Hernodynamic and Organ Blood Flow Responses to Halothane and Sevoflurane Anesthesia During Spontaneous Ventilation Mark W. Crawford, MBBS, FRCPC, Jerrold Lerman, Frederick J. Carmichael, PhD, MD, FRCPC

MD, FRCPC, Victor

Saldivia,

BSC,

and

Department of Anesthesia, the Hospital for Sick Children; Department of Anesthesia, Toronto Western Hospital; and Departments of Anesthesia and Pharmacology, University of Toronto, Toronto, Ontario, Canada

This study compared systemic hemodynamic and organ blood flow responses to equipotent concentrations of halothane and sevoflurane during spontaneous ventilation in the rat. The MAC values for halothane and sevoflurane were determined. Cardiac output and organ blood flows were measured using radiolabeled microspheres. Measurements were obtained in awake rats (control values) and at 1.0 MAC halothane or sevoflurane. The MAC values (mean 4 SEM) for halothane and sevoflurane were 1.10% 5 0.05% and 2.40% k 0.05%, respectively. The Paco, increased to a similar extent in both groups compared with control values. During halothane anesthesia, heart rate decreased by 12%(P < 0.01), cardiac index by 26% ( P < 0.01), and mean arterial blood pressure by 18% ( P < 0.01) compared with control values. Stroke volume index and systemic vascular resistance did not change. During sevoflurane anesthesia, hemodynamic variables remained unchanged compared with control values. Coronary

T

he response of the cardiovascular system to inhaled anesthetics includes alterations in systemic hemodynamics and blood flow to a number of vascular beds. These hemodynamic responses differ when ventilation is spontaneous rather than controlled ( 1 4 ) , owing, in part, to a higher Paco, and a lower mean intrathoracic pressure during spontaneous ventilation. The inhaled anesthetic sevoflurane is a halogenated methyl isopropyl ether with hemodynamic properties that have been studied in venti-

Supported in part by grants from the Medical Research Council of Canada, NIAAA (AA 07631), and Maruishi Pharmaceuticals Inc., Osaka, Japan. Accepted for publication July 21, 1992. Address correspondence to Dr. Crawford, Department of Anesthesia, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1x8.

1000

blood flow decreased by 21% ( P < 0.01) and renal blood flow by 18%( P < 0.01) at 1.0 MAC halothane, whereas both remained unchanged at 1.0 MAC sevoflurane. Cerebral blood flow increased to a greater extent with halothane (63%; P < 0.01) than with sevoflurane (35%; P < 0.05). During halothane anesthesia, hepatic arterial blood flow increased by 48% ( P < 0.01), whereas portal tributary blood flow decreased by 28% (P < 0.01). During sevoflurane anesthesia, hepatic arterial blood flow increased by 70% (P < 0.01) without a concomitant reduction in portal tributary blood flow. Total liver blood flow decreased only with halothane (16%; P < 0.05). In conclusion, for comparable increases in Paco,, systemic hemodynamic and organ blood flow responses to halothane are significantly greater than the responses to sevoflurane at an equipotent concentration of 1.0 MAC in the spontaneously ventilating rat. (Anesth Analg 1992;75:1000-6)

lated animals (5-7). Sevoflurane has a low blood-gas partition coefficient and a nonirritating odor (8,9). These properties augur well for the use of sevoflurane to induce anesthesia in children. It is therefore important to have a clear understanding of the hemodynamic alterations produced when sevoflurane is administered during spontaneous ventilation. Of the inhaled anesthetics currently available, halothane is the most common anesthetic used to induce anesthesia in pediatric patients. Halothane would therefore appear to be a suitable reference anesthetic with which to compare the hemodynamic properties of sevoflurane. The present study was undertaken to compare systemic hemodynamic and organ blood flow responses to 1.0 MAC halothane with those to an equipotent concentration of sevoflurane during spontaneous ventilation in the rat. 01992 by the International Anesthesia Research Society

Anesth Analg 1992;75:1000-6

0003-2999/92/$5.00

ANESTH ANALG 1992;75:100@-6

Methods After the protocol was approved by our Animal Care Committee, Sprague-Dawley rats (weight 260-320 g) were housed in a temperature- and humiditycontrolled environment with a 12-h light/dark cycle. Before the experiments, the rats fasted overnight, with water available ad libitum. The MAC values for halothane (n = 8) and sevoflurane (n = 8) were determined in 16 fasted rats using a tail-clamp technique (10,ll). Rectal temperature was monitored, and normothermia was maintained using radiant heating lamps. During ether anesthesia of 15-20-min duration, polyethylene catheters (Tygon; PE 50) were inserted in the left femoral artery for blood pressure monitoring, blood sampling, and reference sample withdrawal, and the left ventricle via the right common carotid artery for injection of radioactive microspheres, as previously described (12). Placement of the catheter in the left ventricle was verified by monitoring the blood pressure waveform. Incisions were infiltrated with 1%lidocaine, and the cannulas were capped with rubber injection ports and tunneled subcutaneously to the midback of the rat, where they were brought to the skin surface. After the operative procedure, the rats were allowed to recover in a temperature-controlled environment for 4 h. There was no obvious evidence of stress or pain during recovery. In previous studies, we showed that indices of stress, such as blood glucagon level, mean arterial pressure, and heart rate, remain unchanged after these operative procedures (12). After recovery, the rats ( n = 45) appeared comfortable and resumed their usual behavior. They were placed in cylindrical plexiglass chambers through which oxygen (5 L/min) was administered. After 20 min of stable hemodynamics, heart rate, mean arterial pressure, and arterial blood gases were recorded, and cardiac output and organ blood flows were determined using 57Co-labeled microspheres. The rats were then randomly assigned to receive either 1.O MAC halothane or sevoflurane. Thrrty minutes after the start of anesthetic administration, heart rate, mean arterial pressure, and arterial blood gases were measured, and &Sc-labeled microspheres were injected to determine cardiac output and organ blood flows. In previous control studies, values for cardiac output and organ blood flows obtained with %3c-labeled microspheres were similar to those obtained 30 min earlier with 57Co-labeled microspheres in awake rats (F. J. Carmichael et al., unpublished observations). In the present study, all measurements were performed during periods of stable hemodynamics. Throughout the study period, ventilation was spontaneous, and normothermia was maintained using radiant heating

CRAWFORD ET AL. HALOTHANE AND SEVOFLURANE: HEMODYNAMICS

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lamps. Inspired anesthetic concentration was monitored continuously using a calibrated infrared medical gas analyzer (SensorMedics LB 2, Anaheim, CaLif.). Rectal temperatures taken at the end of the experiments were 37.3" 2 0.3"C (mean k SEM). Arterial blood pressure was monitored using a physiograph (Narco Biosystems, Houston, Tex.). Heart rate was determined from the blood pressure waveform. Cardiac output and organ blood flows were measured using 16.5 ? 0.1-pm-diameter radiolabeled microspheres (New England Nuclear, Boston, Mass.). The microspheres, prepared as previously described (13), were suspended in 10% dextran containing 1 drop of Tween-80, agitated for 10 min using a Vortex mixer, and aspirated into polyethylene tubing for gamma-scintillation counting (Nuclear Chicago counter, model 1185, Chicago, Il!.) just before injection. Approximately 40,000-50,000 microspheres were then infused into the left ventricle over 20 s using an infusion pump. A 0.6-mL reference sample that contained 300400 microspheres was obtained from the femoral artery using a withdrawal pump that began to aspirate blood 10 s before the infusion of microspheres and continued for 60 s. The presence of this number of microspheres in the reference sample has been shown to yield valid cardiac output measurements (14). An equal volume of ficoll (0.6 mL, 13%wthol) (Sigma Chemical Co., St. Louis, Mo.), a nonionic synthetic polymer of sucrose, was flushed through the microsphere infusion tubing to replace the volume of blood sampled. The infusion of microspheres and the withdrawal of the reference sample had no demonstrable effect on monitored hemodynamic variables. The net counts infused were the difference between the counts obtained before injection into the left ventricle and those remaining in the polyethylene tubing. At the termination of the study, the rats were killed with intravenous KC1, and the following organs were removed and placed in saline-containing vials for analysis of radioactivity: brain, lungs, heart, liver, kidneys, spleen, stomach, omentum, pancreas, and small and large intestines. All organs were analyzed intact, with the exception of the liver and small intestine, which were each divided into five sections. The mixing of microspheres in the circulation was considered to be adequate if the difference between the right and left renal blood flows was 4 5 % (12). Three rats were eliminated from the study on the basis of this criterion. Mean arterial pressure was calculated as diastolic pressure plus one-third the pulse pressure. Corrections for overlap during counting of the radioisotopes were made. Cardiac index (Qt) (mL.min-'.kg body wt-l) was calculated by the equation

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ANESTH ANALG 1992;75:1000-6

Table 1. Systemic Hemodynamics and Arterial Blood Gases in the Spontaneously Ventilating Rat, Awake (Control)and During 1.0 MAC Halothane or Sevoflurane Halothane (n = 22)

Physioloec variable

Awake

1.0 MAC

HR (beatshin) SVI (mLikg) Qt (mL.min-'.kg-') MAP (mm Hg) SVR (mm Hg.mL-'.min.kg) Paco, (mm Hg)

370 2 8 0.63 2 0.03 232 2 7 106 2 3 0.46 5 0.01 37 2 3 7.39 2 0.02 385 2 11

325 2 6" 0.53 2 0.04 172 2 8" 87 2 4" 0.50 2 0.02 50 2 2" 7.33 2 0.02 410 2 14

Pao, (mm Hg)

Sevoflurane (n = 20) Awake 360 2 0.69 5 250 2 105 2 0.42 2 39 2 7.41 2 391 2

1.0 MAC

362 t lob 0.65 t 0.05' 236 t Bb 103 2 4b 0.44 2 0.02 48 2 3" 7.36 2 0.07 414 t 12

6 0.04 8 2 0.03 2 0.01 16

HR, heart rate; SVI, stroke volume index; Qt, cardiac index; MAP, mean arterial pressure; SVR, systemic vascular resistance; pHa, arterial pH. Values are mean jr SEM. "P < 0.01, compared with respective control. bP < 0.01, compared with halothane. 'P < 0.05, compared with halothane.

Qt =

*

Ci.R Cr.w '

-

where Ci is net counts injected, R the reference sample withdrawal rate, Cr the net counts in the reference sample, and w the body weight (kg). Organ blood flow (Qo) (mL.min-'-kg body wt-*) was calculated by the equation QtGJ QO

=

Ci

'

where Co is net counts in the organ. Systemic vascular resistance (mm Hg.mL-'.min.kg) was calculated as the quotient of the mean arterial pressure and cardiac index. Central venous pressure was assumed to approximate zero. Stroke volume index ( m u g ) was calculated as the quotient of cardiac index and heart rate. Organ vascular resistances (mm Hg.mL-*.min.kg) were calculated as the quotient of the mean arterial pressure and organ blood flow. Portal tributary blood flow (PTBF) was calculated as the sum of the blood flow to the spleen, stomach, omentum, pancreas, and small and large intestines. The contribution of blood flows from the pancreas and omentum, which cannot be readily isolated in the rat, is included in the flows to the small and large intestines. The accuracy of this method as an estimate of PTBF is well validated (1,5,16). Hepatic arterial blood flow (HABF) was determined from the net counts within the liver. Total hepatic blood flow was calculated as the sum of the PTBF and HABF. Cardiac output, stroke volume, organ blood flows, and vascular resistances were indexed to body weight (kg). Because the relationship of organ weight to body weight did not change throughout the study period, there are no differences in the conclusions derived when this form of expression is used as opposed to blood flows expressed per gram organ.

Data are presented as mean SEM. Statistical significance ( P < 0.05) was determined using oneway analysis of variance. Intergroup differences were determined by the least-significant difference method (17).

Results The MAC values (mean -+ SEM) for halothane and sevoflurane were 1.10% k 0.05% and 2.40% 0.0.5%, respectively. The Paco, increased from a control value of 37 k 3 to 50 2 mm Hg with halothane ( P < 0.01) and from 39 4 to 48 2 3 mm Hg with sevoflurane ( P < 0.01) (Table 1). The differences in Paco, at 1.0 MAC were not significant. The pHa and Pao, did not differ between groups either as control values or at 1.0 MAC (Table 1). Control (awake) hemodynamic measurements were similar in the two groups (Table 1).Compared with control measurements, heart rate decreased by 12% ( P < 0.01), cardiac index by 26% ( P < 0.01), and mean arterial pressure by 18% (P < 0.01) during halothane anesthesia (Figure 1). These variables remained unchanged during sevoflurane anesthesia compared with control values (Figure 1).Stroke volume index and systemic vascular resistance did not change during administration of either anesthetic (Table 1). Control organ blood flow measurements were similar in the two groups (Table 2). Compared with control measurements, coronary blood flow decreased by 21% (P < 0.01) (Figure 2) without a significant change in coronary vascular resistance (Table 3 ) during halothane anesthesia. In contrast, neither coronary blood flow (Figure 2) nor coronary vascular resistance (Table 3) changed during sevoflurane administration. Cerebral blood flow increased

*

* *

CRAWFORD ET AL. HALOTHANE AND SEVOFLURANE: HEMODYNAMICS

ANESTH ANALG 1992;75:1O O M

change from

hepatic arterial vascular resistance during halothane anesthesia (Table 3). Similarly, HABF increased by 70% ( P < 0.01) (Figure 3), and hepatic arterial vascular resistance decreased by 42% (P < 0.01) during sevoflurane anesthesia (Table 3). The increase in HABF was associated with a reduction in PTBF during halothane (28%; P < 0.01) but not during sevoflurane anesthesia. Portal tributary vascular resistance did not change during administration of either halothane or sevoflurane (Table 3). Total hepatic blood flow decreased onIy with halothane (16%;P < 0.05) (Figure 3). Splenic blood flow decreased by 38% (P < 0.01) during halothane anesthesia and by 24% ( P < 0.05) during sevoflurane anesthesia (Table 2), with corresponding increases in splenic vascular resistance of 38% (P < 0.05) and 28% (NS), respectively (Table 3). Gastric blood flow decreased by 32% (P < 0.01) after halothane and by 29% (P < 0.01) after sevoflurane (Table Z), with corresponding increases in gastric vascular resistance of 21% (NS) and 42% (P C 0.05), respectively (Table 3). Small and large intestinal blood flows decreased by 27%(P < 0.01) and 14%(P < 0.01), respectively, after halothane (Table 2), with no change in vascular resistances (Table 3).

Halothane

awake value

sevoflurana

0

-10

-20

L

-30

1003

1 ++

Figure 1. Systemic hemodynamic responses to 1.0 MAC halothane or sevoflurane anesthesia in the spontaneously ventilating rat. Data are presented as percent change from the control (awake) values shown in Table 1. HR, heart rate; SVI, stroke volume index; CI, cardiac index; MAP, mean arterial pressure. **P < 0.01, compared with control (awake) value. t P < 0.05, compared with halothane. t t P < 0.01, compared with halothane.

by 63% (P < 0.01) (Figure 2), whereas cerebral vascular resistance decreased by 50% (P < 0.01) (Table 3) during halothane anesthesia. During sevoflurane anesthesia, the changes in cerebral blood flow and vascular resistance were less marked, 35% (P < 0.05) (Figure 2) and 27% (P < 0.05) (Table 3), respectively. Renal blood flow decreased by 18%(P < 0.01) (Figure 2) without a change in renal vascular resistance during halothane anesthesia. Neither renal blood flow (Figure 2) nor renal vascular resistance (Table 3) changed during sevoflurane administration. Blood flow to the lungs was similar in awake and anesthetized rats, suggesting that arteriovenous shunting of microspheres did not occur during anesthesia. The HABF increased by 48% (P < 0.01) (Figure 3) in association with a 44% ( P < 0.01) decrease in

Discussion The present study compared systemic hemodynamic and organ blood flow responses to 1.0 MAC halothane with those to an equipotent concentration of sevoflurane in the spontaneously ventilating rat. It is important to study the hemodynamic effects of inhaled anesthetics during spontaneous ventilation, because this anesthetic technique is commonly used in both pediatric and adult anesthesia, particularly for

Table 2. Organ Blood Flow Responses in the Spontaneously Ventilating Rat, Awake (Control)and During 1.0 MAC

Halothane or Sevoflurane Halothane (n = 22)

Sevoflurane (n

=

20)

Organ blood flow (mL.min-'.kg-')

Awake

1.0 MAC

Awake

1.0 MAC

Coronary Cerebral Renal Splenic Gastric Small intestine Large intestine Hepatic arterial Portal tributary Total hepatic

8.2 2 0.4 3.8 2 0.2 38.9 1.6 4.6 2 0.3 3.1 2 0.2 21.6 f 1.3 8.9 r 0.6 8.6 r 0.7 38.2 2 1.5 46.8 rf: 1.5

6.5 f 0.4" 6.2 2 0.7" 31.9 rf: 1.9" 2.8 f 0 . J 2.1 2 0.2" 15.7 f 0.9" 6.8 2 0.6' 12.7 2 1.1" 27.4 t 1.3" 40.1 f 1.F

9.0 2 0.6 4.3 f 0.3 44.0 t 1.5 5.1 f 0.3 3.4 f 0.2 24.8 f 1.4 8.9 2 0.6 8.7 f 0.7 42.4 f 1.8 51.1 f 1.6

8.9 2 0.4b 5.8 2 0.6',d 44.9 rf: 2.1b 3.9 f 0.4c,d 2.4 rf: 0.2" 25.1 IT 1.5b 7.8 f 0.6 14.8 f 1.1" 39.0 2 1.9' 53.8 t 2.2b

Values are mean f SEM. "P < 0.01, compared with respective control. bP < 0.01, compared with halothane. '6' < 0.05, compared with respective control. dP < 0.05, compared with halothane.

*

CRAWFORD ET AL. HALOTHANE AND SEVOFLURANE: HEMODYNAMICS

% change from

Halothane

awake value

60

*+

t

H

T

avofluram

40

20 0

** 40

Figure 2. Coronary, cerebral, and renal blood flows during 1.0 MAC halothane or sevoflurane anesthesia in the spontaneously ventilating rat. Data are presented as percent change from the control (awake) values shown in Table 2. *P < 0.05, compared with control (awake) value. **P < 0.01, compared with control (awake) value. t P < 0.05, compared with halothane. t t P < 0.01, compared with halothane.

outpatients. Hemodynamic alterations that occur during inhaled anesthesia may be attributed not only to direct pharmacologic effects of the anesthetic, but also to an increase in Paco,. Other factors, including alterations in autonomic outflow, cardiac output, mean arterial pressure, and oxygen requirements, may alter organ blood flow. To help ensure that the conditions of the present study were parallel to those of clinical inhaled anesthesia, no attempt was made to regulate these factors. In agreement with a previous study (18), the increase in Paco, observed in the present study with 1.0 MAC halothane was similar to that with 1.0 MAC sevoflurane. An increase in Paco, of this magnitude might have attenuated the hemodynamic depression induced by the inhaled anesthetics (1,3,19). Nevertheless, the present data demonstrate that for comparable increases in Pacoz during

ANESTH ANALG 1%2;75: 1000-6

spontaneous ventilation, sevoflurane produces minimal hemodynamic alterations compared with halothane. Inspired rather than end-tidal anesthetic concentrations were measured in the present study. An estimation of anesthetic requirement based on inspired anesthetic concentration assumes the equilibration of inspired, alveolar, and brain anesthetic tensions. The time to attain equilibrium is influenced by the solubility of the anesthetic and its effect on minute ventilation (10). In the present study, the effect of sevoflurane on minute ventilation was similar to that of halothane, which negates a differential effect of this variable on equilibration. However, the solubilities of the two anesthetics differ (8,9). For an anesthetic with a blood-gas partition coefficient similar to that of sevoflurane, the ratio of end-tidal to inspired anesthetic concentration has been shown to approach unity within 30 min in the rat (20). In the present study, therefore, it is likely that the inspired concentration of sevoflurane closely reflected the alveolar or end-tidal value when hemodynamic and organ blood flow values were determined. It is probable that the greater solubility of halothane may have delayed equilibration beyond 30 min. However, previous studies in rats report that the end-tidal to inspired ratio of halothane was within 10% of unity after 25-35 min (10). In addition, the use of end-tidal measurements of halothane concentration yielded a MAC value for halothane in the rat similar to that found in the present study (10). Furthermore, had a longer time been allowed for equilibration in the present study, it is probable that even greater differential effects on systemic hemodynamics and organ blood flows would have been observed. Awake values are in agreement with those of previous dose-response studies from this laboratory on the hemodynamic effects of MAC multiples of

Table 3. Vascular Resistances i n t h e Spontaneously Ventilating Rat, Awake (Control) and During 1.0 M A C Halothane or Sevoflurane Control ( n = 22)

Halothane ( n = 22)

Control ( n = 20)

Sevoflurane (n = 20)

12.9 & 0.8 27.9 f 2.2 2.7 .+ 0.1 22.6 f 2.7 34.2 2 2.4 4.9 f 0.4 11.9 5 1.1 12.3 2 1.1 2.8 f 0.1

13.4 2 1.5 14.0 2 1.6" 2.7 2 0.2 31.1 2 3.2' 41.4 2 5.2 5.5 f 0.4 12.8 f 3.7 6.9 2 1.8" 2.2 f 0.2

11.7 f 0.9 24.4 f 2.5 2.4 k 0.1 20.6 2.7 30.1 & 2.4 4.2 ? 0.3 11.8 2 1.1 12.1 2 1.1 2.5 f 0.1

11.6 t 0.8 17.8 2 0.6b 2.3 t 0.1 26.4 2 3.3 42.9 -t 4.2' 4.1 -t 0.3b 13.2 2 1.4 7.0 f 0.7" 2.5 2 0.1

Vascular resistance (mm Hg.mL-'.min.kg) Coronary Cerebral Renal Splenic Gastric Small intestine Large intestine Hepatic arterial Portal tributary ~_________

~~

~

Values are mean -C SEM. "P < 0.01, compared with respective control. bP < 0.05, compared with halothane 'P < 0.05, compared with respective control

*

CRAWFORD ET AL. HALOTHANE AND SEVOFLURANE: HEMODYNAMICS

ANESTH ANALG 1992;75:1000-6

70 change from awake value

Halothane

+*

H

T

-40

1

Sevoflurane

*+

Figure 3. Hepatic arterial (HABF), portal tributay (PTBF), and total hepatic (THBF) blood flows during 1.0 MAC halothane or sevoflurane anesthesia in the spontaneously ventilating rat. Data are presented as percent change from the control (awake) values shown in Table 2. *P < 0.05, compared with control (awake) value. **P < 0.01, compared with control (awake) value. t t P < 0.01, compared with halothane.

sevoflurane (11) and halothane (21). For comparable increases in Paco, in the present study, systemic hemodynamics were affected to a greater extent by halothane than by an equipotent concentration of sevoflurane. Consistent with these findings, sevoflurane decreased hemodynamic variables to only a small extent in newborn swine (22). Greater reductions in stroke volume, cardiac output, and mean arterial pressure were reported to occur during sevoflurane anesthesia in mature swine (5) and in rats (7). The difference between the results of the present study and those in mature swine (5) may be attributed in part either to the hyperdynamic state of the spontaneously breathing awake swine or to the introduction of controlled ventilation during sevoflurane anesthesia. The discrepancy in the study in rats (7) may also be due to an effect of controlled ventilation or, more likely, to the simultaneous presence of two other anesthetics, chloral hydrate and chloralose, in that study. The microsphere technique yields an accurate estimate of organ blood flows, provided that several important criteria are satisfied (12,13,23). The validity of the awake blood flow measurements in the present study is substantiated by previous work from this laboratory (11,12) and from a number of other investigators (13,14,24). The response of the coronary circulation to halothane in the present study is consistent with the reports of other investigators (25). The lack of an effect of sevoflurane on coronary blood flow is of interest, because both a decrease (5) and an increase (6) in coronary blood flow have been reported during sevoflurane anesthesia. The decrease in coronary blood flow may be attributed to the administration of

1005

a general anesthetic in swine with elevated hemodynamic variables in the awake state, whereas the increase in coronary blood flow observed in dogs was associated with a 60% increase in heart rate and thus might have reflected an increase in myocardial oxygen requirement. For comparable increases in Paco,, cerebral blood flow increased, and cerebral vascular resistance decreased to a greater extent during halothane than during sevoflurane anesthesia. This finding suggests that the cerebrovascular effects of halothane exceed those of sevoflurane. In support of this observation, the effects of sevoflurane on cerebral blood flow, cerebral oxygen requirement, and intracranial pressure were recently shown to compare favorably with those of isoflurane (26). During hypercarbia, HABF has been reported to either remain unchanged (27) or to decrease transiently, followed by a return to control values (28). It is unlikely therefore that the increase in HABF observed in the present study with both halothane and sevoflurane is due to an effect of hypercarbia. Indeed, this increase in flow is consistent with the reports of other investigators (5,11,21,29-31) and may represent either a reciprocal change associated with reduced PTBF, in the case of halothane (21), or, a direct pharmacologic action of the inhaled anesthetics on hepatic arterial vasculature. In the present study, the changes in PTBF were not associated with alterations in portal tributary vascular resistance but, rather, paralleled the changes in cardiac output. Although hypercarbia has been associated with portal tributary vasodilation and an increase in flow (27,28), PTBF did not increase under the conditions of the present study. In fact, PTBF decreased with halothane. These observations are consistent with previous reports that inhaled anesthetics may attenuate the response of the portal circulation to hypercarbia (32) and suggest that PTBF depends to a greater extent on changes in cardiac output than on changes in Paco, in the presence of potent anesthetics. In summary, systemic hemodynamics and organ blood flows are disturbed to a greater extent by 1.0 MAC halothane than by an equipotent concentration of sevoflurane during spontaneous ventilation. These results have clinical implications and suggest that sevoflurane may be advantageous when hemodynamic stability is required during an inhaled induction of anesthesia. The authors thank Dr. Robert Creighton for his helpful suggestions in the preparation of this manuscript.

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