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Ventilation-perfusion inhomogeneity increases gas uptake
in anesthesia: computer modeling of gas exchange
Philip J. Peyton, Gavin J. B. Robinson and Bruce Thompson
J Appl Physiol 91:10-16, 2001. ;

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J Appl Physiol
91: 10–16, 2001.

Ventilation-perfusion inhomogeneity increases gas

uptake in anesthesia: computer modeling of gas exchange

PHILIP J. PEYTON,1 GAVIN J. B. ROBINSON,2 AND BRUCE THOMPSON3

Departments of 1Anaesthesia and 3Respiratory Medicine, Austin and Repatriation Medical Centre,
Heidelberg 3084; and 2Department of Anaesthesia and Pain Medicine, The Alfred,
Prahan 3181, Melbourne, Victoria, Australia
Received 4 April 2000; accepted in final form 17 January 2001

Peyton, Philip J., Gavin J. B. Robinson, and Bruce V̇A/Q̇ inhomogeneity on gas exchange in the presence of
Thompson. Ventilation-perfusion inhomogeneity increases a typical inspired mixture of O2 and N2O. The model
gas uptake in anesthesia: computer modeling of gas ex- first employed theoretical log normal distributions. Be-
change. J Appl Physiol 91: 10–16, 2001.—Ventilation- cause distributions of V̇AE and inspired V̇A (V̇AI) may
perfusion (V̇A/Q̇) inhomogeneity was modeled to measure its

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produce different effects, results based on each were
effect on overall gas exchange during maintenance-phase
N2O anesthesia with an inspired O2 concentration of 30%. A compared. In addition, measured distributions of V̇AE
multialveolar compartment computer model was used based and Q̇ published previously by other authors using the
on physiological log normal distributions of V̇A/Q̇ inhomoge- multiple inert-gas elimination technique (6) were mod-
neity. Increasing the log standard deviation of the distribu- eled to see whether the patterns of widening of distri-
tion of perfusion from 0 to 1.75 paradoxically increased O2 butions measured in patients are expected to produce
uptake (V̇O2) where a low mixed venous partial pressure of the same effects on gas exchange as widening of the
N2O [high N2O uptake (V̇N2O)] was specified. With rising smooth theoretical distributions.
mixed venous partial pressure of N2O, a threshold was ob-
served where V̇O2 began to fall, whereas V̇N2O began to rise METHODS
with increasing V̇A/Q̇ inhomogeneity. This phenomenon is a
A computer model was used to calculate the exchange of
magnification of the concentrating effects that V̇O2 and V̇N2O
multiple gases across the alveolar-capillary membrane ac-
have on each other in low V̇A/Q̇ compartments. During
cording to principles of mass balance for each gas. The model
“steady-state” N2O anesthesia, V̇N2O is predicted to paradox-
assumes that, within a compartment, arterial and alveolar
ically increase in the presence of worsening V̇A/Q̇ inhomoge- partial pressures for each gas species are identical. The
neity. independent variables for the calculation of alveolar partial
alveolar-arterial difference; oxygen uptake pressures and gas exchange for each gas are its inspired
fractional concentration, the mixed venous content [or partial
pressure and Ostwald solubility coefficient (␭)], and V̇AE or
THE EFFECT ON GAS EXCHANGE of inhomogeneity of venti- V̇AI and Q̇ for that compartment. The structure and data flow
lation-to-perfusion ratios (V̇A/Q̇) in the lung has been of this model are outlined in more detail in the accompanying
papers (12, 13). The distributions of ventilation and Q̇ given
explored by previous authors (1). Analysis of log nor- to the model were obtained as follows.
mal distributions of expired alveolar ventilation (V̇A;
V̇AE) and blood flow (Q̇) by West (17, 18) and Kelman (8) Theoretical Log Normal Distributions
predicted reduced gas exchange for any gas species.
Log normal distributions of Q̇ and ventilation were gener-
For the sake of simplicity, this early modeling assumed ated. The log SD of the distribution is the index of its spread,
the presence of no soluble accompanying gases in the varying between 0 (homogeneous lung) and 1.75. West (17)
inspired mixture. showed that, for any given mode and log SD, identical results
However, two-compartment modeling of the effect of are obtained with a primary distribution of either Q̇ or
increasing inhomogeneity of ventilation and Q̇ pre- ventilation. Log normal distributions of either V̇AE or V̇AI can
dicted a paradoxical increase in the uptake of one gas be nominated.
when mixtures of two soluble gases are administered, When a log normal distribution of V̇AI was nominated, the
such as is the case during inhalational anesthesia with effect of absorption atelectasis was modeled as follows. No
oxygen and nitrous oxide (N2O). These findings are inspired ventilation was distributed to compartments where
V̇AI/Q̇ was below a critical value at which V̇AE was calculated
presented in the accompanying paper (12). to be less than zero. This is based on similar assumptions to
To determine the clinical relevance of these findings, those made by Dantzker et al. (5) that such compartments
we have extended this study using a computer model of would suffer collapse. Given that steady-state gas exchange
physiological distributions of ventilation and Q̇ to in- was being modeled, it was assumed that perfusion of such
vestigate the predicted effects of differing degrees of
The costs of publication of this article were defrayed in part by the
Address for reprint requests and other correspondence: P. J. Peyton, payment of page charges. The article must therefore be hereby
Dept. of Anaesthesia, Austin & Repatriation Medical Centre, Heidel- marked ‘‘advertisement’’ in accordance with 18 U.S.C. Section 1734
berg 3084, Melbourne, Australia (E-mail: [email protected]). solely to indicate this fact.

10 8750-7587/01 $5.00 Copyright © 2001 the American Physiological Society http://www.jap.org

 VENTILATION-PERFUSION INHOMOGENEITY INCREASES GAS UPTAKE 11

compartments was shunt, with an end-capillary gas content Q̇ (including shunt and dead space), inspired concentrations,
identical to that of mixed venous blood. Both V̇AE and V̇AI for and V̇O2 and V̇CO2 were set at the values given above. The
these compartments were made zero, and the inspired ven- mixed venous N2O partial pressure (Pv៮ N2O) was set at a value
tilation from them was redistributed to the remaining com- giving an V̇N2O of 100 ml/min for the narrower distribution of
partments by multiplying each by a scaling factor to restore each pair.
total V̇AI to its nominated value. Modifications incorporated
by Dantzker et al. to simulate the effect of hypoxic pulmonary
RESULTS
vasoconstriction on the distribution of Q̇ were included. Once
again, perfusion of all compartments was scaled so that total Theoretical Log Normal Distributions
Q̇ remained at the nominated value. An iterative approach is
required for these modifications so that final distributions Paradoxical augmentation of steady-state V̇N2O. A
obtained were consistent with all of the input variables. Pv៮ N2O of 468 Torr was nominated, giving a V̇N2O for a
West (17) demonstrated that 10 compartments are ade- homogeneous lung (0 log SD) of 100 ml/min. Increasing
quate to obtain maximal precision of results for output vari- the log SD of the distribution of Q̇ (increasing inhomo-
ables from such a model. It was found, however, that when
geneity of V̇A/Q̇ matching) produced an increased arte-
collapse of compartments with critically low V̇AI/Q̇ was incor-
porated, 50 compartments were required to avoid noticeable rial partial pressure of N2O (PaN2O) and V̇N2O. This
quantization error because of inclusion or exclusion of com- occurred in the presence of either fixed O2 and CO2
partments with V̇AI/Q̇ values near the critical value. exchange or fixed mixed venous partial pressures of
these gases. The predicted V̇N2O at a log SD of 1.75 was

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Measured Distributions more than twice the value predicted at 0 log SD.
Three pairs of distributions of ventilation and Q̇ were Figure 1 demonstrates that the trend is predicted by
taken from the previously published paper by Dueck et al. models based on log normal distributions of either V̇AE
(6). These were distributions of their subjects 6, 7, and 8. or V̇AI, although the results are quantitatively different
Each pair consisted of a narrower and a wider distribution for each. The increase in V̇N2O at a given Pv៮ N2O was
(taken before and after induction of anesthesia in Dueck’s lower when modeling incorporated the effect of shunt
subjects) whose log SD (as given by Dueck) is listed in because of collapse of compartments with critically low
Table 1. V̇AI/Q̇. Paradoxical augmentation in fact peaked at a
Analysis Performed log SD of ⬃1.25 and then declined using this model.
However, incorporation of the effect of hypoxic pulmo-
Theoretical log normal distributions. A scenario typical of nary vasoconstriction increased uptake somewhat by
the maintenance phase of an inhalational anesthetic was reducing shunt fraction, particularly at more severe
modeled involving administration of an inspired mixture of
30% O2 and 70% N2O. For purposes of comparison, regard- levels of V̇A/Q̇ inhomogeneity.
less of whether a distribution of V̇AE or V̇AI was nominated, Rising Pv៮ N2O. The effect of the Pv៮ N2O on this phenom-
overall V̇AE was held at 4.1 l/min and Q̇ was 4.8 l/min. enon was investigated by repeating the study (Fig. 2)
Parameters examined in the primary analysis were uptakes at different values of Pv៮ N2O between 0 and 600 Torr
of O2 (V̇O2), CO2 (V̇CO2), and N2O (V̇N2O) on a global basis and (where it exceeds PaN2O and net N2O elimination is
by compartment. Analyses were performed with either spec- expected to occur in the homogeneous lung). Mixed
ified mixed venous partial pressures or specified gas uptakes venous partial pressures of O2 and CO2 were held
(or combinations of these for different gases). Where speci- constant. At low Pv៮ N2O where high V̇N2O was simu-
fied, V̇O2 and V̇CO2 were set at 250 and 200 ml/min, respec- lated, PaN2O and V̇N2O fell progressively with increas-
tively.
Measured distributions. The analysis was repeated using ing V̇A/Q̇ inhomogeneity. This fall became less steep as
the three pairs of measured distributions. Gas exchange was Pv៮ N2O rose to a threshold (Pv៮ N2O of ⬃300 Torr in this
calculated and compared for each pair of distributions using scenario), where the slope reversed and V̇N2O increased
the input variables listed above. For purposes of standard- with worsening inhomogeneity. At a Pv៮ N2O of ⱖ300
ization, the distributions were scaled so that overall V̇AE and Torr, paradoxical augmentation of V̇N2O occurs.

Table 1. Results of modeling changes in V̇N2O when moving from narrower to wider distributions measured
using the multiple inert-gas elimination technique
Subject

6 7 8

6b 6b 7b 7b 8b 8b
Distribution No. narrower wider narrower wider narrower wider

log SD blood flow 0.86 1.67 1.42 2.37 1.17 1.95

True inert-gas shunt, % 1.8 26.7 0.0 3.0 0.0 13.8
VD/VT, % 51.0 53.9 38.8 38.4 24.6 49.5
V̇N2O, l/min 0.100 0.095 0.100 0.207 0.100 0.122
Pv̄N2O, Torr 485.5 498.2 498.7
⌬V̇N2O, % ⫺5.0 ⫹107.0 ⫹22.0
The multiple inert-gas elimination technique is by Dueck et al. (6). VD/VT, ratio of dead space to tidal volume; V̇N2O, N2O uptake; Pv̄N2O,
mixed venous partial pressure of N2O; ⌬, change.
12 VENTILATION-PERFUSION INHOMOGENEITY INCREASES GAS UPTAKE

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Fig. 1. Predicted N2O uptake (V̇N2O) with increasing ventilation-to- Fig. 2. Effect of rising Pv៮ N2O on the relationship of V̇N2O to the
perfusion ratio (V̇A/Q̇) inhomogeneity as indexed by the log SD of the severity of V̇A/Q̇ inhomogeneity. In the scenario modeled, with an
distribution of blood flow (Q̇) for a constant mixed venous partial inspired fraction of N2O of 0.7 and constant mixed venous partial
pressure of N2O (Pv៮ N2O) (468 Torr). O2 uptake (V̇O2) (and respiratory pressures of O2 and CO2, the threshold for paradoxical augmentation
quotient) was held constant. Predictions from a model based on a log of V̇N2O was a Pv៮ N2O of 300 Torr.
normal distribution of expired alveolar ventilation (V̇AE), a model
based on a log normal distribution of inspired alveolar ventilation
(V̇AI), are shown. The constant inflow model was also modified to shown. The calculated percent change in V̇N2O, moving
incorporate the effects of alveolar collapse of compartments with from the narrower to the wider distribution of each
critically low V̇AI/Q̇ and also with the effect of hypoxic pulmonary
vasoconstriction (HPV). pair, incorporating the effects of changes in shunt and
dead space, are given in the bottom row. It can be seen
that predicted V̇N2O doubled in subject 7 as the log SD
The slope became steeper as Pv៮ N2O rose, but the
intercept with the ordinate (at log SD of 0) fell progres-
sively, eventually becoming negative. At this point, net
V̇N2O is calculated to be negative for the homogeneous
lung and still positive for the lung with significant
V̇A/Q̇ inhomogeneity, despite identical inspired and
mixed venous gas content.
O2 exchange. V̇O2 was calculated simultaneously
with V̇N2O at increasing Pv៮ N2O (Fig. 3). It was found
that paradoxical augmentation of V̇O2 [and thus arte-
rial O2 partial pressure (PaO2)] occurred as the log SD
of the distribution of perfusion was increased from 0 to
1.75. The augmentation effect was similar in nature
but reciprocal to that found for N2O, in that it dimin-
ished as Pv៮ N2O rose and ceased around the same
threshold Pv៮ N2O, where augmentation of the inert-gas
uptake commenced. At higher values of Pv៮ N2O (lower
V̇N2O), V̇O2 and PaO2 fell with worsening V̇A/Q̇ inhomo-
geneity, as is normally expected, and was demon-
strated in the accompanying paper (13) modeling a low
“maintenance-phase” level of V̇N2O.
Measured Distributions
The results of modeling using the three pairs of
measured distributions are summarized in Table 1. Fig. 3. Effect of rising Pv៮ N2O on the relationship of V̇O2 to the
severity of V̇A/Q̇ inhomogeneity. In an identical scenario to that
The log SD of the distributions as given by Dueck et al. modeled in Fig. 2, the threshold Pv៮ N2O for paradoxical augmentation
(6) are listed in the first row, and the associated values of V̇O2 is the same (300 Torr), but the direction of the effect of rising
for true shunt fraction and dead space fraction are Pv៮ N2O is opposite.
 VENTILATION-PERFUSION INHOMOGENEITY INCREASES GAS UPTAKE 13

of Q̇ increased from 1.42 to 2.37. V̇N2O in subject 8

increased by 22% as the log SD increased from 1.17 to
1.95, despite a doubling of dead space ventilation from
25 to 50% and an increase in true shunt. Predicted
V̇N2O in subject 6 was 5% lower as the log SD increased
from 0.86 to 1.67. This change was seen in the presence
of an increase in true shunt from 2 to 27%.
DISCUSSION

Paradoxical Increase in Inert-gas Uptake

This study applies distributions of ventilation and Q̇,
which are more physiologically realistic than those
used in the simple two-compartment modeling of the
accompanying paper (12). It confirms that, between
certain extremes, increase of uptake of one gas is
predicted with worsening V̇A/Q̇ inhomogeneity with
inspired mixtures of two soluble gases. The clinical

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relevance of this phenomenon needs to be explored, as
previous authors have demonstrated an increase in the
spread of V̇AE/Q̇ throughout the lung after induction of
anesthesia (3, 6, 7, 10, 11, 14).
At first glance, this increase in gas uptake seems Fig. 4. Predicted gas exchange by lung compartment for a lung with
somewhat counterintuitive, given that it has been well log SD for Q̇ of 1.75. V̇AE/Q̇ increases from left to right. V̇N2O is
demonstrated by computer modeling by previous au- plotted along with Q̇, V̇AE, and the balance of V̇O2 and CO2 uptake for
thors (8, 17, 18) that the expected result of increasing that compartment.
inhomogeneity in V̇A/Q̇ matching is a reduction in gas
exchange for all gas species. Modeling of gas elimina- within low V̇A/Q̇ compartments and largely follow the
tion showed that this reduction is maximal for gases distribution of Q̇. This is consistent with the perfusion-
with an Ostwald blood-gas partition coefficient ␭ equal limited nature of uptake of these gases.
to the overall V̇AE/Q̇ of the lung (4). In the presence of Uptake of one gas within the lung will raise the
an overall V̇AE/Q̇ of 0.86, exchange of a gas such as N2O concentration of other gases in the alveolar gas mix-
with a ␭ of 0.47 would be expected to be significantly ture. The net exchange of O2 and CO2 governs the
reduced by V̇A/Q̇ inhomogeneity. Where gas uptake magnitude of the concentrating effects on alveolar N2O
was modeled (18), this value of ␭ was higher, but within each compartment. N2O exchange will also ex-
inert-gas exchange was still predicted to be decreased ert similar effects on O2 and CO2. The asymmetric
at any level of inhomogeneity compared with that in a nature of respiratory gas exchange across the distribu-
perfectly homogeneous lung. tion of V̇A/Q̇ shown in Fig. 4 results in an asymmetric
The important limitation of some of these early stud- concentrating effect on alveolar N2O. This is demon-
ies was that they assumed an insoluble vehicle gas as strated by Fig. 5, which shows the different distribu-
the balance of the inspired mixture. More physiologi- tions of N2O partial pressures in two lungs of differing
cally realistic models have since been applied that degrees of inhomogeneity. In the moderately low V̇A/Q̇
allow for the interdependent exchange of multiple al- compartments, substantial V̇O2 concentrates N2O in
veolar gases, including N2O. Dantzker et al. (5) applied the alveolus and drives V̇N2O there. These compart-
a modified form of such a computer model, involving a ments have the greatest Q̇, and here the concentrating
log normal distribution of V̇AI to demonstrate that lung effect on alveolar N2O is most powerful. Lung units
units with very low V̇A/Q̇ may suffer collapse where gas with moderately low V̇A/Q̇ receive a substantial propor-
uptake exceeds V̇AI. These later models of multiple gas tion of total pulmonary Q̇ and thus would be expected
exchange (5, 6), which looked at O2-N2O mixtures, did to have a dominating influence on the content of these
not explore the relationship of global gas exchange to perfusion-limited gases in arterial blood and thus on
V̇A/Q̇ inhomogeneity. total exchange of these gases.
Examination of the exchange of individual gas spe- Figure 6 demonstrates quantitatively the process of
cies on a compartment-by-compartment basis provides paradoxical augmentation by comparing two lungs of
some insight into the mechanism for paradoxical aug- differing V̇A/Q̇ homogeneity. For both the more uniform
mentation. Figure 4 plots the distribution of exchange and the more inhomogeneous lung, the area under the
of individual gas species in a heterogeneous lung. For N2O curve is the overall V̇N2O. As the SD of the distri-
simplicity, the exchange of O2 and CO2 is shown as a bution increases, there is redistribution of a greater
single plot representing net respiratory gas exchange proportion of total Q̇ to lower V̇A/Q̇ areas. V̇N2O in-
(V̇O2-V̇CO2), where V̇O2 predominates in the lower V̇A/Q̇ creases markedly in these compartments as this oc-
compartments and V̇CO2 in the better ventilated areas. curs, and this increase outweighs the reduced uptake
It shows that V̇O2 and V̇N2O occur predominantly in higher V̇A/Q̇ lung units that occurs as their Q̇ is
14 VENTILATION-PERFUSION INHOMOGENEITY INCREASES GAS UPTAKE

the balance of which is determined by their solubilities,

inspired concentration, and mixed venous content. The
mutual enhancement of uptake that O2 and N2O pos-
sess is limited only by the approach of their alveolar
partial pressures to the mixed venous for each gas
within these compartments and to a lesser extent by
dilution of alveolar gas by CO2.
An interesting manifestation of paradoxical augmen-
tation is that when PaN2O is very close to Pv៮ N2O, such
that net inert-gas exchange is calculated to be negative
for the homogeneous lung, it is still positive for the
lung with significant V̇A/Q̇ inhomogeneity, despite
identical inspired and mixed venous gas content. Ex-
amination of gas exchange in such an inhomogeneous
lung on a compartment-by-compartment basis shows
that N2O is being taken up by low V̇AE/Q̇ units and
eliminated by high V̇AE/Q̇ units, with the balance de-
termining the direction of global gas exchange. This

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“flow through” of gas within the lungs has been pre-
dicted to occur for N2 in the presence of V̇A/Q̇ inhomo-
geneity, and raised urinary N2 has been used as a test
for the severity of chronic pulmonary obstructive dis-
ease (1, 9). It can be seen for other inert gases at
particular ranges of inspired and mixed venous partial
Fig. 5. Distributions of end-capillary N2O partial pressure (Pc⬘N2O) pressures. At high degrees of inhomogeneity, V̇N2O in
across 10 compartments with 2 distributions of Q̇ with low and high low V̇A/Q̇ units is magnified to a considerably greater
degrees of inhomogeneity (log SD of 0.5 and 2.0, respectively).
extent than N2O exchange in other compartments
(Fig. 7).
reduced. Figure 6 shows that, for the overall lung, the Dueck et al. (6) measured V̇N2O in their subjects
concentrating effects of V̇O2 on alveolar N2O are mag- during maintenance-phase anesthesia. However, there
nified by greater inhomogeneity. is no data available in the literature measuring V̇N2O
V̇O2 and V̇N2O produce competing concentrating ef- and changes in V̇A/Q̇ distributions simultaneously.
fects, predominantly in these low V̇A/Q̇ compartments, Most studies employing the multiple inert-gas elimina-

Fig. 7. Distributions of V̇N2O across the lung compartments at a high

Fig. 6. Distributions of V̇N2O and Q̇ across the 10 compartments with Pv៮ N2O plotted at 3 different levels of inhomogeneity of V̇AE/Q̇. In the
2 distributions of Q̇ with low and high degrees of inhomogeneity (log less inhomogeneous lung, N2O is eliminated by all lung units,
SD of 0.25 and 1.75, respectively). The higher V̇N2O and high perfu- whereas, at higher degrees of inhomogeneity, concentrating effects
sion in the moderately low V̇A/Q̇ compartments are obvious in the in low V̇AE/Q̇ compartments predominate, making net N2O exchange
more severely inhomogeneous distribution. positive.
 VENTILATION-PERFUSION INHOMOGENEITY INCREASES GAS UPTAKE 15

tion technique in anesthetized patients have measured The accompanying paper (12) shows that competing
distributions before and after induction of anesthesia concentrating effects of uptake of one gas on the other
to generate widening of these distributions. There are are inevitably present in any lung compartment where
obvious difficulties in directly measuring changes in two gases are being taken up. Logically, the net con-
N2O exchange that occur in patients who are not re- centrating effect can only be in one direction at any
ceiving anesthesia when the first distribution is taken. given time. The position of balance of these processes
For this reason, we have used computer modeling to and the direction of the net concentrating effect are
simulate gas exchange with given V̇A/Q̇ distributions. determined by the relative inspired concentrations and
Where this was applied to Dueck’s published distribu- uptakes of the two gases. In the more complex physio-
tions, the predictions of modeling of both two-compart- logical model presented here, the point of balance is
ment (12) and theoretical log normal distributions complicated by a number of factors not encompassed in
were confirmed; widening inhomogeneity of V̇A/Q̇ in- the simplified treatment given by the accompanying
creases V̇N2O where maintenance-phase levels of inert- paper (12). These are the presence of alveolar CO2
gas exchange are modeled. This also casts some light exchange, the differing solubilities of the gases in-
on the physiological factors that will limit paradoxical volved, and the alinear nature of the dissociation curve
augmentation. These measured distributions were col- for O2, which cause these gases to be taken up un-
lected from patients with significant chronic lung dis- equally in lung compartments of different V̇A/Q̇.
ease and also incorporate varying degrees of true shunt As shown by Figs. 2 and 3, the direction of the overall
concentrating effect changes at a certain Pv៮ N2O and

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and dead space ventilation. The calculated increase in
V̇N2O was greatest for the distributions of subject 7, V̇N2O. Inhomogeneity simply magnifies these existing
where there was no significant change in true shunt or concentrating effects, and thus paradoxical augmenta-
dead space moving from the narrower to the wider tion can only be seen for one gas or the other at any
distribution. Using the distributions of subject 8, an time.
increase in V̇N2O was still predicted, despite a large Clinical Considerations: Inert-gas Exchange
increase in dead space ventilation i.e., a doubling of the
amount of ventilation that was effectively wasted. The Paradoxical augmentation of gas uptake with wors-
greater uptake by perfused lung units still overcame ening V̇A/Q̇ inhomogeneity is predicted, regardless of
the effects of reduced V̇A to them. Similarly, the distri- the nature of the distributions used to generate the
butions of subject 6 predicted only a small reduction in data. It is predicted by simple two-compartment mod-
V̇N2O, despite the superimposition of a large proportion els and more physiologically realistic log normal distri-
of true shunt accompanying the wider distribution. butions. Given the increase in V̇A/Q̇ inhomogeneity
Thus augmentation of V̇N2O in ventilated lung units seen normally in anesthetized patients, paradoxical
largely compensated for the reduction in effective pul- augmentation of V̇N2O is likely to be prevalent in any
monary capillary Q̇ imposed by the increased shunt. patient during maintenance-phase N2O anesthesia.
It is of interest that, in the study by Dueck et al. (6),
the measured V̇N2O was highest (325 ml/min uptake
after 85 min of N2O anesthesia) in subject 7, who
demonstrated the most severe degree of inhomogeneity
of pulmonary Q̇. Examination of the distributions mea-
sured for this subject show that there was a significant
proportion of lung units with low V̇AE/Q̇ at the time of
the measurement. We have shown that it is in these
compartments that the most powerful concentrating
effects occur, which drive the paradoxical increase in
inert-gas exchange.
At higher levels of V̇N2O, augmentation of V̇O2 with
increasing V̇A/Q̇ inhomogeneity is predicted (Fig. 3).
This may produce clinically significant increases in
PaO2 compared with the homogeneous lung. The corre-
sponding clinical scenario is the immediate postinduc-
tion phase. The concentrating and second gas effects of
rapid V̇N2O early in an inhalational anesthetic were
described by Stoelting and Eger (16). They demon-
strated that high V̇N2O raises the alveolar concentra-
tion of accompanying gases, including O2, by contrac-
tion of alveolar volume with or without indrawing of
further inspired gas to replace the lost volume. How-
Fig. 8. Effect of N2 elimination of 10 ml/min from the lungs on
ever, Fig. 3 shows that a more pronounced postinduc- paradoxical augmentation of V̇N2O with increasing V̇A/Q̇ inhomoge-
tion increase in PaO2 is expected at more severe levels neity, compared with a lung with no N2 elimination. Mixed venous
of V̇A/Q̇ inhomogeneity. partial pressures of O2 and CO2 were held constant.
 16 VENTILATION-PERFUSION INHOMOGENEITY INCREASES GAS UPTAKE

It can be seen from Fig. 2 that the phenomenon of At higher levels of V̇N2O, such as are seen in the early
paradoxical augmentation of gas uptake only com- phases after anesthetic induction (and in the absence
mences when the mixed venous partial pressure has of retained alveolar N2), paradoxical augmentation of
risen above a certain threshold (in this scenario 300 V̇O2 with worsening V̇A/Q̇ inhomogeneity is seen in-
Torr). Thus it is a product of a relatively low inspired- stead. The effect on O2 is not seen concurrently with
to-mixed venous partial pressure gradient and com- that for N2O. This is because the effect of inhomogene-
mences when uptake of the gas has declined below a ity is to magnify the existing concentrating effects of
certain value. Consideration of changing gas exchange uptake one gas on the other. These can only operate in
over time shows that this threshold Pv៮ N2O is reached one direction or the other at a time, depending on the
after only a short time after induction of anesthesia. relative uptakes and inspired concentrations of the
Figure 2 shows that, in our scenario, the threshold for gases.
paradoxical augmentation of V̇N2O is at ⬃550 ml/min.
Severinghaus (15) states that the V̇N2O (ml/min) at REFERENCES
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