Case of Post-Ligation Syndrome - March 2024

Author: Dr Punnanee Wutthigate - Division of Neonatology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Online Date: March 13, 2024

“Clinical course and complications in a preterm neonate with a hemodynamically significant patent ductus arteriosus: A case of post ligation cardiac syndrome”

A preterm male infant was born at 25 weeks and 4 days gestation. The mother experienced a complicated pregnancy characterized by prolonged premature rupture of membranes for 4 days, resulting in the eventual diagnosis of chorioamnionitis. Intravenous antibiotics were administered to the mother, along with antenatal steroids before delivery. A cesarean section was performed due to breech presentation and chorioamnionitis. His Apgar scores were 5 and 8 at 1 and 5 minutes, respectively, with a birth weight of 640 grams. He was intubated in the delivery room and brought to the NICU. Surfactant was administered at 2 hours of life. The ventilator settings at that time were: assist-control with volume guarantee at 5 ml/kg, PEEP at 6, and rate 40/min, with a generated PIP of 16-18. The baby required 25-30 % FiO2 to maintain SpO2 at 92-94%. Both umbilical venous and arterial catheters were placed, and arterial blood pressure was monitored. He remained stable from a cardiovascular standpoint. His chest radiography after surfactant administration is shown in Figure 1.

In our unit, we perform echocardiography screening on extremely preterm infants <29 weeks within the first 24 hours of life to evaluate cardiac function, as well as the presence and magnitude of the shunt volume by the patent ductus arteriosus (PDA). The Iowa-reported scoring system is used to identify infants at risk of a hemodynamically significant PDA (HsPDA). Our unit has also adopted their treatment algorithm (1). In this infant, at 18 hours of life, echocardiography revealed a moderate PDA in terms of shunt volume with an Iowa score of 6. Subsequently, intravenous paracetamol (acetaminophen) was administered to accelerate ductal closure, and a follow-up echocardiography was scheduled upon completion of the treatment.

Screening Echocardiography - Day 1

LA:Ao ratio of 2.25 - outlining increased LA diameter relative to the Aorta diameter from the increased pulmonary venous flow leading to LA dilation.

Transductal systolic to diastolic velocity: 151/70. Pulsatile left to right flow with decrease end-diastolic velocities. PDA size 1.4 mm.

Left pulmonary arterial end-diastolic flow velocity of 41 cm/s. Flow from the ductus into the pulmonary artery promotes increased diastolic flow velocity.

Iso-volumetric relaxation time of 42 msec.

Mitral Valve E velocity 56.5 cm/s, E/A < 1.

Pulmonary D wave velocity is 35 cm/s

Left ventricular output was estimated at 350 mL/kg/min. RVO was estimated (not shown here) at 320 mL/kg/min

Flow in celiac artery - there is occasionally forward flow and occasionally absent end-diastolic flow.

Iowa score (1, 2). Additionally, we employ various parameters to assess PDA shunt volumes, including PDA to LPA diameter, transductal peak systolic velocity, and transductal systolic to diastolic velocity. Regarding parameters for evaluating pulmonary hyperperfusion, we examine the end-diastolic blood flow velocity in LPA and the Pul V D wave, among others. Another table from de Boode et al. in Seminars in Fetal and Neonatal Medicine outlines some of the other parameters.

This infant also presented signs of significant pulmonary inflammation and changes on radiography, developing pulmonary interstitial emphysema (PIE) by day 3 of life. This progressed into severe evolving lung disease by day 13. Echocardiography was performed after the end of the first course of intravenous paracetamol (administered for 7 days). The PDA profile at that time remained significant in terms of shunt volume (as seen on “ECHO 2”). As such, the medical team decided to administer a course of oral ibuprofen (doses of 10, then 5, then 5 mg/kg/day for 3 days) to attempt ductal closure.

Day 7 echocardiography

PDA size was 1.9 mm. LPA size was 2.8 mm.

Transductal systolic and diastolic velocity: 1.88/0.62 (both in m/s)

LA/Ao = 1.80 at that time outlining LA dilation.

MV E velocity 72 cm/s, E/A < 1, IVRT 43 cm/s

Forward flow in diastole in the celiac artery

At 14 days of life, the infant was on high-frequency oscillatory ventilation with volume guarantee at 2 ml/kg, MAP at 16, 15 Hz, with a 35-40% FiO2 requirement. Considering the severity of the evolving lung disease, a consensus was reached to administer a course of dexamethasone to facilitate extubation and mitigate lung inflammation. Subsequent improvement allowed for the weaning of mechanical ventilation with an attempt at extubation. He was transitioned to non-invasive ventilatory support for 3 days but then started to experience frequent apnea, necessitating re-intubation.

Chest radiography at day of life 14.

At 28 days of age (29+4 weeks post-menstrual age), with a weight of 1000 grams, we consulted our surgical team for a bedside PDA ligation. Preceding the procedure, a PICC line and peripheral arterial line were inserted, and pre- /post-ductal saturation were monitored. Analgesia and sedation infusion were initiated before the procedure along with milrinone and hydrocortisone due to the high risk for post-ligation cardiac syndrome (PLCS). During the procedure, the infant had several episodes of desaturation and required a temporary increase in mechanical ventilation support settings. The cardiovascular status remained stable during the procedure.

Echocardiographybefore PDA ligation

Total operation time 40 mins

Post-Ligation

At 2 hours post-operatively, the infant developed a significant drop in blood pressure (BP) from the pre-intervention trends, with an arterial blood pressure reading at 54/49 (53) mmHg (notice the extremely narrow pulse pressure). The echocardiography performed at that time demonstrated some degree of biventricular dysfunction with a left ventricular ejection fraction by Simpson’s biplane of 40%, and a left ventricular output estimated at 190 mL/kg/min. The scan also revealed mild aortic insufficiency and mild mitral valve insufficiency.

CXR post PDA ligation

To address the hypotension, the team administered packed red blood cell transfusion (15 ml/kg – to optimize oxygen transport and with a preoperative hemoglobin level of 8.5 g/dl). Milrinone infusion was increased to 0.4 mcg/kg/min, and a low-dose epinephrine infusion was initiated at 0.1 mcg/kg/min. Thereafter, the blood pressure stabilized with an arterial BP at 70/52 (61) mmHg at 12 hours after the PDA ligation. Epinephrine was discontinued after 4 hours of infusion, and milrinone infusion, along with hydrocortisone, were gradually tapered over the next 2 days. A follow-up echocardiography conducted 24 hours after PDA ligation indicated normal cardiac function for both the RV and LV.

2-hour after PDA ligation

Echocardiogram 2-hour after PDA ligation

LV - Ejection Fraction at 40% (Simpson’s biplane)

LVO 190 mL/kg/min

MV E/A 1 - LV free wall E/e’ 8

Follow-up echocardiography conducted 24 hours after PDA ligation

Conclusion of the case

In this case, we demonstrated a preterm infant with HsPDA who developed post-ligation cardiac syndrome (PLCS) after PDA ligation. Infants at high risk of PLCS are gestational age < 26 weeks, BW < 1 kg, postnatal age < 28 days, larger size of PDA, perioperative cardiorespiratory instability, abnormal echocardiography before operation, LVO < 200 ml/kg/min at 1 hour in the postoperative management. Typically, within 1-2 hours post-ligation, infants may experience systemic hypotension due to decreased preload. Then between 6-12 hours post-ligation, diastolic blood pressure tends to increase or be preserved initially, while systolic blood pressure decreases. This phenomenon is attributed to the preterm myocardium’s inability to tolerate sudden exposure to very high afterload, leading to an escalation in LV dysfunction (2).

Discussion:

Post-ligation syndrome, also known as post-ligation cardiac syndrome (PLCS), describes the physiological changes that can occur following the closure of a patent ductus arteriosus (PDA), especially in premature infants. This clinical condition may arise after closure via a catheter-based intervention, as well.

The closure of the PDA results in a sudden decrease in left ventricular preload due to the reduction in pulmonary blood flow (Qp) previously supported by the left-to-right PDA. Simultaneously, there is a sudden increase in left ventricular afterload. Indeed, the left ventricle was previously connected to the low-resistance pulmonary vascular network in parallel to the systemic vasculature and is now transitioned to only the high resistance systemic circulation, leading to a drastic/abrupt increase in afterload. In some cases, the left ventricle may have undergone deconditioning due to prolonged exposure to relatively low afterload (connection to low resistance pulmonary vascular network). The left ventricle may also have experienced a component of chronic coronary steal from the PDA.

The combination of an acute increase in afterload and a decrease in preload can lead to physiological disturbances, resulting in left ventricular dysfunction and subsequent hypotension. Additionally, some infants may develop systemic hypertension shortly after ligation due to the release of a surge in catecholamines. This hypertension can exacerbate left ventricular dysfunction by further increasing afterload. Furthermore, in the context of chronic systemic steal, systemic vascular resistance may have adapted to maintain perfusion pressure in the pre-ligation period. These high SVR may persist after ligation and contribute to increased afterload and systemic hypertension in some patients.

Also, there is a sudden drop in pulmonary blood flow that was previously sustained by the ductus. The body may have adapted by reactionally increasing pulmonary vascular resistance to limit the increase flow/pressure transmission during the period pre-ligation. This increase in PVR, that is reactional, may persist to some degree in the post-ligation stage despite the acute drop in pulmonary blood flow. This may manifest in increase afterload to the right ventricle, which in turn may lead to some degree of right ventricular dysfunction. As such, some infants may showcase biventricular dysfunction. The inflammatory reaction associated with ligation is anecdotally more intense than with catheter-based closure, and has been associated in some patients with increased fluid retention and pulmonary edema in those developping post-ligation respiratory failure. This may be explained by the acute disturbances in pulmonary mechanics superimposed on chronic inflammatory changes of the immature lung. However, some infants will have a dramatic improvement of their pulmonary edema in the post-ligation stage, noticed on the chest radiography, due to the decrease in the left to right ductal shunting volume.

Management strategies typically aim to support the left ventricle by providing inotropes such as epinephrine and reducing afterload with medications like milrinone. Dobutamine may also be considered to enhance inotropic support, although it can elevate heart rate and myocardial oxygen consumption. Fluctuations in blood pressure can pose challenges, especially in patients with catheter-based closure, as they may impact the movement of the device placed in the ductus. Hydrocortisone may be considered in patients that are thought to have some component of relative or absolute adrenal insufficiency.

References

1. Giesinger RE, Hobson AA, Bischoff AR, Klein JM, McNamara PJ. Impact of early screening echocardiography and targeted PDA treatment on neonatal outcomes in "22-23" week and "24-26" infants. Semin Perinatol. 2023;47(2):151721.

2. Rios DR, Bhattacharya S, Levy PT, McNamara PJ. Circulatory Insufficiency and Hypotension Related to the Ductus Arteriosus in Neonates. Front Pediatr. 2018;6:62.

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