Apnea of Prematurity

Definition

• cessation of breathing for more than 20 seconds or shorted if accompanied by
  • bradycardia
  • hypoxemia
  • cyanosis
  • oxygen saturation
  • hypotonia
  • pallor

Intermittent Hypoxia - short and repetitive episodes of hypoxemia and desaturation which not accompanied by bradycardia and apnea

Classification

• central apnea (40%)- inspiratory efforts are absent
• obstructive apnea (10%) - inspiratory efforts present, but airway obstruction is cause of hypoxia
• Mixed apnea (50%) - airway obstruction precedes central apnea most common cause of apnea

Epidemiology

• premature infants (almost all babies <28 weeks)
• present within week of birth
• cease by 34 to 37 weeks of PMA
• apnea in late preterm/term born infants - always associated with serious identifiable causes such as sepsis, hypoglycemia, birth asphyxia, intracranial hemorrhage, seizure, depression

Pathogenesis

• physiological immaturity of the control of breathing mechanisms
• these can be precipitated by
  • chemoreceptor response (decreased sensitivity to high carbon dioxide and low oxygen)
  • reflexes of posterior pharynx, stimulated by suction, choking on secretions
  • airway obstruction due to neck flexion, nasal obstruction
  • REM sleep (which predominate in preterm)
  • antiseizure medication induced breathing inhibition

Management of AOP

Who to monitor

• all preterm babies less than 34 weeks
• in case of ELBW babies (<28 weeks), apnea can persist beyond 40 weeks PMA

Emergency management of Apnea

• check hypoxia, bradycardia, and loss of tone
• stimulate the baby
• if no response to stimulation, start PPV (preferably with T-piece), with mixed air and oxygen
• CPAP and HFNC can be considered
• intubation and ventilation

Management of Apnea after stabilization

• identify the cause

Cause	Signs	Evaluation
Airway	secretion, KMC, feed regurgitation	correct feeding position
Metabolic disorders	Jitteriness, lethargy, fedding difficulty, CNS depression	Glucose, calcium, blood gas, electrolytes
Infection	Not looking well, lethargy, temperature, shock, sugar,	Blood culture, urine culture, CBC, CRP, CSF examination
NEC	feed intolerance, GI aspirate	Abdominal X ray
Anemia	blood loss	Hematocrit
Impaired oxygenation	hypoxia, tachypnea, RD	BG analysis, CXR
Temperature instability	lethargy	monitor temperature
Drugs	antenatal MgSO4, Antinatal AED	check drug level
IVH	seizure, pallor, bulging fontenalle	USG cranium
Inborn errors of metabolism	Jitteriness, poor feeding, lethargy, irritablity, CNS depression	lactate, ammonia, metabolic screening
PDA	tachycardia, bounding pulse, murmur, hyperkinetic precordium	CXR, Echo

Algorithm

Prevention of recurrence

Caffeine

• Drug of choice
• MOA : antagonism of adenosine receptors
• half life 5-7 days
• uses of caffeine in AOP
  1. stimulation of respiratory center of medulla
  2. enhances diaphragmatic contractility
  3. increased sensitivity to carbon dioxide
  4. mild diuretic effect
  5. increases minute ventilation
  6. decreases periodic breathing
• uses of caffeine in BPD
  1. reduce BPD through immunomodulatory effect
  2. antioxidant
  3. antifibrotic
  4. antiapoptotic
  5. regulation of angiogenesis
  6. diuretic effects
• adverse effects of caffeine
  • tachycardia
  • hypoglycemia
  • increased metabolism
  • sleep disturbances
• indications
  • preemies with risk of apnea
  • prior to extubation of ventilated preterm <32 weeks (<34 weeks - WHO)
  • limited prophylactic use
  • earlier caffeine use in 1st 3 days of life is beneficial
• loading at 20 mg/kg over 30 mins followed by 5mg/kg maintenance
• higher doses (30 to 80 mg/kg) can be tried if poor response to conventional doses, increased risk of IVH
• stop caffeine when child reaches 32 weeks (or 34 weeks if child born very preterm)

Aminophylline

• narrow therapeutic range
• increased side effects compared to Caffeine
• loading with 5-6 mg/kg and maintain with 1.5-3 mg/kg q8h - q12h

Oxygen

• free flow oxygen reduces apnea
• can be given as low FiO2

Avoid triggers

• suction to be done carefully
• avoid neck flexion
• avoid hypo/hyperthermia

When to discharge

• apnea free period of 5 to 7 days
• monitored closely at least till 44 weeks PMA, especially with associated BPD
• DTwP is associated with more apnea than DTaP