Journal of Critical Care 57 (2020) 208–213

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Journal of Critical Care

journal homepage: www.journals.elsevier.com/journal-of-critical-care

Patients alter power of breathing as the primary response to changes

in pressure support ventilation
Carl G. Tams, PhD a, Neil R. Euliano, PhD a,⁎, A. Daniel Martin, PT PhD b, Michael J. Banner, PhD RRT b,
Andrea Gabrielli, MD MBA, MHCI, FCCM c, Steven Bonnet, RRT b, Paul J. Stephan, RRT a,
Adam J. Seiver, MD PhD, MBA, FACS, FCCM d, Michael A. Gentile, MBA RRT FAARC FCCM e
a
Convergent Engineering, Gainesville, FL, United States
b
University of Florida Health, Gainesville, FL, United States
c
University of Miami Health System, Miami, FL, United States
d
Philips Healthcare, Carlsbad, CA, United States
e
Duke University Health System, Durham, NC, United States

a r t i c l e i n f o a b s t r a c t

Introduction: The patient-ventilator relationship is dynamic as the patient's health fluctuates and the ventilator
settings are modified. Spontaneously breathing patients respond to mechanical ventilation by changing their pat-
terns of breathing. This study measured the physiologic response when pressure support (PS) settings were mod-
Keywords: ified during mechanical ventilation.
Mechanical ventilation Methods: Subjects were instrumented with a non-invasive pressure, flow, and carbon dioxide airway sensor to
Work of breathing estimate tidal volume, respiratory rate, minute ventilation, and end-tidal CO2. Additionally, a catheter was
Power of breathing used to measure esophageal pressure and estimate effort exerted during breathing. Respiratory function mea-
Pressure support ventilation surements were obtained while PS settings were adjusted 569 times between 5 and 25 cmH2O.
Spontaneous breathing Results: Data was collected on 248 patients. The primary patient response to changes in PS was to adjusting effort
(power of breathing) followed by adjusting tidal volume. Changes in respiratory rate were less definite while
changes in minute ventilation and end-tidal CO2 appeared unrelated to the change in PS.
Conclusion: The data indicates that patients maintain a set minute ventilation by adjusting their breathing rate,
volume, and power. The data indicates that the subjects regulate their Ve and PetCO2 by adjusting power of
breathing and breathing pattern.
© 2020 Elsevier Inc. All rights reserved.

1. Introduction
Mechanical ventilation (MV) is a potentially life-saving support ap-
plied in a critical care setting. The role of mechanical ventilation is to
provide supplemental oxygen, remove CO2, and unload respiratory
muscles. Ventilators measure and display patient performance to assist
practitioners in delivering appropriate clinical care. Settings used during
MV are typically chosen by clinicians and managed via protocol. As pa-
tient clinical status fluctuates, MV settings are changed to meet physio-
logic targets. Inappropriate ventilator settings can cause barotrauma,
volutrauma, hypocapnia, hypercapnia, hypoxemia, asynchrony, respira-
tory muscles atrophy, and/or respiratory muscle fatigue [1–3].
⁎ Corresponding author at: 107 SW 140th Terrace STE 1, Newberry, FL 32669, United
States.
E-mail address: neil@conveng.com (N.R. Euliano).
Many responses to MV are well understood, such as: tidal volume
(VT), respiratory rate (RR), minute ventilation (Ve), and end-tidal CO2
(PetCO2), especially in sedated or passive patients. Actively breathing
patients, however, respond to changes in MV differently, and often, un-
predictably. Previous work has attempted to predict the changes of Ve,
VT, and RR with respect to changes in pressure support (PS) [4]. In addi-
tion to these measures, power of breathing (POB) or work of breathing
(WOB) has shown to have clinical importance for supporting patients
with MV [5,6]. However, patient responses in POB and WOB while Ve
settings are changed are not well documented. Understanding how pa-
tient respiratory system's respond to settings may enable clinicians to
better optimize MV management.
The purpose of this study was to evaluate the respiratory system re-
sponse in actively breathing patients for VT, RR, Ve, POB, WOB, and
PetCO2 when PS settings are changed. Specifically, to evaluate the distri-
bution of responses as observed from patients in a critical care setting.

https://doi.org/10.1016/j.jcrc.2020.03.004
0883-9441/© 2020 Elsevier Inc. All rights reserved.
 C.G. Tams et al. / Journal of Critical Care 57 (2020) 208–213 209

Table 1 Table 3
Patient diagnosis and demographic chart. Average respiratory parameter values for the study population.

Demographic Height (cm) 167 ± 25 Respiratory parameter Mean Standard deviation

Weight (kg) 83 ± 60
PS (cmH2O) 14 7
BMI (kg/m2) 29.8 ± 8.1
POB (J/min) 8.2 5.9
Gender 103 Female / 145 Male
WOB (J/L) 0.38 0.28
Age (yrs) 61 ± 16
PetCO2 (mmHg) 38 9
Diagnosis CHF/ARDS/PE/Pneumonia 69
VT (mL) 501 184
COPD 67
RR (BPM) 20 8
Trauma 18
Ve (L/min) 9.1 3.2
Respiratory Insufficiency 94

2. Methods
After IRB approval was obtained, potential subjects were screened
for qualification. Subjects were enrolled in the study after informed con-
sent was obtained. The study was conducted under the IRB approved
protocols #271-2001 at Shands Hospital (University of Florida) and
#B2004:156 at Health Sciences Centre Winnipeg Hospital (University
of Manitoba).
Inclusion Criteria:
• Adult patients (N18 years of age), intubated and receiving mechanical
ventilation
• Hemodynamic stability (systolic blood pressure N90 mmHg, receiving
no vasopressors, and lack of shock)
• Ability for placement of an esophageal balloon
• Ability to tolerate changes in ventilator support (as determined by the
attending physician)
Exclusion Criteria:
• Pregnancy
• Esophageal function limiting diseases (i.e. severe dysphagia)
• Closed-head injury (trauma)
• Other torso trauma or condition impacting normal sternocleido-
mastoid and diaphragm muscle activity
All patients included in the study were receiving MV for respiratory
assistance via a standardized device (Puritan-Bennett 840, Medtronic,
Boulder, CO). Each patient had stable breathing patterns with accept-
able blood gases as observed by the attending physician for at least
15 min prior to instrumentation. A combined pressure / flow / carbon
dioxide sensor was placed between the Y-piece of the ventilator breath-
ing circuit and endotracheal tube (ETT). The sensor was connected to a
computerized respiratory monitoring system (NICO, Respironics, Carls-
bad, CA). All subjects received either a specialized nasogastric (NG) tube
or an esophageal catheter, both with a built-in balloon capable of main-
taining pressure. The pressure catheter was connected to a pressure
transducer to measure the subject's esophageal pressure (Pes). A pulse
oximeter probe measured oxygen saturation. The data from the ventila-
tor, respiratory monitor, pressure transducer, and physiologic monitor
were synced and collected through proprietary software (Convergent
Engineering, Gainesville, FL) embedded on a laptop computer.
The PS setting was then randomly adjusted by increments of ±5
or ±10 cmH2O from baseline set by the clinical team. The randomized
process was computer generated. The initial PS setting was input. The
total PS change never exceeded an increase/decrease from the initial
PS setting by more than 10 cmH2O and was limited to the range of 5
to 25 cmH2O.
The primary outcome measures of the study were the patient re-
sponses to changed PS settings. Parameters obtained included: power
of breathing (POB, J/min), work of breathing (WOB, J/L), breathing fre-
quency (f, breaths/min), tidal volume (VT, L), minute ventilation
(Ve, L/min), and end tidal CO2 (PetCO2, mmHg). The f, VT, Ve, and
PetCO2 were measured from the respiratory monitor. The POB and
WOB were calculated using the signals from Pes and flow sensors (in-
cluding volume). As often reported in critical care literature, WOB was
normalized by tidal volume and expressed in units of Joules/Liter and
POB was work per unit time and expressed in units of Joules/Minute
[5] The software time synced and stored the measurements with the
ventilator settings for each breath. Additionally, the primary outcome
measures were calculated for each patient at each PS setting as the av-
erage value over the PS setting. Each PS setting was held for at least
15 min, any instances when the breathing pattern was not consistent
for at least 5 min were excluded. A “patient response” was defined as
a combination of the effect of the ventilator on physiology, change in
breathing pattern, and change is effort.
2.1. Data analysis
Six fixed effect one-way ANOVA tests (MATLAB, The MathWorks,
Inc., Natick, MA) were performed to determine what parameter changes
were significant for the PS changes of each respiratory parameter
change and PS change. Another set of ANOVA tests were performed to
determine if the starting PS impacted the respiratory parameter change.
This was done with six fixed effect one-way ANOVA tests (one for each
parameter) on the respiratory parameter change and the initial PS level

Table 2
Patient response categories for each primary outcome measure when +5 cmH2O pressure support is applied.

ΔVt (mL) ΔRR (bpm) ΔMV (L/min) ΔPetCO2 (mmHg) ΔWOB (J/L) ΔPOB (J/min)

Generalized Range Low 360 10 5 35 0.2 5

High 700 30 15 55 1.0 10
Response Category Expected Response Increase Decrease No change No change Decrease Decrease
Opposite Response b−56 N3.3 – – N0.13 N0.8
No Response −56 to 56 3.3 to −3.3 −1.6 to 1.6 −3.3 to 3.3 0.13 to −0.13 0.8 to −0.8
Mild Response 56 to 113 −3.3 to −6.6 b−3.3 & N−1.6 3.3 to 6.6 −0.13 to −0.26 −0.8 to −1.6
or or
N1.6 & b3.3 −3.3 to −6.6
Predicted Response N113 b−6.6 b−3.3 or N3.3 N6.6 b−0.26 b−1.6
or
b−6.6
210 C.G. Tams et al. / Journal of Critical Care 57 (2020) 208–213
Table 4
Response for each respiratory parameter for each PS setting change.
PS Change (cmH2O)
Increased 10 Increased 5
POB (J/min) −4.37 ± 2.79 −3.08 ± 3.54
WOB (J/L) −0.10 ± 0.16 −0.11 ± 0.14
PetCO2 (mmHg) −0.9 ± 1.7 −0.7 ± 2.1
VT (mL) 180 ± 180 90 ± 130
RR (BPM) −6.5 ± 6.2 −2.4 ± 5.0
Ve (L/min) 0.20 ± 1.23 0.41 ± 1.54
(only for the PS change of +5/−5 cmH2O, as there was insufficient data
for analysis for +10/−10 cmH2O). Statistical significance was defined
as p b .05.
We also analyzed the degree of response of each parameter for PS
changes. This analysis measured how often the respiratory parameter
changed when the PS changed. As well as, the response of the respira-
tory parameters' change.
2.2. Evaluating the patient response
The patient's response for each parameter was classified into one of
four response categories. The four categories are; opposite response, no
response, mild response, and predicted response, as listed in Table 2.
The response categories were calculated as a function of a subjec-
tively presumed range. A predicted response is a change in the parame-
ter greater than the range divided by three. A mild response is a change
in the parameter greater than the range divided by six, excluding the
predicted response. No response is a change in the parameter greater
than an opposite range divided by 6 (excluding predicted and mild re-
sponses). An opposite response is a change in the parameter less than
the opposite range divided by six.
3. Results
Data was collected on 248 critically ill patients receiving MV. The pa-
tient diagnoses range from various etiologies are shown in Table 1. The
PS setting on the ventilator was recorded to have changed 569 times;
238 times the PS change was by +5 cmH2O, 33 changes of +10
cmH2O, 252 changes of −5 cmH2O, and 46 changes of −10 cmH2O.
The average respiratory parameter values for the study population are
shown in Table 3.
3.1. Respiratory parameters changes
All of the study respiratory parameters, except Ve, significantly
changed with respect to PS changes, as described in Table 4. Further-
more, the distribution of the changing parameters can be seen in Fig. 1
panels A–F. The largest distinction between the +10 and +5 vs the
−5 and −10 cmH2O distributions, listed in decreasing order, is noticed
in panel F (POB), then in panel E (WOB), and finally in panel A(Vt). The
minimal overlap indicates the expected POB, WOB, and Vt response to
an increase in PS is different than the expected response to a decrease
in pressure support. The distribution of the respiratory rate responses
and PetCO2 responses, Fig. 1 panel B and D, show more overlap; indicat-
ing a less definite response. The distribution of Ve responses, Fig. 1 panel
C, show a large amount of overlap, indicating the Ve response is irre-
spective of PS change.
p value
Decreased 5 Decreased 10
2.29 ± 2.38 4.35 ± 3.68 b0.001
0.08 ± 0.09 0.19 ± 0.32 b0.001
0.8 ± 2.1 0.5 ± 2.0 b0.001
−70 ± 90 −150 ± 180 b0.001
2.8 ± 5.0 5.1 ± 6.1 b0.001
0.01 ± 1.23 −0.04 ± 1.35 0.175
3.2. Patient response
The frequency of the responses, as shown in Table 5, indicate that
when PS is changed by 5 cmH2O the most frequent response for Vt,
RR, Ve, PetCO2, and WOB was “No Response”, only POB frequently elic-
ited a “Predicted Response”. Furthermore, when PS is changed by 10
cmH2O only POB and Vt most frequently elicited a “Predicted
Response”. The Ve and PetCO2 almost always [76%–92%] had “No
Response” to any PS changes.
3.3. Initial PS setting
The initial PS setting had a great impact on the subject's VT when PS
setting was changed either +5 or −5 cmH2O [p = .02 & p b .001]. See
Tables 6 and 7. The Vt changed higher when the initial PS was higher.
For higher initial PS settings (N15 cmH2O) the Vt change was
100–125 mL while the Vt change when initial PS settings were lower
(b10 cmH2O) was only 30–50 mL. POB was found to be correlated
with initial PS settings when the change was +5 [p = .03], but this re-
lationship was not found when decreased by 5 cmH2O [p = .89]. The
other respiratory parameters (WOB, PetCO2, Ve, RR) had insignificant
changes with response to initial PS [p N .05].
4. Discussion
The primary findings of this study are subjects regulate their Ve and
PetCO2 by adjusting other parameters. Furthermore, responses often
counteract the ventilator changes, i.e. subjects breathe harder, faster,
and/or deeper when the ventilator provides less PS. The results indicate
POB is the primary response mechanism reacting to changes in PS. Only
POB had changes when PS changed by 5 cmH2O. The next strongest re-
sponse to changing PS was tidal volumes, but a change is not expected
to occur until the PS changed by 10 cmH2O. The patient's changing re-
sponse of RR and WOB were moderate, while, minute ventilation and
PetCO2 generally did not change when PS levels were changed. Specifi-
cally, results from these patients in this study indicate that when PSV is
changed, POB and Vt change most often. Generally, RR changes less
often and usually changes in the opposite direction of Vt to maintain
Ve. Since RR does not change as frequently in Vt, there is a trend towards
changing Ve.
The clinical implications and applications of these findings are mul-
tifaceted. Understanding how patients respond to PS settings will assist
clinicians in how to titrate PS settings to meet therapeutic objectives.
While some responses can be generalized, individual attention must
be given to patients in order to optimize mechanical ventilation. Specif-
ically, pressure-volume relationships can be measured and managed by
adjustments in PS and measured in a variety of ways, including POB. The
range and results of PS adjustments are based on several indicators, POB
may help refine this process. These results indicate POB is the most
prominent parameter in response to PS level changes. Since excessive
 C.G. Tams et al. / Journal of Critical Care 57 (2020) 208–213 211

(a) (b)

(c) (d)

(e) (f)

Fig. 1. probability density function of the reported patient responses when the pressure support setting is changed on a ventilator by −10 (blue), −5 (magenta), +5 (green), and +10 cm
H2O (red). Panel A is the tidal volume (L) response, panel B is the respiratory rate (bpm) response, panel C is the minute ventilation (L/min) response, panel D is the end tidal CO2 (mmHg)
response, panel E is the work of breathing (J/L) response, and panel F is the power of breathing (J/min) response.
212 C.G. Tams et al. / Journal of Critical Care 57 (2020) 208–213

Table 5 than VT. These results may be somewhat different, when compared
Frequency of patient response to pressure support changes on the ventilator. The percent- with the fundamentals for current PS titration systems. The prevalent
ages in each row sum to 100%. The largest percentage indicating the most frequent
response is marked by an bold.
PS titration settings technologies available today focus on targeting Ve,
VT, RR, and PetCO2 [7]. However, most frequently Ve and PetCO2 did
Parameter PS Opposite No Mild Predicted not change with PS changes; and furthermore, Vt and RR reliably
change response response response response
changed only for PS change of 10 cmH2O.
(cmH2O)
The POB value was found to be the most sensitive respiratory param-
Vt (mL) +10 4% 22% 18% 56%
eter with changes in PS. The correlation between PS changes and the pa-
+5 1% 47% 28% 24%
−5 2% 51% 25% 23% tient response POB change, is consistent with what has been
−10 3% 23% 23% 51% determined by others as well. One research finding was with spontane-
RR (bpm) +10 4% 30% 20% 46% ous breathing trials, which can simply be considered as a large decrease
+5 6% 62% 17% 15% in PS. POB was found to be a better predictor for spontaneous breathing
−5 5% 57% 25% 14%
−10 1% 45% 25% 29%
trial success over Vt, RR, and f/Vt [8]. Another research finding was eval-
MV (L/min) +10 – 79% 20% 1% uating causes for fatigue and atrophy. The investigators reported opti-
+5 – 81% 18% 1% mizing the POB value might even decrease the occurrence of fatigue
−5 – 88% 11% 1% or atrophy [9,10]. Finally, Talmor et al. have focused extensive research
−10 – 76% 23% 1%
efforts on measuring and understanding breathing effort. They conclude
PetCO2 +10 – 89% 8% 2%
(mmHg) +5 – 91% 7% 2% that evaluating the breathing effort provides a better understanding of
−5 – 92% 7% 1% the pathophysiology of patients [11,12].
−10 – 86% 14% 0% The presented study has limitations. We anticipate that other factors
WOB (J/L) +10 6% 41% 41% 12% impact the patient response relationship with mechanical ventilators.
+5 3% 55% 29% 13%
VT depends on lung mechanics (lung compliance and airway resis-
−5 1% 74% 21% 4%
−10 3% 41% 28% 28% tance) however these were not calculated. Additionally, the sedation
POB (J/min) +10 2% 8% 7% 83% levels were not recorded and may limit the active responses when PS
+5 8% 11% 11% 70% settings are changed.
−5 6% 18% 16% 60%
−10 5% 13% 8% 74%

or minimal POB values can lead to fatigue or atrophy, POB can be used in
the decision process to titrate mechanical ventilation. Future evalua-
tions should determine if prospectively targeting POB has impact on pa-
tient outcomes. Basic test lung simulations conclusively demonstrate
that increased PS increases VT and Ve proportionally. However,
in-vivo results by Nava et al. indicate that PS increases by 5 cmH2O sig-
nificantly increased VT while the Ve remained constant [4]. It was con-
cluded that the patients maintained Ve by reducing RR. Our results
confirm the findings by Nava et al. in regard to Ve, VT, and RR and yet
furthermore we found that POB was more sensitive to PS changes
5. Conclusion
Patients responded to changes in PS by changing parameters to
maintain MV and PetCO2. The predominant patient response to PS
changes is changing their effort (POB), a moderately reliable response
is changing their VT, while RR and WOB were unreliable responses.
Since POB is the most frequent parameter that best describes the patient
response to PS setting changes; we therefore conclude, that if POB
would be used in a clinical setting, optimal ventilator settings could be
determined more often.

Table 6
Average patient response to +5 cmH2O based on the initial ventilator pressure setting.

VT (mL) RR (bpm) MV (L/min) PetCO2 (mmHg) WOB (J/L) POB (J/min)

Initial Pressure Setting (cmH2O) b10 49 ± 44 −0.8 ± 3.6 0.5 ± 1.4 −1.0 ± 1.4 −0.08 ± 0.08 −1.8 ± 1.8
[10–15) 85 ± 120 −2.9 ± 5.5 0.2 ± 1.6 −0.9 ± 1.8 −0.11 ± 0.14 −3.1 ± 3.6
[15–20) 123 ± 167 −3.3 ± 5.8 0.4 ± 1.7 0 ± 1.7 −0.12 ± 0.14 −3.7 ± 3.4
b20 116 ± 143 −2.1 ± 3.8 0.3 ± 0.9 −0.7 ± 3.4 −0.12 ± 0.22 −4.0 ± 4.6
ANOVA p value 0.02 0.09 0.73 0.05 0.61 0.03

Table 7
Average patient response to −5 cmH2O based on the initial ventilator pressure setting.

VT (mL) RR (bpm) MV (L/min) PetCO2 (mmHg) WOB (J/L) POB (J/min)

Initial Pressure Setting (cmH2O) b10 −29 ± 28 1.8 ± 2.9 0.2 ± 0.6 0.8 ± 1.5 0.06 ± 0.04 1.9 ± 1.4
[10–15) −39 ± 61 2.0 ± 3.5 0.2 ± 1.0 1.1 ± 1.7 0.08 ± 0.08 2.3 ± 1.8
[15–20) −74 ± 94 3.3 ± 5.9 0.1 ± 1.3 0.7 ± 1.7 0.08 ± 0.09 2.5 ± 2.4
N20 −102 ± 134 4.0 ± 6.5 −0.1 ± 1.3 0.6 ± 3.2 0.07 ± 0.08 2.2 ± 2.3
ANOVA p value b0.001 0.19 0.24 0.54 0.75 0.89
 C.G. Tams et al. / Journal of Critical Care 57 (2020) 208–213 213

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