Ventilating infants with Diaphragmatic Hernia

Snoek KG, et al. Conventional Mechanical Ventilation Versus High-frequency Oscillatory Ventilation for Congenital Diaphragmatic Hernia: A Randomized Clinical Trial (The VICI-trial). Ann Surg. 2015.

There a few few remarkable things about this study; the first is part of the preamble:

Since 2008, all CDH patients born in European countries represented in the CDH EURO consortium have been treated according to a standardized neonatal treatment protocol that was developed at a consensus meeting. After implementation of this protocol, mortality decreased from 33% to 12%. This decrease in mortality rate should be interpreted against of the year upon year variability in mortality rates. Nevertheless, standardization of care is an ideal backcloth to undertake multicenter randomized controlled trials (RCTs).

In this study full term babies with an antenatal diagnosis of CDH were randomized to start on either conventional ventilation (Initial settings were a positive inspiratory pressure (PIP) of 20 to 25 cmH2O and a positive end-expiratory pressure (PEEP) of 3 to 5 cmH2O, with a ventilator rate of 40 to 60/min) or high frequency ventilation (mean airway pressure 13 to 17 cmH2O, frequency 10 to 12 Hz, delta P 30 to 50 cmH2O depending on chest wall vibration). There were a fairly complex list of signs of failure of the initial ventilation mode (If these things happen for at least 3 hours: inability to maintain preductal saturations above 85% or postductal saturations above 70% ; increase in CO2 > 65 mm Hg despite optimization of ventilatory management; PIP > 28 cmH2O; mean airway pressure >17 cmH2O; inadequate oxygen delivery with metabolic acidosis defined as lactate 5 mmol/L and pH < 7.20; hypotension resistant to fluid therapy and inotropic support resulting in a urine output <0.5 ml/kg/hour; oxygenation index of 40). In which case they could be switched to the other ventilation mode, and if that didn’t work they could be placed on ECMO.

The primary outcome of the study was survival without chronic lung disease (oxygen requirement at 28 days). Over 5 years they enrolled 171 patients, far short of the hoped for 200 per group. In the Conventional group 45% died or had chronic lung disease compared to 53% in the HFO group, a difference which may have been due to chance, (p= 0.3). Many of the secondary outcomes were better in the conventional group, there was much less need for ECMO (26% vs 51%), they were ventilated for fewer days,
less often received inhaled nitric oxide, or sildenafil, had a shorter duration of
vasoactive drugs, and less often failed treatment.

I think the study is a remarkable achievement, as far as I can see this is by far the largest RCT of infants with CDH that has ever been performed. Even though it was unfortunately stopped before the full sample size, it looks unlikely that an advantage of initial HFO would have been shown. As we are unlikely to have any other data of this quality for a very long time, I think the conclusion should be that the starting assisted ventilation mode for infants with CDH should be conventional ventilation, unless there is some very good reason for choosing HFO.

We can only hope that this collaborative group will continue to perform important clinical studies in these babies, who remain a group with very high mortality despite the advances of the last several years. I would vote for a good trial of sildenafil, a comparison of different criteria for ECMO, and more studies of different aspects of assisted ventilation. Maybe a study of muscle relaxation as well, if that wasn’t asking too much!

About keithbarrington

I am a neonatologist and clinical researcher at Sainte Justine University Health Center in Montréal
This entry was posted in Neonatal Research. Bookmark the permalink.

6 Responses to Ventilating infants with Diaphragmatic Hernia

  1. winnineo says:

    What I would really like to see in addition to your wish list Keith is a study of Jet ventilation versus conventional from the outset. Very different form of high frequency ventilation so the VICI results should not be extrapolated to HFJV without adequate study.

    • That would certainly be interesting, it would be nice to have some evidence that jet ventilation was good for something! I think the only evidence of benefit right now dates from 1991 when Martin Keszler and a multi-center group showed more rapid resolution of PIE in preterm infants with the use HFJV compared to conventional ventilation, in a smallish study, but no improvement in mortality.
      I think you are right that you shouldn’t extrapolate from oscillation to the jet, and it should be better evaluated, particularly in a modern NICU setting with gentle conventional ventilation. I think it would be hard to get funding for a large enough multi-center trial, but some short term evaluation with physiologic outcomes might give enough data to serve as a background for an RCT with clinical outcomes.

  2. Mike says:

    Dr. Barrington
    Thank you so much for discussing this article in your blog. I think most people would have missed it since it was not published in one of our journals
    It is amazing the focus has shifted to kinder and gentler ventilation in PPHN
    In the last 5 years. I hope we all become brave enough to accept a post ductal Sao2 of 70 and a preductal > 85
    Best regards
    Mike

  3. Thank you, Keith, we were awaiting this publication. A paper needed to be known by neonatologists from an unusual Journal for us. Well designed and conducted trial. However, even when following the European consensus probably has contributed to improved results, CDH is still a disease with different presentations and problems . Many years ago Steven Abman and others have taught us that management should be individually targeted based on the prevailing underlying pathophysiology (lung hypoplasia, pulmonary hypertension and/or cardiac dysfunction). It may well be that the ventilator mode should be chosen based on this evaluation. Perhaps –only perhaps- HFV works better in severe hypoplastic lungs and CMV when there is more hemodynamic compromise…
    Another important issue is ventilatory strategy, not only ventilator mode
    Best regards
    Gonzalo

    • That is certainly an interesting suggestion. Could be tested in a trial also. On the other hand standardized protocolized therapy has been shown many times now to be associated with improved survival in CDH. Although there are no RCTs (as far as I know) protocols of care for CDH do seem to routinely be followed by better outcomes. I think any protocol has to be applied with clinical judgement, and you do need to be ready to adjust therapy based on how the baby responds, but such things as allowing mild hypoxia for the first hour or so, seems to be very successful. This publication is the great lace to start; Puligandla PS, et al. Management of congenital diaphragmatic hernia: a systematic review from the APSA outcomes and evidence based practice committee. J Pediatr Surg. 2015.

  4. Pingback: Interesting comments | Neonatal Research

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