Apnea of Prematurity

1. APNEA OF PREMATURITY
BY DR OKATA ONYEKAKUCHKWU DAVID (MBBS, UPH)
DEPARTMENT OF PAEDIATRICS
S.C.B.U.
UPTH

2. OUTLINE
 Introduction
 Classification
 Epidemiology
 Aetiology
 Pathophysiology
 Clinical Presentation
 Diagnosis
 Treatment
 Prognosis
 Prevention

3. INTRODUCTION
 Prematurity is a term for the broad category of neonates born at less
than 37 weeks' gestation. Preterm birth is the leading cause of neonatal
mortality and the most common reason for antenatal hospitalization.
 Apnea is defined as the cessation of breathing.
 Apnea of prematurity is defined as cessation of breathing by a
premature infant that lasts for more than 20 seconds OR the cessation
of breathing for less than 20 seconds if it is accompanied by hypoxia
(oxygen (O2) desaturation) or bradycardia.

4. INTRODUCTION
 Bradycardia in a premature neonate is considered clinically significant
when the heart rate slows by least 30 bpm from the resting heart rate
(120 – 160bpm).
 An O2 saturation level of less than 85% is considered pathologic in this
age group, as is a decrease in O2 saturation should it persist for 5
seconds or longer.

5. CLASSIFICATION
 Apnea can be classified into 3 categories based on the presence or
absence of upper airway obstruction;
 Central apnea is defined as complete cessation of respiration. Here
there is no signal to breathe being transmitted from the CNS to the
respiratory muscles.
 This is due to immaturity of brainstem control of central respiratory
drive. The premature infant also manifests an immature response to
peripheral vagal stimulation.

6. CLASSIFICATION
 Obstructive apnea is the cessation of airflow in the presence of
continued respiratory effort.
 It occurs due to obstruction of airflow within the airway, particularly at
the level of the pharynx. Once collapsed mucosal adhesive forces tend
to prevent reopening of the airway during expiration. Neck flexion and
excessive secretions would worsen this form of apnoea.
 Mixed apnea is a combination of both types of apnea. Many episodes
of apnea of prematurity may start as either obstructive or central, but
then involve elements of both, becoming mixed in nature.

7. CLASSIFICATION
 Other forms of
 Apnea of infancy occurs when apnea persists in a neonate older than
37 weeks after conception.
 Periodic breathing is defined as periods of regular respiration for as
long as 20 seconds followed by apneic periods of 10 seconds or less
that occur at least 3 times in succession.
 Hypoventilation syndromes

8. CLASSIFICATION
Periodic Breathing Apnea of Prematurity
Respiratory pause here appear to be
self-limited, and ventilation does
continue, albeit cyclically.
Occurs mostly during non REM sleep.
No treatment is required
Respiratory pauses here are normally
associated with swallowing movements
Neonates who have prolonged apnea
may fail to reinitiate ventilation entirely
or do so ineffectively.

9. EPIDERMIOLOGY
 Incidence of Apnea of prematurity is inversely related to gestational
age;
 About 7% of neonates with G.A of 34 – 35 weeks.
 About 15% of neonates with G.A of 32 – 33 weeks.
 About 54% of neonates with G.A of 30 – 31 weeks.
 Nearly 100% of neonates with G.A of ,<29 weeks or weight <10000gm.

10. AETIOLOGY
Potential causes of Apnea of prematurity and bradycardia include;
 Central nervous system; Intraventricular hemorrhage, drugs, seizures, hypoxic
injury, herniation, neuromuscular disorders, Leigh syndrome, brainstem infarction or
anomalies (e.g., olivopontocerebellar atrophy), after general anesthesia
 Respiratory; Pneumonia, obstructive airway lesions, upper airway collapse,
atelectasis, extreme prematurity (<1,000 g), laryngeal reflex, phrenic nerve paralysis,
severe hyaline membrane disease, pneumothorax, hypoxia
 Infectious; Sepsis, necrotizing enterocolitis, meningitis (bacterial, fungal, viral),
respiratory syncytial virus, pertussis
 Gastrointestinal; Oral feeding, bowel movement, esophagitis, intestinal perforation
 Metabolic; ↓ Glucose, ↓ calcium, ↓/↑ sodium, ↑ ammonia, ↑ organic acids, ↑ ambient
temperature, hypothermia
 Cardiovascular; Hypotension, hypertension, heart failure, anemia, hypovolemia,
vagal tone
 Others; Immaturity of respiratory center, sleep state

11. PATHOPHYSIOLOGY
 Ventilatory drive is primarily dependent on response to increased levels
of carbon dioxide (CO2) and acid in the blood. A secondary stimulus is
hypoxia. Responses to these stimuli are impaired in premature infants
due to immaturity of specialized regions of the brain that sense these
changes. In addition, premature infants have an exaggerated response
to laryngeal stimulation (a normal reflex that closes the airway as a
protective measure).

12. PATHOPHYSIOLOGY
 Pathophysiological Mechanisms include,
 1) Central respiratory regulation
 Immaturity and/or depression of the central respiratory drive to the
muscles of respiration have been accepted as key factors in the
pathogenesis of apnea of prematurity. [1] Vulnerability of the ventral surface
of the medulla and adjacent areas in the brainstem to inhibitory
mechanisms is the likely explanation for why apneic episodes occur in
prematurely born infants.
 2) Sleep state and apnea
 In extremely preterm infants, the paucity of quiet sleep, together with an
extremely compliant rib cage, makes paradoxical chest-wall movements
almost a constant phenomenon. Paradoxical chest movement may
predispose the baby to apnea by decreasing functional residual capacity
(FRC) and limiting oxygenation.

13. PATHOPHYSIOLOGY
 3) Upper airway instability and muscles of the chest wall
 Premature infants have pharyngeal or laryngeal obstruction during
spontaneous apnea. Many muscles of the upper airway, especially the
genioglossus muscles, have been widely implicated in mixed and
obstructive apnea affecting both infants and adults.
 4) Effects of adenosine
 Adenosine and its analogs cause respiratory depression. Adenosine
antagonism is proposed as a mechanism to explain the therapeutic effect of
aminophylline.

14. PATHOPYSIOLOGY
 5) Gastroesophageal reflux
 GER and apnea are common in preterm infants. During an apneic
episode, loss of respiratory neural output may be accompanied by a
decrease in lower esophageal tone, and GER occurs.

15. CLINICAL PRESENTATION
 History
 Initial identification and assessment of apnea
 The bedside caregivers—namely, the nurse in the neonatal intensive care
unit (NICU) the respiratory care practitioner—identify the problem for the
physician. Apnea should be distinguished from periodic breathing and
documented. Use of a cardiorespiratory monitor is essential for identifying
apnea of prematurity (AOP) and for monitoring the patient's blood
pressure.
 Pulse oximetry may be helpful for measuring the severity and duration of
central O2 desaturation. Caregivers should attempt to define the type and
severity of the patient's apnea.

16. CLINICAL PRESENTATION
 The University of Washington published indications for different treatments based on
the severity of apnea of prematurity. This classification for apnea of prematurity uses
the terms spontaneous, mild, moderate, or severe. Note the following:
 A spontaneous event might be defined by apnea with minimal physiologic changes,
an event of brief duration, one associated with self-recovery, or an event only
occurring once or twice in 24 hours.
 Mild or moderate events involve apnea, bradycardia, and/or O2 desaturation of
intermediate magnitude. These events require therapeutic interventions less rigorous
than those needed for severe episodes.
 A severe event entails prolonged apnea associated with clinically significant and
persistent bradycardia, as well as O2 desaturation (ie, central cyanosis). A severe event
requires vigorous stimulation, administration of an increased concentration of
inspired O2, and/or assisted ventilation (eg, bag-mask ventilation).

17. CLINICAL PRESENTATION
 Physical Examination
 Physical examination should include observation of the infant's breathing patterns
while he or she is asleep and awake. The prone or supine sleeping positions and other
lying postures may be important during this clinical observation.
 Important to the assessment of neonatal apnea is the identification of airway
abnormalities (eg, choanal obstruction, anomalies of the palate, jaw deformities, neck
masses) and conditions in distant organs that influence breathing (eg, brain
hemorrhages, seizures, pulmonary disorders, congenital heart disease).
 Findings in the head and neck and other obvious major and minor anomalies identified
may suggest chromosomal abnormalities or a malformation syndrome. Appropriate
work-up must then follow.

18. CLINICAL PRESENTATION
 Physical examination elements
 Monitor the baby's cardiac, neurologic, and respiratory status.
 Observe the infant for any signs of breathing difficulty, desaturation, or bradycardia
during feeding.
 Reflex effects of apnea include characteristic changes in heart rate, blood pressure, and
pulse pressure. Note the following:
 Bradycardia may begin within 1.5-2 seconds of the onset of apnea.
 Apneic episodes associated with bradycardia are characterized by decreases in heart rate
of more than 30% below baseline rates.
 This reflex bradycardia is secondary to hypoxic stimulation of the carotid body
chemoreceptor or a direct effect of hypoxia on the heart.
 Transient bradycardias also occur relatively often in very low birth weight infants who also
have apnea of prematurity. [66] These events are not associated with apnea, but they are
presumed to be mediated by an increase in vagal tone.
 Pulse oximetry may reveal clinically significant desaturation. However, pulse oximeters
typically have a delay in recording the event.

19. INVESTIGATION
Apnea of prematurity can be readily identified from other forms of infant apnea such
as obstructive apnea, hypoventilation syndromes, breathing regulation issues during
feeding, and reflux associated apnea with an infant pneumogram or infant
apnea/sleep study.
 Central apnea - Absence of nasal airflow and wall movement (This diagnostic
finding on polysomnography recording may be used in lieu of pneumogram.)
 Obstructive apnea - Lack of airflow despite chest-wall movement
 Mixed apnea - Combined results of central and obstructive apnea
Full blood count; if an infection is suspected
Serum E/U/Cr; if electrolyte derangement is suspected
Chest Radiograph; if child has persistent unexplained lower airway symptoms
(wheezing, repitive regurgitation after feeding)

20. PNEUMOGRAM

21. DIFFERENTIAL DIAGNOSIS
 Differential Diagnoses
 Anemia of Prematurity
 Neonatal Sepsis
 Pediatric Respiratory Failure
 Respiratory Syncytial Virus Infection

22. TREATMENT
 Medical Treatment
 Goal of medical therapy
 The principal goals of treating apnea of prematurity (AOP) are to address
its cause and to provide appropriate medical management. The primary
disease process must be identified and treated.
 When all causes of apnea other than prematurity are excluded during the
diagnostic work-up, apnea of prematurity is the presumptive etiology.
 Stimulation
 Tactile stimulation is usually sufficient to terminate an isolated apneic event
caused by central apnea.

23. TREATMENT
2) Administration of oxygen
 Supplemental oxygenation or bag-mask ventilation is indicated in infants with signs
of bradycardia or desaturation.
3) Use of CPAP
 CPAP has been used to treat apnea in preterm neonates. (CPAP, 2–5 cm H2O)
 CPAP effectively treats mixed and obstructive apnea, but it has little or no effect on
central apnea. This limitation suggests that CPAP may reduce the frequency of
apnea by means of several mechanisms, including stabilization of the partial
pressure of O2 (PaO2) by increasing the functional residual capacity (FRC), by altering
the influence of stretch receptors on respiratory timing, or by splinting the upper
airway in an open position.
 The efficacy of CPAP is related to its ability to splint the upper airway and prevent
airway obstruction

24. TREATMENT
4) Medical Treatment
 Medical treatment is indicated when apneic episodes number 6-10 or more per day; when the infant does
not respond to tactile stimulation; or when an event requires O2 and/or bag-mask ventilation to terminate
apnea, bradycardia, and/or desaturation.
 Methylxanthines
 1) Caffiene; caffeine is a more potent centrally acting respiratory agent with fewer side effects. It binds
competitively to adenosine receptors A1 and A2a causing inhibition. Caffiene increases respiratory rate and
minute volume, stimulates respiratory centres and increases pulmonary blood flow and sensitivity of central
medulla areas to hypercapnia.
 Caffeine therapy may reduce the rate of bronchopulmonary dysplasia in very low-birth-weight infants.
Loading doses of 20 mg/kg of caffeine citrate are followed 24 hr later by maintenance doses of 5 mg/kg/24
hr orally or intravenously.
 2) Theophylline or Aminophylline; Loading doses of 5–7 mg/kg of theophylline (orally) or aminophylline
(intravenously) should be followed by doses of 1–2 mg/kg given every 6–12 hr by the oral or intravenous
routes.
**These doses should be monitored by observation of vital signs, clinical response, and serum drug levels
(therapeutic levels: theophylline, 6–10 μg/mL; caffeine, 8–20 μg/mL).

25. TREATMENT
3) Doxapram, known to be a potent respiratory stimulant, acts predominantly
on peripheral chemoreceptors and has been used in neonates with apnea of
prematurity, but has a limited therapeutic role due to side effects.
**Administration of carbon dioxide
Carbon dioxide is known to be the natural stimulator of breathing, and a
study has shown that if the baseline PCO2 is increased in a premature infant,
facilitated by providing a low concentration of inhaled carbon dioxide, this
abolishes the apneic events in the premature infants; however, it is not as
effective as theophylline and is not practical to deliver constant concentration
of carbon dioxide, and, therefore, it should not be done.

26. PROGNOSIS
 Unless severe, recurrent, and refractory to therapy, apnea of
prematurity does not alter an infant's prognosis. Associated problems
of intraventricular hemorrhage (IVH), bronchopulmonary dysplasia
(BPD), and retinopathy of prematurity are critical in determining the
prognosis for apneic infants. Apnea of prematurity usually resolves by
36 wk Post conception Age and does not predict future episodes of
sudden infant death syndrome. Some infants with persistent apnea are
discharged as long as cardiorespiratory monitoring can be performed
at home. In the absence of significant events, home monitoring can be
safely discontinued after 43 wk PCA.

27. PREVENTION
 General Health Promotion
 Specific Protection
 Early Diagnosis and Treatment
 Limitation of disability
 Rehablitation

28. THANK YOU!