1. APNOEA
By: NICOLE STEVENS

2. Objectives Definition of apnoea
Identify causes and incidence of apnoea
Identify the categories of apnoea
Discuss the pathophysiology of apnoea
Discuss apnoea of prematurity
Identify risk factors for apnoea
Discuss nursing management of apnoea
Pharmacological management of apnoea

3. Introduction Apnoea is a disorder of respiratory control
It more commonly effects preterm infants
Is 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

4. Definition
The 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

5. Causes of Apnoea Day 1 – 2 Sepsis Hypoglycaemia
Impending respiratory failure
Polycythaemia
Days 3 – 6
PDA
Massive IVH
AOP

6. Causes of Apnoea Late Onset Sepsis
Progressive post-extubation atelectasis
Out grown dose of methylxanthine (eg. caffeine)
Presenting symptom of RSV infection

7. Incidence Apnoea occurs in Most infants < 30 wks
About 50% of infants at 30 – 32 wks
About 10% of infants at 34 wks
Usually resolves by 36 wks CA
Good evidence that it is not a risk factor for SIDS
No 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)

8. Categories of Apnoea
Apnoea has three major types: central, obstructive & mixed
CENTRAL APNOEA
No 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

9. Categories of Apnoea Central cont...
An information exchange occurs to (afferent) and from (efferent) the respiratory centre of the brain
An 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
The acidity of any fluid is measured by pH: this is related to the number of hydrogen ions in the soloution. Normal pH for the body is Above 7.4 is considered alkaline and below 7.4 is considered acidic. The chemoreceptors in the brainstem respond to the pH of the CSF. CO2 in the blood rapidly diffuses across to the CSF – if the CO2 level in the blood increases then the CO2, H+ and bicarbonate ion concentrations in the CSF increase, this makes the CSF more acidic and causes hyperventilation. Conversely if the levels drop and the CSF becomes alkaline it causes and inhibition, or depression, of the respiratory centre. In neonates this can occur when they are intubated and overventilated – if they were to be extubated when their CO2 levels are too low there is a high chance that their respiratory drive won’t be strong enough and they would have to be reintubated.

10. Categories of Apnoea
The 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

11. Categories of Apnoea
Other 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
Receptors in the wall of the bronchi respond to irritant substances and cause coughing, breath holding and sneezing. The receptors in the lung tissue and the chest wall are thought to prevent overdistention and conversely act to promote further inspiration when lung volume is low. The information from the these receptors in the lung is carried to the respiratory centre along the vagus nerve (the aortic body also uses this pathway).

12. Categories of Apnoea
Once 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)
The most important muscle for inspiration is the diaphragm. Any disease that affects the efferent pathways from the respiratory centre to C3,4 and 5 and then the phrenic nerve to the diaphragm, may cause severe difficulty in breathing. Trauma to the cervical cord, above C3, is normally fatal for this reason.

13. Categories of Apnoea
So, 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)

14. Categories of Apnoea
Opioid 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

15. Categories of Apnoea OBSTRUCTIVE APNOEA
Results from attempts to breath through an occluded airway
Can be the result of a congenital problem (smaller airway patency)
Other causes of obstructive apnoea are an aspirated foreign body or vocal cord paralysis
Congenital probs: choanal atresia, pierre robin sequence (small lower jaw can’t accommodate normal sized tongue), enlarged tongue (trisomy 21, Beckwith Weiderman syndrome), laryngomalacia (supraglottic inspiratory collapse), tracheomalacia (collapse of the trachea)

16. Categories of Apnoea MIXED APNOEA
Has characterisics of both mixed and obstructive
Eg: 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

17. Primary & Secondary Apnoea
Types 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
Because after delivery of an infant it is impossible to differentiate between primary apnea and secondary apnea, assume the infant is in secondary apnea and begin resuscitation immediately.

18. Apnoea of Prematurity
AOP 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 immaturity
Alterations in CO2 response
Hypoxia
Immature sleep patterns
Greater risk of pharyngeal obstruction
Greater risk of laryngeal obstruction
More reflux induced problems

19. Upper Airway Anatomy
Prematurity can increase the risk of obstruction/apnoea because of an increased risk of collapse/weakness in the pharynx or larynx.
Vagul mediated response secondary to acid reflux exposure. Remembering the vagul nerve is responsible for feeding back to the respiratory centre of the brain. Excessive suctioning also interfers with the vagul pathway and can cause episodes of apnoea.

20. Sleep States
Premature babies are at increased risk of apnoea because of immature sleep patterns
Breathing in infants is strongly influenced by sleep states
Apnoeic spells occur more frequently in REM sleep than active sleep
REM sleep predominates in preterm infants (80% of the day)

21. Differential Diagnosis
Although AOP is the most common cause of apnoea there are other conditions that may cause or aggravate apnoea:
Anatomical anomalies of upper airway
Infection: sepsis, NEC
Temperature disturbances
Metabolic: hyper or hypocalcaemia, hypoglycaemia, hyponatraemia, acid/base disturbances
Haematological: anaemia, polycythaemia
Pulmonary: impending respiratory failure
Debatable if transfusions of PRBC causes a decrease in apnoea in Hb levels of 100 or greater, but does appear to decrease incidence of apnoeas in levels less than this

22. Differential Diagnosis
CVS 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)

23. Monitoring
All infants < 34 wks gestation should be monitored for apnoea
Monitoring 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

24. Evaluation of Apnoea Take a history, including apgar scores
Physical examination
Sepsis risk?
Consider age (GA, and day of life)
See if apnoeic events are associated with feeds
Determine frequency of events and intervention required (if any)
Evaluated associated bradycardia and cyanosis
Repeated apnoeas with quick recovery, or any profound apnoeas need to be reported to medical personnel

25. Investigations
Septic workup (FBE, CRP, blood culture +/- SPA of urine & LP)
Other pathology: Electrolytes, TBG, gases
Chest Xray
Abdominal Xray
Neurological investigations (CrUS, MRI, physical assessment)
Reflux investigations

26. Emergency Management Provide 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 HELP
If still no response, continue IPPV and consider intubation

27. Symptomatic Management
If an infectious aetiology is suspected treat with antibiotics
Correct any electrolyte disturbances
Supportive management for respiratory compromise
Consider 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 supplementation
GI considerations: NEC, obstruction, dysmotility

28. Ongoing Management
Not 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

29. Ongoing Management
Position 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

30. Pharmacological Management
Methylxanthines 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
Methylxanthines promote bronchial smooth muscle relaxation which helps dilate constricted airways, stimulates diuresis to help relieve congestion, and act as a mild cardiac and CNS stimulant. They are well absorbed and readily distributed, but if the GI state is poor then uptake will be irregular.

31. Pharmacological Management
CAFFEINE
Has 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

32. Pharmacological Management
Caffeine 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

33. Pharmacological Management
Caffeine cont...
Other infants may remain symptomatic and continue on caffeine beyond term corrected age
Infants born at < 28wks GA will often remain symptomatic of AOP beyond term corrected age
Because 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)

34. Other Management CPAP Used to manage obstructive and mixed apnoeas
Splints the nasopharynx and prevents pharyngeal collapes
Stabilizes the chest wall musculature
Alters various reflexes
Increases functional residual capacity
Initial settings would be 5 – 7 cm/H2O, adjusted according to clinical response
NETS should be consulted if in a non-NICU centre

35. Parents
Inform 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 treatment
Explain need for ongoing monitoring (including after medications are ceased)
Provide reassurance
Consider CPR training for any parents who have had a baby in a SCN or a NICU

36. 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.
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 – 22.
Neonatal Handbook: Apnoea. (2011).

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