Effects of oxygen and nitric oxide in oxygen on pulmonary arterial pressures of children with congenital cardiac defects.

Inhaled nitric oxide is a specific pulmonary vasodilator. This study was undertaken to assess the effect on pulmonary arterial pressure of administering 100% oxygen compared with nitric oxide in oxygen. Thirteen mechanically ventilated children undergoing routine cardiac catheterization for the investigation of congenital heart disease were studied. Pulmonary arterial pressures were measured during inhalation of 30% oxygen (baseline), 100% oxygen, and nitric oxide (40 parts per million) in oxygen. In addition, in six children the pulmonary/systemic blood flow ratio and pulmonary vascular resistance were calculated using oxygen content, an assumed value for oxygen uptake, and the Fick principle. Results were compared using analysis of variance and the Wilcoxon signed-rank test. Pulmonary arterial pressure decreased from a mean value of 29.5 mmHg (SD 15.1) to 25.6 mmHg (SD 9.3), p = 0.048, after increasing the inspired oxygen fraction from 0.3 to 1.0. The addition of nitric oxide caused a further reduction to 22.9 mmHg (SD 7.9), p = 0.0001. There was no change in systemic arterial pressure or heart rate during the study period, but a small increase occurred in the mean methemoglobin level (1.1% to 1.3%) p = 0.039. Changes in the pulmonary/systemic blood flow ratio and pulmonary vascular resistance (n = 6) were not significant. Nitric oxide in oxygen appears to be a more potent pulmonary vasodilator than oxygen alone in pediatric patients with congenital cardiac defects.

The post-angiocardiography urogram in children: should it be abandoned?

This study examines the value of the urogram radiograph taken after angiocardiography, in children with suspected congenital heart disease, to screen for co-existent urinary tract abnormalities. A retrospective audit of post-angiocardiography urograms over a three year period 1990 to 1993 is presented. 184 urograms obtained in 166 children were reviewed (86 males; mean age 18.1 months). Twenty-five urograms (13.6%) were obtained in cases where the urinary tract had previously been investigated. These urograms contributed no additional information. Image quality was suboptimal in 62 examinations (33.7%), due to gas, faeces or poor opacification, and two lesions were undetected on suboptimal radiographs. Urinary tract abnormalities were detected in 17 patients (10.2%). These lesions were also detectable at sonography. We suggest that routine post-angiocardiography urograms can be abandoned in favour of sonographic screening of the urinary tract in children with congenital heart disease.

Nitric oxide treatment for fulminant pulmonary hypertension.

A 3 year old child with known pulmonary haemosiderosis suffered acute circulatory collapse secondary to raised pulmonary vascular resistance. Nitric oxide inhalation produced a profound improvement in circulatory parameters and gaseous exchange. Nitric oxide may have a therapeutic role in acute pulmonary hypertensive crisis.

Doppler assessment of pulmonary artery pressure during recovery from hyaline membrane disease.

The changes in pulmonary artery pressure during recovery from hyaline membrane disease were studied by serial Doppler echocardiography on 37 preterm infants. Pulmonary artery pressure was assessed noninvasively by its inverse relationship with the ratio of pulmonary artery Doppler time to peak velocity and right ventricular ejection time. The pattern of rise in ratio after the acute phase of hyaline membrane disease divided into three types. In 25 infants the ratio returned to the normal range: in 12 (group 1) at the same time as the fractional inspired oxygen fell below 0.5 and in 13 (group 2) after a delay of at least 24 hours. In 12 infants (group 3) the ratio remained below the normal range during their hospital stay, suggesting pulmonary artery pressure remained high. Infants in group 3 were of significantly lower gestation and required oxygen treatment for significantly longer than infants in groups 1 and 2. Persistently raised pulmonary pressures in group 3 may reflect lung damage either directly affecting pulmonary vasculature or exerting a secondary effect on pulmonary vascular resistance through hypoxaemia.

Doppler assessment of pulmonary artery pressure and extrapulmonary shunting in the acute phase of hyaline membrane disease.

The natural history of pulmonary artery pressure and extrapulmonary shunting in acute hyaline membrane disease was studied by serial Doppler echocardiography in 57 preterm infants, 38 with, and 19 without, hyaline membrane disease. Pulmonary artery pressure was assessed non-invasively by its inverse relationship with the ratio of pulmonary artery Doppler time to peak velocity: right ventricular ejection time. The mean ratio was significantly lower in the infants with hyaline membrane disease. The mean ratio for each infant with hyaline membrane disease varied widely and did not correlate with criteria of maturity or severity of disease. Individual ratios correlated with arterial pH. Between 60-80 hours after birth, 14 of 18 infants with hyaline membrane disease (78%) and one of 19 without (5%) had patent ductus arteriosus. Left to right and bidirectional shunting at ductal and atrial level were common; pure right to left shunting was uncommon. The mean ratio seen with bidirectional shunting was significantly lower than that seen with left to right shunting. Ratios and patterns of extra pulmonary shunting were similar when the fractional inspired oxygen (FIO2) was greater than 0.9 compared with when it was less than 0.9. Pulmonary artery pressure is high during the acute phase of hyaline membrane disease but varies widely among infants. A few infants have extrapulmonary right to left shunting, and these infants are difficult to detect clinically.

Patent ductus arteriosus and cerebral circulation in preterm infants.

The diagnosis of patent ductus arteriosus (PDA) was determined by Doppler examinations of the descending aorta and/or main trunk of the pulmonary artery in a cohort of 120 preterm infants. 55 per cent of the infants had Doppler echocardiographic evidence of ductal patency on the first day of life and this proportion fell to 30 per cent on the second day and 21 per cent on the third day. The incidence remained constant for the rest of the first week. Infants with PDA were significantly more likely to develop periventricular leukomalacia (PVL) than infants without PDA, but the incidence of periventricular haemorrhage was not increased. The cerebral haemodynamic effects of ductal patency were evaluated. Infants with PVL were found to have a significantly higher incidence of retrograde flow in the anterior cerebral artery during diastole, but the study was unable to demonstrate any significant difference in cerebral blood flow velocity between the infants with and without PDA.

Postnatal circulatory adaptation in healthy term and preterm neonates.

Thirty seven healthy infants (18 born at full term and 19 preterm) were studied serially with cross sectional and Doppler echocardiography to compare their postnatal circulatory adaptation. Pulmonary artery pressure was assessed by its inverse relationship with the ratio of pulmonary artery time to peak velocity and right ventricular ejection time measured from Doppler waveform. Patency of the ductus arteriosus and interatrial shunting were assessed by imaging and Doppler ultrasound. The ratio rose after birth in all infants; it rose more slowly in the preterm infants. After 6 hours of age the mean was significantly less in the preterm group, the greatest difference being between 25 and 36 hours. By 73 to 96 hours the difference was no longer significant. There was a trend towards later ductal closure in the preterm infants but this was not significant. Atrial shunting level varied, but some left to right shunting was seen in all infants satisfactorily studied. Pulmonary artery pressure seems to fall more slowly after preterm birth even in the absence of respiratory problems, but ductal shunting persisting for more than three days is unusual in healthy preterm infants.

Severe birth asphyxia and abnormal cerebral blood-flow velocity.

Thirty-four fullterm infants with postasphyxial encephalopathy (PAE) were studied with ultrasound to assess cerebral blood-flow velocity (CBFV). A control group of 126 healthy infants also had CBFV recordings during the first week of life. Measurements for the majority of the asphyxiated group fell into two abnormal patterns in relation to the control group: four had low CBFV (less than 2 SD below the mean) and 17 had high CBFV (greater than or equal to 2 SD above the mean); all had severe PAE. Median age at the first high measurement was 26 hours. There were no statistically significant differences between infants with normal and abnormal CBFV in measurements of PaCO2 or mean arterial blood-pressure. A Pourcelot Resistance Index (PRI) less than 0.55 was common in the presence of high CBFV, but never seen with low measurements. 21 of the 34 infants died of their asphyxial insult and four of the survivors have severe cerebral palsy at a median age of two years. Three of the four with low CBFV died, and no infant with CBFV greater than 3 SD survived without severe impairment. The positive predictive value of CBFV measurements less than 2 SD or greater than 3 SD for death or severe impairment is 94 per cent, compared with 83 per cent for low PRI alone. The authors believe that high CBFV is the result of vasoparalysis of cerebral arterioles and that it represents a form of irreversible cerebral injury.

Cerebral haemodynamic effects of changes in positive end expiratory pressure in preterm infants.

The effects of changes in positive end expiratory pressure (PEEP) on cerebral blood flow velocity, arterial blood gases, and mean arterial pressure were studied in newborn infants. In mechanically ventilated premature infants with severe respiratory disease, an increase in PEEP from 2 to 6 cm H2O was associated with an increase in cerebral blood flow velocity. There was no significant change in mean arterial blood pressure. There was a significant increase in PaO2 and PaCO2 for every stepwise rise in PEEP. Multivariate regression analysis showed that 72% of the effect on cerebral blood flow velocity was attributable to PaCO2 alone and that any change in blood pressure was not likely to contribute to these changes. There was no evidence that changes in PEEP within the commonly used range adversely affected the neonatal cardiovascular or cerebral circulations.

Resistance index, blood flow velocity, and resistance-area product in the cerebral arteries of very low birth weight infants during the first week of life.

Cerebral artery Doppler ultrasound recordings, and intra-arterial pressure measurements have been made from 27 very low birth weight infants during the first week of life. These data were used to calculate Pourcelot's resistance index (RI), mean blood flow velocity, and resistance-area product (RAP), in both the anterior and middle cerebral arteries. There was a good degree of correlation between recordings from different sites on the same occasion, but absolute values were site dependent. Over the first three days of life there was a significant increase in blood flow velocity in each of the vessels, and a significant fall in RI and RAP.

The effect of indomethacin on cerebral blood-flow velocity in premature infants.

The prostaglandin synthetase inhibitor indomethacin is known to cause significant reduction in cerebral blood-flow (CBF) in certain newborn animals. The authors studied the effect of indomethacin on the CBF velocity of small premature infants, using duplex Doppler real-time ultrasound, and made a record of blood pressure (BP) and heart rate. Indomethacin was infused intravenously in five infants. Repeated measurements were made from the anterior cerebral artery for one hour after injection. There was a significant reduction in mean blood-flow velocity of 40 per cent two minutes after the injection, and it remained 35 per cent below pre-dose levels for at least one hour. There was a simultaneous rise of 15 per cent in systemic BP by one minute after injection. It is argued that these these changes represent a significant reduction in CBF, and this may increase the likelihood of border-zone ischaemic infarction in ill premature infants with pre-existing critical cerebral perfusion.

Value of intracranial pressure monitoring of asphyxiated newborn infants.

Twenty-three infants suffering the effects of moderate or severe hypoxic-ischaemic encephalopathy were continuously monitored for intracranial pressure (ICP) by means of a subarachnoid catheter for a total of 1083 hours. Cerebral perfusion pressure (CPP) was also continuously monitored for 21 of the infants. The median age at the start of ICP monitoring was 17 hours, and the opening pressure correlated poorly with maximum sustained pressures. Maximum sustained ICP allowed the infants to be divided into three groups: (1) those with no elevation of ICP (nine), of whom two died and five had a normal outcome; (2) those with sustained rises in ICP which were resistent to treatment (nine), of whom seven died and two survivors are severely handicapped; and (3) those in whom the pressure was elevated but could be controlled medically (five), of whom two survived to be quite normal. No infant with a sustained elevation of ICP of 15mmHg or more survived to be normal, nor any who had had a CPP below 20mmHg for one hour or more. Hypotension was the cause of low CPP in most cases. There was a highly significant correlation between sustained elevation of ICP above 10mmHg and poor outcome, but no correlation between outcome and minimum CPP. It was not possible to predict clinically which infants would develop intracranial hypertension, and some infants with very severe perinatal asphyxia did not develop intracranial hypertension, and some infants with very severe perinatal asphyxia did not develop raised intracranial pressure at any time.

Cerebral artery Doppler ultrasonography for prediction of outcome after perinatal asphyxia.

43 term infants with clinical neurological manifestations of intrapartum asphyxia and who survived for more than 2 days were studied sequentially, while in hospital, with doppler ultrasound examination of the anterior cerebral arteries. 36 survivors with post-asphyxial encephalopathy were followed up for a median of 18 months and none who had had normal doppler measurements (defined by results in 49 non-asphyxiated babies) became seriously handicapped. Of the 18 infants with abnormal waveforms 12 had an adverse outcome (death or handicap). In the asphyxiated infants, doppler examination predicted outcome with an accuracy of 86%. The prediction of adverse outcome by abnormal doppler showed a sensitivity of 100% and a specificity of 81%. All abnormal results had occurred by 62 hours from birth.

Dinamap fails to detect hypotension in very low birthweight infants.

The accuracy of blood pressure measurements obtained from very low birthweight (less than 1500 g) neonates using the Dinamap oscillometric monitor was investigated. Comparisons using umbilical artery measurements showed that the monitor is less reliable in the lower pressure range and specifically that it tends to overestimate pressure in hypotensive infants.

Controlled hypercapnia and neonatal cerebral artery Doppler ultrasound waveforms.

Eleven normal term infants undergoing respiratory assessment involving rebreathing to produce progressive hypercapnia were studied by Doppler ultrasound examination of an anterior cerebral artery during the procedure. A linear increase in end tidal carbon dioxide concentration from 4.5% to a maximum of 8.5% was documented during a period of 4-5 min rebreathing. A corresponding elevation of transcutaneous carbon dioxide tension was shown in the two infants monitored in this way. In all cases the Pourcelot index fell with rising end tidal carbon dioxide concentration. This fall in Pourcelot index was due to an increase in the diastolic frequency of the Doppler waveform. These results are consistent with the view that Pourcelot index correlates with cerebral vascular resistance distal to the site of recording.

Congenital hypothyroidism with hereditary, raised thyroxine binding globulin.

A boy with congenital hypothyroidism and hereditary raised thyroxine binding globulin is described. This hitherto unreported combination resulted in under treatment of the thyroid deficiency until serum thyroid stimulating hormone measurement became routinely available. Inadequate L-thyroxine replacement treatment between 2 and 7 years of age caused retarded bone maturation, poor growth velocity, and probably added to his educational difficulties.

The detection of abnormal neonatal cerebral haemodynamics using principal component analysis of the Doppler ultrasound waveform.

Doppler ultrasound recordings were made from the anterior cerebral arteries of 40 normal full-term babies and 14 mature babies with intracranial pathology. The maximum velocity waveforms were extracted using spectral analysis and further analyzed using the Pourcelot resistance index method and the principal component method. Principal component analysis was found to be superior to the currently widely used resistance index method and may significantly enhance the value of Doppler ultrasound for detecting abnormal cerebral haemodynamics in neonates.