The effect of phototherapy on cerebral blood flow velocity in preterm infants

Cerebral blood flow velocity was studied with two-dimensional/pulsed Doppler ultrasound before, during and after discontinuation of phototherapy in 22 preterm infants (gestational age < or =32 weeks), who were treated for a minimum of 12h with blue-light phototherapy for non-haemolytic hyperbilirubinaemia. Before the cerebral blood flow velocity measurements, patency of the ductus arteriosus was diagnosed by Doppler echocardiography. All infants had normal brain ultrasound scans. Mean cerebral blood flow velocity increased significantly after initiation of phototherapy in all infants. Only in "healthy" (non-ventilated) infants did cerebral blood flow velocity return to pre-phototherapy values (baseline) after discontinuation of phototherapy, whereas in "unhealthy" (ventilated) infants cerebral blood flow velocity did not return to baseline. In 10 infants the ductus arteriosus reopened during phototherapy. In those infants, mean cerebral blood flow velocity returned to pre-phototherapy values after 2 h of phototherapy prior to its discontinuation.     

Transcatheter closure of patent ductus arteriosus in children and adults

AIM: To describe the initial New Zealand experience of transcatheter patent ductus arteriosus closure in adults and children. METHODS: Twenty-three children beyond infancy and four adults with isolated patent ductus arteriosus were selected for transcatheter umbrella closure. Rashkind umbrellas were placed across the patent ductus arteriosus through a percutaneously inserted long venous sheath using the Mullins technique. RESULTS: In 25 of the 27 patients a Rashkind umbrella was placed accurately. In two patients the umbrella could not be placed accurately: in one the procedure was abandoned uneventfully and in one the umbrella embolised to the right pulmonary artery necessitating surgical removal of the device and patent ductus arteriosus closure. There were no other significant complications. A second umbrella insertion is planned in two children for a significant residual leak at 1-year follow up. CONCLUSIONS: Transcatheter patent ductus arteriosus closure is a low risk and usually effective alternative to surgical closure for the majority of patients beyond infancy.     

A comparison of microtubule assembly in brain extracts from young and old rats

The effect of repeated doses of indomethacin on mean peak velocity (MPV) and time-averaged mean velocity in the middle cerebral artery was assessed in 10 ventilated neonates with a patent ductus arteriosus using colour/duplex Doppler technique prior to, and 10, 30, and 120 min after the first and the third dose. Velocities were significantly reduced up to 120 min after the first dose. The third dose resulted in a significant reduction in MPV at 10 and 30 min following treatment. This reduction was half of that observed after the first dose. Systemic blood pressure (BP) and heart rate did not change significantly after each separate dose. However, by the third dose, mean and diastolic BP were significantly increased from pretreatment levels. The attenuated response of cerebral blood flow (CBF) velocities to the third dose of indomethacin compared with the first dose is probably related to altered haemodynamics. Indomethacin should be used cautiously in infants with other conditions which are known to decrease CBF such as hypotension, hypocarbia and polycythaemia.     

Physiologic changes associated with ligation of the ductus arteriosus in preterm infants

Cardiorespiratory and transcutaneous oxygen monitors were used on 13 preterm neonates to examine physiologic changes during ductus arteriosus ligation. Transcutaneous oxygen decreased 30 seconds after left lung deflation; all infants required increases in inspired oxygen and ventilation to correct abnormal values after the left lung was compressed. Transcutaneous oxygen decreased 30 seconds after ductus arteriosus ligation (mean delta tcPO2 = -17 mm Hg +/- 11.4) but increased 150 seconds after left lung inflation (mean delta tcPO2 = 46.9 mm Hg +/- 28.8). Arterial blood pressure increased (mean delta systolic BP = 17.9 mm Hg +/- 9.5) and heart rate decreased 10 seconds after ductus arteriosus ligation. In five neonates, gradual closure of the ductus arteriosus over 40 to 75 seconds resulted in a more gradual increase in blood pressure. Intraventricular hemorrhage was confirmed in two patients after surgery. Ligation of the ductus arteriosus results in an abrupt increase in blood pressure, which may be related to the pathogenesis of intraventricular hemorrhage. We suggest that the ductus arteriosus be closed gradually to allow a more gradual increase in blood pressure.     

Closure of the ductus venosus in premature infants: findings on real-time gray-scale, color-flow Doppler, and duplex Doppler sonography

OBJECTIVE: Our objective was to use gray-scale, color-flow, and duplex Doppler sonography to study the anatomy, flow pattern, and time of closure of the ductus venosus in healthy premature infants. SUBJECTS AND METHODS: We prospectively examined the ductus venosus in 130 premature infants whom we divided into two groups: Group I comprised 27 neonates of gestational age 28-32 weeks, and group II comprised 103 neonates of gestational age 33-36 weeks. Neonates who had undergone umbilical vessel manipulation were excluded from the study. All examinations included gray-scale, color-flow, and duplex Doppler sonography. Patency, length, color flow, and Doppler characteristics of the ductus venosus were recorded. Neonates were examined 1-2 days after birth, 6-7 days after birth, and subsequently every 3-4 days until ductus closure was observed. The time of closure of the ductus for the two groups was compared using the chi-square test. RESULTS: The ductus venosus was patent during the initial examination in 128 of the 130 neonates. Doppler waveform was venous with little variation in velocity. Ductus length slightly exceeded 1 cm in both groups. We found a statistically significant difference in the percentage of infants having a patent ductus venosus after the initial examination: At 1 week after birth, ductus patency was shown in 85% of the infants in group I and in 56% of the infants in group II; at 2 weeks, the respective percentages were 42% and 14%; and at 3 weeks, 27% and 0%. CONCLUSION: The ductus venosus is patent 1-2 days after birth in virtually all premature infants. From 6 days after birth and onward, a significantly greater percentage of smaller premature infants (i.e., 28-32 weeks' gestational age) have a patent ductus venosus than do larger premature infants (i.e., 33-36 weeks' gestational age).     

Ductus arteriosus dilatation by prostaglandin E1 in infants with pulmonary atresia

Infants with pulmonary atresia depend on patency of the ductus arteriosus for survival in the immediate postnatal period. Despite continuing hypoxemia after birth the ductus arteriosus usually constricts, thus reducing pulmonary blood flow. This often occurs while awaiting surgical palliation or correction, leading either to marked deterioration in the infant's condition, or death. In ten infants with pulmonary atresia, we infused prostaglandin E1 (PGE1) at a rate of 0.1 mug/kg/min in six and 0.05 mug/kg/min in four into the descending aorta at the orifice of the ductus arteriosus. The ductus arteriosus was effectively dilated; at the narrowest point the diameter, measured in eight infants, almost doubled. In all ten infants arterial blood PO2 increased, averaging 24.6 mm Hg before and 43.7 mm Hg after the infusion was started. Infusion of PGE1 directly into the aorta adjacent to the ductus arteriosus avoided the complications of pyrexia, muscular twitching, and excitability which may be related to the effects of prostaglandins on the central nervous system.     

Closure of the ductus arteriosus in premature infants by inhibition of prostaglandin synthesis

Inhibition of prostaglandin synthesis constricts the ductus arteriosus in fetal lambs in utero. We administered the inhibitors, aspirin or indomethacin to 18 premature infants with patent ductus arteriosus, and assessed the effects clinically and by echocardiography (left atrial/aortic-root ratio). After aspirin (20 mg per kilogram, every six hours for four doses) the ductus closed permanently in one infant within 24 hours; in another, constriction occurred with clinical improvement, and the third did not respond. In five infants given 0.3 mg per kilogram of indomethacin, complete closure occurred within one day; two of them, who received three doses had an elevated serum creatinine for one week. In one infant the ductus reopened, requiring a second dose of indomethacin 11 days after the first. Ten infants received 0.1 mg per kilogram of indomethacin, and closure occurred within 24 to 30 hours in eight. One had a soft murmur for four days, and one did not respond to two doses of indomethacin. A murmur reappeared after three to seven days in three infants but only one required further treatment. In infants receiving a single dose of 0.3 mg per kilogram, or one or more doses of 0.1 mg per kilogram, renal function was unaltered.     

Controllable graded cerebral ischaemia in the gerbil: studies of cerebral blood flow and energy metabolism by hydrogen clearance and 31P NMR spectroscopy

Patent ductus arteriosus is an uncommon anomaly in adult patients. Surgical closure of patent ductus arteriosus in this age group presents difficult problems to the surgeon. We report our experience of 21 adult patients (19-62 years of age, mean 40 years) who underwent closure of the ductus by transfemoral implantation of a Rashkind double umbrella device. The patients came to light because of atrial fibrillation, congestive heart failure, residual flow after surgical ligation of the duct or because of incidental diagnosis made during physical examination or chest X-ray. In ten patients the pulmonary arterial pressure was normal (systolic pressure < 30 mmHg), in eleven it was elevated (systolic pressure from 30 to 100 mmHg, mean 50 mmHg). In seven patients the duct was clearly calcified and the size of the duct varied from 3 to 9 mm (mean 4.3 mm). In 16 patients the ductus resulted perfectly closed after implantation of the first double umbrella device, two patients had minimal residual aortopulmonary flow, whereas in three patients the residual shunt was significant; two of these also developed haemolysis and went to surgery, in the latter the shunt was completely abolished after implantation of a second 17-mm device 16 months later. In conclusion transcatheter closure of patent ductus arteriosus in adults is feasible, even in the presence of calcifications and/or pulmonary hypertension; taking into account the significant surgical risk, PDA umbrella closure should be considered the first choice procedure in this group of patients.     

Closure of the ductus arteriosus--new insights for critical care

New insights into the closure of the ductus arteriosus may lead to more effective nonsurgical treatment in patent ductus arteriosus. ET-1 agonists may prove useful in future pharmacologic interventions.     

Pharmacokinetics of mefenamic acid in preterm infants with patent ductus arteriosus

The pharmacokinetics of mefenamic acid (MA), 2 mg/kg, were studied in 17 preterm infants with symptomatic patent ductus arteriosus. They were given this dosage orally at 24 h intervals. There were marked inter-individual differences in some of the pharmacokinetic parameters after the first dose; peak plasma concentration (Cmax) varied from 1.2 to 6.1 micrograms/mL with a mean of 3.8 micrograms/mL, time to reach Cmax (tmax) varied from 2 to 18 h with a mean of 7.7 h and plasma half-life (t1/2) varied from 3.8 to 43.6 h with a mean of 18.7 h. The group of infants (10/17) who had ductus closure after the first dose had significantly lower clearance (P < 0.01), longer t1/2 (P < 0.01) and higher 24 h plasma concentration (P < 0.001) compared to the group of infants (7/17) who had no ductus closure after the first dose. It appeared that the plasma concentration of MA had to be above 2.0 micrograms/mL and maintained at this concentration for at least 12 h for MA associated with ductus closure in preterm infants to take effect. In view of the inter-individual variation of plasma MA concentration and the effective plasma concentration, we suggest that measurement of the plasma concentration should be done 24 h after the first dose. This might be useful for safe and effective therapy for infants with ductus closure failure after the first dose.     

Echocardiographic evidence of aortopulmonary collaterals in premature infants after closure of ductus arteriosus

Aortopulmonary collaterals occur in a variety of congenital heart diseases, in chronic pulmonary infection and abscesses, in association with lung tumors, and after multiple pulmonary emboli. In patients with congenital cyanotic heart disease aortopulmonary collaterals mainly occur in conditions with reduced pulmonary blood flow. We investigated 12 preterm low-birth-weight infants, gestational age 29.3+/-3.3 weeks, with respiratory failure who suffered from moderate to severe chronic lung disease after a period of mechanical ventilation. All patients developed aortopulmonary collaterals after closure of a patent ductus arteriosus. Aortopulmonary collaterals could be displayed clearly by color Doppler echocardiography and originated mainly from the descending aorta or the aortic arch. Hypoxic and hypercapnic episodes favored the development of aortopulmonary collaterals, which disappeared after pulmonary hemodynamics and respiratory function had improved. In only one patient coiling of a large col lateral vessel had to be performed. Systemic-to-pulmonary collateral vessels potentially aggravate chronic lung disease by increasing collateral pulmonary blood flow and reducing lung compliance. We conclude that aortopulmonary collaterals occur in bronchopulmonary dysplasia and can cause major problems in ventilated premature infants. Echocardiographic evaluation is important to prevent aggravation of chronic lung disease of infants at risk.     

Effect of antenatal administration of thyrotrophin releasing hormone on fetal flow velocity waveforms

AIM: To determine whether antenatal administration of thyrotrophin releasing hormone (TRH), to promote lung maturation, alters blood flow through the fetal middle cerebral, umbilical artery, or ductus arteriosus and through the maternal uterine arteries. METHODS: The effect of transplacentally administered TRH on the fetal circulation was prospectively evaluated in 30 patients between 24 and 34 weeks' gestation. TRH (400 micrograms) was given to the mother intravenously either as a bolus or an infusion. Fetal effects were determined by measuring the maximum velocity and pulsatility index (PI) in middle cerebral artery, ductus arteriosus, uterine artery and umbilical artery Doppler waveforms. Measurements were made immediately before, and 10 and 60 minutes after maternal TRH administration. RESULTS: Intravenous injection of TRH had no significant effect on PI in the uterine, umbilical, or middle cerebral artery and the ductus arteriosus within 60 minutes of administration in either group. CONCLUSION: The antenatal use of TRH in conjunction with steroids for fetal lung maturity does not affect utero-placental or fetal haemodynamic variables, as measured by Doppler. These findings, therefore, do not support the suggestion that antenatal intravenous administration of TRH either as bolus or infusion may have immediate adverse vascular effects in the fetus.     

Asymptomatic reopening of ductus arteriosus after successful closure by indomethacin in premature infants

Indomethacin has been demonstrated to be effective for closure of hemodynamically symptomatic patent ductus arteriosus (PDA) in premature infants. The five cases in this study had acquired asymptomatic reopening of PDA a long time after successful closure by oral indomethacin. Providing adequate oxygen, giving another course of indomethacin, preventing excessive fluid intake and keeping hematocrit level greater than 40% had been tried to close the ducti but all in vain. However, most could be expected to close spontaneously later. Herein, the possible contributing factors and the treatment rationale are discussed.     

Structure and function of the fibrillar coat of Leptorhynchoides thecatus eggs

From 1950 through 1974, 76 infants with Bochdalek hernias have been surgically repaired. Mortality has been confined to those admitted at under 30 hr of age, and the highest mortality has been among those infants admitted within the first 8 hr of life. A recent increase in mortality is explained by the arrival of a new group of infants who arrived intubated, had large diaphragmatic defects, required postoperative ventilatory assistance, and had hypoplastic lungs at autopsy. Six infants might have benefited from an early intervention to hasten closure of their patent ductus arteriosus. Since we cannot be positive that intubation of these infants prior to arrival will not have a deleterious effect, we urge great discretion in choosing which infants to intubate.     

Cost-effectiveness of transaxillary muscle-sparing same-day operative closure of patent ductus arteriosus

Transaxillary muscle-sparing patent ductus arteriosus closure performed as same-day surgery is described in 10 patients. This approach provides a superb cosmetic result while obviating the need for thoracostomy tube placement.     

Defective oxidation of hydroxyeicosatetraenoic acids in the liver of patients with Zellweger syndrome

Two patients who underwent transcatheter closure of patent ductus arteriosus, one with a Rashkind umbrella device and the other with a coil, suffered from acute hemolysis following the procedure. Hemolysis ceased after deployment of second device(s) within 48 hr without needing to retrieve the first devices in either patient. We conclude that immediate deployment of a second device(s) is an alternative to surgery when acute hemolysis occurs following transcatheter closure of ductus.     

Coil on the loop and selectively enhanced stiffness for improved control: feasibility study in the neonatal ovine model of the large patent ductus arteriosus

RATIONALE AND OBJECTIVES: Several devices have been suggested and tested for interventional closure of the persistent ductus arteriosus. Coils were found effective only in small ducts due to their lack of maneuverability and physical limitation of grip forces leading to risk of embolization. The authors evaluated the feasibility to place single coils with selectively enhanced stiffness into high shunting ductus arteriosus, the coils being deployed and controlled through a veno-arterial loop in a bovine model. METHODS: "Double-cone" shaped, stainless steel coils with enhanced stiffness of the outer rings were mounted on either end on a nitinol core wire. A snap-in mechanism attaches the coil to this delivery wire and is freed by a pusher system of coiled steel wire that is advanced over the core wire. Forming a veno-arterial loop across the patent ductus allows for repositioning into the pulmonary artery or aortic catheter. A chronic lamb model of large patent ductus arteriosus (PDAs) (> or = 9 mm) was used in which ductus patency was secured by a protocol of repetitive angioplasties. Different systems (n = 10) were placed having retrieved the previous coil by a snare after definitive release. RESULTS: Placement of coils was possible in all 10 attempts. The coils were pulled back into the catheters between five and eight times before definitive release. CONCLUSIONS: The device allows controlled placement of single coils in our model of large PDAs and may lead the way to overcome previous limitations of coils. Clinical trials are warranted.     

The contribution of colour Doppler flow imaging to the study of cerebral haemodynamics in the neonate

We investigated the contribution of colour Doppler flow imaging (CDFI) to duplex-ultrasonography of the neonatal brain. In pre- and full-term infants, CDFI facilitated spectral analysis of blood flow velocity wave forms in most major intracranial arteries, enabling blood flow velocity measurements. Moreover CDFI depicted major deep and superficial veins, enabling venous blood flow velocity measurements. Smaller arteries could also be imaged in a substantial number of infants in regions with haemorrhagic or ischaemic lesions. The method may also offer the opportunity to assess regional cerebral blood flow in the neonatal brain, although further study is necessary to determine whether accurate, reproducible flow velocity measurements are possible in these vessels.     

Patent ductus arteriosus in neonates

Patency of the ductus arteriosus is one of the more common problems of the neonate. Although the ductus arteriosus usually closes within the first days of life, persistent patency can complicate the clinical status of a newborn. The ductus arteriosus also may play a role in the pathophysiology of persistent pulmonary hypertension of the newborn and in some forms of congenital heart disease. Diagnosis of patent ductus arteriosus can be suspected clinically but should be verified by echocardiography before treatment. Accurate diagnosis, early intervention and proper treatment are necessary to decrease the immediate risks and minimize the potential for long-term complications.