Propofol/Fentanyl Versus Etomidate/Fentanyl for the Induction of Anesthesia in Patients With Aortic Insufficiency and Coronary Artery Disease

Reinhard Haessler, MD, Christian Madler, MD, Sven Klasing, Dierk Schwender, MD and Klaus Peter, MD

The purpose of this study was to gain information about the hemodynamic effects following the induction of anesthesia with fentanyl and either 1 mg/kg of propofol (P) or 0.25 mg/kg of etomidate (E) in ASA III-IV patients with aortic insufficiency (Al) or coronary artery disease (CAD). Four patient groups resulted: (1) Al and P, n = 10; (2) Al and E, n = 10; (3) CAD and P, n = 6; and (4) CAD and E, n = 8. Hemodynamics were recorded in the awake state, following induction, intubation, and 10 minutes after intubation. No complications occurred in groups 1,2, and 4. In 2 patients of group 3, who suffered from three-vessel CAD, induction resulted in severe hypotension associated with an increase in pulmonary capillary wedge pressure. Because of this, the investigation of group 3 was prematurely terminated after the sixth patient. The following changes were observed under general anesthesia: in all four groups, arterial pressure

I NDUCTION of general anesthesia in patients with cardiac disease must guarantee hemodynamic stability

and should result in a satisfactory anesthetic level in terms of suppression of sensory information processing in the central nervous system. Propofol (P) (Diprivan, ICI, Heidel- burg, Germany) is an effective agent for anesthetic induc- tion and has been used in patients with coronary artery disease (CAD) as well as in patients with valvular heart disease.‘,’ However, marked decreases in arterial pressure and systemic vascular resistance (SVR) can be induced by P in patients with CAD.‘~’ It was suspected that these effects were related to the dosage of P and, therefore, an anes- thetic regimen using a low dosage of P in combination with fentanyl (Janssen Pharmaceuticals, Neuss, Germany) was needed. Before the formal investigation was initiated, the effect of different dosages was tested in a preliminary study. According to clinical observation, 1 mg/kg of P combined with 0.006 mg/kg of fentanyl seemed to be the minimal acceptable dosage. As an additional criterion to assess processing of sensory information, the monitoring of audi- tory evoked potentials was chosen.“’ With the same clinical and electrophysiological monitoring a dosage of 0.20 to 0.25 mg/kg of etomidate (E) combined with 0.006 mg/kg of fentanyl was found to be the minimal acceptable dosage. Taking the literature into consideration,‘,’ a decrease in arterial pressure and even some degree of cardiodepression was expected with P. To avoid overestimation of a possible cardiodepressive effect of Pifentanyl relative to the effects of E/fentanyl, the low dosage of P plus fentanyl was compared with the moderate dose of E of 0.25 mg (instead of 0.20 mg) plus fentanyl.

The purpose of this study was to analyze the hemody- namic effects of Pifentanyl in comparison with E/fentanyl (Hypnomidate; Janssen Pharmaceuticals, Neuss, Germany) used for induction of anesthesia in patients scheduled for either aortic valve replacement or coronary artery bypass grafting (CABG). Of particular interest was the signifi- cance of the cardiodepressive effects and changes in after- load with these pathophysiologically different diseases.

(AP), cardiac index (Cl), and left ventricular stroke work index decreased. Significantly different values between group 1 (Al and P) and 2 (Al and E) were observed for heart rate (HR) (P < E), stroke volume (SV) (P > E), arterial elastance (Ea), and systemic vascular resistance (SW) (P c E); differences between group 3 (CAD and P) and 4 (CAD and E) were seen for AP, Ea. and SW (P -z E each). After tracheal intubation, baseline values of AP and HR were not surpassed in any group. Signs of systolic myocardial dysfunction were present in all groups (P > E). In spite of this, possibly because of the decrease in afterload, a comparable decrease in AP and Cl was observed in groups 1 and 2. In contrast to patients with CAD, patients with Al could be anesthetized as safely with propofol/fentanyl as with etomidate/fentanyl with respect to hemodynamic stability. Copyright o 1992 by W.B. Saunders Company

MATERIALS AND METHODS

After institutional approval and written informed consent, 20 patients with aortic insufficiency (AI) and 14 patients with CAD were studied. Table 1 shows the demographic and preoperative cardiovascular data. All patients had an ejection fraction of 35% or more and were kept on their regimen of cardiac drugs until the morning of surgery. As premeditation, 2 mg of flunitrazepam (Rohypnol; Roche, Grenzach, Germany) was administered orally. Monitoring included a three-lead electrocardiogram (EICG) (Sie- mens) with a CB, lead as a modification of V,, analysis of the expiratory PCO, (Siemens, Ehrlangen, Germany), a 17.gauge femoral artery and a 7F pulmonary artery catheter (Spectramed, Duesseldorf, Germany). Cardiac output (CO) was obtained by triplicate measurements using the thermodilution method (Spec- tramed-CO-computer) with an inline injectate temperature probe. Heart rate (HR), systemic systolic (APs) and diastolic pressures (APd), and pulmonary arterial systolic (PAPS) and diastolic pressures (PAPd), pulmonary capillary wedge pressure (PCWP), and central venous pressure (CVP) were recorded at each of the triplicate measurements. Trend analysis of the ECG did not allow exact judgment of the ST segment, and thus original tracings (20 seconds) of the ECG (CB,) were analyzed at the points of hemodynamic measurements. For the analysis of the ECG, horizon- tal changes of the ST segment of 0.1 mV or more were defined as ischemia. Cardiac index (CI), systemic (SVR) and pulmonary vascular resistances (PVR), stroke volume (SV), arterial elastance (Ea = APslSV) anId right (RVSWI) and left ventricular stroke work index (LVSWI) were calculated. Before induction of anesthe- sia each patient received a mean volume of 8 mL/kg of a balanced electrolyte solution. Hemodynamic measurements were performed in the awake patients, after induction of anesthesia, after tracheal intubation, and 10 minutes after intubation. The patients were randomly assigned to receive P or E, so that the following four patient groups resulted (1) AI and P, n = 10; (2) AI and E, n = 10;

From the Department of Anesthesiology, University of Munich, Klinikum Grosshadem, Munich, Germany; and the Department of Anesthesiology, Oregon Health Sciences University, Portland, OR.

Address reprint requests to Reinhard Haessler, MD, Department of Anesthesiology, Oregon Health Sciences University, 3181 SW Sam Jackson Park Rd, UHS-2, Portland, OR 97201-3098.

Copyright 0 I992 by W.B. Saunders Company 1053-0770/92/0602-0010$03.00/O

Journalof Cardiothoracic and VascularAnesthesia, Vol6, No 2 (April), 1992: pp 173.180 173

174 HAESSLER ET At

Table 1. Demographic/Preoperative Data (SD)

Group 1 Group 2 Al and P Al and E

Group 3 CADand P

Group 4 CAD and t

N

Male

Age (vr) Weight (kg)

Height (cm)

Cardiac index (L/min/m?)

Ejection fraction (mm Hg) LVEDP (mm Hg)

ASA-classification

Nitrates Calcium channel blockers p-Blockers

ACE-inhibitors Digitalis

Diuretics

10 9

50(14)

76 (10)

176 (9)

2.7 (0.4)

60 (12)

15(5) III-IV

l/10

0

0

1110

2110

2110

10 9

46(15)

79 (9) 170 (6)

2.9 (0.3)

62(11)

16 (5) III-IV

0

0

l/10

0

2/10

3/10

6

61 (6)*

72 (8)

171 (9)

2.6 (0.4)

64 161

g(3)* III-IV

616

316

216

l/6

116

116

8

57 (7)t

79 (9) 170(9)

2.6 (0.4)

64 (7) 11 (4)t

III-IV

818

418

318

118

0

118

NOTE. Statistics concerning demographic and cardiovascular data (Kruskal-Wallis test): no significant difference between groups 1 and 2 and

between groups 3 and 4.

Abbreviations: Al, aortic insufficiency; CAD, coronary artery disease; P, propofolifentanyl; E, etomidate/fentanyl; LVEDP, left ventricular end-diastolic pressure.

*Significant differences between groups 1 and 3for age (P < 0.10) and LVEDP (P i 0.10).

tsignificant differences between groups 2 and 4for age (P < 0.05) and LVEDP (P < 0.10).

(3) CAD and P, n = 6; and (4) CAD and E, n = 8 (a number of 10 patients in each CAD-group had been predefined, but the CAD study was prematurely terminated after the sixth patient of the P-group because of severe hemodynamic changes in the P-group). After preoxygenation, anesthesia was induced with 0.25 mg/kg of E and 0.006 mg/kg of fentanyl or 1 mg/kg of P given over 2 minutes and 0.006 mgikg of fentanyl, followed in the P groups by a maintenance dose of 6 mg/kg/hr of P. Each patient received 0.1 mg/kg of pancuronium (Pancuronium; Organon, Teknika, Ob- aschleissheim, Germany) for muscle relaxation. After induction of anesthesia, controlled ventilation was instituted (end-tidal PCO, 35 to 40 mm Hg). As an additional criterion to assess the processing of sensory information, auditory evoked potentials were monitored in the awake patients and after anesthetic induction.

Results are presented as mean values 2 standard deviations. In every patient group, the mean values of all hemodynamic results under general anesthesia were compared with mean baseline values with a Wilcoxon test. Furthermore, the mean values of demographic data, preoperative cardiovascular data, and results of all hemodynamic measurements (including baseline data) of every patient group were compared with values of corresponding groups with a Kruskal-Wallis test. In this manner, group 1 (AI and P) was compared with group 2 (AI and E), group 3 (CAD and P) to group 4 (CAD and E), group 1 (AI and P) to group 3 (CAD and P), and group 2 (AI and E) to group 4 (CAD and E). P-values of 0.01, 0.05, and 0.10 were used.

RESULTS

According to clinical observations and analysis of the auditory evoked potentials, a satisfactory anesthetic level was present in the patients in all four groups.

Aortic Insufficiency

In terms of demographic and preoperative cardiovascu- lar data, the P and E groups were comparable (Table 1). No complications occurred. The following hemodynamic changes were observed (Table 2, Fig 1). After the induction

of anesthesia, both groups showed significant reductions of

APs, APd, PAPS, CI, and LVSWI. Furthermore, in the P group HR, SVR, PVR, and APslSV decreased, CVP increased significantly; whereas in the E group SV and RVSWI decreased. Significant differences among the groups were found for SV and APs/SV (P < 0.01 each), HR (P < 0.05), SVR, PVR, RVSWI (P < 0.1 each) after induc- tion. After intubation, baseline values of APs and HR were not exceeded in any group; however, in the P group both mean values were significantly lower than in the E group (P < 0.05). After intubation, SV was lower than baseline in the E group and APs/SV lower than baseline in the P group, and there was a significant difference among the groups for SV and APs/SV. Under general anesthesia, decreased values of APs, PAPS, CI, and LVSWI in both groups were found. The most consistent significant differ- ences between the E and P groups during general anesthe- sia were due to constantly decreased values in APs/SV and HR in the P group and constantly decreased values in SV in the E group.

CAD

Concerning preoperative demographic and hemody- namic data, the groups were comparable (Table 1). Every patient of the P group had to be placed in a Trendelenburg position (5 degrees) after induction, due to a considerable decrease in AP, in 5 of 6 patients systolic pressure was below 100 mm Hg (Fig 2). In the horizontal position, mean systolic pressure was 82 mm Hg (SD ? 14), diastolic pres- sure 40 mm Hg (SD c 13) after induction. Signs of isch- emia did not occur in the modified V, ECG lead. However, there was an increase in PCWP (+5 and +lO mm Hg) in two patients of the P group during the hypotensive period. Infusion of 10 kg/kg/min of dopamine reestablished stable

PROPOFEL vs ETOMIDATE: Al vs CAD 175

Table 2. Hemodynamic Data, Aortic Regurgitation (Mean f 1 SD)

Awake After Induction After lntubation 10 Minutes After

lntubation

APs (mm Hg)

APd (mm Hg)

PAPS (mm Hg)

PAPd (mm Hg)

PCWP (mm Hg)

CVP (mm Hg)

HR (L/min)

Cl (Llmin/m*)

SVR (dyne. s. cm5)

PVR (dyne. s. cm5)

SV (mL)

APs/SV (mm Hg/mL)

LVSWI (g . m mZ)

RVSWI (g rn. m*)

P 133 (21)

E 128 (21) P 52 (11)

E 49 (9) P 26 (6) E 31 (7) P 11 (3) E 12 (6) P 12 (4) E 13 (5) P 4.1 (3.1) E 4.7 (2.3)

P 70 (11) E 81 (21) P 2.8 (0.7)

E 3.0 (0.7)

P 1132 (197)

E 1065 (267)

P 96 (33) E 110 (33) P 80 (14) E 70 (14) P 1.7 (0.3) E 1.8 (0.4) P 44 (15) E 39 (10) P 9.0 (2.4) E 10.0 (4.6)

go (17)$

101 (17)t

39 (9)$

43 (9)t 22 (5)t

24 (9)t

12 (4) 13 (7)

12 (4) 12 (5)

6.0 (3.4)t 5.4 (2.5)

7 62(ll)t 0.05

L a0 (27) 2.3 (0.4).

2.2 (0.5)t

- a91 (27a)t 0.1

- 1156 (349)

o,T 75 (41)* L 117 (57)

o.oz ;; 1;;;

7 1.2 (0.3)$

O.OL 2.1 (0.8) 30 (9)t

26 (10)t

o,~ a.0 (2.0) L 6.6 (4.2)s

7 93 (II)* O.OE 111 (19)X

40 (10)t

47 (11)

20 (4)t

25 (9)t

9 (3)*

12 (7) 10 (3)t

12 (5) 4.6 (2.6)

5.2 (2.4)

7 64(12)t

“‘? a0 (25)

2.3 (0.3)t

2.3 (0.6)s

987 (252)

1194 (336)

78 (24)

118 (64)

o,oy 72 (12) L 55 (13)$ - 1.4 (0.2)$

0.01 - 2.2 (0.8) 28 (6)$

27 (9)$

6.2 (1.2)t 6.6 (2.5)$

95 (9)t

110 (20)$

40 (1l)t

45 (11)

- 20 (4)t 0.1

L 25 (a)t

9 (5) 12 (6) 10 (3)t 12 (15)

o,~ 4.5 (3.2)

L_._ 5.5 (2.2)X

r--- 63 (12)t 0.05

L 77 (23)t

2.1 (0.4)t

2.5 (0.7)s

1069 (232)

1186 (341)

- 88 (34) O.OL 120 (43)

68 (14)t

58 (i4)t 7 1.5 (0.3)$

0.01 L 2.0 (0.5)

27 (a)*

30 (ll)* 6.0 (1 .g)$

7.4 (3.l)t

NOTE. Differences between P and E groups (Kruskal-Wallis test): 0.1 = P < 0.1; 0.05 = P < 0.05; 0.01 = P < 0.01. Comparison to baseline within

groups (Wilcoxon): ??P < 0.1; tP < 0.05; *P < 0.01.

Abbreviations: P, propofol/fentanyl (n = 10); E, etomidate/fentanyl (n = 10).

conditions. Although myocardial infarction did not occur in any patient, it was decided to terminate the investigation of effects of P in patients with CAD after the sixth patient of the P group.

The distribution and severity of coronary stenoses and the values of preoperative ejection fraction and LVEDP of all patients with CAD are compared in Table 3. In the P group, three of six patients had significant stenoses (> 50%) in all three main coronary vessels. Two of the three patients showed severe reductions in AP and CO and an increase in PCWP after induction of anesthesia. In the E group, 5 of 8 patients had significant stenoses in all three vessels. None of these patients demonstrated critical changes of hemody- namic parameters. There was no association between ejection fraction or LVEDP and hemodynamic results.

The following hemodynamic changes were observed in the six patients of the P group and 8 patients of the E group (Table 4, Fig 1). After induction, reductions of APs, CI, SV, and LVSWI and an increase in CVP in both groups, decreases in APd, PAPd, and SVR and an increase in PCWP only in group P, decreases in PAPS and RVSWI, and increases in SVR and APs/SV were observed only in the E group. There was a significant difference among the groups for APs, APd, CVP, SVR, and APslSV after induction. After intubation, baseline values of APs, APd, and HR were not exceeded in any group; in the P group the

mean values of APd and heart rate (HR) were significantly lower than in the E group. Under general anesthesia, decreased values of APs, APd, SVR, and LVSWI were found in the P group, whereas APs, PAPS, CI were reduced in the E group. The most consistent and significant differ- ences between the E and P groups during general anesthe- sia were found to be the values of APd, SVR, and APs/SV, all of which were Lower in the P group.

AI Versus CAD

AI and CAD are compared in Table 5. There are significant differences between groups 1 (AI and P) and 3 (CAD and P) and between groups 2 (AI and E) and 4 (CAD and E) for the following parameters: cardiac disease and preoperative medication (Table l), age, preoperative LVEDP, and mean baseline values of PAP and PCWP for the two P groups and baseline values of APd, PAP, PCWP, CVP, HR, and SVR for the two E groups (Table 5).

Under general anesthesia, patients of group 1 (AI and P) demonstrate that changes of LVSWI are related to changes of APs, APd, APs/SV, and SVR and are not related to changes of SV (Fig 1 and Table 5). In group 2 (AI and E), LVSWI is related to APs, APd, and SV, but not to APslSV or SVR. In group 3 (CAD and P), LVSWI is associated with APs, APd, SVR, and SV. In group 4 (CAD and E), LVSWI

176 hAESSLER Ei A,

AORTIC INSUFFICIENCY I I PROPOFOL

“=I0 ET‘WTE

I r---

CORONARY ARTERY DISEASE / I PROPOFOL ETDMIDATE

“=6 n=6 ri r-7

3 90 $ 60

_E_ 70

I$ 60

= SD

0

Q 2.6 \ I” 2.4

i 2.0

c 1.6

h 4 1.2

80 E 60 < 40 5

20 q

0

20DDs ii

16DOk

:. 1200~

800 2

0

30 =

70 s

60 %

50

I

20 E

10 g

1 D ::

Fig 1. Hemodynamic parameters for the assessment of preload and afterload and the degree of systolic/diastolic myocardial dysfunc- tion are shown.

is associated with APs and SV, but not with APd. An inverse relationship was found between LVSWI and SVR and APs/SV.

DISCUSSION

Both regimens provided a satisfactory anesthetic level. If hemodynamic stability is to be guaranteed in patients with AI, HR should not decrease, afterload should remain constant or even decrease, and there should be as little systolic or diastolic dysfunction of the myocardium as possible. In this investigation, HR was decreased in the P group and was not decreased in the E group during general anesthesia. The Ea (APs/SV) was used to interpret changes in afterload”: the Ea was decreased in the P group, but not in the E group during anesthesia. According to the reports of Mulier et al,13 Bruessel et a1,l4 and Coetzee et al,” P can result in systolic myocardial dysfunction. It is difficult to judge the extent of systolic or diastolic dysfunction on the basis of the present data because pressure-volume loops were not used; however, the discussion will focus on SV and stroke work indices in relation to filling pressures and parameters indicating afterload, such as arterial pressure,

SVR. and Ea. Diastolic dysl‘unction, caused t+ ,ICLI~C

deterioration in patients with AI, should result in an incrcasc in PC’WP. This was not seen in the E group or 111 the P group. Changes rclatcd to intrinsic systolic dysfunc- tion arc decreased CO, SV. or stroke work while prcload and aftcrload remain constant. This is followed h\ ;I compensatory incrcasc in prcload. The fact that prcload was constant or did not increase was seen in the P and F groups. Unfortunately, afterload was not constant. Ea and SVR decreased in the P group under anesthesia and did not change in the E group. At the same time a comparable decrease in LVSWI was observed in both groups. This implies that P resulted in more extensive intrinsic myocar- dial depression than E. Furthermore, the decrease in SV in the prcscncc of a dccrcasc in afterload in the P group is an indication of intrinsic myocardial depression. In summary. there was a decrease in HR and a distinct degree of intrinsic myocardial depression in the P group. Why then did the P and E groups not differ concerning changes in arterial pressure and CI? This should be related to the dccrcase in afterload after P. The low-dosage regimen using Pifcntanyl and the standard-dosage regimen using E/fentanyl. therc- fore, seemed equally safe and effective for induction of anesthesia in patients with AI, even if different mechanisms were responsible. The present hcmodynamic results can bc compared with results of Aun and Major,’ who studied 10 patients with mitral and aortic valve disease. They adminis- tered 1.5 mgikg of P and found reductions of MAP, SVR. LVSWI, and HR comparable to the changes in these patients. In contrast, they did not find significant changes in CI. There arc two major differences between the studies.

arterial pressure (mmHg)

200

180

160

140

120

100

80

60

40

20

0

Y?Y? QTJP-’

systolic systolic

&YCCPl

\

\

mean Y

mean

T:. . p < 0.05 I

diastolic diastolic

I IIn= I IIn=

propofol etomidate

Fig 2. Changes in arterial pressure after the induction of anesthesia in patients with coronary artery disease; I = awake, II = after induction, all patients are in a horizontal position.

PROPOFEL vs ETOMIDATE: Al vs CAD 177

Table 3. Distribution and Severity of Coronary Stenoses, Ejection Fraction, and Left Ventricular End-Diastolic Pressure in Patients With CAD

Patient

Propofol Group Etomidate Group

1 2 3’ 4 5 6’ 1 2 3 4 5 6 7 8

RCA (p. m. d) m 60% p 100% p 75% m 60% p 75% m 75% p 100% m 100% p 90% p75% p75%

LAD (P. m. d) m 90% d 75% m 100% m 75% m 75% m 100% p 75% m 75% m 60% m 100% p 90% m 100% d 100% m 100%

branch&) 50% 90% 99% 90% 50% 100% 100% 75%

Diagonal

CX (P. d) d 99% ~75% ~90% p 100% ~75% d75% d 99,/o p 75% d90% d90% p99%

posterior descending 99% 90%

marginal branch(es) 90% 1 OO’% 50% 99%

Main artery/branch CX 0 0 cx RCA 0 0 0 0 RCA lntermed 0 0 RCA

without significant + cx

stenosis

EF 72% 56% 66% 61% 60% 69% 59% 60% 54% 60% 60% 70% 73% 73%

LV end-diastolic pres- 5 13 11 8 6 8 10 14 6 7 8 16 7 16

sure (mm Hg)

NOTE. Stenoses in % of diameter. Abbreviations: Cx, circumflex; d, distal; LAD, left anterior descending; m, middle; p, proximal; RCA, right coronary artery: EF, ejection fraction; LV

= left ventricular.

*Patients with severe decrease in AP and increase in PCWP.

which may be responsible for the different results concern- ing CI: (1) P combined with fentanyl versus only P,” and (2) ventilation assisted during induction, which may have influenced transmural filling pressure and venous return, while Aun and Major allowed spontaneous ventilation with increases of PCO,, but unchanged intrapulmonary pres-

sure. Stephan et al” compared two groups of patients under general anesthesia with P and found increased CIs in the group with elevated PCO,.

Providing hemodynamic stability in patients with CAD requires different aims, the balance between oxygen de- mand and supply should not be disturbed. Increases in HR,

Table 4. Hemodynamic Data, CAD (Mean f 1 SD)

Awake After Induction After lntubation 10 min Aftel lntubation

APs (mm Hg)

APd (mm Hg)

PAPS (mm Hg)

PAPd (mm Hg)

PCWP (mm Hg)

CVP (mm Hg)

HR (Limin)

Cl (L/min/m*)

SVR (dyne. s. cmm5)

PVR (dyne. s. cm-5)

SV (mL)

APs/SV (mm Hg/mL)

LVSWI (g m mZ)

RVSWI (g rn. m*)

P E

P

E P

E

P

E

P

E P E

P E P

E P E

P E

P

E P E

P E P E

135 (24)

130 (26) 64 (14)

68 (12)

21 (4) 25 (10)

6.0 (3.0) 8.3 (4.0)

5.2 (2.1) 8.2 (5.7)

3.2 (3.0) 1.8 (1.7)

63 (4) 64 (9)

2.8 (0.7)

2.6 (0.5) 1396 (416) 1416 (319)

113 (15) 122 (41)

82 (16)

80 (21) 1.7 (0.6) 1.7 (0.6)

45 (10) 46 (17)

6.0 (2.0) 7.0 (2.3)

o.oF 89 (16)t - 114 (21)t

7 47 (10)t

‘.‘E 63 (13)

20 (5) 20 (5)”

8.5 (3.5)” 8.6 (3.4)

6.5 (2.5)’

8.3 (3.3) o,T 5.5 (3.2)t

L 2.5 (1.9)t

59 (8) 61 (7)

2.0 (0.5)t

2.3 (0.3)t - 1253 (315)*

“‘5 1617 (399)t

102 (30) 112 (30)

66 (18)t 64 (22)t

7 1.4 (0.4) 0.1

- 1.9 (O.S)* 27 (7)t 34 (14)t

4.5 (2.6) 4.8 (1.6)t

100 (13)t 120 (27)’

r-- 50 (12)t

“‘5 69 (15)

21 (71 20 (5)X

8.2 (5.1)X

8.1 (2.1) 7.7 (5.0)

7.3 (21.)

5.5 (6.0)* 2.3 (1.8)*

o,T 56 (7)t L 62 (8)

2.6 (0.8)

2.4 (0.5)’ 1109 (486)”

1452 (349) 95 (35)

109 (48) 87 (30)

76 (21) 1.3 (0.6)’

1.6 (0.5) 37 (15)’ 44 (17)

4.8 (2.5) 6.4 (2.6)

7 99 (10)t 0.1

L 118 (22)t - 50 (7)t

0.01 L 68 (10)

17 (5) 19 (3)t

7.0 (4.7)

8.4 (1.9)

6.3 (3.9) 7.9 (2.6)

4.2 (3.3) 2.1 (1.6) 56 (7)t

60 (6)* 2.4 (0.5)*

2.1 (0.3)t o,oy 1132 (329)*

- 1666 (253)’

94 (31) 115 (36)

7 82 (18) 0.05

L 67 (12)t - 1.3 (0.5)t

0.05 L 1.8 (0.4)

35 (7)t 36 (10)t

4.8 (2.7) 5.5 (1.7)t

NOTE. Between P and E group (Kruskal-Wallis test): 0.1 = P < 0.1; 0.05 = P < 0.05: 0.01 = P < 0.01. Comparison to baseline within groups

(Wilcoxon): *P < 0.1; tP < 0.05; *P < 0.01.

178 HAESSLER E’ Ai

Table 5. Comparison of CAD and Al Groups

PropofollFentanvl Group

Number of Patients

Preoperative parameters

Age

Left ventricular end-diastolic pressure

(mm Hg)

lntraoperative parameters

APs (mm Hg)

APd (mm Hg)

PAPS (mm Hg)

PAPd (mm Hg)

PCWP (mm Hg)

CVP (mm Hg)

HR (L/min)

Cl (L/min/m*)

SVR (dyne. s. cm--5)

PVR (dyne. s. cm-s)

SV (mL)

APs/SV (mm HglmL)

LVSWI (g rn. m2)

RVSWI (g m*)

Al 10

CAD 6

Al

CAD

-50 (14) 0.1

- 61 (6)

Al

CAD -14.7 (5.3)

“‘“L 8.5 (3.0)

Awake

Al

CAD Al

CAD Al

CAD Al

CAD

Al

CAD A)

CAD

Al

CAD Al

CAD Al

CAD

Al CAD

Al

CAD Al

CAD Al

CAD Al

CAD

133 (21) 135 (24)

52 (11)

64 (14)

7 26 (6)

O.O> 21 (4)

r-- 11 (3) 0.01

-6.0 (3.0)

7 12 (4) 0.01 -5.2 (2.1)

4.1 (3.1)

3.2 (3.0)

70 (11)

63 (4) 2.8 (0.7)

2.8 (0.7) 1132 (197)

1396 (416)

96 (33) 113 (15)

80 (14)

82 (16) 1.7 (0.3)

1.7 (0.6)

44 (15)

45 (IO) 9.0 (2.4)

6.0 (2.0)

After Induction

90 (17)$ 89 (16)t

39 (9)*

47 (10)t 22 (5)X

20 (5) 7 12 (4)

0.1 - 8.5 (3.5)*

7 12 (4) 0.1

- 6.5 (2.5)* 6.0 (3.4)t

5.5 (3.2)t

62 (1l)t

59 (8) 2.3 (0.4)” 2.0 (0.5)t

O.i- 891 (278)t - 1253 (315)*

75 (41)* 102 (30)

76 (15)

66 (18)t 1.2 (0.3)$

1.4 (0.4)

30 (9)t

27 (7)t

8.0 (2.0) 4.5 (2.6)

Etomidate:FentanylGroup -_-...

10

8

r- 46 (15) 0.1

L 57 (7)

0.1 (5.1) - 15.9

L__ 11.3(3.9)

Awake After Induction

128 (21) 101 (17)$ 130 (26) 114 (21)t

7 49 (91 7 43 (9)t

O.OE 68 (12) 0.1 - 63 (13) 7 31 (7) 24

0.1 (9)t

- 25 (10) 20 (5)X

7 12 (6) 13 0.1

(7) -8.3 (4.0) 8.6 (3.4)

r-- 13 (5) “‘E8.2 (5.7)

12 (5) 8.3 (3.3)

r--4.7 (2.3)

“‘>1.8 (1.7)

- 5.4 (2.5)

O.OE 2.5 (1.9)t - 0.05 81 (21) - 0.05 80 (27) L 64 (9) - 61 (7)

3.0 (0.7)

2.6 (0.5) o.oF1065 (267)

-1416 (319)

110 (33) 122 (41)

70 (14)

80 (21) 1.8 (0.4)

1.7 (0.6)

39 (10) 46 (17)

10.0 (4.6) 7.0 (2.3)

2.2 (0.5)t 2.3 (0.3)t

o,oy 1156 (349) - 1617 (399)t

117 (57) 112 (30)

55 (17)t 64 (22)t

2.1 (0.9)

1.9 (0.6)*

o,-- 26 (tO)t - 34 (14)t

6.8 (4.2)* 4.8 (1.6)t

NOTE. There was no significant difference in the Al groups or the CAD groups or between the Al and CAD group for the parameters gender, age, weight, height, preoperative Cl, ejection fraction, and ASA classification. For differences concerning preoperative medication see Table I.

Differences between P and E groups (Kruskal-Wallis-test): 0.1 = P < 0.1; 0.05 = P < 0.05; 0.01 = P < 0.01. Comparison to baseline within groups (Wilcoxon): *P i 0.1; tP < 0.05; *P < 0.01

preload and afterload and contractility increase demand. Increases in HR, preload and afterload, as factors determin- ing wall stress, may also decrease supply by decreasing coronary flow.

In the E group, no major changes of HR were observed under general anesthesia. In the P group, HR was de- creased after intubation and 10 minutes after intubation. Increases, as well as decreases, in HR have been found by different investigators in patients with CAD under anesthe- sia with P. Authors who did not combine fentanyl and P tended to find an increase in HR.‘,’ Investigators who started to use P alone and added fentanyl later4,7.8 initially found no change or an increase in HR; however, after fentanyl was added a decrease in HR was observed.

Ea and SVR showed a decrease in afterload in the P group, and increase in the E group under general anesthe-

sia. The 10% to 21% decrease of SVR in the P group corresponds to changes of SVR found by other investigators under comparable conditions.‘-”

The mean values of preload showed a significant (P < 0.10) increase after induction of anesthesia in the P group and no major changes in the E group under general anesthesia. There was a prominent increase in PCWP (+5 and +lO mm Hg) in two patients of the P group. Two reasons for the increase in PCWP could explain this observation: (1) increased resistance to myocardial inflow caused by an upward shift in the LV diastolic pressure/ volume relation, the compensatory mechanism following intrinsic systolic myocardial depression, and (2) increased resistance to myocardial inflow caused by diastolic myocar- dial dysfunction, ie, disturbance of myocardial relaxation. A decline in the ventricular relaxation rate can be a conse-

PROPOFEL vs ETOMIDATE: Al vs CAD 179

quence of regional or global demand &hernia, but also a result from the application of drugs. Prominent A waves in the PCWP tracing are typically seen in relaxation disorders.

After anesthetic induction with P, decreases in CI, LVSWI, SV, Ea, and SVR were observed, while PCWP increased. This is strong evidence for intrinsic systolic myocardial dysfunction. Possible reasons are a direct nega- tive inotropic effect of P and fentanyl or supply ischemia induced by sudden cessation of coronary blood flow. Signs of ischemia were not detected in the ECG. Therefore, the cardiodepressive effect mediated by P seems to be the main reason for the systolic dysfunction. In the E group, CI, LVSWI, and SV decreased, while Ea and SVR increased, and PCWP was constant after induction of anesthesia. The decreases of SV and SW1 may have been related partly to systolic dysfunction and partly to the increase in afterload. Therefore, P seems to have evoked more pronounced systolic dysfunction than E in patients with CAD.

The most dramatic change in the patients with CAD was a reduction in arterial pressure of 30% after induction of anesthesia with P and fentanyl. A reduction of AP after application of P in patients with CAD is well documented.‘.’ Nevertheless, the decreases in AP in the P group required therapy, because a mean diastolic pressure of 40 mm Hg (SD 13) resulted. The decrease to these low values may be partly because of the low mean baseline PCWP (5.3 mm Hg) in the patients. Patrick et al6 and Vermeyen et al5 studied hemodynamics after P in patients with CAD. Patrick et al reported decreases of APs below 100 mm Hg in 8 of 10 patients whose mean PCWP was 6.6 mm Hg. Vermeyen et al’ found decreases of APs below 100 mm Hg only in 2115 patients with higher baseline PCWP (13 mm Hg). However, even with the low values of PCWP in the present patients, normal loading may have been present. In spite of a fluid load of 8 mL/kg, PCWP may not have increased because of normal LV function with flat pressure- volume curves of the ventricles.

patients with CAD. Among the different cardiac diseases and preoperative medications, there is a difference in age (P < 0.10) and in LVEDP (P < 0.05; P < 0.10). Further- more, a number of mean baseline values are different between the AI and CAD groups (Table 5). With these precautions conclusions can be drawn from a comparison of patients of the four studied groups (Fig 1 and Table 5). In group 1 (AI and P), change of the pressure-associated or afterload-associated component of the stroke work is more related to change of LVSWI than change of the volume- related part. In groups 2 (AI and E) and 3 (CAD and P), changes of both components of stroke work, ie, pressure and volume, are equally related to changes of LVSWI. In group 4 (CAD and E), the volume-associated part of stroke work is more responsible for the decrease in LVSWI than the pressure-related part. This is reflected in the inverse association between LVSWI and APsiSV. After intuba- tion, LVSWI and SV (but not arterial pressure) increased in both groups of patients with CAD, but did not increase in the groups of patients with AI. A selective increase in SV could be indicative of an increase in contractility due to sympathoadrenergic response; however, if this was present, increases in SVR and in HR would be expected at the same time, which was not observed in any group. Moreover, in the P groups, HR was decreased during general anesthesia in spite of low values of arterial pressures. This could be due to either a blockade of sympathoadrenergic responses, or a resetting of baroreflexes.18

In conclusion, P/fentanyl can produce severe hypoten- sion in patients with CAD, apparently predominantly in patients with CAD with severe 3-vessel disease.

The decrease in afterload in combination with systolic and presumably diastolic myocardial dysfunction may ex- plain the serious reductions in AP after administration of P. The analysis of the coronary stenoses and ejection fraction/ LVEDP in every single patient of the CAD groups revealed the following: There was an association between a dramatic decrease in AP and severe 3-vessel coronary stenoses. No association was found regarding ejection fraction or LVEDP. In summary, there was an association between systolic and probably diastolic dysfunction and high-grade three-vessel disease. However, there is no statistical evidence for this finding.

In this study, two diseases with different pathophysiology were chosen to obtain insight into the etiology of hemody- namic effects of P and E. In patients with AI or CAD, Plfentanyl resulted in a more pronounced degree of intrin- sic systolic cardiodepression than E/fentanyl. At the same time, afterload was influenced differently by P or E. This may be one reason that AP and CI were stable in patients with AI in spite of systolic myocardial dysfunction.

It is problematic to compare patients with AI and

This leads to the following recommendations: (1) in patients with AI, both P/fentanyl and E/fentanyl are appropriate for the induction of anesthesia, and (2) in patients with CAD P/fentanyl can induce a significant decrease of systemic arterial pressure and an increase in PCWP. Although there may be a preventive and/or thera- peutic effect by infusing volume, positioning the patient head down, avoiding a decrease in PCO,, and administering catecholamines, the combination of P and fentanyl should not be a standard regimen for anesthetic induction of patients with sevelre CAD.

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