APNEA OF PREMATURITY

Definition and Incidence  

Apnea is defined as the absence of spontaneous breathing or airflow after 20 seconds, or less if associated with bradycardia or cyanosis.  The incidence of apnea increases with decreasing gestational age, and is rare in babies over 35 weeks gestation at birth.                

Birth Weight

Incidence (%)

Over 2500 gm

0.2%

Less than 2500 gm

2% overall

Less than 1800 gm (34 wks)

25%

Less than 1500 gm (32 wks)

54%

Less than 1000 gm (28 wks)

Nearly 100%

Classification

The classification of apnea is as follows:

Central apnea - respiratory efforts are absent

Obstructive apnea - respiratory efforts are present but airflow is impeded

Mixed apnea - elements of both central and obstructive apnea are present during the same episode. 

Etiology/Pathogenesis

Understanding the physiologic mechanisms of respiratory control in the neonate allows for a rational approach to the management of apnea in the neonate.  These chemical and reflex controls of breathing are principally a maturational process. 

1.  Chemoreceptor function:

2. Respiratory reflexes:

3.  Medullary/Respiratory center depression:

4.  Cortical activity:

5.  Obstruction:

Differential Diagnosis

1.  Apnea of prematurity (idiopathic) - Most common form of apnea.  Primarily affects premature infants with onset in the first 7-10 days of life but less common in the first 1-2 days.  It has been suggested that carbon dioxide response is further decreased in preterm infants who exhibit apnea.

2.  Apnea secondary to disease or special procedures

Management and Diagnosis of Apnea

All infants less than 35 weeks at birth or of birth weight < 1800 grams should be monitored for apneic spells for at least 1 week.  Electronic monitoring includes heart rate and respiration.  

Prevention. To prevent apneic episodes, avoid events to the infant that may be precipitating factors. This would include: mechanical stimulation of the posterior pharynx, rapid changes in oxygen, depressant drugs, airway obstruction from improper positioning, cold stimulation to the face, and oral feedings in small or sick infants.

Evaluation.  After the first apneic spell, the infant should be evaluated for a possible underlying cause and treatment initiated if evaluation yields an etiology.

1.Obtain the following:

2. Consider the following if examination and evaluation deem further evaluation is necessary:

Treatment.   When apneic spells are repeated or prolonged (> 2-3 times/hr) or require frequent bag and mask ventilation, treatment should be initiated in order of increasing invasiveness and risk.

  1. Avoid reflexes that may trigger apnea.
  2. Provide oxygen if pulse oximetry shows oxygen saturations under 92%. Then administer oxygen in slightly increased concentrations to maintain the saturations in the 92-95% range. DO NOT ADMINISTER IF OXYGEN SATURATIONS ARE NOTED ABOVE 95%.  Oxygen is hazardous because it increases the risk of ROP.
  3. Continuous positive airway pressure (CPAP) at 8 cmH2O can decrease the number of apneic episodes.  CPAP is effective in mixed and obstructive apnea. Nasal CPAP may increase posterior pharyngeal mucus plugging requiring additional airway care. Adding ventilatory breaths (Sipap) may add additional stimulation.
  4. Increasing afferent stimuli to the infant may help decrease the apneic spells. These include: providing tactile stimulation with mild apneic spells, decreasing the environmental temperature to the low end of the neutral thermal environment.
  5. Increasing the respiratory center activity can be done using drug therapy (see below for dosages). Methylxanthines decrease apnea by: a) central effect to increase the ventilatory response to carbon dioxide, b) increasing the level of cyclic AMP by inhibition of phosphodiesterase or c) improving diaphragmatic contractility. Metabolism of the methylxanthines is variable and unpredictable with much greater half-life than present in the adult.   Because caffeine citrate, which is a metabolite of theophylline, has a much wider therapeutic range than theophylline or aminophylline, toxicity is less likely and has replaced theophylline as the drug of choice. Caffeine can be given PO or IV.
  6. Mechanical ventilation may be necessary if all previous methods of intervention have failed.

Clinical Approach Based Upon Apnea Severity

1. Mild Apnea. Defined as 3 to 4 episodes per day and easily responsive to stimulation. In this situation, close observation and monitoring should be continued with intermittent cutaneous stimulation as necessary.  Decreasing the environmental temperature to the low end of the baby's appropriate neutral thermal environmental range should be considered.

2.  Severe Apnea. Defined as 3-4 episodes per hour or if bag and mask ventilation is required to terminate an episode.  In this situation, once all possible etiologies (sepsis, NEC, electrolyte imbalance) have been evaluated one may begin drug therapy.

a. Caffeine Citrate. Loading dose 20 mg/kg IV. Maintenance dose 5-7.5 mg/kg/1 day. Serum levels are not generally performed.

b. Use of nasal CPAP at 6-8 cm H2O may be initiated before using, or as an adjunct to caffeine.

Use of caffeine has been found to be associated with decreased risk for BPD; therefore, some experts prefer starting caffeine before the onset of apnea in high-risk babies (< 30-31 weeks).

3.  Persistent Apnea.  

Although most infants resolve their apneic spells by 36 weeks post-conceptional age, some persist until 37-40 weeks post-conceptional age.  The infant may require reevaluation to detect an etiology for the apnea (i.e. neurologic problems, feeding problems such as GE reflux and anatomic causes of airway obstruction).

These infants may require restarting caffeine if spells reoccur after discontinuation.  Consideration should be made for evaluation for home monitoring.   Remember that monitoring may help reduce the risk of undetected apneic spells, but studies have shown NO decrease in the incidence of Sudden Infant Death Syndrome (SIDS) associated with use of home monitors. Infants with BPD on home oxygen and any infant discharged on caffeine should receive home monitoring.  Consideration for monitoring may also be given to other high risk populations such as siblings of SIDS victims; these siblings are twice as likely as other babies to have SIDS.   More importantly, the family is often very anxious.  

Generally, infants should be apnea free for 10 days following discontinuation of caffeine before they are discharged home. If caffeine is not administered, a period of 7 days without apnea is the general rule. However, studies suggest a shorter "apnea countdown" for more mature infants.

Reference

Darnall, R.A., Kattwinkel, J., et al. Margin of safety for discharge after apnea in preterm infants. Pediatrics. 100(5):795-801,1997.


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