Methods of Weaning Preterm Babies <30 weeks Off CPAP: A Multicenter Randomized Controlled Trial

CONTEXT

Premature infants, <30 weeks gestational age, require primary or secondary treatment with nasal continuous positive airway pressure (CPAP). There is little evidence to guide weaning from CPAP.

MATERIALS AND METHODS

Three large Australian NICUs conducted a randomized controlled trial between April 2006 and October 2009. The trial was registered with the Australian Trials Network.

Population

Inclusion

Preterm infants <30 weeks gestational age:

• Who were treated with CPAP from birth

• Or required nasal CPAP secondarily following extubation

Exclusion

• CPAP for <24 h

• Parents refused consent or weaning already commenced without consent

• Need for surgery

• Transferred to another hospital

• Oxygen requirements >25%

• Infant <750 g at time of randomization

• Congenital abnormalities

• > Grade 2 intraventricular hemorrhage (IVH)

• Subsequently died

Intervention

The infants received 1 of 3 randomized interventions (method 1, 2, or 3 - see below) when they had achieved the following “Stability Criteria” (must have all 8 criteria for ≥12 hours):

1. CPAP 4-6 cm H₂o

2. Oxygen requirement <25% and not weaning

3. Respiratory rate <60

4. No significant chest recession (sternal/diaphragmatic)

5. Less than 3 episodes of self-reverting apneas (<20 seconds) and/or bradycardias (<100 BPM) and/or desaturations (≤86%) in 1 hour for the previous 6 hours

6. Average saturation >86% most of the time or PaO₂/transcutaneous PaO₂ > 45 mmHg

7. Not currently treated for patent ductus arteriosus or sepsis

8. Tolerated time off CPAP during cares (up to 15 minutes)

Method 1 (M1)

CPAP was taken ‘OFF,’ and the infant remained in crib oxygen or air with a plan to remain off CPAP.

Method 2 (M2)

CPAP was weaned gradually by cycling between intervals of time ‘OFF’ followed by a fixed period of 6 hours ‘ON’ CPAP. When ‘OFF’ CPAP, the infant remained in crib oxygen or air. The period of time ‘OFF’ was gradually increased (by 2-4 hours).

Method 3 (M3)

CPAP was weaned ‘OFF’ as in the second method; however, the infants in this group were given humidified oxygen via 2 mm nasal cannulae at a flow rate of 0.5 l/min during their time ‘OFF.’

Criteria for failed trial ‘OFF’ (at least 2 of the following)

1. Increased work of breathing with respiratory rate >75

2. Increased apnea and/or bradycardia and/or desaturations >2 in 1 hour for the previous 6 hour period

3. Increased O₂ requirement >25% to maintain the oxygen saturation >86% and/or PaO₂/transcutaneous PaO₂ > 45 mmHg

4. pH of <7.2

5. PaCO₂/transcutaneous PaCO² >65 mmHg

6. Major apnea or bradycardia requiring resuscitation.

Outcomes

Primary outcomes

1. Length of time to wean off CPAP

2. And duration of CPAP treatment.

Secondary outcomes

1. Oxygen duration

2. BPD (defined as requiring oxygen at 36 weeks corrected gestational age to maintain oxygen saturations >86%),

3. Length of hospital admission.

Allocation

Computer-generated randomization (ratio of 1:1:1) and stratification by gestational age (<28 weeks and 28-29 weeks).

Blinding

The investigators in this trial were not blinded to study intervention.

Follow-up

All enrolled infants were accounted for at follow-up.

RESULTS

Primary outcomes showed method M1 produced a significantly shorter time to wean from CPAP (P<0.0001) and CPAP duration (P<0.0001). The secondary outcomes duration of oxygen therapy, incidence of BPD, and length of admission all had statistically significant reductions [Table 1].

Table 1.

Main results

DISCUSSION

Previously, there has been insufficient evidence to direct neonatologists in the weaning of preterm infants from nasal continuous positive airway pressure. This randomized controlled trial is one of the first trials to attempt to guide this weaning process. A previous study described that stopping CPAP for 6 hours increased the infants work of breathing, oxygen requirement, and apnea; however, overall, the infant took less time to come off CPAP.[1] Studies where CPAP pressures were weaned gradually were found to be more successful than stopping; however, this may have been because the infant was discontinued from support at a higher pressure without reaching stability.[2] More recently, a study described that replacing CPAP with nasal cannulae oxygen increased the duration of respiratory support without increasing success of weaning.[3]

A combination of change in randomization method and the trial stopping early for efficacy led to an imbalance in the number of subjects in each intervention group in this trial.

A total of 177 preterm infants were enrolled in the study. The trial was stopped early for efficacy, following a planned interim analysis and on the advice of the data monitoring committee. The outcomes were adjusted for gender and Apgar scores due to an imbalance of baseline characteristics during randomization (specifically a higher proportion of females in weaning method 1 and higher Apgar scores in weaning method 3). The results of this randomized trial (using stability and failure criteria) suggest taking babies off CPAP with the aim of keeping them off reduces time on CPAP, length of weaning from support, oxygen duration, BPD, and duration of stay in the neonatal intensive care unit.

Recently, methodologists have suggested that trials stopped early for efficacy were associated with greater effect sizes than RCTs not stopped early. This difference was independent of the presence of statistical stopping rules and was greatest in smaller studies.[4]

In summary, in current neonatal care, CPAP is often weaned according to individual clinical practice. The authors of this paper have demonstrated that using weaning method 1 (stopping CPAP), in conjunction with the study stability and failure criteria, reduces CPAP duration and time to wean CPAP. The authors acknowledge that further trials are needed to confirm these results.

Abstracted from

Todd DA, Wright A, Broom M, Chauhan M, Meskell S, Cameron C, et al. Methods of weaning preterm babies <30 weeks gestation off CPAP: A multicenter randomized controlled trial. Archives of Disease in Childhood Fetal and Neonatal Edition. 2012;97 (4):F236-40.