Elsevier

The Journal of Pediatrics

Volume 141, Issue 3, September 2002, Pages 370-375
The Journal of Pediatrics

Minimal ventilation to prevent bronchopulmonary dysplasia in extremely-low-birth-weight infants,☆☆,

https://doi.org/10.1067/mpd.2002.127507Get rights and content

Abstract

Objective: To determine whether minimal ventilation decreases death or bronchopulmonary dysplasia (BPD). Study design: Infants with birth weight 501 g to 1000 g and mechanically ventilated before 12 hours were randomly assigned to minimal ventilation (partial pressure of carbon dioxide [PCO2] target >52 mm Hg) or routine ventilation (PCO2 target <48 mm Hg) and a tapered dexamethasone course or saline placebo for 10 days, using a 2 × 2 factorial design. The primary outcome was death or BPD at 36 weeks' postmenstrual age. Results: After enrollment of 220 patients, the trial was halted because of unanticipated nonrespiratory adverse events related to dexamethasone therapy. The relative risk for death or BPD at 36 weeks in the minimal versus routine ventilation groups was 0.93 (95% CI, 0.77-1.12; P =.43). Ventilator support at 36 weeks was 1% in the minimal versus 16% in the routine group (P <.01). Major morbidities and long-term outcome were comparable in both treatment groups. Conclusions: With the sample size studied, minimal ventilation did not reduce the incidence of death or BPD. The reduced ventilator support at 36 weeks in the minimal ventilation group warrants further study of this intervention. (J Pediatr 2002;141:370-5)

Section snippets

Study subjects

Patients were recruited between February 1998 and September 1998 at 13 clinical centers of the NICHD Neonatal Research Network (see Appendix). The institutional review board at each center approved the protocol, and informed consent was obtained for each infant. Infants weighing 501 g to 1000 g who were intubated, receiving mechanical ventilation before 12 hours of age, and had an indwelling vascular catheter were eligible for the study. Infants weighing 751 g to 1000 g also were required to

Results

The trial was terminated by the Steering Committee when the interim analysis for the Data Safety and Monitoring Committee showed a higher rate of spontaneous gastrointestinal perforations in the dexamethasone-treated infants.21

Discussion

Although the strategy of minimal ventilation did not significantly decrease death or BPD, the hypothesized treatment effect size is included within the 95% CI of the primary outcome results, suggesting that the lack of findings may be due to the limited sample size of this terminated trial. Although not the primary outcome of this trial, the observation that ventilator support at 36 weeks was reduced suggests a need for further study of minimal ventilation in infants at high risk for BPD.

Acknowledgements

We thank Gordon Avery, MD, Mary D'Alton, MD, John Fletcher, PhD, Christine Gleason, MD, Maureen Maguire, PhD, and Carol Redmond, PhD, for their contributions as members of the Data Safety and Monitoring Committee and to our medical and nursing colleagues and the infants and their parents for participation in the study.

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      When endotracheal intubation is necessary, gentler ventilation strategies have been associated with improved outcomes. These include using the lowest possible ventilator settings, modest permissive hypercapnia, treatment with caffeine, and early extubation when possible [11–13]. Some extremely preterm newborns will benefit from these advancements and survive with limited morbidity.

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    Supported by cooperative agreements with the National Institute of Child Health and Human Development (U10 HD34216; U10 HD34167; U10 HD21373; U10 HD27881; U10 HD21385; U10 HD27853; U10 HD27904; U10 HD21397; U01 HD36790; U10 HD27851; U10 HD21364; U10 HD27871; U10 HD21415; U10 HD27880) and by General Clinical Research Centers grants (M01 RR02635; M01 RR02172; M01 RR00997; M01 RR08084; M01 RR06022; M01 RR08084; M01 RR00070).

    ☆☆

    *Avroy A. Fanaroff, MB, BCh (Case Western Reserve University), Richard A. Ehrenkranz, MD (Yale University), Sheldon B. Korones, MD (University of Tennessee at Memphis), and David K. Stevenson, MD (Stanford University).

    Reprint requests: Waldemar A. Carlo, MD, University of Alabama at Birmingham, Division of Neonatology, 525 New Hillman Building, 619 South 19th St, Birmingham, AL 35233-7335.

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