The Effect of Vasopressin
on
Oxygen Availability
J. L. BERK, M.D.,* J. F. HAGEN, B.A.,t V. J. FRIEDt
Vasopressin has been used with increasing frequency to control gastrointestinal bleeding, the beneficial effect being attributed to marked splanchnic vasoconstriction. Because vasopressin may result in impaired cardiac function and because other potent vasoconstrictive substances have been shown to increase the pulmonary shunt and decrease arterial oxygenation, this study was undertaken to determine the effect of vasopressin on oxygen availability. Ten healthy anesthetized mechanically ventilated dogs received a five hour intravenous vasopressin infusion, 0.005 U/kg/min. The heart rate decreased moderately and briefly. The mean systemic arterial pressure increased and then decreased, both minimally. The pulmonary shunt and the arterial oxygen content decreased slightly. The total systemic resistance increased and the stroke volume decreased, both substantially. The pulmonary artery wedge pressure gradually increased. The oxygen availability decreased markedly. This study demonstrated that a vasopressin infusion causes a marked decrease in oxygen availability due primarily to a decreased stroke volume and, to a lesser extent during the first hour, to a decreased heart rate. The pulmonary shunt did not increase. Increased systemic resistance followed by a gradual increase in the pulmonary wedge pressure suggests that the decreased stroke volume resulted, at least in part, from an increased afterload and left ventricular failure. It is suggested that until the effect of vasopressin on the cardiopulmonary systems and hence oxygen availability is fully studied in critically ill patients, that it be used with caution and with appropriate hemodynamic monitoring.
been used with incontrol gastrointestinal v creasing frequency to bleeding, the beneficial effect being attributed to splanchnic vasoconstriction. Although vasopressin can result in a decrease in the cardiac output, even when given selectively via an intra-arterial infusion, and although other potent vasoconstrictors have been shown to result in a substantial increase in the pulmonary shunt and a decrease in arterial oxygenation, there have been no studies of the effect of vasopressin on
From the Department of Surgery, Case Western Reserve University School of Medicine and Metropolitan General Hospital, Cleveland, Ohio
oxygen availability. 1-3 Knowledge of the effect of vasopressin on oxygen availability is important because patients in whom vasopressin is used may have preexisting cardiopulmonary disease, or in the case of critically ill patients with stress bleeding, may have acute respiratory failure. The present study was prompted by the sudden progression of hypoxia and circulatory failure in several critically ill patients with stress bleeding, which appeared to coincide with a vasopressin infusion. Because the cardiopulmonary failure could have resulted from many causes in these critically ill patients, e.g., pre-existing cardiopulmonary disease, aggravated by sepsis, hypovolemia, and acute respiratory failure, this study was undertaken to determine, in a controlled setting, the effect of a vasopressin infusion on the pulmonary shunt, the cardiac output, and hence the oxygen availability. Methods
V ASOPRESSIN HAS RECENTLY
* Professor of Surgery, Case Western Reserve University School of Medicine. t Research Associate, Department of Surgery. Reprint requests: J. L. Berk, M.D., Metropolitan General Hospital, 3395 Scranton Rd., Cleveland, Ohio 44109.
Ten healthy, mongrel dogs weighing 15-20 kg were fed the afternoon prior to surgery, permitted water ad libitum until the time of surgery, and were anesthetized with intravenous pentobarbital sodium, 30 mg/kg. Ventilation was accomplished through a cuffed endotracheal tube by a mechanical respirator. Oxygenation and ventilation were satisfactory in a supine position in the control group and this position was therefore used in all groups. The animals were sighed every 20 minutes and suctioned as necessary. Non-occlusive catheters were placed in the femoral vein and the aorta, and a Swan-Ganz flowdirected catheterg was inserted into a foreleg vein and passed into the pulmonary artery, the location being determined by the oscilloscopic pressure tracing. Pulmonary and systemic pres-
0003-4932/79/0400/0439 $00.65 i) J. B. Lippincott Company
439
BERK, HAGEN AND FRIED
440
Ann. Surg. * April 1979
TABLE 1. Hemodynamic Changes in Dogs Receiving Vasopressin Infusion, 0.005 Ulkglmin Minutes
Control Heart rate Mean systemic pressure torr Total systemic resistance dyne*sec cm-5 Cardiac output ml/kg/min Mean pulmonary artery pressure-torr Pulmonary artery wedge pressure-torr Total pulmonary resistance dyne sec -cm 5 Shunt 4s/Q x 100 Arterial oxygen content vol % Oxygen transport ml/kg/min *
N
=
149 151
3940
8 5 t
250
15
30
105 ± 9* 164 ± 7*
113 + 8* 159 ± 6
9047 ± 706*
9340 ± 930*
8088 + 707*
6390 ± 566*
6101 ± 788*
5951 ± 708*
5528 ± 771*
82 ± 7*
76 ± 8*
82 ± 5*
100 ± 5*
107 ± 8*
104 ± 10*
118 ± 14*
5 133 ± 9 159 ± 4 6143 ± 1424*
60
123 148
120 5* 5
135 ± 7 144 ± 5
240
180 146 ± 8 143 ± 6
148 ± 9 134 ± 5*
300 155 t 8 137 ± 6
170 ± 14
150 ± 30
8 ± 0.9
6 ± 0.5
7 ± 0.8
7± 1
8 ±1
9± I
11 ± 1*
12 ± 1*
13 ± 2*
0.3 ± 0.7
1 ± 1
3
3±2
4 ± 1*
5 ± 1*
6 ± 1*
6 ± 2*
9 + 3*
218 ± 30
173 ± 29
182 ± 34
135 ± 18
226 ± 70
49
150 ± 24
9 ± 0.7
7 ± 0.8*
19.5 ± 0.8
19.4 ± 0.9
33 ± 8
30 ± 6
±
1*
1% ± 44 4 ± 0.3*
18.0
t
0.7
14 ± 1*
277 ± 62 4
t
0.6*
18.2 ± 0.8 14 ± 1*
5 ± 0.8*
17.9 ± 0.7 14 ± 0.9*
6 ± 0.7*
17.9 ± 0.7 17
0.7*
6 ± 0.9*
18.3 ± 0.7 19 + 1*
181
t
5 ± 0.9*
6 ± 1*
18.4
t
0.9
18.9 + 0.8
19
t
2*
22 ± 2*
10.
sures were measured by strain gauge manometers and continuously recorded. The zero point of the manometers were set at one-half the anteroposterior diameter of the chest. The pulmonary wedge pressure was obtained with the balloon inflated. Cardiac outputs were determined with a densitometer and computer by the dye dilution method using indocyanine green. Simultaneous samples of blood were withdrawn from the pulmonary artery and aorta during at least four respiratory cycles. Blood was analyzed for oxygen and carbon dioxide tensions and pH by the Clark, Severinghaus, and pH electrodes, respectively at 37°. Hemoglobin concentrations were measured by the cyanmethemoglobin method. Expired gases were collected in a Douglas bag for five minute periods and oxygen and carbon dioxide fractions were determined. Oxygen consumption and carbon dioxide production were calculated by the expired gas method and the respiratory quotient was determined. Measurements included cardiac output; mean systemic, pulmonary artery, and pulmonary artery wedge pressures; and Po2, Pco2, pH, and hemoglobin concentrations of mixed venous and arterial blood. After a steady state was achieved and control values obtained, a vasopressin infusion, 0.005 U/kg/min, was begun through the femoral vein. During the infusion measurements were made at five, 15, and 30 minutes and hourly thereafter for five hours. The shunt fraction, and systemic and pulmonary resistances were calculated as previously described.2 Oxygen availability, the product of the cardiac output and the arterial oxygen content, was calculated. Statistical analyses were by the students t-test.
Results The mean values of the hemodynamic changes together with the standard error of the mean are listed in Table 1. Statistically significant changes from control are indicated. The heart rate decreased moderately and after 30 minutes gradually returned to control. The mean systemic arterial pressure increased and then decreased, both minimally. The cardiac output decreased markedly and after one hour gradually increased, always remaining below control. The total systemic resistance immediately increased substantially, and after 30 minutes, gradually decreased, remaining well above control at all times. The pulmonary wedge pressure gradually increased. Both the pulmonary shunt and the arterial oxygen content decreased slightly. The oxygen availability immediately decreased markedly and after 1 hour gradually increased but always remained well below control.
Discussion This study demonstrated that a vasopressin infusion causes a substantial decrease in oxygen availability. The decreased oxygen availability resulted almost exclusively from a fall in the cardiac output due to a decreased stroke volume and to a lesser extent, in the first hour, to a decreased heart rate. The rapid increase in total systemic resistance followed by a gradual increase in the pulmonary wedge pressure suggests that the decreased stroke volume resulted from left ventricular failure which in turn resulted from vasoconstriction and an increased afterload. Coronary
Vol. 189 * No. 4
441
VASOPRESSIN AND OXYGEN AVAILABILITY
vasoconstriction, and a direct depressant effect of vasopressin on the myocardium very likely also conartery
tributed to the left heart failure.3
Previous studies involving catecholamine infusions demonstrated that those substances having a vasoconstrictive component cause a substantial increase in the pulmonary shunt due both to a direct effect on the pulmonary microcirculation and an increased cardiac output.1 The lack of an increase in the pulmonary vascular resistance suggests that vasopressin, in the dose used in this study, does not cause appreciable pulmonary vasoconstriction. Thus the decreased shunt can be explained by the decreased cardiac output. Because a vasopressin infusion can cause a marked decrease in oxygen availability in healthy dogs, it seems reasonable to conclude that vasopressin in similar
doses will result in at least as great a decrease in oxygen availability in patients who already have some degree of cardiopulmonary dysfunction. Until the effects of vasopressin on the cardiopulmonary systems and oxygen availability are fully studied in critically ill patients, it is suggested that it be used with caution and with appropriate hemodynamic monitoring. References 1. Berk, J. L., Hagen, J. F., Tong, R. K., et al.: The Role of Adrenergic Stimulation in the Pathogenesis of Pulmonary Insufficiency. Surgery, 82:366, 1977. 2. Berk, J. L., Hagen, J. F., Koo, R., et al.: Pulmonary Insufficiency Caused by Epinephrine. Ann. Surg., 178:423, 1973. 3. Corliss, R. J., McKenna, D. H., Sialer, S., et al.: Systemic and Coronary Hemodynamic Effects of Vasopressin. Am. J. Med. Sci., 256:293, 1968.
on
Oxygen Availability
J. L. BERK, M.D.,* J. F. HAGEN, B.A.,t V. J. FRIEDt
Vasopressin has been used with increasing frequency to control gastrointestinal bleeding, the beneficial effect being attributed to marked splanchnic vasoconstriction. Because vasopressin may result in impaired cardiac function and because other potent vasoconstrictive substances have been shown to increase the pulmonary shunt and decrease arterial oxygenation, this study was undertaken to determine the effect of vasopressin on oxygen availability. Ten healthy anesthetized mechanically ventilated dogs received a five hour intravenous vasopressin infusion, 0.005 U/kg/min. The heart rate decreased moderately and briefly. The mean systemic arterial pressure increased and then decreased, both minimally. The pulmonary shunt and the arterial oxygen content decreased slightly. The total systemic resistance increased and the stroke volume decreased, both substantially. The pulmonary artery wedge pressure gradually increased. The oxygen availability decreased markedly. This study demonstrated that a vasopressin infusion causes a marked decrease in oxygen availability due primarily to a decreased stroke volume and, to a lesser extent during the first hour, to a decreased heart rate. The pulmonary shunt did not increase. Increased systemic resistance followed by a gradual increase in the pulmonary wedge pressure suggests that the decreased stroke volume resulted, at least in part, from an increased afterload and left ventricular failure. It is suggested that until the effect of vasopressin on the cardiopulmonary systems and hence oxygen availability is fully studied in critically ill patients, that it be used with caution and with appropriate hemodynamic monitoring.
been used with incontrol gastrointestinal v creasing frequency to bleeding, the beneficial effect being attributed to splanchnic vasoconstriction. Although vasopressin can result in a decrease in the cardiac output, even when given selectively via an intra-arterial infusion, and although other potent vasoconstrictors have been shown to result in a substantial increase in the pulmonary shunt and a decrease in arterial oxygenation, there have been no studies of the effect of vasopressin on
From the Department of Surgery, Case Western Reserve University School of Medicine and Metropolitan General Hospital, Cleveland, Ohio
oxygen availability. 1-3 Knowledge of the effect of vasopressin on oxygen availability is important because patients in whom vasopressin is used may have preexisting cardiopulmonary disease, or in the case of critically ill patients with stress bleeding, may have acute respiratory failure. The present study was prompted by the sudden progression of hypoxia and circulatory failure in several critically ill patients with stress bleeding, which appeared to coincide with a vasopressin infusion. Because the cardiopulmonary failure could have resulted from many causes in these critically ill patients, e.g., pre-existing cardiopulmonary disease, aggravated by sepsis, hypovolemia, and acute respiratory failure, this study was undertaken to determine, in a controlled setting, the effect of a vasopressin infusion on the pulmonary shunt, the cardiac output, and hence the oxygen availability. Methods
V ASOPRESSIN HAS RECENTLY
* Professor of Surgery, Case Western Reserve University School of Medicine. t Research Associate, Department of Surgery. Reprint requests: J. L. Berk, M.D., Metropolitan General Hospital, 3395 Scranton Rd., Cleveland, Ohio 44109.
Ten healthy, mongrel dogs weighing 15-20 kg were fed the afternoon prior to surgery, permitted water ad libitum until the time of surgery, and were anesthetized with intravenous pentobarbital sodium, 30 mg/kg. Ventilation was accomplished through a cuffed endotracheal tube by a mechanical respirator. Oxygenation and ventilation were satisfactory in a supine position in the control group and this position was therefore used in all groups. The animals were sighed every 20 minutes and suctioned as necessary. Non-occlusive catheters were placed in the femoral vein and the aorta, and a Swan-Ganz flowdirected catheterg was inserted into a foreleg vein and passed into the pulmonary artery, the location being determined by the oscilloscopic pressure tracing. Pulmonary and systemic pres-
0003-4932/79/0400/0439 $00.65 i) J. B. Lippincott Company
439
BERK, HAGEN AND FRIED
440
Ann. Surg. * April 1979
TABLE 1. Hemodynamic Changes in Dogs Receiving Vasopressin Infusion, 0.005 Ulkglmin Minutes
Control Heart rate Mean systemic pressure torr Total systemic resistance dyne*sec cm-5 Cardiac output ml/kg/min Mean pulmonary artery pressure-torr Pulmonary artery wedge pressure-torr Total pulmonary resistance dyne sec -cm 5 Shunt 4s/Q x 100 Arterial oxygen content vol % Oxygen transport ml/kg/min *
N
=
149 151
3940
8 5 t
250
15
30
105 ± 9* 164 ± 7*
113 + 8* 159 ± 6
9047 ± 706*
9340 ± 930*
8088 + 707*
6390 ± 566*
6101 ± 788*
5951 ± 708*
5528 ± 771*
82 ± 7*
76 ± 8*
82 ± 5*
100 ± 5*
107 ± 8*
104 ± 10*
118 ± 14*
5 133 ± 9 159 ± 4 6143 ± 1424*
60
123 148
120 5* 5
135 ± 7 144 ± 5
240
180 146 ± 8 143 ± 6
148 ± 9 134 ± 5*
300 155 t 8 137 ± 6
170 ± 14
150 ± 30
8 ± 0.9
6 ± 0.5
7 ± 0.8
7± 1
8 ±1
9± I
11 ± 1*
12 ± 1*
13 ± 2*
0.3 ± 0.7
1 ± 1
3
3±2
4 ± 1*
5 ± 1*
6 ± 1*
6 ± 2*
9 + 3*
218 ± 30
173 ± 29
182 ± 34
135 ± 18
226 ± 70
49
150 ± 24
9 ± 0.7
7 ± 0.8*
19.5 ± 0.8
19.4 ± 0.9
33 ± 8
30 ± 6
±
1*
1% ± 44 4 ± 0.3*
18.0
t
0.7
14 ± 1*
277 ± 62 4
t
0.6*
18.2 ± 0.8 14 ± 1*
5 ± 0.8*
17.9 ± 0.7 14 ± 0.9*
6 ± 0.7*
17.9 ± 0.7 17
0.7*
6 ± 0.9*
18.3 ± 0.7 19 + 1*
181
t
5 ± 0.9*
6 ± 1*
18.4
t
0.9
18.9 + 0.8
19
t
2*
22 ± 2*
10.
sures were measured by strain gauge manometers and continuously recorded. The zero point of the manometers were set at one-half the anteroposterior diameter of the chest. The pulmonary wedge pressure was obtained with the balloon inflated. Cardiac outputs were determined with a densitometer and computer by the dye dilution method using indocyanine green. Simultaneous samples of blood were withdrawn from the pulmonary artery and aorta during at least four respiratory cycles. Blood was analyzed for oxygen and carbon dioxide tensions and pH by the Clark, Severinghaus, and pH electrodes, respectively at 37°. Hemoglobin concentrations were measured by the cyanmethemoglobin method. Expired gases were collected in a Douglas bag for five minute periods and oxygen and carbon dioxide fractions were determined. Oxygen consumption and carbon dioxide production were calculated by the expired gas method and the respiratory quotient was determined. Measurements included cardiac output; mean systemic, pulmonary artery, and pulmonary artery wedge pressures; and Po2, Pco2, pH, and hemoglobin concentrations of mixed venous and arterial blood. After a steady state was achieved and control values obtained, a vasopressin infusion, 0.005 U/kg/min, was begun through the femoral vein. During the infusion measurements were made at five, 15, and 30 minutes and hourly thereafter for five hours. The shunt fraction, and systemic and pulmonary resistances were calculated as previously described.2 Oxygen availability, the product of the cardiac output and the arterial oxygen content, was calculated. Statistical analyses were by the students t-test.
Results The mean values of the hemodynamic changes together with the standard error of the mean are listed in Table 1. Statistically significant changes from control are indicated. The heart rate decreased moderately and after 30 minutes gradually returned to control. The mean systemic arterial pressure increased and then decreased, both minimally. The cardiac output decreased markedly and after one hour gradually increased, always remaining below control. The total systemic resistance immediately increased substantially, and after 30 minutes, gradually decreased, remaining well above control at all times. The pulmonary wedge pressure gradually increased. Both the pulmonary shunt and the arterial oxygen content decreased slightly. The oxygen availability immediately decreased markedly and after 1 hour gradually increased but always remained well below control.
Discussion This study demonstrated that a vasopressin infusion causes a substantial decrease in oxygen availability. The decreased oxygen availability resulted almost exclusively from a fall in the cardiac output due to a decreased stroke volume and to a lesser extent, in the first hour, to a decreased heart rate. The rapid increase in total systemic resistance followed by a gradual increase in the pulmonary wedge pressure suggests that the decreased stroke volume resulted from left ventricular failure which in turn resulted from vasoconstriction and an increased afterload. Coronary
Vol. 189 * No. 4
441
VASOPRESSIN AND OXYGEN AVAILABILITY
vasoconstriction, and a direct depressant effect of vasopressin on the myocardium very likely also conartery
tributed to the left heart failure.3
Previous studies involving catecholamine infusions demonstrated that those substances having a vasoconstrictive component cause a substantial increase in the pulmonary shunt due both to a direct effect on the pulmonary microcirculation and an increased cardiac output.1 The lack of an increase in the pulmonary vascular resistance suggests that vasopressin, in the dose used in this study, does not cause appreciable pulmonary vasoconstriction. Thus the decreased shunt can be explained by the decreased cardiac output. Because a vasopressin infusion can cause a marked decrease in oxygen availability in healthy dogs, it seems reasonable to conclude that vasopressin in similar
doses will result in at least as great a decrease in oxygen availability in patients who already have some degree of cardiopulmonary dysfunction. Until the effects of vasopressin on the cardiopulmonary systems and oxygen availability are fully studied in critically ill patients, it is suggested that it be used with caution and with appropriate hemodynamic monitoring. References 1. Berk, J. L., Hagen, J. F., Tong, R. K., et al.: The Role of Adrenergic Stimulation in the Pathogenesis of Pulmonary Insufficiency. Surgery, 82:366, 1977. 2. Berk, J. L., Hagen, J. F., Koo, R., et al.: Pulmonary Insufficiency Caused by Epinephrine. Ann. Surg., 178:423, 1973. 3. Corliss, R. J., McKenna, D. H., Sialer, S., et al.: Systemic and Coronary Hemodynamic Effects of Vasopressin. Am. J. Med. Sci., 256:293, 1968.
