By: NICOLE STEVENS

ObjectivesDefinition of apnoeaIdentify causes and incidence of apnoeaIdentify the categories of apnoeaDiscuss the pathophysiology of apnoeaDiscuss apnoea of prematurityIdentify risk factors for apnoeaDiscuss nursing management of apnoeaPharmacological management of apnoea

IntroductionApnoea is a disorder of respiratory controlIt more commonly effects preterm infantsIs rare among full term healthy infants and, if

present usually indicates an underlying pathology

Several mechanisms have been proposed to explain apnoea, and many clinical conditions have been associated with its development

Apnoea of prematurity (AOP) is seen in infants < 37 wks gestation, with the incidence increasing as gestational age decreases

DefinitionThe cessation of respiratory inflow; it is a

disorder of respiratory control common in premature infants

Pathologic apnoea is defined as a respiratory pause of greater than 20 seconds or any pause in respirations associated with cyanosis, marked pallor, marked hypotonia, or bradycardia (Theobald et al).

Apnoea of prematurity (AOP) is a pathological apnoea with no definable cause in infants < 37 wks gestation, usually presenting between days 3 – 7 of life

Causes of ApnoeaDay 1 – 2SepsisHypoglycaemiaImpending respiratory failurePolycythaemiaDays 3 – 6SepsisImpending respiratory failurePDAMassive IVHAOP

Causes of ApnoeaLate OnsetSepsisProgressive post-extubation atelectasisOut grown dose of methylxanthine (eg.

caffeine)Presenting symptom of RSV infection

IncidenceApnoea occurs inMost infants < 30 wksAbout 50% of infants at 30 – 32 wksAbout 10% of infants at 34 wks

Usually resolves by 36 wks CA

Good evidence that it is not a risk factor for SIDSNo evidence that AOP causes subsequent neurodevelopmental

morbidity, although recurrent apnoea is concerning because of the effects of the repeated episodes of tissue hypoxia (especially on the gut and the brain)

Categories of ApnoeaApnoea has three major types: central, obstructive &

mixedCENTRAL APNOEANo respiratory effort, displayed by a lack of chest wall

movement, and no breath sounds heard on auscultation

The central controlling area for breathing, called the respiratory centre, is in the lower part of the brain stem, in the medulla oblongata

The automatic breathing rhythm is controlled by inspiratory and expiratory neurons; this automatic rhythm can be altered by afferent information

Categories of ApnoeaCentral cont...An information exchange occurs to (afferent) and

from (efferent) the respiratory centre of the brainAn afferent supply of information travels to the

respiratory centre of the brain from central chemoreceptors, peripheral chemoreceptors, other areas of the brain and from the lungs

Chemoreceptors are cells that respond to chemical stimuli; central chemoreceptors are located in a part of the brain stem and they respond to the acidity of the CSF and the output from these cells influences breathing

Categories of ApnoeaThe peripheral chemoreceptors that feedback

to the respiratory centre are the carotid and aortic bodies – which are small pieces of tissue containing chemoreceptors that respond to O2 & CO2 levels in arterial blood

The carotid body in particular provides continual feedback; if the PaO2 goes below 80mmHg or the PaCO2 goes above 40mmHg then there will be an immediate increase in breathing rate

Categories of ApnoeaOther parts of the brain can also provide

feedback to the respiratory centre and cause an alteration in respiratory rate eg: conscious or deliberate hyperventilation, hyperventilation in response to intensely emotional or distressing situations or sights, and hyperventilation in response to massive blood loss (coordinated by the autonomic system in the brainstem and the vasomotor centre in the brain stem)

The lungs: provide feedback via stretch receptors in the elastic tissues of the lung, the chest wall and the pulmonary blood vessels; the bronchi also have receptors cells

Categories of ApnoeaOnce messages are received by the respiratory

centre it will send messages back out to the body via the efferent nerves

They pass down the spinal cord to the diaphragm, intercostal muscles & accessory muscles of inspiration in the neck

The diaphragm is supplied by the phrenic nerve (C3-5)

The intercostal muscles by the segmental intercostal nerves (T1-12)

The accessory muscles by the cervical plexus (C1-4)

Categories of ApnoeaSo, in summary, central apnoea occurs when there

is a lack of respiratory effort due to a failure in the feedback messages getting to the respiratory centre or a failure of the respiratory centre to send the messages out to the peripheral nerves and respiratory muscles required for oxygenation and ventilation

This can be due to immaturity in the system as seen in premature infants who have a decreased response to hypercapnia; head trauma; and toxin-mediated apnoea (analgesics, anaesthetics, infections)

Categories of ApnoeaOpioid drugs, such as morphine, pethidine &

fentanyl (as well as illicit substances such as heroin), depress the respiratory centre’s response to hypercarbia

Some anaesthetic agents may also do this (such as with women that require a GA for caesarean section)

These drugs can cross the placenta to the fetus and when born the infant can have have profound apnoea and require prolonged assistance with IPPV until spontaneous respirations are established

Categories of ApnoeaOBSTRUCTIVE APNOEAResults from attempts to breath through an

occluded airwayCan be the result of a congenital problem

(smaller airway patency)Other causes of obstructive apnoea are an

aspirated foreign body or vocal cord paralysis

Categories of ApnoeaMIXED APNOEAHas characterisics of both mixed and

obstructiveEg: a premature infant with central apnoea

who has an obstruction due to nasal congestion brought on by a viral illness

Gastro oesophogeal reflux is thought to cause this mixed picture as regurgitated gastric contents may occlude the airway and block laryngeal chemoreceptors from sending signals for dilation to the brain

Primary & Secondary ApnoeaTypes of apnoea at delivery:Primary: when asphyxiated the infant responds

with an initial increase in respiratory effort, they then become apnoeic and heart rate drops – but they will be quickly responsive to tactile stimulation +/- IPPV

Secondary: when asphyxia continues beyond primary apnoea, the infant responds with gasping respirations, falling HR and BP; they take a last breath, enter the secondary apnoea phase and death will occur if resuscitation does not commence immediately. Will not be responsive to stimulation

Apnoea of PrematurityAOP is a diagnosis of exclusion and should only be

considered after secondary causes have been excluded

Premature babies are more at risk or apnoea because of :

Central immaturityAlterations in CO2 responseHypoxiaImmature sleep patternsGreater risk of pharyngeal obstructionGreater risk of laryngeal obstructionMore reflux induced problems

Upper Airway Anatomy

Sleep StatesPremature babies are at increased risk of

apnoea because of immature sleep patternsBreathing in infants is strongly influenced by

sleep statesApnoeic spells occur more frequently in REM

sleep than active sleepREM sleep predominates in preterm infants

(80% of the day)

Differential DiagnosisAlthough AOP is the most common cause of

apnoea there are other conditions that may cause or aggravate apnoea:

Anatomical anomalies of upper airwayInfection: sepsis, NECTemperature disturbancesMetabolic: hyper or hypocalcaemia,

hypoglycaemia, hyponatraemia, acid/base disturbances

Haematological: anaemia, polycythaemiaPulmonary: impending respiratory failure

Differential DiagnosisCVS disorders: causes of cardiac failure or

impaired oxygenation eg. PDA, congenital defects, arrhythmias

CNS disorders: IVH, intracranial haemorrhage, seizures, asphyxia, increased intracranial pressure, cerebral abnormalities

Drugs: prenatal (narcotics, betablockers, MgSO4, maternal smoking) and postnatal (sedatives, hypnotics, narcotics, prostaglandin)

MonitoringAll infants < 34 wks gestation should be monitored

for apnoeaMonitoring can be with a full cardiorespiratory

monitor, SaO2 and heart rate monitor or an apnoea monitor only

Type of monitoring required will depend on other factors: gestation of the baby, availability of equipment & what level of care can be provided at the particular hospital

If the preterm baby can not be adequately monitored & managed they need to be moved to a hospital that can provide an appropriate level of care

Evaluation of ApnoeaTake a history, including apgar scores Physical examinationSepsis risk?Consider age (GA, and day of life)See if apnoeic events are associated with feedsDetermine frequency of events and intervention

required (if any) Evaluated associated bradycardia and cyanosisRepeated apnoeas with quick recovery, or any

profound apnoeas need to be reported to medical personnel

InvestigationsSeptic workup (FBE, CRP, blood culture +/-

SPA of urine & LP)Other pathology: Electrolytes, TBG, gasesChest XrayAbdominal XrayNeurological investigations (CrUS, MRI,

physical assessment)Reflux investigations

Emergency ManagementProvide tactile stimulation Reposition, paying attention to minimising

airway obstruction, ie. Get chin off chest – position head in a neutral or slightly extended position

Suction airway briefly, repeat tactile stimulation

Provide IPPV in air/oxygen – CALL FOR HELPIf still no response, continue IPPV and

consider intubation

Symptomatic ManagementIf an infectious aetiology is suspected treat with

antibioticsCorrect any electrolyte disturbancesSupportive management for respiratory compromiseConsider managment of cardiovascular issues eg.

indocid for PDA, inotropes for low BP or poor cardiac contractility

If CNS issues: antiseizure medication, antimicrobials (menigitis), ventricular decompression

Consider PRBC and ongoing iron supplementationGI considerations: NEC, obstruction, dysmotility

Ongoing ManagementNot all episodes of apnoea require treatment;

the following is suggested list from the NETS handbook:

Episodes needing brief stimulation for cyanosis & bradycardia: > 6 events every 12 hrs

Episodes needing vigorous stimulation & oxygen: > 1 event every 24 hrs

Episodes needing IPPV +/- oxygen: > 1 event every 24 hrs

Ongoing ManagementPosition infant to avoid upper airway

obstruction (neck rolls, prone or side lying)Give smaller volume feeds (increase frequency

with smaller volumes and/or reduce TFI if possible), to avoid excessive stomach distention

Consider maintaining temperature at lower end of normal spectrum

Low amounts of ambient oxygen (ie cot oxygen at 23-24%) – must have continuous SaO2 monitoring, and upper limit lowered to prompt weaning to avoid hyperoxia

Pharmacological ManagementMethylxanthines and continuous positive airway

pressure (CPAP) form the mainstay of treatment of apnoea in neonates; mechanical ventilation is reserved for when the apnoea is resistent to these treatments

Methylxanthines include caffeine and theophylline(oral form) & aminophylline(IV form); are thought to stimulate breathing efforts in neonates and have been used in clinical practice since the 1970’s

Cochrane review (2010) suggests caffeine preferable to theophylline

Pharmacological ManagementCAFFEINEHas a comparable efficacy to theophylline but

with less side effects, and does not require regular blood sampling for levels

Caffeine has a longer half life (so only requires once daily administration), more reliable enteral absorption and there are less instances of having to reduce doses due to tachycardia and feed intolerance

Different institutions will vary in practice guidelines for prophylactic administration and maintenance doses

Pharmacological ManagementCaffeine cont..Loading dose 20mg/kg (IV or oral)Then maintenance dose of 5mg/kg daily(may

see increases in this dose in symptomatic infant to 10mg/kg)

Dose may be ceased in the asymptomatic infant from 34-36wks CA, or in some cases, the infant may be allowed to ‘grow out of the dose’ – not increasing the dose as the infants weight increases

Pharmacological ManagementCaffeine cont...Other infants may remain symptomatic and

continue on caffeine beyond term corrected ageInfants born at < 28wks GA will often remain

symptomatic of AOP beyond term corrected ageBecause of caffeines long half life (approx.

100hrs) infants should be monitored for 5 – 7 days post cessation of medication (apnoea monitors are usually sufficient if the infant is otherwise well)

Other ManagementCPAPUsed to manage obstructive and mixed apnoeasSplints the nasopharynx and prevents

pharyngeal collapesStabilizes the chest wall musculatureAlters various reflexesIncreases functional residual capacityInitial settings would be 5 – 7 cm/H2O, adjusted

according to clinical responseNETS should be consulted if in a non-NICU

centre

ParentsInform and educate parents of risk of apnoea

(particularly if they have had a premature baby)

Inform if apnoeas are occurring and if treatment is required

Explain expected length of treatmentExplain need for ongoing monitoring

(including after medications are ceased)Provide reassuranceConsider CPR training for any parents who

have had a baby in a SCN or a NICU

Reference List Aggarwal,R.,Singhal,A.,Deorar,A.,& Paul,V. Apnea in the Newborn.

Division of Neonatolgy. Department of Paediatrics. All India Institute of Medical Sciences. www.newbornwhocc.org

Hansen, T.N., Cooper, T.R. and Weisman, L.E. (1995) Neonatal Respiratory Diseases handbooks in Health Care Co., Newtown, Pennsylvania

Theobald,K.,Botwinski,C.,Albanna,S.& McWilliam,P. (2000). Apnea of Prematurity: Diagnosis, Implications for Care and Pharmacologic Management. Neonatal Network, Vol 19. No. 6 17 – 22.

Neonatal Handbook: Apnoea. (2011). www.rch.org.au/nets/handbook