Extubation failure in the very preterm infant


Professeur titulaire, Département de Pédiatrie, Université de Montréal, Chef de Service de Néonatalogie, CHU Sainte Justine, Montreal, Canada


Many very preterm infants require assisted ventilation. After resolution of their initial pulmonary dysfunction, when extubated they are at risk of failure due to poor respiratory drive, atelectasis, residual pulmonary function abnormalities, or intercurrent illness. Keeping such infants extubated will decrease lung injury and improve long-term pulmonary and perhaps even neurologic outcomes. On the other hand, if failure of extubation could be accurately predicted, then extubation could be deferred and the trauma of reintubation after a brief failed extubation, with increased work of breathing, hypoventilation, and respiratory acidosis, could be avoided.

Prediction of extubation failure

Several studies have examined factors associated with failure of extubation. The contribution in this issue of Jornal de Pediatria from Hermeto et al.1 confirms that infants with lower gestational ages are more likely to fail extubation; other factors which they investigated did not independently predict extubation failure. They also showed an association between extubation failure and both severe intracranial hemorrhage and patent ductus arteriosus. As the authors point out, the causal relationship between these findings is uncertain; in both cases the abnormal finding could be caused by, or could cause, failure of extubation. Their finding confirms that attempts to prevent extubation failure should be focused on the most immature infants. Other studies have examined physiologic or clinical measurements as a means of predicting successful extubation in individual infants, unfortunately there is no clear evidence that any specific test or physiologic measurement can adequately predict a successful extubation.

The maximal inspiratory force, that is, the most negative pressure that an infant can generate during an airway occlusion, has been suggested as a way of determining the capacity of an infant to tolerate extubation. However, this measure, like many others, is very dependent on the state of arousal of the infant, thus it varies from one minute to the next and has not proved helpful in predicting extubation failure.2

More sophisticated measurements, such as a low post-extubation functional respiratory capacity, have been shown to be statistically associated with extubation failure,3 but in that study low gestational age was in fact a better predictor.

The test which appears to have the greatest potential currently is the minute ventilation test of Gillespie et al,4 a measurement of minute ventilation during complete ventilator support followed by a repeat during 10 minutes of continuous positive airway pressure (CPAP). If the infant is capable of maintaining a minute ventilation at least 50% as high during CPAP, then successful extubation is likely. A randomized controlled trial showed that the use of this test significantly decreased the duration of assisted ventilation,4 although the very early extubations were associated with a higher rate of extubation failure.

Kamlin et al.5 evaluated another test of the ability to breathe spontaneously, the spontaneous breathing test, in which there is a short trial period of endotracheal CPAP. A failed test is defined as a bradycardia (≤ 100/min) for > 15 seconds or SpO2 below 85% despite a 15% increase in FiO2. They also demonstrated that minute ventilation falls by a greater amount during this 3-minute test for infants who fail extubation than among those who succeed.5 Further confirmation of the utility of this test will probably require a randomized controlled trial.

Prevention of extubation failure

An evidence-based review of strategies to reduce extubation failure shows the following:

- Immature infants are more likely to be successfully extubated if they are not weaned to endotracheal CPAP prior to extubation, but extubated from low ventilator settings.

- It is uncertain whether weaning using synchronized intermittent mandatory ventilation (SIMV) and reducing the rate, or using assist control and weaning the pressure is preferable. Similarly, it is unclear whether newer modes of volume ventilation or pressure support ventilation improve the chances of successful extubation.

- Nasal CPAP after extubation is preferable to no pressure support.

- The method for generating the positive pressure appears to be unimportant, specifically the infant flow device is no better than other means of generating a positive pressure, it is possible that bubble CPAP is preferable to the infant flow device,6 but this requires confirmation.

- Nasal ventilation using the Infant Star® ventilator with peak inspiratory pressures greater than 14 cmH2O is preferable to CPAP,7 in contrast, bi-level positive airway pressure (BiPAP) using the infant flow device is no better than CPAP.8

- The infant should probably have binasal prongs rather than a single nasal prong.

- Immature infants receiving methylxanthines prior to extubation have reduced extubation failure; more specifically, caffeine has been shown to decrease bronchopulmonary dysplasia9 and to improve long-term outcomes10 and should probably be the methylxanthine of choice.

- Additional respiratory stimulants, such as doxapram, do not further improve extubation success.11

Extubating the very immature infant

These considerations lead to the following recommendations: very preterm infants should be extubated as early as possible, since the maneuver is likely to be successful, perhaps using the minute ventilation test, with infants receiving more than 40% oxygen, and those who already have a low lung volume prior to extubation are unlikely to be successful. Apart from these limitations, most infants deserve an attempt to extubate as long as a reintubation can be achieved with little trauma, with experienced intubators and good premedication. Infants should receive a loading dose of 20 mg/kg of caffeine citrate prior to extubation, followed by a maintenance dose of 5 mg/kg/day and should be extubated from low ventilator settings. After extubation, they should be supported with nasal ventilation. As the Infant Star® ventilator is no longer available, and there is no other method of reliably synchronizing nasal ventilation, non-synchronized nasal ventilation with pressures of at least 14 cmH2O peak and 6 cmH2O positive end-expiratory pressure (PEEP) and a rate of 20 per minute should be initiated. In general, 72 hours of nasal ventilation would be a minimum, followed by CPAP or a trial of unsupported breathing depending on the clinical condition.


Early extubation of very preterm infants holds promise for reducing lung injury. Unfortunately, as Hermeto et al. showed, the infants most at risk are those most likely to fail. Selection of those individuals who are most likely to be successful is currently unsatisfactory and further research is required. Application of evidence-based interventions, as described above, will give all babies the greatest chance to remain extubated after the initial attempt and the opportunity to minimize the long-term consequences of lung injury.


  • 1. Hermeto F, Martins BM, Ramos JR, Bhering CA, Sant'Anna GM. Incidence and main factors associated with extubation failure in newborns with birth weight ≤ 1,250 grams. J Pediatr (Rio J). 2009;85:397-402.
  • 2. Barrington KJ, Finer NN. A randomized, controlled trial of aminophylline in ventilatory weaning of premature infants. Crit Care Med. 1993;21:846-50.
  • 3. Kavvadia V, Greenough A, Dimitriou G. Prediction of extubation failure in preterm neonates. Eur J Pediatr. 2000;159:227-31.
  • 4. Gillespie LM, White SD, Sinha SK, Donn SM. Usefulness of the minute ventilation test in predicting successful extubation in newborn infants: a randomized controlled trial. J Perinatol. 2003;23:205-7.
  • 5. Kamlin CO, Davis PG, Morley CJ. Predicting successful extubation of very low birthweight infants. Arch Dis Child Fetal Neonatal Ed. 2006;91:F180-3.
  • 6. Gupta S, Sinha SK, Tin W, Donn SM. A randomized controlled trial of post-extubation bubble continuous positive airway pressure versus Infant Flow Driver continuous positive airway pressure in preterm infants with respiratory distress syndrome. J Pediatr. 2009;154:645-50.
  • 7. Barrington KJ, Bull D, Finer NN. Randomized trial of nasal synchronized intermittent mandatory ventilation compared with continuous positive airway pressure after extubation of very low birth weight infants. Pediatrics. 2001;107:638-41.
  • 8. O'Brien K, Campbell C, Havlin L, Wenger L. Shah V. Infant flow biphasic NCPAP versus infant flow CPAP for the facilitation of successful extubation in infants 1250 grams: A randomized controlled trial. Paediatrics and Child Health. 2009:14;11A (abstract).
  • 9. Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, et al. Caffeine therapy for apnea of prematurity. N Engl J Med. 2006;354:2112-21.
  • 10. Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, et al. Long-term effects of caffeine therapy for apnea of prematurity. N Engl J Med. 2007;357:1893-902.
  • 11. Barrington KJ, Muttitt SC. Randomized, controlled, blinded trial of doxapram for extubation of the very low birthweight infant. Acta Paediatr. 1998;87:191-4.

  • Extubation failure in the very preterm infant
    Keith J. Barrington

Publication Dates

  • Publication in this collection
    28 Oct 2009
  • Date of issue
    Oct 2009
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