Effect of prolongation of expiratory time on dynamic

hyperination in mechanically ventilated patients with severe

asthma
James W. Leatherman, MD; Charles McArthur, RRT; Robert S. Shapiro, MD
A
lthough controlled hypoventi-
lation with permissive hyper-
capnia is currently the pre-
ferred ventilatory strategy for
management of status asthmaticus (16),
the degree to which ventilation should be
limited is not well established. Tuxen and
Lane (7) found that excessive dynamic
hyperination (DHI) predicted the devel-
opment of hypotension and barotrauma
during mechanical ventilation of severe
asthma, and Williams et al. (8) found that
the degree of DHI increased signicantly
when expiratory time was shortened by
increasing the respiratory rate or by de-
creasing the inspiratory ow rate. How-
ever, patients in the latter study were
only studied at three levels of minute
ventilation: 10, 16, and 26 L/min (8). It is
uncertain to what extent changes in ex-
piratory time would affect DHI at lower
levels of minute ventilation. This study
was designed to assess the effect of pro-
longation of expiratory time on DHI in
mechanically ventilated patients with sta-
tus asthmaticus whose baseline minute
ventilation approximated 10 L/min.
PATIENTS AND METHODS
Twelve patients (four men, eight women)
aged 1956 yrs (median, 34 yrs) who under-
went mechanical ventilation for status asth-
maticus were evaluated (Table 1). Clinical in-
dications for intubation were altered
mentation, evidence of fatigue, or both. All
patients were studied within 24 hrs of intuba-
tion while being mechanically ventilated
(Adult-Star Ventilator, Infrasonics) in the as-
sist-control mode with a square inspiratory
ow waveform and no applied positive end-
expiratory pressure (PEEP). The tidal volume
and inspiratory ow rate that had been se-
lected by the patients primary physician were
maintained during the study. At the time of
study, all patients were without spontaneous
respiratory efforts as a result of sedation with
propofol and fentanyl, with or without neuro-
muscular paralysis.
Airway pressurespeak pressure (Ppk),
plateau pressure (Pplat), and auto-PEEP
were measured at respiratory rates of 18, 12,
and 6 breaths/min. Measurements were made
after a minimum of ve to six breaths at the
given rate. Both Ppk and Pplat were recorded
from the ventilators digital display. A 2-sec
inspiratory pause was used to measure Pplat.
The ventilators automated auto-PEEP pro-
gram results in an unacceptably brief (1 sec)
end-expiratory pause. Therefore, auto-PEEP
was measured by manual occlusion, as previ-
ously described (9). Briey, after a pressure
recording device had been placed between the
endotracheal tube and the Y-piece through
use of a T adapter, the ventilator circuit was
removed during expiration and the open end
of the T adapter was manually occluded for
several seconds at end-expiration to seal the
airway and thereby permit measurement of
auto-PEEP. In seven cases, auto-PEEP was
measured with a variable reluctance pressure
transducer (Validyne MP-45) and in ve cases
with an anaeroid manometer (Boehringer,
From the Division of Pulmonary and Critical Care
Medicine, Hennepin County Medical Center, Minneap-
olis, MN.
Copyright 2004 by the Society of Critical Care
Medicine and Lippincott Williams & Wilkins
DOI: 10.1097/01.CCM.0000130993.43076.20
Objective: To assess the effect of a decrease in respiratory rate
on dynamic hyperination, as determined by changes in plateau
airway pressure, in patients with status asthmaticus whose base-
line minute ventilation approximated 10 L/min.
Design: Observational descriptive study.
Setting: Medical intensive care unit.
Patients: Twelve patients with severe asthma mechanically
ventilated in the assist control mode with a tidal volume of 613
100 mL and an inspiratory ow rate of 79 4 L/min.
Interventions: A decrease in respiratory rate from 18 to 12 and
6 breaths/min.
Measurements and Main Results: Plateau airway pressure
decreased by approximately 2 cm H
2
O (25.4 2.8 vs. 23.3 2.6
cm H
2
O, p < .01) when respiratory rate was decreased from 18 to
12 breaths/min (increase in expiratory time 1.7 secs) and by a
similar amount (23.3 2.6 vs. 21.3 2.9 cm H
2
O, p < .01) when
respiratory rate was decreased from 12 to 6 breaths/min (in-
crease in expiratory time 5 secs). Peak airway pressure was
similar at the three respiratory rates (66.8 8.7 vs. 66.4 9.5 vs.
67.8 11.1 cm H
2
O at 18, 12, and 6 breaths/min, respectively).
End-expiratory ow rates (n 7) were 61.4 12.6, 38.6 4.5,
and 23.1 5.8 mL/sec at respiratory rates of 18, 12, and 6
breaths/min, respectively.
Conclusions: Prolongation of expiratory time decreases dynamic
hyperination in patients with status asthmaticus, as evidenced by a
reduction in plateau airway pressure, but the magnitude of this effect
is relatively modest when baseline minute ventilation is <10 L/min,
because of the low end-expiratory ow rates. Since ow progres-
sively decreases throughout expiration, the reduction in dynamic
hyperination resulting from a given prolongation of expiratory time
will depend on the baseline respiratory rate (i.e., less reduction in
dynamic hyperination at a lower respiratory rate). Changes in peak
airway pressure may not always reect the changes in dynamic
hyperination that result from prolongation of expiratory time. (Crit
Care Med 2004; 32:15421545)
1542 Crit Care Med 2004 Vol. 32, No. 7
Riverside, CA), both devices having been cali-
brated previously. In seven cases expiratory
ow was also measured at the proximal end of
the endotracheal tube, using a pneumota-
chometer (Hans Rudolph 3700b, Kansas City,
MO) that had been calibrated by a ow rota-
meter in the range of 10200 mL/sec.
After data collection was completed, the
information was given to the patients primary
physician to assist in decision making regard-
ing choice of ventilator settings. Since the
information obtained during the study period
was being used to aid in bedside decision mak-
ing, the hospitals human research committee
approved the analysis and publication of data
that had been collected without need for in-
formed consent. Data are expressed as mean
SD. Statistical comparisons were done by Stu-
dents t-test.
RESULTS
At the time of study, tidal volume was
613 100 mL and inspiratory ow rate
was 79 4 L/min (Table 2). Expiratory
time was 2.9 0.1 secs at a respiratory
rate of 18 breaths/min, 4.5 0.1 secs at
a rate of 12 breaths/min, and 9.5 0.1
secs at a rate of 6 breaths/min.
As expected, Pplat decreased when re-
spiratory rate was lowered from 18 to 12
breaths/min (25.4 2.8 vs. 23.3 2.6
cm H
2
O, p .001). When the respiratory
rate was further decreased from 12 to 6
breaths/min, there was a similar reduc-
tion in Pplat (23.3 2.6 vs. 21.3 2.9
cm H
2
O, p .001; Fig. 1). Like Pplat,
auto-PEEP decreased when the respira-
tory rate was lowered from 18 to 12
breaths/min (14.8 3.0 vs. 12.3 3.0
cm H
2
O, p .001) and decreased further
when the rate was changed from 12 to 6
breaths/min (12.3 3.0 vs. 8.9 3.6 cm
H
2
O, p .001) (Fig. 1). In contrast to
Pplat and auto-PEEP, Ppk did not change
when the respiratory rate was lowered
from 18 to 12 breaths/min (66.8 8.7 vs.
66.4 9.5 cm H
2
O, p .8) or from 12 to
6 breaths/min (66.4 9.5 vs. 67.8 11.1
cm H
2
O, p .8; Fig. 1). Accordingly,
ow-resistive pressure (Ppk Pplat) in-
creased when respiratory rate was de-
creased from 18 to 12 breaths/min (41.4
9.1 vs. 43.1 10.1 cm H
2
O, p .01)
and increased further when respiratory
frequency was changed from 12 to 6
breaths/min (43.1 10.1 vs. 46.6 11.4
cm H
2
O, p .01). There was considerable
variability in the response of Ppk to low-
ering of respiratory rate (Table 2).
In seven cases expiratory ow tracings
were used to determine instantaneous
end-expiratory ow at each of the three
respiratory rates. End-expiratory ow was
61.4 12.6 mL/sec at a respiratory rate
of 18 breaths/min, 38.6 4.5 mL/sec at a
rate of 12 breaths/min, and 23.1 5.8
mL/sec at a rate of 6 breaths/min (Fig. 2).
An expiratory ow tracing for an individ-
ual patient is shown in Figure 3.
DISCUSSION
The rst large study to report on the
use of intentional hypoventilation for
management of status asthmaticus was
published by Darioli and Perret in 1984
(10). These investigators reasoned that,
in the setting of severe asthma, it may be
safer to limit the degree of pulmonary
hyperination than to attempt to correct
hypercapnia by increasing the ventilator
tidal volume and respiratory rate. The
fact that none of the 34 patients managed
with this novel approach died or devel-
oped barotrauma was striking given the
considerable mortality and morbidity
rates reported in earlier series of mechan-
ical ventilation for status asthmaticus
(11). Three years later, Tuxen and Lane
(8) examined three levels of minute ven-
Table 1. Patient demographics and baseline data
Age, median (range) 34 (1956)
Gender, M/F 4/8
Peri-intubation arterial blood gas
pH 7.07 0.11
PaCO
2
95 26
PaO
2
191 109
Initial ventilator settings
Tidal volume, L 0.613 0.100
Respiratory rate, breaths/min 15 2
Minute ventilation, L/min 9.02 1.00
Inspiratory ow rate, L/min 78 4
Postintubation arterial blood gas
pH 7.18 0.10
PaCO
2
68 15
PaO
2
135 47
Table 2. Ventilator settings and airway pressure values for individual patients at respiratory rates of 18, 12, and 6
Patient
V
T
,
L
Flow
insp
,
L/min
P
pk
, cm H
2
O P
plat
, cm H
2
O Auto-PEEP, cm H
2
O
18 12 6 18 12 6 18 12 6
1 0.600 80 63 60 58 27 24 21 11 10 5
2 0.600 80 74 72 72 28 26 24 18 15 14
3 0.500 80 69 72 77 24 23 23 11 8 5
4 0.600 80 72 72 77 24 21 19 15 12 8
5 0.900 85 50 49 48 29 27 25 14 12 8
6 0.600 80 78 77 76 29 26 25 20 17 14
7 0.650 80 62 60 65 27 25 22 16 12 9
8 0.600 70 75 76 77 24 23 21 12 10 8
9 0.600 80 62 60 59 27 24 21 19 17 13
10 0.600 70 56 56 57 20 18 15 12 8 3
11 0.500 80 76 79 85 23 21 19 15 13 10
12 0.600 80 65 64 63 23 22 20 15 13 10
Mean 0.613 79 66.8 66.4 67.8 25.4 23.3 21.3 14.8 12.3 8.9
SD 0.100 4 8.7 9.5 11.1 2.8 2.6 2.9 3.0 3.0 3.9
V
T
, tidal volume; Flow
insp
, inspiratory ow rate; P
pk
, peak airway pressure; P
plat
, plateau airway pressure; PEEP, positive end-expiratory pressure.
1543 Crit Care Med 2004 Vol. 32, No. 7
tilation (10, 16 and 26 L/min) and three
inspiratory ow rates (40, 70, and 100
L/min) in patients with severe air ow
obstruction, using the volume of gas ex-
haled during a prolonged apnea as the
principal indicator of DHI. Their most
important nding was that DHI increased
markedly as minute ventilation was in-
creased (8). In addition, at the two higher
levels of minute ventilation, DHI was in-
creased when expiratory time was short-
ened by a reduction in inspiratory ow
rate (8).
Our study was designed to address the
effect of expiratory time on the severity of
DHI in mechanically ventilated patients
with severe asthma at a minute ventila-
tion 10 L/min. As recommended previ-
ously (3, 5, 12, 13, 14), Pplat was used as
a principal indicator of change in DHI.
Although Pplat is of course inuenced by
the compliance of the lung and chest
wall, the change in Pplat at constant tidal
volume in response to prolongation of
expiratory time will reect the change in
DHI. As expected, prolongation of expira-
tory time resulted in a decrease in Pplat.
However, Pplat only decreased by a little
over 2 cm H
2
O when the respiratory rate
was lowered from 18 to 12 breaths/min
and by a similar amount when the rate
was further lowered further to 6 breaths/
min. Therefore, even when expiratory
time was prolonged by almost 7 secs,
Pplat decreased 5 cm H
2
O.
These changes in Pplat are predictable
in light of the measured values of end-
expiratory ow (Fig. 2). Average end-
expiratory ow rates were approximately
60 mL/sec at a respiratory rate of 18
breaths/min, 40 mL/sec at a rate of
12 breaths/min, and 20 mL/sec at a rate
of 6 breaths/min. Assuming a respiratory
system compliance of 60 mL/cm H
2
O (the
average value for our patients), to achieve
a 2 cm H
2
O decrease in Pplat (120 mL
reduction in lung volume) would require
that expiratory time be prolonged by 2
secs if expiratory ow rate was 60 mL/sec,
by 3 secs if the ow rate was 40 mL/sec,
and by 6 secs if it was 20 mL/sec. There-
fore, the benet derived from prolonga-
tion of expiratory time becomes progres-
sively less the lower the baseline
respiratory rate.
A high inspiratory ow rate (e.g., 100
L/min) has been advocated for manage-
ment of mechanically ventilated patients
with severe asthma to maximize expira-
tory time for any given respiratory fre-
quency (24, 12). However, at the tidal
volumes and respiratory rates used in this
study, the end-expiratory ow rates that
were measured would predict a minimal
impact of inspiratory ow rate on the
severity of DHI. For example, when tidal
volume is 600 mL, an increase in inspira-
tory ow rate from 60 L/min (1 L/sec) to
120 L/min (2 L/sec) will lengthen expira-
tion by 0.3 secs. With an end-expiratory
ow rate of 60 mL/sec, this would reduce
end-expiratory lung volume by only 20
mL. The trivial effect of inspiratory ow
rate on DHI at lower levels of minute
ventilation is consistent with the data
presented by Tuxen and Lane (8), in that
they noted a signicant impact of inspira-
tory ow rate on DHI only at higher lev-
els of minute ventilation.
One of the unanticipated ndings in
our study was that the average Ppk did
not change signicantly as respiratory
rate was decreased, with the response be-
ing variable among patients. In some
cases prolongation of expiratory time led
to nearly equivalent reductions in Ppk
and Pplat, without a change in inspira-
tory ow-resistive pressure (i.e., Ppk
Pplat). However, in other cases Ppk re-
mained unchanged (or even increased
slightly) as Pplat decreased, indicating
that ow-resistive pressure had in-
creased. The effect of lung volume on
total respiratory system resistance is
complex, with a decrease in lung volume
resulting in a simultaneous increase in
intrinsic airways resistance and a de-
crease in additional tissue resistance (15).
At the high inspiratory ow rates used in
our study, the effect on intrinsic airways
resistance may become more important
(15), and this could possibly account in
part for the observation that some pa-
tients showed an increase in ow-
resistive pressure as respiratory rate was
lowered. In addition, it is possible that
prolongation of expiratory time could al-
low more opportunity for airway closure
(9), and this could conceivably contribute
to an increase in ow-resistive pressure.
Regardless of the mechanism, our data
suggest that in some patients Ppk may
not reect changes in DHI that result
from prolongation of expiratory time.
Figure 1. Peak airway pressure, plateau pressure,
and auto-positive-end expiratory pressure (PEEP)
for respiratory rates of 18, 12, and 6 breaths/min.
Values are mean SD. *p .01.
Figure 2. End-expiratory ow rates in seven pa-
tients for respiratory rates of 18, 12, and 6
breaths/min. Values are mean SD.
Figure 3. Expiratory ow tracing from an indi-
vidual patient.
A
lthough prolonga-
tion of expiratory
time decreases the
degree of dynamic hyperin-
ation in patients with sta-
tus asthmaticus, as evi-
denced by a reduction in
plateau pressure, the magni-
tude of this effect is rela-
tively modest when baseline
minute ventilation is 10
L/min.
1544 Crit Care Med 2004 Vol. 32, No. 7
The most important ventilatory de-
terminant of DHI in status asthmaticus
is minute ventilation (6), and use of a
minute ventilation that produces exces-
sive DHI increases the risks of hypoten-
sion and barotrauma (8). In close agree-
ment with previous recommendations
(35), we believe that reasonable initial
ventilator settings for status asthmati-
cus would be a tidal volume of 89
mL/kg, a respiratory rate of 1214
breaths/min, and an inspiratory ow
rate of 60 L/min. Based on the results of
our study, most patients who trigger
the ventilator at slightly higher rates
are unlikely to experience signicant
worsening of their DHI and may derive
only limited benet from more aggres-
sive restriction of minute ventilation.
In addition, a highly restrictive ventila-
tory strategy (e.g., 10 breaths/min)
may require deep sedation or paralysis,
potentially increasing the likelihood of
prolonged intubation (16) and risk of
myopathy (17). On occasion, the sever-
ity of air ow obstruction is such that
the initial ventilator settings men-
tioned previously result in a Pplat 30
cm H
2
O, a level above which algorithms
for management of status asthmaticus
call for a reduction in respiratory rate
to reduce DHI (3, 4, 12). We agree with
this recommendation, because even a
relatively small decrease in the amount
of DHI could be of clinical importance
in certain patients with fulminant
asthma, especially in the presence of
hemodynamic instability or barotrau-
mas. Nonetheless, in such patients dra-
matic reductions in DHI will more of-
ten follow improvement in air ow
obstruction than ventilator manipula-
tion.
CONCLUSION
Although prolongation of expiratory
time decreases the degree of DHI in pa-
tients with status asthmaticus, as evi-
denced by a reduction in Pplat, the mag-
nitude of this effect is relatively modest
when baseline minute ventilation is 10
L/min. Furthermore, the lower the base-
line respiratory rate, the less the impact a
given prolongation of expiratory time will
have on the degree of DHI, because expi-
ratory ow rates become progressively
lower as expiratory time is prolonged. In
addition, the small increment in expira-
tory time that can be achieved with use of
a high inspiratory ow rate will have
minimal impact on DHI when minute
ventilation is 10 L/min, because of the
low end-expiratory ow rates at this level
of minute ventilation. Finally, the de-
crease in DHI resulting from prolonga-
tion of expiratory time is not always ac-
companied by a reduction in Ppk.
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