Tom Stiris

Inhaled nitric oxide therapy in neonates and children: reaching a European consensus

Inhaled nitric oxide (iNO) was first used in neonatal practice in 1992 and has subsequently been used extensively in the management of neonates and children with cardiorespiratory failure. This paper assesses evidence for the use of iNO in this population as presented to a consensus meeting jointly organised by the European Society of Paediatric and Neonatal Intensive Care, the European Society of Paediatric Research and the European Society of Neonatology. Consensus Guidelines on the Use of iNO in Neonates and Children were produced following discussion of the evidence at the consensus meeting.

Effect of the cyclo-oxygenase blocker ibuprofen on cerebral blood volume and cerebral blood flow during normocarbia and hypercarbia in newborn piglets.

Indomethacin modifies baseline cerebral haemodynamics and metabolism, as well as vasomotor adaptive responses. However, the significance of arachidonic acid metabolites in the regulation of cerebral circulation remains unclear. A study was made of the effect of inhibition of the cyclo‐oxygenase pathway on baseline cerebral haemodynamics and CO2‐induced vasodilation using the more specific cyclo‐oxygenase blocker ibuprofen in a neonatal pig model. Two methods were used: radiolabelled microspheres to measure cerebral blood flow and near infrared spectroscopy to calculate absolute changes in cerebral blood volume. The relationship between CO2‐induced changes in these two haemodynamic parameters was evaluated. Fifteen newborn piglets <7 d old received an i.v. infusion of either ibuprofen (30 mg/kg) (IB group, n= 8) or saline (control group, n= 7). Cerebral blood flow and absolute changes in cerebral blood volume were measured while the piglets were breathing room air at baseline and 30 min after infusion of ibuprofen or saline, and 15 min and 30 min after inducing hypercarbia. Global and regional cerebral blood flow (ml/hg/min) and absolute changes in cerebral blood volume (ml/hg) did not vary between baseline and 30 min after infusion of ibuprofen or saline. During hypercarbia, global and regional cerebral blood flow and absolute changes in cerebral blood volume increased significantly in both the ibuprofen and control groups (p < 0.01). The mean percentage increases in blood flow and blood volume at each measurement were almost identical, with approximately 90% of the increase in both parameters occurring after 15 min of hypercarbia, then reaching a plateau. However, we found no agreement between cerebral blood flow changes and absolute changes in cerebral blood volume. We conclude that ibuprofen did not alter either baseline cerebral circulation or physiological CO2‐induced vasodilation in newborn pigs. We speculate that hypercarbic cerebral vasodilation could be caused either by mediators other than the cyclo‐oxygenase metabolites of arachidonic acid or by a direct effect on vessel walls.

The Effect of Arterial Pco2-Variations on Ocular and Cerebral Blood Flow in the Newborn Piglet

ABSTRACT: The response of ocular and cerebral blood flow to different arterial Pco2 levels was studied in ventilated paralyzed newborn piglets with the radionuclidelabeled microsphere method. The retina and the choroid have different blood flow responses to variations in arterial Pco2 levels. Retinal blood flow (ml/g/min) was increased during hypercarbia, from 0.26 ± 0.03 at baseline to 0.51 ± 0.07 (Paco2 8.7 ± 0.2 kPa) and 0.62 ± 0.07 (Paco2 11.0 ± 0.2 kPa). However, no significant change was found in choroidal blood flow during hypercarbia. Cerebral blood flow was more responsive to Paco2 than retinal blood flow, increasing from 0.71 ± 0.03 at baseline to 2.25 ± 0.25 (Paco2 8.7 ± 0.2) and 1.77 ± 0.13 (Paco2 11.0 ± 0.2). Hypocarbia did not influence either retinal or choroidal blood flow.

Automated spectral EEG analyses of premature infants during the first three days of life correlated with developmental outcomes at 24 months.

Background: Spectral EEG analysis using automated quantification of total absolute band power (tABP) for long-term brain monitoring is reliable. We hypothesised that tABP during the first critical days of life could be a useful tool for predicting later developmental outcomes. Objective: To determine whether measuring EEG background activity in premature infants with automated tABP quantification during the first 3 days of life correlated with their developmental outcomes at 24 months. Methods: Preterm infants (group 1, gestational age, GA 24–28 weeks and group 2, GA 28–31 weeks) were continuously monitored by EEG for 3 days after birth. Their developmental outcomes were assessed using the Bayley-II and Peabody-2 developmental tests at 24 months. Their respective indices were calculated. Normal (index ≥85) and abnormal (index <85) outcomes were correlated with the tABP. Results: In group 1, the tABP was significantly lower in the abnormal infants than in the normal infants. The specificity and negative predictive value were also high for all of the tests that were applied in this group. In group 2, there was no correlation between the tABP and developmental outcome. Conclusion: This study found that extremely premature infants with poor developmental outcomes had significantly lower tABP values in their first days of life compared to infants from the same group with normal outcomes. This method may be useful in predicting later outcomes in extremely premature infants and has the advantage of being automated.

Effect of dexamethasone therapy on cerebral and ocular blood flow velocity in premature infants studied by colour Doppler flow imaging

Abstract Although dexamethasone (DEX) is used widely in neonates with chronic, and even recently with acute respiratory disease, its potential side-effects on human cerebral and ocular haemodynamics remain unknown. The effects of DEX on cerebral and ocular blood flow velocities were assessed in preterm infants with lung disease and mechanical ventilation. Ten ventilated preterm infants received DEX (0.25 mg/kg/12 h) for ongoing chronic lung disease or extubation failure. Colour Doppler flow imaging studies of the internal carotid, anterior cerebral and ophthalmic arteries were made before and 10, 30, 60, 120 and 240 min after the 1st, 3rd, and 5th doses of DEX. Peak systolic, temporal mean, and end-diastolic flow velocities and the resistence index (RI) of Pourcelot were determined. The brain was examined by ultrasonography before and at the end of each Doppler study. All patients were continuously monitored for transcutaneous blood gases and blood pressure. All flow velocities and the RI of the internal carotid, anterior cerebral and ophthalmic arteries showed a similar trend throughout the study. The means of the values averaged for the 240 min of cerebral and ocular blood flow velocity with each dose were progressively higher and the values of the RI progressively lower up to the 5th dose. The most significant changes occurred in end-diastolic flow velocity and consisted of a percentage increase between the 1st and 5th dose of 72% in the internal carotid artery, 102% in the anterior cerebral artery and 84% in the ophthalmic artery. Changes in arterial blood pressure followed a pattern similar to that of changes in blood flow velocity. Conclusions Dexamethasone increments cerebral and ocular blood flow velocity. We speculate that this finding may be relevant to the development of brain and retinal injury.

Cerebral Blood Flow during Experimental Hypoxaemia and lschaemia in the Newborn Piglet

Odden, J.‐P., Stiris, T., Hansen, T. W. R. and Bratlid, D. (Neonatal Research Laboratory, Department of Paediatric Research, Institute for Surgical Research and Department of Paediatrics, Rikshospitalet, University of Oslo, Oslo, Norway). Cerebral blood flow during experimental hypoxaemia and ischaemia in the newborn piglet. Acta Paediatr Scand Suppl 360: 13, 1989.

Feasibility of Long-Term Continuous EEG Monitoring During the First Days of Life in Preterm Infants: An Automated Quantification of the EEG Activity

Long-term EEG monitoring (LTM) with several electrodes could be a useful tool for surveillance of the brain during the first critical days of life. This study aimed to assess the feasibility of multichannel LTM for automated analysis of EEG activity from d 1 to 3 using eight electrodes. Premature infants (GA <31 wk; n = 48) were continuously monitored for 3 d. EEG monitoring for a total of 3257 h was successfully performed. Total absolute band power (tABP) was calculated per second. Artifacts were removed visually or by an algorithm removing the highest 5, 10, 15, and 20% tABPs. NS difference was found between the trends of visually edited and 5% mathematically trimmed data. Two groups were compared (24 ≤ GA < 28 wk and 28 ≤ GA < 31 wk) using the median of tABP for all frequency bands per day. The results showed that tABP differed between groups. The changes of tABP d 1–3 were equal in both groups. Automatically assessed LTM confirms that the EEG activity depends on GA. However, it reveals that the early changes (d 1–3) are independent of GA. The study demonstrates the feasibility of multichannel LTM and the possibility of developing automated EEG analyses.

Cerebral haemodynamics in preterm infants after exposure to dexamethasone

AIM To determine changes in brain haemodynamics produced by dexamethasone; to evaluate the pathophysiological conditions involved in the effect of dexamethasone. METHODS A prospective study was made of 12 ventilated preterm infants who received dexamethasone (0.25 mg/kg/12 hours) for ongoing chronic lung disease or extubation failure. Cerebral blood flow (CBF), absolute cerebral blood volume (CBV), and cerebral blood volume changes (ΔCBV) were estimated by near infrared spectroscopy, before and 10, 30, 60, 120, 180 and 240 minutes after the first, third, and fifth doses of dexamethasone. All patients were monitored continuously using pulse oximetry, transcutaneous blood gases, and blood pressure. RESULTS There were significant short term changes in ΔCBV on each day of the study; ΔCBV increased significantly at 240 minutes compared with values before the first dose, and from 120 minutes onward during the third and fifth doses. However, mean CBV values averaged over 240 minutes after the first, third, and fifth doses did not vary. Mean CBF values averaged over 240 minutes increased progressively up to the fifth dose (significant differences between the first and fifth dose). The short term changes in CBF consisted of a significant increase 60 minutes after dexamethasone administration compared with the before and 10 minute values in every study. Blood pressure was significantly higher in the third and fifth doses than in the first dose. Blood pressure showed no short term changes. There was no correlation between CBF and blood pressure changes. TcPCO2 (transcutaneous PCO2) decreased significantly throughout the study period, with the average mean value in the fifth dose significantly lower than in the first dose. Nevertheless, no short term changes in TcPCO2were observed. CONCLUSIONS Postnatal systemic dexamethasone administration produced significant changes in cerebral haemodynamics that seemed to be related to both a direct effect on regional vessel walls and the cumulative effect of dexamethasone.

Hypothermia makes cerebral resistance index a poor prognostic tool in encephalopathic newborns.

Background: Severe neonatal encephalopathy (NE) of hypoxic-ischaemic origin may cause death or life-long disability. Acute encephalopathy may also affect cerebrovascular control. Pourcelots cerebrovascular resistance index (RI) ≤0.55 was predictive of poor outcome in normothermic NE infants. Recent studies have questioned its predictive power during therapeutic hypothermia (HT). Objective: To assess the predictive power of RI during HT and after rewarming. Methods: 45 infants with NE treated with HT for 72 h had their RI calculated during early (median 11 h) and late (median 62 h) cooling and after rewarming (median 89 h). Poor outcome was defined as death or abnormalities on day 10 magnetic resonance imaging shown to predict severe neuromotor disability. Results: RI ≤0.55 during cooling did not differentiate between good and poor outcome (late cooling, p = 0.08), but was powerful after rewarming (p = 0.004). RI ≤0.55 predicted true poor outcome in 43% (95% confidence interval (CI): 12, 80) during late cooling and in 100% (95% CI: 31, 100) after rewarming. RI >0.55 predicted good outcome in 86% (95% CI: 69, 95) during late cooling and in 89% (95% CI: 74, 96) after rewarming. Conclusions: Low RI is not predictive of poor outcome during HT in NE infants, but regains the predictive power seen in normothermic infants after rewarming.

Human papillomavirus vaccination crisis in Japan.

The European Academy of Paediatrics (EAP) is gravely concerned about the human papillomavirus (HPV) vaccination crisis in Japan and particularly about the negative position taken by governmental authorities. Given that the HPV vaccine is both safe and effective, there is no recognizable reason to date to withhold this lifesaving and cost effective public health measure from a population. Therefore, the EAP strongly encourages the Japanese health authorities to actively support HPV vaccination for the future health of their children and adolescents.