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Key messages

  • Apnoea of prematurity is a diagnosis of exclusion at under 34 weeks.
  • Management of apnoea requires acute resuscitation followed by diagnosis and treatment of specific causes.
  • Apnoea on day 1 may not be due to idiopathic apnoea of prematurity. Consider sepsis or impending respiratory failure.
  • Symptomatic control with medication or ventilation may be required.
  • Apnoea of prematurity is not a risk factor for SIDS.

Apnoea is defined as no effective respiratory effort for ≥ 20 seconds or for > 10 seconds if associated with bradycardia (< 100 bpm), oxygen desaturation, cyanosis or pallor. Apnoea may be classified as one of the following:

  • Central apnoea - a pause of alveolar ventilation due to immaturity of neurological controls. There is a complete cessation of both chest movement and airflow. Central apnoea (10-25 per cent of all apnoea) may be provoked by vagal stimulation such as oral or nasal suctioning or the passage of a nasogastric tube.
  • Obstructive apnoea - a pause in alveolar ventilation due to obstruction of the upper airway (usually at the level of the pharynx). There may or may not be respiratory effort but there is no airflow - not detected by motion-sensing monitors (10-25 per cent of all apnoea).
  • Mixed apnoea - a combination of central and obstructive apnoea (50-75 per cent of all apnoea), whereby persisting airway obstruction leads to central nervous system (CNS) depression due to hypoxia and acidosis.

Apnoea is distinguished from periodic breathing (respiratory pauses > three seconds' duration with less than 20 seconds of respiration between pauses), which may occur normally.

Apnoea occurs in:

  • most infants < 30 weeks
  • about 50 per cent of infants at 30-32 weeks
  • about 10 per cent of infants at 34 weeks.

Apnoea of prematurity usually resolves by the time the infant is 36 weeks postmenstrual age.

Current evidence supports that apnoea of prematurity is not a risk factor for SIDS.

There is no evidence that apnoea of prematurity will cause subsequent neurodevelopmental morbidity although recurrent apnoea causes concern because of effects of repeated episodes of tissue hypoxia (especially on the gut and brain).

Infants at risk of apnoea should have cardiorespiratory monitoring +/- oxygen saturation monitoring. Alarms should be set appropriately with heart rate 100 beats per minute and apnoea delay at 20 seconds. When alarms are triggered, the infant should be assessed for colour, perfusion, position, respiratory rate and effort, heart rate, oxygen saturation and state.

Contributing factors for apnoea

Apnoea occurs with increasing frequency the more immature the infant. Various conditions may contribute to or aggravate apnoea.

Sepsis

See sepsis

Anatomical anomalies of the upper airway

Upper airway anomalies that may cause apnoea include:

  • choanal atresia
  • micrognathia
  • macroglossia
  • tracheomalacia.

Temperature disturbance 

Temperature disturbances that may cause apnoea include:

  • hypothermia
  • hyperthermia.

Metabolic

Metabolic conditions that may cause apnoea include:

  • hypercalcaemia
  • hypoglycaemia
  • hyponatremia
  • hypocalcaemia
  • hypermagnesemia
  • hyperammonemia
  • acid-base disturbances.

Haematological

Haematological conditions that may cause apnoea include:

Pulmonary

Pulmonary conditions that may cause or contribute to apnoea:

CVS

Causes of cardiac failure or impaired oxygenation include:

  • PDA
  • congenital heart defects
  • arrhythmias
  • shock.

CNS

Central nervous system conditions that may cause apnoea include:

  • intraventricular haemorrhage
  • intracranial haemorrhage
  • seizures
  • asphyxia
  • hypoxic ischaemic encephalopathy
  • increased intracranial pressure
  • cerebral abnormalities.

Medication - prenatal

Medication used prenatally that may cause apnoea in neonates include:

  • narcotics
  • beta-blockers
  • magnesium.

Medication - postnatal

Medication used postnatally that may cause apnoea in neonates include:

  • sedatives
  • hypnotics
  • narcotics
  • prostaglandin (PGE1).

Causes of apnoea according to age

Apnoea on day 1 is not normal and a sudden increase in severity/frequency of episodes suggests new pathology.

The following lists important potential causes of apnoea according to age of occurrence.

  • Day 1-2 
  • Days 3-6
    • Sepsis
    • Impending respiratory failure
    • PDA
    • Significant IVH
    • Apnoea of prematurity
  • Late
    • Sepsis
    • Progressive post-extubation atelectasis
    • Outgrown dose of theophylline/caffeine
    • Presenting symptom of RSV or other respiratory infection.

Investigations

A thorough physical examination is mandatory with emphasis on cardiorespiratory and neurological status. It is important to determine the underlying cause of apnoea.

If sepsis or metabolic factors are suspected a septic screen and blood glucose estimation will be required.

Further tests are determined by the need to look for specific conditions (see contributing factors) causing or aggravating apnoea.

Management

Managing an acute apnoeic episode

During an acute apnoeic episode you should:

  • position the neck in a neutral position or slightly extended to minimise potential airway obstruction - consider the prone position, ensuring neonate has full cardio respiratory monitoring
  • stimulate the baby by gentle rubbing of the soles of feet or back
  • aspirate airway, if no response briefly suction the oropharynx then repeat stimulation
  • commence bag-and-mask or Neopuff ventilation if no response to stimulation using the amount of oxygen the infant was receiving prior to the apnoea (not 100 per cent). Only increase the concentration of oxygen (by steps of 5-10 per cent) if the infant’s condition fails to improve despite effective ventilation.
  • use ongoing positive pressure ventilation if there is still no respiratory effort.

Managing specific causes

Treatments will depend on the specific cause of the apnoea. Ensure adequate cardiorespiratory and oximetry monitoring.

Symptomatic management

Various methods can be used to provide symptomatic control of apnoea until the infant 'out grows' this problem.

When is symptomatic treatment useful? There is no 'right' answer to this question. 

The following suggestions fall within the spectrum accepted at most neonatal units:

  • Episodes needing brief stimulation for cyanosis + bradycardia: > six every 12 hours.
  • Episodes needing vigorous stimulation +/- oxygen: > one every 24 hours.
  • Episodes needing positive pressure ventilation (PPV) +/- oxygen: > one episode every 24 hours.

Attention should be given to positioning the infant to avoid obstruction of the upper airway.

Avoid noxious stimuli and ensure careful handling.

Feeds may be given more frequently as smaller boluses to avoid excessive distension of the stomach.

Some infants benefit from maintaining their thermal environment in the lower part of the neutral thermal range.

Low flow oxygen into the incubator (approximately 23-24 per cent) or low flow oxygen via nasal prongs may help when levels of oxygenation between apnoeas are borderline satisfactory. If used continuous saturation monitoring is needed to avoid risks of hyperoxia (for example, retinopathy of prematurity in infants < 30 weeks’ gestation). Target oxygen saturation levels should be maintained between 91 and 95 per cent.

Pharmacological management

Caffeine has advantages because of its higher therapeutic ratio, once daily dosing, lack of need to assay blood levels and fewer adverse events.

Caffeine has been more rigorously evaluated in clinical trials compared with theophylline/aminophylline. 

Caffeine improves survival without neurodevelopmental disability in VLBW infants at 18-21 months of age.

Dosages Caffeine citrate
Loading dose 20 mg/kg IV or oral
Maintenance  dose

5 mg/kg daily, IV or oral

Commence 24 hours after loading dose
Increase up to maximum 10 mg/kg daily if no response

Note: 20 mg caffeine citrate = 10 mg caffeine base

Side effects

In general, the side effects of caffeine predominantly involve the central nervous system (such as irritability and seizures).

Medication is usually stopped when the infant is ≥ 34 weeks' gestation and apnoea free for one to two weeks. Cardiorespiratory monitoring should be continued for 48 hours after medication is stopped. 

Since elimination of caffeine is affected by postnatal age, it is suggested that infants receiving caffeine should remain in hospital for seven to 10 days after cessation of treatment.

In the most premature infants (< 28 weeks' gestation) apnoea frequently persists beyond 36 weeks postmenstrual age and may persist beyond 40 weeks corrected age.

Positive airway pressure

Positive distending airway pressure treats both obstructive and mixed apnoea. The proposed mechanisms of action are that it:

  • prevents pharyngeal collapse by splinting the nasopharynx
  • stabilises the chest wall musculature
  • alters various reflexes (Hering-Breuer, intercostal inspiratory inhibitory)
  • increases functional residual capacity (FRC).

Nasal CPAP may be given by various techniques - most simply via a cut down endotracheal tube inserted 2 cm into one nostril. Initial pressure settings for nasal CPAP are 5-7 cm H2O, which may be adjusted according to clinical response.

This should only be used in larger units that can safely provide CPAP.  Smaller units may use this technique following consultation with PIPER pending transfer.

Possible side effects

Possible side effects of positive distending pressure include:

  • barotrauma
  • air leak pneumothorax
  • nasal irritation
  • pressure area
  • abdominal distension
  • feed intolerance.

Positive pressure ventilation (PPV)

When uncontrolled by other means intubation and positive pressure ventilation will be required.

Initial ventilator settings will use short inspiratory times and minimal  positive inspiratory pressure (PIP) to minimise risk of lung injury.

Areas of uncertainty in clinical practice

Minimising apnoea after extubation from PPV

Both CPAP and caffeine will reduce post-extubation apnoea.

The place of blood transfusion in treatment of apnoea

The presence and severity of apnoea correlate poorly with the presence of anaemia. Methylxanthines have been shown superior to blood transfusion in improving symptoms of apnoea in anaemic infants. The clinical benefits from transfusion appear greater the more severe the level of anaemia (the effects are trivial when the haemoglobin is about 100 g/L).

Doxapram as medication for symptomatic control of apnoea

Doxapram cannot be recommended for the treatment of apnoea. It is contraindicated in newborns and small children, mainly due to the presence of benzyl alcohol, which is included as a preservative.

Caffeine for Apnoea Prematurity (CAP) trial

The CAP trial found that caffeine reduced the rates of death or disability, cerebral palsy and cognitive delay at 18-21 months corrected age when compared with placebo. At five years, caffeine reduced the overall severity of gross motor impairments and there was no evidence of any long term adverse effects. Long-term follow up continues.

Use of oxygen by nasal cannula to control apnoea

High oxygen flows given by nasal cannulae may achieve significant positive distending pressures.

Possible side effects include inadequate heating and humidification leading to temperature control problems and increased nasal irritation. Pressures generated are not able to be monitored with this system.

More information

Clinical

Cochrane database

References

  • Management of apnoea and bradycardia in the newborn. M. Balain & S. Oddie. (2013) Paediatrics and Child Health 24:1, pages 17-22.
  • Caffeine therapy for apnoea of prematurity. Schmidt, B., Roberts, RS., Davis, P. et al. N Engl J Med 2006; 354: 2112 -2121.
  • Survival without disability to age 5 years after neonatal caffeine therapy for apnoea of prematurity. JAMA 2012; 307: 275-282.
  • Effect of blood transfusion on apnoea, bradycardia and hypoxemia in preterm infants C.F.Poets, U.Pauls, B.Bohnhorst Eur J Pediatr (1997)156: 311-316
  • Transfusion-induced changes in the breathing pattern of healthy preterm anemic infants P.Sasidharan, R.Heimler Ped. Pulmonlogy (1992)12(3):170-3
  • Relationship between determinants of oxygen delivery and respiratory abnromalities in preterm infants with anemia E.M.Bifano, F.Smith, J.Borer J.Pediatr 120(2Pt1):292-6, 1992 Feb
  • High-flow nasal cannulae in the management of apnea of prematurity: A comparison with conventional nasal continuous positive airway pressure C.Sreenan, R.P.Lemke, A. Hudson-Mason, H.Osiovich Pediatrics 2001 107(5) 1081-3
  • A primer on apnea of prematurity L.A. Stokowski Adv Neonatal Care 2005 5 155-170
  • Current options in the management of apnea of prematurity J Bhatia Clin Paediatr 2000 39 327-36
  • Apnoea of prematurity RJ Martin, JM Abu-Shaweesh, TM Baird Paediatr Respir Rev 2004 5 (Suppl A) S377-82

Get in touch

Victoria Maternity and Newborn Clinical Network
Safer Care Victoria

Version history

First published: August 2014

Last web update: October 2018

Review by: October 2018

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Page last updated: 21 Nov 2018