Potentially Unbalanced Circulation in Neonatal Congenital Heart Disease, managment of (1281)

The structurally normal heart pumps an equal volume of blood to the pulmonary and systemic circulations with the volume of blood leaving the heart from the left side equaling the volume of blood returning to the right. The balance of pulmonary and systemic blood flow (Qp:Qs) is therefore equal to 1.ⁱ 

In the presence of specific anatomical anomalies, the pulmonary and systemic circulations operate with physiological overlap, effectively functioning in parallel rather than in series. Consequently, the distribution of cardiac output to each circuit is not fixed but is dynamically determined by the relative vascular resistance in the pulmonary and systemic vascular beds.

Therefore, for any given cardiac output, a rise in pulmonary blood flow will mean a reduction in systemic blood flow and vice versa. In the newborn, systemic vascular resistance is relatively high and pulmonary vascular resistance, which is initially high, falls steadily over the first few weeks of life.

When the balance of blood flow shifts towards either pulmonary or systemic, there will be significant and likely detrimental effects for the patient as described below.

Pulmonary Over Perfusion

Pulmonary over perfusion (Qp>Qs) is rare in the newborn due to innate high pulmonary vascular resistance following birth but can occur with some lesions and ratios >1.5:1 may cause the following complications: 

• Respiratory distress in a pink baby (‘high’ saturations).
• Lactic acidosis (due to systemic tissue under perfusion)
• Hypotension and wide pulse pressure
• Hepatic, renal failure and multi-organ failure
• Death

Pulmonary Under Perfusion 

Pulmonary under perfusion (Qp<Qs) may occur with pulmonary hypertension or certain obstructive lesions and can be tolerated to a degree but ratios of >1:1.5 may cause the following: 

• Profound cyanosis (‘low’ saturations).
• Lactic acidosis (due to tissue hypoxia)
• Normo/Hypotension with narrow pulse pressure
• Death

Careful monitoring is required to identify any decompensation in the unbalanced circulation. However, it is vital to understand that the relationship between arterial oxygen saturations (SaO2) or mixed venous saturations (SvO2) and oxygen delivery (DO2) are not linear.

Optimal Oxygen Delivery

Our goal for managing these patients is to optimise oxygen delivery to tissues. Due to the balancing act of resistances within systemic and pulmonary vascular circulation, it is not as easy as aiming for higher saturations and normal blood pressure. The following are some illustrations to highlight the challenges and guide management decisions.

Arterial Oxygen Saturations vs. Oxygen Delivery

This model of a univentricular circulation (Figure 4) suggests that optimal tissue oxygen delivery occurs at around SaO₂ 60-70% with rapid reduction in oxygen delivery with saturations >75%. This is because the high pulmonary blood flow required to achieve high SaO₂ compromises systemic perfusion. Conversely, babies with relatively low arterial saturations may have better tissue oxygen delivery.ⁱⁱ  A saturation target of 60-70% is rarely recommended, and individual targets should be sought from named or on-call cardiologist.

This theoretical model demonstrates that for any given saturation an optimisation of cardiac output can dramatically increase tissue oxygen delivery and that higher oxygen saturations can have a rapidly detrimental effect on tissue oxygen delivery.

Venous Saturations vs. Oxygen Delivery

The relationship between venous saturations (SvO₂) and tissue oxygen delivery are also complex in balanced circulations. Measuring true venous saturations in balanced circulations (via UVC) is not practical and is not commonly done. The use of Near Infrared Spectroscopy (NIRS) monitoring allows an approximation of regional tissue saturations which can be monitored in real time (see below).

Arterial-Venous Oxygen Difference

Since infants with cyanotic congenital heart disease do not have normal arterial oxygen saturations, a simpler way to consider the relationship between SaO₂ and tissue oxygen delivery would be to consider the Arterial-Venous Oxygen Difference (A-VO₂)

Optimal tissue oxygen delivery occurs when the A-VO2 is between 10-20% yet this simple value does not take into account the cardiac output state of the baby and as table 2 demonstrates this can lead to misinterpretation of clinical status of the baby based solely on saturations.  

NIRS Monitoring

In clinical practice, it may be easier to consider the difference between arterial saturations (SaO₂) and regional saturations (rSO₂) using near infrared spectroscopy (NIRS). This can be expressed as Fractional Tissue Oxygen Extraction (FTOE) - a rising index is consistent with inadequate tissue oxygen delivery:

Data taken from animal studies determined that: 

• Hyperoxia_FTOE is indicated with  FTOE ≤ 0.1
• Normoxia_FTOE a FTOE > 0.1 and ≤0.4
• Hypoxia_FTOE a FTOE > 0.4

A real-time measure of A-VO₂ can be estimated using pulse oximetry and regional NIRS saturations (SpO₂ – rSO₂). A typical arterial venous difference is 10%-20% and rising gaps should prompt clinical review. More information on NIRS monitoring can be found in the NIRS guideline on the perinatal network website. When interpreting NIRS it is important to remember that there isn’t an absolute normal value but it is vital to follow trends. Arterial blood should always have the highest oxygen saturation (SaO2) but for regional saturations the renal beds (rSO2R) have the highest saturations (high blood flow and low metabolic demands) followed by cerebral saturations (rSO2C) and venous saturations (SvO2). 

The following rules of thumb are useful:

Note: Using the Invos Somanetic neonatal probe the lower limit of normal for cerebral saturation is considered to be 63%. Absolute NIRS values vary with different manufacturer probes. Check relevant documentation locally for these values.

Routine Care

If there is no immediate life-threatening instability after a period of initial post-natal stabilisation, an individualised care plan should be agreed upon with the consultant cardiologist.

Delivery Room Care

Standard delivery room care should be followed as per NLS guidance, however, consider the following when there is a known cardiac anomaly.

• Consultant neonatologist should be aware of the delivery and if practical consultant cardiologist should be consulted during hours prior to the birth to obtain a provisional plan and whether they want an echo or contacted overnight
• An individualised birth plan should be available from antenatal fetal medicine assessment but confirmation of this plan should be sought from the cardiologist on-call
• An experienced paediatric registrar or consultant should be present
• Resuscitation, if required, should focus on airway and breathing as per NLS guidelines
• Oxygen should only be administered with care and consideration
• If IPPV is required set O₂ blender to 21% initially and adjust as per agreed saturation targets
• Allow parents to have time with baby if no respiratory distress and saturations acceptable (see below)
• Transfer to NICU and contact on-call cardiology registrar/consultant during hours o Overnight, if there is a clear foetal medicine plan for postnatal management, and the baby behaves as predicted, it may not be essential to call the cardiology registrar or consultant until morning.
• Where there is severe cyanosis after delivery room stabilisation an urgent septostomy may be required and cardiology should be contacted as soon as possible. This is particular to transposition of the great arteries with intact ventricular septum and hypoplastic left heart with restrictive atrial septum.

Oxygen in Delivery Room

Oxygen delivery and saturation targets will vary depending on underlying pathology. Cardiac conditions at risk of being unbalanced can be potentially cyanotic or mildly / acyanotic. Below is an example of conditions which can be grouped in this way and their suggested oxygen targets (if not agreed prior to delivery). A discussion with cardiology once baby is delivered will be essential to clarify acceptable targets. Always consider the co-existence of respiratory disease, especially in the pre-term baby and manage appropriately. 

Many babies will transiently require oxygen to help to transition but its use should be minimised to target saturations below. Admission Investigations

• Early Group and Save x2 should be performed in all babies admitted with major congenital heart disease
• Early Cardiac genetics and DiGeorge screen is routine practice in these patients
• Baseline cranial and renal ultrasound is routine practice but may be limited to dysmorphic babies, Di George positive or babies who will require bypass in the immediate neonatal period
• Echocardiography should be performed by the cardiology registrar or cardiac physiologist when available to establish baseline anatomy and function. Plan for out of hours vs delayed early morning echo should be discussed prior to birth.

Monitoring

Infants with complex congenital heart disease and a potentially unbalanced circulation should have the following monitoring on admission to the neonatal unit as standard. These are designed to identify early decompensation and highlight the need for intervention. The emphasis should be on monitoring trends, and acceptable parameters will vary between patients. 

UAC and UVC should be strongly considered for early care in any baby requiring PGE2 infusion and likely to need a septostomy. However, a PICC line is often preferrable to a UVC. Decision about arterial line will depend on the stability and size of the baby and consultant assessment. The combination of NIRS, saturations and capillary gases can be very effective. 

• Standard cardio-respiratory monitoring
• SpO₂ (pre and post ductal)
  • A rising SpO₂ may indicate pulmonary over circulation
  • >75% indicates Qp>Qs but this may be tolerated if NIRS, clinical condition and other parameters are satisfactory
• Blood Pressure
  • Mean BP 30 - 40mmHg but size and gestation dependent
  • Avoid diastolic pressure < 20 mmHg
• Gases (6 hourly blood gases minimal even if stable)
  • Lactate > 2 mmol/l requires review
  • Rising Base Excess prompts review Intravenous / arterial access
  • If prostoglandin (PGE2) dependent will need secure form of IV access (either UVC or PICC) and a 2^nd point of access in case of failure
  • Arterial access via UAC or peripheral should be at discretion of the consultant
  • NIRS monitoring can be particularly useful in the absence of arterial access
• UVC
  • May be used for CVP monitoring if tip is in an appropriate position
  • May be used to validate NIRS but not routine central venous saturation sampling
  • Consider if single or double lumen is more appropriate
    • A single lumen UVC may help provide access for septostomy and should be particularly considered in infants with TGA
    • If for secure point of access to give PGE2 then a double lumen UVC is preferred
• NIRS cerebral (forehead) and somatic (renal) probes
  • Provides important information about brain and other end organ perfusion
  • rSO2 is generally 10 - 20% < SpO2
  • rSO2Renal is generally 10 - 15% > rSO2Cranial (but will vary with cardiac anatomy)
  • Cerebral or Somatic rSO2 of < 40% is indicative of inadequate O2 delivery and requires urgent intervention but cerebral NIRS should aim for > 63%.

Table 4: Overview of Monitoring Modalities in Neonatal Circulation

Routine Drugs

• Elective initiation of PGE2 should be discussed with the cardiology team but will always be initiated in an emergency by neonatology
• Caffeine may be considered for apnoea in an otherwise well self-ventilating infant on PGE2
• Other drugs used for circulation manipulation are mentioned in the emergency guides (see below) and a plan for initiation be agreed, if practical, with the named consultant cardiologist.

Enteral Feeding / Fluids

Incidence of cardiac NEC, whether in term or preterm infants, is estimated at between 3 and 5% with higher rates (6-9%)ⁱⁱⁱ in infants with HLHS. Infants under this pathway should have TPN started and supplemental EBM started as per high risk pathway unless stable. Stable term infants with lactate < 2 mmol/l and no respiratory distress should be encouraged to breast feed or have incremental EBM or DEBM when MEBM is not available. Fortifiers are avoided in these infants. 

See enteral feeding guideline for more details.

Resuscitation Principles

Individual patient management will vary depending on physiology, but these action points are the practical steps to deliver the principles above. 

• Large doses of Prostaglandin (10 - 100 nanogram/kg/min) may be required if a PDA has constricted in duct dependant lesions
• Intubation and ventilation will be essential in these circumstances
  • Apnoeas associated with prostaglandin or respiratory acidosis / failure
  • To reduce the metabolic demand associated with spontaneous respiration in those with evidence of significant QP/QS imbalance
• Vasodilatation and inotropic support are likely to be required to promote systemic blood flow and support cardiac function
• Correct anaemia and/or hypovolaemia cautiously aiming for Hb targets >14g/dl
• Assume sepsis and treat with appropriate antibiotics
• Review sedation and consider muscle relaxation
• Repeat CXR to assess for pulmonary oedema and consider other respiratory causes such as RDS
• Urgent Echo to assess anatomy, ventricular filling and function
• Consider and discuss if further cardiac interventions are needed

Clinical assessment

Using these parameters with a clinical examination and an echocardiogram should confirm whether the infant is in a low, normal, or high output state and whether Qp:Qs is equal or favoring pulmonary or systemic circulation

Emergency Management Flow Chart

Flow Chart 1: Pathway of Assessment Parameters which indicate either Qp:Qs 1, >1 or <1

This chart summarises and suggests parameters and clinical signs that can indicate an imbalance in Qp:Qs and what actions should be considered. This chart should not be used as a replacement for timely discussion with the named cardiologist and should never be used in lieu of review by the consultant neonatologist.

Intubation

Intubation and ventilation of the infant with a balanced circulation may have considerable adverse effects on the “balance of circulation”. “Well” infants should only be electively intubated if it is required for investigations and imaging. “Unwell” infants, however, may require emergency or semi-elective intubation. A consultant should always be present, unless delay will compromise the infant, and the following approach should be adopted.

Induction with the following combination of drugs is recommended to reduce the potential for cardiac depression when giving standard dose opioids with the use of ketamine which is less likely to cause this effect. For guidance on the use of Ketamine in neonatal unit see Ketamine guideline and monograph for more details. A summary of the drug and effects is detailed in appendix 2.

• • Ketamine 2 mg/kg
  • Fentanyl 2.5 micrograms/kg (half standard intubation dose)
  • Suxamethonium 2mg/kg
    
• Manual IPPV circuits should be connected to an air oxygen blender initially set to 21% -unless profoundly cyanosed where more liberal oxygen use can be beneficial to reduce PVR
• BP should be carefully monitored throughout, and volume should be immediately available as may be necessary if hypotension develops. Several 5ml/kg aliquots should be prepared and ready to give
• Previously described monitoring should be in place
• Intubation should always be by the most skilled member of the team available
• Ventilate with continuing sedation and paralysis to avoid hyperventilation and reduce O₂ consumption

The goal in the management of infants with a balanced circulation is to maintain adequate tissue oxygenation and perfusion within the limitations of a parallel circulation. 

There a many different approaches to management of pulmonary over or under circulation and below are the principles of possible management strategies and their rationale. These should always be taken into consideration with on-call or named cardiologist if practical.

Ways to Influence Circulation

Respiratory Support

Newborns with a balanced circulation may develop respiratory distress associated with primary lung pathology such as surfactant deficient RDS, TTN, infection or due to congenital lung malformations. Respiratory distress should be supported with nasal CPAP and, where required, ventilation (see intubation and ventilation).  

Apnoea induced by PGE2 may occasionally require ventilation but this should be avoided where possible by reducing the dose of PGE2. Alternatively, minor degrees of respiratory instability may be controlled with CPAP and/or caffeine.  

Blood Transfusion

A simple and effective way of increasing O2 delivery is to optimise oxygen carrying capacity of the blood. Guidelines on thresholds for transfusion in this population vary and are based on low quality evidence. ^iv There are no absolute trigger values for transfusion but a slightly higher threshold of 120mg/dL as per Neonatal Transfusion Guideline should be adopted but often higher targets of 140mg/dL are optimal.

Preload

Ensure adequate filling of the heart and systemic circulation to maintain preload. This can be assessed clinically (assessing skin turgor, mucous membranes, and by the effect of gentle pressure on the liver) and echocardiographically.  

The systemically under perfused infant may require reduction in peripheral vascular resistance but this should not be undertaken without ensuring adequate preload or having additional volume immediately available.  

Inotropes and Inodilators

Increasing cardiac output can have a significant effect in improving oxygen delivery (Figures 4 - 5  & Table 2), after ensuring adequate volume loading. Milrinone and dobutamine are both vasodilating inotropes and are particularly useful if Qp>Qs. Milrinone is generally the inotrope of choice, particularly if there is ventricular dysfunction. However care must be taken to avoid significant hypotension due to concurrent systemic vasodilation which may compromise coronary perfusion.   

Adrenaline, noradrenaline and dopamine will increase cardiac output but at the risk of increasing systemic vascular resistance if used at higher doses. Low dose adrenaline infusions may be a useful adjunct. Dopamine use in neonatal practice has become less common due to newer studies showing adverse relationship with neurodevelopmental outcomes.

Vasodilators

Sodium nitroprusside (SNP) may be suggested in cases where pulmonary over perfusion is present. SNP is a short acting non-selective hypotensive agent / vasodilator which should be titrated slowly and extreme caution used when changing lines / fluids as sudden changes to rates can result in significant blood pressure fluctuations. 

Vasocontrictors

Noradrenaline is an α1 and a weak β1 adrenoreceptor agonist which may be used where inadequate contractility is noted. Higher doses may cause peripheral ischemia and increase myocardial oxygen consumption and lower doses should be titrated up with caution.  

Vasopressin activates V1 receptors, causing systemic vasocontriction and does not affect ventricular filling through chronotropy and may improve the pulmonary to systemic blood flow ratio in cases of pulmonary under circulation. There is no current neonatal monograph for its use and limited data from studies in the preterm population^v. Vasopressin has also been described to be associated with a pulmonary vasodilation effect, through the production of nitric oxide within the pulmonary endothelium. Hyponatraemia is a common side-effect.  

Phenylephidrine is an α1 adrenoreceptor agonist which preferentially causes systemic venous vasoconstriction and may be useful in cases of systemic overcirculation. It is a less potent alternative to noradrenaline and does not have the same inotropic effects. A reduction of heart rate is common which may be useful in cases of inadequate filling due to tachycardia.

Ventilation

Ventilation may be required to manage primary lung pathology, pulmonary over circulation with significant respiratory distress or severe cyanosis +/- pulmonary hypertension. Particular care should be taken during intubation to avoid hypoxia and drops in diastolic blood pressure (see intubation). Ventilation strategies should aim to maintain pCO₂ in the upper range of normal and utilise mild elevations of PEEP to reduce pulmonary blood flow if Qp>Qs. However, low minute ventilation (low tidal volume +/- very low rate) should be avoided to prevent atelectasis. The ventilated infant must be adequately sedated and muscle relaxed both to allow control of the respiratory rate and to reduce the metabolic rate and oxygen requirements.

Table 5: Summary of effects of ventilation strategies in PVR, SVR and the balance of pulmonary and systemic circulation.

Sedation

Care should be taken to adequately sedate ventilated infants and reduce any pain. Self-ventilating infants should not have prolonged periods of agitation. This is best achieved by good neonatal nursing care, encouraging appropriate parental handling, and enteral feeds where possible.  

Agitation itself can cause a shift in circulatory balance and prolonged periods of agitation should prompt an urgent medical review with consideration of ventilation and paralysis if needed to optimise tissue oxygen delivery.

Summary of Actions

Following table summaries the effect of various basic interventions and commonly used intensive care drugs on myocardial contractility, PVR and SVR. This should be used in conjunction with the other reference guides and the appropriate neonatal monographs when considering these drugs.

Table 6: Effects of basic interventions and commonly used drugs on contractility, PVR and SVR

1. Ventilation at optimal PEEP can decrease PVR. However, inadequate PEEP (atelectasis, alveolar derecruitment, hypoxic pulmonary vasoconstriction) or excessive PEEP (mechanical compression of extra-alveolar vasculature) can increase PVR.
2. The degree of increase in PVR depends on pulmonary arterial medial sensitivity. As a result, the relative increases in PVR and SVR can be unpredictable.
3. Cardiac output may be either increased by the direct sympathomimetic effects of ketamine (increased SVR and HR) or decreased in patients with depressed ventricular function.

The following are meant to be used as quick reference guides to aid the emergent management of a baby with compromised and unbalanced circulation. A thorough assessment should be sought where practical including blood gas analysis and echocardiography however with time critical decisions these are not always readily available but should be obtained at earliest opportunity.

Flow chart 1: Management options to consider with different concerns in a patient with unbalanced circulation

The following table summarises the effect of various basic interventions and commonly used intensive care drugs on myocardial contractility, PVR and SVR. This should be used in conjunction with the other reference guides and the appropriate neonatal monographs when considering these drugs.  Adapted from “The single ventricle pathway in paediatrics for anaesthetists”^vi 

1. Ventilation at optimal PEEP can decrease PVR. However, inadequate PEEP (atelectasis, alveolar derecruitment, hypoxic pulmonary vasoconstriction) or excessive PEEP (mechanical compression of extra-alveolar vasculature) can increase PVR.
2. The degree of increase in PVR depends on pulmonary arterial medial sensitivity. As a result, the relative increases in PVR and SVR can be unpredictable.
3. Cardiac output may be either increased by the direct sympathomimetic effects of ketamine (increased SVR and HR) or decreased in patients with depressed ventricular function.

Ketamine

Use of ketamine is not commonly considered in the NICU. Below is a quick reference guide to its use. For more information please refer to the GGC guideline and monograph.