British Journal of Anaesthesia 1992; 69: 36-39
HAEMODYNAMIC EFFECTS OF ISOFLURANE DURING PROPOFOL ANAESTHESIA C. VERBORGH, D. VERBESSEM AND F. CAMU
SUMMARY
KEY WORDS Anaesthetics, intravenous: propofol. Anaesthetics, volatile: isoflurane. Arterial pressure: drug effects. Heart: haemodynamic effects.
The use of isoflurane for inducing hypotension during neurosurgery is well established [1,2]. Its haemodynamic effects have been studied in volunteers breadiing room air [3] and in surgical patients receiving nitrous oxide [4]. Because of its favourable pharmacokinetic [5—7] and cerebrovascular [8,9] profile, propofol is used increasingly for maintenance of anaesthesia during neurosurgery. However, haemodynamic properties of isoflurane during propofol anaesthesia have not yet been documented. As both isoflurane and propofol reduce systemic vascular resistance (SVR) in a dose-dependent manner, [3, 10], we felt that haemodynamic evaluation of simultaneous use was indicated before further clinical evaluation as a hypotensive technique. Therefore we designed this cross-over dose-response study in which the haemodynamic responses to different concentrations of isoflurane during continuous administration of propofol were evaluated.
TABLE I. Sequence of isoflurane administration (MAC) Patient No. 1
2 3 4 5 6 7 8 9 10
MAC sequence 0.00 0.75 1.00 1.00 0.00 0.75 0.25 0.50 0.25 0.50
0.50 1.00 0.00 0.00 0.75 0.25 0.50 0.25 0.75 1.00
0.75 0.00 0.50 0.25 1.00 1.00 0.00 0.75 0.50 0.25
0.25 0.25 0.75 0.75 0.50 0.50 1.00 0.00 1.00 0.00
1.00 0.50 0.25 0.50 0.25 0.00 0.75 1.00 0.00 0.75
CHRISTIAN VERBORGH*, M.D. ; DAISY VERBESSEM, M.D. ; FREDERIC
PATIENTS AND METHODS
The study was approved by the University Ethics Committee. We studied patients, ASA I—II, undergoing major surgery. Patient consent was obtained
CAMU, M.D.; Department of Anaesthesiology, Flemish Free University of Brussels, Brussels, Belgium. Accepted for Publication: January 6, 1992. •Address for correspondence: Academish Ziekenhuis V.U.B., Department Anesthesiologie, Laarbeeklaan 101, B-1090 Brussels, Belgium.
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We have studied haemodynamic responses to 0, 0.25, 0.5, 0.75 and 1 MAC isoflurane administration in 10 patients during a zero-order propofol infusion and normocapnia. Isoflurane reduced mean arterial pressure (MAP), systemic vascular resistance and left ventricular stroke work in a dose-dependent manner (29%, 38% and 33%. respectively, at 1 MAC), while cardiac output (CO), stroke volume (SV) and heart rate were not affected significantly. Mean pulmonary artery pressure, pulmonary vascular resistance and right ventricular stroke work decreased by 13%, 10% and 17%, respectively (not significant). -Pulmonary capillary wedge pressure and central venous pressure were affected minimally, while intrapulmonary shunting and PaOj remained constant. It is concluded that administration of isoflurane during infusion of propofol caused a dose-dependent decrease in MAP as a result of afterload reduction without modification in CO or SV.
the day before surgery. No patient had a history of pulmonary, cardiac, hepatic or renal disease. Premedication was with lorazepam 1 mg orally. After arrival of the patient in theatre, an i.v. cannula was inserted and 5 % glucose in Ringer solution was administered at a rate of 20 ml h"1. Anaesthesia was induced with a three-step infusion of propofol: 0.35 mg kg"1 min"1 for 5 min, 0.2 mg kg"1 min"1 for 10 min and 0.1 mg kg"1 min"1 for the remainder of the observation period. After loss of consciousness, pancuronium 0.08 mg kg"1 was given, the trachea intubated and lungs ventilated with 40 % oxygen in air. End-tidal carbon dioxide partial pressure was maintained at 5.5 kPa (Capnomac, Datex). A SwanGanz catheter was inserted. Different concentrations of isoflurane (0, 0.25, 0.50, 0.75 and 1 MAC) were administered in random sequence (table I) and between the different steps sufficient time was provided to allow equilibrium to occur as judged by inspiratory and expiratory measurements of isoflurane concentrations (Capnomac, Datex, Finland). At each step, heart rate (HR), systemic arterial pressure (SAP), central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP) and mean pulmonary artery pressure (MPAP) were recorded (HP 78353A) and cardiac output (CO) was measured in triplicate (Edwards CO computer). Blood-gas analysis was obtained at 0,0.5 and 1 MAC isoflurane (Instrumentation Laboratory BGM 1312). Haemodynamic variables were recorded when they
ISOFLURANE-PROPOFOL HAEMODYNAMICS
37
TABLE II. Haemodynamic variables (mean (SEM). * P < 0.05; ** P < 0.01 compared with MAC 0 MAC isofluraae
HR (beat min"1) CO (litre min"1) SV (ml min-1) SAP (mm Hg) CVP (mm Hg) MPAP (mm Hg) PCWP (mm Hg)
0.00
0.25
0.50
72(4) 6.4 (0.5) 91(7) 83(4) 5(2) 15(2) 8(2)
74(4) 7.0 (0.5) 96(6) 72 (4)* 4(1) 14(2) 7(2)
74(4) 6.9 (0.5) 94(5) 65 (4)** 4(1) 13(1) 6(1)
0.75
1.00
75(4) 75(4) 6.6 (0.5) 6.6 (0.5) 88(5) 87(5) 62 (3)** 59 (2)** 4(1) 4(1) 13(1) 13(1) 7(1) 6(1)
TABLE III. Calculated haemodynamic variables (mean (SEM). **P < 0.01 compared with MAC 0 MAC isoflurane
SVR
(dyn s cm"6) PVR
(dyn s cm"5) LVSW (g m bear 1 ) RVSW (g m bear 1 ) (Ca^ — CvoJ
(ml dl"1) Do, (ml min"1) Ko, (ml min"1) ERo, (%) Qs/Qt (%)
1019 (80)
0.25 801 (70)**
0.50 742 (77)**
0.75
1.00
718(61)**
689 (51)**
91 (16)
85(11)
85(7)
84(9)
82(11)
93(9)
87(10)
76 (7)**
66 (6)**
62 (5)**
12(1)
12(1)
11(1)
11(1)
10(1)
3.2(0.1)
3.1(0.1)
3.2 (0.3)
1275 (134) 202(17) 0.16(0.01) 1.6(0.1)
1367 (127) 215(21) 0.16(0.01) 1.5(0.1)
1294(111) 205(18) 0.16(0.01) 1.6(0.1)
were stable after the equilibration period. After the study, fentanyl and pancuronium were administered and surgery commenced. Using standard formulae, the following variables were calculated: stroke volume (SV), systemic and pulmonary vascular resistance (SVR, PVR), left and right ventricular stroke work (LVSW, RVSW). Oxygen consumption (Vo2), oxygen delivery (Z>o2), oxygen extraction ratio (ERos), arteriovenous oxygen difference (CaOi — CvOi) and shunt fraction (Qs/Qt) were also calculated. Data were analysed statistically by one-way analysis of variance and Wilcoxon signed rank test as appropriate.
RESULTS
. We studied 10 patients (six male) of mean age 48 yr (range 30-61 yr), mean weight 76 (SEM 3) kg (range 62-90 kg), mean height 171 (3) cm (range 154187 cm) and mean body surface area 1.88 (0.04) m1 (range 1.70-2.03 m1). The mean (SEM) time between start of the propofol infusion and the first measurement was 51 (7) min. Mean time between measurements was 14 (5) min. As three consecutive cardiac output measurements were performed for one evaluation, necessitating 10 ml of saline on each attempt, total fluid infusion rate was approximately 140 ml h"1. Compared with control values, maximum increase in HR was 4% (table II). SV increased initially by 5% with small MAC values, but was reduced by 4 % at 1 MAC isoflurane. CO increased by 9 % at
0.25 MAC and 3 % at 1 MAC. None of these changes was significant. A dose-dependent and significant reduction in SAP was apparent at 0.25 MAC and there was a 29% decrease at 1 MAC (P < 0.01). SVR decreased gradually with increasing isoflurane concentrations and was reduced to a minimum at 1 MAC (P < 0.01), which corresponded to a 38% reduction compared with control values (table III). The calculated LVSW showed a similar decrease, to a maximum reduction of 33% at 1 MAC (P < 0.01). CVP and PCWP were maintained within control values. MPAP, PVR and RVSW decreased by 13 %, 10% and 17%, respectively, (ns) (table II). Bloodgas analysis revealed mean Pa^ values of 20.7 (2.1), 20.3 (2.0) and 20.3 (2.1) kPa at 0, 0.5 and 1 MAC isoflurane, respectively. Fo 2 , (Ca^ — CvOt), Qs/Qt and ERo2 varied only slightly, while Do2 increased by 7% at 0.5 MAC (table III).
DISCUSSION
We found that administration of isoflurane at doses up to 1 MAC during a zero-order propofol infusion decreased SAP, SVR and LVSW in a dosedependent fashion, without affecting CO, SV or HR. MPAP, PVR and RVSW decreased, but not significantly. Haemodynamic variables after 60 min of an identical zero-order infusion of propofol in another report [10] were similar, with the exception of SAP, SVR and LVSW. These differences in haemodynamic data may be attributable to our selection of younger patients in this study; clearance of propofol
Downloaded from http://bja.oxfordjournals.org/ at Thomas Jefferson University, Scott Library on March 10, 2015
0.00
38
In conclusion, we have demonstrated that isoflurane supplementation of propofol anaesthesia was associated with a dose-dependent decrease in SAP resulting from a reduction in SVR and not in SV or CO. Although further documentation on cerebral blood flow and metabolism with this technique is mandatory, we think its use could offer advantages during neurosurgery.
REFERENCES 1. Lam AM, Gelb AW. Cardiovascular effects of isofluraneinduced hypotension for cerebral aneurysm surgery. Anesthesia and Analgesia 1983; 62: 742-748. 2. Frost EAM. Inhalation anaesthetic agents in neurosurgery. British Journal of Anaesthesia 1984; 56: 47S-56S. 3. Stevens WC, Cromwell TH, Halsey MH, Eger El II, Shakespeare TF, Bahlman SH. The cardiovascular effects of a new inhalation anesthetic, Forane, in human volunteers at constant arterial carbon dioxide tension. Anesthesiology 1971; 35:8-16. 4. Dolan WM, Stevens WC, Eger El II, Cromwell TH, Halsey MJ, Shakespeare TF, Miller RD. The cardiovascular and respiratory effects of isoflurane-nitrous oxide anaesthesia. Canadian Anaesthetists Society Journal 1974; 21: 557-568. 5. Sebel PS, Lowdon JD. Propofol: a new intravenous anesthetic. Anesthesiology 1989; 71: 260-277. 6. Gepts E, Camu F, Cockshott ID, Douglas EJ. Disposition of propofol administered as constant rate intravenous infusions in humans. Anesthesia and Analgesia 1987; 66: 1256-1263. 7. Kanto J, Gepts E. Pharmacokinetic implications for the clinical use of propofol. Clinical Pharmacokinetics 1989; 17: 308-326. 8. Stephan H, Sonntag H, Schenk HD, Kohlhausen S. Einfluss von Disoprivan (Propofol) auf die Durchblutung und den Sauerstoff verbrauch des Gehirns und die CO,-Reaknvitfit der Himgefasse beim Menschen. Anaesthestst 1987; 36: 60-65. 9. Vandesteene A, Trempont V, Engelman E, Deloof T, Focroul M, Schoutens A, De Rood M. Effect of propofol on cerebral blood flow and metabolism in man. Anaesthesia 1988; 43: (Suppl.): 42-13. 10. Claeys MA, Gepts E, Camu F. Haemodynamic changes during anaesthesia induced and maintained with propofol. British Journal of Anaesthesia 1988; 60: 3-9. 11. Kirkpatrick T, Cockshott ID, Douglas EJ, Nimmo WS. Pharmacokinetics of propofol (Diprivan) in elderly patients. British Journal of Anaesthesia 1988; 60: 146-150. 12. Stephan H, Sonntag H, Schenk HD, Kettler D, Khambatta HJ. Effects of propofol on cardiovascular dynamics, myocardial blood flow and myocardial metabolism in patients with coronary artery disease. British Journal of Anaesthesia 1986; 58: 969-975. 13. Gelman S, Fowler KC, Smith LR. Regional blood flow during isoflurane and halothane anesthesia. Anesthesia and Analgesia 1984; 63: 557-565. 14. Roily G, Versichelen L, Moerman E. Cardiovascular, metabolic and hormonal changes during isoflurane N,O anaesthesia. European Journal of Anaesthetiology 1984; 1: 327-334. 15. Ebert TJ. Differential effects of nitrous oxide on baroreflex control of heart rate and peripheral sympathetic nerve activity in humans. Anesthesiology 1990; 72: 16-22. 16. Smith NT, Eger El n, Stoelting RK, Whayne TF, Cullen D, Kadis LB. The cardiovascular and sympathomimetic responses to the addition of nitrous oxide to halothane in man. Anesthesiology 1970; 32: 410-421. 17. Cromwell TH, Stevens WC, Eger El II, Shakespeare TF, Halsey MJ, Bahlman SH, Fourcade HE. The cardiovascular effects of compound 469 (Forane) during spontaneous ' ventilation and CO, challenge in man. Anesthesiology 1971; 35: 17-25. 18. Stowe DF, Dujic Z, Bosnjak ZJ, Kalbfleisch JH, Kampine JP. Volatile anesthetics attenuate sympathomimetic actions on the guinea pig SA node. Anesthesiology 1988; 68: 887-894. 19. Seagard JL, Elegbe EO, Hopp FA, Bosnjak ZJ, Von Colditz JH, Kalbfleisch JH, Kampine JP. Effects of isoflurane on the baroreceptor reflex. Anesthesiology 1983; 59: 511-520. 20. Kotrly KJ, Ebert TJ, Vucins E, Igler FO, Barney JA, Kampine JP. Baroreceptor reflex control of heart rate during isoflurane anesthesia in humans. Anesthesiology 1984; 60: 173-179. 21. Blake DW, Jover B, Me Grath BP. Haemodynamic and heart rate reflex responses to propofol in the rabbit. Comparison with Althesin. British Journal of Anaesthesia 1988; 61: 194-199. 22. Cullen PM, Turtle M, Prys-Roberts C, Way WL, Dye J.
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is diminished in the elderly [11] and cumulation of the drug may have led to a different haemodynamic response in the patients of Claeys and colleagues [10]. A larger infusion regimen (0.2 mgkg~1min"1) with the same induction dose or preoperative drug therapy could have been responsible for the smaller values for CO, SV and SAP found in 11 patients scheduled for coronary surgery [12]. In our study, MAC concentrations of isoflurane were given in random, rather than increasing or decreasing, order. By abolishing the time factor in this study, we have neutralized the possible effect of accumulation of propofol in the deep compartment on the haemodynamic observations. Indeed, although plasma concentrations of propofol seemed to change very little over several hours of infusion, modification of pharmacokinetic values, caused by changes in hepatic blood flow during administration of isoflurane [13], cannot be excluded. Isoflurane was evaluated in similar circumstances in combination with 50% nitrous oxide using non-invasive monitoring [14]. SAP, HR and CO were greater compared with our values, while SV was similar after 5 min ventilation with 1.3 vol % isoflurane. These differences might result from the sympathomimetic activity of nitrous oxide [4, 15, 16]. In two reports in which 1.2 vol % isoflurane in oxygen was evaluated, CO did not change compared with control, as shown in our study [4, 17]. In those reports, HR increased significantly and SV diminished equally, whereas in our study only a moderate increase in HR and concomitant decrease in SV were observed. Although animal data suggest that isoflurane by itself may be responsible for reducing HR, either by decreasing sinus rate [18] or by attenuating arterial baroreceptor control [19, 20], the lack of increase in HR in our study was probably caused by propofol. The underlying mechanism for this phenomenon is the resetting of the baroreceptor set point as shown in the rabbit [21] and man [2] or a direct effect on sinus activity [23]. When administered in air at the same [24] or somewhat greater concentration [25] in patients with coronary artery disease, isoflurane tended to produce a greater HR and SAP and a smaller CO compared with our study. Greater values of SVR have been reported also [25]. An additive effect of propofol may account for the differences in SAP and SVR [8], whereas preoperative cardioprotective medication, impaired ventricular wall motility, or both, may have had an effect, as CI was decreased in these patients. Similar haemodynamic findings were observed in the control series of a study demonstrating constant shunt fractions during hypotension with isoflurane [26]—a finding that we confirmed in our study, even in the presence of propofol.
BRITISH JOURNAL OF ANAESTHESIA
ISOFLURANE-PROPOFOL HAEMODYNAMICS Effect of propofol anesthesia on baroreflex activity in humans. Anesthesia and Analgesia 1987; 66: 1115-1120. 23. Colson P, Bartlet H, Roquefeuill B, Eledjam JJ. Mechanism of propofol bradycardia. Anesthesia and Analgesia 1988; 67: 906-907. 24. Khambatta HJ, Sonntag H, Larsen R, Stephan H, Stone JG, Kettler D. Global and regional myocardial blood flow and metabolism during equipotent halothane and isofluranc anesthesia h patients with coronary artery disease. Anesthesia and Analgesia 1988; 67: 936-942.
39 25. Moffitt EA, Barker RA, Glenn JJ, Imrie DD, Delcampo C, Landymore RW, Kinley CE, Murphy DA. Myocardial metabolism and hemodynamic responses with isoflurane anesthesia for coronary arterial surgery. Anesthesia and Analgesia 1986; 65: 53-61. 26. Nicholas JF, Lam AM. Isoflurane induced hypotension docs not cause impairment in pulmonary gas exchange. Canadian Anaesthetists Society Journal 1984; 31: 352-358.
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HAEMODYNAMIC EFFECTS OF ISOFLURANE DURING PROPOFOL ANAESTHESIA C. VERBORGH, D. VERBESSEM AND F. CAMU
SUMMARY
KEY WORDS Anaesthetics, intravenous: propofol. Anaesthetics, volatile: isoflurane. Arterial pressure: drug effects. Heart: haemodynamic effects.
The use of isoflurane for inducing hypotension during neurosurgery is well established [1,2]. Its haemodynamic effects have been studied in volunteers breadiing room air [3] and in surgical patients receiving nitrous oxide [4]. Because of its favourable pharmacokinetic [5—7] and cerebrovascular [8,9] profile, propofol is used increasingly for maintenance of anaesthesia during neurosurgery. However, haemodynamic properties of isoflurane during propofol anaesthesia have not yet been documented. As both isoflurane and propofol reduce systemic vascular resistance (SVR) in a dose-dependent manner, [3, 10], we felt that haemodynamic evaluation of simultaneous use was indicated before further clinical evaluation as a hypotensive technique. Therefore we designed this cross-over dose-response study in which the haemodynamic responses to different concentrations of isoflurane during continuous administration of propofol were evaluated.
TABLE I. Sequence of isoflurane administration (MAC) Patient No. 1
2 3 4 5 6 7 8 9 10
MAC sequence 0.00 0.75 1.00 1.00 0.00 0.75 0.25 0.50 0.25 0.50
0.50 1.00 0.00 0.00 0.75 0.25 0.50 0.25 0.75 1.00
0.75 0.00 0.50 0.25 1.00 1.00 0.00 0.75 0.50 0.25
0.25 0.25 0.75 0.75 0.50 0.50 1.00 0.00 1.00 0.00
1.00 0.50 0.25 0.50 0.25 0.00 0.75 1.00 0.00 0.75
CHRISTIAN VERBORGH*, M.D. ; DAISY VERBESSEM, M.D. ; FREDERIC
PATIENTS AND METHODS
The study was approved by the University Ethics Committee. We studied patients, ASA I—II, undergoing major surgery. Patient consent was obtained
CAMU, M.D.; Department of Anaesthesiology, Flemish Free University of Brussels, Brussels, Belgium. Accepted for Publication: January 6, 1992. •Address for correspondence: Academish Ziekenhuis V.U.B., Department Anesthesiologie, Laarbeeklaan 101, B-1090 Brussels, Belgium.
Downloaded from http://bja.oxfordjournals.org/ at Thomas Jefferson University, Scott Library on March 10, 2015
We have studied haemodynamic responses to 0, 0.25, 0.5, 0.75 and 1 MAC isoflurane administration in 10 patients during a zero-order propofol infusion and normocapnia. Isoflurane reduced mean arterial pressure (MAP), systemic vascular resistance and left ventricular stroke work in a dose-dependent manner (29%, 38% and 33%. respectively, at 1 MAC), while cardiac output (CO), stroke volume (SV) and heart rate were not affected significantly. Mean pulmonary artery pressure, pulmonary vascular resistance and right ventricular stroke work decreased by 13%, 10% and 17%, respectively (not significant). -Pulmonary capillary wedge pressure and central venous pressure were affected minimally, while intrapulmonary shunting and PaOj remained constant. It is concluded that administration of isoflurane during infusion of propofol caused a dose-dependent decrease in MAP as a result of afterload reduction without modification in CO or SV.
the day before surgery. No patient had a history of pulmonary, cardiac, hepatic or renal disease. Premedication was with lorazepam 1 mg orally. After arrival of the patient in theatre, an i.v. cannula was inserted and 5 % glucose in Ringer solution was administered at a rate of 20 ml h"1. Anaesthesia was induced with a three-step infusion of propofol: 0.35 mg kg"1 min"1 for 5 min, 0.2 mg kg"1 min"1 for 10 min and 0.1 mg kg"1 min"1 for the remainder of the observation period. After loss of consciousness, pancuronium 0.08 mg kg"1 was given, the trachea intubated and lungs ventilated with 40 % oxygen in air. End-tidal carbon dioxide partial pressure was maintained at 5.5 kPa (Capnomac, Datex). A SwanGanz catheter was inserted. Different concentrations of isoflurane (0, 0.25, 0.50, 0.75 and 1 MAC) were administered in random sequence (table I) and between the different steps sufficient time was provided to allow equilibrium to occur as judged by inspiratory and expiratory measurements of isoflurane concentrations (Capnomac, Datex, Finland). At each step, heart rate (HR), systemic arterial pressure (SAP), central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP) and mean pulmonary artery pressure (MPAP) were recorded (HP 78353A) and cardiac output (CO) was measured in triplicate (Edwards CO computer). Blood-gas analysis was obtained at 0,0.5 and 1 MAC isoflurane (Instrumentation Laboratory BGM 1312). Haemodynamic variables were recorded when they
ISOFLURANE-PROPOFOL HAEMODYNAMICS
37
TABLE II. Haemodynamic variables (mean (SEM). * P < 0.05; ** P < 0.01 compared with MAC 0 MAC isofluraae
HR (beat min"1) CO (litre min"1) SV (ml min-1) SAP (mm Hg) CVP (mm Hg) MPAP (mm Hg) PCWP (mm Hg)
0.00
0.25
0.50
72(4) 6.4 (0.5) 91(7) 83(4) 5(2) 15(2) 8(2)
74(4) 7.0 (0.5) 96(6) 72 (4)* 4(1) 14(2) 7(2)
74(4) 6.9 (0.5) 94(5) 65 (4)** 4(1) 13(1) 6(1)
0.75
1.00
75(4) 75(4) 6.6 (0.5) 6.6 (0.5) 88(5) 87(5) 62 (3)** 59 (2)** 4(1) 4(1) 13(1) 13(1) 7(1) 6(1)
TABLE III. Calculated haemodynamic variables (mean (SEM). **P < 0.01 compared with MAC 0 MAC isoflurane
SVR
(dyn s cm"6) PVR
(dyn s cm"5) LVSW (g m bear 1 ) RVSW (g m bear 1 ) (Ca^ — CvoJ
(ml dl"1) Do, (ml min"1) Ko, (ml min"1) ERo, (%) Qs/Qt (%)
1019 (80)
0.25 801 (70)**
0.50 742 (77)**
0.75
1.00
718(61)**
689 (51)**
91 (16)
85(11)
85(7)
84(9)
82(11)
93(9)
87(10)
76 (7)**
66 (6)**
62 (5)**
12(1)
12(1)
11(1)
11(1)
10(1)
3.2(0.1)
3.1(0.1)
3.2 (0.3)
1275 (134) 202(17) 0.16(0.01) 1.6(0.1)
1367 (127) 215(21) 0.16(0.01) 1.5(0.1)
1294(111) 205(18) 0.16(0.01) 1.6(0.1)
were stable after the equilibration period. After the study, fentanyl and pancuronium were administered and surgery commenced. Using standard formulae, the following variables were calculated: stroke volume (SV), systemic and pulmonary vascular resistance (SVR, PVR), left and right ventricular stroke work (LVSW, RVSW). Oxygen consumption (Vo2), oxygen delivery (Z>o2), oxygen extraction ratio (ERos), arteriovenous oxygen difference (CaOi — CvOi) and shunt fraction (Qs/Qt) were also calculated. Data were analysed statistically by one-way analysis of variance and Wilcoxon signed rank test as appropriate.
RESULTS
. We studied 10 patients (six male) of mean age 48 yr (range 30-61 yr), mean weight 76 (SEM 3) kg (range 62-90 kg), mean height 171 (3) cm (range 154187 cm) and mean body surface area 1.88 (0.04) m1 (range 1.70-2.03 m1). The mean (SEM) time between start of the propofol infusion and the first measurement was 51 (7) min. Mean time between measurements was 14 (5) min. As three consecutive cardiac output measurements were performed for one evaluation, necessitating 10 ml of saline on each attempt, total fluid infusion rate was approximately 140 ml h"1. Compared with control values, maximum increase in HR was 4% (table II). SV increased initially by 5% with small MAC values, but was reduced by 4 % at 1 MAC isoflurane. CO increased by 9 % at
0.25 MAC and 3 % at 1 MAC. None of these changes was significant. A dose-dependent and significant reduction in SAP was apparent at 0.25 MAC and there was a 29% decrease at 1 MAC (P < 0.01). SVR decreased gradually with increasing isoflurane concentrations and was reduced to a minimum at 1 MAC (P < 0.01), which corresponded to a 38% reduction compared with control values (table III). The calculated LVSW showed a similar decrease, to a maximum reduction of 33% at 1 MAC (P < 0.01). CVP and PCWP were maintained within control values. MPAP, PVR and RVSW decreased by 13 %, 10% and 17%, respectively, (ns) (table II). Bloodgas analysis revealed mean Pa^ values of 20.7 (2.1), 20.3 (2.0) and 20.3 (2.1) kPa at 0, 0.5 and 1 MAC isoflurane, respectively. Fo 2 , (Ca^ — CvOt), Qs/Qt and ERo2 varied only slightly, while Do2 increased by 7% at 0.5 MAC (table III).
DISCUSSION
We found that administration of isoflurane at doses up to 1 MAC during a zero-order propofol infusion decreased SAP, SVR and LVSW in a dosedependent fashion, without affecting CO, SV or HR. MPAP, PVR and RVSW decreased, but not significantly. Haemodynamic variables after 60 min of an identical zero-order infusion of propofol in another report [10] were similar, with the exception of SAP, SVR and LVSW. These differences in haemodynamic data may be attributable to our selection of younger patients in this study; clearance of propofol
Downloaded from http://bja.oxfordjournals.org/ at Thomas Jefferson University, Scott Library on March 10, 2015
0.00
38
In conclusion, we have demonstrated that isoflurane supplementation of propofol anaesthesia was associated with a dose-dependent decrease in SAP resulting from a reduction in SVR and not in SV or CO. Although further documentation on cerebral blood flow and metabolism with this technique is mandatory, we think its use could offer advantages during neurosurgery.
REFERENCES 1. Lam AM, Gelb AW. Cardiovascular effects of isofluraneinduced hypotension for cerebral aneurysm surgery. Anesthesia and Analgesia 1983; 62: 742-748. 2. Frost EAM. Inhalation anaesthetic agents in neurosurgery. British Journal of Anaesthesia 1984; 56: 47S-56S. 3. Stevens WC, Cromwell TH, Halsey MH, Eger El II, Shakespeare TF, Bahlman SH. The cardiovascular effects of a new inhalation anesthetic, Forane, in human volunteers at constant arterial carbon dioxide tension. Anesthesiology 1971; 35:8-16. 4. Dolan WM, Stevens WC, Eger El II, Cromwell TH, Halsey MJ, Shakespeare TF, Miller RD. The cardiovascular and respiratory effects of isoflurane-nitrous oxide anaesthesia. Canadian Anaesthetists Society Journal 1974; 21: 557-568. 5. Sebel PS, Lowdon JD. Propofol: a new intravenous anesthetic. Anesthesiology 1989; 71: 260-277. 6. Gepts E, Camu F, Cockshott ID, Douglas EJ. Disposition of propofol administered as constant rate intravenous infusions in humans. Anesthesia and Analgesia 1987; 66: 1256-1263. 7. Kanto J, Gepts E. Pharmacokinetic implications for the clinical use of propofol. Clinical Pharmacokinetics 1989; 17: 308-326. 8. Stephan H, Sonntag H, Schenk HD, Kohlhausen S. Einfluss von Disoprivan (Propofol) auf die Durchblutung und den Sauerstoff verbrauch des Gehirns und die CO,-Reaknvitfit der Himgefasse beim Menschen. Anaesthestst 1987; 36: 60-65. 9. Vandesteene A, Trempont V, Engelman E, Deloof T, Focroul M, Schoutens A, De Rood M. Effect of propofol on cerebral blood flow and metabolism in man. Anaesthesia 1988; 43: (Suppl.): 42-13. 10. Claeys MA, Gepts E, Camu F. Haemodynamic changes during anaesthesia induced and maintained with propofol. British Journal of Anaesthesia 1988; 60: 3-9. 11. Kirkpatrick T, Cockshott ID, Douglas EJ, Nimmo WS. Pharmacokinetics of propofol (Diprivan) in elderly patients. British Journal of Anaesthesia 1988; 60: 146-150. 12. Stephan H, Sonntag H, Schenk HD, Kettler D, Khambatta HJ. Effects of propofol on cardiovascular dynamics, myocardial blood flow and myocardial metabolism in patients with coronary artery disease. British Journal of Anaesthesia 1986; 58: 969-975. 13. Gelman S, Fowler KC, Smith LR. Regional blood flow during isoflurane and halothane anesthesia. Anesthesia and Analgesia 1984; 63: 557-565. 14. Roily G, Versichelen L, Moerman E. Cardiovascular, metabolic and hormonal changes during isoflurane N,O anaesthesia. European Journal of Anaesthetiology 1984; 1: 327-334. 15. Ebert TJ. Differential effects of nitrous oxide on baroreflex control of heart rate and peripheral sympathetic nerve activity in humans. Anesthesiology 1990; 72: 16-22. 16. Smith NT, Eger El n, Stoelting RK, Whayne TF, Cullen D, Kadis LB. The cardiovascular and sympathomimetic responses to the addition of nitrous oxide to halothane in man. Anesthesiology 1970; 32: 410-421. 17. Cromwell TH, Stevens WC, Eger El II, Shakespeare TF, Halsey MJ, Bahlman SH, Fourcade HE. The cardiovascular effects of compound 469 (Forane) during spontaneous ' ventilation and CO, challenge in man. Anesthesiology 1971; 35: 17-25. 18. Stowe DF, Dujic Z, Bosnjak ZJ, Kalbfleisch JH, Kampine JP. Volatile anesthetics attenuate sympathomimetic actions on the guinea pig SA node. Anesthesiology 1988; 68: 887-894. 19. Seagard JL, Elegbe EO, Hopp FA, Bosnjak ZJ, Von Colditz JH, Kalbfleisch JH, Kampine JP. Effects of isoflurane on the baroreceptor reflex. Anesthesiology 1983; 59: 511-520. 20. Kotrly KJ, Ebert TJ, Vucins E, Igler FO, Barney JA, Kampine JP. Baroreceptor reflex control of heart rate during isoflurane anesthesia in humans. Anesthesiology 1984; 60: 173-179. 21. Blake DW, Jover B, Me Grath BP. Haemodynamic and heart rate reflex responses to propofol in the rabbit. Comparison with Althesin. British Journal of Anaesthesia 1988; 61: 194-199. 22. Cullen PM, Turtle M, Prys-Roberts C, Way WL, Dye J.
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is diminished in the elderly [11] and cumulation of the drug may have led to a different haemodynamic response in the patients of Claeys and colleagues [10]. A larger infusion regimen (0.2 mgkg~1min"1) with the same induction dose or preoperative drug therapy could have been responsible for the smaller values for CO, SV and SAP found in 11 patients scheduled for coronary surgery [12]. In our study, MAC concentrations of isoflurane were given in random, rather than increasing or decreasing, order. By abolishing the time factor in this study, we have neutralized the possible effect of accumulation of propofol in the deep compartment on the haemodynamic observations. Indeed, although plasma concentrations of propofol seemed to change very little over several hours of infusion, modification of pharmacokinetic values, caused by changes in hepatic blood flow during administration of isoflurane [13], cannot be excluded. Isoflurane was evaluated in similar circumstances in combination with 50% nitrous oxide using non-invasive monitoring [14]. SAP, HR and CO were greater compared with our values, while SV was similar after 5 min ventilation with 1.3 vol % isoflurane. These differences might result from the sympathomimetic activity of nitrous oxide [4, 15, 16]. In two reports in which 1.2 vol % isoflurane in oxygen was evaluated, CO did not change compared with control, as shown in our study [4, 17]. In those reports, HR increased significantly and SV diminished equally, whereas in our study only a moderate increase in HR and concomitant decrease in SV were observed. Although animal data suggest that isoflurane by itself may be responsible for reducing HR, either by decreasing sinus rate [18] or by attenuating arterial baroreceptor control [19, 20], the lack of increase in HR in our study was probably caused by propofol. The underlying mechanism for this phenomenon is the resetting of the baroreceptor set point as shown in the rabbit [21] and man [2] or a direct effect on sinus activity [23]. When administered in air at the same [24] or somewhat greater concentration [25] in patients with coronary artery disease, isoflurane tended to produce a greater HR and SAP and a smaller CO compared with our study. Greater values of SVR have been reported also [25]. An additive effect of propofol may account for the differences in SAP and SVR [8], whereas preoperative cardioprotective medication, impaired ventricular wall motility, or both, may have had an effect, as CI was decreased in these patients. Similar haemodynamic findings were observed in the control series of a study demonstrating constant shunt fractions during hypotension with isoflurane [26]—a finding that we confirmed in our study, even in the presence of propofol.
BRITISH JOURNAL OF ANAESTHESIA
ISOFLURANE-PROPOFOL HAEMODYNAMICS Effect of propofol anesthesia on baroreflex activity in humans. Anesthesia and Analgesia 1987; 66: 1115-1120. 23. Colson P, Bartlet H, Roquefeuill B, Eledjam JJ. Mechanism of propofol bradycardia. Anesthesia and Analgesia 1988; 67: 906-907. 24. Khambatta HJ, Sonntag H, Larsen R, Stephan H, Stone JG, Kettler D. Global and regional myocardial blood flow and metabolism during equipotent halothane and isofluranc anesthesia h patients with coronary artery disease. Anesthesia and Analgesia 1988; 67: 936-942.
39 25. Moffitt EA, Barker RA, Glenn JJ, Imrie DD, Delcampo C, Landymore RW, Kinley CE, Murphy DA. Myocardial metabolism and hemodynamic responses with isoflurane anesthesia for coronary arterial surgery. Anesthesia and Analgesia 1986; 65: 53-61. 26. Nicholas JF, Lam AM. Isoflurane induced hypotension docs not cause impairment in pulmonary gas exchange. Canadian Anaesthetists Society Journal 1984; 31: 352-358.
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