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Recently, Josh Farkas and Scott Weingart gave a series of engrossing posts and podcasts on asthma. I especially liked their deliberations on mechanical ventilation which inspired me – no pun intended – to create a vodcast of my own and, like a novice troubleshooting a ventilator alarm, poke and prod at the sparse evidence base from which many of our current recommendations flow.
An acute exacerbation of asthma is typified by an inability to completely evacuate the alveolus [1-3]. Ultimately, this results at the cross-roads of three synchronic events: 1. Decreased pressure gradient for expiratory flow 2. Increased resistance to expiratory flow and 3. Diminished time for expiration. While some will lump the first two problems into a ‘prolonged respiratory time constant,’ this only applies to the passive patient  in a straightforward manner.
Difficulty generating a pressure gradient for expiration [from the alveolus towards the mouth] is the result of diminished pulmonary elastic recoil – commonly thought to characterize only emphysema – culminating in less alveolar pressure for any given achieved lung volume [5, 6]. Further, during an exacerbation of asthma, the chest wall can also retard expiration; from the persistent activation of inspiratory muscles during expiration . Importantly, overly active muscles of inspiration can be externally off-loaded by a ventilator  – one potential method by which external airway pressure combats air-trapping.
In addition to the above, expiratory airway resistance also prevents adequate emptying of the lungs. The reasons resistance rises are manifold: smooth muscle constriction, deposition of mucous, fibrin and blood as well as dynamic airway compression  – all of which may lead to early airway closure . Early airway closure may be an unrecognized event in asthma, yet gas trapped behind closed airways will ‘hide’ from the ventilator during an end-expiratory hold – leading to an inappropriately low auto-PEEP value for degree of hyperinflation [10-12].
Finally, high respiratory rate – by itself – can prevent full expiration, simply because expiratory time becomes too short. In passive patients, where expiration follows a typical exponential decay, an expiratory time that is less than 3-4 time pulmonary time constants favours incomplete alveolar emptying .
It has been known for at least 40 years that the functional residual capacity [FRC] can double during an acute exacerbation of asthma  – approaching the equilibrium volume of the chest wall [see video]. Additionally, during an asthma exacerbation, gas volume from FRC to end-inspiration of 20 mL/kg was associated with pulmonary and hemodynamic risk .
Yet the opposite side of the coin is also true; the acute asthmatic cannot inspire. With creeping hyperinflation, the lung and chest wall lose their mechanical advantage and inspiration insidiously becomes energetically inefficient. Crucially, rising respiratory effort is synchronous with air-trapping – long before the patient doubles his or her FRC. The reason is that dynamic hyperinflation generates auto-PEEP – as a function of trapped volume and respiratory system compliance. Auto-PEEP demands an energetic investment prior to inspiratory flow. Additionally, the respiratory muscles operate at an unfavourable position on their length-tension curve and stored elastic recoil of the chest wall is lost as it expands. Finally, breathing takes place at the upper, less compliant portion of the respiratory system, which makes inspiratory work of breathing unfavourable  [see video].
As demonstrated in the vodcast, the application of PEEP unloads the muscles of inspiration when the patient initiates a breath. Ironically, PEEP by itself acts as pressure support in that it both promotes inspiration and, to the extent that there is waterfall physiology [described below], PEEP is functionally absent during expiration !
All IPAP, no EPAP
While it is generally accepted that PEEP is beneficial during an asthma exacerbation when there is inspiratory effort [1-3, 16], it has been argued that the application of PEEP during passive, controlled ventilation is dangerous [2, 3]. The suggestion that PEEP is harmful – in the absence of inspiratory effort – undoubtedly traces back to a landmark study by Tuxen in 1989 . In this study, 6 paralyzed patients [4 with asthma] were ventilated with ZEEP and PEEP levels of 5, 10 and 15 cm H2O. Importantly, auto-PEEP was not measured, nor were patients studied for expiratory flow limitation. Each level of PEEP progressively increased lung volume without any beneficial effects; from this, PEEP was deemed hazardous. Interestingly, Tuxen referenced case reports that did find physiological benefit to PEEP in asthmatics on controlled ventilation, but were explained away as fortuitous – unrelated to PEEP.
While the results of Tuxen have been considered conclusive for decades [2, 3], the thoughtful contemporaneous commentary by Marini  seems largely forgotten. In it, Marini argues that when expiratory flow limitation is absent [i.e. no ‘waterfall’ physiology], then yes, PEEP will only increase end-expiratory lung volume . But when there is ‘waterfall’ physiology – when the downstream pressure from the alveolus is not the mouth, but rather a ‘choke point’ in the airway  – then the application of PEEP at the mouth will have no effect on airflow until PEEP is equal to the value of the collapse pressure at the choke point. This is called ‘waterfall physiology’ because the flow of gas through the airway is independent of the pressure at the mouth, just as the flow of water over the cusp of a waterfall is unaffected by the level of water in the river below. However, were the level of the river to rise to the waterfall’s crest, then the river would start to affect flow – just as raising PEEP at the mouth to the choke point pressure would only then begin to retard expiration  [see figure 1].Waterfall physiology explains why obstructive patients purse-lip breath  – as above, the generated PEEP unloads inspiration, but has no functional effect on expiration so long as the generated PEEP is below the airway closing pressure. Waterfall physiology also explains why subsequent investigations in obstructed patients [including asthma] have found that PEEP may worsen hyperinflation in some, but also have no effect on lung volume until about 80% of the auto-PEEP value is achieved at the mouth [20-22]. Additionally, in others, the application of PEEP can even open closed airways and release trapped volume [20, 23, 24] – consistent with some of the case reports  initially referenced by Tuxen!
How is this operationalized at the bedside? We turn to Marini’s suggestion in 1989 – increase PEEP incrementally with iterative assessments of the plateau pressure [Pplat – in theory, one could also use the stress index]. If PEEP and Pplat rise equally, then there is hyperinflation. If Pplat does not rise, or even drops – then you might be chasin’ waterfalls.
Dr. Kenny is the cofounder and Chief Medical Officer of Flosonics Medical; he is also the creator and author of a free hemodynamic curriculum at heart-lung.org
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