Post ROSC care

Cite this article as:
Costas Kanaris. Post ROSC care, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.29109

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.

This is his capillary gas on arrival in the ED
  1. What are your clinical priorities?
  2. What clinical problems do you anticipate in the immediate post-arrest phase?
  3. Who do you call for help?
  4. What do you do with the family whilst you’re managing the patient?
  5. What investigations do you need?

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. 

We can minimize the extent of secondary brain injury with simple proactive, neuroprotective measures:

  • Strict normothermia
  • Aggressive seizure prophylaxis
  • Avoiding hypoxia and hyperoxia
  • Tight circulatory monitoring and support
  • Patient position
  • Eucapnia and normoventilation
  • Vigilant glucose monitoring
  • Frequent neurological assessment, especially before the administration of anaesthetic agents and paralysis

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.  

If you have given a paralytic for intubation, do not fall into the trap of thinking that the patient is not seizing, only an EEG or CFAM can tell you that. It is better to err on the side of caution.

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.

Seizures Module

Cite this article as:
Peter Tormey. Seizures Module, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.27858
TopicSeizures
AuthorPeter Tormey
DurationUp to 2 hours
Equipment requiredNone

Basics (10 mins)

Main session: (2 x 15 minute) case discussions covering the key points and evidence

Advanced session: (2 x 20 minutes) case discussions covering grey areas, diagnostic dilemmas; advanced management and escalation

Quiz (10 mins)

Infographic sharing (5 mins): 5 take home learning points

We also recommend sharing a copy of your local guideline.

Unprovoked seizures are common in children with around 8% having a seizure by 15 years of age

  • Most seizures are brief, self-limiting and generally cease within 5 minutes
  • Convulsive status epilepticus is the most common paediatric neurological emergency worldwide and the 2nd most common reason for PICU admission in the UK.
  • A seizure is the clinical expression of abnormal, excessive, synchronous discharges of neurons residing primarily in the cerebral cortex

Was the seizure a primary event or secondary to something else?

Seizures can be due to an underlying epilepsy or can be acute symptomatic seizures due to:

  • Hyponatraemia
  • Hypoglycaemia
  • Hypocalcaemia
  • High fever
  • Toxin exposure
  • Intracranial bleeding
  • Meningitis

Was this really a seizure or should I consider other differentials?

Tonic clonic activity and incontinence are not specific for seizures so always consider differential diagnoses.

  • Differential diagnosis of a seizure:
    • Vasovagal syncope
    • Blue breath holding spell
    • Reflex anoxic seizure
    • Arrhythmia
    • Non-epileptic paroxysmal event

Seek out clues in the history:

A sudden fright or minor trauma followed by the child turning pale and seizing is suggestive of a reflex anoxic event secondary to a vagal reflex. Hypoxia can induce a short tonic-clonic event that looks like a generalized tonic-clonic seizure but the child will recover quickly.

A history of a temper tantrum crescendo-ing into the child holding their breath, turning blue and then seizing might make you think of a breath holding attack. Again, this child will recover quickly.

Standing in a hot, stuffy room, feeling lightheaded with some visual changes and echoey hearing sounds vasovagal. Compare this to a child who describes palpitations or is exercising before the event; this child could have had an arrhythmia.

A 7-year-old boy called Simon is brought to the ED by his parents. At approximately 7am they were awoken by noises coming from his room. They ran in and noticed that the left side of his face was jerking and he was drooling and making gurgling sounds. He wasn’t responding to them.

The movements stopped after 2 minutes. He was drowsy for a few minutes after and had difficulty talking and expressing himself for 15-20minutes after. They also noticed there was a slight drooping on one side of his mouth for 15-20 minutes.

He has now fully recovered and is bright and alert in ED with GCS 15/15 and a normal neurological exam.

What are some of the key elements of Simon’s past medical history that you must ascertain?

How would you classify his seizure? 

Are there clues in the history as to what specific seizure disorder he may have?

Would you perform any investigations at this point?

Does he need to be admitted? Does he need treatment? What follow up will you arrange?

Any history of hypoxic injury at birth?

Did he have any delay in meeting his developmental milestones?

How does his school performance compare to that of his peers?

Is there any history of similar events? Or unusual behaviours or word-finding difficulties on waking from sleep?

The key here is to determine if Simon is an otherwise well child or if there are details in his medical history, such as developmental delay, that may make him more prone to developing epilepsy

It is also important to determine if he perhaps has had more subtle seizures in the past that may have been missed

This is an opportunity to look at the International League Against Epilepsy infographic.

Simon has had a focal motor seizure with impaired awareness.

Specific seizure disorder: Simon’s seizure would be most in keeping with a clinical diagnosis of benign childhood epilepsy with centrotemporal spikes (BCETS) also known as benign rolandic epilepsy.

BCETS usually presents in early school age children with normal development. The most common seizure type is a focal motor seizure involving the face. There may or may not be impaired awareness. They can also be associated with facial numbness, hypersalivation, drooling, dysphasia and speech arrest. Motor activity in the upper, but not lower, limbs is common.  They may also progress to a generalized tonic-clonic seizure. Approximately 75% of seizures occur at night or on awakening and, therefore, can be easily missed. Patients may have a post-ictal paresis, often of one side of the face which can be concerning for a cerebrovascular accident. 


A blood glucose should be checked. 

Electrolytes are often checked with a first seizure but their utility decreases with patient age and degree of recovery. 5

As this history is strongly in keeping with a diagnosis of BCETS, an EEG is not strictly necessary to confirm the diagnosis, however, your local guideline for first seizure management should be followed.

There is no indication for neuroimaging at present.

Patients generally do not need to be admitted after a first seizure with no red flags:

  • Seizure related to head injury
  • Developmental delay or regression
  • Headache prior to seizure   
  • Bleeding disorder or on anticoagulant medication
  • Drug or alcohol use
  • Focal neurological signs or incomplete recovery
  • Seizure >5 minutes
  • Social concerns e.g. parental coping mechanisms or concerns over parental ability to recognize and seek medical attention if another seizure were to occur

Patients with an uncomplicated first seizure generally do not need to be commenced on treatment. BCETS in particular generally has a benign course and rarely requires treatment. 

All children who have a first seizure episode should be referred for paediatric follow up. This may be General Paediatric or Paediatric Neurology follow up and local referral pathways should be consulted. 

The International League Against Epilepsy have a useful infographic for managing a first seizure:

https://www.ilae.org/patient-care/first-seizure

For more information on managing a 1st afebrile seizure see: 

https://dontforgetthebubbles.com/first-afebrile-seizure/

Emily is a 4-year-old girl brought to ED with episodes of disturbed sleep for the last 3 weeks. This is her 4th visit to ED. She was previously diagnosed with “night terrors” and reassured. Her mum is concerned because the episodes are now occurring each night, having previously been 1-2 per week.

Her mum has videos of the episodes, which she shows you. The events usually occur shortly after going asleep. In the videos Emily wakes from sleep, looks terrified and stares straight ahead. The episodes go on for 2-3minutes. She usually vomits or retches towards the end of the episode. She goes back to sleep after. She is well during the day.

What could be going on here?

What interesting details in the history might lead you towards a specific diagnosis?

What could help differentiate between epileptic and non-epileptic events in this case?

What is the prognosis for these patients?

These episodes sound unusual and their frequency and severity seems more pronounced that what could be put down to normal variance in sleep pattern and arousal. Emily’s symptoms are not likely to be simple night terrors.

Seizures commonly occur in sleep and as a result can be missed or present subtly or without characteristic features.

There are several features in the history that would suggest Panayiotopoulous Syndrome (PS). 

PS is a focal epilepsy that occurs in children aged 1-14 years with a mean age of 5 years. The seizures are usually nocturnal

It is thought PS accounts for 6% of children with epilepsy.

There is a strong association with vomiting (70-85%) of patients. Visual symptoms are also closely related, given the seizures originate in the occipital lobe. Autonomic features can also be seen: pallor, tachycardia, miosis, coughing and hypersalivation.

They may also have head or eye deviation and focal or generalized clonic activity.

The diagnosis of PS is often delayed due to misdiagnosis with other causes of vomiting and autonomic manifestatons e.g encephalitis, migraine, syncope or gastroenteritis.

PS could easily be clinically misdiagnosed as night terrors. Night terrors are dramatic awakenings that usually happen during the first few hours of sleep. They share several characteristics with PS but there are also some subtle differences highlighted in the table below:

Clinical FeaturePSNight Terrors
Usual duration 5-10min++
Occur during the first few hours of sleep++
Autonomic Symptoms e.g tachycardia, tachypnea, sweating+++
Impaired awareness++
Child looks scared++
Starring+++
Running or walking around during episode++
Screaming++
Vomiting++
Thrashing of arms and legs++

Table 1. Clinical characteristics of PS and night terrors

It is not unreasonable to clinically diagnose night terrors if they present with characteristic events, more in keeping with night terrors than PS. However, if there are unusual features, such as vomiting, or exaggerated autonomic symptoms, or in a child who represents, then an alternative diagnosis should be considered. 

An inter-ictal EEG will usually be diagnostic in PS with occipital spikes, which are enhanced in sleep, the characteristic feature. In a child with unusual events occurring in sleep and a normal EEG, a video telemetry EEG may be useful to try and capture and characterise the events and outrule seizures as a possibility.

PS usually has a benign course with spontaneous remission commonly occurring within 2-3 years of onset. 

Seizures are generally infrequent but oxcarbazepine may be required to reduce seizure frequency.

Emma is a 3-year-old girl with a background of refractory epilepsy and developmental delay. Her current medications include levetiracetam, sodium valproate, clobazam and lamotrigine.

She is PEG fed but has been vomiting up her feeds for the last 2 days and mum is unsure if her medications have been staying down.

She normally has up to 20 short seizures per day at home, but this has been increasing in the last 2 days.

You get a pre-alert from the ambulance service: Emma has been having a generalised tonic clonic seizure for 15 minutes. Her mum gave her buccal midazolam at 5 minutes, but it has not had any effect.

The ambulance crew ask you can they repeat the dose of buccal midazolam?

Emma arrives in resus with the seizure ongoing. What is your management plan?

Emma has had two doses of benzodiazepines. What would be your next line agent? Who else should you be calling at this stage?

You decide to suggest 2 papers, the ConSEPT and EcLiPSE papers for your department’s next journal club and to discuss what effect they will have on your department’s practice. One issue you foresee is that a lot of the patients you see are already on maintenance levetiracetam.

Does this preclude children on maintenance levetiracetam from receiving IV levetiracetam in status epilepticus, as is the case with the use of phenytoin in patients who take it as maintenance treatment?

Emma’s seizure terminated with the second line agent and she was admitted under neurology for IV fluids and ongoing management of her seizures until she could tolerate her medications by PEG again. In this case her status epilepticus was likely due to her vomiting up her medications.

Had Emma’s seizure not stopped after the loading dose of phenytoin, what would your next steps be?

There is a risk of respiratory depression with any benzodiazepine. 

A Cochrane review9 in 2018 found that 25/346 (7.2%) patients treated with buccal midazolam experienced respiratory depression. There was no statistically significant difference in risk of respiratory depression between buccal midazolam and other benzodiazepines, administered via various routes. 

The drug information leaflet or Summary of Product Characteristics (SPC) for Buccolam® and Epistatus® recommend that only a single dose be administered at home by a caregiver and that additional doses should only be administered after seeking medical advice and, preferably, under medical supervision.

In this case, it would be reasonable to advise a second dose of buccal midazolam, presuming the paramedics had the necessary equipment and skillset to manage any respiratory depression that may occur. 

Factors that may influence your decision are: the ETA of the ambulance and if the child has a history of respiratory depression with benzodiazepines.

She should be managed as per the APLS guideline (please note this is the Australian APLS guideline and has been updated to include the use of levetiracetam as a second line agent. This has not yet been included in the UK APLS guideline, see discussion below):

At this point you should be informing PICU about the patient and your PEM consultant if you haven’t done so already.

The CONCEPT and ECLIPSE trials were published concurrently in May 2019.

These two studies looked at whether levetiracetam is non-inferior to phenytoin as a second line treatment in the management of convulsive status epilepticus in children.

This question was posed as phenytoin is linked to many adverse events including liver damage, Steven-Johnson syndrome, extravasation and reports of death due to dosing errors. As a result, and because of its biopharmacology, it is a resource-intensive drug to make up in an emergency.

Levetiracetam can be given over 5 minutes (phenytoin takes 20 minutes to infuse), is more compatible with IV fluids, has less drug interactions, and has a lower risk of adverse events.

The infographic below provides a nice summary:

You can find a more detailed summary at: https://dontforgetthebubbles.com/consept-eclipse-status-epilepticus/

It’s important to note that the primary outcomes of the two studies were different:

ConSEPT – The primary outcome was seizure cessation 5 minutes after the drug infusion and where possible the seizure cessation was verified independently via a video recording to reduce observer bias between the two groups.

EcLiPSE – In a key difference to the ConSEPT study the primary outcome was time “from randomisation to cessation of all visible signs of convulsive activity, defined as cessation of all continuous rhythmic clonic activity, as judged by the treating clinician”. As per the inclusion criteria this a very real world pragmatic approach.

The two studies concluded:

ConSEPT – Levetiracetam is not superior to phenytoin as a second line agent for convulsive status epilepticus

EcLiPSE – There is no significant difference between phenytoin and levetiracetam in the second-line treatment of paediatric convulsive status epilepticus for any outcome, including time to seizure cessation

Here is a section of the commentary from the post:

“While there were differences between the study designs, the primary outcome measure of timing being the largest, the fact that both studies found no difference probably means head-to-head there is little difference.

The nature of the statistical analysis means that both groups rightly point out that in their cohorts levetiracetam wasn’t superior in outcomes to phenytoin. A future pooled analysis could still demonstrate a difference, but it seems unlikely that a critical difference will be seen (especially for the safety element).

Given the wealth of evidence on the side effects of phenytoin it is surprising the incident rates were relatively low. Whether in study conditions more care was taken with drawing up and delivering the drug or that previous safety reviews were heterogenous in their inclusion criteria is difficult to know. However, the time to draw up phenytoin, and the background concerns on its potential harm, will lead some to suggest that the switch to levetiracetam is a logical one, regardless of its effectiveness against phenytoin.

The challenge faced by many units is a capacity for PICU beds. Because phenytoin is given over 20 minutes there is time to prepare for airway/anaesthetic intervention if it is unsuccessful in terminating the seizure. The use of levetiracetam may cause some to wonder if they should then try phenytoin either as a stop gap to bed availability or because the time in status now seems ‘shorter’ than normal. These are not statistical issues, these are pragmatic clinical conundrums.

The absence of a clear winner will further fuel this debate meaning it is unlikely in the immediate future we are going to see a change from the ALSG or similar organisations. However, local units may decide, in the clear absence of harm from levetiracetam, that it is a drug they should be adding into their treatment protocols.”

The EcLiPSE trial2 did not report any increase in adverse events in children who were on maintenance leveltiracetam and received a loading dose of IV levetiracetam. The ConSEPT trial excluded all patients who were on maintenance levetiracetam and phenytoin.

The use of phenytoin in status epilepticus in patients who are on maintenance phenytoin is avoided due to its potential cardiovascular side effects. As levetiracetam does not share these side effects and is generally safe and well tolerated it is reasonable to use it in children who are already on maintenance therapy. 

The EcLiPSE trial2 did not report any increase in adverse events in children who were on maintenance leveltiracetam and received a loading dose of IV levetiracetam. The ConSEPT trial excluded all patients who were on maintenance levetiracetam and phenytoin.

The use of phenytoin in status epilepticus in patients who are on maintenance phenytoin is avoided due to its potential cardiovascular side effects. As levetiracetam does not share these side effects and is generally safe and well tolerated it is reasonable to use it in children who are already on maintenance therapy. 

The current APLS guidance in the UK would be to proceed with RSI. As we have discussed above, the Australian APLS guidelines have changed, in view of the results of the ConSEPT and EcLiPSE, to include the use of an additional second line agent prior to proceeding to RSI. As reported in the ConSEPT trial, treatment with one drug and then the other reduced the failure rate by more than 50% at the expense of only an additional 10 minutes. 

For further discussions on advanced seizure management and RSI, the following podcast is recommended:

https://broomedocs.com/2019/06/paediatric-status-epilepticus-debate/

Caroline is a 13-year old girl who presents to ED with a first seizure. Her parents describe a generalised tonic clonic seizure that lasted 20 minutes.

She is an otherwise well girl who is doing well in school. The only concern in her past medical history is that she has been having frequent syncopal episodes for the last 12 months. She has been seen by her GP for this who reassured her that syncopal events were common on her age group and advised her to drink plenty of fluids and try and avoid triggers.

Her neurological exam is normal.

How would you proceed? 

Are there any investigations you could perform in the department to investigate the syncopal episodes she reports?

Is there any link between syncope or arrhythmogenic events and seizures?

Caroline is admitted for further cardiac investigations. She also has an EEG diagnostic for frontal lobe epilepsy which is linkced to ion channel abnormalities.

A blood glucose should be checked. If she has returned to her baseline and there were no red flags with regard to the seizure it would be reasonable to arrange outpatient follow up as per departmental protocol and advise her parents what to do if she should have further seizures.

An ECG and a lying-standing blood pressure should be performed.

Caroline has an ECG performed which has features consistent with Type 1 Brugada syndrome.

Seizures may be triggered by cerebral hypoperfusion due to an arrhythmic event. They can often be treated as a primary seizure and the underlying cardiac abnormality may be missed. Long QT syndrome in particular can present with seizures and almost half of affected patients are initially misdiagnosed and treated for epilepsy before the correct diagnosis is made.

Seizures can also be seen as a primary neurological abnormality, related to the cardiac abnormality. Brugada Syndrome is an autosomal dominant condition characterized by ECG alterations and a predisposition to tachyarrhythmias and sudden death. It is caused by a mutation in the genes SCNA5 and SCN1A. SCN5A codes for the alpha subunit of the voltage-gated sodium channel. As the condition is a channelopathy it can also be associated with epileptic seizures with the channelopathy affecting neuronal pathways. 

Caroline has a ECG which is consistent with features of Type 1 Brugada Syndrome.

There is coved ST segment elevation in V1 and V2 with a negative T wave. This is the only ECG abnormality that is potentially diagnostic and is often referred to as Brugada sign.

For an approach to the paediatric ECG have a look at the following DFTB post:

https://dontforgetthebubbles.com/approaching-the-paediatric-ecg/

For further reading on the specific ECG findings in Brugada Syndrome, please see:

https://litfl.com/brugada-syndrome-ecg-library/

Which symptom is more commonly seen with Panayiotopoulos syndrome than night terrors?

A: Staring

B: Terrified expression

C: Vomiting

D: Thrashing of arms and legs

E: Tachypnoea

70-85% of seizures in PS are associated with vomiting. Vomiting is not usually described in night terrors. The diagnosis of night terrors should be carefully applied to children having events disturbing their sleep that have a strong
association with vomiting.

Which of the following are side effects of phenytoin but not levetiracetam?

A: Mood disturbance

B: Cardiovascular toxicity 

C: Purple glove syndrome

D: Gingival hypertrophy

E: Stevens Johnson syndrome

The correct answers as B, C, & D

Although levetiracetam and phenytoin have several common side effects, cardiovascular toxicity, purple glove syndrome and gingival hypertrophy are more specific to phenytoin and are not generally seen with levetiracetam. Mood
disturbance is one of the most common side effects of levetiracetam. Stevens Johnson syndrome is also reported with levetiracetam.



Which of the following ECG findings are seen in Brugada syndrome:

A: Coved ST segment elevation in V1-3, >2mm

B: Prolonged PR interval

C: Negative T wave

D: Saddleback ST elevation, >2mm

E: LVH voltage criteria

The correct answers are A, C, & D

  • Brugada Type 1 has coved ST segment elevation in V1-3, >2mm, followed by a negative T wave. This is often referred to as Brugada sign.
  • Brugada Type 2 has >2mm of saddleback-shaped ST elevation
  • Brugada Type 3 can have the morphology of type 1 or 2 but with <2mm ST segment
  • elevation
  • Prolonged PR interval and LVH voltage criteria are not characteristic features of Brugada syndrome

1. Clinical Practice Guidelines : Afebrile seizures [Internet]. [cited 2020 Apr 20]. Available from: https://www.rch.org.au/clinicalguide/guideline_index/Afebrile_seizures/

2. Lyttle MD, Rainford NEA, Gamble C, Messahel S, Humphreys A, Hickey H, et al. Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial. Lancet. 2019 May 25;393(10186):2125–34

3. https://www.uptodate.com/contents/seizures-and-epilepsy-in-children-classification-etiology-and-clinical-features?search=seizures%20in%20children&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1

4. https://www.ilae.org/education/infographics

5. https://dontforgetthebubbles.com/first-afebrile-seizure/

6. Michael M, Tsatsou K, Ferrie CD. Panayiotopoulos syndrome: An important childhood autonomic epilepsy to be differentiated from occipital epilepsy and acute non-epileptic disorders. Vol. 32, Brain and Development. Elsevier; 2010. p. 4–9.

7. Ferrie CD, Grünewald RA. Panayiotopoulos syndrome: A common and benign childhood epilepsy. Vol. 357, Lancet. Elsevier Limited; 2001. p. 821–3.

8. Weir E, Gibbs J, Appleton R. Panayiotopoulos syndrome and benign partial epilepsy with centro-temporal spikes: A comparative incidence study. 2018 [cited 2020 May 4]; Available from https://doi.org/10.1016/j.seizure.2018.03.002

9. Mctague A, Martland T, Appleton R. Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children. Vol. 2018, Cochrane Database of Systematic Reviews. John Wiley and Sons Ltd; 2018.

10. Dalziel SR, Borland ML, Furyk J, Bonisch M, Neutze J, Donath S, et al. Levetiracetam versus phenytoin for second-line treatment of convulsive status epilepticus in children (ConSEPT): an open-label, multicentre, randomised controlled trial. Lancet. 2019 May 25;393(10186):2135–45.

11. Sandorfi G, Clemens B, Csanadi Z. Electrical storm in the brain and in the heart: Epilepsy and Brugada syndrome. Mayo Clin Proc. 2013 Oct 1;88(10):1167–73.

12. Camacho Velásquez JL, Rivero Sanz E, Velazquez Benito A, Mauri Llerda JA. Epilepsy and Brugada syndrome. Neurol (English Ed. 2017 Jan 1;32(1):58–60.



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Prepare for transport: Costas Kanaris at DFTB19

Cite this article as:
Team DFTB. Prepare for transport: Costas Kanaris at DFTB19, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.22605

Costas Kanaris is a paediatric intensivist working in Manchester. He is also internet-famous for his challenging #fridayquiz in which he presents a case, drip-feeding information, as the Twitter audience figure out the diagnosis and the best way to treat the patient in front of them.

This time he tries it in front of a live studio audience. Here is a teaser to tickle your brain.

 

This talk was recorded live at DFTB19 in London, England. With the theme of  “The Journey” we wanted to consider the journeys our patients and their families go on, both metaphorical and literal.

If you want our podcasts delivered straight to your listening device then subscribe to our iTunes feed or check out the RSS feed. If you are more a fan of the visual medium then subscribe to our YouTube channel. Please embrace the spirit of FOAMed and spread the word.

iTunes Button
 

 

Bubble Wrap Live – Top 5 papers in PEM: Edward Snelson at DFTB19

Cite this article as:
Team DFTB. Bubble Wrap Live – Top 5 papers in PEM: Edward Snelson at DFTB19, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.22057

In the three years since we launched the Bubble Wrap segment, we have been able to highlight a number of key articles in paediatric research.  In this talk from the popular Bubble Wrap Live! sessions, Edward Snelson brought us his top five favourite articles from the world of paediatric emergency medicine.

He eloquently confronts his own biases and suggests a more critical way of looking at the patient in front of us.

 

Here are the five articles Edward chose.

Foster SJ, Cooper MN, Oosterhof S, Borland ML. Oral prednisolone in preschool children with virus-associated wheeze: a prospective, randomised, double-blind, placebo-controlled trial. The Lancet Respiratory Medicine. 2018 Feb 1;6(2):97-106.
 
Kuppermann N, Dayan PS, Levine DA, Vitale M, Tzimenatos L, Tunik MG, Saunders M, Ruddy RM, Roosevelt G, Rogers AJ, Powell EC. A clinical prediction rule to identify febrile infants 60 days and younger at low risk for serious bacterial infections. JAMA pediatrics. 2019 Apr 1;173(4):342-51.
 
Borland ML, Dalziel SR, Phillips N, Lyttle MD, Bressan S, Oakley E, Hearps SJ, Kochar A, Furyk J, Cheek JA, Neutze J. Delayed presentations to emergency departments of children with head injury: a PREDICT study. Annals of emergency medicine. 2019 Jan 14.
 
Abe T, Aoki M, Deshpande G, Sugiyama T, Iwagami M, Uchida M, Nagata I, Saitoh D, Tamiya N. Is Whole-Body CT Associated With Reduced In-Hospital Mortality in Children With Trauma? A Nationwide Study. Pediatric Critical Care Medicine. 2019 Jun 1;20(6):e245-50.
 
Lyttle MD, Rainford NE, Gamble C, Messahel S, Humphreys A, Hickey H, Woolfall K, Roper L, Noblet J, Lee ED, Potter S. Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial. The Lancet. 2019 May 25;393(10186):2125-34.
 
 
DoodleMedicine sketch by @char_durand
 
 

This talk was recorded live at DFTB19 in London, England. With the theme of  “The Journey” we wanted to consider the journeys our patients and their families go on, both metaphorical and literal. DFTB20 will be held in Brisbane, Australia.

If you want our podcasts delivered straight to your listening device then subscribe to our iTunes feed or check out the RSS feed. If you are more a fan of the visual medium then subscribe to our YouTube channel. Please embrace the spirit of FOAMed and spread the word.

iTunes Button
 

 

Cannabinoids in Epilepsy at DFTB17

Cite this article as:
Team DFTB. Cannabinoids in Epilepsy at DFTB17, Don't Forget the Bubbles, 2018. Available at:
https://doi.org/10.31440/DFTB.16227

John Lawson is a paediatric neurologist at Sydney Children’s Hospital in Randwick. He has been Lead Investigator in the NSW Medical Cannabis in Epilepsy trial and is one of Australia’s leading experts on its use in near intractable seizures.

This is an almost evidence-free zone as the popular press has taken up the fight on behalf of patients.

So what are doctors to do, when parents come to them asking them to prescribe cannabis to their one year old child? This is not a talk about the wholesale legalisation of marijuana but about how, once again, we need to take a closer look at the evidence.


This double-blinded, placebo controlled trial reported in last years NEJM sets the scene for the the potential beneficial effects of cannabidiols.

Go ahead and watch the talk…

You can read this latest paper, a narrative review of some of the challenges facing the use of medical cannabis in the Medical Journal of Australia.

Chen KA, Farrar MA, Cardamone M, Lawson JA. Cannabis for paediatric epilepsy: challenges and conundrums. The Medical Journal of Australia. 2018 Feb 19;208(3):132-6.