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Original Investigation |

Effects of Multiple Ventilation Courses and Duration of Mechanical Ventilation on Respiratory Outcomes in Extremely Low-Birth-Weight Infants

Erik A. Jensen, MD1; Sara B. DeMauro, MD, MSCE1; Michael Kornhauser, MD2; Zubair H. Aghai, MD3; Jay S. Greenspan, MD3; Kevin C. Dysart, MD1
[+] Author Affiliations
1Division of Neonatology, Department of Pediatrics, The Children’s Hospital of Philadelphia and The University of Pennsylvania School of Medicine, Philadelphia
2Alere Inc, Waltham, Massachusetts
3Division of Neonatology, Nemours/Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania
JAMA Pediatr. 2015;169(11):1011-1017. doi:10.1001/jamapediatrics.2015.2401.
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Importance  Extubation failure is common in extremely preterm infants. The current paucity of data on the adverse long-term respiratory outcomes associated with reinitiation of mechanical ventilation prevents assessment of the risks and benefits of a trial of extubation in this population.

Objective  To evaluate whether exposure to multiple courses of mechanical ventilation increases the risk of adverse respiratory outcomes before and after adjustment for the cumulative duration of mechanical ventilation.

Design, Setting, and Participants  We performed a retrospective cohort study of extremely low-birth-weight (ELBW; birth weight <1000 g) infants born from January 1, 2006, through December 31, 2012, who were receiving mechanical ventilation. Analysis was conducted between November 2014 and February 2015. Data were obtained from the Alere Neonatal Database.

Exposures  The primary study exposures were the cumulative duration of mechanical ventilation and the number of ventilation courses.

Main Outcomes and Measures  The primary outcome was bronchopulmonary dysplasia (BPD) among survivors. Secondary outcomes were death, use of supplemental oxygen at discharge, and tracheostomy.

Results  We identified 3343 ELBW infants, of whom 2867 (85.8%) survived to discharge. Among the survivors, 1695 (59.1%) were diagnosed as having BPD, 856 (29.9%) received supplemental oxygen at discharge, and 31 (1.1%) underwent tracheostomy. Exposure to a greater number of mechanical ventilation courses was associated with a progressive increase in the risk of BPD and use of supplemental oxygen at discharge. Compared with a single ventilation course, the adjusted odds ratios for BPD ranged from 1.88 (95% CI, 1.54-2.31) among infants with 2 ventilation courses to 3.81 (95% CI, 2.88-5.04) among those with 4 or more courses. After adjustment for the cumulative duration of mechanical ventilation, the odds of BPD were only increased among infants exposed to 4 or more ventilation courses (adjusted odds ratio, 1.44; 95% CI, 1.04-2.01). The number of ventilation courses was not associated with increased risk of supplemental oxygen use at discharge after adjustment for the length of ventilation. A greater number of ventilation courses did not increase the risk of tracheostomy.

Conclusions and Relevance  Among ELBW infants, a longer cumulative duration of mechanical ventilation largely accounts for the increased risk of chronic respiratory morbidity associated with reinitiation of mechanical ventilation. These results support attempts of extubation in ELBW infants receiving mechanical ventilation on low ventilator settings, even when success is not guaranteed.

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Adjusted Probability of Developing Bronchopulmonary Dysplasia (BPD)

Probabilities are based on the cumulative duration of mechanical ventilation for infants exposed to 1, 2, 3, or 4 or more separate courses of mechanical ventilation and are adjusted for birth weight, gestational age, small for gestation age, sex, birth year, surfactant exposure, postnatal dexamethasone treatment, patent ductus arteriosus treatment, bacterial sepsis, and diagnosis of necrotizing enterocolitis. Plots were generated using locally weighted scatterplot smoothing (LOWESS).

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