Talk:Cardiovascular System - Patent Ductus Arteriosus

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Cite this page: Hill, M.A. (2019, June 18) Embryology Cardiovascular System - Patent Ductus Arteriosus. Retrieved from


Predictors of Respiratory Improvement 1 Week after Ligation of Patent Ductus Arteriosus in Preterm Infants

Hsu KH1, Wong P2, Subramanyan RK3, Evans J4, Noori S5. Author information Abstract OBJECTIVE: To characterize preterm infants that demonstrates respiratory improvement 7 days after ligation of a patent ductus arteriosus (PDA). STUDY DESIGN: We performed a 2-phase study of preterm infants (birthweight <1500 g between 2010 and 2016). We first did a retrospective analysis using regression modeling of ligation population. We then performed a case-control study comparing a ligation group with infants matched by gestational age, postnatal age, and preligation respiratory condition (ventilator mode, mean airway pressure [MAP], and fraction of inspired oxygen [FiO2]). Respiratory improvement was defined as either extubation, downgrading of ventilatory mode, reduction in MAP >25%, or decrease in FiO2 >25%. RESULTS: Forty-five (42%) of 107 preterm infants (gestational age 25.5 ± 1.7 weeks) with ligation showed respiratory improvement at 7 days. Infants on high frequency ventilation (HFV) were more likely to have respiratory improvement (aOR 5.03, 95% CI [1.14-22.18]). In matched-control analysis of 89 pairs, there was no difference in respiratory improvement. Among infants on HFV, the ligation group had an increase in MAP during 3 days prior to ligation. For infants on conventional ventilation, the ligation group had higher MAP and FiO2 than the control group during the first 2-3 postoperative days. CONCLUSIONS: Among infants undergoing PDA ligation, those on HFV were more likely to have respiratory improvement in the first week, possibly because of the prevention of further respiratory deterioration. For infants on conventional ventilation, ligation was associated with higher respiratory support in the immediate postligation period without respiratory benefits at 7 days. As HFV was used as a rescue mode, our findings suggest that those with worse lung disease may achieve greater short term benefit from PDA ligation. Copyright © 2018 Elsevier Inc. All rights reserved. KEYWORDS: high frequency ventilation; very low birth weight infants PMID: 30348438 DOI: 10.1016/j.jpeds.2018.09.061


Preterm patent ductus arteriosus: A continuing conundrum for the neonatologist?

Semin Fetal Neonatal Med. 2015 Mar 25. pii: S1744-165X(15)00040-2. doi: 10.1016/j.siny.2015.03.004. [Epub ahead of print]

Evans N1.

Abstract How to manage the preterm patent ductus arteriosus (PDA) remains a conundrum. On the one hand, physiology and statistical association with adverse outcomes suggest that it is pathological. On the other hand, clinical trials of treatment strategies have failed to show any long-term benefit. Ultrasound studies of PDA have suggested that the haemodynamic impact may be much earlier after birth than previously thought (in the first hours); however, we still do not know when to treat PDA. Studies that have tested symptomatic or pre-symptomatic treatment are mainly historical and have not tested the effect of no treatment. Prophylactic treatment is the best-studied regimen but improvements in some short-term outcomes do not translate to any difference in longer-term outcomes. Neonatologists have been reluctant to engage in trials that test treatment against almost never treating. Observations of very early postnatal haemodynamic significance suggest that targeting treatment on the basis of the early postnatal constrictive response of the duct may optimize benefits. A pilot trial of this strategy showed reduction in the incidence of pulmonary haemorrhage but more trials of this strategy are needed. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved. KEYWORDS: Ductus arteriosus; Ibuprofen; Indomethacin; Infant premature; Systemic blood flow; Ultrasound PMID 25818393


Noninvasive technique for the diagnosis of patent ductus arteriosus in premature infants by analyzing pulse wave phases on photoplethysmography signals measured in the right hand and the left foot

PLoS One. 2014 Jun 3;9(6):e98763. doi: 10.1371/journal.pone.0098763. eCollection 2014.

Goudjil S1, Imestouren F2, Armougon A2, Razafimanantsoa L3, Mahmoudzadeh M4, Wallois F4, Leke A2, Kongolo G1.


OBJECTIVE: To evaluate the impact of patent ductus arteriosus (PDA) on the pulse phase difference (PPD) between the left foot (postductal region) and the right hand (preductal region). MATERIALS AND METHODS: PPD was determined from arterial photoplethysmography signals (pulse waves) measured by infrared sensors routinely used for pulse oximetry in 56 premature infants less than 32 weeks gestation. Only infants with significant PDA (sPDA) diagnosed by echocardiography were treated with ibuprofen (for 3 days). Patients were classified according to whether or not they responded (Success/Failure) to this treatment. The Control group was composed of infants in whom ductus had already closed spontaneously at the time of the first echocardiography. The 3 groups were compared in terms of PPD at the beginning (T1) and at the end (T2) of the study. For patients in the Failure (n = 17) and Success groups (n = 18), T1 corresponded to the first day of treatment and T2 to the day after completion of the course of ibuprofen. In the Control group (n = 21), T1 corresponded to 1 to 3 days of life (DOL), and T2 to 4-6 DOL. RESULTS: Compared to the Control group, PPD was higher in the Failure (at T1 and T2) and Success (at T1) groups characterized by sPDA. After ibuprofen therapy, PPD in the Success group decreased to about the level observed in the Control group. The area under the ROC curve of PPD for the diagnosis of sPDA was 0.98 (95% CI 0.96-1); for an optimal cut-off of PPD ≥1.65 deg/cm, the sensitivity was 94.2% and the specificity was 98.3%. CONCLUSION: In this study, PPD was correlated with ductus arteriosus status evaluated by echocardiography, indicating involvement of the ductal shunt in the mechanism of redistribution in systemic vascular territories. PPD can be considered for the diagnosis of hemodynamically significant PDA. PMID 24892695

Efficacy of Paracetamol on Patent Ductus Arteriosus Closure may be Dose Dependent: Evidence from human and murine studies

Pediatr Res. 2014 Jun 18. doi: 10.1038/pr.2014.82. [Epub ahead of print]

El-Khuffash A1, Jain A2, Corcoran D1, Shah PS2, Hooper CW3, Brown N3, Poole SD3, Shelton EL3, Milne GL4, Reese J3, McNamara PJ5.


Background:We evaluated the clinical effectiveness of variable courses of paracetamol on patent ductus arteriosus (PDA) closure and to examine its effect on the in vitro term and preterm murine ductus arteriosus (DA).Methods:Neonates received one of three paracetamol regimens: short course of oral paracetamol (SCOP); long course of oral paracetamol (LCOP); intravenous paracetamol for 2-6 days (IVP). Pressure myography was used to examine changes in vasomotor tone of the preterm and term mouse DA in response to paracetamol or indomethacin. Their effect on prostaglandin synthesis by DA explants was measured by mass spectroscopy.Results:Twenty-one preterm infants were included. No changes in PDA hemodynamics were seen in SCOP infants (n=5). The PDA became less significant and eventually closed in 6 LCOP infants (n=7). PDA closure was achieved in eight IVP infants (n=9). On pressure myograph, paracetamol induced a concentration-dependent constriction of the term mouse DA, up to 30% of baseline (p<0.01), but required >1uM. Indomethacin induced greater DA constriction and suppression of prostaglandin synthesis (p<0.05).Conclusion:The clinical efficacy of paracetamol on PDA closure may depend on the duration of treatment and the mode of administration. Paracetamol is less potent than indomethacin for constriction of the mouse DA in vitro.Pediatric Research (2014); doi:10.1038/pr.2014.82.

PMID 24941212

Efficacy of paracetamol for the treatment of patent ductus arteriosus in preterm neonates

Ital J Pediatr. 2014 Feb 20;40(1):21. doi: 10.1186/1824-7288-40-21.

Terrin G1, Conte F, Scipione A, Bacchio E, Conti MG, Ferro R, Ventriglia F, De Curtis M.

Abstract Inhibitors of the cyclo-oxygenase component of prostaglandin-H2 synthetase, namely indomethacin and ibuprofen, are commonly used in the treatment of hemodynamically significant patent ductus arteriosus. These drugs are associated with serious adverse events, including gastrointestinal perforation, renal failure and bleeding. The role of paracetamol, an inhibitor of the peroxidase component of prostaglandin-H2 synthetase, has been proposed for the treatment of patent ductus arteriosus. We report a series of 8 neonates (birth weight: 724 ± 173 g; gestational age: 26 ± 2 weeks) treated with paracetamol for a hemodynamically significant patent ductus arteriosus, because of contraindications to ibuprofen or indomethacin. Successful closure was achieved in 6 out of 8 babies (75%). Median ductal diameter was significantly reduced after treatment (from 1.2 mm, range 1.0-2.5 mm to 0.6 mm, range 0.0-2.5 mm, p = 0.038). No adverse or side effects were observed during treatment. On the basis of these results, paracetamol could be considered a promising and safe therapy for the treatment of patent ductus arteriosus in neonates.

PMID 24555510


Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight infants

Cochrane Database Syst Rev. 2013 Apr 30;4:CD003481. doi: 10.1002/14651858.CD003481.pub5.

Ohlsson A, Walia R, Shah SS.


BACKGROUND: Indomethacin is used as standard therapy to close a patent ductus arteriosus (PDA) but is associated with reduced blood flow to several organs. Ibuprofen, another cyclo-oxygenase inhibitor, may be as effective as indomethacin with fewer side effects. OBJECTIVES: To determine the efficacy and safety of ibuprofen for closing a PDA in preterm and/or low birth weight infants. Seperate comparisons are presented for 1. ibuprofen (iv) compared with placebo; 2. ibuprofen (oral) compared with placebo; 3. ibuprofen (oral or iv) compared with other cyclo-oxygenase inhibitors (given iv or orally); 4. ibuprofen (oral) versus indomethacin (given iv or orally); 5. ibuprofen (oral) versus iv ibuprofen; 6. high dose versus standard dose of iv ibuprofen; 7. early versus expectant administration of iv ibuprofen. SEARCH METHODS: We searched The Cochrane Library, MEDLINE, EMBASE,,,, and personal files in July 2012. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials of ibuprofen for the treatment of a PDA in newborn infants. DATA COLLECTION AND ANALYSIS: Data collection and analysis conformed to the methods of the Cochrane Neonatal Review Group. MAIN RESULTS: Twenty-seven studies are included in this review. One study (n = 136) compared iv ibuprofen versus placebo. Ibuprofen reduced the composite outcome of infant deaths, infants who dropped out or required rescue treatment; risk ratio (RR) 0.58 (95% confidence interval (CI) 0.38 to 0.89); risk difference (RD) -0.22 (95% CI -0.38 to -06); number needed to benefit (NNTB) 5 (95% CI 3 to 17). One study (n = 64) compared oral ibuprofen with placebo. There was a significant reduction in the failure rate to close a PDA; RR 0.26 (95% CI 0.11 to 0.62); RD -0.44 (95% CI -0.65 to -0.23); NNTB 2 (95% CI 2 to 4). Failure rates for PDA closure with ibuprofen (oral or iv) compared with indomethacin (oral or iv) was reported in 20 studies (n = 1019 infants). There was no significant difference between the groups; typical RR 0.98 (95% CI 0.80 to 1.20) I(2) = 0%; typical RD -0.01 (95% CI -0.06 to 0.05); I(2) = 0%. The risk of developing necrotising enterocolitis (NEC) was reduced for ibuprofen (15 studies (n = 865); typical RR 0.68 (95% CI 0.47 to 0.99); typical RD -0.04 (95% CI -0.08 to -0.00; (P = 0.04); NNTB 25 (95% CI 13, infinity); I(2) = 0%). The duration of ventilatory support was reduced with ibuprofen (oral or iv) compared with iv or oral indomethacin (six studies, n = 471) mean difference (MD) -2.35 days (95% CI -3.71 to -0.99); I(2) = 19%. Failure rates for PDA closure with oral ibuprofen compared with indomethacin (oral or iv) were reported in seven studies (n = 189 infants). There was no significant difference between the groups; typical RR 0.82 (95% CI 0.52 to 1.29); typical RD -0.06 (95% CI -0.18 to 0.06). The risk of NEC was reduced with oral ibuprofen compared with indomethacin (oral or iv) six studies (n = 166); typical RR 0.44 (95% CI 0.23 to 0.82); RD -0.15 (95% CI -0.25 to -0.04); NNTB 7 (95% CI 4 to 25). There was no heterogeneity for this outcome. There was a decreased risk of failure to close a PDA with oral ibuprofen compared with iv ibuprofen, three studies (n = 236) typical RR 0.37 (95% CI 0.23 to 0.61); typical RD -0.24 (95% CI -0.35 to -0.13); NNTB 4 (95% CI 3 to 8). There was less evidence of transient renal insufficiency in infants who received ibuprofen compared with indomethacin. High dose versus standard dose of iv ibuprofen and early versus expectant administration of iv ibuprofen have only been studied in two trials. AUTHORS' CONCLUSIONS: Ibuprofen is as effective as indomethacin in closing a PDA and reduces the risk of NEC and transient renal insufficiency. Given the reduction in NEC ibuprofen currently appears to be the drug of choice. Oro-gastric administration of ibuprofen appears at least as effective as iv administration. Too few patients have been enrolled in studies assessing the effectiveness of a high dose of ibuprofen versus the standard dose and early versus expectant administration of ibuprofen to make recommendations. Studies are needed to evaluate the effect of ibuprofen compared with indomethacin treatment on longer-term outcomes in infants with PDA. Update of Cochrane Database Syst Rev. 2010;(4):CD003481.

PMID 23633310


Ductal ligation in the very low-birth weight infant: simple anesthesia or extreme art?

Paediatr Anaesth. 2012 Jun;22(6):558-63. doi: 10.1111/j.1460-9592.2012.03846.x. Epub 2012 Apr 10.

Wolf AR. Source Paediatric Anaesthesia and Intensive Care, Bristol Royal Children's Hospital, Bristol, UK.


Management of the very low-birth weight infant in the neonatal intensive care unit (NICU) is geared to provide optimal outcome not only in term of survival but increasingly with a goal of limitation of long-term neurological and pulmonary morbidities. Careful follow-up studies have demonstrated that relatively small variations in oxygenation and gas exchange, ventilator management, and other management modalities can have long-term consequences. Within this context, there are good data that closure of a clinically significant patent ductus arteriosus has outcome benefit, but little data on the idealized anesthetic to manage such fragile patients. Does the anesthetic management matter? Given the attention to detail within the NICU, it would seem prudent to try to choose techniques that limit changes in hemodynamics, gas exchange, and ventilation within the context of the surgery. Anesthesia for ductal ligation in the very low-birth weight infant may need to be judged by more than simple survival and brings into question the current techniques and monitoring used. © 2012 Blackwell Publishing Ltd.

PMID 22489639


Treatment of patent ductus arteriosus with bidirectional flow in neonates

Early Hum Dev. 2011 May;87(5):381-4. Epub 2011 Mar 12.

Ethington PN, Smith PB, Katakam L, Goldberg RN, Cotten CM. Source Department of Pediatrics, Duke University, Durham, NC 27710, United States.

Abstract BACKGROUND: Patent ductus arteriosus is a common occurrence among prematurely born neonates and is believed to play a role in the development of other complications of prematurity including intraventricular hemorrhage, bronchopulmonary dysplasia, and necrotizing enterocolitis. The clinical decision to treat the patent ductus arteriosus is complicated by the lack of evidence available regarding clinical conditions under which closure should be attempted. STUDY AIMS: To compare clinical outcomes for neonates who underwent treatment of patent ductus arteriosus exhibiting bidirectional blood flow versus those with flow that was left to right. STUDY DESIGN: Cohort study of all neonates with patent ductus arteriosus in which medical closure was attempted at the Duke University between January 2002 and October 2007. OUTCOME MEASURES: Death and other important clinical conditions. RESULTS: We identified 20 neonates with bidirectional flow out of 317 cases in which medical closure of patent ductus arteriosus was attempted. There was no significant increase in overall complications due to closure of a bidirectional patent ductus arteriosus [40% (8/20)] versus ones with left to right shunting [38% (111/297) p=0.82]. Death occurred in 15% (3/20) with bidirectional PDA compared to 11% (34/297) in the left to right group, p=0.72. CONCLUSION: The trend in mortality is worrisome but does not contraindicate an aggressive approach to the clinically significant PDA that has bidirectional flow at the time of the echocardiogram. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

PMID 21402454


The Botallo mystery

Clin Cardiol. 1999 Jun;22(6):434-6.

Fransson SG.

In several dictionaries the name of Botallo appears as eponym for three cardiovascular anatomical structures: the foramen ovale, the ductus arteriosus, and the ligamentum arteriosum, and in an anatomical atlas based on international nomenclature it is still linked to both the ductus arteriosus and its corresponding ligament. Some, however, claim that the Botallo eponym for the ductus arteriosus is erroneous, and that his original description in 1564 is only a note and remains just a short passage in his book Opera Omnia, a Leiden edition not printed until 1660.The structures he described were already known, and the word rediscovery is sometimes used in connection with Botallo?

PMID 10376187