood transfusion, but it has been difficult to establish a convincing link between raised lactate concentrations and significant anemia because even anemic infants have lactate concentrations that are within or close to the normal range. Lactate concentrations may be affected by the haematocrit of the blood sample. Peripheral FOE can be measured by using near infrared spectroscopy with partial venous occlusion and has been studied in preterm infants with symptomatic and asymptomatic anaemia. Mean (SD) FOE was significantly higher in symptomatic [0.425 (0.06)] (P< .01) but not asymptomatic [0.334 (0.05)] compared to controls [0.352 (0.06)], (P = .22). After transfusion there was a significant fall in FOE in symptomatic infants to 0.367 (0.06) (P = .001) but there was no change in infants who were asymptomatic. FOE correlated with other measures known to reflect the adequacy of oxygen availability during anemia. These results suggest that peripheral FOE may be suitable as a guide to the need for blood transfusions. A pilot randomized controlled trial is currently being undertaken to test this hypothesis.

A pilot randomised controlled trial of peripheral fractional oxygen extraction to guide blood transfusions in preterm infants.

BACKGROUND: Peripheral fractional oxygen extraction (FOE) may be a better indicator of the need for transfusion than the haemoglobin concentration (Hb) because it is a measure of the adequacy of oxygen delivery to meet demand. A randomised controlled trial of the use of peripheral FOE to guide the need for blood transfusions in preterm infants was carried out to test this hypothesis. METHOD: Infants less than 1500 g birth weight who were stable and less than 2 weeks old were randomised to receive transfusions guided by either a conventional protocol based on Hb (conventional group) or a protocol based on measurements of peripheral FOE made by near infrared spectroscopy (NIRS group). Measurements of Hb and FOE were made on all infants from randomisation until discharge. The primary outcome measures were number of transfusions received, rate of weight gain, and postmenstrual age at discharge. RESULTS: Thirty seven infants were randomised to each group. Birth weight (median, range) (1200, 1004-1373 v 1136, 1009-1285 g) and Hb (median, range) at randomisation (160, 149-179 v 155, 145-181 g/l) did not differ between the two groups. The total number of transfusions given to the NIRS group was 56 and to the conventional group 84. The median number of transfusions per infant, the median volume of blood transfused to each group, and the total number of donors to which infants were exposed were similar in the two groups. Infants transfused according to the conventional protocol were more likely to be transfused earlier and at a higher Hb than those transfused in the NIRS group. Infants in the conventional group spent a significantly shorter period than those in the NIRS group with Hb < 100 g/l. Of the 56 transfusions given to the NIRS group, 33 (59%) were given because of clinical concerns rather than because of high FOE. There was no difference in the rate of weight gain, rate of linear growth, postmenstrual age at discharge, or the incidence of chronic lung disease or retinopathy of prematurity. CONCLUSIONS: FOE measurements failed to identify many infants felt by clinicians to require blood transfusion. This may have been because clinicians relied on conventional indicators of transfusion that are vague and non-specific, or a peripheral FOE of 0.47 alone may not be a sensitive enough predictor of the need for transfusion. This requires further study.

Effect of blood transfusion on lipid peroxidation in preterm infants.

OBJECTIVE: To see whether there was a link between blood transfusion and lipid peroxidation as measured by urinary malondialdehyde (MDA) concentration in preterm infants. METHODS: Urine samples were collected before and after blood transfusions in preterm infants. Twenty blood transfusion episodes were studied in 12 infants (some infants were studied on more than one occasion). Twenty two infants who had not received a transfusion were used as controls. All infants were preterm and less than 1500 g birth weight. Urinary MDA was measured using a thiobarbituric acid assay and expressed as nmol/mg creatinine. RESULTS: The median (interquartile range) urinary MDA concentration before transfusion was 9.1 (6.4-12.6) nmol/mg, and was not significantly different from that in the 22 non-transfused infants (11.3 (7.3-15.6) nmol/mg). There was a significant increase 24 hours after transfusion to 14.6 (7.3-23.7) nmol/mg, but it decreased to 10.1 (6.6-15.4) nmol/mg when measured a median (range) of 6 (3-9) days later. CONCLUSIONS: Blood transfusions were associated with evidence of increased lipid peroxidation. If lipid peroxidation contributes to the pathogenesis of retinopathy of prematurity and chronic lung disease, these results suggest an explanatory mechanism.

Randomised controlled trial of oral vitamin A supplementation in preterm infants to prevent chronic lung disease.

BACKGROUND: Intramuscular supplementation with vitamin A in large doses may reduce the incidence of chronic lung disease. AIM: To investigate whether oral supplementation with vitamin A would reduce the incidence of chronic lung disease in a group of extremely low birthweight infants. METHODS: Infants with birth weight < 1000 g were randomised at birth to receive oral vitamin A supplementation (5000 IU/day) or placebo for 28 days. The primary outcome was oxygen dependency at 28 days of age or death. RESULTS: A total of 154 infants were randomised; 77 received vitamin A (median birth weight (interquartile range) 806 (710-890) g), and 77 received placebo (median birth weight (interquartile range) 782 (662-880) g). Plasma vitamin A concentrations in the supplemented group were significantly higher at 24 hours of age but did not differ significantly at birth, 12 hours of age, 7 days, or 28 days of life. There were no significant differences in the proportion of infants who survived, required oxygen at 28 days, required oxygen at 36 weeks postmenstrual age, survived without chronic lung disease at 36 weeks, survived without significant retinopathy, or who survived without significant intraventricular haemorrhage. CONCLUSIONS: Oral supplementation with 5000 IU vitamin A in extremely low birthweight infants does not significantly alter the incidence of chronic lung disease. However, this dose may have been inadequate to achieve optimal serum retinol concentrations.

Percutaneous femoral arterial and venous catheterisation during neonatal intensive care.

BACKGROUND: Femoral vessel catheterisation is generally avoided in the neonatal period because of technical difficulties and the fear of complications. AIM: To review the use of femoral arterial and venous catheters inserted percutaneously on the neonatal intensive care unit. METHODS: Infants admitted to one of two regional neonatal intensive care units who underwent femoral vessel catheterisation were identified. Information collected included basic details, indication for insertion of catheter, type of catheter and insertion technique, duration of use, and any catheter related complications. RESULTS: Sixty five femoral catheters were inserted into 53 infants. The median gestational age was 29 weeks (range 23-40). Twenty three femoral arterial catheters (FACs) were inserted into 21 infants and remained in situ for a median of three days (range one to eight). Twelve (52%) FACs remained in place until no longer required, and four (17%) infants developed transient ischaemia of the distal limb. Forty two femoral venous catheters (FVCs) were inserted into 40 infants and remained in situ for a median of seven days (range 1-29). Twenty seven (64%) FVCs remained in place until no longer required, and eight (19%) catheters were removed because of catheter related bloodstream infection. CONCLUSIONS: FACs and FVCs are useful routes of vascular access in neonates when other sites are unavailable. Complications from femoral vessel catheterisation include transient lower limb ischaemia with FACs and catheter related bloodstream infection.

Increased survival and deteriorating developmental outcome in 23 to 25 week old gestation infants, 1990-4 compared with 1984-9.

AIMS: To assess whether changes in survival over time in infants of 23 to 25 weeks of gestational age were accompanied by changes in the incidence of disability in childhood during an 11 year period. METHODS: Obstetric and neonatal variables having the strongest association with both survival to discharge from a regional neonatal medical unit and neurodevelopmental disability in 192 infants of 23 to 25 weeks of gestation, born in 1984 to 1994, were studied as a group and in two cohorts (1984 to 1989 n = 96 and 1990 to 1994 n = 96). The data collected included CRIB (clinical risk index for babies) scores and cranial ultrasound scan findings. The children were followed up at outpatient clinics. RESULTS: Between 1984 and 1989 (cohort 1) and 1990 and 1994 (cohort 2) the rate of survival to discharge increased significantly from 27% to 42% and the rate of disability in survivors increased from 38% to 68%; most of this increase was in mild disability. The proportions of survivors with cerebral palsy did not alter significantly (21% vs 18%), but more survivors with blindness due to retinopathy of prematurity (4% vs 18%), myopia (4% vs 15%) and squints (8% vs 13%) contributed to the increased rate of disability. Clinically significant cranial ultrasound findings and a high CRIB score were strongly associated with death. A high CRIB score was most strongly associated with disability. CONCLUSIONS: The rise in disability with improved survival was not due to cerebral palsy; rather the main contributors were blindness due to retinopathy, myopia, and squint. The causes of these disabilities seem to be linked to high CRIB scores. A system of regular and skilled retinal examination and access to facilities for retinal ablation should be in place in all neonatal units which undertake the care of such extremely preterm infants.

Peripheral oxygenation in preterm infants.

When tissue oxygenation is impaired, compensatory mechanisms occur, including a redistribution of blood flow in order to maintain oxygen delivery to vital organs, resulting in a fall in peripheral blood flow. Monitoring peripheral oxygenation therefore has potential benefits as it may provide an early warning of changes in the state of tissue oxygenation. Clinical assessments of the state of peripheral perfusion are common, and several physiological measurements have been described or used which are able to monitor peripheral oxygenation. Some of the available methods and their clinical implications will be reviewed. Near infrared spectroscopy is a particularly promising technique that has only recently been used in the preterm neonate to quantify peripheral oxygenation. It may be of potential value in understanding pathophysiological changes that occur in certain situations and needs further assessment to determine whether it may be useful to guiding clinical interventions.

Isolated cerebral cortical tears in children: aetiology, characterisation and differentiation from non-accidental head injury.

A wide spectrum of intracranial injuries has been described as complicating difficult birth, particularly following instrumental delivery. We describe five children in whom isolated cortical tears were observed on MRI. Four cases were characterised by a difficult instrumental delivery. None of the children developed long-term neurological sequelae. As far as we are aware, isolated cerebral cortical tears have not been reported previously although recognition of this injury pattern is important because of its possible misinterpretation as a marker of a non-accidental head injury. Other differential diagnoses that should be considered include cerebral infarcts, schizencephaly and accidental head injury. The importance of high-quality cross-sectional brain imaging in newborn infants with seizures is emphasised.

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.

Peripheral oxygenation in hypotensive preterm babies.

Monitoring oxygenation in peripheral tissues of preterm babies may be useful in understanding the redistribution of blood flow during hypotension. Hemoglobin flow and venous saturation were measured in the forearm using near infrared spectroscopy with venous occlusion and were used to calculate fractional oxygen extraction, oxygen delivery, and oxygen consumption. Thirty ventilated preterm babies (median birth weight 976 g) were studied; 15 were hypotensive and 15 normotensive. Treatment for hypotension was dopamine alone (median dose 5 microg/kg/min) in eight cases, 4.5% human albumin solution (20 mL/kg) with dopamine in five cases, and only a blood transfusion (20 mL packed cells/kg) in two cases. There was a weak correlation between hemoglobin flow and mean arterial blood pressure (r = 0.40, p = 0.03). In hypotensive compared with normotensive babies, there was a significantly lower median hemoglobin flow (10.2 versus 20.2 micromol/100 mL/min, p = 0.0006), forearm oxygen delivery (37.8 versus 75.2 micromol/100 mL/min, p = 0.0008), and oxygen consumption (11.0 versus 23.9 micromol/100 mL/min, p = 0.006), but the fractional oxygen extraction (0.327 versus 0.306, p = 0.48) and the blood lactate concentration (1.22 versus 1.20 mmol/L, p = 0.44) were similar. Following treatment of hypotension, oxygen delivery (p = 0.02) and oxygen consumption (p = 0.04) increased to 64.2 and 21.7 micromol/100 mL/min, respectively, but fractional oxygen extraction (p = 0.81) and blood lactate concentration (p = 0.94) after treatment were unchanged. VO2 was variable in the forearm of human infants. It reduced when DO2 was low, and there was no evidence of tissue injury or switch to anaerobic metabolism. Measurements of peripheral tissue oxygenation seem to be of some value in understanding the pathophysiologic changes that occur with hypotension.

Cerebral oxygenation during cardiopulmonary bypass.

Cerebral fractional oxygen extraction (FOE) was monitored in 30 children, using near infrared spectroscopy during cardiopulmonary bypass, to investigate the effect of hypothermia and circulatory arrest. One group of children (n = 15) underwent profound hypothermia with total circulatory arrest (n = 8) or continuous flow (n = 7). Another group (n = 15), of whom only one had circulatory arrest, underwent mild (n = 6) or moderate (n = 9) hypothermia. The mean FOE (SD) before bypass was 0.35 (0.12) and this correlated negatively with the preoperative arterial oxygen content (r = -0.58). Between the stage of cooling on bypass and cold bypass there was a reduction in FOE in all groups. Between cold bypass and rewarming there was an increase in FOE only in the groups with continuous flow. In the circulatory arrest group, the FOE remained low during rewarming and was significantly lower than that of the continuous flow group. No patients died and none had neurological abnormalities postoperatively. Apparent changes in oxidised cytochrome oxidase concentration were also monitored using near infrared spectroscopy. There was a fall in cytochrome aa3 on starting cardiopulmonary bypass, but there were no significant differences in the changes in cytochrome aa3 between any stage in any of the patient groups. Using this non-invasive technique, cooling was shown to reduce cerebral FOE. During rewarming on bypass there was an increase in cerebral FOE only in patients who had had continuous flow bypass. In contrast, the cerebral FOE in those with circulatory arrest remained constant after arrest and during the duration of the study. This may have implications for the timing of hypoxic brain injury.

Peripheral oxygenation and anemia in preterm babies.

A measurement of tissue oxygenation may be a better marker of transfusion need than the Hb concentration. Peripheral fractional oxygen extraction, oxygen consumption, and oxygen delivery were measured noninvasively using near infrared spectroscopy in babies, some of whom were given blood transfusions. The above indicators of oxygenation were measured in 96 preterm babies. The decision to transfuse was based on a standard protocol. Transfusions were not considered necessary for babies in group 1 but were given to those in groups 2 (asymptomatic) and 3 (symptoms attributed to anemia). Hb and Hb fraction F (HbF) were measured in each baby. Oxygenation, Hb, and HbF measurements were made again 12-24 h after transfusion, and red cell volume (RCV) was calculated. Fractional oxygen extraction was significantly higher in symptomatic (0.43 +/- 0.06) but not asymptomatic (0.33 +/- 0.05) babies compared with control subjects (0.35 +/- 0.06). Oxygen consumption and oxygen delivery were similar in the three groups before transfusion. After transfusion the mean fractional oxygen extraction fell significantly in symptomatic but not in asymptomatic babies. There was no significant change in either oxygen consumption or oxygen delivery in symptomatic babies. The asymptomatic group had no change in oxygen extraction or oxygen consumption after transfusion, although oxygen delivery increased significantly. Fractional oxygen extraction correlated with HbF (n = 66, r = 0.49, p < 0.001) and RCV (n = 19, r = -0.48, p = 0.04) and there was a weak correlation with Hb (n = 94, r = -0.21, p = 0.04). Peripheral fractional oxygen extraction monitored noninvasively correlated with variables known to determine oxygen availability to the tissues, namely RCV and HbF, and was higher in babies with symptomatic anemia and decreased after transfusion.