WHO SHOULD BE GIVEN PROSTAGLANDIN?

Most textbooks of paediatric cardiology contain comprehensive lists of the types of lesion that may warrant prostaglandin infusion. Although these lists are diagnosis based, a full sequential diagnosis will rarely be available during the initial phase of the resuscitation, so that the decision has to be based on clinical findings. A study that applied information theory6 to this decision making process concluded the following.

(1)

The risk of withholding prostaglandin infusion in a patient with a prostaglandin sensitive lesion will depend on the patient's clinical condition. Thus, although a relatively well patient with a prostaglandin sensitive lesion may well survive a transport without prostaglandin, it is unlikely that a patient in extremis will. As a result, the threshold for starting prostaglandin should be lower in the latter group.

(2)

The most useful clinical finding to discriminate patients with potentially prostaglandin sensitive lesions is the presence of cyanosis. In the cyanosed neonate, the probability of a prostaglandin sensitive lesion is increased by the presence of a murmur, whereas in a non-cyanosed patient, it is increased by the presence of abnormal pulses.

(3)

Using the combination of signs (cyanosis, a murmur, or abnormal pulses), in association with the general condition of the patient, the study concluded that, in an infant in extremis, the presence of cyanosis or abnormal pulses alone was associated with a sufficient probability of a prostaglandin sensitive lesion to indicate prostaglandin infusion. In the cyanosed infant, without a murmur and in whom the peripheral pulses were normal, although this point may be debated, it may be appropriate to withhold prostaglandin infusion for transfer, if the child is otherwise well.

THE CRITICALLY ILL NEONATE WITH CONGENITAL HEART DISEASE WHO IS UNRESPONSIVE TO PROSTAGLANDIN

Although there are no congenital cardiac lesions for which prostaglandin is contraindicated as such, not all cyanosed neonates respond to prostaglandin. The most commonly seen example of this is obstructed total anomalous pulmonary venous drainage, for which, at best, the agent will reduce the pulmonary vascular resistance but, by increasing pulmonary blood flow, may exacerbate the venous congestion because of obstructed return. Another example is transposition of the great arteries with intact ventricular septum and an intact or restrictive atrial septum, when emergency atrial septostomy (fig 1) is the only measure that will keep these patients alive.

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Figure 1

Balloon atrial septostomy in a neonate with transposition of the great arteries. The septostomy catheter has been inserted into the umbilical vein, and has been passed from the right atrium (RA) across the foramen ovale (arrow). After inflation of the balloon (B) in the left atrium (LA), the catheter is pulled back across the atrial septum, thus enlarging the interatrial communication.

DIFFERENTIATING A CRITICALLY OBSTRUCTED SYSTEMIC CIRCULATION FROM SEVERE SEPSIS

Most neonates who are referred to a specialist cardiac centre will have been empirically started on antibiotics before transfer. The clinical distinction between an obstructed systemic circulation—for example, coarctation of the aorta, critical aortic stenosis, hypoplastic left heart syndrome—and severe sepsis remains extremely difficult, as the incidence of the two is about the same. A study that assessed the use of clinical findings to distinguish these two entities suggested that most of the available clinical variables, either alone or in combination, had insufficient sensitivity to provide an accurate differentiation.7 In this study, although a murmur or weak pulses occurred commonly in infants with an obstructed systemic circulation, 22 of the 47 patients with this type of cardiac lesion did not have a cardiac murmur at presentation.7 Furthermore, it would be fair to say that a sick neonate with systemic sepsis may have reduced peripheral pulses secondary to a low cardiac output. It may be considered therefore that, given the insensitivity of clinical examination, on site echocardiography should be available.

ARRHYTHMIA

In all neonates with suspected congenital heart disease, 12 lead electrocardiography (ECG) should routinely be performed. Arrhythmias, for example congenital complete heart block or tachyarrhythmias, can be caused by congenital heart disease8 (Ebsteins malformation, congenitally corrected transposition of the great arteries, etc) or intracardiac tumours,9 but can also occur in the neonate with a structurally normal heart.8The key features to establish when examining a neonatal ECG are that there is a regular narrow QRS complex, with a rate of 100–150, each complex being preceded by a P wave, which is upright in lead I and aVF. Of course, these guidelines are not absolute, as sinus rates exceeding these levels may be encountered in the sick neonate.

Neonatal bradyarrhythmia or tachyarrhythmia can present with shock, with clinical signs and symptoms similar to those of a critically obstructed systemic circulation. One potential clinical manifestation of longstanding (in other words in utero) arrhythmias may be the presence of hydrops,10 ,11 which carries with it a poor prognosis.11 All neonates with an arrhythmia require echocardiography to exclude associated intracardiac defects, but prompt diagnosis and treatment of a tachyarrhythmia can often rapidly reverse a spiralling clinical situation, and should not be delayed. A diagnosis of complete heart block in the neonate with a low cardiac output should prompt the neonatologist to seek early advice from a paediatric cardiologist, as medical treatment—for example, isoprenaline—and urgent transfer for insertion of a pacemaker may be necessary.10

DIFFERENTIATING CRITICALLY OBSTRUCTED PULMONARY CIRCULATION OR OBSTRUCTED PULMONARY VENOUS DRAINAGE FROM PERSISTENT PULMONARY HYPERTENSION

The clinical distinction between persistent pulmonary hypertension and a duct dependent pulmonary circulation can be extremely challenging without echocardiography. This is especially difficult in the term neonate with persistent fetal circulation (PFC) without parenchymal lung disease. Indeed cyanotic congenital heart disease “masquerading as PFC” was diagnosed in 9% of neonates after institution of extracorporeal membrane oxygenation (ECMO) support for treatment of apparent intractable hypoxic respiratory failure.12Infants with PFC may well fail a nitrogen washout test because of right to left shunting at the intracardiac and ductal levels, and early radiological examination is often of little help because the lung fields in both settings will be oligaemic, albeit for completely different reasons.

A prostaglandin infusion may provide a useful “diagnostic test” in this situation, normally resulting in considerable improvement in the infant with duct dependent congenital heart disease. However, its beneficial effects on the pulmonary vascular resistance may also lead to improved oxygenation with prostaglandin treatment in patients with PFC. The algorithm for treating PFC will often include a trial of inhaled nitric oxide; this is unlikely to provide much benefit to the patient with congenital heart disease, unless, of course, this coexists with a degree of transient pulmonary hypertension! In summary, if there remains any doubt as to the causes of persistent cyanosis in the neonate in whom CO₂ clearance is relatively easy to achieve, with radiologically normal (or oligaemic) lungs, early echocardiography should be sought.

DIFFERENTIATING CONGENITAL HEART DISEASE FROM PARENCHYMAL LUNG DISEASE

An important lesion that can masquerade as “parenchymal” lung disease with persistent pulmonary hypertension is obstructed total anomalous pulmonary venous drainage (TAPVD). Again, this is quite often diagnosed echocardiographically at the stage when neonates with “respiratory failure” present for ECMO support.12Infants presenting with obstructed TAPVD often have an unremarkable clinical cardiovascular examination. Textbooks describe the traditional cottage loaf or snowman radiographic appearance in obstructed TAPVD; however, radiographs of these infants are often obtained as an emergency measure in suboptimal conditions. In practice, TAPVD is often clinically and radiologically indistinguishable from diseases of the lung parenchyma, such as pneumonia, meconium aspiration, and early emphysema (fig 2), and in this situation early echocardiography should be considered to either make or exclude the diagnosis.

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Figure 2

Chest radiograph of a hypoxic infant referred on the first day of life for extracorporeal membrane oxygenation support with a presumed diagnosis of persistent pulmonary hypertension secondary to meconium aspiration. Cardiac echocardiography showed an obstructed infradiaphragmatic total anomalous pulmonary venous connection.

In short, unless there is a clear cut cause for parenchymal lung disease, or indeed an appropriate response to conventional therapeutic manoeuvres, the diagnostic test required to make this distinction remains echocardiography.

“BALANCING THE CIRCULATIONS” IN THE INFANT WITH CRITICALLY OBSTRUCTED SYSTEMIC CIRCULATION

These infants most commonly present with clinical signs of systemic hypoperfusion, with acidosis and hypotension, and often with signs of end organ impairment. Peripheral pulses are often globally reduced; if there is obstruction within the aortic arch, the femoral pulses will be weaker than the right brachial pulse, or indeed may be absent. In these infants, resuscitation should aim to optimise systemic oxygen delivery and prevent metabolic acidosis, which can be the cause of increased operative mortality.13

Two fundamental principles underlie the resuscitation of these infants. Firstly, ductal patency (to provide systemic blood flow) is vital for early survival; thus all patients in whom this diagnosis is suspected should be started on prostaglandin infusion at a rate appropriate to maintain ductal patency. Apnoea secondary to prostaglandin infusion is a relatively common indication for intubation in these patients, but not necessarily an indication to reduce the dose and never an indication to stop the infusion. Secondly, when ductal patency has been established, attention must be directed to the balance between the systemic and pulmonary blood flows. In these patients, the systemic, myocardial, and pulmonary circulations are in parallel and in constant dynamic competition with one another. In short, increases in pulmonary blood flow lead to reductions in systemic and myocardial blood flow,14 ,15 with continuing signs of poor peripheral perfusion, metabolic acidosis, oliguria, and myocardial dysfunction. Pulmonary overcirculation should be pre-emptively managed by using measures that restrict pulmonary blood flow, in order to allow adequate perfusion of the systemic and myocardial vascular beds. In summary:

(1)

Prostaglandin infusion must be started at a rate sufficient to maintain ductal patency.

(2)

Ventilatory parameters should be adjusted to manipulate the pulmonary vascular resistance to avoid pulmonary overcirculation, so as to maintain a pulmonary to systemic blood flow ratio of about 1:1. This goal can usually be achieved by applying a modest level of positive end expiratory pressure (4–6 cm H₂O), ventilating in room air in the first instance, and adjusting inspiratory pressures, rate, or tidal volumes to achieve an arterial CO₂ tension of 5–6 kPa and a systemic saturation of 75–85%, avoiding respiratory alkalosis.

(3)

If signs of low cardiac output persist, the patient should be reassessed to ensure that the prostaglandin infusion is adequate and intravascular volume is satisfactory, and anaemia should be corrected. If the systemic blood pressure allows, a low dose nitroprusside infusion may improve metabolic acidosis. Otherwise, a low dose inotrope infusion may be of benefit in arresting the vicious cycle of metabolic acidosis and worsening ventricular function. In general, high dose inotrope infusions should be avoided because they may increase systemic vascular resistance, thus forcing more blood into the lungs and worsening the pulmonary to systemic blood flow distribution.