Title: Figure 4. (A) a mild responder, (B) a moderate responder, and (C) a severe responder. The top panels display the arterial blood gas measurements which were taken periodically. The middle and bottom panels display the dynamic R and E estimates
1Tracking Severity and Distribution of Lung
Disease During Mechanical Ventilation Application
s to Bronchoconstriction and Respiratory Distress
Syndrome C. Bellardine1, E.P. Ingenito2, A.
Hoffman3, F. Lopez4, W. Sanborn4, and K.R.
Lutchen1 1Biomedical Engineering, Boston
University, Boston, MA, 2Pulmonary Division,
Brigham and Women's Hospital, Boston, MA, 3Tufts
Veterinary School of Medicine, N. Grafton, MA,
4Puritan Bennett/Tyco Healthcare, Pleasanton, CA
INTRODUCTION
RESULTS I (Figure 3 Bronchoconstriction)
RESULTS III (Figure 5 Correlations)
- Mechanical ventilation is required when a
patient cannot generate sufficient pressures to
maintain ventilation. The lungs ability to
generate these pressures is governed primarily by
the elastic recoil and the resistance of the
respiratory system (E and R). - With lung disease, R and E become elevated and
increasingly more frequency dependent. The R and
E from 0.1 to 8 Hz reflect the level and pattern
of lung disease 1 and these data would aid in
evaluating the efficacy of mechanical
ventilation. Modern clinical ventilators apply
simple flow waveforms containing energy primarily
at one frequency. Therefore, the frequency
dependence of R and E cannot be tracked. - We have recently invented new broadband
ventilation patterns known as Enhanced Ventilator
Waveforms (EVWs) which contain discrete
frequencies (from 0.1 to 8 Hz) blended to provide
a tidal breath followed by a passive exhalation
2 (Fig 1). In principle, these waveforms allow
for estimation of R and E from 0.1 to 8 Hz during
ventilation.
Figure 1. EVW flow and volume are plotted vs.
time. Note the enhanced frequency content in the
inspiratory flow waveform and also the passive
expiratory sections.
- Figure 5. Correlation between decrease in
arterial PaO2 levels and increases in
heterogeneity (A) and airway closure (B). Within
both bronchoconstriction (blue) and RDS (red)
models, data revealed a range of constriction
conditions. The degree of heterogeneity and
airway closures quantified from EVW data was
strongly correlated with significant drops in O2.
Both increased heterogeneity and airway closures
are consistent with a substantial degradation of
ventilation distrubution.
(A)
(B)
(C)
Figure 3. (A) a mild responder, (B) a moderate
responder, and (C) a severe responder. The top
panels display the arterial blood gas
measurements which were taken periodically. The
middle and bottom panels display the dynamic R
and E estimates calculated from the EVW. Data
corresponding to baseline, initial response,
final response, and albuterol is shown. With
increased severity of response, the R and E are
elevated at all frequencies. The severe
responder shows significant evidence of airway
closure (elevated E at 0.2 Hz) and heterogeneous
constriction (more frequency dependence). This
should impact ventilation distribution. In fact,
oxygen levels are extremely depressed and carbon
dioxide levels are elevated.
GOAL
SUMMARY
To advance the delivery of an EVW for routine
clinical ventilation and evaluate whether the
frequency dependence of R and E provide insight
on degradation of lung gas exchange function.
- In all sheep the EVW sustains ventilation
similarly to conventional ventilation but the EVW
permitted insight on the level and distribution
of lung disease. - Data during bronchoconstriction revealed a range
of constriction conditions from mild and
homogeneous to severe and heterogeneous with
airway closures. Often there was lack of
complete improvement in R and E with albuterol or
recruitment maneuvers. This was consistent with
a pattern of airway closures that would not
reopen. - In the ARDS lung injury model, the EVW revealed
the progression of the disease and showed that
the extent of the defects in ventilation were
consistent with the heterogeneity of constriction
and airway closure. - Detailed analysis of all data (Figure 5)
indicated that the degradation in PaO2 (gas
exchange) was highly correlated with features of
dynamic R and E associated with functional airway
closures and heterogeneities. Both features
would imply degradation in ventilation
distribution leading to poor ventilation-perfusion
matching. - We conclude that the EVW is a viable new
ventilation method that can simultaneously
provide clinically unique information regarding
the mean level and heterogeneity of lung
constriction. The degree of heterogeneity
directly reflects the mechanical requirements of
breathing and potential ventilation-perfusion
mismatches. This unique information could be the
basis to of more knowledgeable and effective
clinician intervention with regards to treatment
and ventilator weaning strategies.
METHODS
RESULTS II (Figure 4 RDS Model)
- The EVW was applied in 5 sheep before and after
a bronchial challenge. - Measured arterial O2 and CO2. EVW processed to
obtain dynamic inspiratory R and E vs. frequency. - PROTOCOL
- Stabilize sheep on conventional ventilation for
15 minutes - Collect baseline dynamic R and E measurements
- Deliver nebulized carbochol (16mg/ml for 2
minutes). Monitor response through blood gas and
R and E. - Deliver albuterol MDI. Obtain final R and E
estimates. - The EVW was then applied in the same 5 sheep
before and during an oleic acid lung injury model
of ARDS and blood gases were once again tracked
along with lung mechanics.
Figure 2. The EVW was implemented in a prototype
of the NPB840 (Puritan Bennett/Tyco Healthcare)
ventilator shown above.
DATA ANALYSIS
- The flow and pressure at the airway opening were
measured (Qao and Pao, respectively). The
inspiratory segments of the pressure and flow
data were then isolated and fit to a
trigonometric Fourier Series using the technique
previously described by Kaczka 2. - The corresponding low frequency components of R
and E were recalculated to adjust for transient
artifacts. The Qao and Pao were low pass filtered
to isolate the low frequency components and fit
to the following equation using a standard linear
regression. Low frequency R and E were then
re-estimated. -
REFERENCES
(A)
(B)
(C)
- Lutchen, K.R. and B. Suki. Understanding
pulmonary mechancis using the forced oscillation
technique. Bioengineering Approaches to
Pulmonary Physiology and Medicine. 1996. - Kaczka, D.W., E. Ingenito, and K.R. Lutchen. A
technique to determine inspiratory impedance
during mechanical ventilation Implications for
flow limited patients. Annals of Biomedical
Engineering. 27 340-355, 1999.
Figure 4. (A) a mild responder, (B) a moderate
responder, and (C) a severe responder. The top
panels display the arterial blood gas
measurements which were taken periodically. The
middle and bottom panels display the dynamic R
and E estimates calculated from the EVW. With
increased severity of RDS, there were increased
airway closures, increased heterogeneity or
frequency dependence of both R and E, and
elevated R and E values at all frequencies.
Also, with increased severity, note the
depression of oxygen levels and increase of
carbon dioxide levels.