Ligation of the Patent Ductus Arteriosus in Preterm Infants:
Understanding the Physiology
Afif F. El-Khuffash, MD1, Amish Jain, MD2,3,4, and Patrick J. McNamara, MD2,3,4,5
T
he diagnosis and management of preterm neonates
with a patent ductus arteriosus (PDA) that fails to close
after medical management poses a major challenge.
The association of prolonged ductal patency with morbidities
including feeding intolerance, necrotizing enterocolitis
(NEC), severe intraventricular hemorrhage (IVH), metabolic
acidosis, renal failure, increased ventilator dependence,
bronchopulmonary dysplasia (BPD), and pulmonary
hemorrhage are well recognized.1,2 In addition, a PDA failing
medical treatment is associated with a 4- to 7-fold increase
in mortality.3 This association remains significant after
adjustment for gestation, birth weight, disease severity, and
other comorbidities, including IVH, NEC, and sepsis.
The decision to perform surgical PDA ligation has been
challenged recently, owing to its possible association with ad-
verse neurologic outcomes.4,5 The magnitude of postoperative
instability in some patients often dissuades neonatologists
from choosing surgery.6 Neonatologists face uncertainty
regarding the optimal approach to this patient population.
In this article, we outline the concerns surrounding PDA
ligation, review the selection process for intervention, and
discuss the perioperative physiological changes that may
explain the link between ligation and adverse neurodevelop-
mental outcomes. In addition, we propose a postoperative
management strategy aimed at minimizing hemodynamic
compromise after PDA ligation.
The Ligation Decision?
The appropriateness and optimal timing of surgical ligation
is the subject of much debate and recent controversy. In gen-
eral, surgical intervention is contemplated if medical treat-
ment fails and the PDA remains hemodynamically
significant, based on clinical and echocardiography markers
(discussed later). In some centers, surgery may be considered
the first-line treatment in infants with NEC, IVH, pulmonary
BPD Bronchopulmonary dysplasia
CBV Cerebral blood volume
IVH Intraventricular hemorrhage
IVRT Isovolumic relaxation time
LV Left ventricular
LVO LV output
NEC Necrotizing enterocolitis
NIRS Near-infrared spectroscopy
PDA Patent ductus arteriosus
PLCS Postligation cardiac syndrome
SVR Systemic vascular resistance
TOI Tissue oxygenation index
VCFc Velocity of circumferential fiber shortening
1100
hemorrhage, thrombocytopenia, or severe oliguria, although
there is no evidence to support this approach.7 It is also pos-
sible that delays between attempted medical treatments and
surgical ligation may contribute to complications.3 In con-
trast, earlier surgery subjects patients to the adaptive risks
of surgical ligation.
Cardiovascular Adaption to PDA Ligation
Surgical ligation of a PDA leads to sudden changes in cardio-
vascular physiology, specifically a rise in left ventricular (LV)
afterload and a fall in LV preload (Figure 1), with a resulting
sudden drop in LV output (LVO).8-10 The relative
contributions of altered preload and altered afterload to
postoperative instability require further characterization.
This may enable the identification of more physiologically
appropriate treatments.
Our understanding of postligation cardiovascular physiol-
ogy has improved substantially over the last 2 decades. The
physiological factors contributing to cardiovascular instabil-
ity were first characterized in premature baboons. Specifically,
a temporal relationship between impaired LV performance
and increased systemic vascular resistance was identified, co-
inciding with changes in arterial pressure.11 Subsequent pro-
spective observational studies in human neonates have also
demonstrated declining LV performance in the immediate
postoperative period, coinciding with decreased pulmonary
venous return (preload) and increased systemic vascular
resistance (afterload). The clinical effects of this low cardiac
output state become apparent usually at 6-12 hours after
ligation.10-12
The recent prospective observational study conducted at
our center is the largest to date, and the first to characterize
myocardial performance at the peak time of clinical stability.6
Impairment in indices of LV systolic performance, namely
LV shortening fraction and the velocity of circumferential fi-
ber shortening (VCFc), was identified 8 hours after surgical
intervention, which coincided with clinical deterioration.
Given that the effect of preload change is greatest within
the first 1-2 hours after surgery, this change is unlikely the
major determinant of this deterioration. An increase in the
From the 1Department of Pediatrics, The Rotunda Hospital, Dublin, Ireland;
2
Department of Pediatrics, Mount Sinai Hospital; 3Division of Neonatology, The
Hospital for Sick Children; 4Department of Pediatrics, University of Toronto; and
5
Physiology and Experimental Medicine Program, The Hospital for Sick Children,
Toronto, Ontario, Canada
The authors declare no conflicts of interest.
0022-3476/$ - see front matter. Copyright ª 2013 Mosby Inc.
All rights reserved. http://dx.doi.org/10.1016/j.jpeds.2012.12.094

Figure 1. Physiological determinants of PLCS in preterm in-
fants. Ao, aorta; LA, left atrium.
slope of the inverse relationship between end-systolic wall
stress and VCFc suggests that the changes in myocardial per-
formance are related to LV afterload. The timing of the clin-
ical deterioration (8-12 hours after surgery) coincides with
the period of maximal afterload exposure.6 Infants weighing
<1000 g were at greatest risk of compromise, which is biolog-
ically plausible, considering that the preterm myocardium is
not conditioned to handle substantial changes in either pre-
load or afterload. Both animal and preterm human data have
shown that VCFc, a load-dependent measure of contractility,
is inversely proportional to end-systolic wall stress, a measure
of LV afterload.13,14 Clinical studies of therapeutic interven-
tions provide biological validation for the role of LV afterload
in the pathogenesis of disease. In a retrospective cohort study,
Lemyre et al15 found that intraoperative volume support did
not reduce the need for postoperative inotropic agents. In
contrast, in another study, early administration of milrinone,
an inotropic drug with vasodilator properties, to infants with
low cardiac output led to a reduction in postoperative hemo-
dynamic instability.9
Pulmonary Adaption to PDA Ligation
The presence of prolonged left-to-right shunting across the
PDA leads to altered pulmonary compliance. Preterm ba-
boons (125 days [67%] gestation) exposed to a moderated-
size PDA demonstrated impaired pulmonary function and ar-
rested alveolar development and surface area compared with
age-matched fetuses (140 days gestation).16 Several human
studies have demonstrated decreased lung compliance in pre-
term infants with PDA compared with controls, without
changes in airway resistance. Infants treated with indometha-
cin demonstrated improved lung compliance after successful
medical PDA closure.17-19 The changes in lung compliance af-
ter PDA ligation are more profound. In a group of 16 preterm
infants, dynamic lung compliance improved, coupled with
Vol. 162, No. 6
June 2013
increases in tidal volume and minute ventilation.20 It is pru-
dent to consider these changes after ligation, given that lung
overdistention could possibly further compromise vena
cava and pulmonary venous flow, leading to impaired ven-
tricular filling and contributing to decreased cardiac output.
Immediate and Short-Term Surgical
Complications
Changes in cardiopulmonary physiology after surgery may
lead to a postligation cardiac syndrome (PLCS) in up to
50% of infants.21 In this prospective observational study,
we defined PLCS as systolic blood pressure below the 3rd
percentile expected for gestational age requiring 1 or more
cardiotropic agents and accompanied by ventilation or oxy-
genation failure. This definition may be too restrictive, how-
ever; PLCS is likely a spectrum disorder of varying severity,
with some infants developing profound hypotension and
others suffering exclusively from ventilation and oxygena-
tion failure. Onset is typically 6-12 hours after ligation and
is related to increased afterload.6,22 A recent study reported
higher mortality in infants with PLCS compared with
controls (33% vs 11%).21
Several preoperative risk factors for PLCS have been iden-
tified. In an earlier study, we found that younger postnatal age
at the time of ligation was associated with increased need for
postoperative cardiotropic support.22 Other studies have re-
ported an increased risk of PLCS in infants born at <26 weeks’
gestation or at a birth weight of <750-1000 g.23-25 In addition,
compared with infants weighing >1000 g, those weighing
<1000 g are more likely to develop low postoperative LVO
(defined as <170 mL/kg/minute in this study), lower shorten-
ing fraction, systolic blood pressure below the 3rd percentile,
and an increased need for inotropic agents (30% vs 4%).6
Some investigators have attempted to use echocardiography
to predict PLCS. PDA size before ligation was found to
have a negative correlation with postoperative LVO,10 and
an inverse correlation between peak velocity across the PDA
and postoperative ventilator dependence has been reported.24
Our group recently reported that LVO <200 minute/kg/
minute measured within 1 hour after PDA ligation predicted
100% of infants who subsequently developed PLCS.9
Direct surgery-related complications include intraopera-
tive bleeding, pneumothorax, vocal cord paralysis, chylo-
thorax, scoliosis, and phrenic nerve injury. The collective
incidence of these complications is usually low.26 In a large
series of 306 ligations, Mikhial et al27 reported a 2% incidence
of intraoperative bleeding, a <5% incidence of air leaks, and
no direct surgery-related deaths.
Long-Term Complications
Intraoperative Cerebral Hemodynamic Changes
Reports linking PDA ligation with adverse long term neuro-
developmental outcomes are conflicting.4,28 Nevertheless, it
is important for clinicians to understand the intraoperative
and postoperative physiological alterations that may affect
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cerebral function. Changes in cerebral hemodynamics and
electrical activity during PDA ligation have been studied us-
ing near-infrared spectroscopy (NIRS), Doppler assessment
of cerebral blood volume (CBV), and amplitude-integrated
electroencephalography. Assessment of the tissue oxygena-
tion index (TOI) using NIRS has yielded conflicting results.
Estimation of TOI uses spatially resolved spectroscopy to re-
flect cerebral oxygenation with a high degree of sensitivity
and specificity. TOI is a surrogate marker of tissue oxygena-
tion, with lower values indicating higher oxygen extraction
and hence lower supply.29 Zaramella et al30 examined the ef-
fect of PDA clipping on cerebral TOI and CBV using a com-
bination of NIRS and Doppler assessments and found a drop
in TOI, indicating increased tissue oxygen extraction, but no
change in CBV after clipping. In contrast, more recent studies
demonstrated a sudden surge in CBV immediately after clip-
ping, returning to preoperative baseline within 5-10 min-
utes.31,32 In addition, there was a concurrent but transient
increase in TOI persisting for up to 20 minutes after ligation.
None of these studies found any change in heart rate or blood
pressure during the monitoring period; thus, these data
might not be representative of the sickest patients who de-
velop PLCS. There have been no studies investigating CBV
and TOI in infants with PLCS, and the relationship of abnor-
mal CBV or TOI with brain injury or long-term neurologic
outcomes has not yet been investigated.
Lemmers et al33 performed combined amplitude-
integrated electroencephalography and NIRS monitoring in
20 preterm infants before and after PDA ligation, and found
lower cerebral oxygen saturation and increased fractional ox-
ygen extraction during the induction phase. Some of these in-
fants had cerebral oxygen saturation as low as 35%,
approximating levels known to cause functional and mor-
phological brain injury in experimental animal models.34 Ce-
rebral oxygen saturation increased steadily throughout the
first 24 hours after ligation, with a concurrent decrease in
fractional oxygen extraction to values comparable to those
seen in infants without PDA. Infants with the most pro-
nounced drop in cerebral oxygen saturation had the most sig-
nificant drop in cerebral electric activity. These changes also
coincided with a fall in blood pressure after induction, sug-
gesting that any negative impact on the brain may be an effect
of anesthesia rather than of PDA closure.
The anesthetic technique was relatively uniform in most
studies. Infants usually receive opioids (fentanyl or sufenta-
nil) and a muscle relaxant (pancuronium) for induction, fol-
lowed by an opioid infusion to maintain anesthesia.
Inhalation agents are seldom used.35 The agent and/or dosage
could possibly influence electrical brain activity intraopera-
tively. Interestingly, Janvier et al35 demonstrated that inade-
quate anesthesia during ligation is associated with an
unstable postoperative respiratory course accompanied by
hypotension. Anesthetic drugs used routinely during neona-
tal surgery were found to cause apoptotic neurodegeneration
in the developing rat brain.36 The impact of anesthesia in the
setting of other types of neonatal surgery may provide valu-
able insights.
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Long-Term Clinical Sequelae
Data from the Trial of Indomethacin Prophylaxis in Preterm
Infants were reexamined to determine whether surgical clo-
sure of a PDA is a risk factor for BPD, severe retinopathy of
prematurity, and neurosensory impairment at age 18
months.4 In that trial, more than half (53%) of survivors
who underwent PDA ligation had neurosensory impairment,
compared with 34% of survivors who received only medical
therapy. Both BPD and severe retinopathy of prematurity
were also more common after surgical PDA closure. Mortality
was lower in infants who underwent surgical PDA ligation
(14% vs 22%; P = .095). The authors concluded that surgical
PDA ligation may be associated with increased risks of BPD,
severe retinopathy of prematurity, and neurosensory impair-
ment in extremely low birth weight infants. The biological ex-
planation for this association is quite complex: (1) brain injury
secondary to prematurity might have preceded surgery in
many patients; (2) the infants who underwent surgery were
sicker, with more severe ductal illness; and (3) perioperative
or intraoperative events such as hypothermia, cardiorespira-
tory instability, or exposure to anesthetic drugs may contrib-
ute directly to poor outcome. A major omission from this
analysis was the failure to consider duration of exposure to
a hemodynamically significant PDA as a potential contribut-
ing factor, particularly in those patients with end-organ blood
flow compromise. It is plausible that surgical ligation is a sur-
rogate marker for illness severity and heightened risk of abnor-
mal outcome. It is also possible that the PLCS may contribute
to the poor neurodevelopmental outcome, but this has not
been studied to date. It would be premature to draw any con-
clusions regarding the appropriateness of a decision to per-
form or not perform PDA ligation based on these data.
An association between PDA and subsequent development
of chronic lung disease was reported in 446 infants born at
<28 weeks’ gestation. This effect was independent of gesta-
tional age, other PDA-related variables, or other perinatal
risk factors known to be associated with chronic lung
disease.28 In contrast, some investigators have reported that
PDA ligation is well tolerated, with evidence of early respira-
tory benefit. In a retrospective study of 125 infants, with a me-
dian gestational age of 26 weeks at birth, the median time to
extubation after PDA ligation was 5 days (IQR, 3-10 days).37
The 30-day and 1-year mortality rates were 4.8% and 12.8%,
respectively, and the rate of neurologic disability in survivors
was 32%. All deaths occurred in the ventilated group and
were attributable mainly to BPD. Interestingly, lack of med-
ical treatment of PDA before ligation was associated with
death at 1 year.37 These findings add to the growing uncer-
tainty regarding the benefits and risks of surgical ligation of
PDA during the neonatal period.
Refining the Ligation Decision
Selecting patients for PDA ligation poses challenges. Accord-
ing to some commentators, the lack of hard evidence of a ben-
efit from PDA closure negates the need to treat unless
intractable hypotension or refractory congestive heart failure
El-Khuffash, Jain, and McNamara
June 2013 MEDICAL PROGRESS

occurs. Conversely, others argue that a PDA is pathological
and thus should always be treated.5,38 Reconciling these polar
opposite viewpoints has led to confusion among physicians
and has complicated the decision making process. It is our
view that consideration of the PDA as a dichotomous entity
represents a physiological oversimplification; rather, it is
a physiological continuum in which shunt volume is influ-
enced by ductal diameter and transductal resistance. Although
it is not possible to measure PDA shunt volume, the magni-
tude may be estimated and classified as small, moderate, or
large according to surrogate echocardiographic markers of
pulmonary overcirculation and systemic hypoperfusion.
In response to escalating numbers of requests for PDA liga-
tion at The Hospital for Sick Children in Toronto and pro-
longed surgical wait times, a categorization system was
established based on strict clinical criteria and echocardiogra-
phy markers of pulmonary overcirculation and systemic hy-
poperfusion.2 The purpose of the categorization system was
to streamline the decision making process and assist with
case prioritization and triaging through more objective eval-
uation of PDA severity and hemodynamic significance. In ad-
dition, PDA category was linked to surgical wait times. The
operationalization of this system was such that admission
for surgical consideration occurred within 24 hours for cate-
gory I cases, within 3 days for category II cases, and within 7
days for category III cases. Since the system’s introduction
in 2005, the number of PDA ligations performed at the hospi-
tal has decreased by more than 50%.39 The components of the
categorization system are summarized in the Table.
Markers of Pulmonary Overcirculation
The increase in effective pulmonary blood flow may be esti-
mated by the left atrial-to-aortic ratio, which uses the rela-
tively fixed diameter of the aorta to assess the degree of left
atrial volume loading.40 This ratio correlates with increased
pulmonary flow attributable to a high-volume left-to-right
transductal shunt; the optimal threshold ratio, $1.5, predicts
a significant PDA, although the measurement is prone to op-
erator- dependent error.41 In the developing fetus and pre-
term infant, the early phase of passive filling (E wave) is
less than the late active phase (A wave), resulting in an E/A
ratio of <1.0. This is related to developmental immaturity
of the preterm myocardium, which leads to poor myocardial
compliance and impaired diastolic performance, thereby
limiting passive flow.42 In neonates with a hemodynamically
significant PDA, an increase in early transmitral flow occurs
secondary to increased left atrial pressure, resulting in pseu-
donormalization of the E/A ratio (>1.0), resembling the pat-
tern seen in older children. Isovolumic relaxation time
(IVRT), the interval between closure of the aortic valve and
opening of the mitral valve, is prolonged in the fetus and im-
mature neonate. IVRT is also decreased in neonates with
a significant PDA, owing to early pressure-related valve clo-
sure/opening.43,44 In one study, mean IVRT was shorter in
neonates with PDA compared with those with a closed
duct (45  7 ms vs 55.3  5 ms; P < .01).43 An additional
marker of increased pulmonary shunting is high LVO
(>350 mL/minute/kg), which reflects increased pulmonary
venous return, left heart preload, and stroke volume with
compensatory augmentation in LV performance. It must be
recognized that E/A ratio, IVRT, and high LVO may be
underestimated in the presence of a high-volume left-to-right
atrial shunt, which itself may be a marker of left heart volume
and pressure loading secondary to a significant PDA.
Markers of Systemic Hypoperfusion
Celiac and mesenteric artery blood flow drop in the presence
of a PDA, despite a rising LVO.45 Neonates with low diastolic

Table. Criteria for triaging preterm infants referred for PDA ligation at The Hospital for Sick Children, Toronto
Clinical criteria*
Category 1
Profound pulmonary hemorrhage with significant oxygenation difficulty (TOI >15 or MAP >12 and FiO2 >0.5)

Low cardiac output syndrome or rapidly progressive cardiorespiratory failure requiring 2 or more inotropic agents
Category 2
Deteriorating respiratory status (TOI >15 or mean arterial pressure >12 and fraction of inspired oxygen >0.5)

Preterm born at <26 weeks’ gestation with a large, hemodynamically significant PDA in whom medical treatment is contraindicated

Low cardiac output syndrome or cardiorespiratory failure requiring 1 or more inotropic agents

Neonate with NEC and a large PDA believed to be a significant contributor to clinical instability
Category 3
Inability to extubate or wean from respiratory support

Cardiac failure associated with failure to thrive
Echocardiography criteria† A. PDA diameter B. Pulmonary overcirculationz C. Systemic hypoperfusion
Moderate-volume shunt 1.5-3.0 mm with unrestrictive At least 2 of the following: Absent diastolic flow in at least 2 of the following:
(A + B and/or C) pulsatile flow (Vmax <2 m/s)
LA:Ao 1.5-2.0
Abdominal aorta

IVRT 45-55 ms
Celiac trunk

E:A 1.0
Middle cerebral artery

LVO 300-400 mL/kg/min
Large-volume shunt >3.0 mm with unrestrictive At least 2 of the following: Reversed diastolic flow in at least 2 of the following:
(A + B + C) pulsatile flow (Vmax <2 m/s)
LA:Ao >2.0
Abdominal aorta

IVRT <45 ms
Celiac trunk

E:A >1.0
Middle cerebral artery

LVO >400 mL/kg/min

E:A, E wave:A wave; FiO2, fraction of inspired oxygen; LA:Ao, left arterial:aortic; MAP, mean arterial pressure; Vmax, maximum flow velocity.
*Clinical criteria must be interpreted in the setting of a PDA and the absence of sepsis, NEC, and coagulopathy.
†PDA ligation triage is performed based primarily on clinical criteria, but echocardiographic signs must be consistent with at least a moderate-volume shunt.
zMight not be reliable in the presence of a large atrial septal defect (>2.0 mm), which may offload the left atrium, resulting in pseudonormalization of echocardiographic markers.

Ligation of the Patent Ductus Arteriosus in Preterm Infants: Understanding the Physiology 1103
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Figure 2. Clinical algorithm for infants undergoing PDA ligation. ACTH, adrenocorticotropic hormone; echo, echocardiogram.
flow velocity in the superior mesenteric artery and celiac ar-
tery are at increased risk of developing NEC.46 Preterm in-
fants with a PDA have lower end-diastolic and mean
middle cerebral artery flow velocities compared with con-
trols.47 A rise in middle cerebral artery flow velocity after
PDA ligation was demonstrated when compared with preop-
erative measurements.48 Although the clinical relevance of al-
tered middle cerebral artery flow is unclear, it may explain the
link between the development of a PDA and IVH. Absent or
reversed diastolic flow in the renal vessels is also indicative of
a significant left-to-right shunt.49,50
Recently Jhaveri et al51 reported a reduced incidence of
NEC after introduction of a preoperative stratification sys-
tem similar to the one described by McNamara et al.6 These
data reaffirm the need for, and potential benefits of, a more
comprehensive clinical and echocardiographic assessment
of infants undergoing PDA ligation.
Postoperative Management
The approach to postoperative care of patients undergoing
PDA ligation surgery should consider the physiological
consequences of afterload and impaired LV performance,
as well as the pathological consequences of the procedure
itself (eg, pneumothorax, lung hyperinflation) and possible
adrenal gland suppression. Targeted neonatal echocardiog-
raphy should be used to assess postoperative myocardial
function and guide prophylactic or early treatments. Vaso-
pressors, such as dopamine and epinephrine, should be
avoided in the face of increased afterload, with preferential
consideration to agents that reduce afterload (eg, milri-
none, dobutamine) and improve contractility. Volume re-
placement should be considered in view of the reduced
preload.
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Vol. 162, No. 6
We have developed a standardized approach, starting
with a rapid adrenocorticotropic hormone response stress
test performed preoperatively to assess adrenal gland perfor-
mance, which may be compromised secondary to systemic
hypoperfusion. An inadequate stress response secondary to
chronic adrenal gland hypoperfusion from a significant
PDA may be a contributing factor to PLCS.52 Infants with
an inadequate response, defined as rise in cortisol of <500
nmol/L,53 should be considered for early use of hydrocorti-
sone; specifically, in the setting of low diastolic pressure and
refractory postoperative hemodynamic instability. Routine
echocardiographic assessment of LV performance is per-
formed in all patients at 1 hour after surgical ligation. In-
fants with LVO <200 mL/kg/minute are considered at
high risk of developing PLCS and are given intravenous mil-
rinone (0.33 mg/kg/minute) in an attempt to reduce after-
load and improve diastolic dysfunction, as well as a bolus
of normal saline to counteract any effect of reduced preload,
characterized by reduced LV end-diastolic volume and re-
duced left atrial diameter. Further volume replacement is
given if there is evidence of low diastolic blood pressure
or increased fluid losses, especially in the event of fluid
loss from intrathoracic drains. Serial blood pressure moni-
toring is performed to ensure maintenance of systolic and
diastolic arterial pressures above the 3rd percentile for any
given gestational age. Second-line inotropic agents are usu-
ally considered in cases of isolated low systolic arterial pres-
sure (6-12 hours) suggestive of low cardiac output, most
likely secondary to impaired LV systolic performance. This
situation is usually managed with dobutamine (for addi-
tional chonotropic support and afterload reduction) and
further volume replacement in addition to the milrinone.
Care should be taken to avoid a drop in diastolic pressure
El-Khuffash, Jain, and McNamara
June 2013
secondary to excessive vasodilation. Early (<4 hours) low
diastolic pressure is not typical of PLCS and is suggestive
of hypovolemia, pneumothorax, or lung hyperinflation.
Second-line agents may be initiated before the 3rd percentile
for blood pressure is reached if other clinical signs of hemo-
dynamic instability become apparent, including a rising
lactate concentration, a falling urine output, and an evolving
metabolic acidosis. Intractable diastolic hypotension is man-
aged with volume replacement, dopamine, and intravenous
hydrocortisone particularly, if the preoperative adrenocoti-
cotropic hormone stimulation test yielded suboptimal re-
sults (Figure 2).
Discussion
Infants undergoing PDA ligation represent a high-risk popu-
lation by virtue of their severe illness and complex preopera-
tive and postoperative courses, all of which may contribute to
poor neurodevelopmental outcomes. The surgical procedure
itself is unlikely to directly contribute to brain injury.
Chronic left-to-right shunting before ligation, intraoperative
compromise of cerebral oxygen saturation, and postopera-
tive hemodynamic instability secondary to the physiological
effects of the procedure are more biologically plausible con-
tributors to brain injury. We believe that surgical PDA liga-
tion should remain a treatment option for certain infants
with a hemodynamically significant PDA, but a comprehen-
sive preoperative clinical and echocardiographic evaluation is
required in all cases to determine the nature of the shunt vol-
ume and evaluate physiological consequences. Further re-
search on characterizing myocardial function before and
after surgery is needed, along with assessment of therapies
aimed at improving ventricular loading conditions. The im-
pact of such therapies on neurodevelopment outcome should
be examined as well. n
Submitted for publication Sep 11, 2012; last revision received Nov 13, 2012;
accepted Dec 28, 2012.
Reprint requests: Patrick J. McNamara, MD, Hospital for Sick Children, 555
University Ave, Toronto, ON, Canada MG5 1X8. E-mail: patrick.mcnamara@
sickkids.ca
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