Br.J. Anaesth. (1975), 47, 813
WHOLE-BODY AND ORGAN Vo2 CHANGES WITH ENFLURANE, ISOFLURANE, AND HALOTHANE R. A. THEYE AND J. D. MICHENFELDER SUMMARY
We have established previously for halothane and isoflurane that the pattern of individual organ contributions to the whole-body decrease in oxygen consumption (Vo2) is similar, that the decrease in myocardial Vo2 is the major component for each, and that the decrease in Vo2 in other organs contributes to a lesser extent (Theye, 1972; Theye and Michenfelder, 1975). These findings support our contention that anaesthetic agents are not general metabolic depressants and help to emphasize that the decrease in whole-body Vo2 with anaesthesia represents a summation of events in individual organs in which an anaesthetic-induced change in function results in a change in metabolic requirements. The present study extended this inquiry to the effects of enflurane and the findings provide the basis for a comparative summary of the effects of halothane, isoflurane, and enflurane in these regards. MATERIAL AND METHODS
In all studies, unpremedicated dogs were anaesthetized with enflurane in a mixture of oxygen in nitrogen. The trachea was intubated with the aid of suxamethonium, which was continued thereafter at a rate of 150 mg/hr. Ventilation was provided by a Harvard pump and nonrebreathing system with appropriate adjustments of the inspired oxygen RICHARD A. THEYE, M.D., JOHN D. MICHENFELDER, M.D.,
Department of Anesthesiology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55901, U.S.A.
concentration (Fio2) and ventilatory volume to maintain PaO2 and PaC02 at 150±5 and 40±2 mm Hg, respectively (mean±SEM). Body and organ temperatures were maintained at 37.0±0.2°C by surface warming. Expired enflurane concentrations were determined by infrared analysis. Intravascular pressures were transduced by strain gauges. Blood-gas values were measured by electrodes at 37.0°C. Blood oxygen content was calculated from Po2 and oxyhaemoglobin concentration (IL CO-Oximeter). Whole-body and organ Vo2 were calculated by means of the Fick equation, using appropriate values for blood flow rate (0) and the arteriovenous oxygen content difference (Cao2—Cv02), and were expressed relative to whole-body weight as determined before induction of anaesthesia. Left and right ventricular external work was calculated from total Q, mean systemic and pulmonary arterial pressures, respectively, and a previously described constant (Theye, 1967). At autopsy, catheter positions were confirmed and organ weights were determined. Values in the dog for minimum alveolar concentration (MAC) of 2.2,1.48, and 0.87%, for enflurane, isoflurane, and halothane, respectively, were the reference points for establishing equivalent levels of enflurane anaesthesia (Joas, Stevens and Eger, 1971). The effect of enflurane on whole-body Vo2 and haemodynamics was determined in 10 dogs (weights: whole-body, 17±2 kgj'heart, 106±17 g). Catheters
Downloaded from http://bja.oxfordjournals.org/ at University of California, San Francisco on December 22, 2014
This study was designed to determine the effects of ennurane on canine whole-body and individual organ oxygen consumption (Vo2). Whole-body, myocardial, splanchnic, renal, and skeletal muscle Vo2 were determined at enflurane concentrations equivalent to those used in previous studies with halothane and isoflurane. With increasing enflurane concentrations, whole-body Vo2 decreased progressively. The major component of the decrease was a reduction in myocardial Vo2 resulting from a decrease in myocardial external work as a result of a decrease in cardiac output and arterial pressure. Other organs contributed to a lesser extent to the overall decrease in whole-body Vo2. In each respect the findings with enflurane were not significantly different from those with halothane and isoflurane. These findings add support to the view that anaesthetic agents are not general metabolic depressants and that observed changes in whole-body Vo2 reflect the summated changes in individual organ Vo2 occasioned by an anaesthetic-induced change in organ function and metabolic requirements.
BRITISH JOURNAL OF ANAESTHESIA
814
RESULTS
With increases in the enflurane concentration, wholebody Vo2 decreased progressively (table I); at the greatest concentration the average decrease was 29%. Myocardial Vo2 also decreased progressively, but at a greater rate, resulting in a decrease in the ratio of myocardial to whole-body Vo». The decrease in myocardial Vo2 directly reflected the progressive decrease in myocardial external work, which resulted
from decreases in cardiac output and arterial pressure. The only statistically significant differences between these findings and those with isoflurane and halothane occurred at the greatest anaesthetic concentrations; these differences consisted of a lesser arterial pressure with enflurane than with either isoflurane or halothane and a lesser cardiac output and myocardial Vo2 with enflurane than with isoflurane (t test; unpaired data). The relationship between myocardial Vo2 and left ventricular external work with enflurane anaesthesia established in the right-heart bypass studies was not significantly different from those established previously for isoflurane and halothane (fig. 1). The data from all three studies were pooled to yield a single regression equation: y=2.61+(l.86x^0.16), which was used to calculate the myocardial Vo2 values for the whole-body studies in table I. 24
r
- Halothane Isoflurane 'Enflurane
o o 16
o 5
0 EXTERNAL
4 8 WORK, LV, kg-m/mln
FIG. 1. Regression lines relating myocardial Vo2 (y; ml/min/ 100 g) and left ventricular (LV) work (x; kg-m/min) during anaesthesia with enflurane [y=3.17+(1.68x±0.24)], isoflurane [y=3.21+(1.78x±0.09)] 5 and halothane [y = 1.44 + (2.13x±0.29)] (±SEM).
The effects of enflurane on splanchnic, renal, and skeletal muscle blood flow are summarized in table II. Vo2 values are presented relative to wholebody weight; the blood flow values are based on actual flows of the organ studied. The findings in the gastrocnemius-plantaris group (actual weight, 61 ± 7 g) have been extrapolated to whole-body skeletal muscle using the assumptions applied previously with isoflurane and halothane (0.5% value, 35% of wholebody Vo 2 ; 3.8% value, based on the 16% reduction observed in the muscle studied). With increases in the enflurane concentration, splanchnic, renal, and skeletal muscle Vo2 decreased 19,30 and 16% respectively.
Downloaded from http://bja.oxfordjournals.org/ at University of California, San Francisco on December 22, 2014
were placed in the carotid and pulmonary arteries, the right atrium, and the outflow tract of the right ventricle for measurement of pressures, determination of 0 by the indocyanine green dye dilution technique, and sampling of arterial and mixed venous blood. Observations were made in triplicate at enflurane concentrations of 0.5, 2.2, 2.8, and 3.8% in this sequence and, in alternate dogs, in the reverse sequence. (For convenience, results are presented only in terms of increasing concentration.) One hour elapsed at each enflurane concentration with observations in the final 30 min. During these studies myocardial Vo2 was calculated from the values for external work observed and the relationship between myocardial external work and Vo2, as described subsequently. The relationship between myocardial external work and Vo2 during enflurane anaesthesia was determined in four additional dogs (weights: wholebody, 20±2 kg; heart, 127±25 g). Right-heart bypass was established after ligation of the azygos vein, appropriate cannulations of the right atrium, superior and inferior venae cavae, and pulmonary trunk, and preparation of an extracorporeal apparatus that included a reservoir, pump, and heat exchanger. This approach provided for isolation and collection of all myocardial venous flow with opportunities for determination of myocardial 0 (timed collection in graduated cylinder) and (Ca02—Cv02) (Theye, 1967). Observations were made in triplicate at enflurane concentrations of 0.5 and 3.8%. At each concentration, left ventricular work was arranged to approximate to that observed in the whole-body studies by appropriate modifications of blood volume and rightheart bypass pump flow rates. Splanchnic and renal Vo2 (six dogs) and gastrocnemius-plantaris group bilateral muscle Vo2 (six dogs) were determined at enflurane concentrations of 0.5 and 3.8% by surgical methods that provide for separation, direct collection, measurement, and return of the venous blood flow from these organs (Theye and Michenfelder, 1975).
Vo2 CHANGES WITH ENFLURANE, ISOFLURANE, HALOTHANE TABLE I.
815
Metabolic and haemodynamic responses to enflurane (10 dogs: 37°C).
Enflurane expired ( %)
0.27 0.07 0.01
6.44 1.21 0.19
3.8
Mean SEM
Mean iSEM
5.51* 0.19 0.63* 0.05 0.11* 0
5.11* 0.14 0.53* 0.02 0.10* 0
Mean
SEM
4.57* 0.10 0.43* 0.02 0.09* 0
190
9
104
6
87*
5
70*
7
114 18 2
5 1 1
78* 13* 2
2 1 0
70* 12* 3
1 1 0
58* 12* 4*
3 1 1
0.27 0.08
5.34 0.86
2.03* 0.13 0.33* 0.04
1.04* 0.14 0.22* 0.03
1.51* 0.10 0.27* 0.02
•Significantly different (P
WHOLE-BODY AND ORGAN Vo2 CHANGES WITH ENFLURANE, ISOFLURANE, AND HALOTHANE R. A. THEYE AND J. D. MICHENFELDER SUMMARY
We have established previously for halothane and isoflurane that the pattern of individual organ contributions to the whole-body decrease in oxygen consumption (Vo2) is similar, that the decrease in myocardial Vo2 is the major component for each, and that the decrease in Vo2 in other organs contributes to a lesser extent (Theye, 1972; Theye and Michenfelder, 1975). These findings support our contention that anaesthetic agents are not general metabolic depressants and help to emphasize that the decrease in whole-body Vo2 with anaesthesia represents a summation of events in individual organs in which an anaesthetic-induced change in function results in a change in metabolic requirements. The present study extended this inquiry to the effects of enflurane and the findings provide the basis for a comparative summary of the effects of halothane, isoflurane, and enflurane in these regards. MATERIAL AND METHODS
In all studies, unpremedicated dogs were anaesthetized with enflurane in a mixture of oxygen in nitrogen. The trachea was intubated with the aid of suxamethonium, which was continued thereafter at a rate of 150 mg/hr. Ventilation was provided by a Harvard pump and nonrebreathing system with appropriate adjustments of the inspired oxygen RICHARD A. THEYE, M.D., JOHN D. MICHENFELDER, M.D.,
Department of Anesthesiology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55901, U.S.A.
concentration (Fio2) and ventilatory volume to maintain PaO2 and PaC02 at 150±5 and 40±2 mm Hg, respectively (mean±SEM). Body and organ temperatures were maintained at 37.0±0.2°C by surface warming. Expired enflurane concentrations were determined by infrared analysis. Intravascular pressures were transduced by strain gauges. Blood-gas values were measured by electrodes at 37.0°C. Blood oxygen content was calculated from Po2 and oxyhaemoglobin concentration (IL CO-Oximeter). Whole-body and organ Vo2 were calculated by means of the Fick equation, using appropriate values for blood flow rate (0) and the arteriovenous oxygen content difference (Cao2—Cv02), and were expressed relative to whole-body weight as determined before induction of anaesthesia. Left and right ventricular external work was calculated from total Q, mean systemic and pulmonary arterial pressures, respectively, and a previously described constant (Theye, 1967). At autopsy, catheter positions were confirmed and organ weights were determined. Values in the dog for minimum alveolar concentration (MAC) of 2.2,1.48, and 0.87%, for enflurane, isoflurane, and halothane, respectively, were the reference points for establishing equivalent levels of enflurane anaesthesia (Joas, Stevens and Eger, 1971). The effect of enflurane on whole-body Vo2 and haemodynamics was determined in 10 dogs (weights: whole-body, 17±2 kgj'heart, 106±17 g). Catheters
Downloaded from http://bja.oxfordjournals.org/ at University of California, San Francisco on December 22, 2014
This study was designed to determine the effects of ennurane on canine whole-body and individual organ oxygen consumption (Vo2). Whole-body, myocardial, splanchnic, renal, and skeletal muscle Vo2 were determined at enflurane concentrations equivalent to those used in previous studies with halothane and isoflurane. With increasing enflurane concentrations, whole-body Vo2 decreased progressively. The major component of the decrease was a reduction in myocardial Vo2 resulting from a decrease in myocardial external work as a result of a decrease in cardiac output and arterial pressure. Other organs contributed to a lesser extent to the overall decrease in whole-body Vo2. In each respect the findings with enflurane were not significantly different from those with halothane and isoflurane. These findings add support to the view that anaesthetic agents are not general metabolic depressants and that observed changes in whole-body Vo2 reflect the summated changes in individual organ Vo2 occasioned by an anaesthetic-induced change in organ function and metabolic requirements.
BRITISH JOURNAL OF ANAESTHESIA
814
RESULTS
With increases in the enflurane concentration, wholebody Vo2 decreased progressively (table I); at the greatest concentration the average decrease was 29%. Myocardial Vo2 also decreased progressively, but at a greater rate, resulting in a decrease in the ratio of myocardial to whole-body Vo». The decrease in myocardial Vo2 directly reflected the progressive decrease in myocardial external work, which resulted
from decreases in cardiac output and arterial pressure. The only statistically significant differences between these findings and those with isoflurane and halothane occurred at the greatest anaesthetic concentrations; these differences consisted of a lesser arterial pressure with enflurane than with either isoflurane or halothane and a lesser cardiac output and myocardial Vo2 with enflurane than with isoflurane (t test; unpaired data). The relationship between myocardial Vo2 and left ventricular external work with enflurane anaesthesia established in the right-heart bypass studies was not significantly different from those established previously for isoflurane and halothane (fig. 1). The data from all three studies were pooled to yield a single regression equation: y=2.61+(l.86x^0.16), which was used to calculate the myocardial Vo2 values for the whole-body studies in table I. 24
r
- Halothane Isoflurane 'Enflurane
o o 16
o 5
0 EXTERNAL
4 8 WORK, LV, kg-m/mln
FIG. 1. Regression lines relating myocardial Vo2 (y; ml/min/ 100 g) and left ventricular (LV) work (x; kg-m/min) during anaesthesia with enflurane [y=3.17+(1.68x±0.24)], isoflurane [y=3.21+(1.78x±0.09)] 5 and halothane [y = 1.44 + (2.13x±0.29)] (±SEM).
The effects of enflurane on splanchnic, renal, and skeletal muscle blood flow are summarized in table II. Vo2 values are presented relative to wholebody weight; the blood flow values are based on actual flows of the organ studied. The findings in the gastrocnemius-plantaris group (actual weight, 61 ± 7 g) have been extrapolated to whole-body skeletal muscle using the assumptions applied previously with isoflurane and halothane (0.5% value, 35% of wholebody Vo 2 ; 3.8% value, based on the 16% reduction observed in the muscle studied). With increases in the enflurane concentration, splanchnic, renal, and skeletal muscle Vo2 decreased 19,30 and 16% respectively.
Downloaded from http://bja.oxfordjournals.org/ at University of California, San Francisco on December 22, 2014
were placed in the carotid and pulmonary arteries, the right atrium, and the outflow tract of the right ventricle for measurement of pressures, determination of 0 by the indocyanine green dye dilution technique, and sampling of arterial and mixed venous blood. Observations were made in triplicate at enflurane concentrations of 0.5, 2.2, 2.8, and 3.8% in this sequence and, in alternate dogs, in the reverse sequence. (For convenience, results are presented only in terms of increasing concentration.) One hour elapsed at each enflurane concentration with observations in the final 30 min. During these studies myocardial Vo2 was calculated from the values for external work observed and the relationship between myocardial external work and Vo2, as described subsequently. The relationship between myocardial external work and Vo2 during enflurane anaesthesia was determined in four additional dogs (weights: wholebody, 20±2 kg; heart, 127±25 g). Right-heart bypass was established after ligation of the azygos vein, appropriate cannulations of the right atrium, superior and inferior venae cavae, and pulmonary trunk, and preparation of an extracorporeal apparatus that included a reservoir, pump, and heat exchanger. This approach provided for isolation and collection of all myocardial venous flow with opportunities for determination of myocardial 0 (timed collection in graduated cylinder) and (Ca02—Cv02) (Theye, 1967). Observations were made in triplicate at enflurane concentrations of 0.5 and 3.8%. At each concentration, left ventricular work was arranged to approximate to that observed in the whole-body studies by appropriate modifications of blood volume and rightheart bypass pump flow rates. Splanchnic and renal Vo2 (six dogs) and gastrocnemius-plantaris group bilateral muscle Vo2 (six dogs) were determined at enflurane concentrations of 0.5 and 3.8% by surgical methods that provide for separation, direct collection, measurement, and return of the venous blood flow from these organs (Theye and Michenfelder, 1975).
Vo2 CHANGES WITH ENFLURANE, ISOFLURANE, HALOTHANE TABLE I.
815
Metabolic and haemodynamic responses to enflurane (10 dogs: 37°C).
Enflurane expired ( %)
0.27 0.07 0.01
6.44 1.21 0.19
3.8
Mean SEM
Mean iSEM
5.51* 0.19 0.63* 0.05 0.11* 0
5.11* 0.14 0.53* 0.02 0.10* 0
Mean
SEM
4.57* 0.10 0.43* 0.02 0.09* 0
190
9
104
6
87*
5
70*
7
114 18 2
5 1 1
78* 13* 2
2 1 0
70* 12* 3
1 1 0
58* 12* 4*
3 1 1
0.27 0.08
5.34 0.86
2.03* 0.13 0.33* 0.04
1.04* 0.14 0.22* 0.03
1.51* 0.10 0.27* 0.02
•Significantly different (P
