The High Frequency Ventilation in Premature Infants Study (HIFI)

Objectives:

To evaluate the hypothesis that high frequency oscillatory ventilation in preterm infants would reduce the incidence of mortality and pulmonary complications compared to conventional mechanical ventilation.

Background:

With the introduction of mechanical ventilation in preterm infants, mortality and morbidity significantly improved but remained high. The improvement in survival that accompanied the use of mechanical ventilation also brought about an increase in the incidence of pulmonary complications. The principal complication occurs in the form of bronchopulmonary dysplasia. Barotrauma and oxygen toxicity are considered to be in the pathogenesis for this disorder. Considerable interest in high frequency ventilation for preterm infants was generated when animal studies indicated high frequency ventilation to be effective in promoting gas exchange without apparent adverse effects. High Frequency Ventilation (HFV) delivers small tidal volumes at high frequencies of 4 to 15 Hz, and animal studies had indicated that HFV was associated with effective gas exchange, less barotrauma, and lower mean airway pressure. However, the efficacy and safety of HFV in preterm infants had not been studied. The HIFI Planning Phase was initiated in August 1984, and recruitment and intervention began in February 1986. Follow-up studies continued thru September 1988.

Subjects:

Infants were eligible if they weighed between 750 and 2000 grams at birth, had respiratory failure in the first 24 hours of life, and had been treated with conventional mechanical ventilation for less than 12 hours prior to randomization. Infants weighing between 750 and 1250 grams were eligible independently of their respiratory failure while infants weighing between 1250 and 2000 grams were eligible only if they had severe lung disease. Infants were excluded if they had any of the following: meconium aspiration, neuromuscular conditions affecting respiration, hydrops fetalis, congenital heart disease, except for patent ductus arteriosus, major malformations, diaphragmatic hernia, hydroplastic lungs, or multiple births of three or more infants. The endpoints of the study included incident bronchopulmonary dysplasia, need for ventilatory support at 72 hours and 28 days postnatal age, crossover between the two arms, and mortality prior to the postnatal 28th day. A total of 685 infants were randomized into the study. Treatment could not be initiated in 12 infants due to early mortality or withdrawal of parental consent, therefore a total of 673 infants were enrolled.

Conclusions:

Bronchopulmonary dysplasia incidence was similar in the two groups as was mortality and the need for ventilatory support during the first 28 days. There was a significantly greater rate of pneumoperitoneum of pulmonary origin in the high frequency group as was a greater incidence rate of intracranial hemorrhage. (NEJM, 1989; 320:88-93)