Apnea Type	Type of Intervention	Treatment Indication
Spontaneous	No intervention required	Frequent episodes associated with desaturations (SaO2 <80%) and/or bradycardia (HR <90); e.g., one or more per hour over a long period of time such as 12-24 hours
Mild	Light touch, stroke back. Associated with desaturations <80% and bradycardia <90	Multiple episodes; more than 6 over a 12 hour period or 12 over a 24 hour period
Moderate	Move infant, i.e. roll over, reposition, etc. Oxygen administered	More than 2 episodes in a 24 hour period
Severe	Prolonged vigorous stimulation. PPV with or without oxygen	More than 1 episode in a 24 hour period

Note:Apnea, bradycardia, and/or cyanotic spells associated with feeding, handling, suctioning, mucus plugging, etc. should not be counted when determining whether to initiate methylxanthine therapy.

  Adverse Effects of Methylxanthine Therapy :(11)

• Excessive diuresis
• Increased blood sugar levels
• Increased cerebral metabolic rate (X2-3)
• Increased plasma glycerol
• Decreased anoxic survival in animal studies
• Increased lung glycogen metabolism
• Increased cardiac output
• Decrease cholesterol synthesis in glial cells
• Decreased cerebral blood flow
• Decreased cerebral cell growth and division
• Decreased retinal blood flow

Doxapram :

If theophylline therapy fails to reduce the frequency of apneic spells, a trial of the respiratory stimulant doxapram may be considered (12). Doxapram is administered only as a continuous infusion, initially at a rate of 1.0 to 1.5 mg/kg per hour. Once control is obtained, the infusion is decreased. Although increased doses up to 2.5 mg/kg per hour may be effective in infants who continue to have apnea at lower doses, the risk of toxicity is considerably increased.

Toxicity includes hyperactivity, jitteriness, seizure, hyperglycemia, mild liver dysfunction, and hypertension. Although these abnormalities resolve following discontinuation of the drug, toxicity and the need for continuous parenteral administration limit is widespread use.

Continuous Positive Airway Pressure (CPAP) :

CPAP is effective in treating both obstructive and mixed apnea, but not central apnea. CPAP is most commonly delivered by nasal prongs or by an endotracheal tube placed in the nasopharynx. Candidates for NCPAP consideration would be infants with moderate to severe apnea i.e. > 8 episodes in a 12 hour period or 2 episodes in 24 hours requiring bag and mask ventilation.

Apnea that continues inspite of optimum methylxanthine treatment may respond to low-level CPAP. Accordingly, a trial of CPAP (4-5 cmH2O) is warranted in addition to or as an alternative to ineffective methylxanthine treatment. Frequent apnea associated with marked bradycardia and/or arterial oxygen desaturation refractory to methylxanthines and/or CPAP should be treated with positive pressure ventilation.

Intermittent Mandatory Ventilation (IMV) :

If significant apnea persists despite using both pharmacotherapy and CPAP, the infant should be intubated and ventilated. Initial settings need to be clinically adjusted to prevent episodes of desaturation or cyanosis. In order to minimize barotrauma, short inspiratory times should be used along with minimal peak inspiratory and expiratory pressures. The infant may need to remain on a minimal rate for a few weeks while the respiratory control system matures.