Supportive Non-ventilation Strategies for ARDS

Management of ARDS is not all flashy physiology and pressure-volume circus tricks.There are numerous supportive strategies which help the ARDS patient, working quietly in the background.

This is a favourite topic of CICM examiners. The following past paper SAQs involve the ventilation of ARDS:

In brief summary, these are the non-ventilator adjunctive therapies for ARDS:

  • Minimization of dead space ventilation - Remove as much tubing as you can.
  • Low-carbohydrate high-fat nutrition - Keep them off the carbs, and don't overfeed.
  • Neuromuscular blockade improves survival, not just gas exchange.
  • Sedation decreases energy expenditure and improves ventilator synchrony
  • Fluid management should have a goal of neutral balance (keep em dry)

Minimization of dead space ventilation in ARDS

When one hears it said that the hypercapnea is "permissive", and when people mention that it has no ill effects in the long run, one is left with the impression that everything is ok and we should just ignore the PCO2. However, this is not the case; respiratory acidosis in ARDS is in fact far from desirable.

There are four major causes of hypercapnea in ARDS:

  • Hypoventilation: due to low tidal volume ventilation.
  • Incomplete CO2 exhalation due to a high respiratory rate: as you try to compensate for the low tidal volumes, you will increase the respiratory rate, which in turn decreases the amount of time allocated to expiration of alveolar CO2; the CO2 remaining in the air passages at the end of such an incomplete expiration will get recirculated back into the alveoli with the next breath.
  • "Plastic dead space": on top of your own airways acting as a CO2 recirculation reservoir, the cruel intensivist has attached a metre or so of corrugated tubing, to act as even more dead space.
  • Hypercatabolic/hypermetabolic state: the total body oxygen consumption, and thus the total body CO2 production, is increased because of the extreme stress produced by the disease state itself.

This has negative consequences. Your respiratory centres, bathed in such acidic body fluid, will produce a powerful urge to breathe. This is counterproductive, as the whole ventilation strategy revolves around breathing less, not more. The consequences of this are escalating sedation requirements.

Not only that, but increased alveolar CO2 decreases the concentration of other gases, most notably oxygen - so your FiO2, fresh and pure at the ventilator valve, may be diluted by the time it gets to the business end of the endotracheal tube.

So, how does one defeat these causes of hypercapnoea?

First of all, you cant do much about the low tidal volumes. Those are a priority.

Furthermore, you cant do much about the respiratory rate (the minute volume needs to stay within a reasonable range). And usually you wont be able to adjust the I:E ratio to improve expiratory time, because this will sacrifice oxygenation (by decreasing inspiratory time).

However, you can prune away the plastic dead space.

1) Remove the heat-moisture exchanger, and replace it with a humidifier.

This move can save you about 10-20ml of dead space; it seems to result in a small but statistically significant reduction in PaCO2, about 5mmHg. Several authors have concluded that it is a safe and cost-effective technique for decreasing hypercapnea in ARDS.

2) Get rid of as much ventilator tubing as you can.

This can also save you about 30ml of dead space, and decrease your PaCO2 by about 6mmHg on average.


This is a slightly fancier technique involving aspirating tracheobronchial gas and then flushing the circuit with fresh gas at the end of expiration. It seems to work very well, decreasing PaCO2 by up to 40% even at a respiratory rate of 60 breath per minute (at least in healthy Swedish pigs). However, this may require you to purchase a ventilator pimped out with the appropriate gear.

Now, how to decrease the rate of CO2 production in the patient?

This is a question of energy supply and energy demand.

Adjusting nutrition to satisfy requirements while decreasing CO2 production

Being affected by ARDS is hard work. Its certainly an interesting weight loss strategy. The inflammatory response results in a greatly increased rate of metabolism. And, because (conventionally) most human metabolism is aerobic, this results in a corresponding increase in CO2 production. One study from the 90s suggests that hypermetabolism-related CO2 excess accounts for about 50% of the increased ventilation demands in ARDS patients.

So, how to overcome this problem? On one hand, these people need optimal nutrition. On the other, we cant let them turn into churning CO2 factories.

Well, the first step is not to OVER-feed them. There is at least one case report of hypercapnea being exacerbated by hypercaloric feeding.

As for using those enteral nutrition formulae which have increased ratio of fat, hoping to decrease CO2 production by limiting carbohydrate intake... The scientific foundation of this has been discussed elsewhere. The empirical evidence in support of this practice is far from solid.

Somehow, much greater attention has been directed at feeding ARDS patients some sort of Immunomodulatory cocktail, hoping to modify the inflammatory process and to decrease the oxidative damage in the lung.

Neuromuscular blockade for ARDS patients

The use of neuromuscular junction blockers in ARDS is a pretty standard response to poor lung compliance. This was asked about in Question 21 from the first paper of 2016, as a "critically evaluate" question, and is therefore subjected to the usual treatment.

Rationale for the use of neuromuscular blockade in ARDS

  • Improve chest wall compliance: The lung compliance is already poor enough; removing chest wall compliance from the equation helps to prevent absurdly high peak pressures
  • Improved patient-ventilator synchrony: Many of these patients end up ventilated with such perverse pressure/volume combinations that without paralysis there would be a constant and counterproductive battle of patient versus ventilator. True, this is something one could achieve with haemodynamically disastrous doses of sedation, but ... why would you?
  • Recruitment manoeuvres  generally require paralysis for the abovementioned reasons; if the patient tries to exhale or cough during one of these manoeuvres, a pneumothorax may occur.
  • Prone ventilation usually requires paralysis
  • Decrease skeletal muscle metabolism: this is a hidden benefit, which is frequently overlooked. Neuromuscular blockade prevents the skeletal muscle from performing anything but the very barest baseline of metabolic work; the ATP production in the muscle fibres drops to whatever is required to maintain ionic concentration gradients. This decreases the oxygen extraction ratio for a large percentage of your patients tissues. Oxygenated blood, formerly directed into muscles, is redistributed into splanchnic vascular beds. Indeed, in a study performed on ICU patients with respiratory failure, the oxygen extraction ratio was found to by decrease 5% (from 36% to 31%).
  • Improved assessment of respiratory mechanics: without the interference of respiratory muscles, the lung compliance can be assessed more correctly, and the pressure-volume loops are more meaningful

Disadvantages of sustained neuromuscular blockade

  • This strategy is contrary to the normal strategy of ventilating patients with the most spontaneous mode possible, to preserve their muscle strength and to increase their comfort.
  • Longer duration of ventilation and longer ICU stay (Arroliga et al, 2005)
  • Increased risk of critical illness polyneuromyopathy
  • Increased risk of pressure areas
  • Increased risk of DVTs
  • Accumulation of paralytic agents (unless you use something like cisatracurium)
  • Risk of paralysed awareness
  • Increased nursing care

Evidence for the efficacy of neuromuscular blockade in ARDS

  • Papazian et al, 2010 -  a 48 hour course of cisatracurium early in the progress of severe ARDS. The authors found a 10% absolute risk reduction of 90-day mortality (31.6% vs 40.7%) associated with the use of neuromuscular blockade, without any increase in the risk of ICU-acquired weakness. , This places cisatracurium in the rare category of things which have been supported by positive trials.  Alongside low tidal volume ventilation and low delta-P, this is one of the strategies which can be strongly recommended. Unfortunately, as the college mention in their answer to Question 21 from the first paper of 2016, the study has several weak points:
    • Papazian et al only enrolled 25% of the eligible patients. 10% of patients excluded due to 'other reason', whatever that means.
    • 21% of the patients had PA catheters, which is totally contrary to modern Australian practice
    • 30% of the patients received nitric oxide, which has been thoroughly discredited in the literature and has fallen into disuse in Australia
    • Papazian et al used a surprisingly low PEEP, around 9 cmH2O on average.
    • The groups differed in their use of steroids (39% in treatment arm, 45% in placebo)
    • The mortality from ARDS was much lower than predicted, which underpowered the study.
  • Blanch et al, 2015 - a prospective study which observed that ventilator asynchrony is associated with a higher in-hospital mortality.

Deep sedation for ARDS patients

Once you start using neuromuscular blockers, you are sort of obliged to sedate the patients heavily. It would not do to add PTSD to their already harrowing experience of the ICU, by allowing them to experience everything from inside a motionlessly unresponsive body.

But, psychological and moral considerations aside, there is a crudely physiological benefit to good solid sedation in these people. It improves tolerance of low tidal volume ventilation. Plus, in the same way as neuromuscular blockade decreases the oxygen extraction ratio, so sedation decreases whole body oxygen demand (particularly in patients who aren't paralysed).

Thus, one might conclude that sedation in ARDS is a good thing. As always, use in moderation.

Fluid management in ARDS

Keep them dry. Yes, of course the disorder is by definition not related to fluid overload or heart failure, but the capillary permeability is high. With such permeable capillaries, less hydrostatic pressure is required to push fluid out into the interstitium. Thus, one would not wish to be cavalier with one's fluid management in these people.

This is supported by at least one trial. The patients randomised to a "conservative" fluid strategy had less ventilated days and better gas exchange, though hard outcomes remained the same. However, the trial had some crippling weirdness about it, which limits its applicability to ICU in Australia.

It was an odd design. Fluid management was guided by CVP measurements. The "liberal" group targeted a CVP over 10-14mmHg, and the "conservative" group targeted a CVP under 10mmHg. So of course the "liberal" group was about 7 litres positive at the end. This could be because in the protocol, the "liberal" patients with good urine output cardiac index and MAP still ended up getting a fluid bolus if the CVP dropped below 10mmHg.

Surely, this is bizarre fluid management.

All the same, the principle is probably sound. So perhaps the CVP is not a very good parameter to hang your fluid management on, but the use of PiCCO to watch over the extravascular lung water seems to be associated with a more intelligent fluid resuscitation strategy in severe sepsis, and with less progression to ARDS

In summary, one ought to aim for a goal of neutral fluid balance, and fluid resuscitation should be guided by sophisticated haemodynamic monitoring.



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