Michael Weindling

Use of Tissue Oxygenation Index and Fractional Tissue Oxygen Extraction as Non-Invasive Parameters for Cerebral Oxygenation

Objective: To evaluate the relation between cerebral tissue oxygenation index (TOI), measured with spatially resolved spectroscopy (SRS), and the different oxygenation parameters. To evaluate the relation between a new parameter named fractional tissue oxygen extraction (FTOE) and the cerebral fractional oxygen extraction (FOE). Methods: Six newborn piglets were measured at 33, 35, and 37°C and in hypocapnia. Mean arterial blood pressure (MABP), haemoglobin (Hb), peripheral oxygen saturation (S_aO₂) and P_aCO₂ were measured at each step. Cerebral blood flow (CBF) was measured by injection of coloured microspheres into the left atrium. Jugular bulb oxygen saturation (JVS), cerebral arterial and venous oxygen content (C_aO₂ and C_vO₂) and FOE were calculated. TOI of the brain was calculated and FTOE was introduced as (S_aO₂ – TOI)/S_aO₂. The correlation was calculated with an ANCOVA test. Results: There was a positive correlation (R = 0.4 and p = 0.011) between TOI and JVS. No correlation was found with CBF, MABP or Hb. There was a positive correlation between P_aCO₂ and cerebral TOI (R = 0.24 and p = 0.03). FTOE correlated well with FOE (R = 0.4 and p = 0.016) and there was a negative correlation between FTOE and P_aCO₂ (R = 0.24, p = 0.03). Conclusion: The measurement of TOI and FTOE by SRS correlated well with the cerebral venous saturation and FOE, respectively.

Peripheral haemodynamics in newborns: Best practice guidelines

Peripheral haemodynamics refers to blood flow, which determines oxygen and nutrient delivery to the tissues. Peripheral blood flow is affected by vascular resistance and blood pressure, which in turn varies with cardiac function. Arterial oxygen content depends on the blood haemoglobin concentration (Hb) and arterial pO2; tissue oxygen delivery depends on the position of the oxygen-dissociation curve, which is determined by temperature and the amount of adult or fetal haemoglobin. Methods available to study tissue perfusion include near-infrared spectroscopy, Doppler flowmetry, orthogonal polarisation spectral imaging and the peripheral perfusion index. Cardiac function, blood gases, Hb, and peripheral temperature all affect blood flow and oxygen extraction. Blood pressure appears to be less important. Other factors likely to play a role are the administration of vasoactive medications and ventilation strategies, which affect blood gases and cardiac output by changing the intrathoracic pressure.

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.

Periventricular haemorrhage and periventricular leukomalacia

Periventricular haemorrhage (PVH) and cystic periventricular leukomalacia (PVL) are two conditions which are associated but different. They are important because both indicate serious brain injury and both conditions occur in fetuses of less than 32 weeks of gestation. They may, however, occur together or separately. PVH is characterised by bleeding into and sometimes around the cerebral ventricles ; it is benign unless the haemorrhage involves the surrounding brain parenchyma. PVL is a disorder characterised by the appearance of cysts around the ventricles. Cystic PVL and PVH which involves the parenchyma indicate cerebral white matter injury and are strongly associated with the later development of neurological impairment, particularly cerebral palsy (Weindling et al. 1985a; Volpe 1989; Levene 1990; Gaffney et al. 1994). PVL and severe forms of PVH occur in brains which have been subjected to a disturbed blood supply. The developing brain is vulnerable to ischaemia for two reasons: first, because so much of the cardiac output, probably around 70%, goes to the brain; and secondly, because of the arrangement of its cerebrovasculature. A reduction in cardiac output or hypotension is likely to affect the perfusion of vulnerable areas of the brain. The effects of hypoxia and ischaemia on the developing human brain depend on its state of development, which is closely related to gestational age. Hence, an understanding of the developing cerebrovascular anatomy is helpful in appreciating the difference between PVH and PVL. Knowledge of cerebrovascular anatomy and organisation owes a great deal to the work of Pape and Wigglesworth (1979). Neuroblasts, which will eventually form the cerebral cortex, originate in the germinal matrix. Cells migrate from the subependymal region to the cortex from the second until the fifth month of gestation, guided by complex glial and neuronal interactions, with each successive wave of migrating cells taking up a more superficial position. By 28 weeks, migration to the cortex has virtually stopped.

Insights into early brain development from modern brain imaging and outcome studies

Recent brain imaging and outcome studies of infants born at very early gestation have cast new light on brain development at a vulnerable stage. Some of these new developments are reviewed in this editorial.

Comparison of cerebral tissue oxygenation values in full term and preterm newborns by the simultaneous use of two near-infrared spectroscopy devices: an absolute and a relative trending oximeter

Abstract. The aim of this study is to compare a two-wavelength light emitting diode–based tissue oximeter (INVOS), which is designed to show trends in tissue oxygenation, with a four-wavelength laser–based oximeter (FORE-SIGHT), designed to deliver absolute values of tissue oxygenation. Simultaneous values of cerebral tissue oxygenation (StO2) are measured using both devices in 15 term and 15 preterm clinically stable newborns on the first and third day of life. Values are recorded simultaneously in two periods between which oximeter sensor positions are switched to the contralateral side. Agreement between StO2 values before and after the change of sensor position is analyzed. We find that mean cerebral StO2 values are similar between devices for term and preterm babies, but INVOS shows StO2 values spread over a wider range, with wider standard deviations than shown by the FORE-SIGHT. There is relatively good agreement with a bias up to 3.5% and limits of agreement up to 11.8%. Measurements from each side of the forehead show better repeatability for the FORE-SIGHT monitor. We conclude that performance of the two devices is probably acceptable for clinical purposes. Both performed sufficiently well, but the use of FORE-SIGHT may be associated with tighter range and better repeatability of data.

Magnetic resonance imaging (MRI) in obstetrics. II. Fetal anatomy

Dear Sir, The paper by Powell et al. [Br J Obstet Cynaecol (1988) 95,3&46] sets out well the potential and limitations of conventional magnetic resonance imaging (MRI) in obstetrics with respect to fetal anatomy. We agree with the authors’ conclusion that the future mode of choice is likely to be based on the echo planar technique. This does, however, require specialist equipment and is not easily implemented on the current generation of MR equipment. We find there is greater potential and fewer limitations in the use of the fast-scan (or gradient echo) technique. We use a General Electric 1.5 T Signa System within the guidelines laid down by the National Radiological Protection Board (1983). By using short TR (repetition time) a single image can be obtained in 3-Y s . This allows a series of images in one axis to be obtained in 3C90 s, and images in all three axes in approximately 1.5-4.5 min. Sukequent diagnostic images from a specific region can then be obtained in a further 5 min.

Gross motor functional abilities and periventricular leukomalacia

Van Haastart and colleagues have explored the link between disturbed motor function and periventricular leukomalacia (PVL), diagnosed during the period just after birth in a group of very preterm babies. The children were examined at four time points: at an average age of 9 months, 16 months, 24 months, and 7 years (although the age range at this last time point was extraordinarily wide, ranging between just over 2 years and 16 years). The striking finding was that there was a very strong association between the early diagnosis of PVL and later gross motor outcome. Although the relationship between different PVL grades in preterm infants and subsequent gross motor function classified using the Gross Motor Function ClassificationSystem (GMFCS) has notpreviously been reported, the link between PVL and cerebral palsy (CP) is not novel.Unsurprisingly, thechildrenwiththeworstgradeofPVLgenerallyhad theworstoutcome. The issue which troubles clinicians is what to do with the information. Their difficulty is that the association is not invariable. As the authors point out, only infants with PVL who subsequently developed CP were eligible for the study and several studies have shown that between 4 and 10% of infants with a cranial ultrasound diagnosis of grade I PVL will go on to develop CP. Furthermore, magnetic resonance imaging studies have shown that a major problem for these children is diffuse white matter injury (WMI), which is associated with cognitive impairment. Van Haastart and colleaguessuggest that theirfindingshave implications forcounselling and intervention. But the difficulty is that, while there is a strong association between grade of PVL and outcome, there are individuals who differ from the general rule. For example, two children (2 ⁄26) with the severest grade of PVL had the mildest outcome as assessed by the GMFCS. So how should parents be counselled?And what sortof interventionsareavailable? Clinicians need to advise parents reliably and treat children to optimize outcome. But most children with diffuse WMI show no physical abnormality until they are several months old and learning difficulties sometimes only become apparent after several years. The problem is that intervention in the absence of physical signs has not been shown to have any effect on motor outcome. One approach is to advise parents about the uncertainty of outcome, advise themaboutwhat to lookout for,andexplain thatallpossible support will be given to them if their child does develop signs of impairment.Theadvice isoften to ‘travelhopefully’. As with all good pieces of research, this work by van Haastart and colleagues raises further questions. What effect does this wellmeant information have for parents, are there interventions to improve outcome in the light of the diagnosis of diffuse WMI, and, most importantly, canWMIbeprevented?

Nose bleeds, child protection and the difficulties faced by paediatricians

Whereas nosebleeds in older children are relatively common and usually benign, nosebleeds in young babies are very uncommon. The estimated incidence is 0.94 per 10 000 of children <2-year-old (1). In the older child, epistaxis usually occurs from the anterior portion of the nasal septum (Little’s area), which has a rich blood supply. Sometimes it is caused by nose-picking (rhinotillexis), sometimes it occurs because the atmosphere is dry and sometimes spontaneous bleeding affects the young male adolescent because of the relatively rapid growth of the mid-face during puberty. The situation for the infant is quite different. When a young baby bleeds from the nose, or is reported to have had a nosebleed, the event raises the strong possibility in the minds of some experts in child abuse that it may have occurred because of attempted suffocation. The situation is put succinctly by Edmund Hey in this issue (2): ‘Simple nose bleeds are rare in the first year of life, and nose bleeds that cannot be explained as due to accidental trauma, and are not the first manifestation of some overt haemostatic disorder, even rarer’. The context of Hey’s helpful review is worth summarising for the benefit of readers who are not familiar with what has been happening in the field of child protection in the United Kingdom (UK). The UK body that regulates doctors is the General Medical Council (GMC), which was established by Act of Parliament in 1858. It registers (licenses) doctors to practise medicine in the United Kingdom. Its stated purpose is, inter alia, to protect the safety of the public by ensuring proper standards in the practice of medicine. (The GMC also ensures the quality of undergraduate medical education.) If a member of the public complains about a doctor, the GMC is obliged to review and investigate all complaints. In practice, this has meant that parents who are considered to have harmed their

OPIATES AND INTERMEDIARY METABOLISM IN VENTILATED PRETERM BABIES

There are few data which indicate benefit from the use of opiates during mechanical ventilation in preterm babies. We have investigated the effect of sedative doses of alfentanil on intermediary metabolism.Ventilated preterm babies were randomised to receive alfentanil (20 ug/kg bolus & 5 ug/kg/hr) or placebo as a pilot study. Samples were taken pre-dose, 1 hour post-dose and twice daily during infusion. No other change in routine management occurred during the trial. Median birthweight of the study group was 1300g (r:726-2352g), gestation: 29 weeks (26-36 weeks).Twelve babies received alfentanil from a median age of 16 hours (r: 12-36) after birth and 12 babies a placebo infusion from 24 hours (r:10-32). No differences in heart rate, blood pressure or pH were seen between the study groups and similar rates of perinatal complications were seen in each group.During the administration of alfentanil, glucose rose by 2.02 mmol/l (sem: 1.67) compared to a fall of 0.87 mmol/l (2.94) in the placebo group 1 hour post-dose, and remained on average 1.27 (1.71) mmol/l higher than baseline over the next 24 hours, compared to 2.64 (1.78) mmol/l less among controls. Similar rises in lactate, pyruvate, glycerol were observed in the alfentanil group which persisted over the next 24 hours, in contrast to the anticipated falt. There were no differences in urinary catecholamine excretion.These data suggest that sedative doses of alfentanil may have no immediate metabolic benefit.