Or some pointers on clinical management following the successful return of spontaneous circulation in children. 

It’s 5:40 am at Bubblesville ED. The red phone rings. The paramedic crew informs you that they are five minutes away with a 7 kg, 6-month-old, previously thriving, baby boy called Tarquin. He has had a witnessed out of hospital cardiac arrest at home and there was no prodromal illness according to the family. He choked during a breastfeed, turned blue, and stopped breathing. He had 5 minutes of CPR by the parents by the time the ambulance arrived and had ROSC by the paramedic team after a further 8 minutes. The rhythm strip was consistent with a PEA arrest. They are hand-ventilating him through an LMA.

A systematic, collaborative, well-led approach to advanced paediatric life support can maximize the chances of the clinical team achieving a return of spontaneous circulation in a child that has arrested. We’ve seen the drill be before. We can go through our algorithms expertly and the 5-H’s and 5-T’s roll off the tongue, even under duress. The return of a pulse is heralded as the “hallelujah moment”, almost as if the patient is now healthy and safe and all we have to do is wait for the paediatric critical care retrieval team to arrive.

Whilst traditional APLS teachings are vital for the dissemination of knowledge and it’s application in everyday clinical life, their main focus is on the initial phase of achieving a pulse with very little attention placed on the all-important post-resuscitation phase.  This part of care is crucial, not only if we are to minimize secondary brain injury to the child but also to improve the chances of permanent returns of spontaneous circulation. Good short and long term outcomes rely heavily on how well we manage the post-resuscitation stage. 

There are four phases of cardiac arrest:-

Phase one: Prevention. This is the pre-arrest phase. Child safety and injury prevention strategies are in place to recognize deterioration. Adequate monitoring by using early warning systems and a pro-active approach to management is likely to contribute to avoiding an arrest.

Phase two: No flow arrest. This is a period of cardiac arrest prior to us commencing CPR. Our aim here is to minimize the time it takes to start life support. It is key that we involve the cardiac arrest team quickly, we start chest compressions early, and that we do not delay defibrillation if this is needed. 

Phase three: Low flow resuscitation. This phase describes when CPR is in progress. The aim is to achieve high-quality CPR in order to allow adequate coronary and cerebellar perfusion. Maintaining good ventilation and oxygenation whilst avoiding aggressive over-ventilation is paramount. It is during this phase that we systematically approach and threaten the reversible causes of cardiac arrest. 

Phase four: This is the post-resuscitation phase after ROSC has been achieved. Our aim here is to optimize coronary and cerebral perfusion. Neuroprotection and treatment of arrhythmias as well as treatment of post-cardiac arrest syndrome come under this phase. 

Adult v paediatric arrest: What’s the difference?

Out of hospital cardiac arrests in children >16 years of age are relatively rare – reported at 8-20/100000/ year. The incidence is only comparable to that of the adult population, estimated at 70/100000/year. The incidence of in-hospital paediatric arrests is much higher, with a nearly one-hundred-fold increase, compared to the out-of-hospital incidence for the <16’s. 

Survival, and especially a “good” survival from a neurological perspective still remain poor. Out of hospital survival rates are estimated to be 5 – 12%. Only 0.3 to 4% of those that survive have no long-term neurological insult.

Children have cardiac arrests due to severe respiratory insult or circulatory collapse, in the main. Either can lead to a respiratory arrest coupled with hypoxia, which then results in a cardiac arrest. The overwhelming majority of cardiac arrests present with a non-shockable rhythm.  It is also worth noting that almost half of the paediatric population that have a cardiac arrest have other chronic comorbidities such as respiratory conditions e.g. asthma, congenital cardiac disorders, or neurodisability. 

In the adult population, cardiac arrest is more likely due to long-term comorbidities such as ischaemic heart disease. This contributes to the development of an acute myocardial insult and (usually) a shockable rhythm. Understanding the difference in pathology leading to a cardiac arrest between adults and children is vital. Reversing the cause of the respiratory compromise can make the impalpable pulse palpable, allowing us to perfuse our patient once again. 

The recommended CPR ratio of 15:2 for children aims to provide adequate ventilation for oxygenation as well as satisfactory cardiac compressions to maintain sufficient perfusion of the coronary and cerebral circulation. Adult studies looking at compression-only CPR in patients with VF arrest have shown that success in achieving ROSC is due to pre-existing pre-arrest aortic blood oxygen and pulmonary oxygen stores.  As a mere 14% of cardiac arrests are due to a shockable rhythm, combining ventilation and compressions is vital. 

What is the Post Cardiac Arrest Syndrome (PCAS)? 

PCAS describes the period in which our patients are at the highest risk of developing ventricular arrhythmias and reperfusion injuries after ROSC. This is secondary to prolonged ischaemia then reperfusion of vital organs, primarily the myocardium and central nervous system. Its systemic effects are not dissimilar to those encountered in severe sepsis. There are four stages to PCAS:

• Immediate post-arrest – First 20 minutes. 
• Early post-arrest – 20 minutes to 6-12 hours. 
• Intermediate phase – 6-12 hours up to 72 hours.
• Recovery phase – From 72h onwards. 

Neuroprotection

Even high-quality closed-chest CPR can only achieve 50% of normal cerebral blood flow at best. It is not a secret that the brain does not tolerate hypoxia or ischaemia, the effects on both of these processes are exponential during a cardiac arrest, the longer the downtime, the worse the neurological hit. 

The pathophysiological cascade for neurodegeneration following cardiac arrest is complex and multi-factorial. Following a hypoxic or ischaemic period the brain develops cerebral oedema and cerebral hyperaemia. There is impaired cerebral vascular reactivity and like any other organ trying to reperfuse, the post-ischaemic biochemical cascade is activated. All these factors contribute to a secondary brain injury. Of course, the duration of hypoxia will in large part dictate how severe the primary brain injury is and whether the patient is likely to survive or not. Brain injury can manifest as myoclonus, stroke, seizures, coma, or brain death. 

Strict normothermia

Therapeutic hypothermia following a cardiac arrest during the intermediate phase (after VF in adults), as well as newborns with birth asphyxia, has shown some correlation with better neurological outcomes and reduced neurodisability.  Similarly, there is strong evidence linking core temperature above 38° with worse neurological outcomes in patients following cardiac arrest. There is a wide variation in practice in relation to therapeutic hypothermia.  Mild hypothermia after paediatric cardiac arrest is in the policy of some PICU’s. Patients are cooled to 33-34°C for 1 – 2 days and are then gradually rewarmed. Paralysis can be used as an adjunct to stop shivering. Temperatures below 32°C should be avoided as they are associated with worse survival, immunosuppression, arrhythmias, coagulopathies, and infections.  The decision to “cool” must be made early and in conjunction with your critical care transport team. You have many tools at your disposal to achieve this such as cold IV fluids, cooling blankets, and catheters. 

What is, and should be, more aggressively targeted is strict normothermia (temperatures between 36-37°C), and depending on local practice hypothermia can be targeted to 33-36°C. Avoidance of pyrexia is crucial. Fever can result in an increased metabolic demand of the brain. This contributes to more ischemic injury and more infarcts as the threshold for ischemia in the injured brain is lower than that of the normal brain. The brain can no longer auto-regulate the mismatch between cerebral blood flow and metabolic demand.

Aggressive seizure prophylaxis

Seizures after paediatric cardiac arrest can occur in up to 47% of cases. 35% of these can lead to refractory status epilepticus.  Whilst CFAM/EEG monitoring is unlikely to be available in your local PED, it is important to have a low threshold to administer a long-acting anti-epileptic or a continuous infusion of a short-acting medicine to prevent/avoid this from happening. Ideally, a continuous infusion of midazolam +/- levetiracetam (less arrhythmogenic than phenytoin but both will work) and standard national guidelines should be followed. 

Clues as to whether a patient is still fitting include:

• Unexpected changes in the pupillary size (beware of the child that had atropine on induction with the “fixed dilated pupils”).
• Sudden changes in BP or heart rate.  

Avoiding hypoxia and hyperoxia

Avoiding hypoxia and hyperoxia are also key components in minimizing secondary brain injury.  Whilst hypoxia will further exacerbate secondary brain injury, hyperoxia  (PaO2 > 40 kPa) is also be associated with worse survival due to oxygen free-radical formation that can inactivate intracellular enzymes, damage DNA, and destroy lipid membranes. It is reasonable to have high concentration oxygen therapy during the low-flow resuscitation and early post-resuscitation phases (as the commonest causes are respiratory). In the subsequent phases, we should target oxygen saturations between 94 and 96% and be proactive in how we reduce the FiO2 whilst avoiding hypoxia. There is a caveat in cases of severe anaemia or carbon monoxide poisoning. Then it is clinically appropriate for the highest concentration of oxygen to be administered.

Tight circulatory monitoring and support

Inotropic support may also be needed early. A degree of myocardial dysfunction/stunning is expected following CPR. To ensure adequate cerebral perfusion we need to target an age-specific, physiologically normal blood pressure. Both hypo and hypertension can exacerbate secondary brain injury. Because of this, monitoring the blood pressure through an arterial line is preferred. If the local set-up or skillset does not allow for arterial line placement, especially in smaller children, having non invasive blood pressure on 1-2 minute cycles can be a useful proxy.  

The paediatric myocardium is much more resilient than its adult counterpart.  If the arrest is not secondary to congenital heart disease the paediatric heart can regain normal function within 12-24 hours.  During the first 20 minutes following ROSC poor cardiac function is due to profound systemic vasoconstriction and cellular acidosis. We can support the myocardium by supplying adequate fluid resuscitation, targeting normal (age-appropriate) blood pressure and inotropic support. Point of care ultrasound, CVP monitoring, or assessing for hepatomegaly/rales if there is no access to the former, can help us prevent fluid overload. 

Inotrope choice is usually made with the help of the critical care team and depends on the balance between the need for inotropy and vasoconstriction.  Adrenaline is preferred for inotropy, noradrenaline for vasoconstriction.  Be aware that severe acidosis can cause catecholamine resistance, so giving some bicarbonate if the pH <7 may help your inotropes work better. Routine administration of bicarbonate has not been shown to improve clinical outcomes. There are some special circumstances in which we should consider its use such as cases of hyperkalaemia or hypermagnesaemia and arrests due to tricyclic antidepressant overdose. 

Patient position

The patient position that can achieve optimum cerebral perfusion is with the patient semi-sat up at a 30-45 degree angle.

Eucapnia and normoventilation

Avoidance of hypercapnia or hypocapnia is important in preventing secondary brain injury. It is, therefore, recommended that eucapnia is achieved by targeting a PaCO2 between 4.5 and 5.5 kPa. Hyperventilation can cause hypoxia and increase intracranial pressure due to hyperaemia, it can also cause further cerebral ischemia. As the intrathoracic pressures increase, cardiac venous return is impaired. Since the myocardium is already injured this can have catastrophic effects causing the BP to plummet and subsequently impair cerebral perfusion.

Vigilant glucose monitoring 

Following ROSC, children are also at risk of developing hypoglycemia (glucose <3 mmol/L). There is good evidence to suggest that hypoglycaemia negatively impacts neurological outcome and cause hypoglycaemic seizures, especially in the younger ages. Vigilant glucose monitoring and correction as per APLS guidelines is important. If regular dextrose boluses are needed, consider a continuous glucose infusion. If the patient mounts an adequate stress response, they may become hyperglycaemic.  There is no evidence to suggest that aggressive glucose control with insulin in the non-diabetic patient is beneficial; wait with watchful deliberation and the glucose will usually return to normal levels with no intervention.

Frequent neurological assessment

It is important to frequently assess neurological status frequently after ROSC as this can help us prognosticate. Take the time to do a very quick assessment ideally before the administration of anaesthetic agents and paralysis. Document clearly pupillary size/reactivity, GCS (and its break down) and any respiratory effort or gasping. 

Adjunctive investigations

Following ROSC a number of investigations will be needed to guide diagnosis and therapy. Routine bloods such as renal function, electrolytes, liver function tests, full blood count, and clotting are a basic standard. In cases of lactaemia and/or severe metabolic acidosis ammonia and toxicology is useful. Arterial blood sampling is invaluable to allow quick correction of any electrolyte abnormalities and help titrate ventilation settings and (in part) guide inotropic support. Arterial samples will also help uncover any exposure to carbon monoxide, especially in burns cases. 

From an imaging perspective, a chest X-ray is vital in ascertaining tube positioning and lung pathology as well as cardiac contours in case a congenital or acquired heart disease is suspected. Head CT is obviously useful in cases in keeping with traumatic arrest and NAI but timing of the CT and whether it should take place pre-departure to PICU or after depends largely on local trauma network protocols so should ideally be discussed with the regional trauma team lead and paediatric critical care transport team. 

Children that die or arrest unexpectedly in the UK are subject to a sudden unexpected death in infancy investigation (SUDI) so the appropriate referrals need to be made to the child protection team, police and social care. It is important to clarify that even near-miss cases merit triggering the same SUDI process to ensure that any NAI cases don’t slip through the net. 

Transport pearls

After ROSC the patients will need stabilisation and transfer to PICU for on-going management. Depending on the geographical location of your hospital and the availability of a critical care retrieval service you may have to transfer the patient yourselves or look after them until he/she is retrieved by transport team. A good transport and adequate neuroprotection can be achieved by applying these simple pearls: 

1. Aggressive temperature monitoring and control between 33°C and 37°C.
2. Monitor for seizures and pre-empt with long-acting antiepileptic accordingly.
3. Correct electrolytes and hypoglycaemia and monitor frequently.
4. Nurse the patient a 45° degree angle.
5. Aim for a higher end of normal BP and use inotropes to achieve this. If you can’t insert an arterial line, have the NIVBP cycle every couple of minutes. 
6. In cases of trauma, blood products should be used for volume. In an atraumatic arrest, balanced solution boluses are less harmful than 0.9% saline; don’t forget that you are still likely to need blood products. 
7. Aim for a pCO2 of 4.5-5.5 kPa; use your continuous EtCO2 monitor to titrate ventilation. 
8. Vigilant and through history/examination to rule out NAI. Free up a member of the team to do a thorough history from the family, always suspect NAI until proven otherwise especially in children under 6 months. 
9. Know your anaesthetic drug side-effects (atropine dilates pupils for example so impairs our ability to monitor for seizures). Primum non nocere. 
10. Intraosseous access can be used instead of a central line, have a low threshold to insert one and do it early.
11. Have a member of the team check-in with the family every 10-15 minutes to explain what is happening, this is a bad day at work for you but probably the worst day of their lives. 

Conclusion

Achieving ROSC is an important step to give our patients a shot at survival. In some cases, achieving ROSC can only give us enough time to prognosticate and understand that survival is not possible. In some other cases ROSC can be the stepping-stone for a good, meaningful survival with a good quality of life. To achieve that, we must be able to apply good quality post–ROSC care and aggressive, pre-emptive neuroprotection. Learn the PCAS disease process to beat the PCAS disease process.  The APLS algorithm has become the bread and butter of anyone that is involved in paediatric care. Understanding and applying the principles of post-cardiac arrest syndrome is equally vital in improving survival outcomes for our patients. Learn the pearls, use them, teach them and I guarantee that it will make a difference.