Caffeine Treatment and Apnoea Monitoring


Reviewed by Clinical Practice Committee
July 2015
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Apnoea of prematurity


Apnoea of prematurity (AOP) is defined as cessation of breathing that lasts for more than 15 seconds and is accompanied by desaturation (SpO2 ≤80%) or bradycardia (HR ≤2/3 of baseline HR) lasting ≥ 4 seconds in infants born under 37 weeks’ gestation1, 2. The incidence of AOP is inversely correlated with gestational age and birth weight. Seven percent of neonates born at 34 to 35 weeks’ gestation, 15% at 32 to 33 weeks, 54% at 30 to 31 weeksc, and nearly all infants born at <29 weeks’ gestation or <1,000 g exhibit AOP4.Onset of AOP is usually between days 2 to 7 of life, peaking around day 3. AOP is due primarily to immaturity of respiratory homeostatic mechanisms and control of the upper airway (Table 1)5, but may be exacerbated by other complications of prematurity (see below). Most apnoeas in preterm infants are of mixed type, i.e., central and obstructive.

Table 1. Pathophysiologic mechanisms involved in AOP6

Central Mechanisms Peripheral reflex pathways Other
  • Decreased central chemosensitivity
  • Hypoxic ventilator depression
  • Upregulated inhibitor neurotransmitters (GABA, adenosine)
  • Impaired astrocyte development
  • Decreased carotid body activity

  • Increased carotid body activity

  • Laryngeal chemoreflex

  • Excessive bradycardic response to hypoxia

  • Genetic predisposition
  • Sepsis
  • Cytokines
  • Billirubin

Differential diagnosis of apnoea

A baby having apnoea needs a full assessment especially if the onset is before day 1 or after day 7. Potential causal or exacerbating factors need to be considered and excluded e.g. (this is not an exhaustive list).

Apnoea in a late preterm or term baby and late-onset apnoea or apnoea with onset on day1 would suggest the need to evaluate for other cause(s), predominantly sepsis.

Management of AOP

  1. Consider other causes of apnoea / treat accordingly – as above
  2. Positioning – Prone positioning can reduce frequency of AOP by improving thoracoabdominal synchrony and stabilising the chest wall7,8 .
  3. Optimise respiratory support. Consider starting or increasing positive pressure support, eg, CPAP at 6-8 cm H2O. CPAP enhances functional residual capacity, reduces the work of breathing, improves oxygenation and decreases bradycardia9. If the baby remains unstable on CPAP and caffeine citrate, consider NIPPV10. Intubation and mechanical ventilation should be considered if apnoeas require repeated IPPV via neopuff or significant stimulation (discuss with consultant).
  4. Caffeine citrate – Caffeine citrate treatment is effective in preventing or reducing AOP. In the CAP trial, caffeine citrate also reduced the incidence of BPD, severe ROP, use of postnatal steroids, cerebral palsy and cognitive delay at 18 to 21 months, especially if started within first 3 days in infants <1250g on positive pressure support11,12 . Benefits in motor function and visual perception persisted at 5 years of age13. Short-term use of high dose caffeine citrate (20 mg/kg) has been shown to reduce extubation failure in premature infants14
  5. Doxapram - Use of doxapram infusion can be considered if AOP continues to be a significant clinical problem despite high dose caffeine citrate and CPAP. The safety and efficacy of doxapram have only been studied in observational studies and caution should be exercised15,16.
  6. Transfusion may help increase O2 carrying capacity of the blood but the evidence is limited17 – consider in babies if obviously very anaemic.

There are no fixed guidelines on the initiation of any of these treatments, as the assessment of apnoea tends to be subjective, and each baby needs individual assessment. In general, exercise caution in giving caffeine citrate to babies with acute respiratory problems; apnoea often indicates respiratory deterioration needing respiratory support, not caffeine citrate, especially in the first 48-72 hours of life.

Monitoring babies with apnoea

Monitoring Caffeine Citrate Therapy

It is not necessary to do routine levels on stable babies20. Serum concentrations should be obtained if toxicity is suspected. Therapeutic range is: 26-150 micromol/L and toxicity is unlikely at <400 micromol/L. Testing is a send-away to Christchurch hospital.

Discontinuing Caffeine Citrate


Going home on Caffeine Citrate

Caffeine Citrate therapy in term infants

Caffeine citrate is sometimes prescribed in term infants with apnoeas or desaturation episodes. There is some observational data of its use in term infants with apnoea related to other reasons such as bronchiolitis21. Use for apnoea or desaturation in term infants is not very common and will usually be a consultant decision with or without the involvement of the respiratory team.


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