Strategy of Dagnosis and Treatment for Hemodynamically Significant Patent Ductus Arteriosus in Preterm Infants

Jung Ha Lee

doi:10.14734/kjp.2013.24.2.72

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Lee: Strategy of Dagnosis and Treatment for Hemodynamically Significant Patent Ductus Arteriosus in Preterm Infants

Original Article

Korean J Perinatol 2013;24(2):72-81.

Published online: 19 June 2013

DOI: https://doi.org/10.14734/kjp.2013.24.2.72

Strategy of Dagnosis and Treatment for Hemodynamically Significant Patent Ductus Arteriosus in Preterm Infants

Jung Ha Lee, M.D., Ph.D.

Department of Pediatrics, Ilsan Hospital, Dongguk University, Goyang, Korea

책임저자 : 이정하, 410-773 경기도 고양시 일산동구 식사동 814 동국대학교 일산병원 소아청소년과 전화 : 031)961-7187, 전송 : 031) 961-7188

Received 7 June 2013 Revised 23 June 2013 Accepted 24 June 2013

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Patent ductus arteriosus (PDA) is a major morbidity in preterm infants, especially in extremely premature infants less than 28 weeks. Early diagnosis of hemodynamically significant PDA (hs-PDA) is not easy because the symptoms of PDA in preterm infants are non-specific. Echocardiography is a good diagnostic tool for early detection of PDA. Clinical investigation has been continued to establish a criteria for selecting an infant who needs early targeted treatment of PDA by echocardiography. The biomarkers such as brain natriuretic peptide (BNP) and N-terminal pro-BNP (NTpBNP) are currently under research as a diagnostic and prognostic marker of PDA. Cyclooxygenase (COX) inhibitor is the treatment of choice and highly effective for PDA closure in preterm infants. Oral ibuprofen is emerging as a better alternative because it is as effective as indomethacin with fewer side effects. PDA ligation is a treatment option for hs-PDA when medical treatment is failed. There is lack of long term benefits of such treatments to induce ductal closure. Thus, it is prudent to treat an infant with clinically significant PDA on the basis of gestational age, birth weight, clinical status, and echocardiographic findings. Better diagnostic tools to identify infants who might benefit from ductal closure are needed.

Keywords: Patent ductus arteriosus, Preterm, Management, Ibuprofen

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Table 1.

Rates of Spontaneous Ductus Arteriosus Closure (%)^17-20

	Closed on Day 4	Closed on Day 7	Closed at Discharge
Gestational age
Full term	100	100	100
30 weeks	90	98	98
27-28 weeks	22	36	NA
25-26 weeks	20	32	NA
24 weeks	8	13	NA
Birth weight
1,000-1,500 g	35	67	94
<1,000 g	21	34	NA

NA, no data available. Quoted from Semin Perinatol 2012;36:123-9.

Table 2.

Proposed Staging System (Adapted from McNamara and Hellman, Unpublished Clinical Triaging System for Ligation of a Patent Ductus Arteriosus (PDA)) for Determining the Magnitude of the Haemodynamically Significant Ductus Arteriosus (HSDA), Which Is Based on Clinical and Echocardiographic Criteria

Clinical	Echocardiography
C1 Asymptomatic	E1 No evidence of ductal flow on two-dimensional or Doppler interrogation
C2 Mild Oxygenation difficulty (OI <6) Occasional (<6) episodes of oxygen desaturation, bradycardia or apnoea Need for respiratory support (nCPAP) or mechanical ventilation (MAP <8) Feeding intolerance (>20% gastric aspirates) Radiologic evidence of increased pulmonary vascularity	E2 Small non-significant ductus arteriosus Transductal diameter <1.5 mm Restrictive continuous transductal flow (DA Vmax >2.0 m/s) No signs of left heart volume loading (eg, mitral regurgitant jet >2.0 m/s or LA:Ao ratio >1.5:1) No signs of left heart pressure loading (eg, E/A ratio >1.0 or IVRT >50) Normal end-organ (eg, superior mesenteric, middle cerebral) arterial diastolic flow
C3 Moderate Oxygenation difficulty (OI 7-14) Frequent (hourly) episodes of oxygen desaturation, bradycardia or apnoea Increasing ventilation requirements (MAP 9-12) Inability to feed due to marked abdominal distension or emesis Oliguria with mild elevation in plasma creatinine Systemic hypotension (low mean or diastolic BP) requiring a single cardiotropic agent Radiological evidence of cardiomegaly or pulmonary oedema Mild metabolic acidosis (pH 7.1-7.25 and/or base deficit -7 to -12.0)	E3 Moderate HSDA Transductal diameter 1.5-3.0 mm Unrestrictive pulsatile transductal flow (DA Vmax<2.0 m/s) Mild-moderate left heart volume loading (eg, LA:Ao ratio 1.5 to 2:1) Mild-moderate left heart pressure loading (eg, E/A ratio >1.0 or IVRT 50-60) Decreased or absent diastolic flow in superior mesenteric artery, Middle cerebral artery or renal artery
C4 Severe Oxygenation difficulty (OI >15) High ventilation requirements (MAP >12) or need for high-frequency modes of ventilation Profound or recurrent pulmonary haemorrhage “NEC-like” abdominal distension with tenderness or erythema Acute renal failure Haemodynamic instability requiring >1 cardiotropic agent Moderate-severe metabolic acidosis (pH<7.1) or base deficit >-12.0	E4 Large HSDA Transductal diameter >3.0 mm Unrestrictive pulsatile transductal flow Severe left heart volume loading (eg, LA:Ao ratio >2:1, mitral regurgitant jet >2.0 m/s) Severe left heart pressure loading (eg, E/A ratio >1.5 or IVRT >60) Reversal of end-diastolic flow in superior mesenteric artery, middle cerebral artery or renal artery

Abbreviations: BP, blood pressure; DA Vmax, ductus arteriosus peak velocity; E/A, early passive to late atrial contractile phase of transmitral filling ratio; IVRT, isovolumic relaxation time; LA: Ao ratio, left atrium to aortic ratio; MAP, mean airway pressure; nCPAP, nasal continuous positive airway pressure; NEC, necrotising enterocolitis; OI, oxygenation index. Patients should be assigned both a clinical and echocardiography stage (eg, neonate with severe oxygenation failure, pulmonary haemorrhage and a 3.2 mm unrestrictive left-to-right shunt will be C4-E4 class HSDA). Detailed discussion of the echocardiography parameters is beyond the scope of this perspective. Quoted from Arch Dis Child Fetal Neonatal Ed 2007;92:F424-7.

Table 3.

Comparison of Echocardiographic Markers of Hemodynamically Significant Patent Ductus Arteriosus

	No PDA	Small	Moderate	Large
Characteristics of the ductus arteriosus
Transductal diameter (mm)	0	<1.5	1.5-3	>3
Ductal velocity V _max (cm/s)	0	>2	1.5-2	<1.5
Antegrade PA diastolic flow (cm/s)	0	>30	30-50	>50
Pulmonary overcirculation 25-26 weeks
Left atrial/aortic ratio	1.13±0.23	<1.4:1	1.4 -1.6:1	>1.6:1
Left ventricular/aortic ratio	1.86±0.29	-	2.15±0.39	2.27±0.37
E wave/A wave ratio	<1	<1	1-1.5	>1.5
IVRT (ms)	<55	46-54	36-45	<35
LVSTI	0.34±0.09	-	0.26±0.03	0.24±0.07
Systemic hypoperfusion
Retrograde diastolic flow (%)	10	<30	30-50	>50
Aortic stroke volume (mL/kg)	≤2.25	-	-	≥2.34
Left ventricular output (mL/kg/min)	190-310	-	-	>314
LVO/SVC flow ratio	2.4±0.3	-	-	4.5±0.6

Abbreviations: LVO, left ventricular output; SVC, superior vena cava; LVSTI, left ventricular stroke volume index; IVRT, isovolumic relaxation time; PWD, pulse wave Doppler; CWD, continuous wave Doppler; PA, pulmonary artery. Quoted from Eur J Pediatr 2009;168:907-14.

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