dcta anaesth. stand. 1975, 19, 146-153
Effect of Controlled Halothane Anaesthesia on Splanchnic Blood Flow and Cardiac Output in the Dog L. THULIN, M. ANDREEN and L. IRESTEDT The Central Department of Anaesthesia and the Thoracic Surgery Research Laboratory, Karolinska Hospital, Stockholm, Sweden
Effects of halothane anaesthesia on splanchnic blood flow and cardiac output were studied in six dogs. Blood flows in the hepatic artery, the superior mesenteric artery and the portal vein were measured electromagnetically. Cardiac output was measured by thermodilution. Depth of anaesthesia, ventilation, acid-base state and body temperature were controlled. Cardiac output and blood flows in the hepatic artery, the superior mesenteric artery and the portal vein decreased significantly to 73%, 54%, 59% and 60% of control values, respectively. Total peripheral vascular resistance decreased significantly, while mesenteric and portal resistance remained essentially unchanged and hepatic arterial resistance showed a significant increase. It is suggested that the difference between the various vascular responses may he caused by a differentiated release from baroreceptor inhibition in various parts of the bulbar vasomotor center.
Receiued 6 Sehteniber, acceptedf o r publication 4 October 1974
The influence of halothane anaesthesia on MATERIAL AND METHODS splanchnic blood flow has been studied both Six mongrel dogs weighing between 16 and 29 kg were in man and in experimental animals. It has anaesthetized with pentobarbital (30 mg/kg) intrabeen shown that halothane anaesthesia venously. During the surgical preparation, anaesthesia decreases estimated hepatic blood flow was maintained with 70% nitrous oxide in oxygen and supplementary doses of pentobarbital. The animals (PICHLMAYR et al. 1966, EPSTEIN et al. 1966, were intubated endotracheally, and intermittent posiPRICE et al. 1966, AHLGREN et al. 1967), tive pressure ventilation was provided with a n Engstrom & respirator (LKB Medical, Stockholm, Sweden). intestinal blood flow (WESTERMARK W ~ L I N 1969), hepatic arterial flow and Ventilation was adjusted according to arterial Pco, in portal venous flow (SUUTARINEN et al. 1964, order to achieve normocapnia. Respiratory frequency was set at 20 per minute. GALINDO1965). Halothane-induced changes in various parts of the splanchnic circulation Measurements and surgical preparation (Fig. 1 ) and cardiac output have not been correlated Cardiac output. Cardiac output was measured by thermodilution (ANDREEN 1974). Ten ml of a solution of previously. The purpose of the present investigation was 5.0% glucose in water at room temperature were injected as a thermal indicator bolus. The injections to study simultaneous changes in cardiac out- were made into the right atrium through a cannula put and blood flow in the hepatic artery, the inserted via the right external jugular vein. Detection superior mesenteric artery and the portal vein of the indicator was made with a thermistor mounted during halothane anaesthesia. Special regard at the tip of a floating catheter introduced into the was taken to factorsinfluencing haemodynamic pulmonary artery. A cardiac output computer (Type 3750, Devices Instruments Ltd, Welwyn Garden City, effects of halothane: level of anaesthesia, U.K.) was used. arterial carbon dioxide tension, hydrogen ion concentration and body temperature. Rloodjows. Blood flows were measured elcctromagneti-
HALOTHANE, SPLANCHNIC BLOOD FLOW AND CARDIAC OUTPUT IN DOG
147
PA pulm
- __
Thermistor
P Vporta QA rnes sy, PAorta
cally. The abdomen of the dog was opened through a right subcostal incision. Calibrated flow probes were placed on the common hepatic artery, the superior mesenteric artery and the portal vein. The superior pancreaticoduodenal artery was ligated, i.e., proper hepatic blood flow was measured. Occlusion snares were placed distally to the probes. Dissection was made without severing perivascular nerves. Squarewave electromagnetic flowmeters (Nycotron AS, Drammen, Norway) were used for simultaneous measurements of the blood flows.
Blood pressures. Blood pressures were measured electromechanically in the abdominal aorta, the portal vein and in the pulmonary artery. The aortic catheter was
Fig. 1. Schematic illustration of the experimental set up. Pressure catheters were placed in the pulmonary artery, the aorta and the portal vein. A thermistor was mounted at the tip of the pulmonary artery catheter for measurement of cardiac output by thermodilution. Electromagnetic flow probes were placed on the hepatic artery, the portal vein and the superior mesenteric artery for measurement of = pulblood flow (PApulrn monary arterial pressure; RA = right atrium; LA = left atrium; R V = right ventricle; LV = left ventricle; Q A h e D = hepatic arterial bIood flow; Pveorta= portal venous pressure; QAme. s u p = superior mesenteric arterial blood flow; PA,,,, = aortic pressure)
inserted through a femoral artery. The portal catheter was inserted through a small mesenteric tributary. The pulmonary artery ratheter was inserted through the jugular vein cannula. The pressure catheters were connected to Statham transducers. Mean blood flows and mean blood pressures were continuously recorded on a Grass Polygraph. Heart rate and blood temperature. Heart rate was calculated from the pulmonary artery pressure curve. Blood temperature was registered with the intravascular thermistor mounted at the tip of the pulmonary artery catheter.
Blood gases and acid-base jtate. Arterial Po2 was deter-
148
L . THULIN, M . ANDREEN AND L . IRESTEDT
mined with an oxygen electrode (Radiometer, Copention in arterial blood was found to be 24.5 f4 hagen, Denmark). Arterial Pcoz and p H were determg % (2fs.d.). mined according to ASTRUP(1956) with a pH-electrode (Radiometer, Copenhagen, Denmark). Base excess Heart rate. Before halothane, the mean heart was calculated according to SIGGAARD-ANDERSEN & rate was 165f23 beats per min, which ENCEL(1960).
Halothane concentration in blood. Arterial halothane concentration was determined by gas chromatography (HALLBNet al. 1970). Experimental procedure After completed preparation, 30 minutes were allowed to elapse to establish a steady state during which all parameters were checked. No further pentobarbital was given during this period. Halothane was added to the nitrous oxide-oxygen mixture in a concentration of 1-2% by the use of a Vapor vaporizer (Dragerwerk, Liibeck, West-Germany) (HILL1963). The halothane anaesthesia led to a decrease in arterial blood pressure of 60% of control value. This level was maintained for 10 min. Blood was then sampled for determination of halothane concentration, blood gases and acid-base state. Cardiac output was measured at the same time. Blood flows and pressures were continuously measured. The halothane exposure lasted on the average 49 (k18) min. One exposure of halothane per animal was made. Arterial Pco, was maintained between 35-45 mmHg and base excess between +0.5 and -3.0. Arterial Po* varied between 100 and 175 mmHg. Metabolic acidosis was corrected when necessary with 0.6 M sodium bicarbonate. Body temperature was maintained between 36" C and 37" C by means of a heat pad. Blood loss was kept a t a minimum. Isotonic saline, glucose and Ringer's solution were infused continuously throughout the experiment. The speed of the infusions was controlled so as to deliver a volume of approximately 0.15 ml/kg body weight per minute including the thermal indicator injections.
Calculations Vascular resistances were calculated according to the general formula [R = AP/Q], where R denotes resistance, AP blood pressure gradient in mmHg, and Q blood flow in ml/min. Caval venous pressure was assumed to be 0 mmHg. Means and standard deviations (X+ s.d.) of control and experimental values were calculated. Student's t-tests for paired values were used to establish the statistical significance of the observed changes. A P-value of 0.05 or less was accepted as significant.
RESULTS
Halothane concentration. Halothane concentra-
declined significantly during anaesthesia to 126f20 (Table 1).
Blood pressures. Before halothane, the mean aortic pressure was 154k60 mmHg, portal pressure was 1 3 + 5 mmHg and pulmonary arterial pressure was 10 f 1 mmHg. Following halothane, the mean aortic pressure and portal pressure decreased significantly to 93+35 mmHg (60% of control value) and 95-2 mmHg (68% of control), respectively. Pulmonary arterial pressure remained unchanged (Table 1). Cardiac output. Before halothane anaesthesia, the mean cardiac output was 89.2k17.0 ml/kg min-'. Following anaesthesia, the mean cardiac output declined significantly to 64.8+ 17.0 ml/kg min-' (73% of control) (Table 2). Stroke volume decreased insignificantly to 93% of control value. Splanchnic blood jlows. The mean hepatic arterial blood flow before halothane anaesthesia was 9.9f4.0 ml/kg min-', the mean superior mesenteric arterial flow 16.0f 3.8 ml/kg min-' and the mean portal venous flow was 25.8f7.3 ml/kg min-l. Following halothane, these flows decreased significantly : in the hepatic artery to 5.3k2.2 ml/kg min-' (54% of control), in the superior mesenteric artery to 9.513.1 ml/kg min-' (59%) and in the portal vein to 15.4k6.8 ml/kg min-' (60% of control) (Table 2). The total hepatic blood flow decreased significantly from 35.7k10.0 ml/kg min-' to 20.7f8.6 ml/kg min-' (58% of control). The ratio between hepatic arterial and portal venous blood supply to the liver was not altered by halothane. Similarly, the superior mesenteric contribution to total portal flow remained unchanged. Vascular resistances. Total peripheral resistance,
HALOTHANE, SPLANCHNIC BLOOD FLOW AND CARDIAC OUTPUT IN DOG
149
Table 1 Effects of halothane on heart rate and blood pressure in six dogs. ~~
~~
~~
Heart rate
Blood pressure (mmHg) Aorta
1 1 Portal vein
Pulmonary artery
Control value f
s.d.
165 23
154 60
13 5
10 1
126 20
93 35
9 2
11
Following halothane f
s.d.
**
Significance of difference
**
3
*
from control values
* 0.01
Effect of Controlled Halothane Anaesthesia on Splanchnic Blood Flow and Cardiac Output in the Dog L. THULIN, M. ANDREEN and L. IRESTEDT The Central Department of Anaesthesia and the Thoracic Surgery Research Laboratory, Karolinska Hospital, Stockholm, Sweden
Effects of halothane anaesthesia on splanchnic blood flow and cardiac output were studied in six dogs. Blood flows in the hepatic artery, the superior mesenteric artery and the portal vein were measured electromagnetically. Cardiac output was measured by thermodilution. Depth of anaesthesia, ventilation, acid-base state and body temperature were controlled. Cardiac output and blood flows in the hepatic artery, the superior mesenteric artery and the portal vein decreased significantly to 73%, 54%, 59% and 60% of control values, respectively. Total peripheral vascular resistance decreased significantly, while mesenteric and portal resistance remained essentially unchanged and hepatic arterial resistance showed a significant increase. It is suggested that the difference between the various vascular responses may he caused by a differentiated release from baroreceptor inhibition in various parts of the bulbar vasomotor center.
Receiued 6 Sehteniber, acceptedf o r publication 4 October 1974
The influence of halothane anaesthesia on MATERIAL AND METHODS splanchnic blood flow has been studied both Six mongrel dogs weighing between 16 and 29 kg were in man and in experimental animals. It has anaesthetized with pentobarbital (30 mg/kg) intrabeen shown that halothane anaesthesia venously. During the surgical preparation, anaesthesia decreases estimated hepatic blood flow was maintained with 70% nitrous oxide in oxygen and supplementary doses of pentobarbital. The animals (PICHLMAYR et al. 1966, EPSTEIN et al. 1966, were intubated endotracheally, and intermittent posiPRICE et al. 1966, AHLGREN et al. 1967), tive pressure ventilation was provided with a n Engstrom & respirator (LKB Medical, Stockholm, Sweden). intestinal blood flow (WESTERMARK W ~ L I N 1969), hepatic arterial flow and Ventilation was adjusted according to arterial Pco, in portal venous flow (SUUTARINEN et al. 1964, order to achieve normocapnia. Respiratory frequency was set at 20 per minute. GALINDO1965). Halothane-induced changes in various parts of the splanchnic circulation Measurements and surgical preparation (Fig. 1 ) and cardiac output have not been correlated Cardiac output. Cardiac output was measured by thermodilution (ANDREEN 1974). Ten ml of a solution of previously. The purpose of the present investigation was 5.0% glucose in water at room temperature were injected as a thermal indicator bolus. The injections to study simultaneous changes in cardiac out- were made into the right atrium through a cannula put and blood flow in the hepatic artery, the inserted via the right external jugular vein. Detection superior mesenteric artery and the portal vein of the indicator was made with a thermistor mounted during halothane anaesthesia. Special regard at the tip of a floating catheter introduced into the was taken to factorsinfluencing haemodynamic pulmonary artery. A cardiac output computer (Type 3750, Devices Instruments Ltd, Welwyn Garden City, effects of halothane: level of anaesthesia, U.K.) was used. arterial carbon dioxide tension, hydrogen ion concentration and body temperature. Rloodjows. Blood flows were measured elcctromagneti-
HALOTHANE, SPLANCHNIC BLOOD FLOW AND CARDIAC OUTPUT IN DOG
147
PA pulm
- __
Thermistor
P Vporta QA rnes sy, PAorta
cally. The abdomen of the dog was opened through a right subcostal incision. Calibrated flow probes were placed on the common hepatic artery, the superior mesenteric artery and the portal vein. The superior pancreaticoduodenal artery was ligated, i.e., proper hepatic blood flow was measured. Occlusion snares were placed distally to the probes. Dissection was made without severing perivascular nerves. Squarewave electromagnetic flowmeters (Nycotron AS, Drammen, Norway) were used for simultaneous measurements of the blood flows.
Blood pressures. Blood pressures were measured electromechanically in the abdominal aorta, the portal vein and in the pulmonary artery. The aortic catheter was
Fig. 1. Schematic illustration of the experimental set up. Pressure catheters were placed in the pulmonary artery, the aorta and the portal vein. A thermistor was mounted at the tip of the pulmonary artery catheter for measurement of cardiac output by thermodilution. Electromagnetic flow probes were placed on the hepatic artery, the portal vein and the superior mesenteric artery for measurement of = pulblood flow (PApulrn monary arterial pressure; RA = right atrium; LA = left atrium; R V = right ventricle; LV = left ventricle; Q A h e D = hepatic arterial bIood flow; Pveorta= portal venous pressure; QAme. s u p = superior mesenteric arterial blood flow; PA,,,, = aortic pressure)
inserted through a femoral artery. The portal catheter was inserted through a small mesenteric tributary. The pulmonary artery ratheter was inserted through the jugular vein cannula. The pressure catheters were connected to Statham transducers. Mean blood flows and mean blood pressures were continuously recorded on a Grass Polygraph. Heart rate and blood temperature. Heart rate was calculated from the pulmonary artery pressure curve. Blood temperature was registered with the intravascular thermistor mounted at the tip of the pulmonary artery catheter.
Blood gases and acid-base jtate. Arterial Po2 was deter-
148
L . THULIN, M . ANDREEN AND L . IRESTEDT
mined with an oxygen electrode (Radiometer, Copention in arterial blood was found to be 24.5 f4 hagen, Denmark). Arterial Pcoz and p H were determg % (2fs.d.). mined according to ASTRUP(1956) with a pH-electrode (Radiometer, Copenhagen, Denmark). Base excess Heart rate. Before halothane, the mean heart was calculated according to SIGGAARD-ANDERSEN & rate was 165f23 beats per min, which ENCEL(1960).
Halothane concentration in blood. Arterial halothane concentration was determined by gas chromatography (HALLBNet al. 1970). Experimental procedure After completed preparation, 30 minutes were allowed to elapse to establish a steady state during which all parameters were checked. No further pentobarbital was given during this period. Halothane was added to the nitrous oxide-oxygen mixture in a concentration of 1-2% by the use of a Vapor vaporizer (Dragerwerk, Liibeck, West-Germany) (HILL1963). The halothane anaesthesia led to a decrease in arterial blood pressure of 60% of control value. This level was maintained for 10 min. Blood was then sampled for determination of halothane concentration, blood gases and acid-base state. Cardiac output was measured at the same time. Blood flows and pressures were continuously measured. The halothane exposure lasted on the average 49 (k18) min. One exposure of halothane per animal was made. Arterial Pco, was maintained between 35-45 mmHg and base excess between +0.5 and -3.0. Arterial Po* varied between 100 and 175 mmHg. Metabolic acidosis was corrected when necessary with 0.6 M sodium bicarbonate. Body temperature was maintained between 36" C and 37" C by means of a heat pad. Blood loss was kept a t a minimum. Isotonic saline, glucose and Ringer's solution were infused continuously throughout the experiment. The speed of the infusions was controlled so as to deliver a volume of approximately 0.15 ml/kg body weight per minute including the thermal indicator injections.
Calculations Vascular resistances were calculated according to the general formula [R = AP/Q], where R denotes resistance, AP blood pressure gradient in mmHg, and Q blood flow in ml/min. Caval venous pressure was assumed to be 0 mmHg. Means and standard deviations (X+ s.d.) of control and experimental values were calculated. Student's t-tests for paired values were used to establish the statistical significance of the observed changes. A P-value of 0.05 or less was accepted as significant.
RESULTS
Halothane concentration. Halothane concentra-
declined significantly during anaesthesia to 126f20 (Table 1).
Blood pressures. Before halothane, the mean aortic pressure was 154k60 mmHg, portal pressure was 1 3 + 5 mmHg and pulmonary arterial pressure was 10 f 1 mmHg. Following halothane, the mean aortic pressure and portal pressure decreased significantly to 93+35 mmHg (60% of control value) and 95-2 mmHg (68% of control), respectively. Pulmonary arterial pressure remained unchanged (Table 1). Cardiac output. Before halothane anaesthesia, the mean cardiac output was 89.2k17.0 ml/kg min-'. Following anaesthesia, the mean cardiac output declined significantly to 64.8+ 17.0 ml/kg min-' (73% of control) (Table 2). Stroke volume decreased insignificantly to 93% of control value. Splanchnic blood jlows. The mean hepatic arterial blood flow before halothane anaesthesia was 9.9f4.0 ml/kg min-', the mean superior mesenteric arterial flow 16.0f 3.8 ml/kg min-' and the mean portal venous flow was 25.8f7.3 ml/kg min-l. Following halothane, these flows decreased significantly : in the hepatic artery to 5.3k2.2 ml/kg min-' (54% of control), in the superior mesenteric artery to 9.513.1 ml/kg min-' (59%) and in the portal vein to 15.4k6.8 ml/kg min-' (60% of control) (Table 2). The total hepatic blood flow decreased significantly from 35.7k10.0 ml/kg min-' to 20.7f8.6 ml/kg min-' (58% of control). The ratio between hepatic arterial and portal venous blood supply to the liver was not altered by halothane. Similarly, the superior mesenteric contribution to total portal flow remained unchanged. Vascular resistances. Total peripheral resistance,
HALOTHANE, SPLANCHNIC BLOOD FLOW AND CARDIAC OUTPUT IN DOG
149
Table 1 Effects of halothane on heart rate and blood pressure in six dogs. ~~
~~
~~
Heart rate
Blood pressure (mmHg) Aorta
1 1 Portal vein
Pulmonary artery
Control value f
s.d.
165 23
154 60
13 5
10 1
126 20
93 35
9 2
11
Following halothane f
s.d.
**
Significance of difference
**
3
*
from control values
* 0.01
