Cardiac arrest and post resuscitation of the brain

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Invited papers presented at the EPNS 2011 Cavtat meeting

Cardiac arrest and post resuscitation of the brain

Fenella Kirkhama,b,*aUCL Institute of Child Health, UKb Southampton General hospital, London WCIN 2AP, UK

a r t i c l e i n f o

Article history:

Received 28 March 2011

Accepted 17 April 2011

Keywords:

Hypoxic-ischaemic encephalopathy

Out-of-hospital cardiac arrest

In-hospital cardiac arrest

Near drowning

Electroencephalography

Evoked potentials

Prognosis

Hypothermia

Extracorporeal membrane

oxygenation

a b s t r a c t

Primary out-of-hospital cardiac arrest in childhood is rare but survival is a little better for

children than for adults, although the prognosis for infants is very poor. Hypoxic-

ischaemic encephalopathy after in-hospital cardiac arrest in children undergoing

complicated treatment for previously untreatable conditions is now a common problem

and is probably increasing. An additional ischaemic insult worsens the prognosis for other

encephalopathies, such as that occurring after accidental or non-accidental head injury.

For near-drowning, the prognosis is often good, provided that cardiopulmonary resusci-

tation (CPR) is commenced immediately, and the child gasps within 40 minutes of rescue

and regains consciousness soon afterwards. The prognosis is much worse for the nearly

drowned child admitted to casualty or the emergency room deeply unconscious with fixed

dilated pupils, requiring continuing CPR and with an arterial pH <7, especially if there is

little recovery by the time of admission to the intensive care unit. The use of adrenaline,

sodium bicarbonate and calcium appears to worsen prognosis. Neurophysiology, specifi-

cally serial electroencephalography and evoked potentials, is the most useful tool prog-

nostically, although neuroimaging and biomarkers may play a role. In a series of 89

patients studied after cardiac arrest in three London centres between 1982 and 1985, 39%

recovered consciousness within one month. Twenty seven percent died a cardiac death

whilst in coma, and the outcome in the remainder was either brain death or vegetative

state. EEG and initial pH were the best predictors of outcome in this study. Seizures

affected one third and were associated with deterioration and worse outcome. The advent

of extracorporeal membrane oxygenation (ECMO) and the positive results of hypothermia

trials in neonates and adults have rekindled interest in timely management of this

important group of patients.

ª 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights

reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3802. Specific causes of hypoxic-ischaemic encephalopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 380

2.1. Trauma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3802.2. Near drowning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 380

* Corresponding author. UCL Institute of Child Health, UKE-mail address: [email protected].

Official Journal of the European Paediatric Neurology Society

e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y 1 5 ( 2 0 1 1 ) 3 7 9e3 8 9

1090-3798/$ e see front matter ª 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.doi:10.1016/j.ejpn.2011.04.009


2.3. Sudden infant death . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3812.4. Electrocution injuries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3812.5. Lightning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 381

3. Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3813.1. Resuscitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3813.2. Prevention of secondary brain damage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 382

3.2.1. Management of intracranial hypertension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3823.2.2. Management of seizures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3823.2.3. Hypothermia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383

4. Outcome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3834.1. Patterns of neurological damage in survivors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383

4.1.1. Persistent vegetative state . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3834.1.2. Visual problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3834.1.3. Motor disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383

5. Prediction of outcome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3845.1. General information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 384

5.1.1. Age . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3845.1.2. Underlying aetiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3845.1.3. Nature of arrest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3845.1.4. Duration of arrest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 384

5.2. Clinical signs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3845.3. Neurophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 384

5.3.1. Conventional electrophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3845.3.2. Monitoring EEG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3855.3.3. Evoked potentials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 385

5.4. Neuroradiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3855.5. Biochemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 385

6. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 386Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 386References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 386

1. Introduction

Unexpected cardiac arrest in a previously well child is

uncommon,1e4 but occurs in infants (sudden infant death

syndrome),5 occasionally during exercise or as a consequence

of accidents such as trauma, near drowning, electrocution and

strangulation. In a North American study, the incidence of

paediatric out-of-hospital cardiac arrest was 8.04 per 100,000

person-years (72.71 in infants, 3.73 in children, and 6.37 in

adolescents) versus 126.52 per 100,000 person-years for adults.

Survival for all pediatric out-of-hospital cardiac arrest was

6.4% (3.3% for infants, 9.1% for children, and 8.9% for adoles-

cents) versus 4.5% for adults (P ¼ 0.03). In a Korean study, the

incidence of paediatric out-of-hospital cardiac arrest was 4.2

per 100,000 person-years (67.1 in infants, 2.5 in children, and

3.5 in adolescents).4 The improvement in the management of

complex conditions in children means that in-hospital

paediatric cardiopulmonary resuscitation is now common-

place in casualty, on the ward, in theatre and in intensive

care.6,7 Kirkham10 studied 89 children with HIE presenting to

three London hospitals between 1982 and 1985, only 4% of

whom had suffered an out-of-hospital arrest. The underlying

aetiology was cardiological in 72%, respiratory in 15% and

neurological in 6%. If ventilation is available, the prognosis for

in-patient paediatric cardiac arrest is better than for out-of-

hospital resuscitations, with an overall hospital survival of

20.9% and 16.1% having favorable neurological outcomes in

one study.8 However, survival is unusual without ventilation.9

2. Specific causes of hypoxic-ischaemicencephalopathy

2.1. Trauma

Accidental and non-accidental traumatic brain injury is

common; cardiorespiratory arrest may be secondary to the

severity of the head injury, to haemorrhage from associated

injuries or to brain stem or spinal cord damage and is a very

poorprognostic sign.11e15 In a recent series, 3/28 (11%) survived

to hospital discharge, 2 with respiratory arrest neurologically

intact; none survived if CPR was required for > 20 mins.11

2.2. Near drowning

Even in water-oriented societies, immersion accidents are

relatively rare (incidence 3e6 per 100,000,16 but over half the

children admitted to hospital survive17,18 and they often

require intensive management. The prognosis for the child

pulled from the water apparently dead is excellent, provided



that cardiopulmonary resuscitation is commenced immedi-

ately, that the child gasps within 40 min of rescue and regains

consciousness soon afterwards. The prognosis is much worse

for the child admitted to casualty or the emergency room

deeply unconscious (Glasgow coma score less than 519) with

fixed dilated pupils and apnoea,20 without a detectable pulse21

and therefore requiring continuing cardiopulmonary resusci-

tation, especially if there is little recovery by the time of

admission to the intensive care unit.22 In a meta-analysis,5 for

this group, 23% survived and 6% had good neurological

outcome. Laboratory measures suggesting poor outcome

include an arterial pH of less than 7.0023,24 and hyper-

glycaemia.25,26 Persistent seizures are a poor prognostic

sign.18 Several authors have found EEG to be a useful predictor

of outcome, particularly if there is deterioration compared

with the record performed at 24 h.27e29 Evoked potentials may

also be useful.30,31 None of these poor prognostic indicators

precludes a good outcome,18 although a combination makes

severe handicap or vegetative survival likely, since moderate

handicap is rare after near-drowning.32 Apparently miracu-

lous recoveries have occurred, mainly of children who have

been submerged in very cold water for long periods18 and

present to Casualty with a temperature of less than 33 �C.21

2.3. Sudden infant death

The risk factors for sudden infant death syndrome include

sleeping in the prone position, bed-sharing,maternal smoking

and alcohol use and infection or other illness. Childrenmay be

found to have died of presumed prolonged QT syndrome

secondary to cardiac ion channel mutations (diagnosable on

DNA from Guthrie) metabolic disease such as medium chain

acyl-coA deficiency carnitine palmitoyltransferase 1A vari-

ants or to be the victims of child abuse. Compared with the

extensive literature on the epidemiology and aetiology of

sudden infant death (SID), there is very little data available on

the prognosis for those infants who are resuscitated at the

scene or in hospital (“near-miss”SID). Infants presenting in

status epilepticus may have been the victims of hypoxic-

ischaemic events akin to “near-miss” episodes. Con-

stantinou33 described the clinical course in 14 patients. Half

were deeply unconscious on admission and succumbed

within 3 days. Five appeared conscious initially but later

deterioratedwith persistent status epilepticus, deep coma and

signs of brain stem dysfunction; the other two survivors were

unconscious on admission but also developed status epi-

lepticus. Overall the prognosis was extremely poor; only one

child survived without severe brain damage.

2.4. Electrocution injuries

These are unusual events in childhood, but can be devastating

in their consequences. Small children are most at risk of

electrocution in the home, while older boys are more

commonly involved in high tension electrical injuries.

Neurological problems can be directly caused by the electrical

injury or are secondary to the associated cardiac arrest.34

There is also evidence for late demyelination, particularly in

the spinal cord, and late extrapyramidal disorders.35 Atonic

and myoclonic seizures are not uncommon in the longterm,

and there is a very high incidence of emotional disorders in

adults. Children may occasionally recover after prolonged

coma.36

2.5. Lightning

Lightning injuries can occur at any age, but there are few

published data in children. Again, the pathology, which may

include haemorrhage, results either directly from the injury or

as a consequence of cardiac arrest.37 The prognosis is poor

with a 30% mortality and sequelae (not necessarily neuro-

logical) in the majority of survivors; cardiopulmonary arrest,

loss of consciousness at the scene and leg or cranial burns

suggest a poor prognosis. Acutely, the neurological manifes-

tations in children can include coma, seizures and ataxia;

changes in memory and mood can persist for long periods of

time.38

3. Management

3.1. Resuscitation

The prime aims of emergency resuscitation attempts are to

restore spontaneous circulation whilst maintaining suffi-

cient myocardial and cerebral blood flow to prevent irre-

versible ischaemic damage. Most studies of CPR have been

conducted in adults, in whom spontaneous circulation is

often successfully restored after cardioversion of ventricular

fibrillation or tachycardia. External cardiac massage (ECM),

introduced in the early 1960s, almost completely replaced

the previously standard open cardiac massage (OCM), as it

was less invasive and could be performed by anybody

anywhere. For children who have out-of-hospital cardiac

arrests from non-cardiac causes, conventional CPR (with

rescue breathing) by bystander is the preferable approach to

resuscitation, while for arrests of cardiac causes, either

conventional or compression-only CPR is similarly effec-

tive.39 As there is evidence for better outcome after in-

patient resuscitation by a paediatric trainee,6 Paediatric

Advanced Life Support (PALS) training should be mandatory

for doctors looking after children.40 For in-hospital arrests, it

is possible to generate higher mean arterial, coronary and

cerebral perfusion pressures with OCM41,42 and it may be

possible to institute emergency cardiopulmonary bypass or

extracorporeal membrane oxygenation,43e50 but this tech-

niques is invasive, requiring a highly experienced team and

there is currently little evidence for benefit.

Hyperoxia and hypocapnia51 should be avoided. The

drugs commonly used during cardiac arrest include the

inotrope adrenaline (epinephrine), sodium bicarbonate and

calcium but there are concerns that all three worsen

outcome. The prognosis is poor for children requiring

adrenaline for drowning and other causes of out-of-hospital

cardiac arrest.6,52 In Moler’s recent multicentre series,

receiving more than three doses of adrenaline was associ-

ated with poor outcome in 96% (44 of 46) of cases.52 Terli-

pressin may be an alternative.53 In addition to longstanding

concerns over the use of calcium,54 the use of sodium

e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y 1 5 ( 2 0 1 1 ) 3 7 9e3 8 9 381


bicarbonate/tromethamine also appears to be a predictor of

death.49,55

3.2. Prevention of secondary brain damage

Some patients recover consciousness very soon after a brief

episode of cardiac arrest and usually make a full recovery. In

others, the brainmay be severely and irreversibly damaged by

the initial insult; most of these patients either fulfil the clinical

criteria for brain stem death or have neurophysiological

evidence of a poor prognosis within 24 h of the event. It is the

management of the intermediate group, who remain uncon-

scious but with some evidence of brain stem function clini-

cally and cortical function neurophysiologically, which

remains extremely controversial, particularly as some

patients appear to deteriorate secondarily. Whilst awaiting

results of further studies, there are a few management strat-

egies which can be recommended as being probably safe but

of unproven efficacy; these should preferably be reserved for

the intermediate group who remain unconscious but without

evidence of irreversible damage.

3.2.1. Management of intracranial hypertension

3.2.1.1. Cardiac arrest. There are very few published data,

and many groups have given up monitoring and aggressively

managing intracranial hypertension in children with HIE for

fear of increasing the number of children left severely hand-

icapped or in a persistent vegetative state.56 However, as good

outcome has been reported in some cases in whom intracra-

nial hypertension has been vigorously prevented or managed,

e.g. with surgical decompression,57 monitoring should be

considered for the individual child. Intracranial pressure was

monitored in 18 of the patients in the Guy’s paediatric study57

andwas persistently raised (mean ICP greater than 10mmHg)

in 10 of these. The two children with good outcome and the

child who made a cognitive recovery but was left with

a spastic quadriparesis (probably due to a posterior fossa

haematoma) all had mean ICP between 9 and 15 mm Hg and

maximum ICP up to 35 mm Hg (i.e. above the normal range,

but mean CPP was maintained above 60 mmHg and CPP never

fell below 37 mm Hg. In the other 15 children, either the EEG

prior to ICP monitoring suggested a poor outcome58 or mean

CPP could not be maintained above 60 mm Hg and minimum

CPP above 40 mm Hg because of poor cardiac function or

persistent intracranial hypertension. Opening, maximum and

mean ICP did not predict outcome, but minimum and mean

CPP did.

Appropriate candidates have been well-resuscitated using

modern cardiopulmonary resuscitation techniques, so that

the EEG has recovered to diffuse slowing or better, despite

continuing unconsciousness or sedation for ventilation.

Cerebral perfusion pressure (CPP)must be frequently recorded

and managed appropriately.

3.2.1.2. Near drowning. Intracranial hypertension is

a common but not universal feature of the encephalopathy

which follows serious near-drowning incidents,59,60 although

again, whether or not treatment prevents secondary deterio-

ration is much more controversial.22,61 Intracranial

hypertension,59 low cerebral perfusion pressure,60 and low

cerebral blood flow25 are all predictors of death but do not

distinguish between intact and vegetative survival.Criteria for

ICP monitoring should be the same as for HIE.

3.2.2. Management of seizuresSeizures are not uncommon after cardiac arrest in children.

After near miss sudden infant death, a brief seizure may be

compatible with good outcome but status epilepticus carries

a very poor prognosis62 even if the child had recovered

consciousness between the event and the onset of

seizures.33,63 Many children are sedated and paralysed for

ventilation after cardiac arrest and so observation of seizures

may be impossible. There are very few data on the prevalence

of non-convulsive seizures (NCS) or non-convulsive status

epilepticus (NCSE) in childhood hypoxic-ischaemic encepha-

lopathy. NCSE is common in neonates after asphyxia, and in

comatose adults, and appears to predict death and poor

outcome. One third of the children in the Guy’s study10 had

a clinical fit or an EEG seizure discharge at some stage post-

arrest. Short seizures did not preclude good outcome, but

seizures or electrical discharges lasting longer than 20 min

were associated with secondary deterioration. It is becoming

widespread practice that unconscious children have an EEG to

determine establish whether clinically recognised seizures

have terminated or to distinguish subtle seizures from

movement disorders secondary to drug withdrawal.64e66

Routine or continuous EEG (cEEG) with or without video

recording seems to diagnose non-convulsive seizures or non-

convulsive status epilepticus (NCS or NCSE) and there is some

evidence for an association with outcome.66

There is a good case for giving therapeutic doses of

conventional anticonvulsants, e.g. benzodiazepines,

phenobarbitone, phenytoin, to children after global ischae-

mic insults either prophylactically or as treatment for clin-

ical seizures or electroencephalographic discharges,

particularly if the EEG background is compatible with good

prognosis. Continuous infusion of short-acting benzodiaz-

epines, such as midazolam, may be of benefit in certain

selected patients with status epilepticus. Chlormethiazole is

not recommended for the control of seizures after cardiac

arrest since the fluid volume is substantial and there is

a significant risk of volume overload if the patient has

a degree of acute renal failure. Although there are concerns

about the drug’s effect on the cardiac conducting system, it

is probably safe to use phenytoin (loading dose 20 mg/kg,

then 5 mg/kg/day in 2 divided doses with regular drug

levels) in patients who do not have ongoing cardiac

dysrhythmias provided that the drug is infused over at least

45 min. Phenobarbitone may also be effective in controlling

seizures in unconscious patients and again, it may be worth

pushing the drug dose towards the top end of the thera-

peutic range as additional sedation is not usually a problem.

Thiopentone coma is contraindicated because there are

significant problems with cardiac depression67,68 and with

diagnosing irreversible brain damage and this management

strategy has now been largely abandoned. Other anaes-

thetics such as ethomidate and althesin either do not have

a significant protective effect after ischaemia or are associ-

ated with unacceptable side effects.



3.2.3. HypothermiaThepublicationof randomisedcontrolled trials showingbenefit

in terms of survival and neurological outcome for hypothermia

in adults69e73 and neonates74e79 with hypoxia-ischaemia has

reopened the question of whether children who have had

a cardiac arrest would benefit from maintenance of hypo-

thermia, e.g. after near drowning, or immediate cooling, e.g.

after in- or out-of-hospital cardiac arrest of other aetiologies.

Although return of consciousness was commoner after resus-

citationduring thecoldseason inoneseries79 andhyperthermia

in the first 24 hours post-arrest predicts poor neurological

outcome,7 mortality was not related to hyperthermia7 and

return-of-circulation is more likely with a higher lowest

temperature recorded.52 Clinical experience with the use of

hypothermia in children with near-drowning suggested that

moderate hypothermia of 30e33� centigrade is associated with

a very significant risk of neutropaenia and infection.67 Mild

hypothermia has been used after cardiac arrest in children, but

typically in those predicted to do worse80; at present the avail-

able data do not make the case for benefit but it is clear that

randomisedtrialsareneeded.81e83Arecentsurveryofpaediatric

intensivists in theUnitedKingdomfound that abouthalfdiduse

cooling for children who had had a cardiac arrest for a median

durationof24e48h (range4e72h)atmediantarget temperature

of 34 �Ce35 �C (range 32 �Ce37 �C).More that two thirds of those

using hypothermia for children targetted a temperature range

higher than that applied in the published adult and neonatal

studies (33 � 1 �C), perhaps because of the previous negative

experience with lower temperatures in children.There may be

a case for selective cooling of the head or a reduction of the core

temperature to 32e34 �C after cardiac arrest in some children

despite the lack of controlled trials.82,83 If a cooling turban or

blanket is available, hypothermia may be initiated quickly

during in-hospital cardiac arrest and may be discontinued

equally rapidly for clinical examinations or if there are

unwanted effects. It will be interesting to see if xenon has

a synergystic effect.

4. Outcome

The outcome for cardiac arrest varies greatly from series to

series, depending on the selection of patients. For in-patients,

up to 64% are successfully resuscitated in paediatric series.

Survival drops rapidly so that longterm mortality reaches

60e90% even in children. In a recent series, 27% of children

survived and 18% had good neurological outcome, percent-

ages which were better than adults despite a lower proportion

with ventricular fibrillation as the first rhythm.84 The

proportion of those resuscitated from out-of-hospital arrest

tends to be lower,5 but in some series more awaken and

survive to discharge.

Overall, the prognosis for hypoxic-ischaemic encephalop-

athy in childhood is poor.33,85 In our series of 89 patients,10

only 35% recovered consciousness within one month and

just over a third of these had good outcome at follow up at

least 2 years later. Twenty seven percent died a cardiac death

whilst in coma, and the outcome in the remainder was either

brain death or vegetative state. In another paediatric series of

patients resuscitated in the emergency room, only 5 of 91

patients were discharged from hospital and only 2 of these

were normal.86 There was a higher survival rate (20%) in

O’Rourke’s series but none were normal.87

4.1. Patterns of neurological damage in survivors

There are few longterm follow-up data on children who have

suffered a cardiac arrest. It may be very difficult to document

specific neurological handicaps in a young child and these

may change with time in the developing brain. Occasionally,

considerable recovery takes place in the first year after injury

although this is more likely in the cognitive and visual

spheres; a severe mixed motor disorder apparent soon after

an ischaemic event usually persists andmay sometimesmask

improvement in intellectual function.

Survivors of near-drowning in childhood either make an

excellent recovery, sometimes withminormotor problems, or

are left in a vegetative state.32 However, for other causes of

cardiac arrest in the Guy’s study of paediatric cardiac arrest,10

moderate (n ¼ 3) and severe (n ¼ 7) handicap were seen at the

one month follow-up as well as vegetative state (n ¼ 3), but

good outcome (n ¼ 21) with no obvious deficit was also

common. Some of these children had died of their underlying

disease by the time of the more detailed two year follow-up,

but again in the survivors, good outcome or moderate hand-

icap were much commoner than severe handicap.

4.1.1. Persistent vegetative statePersistent vegetative state (PVS) may be defined as a state of

consciousness without awareness and is well recognised in

children after severe ischaemic insults.88 Although PVS is

a common outcome after intensive therapy for paediatric

near-drowning,25 the overall incidence appears to be lower in

children with HIE than in adults.89 For example in the Guy’s

study10 none of the 3 in a PVS at one month survived for more

than a year.

4.1.2. Visual problemsBlindness is a common consequence of coma due to cardiac

arrest in children.33,90 The occipital cortex is particularly

vulnerable to ischaemic damage either because the posterior

cerebral circulation is compromised directly or when there is

border zone ischaemia between the posterior and middle

cerebral arteries. In addition there is some evidence for

a retinopathy after cardiac arrest in childhood.91 Vision

recovers to some extent in many patients and some children

who are apparently blind for 2e3months after hypotension or

cardiac arrest eventually make a good recovery.90

4.1.3. Motor disordersQuadriparesis (often mixed dystonic and spastic) is a rela-

tively common consequence of HIE in infants and young

children.33 Dystonia with a delay in onset (mean delay 12.9

years) has been well described after hypoxic-ischaemic

insults in children and may respond to treatment with anti-

cholinergics or L-Dopa.35 A transient dystonic syndrome with

onset a few days after the insult has also been recognised and

may be related to changes in the balance of neurotransmit-

ters. Action myoclonus may occasionally develop and



sometimes responds to sodium valproate or clonezepam.

Spinal cord damage has been described.

5. Prediction of outcome

A number of papers have been published addressing the

problems of whether survival and neurological outcome can

be predicted after cardiac arrest and if so, which variables give

the best prediction and how soon after cardiac arrest a reliable

picture can be obtained. Authors have looked at general

information about the patient available at the time of the

arrest or soon afterwards, at clinical examination and at the

results of additional investigations such as EEG, biochemical

markers and neuroradiology.

5.1. General information

5.1.1. AgeBell and Hodgson92 found that coma was commoner in those

aged less than 10 years than in adults, but overall outcome

was not worse in the younger patients. In the Guy’s study,10

those who recovered conciousness by one month were

significantly younger (median 5 months) than those who did

not (median 2 years).

5.1.2. Underlying aetiologyThe range of conditions underlying cardiac arrest in childhood

is very wide and aetiology does not appear to be predictive of

outcome.10 Coma before cardiopulmonary resuscitation is

predictive of poor outcome, however. In Von Seggern’s

series,93 76% of those who were alert before cardiac arrest

survived more than 24 h whereas only 30% of those who were

unconscious survived more than 24 h. The outcome for

cardiac (rather than respiratory) arrest in the context of

trauma is poor.5,11 Prognosis is less good for obese children.94

5.1.3. Nature of arrestThere is no doubt that mortality and morbidity are lower for

respiratory than for cardiac or cardiorespiratory arrests. In

adults, the prognosis for survival and/or good neurological

outcome appears to be better if cardiac arrest is due to

ventricular fibrillation, which is less common in paediatric

arrests,86 than if it is due to asystole.

5.1.4. Duration of arrestFor arrests occurring in the emergency room86 or on the

general ward6 those who survive neurologically intact are

promptly resuscitated and respond rapidly. The situation

may be different for those who arrest in theatre or on ITU

and who receive prompt and effective resuscitation. Von

Seggern93 found that 26% of those requiring more than an

hour for stabilisation were alive and awake at 24 h. In the

Guy’s study,10 duration of cardiac arrest (asystole or rarely

VF) and of hypotension were both highly significantly related

to the one month outcome, but an occasional patient with an

arrest time of up to an hour made a good recovery. The

results were not affected by the time to resuscitation in this

study.

5.2. Clinical signs

There is no doubt that survival and good neurological

outcome are less common for those in coma after cardiac

arrest and that duration of coma is predictive of outcome.92

The timing of the clinical examination is very important

and there is a lot of evidence that serial testing is preferable to

a single examination. Although some isolated clinical signs

and combinations of signs appear to be highly predictive of

good or poor outcome, it may be impossible to predict

outcome accurately at an early enough stage to influence

management. In the Guy’s study,10 18 of the 43 children who

recovered consciousness within the first month apparently

had a modified Glasgow coma score less than 9 at 24 h, and 12

remained in this condition at 72 h. The problem with this

study of mainly in-patient arrest was that the children were

sedated and often also paralysed for ventilation, and

although efforts were made to withold drugs prior to exami-

nations, clinical signs may have been obscured. EEG added

a great deal of information, particularly within the first 24 h

(see below).

Clinical deterioration after initial improvement is well

recognised after paediatric cardiac arrest33,85 and is associated

with poorer outcome. In our paediatric series of 89 patients,10

23 showed partial recovery of consciousness and of brain stem

function, and recovery of the EEG to diffuse slowing or better,

and then deteriorated with poor eventual neurological

outcome. Factors associatedwith this secondary deterioration

included prolonged seizures (longer than 20 min), a positive

fluid balance of more than 7%, and a mean arterial pressure,

averaged over the first 24 h, of less than 50 mm Hg.

Absent pupillary response to light is common immediately

after cardiac arrest and may be compatible with recovery. It is

important to exclude drug effects, particularly atropine.

However, only one patient in the Guy’s paediatric series,10

with an absent pupillary response to light at 6 h regained

consciousness within the first month. In Moler’s recent mul-

ticentre series, bilaterally reactive pupils at 12 h were associ-

ated with lower mortality.52

5.3. Neurophysiology

Most children arrest in the context of another illness. As part

of their management, they are often already paralysed on the

intensive care unit, and are thus not accessible for clinical

examination. There is therefore a considerable literature

about the prediction of outcome using neurophysiological

techniques after paediatric cardiac arrest.95

5.3.1. Conventional electrophysiology

5.3.1.1. Background EEG. Several authors have described

grading systems for looking at EEGs after cardiac arrest.95,96 It

is clear that, in the absence of sedating drugs, EEGs which are

isoelectric or show only burst suppression are associated with

poor outcome,95 particularly if these patterns persist for more

than 24 h after cardiac arrest. A normal EEGwithin the first few

hours after cardiac arrest is usually predictive of goodoutcome

provided that no other insult supervenes. Intermediate grad-

ings, such as diffuse slowing with or without some faster



frequencies present, have less predictive power but combi-

nations of features in EEGs undertaken within the first week

after cardiac arrest often allow accurate prognosis.97 Serial

EEGs appear to be useful prognostically in non-traumatic

coma including hypoxic-ischaemic encephalopathy.58,62

Few authors have compared the predictive power of EEG

with clinical signs. Tardieu62 found EEG to be less useful than

clinical signs in distinguishing survivors with and without

handicap after mainly out-of-hospital cardiac arrest in

infancy; the EEG often deteriorated in those who were not

fully awake by 8 h. In contrast, in the Guy’s series of 89 mainly

in-patient paediatric arrests, the EEG pattern at 6 h, recorded

on either a three channel system (Oxford Medilog) or a cere-

bral function monitor (Medaid Ltd), was more powerful in the

prediction of outcome in a discriminant analysis than 6 h

Glasgow coma score, 6 h brain stem score or immediate

arterial pH,10 although again the EEG often deteriorated in

those initially predicted to do well.

5.3.1.2. Discharges. Electroencephalographic status epi-

lepticus may occur without obvious motor manifestations.

The appearance of intermittent spikes and sharp waves or

frank discharges is associated with the likelihood of a poor

final outcome but is not uniformly fatal if the background EEG

is continuous.

5.3.2. Monitoring EEGSeveral centres have used either the original cerebral

function monitor, which records an amplitude trace only, or

the cerebral function analysing monitor (CFAM),66,98 or the

compressed spectral array (CSA),98,99 both of which display

amplitude and frequency. Using the CFAM, the traces may

be graded although subtle features may not be recognised.

For the CSA, an unchanging trace is usually associated with

poor outcome. Deterioration of the pattern is also a poor

prognostic sign, but this may be more distressing for rela-

tives and nursing staff than serial EEGs. EEG monitoring

may be useful in the management of status epilepticus, but

should assist the interpretation of, rather than replacing,

serial EEGs.100

5.3.3. Evoked potentialsVisual, auditory brain stem and somatosensory evoked

potentials have been elicited in several studies of chil-

dren28,101-107 in non-traumatic coma including HIE. Brain stem

and somatosensory evoked potential have a role in the

prediction of outcome, particularly if the EEG is in an inter-

mediate group. Somatosensory evoked potentials appear to be

the most useful, while visual evoked potentials may be

misleading90 but predictive value is greater if the data from all

three modalities are combined.

5.4. Neuroradiology

Neuroimaging performed soon after cardiac arrest may show

cerebral swelling with effacement of the sulci or widespread

loss of grey-white differentiation or low density in the basal

ganglia or in the watershed regions. The “reversal sign” with

low density in the cerebral hemispheres and relatively higher

densities in the basal ganglia on computed tomography is not

uncommon.108 All these patterns are associated with poor

prognosis, but a normal CT scan does not guarantee a good

outcome.62 Several series have found this modality to be

useful prognostically109,110 T2-weighted, diffusion (Fig. 1) and

perfusion magnetic resonance imaging and proton spectros-

copy may be useful but must be interpreted with caution by

experts.106,111e118

5.5. Biochemistry

High blood glucose predicts poor outcome on admission after

out-of-hospital cardiac arrest and near-drowning25 although

the effect may be due to the duration of cardiopulmonary

resuscitation or the dose of adrenaline. In the Guy’s study of

mainly in-patient arrests, the first glucose after the arrest was

higher in those who did not recover consciousness than in

those who did (median 10.0 vs 7.7) but this did not reach

statistical significance (p ¼ 0.08).10

Acidosis on admission is associated with poor outcome

after paediatric near-drowning and the pH of the first gas was

highly significantly lower in those who did not recover

Figure 1 e Diffusion-weighted imaging in paediatric hypoxic-ischaemic encephalopathy A. Bilateral abnormality after

several cardiac arrests in an infant with supraventricular tachycardia B. White matter abnormality after near-drowning C.

Bilateral globus pallidus abnormality after near-drowning in a child who remained cognitively intact.



consciousness compared with those who did (mean 7.058 vs.

7.238) in the Guy’s paediatric study,10 and this variable was an

important discriminant in the prediction of outcome.

A number of authors have looked at the prediction of

outcome using serummarkers such as procalcitonin,119 S-100

and neuron specific enolase120,121 but there are not enough

data currently to determine whether they sufficiently sensi-

tive or specific to be used clinically.

6. Summary

Cardiac arrest in childhood is a different clinical problem from

that in adulthood as myocardial infarction is rare, but out-of-

hospital arrest does occur for a variety of reasons andwith the

increasing number of therapeutic options for serious but not

necessarily fatal disease, in-patient cardiac arrest and

hypoxic-ischaemic encephalopathy are not uncommon. The

prognosis for patients who are unconscious on admission

after out-of-hospital arrest (including sudden infant death

and near-drowning) is poor, and can usually be predicted by

clinical signs and general information about the arrest. The

outcome for children who suffer an in-patient cardiac or

respiratory arrest or profound hypotension is often deter-

mined by underlying illness. Since clinical signs are often

obscured, additional prognostic information from investiga-

tions such as EEG, evoked potentials and neuroimaging may

be very useful. In both groups, there are patients who would

be predicted to survive intact but who deteriorate secondarily

and either die or survive in a vegetative state. Neurophysi-

ology may also useful in identifying this group, who may

benefit from hypothermia and control of intracranial hyper-

tension and status epilepticus. Randomised controlled trials

of therapeutic hypothermia for paediatric cardiac arrest are

urgently needed. Other treatments proposed on the basis of

basic science research into pathogenesis of ischaemic damage

cannot be recommended at the present time.

Acknowledgements

Dr Kirkham was supported by the British Heart Foundation.

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Cardiac arrest and post resuscitation of the brain