[Pathology, clinical aspects, and theory of patent ductus arteriosus].
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PURPOSE: We reviewed our experience with the treatment of patent ductus arteriosus (PDA), and compared two therapeutic techniques; muscle-sparing thoracotomy (MST) and thoracoscopic PDA ligation (TPDAL). METHODS: We reviewed the clinical records and operative reports of 19 nonnewborn patients who were treated at our institution for PDA. Eleven patients underwent TPDAL and eight patients MST. The TPDAL patients underwent thoracoscopic clipping (ligation) of the PDA, whereas the MST group had a complete division of the ductus. A two-tailed Student's t test was used to calculate the 95% confidence intervals for length of operation, number of doses of intravenous narcotics and hospital stay. Costs were also compared. RESULTS: All patients underwent diagnostic echocardiography in the evaluation of an asymptomatic murmur. Both groups were similar in age (average, 4 years) and gender. All procedures were performed electively. Two thoracoscopic attempts were aborted, one for bleeding and the other for inadequate clip size. The length of the procedure averaged 1.3 hours +/- 0.330 SD for TPDAL versus 1.4 hours +/- 0.335 SD for MST. Five of the nine successful TPDAL patients were admitted to the Pediatric Intensive Care Unit (PICU) with an average length of stay of 20 hours, and two of eight MST patients stayed in the PICU for average of 18 hours. All patients were extubated after the procedure. Chest tubes were placed in two TPDAL patients and three MST patients. However, two patients who underwent TPDAL required tube thoracostomy for persistent postoperative pneumothorax. Average number of intravenous narcotics administered for the TPDAL was 1.2 doses per patient and for MST, 1.75 doses per patient. Mean hospital stay for TPDAL was 1.33 +/- 0.71 SD days and for MST 1.8 +/- 0.83 SD days. Ninety-five percent (95%) confidence intervals for the difference in means demonstrated no difference between the two groups for length of operation, hospital stay, or number of doses of intravenous narcotics administered. CONCLUSIONS: The authors were unable to identify any benefit to thoracoscopic patent ductus arteriosus ligation versus muscle-sparing thoracotomy in terms of hospital stay, length of operation, or morbidity. Additionally, with MST there is a complete division of the PDA theoretically decreasing the risk of recurrence in comparison with clip ligation.
A very large patent ductus arteriosus was closed completely using an Amplatzer Duct Occluder. This represents the largest patent ductus arteriosus to undergo closure with this endovascular technique.
The administration of a single intravenous injection of indomethacin was followed by a major constrictive effect on the ductus in 36 of 42 very-low-birth-weight (less than or equal to 1000 gm) infants with symptomatic patent ductus arteriosus (PDA). In 26 of the 36 responders, the effect was sustained; symptomatic PDA recurred in the remaining 10. Infants who experienced a recurrence of symptomatic PDA had lower birth weights and had received indomethacin at an earlier postnatal age than did infants with a sustained effect. These results may be explained by differences in the production and clearance of prostaglandins or in the sensitivity of the ductus to prostaglandin effects between infants with a recurrence and infants with sustained constriction of PDA.
In an infant with patent ductus arteriosus and pulmonary hypertension, elevated pulmonary vascular resistance persisted following ligation of the ductus. Histologic examination of a pulmonary biopsy at two years of age and tissue obtained at autopsy at three years of age showed obstructive pulmonary vascular disease. The question as to whether the organic vascular lesions are secondary to the effects of the patent ductus or part of pulmonary hypertension cannot be resolved. The age of the patient favors a primary etiology.
A model of patent ductus arteriosus in premature lambs was created to examine the lamb's ability to handle the volume load imposed by a patent ductus arteriosus and to determine the lamb's ability to handle any additional volume load. Fifteen preterm lambs [133 +/- 2 (+/- SD) days gestation, term 145 days], whose ductal diameter could be regulated with a mechanical occluder, were studied to determine the independent effects of ductus patency and a saline volume load (50 ml/kg over 3 min) on left ventricular output and its distribution. During a saline infusion, preterm lambs with a closed ductus could only increase their stroke volume by 40% above baseline stroke volume. When challenged with a saline infusion, lambs with an open ductus still were able to increase their stroke volume significantly; the maximal increase in stroke volume during the saline load with the ductus open was 70% above baseline stroke volume. We hypothesize that the associated reduced left ventricular afterload plays a significant role in the preterm lamb's ability to increase its stroke volume when challenged with a patent ductus arteriosus. Even with a patent ductus arteriosus, the lamb still has the ability to handle additional volume loads.
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.
The physiological role of the prostaglandin E2 receptor EP4 subtype was investigated by generation of EP4-deficient-mice by gene targeting. Loss of the EP4 receptor was not lethal in utero, but most EP4 (-/-) neonates became pale and lethargic approximately 24 h after birth and died within 72 h. Less than 5% of the EP4 (-/-) mice survived and grew normally more than a year. Histological examination revealed that the ductus arteriosus in dead neonates remained open, while it was partially closed in the survivors. In situ hybridization study showed that EP4 mRNA was strongly expressed in the ductus. These results suggest that neonatal death is at least partly due to patent ductus arteriosus and that the EP4 receptor plays a role in regulation of the patency of this vessel. They also indicate that normal function of the EP4 receptor is essential in neonatal adaptation of the circulatory system.
A technique for closure of patent ductus arteriosus in the elderly cases is described. We have operated on eleven adult cases of patent ductus arteriosus cases in 10 years. In five cases cardiopulmonary bypass used and in the other six cases it was not used. The cardiopulmonary bypass was used especially for the patients with pulmonary hypertension (pulmonary artery mean pressure greater than 40 mmHg), or high aged (older than 40 years) patients. No operative death have occurred in both groups, and no complication from air embolism or hemorrhage have been encountered. The technique embodies the profound hypothermia, low flow, and direct suture of the pulmonary end of the ductus arterious through a pulmonary arteriotomy. The ductus has been obstructed by using a Hegar's dilator before core cooling was started. Hegar's dilator is useful for establishing profound hypothermia and satisfactory visualization of the operative field.
BACKGROUND: Surgical closure of patent ductus arteriosus in adult patients may be problematic. Transcatheter closure of patent ductus arteriosus is an established procedure. Recently, transcatheter closure of patent ductus arteriosus using the Amplatzer duct occluder has been shown to be safe and efficacious. We present our experience with this device in adults. METHODS AND RESULTS: Between January 2000 and January 2002,41 adult patients (31 females and 10 males) with a patent ductus arteriosus were referred for closure with the Amplatzer duct occluder. The median age was 35.6 years (range 18-70.7 years) and the median weight was 65.8 kg (range 32.7-164.5 kg). Of these 41 patients, 37 underwent attempted closure of the patent ductus arteriosus using the Amplatzer duct occluder. The device was successfully deployed in all patients except 1. Complete angiographic closure was seen Immediately after device deployment in 29 out of 36 patients (81%). Complete echocardiographic closure was demonstrated within 24 hours post-procedure in 34 out of 36 patients (94%), and at 6-month follow-up in 35 out of 36 patients (97%). No complications related to device implantation occurred in any patient. CONCLUSIONS: Closure of patent ductus arteriosus using the Amplatzer duct occluder is safe and effective in adults.
The association between large, left-sided patent ductus arteriosus and severe, peripheral, right pulmonary artery stenosis with no other cardiac malformation is an unreported condition that might be misdiagnosed as pulmonary hypertension due to long-standing ductal shunt. A 57-year-old man with supposed hypertensive patent ductus arteriosus underwent confirmatory cardiac catheterization. At angiography, a severe pre-hilar right pulmonary artery stenosis (peak pressure gradient, 65 mmHg) was found to complicate the hemodynamic picture of a moderate-to-large patent ductus arteriosus (QP/QS, 1.7:1), by causing pulmonary hypertension (mean pressure, 65 mmHg) and left-to-right pulmonary flow imbalance. Both lesions were treated in a single procedure of right pulmonary artery stenting and patent ductus arteriosus closure, after which the pulmonary artery pressure significantly decreased (mean, 35 mmHg). In our opinion, a thorough hemodynamic evaluation followed by pulmonary angiography should be mandatory before proceeding to patent ductus arteriosus closure in the adult patient who has "hypertensive" ductus, in whom possible associated malformations can be missed due to a poor echocardiographic window.
Untreated patent ductus arteriosus carries a higher risk in adults than in children, especially when the defect is large (>4.0 mm in diameter), short, or friable. Therefore, various technical precautions have been suggested for application during surgical closure of a patent ductus arteriosus in an adult. We report the case of a 47-year-old woman with a patent ductus arteriosus who underwent transpulmonary surgical closure of the ductus under hypothermic total circulatory arrest. We discuss the technique in light of the current English-language medical literature.
The maturation of the lung is one of the greatest challenges the premature infant must face after birth. Premature infants have been observed to have a higher prevalence of patency of the ductus arterious, presenting the physician with a dilemma and a challenge. This article discusses the clinical and pathophysiologic manifestations and the management of patent ductus arteriosus in the premature infant.
BACKGROUND: The patent ductus arteriosus (PDA) is an important problem in premature infants. Surgical PDA ligation is usually only be considered when medical treatment has either failed or was contraindicated. The aims of our study were to determine the mortality and morbidity following patent ductus arteriosus ligation in premature infants, and whether prostaglandin synthetase inhibitor (PSI) use prior to ligation affects outcome. METHODS: A retrospective case note review study to determine the outcome of premature infants undergoing patent ductus arteriosus ligation in one tertiary neonatal intensive care unit and two paediatric cardiothoracic centres. RESULTS: We had follow-up data on 87 infants. Cumulative mortality rates at 7 days, 30 days and at hospital discharge were 2%, 8% and 20% respectively. The incidence of chronic lung disease, intraventricular haemorrhage, necrotising enterocolitis and retinopathy of prematurity were 77%, 39%, 26% and 28% respectively. There was no difference in mortality, incidence of chronic lung disease or duration of oxygen dependence between those who had and those who had not received a PSI prior to surgical ligation. In those who had received 2 or more courses of PSI prior to surgical ligation, there was a trend to increase in the duration of oxygen therapy and chronic lung disease, but no difference in mortality. CONCLUSION: This study shows that patent ductus arteriosus ligation is a relatively safe procedure (30 day survival 92%) but there is substantial late mortality and a high incidence of morbidity in the survivors. 2 or more courses of PSI prior to surgical ligation trends to increased oxygen dependence and chronic lung disease. This high risk population requires careful follow-up. A definitive prospective cohort study is lacking.
BACKGROUND: Patent ductus arteriosus is a risk factor for the development of necrotizing enterocolitis. The use of indomethacin to treat patent ductus arteriosus in preterm infants may either decrease the incidence of necrotizing enterocolitis by stabilizing or closing the ductus arteriosus or increase its incidence by a direct constricting effect on mesenteric blood vessels. The authors sought to evaluate the interrelationship between patent ductus arteriosus, treatment with indomethacin and the risk of necrotizing enterocolitis in very low birth weight infants. METHOD: The Israel National database includes prospectively collected data on 99% of all very low birth weight infants in Israel. The study population comprised 6146 infants of 24-34 weeks' gestation born between 1995 and 2000. The effect of patent ductus arteriosus on necrotizing enterocolitis was assessed using multiple regression analysis. RESULTS: Necrotizing enterocolitis occurred in 5.5% (n = 343) of all infants, in 9.4% of infants with patent ductus arteriosus and in 8.9% of infants who received indomethacin. The occurrence of necrotizing enterocolitis was independently associated with the presence of patent ductus arteriosus among infants not treated with indomethacin (odds ratio, 1.85) and those who received indomethacin therapy (odds ratio, 1.53). Indomethacin therapy in absence of patent ductus arteriosus was not associated with an increased risk of necrotizing enterocolitis (odds ratio, 0.72). CONCLUSIONS: Patent ductus arteriosus is an independent risk factor for the development of necrotizing enterocolitis in very low birth weight infants. Therapy with indomethacin did not have a significant effect on the risk for necrotizing enterocolitis.
Failure of the ductus arteriosus to close within 48-96 hours of postnatal age results in a left to right shunt across the ductus and overloading of the pulmonary circulation. This is more likely to happen in premature neonates with respiratory distress syndrome. Deterioration in the respiratory status on day 3-4 in a ventilated neonate and unexplained metabolic acidosis may be the earliest indicators of a patent ductus arteriosus (PDA). Indomethacin is the main stay of medical management of PDA in preterm neonates. Guidelines for administration of indomethacin have been described in the protocol. Restricted fluid therapy may be beneficial in the prevention of PDA in preterm neonates. Presence of PDA in a term neonate should be investigated to rule out an underlying congenital heart disease.
Differentiation of a hemodynamically significant cardiovascular abnormality from lung disease in the newborn infant may remain problematic after clinical, radiographic, and echocardiographic evaluation. Single-view aortography was performed in 38 preterm and one full term infant in the neonatal special care nursery. Special lateral views were obtained consisting of either a horizontal x-ray beam with oblique angulation of the supine patient or a vertical bean with 30 degree head-up angulation of the patient. These views projected the ductus caudal to the aortic arch and enabled visualization of the entire length of the ductus and focal constrictions of the ductus. The severity of patent ductus arteriosus was judged by anatomic (diameter of the ductus compared to the descending aorta) and physiologic (preferential opacification of the aortic arch or pulmonary circulation) criteria.
UNLABELLED: Interruption of patent ductus arteriosus (PDA) using video-assisted thoracoscopic surgery (VATS) has recently been introduced into clinical practice. To study cardiovascular and pulmonary function during VATS, we treated 16 newborn pigs (weight 1421+/-44 g) with PDA with conventional surgical interruption (CSI; n = 7) or interruption via VATS (n = 9). Measurements of hemodynamics and gas exchange were performed before, during, and after surgery. Systemic perfusion was calculated using Fick's equation. Stress hormones (ACTH, epinephrine, and norepinephrine) were determined before and after surgery. The duration of the surgical procedure was 41+/-8 min for CSI and 49+/-9 min for VATS (mean+/-SEM). With VATS, PaO2 decreased during and after surgery (P < 0.05), whereas alveolar-arterial PO2 difference (PA-aO2) and PaCO2 were increased (P < 0.05). Compared with CSI after surgery, PaO2 with VATS was decreased (130+/-10 vs 171+/-12 mm Hg; P < 0.05). Systemic perfusion was lower during VATS (76.7% of baseline) than during CSI (107% of baseline; P < 0.05). Heart rate, mean arterial pressure, and right ventricular end-diastolic pressure remained unchanged with both treatments. Stress hormones were comparable between groups. We conclude that systemic perfusion and oxygenation were impaired during VATS compared with CSI. Therefore, VATS may be contraindicated in pediatric patients with minor cardiopulmonary reserve. IMPLICATIONS: We studied the cardiopulmonary effects of endoscopic interruption of the patent ductus arteriosus in an animal model of newborn pigs. Gas exchange and systemic perfusion were impaired compared with conventional interruption of the patent ductus arteriosus after thoracotomy.