Acta anaesth. scand. 1975, 19, 238-244
The Effect of Controlled Halothane Anaesthesia on Splanchnic Oxygen Consumption in the Dog M. ANDREEN, L. IRESTEDT and L. THULIN The Department of Anaesthesia and the Thoracic Surgery Research Laboratory, Karolinska Hospital, Stockholm, Sweden
T h e influence of halothane anaesthesia on splanchnic oxygen flow and oxygen uptake was studied in seven dogs. Mean oxygen supply to the liver and the portally-drained tissues decreased significantly to 44% and 530,4 of control values, respectively, while mean oxygen consumption diminished insignificantly to 68%, and 82% of control values, respectively. There was a fall in the oxygen flow/ oxygen consumption ratio in all animals following halothane. The relatively unimpaired oxygen uptake, in spite of a diminished oxygen supply, led to a n increased extraction of oxygen by the tissues. Some factors affecting oxygen utilisation during halothane anaesthesia are discussed.
Received 20 J a ~ ~ ~ a accepted ry, f o r Publication 10 February 1975
Splanchnic blood flow is diminished during contradictory and naturally difficult to halothane anaesthesia (PRICE et al. 1966, compare with those from in vivo studies. I n the present study, we measured oxygen THULIN et al. 1974). Reports on concomitant changes in total splanchnic and hepatic consumption within the liver and the oxygen consumption are sparse and contra- portally-drained viscera, i.e., the intestine, dictory. Splanchnic oxygen consumption the pancreas and the spleen, simultaneously, during halothane anaesthesia in man was before and following halothane anaesthesia. studied by PRICEet al. (1966). No consistent By measuring blood flow and blood oxygen changes were obtained, although estimated content, i.e., oxygen flow to the organs, it hepatic blood flow was decreased. THEYE was possible to relate changes in oxygen et al. (1972) reported conflicting findings in consumption to changes in oxygen supply. dogs, i.e., a decrease in splanchnic oxygen Special attention was paid to factors which consumption occurred, while splanchnic are known to influence the haeniodynamic blood flow was maintained. These authors effects of halothane: level of anaesthesia, were able to estimate hepatic oxygen con- arterial carbon dioxide tension, hydrogen ion sumption and noted that the decrease in concentration and body temperature. splanchnic oxygen uptake during halothane anaesthesia was wholly explained by a decrease in the hepatic oxygen uptake. MATERIAL AND METHODS I n vitro studies on hepatic oxygen con- Seven mongrel dogs, weight 16-29 kg, which had fasted sumption during halothane exposure have overnight were anaesthetized with pentobarbital been performed on isolated, perfused livers (30 mg/kg) intravenously. During the surgical pro(BOMBECK et al. 1969, BIEBUYCK et al. 1972a) cedure, anaesthesia was maintained with 70% nitrous oxide in oxygen and supplementary doses of pentoand on liver slices (HOECHet al. 1966, barbital. The animals were endotracheally intubated BESOMBE& LONGMUIR1971). The results and intermittent positive pressure ventilation was from these in vitro studies are somewhat provided by an Engstrom respirator (LKB Medical,
H A L O T H A N E A N D S P L A N C H N I C O X Y G E N CONSUMPTION I N DOG
239
concentration of 1-2% by a Vapor vaporizer (WagerStockholm, Sweden) at a frequency of 20/min. Ventilawerk, Lubeck, West Germany) (HILL1963). The anition was adjusted according to arterial Pcoz in order to mals were anaesthetized so that arterial blood pressure achieve normocapnia. For details of the surgical preparation, see THULINdecreased to about 60% of control values. This level was maintained for 10 min. Blood was then sampled et al. (1974). simultaneously for determinations of oxygen and carbon dioxide contents and arterial halothane concenBlood pressure. Arterial blood pressure was measured tration. The halothane exposure lasted for 4 7 1 17 min. through a catheter in the abdominal aorta inserted One exposure of halothane per animal was made. into a femoral artery and connected to a Statham Arterial blood gases and acid-base state wcre checked transducer. This catheter was also used for arterial at regular intervals. Arterial Pco2 was maintained blood sampling. between 35 and 45 mmHg and base excms between Mean blood flows and mean arterial pressure were +0.5 and -3 mEg/l. Metabolic acidosis was corcontinuously recorded on a Grass Polygraph. rected when necessary with 0.6 M sodium bicarbonate. BloodJlows. Blood flows were measured electromagneti- Body temperature was maintained brtween 36" and 37°C by means of a heating pad. cally in the hepatic artery proper and the portal vein. Total blood loss was about 100 ml. Isotonic saline, Square-wave electromagnetic flow meters (Nycotron glucose and Ringer's solution were infused continuLtd., Drammen, Norway) were used. ously throughout the experiment. The speed of the infusions was controlled so as to deliver a volume of Oxygen content and carbon dioxide content. Oxygen and 0.15 ml/kg body weight/min. carbon dioxide contents were determined by the Van Slyke manometric technique (VAN SLYKE& NEILL 1924) in simultaneously collected arterial, portal and Calculatious hepatic venous blood. Portal blood was sampled through a catheter inserted via a small mesenteric OxygenJlow. Oxygen flow to the portally-drained tissues, tributary with its tip located close to the liver. Hepatic i.e., the intestine, the pancreas and the spleen, was venous blood was sampled through a catheter intro- determined as the product of arterial oxygen content duced through the right external jugular vein. The and portal blood flow. Oxygen flow to the liver was proper location of this catheter was verified at autopsy. calculated by adding hepatic arterial oxygen flow and portal venous oxygen flow. Bloodgasesandacid-base state. Arterial Poz was determined with a n oxygen electrode (Radiometer, Copenhagen, Oxygen consumption. Oxygen consumption within the Denmark). Arterial Pcoz and p H were determined portally-drained tissues was calculated as the product according to ASTRUP (1956) with a pH-electrode of arterio-portal oxygen difference and portal blood (Radiometer, Copenhagen, Denmark). Base excess was calculated according to SIGGAARD-ANDERSEN & ENGEL flow. Hepatic oxygen consumption was determined as the difference between oxygen flow to the liver and (1960). oxygen flow leaving the liver. The latter was calculated as the product of hepatic venous oxygen content and Halothane concentration in blood. Arterial halothane contotal hepatic blood flow. centration was determined by gas chromatography ( H A L L et ~ Nal. 1970).
Experimental procedure
Respiratory quotient. The respiratory quotients of the portally-drained tissues and of the liver were calculated as the ratio between carbon dioxide production and oxygen consumption. Hepatic carbon dioxide production was determined as the difference between carbon dioxide lraving the liver by the hepatic veins and carbon dioxide entering the liver by the hepatic artery and the portal vein.
After completed preparation of the animal, an interval of 30 minutes was allowed to elapse to permit the circulatory variables under study to stabilise. No further pentobarbital was given during this period. Blood samples for measurements of arterial, portal and hepatic venous oxygen and carbon dioxide contents were taken immediately before the halothane exposure. Halothane was added to the nitrous oxide-oxygen mixture in a
Statistics. Means and standard deviations (ifs.d.) of controls and experimental values were calculated. Student's t-test for paired values was used to establish the statistical significance of the observed changes. The following probability ( P ) levels of significance were used: PGO.OO1 = ***; 0.001 0.05 = n.s.
Temperature. Blood temperature was measured with an intravascular thermistor (Devices Instruments Ltd., Welwyn Garden City, England) located in the pulmonary artery.
240
M. ANDREEN, L. IRESTEDT AND L. THULIN
RESULTS
ml/kg min-' to 4.3k3.0 ml/kg min-' (53% of control value) following halothane exposure (0.01
The Effect of Controlled Halothane Anaesthesia on Splanchnic Oxygen Consumption in the Dog M. ANDREEN, L. IRESTEDT and L. THULIN The Department of Anaesthesia and the Thoracic Surgery Research Laboratory, Karolinska Hospital, Stockholm, Sweden
T h e influence of halothane anaesthesia on splanchnic oxygen flow and oxygen uptake was studied in seven dogs. Mean oxygen supply to the liver and the portally-drained tissues decreased significantly to 44% and 530,4 of control values, respectively, while mean oxygen consumption diminished insignificantly to 68%, and 82% of control values, respectively. There was a fall in the oxygen flow/ oxygen consumption ratio in all animals following halothane. The relatively unimpaired oxygen uptake, in spite of a diminished oxygen supply, led to a n increased extraction of oxygen by the tissues. Some factors affecting oxygen utilisation during halothane anaesthesia are discussed.
Received 20 J a ~ ~ ~ a accepted ry, f o r Publication 10 February 1975
Splanchnic blood flow is diminished during contradictory and naturally difficult to halothane anaesthesia (PRICE et al. 1966, compare with those from in vivo studies. I n the present study, we measured oxygen THULIN et al. 1974). Reports on concomitant changes in total splanchnic and hepatic consumption within the liver and the oxygen consumption are sparse and contra- portally-drained viscera, i.e., the intestine, dictory. Splanchnic oxygen consumption the pancreas and the spleen, simultaneously, during halothane anaesthesia in man was before and following halothane anaesthesia. studied by PRICEet al. (1966). No consistent By measuring blood flow and blood oxygen changes were obtained, although estimated content, i.e., oxygen flow to the organs, it hepatic blood flow was decreased. THEYE was possible to relate changes in oxygen et al. (1972) reported conflicting findings in consumption to changes in oxygen supply. dogs, i.e., a decrease in splanchnic oxygen Special attention was paid to factors which consumption occurred, while splanchnic are known to influence the haeniodynamic blood flow was maintained. These authors effects of halothane: level of anaesthesia, were able to estimate hepatic oxygen con- arterial carbon dioxide tension, hydrogen ion sumption and noted that the decrease in concentration and body temperature. splanchnic oxygen uptake during halothane anaesthesia was wholly explained by a decrease in the hepatic oxygen uptake. MATERIAL AND METHODS I n vitro studies on hepatic oxygen con- Seven mongrel dogs, weight 16-29 kg, which had fasted sumption during halothane exposure have overnight were anaesthetized with pentobarbital been performed on isolated, perfused livers (30 mg/kg) intravenously. During the surgical pro(BOMBECK et al. 1969, BIEBUYCK et al. 1972a) cedure, anaesthesia was maintained with 70% nitrous oxide in oxygen and supplementary doses of pentoand on liver slices (HOECHet al. 1966, barbital. The animals were endotracheally intubated BESOMBE& LONGMUIR1971). The results and intermittent positive pressure ventilation was from these in vitro studies are somewhat provided by an Engstrom respirator (LKB Medical,
H A L O T H A N E A N D S P L A N C H N I C O X Y G E N CONSUMPTION I N DOG
239
concentration of 1-2% by a Vapor vaporizer (WagerStockholm, Sweden) at a frequency of 20/min. Ventilawerk, Lubeck, West Germany) (HILL1963). The anition was adjusted according to arterial Pcoz in order to mals were anaesthetized so that arterial blood pressure achieve normocapnia. For details of the surgical preparation, see THULINdecreased to about 60% of control values. This level was maintained for 10 min. Blood was then sampled et al. (1974). simultaneously for determinations of oxygen and carbon dioxide contents and arterial halothane concenBlood pressure. Arterial blood pressure was measured tration. The halothane exposure lasted for 4 7 1 17 min. through a catheter in the abdominal aorta inserted One exposure of halothane per animal was made. into a femoral artery and connected to a Statham Arterial blood gases and acid-base state wcre checked transducer. This catheter was also used for arterial at regular intervals. Arterial Pco2 was maintained blood sampling. between 35 and 45 mmHg and base excms between Mean blood flows and mean arterial pressure were +0.5 and -3 mEg/l. Metabolic acidosis was corcontinuously recorded on a Grass Polygraph. rected when necessary with 0.6 M sodium bicarbonate. BloodJlows. Blood flows were measured electromagneti- Body temperature was maintained brtween 36" and 37°C by means of a heating pad. cally in the hepatic artery proper and the portal vein. Total blood loss was about 100 ml. Isotonic saline, Square-wave electromagnetic flow meters (Nycotron glucose and Ringer's solution were infused continuLtd., Drammen, Norway) were used. ously throughout the experiment. The speed of the infusions was controlled so as to deliver a volume of Oxygen content and carbon dioxide content. Oxygen and 0.15 ml/kg body weight/min. carbon dioxide contents were determined by the Van Slyke manometric technique (VAN SLYKE& NEILL 1924) in simultaneously collected arterial, portal and Calculatious hepatic venous blood. Portal blood was sampled through a catheter inserted via a small mesenteric OxygenJlow. Oxygen flow to the portally-drained tissues, tributary with its tip located close to the liver. Hepatic i.e., the intestine, the pancreas and the spleen, was venous blood was sampled through a catheter intro- determined as the product of arterial oxygen content duced through the right external jugular vein. The and portal blood flow. Oxygen flow to the liver was proper location of this catheter was verified at autopsy. calculated by adding hepatic arterial oxygen flow and portal venous oxygen flow. Bloodgasesandacid-base state. Arterial Poz was determined with a n oxygen electrode (Radiometer, Copenhagen, Oxygen consumption. Oxygen consumption within the Denmark). Arterial Pcoz and p H were determined portally-drained tissues was calculated as the product according to ASTRUP (1956) with a pH-electrode of arterio-portal oxygen difference and portal blood (Radiometer, Copenhagen, Denmark). Base excess was calculated according to SIGGAARD-ANDERSEN & ENGEL flow. Hepatic oxygen consumption was determined as the difference between oxygen flow to the liver and (1960). oxygen flow leaving the liver. The latter was calculated as the product of hepatic venous oxygen content and Halothane concentration in blood. Arterial halothane contotal hepatic blood flow. centration was determined by gas chromatography ( H A L L et ~ Nal. 1970).
Experimental procedure
Respiratory quotient. The respiratory quotients of the portally-drained tissues and of the liver were calculated as the ratio between carbon dioxide production and oxygen consumption. Hepatic carbon dioxide production was determined as the difference between carbon dioxide lraving the liver by the hepatic veins and carbon dioxide entering the liver by the hepatic artery and the portal vein.
After completed preparation of the animal, an interval of 30 minutes was allowed to elapse to permit the circulatory variables under study to stabilise. No further pentobarbital was given during this period. Blood samples for measurements of arterial, portal and hepatic venous oxygen and carbon dioxide contents were taken immediately before the halothane exposure. Halothane was added to the nitrous oxide-oxygen mixture in a
Statistics. Means and standard deviations (ifs.d.) of controls and experimental values were calculated. Student's t-test for paired values was used to establish the statistical significance of the observed changes. The following probability ( P ) levels of significance were used: PGO.OO1 = ***; 0.001 0.05 = n.s.
Temperature. Blood temperature was measured with an intravascular thermistor (Devices Instruments Ltd., Welwyn Garden City, England) located in the pulmonary artery.
240
M. ANDREEN, L. IRESTEDT AND L. THULIN
RESULTS
ml/kg min-' to 4.3k3.0 ml/kg min-' (53% of control value) following halothane exposure (0.01
