•
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Slowing of Hepatic Blood Flow by Halothane: Angiographic Manifestations 1
Diagnostic Radiology
Paul E. Berger, M.D., J. A. Gordon Culham, M.D., Charles R. Fitz, M.D., and Derek C. Harwood-Nash, Ch.B., F.R.C.P.(C) Extreme slowing of hepatic arterial flow occurred in 2 children who had angiographic examination under general anesthesia with halothane. The incidence of this striking angiographic "halothane effect" was 32 %. It was thought to be caused by a specific increase in hepatic vasomotor tone at the arterial, sinusoidal or venous leYel. The functional significance of this effect is unclear and its role in the production of hepatic dysfunction or massive hepatic necrosis is conjectural. No untoward effects were noted in our patients. INDEX TERMS:
•
Anesthesia. Arteries, hepatic • Liver, blood flow
Radiology 118:303-306, February 1976
was introduced for clinical use as a general anesthetic in 1956, and is used today extensively because of its safety and pharmacologic properties. Early reports suggested an increased incidence of liver injury associated with halothane anesthesia (13). However, no definitive evidence was forthcoming. A reversible increase in vasomotor tone specific to hepatic vasculature which produces a very striking angi-
H
ographic appearance has occurred in children who have had angiographic examination under general anesthesia with halothane. Two cases are presented in detail.
ALOTHA NE
CASE REPORTS CASE I:
K. 0., a 4-year-old girl with known neurofibromatosis,
Fig. 1. CASE I. Aortogram. Note paucity of contrast material within the hepatic arteries (arrows) despite excellent visualization of the inferior phrenic, splenic, superior mesenteric and renal arteries (subtraction technique). Fig. 2. CASE I. A. Celiac axis catheterization, midarterial phase. Markedly diminished arterial perfusion to the liver with left gastric, gastroduodenal and gastroepiploic arteries is well visualized (subtraction technique). B. Venous phase. Residual contrast material is seen in the hepatic artery branches. The portal vein is small (arrows) (subtraction technique). 1
From the Department of Radiology, The Hospital for Sick Chiidren, Toronto, Ontario. Accepted for publication in August 1975.
303
shan
304
PAUL
E.
BERGER AND OTHERS
February 1976
Fig. 3. CASE II. A. Aortogram. A very large mass is seen in the upper pole of the left kidney, displacing the aorta to the right. Note normal hepatic flow to the liver on this initial study (halothane 0.5%). B. Selective left renal angiogram. The abnormal vascularity in the tumor of the upper pole, left kidney, was pathologically diagnosed as Wilms' tumor.
was first seen at the age of 21/2 years for proptosis of the left eye. Pneumoencephalography and cerebral arteriography were performed under general anesthesia using halothane (0.5-1.5 %) as the anesthetic agent. A diagnosis of left optic nerve and optic chiasm glioma was made. Two weeks later, a left frontal craniotomy and orbital deroofing with total resection of the optic glioma was performed. Anesthesia at that time was halothane 0.5 %. She had another operative procedure four days later for orbital decompression following development of pulsatile proptosis. Again, halothane anesthesia was used up to a concentration of 3 % . Her second admission was for evaluation of intermittent vomiting. At this time, she also underwent computed tomography of the orbits but no residual tumor was demonstrated. The child was given general anesthesia, 1.0-1.5 % halothane. She was subsequently admitted for evaluation of intermittent blood pressure elevations up to 130/90 mm Hg noted for three months prior to admission. Work-up included an excretory urogram, blood urea nitrogen, creatinine, chest x-ray, urinalysis, alkaline phosphatase, and electrolytes, all of which were normal. Because of the known association of neurofibromatosis with renal artery stenosis, a renal arteriogram was requested. The patient received general anesthesia, halothane 1.0 %. On the initial aortogram, little contrast material was noted within the hepatic arteries (Fig. 1). Although the inferior phrenic, splenic and superior mesenteric arteries were all demonstrated, there was poor visualization of the hepatic arteries distal to the common hepatic. Subsequent selective catheterization of the celiac axis was performed with passage of the catheter just distal to the origin of the splenic artery. The proximal portion of the common and proper hepatic arteries appeared normal. The gastroduodenal and pancreatic arcades were grossly normal. Flow in the proximal hepatic arteries was extremely slow (Fig 2, A). Perfusion to the right lobe of the liver from the hepatic artery appeared markedly diminished. There was still residual contrast material in two branches of the hepatic artery
on the venous phase. Filling of the portal vein was also noted (Fig 2, B). The patient tolerated the procedure well. Because of the unusual arteriogram, further evaluation of the liver was indicated, and included serum glutamic oxaloacetic transaminase (SGOT), alkaline phosphatase, bilirubin and protein electrophoresis, all of which were normal. A liver-spleen scan was also normal. The patient remains well six months later. CASE II. M. S. This 3-year-old girl presented with vague abdominal pain and was noted to have a mass in the left side of the abdomen. The liver was not enlarged. The remainder of the examination was normal. Work-up included excretory urography, done at the referring hospital, which showed a large mass in the upper pole of the left kidney with distortion of the upper pole calyceal system. Chest x rays and liver and bone scans were normal. An angiogram was requested and obtained with the child under general anesthesia with a maintenance level of 0.5 % halothane. The aortogram (Fig 3, A) and selective left renal angiogram (Fig 3, B) showed a huge mass in the upper pole of the left kidney with abnormal vascularity. The right kidney was angiographically normal. A selective hepatic injection showed a t-ern area of slightly irregular vascularity with an unusual blush suggesting the possibility of an hepatic metastasis. The following day, a left radical nephrectomy was performed. The liver was palpated and appeared grossly normal. Pathology studies revealed Wilms' tumor, negative lymph nodes, and a normal adrenal gland. Because of the possibility of hepatic metastases, repeat selective hepatic angiography was performed two months later. Halothane anesthesia, 1.0 %, was again used . At fluoroscopy and on subsequent filming, a markedly slowed hepatic arterial flow was noted with reflux of contrast material into the splenic and gastroduodenal arteries (Fig 4, A). Flow was extremely slow through the major intrahepatic arteries. On the venous phase, filling of the splenic and portal veins was seen but a marked amount of residual contrast material was revealed in the hepatic arteries (Fig 5, A). The portal vein mea-
Vol. 118
SLOWING OF HEPATIC BLOOD FLOW BY HALOTHANE
Fig. 4. A and B. CASE II. A. Celiac arteriogram, midarterial phase (halothane anesthesia, 1.0%). A markedly diminished amount of contrast material is seen within the liver despite excellent visualization of the splenic, gastroduodenal and right gastroepiploic arteries. B. Same patient. Celiac arteriogram, midarterial phase without halothane anesthesia. Hepatic arterial flow is normal.
sured 1.3 em. Because of our previous experience, it was felt that this was most likely the effect of the halothane anesthesia. Halothane was terminated and curare. nitrous oxide, and oxygen substituted. The catheter was left in place within the hepatic artery and every 5 minutes a test injection was performed. These showed progressive improvement in the flow rate to the liver. At 25 minutes, the flow had markedly increased. A repeat power injection was done with the catheter in the same position as in the first injection. An identical amount of contrast agent and the same rate of injection and film sequence were used. The repeat study demonstrated normal hepatic arterial flow (Fig 4, B). Both intrahepatic arterial circulation and venous phase were normal. The portal vein was also seen (Fig 5, B) and measured 1.6 em, an increase of 3 mm over the previous study- Liver function studies, performed immediately following the procedure, revealed a normal alkaline phosphatase and SGOT. No adverse effects were noted. FOllow-up at two months showed no evidence of liver dysfunction.
DISCUSSION
Halothane is perhaps the most extensively used general anesthetic agent available. Its low toxicity is recognized, and reports of adverse effects from its use are few. Several reports however, have suggested an in-
305
Diagnostic Radiology
Fig. 5. A and B. CASE II. A. Venous phase with halothane anesthesia. Contrast substance remains in the hepatic arteries. The splenic vein (white arrows) and portal vein (black arrows) are visualized. The portal vein measured 1.3 cm. B. Venous phase without halothane anesthesia. There is no evidence of hepatic arteries and the portal venous system appears normal. The portal vein measured 1.6 cm (arrows).
creased incidence of liver injury associated with its use (1-3). Brody and Sweet (1) reported 4 cases in which massive hepatic necrosis developed following surgical procedures performed under halothane anesthesia. Three of these proved fatal. Lindenbaum and Leifer (2) reported 9 cases in which postoperative hepatic necrosis followed the use of halothane. The clinical course was somewhat variable and 1 patient died in hepatic coma following the use of methoxyflurane after a recent exposure to halothane. Bunker and Blumenfeld (3) reported 2 fatalities due to massive liver necrosis after halothane anesthesia. Despite extensive research, no definitive evidence of a cause-and-effect relationship between halothane and hepatic necrosis has been conclusively demonstrated. Epstein et at. (4), studying its effect on the splanchnic circulation, showed a statistically significant reduction of systemic arterial pressure and estimated hepatic blood flow following administration of Halothane anesthesia. The splanchnic vascular resistance was not consistently changed. The hepatic venous pressure was inconsis-
306
PAUL
E. BERGER AND OTHERS
tently affected. They measured arterial pressure by a needle in the femoral artery and considered that the nearly equal reductions each in perfusion, pressure and blood flow which accompanied the administration of halothane was due to hypotension. Their results suggested a decrease in vasomotor tone. They were unable to document any functional significance of the reduction in hepatic perfusion and stated that "barring a selective ischemia of hepatic substructures for which there is no evidence to our knowledge, any peculiarly halothanerelated effects on the integrity of the liver would seem not to be ascribable to a change in nutrient blood flow." Price et al. (5) showed that 1.5 % halothane diminished hepatic blood flow without affecting splanchnic oxygen consumption. They attributed the reduction in hepatic blood flow to a reduction in systemic arterial pressure. Libonati et al. (6) studied the effects of methoxyflurane (Penthrane) in 12 healthy male volunteers. They found that methoxyflurane in an end-expired concentration of 0.2% reduced splanchnic blood flow by 50% and hepatic venous oxygen tension by 30 %. Splanchnic oxygen consumption was not affected and there was no biochemical evidence of ischemic hypoxia. The reduction in blood flow was caused by arterial hypotension and increased splanchnic vascular resistance. Arteriograms obtained during methoxyflurane anesthesia showed a marked "vasoconstriction" of the hepatic arteries, the arterial supply to the other abdominal viscera remaining unaffected. They were unable to tell whether the portal vein constricts as markedly as the artery, but their estimations of splanchnic blood volume suggested that some venoconstriction also occurred. They stated that halothane did not produce this type of vascular pattern. Their published arteriograms however, are very similar to ours and it is evident from our cases that halothane may indeed produce a striking increase in vasomotor tone specific to hepatic circulation, with sparing of arterial supply to the other abdominal viscera. We have demonstrated marked slowing of hepatic arterial flow with halothane and feel that it may be due to an increase in hepatic vasomotor tone. Whether this effect is primarily at the hepatic arterial, sinusoidal or venous level is unknown.
February 1976
A review of our 25 most recent aortograms obtained when halothane was the anesthetic agent show this "halothane effect" or a slowing of the hepatic arterial flow in 8 cases for an incidence of 32 % . The functional significance of this effect is unclear. Both of our patients recovered uneventfully and followup liver function studies and liver-spleen scan were normal. No evidence of hepatic dysfunction was evident biochemically or clinically. Any role that this halothane effect may have on the production of hepatic dysfunction or massive hepatic necrosis is strictly conjectural at this point. We no longer use halothane anesthesia in the angiographic investigation of possible liver abnormalities. Local anesthesia and sedation with an intramuscular injection of a mixture of meperidine, promethazine and chlorpromazine is used when possible. A relaxant method using curare, nitrous oxide and oxygen may also be used but Cooperman et al. (7) demonstrated a significant increase in splanchnic vascular resistance and a decrease in splanchnic blood flow with this method. Department of Radiology and Nuclear Medicine Children's Hospital of Buffalo 219 Bryant St. Buffalo, N. Y. 14222
REFERENCES 1. Brody GL, Sweet RB: Halothane anesthesia as a possible cause of massive hepatic necrosis. Anesthesiology 24:29-37, JanFeb 1963 2. Lindenbaum J, Leifer E: Hepatic necrosis associated with halothane anesthesia. New Engl J Med 268:525-530, 7 Mar 1963 3. Bunker JP, Blumenfeld CM: Liver necrosis after halothane anesthesia. Cause or coincidence? New Engl J Med 268:531-534, 7 Mar 1963 4. Epstein RM, Deutsch S, Cooperman LH: Splanchnic circulation during halothane anesthesia and hypercapnia in normal man. Anesthesiology 27:654-661, Sep-Oct 1966 5. Price HL, Deutsch S, Davidson IA: Can general anesthetics produce splanchnic visceral hypoxia by reducing regional blood flow? Anesthesiology 27:24-32, Jan-Feb 1966 6. Libonati M, Maisch E, Price HL, et al: Splanchnic circulation in man during methoxyflurane anesthesia. Anesthesiology 38:466472, May 1973 7. Cooperman LH, Warden JC, Price HL: Splanchnic circulation during nitrous oxide anesthesia and hypocarbia in normal man. Anesthesiology 29:254-258, Mar-Apr 1968
•
Slowing of Hepatic Blood Flow by Halothane: Angiographic Manifestations 1
Diagnostic Radiology
Paul E. Berger, M.D., J. A. Gordon Culham, M.D., Charles R. Fitz, M.D., and Derek C. Harwood-Nash, Ch.B., F.R.C.P.(C) Extreme slowing of hepatic arterial flow occurred in 2 children who had angiographic examination under general anesthesia with halothane. The incidence of this striking angiographic "halothane effect" was 32 %. It was thought to be caused by a specific increase in hepatic vasomotor tone at the arterial, sinusoidal or venous leYel. The functional significance of this effect is unclear and its role in the production of hepatic dysfunction or massive hepatic necrosis is conjectural. No untoward effects were noted in our patients. INDEX TERMS:
•
Anesthesia. Arteries, hepatic • Liver, blood flow
Radiology 118:303-306, February 1976
was introduced for clinical use as a general anesthetic in 1956, and is used today extensively because of its safety and pharmacologic properties. Early reports suggested an increased incidence of liver injury associated with halothane anesthesia (13). However, no definitive evidence was forthcoming. A reversible increase in vasomotor tone specific to hepatic vasculature which produces a very striking angi-
H
ographic appearance has occurred in children who have had angiographic examination under general anesthesia with halothane. Two cases are presented in detail.
ALOTHA NE
CASE REPORTS CASE I:
K. 0., a 4-year-old girl with known neurofibromatosis,
Fig. 1. CASE I. Aortogram. Note paucity of contrast material within the hepatic arteries (arrows) despite excellent visualization of the inferior phrenic, splenic, superior mesenteric and renal arteries (subtraction technique). Fig. 2. CASE I. A. Celiac axis catheterization, midarterial phase. Markedly diminished arterial perfusion to the liver with left gastric, gastroduodenal and gastroepiploic arteries is well visualized (subtraction technique). B. Venous phase. Residual contrast material is seen in the hepatic artery branches. The portal vein is small (arrows) (subtraction technique). 1
From the Department of Radiology, The Hospital for Sick Chiidren, Toronto, Ontario. Accepted for publication in August 1975.
303
shan
304
PAUL
E.
BERGER AND OTHERS
February 1976
Fig. 3. CASE II. A. Aortogram. A very large mass is seen in the upper pole of the left kidney, displacing the aorta to the right. Note normal hepatic flow to the liver on this initial study (halothane 0.5%). B. Selective left renal angiogram. The abnormal vascularity in the tumor of the upper pole, left kidney, was pathologically diagnosed as Wilms' tumor.
was first seen at the age of 21/2 years for proptosis of the left eye. Pneumoencephalography and cerebral arteriography were performed under general anesthesia using halothane (0.5-1.5 %) as the anesthetic agent. A diagnosis of left optic nerve and optic chiasm glioma was made. Two weeks later, a left frontal craniotomy and orbital deroofing with total resection of the optic glioma was performed. Anesthesia at that time was halothane 0.5 %. She had another operative procedure four days later for orbital decompression following development of pulsatile proptosis. Again, halothane anesthesia was used up to a concentration of 3 % . Her second admission was for evaluation of intermittent vomiting. At this time, she also underwent computed tomography of the orbits but no residual tumor was demonstrated. The child was given general anesthesia, 1.0-1.5 % halothane. She was subsequently admitted for evaluation of intermittent blood pressure elevations up to 130/90 mm Hg noted for three months prior to admission. Work-up included an excretory urogram, blood urea nitrogen, creatinine, chest x-ray, urinalysis, alkaline phosphatase, and electrolytes, all of which were normal. Because of the known association of neurofibromatosis with renal artery stenosis, a renal arteriogram was requested. The patient received general anesthesia, halothane 1.0 %. On the initial aortogram, little contrast material was noted within the hepatic arteries (Fig. 1). Although the inferior phrenic, splenic and superior mesenteric arteries were all demonstrated, there was poor visualization of the hepatic arteries distal to the common hepatic. Subsequent selective catheterization of the celiac axis was performed with passage of the catheter just distal to the origin of the splenic artery. The proximal portion of the common and proper hepatic arteries appeared normal. The gastroduodenal and pancreatic arcades were grossly normal. Flow in the proximal hepatic arteries was extremely slow (Fig 2, A). Perfusion to the right lobe of the liver from the hepatic artery appeared markedly diminished. There was still residual contrast material in two branches of the hepatic artery
on the venous phase. Filling of the portal vein was also noted (Fig 2, B). The patient tolerated the procedure well. Because of the unusual arteriogram, further evaluation of the liver was indicated, and included serum glutamic oxaloacetic transaminase (SGOT), alkaline phosphatase, bilirubin and protein electrophoresis, all of which were normal. A liver-spleen scan was also normal. The patient remains well six months later. CASE II. M. S. This 3-year-old girl presented with vague abdominal pain and was noted to have a mass in the left side of the abdomen. The liver was not enlarged. The remainder of the examination was normal. Work-up included excretory urography, done at the referring hospital, which showed a large mass in the upper pole of the left kidney with distortion of the upper pole calyceal system. Chest x rays and liver and bone scans were normal. An angiogram was requested and obtained with the child under general anesthesia with a maintenance level of 0.5 % halothane. The aortogram (Fig 3, A) and selective left renal angiogram (Fig 3, B) showed a huge mass in the upper pole of the left kidney with abnormal vascularity. The right kidney was angiographically normal. A selective hepatic injection showed a t-ern area of slightly irregular vascularity with an unusual blush suggesting the possibility of an hepatic metastasis. The following day, a left radical nephrectomy was performed. The liver was palpated and appeared grossly normal. Pathology studies revealed Wilms' tumor, negative lymph nodes, and a normal adrenal gland. Because of the possibility of hepatic metastases, repeat selective hepatic angiography was performed two months later. Halothane anesthesia, 1.0 %, was again used . At fluoroscopy and on subsequent filming, a markedly slowed hepatic arterial flow was noted with reflux of contrast material into the splenic and gastroduodenal arteries (Fig 4, A). Flow was extremely slow through the major intrahepatic arteries. On the venous phase, filling of the splenic and portal veins was seen but a marked amount of residual contrast material was revealed in the hepatic arteries (Fig 5, A). The portal vein mea-
Vol. 118
SLOWING OF HEPATIC BLOOD FLOW BY HALOTHANE
Fig. 4. A and B. CASE II. A. Celiac arteriogram, midarterial phase (halothane anesthesia, 1.0%). A markedly diminished amount of contrast material is seen within the liver despite excellent visualization of the splenic, gastroduodenal and right gastroepiploic arteries. B. Same patient. Celiac arteriogram, midarterial phase without halothane anesthesia. Hepatic arterial flow is normal.
sured 1.3 em. Because of our previous experience, it was felt that this was most likely the effect of the halothane anesthesia. Halothane was terminated and curare. nitrous oxide, and oxygen substituted. The catheter was left in place within the hepatic artery and every 5 minutes a test injection was performed. These showed progressive improvement in the flow rate to the liver. At 25 minutes, the flow had markedly increased. A repeat power injection was done with the catheter in the same position as in the first injection. An identical amount of contrast agent and the same rate of injection and film sequence were used. The repeat study demonstrated normal hepatic arterial flow (Fig 4, B). Both intrahepatic arterial circulation and venous phase were normal. The portal vein was also seen (Fig 5, B) and measured 1.6 em, an increase of 3 mm over the previous study- Liver function studies, performed immediately following the procedure, revealed a normal alkaline phosphatase and SGOT. No adverse effects were noted. FOllow-up at two months showed no evidence of liver dysfunction.
DISCUSSION
Halothane is perhaps the most extensively used general anesthetic agent available. Its low toxicity is recognized, and reports of adverse effects from its use are few. Several reports however, have suggested an in-
305
Diagnostic Radiology
Fig. 5. A and B. CASE II. A. Venous phase with halothane anesthesia. Contrast substance remains in the hepatic arteries. The splenic vein (white arrows) and portal vein (black arrows) are visualized. The portal vein measured 1.3 cm. B. Venous phase without halothane anesthesia. There is no evidence of hepatic arteries and the portal venous system appears normal. The portal vein measured 1.6 cm (arrows).
creased incidence of liver injury associated with its use (1-3). Brody and Sweet (1) reported 4 cases in which massive hepatic necrosis developed following surgical procedures performed under halothane anesthesia. Three of these proved fatal. Lindenbaum and Leifer (2) reported 9 cases in which postoperative hepatic necrosis followed the use of halothane. The clinical course was somewhat variable and 1 patient died in hepatic coma following the use of methoxyflurane after a recent exposure to halothane. Bunker and Blumenfeld (3) reported 2 fatalities due to massive liver necrosis after halothane anesthesia. Despite extensive research, no definitive evidence of a cause-and-effect relationship between halothane and hepatic necrosis has been conclusively demonstrated. Epstein et at. (4), studying its effect on the splanchnic circulation, showed a statistically significant reduction of systemic arterial pressure and estimated hepatic blood flow following administration of Halothane anesthesia. The splanchnic vascular resistance was not consistently changed. The hepatic venous pressure was inconsis-
306
PAUL
E. BERGER AND OTHERS
tently affected. They measured arterial pressure by a needle in the femoral artery and considered that the nearly equal reductions each in perfusion, pressure and blood flow which accompanied the administration of halothane was due to hypotension. Their results suggested a decrease in vasomotor tone. They were unable to document any functional significance of the reduction in hepatic perfusion and stated that "barring a selective ischemia of hepatic substructures for which there is no evidence to our knowledge, any peculiarly halothanerelated effects on the integrity of the liver would seem not to be ascribable to a change in nutrient blood flow." Price et al. (5) showed that 1.5 % halothane diminished hepatic blood flow without affecting splanchnic oxygen consumption. They attributed the reduction in hepatic blood flow to a reduction in systemic arterial pressure. Libonati et al. (6) studied the effects of methoxyflurane (Penthrane) in 12 healthy male volunteers. They found that methoxyflurane in an end-expired concentration of 0.2% reduced splanchnic blood flow by 50% and hepatic venous oxygen tension by 30 %. Splanchnic oxygen consumption was not affected and there was no biochemical evidence of ischemic hypoxia. The reduction in blood flow was caused by arterial hypotension and increased splanchnic vascular resistance. Arteriograms obtained during methoxyflurane anesthesia showed a marked "vasoconstriction" of the hepatic arteries, the arterial supply to the other abdominal viscera remaining unaffected. They were unable to tell whether the portal vein constricts as markedly as the artery, but their estimations of splanchnic blood volume suggested that some venoconstriction also occurred. They stated that halothane did not produce this type of vascular pattern. Their published arteriograms however, are very similar to ours and it is evident from our cases that halothane may indeed produce a striking increase in vasomotor tone specific to hepatic circulation, with sparing of arterial supply to the other abdominal viscera. We have demonstrated marked slowing of hepatic arterial flow with halothane and feel that it may be due to an increase in hepatic vasomotor tone. Whether this effect is primarily at the hepatic arterial, sinusoidal or venous level is unknown.
February 1976
A review of our 25 most recent aortograms obtained when halothane was the anesthetic agent show this "halothane effect" or a slowing of the hepatic arterial flow in 8 cases for an incidence of 32 % . The functional significance of this effect is unclear. Both of our patients recovered uneventfully and followup liver function studies and liver-spleen scan were normal. No evidence of hepatic dysfunction was evident biochemically or clinically. Any role that this halothane effect may have on the production of hepatic dysfunction or massive hepatic necrosis is strictly conjectural at this point. We no longer use halothane anesthesia in the angiographic investigation of possible liver abnormalities. Local anesthesia and sedation with an intramuscular injection of a mixture of meperidine, promethazine and chlorpromazine is used when possible. A relaxant method using curare, nitrous oxide and oxygen may also be used but Cooperman et al. (7) demonstrated a significant increase in splanchnic vascular resistance and a decrease in splanchnic blood flow with this method. Department of Radiology and Nuclear Medicine Children's Hospital of Buffalo 219 Bryant St. Buffalo, N. Y. 14222
REFERENCES 1. Brody GL, Sweet RB: Halothane anesthesia as a possible cause of massive hepatic necrosis. Anesthesiology 24:29-37, JanFeb 1963 2. Lindenbaum J, Leifer E: Hepatic necrosis associated with halothane anesthesia. New Engl J Med 268:525-530, 7 Mar 1963 3. Bunker JP, Blumenfeld CM: Liver necrosis after halothane anesthesia. Cause or coincidence? New Engl J Med 268:531-534, 7 Mar 1963 4. Epstein RM, Deutsch S, Cooperman LH: Splanchnic circulation during halothane anesthesia and hypercapnia in normal man. Anesthesiology 27:654-661, Sep-Oct 1966 5. Price HL, Deutsch S, Davidson IA: Can general anesthetics produce splanchnic visceral hypoxia by reducing regional blood flow? Anesthesiology 27:24-32, Jan-Feb 1966 6. Libonati M, Maisch E, Price HL, et al: Splanchnic circulation in man during methoxyflurane anesthesia. Anesthesiology 38:466472, May 1973 7. Cooperman LH, Warden JC, Price HL: Splanchnic circulation during nitrous oxide anesthesia and hypocarbia in normal man. Anesthesiology 29:254-258, Mar-Apr 1968
