Halothane respiratory
and enflurane anesthesia and mechanics in prone dogs
CHARLES R. RICH, KAI REHDER, THOMAS J. KNOPP, AND ROBERT E. HYATT Departments of Anesthesiology and Physiology and Biophysics, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55901
RICH, CHARLES R., KAI REHDER, THOMAS J. KNOPP, AND ROBERT E. HYATT. Halothane and enflurane anesthesia and respiratory mechanics in prone dogs. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 46(4): 646-653, 1979.-Functional residual capacity (FRC), total lung capacity (TLC), and static deflation pressure-volume curves of the total respiratory system, lungs, and chest wall were measured in eight trained prone dogs with permanent tracheostomies first during the awake state and then during halothane (1.3-2.8 minimal alveolar concentrations (MAC) or enflurane (1.4-1.9 MAC) anesthesia. The mean of the difference between TLC and TLC (awake) was -0.05 liter for halothane and -0.07 liter for enflurane anesthesia; the reduction in TLC was significant (P c 0.05) only for enflurane. Mean FRC did not change with either halothane or enflurane anesthesia. Halothane anesthesia had no significant effect on the elastic recoil pressures of the total respiratory system, lungs, and chest wall. Compliance of the total respiratory system increased significantly (P < 0.05) with halothane. In contrast, enflurane significantly (P < 0.05) increased the elastic recoil pressures of the total respiratory system and of the chest wall. Compliance of the lung decreased significantly with enflurane anesthesia (P < 0.05). Some of the dogs had paradoxic motion of the thoracic wall. The wall moved inward during inspiration, recoiled outward at end inspiration, and had a normal motion during expiration. Tidal volumes were consistently larger and respiratory frequencies consistently less during 1.6 MAC of enflurane than during 1.6 MAC of halothane anesthesia. No consistent dose-response effect on any of the measured variables was observed with either anesthetic.
In trained prone dogs, respiratory mechanics and lung volumes were examined before and after induction of anesthesia with halothane or enflurane at various concentrations. We found that the respiratory system of these dogs responded differently to induction of anesthesia than did the respiratory system of supine (19) or prone (13) man anesthetized with thiopental sodium. Furthermore, the effects on the mechanics of the respiratory system of prone dogs were different with halothane than with enflurane anesthesia. METHODS
Dogs with permanent tracheostomies were trained to lie quietly prone in a specially designed air-conditioned volume-displacement body plethysmograph. The dogs were conditioned to tolerate the insertion of a balloon into the esophagus and of a cuffed endotracheal tube into the trachea. They were trained to accept temporary occlusion of the airway for determinations of thoracic gas volume and to tolerate determinations of inflation and deflation quasi-static pressure-volume (PV) curves. Lung volumes were measured by body plethysmography; the characteristics of the body plethysmograph have been described (6). Pleural pressure (Ppl) was estimated from esophageal pressure (Pes). The Pes was detected by a latex balloon (lo-cm length, 3.5cm perimeter) in the lower third of the esophagus. Pes was transmitted PV curves; lung volumes; recoil pressures; compliances; awake through an 80-cm polyethylene tube and sensed by a dogs strain gauge (Statham PMl3l). The position of the balloon in the esophagus was confumed in each dog by roentgenograms of the chest. The balloon was inflated GENERAL ANESTHESIA in recumbent man reduces the with 0.6-1.2 ml of air, the volume depending on the PV functional residual capacity (FRC) (14), increases the characteristics of the balloon. The gas volume was reelastic recoil pressures, and reduces the compliances of peatedly tested throughout each study. Lateral airway the lung and respiratory system (19). The mechanisms pressure (Pao) was measured inside the trachea, 3 cm for these changes are still not understood and need to be from the distal opening of the endotracheal tube. Transelucidated because the changes may contribute to the pulmonary pressure (PL) was estimated from the differfrequently observed impaired pulmonary gas exchange ence between Pao and Pes. To exclude artifacts, PL was during general anesthesia (1). In a recent study from our required to remain constant during inspiratory efforts laboratory, Lai and co-workers (10) found that, in dogs against the temporarily occluded airway, except for the in various positions, anesthesia with thiopental sodium small changes due to gas expansion. had no significant effect on respiratory mechanics and Inspiratory gas (30% 02 in 70% N2) flowed from a tank FRC. In the present study, we examined, in prone dogs, (contents analyzed by duplicate Haldane analyses) the effect of halothane and enflurane anesthesia on these through vaporizers specific for halothane (Fluotec Mark variables as a continuation of our search for a dog model I, Cyprane Ltd., UK) or enflurane (Ohio enflurane vathat will allow a detailed study of the mechanisms of porizer, Ohio Medical Products, Madison, WI 53701) into a E-liter reservoir bag and from there through a largeanesthesia-induced changes in respiratory mechanics. 0161-7567/79/00004000$01.25
Copyright
0 1979 the American
Physiological
Society
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HALOTHANE-ENFLURANE
ANESTHESIA
AND
RESPIRATORY
bore three-way valve (Hans-Rudolph valve) and a pneumotachograph (Fleisch no. 1) to the dog. Expiratory gas flowed from the dog through the endotracheal tube, the pneumotachograph, and the Hans-Rudolph valve either into the atmosphere or via a 3-mm orifice and a solenoid valve into a 260-liter drum, which was evacuated to a pressure of -90 cmHz0. The negative pressure was used for stepwise deflation of the lungs. The l&liter reservoir bag was contained in a rigid box in which the pressure could be varied between ambient and 30 cmHz0 for inflating the lungs. Inspiratory and expiratory gas flow rates were determined by a calibrated pneumotachograph. Addition of halothane or enflurane to the inspirate did not cause a measurable change in the calibration of the pneumotachograph. Inspiratory and expiratory concentrations of halothane or enflurane were measured intermittently with an infrared gas analyzer (Beckman LB-2) calibrated with three known concentrations of halothane or enflurane. Expired concentrations of carbon dioxide were measured intermittently with an infrared analyzer (Beckman LB-l) calibrated with three known concentrations of carbon dioxide. Arterial blood pressure in the abdominal aorta was sensed by a pressure transducer (Statham P37A). All signals were recorded on an eight-channel recorder (Hewlett-Packard HP 7788A). Rectal temperature was detected by a thermistor probe (Yellow Springs Instrument); body temperature was maintained (mean t SD, 36.6 t 0.2”C) by warming blankets, or by circulating warm air through the airconditioning system of the body plethysmograph, or by both means. Arterial blood gases were determined by appropriate electrodes only in the anesthetized dogs. PROCEDURE
After the dog was positioned, several minutes were allowed for stabilization of the plethysmograph temperature. Then, while the dog was awake, three measurements of thoracic gas volume at FRC were performed. Immediately after, transpulmonary pressure, inspiratory and expiratory gas flow rates, and changes in lung volume were recorded for approximately 15 breaths at a paper speed of 2.5 cm/s. The measurements of thoracic gas volume were then repeated. The lungs were then inflated from FRC to an airway pressure of 30 cmHz0 (the volume achieved will be called TLC), deflated to FRC, and again inflated to an airway pressure of 30 cmHn0. Quasi-static deflation PV curves were then obtained by stepwise (breath holding for 3 s) deflation of the lungs, either until no more gas could be withdrawn or until the dog became uncomfortable. The latter usually occurred at a PL of approximately -4 cmHa0. After the dog had resumed spontaneous breathing, the entire procedure was repeated two times. The dog was removed from the body plethysmograph. Anesthesia was induced with 70% N20 and 30% Oz. After the induction of anesthesia with N20 was completed, halothane or enflurane vapor was added to the inspirate. The administration of N20 was discontinued after a few minutes and the inspired gas mixture was changed to 30% 02 and 70% N2 with the desired concentration of the volatile anesthetic. The dog was then reDositioned in the
647
MECHANICS
body plethysmograph. The data collection procedure was the same as for the dogs while awake and was begun 5% 171 min after induction of anesthesia or 40-66 min after the inspired anesthetic concentration was changed. The length of the latter time interval was determined by the time required for the ratio of end-tidal to inspired halothane or enflurane concentration to equal or exceed 0.85. Anesthetic concentrations of halothane and enflurane were expressed as minimal alveolar concentration (MAC) (2); 1 MAC of halothane was taken to be 0.87% (3) and 1 MAC of enflurane 2.20% (4). Because measurements were done in a given dog at several MAC levels (1.3, 1.6, 2.0, 2.3, and 2.8 MAC for halothane and 1.4, 1.6, and 1.9 MAC for enflurane), time intervals between the induction of anesthesia and the final measurement were as long as 7 h. In three dogs, the effect of time was examined by repeating all measurements at a constant inspiratory concentration of halothane (two dogs) or enflurane (one dog) during a period of 6-9 h. There was no alteration of the respiratory mechanics and FRC with time. RESULTS
Eight male mongrel dogs (13.5-25.5 kg) were studied. Six dogs were studied while awake, on 3-8 different nonconsecutive days and the other two were each studied once (Table 1). During halothane anesthesia, six of the same eight dogs were also studied on two different nonconsecutive days and two were studied once. During enflurane anesthesia, two of the dogs were studied on two different days and four were studied once. Reproducibility Lung uolumes. We analyzed the reproducibility of the measurements of FRC and TLC to evaluate the variability between days and within days. There were 710 measurements of FRC and 121 of TLC for the awake state in the eight dogs (Table 1). There were also 254 measurements of FRC and 42 of TLC for 1.6 MAC of halothane and 166 of FRC and 33 of TLC for 1.6 MAC of enflurane. The mean total variability (overall standard deviation for a particular dog and state) of the FRC and TLC measurements was about 2.6 times that of the within-day variability, indicating the predominance of the betweenday variability. Total and within-day variabilities were 1. Within-day and between-day reproducibility in eight awake prone dogs _.-_-_-_ - -_._-. f-- -~--- ---- ---- -------- -~ ~-~ --~-
TABLE
of FRC_---.-______.and TLC
TLC
FRC
Dog No.
c&
1 2
6 5
n, replicates
Overall mean, liters
SD*, liter
SD?, liter
cl&
122 106
1.00 1.04
0.07 0.05
0.09 0.09
6 6
n, replicares
16 19
,i,ii,~,~,~~i,1,li
all
Estimate of within-day standard standard deviation of anv single
deviations. measurement.
Overall mean, liters
SD*, liter
SD-t, liter
2.65 2.43 1.45 1.93 1.91 2.01 2.35 2.76
0.07 0.05 0.02 0.06 0.08 0.06 0.04 0.17
0.07 0.12 0.09 0.16 0.15 0.17
t Estimate
f over-
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RICH, REHDER,
648 similar to those in the awake state during either enflurane or halothane anesthesia. PV curves. The reproducibility of recoil pressures was evaluated visually by plotting for each dog all measured recoil pressures vs. all corresponding lung volumes. Reproducibility of recoil pressures in both awake and anesthetized states was best for the lung, whereas recoil pressures for the chest wall and for the total respiratory system showed more variability (Fig. 1). The within-day and the between-day reproducibility appeared to be simStatic compliances were measured over a 300~ml volume range above FRC (awake) and were determined from the mean PV curves for a given day. Reproducibility of the static compliances was not analyzed because only a limited number of replicate between-day determinations were obtained. Effect of Anesthesia Lung volumes. For each dog, average values were calculated for each day of study for both states. The mean value for the group was calculated from these average values. The mean of the difference between TLC and TLC (awake) was -0.05 liter for halothane and -0.07 liter for enflurane anesthesia; the reduction in TLC was significant (P < 0.05) only for enflurane (Table 2). Individual dogs showed consistent changes in FRC on repeated studies. The mean of the difference between FRC and FRC (awake) was -0.02 liter with halothane and -0.05 liter with enflurane anesthesia; the reduction in FRC was not significant with either anesthetic (Table 2). To examine the possible effect of body habitus on direction and magnitude of change in FRC, the relationship between the changes in FRC caused by anesthesia and the ratio of body length to weight was examined by linear regression analysis. There was a significant (P < 0.02) positive correlation for both halothane and enflurane, i.e., the short and heavy dogs tended to show the largest reductions in FRC. PV curves. Complete PV curves could not be obtained for dogs that became uncomfortable at low airway pressures. Also, not all dogs were studied at the five levels of halothane anesthesia or the three levels of enflurane
Total
0’ -30
’ -20
’ -10
system
’ 0
POO, cm FIG.
occasions
1. Quasi-static PV curves 49 days apart; different
’ IO
l-l20
’
’ 30
Tidal Volume and Respiratory Frequency Tidal volumes were consistently larger and respiratory 2. Mean (range) values for lung volumes of awake and anesthetized prone dogs* -----.--. -~~_ -~ -- - .---. TABLE
Anesthetic
Awake
Halothane, 1.6 MAC
-20
-10
PL,
obtained in one awake dog on two days are indicated by crosses (x) or
FRC, liters
TLC, liters
State
2.20 (1.37 to 2.76)
0.90 (0.54 to 1.09)
2.15 (1.41 to 2.74) . -0.05 ’ (-0.18 to 0.03)
0.89 (0.62 to 1.11) . -0.02 ’ (-0.28 to 0.12)
2.08 (1.51 to 2.66)
0.83 (0.68 to 1.05)
2.01 (1.45 to 2.61) -0.07-t (-0.14 to 0.02)
0.78 (0.61 to 0.95) -0.05 (-0.12 to 0.03)
(8 dogs) Anesthetized Anesthetizedawake Enflurane, 1.6 MAC (6 dogs)
Awake
Anesthetized Anesthetizedawake
Values are means with ranges in parentheses. * Data were obtained when both awake and anesthetized states were studied on the same day. t Mean of differences significantly different from zero by paired t test (P < 0.05).
Chest
1
-,30
AND HYATT
anesthesia on a given day because of the long duration of the study. Recoil pressures of the total respiratory system (Pao), lung (PL), and chest wall (Pes) did not change significantly (P > 0.05) with any of the five examined MAC levels of halothane at any lung volume (Figs. 2 and 3). In contrast, enflurane anesthesia resulted in a significant (P < 0.05) increase in the recoil pressure of the total respiratory system at most lung volumes with the two examined MAC levels (Figs. 3 and 4). This increase appeared to be due to changes in the chest wall and not the lung. The static compliance of the total respiratory system (Crs) increased significantly (P < 0.05) with halothane anesthesia (Table 3). This increase appeared to be due to changes of the chest walI (Cw), which were not significant (P = 0.09). In contrast, with enflurane anesthesia, the static compliance of the lung (CL) decreased significantly (P < 0.05). Compliances of the respiratory system and chest wall did not change significantly with enflurane.
Lung
20
KNOPP,
0
cm
IO
40
20
30
- -30
’
-20
’ -10
wall
’
’
’
4
0
IO
20
30
PUS, cm
t-l20
doti (0). Recoil pressures of lung showed did those of chest wall or total respiratory
better reproducibility system.
than
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HALOTHANE-ENFLURANE
ANESTHESIA
AND
RESPIRATORY
649
MECHANICS
Halothane 1.6 MAC
I
YO ’
”
-10
-5
0
L
.
.
I
.
5
0
+
I
’
r
IO
AP (anesth Total
MAC
2.3
l
-10
- awake),
system
-5
i.
00
0
.
IO
5
cm Hz0
Lung Halothane
FIG. 2. Lung volume expressed as percent of TLC (awake) plotted as a function of changes in recoil pressures between halothane anesthesia and awake state. Each dog is represented with one mean value for each lung volume. There was no significant effect of halothane anesthesia on recoil pressure at any lung volume (# 0.05 < P < 0.1, paired t test). Although not shown, same was true at 1.3, 2.0, and 2.8 MAC of halothane.
Chest
( I .6
MAC)
100
I I/
60
wall
,,
/ H--
60
40
* / ,I
,
Enf lurone
( I .6 MAC 1
FIG. 3. Mean quasi-static PV curves for the awake (SOW line) and anesthetized (dashed Line) states.
. .--
40
/I I0/
-
POO,
cm
Hz0
PL,
cm
H20
frequencies consistently less during enflurane than halothane anesthesia (Fig. 5). This comparison was made with both agents at 1.6 MAC and at similar arterial carbon dioxide tensions. Dose Response The dose responses of aI.l variables were tested by linear regression analysis. The slopes relating each of the variables to the MAC level of halothane or enflurane were not significantly different from zero. This indicates that there was no significant dose response effect over the range of 1.3-2.8 MAC of halothane and 1.4-1.9 MAC
POS,
cm
t-i20
of enflurane on any of the examined variables. The mean (t SE) value for Pace, during 1.6 MAC of halothane was 42 t 1 Torr and that for 1.6 MAC of enflurane 47 t 2 Torr; these mean values were not significantly different. Mean (+ SE) values for Pao, were 125 t 3 and 129 t 3 Torr for 1.6 MAC of halothane and enflurane anesthesia, respectively; these values were not significantly different . DISCUSSION
The purpose of this study was to determine if prone dogs anesthetized with halothane or enflurane could
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650
RICH,
REHDER,
KNOPP,
AND
HYATT
Enf lurane I .6 MAC
I .4 MAC
t
1.9
FIG. 4. Lung volume expressed as percent of TLC (awake) plotted as a function of difference in recoil pressures between enflurane anesthesia and awake state. Each dog is represented with one mean value for each lung volume. Values at MAC are not shown because only three dogs were studied at that
< 0.05 and $ 0.05 < P < 0.1 (paired
t test).
Pes
z* .+ -10
-5
0
5
IO
* : .t -10
AP (onesth - awake),
-5
Halothane, 1.6 MAC
State Awake
(8dogs) Anesthetized Anesthetizedawake
Enflurane, 1.6 MAC
Awake
0
--
Cm, l/cmHsO
CL, l/cmHzO
cw, l/cmHzO
0.039 (0.018 to 0.057)
0.148 (0.071 to 0.250)
0.065 (0.035 to 0.111)
0.056 (0.028 to 0.083) 0.017t (-0.008 to 0.041)
0.147 (0.079 to 0.240) -0.001 (-0.088 to 0.033)
0.098 (0.046 to 0.166) 0.033 (-0.042 to 0.097)
0.046 (0.028 to 0.063)
0.147 (0.088 to 0.207)
0.067 (0.036 to 0.103)
0.050 (0.033 to 0.071) 0.004 (-0.013 to 0.027)
0.132 (0.075 to 0.185) -0.015t (-0.031 to -0.001)
0.077 (0.052 to 0.120) 0.009 (-0.028 to 0.064)
(6dogs) Anesthetized Anesthetizedawake
Values are means with ranges in parentheses. * Data were obtained when both awake and anesthetized states were studied on the Same day. t Mean of differences significantly different from zero by paired t test (P c 0.05).
serve as a model to study the mechanisms for the altered respiratory mechanics that have been observed in recumbent man on induction of general anesthesia with various agents. We found that, in general, dogs in the prone position, anesthetized with halothane or enflurane, cannot be used to study the mechanisms of the altered respiratory mechanics occurring in supine anesthetized man. However, the possibility exists that individual prone dogs, dogs in other body positions, or dogs anesthetized with other agents may respond to general anesthesia in a manner similar to that in man.
Comments
IO
5
cm Hz0
TABLE 3. Mean (range) values for compliance of awake and anesthetized prone dogs* -- _._--. - -- -.. Anesthetic
0
on A4ethodology
In recumbent man the mean reduction of FRC values reported in the literature following induction of general anesthesia varies considerably, with a mean reduction of about 16% of the supine awake FRC (reductions range
l
O0
1
1
-4
-8
I
-12
I
-16
I
-20
A f, breathdmin 5. Tidal volume and respiratory frequency at 1.6 MAC halothane anesthesia was subtracted from values measured in same dog at 1.6 MAC enflurane anesthesia, AVT and Af, respectively. Each dot represents mean change for one dog. Tidal volumes were consistently larger and respiratory frequencies consistently less during enflurane than halothane anesthesia. FIG.
from -3 to +39%) (14). If one assumes a mean value of 0.90 liter for FRC in awake prone dogs (Table I), then one would anticipate a mean decrease in FRC of about 144 ml if the response in the dog was similar to that in man. Analysis of our data for reproducibility of the lung volume determinations indicates that, with our method, we could detect a significant change in FRC of 50 ml or more for a given dog. (This was calculated for dog 5 who had only 13 measurements of FRC while awake and 16 measurements while anesthetized; for all other dogs, differences of less than 0.05 liter would have been significant. ) Reproducibility of recoil pressure measurements for the lung was better than that for chest wall and total respiratory system, presumably because the dogs were not always completely relaxed. The average absolute difference between our replicate measurements and the mean values for recoil pressure of the total respiratory system at lung volumes near 60% TLC was less than 1
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HALOTHANE-ENFLURANE
ANESTHESIA
AND RESPIRATORY
cmHzO (61 sets of replicate measurements). This variability compares favorably with that reported for relaxed man by Van Lith and co-workers (17), who found that recoil pressure measurement scatter was equal to 19% of the mean (according to Fig. 3 of Ref. 17, approximately 16 cmH20) determined at a lung volume equal to FRC plus 1.5 liters. In prone dogs, anesthesia induced with thiopental sodium causes a significant decrease in esophageal elastance (9). We do not know whether halothane or enflurane affects esophageal elastance, and the possibility that our estimates of pleural pressure from esophageal pressure may have been influenced by such an effect cannot be ruled out. In prone dogs anesthetized with pentobarbital sodium, extrapolated esophageal pressure reflects local pleural pressure, but the latter may not reflect the overall elastic behavior of the lung or chest wall (7). Effect of Anesthesia on Static Lung Volumes and PV Curves Lung volumes. To our knowledge, no anesthetic agent has produced significant reductions of FRC in dogs in any recumbent position. In contrast, in recumbent man, significant reductions in FRC have been observed with most anesthetic agents (14). In prone beagle dogs, fentanyl-droperidol anesthesia increases FRC significantly, but if pentobarbital sodium was added, the increase was not significant (12). Thiopental sodium anesthesia had no significant effect on FRC in prone mongrel dogs (9, 10). Similarly, we found in our study that halothane or enflurane anesthesia did not reduce the mean FRC significantly, but we observed differences between individual dogs in terms of their response of FRC. With halothane anesthesia, we observed significant and consistent reductions in FRC in two of eight dogs, and in the same dogs, enflurane anesthesia reduced FRC. In prone anesthetized-paralyzed man, we found, in four of five subjects, a reduction in FRC with thiopental sodium anesthesia (13). Although muscle paralysis cannot be ruled out as the cause for this difference, we believe that this is unlikely because, in anesthetized supine man, muscle paralysis does not further reduce FRC (19). The difference between dog and man may be related to the differences in the configuration and deformability of the chest wall. More work is necessary to elucidate the mechanisms for the different responses. PV curve. Neither halothane nor enflurane anesthesia had a significant effect on the mean static recoil pressure of the lung. Similarly, Lai and co-workers (10) found no change in the static recoil pressure of the lung in prone dogs anesthetized with thiopental sodium. These observations are in contrast to studies in man by Westbrook and co-workers (19), who noted, in five supine men anesthetized with thiopental sodium and meperidine, a consistent increase of the elastic recoil pressure of the lung. We have no explanation for the reduction in lung compliance with enflurane anesthesia. Halothane and enflurane had different effects on the mean static recoil pressure of the chest wail. Although enflurane increased recoil pressures in all dogs at nearly ail lung volumes, halothane tended to increase mean
MECHANICS
651
recoil pressure at low lung volumes but to decrease recoil pressure at high lung volumes. These observations are in agreement with no change in mean compliance of the chest wall with enflurane and an increased mean compliance of the chest wall with halothane. The largest increases in recoil pressure of the chest wall at FRC tended to occur in those dogs who showed consistent decreases in FRC. The most likely mechanism for the altered recoil pressure of the chest wall is a change in the mechanical properties of the muscles of the thoracic cage. Anesthetics can have either a direct effect on the muscles or an indirect effect mediated via the nervous system (or both). Whatever the mechanism, our study suggests that enflurane, thiopental sodium, and halothane all have different effects on the muscles of the thoracic cage. This conclusion is supported by the clinical observation that these agents have different relaxant effects on muscle. Effect of Anesthesia on Dynamic “Transpulmonary Pressure” We measured pulmonary resistance (RL) by the isovolume method (5), using the esophageal pressure changes as an estimate of overall pleural pressure changes. In the awake dogs, we observed a mean (t SE) pulmonary resistance of 1.02 t 0.14 cmHsO/(!/s), which is in good agreement with the mean pulmonary resistance of 1.30 t 0.09 cmHzO/(l/s) found for prone dogs by Gillespie and Hyatt (6). We noted “negative values of pulmonary resistance” with halothane anesthesia in five of eight dogs and with enflurane anesthesia in five of six dogs. The “negative resistance” values were associated with observations of uncoordinated motion of the thoracic wall, i.e., the wall moved inward during inspiration. At end inspiration, the thoracic wall recoiled outward and the pattern of expiratory movement was apparently similar to that observed with the dogs awake. For dogs who had a “negative resistance,” dynamic PV loops were plotted for both states (Fig. 6). The dynamic PV loops were normal for the awake state but were reversed for the anesthetized state. A possible explanation for the reversal of the dynamic PV loop is illustrated in Fig. 7. For simplicity, we consider only elastic pressure changes. We assume that Pes reflects the radial stress acting on the lungs. During uniform expansion (top panel) from FRC (A) to FRC + VT (B) (tidal volume), radial stress increases from 2 to 6 cmH20. Deflation is also uniform, and thus the lung would move from B to A, as depicted by the dashed line on the PV plot (middle panel). During anesthesia, the lung is assumed to be first expanded by the diaphragm in a uniaxial manner so that the width of the region does not change, that is, the sides are constrained. Under these conditions, as Rodarte (15) has discussed, radial stress (Pes) wiIl change less than during uniform expansion. The lung will inflate along the solid PV line A to B’ (middle panel). Assume that at end inspiration the diaphragm relaxes and the lung simultaneously undergoes an isovolume radial expansion achieving the uniform shape of FRC + VT (B, bottom panel). Pes increases from 4 to 6 cmHz0
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652
RICH,
a
FRC
A (POO -Pd, FIG.
cm
l-i20
6. Dynamic
the awake anesthesia,
PV loop for one spontaneously (solid Line) and anesthetized (dashed the loop was reversed. FRC
rl
A
FRC
Uniform
breathing lin ,e) states.
dog in During
+ VT
expansion b
2 cm H20
B
6 cm Hz0
4
L
6
FIG. 7. Model for explaining reversed dynamic PV loops during anesthesia. It is assumed that esophageal pressure (Pes) reflects radial stress acting on lung. Uniform and nonuniform expansions produce a different radial stress. For further explanation, see text.
along the solid line and the PV goes from B’ to B (middle panel). Deflation follows the uniform path-the dashed PV line B to A. Thus, the quasi-static PV plot shows a reverse loop. With better information on the precise pattern of expansion of the respiratory system under anesthesia, it should be possible to model the full dynamic loop seen in Fig. 6. Under these conditions, a
KNOPP,
AND
HYATT
dissociation can occur between the regional and the overall changes in transpulmonary pressure. Further analysis of this interesting behavior is warranted. The simplified model that is presented is supported by the fact that mechanical ventilation of the lungs in every instance immediately converted the dynamic PV loop to normal. The literature on anesthesia contains many observations of uncoordinated motion of the chest wall in anesthetized patients. In 1925, Miller (11) first described a progressive ascending paralysis of the muscles of the respiratory system as a result of the inhalation of a general anesthetic. He observed that the intercostal muscles were paralyzed once a certain depth of anesthesia was reached. More recently, Jones et al. (8) observed, in eight subjects, a consistent reduction in the contribution of the chest wall to the tidal volume as a result of anesthesia. In some of the patients, Jones and co-workers (8) observed a “rocking ventilation” with halothane, that is, a complete phase reversal between diaphragm and chest wall. Similarly, Tusiewicz and co-workers (16) found, in five children anesthetized with halothane, a large reduction in the contribution of the rib cage to tidal volume during CO2 challenge. These authors attributed this reduction to a rapid and profound depression of intercostal activity with halothane anesthesia. They pointed out that, if the active stabilization of the rib cage by intercostal muscle contraction is lost, the chest would be sucked in as the diaphragm contracts, that is, an uncoordinated motion may occur. Tidal
B’
REHDER,
Volume and Respiratory
Frequency
In dogs, the effect of either halothane or enflurane anesthesia on tidal volume and respiratory frequency is difficult to determine because the respiratory frequencies vary greatly within and between dogs in the awake state. Therefore, we compared both respiratory frequency and tidal volume in the anesthetized state at 1.6 MAC and found that halothane and enflurane appear to have different effects on the control of ventilation in dogs. Tidal volumes were consistently larger and respiratory frequencies consistently less during enflurane than halothane anesthesia. Although this occurred at the same MAC level, these different effects may represent different levels of depth of anesthesia. Because 1 MAC represents only one point on the dose-response curve, comparisons of multiples of MAC may not indicate equal depths of anesthesia (18). This is unlikely, however, because we found no further changes in tidal volume and respiratory frequency by increasing or decreasing the halothane or enflurane concentration. We are not aware of well-controlled studies in man or dog of the effect of halothane or enflurane anesthesia on the tidal volume and respiratory frequency. In summary, mongrel prone dogs anesthetized with either halothane or enflurane did not show a reduction in mean FRC in conjunction with an increase in lung recoil and decrease in lung compliance. Prone dogs as a group, therefore, cannot be used as a model to study the mechanisms for the altered respiratory mechanics in anesthetized man. Furthermore, we conclude that halo-
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HALOTHANE-ENFLURANE
ANESTHESIA
AND
RESPIRATORY
thane and enflurane have different effects on the PV curves of the chest wall in prone dogs. The control of ventilation also seems to be affected differently by halothane and enflurane. In some dogs, we observed a paradoxic motion of the chest wall during anesthesia that could be immediately converted by mechanical inflation of the lungs. The authors
thank
Mr.
Kenneth
Offord
for statistical
analysis,
653
MECHANICS
Mr.
Mark Schroeder for expert technical help, Mrs. Kathleen Street and Mr. Jerry Rach for careful data analysis, and Ms. Carol Mickow for excellent secretarial assistance. This investigation was supported in part by Research Grants HL12090, HL-14593, and HL-21584 from the National Institutes of Health. Address reprint requests to: K. Rehder, Mayo Clinic, 200 First St. SW, Rochester, MN 55901.
Received
19 June
1978; accepted
in final
form
8 November
1978.
REFERENCES 1. CAMPBELL, E. J. M., J. F. NUNN, AND B. W. PECKETT. A comparison of artificial ventilation and spontaneous respiration with particular reference to ventilation-bloodflow relationships. Br. J. Anaesth. 30: 166-175, 1958. 2. EGER, E. I., II. Anesthetic Uptake and Action. Baltimore, MD: Williams & Wilkins, 1974. 3. EGER, E. I., II, B. BRANDSTATER, L. J. SAIDMAN, M. J. REGAN, J. W. SEVERINGHAUS, AND E. S. MUNSON. Equipotent alveolar concentrations of methoxyflurane, halothane, diethyl ether, fluroxene, cyclopropane, xenon and nitrous oxide in the dog. AnesthesioZogy 26: 771-777, 1965. 4. EGER, E. I., II, C. LUNDGREN, S. L. MILLER, AND W. C. STEVENS. Anesthetic potencies of sulfur hexafluoride, carbon tetrafluoride, chloroform and Ethrane in dogs: correlation with the hydrate and lipid theories of anesthetic action. Anesthesiology 30: 129-1351969. 5. FRANK, N. R., J. MEAD, AND B. G. FERRIS, JR. The mechanical behavior of the lungs in healthy elderly persons. J. CZin. Invest. 36: x80-1687,1957. 6. GILLESPIE, D. J., AND R. E. HYATT. Respiratory mechanics in the unanesthetized dog. J. Appl. Physiol. 36: 98-102, 1974. 7. GILLESPIE, D. J., Y.-L. LAI, AND R. E. HYATT. Comparison of esophageal and pleural pressures in the anesthetized dog. J. AppZ. Physiol. 35: 709-713, 1973. 8. JONES, J. G., D. FAITHFULL, AND B. D. MINTY. The relative contribution to tidal breathing of the chest wall and the abdomen in awake and anaesthetized subjects (Abstract). Br. J. Anaesth. 48: 812, 1976. 9. LAI, Y.-L., J. R. RODARTE, AND R. E. HYATT. Esophageal elastance in awake and anesthetized recumbent dogs. J. AppZ. PhysioZ. 41:
272-275, 1976. 10. LAI, Y.-L., J. R. RODARTE, AND R. E. HYATT. Respiratory mechanics in recumbent animals anesthetized with thiopental sodium. J. AppZ. Physiol.: Respirat. Environ. Exercise Physiol. 46: 716-720, 1979. 11. MILLER, A. H. Ascending respiratory paralysis under general anesthesia. J. Am. Med. Assoc. 84: 201-202, 1925. 12. MUGGENBURG, B. A., AND J. L. MAUDERLY. Cardiopulmonary function of awake, sedated, and anesthetized beagle dogs. J. AppZ. Physiol. 37: 152-157, 1974. 13. REHDER, K., T. J. KNOPP, AND A. D. SESSLER. Regional intrapulmonary gas distribution in awake and anesthetized-paralyzed prone man. J. AppZ. Physiol.: Respirat. Environ. Exercise Physiol. 45: 528-535, 1978. 14. REHDER, K., A. D. SESSLER, AND H. M. MARSH. General anesthesia and the lung. Am. Rev. Respir. Dis. 112: 541-563, 1975. 15. RODARTE, J. R. Importance of lung material properties in respiratory system mechanics. Physiologist 20: 21-25, 1977. 16. TUSIEWICZ, K., A. C. BRYAN, AND A. B. FROESE. Contributions of changing rib cage-diaphragm interactions to the ventilatory depression of halothane anesthesia. Anesthesiology 47: 327-337, 1977. 17. VAN LITH, P., F. N. JOHNSON, AND J. T. SHARP. Respiratory elastances in relaxed and paralyzed states in normal and abnormal men. J. AppZ. Physiol. 23: 475-486, 1967. 18. WAUD, B. E., AND D. R. WAUD. On dose-response curves and anesthetics (Editorial). Anesthesiology 33: l-4, 1970. 19. WESTBROOK, P. R., S. E. STUBBS, A. D. SESSLER, K. REHDER, AND R. E. HYATT. Effects of anesthesia and muscle paralysis on respiratory mechanics in normal man. J. AooZ. PhysioZ. 34: 81-86. 1973.
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and enflurane anesthesia and mechanics in prone dogs
CHARLES R. RICH, KAI REHDER, THOMAS J. KNOPP, AND ROBERT E. HYATT Departments of Anesthesiology and Physiology and Biophysics, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55901
RICH, CHARLES R., KAI REHDER, THOMAS J. KNOPP, AND ROBERT E. HYATT. Halothane and enflurane anesthesia and respiratory mechanics in prone dogs. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 46(4): 646-653, 1979.-Functional residual capacity (FRC), total lung capacity (TLC), and static deflation pressure-volume curves of the total respiratory system, lungs, and chest wall were measured in eight trained prone dogs with permanent tracheostomies first during the awake state and then during halothane (1.3-2.8 minimal alveolar concentrations (MAC) or enflurane (1.4-1.9 MAC) anesthesia. The mean of the difference between TLC and TLC (awake) was -0.05 liter for halothane and -0.07 liter for enflurane anesthesia; the reduction in TLC was significant (P c 0.05) only for enflurane. Mean FRC did not change with either halothane or enflurane anesthesia. Halothane anesthesia had no significant effect on the elastic recoil pressures of the total respiratory system, lungs, and chest wall. Compliance of the total respiratory system increased significantly (P < 0.05) with halothane. In contrast, enflurane significantly (P < 0.05) increased the elastic recoil pressures of the total respiratory system and of the chest wall. Compliance of the lung decreased significantly with enflurane anesthesia (P < 0.05). Some of the dogs had paradoxic motion of the thoracic wall. The wall moved inward during inspiration, recoiled outward at end inspiration, and had a normal motion during expiration. Tidal volumes were consistently larger and respiratory frequencies consistently less during 1.6 MAC of enflurane than during 1.6 MAC of halothane anesthesia. No consistent dose-response effect on any of the measured variables was observed with either anesthetic.
In trained prone dogs, respiratory mechanics and lung volumes were examined before and after induction of anesthesia with halothane or enflurane at various concentrations. We found that the respiratory system of these dogs responded differently to induction of anesthesia than did the respiratory system of supine (19) or prone (13) man anesthetized with thiopental sodium. Furthermore, the effects on the mechanics of the respiratory system of prone dogs were different with halothane than with enflurane anesthesia. METHODS
Dogs with permanent tracheostomies were trained to lie quietly prone in a specially designed air-conditioned volume-displacement body plethysmograph. The dogs were conditioned to tolerate the insertion of a balloon into the esophagus and of a cuffed endotracheal tube into the trachea. They were trained to accept temporary occlusion of the airway for determinations of thoracic gas volume and to tolerate determinations of inflation and deflation quasi-static pressure-volume (PV) curves. Lung volumes were measured by body plethysmography; the characteristics of the body plethysmograph have been described (6). Pleural pressure (Ppl) was estimated from esophageal pressure (Pes). The Pes was detected by a latex balloon (lo-cm length, 3.5cm perimeter) in the lower third of the esophagus. Pes was transmitted PV curves; lung volumes; recoil pressures; compliances; awake through an 80-cm polyethylene tube and sensed by a dogs strain gauge (Statham PMl3l). The position of the balloon in the esophagus was confumed in each dog by roentgenograms of the chest. The balloon was inflated GENERAL ANESTHESIA in recumbent man reduces the with 0.6-1.2 ml of air, the volume depending on the PV functional residual capacity (FRC) (14), increases the characteristics of the balloon. The gas volume was reelastic recoil pressures, and reduces the compliances of peatedly tested throughout each study. Lateral airway the lung and respiratory system (19). The mechanisms pressure (Pao) was measured inside the trachea, 3 cm for these changes are still not understood and need to be from the distal opening of the endotracheal tube. Transelucidated because the changes may contribute to the pulmonary pressure (PL) was estimated from the differfrequently observed impaired pulmonary gas exchange ence between Pao and Pes. To exclude artifacts, PL was during general anesthesia (1). In a recent study from our required to remain constant during inspiratory efforts laboratory, Lai and co-workers (10) found that, in dogs against the temporarily occluded airway, except for the in various positions, anesthesia with thiopental sodium small changes due to gas expansion. had no significant effect on respiratory mechanics and Inspiratory gas (30% 02 in 70% N2) flowed from a tank FRC. In the present study, we examined, in prone dogs, (contents analyzed by duplicate Haldane analyses) the effect of halothane and enflurane anesthesia on these through vaporizers specific for halothane (Fluotec Mark variables as a continuation of our search for a dog model I, Cyprane Ltd., UK) or enflurane (Ohio enflurane vathat will allow a detailed study of the mechanisms of porizer, Ohio Medical Products, Madison, WI 53701) into a E-liter reservoir bag and from there through a largeanesthesia-induced changes in respiratory mechanics. 0161-7567/79/00004000$01.25
Copyright
0 1979 the American
Physiological
Society
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HALOTHANE-ENFLURANE
ANESTHESIA
AND
RESPIRATORY
bore three-way valve (Hans-Rudolph valve) and a pneumotachograph (Fleisch no. 1) to the dog. Expiratory gas flowed from the dog through the endotracheal tube, the pneumotachograph, and the Hans-Rudolph valve either into the atmosphere or via a 3-mm orifice and a solenoid valve into a 260-liter drum, which was evacuated to a pressure of -90 cmHz0. The negative pressure was used for stepwise deflation of the lungs. The l&liter reservoir bag was contained in a rigid box in which the pressure could be varied between ambient and 30 cmHz0 for inflating the lungs. Inspiratory and expiratory gas flow rates were determined by a calibrated pneumotachograph. Addition of halothane or enflurane to the inspirate did not cause a measurable change in the calibration of the pneumotachograph. Inspiratory and expiratory concentrations of halothane or enflurane were measured intermittently with an infrared gas analyzer (Beckman LB-2) calibrated with three known concentrations of halothane or enflurane. Expired concentrations of carbon dioxide were measured intermittently with an infrared analyzer (Beckman LB-l) calibrated with three known concentrations of carbon dioxide. Arterial blood pressure in the abdominal aorta was sensed by a pressure transducer (Statham P37A). All signals were recorded on an eight-channel recorder (Hewlett-Packard HP 7788A). Rectal temperature was detected by a thermistor probe (Yellow Springs Instrument); body temperature was maintained (mean t SD, 36.6 t 0.2”C) by warming blankets, or by circulating warm air through the airconditioning system of the body plethysmograph, or by both means. Arterial blood gases were determined by appropriate electrodes only in the anesthetized dogs. PROCEDURE
After the dog was positioned, several minutes were allowed for stabilization of the plethysmograph temperature. Then, while the dog was awake, three measurements of thoracic gas volume at FRC were performed. Immediately after, transpulmonary pressure, inspiratory and expiratory gas flow rates, and changes in lung volume were recorded for approximately 15 breaths at a paper speed of 2.5 cm/s. The measurements of thoracic gas volume were then repeated. The lungs were then inflated from FRC to an airway pressure of 30 cmHz0 (the volume achieved will be called TLC), deflated to FRC, and again inflated to an airway pressure of 30 cmHn0. Quasi-static deflation PV curves were then obtained by stepwise (breath holding for 3 s) deflation of the lungs, either until no more gas could be withdrawn or until the dog became uncomfortable. The latter usually occurred at a PL of approximately -4 cmHa0. After the dog had resumed spontaneous breathing, the entire procedure was repeated two times. The dog was removed from the body plethysmograph. Anesthesia was induced with 70% N20 and 30% Oz. After the induction of anesthesia with N20 was completed, halothane or enflurane vapor was added to the inspirate. The administration of N20 was discontinued after a few minutes and the inspired gas mixture was changed to 30% 02 and 70% N2 with the desired concentration of the volatile anesthetic. The dog was then reDositioned in the
647
MECHANICS
body plethysmograph. The data collection procedure was the same as for the dogs while awake and was begun 5% 171 min after induction of anesthesia or 40-66 min after the inspired anesthetic concentration was changed. The length of the latter time interval was determined by the time required for the ratio of end-tidal to inspired halothane or enflurane concentration to equal or exceed 0.85. Anesthetic concentrations of halothane and enflurane were expressed as minimal alveolar concentration (MAC) (2); 1 MAC of halothane was taken to be 0.87% (3) and 1 MAC of enflurane 2.20% (4). Because measurements were done in a given dog at several MAC levels (1.3, 1.6, 2.0, 2.3, and 2.8 MAC for halothane and 1.4, 1.6, and 1.9 MAC for enflurane), time intervals between the induction of anesthesia and the final measurement were as long as 7 h. In three dogs, the effect of time was examined by repeating all measurements at a constant inspiratory concentration of halothane (two dogs) or enflurane (one dog) during a period of 6-9 h. There was no alteration of the respiratory mechanics and FRC with time. RESULTS
Eight male mongrel dogs (13.5-25.5 kg) were studied. Six dogs were studied while awake, on 3-8 different nonconsecutive days and the other two were each studied once (Table 1). During halothane anesthesia, six of the same eight dogs were also studied on two different nonconsecutive days and two were studied once. During enflurane anesthesia, two of the dogs were studied on two different days and four were studied once. Reproducibility Lung uolumes. We analyzed the reproducibility of the measurements of FRC and TLC to evaluate the variability between days and within days. There were 710 measurements of FRC and 121 of TLC for the awake state in the eight dogs (Table 1). There were also 254 measurements of FRC and 42 of TLC for 1.6 MAC of halothane and 166 of FRC and 33 of TLC for 1.6 MAC of enflurane. The mean total variability (overall standard deviation for a particular dog and state) of the FRC and TLC measurements was about 2.6 times that of the within-day variability, indicating the predominance of the betweenday variability. Total and within-day variabilities were 1. Within-day and between-day reproducibility in eight awake prone dogs _.-_-_-_ - -_._-. f-- -~--- ---- ---- -------- -~ ~-~ --~-
TABLE
of FRC_---.-______.and TLC
TLC
FRC
Dog No.
c&
1 2
6 5
n, replicates
Overall mean, liters
SD*, liter
SD?, liter
cl&
122 106
1.00 1.04
0.07 0.05
0.09 0.09
6 6
n, replicares
16 19
,i,ii,~,~,~~i,1,li
all
Estimate of within-day standard standard deviation of anv single
deviations. measurement.
Overall mean, liters
SD*, liter
SD-t, liter
2.65 2.43 1.45 1.93 1.91 2.01 2.35 2.76
0.07 0.05 0.02 0.06 0.08 0.06 0.04 0.17
0.07 0.12 0.09 0.16 0.15 0.17
t Estimate
f over-
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RICH, REHDER,
648 similar to those in the awake state during either enflurane or halothane anesthesia. PV curves. The reproducibility of recoil pressures was evaluated visually by plotting for each dog all measured recoil pressures vs. all corresponding lung volumes. Reproducibility of recoil pressures in both awake and anesthetized states was best for the lung, whereas recoil pressures for the chest wall and for the total respiratory system showed more variability (Fig. 1). The within-day and the between-day reproducibility appeared to be simStatic compliances were measured over a 300~ml volume range above FRC (awake) and were determined from the mean PV curves for a given day. Reproducibility of the static compliances was not analyzed because only a limited number of replicate between-day determinations were obtained. Effect of Anesthesia Lung volumes. For each dog, average values were calculated for each day of study for both states. The mean value for the group was calculated from these average values. The mean of the difference between TLC and TLC (awake) was -0.05 liter for halothane and -0.07 liter for enflurane anesthesia; the reduction in TLC was significant (P < 0.05) only for enflurane (Table 2). Individual dogs showed consistent changes in FRC on repeated studies. The mean of the difference between FRC and FRC (awake) was -0.02 liter with halothane and -0.05 liter with enflurane anesthesia; the reduction in FRC was not significant with either anesthetic (Table 2). To examine the possible effect of body habitus on direction and magnitude of change in FRC, the relationship between the changes in FRC caused by anesthesia and the ratio of body length to weight was examined by linear regression analysis. There was a significant (P < 0.02) positive correlation for both halothane and enflurane, i.e., the short and heavy dogs tended to show the largest reductions in FRC. PV curves. Complete PV curves could not be obtained for dogs that became uncomfortable at low airway pressures. Also, not all dogs were studied at the five levels of halothane anesthesia or the three levels of enflurane
Total
0’ -30
’ -20
’ -10
system
’ 0
POO, cm FIG.
occasions
1. Quasi-static PV curves 49 days apart; different
’ IO
l-l20
’
’ 30
Tidal Volume and Respiratory Frequency Tidal volumes were consistently larger and respiratory 2. Mean (range) values for lung volumes of awake and anesthetized prone dogs* -----.--. -~~_ -~ -- - .---. TABLE
Anesthetic
Awake
Halothane, 1.6 MAC
-20
-10
PL,
obtained in one awake dog on two days are indicated by crosses (x) or
FRC, liters
TLC, liters
State
2.20 (1.37 to 2.76)
0.90 (0.54 to 1.09)
2.15 (1.41 to 2.74) . -0.05 ’ (-0.18 to 0.03)
0.89 (0.62 to 1.11) . -0.02 ’ (-0.28 to 0.12)
2.08 (1.51 to 2.66)
0.83 (0.68 to 1.05)
2.01 (1.45 to 2.61) -0.07-t (-0.14 to 0.02)
0.78 (0.61 to 0.95) -0.05 (-0.12 to 0.03)
(8 dogs) Anesthetized Anesthetizedawake Enflurane, 1.6 MAC (6 dogs)
Awake
Anesthetized Anesthetizedawake
Values are means with ranges in parentheses. * Data were obtained when both awake and anesthetized states were studied on the same day. t Mean of differences significantly different from zero by paired t test (P < 0.05).
Chest
1
-,30
AND HYATT
anesthesia on a given day because of the long duration of the study. Recoil pressures of the total respiratory system (Pao), lung (PL), and chest wall (Pes) did not change significantly (P > 0.05) with any of the five examined MAC levels of halothane at any lung volume (Figs. 2 and 3). In contrast, enflurane anesthesia resulted in a significant (P < 0.05) increase in the recoil pressure of the total respiratory system at most lung volumes with the two examined MAC levels (Figs. 3 and 4). This increase appeared to be due to changes in the chest wall and not the lung. The static compliance of the total respiratory system (Crs) increased significantly (P < 0.05) with halothane anesthesia (Table 3). This increase appeared to be due to changes of the chest walI (Cw), which were not significant (P = 0.09). In contrast, with enflurane anesthesia, the static compliance of the lung (CL) decreased significantly (P < 0.05). Compliances of the respiratory system and chest wall did not change significantly with enflurane.
Lung
20
KNOPP,
0
cm
IO
40
20
30
- -30
’
-20
’ -10
wall
’
’
’
4
0
IO
20
30
PUS, cm
t-l20
doti (0). Recoil pressures of lung showed did those of chest wall or total respiratory
better reproducibility system.
than
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HALOTHANE-ENFLURANE
ANESTHESIA
AND
RESPIRATORY
649
MECHANICS
Halothane 1.6 MAC
I
YO ’
”
-10
-5
0
L
.
.
I
.
5
0
+
I
’
r
IO
AP (anesth Total
MAC
2.3
l
-10
- awake),
system
-5
i.
00
0
.
IO
5
cm Hz0
Lung Halothane
FIG. 2. Lung volume expressed as percent of TLC (awake) plotted as a function of changes in recoil pressures between halothane anesthesia and awake state. Each dog is represented with one mean value for each lung volume. There was no significant effect of halothane anesthesia on recoil pressure at any lung volume (# 0.05 < P < 0.1, paired t test). Although not shown, same was true at 1.3, 2.0, and 2.8 MAC of halothane.
Chest
( I .6
MAC)
100
I I/
60
wall
,,
/ H--
60
40
* / ,I
,
Enf lurone
( I .6 MAC 1
FIG. 3. Mean quasi-static PV curves for the awake (SOW line) and anesthetized (dashed Line) states.
. .--
40
/I I0/
-
POO,
cm
Hz0
PL,
cm
H20
frequencies consistently less during enflurane than halothane anesthesia (Fig. 5). This comparison was made with both agents at 1.6 MAC and at similar arterial carbon dioxide tensions. Dose Response The dose responses of aI.l variables were tested by linear regression analysis. The slopes relating each of the variables to the MAC level of halothane or enflurane were not significantly different from zero. This indicates that there was no significant dose response effect over the range of 1.3-2.8 MAC of halothane and 1.4-1.9 MAC
POS,
cm
t-i20
of enflurane on any of the examined variables. The mean (t SE) value for Pace, during 1.6 MAC of halothane was 42 t 1 Torr and that for 1.6 MAC of enflurane 47 t 2 Torr; these mean values were not significantly different. Mean (+ SE) values for Pao, were 125 t 3 and 129 t 3 Torr for 1.6 MAC of halothane and enflurane anesthesia, respectively; these values were not significantly different . DISCUSSION
The purpose of this study was to determine if prone dogs anesthetized with halothane or enflurane could
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650
RICH,
REHDER,
KNOPP,
AND
HYATT
Enf lurane I .6 MAC
I .4 MAC
t
1.9
FIG. 4. Lung volume expressed as percent of TLC (awake) plotted as a function of difference in recoil pressures between enflurane anesthesia and awake state. Each dog is represented with one mean value for each lung volume. Values at MAC are not shown because only three dogs were studied at that
< 0.05 and $ 0.05 < P < 0.1 (paired
t test).
Pes
z* .+ -10
-5
0
5
IO
* : .t -10
AP (onesth - awake),
-5
Halothane, 1.6 MAC
State Awake
(8dogs) Anesthetized Anesthetizedawake
Enflurane, 1.6 MAC
Awake
0
--
Cm, l/cmHsO
CL, l/cmHzO
cw, l/cmHzO
0.039 (0.018 to 0.057)
0.148 (0.071 to 0.250)
0.065 (0.035 to 0.111)
0.056 (0.028 to 0.083) 0.017t (-0.008 to 0.041)
0.147 (0.079 to 0.240) -0.001 (-0.088 to 0.033)
0.098 (0.046 to 0.166) 0.033 (-0.042 to 0.097)
0.046 (0.028 to 0.063)
0.147 (0.088 to 0.207)
0.067 (0.036 to 0.103)
0.050 (0.033 to 0.071) 0.004 (-0.013 to 0.027)
0.132 (0.075 to 0.185) -0.015t (-0.031 to -0.001)
0.077 (0.052 to 0.120) 0.009 (-0.028 to 0.064)
(6dogs) Anesthetized Anesthetizedawake
Values are means with ranges in parentheses. * Data were obtained when both awake and anesthetized states were studied on the Same day. t Mean of differences significantly different from zero by paired t test (P c 0.05).
serve as a model to study the mechanisms for the altered respiratory mechanics that have been observed in recumbent man on induction of general anesthesia with various agents. We found that, in general, dogs in the prone position, anesthetized with halothane or enflurane, cannot be used to study the mechanisms of the altered respiratory mechanics occurring in supine anesthetized man. However, the possibility exists that individual prone dogs, dogs in other body positions, or dogs anesthetized with other agents may respond to general anesthesia in a manner similar to that in man.
Comments
IO
5
cm Hz0
TABLE 3. Mean (range) values for compliance of awake and anesthetized prone dogs* -- _._--. - -- -.. Anesthetic
0
on A4ethodology
In recumbent man the mean reduction of FRC values reported in the literature following induction of general anesthesia varies considerably, with a mean reduction of about 16% of the supine awake FRC (reductions range
l
O0
1
1
-4
-8
I
-12
I
-16
I
-20
A f, breathdmin 5. Tidal volume and respiratory frequency at 1.6 MAC halothane anesthesia was subtracted from values measured in same dog at 1.6 MAC enflurane anesthesia, AVT and Af, respectively. Each dot represents mean change for one dog. Tidal volumes were consistently larger and respiratory frequencies consistently less during enflurane than halothane anesthesia. FIG.
from -3 to +39%) (14). If one assumes a mean value of 0.90 liter for FRC in awake prone dogs (Table I), then one would anticipate a mean decrease in FRC of about 144 ml if the response in the dog was similar to that in man. Analysis of our data for reproducibility of the lung volume determinations indicates that, with our method, we could detect a significant change in FRC of 50 ml or more for a given dog. (This was calculated for dog 5 who had only 13 measurements of FRC while awake and 16 measurements while anesthetized; for all other dogs, differences of less than 0.05 liter would have been significant. ) Reproducibility of recoil pressure measurements for the lung was better than that for chest wall and total respiratory system, presumably because the dogs were not always completely relaxed. The average absolute difference between our replicate measurements and the mean values for recoil pressure of the total respiratory system at lung volumes near 60% TLC was less than 1
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HALOTHANE-ENFLURANE
ANESTHESIA
AND RESPIRATORY
cmHzO (61 sets of replicate measurements). This variability compares favorably with that reported for relaxed man by Van Lith and co-workers (17), who found that recoil pressure measurement scatter was equal to 19% of the mean (according to Fig. 3 of Ref. 17, approximately 16 cmH20) determined at a lung volume equal to FRC plus 1.5 liters. In prone dogs, anesthesia induced with thiopental sodium causes a significant decrease in esophageal elastance (9). We do not know whether halothane or enflurane affects esophageal elastance, and the possibility that our estimates of pleural pressure from esophageal pressure may have been influenced by such an effect cannot be ruled out. In prone dogs anesthetized with pentobarbital sodium, extrapolated esophageal pressure reflects local pleural pressure, but the latter may not reflect the overall elastic behavior of the lung or chest wall (7). Effect of Anesthesia on Static Lung Volumes and PV Curves Lung volumes. To our knowledge, no anesthetic agent has produced significant reductions of FRC in dogs in any recumbent position. In contrast, in recumbent man, significant reductions in FRC have been observed with most anesthetic agents (14). In prone beagle dogs, fentanyl-droperidol anesthesia increases FRC significantly, but if pentobarbital sodium was added, the increase was not significant (12). Thiopental sodium anesthesia had no significant effect on FRC in prone mongrel dogs (9, 10). Similarly, we found in our study that halothane or enflurane anesthesia did not reduce the mean FRC significantly, but we observed differences between individual dogs in terms of their response of FRC. With halothane anesthesia, we observed significant and consistent reductions in FRC in two of eight dogs, and in the same dogs, enflurane anesthesia reduced FRC. In prone anesthetized-paralyzed man, we found, in four of five subjects, a reduction in FRC with thiopental sodium anesthesia (13). Although muscle paralysis cannot be ruled out as the cause for this difference, we believe that this is unlikely because, in anesthetized supine man, muscle paralysis does not further reduce FRC (19). The difference between dog and man may be related to the differences in the configuration and deformability of the chest wall. More work is necessary to elucidate the mechanisms for the different responses. PV curve. Neither halothane nor enflurane anesthesia had a significant effect on the mean static recoil pressure of the lung. Similarly, Lai and co-workers (10) found no change in the static recoil pressure of the lung in prone dogs anesthetized with thiopental sodium. These observations are in contrast to studies in man by Westbrook and co-workers (19), who noted, in five supine men anesthetized with thiopental sodium and meperidine, a consistent increase of the elastic recoil pressure of the lung. We have no explanation for the reduction in lung compliance with enflurane anesthesia. Halothane and enflurane had different effects on the mean static recoil pressure of the chest wail. Although enflurane increased recoil pressures in all dogs at nearly ail lung volumes, halothane tended to increase mean
MECHANICS
651
recoil pressure at low lung volumes but to decrease recoil pressure at high lung volumes. These observations are in agreement with no change in mean compliance of the chest wall with enflurane and an increased mean compliance of the chest wall with halothane. The largest increases in recoil pressure of the chest wall at FRC tended to occur in those dogs who showed consistent decreases in FRC. The most likely mechanism for the altered recoil pressure of the chest wall is a change in the mechanical properties of the muscles of the thoracic cage. Anesthetics can have either a direct effect on the muscles or an indirect effect mediated via the nervous system (or both). Whatever the mechanism, our study suggests that enflurane, thiopental sodium, and halothane all have different effects on the muscles of the thoracic cage. This conclusion is supported by the clinical observation that these agents have different relaxant effects on muscle. Effect of Anesthesia on Dynamic “Transpulmonary Pressure” We measured pulmonary resistance (RL) by the isovolume method (5), using the esophageal pressure changes as an estimate of overall pleural pressure changes. In the awake dogs, we observed a mean (t SE) pulmonary resistance of 1.02 t 0.14 cmHsO/(!/s), which is in good agreement with the mean pulmonary resistance of 1.30 t 0.09 cmHzO/(l/s) found for prone dogs by Gillespie and Hyatt (6). We noted “negative values of pulmonary resistance” with halothane anesthesia in five of eight dogs and with enflurane anesthesia in five of six dogs. The “negative resistance” values were associated with observations of uncoordinated motion of the thoracic wall, i.e., the wall moved inward during inspiration. At end inspiration, the thoracic wall recoiled outward and the pattern of expiratory movement was apparently similar to that observed with the dogs awake. For dogs who had a “negative resistance,” dynamic PV loops were plotted for both states (Fig. 6). The dynamic PV loops were normal for the awake state but were reversed for the anesthetized state. A possible explanation for the reversal of the dynamic PV loop is illustrated in Fig. 7. For simplicity, we consider only elastic pressure changes. We assume that Pes reflects the radial stress acting on the lungs. During uniform expansion (top panel) from FRC (A) to FRC + VT (B) (tidal volume), radial stress increases from 2 to 6 cmH20. Deflation is also uniform, and thus the lung would move from B to A, as depicted by the dashed line on the PV plot (middle panel). During anesthesia, the lung is assumed to be first expanded by the diaphragm in a uniaxial manner so that the width of the region does not change, that is, the sides are constrained. Under these conditions, as Rodarte (15) has discussed, radial stress (Pes) wiIl change less than during uniform expansion. The lung will inflate along the solid PV line A to B’ (middle panel). Assume that at end inspiration the diaphragm relaxes and the lung simultaneously undergoes an isovolume radial expansion achieving the uniform shape of FRC + VT (B, bottom panel). Pes increases from 4 to 6 cmHz0
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652
RICH,
a
FRC
A (POO -Pd, FIG.
cm
l-i20
6. Dynamic
the awake anesthesia,
PV loop for one spontaneously (solid Line) and anesthetized (dashed the loop was reversed. FRC
rl
A
FRC
Uniform
breathing lin ,e) states.
dog in During
+ VT
expansion b
2 cm H20
B
6 cm Hz0
4
L
6
FIG. 7. Model for explaining reversed dynamic PV loops during anesthesia. It is assumed that esophageal pressure (Pes) reflects radial stress acting on lung. Uniform and nonuniform expansions produce a different radial stress. For further explanation, see text.
along the solid line and the PV goes from B’ to B (middle panel). Deflation follows the uniform path-the dashed PV line B to A. Thus, the quasi-static PV plot shows a reverse loop. With better information on the precise pattern of expansion of the respiratory system under anesthesia, it should be possible to model the full dynamic loop seen in Fig. 6. Under these conditions, a
KNOPP,
AND
HYATT
dissociation can occur between the regional and the overall changes in transpulmonary pressure. Further analysis of this interesting behavior is warranted. The simplified model that is presented is supported by the fact that mechanical ventilation of the lungs in every instance immediately converted the dynamic PV loop to normal. The literature on anesthesia contains many observations of uncoordinated motion of the chest wall in anesthetized patients. In 1925, Miller (11) first described a progressive ascending paralysis of the muscles of the respiratory system as a result of the inhalation of a general anesthetic. He observed that the intercostal muscles were paralyzed once a certain depth of anesthesia was reached. More recently, Jones et al. (8) observed, in eight subjects, a consistent reduction in the contribution of the chest wall to the tidal volume as a result of anesthesia. In some of the patients, Jones and co-workers (8) observed a “rocking ventilation” with halothane, that is, a complete phase reversal between diaphragm and chest wall. Similarly, Tusiewicz and co-workers (16) found, in five children anesthetized with halothane, a large reduction in the contribution of the rib cage to tidal volume during CO2 challenge. These authors attributed this reduction to a rapid and profound depression of intercostal activity with halothane anesthesia. They pointed out that, if the active stabilization of the rib cage by intercostal muscle contraction is lost, the chest would be sucked in as the diaphragm contracts, that is, an uncoordinated motion may occur. Tidal
B’
REHDER,
Volume and Respiratory
Frequency
In dogs, the effect of either halothane or enflurane anesthesia on tidal volume and respiratory frequency is difficult to determine because the respiratory frequencies vary greatly within and between dogs in the awake state. Therefore, we compared both respiratory frequency and tidal volume in the anesthetized state at 1.6 MAC and found that halothane and enflurane appear to have different effects on the control of ventilation in dogs. Tidal volumes were consistently larger and respiratory frequencies consistently less during enflurane than halothane anesthesia. Although this occurred at the same MAC level, these different effects may represent different levels of depth of anesthesia. Because 1 MAC represents only one point on the dose-response curve, comparisons of multiples of MAC may not indicate equal depths of anesthesia (18). This is unlikely, however, because we found no further changes in tidal volume and respiratory frequency by increasing or decreasing the halothane or enflurane concentration. We are not aware of well-controlled studies in man or dog of the effect of halothane or enflurane anesthesia on the tidal volume and respiratory frequency. In summary, mongrel prone dogs anesthetized with either halothane or enflurane did not show a reduction in mean FRC in conjunction with an increase in lung recoil and decrease in lung compliance. Prone dogs as a group, therefore, cannot be used as a model to study the mechanisms for the altered respiratory mechanics in anesthetized man. Furthermore, we conclude that halo-
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HALOTHANE-ENFLURANE
ANESTHESIA
AND
RESPIRATORY
thane and enflurane have different effects on the PV curves of the chest wall in prone dogs. The control of ventilation also seems to be affected differently by halothane and enflurane. In some dogs, we observed a paradoxic motion of the chest wall during anesthesia that could be immediately converted by mechanical inflation of the lungs. The authors
thank
Mr.
Kenneth
Offord
for statistical
analysis,
653
MECHANICS
Mr.
Mark Schroeder for expert technical help, Mrs. Kathleen Street and Mr. Jerry Rach for careful data analysis, and Ms. Carol Mickow for excellent secretarial assistance. This investigation was supported in part by Research Grants HL12090, HL-14593, and HL-21584 from the National Institutes of Health. Address reprint requests to: K. Rehder, Mayo Clinic, 200 First St. SW, Rochester, MN 55901.
Received
19 June
1978; accepted
in final
form
8 November
1978.
REFERENCES 1. CAMPBELL, E. J. M., J. F. NUNN, AND B. W. PECKETT. A comparison of artificial ventilation and spontaneous respiration with particular reference to ventilation-bloodflow relationships. Br. J. Anaesth. 30: 166-175, 1958. 2. EGER, E. I., II. Anesthetic Uptake and Action. Baltimore, MD: Williams & Wilkins, 1974. 3. EGER, E. I., II, B. BRANDSTATER, L. J. SAIDMAN, M. J. REGAN, J. W. SEVERINGHAUS, AND E. S. MUNSON. Equipotent alveolar concentrations of methoxyflurane, halothane, diethyl ether, fluroxene, cyclopropane, xenon and nitrous oxide in the dog. AnesthesioZogy 26: 771-777, 1965. 4. EGER, E. I., II, C. LUNDGREN, S. L. MILLER, AND W. C. STEVENS. Anesthetic potencies of sulfur hexafluoride, carbon tetrafluoride, chloroform and Ethrane in dogs: correlation with the hydrate and lipid theories of anesthetic action. Anesthesiology 30: 129-1351969. 5. FRANK, N. R., J. MEAD, AND B. G. FERRIS, JR. The mechanical behavior of the lungs in healthy elderly persons. J. CZin. Invest. 36: x80-1687,1957. 6. GILLESPIE, D. J., AND R. E. HYATT. Respiratory mechanics in the unanesthetized dog. J. Appl. Physiol. 36: 98-102, 1974. 7. GILLESPIE, D. J., Y.-L. LAI, AND R. E. HYATT. Comparison of esophageal and pleural pressures in the anesthetized dog. J. AppZ. Physiol. 35: 709-713, 1973. 8. JONES, J. G., D. FAITHFULL, AND B. D. MINTY. The relative contribution to tidal breathing of the chest wall and the abdomen in awake and anaesthetized subjects (Abstract). Br. J. Anaesth. 48: 812, 1976. 9. LAI, Y.-L., J. R. RODARTE, AND R. E. HYATT. Esophageal elastance in awake and anesthetized recumbent dogs. J. AppZ. PhysioZ. 41:
272-275, 1976. 10. LAI, Y.-L., J. R. RODARTE, AND R. E. HYATT. Respiratory mechanics in recumbent animals anesthetized with thiopental sodium. J. AppZ. Physiol.: Respirat. Environ. Exercise Physiol. 46: 716-720, 1979. 11. MILLER, A. H. Ascending respiratory paralysis under general anesthesia. J. Am. Med. Assoc. 84: 201-202, 1925. 12. MUGGENBURG, B. A., AND J. L. MAUDERLY. Cardiopulmonary function of awake, sedated, and anesthetized beagle dogs. J. AppZ. Physiol. 37: 152-157, 1974. 13. REHDER, K., T. J. KNOPP, AND A. D. SESSLER. Regional intrapulmonary gas distribution in awake and anesthetized-paralyzed prone man. J. AppZ. Physiol.: Respirat. Environ. Exercise Physiol. 45: 528-535, 1978. 14. REHDER, K., A. D. SESSLER, AND H. M. MARSH. General anesthesia and the lung. Am. Rev. Respir. Dis. 112: 541-563, 1975. 15. RODARTE, J. R. Importance of lung material properties in respiratory system mechanics. Physiologist 20: 21-25, 1977. 16. TUSIEWICZ, K., A. C. BRYAN, AND A. B. FROESE. Contributions of changing rib cage-diaphragm interactions to the ventilatory depression of halothane anesthesia. Anesthesiology 47: 327-337, 1977. 17. VAN LITH, P., F. N. JOHNSON, AND J. T. SHARP. Respiratory elastances in relaxed and paralyzed states in normal and abnormal men. J. AppZ. Physiol. 23: 475-486, 1967. 18. WAUD, B. E., AND D. R. WAUD. On dose-response curves and anesthetics (Editorial). Anesthesiology 33: l-4, 1970. 19. WESTBROOK, P. R., S. E. STUBBS, A. D. SESSLER, K. REHDER, AND R. E. HYATT. Effects of anesthesia and muscle paralysis on respiratory mechanics in normal man. J. AooZ. PhysioZ. 34: 81-86. 1973.
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