Ventilation strategies for ARDS

Mechanical ventilation for ARDS is a topic of great interest to the intensivist, for a variety of reasons, not the least of which is the tendency of the CICM examiners to ask questions about it in the Part II exam. Other conditions (pneumonia, pulmonary oedema) are much more common and occupy more ICU beds, but have commanded less examiner attention because these conditions are less sexy and discussions of these in the literature are not as animated as the discussions of ARDS ventilation. With that said, ARDS is not exactly uncommon - a 2016 incidence survey (Bellani et al) determined that about 10% of all ICU admissions are with ARDS, and of all the ventilated patients in their 50 participating countries about 25% of all patients were intubated because of ARDS. In short, it's worth knowing about.

The following past paper SAQs involve the ventilation of ARDS:

In general, the College had asked about "ventilator settings" or "ventilator strategies" or "steps to improve oxygenation".  This chapter focuses on answering such questions with a pre-chewed bolus of literature recommendations, sufficiently brief and systematic to help trainees generate an impression of confident competence among casual onlookers. 

In brief summary:

  • Initial ventilator settings
    • Use a Pressure Control mode (it may be safer, though the evidence is not strong)
      • Higher mean airway pressure, and better recruitment of slow time-constant lung units with a decelarating ramp flow waveform
    • Lung-protective ventilation: use low tidal volumes (4-8ml/kg of predicted body weight)
    • Open-lung ventilation: avoid derecruitment by using a higher PEEP
    • As the ARDS severity increases, consider using a higher PEEP. 
    • Optimise PEEP using any number of strategies, including:
      • ARDSNet tables
      • Lower inflection point or the pressure-volume curve 
      • Stepwise derecruitment manoeuvre
    • Optimise the driving pressure (ΔP) -that means, using a higher PEEP and aiming for a lower plateau pressure (Amato et al, 2015.
    • Accept a level of "permissive hypercapnea"
  • Manoeuvres to improve oxygenation
  • Strategies to manage refractory hypoxia
    • Prone ventilation, ideally for 16 hours a day (PROSEVA, 2013) - ATS guidelines recommend 12 hours as the minimum 
    • APRV, when you can't prone for whatever reason  
    • Inhaled pulmonary vasodilators may improve oxygenation, but not mortality 
    • High frequency oscillatory ventilation may not improve mortality among all-comers (OSCAR, 2013) or it may actually increase mortality (OSCILLATE, 2013) but some authors feel that there were problems with methodology. The 2017 ATS guidelines recommend not to use it routinely.
    • ECMO may improve survival (CESAR, 2009) ...or it may not (EOLIA, 2018)

In terms of published peer-reviewed references for this, it is difficult to ignore the massive proliferation of published guidelines:

A summary of all these guidelines is thankfully also available (Fujishima, 2023), and contains some useful comparisons, which have been reproduced below. Another excellent reference is the article by Bein et al (2016), which somehow appears to be freely available in spite of being a part of the evil Springer-Verlag empire; but in all honesty it is not necessary to make suggestions about reading material here, as one cannot walk three steps in any direction through the literature without tripping over a high-quality peer-reviewed resource. The real skill is in managing the excess of information in a way that produces a synthesis for the reader who is not interested in academic wank. What follows is exactly this: first a discussion of the ventilator strategies for ARDS management, and then a round-up of what the guidelines say about them. 

Which mode of ventilation should I choose?

According to the Examiners of the College of Intensive Care Medicine, it doesn’t really matter. In Question 20 from the second paper of 2014, the college recommends one "use a mode with which one is familiar". This is a weird thing to say, particularly coming from a group of intensivists whose expertise is trusted with determining the expertise of other intensivists. Let us examine the implications of choosing different control variables for the mechanical ventilation of ARDS.

Choice of mode control variable for ventilation in ARDS

Overall, historically intensivists tend to prefer pressure control ventilation over volume control when it comes to ARDS. The rationale for this comes from the expectation that the square pressure waveform generated by the use of pressure as the control variable is probably better for oxygenation. Consider that the pressure control mode has the following advantages:

  • Higher  mean airway pressure, for any given peak airway pressure
  • Long time spent at maximum pressure (allowing alveoli with slow time constants to be recruited)
  • Inherently safe (controlled pressure level is not exceeded as it is a limit variable)

Sure, if you set up a volume control mode, you will still keep your peak airway pressure under 28-30 cmH2O, and so there shouldn't be any VILI. However, most of the inspiratory time will be spent a relatively low pressure, and there is probably going to be only a tiny fraction of end-inspiratory time during which the pressure will be maximal. In short, for any given peak airway pressure, you'll not be getting your money's worth of oxygenation. 

Lung protective ventilation: choosing a tidal volume and respiratory rate.

If one were to look for some sort of definition for this often-used term, one would come up with articles like this one by Camporota & Hart (2012), which define it as:

"...the provision of mechanical ventilation with static inspiratory pressures (plateau pressure) of less than 30 cm of water and tidal volumes normalised to predicted body weight"

Specifically, those volumes would have to be small. The ARDS network group of investigators published the results of the ARMA trial in 2000, which remains among the best-known studies in ICU literature. The group randomised patients to be ventilated with either 6ml/kg or 12ml/kg tidal volumes; the mortality difference was 31% vs 40% in favour of the smaller volumes. A subsequent meta-analysis has confirmed this mortality reduction. 

In this fashion, a 70kg person is ventilated with volumes of around 350-400ml, at a rate of 16 breaths per minute. The discomfort of breathing in such an unnaturally shallow way requires more sedation than would otherwise be required with conventional ventilation.

One starts at 8ml/kg of predicted body weight; over the following few hours one adjusts this down to 6ml/kg, while increasing the respiratory rate. The maximum plateau pressure is maintained around 30cmH2O, although 28cmH2O may be a more sensible limit.

Among the downsides of this strategy, the generally well tolerated respiratory acidosis is only one. Some authors have wondered whether some of the beneficial effects of lung protective ventilation may actually be the result of auto-PEEP, which develops when a higher respiratory rate is used. Others have questioned the influence of the increased sedation requirements; however these do not seem to be a constant feature- you only need deep sedation of the first day or so. Furthermore, it is probably unwise to extrapolate this strategy to patients with normal lungs.

In summary, the key issues are:

  • Tidal volume factors into minute volume, and determines CO2 removal
  • Tidal volume also determines the degree of lung inflation and recruitment of atelectatic lung
  • Adequate tidal volumes are important in ensuring patient comfort and decreasing sedation requirements
  • Low tidal volume (6ml/kg) works well for ARDS patients, prevents volutrauma and improves survival; however its disadvantages are hypercapnia and need for higher levels of sedation.

A further point is to mention that the tidal volume should be adjusted to predicted body weight, the formula for which is:

males = 50 + 0.91[height (cm) - 152.4]

females = 45.5 + 0.91[height (cm)-  152.4] 

The ARDSNET website has a lookup table which for some reason uses the Imperial system. 

Open lung ventilation: choosing the "ideal" PEEP setting

The “open lung” is the welcoming term used to describe a state in which all available alveoli are aerated throughout the ventilatory cycle. I suppose the opposite would be “closed lung” ventilation, where the alveoli are all collapsed. Looking for a formal definition, one comes up somewhat short. The term was probably coined by Burkhart Lachmann (1992), and then popularised by Marcelo Amato (for example in his 1995 article describing what he called a "protective" strategy,  about 6 years before the ARMA trial). Lachmann apparently presented this concept as early as 1982, but not until 1992 was there even animal data to support his idea. As far as definitions go, Lachmann's is sufficiently descriptive to quote in an exam. Open lung ventilation, according to his 1992 paper, is:

"...optimal ventilator mode which produce [sic] minimal pressure swings during the ventilatory cycle and keep the lung volume equal to or just above the FRC level "

The aim of this approach is to reduce the trauma induced by constant collapse and reinflation of alveoli, the so-called “cyclic atelectasis” which is thought to be a major cause of lung injury in ARDS ventilation. The idea is, with all your alveoli recruited you'll get decent tidal volumes with some minimum of "pressure amplitude", or driving pressure - i.e. the difference between your PEEP and your inspiratory pressure setting on a pressure control mode.

There are two trials to describe and support this technique, and though both show promise, each is hobbled by problems with methodology. Amato et al (1998) got excellent positive signals in hard outcomes (mortality down from 71% to 38%) but most people would point out that this was an unusually high institutional mortality from ARDS (should be around 45% for even severe ARDS). On top of that, the trial suffered from a  tendency to enrol Brazilian patients with leptospirosis, and the tendency to ventilate the control group with high volumes. A more recent trial by Villar et al (2006) demonstrated more realistic-sounding mortality benefits (53% vs 32%, in favour of opening lungs).

survival graph from Villar et al (2006)

The use of open lung ventilation rests in setting the PEEP around 2 cm H2O above the “critical opening pressure”, the PEEP at which the majority of alveoli remain inflated at end expiration. The FRC is therefore raised above the critical closing volume. The problem with this is obviously the finding of that critical opening pressure (or volume). ARDS is a heterogeneous condition, and for any given PEEP there will always be lung units which are overdistended, and others which are collapsing on expiration.

The art and science of determining the optimal PEEP for open lung ventilation is discussed elsewhere. In brief, one can use the following strategies:

Sensible bedside options

  • Keep PEEP at some arbitrary (high) value: higher levels of PEEP have been associated with improved survival on the basis of a meta-analysis (Briel et al, 2013).
  • Adjust depending on FiO2 (ARDSNet protocol) - in this protocol, worsening hypoxia is matched by an escalation of PEEP, from a PEEP of 5 cmH2O at 30% FiO2 to a PEEP of 22-24 at 100% FiO2.
  • Lower inflection point: the pressure-volume loop can be used to determine the "critical opening pressure" of the alveoli, and the PEEP set to something slightly above this. 
  • Maximal static compliance: the PEEP can be adjusted up or down to determine the maximal compliance; at the optimal PEEP, compliance will be maximal - and increasing the PEEP beyond this magical point will do little to improve the compliance.

Experimental and research options

  • Intra-pulmonary shunt: if the patient already has a PA catheter with continuous SvO2 monitoring, one can adjust PEEP until the SvO2 reaches a maximum value. However, one would not insert a PA catheter purely for this purpose.
  • CT of the chest:  it is possible to determine the ideal PEEP by looking at repeated CT scans of the patients at different pressures. The exposure to radiation alone is enough to make this an undesirable option, let alone the logistics.
  • Oesophageal balloon manometry: one may be able to measure pleural pressure using an oesophageal balloon, and therefore calculate the transpulmonary pressure. If it were not for the cumbersome nature of the measurements, this might be the gold standard for PEEP titration.
  • Electrical impedance tomography: the electrical resistance of the thorax should plateau at the point where all the recruitable alveoli are recruited (Long et al, 2015); one may even be able to assess the degree of ventilatory inhomogeneity (and how this changes with recruitment manoeuvres).

High PEEP ventilation

How high, you ask? There are three trials to examine: ALVEOLI, LOVS and EXPRESS. The findings have been compiled into a nice meta-analysis. The high-PEEP groups averaged around 12-15 cmH2O; the low-PEEP groups had about 8-9 cmH2O. Though overall there was no in-hospital mortality benefit, the authors were forced to conclude that there seems to be a small (5%) mortality benefit for the most severe groups, i.e. those with a PaO2/FiO2 ratio less than 200.

In short, the more severe your ARDS gets, the higher a PEEP you ought to use, up to a possible limit of around 15-20. Though the ARDSNet protocol goes all the way up to 24, one might consider stopping short of this value in patients of a normal weight.

Obsessing over alveolar plateau pressure

Barotrauma occurs when alveoli are stretched beyond their breaking point, and in ARDS this may occur due to the pressures required to generate even low tidal volumes. The 2017 ATS guidelines recommend that plateau pressure be limited to 30 cm H2O, and ideally as low as 28 cm H2O. 

Manipulating the I:E ratio

If lung compliance appears to be poor, one could also consider decreasing the I:E ratio (eg. to 1:1.5, 1:1 or even 2:1). However one does this with the knowledge that the benefit seems to be largely theoretical and manipulating the I :E ratio does not seem to improve survival, even though it may improve oxygenation.

Recruitment manoeuvres

Recruitment manoeuvres and their attendant complications are discussed in a separate chapter. Typically, one performs one of these by applying a high pressure (say, 40 cmH2O) for a short time (say, 40 seconds or so). One is immediately rewarded with hypotension, and possibly also pneumothorax. Oxygen saturation also drops- because the additional positive pressure is transmitted to the pulmonary arteries, suddenly doubling the pulmonary arterial pressure and causing a transient, frightening episode of right heart failure.

Does this strategy improve survival? Probably not, according to this Cochrane review. In fact, in the ART trial (Cavalcanti et al, 2017) they probably caused harm.  But, they can improve oxygenation temporarily. One can see the benefit of recruitment manoeuvres in patients who have accidentally become disconnected from the ventilator. The 2017 ATS guidelines were published in May of 20117, whereas the ART trial came out in September that year, and so the ATS guidelines still recommend recruitment manoeuvres whereas the rest of the world probably does not. In fact, in their answer to Question 8 from the first paper of 2018 the college remarked that if any trainee who confesses to the routine use of recruitment manouvres, "they were should be marked down" by the examiners. 

Neuromuscular junction blockers

In our pursuit for control over ventilation physiology, we often grope around for the cisatracurium ampoule. The switching off of muscles has several benefits in ARDS. Firstly, the contribution of chest wall compliance to lung compliance is removed. One may find that ventilation at a desirably low plateau pressure is only possible while the patient is paralysed. Secondly, the whole-body oxygen demand is decreased (as there are no contracting muscles at work) and so oxygenation of the still-active organs is improved. Overall, this strategy (one study found)  leads to a sustained improvement in oxygenation. Of course, one cannot treat one’s muscle fibres as mere obstructive oxygen thieves, hanging parasitically from one’s skeleton. Sustained neuromuscular blockade has its disadvantages

Rescue strategies

So, the patient has:

  • TOF of zero
  • Optimal fluid balance
  • Tidal volumes as low as you can manage, with a safe plateau pressure
  • An eyewateringly high CO2 which you are "permitting", as if you have a choice;
  • A PEEP as high as you can safely tolerate
  • An I:E ratio that maximises I, and a nice square alveoli-hugging pressure waveform

What other strategies can you resort to?

Well: you could try

And when all else fails, there is always VV ECMO. In fact one might make the argument that ECMO should not be resorted to as late as this, when everything else has failed; as that may represent a missed opportunity to protect and rest the lungs. Where confidence and resources permit, VV ECMO may be used earlier, so that one need not persist with injurious ventilation. 

A summary of the existing ARDS guidelines

What they all agree on:

  • Low tidal volumes, obviously.
  • Low plateau pressure.
  • Restrictive fluid management. Everyone seems to agree that a wet lung is the devil's playground. Keep them on the dry side, just enough volume to prevent alveolar dead space.
  • Prone ventilation.  There is no argument that it helps; though there is some division as to who should be proned, and for how long.
  • High frequency oscillation. All are broadly in agreement that it is a terrible idea.
  • Muscle relaxants. Everyone agrees that these could be resorted to in a pinch, but only for the most severe cases, and ideally for no more than 48 hours.

What they disagree about are mainly the adjunctive therapies:

  • Inhaled pulmonary vasodilators. Basically everybody is against these, except for the 2019 French guidelines, who suggest you think about using nitric oxide on the desperately hypoxic proned patients before flipping them over and cannulating them for ECMO.
  • High PEEP. Though all guidelines seem to recommend a higher PEEP for more severe ARDS, the level of recommendation varies considerably. The Surviving Sepsis Guidelines of 2021 for some reason give it a full endorsement (but what are they doing making ARDS recommendations anyway); whereas the joint ATS/ESICM/SCCM guideline from 2017 only gives it a lukewarm "expert recommendation". The 2023 ESICM guidelines do not make any recommendation because there is "high level of evidence of no effect".
  • Recruitment manoeuvres.  The 2019 French guidelines and the 2023 ESICM guidelines strongly recommend against their routine use, and the 2022 Japanese guidelines are conditionally against them, but they are outliers: everyone else is cautiously supportive. This is bizarre, as most of these were published long after ART killed PHARLAP.
  • Steroids. The 2022 Japanese guidelines are supportive; but weirdly they support 1-2mg/kg of methylprednisolone for seven days, and not the DEXA-ARDS dose (dexamethasone 20mg for 5 days, then 10mg for another 5 days). They did quote DEXA-ARDS as one of the studies they assessed. The rationale for the choice of low-dose steroids was mainly related to risk, which was viewed as unacceptably high (whereas the lower doses were apparently safer). Of the other guidelines, most pre-date DEXA-ARDS, and still offer differing opinions: the 2019 UK guidelines just suggested more research, whereas the Korean and Scandinavian guidelines are strongly opposed to their use, and the 2019 French guidelines do not mention them at all.


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