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REVIEW

CURRENT
OPINION Dissipation of energy during the respiratory cycle:
conditional importance of ergotrauma to structural
lung damage
John J. Marini

Purpose of review
To describe and put into context recent conceptual advances regarding the relationship of energy load and
power to ventilator-induced lung injury (VILI).
Recent findings
Investigative emphasis regarding VILI has almost exclusively centered on the static characteristics of the
individual tidal cycle – tidal volume, plateau pressure, positive end-expiratory pressure, and driving
pressure. Although those static characteristics of the tidal cycle are undeniably important, the ‘dynamic’
characteristics of ventilation must not be ignored. To inflict the nonrupturing damage we identify as VILI,
work must be performed and energy expended by high stress cycles applied at rates that exceed the
capacity of endogenous repair. Machine power, the pace at which the work performing energy load is
applied by the ventilator, has received increasing scrutiny as a candidate for the proximate and integrative
cause of VILI.
Summary
Although the unmodified values of machine-delivered energy or power (which are based on airway
pressures and tidal volumes) cannot serve unconditionally as a rigid and quantitative guide to ventilator
adjustment for lung protection, bedside consideration of the dynamics of ventilation and potential for
ergotrauma represents a clear conceptual advance that complements the static parameters of the individual
tidal cycle that with few exceptions have held our scientific attention.
Keywords
acute respiratory distress syndrome, driving pressure, energy, ergotrauma, power, ventilator-induced lung injury

INTRODUCTION modifiers of the potential for the purely mechanical

For more than three decades, the investigative
emphasis in ventilator-induced lung injury (VILI)
has centered on the static characteristics of the
individual tidal cycle. As understanding has
evolved, concern regarding the VILI-initiating var-
iables has progressed from tidal volume [1] to
plateau pressure (Pplat) [2], to avoidance of ‘atelec-
trauma’ by the open lung approach [3] to driving
pressure [4]. The inescapable logic of focusing on the
lung by utilizing transalveolar pressure rather than
airway pressures has now been acknowledged and
cautiously implemented at the bedside using the
esophageal balloon catheter [5]. The important roles
of mechanical heterogeneity [6], reduced aerating
lung capacity [7], disease stage and VILI predisposi-
tion [8,9], vigor of spontaneous breathing efforts
&
[10 ], and such modifying conditions as pH [11]
and vascular pressure [12] have been recognized as
stress levers of applied airway pressure to cause
injury.
Tidal cycle characteristics, ventilator-induced
lung injury, and outcome: missing
mechanistic links
Statistical analysis has shown the association of ven-
tilator strategies focused on the individual tidal cycle
with mortality, with the presumed intermediary
being VILI. In fact, despite biological implausibility
University of Minnesota, Minneapolis/St. Paul, Minnesota, USA
Correspondence to John J. Marini, MD, Regions Hospital MS 11203B,
640 Jackson St, St. Paul, MN 55101, USA. Tel:/fax: +1 (651) 254 3411;
e-mail: John.J.Marini@healthpartners.com
Curr Opin Crit Care 2017, 23:000–000
DOI:10.1097/MCC.0000000000000470

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Respiratory system
KEY POINTS
 The mechanical stimulus for VILI involves breathing
frequency and dynamic features of the tidal cycle as
well as the static elements of inflation such as Pplat,
PEEP, and driving pressure.
 The energy load imposed by repeated tidal inflation
(power) plays a central role in the injury process.
 The ergotrauma caused by ventilating power is
conditioned by several forms of stress focusing that
occur within the mechanically nonhomogeneous
injured lung.
 Limiting energy load, mechanical heterogeneity, and
damaging strain represent rational targets for
implementing safe positive pressure ventilation.
some data have also been interpreted to suggest that
there may be no clearly safe lower limits for Pplat or
tidal volume in patients with acute respiratory dis-
tress syndrome (ARDS) [13]. Whether such observa-
tions indicate an opportunity to improve outcome by
aggressive lowering of Pplat or simply reflect the ven-
tilation demands associated with the severity of ill-
ness has not been entirely resolved. Laboratory
experiments have shown that pressure and strain
thresholds exist that are required to provoke VILI
[14] and that different species have different capabil-
ities to withstand transalveolar pressures [15].
In placing ventilation strategy, VILI, and out-
come into their proper perspective, it should be
recognized that for many years, physicians had
applied tidal volumes and pressures that, in retro-
spect, predisposed to lung damage [16]. Yet, many
patients treated in that way did survive their acute
illnesses, suggesting that VILI either did not occur in
those survivors or, more likely, that the tidal char-
acteristics alone did not play the definitive roles in
determining eventual outcome. Moreover, even
today tight mechanistic linkages between VILI
and organ failure have not been convincingly estab-
lished. We still await a satisfying explanatory mech-
anism for the correlation between ventilation
approach and clinical outcome.
Although the static characteristics of the tidal
cycle [Pplat, positive end-expiratory pressure (PEEP)
and their difference – the ‘driving’ pressure] are
undeniably important, the ‘dynamic’ characteristics
&
of ventilation must not be ignored [17,18 ]. Collagen
scaffolding provides the lung with an impressive
capacity to withstand high inflation pressures [19].
Indeed, deep nonrepeated inflation events, even to
high lung volumes and driving pressures that
approach total lung capacity and vital capacity,
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respectively, do not produce lasting permeability
lung edema or inflammatory change. To inflict the
nonrupturing damage of the nature we identify as
VILI, work must be performed and energy expended
by high stress cycles applied at rates that exceed the
capacity of endogenous repair. Therefore, in an
attempt to determine the root mechanical cause of
VILI, attention has recently been redirected toward
understanding the energy and power applied to the
lung and to their potential contribution to VILI
& && &&
(ergotrauma) [20 ,21 ,22 ,23].
Essential concepts and definitions of global
energy and power
Mechanical work is accomplished when an object
such as the lung is moved in response to an unbal-
anced force [24,25]. For any object, a force that is
unopposed (creating a force gradient) will accelerate
the object’s mass: force ¼ mass  acceleration
(Fig. 1). The accelerating force gradient may be
reduced or eliminated by the opposing forces of
friction and elastance. Energy is the capacity to
perform work. A fixed amount of mechanical energy
can transition among its varied forms but as a con-
served quantity, must always be accounted for. The
mechanical energy of a system can be potential
(static) or kinetic (motion). Kinetic energy may
be deform or damage a structure, overcome friction
to produce heat, or convert to potential energy.
Power is the rate of energy expenditure and
work performance.
With reference to the lung, where we deal with
pressures that produce volume changes, pressure is
force per unit area and volume is area  length.
Therefore, the product of pressure applied and the
volume change that results is a force–length quan-
tity that quantifies the work accomplished [24,25].
Definions in Energecs of Venlaon
• Work = Force x Length
(Work = Producve Energy)
• Pressure = Force/Area
• Volume = Area x Length
• Press x Vol = [Force/Area] x [Area x Length]
• Pressure x Volume = Work
• [Pressure x [Volume/Time] = Power
Units: Energy (joules) Power: joules/sec (was)
FIGURE 1. Definitions of the key variables relevant to
ergotrauma.
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Pressures that do not move the lung, for example,
Pplat and PEEP, do not perform work or expend
energy, but rather store it as ‘potential’ energy.
The term ‘stress’ refers to a force applied above
the relaxed baseline (for the lung, loosely related to
transpulmonary pressure), whereas strain is the
resulting elongation (loosely related to volume
change) [14,26]. The product of tidal stress and
strain can be thought of as correlating with the
global energy required per inflation cycle. As it
expands during the breath, the respiratory system
starts from the potential energy corresponding to
total PEEP (PEEPT ¼ PEEP þ auto-PEEP) and inflates
to the end-inspiratory value (Pplat). The tidal energy
is required to unfold and deform the lung’s struc-
ture, overcome surface forces, and build elastic
strain within the lung and chest wall. From that
stressed end-inspiratory position the respiratory sys-
tem holds the stored potential energy which
drives expiration.
The equation of motion of the respiratory sys-
tem describes the components of the applied pres-
sure that must be supplied to inflate the respiratory
system – the series-coupled lung and chest wall.
Trans-pulmonary rather than airway pressure
expands and performs work upon the lung. Three
major components comprise the inflating pressure:
flow resistive, tidal elastic (driving pressure), and
starting pressure above the baseline value, PT
&
[20 ,25] (Fig. 2). When constant flow is delivered,
the contribution of tidal driving pressure to the
energy required per cycle is multiplied by 1/2
because the energy cost of further volume incre-
ments by this pressure component builds continu-
ously during inflation [25] (Fig. 3). Energy expended
across frictional resistance dissipates irretrievably
as heat.
Simplified Equaons for Moon,
Inspiratory Energy & Power
Equaon of Moon: Ptot = V x [ flow R + ∫ flow dt /2C+ PEEPtot]
Energy = V x Ptot = V x [ flow R + ∫ flow dt /2C+ PEEPtot]
Power = VE x Ptot = VE x [ flow R + ∫ flow dt /2C+ PEEPtot]
V= dal volume; R= resistance; C=compliance; Ptot=Machine inflaon pressure;
PEEPtot = Applied PEEP + auto-PEEP; VE = minute venlaon; ∫dt = dal interval
FIGURE 2. Simplified equations of motion, work, and power
using measurable bedside variables. PEEP, positive end-
expiratory pressure.
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Dissi pation of energy during the respiratory cycle Marini
Machine Work Components of the Passive Inflaon Cycle
VT
Volume
Ptot = Flow x R + Vt /2C + PEEPtot
PEEP1 PEEP2
Pressure
FIGURE 3. Schematic depiction of inflation work performed
by the machine during passive inflation with constant flow at
two tidal volumes and PEEP levels. The pressure–volume
areas correspond to the work contributions of resistance,
driving pressure, and PEEP. PEEP, positive end-expiratory
pressure.
Mechanical power, defined as work per unit
time, describes the intensity of energy application.
Although power is the term that has been accurately
applied to the product of inflation energy per cycle
and the number of cycles per minute (breathing
&&
frequency) [21 ], power can be considered on any
time scale. The contours of the energy and ‘instan-
taneous’ (within cycle) power profiles are shaped by
flow, the rate of change of lung volume. During
inflation by modern ventilators, these flow profiles
typically are constant or linearly or exponentially
decelerating. Within the bounds of a single inflation
cycle, the stress intensity is the dPalv/dT, where Palv is
alveolar pressure. This ‘transpulmonary’ pressure
slope defines the instantaneous intensity of the
applied inflation energy relevant to the lung and
helps describe ‘power’ on a much shorter time
scale. (Within-cycle power is the product of pressure
and flow). Thus, inspiratory flow magnitude and
profile are of interest to the energetics of VILI and
have been shown experimentally to influence its
severity [27,28].
Because the pressure gradient for expiration is
the decaying alveolar pressure minus PEEPT, expira-
tory flow (and consequently the expiratory power)
profiles are invariably decelerating. As exhalation
proceeds, stored potential energy is used to reshape
the lung to its initial conformation and to overcome
the resistance of tissues, airways and circuitry. Much
of the tidal elastic and ‘PEEP-related’ components
of machine energy needed for inflation are
accounted for (recovered) as the force gradient of
airway pressure dissipates across the exhalation
valve [29]. End-inspiratory potential energy is
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Respiratory system
depleted and transformed as it converts to kinetic
energy and heat during exhalation. The inflation
energy is a conserved value that cannot both cause
damage and dissipate as heat. To understand how
small unaccounted for (unrecovered) amounts of
global energy and power could initiate VILI damage
it is important to acknowledge the force-altering
mechanisms that occur at the microscopic level in
mechanically heterogeneous lungs.
Dynamic micromechanics relevant to
ventilator-induced lung injury
Recognition that the aeratable capacity of the lung
in ARDS is small and that reduced respiratory system
compliance can largely be attributed to the reduced
number of inflating units has directed attention to
the micromechanics of injury [30]. Shearing forces
and tissue tensions arising from regional transpul-
monary pressures may be intensified by geometric
interdependence [6], viscoelastic drag [26], and pro-
gressive depletion of the elements that bear stress.
At this microscopic level, the stresses and strains
are conditioned by the stress amplification and
progressive loading that arise at mechanically het-
erogeneous interfaces between open and closed
units. The amplification factor depends in nonlinear
fashion upon stress (pressure) amplitude, the local
geometry, and the rate of inflation. Both static and
dynamic pressures are relevant [31]. At the upper
limits of global plateau airway pressure, quantitative
CT analysis of ARDS lungs indicates that the rele-
vant amplification factor may exceed 2.0 but is
likely less than the oft-quoted 4.5 suggested by
oversimplified (but conceptually instructional) geo-
&
metric models of Mead et al. [6,20 ].
The ‘effective’ stresses and strains are almost
certainly conditioned by viscoelastance, in which
the drag of lung tissues that are reluctant to move
increases the local fiber tensions that oppose ongo-
ing alveolar distention [30]. Slowing the rate of
expansion (dP/dT) reduces the impact of a given
driving pressure excursion [27].
It has been convincingly suggested that repeated
high strains may initiate inflammatory signaling
without overtly catastrophic structural disruption
of the cell membrane itself [32]. However, at a more
granular level, it has not been ruled out that tidally
repeated protein disruptions, microfractures or
other physical damage to the extracellular microen-
vironment or matrix may be the proximate instiga-
tors of the inflammatory injury [33]. Such damage
has implications for structural disruption as well.
Once some critical value threshold value of tension
is surpassed, the weakest and most vulnerable sup-
porting elements of the extracellular matrix break
4 www.co-criticalcare.com
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Shared Strain Progressively Increased Loading
4 Kilo per rope
2 Kilo per rope
12 Kilo 12 Kilo
FIGURE 4. Principle of stress amplification by progressive
loading. As load bearing elements of the structure are
depleted, additional stress is experienced by those
remaining. In this illustrative example, ropes acting in
parallel bear a weight of 12 k. Load per rope doubles when
half are missing.
and no longer help distribute stress. With each
cycle, breakage then may sequentially increase the
strain and effective energy focused on other load-
bearing elements, thereby serving as yet another
stress amplifying mechanism (Fig. 4).
‘Materials failure’ might occur when structural
integrity is compromised by repeated cycling, with
each cycle causing additional microscopic fracture.
Such progression would help account for the exper-
imental observation that prone positioning delays
injury development but does not modify its even-
tual severity [34].
Given these stress amplifiers, the measurable
global transpulmonary pressures and volumes at
the airway opening may seriously underestimate
the actual tissue tensions at this local level that
result in damage. Perhaps such amplification par-
tially explains the point-wise development and
propagation of inflammation and focal hyperinfla-
tion observed at modest (lung protective) tidal vol-
&&
umes [35 ,36]. Anti-inflammation responses and
structural repair are quickly initiated at the time
of damage [37]. These include lipid trafficking to
the stretched cellular membrane surface [38,39], but
relatively little is known about the pace and trajec-
tory of this process. Minor insults to the alveolar–
capillary barrier may reverse within seconds ([40]
Dreyfuss et al.), whereas more vigorous and rapidly
recurring stresses initiate inflammation and cellular
death [32].
Sequential breakdown of the supporting net-
work of the lung may help explain the need to
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reduce the number as well as the amplitude of
potentially damaging cycles applied per unit time
as well as the potential for eventually exceeding
the threshold value for damaging overstretch by
unchanging transpulmonary pressures. Once a
threshold of microstrain is exceeded, unrecovered
straining energy of the tidal cycle may initiate a
cascading sequence of injury that progressively
accelerates. Whether it is the cumulative number
of such damaging cycles that matters or, more likely,
the intensity with which they are applied (fre-
quency) is currently unknown [41].
Conditional value and cautions in using
measured energy and power to approximate
ventilator-induced lung injury risk
From first principles, it is clear that for structural
change to occur, energy must be expended and
work be performed on the lung. It is also clear that
the time interval over which that cumulative
energy load is applied should be relevant to the
potential for damage. It has been proposed that
quantifying machine-delivered energy load or
power may provide a useful integrative index of
&& &&
mechanical VILI risk [21 ,22 ]. This concept holds
strong appeal; of the factors that have been demon-
strated experimentally to influence injury risk, all
are contained within the equation of motion. These
embedded factors include the driving pressure,
Pplat, flow rate, and frequency. Cycle energy is,
therefore, an inclusive variable that must in some
fundamental way relate to VILI, and trends in power
delivery should relate to the observed severity of
lung injury. Regarding power itself, there appears to
be a threshold value of intensity that – like strain –
must be crossed to inflict experimental damage
[42]. For a given patient with unchanging tidal
volume, it is reasonable to assume that reducing
VE and, therefore, lowering the exposure to one or
more of these power variables will reduce the hazard
to that individual. We are some distance away,
however, from the idea that reducing the raw
values of energy and power exposure by manipula-
tion of any of their individually embedded deter-
minants will effectively reduce damage in parallel
fashion [43].
For multiple reasons, the raw, unmodified val-
ues of machine-delivered energy or power (which
are based on airway pressures and tidal volumes)
cannot serve unconditionally as a guide to ventila-
tor adjustment for lung protection. One key factor
relates to lung capacity. A given quantity of inflation
energy will have the capacity to inflict more injury
upon a smaller lung than a larger one. Moreover, the
presumably harmless chest wall movement also taps
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Dissi pation of energy during the respiratory cycle Marini
the machine’s power. Regional stresses and power
&&
applications vary site-to-site [35 ], and thresholds
for both strain and power must be crossed for VILI to
ensue [14,19,42]. The vulnerability of the lung to
sustain injury is of clear importance, as are cofactors
such as temperature [44] and vascular pressure [12].
As an example, healthy athletes subject their lungs
to energy loads and inspiratory excursions of esoph-
ageal pressure for hours that far exceed those expe-
rienced by intubated patients without experiencing
adverse effects or injury [45]. If the same minute
ventilation is delivered by an increase in the fre-
quency rather than tidal volume, less damage is
expected to result. This is for two potential reasons
– less damaging strain per cycle; less total energy
(and power) applied.
Importantly, not all elements of the equation of
motion hold equal potential to injure lung paren-
chyma. Flow resistance dissipates energy along the
endotracheal tube and conducting airways before
the delicate parenchymal structures are encoun-
tered. Driving pressure is the component of inspira-
tory energy related to incremental dynamic strain.
Viewed from a global perspective, the product of
driving pressure and minute ventilation, adjusted
for the size of the baby lung by the ratio of expected
to observed compliance, seems likely to correlate as
well or better than the raw value of machine-deliv-
ered power with VILI potential [43].
This is not to say that flow and (transpulmo-
nary) PEEP are not influential in causing injury, only
that their contributions are not proportional to their
values within the equation of motion. Faster flow
means that the parenchyma of the baby lung is
stretched faster, accentuating dPalv/dT and the stress
focusing drag of viscoelastance. Although PEEP-
related inflation energy largely dissipates during
exhalation, higher PEEP for the same tidal volume
brings the dynamic strain at unopened junctional
units closer to their injuring threshold for strain,
especially at points of stress focusing. On the flip
side, for the same Pplat, increasing PEEP reduces the
dynamic strain.
As already noted, relatively little of the energy
applied to the lung during inflation cannot be
accounted for in ways that do not involve elastic
storage and dissipation against resistance during
both phases of the respiratory cycle. With the focus
on inflation, damaging energy and power would
appear to relate to the unrecovered straining energy
that does not help deflate the lung. However, the
possibility that energy released into the lung paren-
chyma upon exhalation might produce lung injury
has been suggested by experiments that demon-
strate that slowing deflation may reduce the severity
of pulmonary edema [46].
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