British Journal of Anaesthesia 1991; 67: 618-620
HAEMODYNAMIC EFFECTS OF PROPOFOL: INDUCTION WITH 2.5 MG K G 1 J. E. FAIRFIELD, A. DRITSAS AND R. J. BEALE
SUMMARY Serial measurements of haemodynamic variables were performed at 1-min intervals in nine ASA I, unpremedicated patients before and for 5 min after induction of anaesthesia with propofol 2.5 mg kg'1. End-tidal carbon dioxide concentration was maintained within the normal range. Stroke volume and left ventricular function were measured by Doppler and cross-sectional echocardiography at the aortic valve. Systemic arterial pressure was measured by automated oscillotonometry and heart rate by electrocardiograph. Stroke volume, cardiac output, systemic vascular resistance, left ventricular stroke work and rate-pressure product were calculated. There was a decrease at all time points in systolic, mean and diastolic arterial pressure. There was an initial increase in heart rate and cardiac output, with a subsequent decrease to less than baseline. There was an initial decrease in systemic vascular resistance followed by partial recovery, and a delayed decrease in left ventricular function as measured by peak aortic blood flow velocity and acceleration. KEY WORDS Measurement techniques: Doppler ultrasound, echocardiography. Anaesthetics, intravenous: propofol.
Propofol has been shown consistently to cause a decrease in arterial pressure; decreases in both systemic vascular resistance and cardiac output have been reported. However, interpretation of some studies is complicated by the use of other drugs which affect the cardiovascular system, or the inclusion of patients with cardiovascular disease. We have used the technique of Doppler echocardiography, combined with automated noninvasive recording of arterial pressure to in-
vestigate the effects of an induction dose of propofol on the cardiovascular system of young, ASA I unpremedicated adults. METHODS AND RESULTS
With Ethics Committee approval, we studied 15 unpremedicated ASA I patients undergoing extraction of wisdom teeth under general anaesthesia. Under local anaesthesia, a 16-gauge cannula was inserted into a large forearm vein. Baseline measurements of arterial pressure, heart rate and ascending aortic flow were made using a Datex Cardiocap non-invasive arterial pressure monitor, and a Vingmed Sonotron CFM 750 continuous wave Doppler echocardiograph. Ascending aortic blood flow was studied using a 1.9MHz M-mode transducer positioned in the suprasternal notch. Anaesthesia was induced with propofol 2.5 mg kg"1 (mixed with lignocaine 0.125 mg kg"1) given over 20 s. When consciousness was lost, 100% oxygen was administered via a Bain type coaxial breathing system. End-tidal carbon dioxide concentration was measured at the face mask using the Datex Cardiocap and ventilation was assisted to maintain the measured end-tidal carbon dioxide concentration constant. The electrocardiogram (with measured heart rate) was displayed continuously and arterial pressure was measured before induction and at 1 -min intervals thereafter. The aortic blood velocity profile was recorded
J. E. F AIRFIELD, M.B., CH.B., F.C.ANAES., R. J. HEALS, M.B., B.S., F.C.ANAES. (Department of Anaesthetics); A. DRITSAS*, M.D.
(Department of Cardiology); United Medical and Dental Schools, Guy's Hospital, London SE1 9RT. Accepted for Publication: June 8, 1991. •Present address: Department of Cardiology, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London W12 0NN.
HAEMODYNAMIC EFFECTS OF PROPOFOL
619
TABLE I. Mean values for all the measured and calculated haemodynamic variables ( 9 5 % confidence intervals for the mean) before induction of anaesthesia with propofol 2.5 mg kg'' and at 1-im'n intervals for 5 min thereafter in nine patients, together with the probabilities, calculated by the paired t test, that the measured changes differ from baseline by chance alone Time after induction (min)
Mean arterial pressure (mmHg)
Baseline
1
2
3
4
5
88 (83-92)
1.18 (1.01-1.34)
78 (68-88) 0.017 81 (73-89) 0.037 1.26 (1.11-1.40)
74 (68-79) < 0.001 72 (64-81) 0.70 1.13 (1.04-1.23)
70 (62-78) 0.003 71 (64-77) 0.83 1.10 (1.01-1.19)
68 (62-74) < 0.001 65 (60-71) 0.053 1.05 (0.95-1.15)
67 (63-71) < 0.001 65 (58-71) 0.012 1.10 (1.00-1.20)
19.5 (15.1-23.9)
0.13 20.4 (16.6-24.1)
0.48 19.3 (16.0-22.5)
0.14 18.9 (15.7-22.2)
0.031 18.4 (15.3-21.4)
0.14 18.5 (14.8-22.3)
1505 (1224-1786)
0.11 69.1 (61.4-76.8) 0.39 5.58 (5.00-6.16) 0.050 1145 (947-1344)
0.70 66.5 (59.8-73.2) 0.29 4.80 (4.30-5.31) 0.81 1260 (1107-1413)
0.37 65.1 ' (58.4-71:9) 0.056 4.62 (4.02-5.21) 0.34 1261 (1043-1479)
0.18 64.1 (57.5-70.8) 0.023 4.19 (3.78-^1.59) 0.020 1322 (1157-1486)
0.14 64.7 (56.4-73.0) 0.019 4.18 (3.74-^1.62) 0.002 1323 (1128-1518)
74.5 (67.9-81.2)
0.005 66.4 (57.3-75.4)
0.029 60.6 (55.4-65.7)
0.042 56.1 (50.1-62.1)
0.079 53.2 (47.5-58.8)
0.023 53.1 (46.9-59.3)
0.069 6443 (5252-7633) 0.80
< 0.001 5474 (4492-6456) 0.015
< 0.001 5067 (4157-5977) 0.003
< 0.001 4524 (3757-5290) < 0.001
< 0.001 4430 (3859-5001) < 0.001
P Heart rate (beat min"1) P Peak aortic blood velocity (m s-1) P Peak aortic blood acceleration (m »-«)
71 (64-79)
P Stroke volume (ml)
68.2 59.9-76.5)
P Cardiac output (litre min"1) P Systemic vascular resistance (dyn s cm"6) P Left ventricular stroke work (gm) P Rate-pressure product (beat min"1 mm Hg) P
4.87 (4.15-5.59)
6324 (5466-7183)
onto video tape for later analysis. After 5 min the study was concluded, an additional dose of propofol was administered and anaesthesia and surgery then proceeded as normal. The video tape recordings of aortic blood flow made before induction and at 1, 2, 3, 4 and 5 min after induction were analysed. At each time point, mean values were derived for peak aortic blood velocity, peak aortic blood acceleration and aortic blood velocity integral. From the Doppler measured variables, measured aortic root diameter (which we assumed did not change during the course of the study), measured arterial pressure and measured heart rate, we were able to calculate stroke volume, left ventricular stroke work, cardiac output, systemic vascular resistance and rate-pressure product. The data from four patients were not analysed: one because an additional dose of propofol was
required to induce anaesthesia, and three because the aortic flow measurements were technically unsatisfactory. Two other patients were very anxious, with pre-induction heart rates greater than 100 beat min"1; data from these two patients are not included in the results. The mean age of the nine patients (five male) for whom results are reported was 23 yr (95 % confidence interval (CI) 20-26), mean weight 67 kg (95 % CI 59-75). Immediately after injection of propofol there was a marked reduction in systemic vascular resistance (32%), tachycardia (15%), and increased cardiac output (18%), but no significant change in stroke volume. The decrease in systemic vascular resistance predominated and the mean arterial pressure decreased (11%). There was a small increase in both peak aortic blood flow (8 %) and acceleration (6 %).
BRITISH JOURNAL OF ANAESTHESIA
620
From about 2 min after injection of propofol and until the end of the study, systemic vascular resistance returned towards the resting value, but even after 5 min it was less than baseline (11 %). The heart rate decreased to less than baseline (8%), despite the less than normal systemic vascular resistance. Stroke volume decreased slightly (5.5 %) and there was a progressive reduction in cardiac output (15 %). Mean arterial pressure decreased further (33%). Peak aortic blood acceleration and velocity decreased (3% and 9%, respectively). As would be expected from a simultaneous reduction in stroke volume, mean arterial pressure and heart rate, both the left ventricular stroke work and the rate-pressure product were reduced (28% and 29%, respectively). Mean measured and derived haemodynamic variables for the group, 95 % CI for the means and P values calculated for the difference from baseline using the paired t test (no allowance made for the effect of multiple tests) are presented in table I. COMMENT
It is now well recognized that induction of anaesthesia with propofol causes a reduction in systemic arterial pressure, reportedly because of decrease in cardiac output [1], decrease in systemic vascular resistance [2], or both [3]. In this study we used the technique of Doppler aortic blood flow velocity measurement together with cross-sectional echocardiography to calculate stroke volume, peak aortic blood velocity and peak aortic blood acceleration. The principles and practice of the use of Doppler ultrasound for blood flow determination have been described previously [4]. Propofol appears to have a biphasic effect on the cardiovascular system. First, immediately after injection, the decrease in systemic vascular resistance predominated and the mean arterial pressure decreased, despite an increase in heart rate. From the time sequence it is likely that the
tachycardia was baroreflex mediated, although a direct myocardial or central effect can not be excluded. In view of the known effects of vasodilatation on peak aortic blood flow and acceleration, the increase in these variables does not necessarily imply an increase in myocardial contractility. Second, from about 2 min after injection, despite the less than normal systemic vascular resistance, heart rate and stroke volume decreased to less than baseline. These results are consistent with the findings that the baroreceptor reflex is "reset" at a smaller pressure value than normal by propofol [5]. The indices of left ventricular function were reduced, despite the continued decreased systemic vascular resistance; this may reflect either direct myocardial depression or a reduction in ventricular filling as a result of the peripheral vasodilatation. These results help to explain differences found between previous studies. Propofol appears to affect the cardiovascular system in a biphasic manner. First, there is a marked reduction in systemic vascular resistance with an associated tachycardia, an increase in cardiac output and a decrease in arterial pressure. Second, the systemic vascular resistance increases towards normal, there is a decrease in heart rate and cardiac output, and a further decrease in arterial pressure. REFERENCES 1. Lepage JM, Pinaud ML, Helias JH, Juge CM, Cozian AY, Farinotti R, Souron R. Left ventricular function during propofol and fentanyl anesthesia in patients with coronary artery disease: Assessment with a radionuclide approach. Anesthesia and Analgesia 1988; 67: 949-955. 2. Lipman M, Paicius R, Gingerich S, Owens R, Mok MS, Chamey J, Lee TS, Harley D, Verespej J, Appel P. A controlled study of the hemodynamic effects of propofol vs thiopental during anesthesia induction. Anesthesia and Analgesia 1986; 65: S89. 3. Grounds RM, Twigley AJ, Carli JG, Whitwam JG, Morgan M. The haemodynamic effects of intravenous induction. Anaesthesia 1985; 40: 735-740. 4. Vieli A. Doppler flow determination. British Journal of Anaesthesia 1988; 60: 107S-112S. 5. Cullen PM, Turtle M, Prys-Roberts C, Way WL, Dye J. Effect of propofol anesthesia on baroreflex activity in humans. Anesthesia and Analgesia 1987; 66: 1115-1120.
HAEMODYNAMIC EFFECTS OF PROPOFOL: INDUCTION WITH 2.5 MG K G 1 J. E. FAIRFIELD, A. DRITSAS AND R. J. BEALE
SUMMARY Serial measurements of haemodynamic variables were performed at 1-min intervals in nine ASA I, unpremedicated patients before and for 5 min after induction of anaesthesia with propofol 2.5 mg kg'1. End-tidal carbon dioxide concentration was maintained within the normal range. Stroke volume and left ventricular function were measured by Doppler and cross-sectional echocardiography at the aortic valve. Systemic arterial pressure was measured by automated oscillotonometry and heart rate by electrocardiograph. Stroke volume, cardiac output, systemic vascular resistance, left ventricular stroke work and rate-pressure product were calculated. There was a decrease at all time points in systolic, mean and diastolic arterial pressure. There was an initial increase in heart rate and cardiac output, with a subsequent decrease to less than baseline. There was an initial decrease in systemic vascular resistance followed by partial recovery, and a delayed decrease in left ventricular function as measured by peak aortic blood flow velocity and acceleration. KEY WORDS Measurement techniques: Doppler ultrasound, echocardiography. Anaesthetics, intravenous: propofol.
Propofol has been shown consistently to cause a decrease in arterial pressure; decreases in both systemic vascular resistance and cardiac output have been reported. However, interpretation of some studies is complicated by the use of other drugs which affect the cardiovascular system, or the inclusion of patients with cardiovascular disease. We have used the technique of Doppler echocardiography, combined with automated noninvasive recording of arterial pressure to in-
vestigate the effects of an induction dose of propofol on the cardiovascular system of young, ASA I unpremedicated adults. METHODS AND RESULTS
With Ethics Committee approval, we studied 15 unpremedicated ASA I patients undergoing extraction of wisdom teeth under general anaesthesia. Under local anaesthesia, a 16-gauge cannula was inserted into a large forearm vein. Baseline measurements of arterial pressure, heart rate and ascending aortic flow were made using a Datex Cardiocap non-invasive arterial pressure monitor, and a Vingmed Sonotron CFM 750 continuous wave Doppler echocardiograph. Ascending aortic blood flow was studied using a 1.9MHz M-mode transducer positioned in the suprasternal notch. Anaesthesia was induced with propofol 2.5 mg kg"1 (mixed with lignocaine 0.125 mg kg"1) given over 20 s. When consciousness was lost, 100% oxygen was administered via a Bain type coaxial breathing system. End-tidal carbon dioxide concentration was measured at the face mask using the Datex Cardiocap and ventilation was assisted to maintain the measured end-tidal carbon dioxide concentration constant. The electrocardiogram (with measured heart rate) was displayed continuously and arterial pressure was measured before induction and at 1 -min intervals thereafter. The aortic blood velocity profile was recorded
J. E. F AIRFIELD, M.B., CH.B., F.C.ANAES., R. J. HEALS, M.B., B.S., F.C.ANAES. (Department of Anaesthetics); A. DRITSAS*, M.D.
(Department of Cardiology); United Medical and Dental Schools, Guy's Hospital, London SE1 9RT. Accepted for Publication: June 8, 1991. •Present address: Department of Cardiology, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London W12 0NN.
HAEMODYNAMIC EFFECTS OF PROPOFOL
619
TABLE I. Mean values for all the measured and calculated haemodynamic variables ( 9 5 % confidence intervals for the mean) before induction of anaesthesia with propofol 2.5 mg kg'' and at 1-im'n intervals for 5 min thereafter in nine patients, together with the probabilities, calculated by the paired t test, that the measured changes differ from baseline by chance alone Time after induction (min)
Mean arterial pressure (mmHg)
Baseline
1
2
3
4
5
88 (83-92)
1.18 (1.01-1.34)
78 (68-88) 0.017 81 (73-89) 0.037 1.26 (1.11-1.40)
74 (68-79) < 0.001 72 (64-81) 0.70 1.13 (1.04-1.23)
70 (62-78) 0.003 71 (64-77) 0.83 1.10 (1.01-1.19)
68 (62-74) < 0.001 65 (60-71) 0.053 1.05 (0.95-1.15)
67 (63-71) < 0.001 65 (58-71) 0.012 1.10 (1.00-1.20)
19.5 (15.1-23.9)
0.13 20.4 (16.6-24.1)
0.48 19.3 (16.0-22.5)
0.14 18.9 (15.7-22.2)
0.031 18.4 (15.3-21.4)
0.14 18.5 (14.8-22.3)
1505 (1224-1786)
0.11 69.1 (61.4-76.8) 0.39 5.58 (5.00-6.16) 0.050 1145 (947-1344)
0.70 66.5 (59.8-73.2) 0.29 4.80 (4.30-5.31) 0.81 1260 (1107-1413)
0.37 65.1 ' (58.4-71:9) 0.056 4.62 (4.02-5.21) 0.34 1261 (1043-1479)
0.18 64.1 (57.5-70.8) 0.023 4.19 (3.78-^1.59) 0.020 1322 (1157-1486)
0.14 64.7 (56.4-73.0) 0.019 4.18 (3.74-^1.62) 0.002 1323 (1128-1518)
74.5 (67.9-81.2)
0.005 66.4 (57.3-75.4)
0.029 60.6 (55.4-65.7)
0.042 56.1 (50.1-62.1)
0.079 53.2 (47.5-58.8)
0.023 53.1 (46.9-59.3)
0.069 6443 (5252-7633) 0.80
< 0.001 5474 (4492-6456) 0.015
< 0.001 5067 (4157-5977) 0.003
< 0.001 4524 (3757-5290) < 0.001
< 0.001 4430 (3859-5001) < 0.001
P Heart rate (beat min"1) P Peak aortic blood velocity (m s-1) P Peak aortic blood acceleration (m »-«)
71 (64-79)
P Stroke volume (ml)
68.2 59.9-76.5)
P Cardiac output (litre min"1) P Systemic vascular resistance (dyn s cm"6) P Left ventricular stroke work (gm) P Rate-pressure product (beat min"1 mm Hg) P
4.87 (4.15-5.59)
6324 (5466-7183)
onto video tape for later analysis. After 5 min the study was concluded, an additional dose of propofol was administered and anaesthesia and surgery then proceeded as normal. The video tape recordings of aortic blood flow made before induction and at 1, 2, 3, 4 and 5 min after induction were analysed. At each time point, mean values were derived for peak aortic blood velocity, peak aortic blood acceleration and aortic blood velocity integral. From the Doppler measured variables, measured aortic root diameter (which we assumed did not change during the course of the study), measured arterial pressure and measured heart rate, we were able to calculate stroke volume, left ventricular stroke work, cardiac output, systemic vascular resistance and rate-pressure product. The data from four patients were not analysed: one because an additional dose of propofol was
required to induce anaesthesia, and three because the aortic flow measurements were technically unsatisfactory. Two other patients were very anxious, with pre-induction heart rates greater than 100 beat min"1; data from these two patients are not included in the results. The mean age of the nine patients (five male) for whom results are reported was 23 yr (95 % confidence interval (CI) 20-26), mean weight 67 kg (95 % CI 59-75). Immediately after injection of propofol there was a marked reduction in systemic vascular resistance (32%), tachycardia (15%), and increased cardiac output (18%), but no significant change in stroke volume. The decrease in systemic vascular resistance predominated and the mean arterial pressure decreased (11%). There was a small increase in both peak aortic blood flow (8 %) and acceleration (6 %).
BRITISH JOURNAL OF ANAESTHESIA
620
From about 2 min after injection of propofol and until the end of the study, systemic vascular resistance returned towards the resting value, but even after 5 min it was less than baseline (11 %). The heart rate decreased to less than baseline (8%), despite the less than normal systemic vascular resistance. Stroke volume decreased slightly (5.5 %) and there was a progressive reduction in cardiac output (15 %). Mean arterial pressure decreased further (33%). Peak aortic blood acceleration and velocity decreased (3% and 9%, respectively). As would be expected from a simultaneous reduction in stroke volume, mean arterial pressure and heart rate, both the left ventricular stroke work and the rate-pressure product were reduced (28% and 29%, respectively). Mean measured and derived haemodynamic variables for the group, 95 % CI for the means and P values calculated for the difference from baseline using the paired t test (no allowance made for the effect of multiple tests) are presented in table I. COMMENT
It is now well recognized that induction of anaesthesia with propofol causes a reduction in systemic arterial pressure, reportedly because of decrease in cardiac output [1], decrease in systemic vascular resistance [2], or both [3]. In this study we used the technique of Doppler aortic blood flow velocity measurement together with cross-sectional echocardiography to calculate stroke volume, peak aortic blood velocity and peak aortic blood acceleration. The principles and practice of the use of Doppler ultrasound for blood flow determination have been described previously [4]. Propofol appears to have a biphasic effect on the cardiovascular system. First, immediately after injection, the decrease in systemic vascular resistance predominated and the mean arterial pressure decreased, despite an increase in heart rate. From the time sequence it is likely that the
tachycardia was baroreflex mediated, although a direct myocardial or central effect can not be excluded. In view of the known effects of vasodilatation on peak aortic blood flow and acceleration, the increase in these variables does not necessarily imply an increase in myocardial contractility. Second, from about 2 min after injection, despite the less than normal systemic vascular resistance, heart rate and stroke volume decreased to less than baseline. These results are consistent with the findings that the baroreceptor reflex is "reset" at a smaller pressure value than normal by propofol [5]. The indices of left ventricular function were reduced, despite the continued decreased systemic vascular resistance; this may reflect either direct myocardial depression or a reduction in ventricular filling as a result of the peripheral vasodilatation. These results help to explain differences found between previous studies. Propofol appears to affect the cardiovascular system in a biphasic manner. First, there is a marked reduction in systemic vascular resistance with an associated tachycardia, an increase in cardiac output and a decrease in arterial pressure. Second, the systemic vascular resistance increases towards normal, there is a decrease in heart rate and cardiac output, and a further decrease in arterial pressure. REFERENCES 1. Lepage JM, Pinaud ML, Helias JH, Juge CM, Cozian AY, Farinotti R, Souron R. Left ventricular function during propofol and fentanyl anesthesia in patients with coronary artery disease: Assessment with a radionuclide approach. Anesthesia and Analgesia 1988; 67: 949-955. 2. Lipman M, Paicius R, Gingerich S, Owens R, Mok MS, Chamey J, Lee TS, Harley D, Verespej J, Appel P. A controlled study of the hemodynamic effects of propofol vs thiopental during anesthesia induction. Anesthesia and Analgesia 1986; 65: S89. 3. Grounds RM, Twigley AJ, Carli JG, Whitwam JG, Morgan M. The haemodynamic effects of intravenous induction. Anaesthesia 1985; 40: 735-740. 4. Vieli A. Doppler flow determination. British Journal of Anaesthesia 1988; 60: 107S-112S. 5. Cullen PM, Turtle M, Prys-Roberts C, Way WL, Dye J. Effect of propofol anesthesia on baroreflex activity in humans. Anesthesia and Analgesia 1987; 66: 1115-1120.
