Talk:Cardiovascular System - Patent Ductus Arteriosus

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2014

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.

Abstract

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

2013

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.

Abstract

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, Clincialtrials.gov, Controlled-trials.com, www.abstracts2view.com/pas, 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

2012

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.

Abstract

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

2011

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