Intermittent positive-pressure ventilation similar to continuous positive airway pressure in preventing lung injury in preemies



The incidence of severe lung injury in extremely premature neonates with bronchopulmonary dysplasia given nasal intermittent positive-pressure ventilation is not significantly different for those who receive nasal continuous positive airway pressure, a randomized study of more than 1,000 infants shows.

"Although somewhat discouraging, this research is significant, as it refutes the common assumption that the noninvasive therapies being used are reducing severe lung injury in these tiny babies," said lead author Dr. Haresh Kirpalani, attending neonatologist at the Children’s Hospital of Philadelphia, in a statement about the results. "The study alerts us that we still need to develop new therapies for babies to avoid lung injury and [bronchopulmonary dysplasia]."

Dr. Haresh Kirpalani

Neonatologists often introduce the noninvasive therapies of nasal intermittent positive-pressure ventilation (IPPV) and nasal continuous positive airway pressure (CPAP) early in the lives of extremely low-birth-weight neonates. Their goal is to avoid potentially severe scarring and inflammation of the lungs that can result from the more invasive respiratory technique of endotracheal intubation and mechanical ventilation. Bronchopulmonary dysplasia (BPD) is a leading cause of neurological injury and death in this cohort.

Previously, a meta-analysis of trials of early nasal CPAP vs. intubation and ventilation showed that nasal CPAP is associated with a lower risk of BPD. Still, Dr. Kirpalani and his colleagues quoted several studies showing that 34%-83% of extremely low-birth-weight infants given nasal CPAP require subsequent intubation. Meanwhile, nasal IPPV has been associated with nasal trauma and necrotizing enterocolitis. Only small randomized trials have compared nasal CPAP with nasal IPPV, commonly used in extremely low-birth-weight infants in several countries.

Researchers in the current study enrolled infants in 10 countries between May 7, 2007, and June 29, 2011. Eligible infants weighed less than 1,000 grams, had a gestational age of less than 30 weeks, and were candidates for noninvasive respiratory support. Infants expected to die were excluded, as were those with congenital abnormalities, a need for surgery, or a neuromuscular disorder. Key baseline characteristics in the study were similar, although the proportion of male infants was higher in the nasal IPPV group (52.6%) than in the nasal CPAP group (46.1%).

Of the 497 infants assigned by researchers to nasal IPPV, 38.4% of those for whom sufficient data were available reached the primary outcome of death before 36 weeks of postmenstrual age or survival with BPD (N. Engl. J. Med. 2013;369:611-20). In a similar group of 490 infants given nasal CPAP, 36.7% reached the primary outcome (adjusted odds ratio, 1.09; 95% CI, 0.83-1.43; P = .56).

Dr. Kirpalani and his associates found no significant difference in rates of other neonatal complications between the two treatment groups.

Of the surviving infants, 58.3% in the nasal IPPV group needed postrandomization intubation, as did 59.1% in the nasal CPAP group. According to the researchers, the high number of reintubations in both groups indicates the difficulty in discontinuing respiratory support, despite the equally high use of caffeine at least once to mitigate the level of BDP in both groups (98.8% of the nasal IPPV group; 99.4% of the nasal CPAP group).

The researchers noted that despite guidelines for weaning, extubation, and reintubation, a potential for bias existed because their study did not permit blinding. However, the authors wrote that one strength of their study was their objective assessment of BPD in their study groups, determined by a standardized, blinded oxygen-reduction test. In the 20 infants for whom oxygen-reduction data were not available, similar data were obtained in a secondary analysis that used National Institutes of Health criteria for BPD.

They concluded that although the overall rates of the primary outcome of death or survival with BPD were similar in the two groups, "on the basis of the 95% confidence interval around the adjusted odds ratio, our results are compatible with an efficacy that ranges from a 21% reduction to a 35% increase in the risk of this outcome with the use of nasal IPPV versus nasal CPAP. These findings call into question the current widespread use of nasal IPPV."

The study was funded by the Canadian Institutes of Health Research. Dr. Kirpalani said he has no conflicts of interest related to this study.

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