Cerebral blood flow and EEG changes in preterm infants with patent ductus arteriosus

It is unknown whether the decreased cerebral blood flow seen in infants with a large patent ductus arteriosus is associated with cerebral dysfunction. Decreased cerebral blood flow in adult human and animal models has been associated with altered electroencephalography (EEG), spectral-analyzed EEG, and EEG response to photic stimulation. Cerebral blood flow velocity, EEG, spectral analysis of EEG, and photic alteration of EEG spectra were evaluated in 8 infants before and after closure of a significant patent ductus arteriosus and in 10 control infants without a patent ductus arteriosus. All infants with patent ductus arteriosus had moderate or large shunts associated with a 25% mean reduction in cerebral blood flow velocity. There were no differences, however, in EEG, spectral analysis of EEG, or photic alteration of the spectral analysis for these infants before and after patent ductus arteriosus closure as compared to controls. It is concluded that the degree of decreased cerebral blood flow in infants with a significant patent ductus arteriosus is not sufficient to cause measurable alteration in electrocortical activity.     

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.     

Surgical ligation of patent ductus arteriosus in very low birth weight infants: is it safe?

We evaluated the outcome of a combined medical and surgical treatment of patent ductus arteriosus (PDA) in newborns weighing less than 1500 g. Charts were retrospectively reviewed for 76 newborns with a PDA between 1993 and 1997. Thirteen infants had pre-existing conditions prohibiting the use of indomethacin; eight were managed surgically, five medically. The remaining 63 infants received indomethacin therapy. Thirty-two medical failures occurred, requiring surgical ligation of the PDA. Those requiring surgery had a lower average birth weight (847 versus 997 g) and gestational age (26 versus 28 weeks; P < 0.05). Indomethacin treatment was successful in 27 infants. There were only three operative complications: a small pneumothorax, wound bleeding, and a small aortic tear. All recovered uneventfully and no deaths were attributable to the surgical procedure itself. There was no difference in the incidence of respiratory distress syndrome, duration of intubation, sepsis, neonatal enterocolitis, renal dysfunction, bleeding disorders, or intraventricular hemorrhage among both groups. Surgical ligation of a PDA is associated with a high success rate, a low incidence of complications, and no additional morbidity than indomethacin alone. We propose that surgical ligation should be regarded as a first line therapy for very small premature infants who are at higher risk of medical failure.     

Transcatheter occlusion of residual patent ductus arteriosus after surgical ligation

It is known that cellular signals produced in response to an inappropriate spindle formation cause the cell to be arrested at metaphase (M) in the cell cycle. We report here that the 42-kDa isoform of MAPK (ERK2) was tyrosyl-phosphorylated and activated in response to epidermal growth factor (EGF) in interphase but not in M-arrested HeLa cells. However, the basal level of activity of M-arrested cells was higher than that of interphase, although the overall tyrosyl phosphorylation content was small. Further, the EGF receptor and its associated proteins GTPase-activating protein and phospholipase C were phosphorylated in M-arrested cells to a lower extent than they were in interphase. This implies that in spite of its high level of basal activity, the scarcity of MAPK activation in mitosis in response to EGF stems from an early impairment of phosphorylation of the receptor and neighboring proteins. The biological significance of these results underlies the importance of keeping the cell sheltered from extracellular signals when it undergoes division.     

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.     

Acquired aortic coarctation after surgical operation of ductus arteriosus in a preterm infant

The coarctation of the aorta can be acquired or secondary to the surgical correction of congenital anomalies of the great vessels. We report the cases of two newborns operated for patency of the ductus arteriosus (normal aortic arch and a great left-to-right-shunt). During the postoperative period the patients were asymptomatic and the echocardiogram showed no abnormalities. Later, both patients developed coarctation of the aorta. This is the first report of this condition during the neonatal period.     

Surgical management of patent ductus arteriosus in low body weight infants]

Between January 1980 and December 1994, seventeen premature infants weighing less than 2500 g underwent surgical management for the isolated patent ductus arteriosus (PDA). Indometacine therapy for closure of PDA was not effective for all these patients. In terms of the body weight at birth, they were divided into two groups; Group I (G-I) consisted of ten patients with birth weight less than 1000 g and Group II (G-II) of seven patients weighing more than 1000 g. The age at operation was 22.1 +/- 15.4 days in the G-I and 14.3 +/- 11.4 days in the G-II. The ductus was ligated in all patients but one of the G-II, in whom it was divided. There were five (50%) hospital deaths in the G-I and none in the G-II. The causes of death in the G-I were related to necrotizing enterocolitis (NEC) in two and infant respiratory distress syndrome (IRDS), acute renal failure, and broncho-esophagial fistula in each. The age at operation tended to be older in nonsurvivors rather than in survivors in the G-I (28.0 +/- 16.8 days vs. 16.2 +/- 14.0 days, respectively, but the difference did not reach significance). Before surgery, all patients in the G-I required mechanical ventilator support and nine of them were associated with IRDS. In contrast, only two patients in the G-II needed mechanical ventilation preoperatively. The postoperative period of intubation was also significantly longer in the G-I than in the G-II (51.6 +/- 35.2 days vs. 2.2 +/- 1.5 days, respectively, p < 0.05). In conclusions, the surgery for PDA can be safely performed even in small premature babies weighing less than 1000 g. When medical therapy for PDA is not effective in the premature patients, the surgical management should be considered as early as possible before their conditions become worse due to such critical complications as NEC, IRDS, and renal failure.     

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.     

False aneurysm of aorta following ligation of patent ductus arteriosus: a case report

An apparatus "artificial kidney" has been constructed to improve the equipment for controlling and regulating the blood composition in the extracorporeal loop. The apparatus provides for regeneration of the dialyzing solution, ensures individual action on the blood composition, eliminates the discharge from the body of such useful substances as vitamins and amino acids and reduces the consumption of the dialyzing solution. The unit is intended for treating patients with chronic renal insufficiency.     

Truncus arteriosus with patent ductus arteriosus and normal aortic arch

In hearts with a common arterial trunk (truncus arteriosus), there is almost always an inverse development of the aortic arch and the ductus arteriosus. Truncus with a normal aortic arch and a patent ductus is a rare echocardiographic and surgical finding. In this report, we describe 2 neonates in whom truncus arteriosus with a normal aortic arch and a medium or large patent ductus was diagnosed by preoperative echocardiography (without catheterization) and confirmed intraoperatively.     

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.     

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.     

"Silent" patent ductus arteriosus and bronchopulmonary dysplasia in low birth weight infants

We conducted a clinical study on the antecedents of bronchopulmonary dysplasia (BPD) in 290 premature RDS infants with < or = 1.75 kg birth weight (BW). They were enrolled in a prospective trial of indomethacin treatment for "silent" patent ductus arteriosus (PDA), screened by 2-D echocardiographic and pulsed Doppler evaluation on the third day of life. The trial took place at the NICU of the Pediatric Department of Padua University between January 1987 and December 1991. Out of 290 infants screened, 96 had evidence of "silent" PDA (33%) and 77 responded to indomethacin treatment (80%). Comprehensively 79 (27%) developed BPD, and from these the incidence of BPD was statistically increased in infants with "silent" PDA, 47 out of 96 (49 +/- 9%), with respect to 32 out of 194 (16 +/- 3%) preterm infants without PDA. Statistical analysis showed that in preterm infants with "silent" PDA the development of BPD was correlated at 99% C.L. to their low BWs (mean BW = 1.13 kg): in fact the mean and the mode of BW distributions were statistically lower in the presence of BPD, 1.03 kg versus 1.24 kg, and 0.88 kg versus 1.65 kg respectively. Moreover, the preterm infants with "silent" PDA unresponsive to the first course of indomethacin and/or submitted later to surgical closure, presented a statistically lower BW with respect to the early responders, 1.06 kg versus 1.18 kg, and at the same time a statistically higher incidence of BPD (63 +/- 20% versus 43 +/- 9%). From these data we conclude that, although "silent", PDA increase per se the incidence of BPD, even if benefits from an early induced closure. Furthermore, a lower BW of infants affected by "silent" PDA represents a contributing factor to the development of BPD.     

Doppler ultrasonic flow detection as an adjunct in the diagnosis of patent ductus arteriosus in premature infants

Since ligation of a patent ductus arteriosus in the neonate with idiopathic respiratory distress syndrome seems to improve the clinical condition of the infant, we have attempted to identify those neonates earlier with the noninvasive Doppler ultrasonic technique, recording brachial arterial flow signals. Sixteen patients were studied. In the 5 with reversed brachial flow who were operated upon, ligation of a PDA resulted in improvement and postoperative correction of brachial flow reversal as evidenced by the Doppler ultrasonic technique.     

Aneurysm of the nonpatent ductus arteriosus in the newborn

Aneurysm of the nonpatent ductus arteriosus in the newborn is a rare, but potentially fatal condition. Of reported ductal aneurysm up to 1969, diagnosis was made at autopsy only. We report here to our knowledge for the first time on a two week old infant with correct preoperative angiographic diagnosis followed by a successful surgical cure.