A systematic review published in 2011 of the studies comparing pressure to volume ventilation stated that there was ‘reduced death/BPD, duration of ventilation, pneumothoraces, hypocarbia and periventricular leukomalacia/severe intraventricular hemorrhage’ using volume targeted ventilation.’

I think it may be true that volume ventilation is preferable, but I also really don’t think there are adequate data in published trials to state that with any confidence.

Lets quickly review the data in that systematic review.

There are 9 trials, almost all with tiny sample sizes. between 34 and 57, one was 109, and the largest was 213. The studies used different ventilators, made different comparisons, some used different triggering techniques in the two arms of the study, and in many the actual comparisons were unclear. 3 of the trials, including the largest, used the Servo300, pressure regulated volume control mode, which is completely inappropriate for volume ventilation in the small infant.

Let me explain.

The Servo 300 measures the volumes at each end of the ventilator circuit, so the actual infant tidal volumes are always different to the measured volumes, by an amount equivalent to the pressure differential between PEEP and pip multiplied by the compliance of the circuit. In other words, the volume you have to set depends on the relative compliance of the babies lungs and the ventilator circuit. That makes it very difficult to set up appropriately in clinical practice, and means you need to change the volume if the babies compliance changes. Which rather defeats the purpose of volume ventilation.

I’ll give you an example: the compliance of the circuits we used to use with the Servo300 was about 1  ml/cmH2O. So if you put a 1 kg baby on the Servo, before giving him surfactant you might set the ventilator to give a volume of 20 mL, that would give a pressure of 22 /6. The 16 cmH2O pressure difference between inspiration and expiration leads to a volume difference in the circuit of about 16 mL between inspiration and expiration and the baby gets a tidal volume of 4 mL, which is about right, the dynamic lung compliance is about 0.25 mL/cmH2O.

But then you give surfactant, the babies compliance improves dramatically within a few minutes, the tidal volume is still set to 20 mL, but the babies lungs are better (dynamic compliance increases to 1 mL/cmH2O), the peak pressure falls to 16, the ventilator ‘tidal volume’ is now going to be 11, and the infant tidal volume is now 10 mL. The infant is set up for volutrauma, which is what volume ventilation is supposed to prevent!

The only way you can use this ventilator safely is to constantly adjust the delivered Vt, depending on the measured pressures, to give the calculated, infant, Vt that you want: that is not exactly what volume ventilation is supposed to be all about. It is why we now have ventilators which measure the volume actually delivered to the infant, at the patient ‘Y’. It is also why the publication of the largest trial did not state what volume they used, the ventilators were set up as follows

Target PaO₂ values were 45 to 60 torr for infants born at 24 to 26 weeks’ gestation, 50 to 70 torr for infants born at 27 to 28 weeks’ gestation, and 60 to 80 torr for infants born at more than 28 weeks’ gestation. Target PaCO₂ values were 45 to 55 torr regardless of gestational age at birth. Specific ventilator settings to achieve these targets were determined by the clinical team’

So there was no particular tidal volume in the protocol, it was frequently changed in order to get the blood gases that they wanted, and the tidal volumes needed on PRVC were 16 mL/kg with a standard deviation of 5, that is mostly between 6 and 26 mL/kg! (those are the Vt’s measured by the ventilator, the Vt of the baby and of the circuit)

Not surprisingly the authors of that study found no difference in any clinical outcome between PRVC and SIMV, also mostly using the Servo300 ventilator.

The much smaller 1st Polish study that also used the Servo300 started the babies on a tidal volume of 5 to 6 mL/kg. and added 4 to 5 mL for the ‘compressible volume of the circuit’ which doesn’t make much sense, given that the circuit tidal volume varies depending on the pressures, that study was also a comparison with non-synchronized IMV using the Bearcub or Sechrist ventilators. The 2nd Polish study using the Servo300 I haven’t read as it is in Polish, but I don’t think I’ll bother given my comments above.)

So basically we can discount the studies using the Servo300 as being studies of volume ventilation compared to pressure (D’Angio’s study is more really a study of assist/control vs SIMV). we are left then with 6 RCTs including a total of 304 randomized babies.

None of those individual trials found a significant difference in any one of the outcomes listed as being benefits of volume ventilation. Some of those outcomes, hypocarbia for example, are based on vanishingly small subgroups of babies. For hypocarbia the n is 58!

The Cochrane review does something that the version published in neonatology (by the same authors, including the same trials) does not, that is, it divides the trials into those that were really just a comparison of volume versus pressure ventilation, and those where there were other differences in ventilator management between the groups (which they called ‘hybrid’ studies). The 3 Servo300 trials are in the hybrid subgroup. The outcome death or BPD actually therefore depends on the data from less than 200 babies, from 3 trials, none of which individually had a difference, and with an upper limit of the 95% confidence interval of 0.96. None of the other dichotomous outcomes were different in the group of studies that only investigated volume compared to pressure ventilation.

That is pretty weak stuff to make a decision on ventilator management that will affect millions of babies.

If you decide that there were no advantages to pressure ventilation, so you might as well start with volume, just in case it is true that it is better, then what tidal volume should you choose? Sinha used 5 to 8  mL/kg (I am not clear why the range) Lista and Keszler used 5 mL, Singh used 4 to 6 mL/kg, and Cheena used 4 mL/kg. In most of those studies control groups were pressure ventilated babies in whom the clinical staff adjusted the pressures to try and give an average tidal volume that was the same as the volume ventilated group. So it looks like 5 mL/kg is the most studied, but that was chosen rather arbitrarily, and it may not be optimal, we just don’t know. But lets assume for the moment that we are going to use 5 mL/kg, should that be with SIMV or A/C? If with A/C is that a PSV mode or one with constant Ti? If SIMV should we have pressure support between assisted breaths or not? These are not questions that are exclusive to volume ventilation, but they are potentially important variables that could easily affect outcomes of very preterm babies.

There are also other unanswered questions, such as: what is the maximum leak that was allowed before switching to pressure? If the ETT leak is too great there is a risk that the ventilator will increase pressures right up to the limit to try to achieve the measured volume that you want, so at some point the clinicians should say, this is not working, we have to ventilate by pressure (or switch to High Frequency Ventilation or something).

My overall verdict on this is that the advantages of volume ventilation in terms of improving clinical outcomes are ‘not proven’. Many other physicians agree, as a result there are still substantial numbers who continue to use pressure ventilation.

So what we need is more ‘clinical effectiveness research’. Research which compares current protocols of care, to produce robust data on which future practice can rely. Ohhh dear, back to the SUPPORT controversy!

In fact, the reason I started writing this post was for just that reason, to write some more about comparative effectiveness research, and the ethical implications. See next post.