Three Part Question
In [very-low-birth-infants with respiratory distress syndrome] is [elective high frequency oscillatory ventilation using high volume strategy better than conventional mechanical ventilation] in [decreasing chornic lung disease or mortality at 36 weeks corrected gestational age]?
A 26 week infant is about to be delivered by emergency caesarean section to a mother with placental abruption and fetal distress. No antenatal steroids have been administered to the mother. You are called to attend the delivery. You are setting up the equipment when the respiratory therapist suggests that we should use high frequency oscillatory ventilation (HFOV) as primary mode of ventilation. He also cites few articles suggesting benefit of high volume strategy HFOV over conventional ventilation (CV). You wonder if there is enough evidence to support the intervention.
Secondary sources- Cochrane Library (Issue 4, 2002), MEDLINE (1996-2002).
Cochrane: 'high frequency ventilation' AND 'infant, newborn' OR 'infant, preterm'.
Medline: 'high frequency ventilation' and 'infant, newborn' OR 'infant, preterm' AND 'chronic lung disease OR bronchopulmonary dysplasia' AND 'randomised clinical trial'.
One systematic review found. Overall, 13 RCTs of HFOV vs CV were found in the search, of which eight met the eligibility criteria of the Cochrane review and are included in the review. Two RCTs have been published since the Cochrane update. The remaining four trials have not been published in sufficient details for analysis.
|Author, date and country
||Study type (level of evidence)
|Henderson-Smart DJ et al,|
|13 RCTs (over a period of 12 years) comparing HFOV vs CV for acute pulmonary dysfunction, mainly due to RDS in preterm infants
Randomisation and commencement of treatment was in the first 12 hours of life||Systematic review (1a)||CLD or mortality at 36 weeks CGA||Summary relative risk (RR) for death or CLD at 36 weeks CGA was 0.82 (95% CI 0.69, 0.99) (5 trials and n=788)||Changing obstetric and neonatal practices may influence the genesis of CLD
Interventions vary according to type of ventilator used and strategy for HFOV and CV|
|Grade 3 or 4 IVH||Summary RR 1.22 (95% CI 0.87, 1.70) (6 trials and n=880)|
|Any pulmonary air leak||Summary RR 1.54 (95% CI 0.98, 2.42) (4 trials and n=663)|
|Johnson et al,|
|797 infants between 23-28 weeks gestation and needing intubation since birth. Infants with major congenital malformations and those needing transfer to some other hospital were excluded from the trial
Infants assigned to HFOV or CV within first 1 hour after birth. Switching of ventilation strategy was permitted after 120 hours or in first 120 hours if there was treatment failure||RCT (1b)||CLD or Death at 36 weeks CGA||RR 0.98 (95% CI 0.89, 1.08)||Most infants were changed to CV for weaning purposes
Time spent on HFOV (median 3 days, IQR 1-6 days)|
|Pulmonary airleaks||RR 0.88 (95% CI 0.65, 1.20)|
|Grade 3 or 4 IVH||RR 0.69 (0.46, 1.01)|
|Courtney et al,|
|498 infants between 601-1200 grams, appropriate for gestational age, received one dose of surfactant, requiring CV with FiO2 of at least 0.25 and mean airway pressure of 6 cms, < 4 hours of age, and expected to need mechanical ventilation for more than 24 hours||RCT (1b)||CLD or death at 36 weeks CGA||RR 0.79 (95% CI 0.69, 0.96)|
RD -0.11 (95% CI -0.20, -0.02)
NNT 9 (95% CI 5, 50)
|Conservative extubation criteria for CV (FiO2 < or = 0.25 and MAP < or = 5)|
|Pulmonary airleaks||RR 0.99 (95% CI 0.63, 1.56) (n=498 infants)|
|Grade 3 or 4 IVH||RR 1.02 (95% CI 0.71, 1.49) (n=498 infants)|
Chronic lung disease (CLD) remains a serious and common problem among very low birth weight infants despite the use of antenatal steroids and postnatal surfactant therapy to decrease the incidence and severity of respiratory distress syndrome. This condition affects nearly third of all very low birth weight infants with RDs (Henderson-Smart et al). the etiology of CLD is multifactorial and lung inflammation due to mechanical ventilation, oxygen toxicity or infection contributes to its development. A well done systematic review (Henderson-Smart et al) did not find any substantial advantage of HFOV over CV in managment of preterm infants with RDS. the authors concluded that the borderline benefits of HFOV in terms of CLD appear to be outweighed by concerns about increased rates of IVH and airleaks.
The two largest contemporary trials (Johnson et al and Courtney et al) published recently showed contrasting results. The results of the study by Johnson et al. were similar to majority of previous trials which did not show a difference between the 2 modes of ventilation for the combined outcome of CLD or death. In contrast, Courtney et al found a small difference of borderline statistical significance favouring HFOV group. These 2 trials are very different in their ventilatory strategy. The trial by Johnson provided target guidelines for blood gases and specified only the inspiratory time and ventilatory rate. Rest of the ventilatory management was at the discretion of the attending clinician and reflects common NICU practice around the world. On the other hand, the ventilatory strategy in the study by Courtney et al. was strictly protocol based.
So, what do we find? Even in the most well controlled situations and experienced hands, HFOV does not confer a significant advantage in terms of CLD and mortality at 36 weeks.
We extracted data from the Cochrane systematic review (Henderson-Smart et al) for the trials comparing HFOV using high volume strategy versus CV and combined that with the data from the trials by Johnson et al and Courtney et al. The resulting meta-analysis (7 trials and 2069 infants) showed a borderline statistically significant reduction in the incidence of CLD or death in the HFOV group (summary RR 0.90, 95% CI 0.80 to 0.98; NNT 20, 95% CI 11 to 100). There was no evidence of difference in the incidence of grade 3 or 4 IVH (summary RR 0.97, 95% CI 0.78 to 1.19) or pulmonary airleaks (summary RR 1.04, 95% CI 0.87, 1.25).
Clinical Bottom Line
The etiology of chronic lung disease is multifactorial and choice of ventilation does not affect its incidence.
High-frequency Oscillatory Ventilation (HFOV) is probably not superior to conventional ventilation as primary mode of ventilation in preterm infants with respiratory distress syndrome for prevention of chronic lung disease or mortality at 36 weeks. However, use of HFOV is safe and not associated with increased risk of intraventricular haemorrhage or airleaks.
Important long term neuro-developmental outcomes should be addressed for infants treated with HFOV, as should the economic effects of introducing a new mode of ventilation.
Level of Evidence
Level 1 - Recent well-done systematic review was considered or a study of high quality is available.
- Henderson-Smart DJ, Bhuta T, Cools F, et al. Elective high-frequency oscillatory ventilation versus conventional ventilation for acute pulmonary dysfunction in preterm infants. Cochrane Library, Issue 4, 2002 Oxford: Update Software.
- Johnson AH, Peacock JL, Greenough A, et al. High-frequency ventilation for the prevention of chronic lung disease of prematurity. New Engl J Med 2002;347(9):633-42.
- Courtney SE, Durand DJ, Asselin JM, et al. High-frequency oscillatory ventilation versus conventional mechanical ventilation for very-low-birth-weight infants. New Engl J Med 2002;347(9):643-52.