- Email: [email protected]
Target-controlled infusion or manually controlled infusion of propofol in high-risk patients with severely reduced left ventricular function
Target-Controlled Infusion or Manually Controlled Infusion of Propofol in High-Risk Patients With Severely Reduced Left Ventricular Function Andreas Lehmann, MD, Joachim Boldt, MD, Reni Ro¨mpert, MD, Elfi Thaler, Bernhard Kumle, MD, and Udo Weisse >2 L/min/m2 in significantly more patients of the TCI group than of the MCI group. Mean dose of propofol was higher in the TCI patients (6.0 ⴞ 1.0 mg/kg/hr) than in the MCI patients (3.0 ⴞ 0.4 mg/kg/hr) (p < 0.05), whereas doses of remifentanil did not differ. Time to extubation was significantly shorter in the MCI (11.9 ⴞ 2.4 min) versus the TCI group (15.6 ⴞ 6.8 min). Costs were significantly lower in MCI patients ($34.73) than in TCI patients ($44.76). Conclusions: In patients with severely reduced left ventricular function, TCI and MCI of propofol in combination with remifentanil showed similar hemodynamics. TCI patients needed inotropic support more often than MCItreated patients. Although extubation time was longer in TCI patients and costs were higher, both anesthesia techniques can be recommended for early extubation after implantation of a cardioverter-defibrillator. Copyright © 2001 by W.B. Saunders Company
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sure (LVEDP) of ⬎14 mmHg measured within 3 months before surgery. All ICDs were implanted subpectorally on the left side of the patients. Ventricular and dual-chamber atrioventricular ICDs were used. A right ventricular electrode was placed transvenously when using single-chamber systems. Patients with dual-chamber systems received 2 electrodes placed transvenously, 1 in the right ventricle and 1 in the right atrium. At the end of surgery, the wound was infiltrated with local anesthetic (20mL of mepivacaine 1%) for postoperative analgesia. The patients were premedicated with 1 to 2 mg of lorazepam orally 1 hour before starting anesthesia. Hemodynamic monitoring consisted of a 5-lead electrocardiogram, radial artery cannulation, and a pulmonary artery catheter (7.5F, EFV/OTD catheter, Baxter, Irvine, CA) placed via the right internal jugular vein. All catheters were placed in the awake patient using local anesthesia. Hemodynamic monitoring consisted of measuring heart rate, mean arterial pressure, central venous pressure, mean pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac output (thermodilution method), and mixed venous oxygen saturation (fiberoptic reflectance spectrophotometry). Cardiac index, stroke volume, left and right ventricular stroke work index, systemic vascular resistance, and pulmonary vascular resistance were calculated from standard
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Objective: To compare hemodynamics, time to extubation, and costs of target-controlled infusion (TCI) with manually controlled infusion (MCI) of propofol in high-risk cardiac surgery patients. Design: Prospective, randomized. Setting: Major community university-affiliated hospital. Participants: Twenty patients undergoing first-time implantation of a cardioverter-defibrillator with severely reduced left ventricular function (left ventricular ejection fraction <30%). Interventions: Anesthesia was performed using remifentanil, 0.2 to 0.3 g/kg/min, and propofol. Propofol was used as TCI (plasma target concentration, 2 to 3 g.mL; n ⴝ 10) or MCI (2.5 to 3.5 mg/kg/hr; n ⴝ 10). Measurements and Main Results: Hemodynamics were measured at 6 data points: T1, before anesthesia; T2, after intubation; T3, after skin incision; T4, after first defibrillation; T5, after third defibrillation; and T6, after extubation. There were no significant hemodynamic differences between the 2 groups. Dobutamine was required to maintain cardiac index
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ROPOFOL WAS introduced in anesthesia in the early 1980s.1 As a fast-acting intravenous drug, propofol has a favorable pharmacokinetic profile for induction and maintenance of anesthesia as total intravenous anesthesia. The development of computer-assisted, target-controlled infusion (TCI) systems of propofol provided the anesthesiologist with a convenient method to deliver anesthetics with direct control of the blood concentration.2 TCI systems for propofol are based on averaged pharmacokinetic models derived from large population samples, specific pharmacokinetic variables for propofol, and infusion-controlled algorithms.3,4 TCI systems are commercially available and are gaining increasing acceptance. In a prospective, randomized multicenter study comparing TCI with manually controlled infusion (MCI) of propofol, most investigators expressed an overall preference (93%) for TCI and found it easier (76%) to handle than conventional propofol application.5 The use of TCI allows titration of the concentration against clinical effects in individual patients. This individual titration of an intravenous drug, similar to an inhalation agent, reduces the incidence of an inadequate depth of anesthesia compared with MCI.5 Using TCI of propofol increased the amount of used drug,6 however, and increased the recovery times from anesthesia compared with MCI.5 Only limited data are available comparing both anesthesia techniques in patients with severely reduced ventricular function. The aim of this study was to compare MCI with TCI of propofol in a high-risk group of patients receiving implantable cardioverter-defibrillators (ICDs).
KEY WORDS: target-controlled infusion, propofol, remifentanil, reduced left ventricular function
MATERIALS AND METHODS
Twenty patients undergoing first implantation of ICD were included in the study after informed consent was obtained according to the protocol of the ethics study board of the hospital. The inclusion criteria were left ventricular ejection fraction (LVEF) ⬍30% and left ventricular end-diastolic pres-
From the Departments of Anesthesiology and Intensive Care Medicine and Cardiac Surgery, Klinikum der Stadt Ludwigshafen, Ludwigshafen, Germany. Address reprint requests to Joachim Boldt, MD, Department of Anesthesiology and Intensive Care Medicine, Klinikum der Stadt Ludwigshafen, Postfach 21 73 52, D-67073 Ludwigshafen, Germany. E-mail: [email protected] Copyright © 2001 by W.B. Saunders Company 1053-0770/01/1504-0008$35.00/0 doi:10.1053/jcan.2001.24979
Journal of Cardiothoracic and Vascular Anesthesia, Vol 15, No 4 (August), 2001: pp 445-450
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Table 1. Demographic Data and Data From the Perioperative Period
Patients (n) Age (y) Gender (M/F) Height (cm) Weight (kg) LVEF (%) LVEDP (mmHg) NYHA class (I/II/III/IV) 1/2 chamber (n)* Duration of surgery (min) Duration of anesthesia (min) Time of extubation (min)†
MCI
TCI
10 62 ⫾ 5 8/2 171 ⫾ 9 84.4 ⫾ 14.5 22.6 ⫾ 3.4 19.5 ⫾ 4.3 0/5/5/0 1/9 82 ⫾ 36 134 ⫾ 43 11.9 ⫾ 2.4
10 61 ⫾ 9 9/1 175 ⫾ 9 83.8 ⫾ 15.2 22.6 ⫾ 7.4 18.0 ⫾ 9.6 0/4/6/0 3/7 73 ⫾ 11 123 ⫾ 10 15.6 ⫾ 6.8‡
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formulae (Explorer, Baxter, Irvine, CA). The following data points were defined: T1, before induction of anesthesia while the patient was awake; T2, 3 minutes after intubation; T3, after skin incision; T4, after the first defibrillation; T5, after the third defibrillation; and T6, 5 minutes after extubation. Anesthesia in both groups was started after the first hemodynamic measurements were completed. The patients were prospectively randomized into 1 of the following 2 groups using a closed-envelope system: Group 1 patients (n ⫽ 10) received MCI of propofol. Anesthesia was induced with a bolus of propofol, 0.7 to 1.0 mg/kg, and a continuous infusion of remifentanil, 1 g/kg/min. Tracheal intubation was facilitated by cisatracurium, 0.15 mg/kg. Anesthesia was maintained by continuous infusion of propofol, 2.5 to 3.5 mg/kg/hr, and remifentanil, 0.3 g/kg/min, according to patient need. Group 2 patients (n ⫽ 10) received TCI of propofol. Propofol was infused using a TCI device (Graseby 3500 Disoprifusor, Graseby Medical Ltd, Watford, UK). Anesthesia was induced with a plasma target concentration of propofol of 3 g/mL. A continuous infusion of 1 g/kg/min of remifentanil was added. After intubation, plasma target concentration of propofol was adjusted to 2 to 3 g/mL according to the needs of the patient, and the infusion rate of remifentanil was reduced to 0.3 g/kg/ min. Cisatracurium was used as in the other group. In both groups, all patients were ventilated to normocapnia (36 to 44 mmHg) with oxygen in air (fraction of inspired oxygen, 0.4). The continuous infusions of propofol and remifentanil were stopped at beginning of skin closure. When mean arterial pressure decreased to ⬍60 mmHg and pulmonary capillary wedge pressure was ⬍12 mmHg, colloids (gelatin) were given, and, until adequate volume load was achieved, a vasopressor (norepinephrine) was used to immediately restore mean arterial pressure. When cardiac index decreased to ⬍2.0 L/min/m2 despite adequate volume administration, dobutamine, 2 g/kg/ min, was started. The dose of dobutamine was increased until cardiac index was ⬎2.0 L/min/m2. When cardiac index was not adequately increased by dobutamine, epinephrine was given. Time from end of the infusion of propofol and remifentanil until the patient opened his or her eyes and underwent tracheal extubation was documented. All patients were visited postoperatively on the next day. Patients were asked about their satisfaction with the anesthesia and whether they had postoperative pain. They were also asked if they would like this type of anesthesia again. The costs for the anesthetic drugs were taken from the actual hospital pharmacy list (propofol, $7.91/500 mg; remifentanil, $22.06/5 mg; dobutamine, $1.89/250 mg; epinephrine, $0.36/l mg; norepinephrine, $0.33/l mg). Cost analysis did not include costs for oxygen, air, staff, and disposables. Fixed costs for anesthesia machines and monitoring equipment were not considered. The exchange rate from Deutsch Mark to U.S. dollars was 2.04. Data are presented as mean ⫾ SD unless otherwise indicated. For statistical analysis, SPSS/PC⫹ software (V4.0 SPSS, Inc, Chicago, IL) was used. Hemodynamics were analyzed using 2-factorial analysis of variance for repeated measurements. For significant findings, post hoc t-tests were applied at the endpoint of each measurement. In case of multiple comparisons, p values were corrected according to Bonferroni. Fisher’s exact
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NOTE. Data are mean ⫾ SD. Abbreviations: MCI, manually controlled infusion, TCI, target-controlled infusion; LVEF, left ventricular ejection fraction; LVEDP, left ventricular end-diastolic pressure; NYHA, New York Heart Association. *1- or 2-chamber cardioverter-defibrillator. †Time from stopping propofol/remifentanil infusion until extubation. ‡p ⬍ 0.05 different from the other group.
test, chi-squared test, Mann-Whitney U-test, and nonpaired t-test were also used when appropriate; p values ⬍ 0.05 were considered significant. RESULTS
There were no significant differences between the 2 groups with respect to demographic and perioperative data (Table 1). All patients were classified as American Society of Anesthesiologists class IV. Left ventricular function was severely reduced in both groups (MCI, LVEF, 22.6 ⫾ 3.4%; TCI, LVEF, 22.6 ⫾ 7.4%). Duration of anesthesia and duration of surgery did not differ between the 2 groups (Table 1). After stopping the infusion of propofol and remifentanil, the patients of the MCI group opened their eyes in 9.3 ⫾ 3.4 minutes (TCI group, 12.6 ⫾ 5.4 minutes; p ⬍ 0.05). MCI patients were extubated significantly earlier (11.9 ⫾ 2.4 minutes) than TCI patients. (15.6 ⫾ 6.8 minutes). Postoperative analgesia was adequately provided by infiltration of the wound with local anesthetics by the surgeon. In both groups, only 3 patients needed additional piritramide, up to 15 mg (analgesic potency in comparison with morphine [⫽ 1] is 0.7) during the first postoperative night. No patient complained about pain after the first night. In both groups, no patient reported awareness during anesthesia. Of patients in both groups, 80% would like the same type of anesthesia next time. TCI patients received twice as much propofol as MCI patients (mean dose, MCI, 3.0 ⫾ 0.4 mg/kg/hr; TCI, 6.0 ⫾ 1.0 mg/kg/hr; p ⬍ 0.05 [Fig 1]; total dose per patient, MCI, 584 ⫾ 251 mg; TCI, 1011 ⫾ 237 mg; p ⬍ 0.05). The dose of remifentanil did not differ between the 2 groups (mean dose, MCI, 0.27 ⫾ 0.05 g/kg/min; TCI, 0.27 ⫾ 0.08 g/kg/min). Hemodynamics were not significantly different at any time between the 2 groups (Table 2). Heart rate dropped significantly during anesthesia in both groups. Mean arterial pressure
TARGET-CONTROLLED VERSUS MANUALLY CONTROLLED PROPOFOL INFUSION
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was significantly reduced at T2, T3, and T4 (MCI) and T2 and T3 (TCI). The lowest observed mean arterial pressure did not differ between the 2 groups (MCI, 58 ⫾ 8 mmHg; TCI, 57 ⫾ 7 mmHg). The lowest mean arterial pressure always occurred during induction of anesthesia. There were no differences in crystalloid (MCI, 960 ⫾ 286 mL; TCI, 1060 ⫾ 205 mL) or colloid (MCI, 430 ⫾ 340 mL; TCI, 295 ⫾ 261 mL) volume replacement. Four patients of the MCI group needed a continuous infusion of dobutamine (mean dose, 1.0 ⫾ 1.4 g/kg/min), whereas 8 of the TCI group patients needed dobutamine (mean dose, 2.2 ⫾ 1.9 g/kg/min; p ⬍ 0.05) (Table 3). Bolus administration of epinephrine was necessary in 2 MCI and 4 TCI patients, whereas norepinephrine was used in 3 MCI and 2 TCI patients. No continuous infusion of epinephrine or norepinephrine was necessary in any of the patients. TCI anesthesia ($44.76) was significantly more expensive per patient than MCI anesthesia ($34.73) (Table 4). The costs
Fig 1. Dose of propofol used. Mean (SD). MCI, manually controlled infusion of propofol; TCI, target-controlled infusion of propofol. *p < 0.05 between the 2 groups.
Table 2. Hemodynamic Data T1
61 ⫾ 14* 60 ⫾ 13*
92 ⫾ 14 88 ⫾ 11
T3
T4
T5
T6
58 ⫾ 12* 59 ⫾ 14*
59 ⫾ 11* 68 ⫾ 17
63 ⫾ 9* 66 ⫾ 16
86 ⫾ 19 89 ⫾ 15
60 ⫾ 9* 63 ⫾ 8*
70 ⫾ 9* 73 ⫾ 14*
74 ⫾ 12* 76 ⫾ 13
77 ⫾ 12 77 ⫾ 10
96 ⫾ 14 98 ⫾ 15
29.4 ⫾ 8.1 30.5 ⫾ 9.1
21.4 ⫾ 9.3 23.8 ⫾ 7.9
26.0 ⫾ 7.0 27.9 ⫾ 10.4
25.4 ⫾ 5.1 26.9 ⫾ 6.0
26.3 ⫾ 6.5 26.3 ⫾ 6.1
41.6 ⫾ 10 40.1 ⫾ 7.4
7.5 ⫾ 4.9 8.5 ⫾ 6.1
8.5 ⫾ 4.5 9.6 ⫾ 4.6
11.7 ⫾ 4.0 12.0 ⫾ 4.9
11.3 ⫾ 4.8 11.5 ⫾ 4.5
10.8 ⫾ 4.8 11.1 ⫾ 4.5
13 ⫾ 4.5 12.9 ⫾ 4.3
18.4 ⫾ 11.8 19.7 ⫾ 7.5
13.4 ⫾ 9.1 14.8 ⫾ 6.3
16.6 ⫾ 6.8 18.9 ⫾ 7.8
16.3 ⫾ 7.0 17.1 ⫾ 3.1
16.6 ⫾ 7.5 15.3 ⫾ 2.9
23.4 ⫾ 9.7 23.4 ⫾ 8.3
2.6 ⫾ 0.5 2.6 ⫾ 0.3
2.5 ⫾ 0.6 2.3 ⫾ 0.4
2.2 ⫾ 0.6 2.3 ⫾ 0.5
2.1 ⫾ 0.4 2.6 ⫾ 0.6
2.2 ⫾ 0.3 2.5 ⫾ 0.6
2.8 ⫾ 0.6 2.5 ⫾ 0.6
1341 ⫾ 269 1340 ⫾ 252
913 ⫾ 349 949 ⫾ 256
1116 ⫾ 257 1079 ⫾ 256
1216 ⫾ 363 1078 ⫾ 267
1206 ⫾ 277 1151 ⫾ 302
1258 ⫾ 277 1360 ⫾ 369
160 ⫾ 51 168 ⫾ 65
147 ⫾ 52 160 ⫾ 65
154 ⫾ 29 156 ⫾ 57
162 ⫾ 63 156 ⫾ 47
178 ⫾ 57 188 ⫾ 59
245 ⫾ 94 268 ⫾ 79
32.5 ⫾ 11.0 31.6 ⫾ 12.9
25.7 ⫾ 8.0 24.7 ⫾ 5.6
28.0 ⫾ 8.0 29.5 ⫾ 9.4
27.3 ⫾ 7.5 31.0 ⫾ 10.4
29.0 ⫾ 7.2 31.5 ⫾ 8.6
32.9 ⫾ 9.1 31.0 ⫾ 14.2
9.0 ⫾ 4.0 9.8 ⫾ 3.3
7.4 ⫾ 2.2 7.5 ⫾ 2.4
8.3 ⫾ 2.4 9.4 ⫾ 3.3
7.1 ⫾ 1.6 8.0 ⫾ 1.8
7.7 ⫾ 1.6 8.4 ⫾ 2.7
13.7 ⫾ 4.6 10.9 ⫾ 3.1
70 ⫾ 6 71 ⫾ 4
77 ⫾ 4 78 ⫾ 4
72 ⫾ 6 75 ⫾ 5
70 ⫾ 5 74 ⫾ 5
70 ⫾ 6 73 ⫾ 6
68 ⫾ 10 63 ⫾ 11
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83 ⫾ 18 76 ⫾ 15
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HR (beats/min) MCI TCI MAP (mmHg) MCI TCI MPAP (mmHg) MCI TCI CVP (mmHg) MCI TCI PCWP (mmHg) MCI TCI CI (L/min/m2) MCI TCI SVR (dyne/sec/cm⫺5) MCI TCI PVR (dyne/sec/cm⫺5) MCI TCI LVSWI (g/m/m2/beat) MCI TCI RVSWI (g/m/m2/beat) MCI TCI SvO2 (%) MCI TCI
T2
Abbreviations: T1, before induction of anesthesia; T2, after intubation; T3, at skin incision; T4, after first defibrillation; T5, after third defibrillation; T6, after extubation; MCI, manually controlled infusion of propofol; TCI, target-controlled infusion of propofol; HR, heart rate; MAP, mean arterial pressure, MPAP, mean pulmonary arterial pressure; CVP, central venous pressure; PCWP, pulmonary capillary wedge pressure; CI, cardiac index; SVR, systemic vascular resistance; PVR, pulmonary vascular resistance; LVSWI, left ventricular stroke work index; RVSWI, right ventricular stroke work index; SvO2, mixed venous oxygen saturation. *p ⬍ 0.05 different from baseline value.
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Table 3. Use of Catecholamines
Dobutamine Patients (n) Range (g/kg/min) Epinephrine Patients (n) Range (g) Norepinephrine Patients (n) Range (g)
MCI
TCI
4 2.0-2.9
8* 2.8-4.8
2 5-10
4 5-15
3 10-20
2 10-20
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NOTE. Dobutamine was given as continuous infusion, whereas epinephrine and norepinephrine were given as boli. Abbreviations: MCI, manually controlled infusion of propofol; TCI: target-controlled infusion of propofol. *p ⬍ 0.05 different from the other group.
for muscular relaxation and fluid replacement were not analyzed because they did not differ between the 2 groups. DISCUSSION
manual induction and significantly higher maintenance levels with TCI. In the present study, TCI nearly doubled the dose of propofol used compared with MCI. Whether TCI of propofol improves quality of anesthesia compared with MCI is controversial. In a multicenter study, most anesthesiologists expressed an overall preference for TCI (93%) and found it easier to use (76%) than MCI.5 In 160 patients breathing spontaneously via laryngeal mask airway, Russell et al28 showed that induction of anesthesia and positioning of laryngeal mask were faster and safer in TCI patients compared with MCI patients. These investigators showed fewer movements of TCI patients at skin incision and during surgery. Recovery times were most likely prolonged because the amount of propofol was significantly higher in TCI patients. Hunt-Smith et al26 did not find different recovery times from anesthesia comparing TCI with MCI anesthesia. Recovery times in the present study were significantly longer in TCI than in MCI patients. No patient of any group complained about awareness or intraoperative recall postoperatively, and the acceptance for TCI or MCI was similar. Hemodynamic data from this study suggest that both techniques of propofol anesthesia provided stable hemodynamics in this patient population. Significantly more patients in the TCI group than in the MCI group needed inotropic support with dobutamine, however. The higher doses of propofol in the TCI group appear to be the reason why more inotropic support in the patients with severely reduced left ventricular function in this study was required to maintain a cardiac index ⬎2.0 L/min/m2. In a study in dogs with dilated cardiomyopathy,29
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General and local anesthesia are used for implantation of ICDs.7-12 Anesthetic techniques using deep sedation without adequate monitoring in a group of high-risk patients cannot be recommended because of safety reasons.8,11 There are many possible complications (eg, pneumothorax, hemothorax, rupture of subclavian vein, hematoma, and failure of successful defibrillation by the ICD requiring external defibrillation).12-16 General anesthesia is commonly used for implantation of ICDs. The hemodynamic consequences of propofol were shown in several studies.17-20 In cardiac surgery, total intravenous anesthesia with propofol combined with an opioid is commonly used,17,18 especially for fast-track procedures.18,19 Total intravenous anesthesia has been used for patients with reduced left ventricular function.7,20 Combination with an opioid (eg, remifentanil) allows dose reduction of propofol, providing better hemodynamic stability.18,21 Recommended calculated plasma concentrations of propofol vary from 4 to 6 g/mL for induction of anesthesia in healthy, unpremedicated patients scheduled for minor orthopedic surgery.22 For maintenance of anesthesia, adequate target plasma concentration was reported to vary between 3.5 and 4.5 g/mL in patients undergoing major surgery,23 and between 4 and 6 g/mL in orthopedic surgery patients.24 Elderly patients needed lower propofol target concentrations compared with younger patients.23 Olivier et al18 reported use of TCI of propofol combined with remifentanil in 50 patients undergoing cardiac surgery with cardiopulmonary bypass. Because of the combination with remifentanil (0.25 to 1.0 g/kg/min), they reduced the calculated plasma concentration of propofol to 1.5 to 2.0 g/mL,18 which is lower than the dose used in the patients in the present study (2.0 to 3.0 g/mL), most likely because of higher doses of remifentanil. Different studies comparing TCI with MCI of propofol showed that induction doses of TCI-based anesthesia are lower than with MCI. During maintenance of anesthesia, however, TCI delivers significantly higher doses of propofol than MCI.5,6,26,27 Using computer simulations, Struys et al27 showed an overshoot in propofol blood and effect-site concentrations with
Table 4. Cost Analysis MCI
TCI
Propofol Used (total) Wasted (total) Costs (total) Costs (per patient) Remifentanil Used (total) Wasted (total) Costs (total) Costs (per patient) Dobutamine Used and wasted (total) Costs (total) Costs (per patient) Epinephrine Used and wasted (total) Costs (total) Costs (per patient) Norepinephrine Used and wasted (total) Costs (total) Costs (per patient)
10 patients 5837 mg 1663 mg $118.60 $11.86 10 patients 29,780 mg 20,220 mg $220.64 $22.06 4 patients 1000 mg $6.43 $0.64 2 patients 2 mg $0.72 $0.07 3 patients 3 mg $0.99 $0.1
10 patients 10114 mg* 3386 mg* $213.49* $21.35* 10 patients 27,060 mg 22,940 mg $220.64 $22.06 8 patients* 2000 mg* $12.86* $1.28* 4 patients 4 mg $1.43 $0.14 2 patients 2 mg $0.66 $0.07
Total costs per patient
$34.73
$44.76*
Abbreviations: MCI, manually controlled infusion of propofol; TCI, target-controlled infusion of propofol. *p ⬍ 0.05 different from the other group.
TARGET-CONTROLLED VERSUS MANUALLY CONTROLLED PROPOFOL INFUSION
complained about pain at a median time of 21 minutes after surgery. ICD implantation is not harmful and painful.36 Postoperative pain can be compared with that of pacemaker implantation. Postoperative analgesia in the patients in this study could easily be provided by infiltration of the wound by local anesthetics and, if necessary, by moderate doses of an opioid. It is difficult to compare cost analysis from other studies because of the different acquisition costs of anesthetic drugs, which vary widely from area to area and may rapidly change. In high-risk patients, a tremendous cost reduction is possible if postoperative treatment in an intensive care unit can be avoided. None of the patients in this study had severe complications, and no patient needed sustained postoperative inotropic or ventilatory support. TCI anesthesia required more anesthetic drugs and more inotropic support than MCI. In conclusion, MCI and TCI of propofol in combination with remifentanil in patients with severely reduced left ventricular function showed similar hemodynamics, were well controllable, and allowed early extubation after implantation of ICDs. TCI doubled the dose of propofol used compared with MCI, resulting in higher costs. This increased dose was associated with a greater need for inotropic support in these high-risk patients and slightly delayed emergence from anesthesia compared with patients with MCI-based anesthesia technique.
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propofol reduced left ventricular preload, afterload, and regional chamber stiffness; caused direct negative inotropic effects; and impaired early diastolic left ventricular filling. Because many patients receiving an ICD suffer from dilated cardiomyopathy, this animal model may represent the hemodynamic situation of these patients. Izquierdo et al30 reported that 25% of their ICD patients “required dobutamine for sustained hypotension.” Hachenberg et al31 needed a positive inotropic intervention in 40% of their patients receiving an ICD. In patients with dilated cardiomyopathy, total extracellular fluid volume was elevated.32 Propofol is mostly eliminated by the liver, but there is an extensive uptake and first-pass elimination in the lungs.33 The augmented extracellular fluid volume and chronic congestion of the lungs in patients with chronic heart failure might alter pharmacokinetics of propofol so that the pharmacokinetic parameters used for the TCI pumps do not predict the actual plasma concentrations in these patients well. Bailey et al34 showed that pharmacokinetics of propofol in adult patients undergoing cardiac surgery with extracorporeal circulation were dissimilar from those reported for other adult patients. One of the major disadvantages of remifentanil is the rapid disappearance of any analgesic effect in the postoperative period. Dershwitz et al35 reported that 92% of their patients
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1. Russell D: Intravenous anaesthesia: manual infusion schemes versus TCI systems. Anaesthesia 53:42-45, 1998 (suppl 1) 2. Gray JM, Kenny GN: Development of the technology for ‘Diprifusor’ TCI systems. Anaesthesia 53:22-27, 1998 (suppl 1) 3. Coetzee JF, Glen JB, Wium CA, Boshoff L: Pharmacokinetic model selection for target-controlled infusions of propofol. Anesthesiology 82:1328-1345, 1995 4. White M, Kenny GN: Intravenous propofol anaesthesia using a computerised infusion system. Anaesthesia 45:204-209, 1990 5. Servin FS: TCI compared with manually controlled infusion of propofol: A multicentre study. Anaesthesia 53:82-86, 1998 (suppl 1) 6. Fechner J, Albrecht S, Ihmsen H, et al: Predictability and precision of ‘target-controlled infusion’ (TCI) of propofol with the ‘Disoprifusor TCI’ system. Anaesthesist 47:663-668, 1998 7. Lehmann A, Boldt J, Zeitler C, et al: Total intravenous anesthesia with remifentanil and propofol for implantation of cardioverter-defibrillators in patients with severely reduced left ventricular function. J Cardiothorac Vasc Anesth 13:15-19, 1999 8. Natale A, Kearney MM, Brandon MJ, et al: Safety of nurseadministered deep sedation for defibrillator implantation in the electrophysiology laboratory. J Cardiovasc Electrophysiol 7:301-306, 1996 9. Pacifico A, Cedillo-Salazar FR, Nasir N, et al: Conscious sedation with combined hypnotic agents for implantation of implantable cardioverter-defibrillators. J Am Coll Cardiol 30:769-773, 1997 10. Pacifico A, Wheelan KR, Nasir N, et al: Long-term follow-up of cardioverter-defibrillator implanted under conscious sedation in pectoral subfascial position. Circulation 95:946-950, 1997 11. Stix G, Anvari A, Grabenwoger M, et al: Implantation of unipolar cardioverter/defibrillator system under local anesthesia. Eur Heart J 17:764-768, 1996 12. Tung RT, Bajaj AK: Safety of implantation of a cardioverterdefibrillator without general anesthesia in an electrophysiology laboratory. Am J Cardiol 75:908-912, 1995
13. Strickberger SA, Hummel JD, Daoud E, et al: Implantation by electrophysiologists of 100 consecutive cardioverter-defibrillators with non-thoracotomy lead systems. Circulation 90:868-872, 1994 14. Fitzpatrick AP, Lesh MD, Epstein LM, et al: Electrophysiological laboratory, electrophysiologist-implanted, nonthoracotomy-implantable cardioverter/defibrillators. Circulation 89:2503-2508, 1994 15. Trappe HJ, Pfitzner P, Heintze J, et al: Cardioverter-defibrillator implantation in the heart catheterization laboratory— observations with 105 patients. Z Kardiol 84:385-393, 1995 16. Blakeman BP, Sullivan HJ, Montoya A, et al: Nonthoracotomy lead system for implantable defibrillator. J Thorac Cardiovasc Surg 106:1040-1047, 1993 17. Phillips AS, McMurray TJ, Mirakhur RK, et al: Propofol-fentanyl anesthesia: A comparison with isoflurane-fentanyl anesthesia in coronary artery bypass grafting and valve replacement surgery. J Cardiothorac Vasc Anesth 8:289-296, 1994 18. Olivier P, Sirieix D, Dassier P, et al: Continuous infusion of remifentanil and target-controlled infusion of propofol for patients undergoing cardiac surgery: A new approach for scheduled early extubation. J Cardiothorac Vasc Anesth 14:29-35, 2000 19. Myles PS, Buckland MR, Weeks AM, et al: Hemodynamic effects, myocardial ischemia, and timing of tracheal extubation with propofol-based anesthesia for cardiac surgery. Anesth Analg 84:12-19, 1997 20. Sherry KM, Sartain J, Bell JH, Wilkinson GA: Comparison of the use of a propofol infusion in cardiac surgical patients with normal and low cardiac output states. J Cardiothorac Vasc Anesth 9:368-372, 1995 21. Vuyk J, Engbers FH, Burm AGL, et al: Pharmacodynamic interaction between propofol and alfentanil when given for induction of anesthesia. Anesthesiology 84:288-299, 1996 22. Casati A, Fanelli G, Casaletti E, et al: The target plasma concentration of propofol required to place laryngeal mask versus cuffed oropharyngeal airway. Anesth Analg 88:917-920, 1999
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30. Izquierdo E, Matute P, Gomar C, Nalda MA: Implantable automatic cardioverter-defibrillator: Anesthesia experience. Rev Esp Anestesiol Reanim 42:424-427, 1995 31. Hachenberg T, Hammel D, Mollhoff T, et al: Cardiopulmonary effects of internal cardioverter-defibrillator implantation. Acta Anaesthesiol Scand 35:626-630, 1991 32. Galatius S, Bent-Hansen L, Wroblewski H, Kastrup J: Plasma clearance of polyfructosan and extracellular body fluid distribution in idiopathic dilated cardiomyopathy and after heart transplantation. Am J Cardiol 85:843-848, 2000 33. Kuipers JA, Boer F, Olieman W, et al: First-pass uptake and pulmonary clearance of propofol: Assessment with recirculatory indocyanine green pharmacokinetic model. Anesthesiology 91:1780-1787, 1999 34. Bailey JM, Mora CT, Shafer SL: Pharmocokinetics of propofol in adult patients undergoing coronary revascularization. The Multicenter Study of Perioperative Ischemia Research Group. Anesthesiology 84:1288-1297, 1996 35. Dershwitz M, Randel GI, Rosow CE, et al: Initial clinical experience with remifentanil, a new opioid metabolized by esterases. Anesth Analg 81:619-623, 1995 36. Frame R, Brodman R, Gross J, et al: Initial experience with transvenous implantable cardioverter defibrillator lead systems: Operative morbidity and mortality. Pacing Clin Electrophysiol 16:149-152, 1993
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23. Swinhoe CF, Peacock JE, Glen JB, Reilly CS: Evaluation of the predictive performance of a ‘Diprifusor’ TCI system. Anaesthesia 53:61-67, 1998 (suppl 1) 24. Servin FS, Marchand-Maillet F, Desmonts JM: Influence of analgesic supplementation on the target propofol concentrations for anaesthesia with ‘Diprifusor’ TCI. Anaesthesia 53:72-76, 1998 (suppl 1) 25. Strachan AN, Edwards ND: Randomized placebo-controlled trial to assess the effect of remifentanil and propofol on bispectral index and sedation. Br J Anaesth 84:489-490, 2000 26. Hunt-Smith J, Donaghy A, Leslie K, et al: Safety and efficacy of target-controlled infusion (Diprifusor) versus manually controlled infusion of propofol for anaesthesia. Anaesth Intensive Care 27:260-264, 1999 27. Struys M, Versichelen L, Thas O, et al: Comparison of computer-controlled administration of propofol with two manually controlled infusion techniques. Anaesthesia 52:41-50, 1997 28. Russell D, Wilkes MP, Hunter SC, et al: Manual compared with target-controlled infusion of propofol. Br J Anaesth 75:562566, 1995 29. Pagel PS, Hettrick DA, Kersten JR: Cardiovascular effects of propofol in dogs with dilated cardiomyopathy. Anesthesiology 88:180189, 1998
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sure (LVEDP) of ⬎14 mmHg measured within 3 months before surgery. All ICDs were implanted subpectorally on the left side of the patients. Ventricular and dual-chamber atrioventricular ICDs were used. A right ventricular electrode was placed transvenously when using single-chamber systems. Patients with dual-chamber systems received 2 electrodes placed transvenously, 1 in the right ventricle and 1 in the right atrium. At the end of surgery, the wound was infiltrated with local anesthetic (20mL of mepivacaine 1%) for postoperative analgesia. The patients were premedicated with 1 to 2 mg of lorazepam orally 1 hour before starting anesthesia. Hemodynamic monitoring consisted of a 5-lead electrocardiogram, radial artery cannulation, and a pulmonary artery catheter (7.5F, EFV/OTD catheter, Baxter, Irvine, CA) placed via the right internal jugular vein. All catheters were placed in the awake patient using local anesthesia. Hemodynamic monitoring consisted of measuring heart rate, mean arterial pressure, central venous pressure, mean pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac output (thermodilution method), and mixed venous oxygen saturation (fiberoptic reflectance spectrophotometry). Cardiac index, stroke volume, left and right ventricular stroke work index, systemic vascular resistance, and pulmonary vascular resistance were calculated from standard
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Objective: To compare hemodynamics, time to extubation, and costs of target-controlled infusion (TCI) with manually controlled infusion (MCI) of propofol in high-risk cardiac surgery patients. Design: Prospective, randomized. Setting: Major community university-affiliated hospital. Participants: Twenty patients undergoing first-time implantation of a cardioverter-defibrillator with severely reduced left ventricular function (left ventricular ejection fraction <30%). Interventions: Anesthesia was performed using remifentanil, 0.2 to 0.3 g/kg/min, and propofol. Propofol was used as TCI (plasma target concentration, 2 to 3 g.mL; n ⴝ 10) or MCI (2.5 to 3.5 mg/kg/hr; n ⴝ 10). Measurements and Main Results: Hemodynamics were measured at 6 data points: T1, before anesthesia; T2, after intubation; T3, after skin incision; T4, after first defibrillation; T5, after third defibrillation; and T6, after extubation. There were no significant hemodynamic differences between the 2 groups. Dobutamine was required to maintain cardiac index
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ROPOFOL WAS introduced in anesthesia in the early 1980s.1 As a fast-acting intravenous drug, propofol has a favorable pharmacokinetic profile for induction and maintenance of anesthesia as total intravenous anesthesia. The development of computer-assisted, target-controlled infusion (TCI) systems of propofol provided the anesthesiologist with a convenient method to deliver anesthetics with direct control of the blood concentration.2 TCI systems for propofol are based on averaged pharmacokinetic models derived from large population samples, specific pharmacokinetic variables for propofol, and infusion-controlled algorithms.3,4 TCI systems are commercially available and are gaining increasing acceptance. In a prospective, randomized multicenter study comparing TCI with manually controlled infusion (MCI) of propofol, most investigators expressed an overall preference (93%) for TCI and found it easier (76%) to handle than conventional propofol application.5 The use of TCI allows titration of the concentration against clinical effects in individual patients. This individual titration of an intravenous drug, similar to an inhalation agent, reduces the incidence of an inadequate depth of anesthesia compared with MCI.5 Using TCI of propofol increased the amount of used drug,6 however, and increased the recovery times from anesthesia compared with MCI.5 Only limited data are available comparing both anesthesia techniques in patients with severely reduced ventricular function. The aim of this study was to compare MCI with TCI of propofol in a high-risk group of patients receiving implantable cardioverter-defibrillators (ICDs).
KEY WORDS: target-controlled infusion, propofol, remifentanil, reduced left ventricular function
MATERIALS AND METHODS
Twenty patients undergoing first implantation of ICD were included in the study after informed consent was obtained according to the protocol of the ethics study board of the hospital. The inclusion criteria were left ventricular ejection fraction (LVEF) ⬍30% and left ventricular end-diastolic pres-
From the Departments of Anesthesiology and Intensive Care Medicine and Cardiac Surgery, Klinikum der Stadt Ludwigshafen, Ludwigshafen, Germany. Address reprint requests to Joachim Boldt, MD, Department of Anesthesiology and Intensive Care Medicine, Klinikum der Stadt Ludwigshafen, Postfach 21 73 52, D-67073 Ludwigshafen, Germany. E-mail: [email protected] Copyright © 2001 by W.B. Saunders Company 1053-0770/01/1504-0008$35.00/0 doi:10.1053/jcan.2001.24979
Journal of Cardiothoracic and Vascular Anesthesia, Vol 15, No 4 (August), 2001: pp 445-450
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Table 1. Demographic Data and Data From the Perioperative Period
Patients (n) Age (y) Gender (M/F) Height (cm) Weight (kg) LVEF (%) LVEDP (mmHg) NYHA class (I/II/III/IV) 1/2 chamber (n)* Duration of surgery (min) Duration of anesthesia (min) Time of extubation (min)†
MCI
TCI
10 62 ⫾ 5 8/2 171 ⫾ 9 84.4 ⫾ 14.5 22.6 ⫾ 3.4 19.5 ⫾ 4.3 0/5/5/0 1/9 82 ⫾ 36 134 ⫾ 43 11.9 ⫾ 2.4
10 61 ⫾ 9 9/1 175 ⫾ 9 83.8 ⫾ 15.2 22.6 ⫾ 7.4 18.0 ⫾ 9.6 0/4/6/0 3/7 73 ⫾ 11 123 ⫾ 10 15.6 ⫾ 6.8‡
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formulae (Explorer, Baxter, Irvine, CA). The following data points were defined: T1, before induction of anesthesia while the patient was awake; T2, 3 minutes after intubation; T3, after skin incision; T4, after the first defibrillation; T5, after the third defibrillation; and T6, 5 minutes after extubation. Anesthesia in both groups was started after the first hemodynamic measurements were completed. The patients were prospectively randomized into 1 of the following 2 groups using a closed-envelope system: Group 1 patients (n ⫽ 10) received MCI of propofol. Anesthesia was induced with a bolus of propofol, 0.7 to 1.0 mg/kg, and a continuous infusion of remifentanil, 1 g/kg/min. Tracheal intubation was facilitated by cisatracurium, 0.15 mg/kg. Anesthesia was maintained by continuous infusion of propofol, 2.5 to 3.5 mg/kg/hr, and remifentanil, 0.3 g/kg/min, according to patient need. Group 2 patients (n ⫽ 10) received TCI of propofol. Propofol was infused using a TCI device (Graseby 3500 Disoprifusor, Graseby Medical Ltd, Watford, UK). Anesthesia was induced with a plasma target concentration of propofol of 3 g/mL. A continuous infusion of 1 g/kg/min of remifentanil was added. After intubation, plasma target concentration of propofol was adjusted to 2 to 3 g/mL according to the needs of the patient, and the infusion rate of remifentanil was reduced to 0.3 g/kg/ min. Cisatracurium was used as in the other group. In both groups, all patients were ventilated to normocapnia (36 to 44 mmHg) with oxygen in air (fraction of inspired oxygen, 0.4). The continuous infusions of propofol and remifentanil were stopped at beginning of skin closure. When mean arterial pressure decreased to ⬍60 mmHg and pulmonary capillary wedge pressure was ⬍12 mmHg, colloids (gelatin) were given, and, until adequate volume load was achieved, a vasopressor (norepinephrine) was used to immediately restore mean arterial pressure. When cardiac index decreased to ⬍2.0 L/min/m2 despite adequate volume administration, dobutamine, 2 g/kg/ min, was started. The dose of dobutamine was increased until cardiac index was ⬎2.0 L/min/m2. When cardiac index was not adequately increased by dobutamine, epinephrine was given. Time from end of the infusion of propofol and remifentanil until the patient opened his or her eyes and underwent tracheal extubation was documented. All patients were visited postoperatively on the next day. Patients were asked about their satisfaction with the anesthesia and whether they had postoperative pain. They were also asked if they would like this type of anesthesia again. The costs for the anesthetic drugs were taken from the actual hospital pharmacy list (propofol, $7.91/500 mg; remifentanil, $22.06/5 mg; dobutamine, $1.89/250 mg; epinephrine, $0.36/l mg; norepinephrine, $0.33/l mg). Cost analysis did not include costs for oxygen, air, staff, and disposables. Fixed costs for anesthesia machines and monitoring equipment were not considered. The exchange rate from Deutsch Mark to U.S. dollars was 2.04. Data are presented as mean ⫾ SD unless otherwise indicated. For statistical analysis, SPSS/PC⫹ software (V4.0 SPSS, Inc, Chicago, IL) was used. Hemodynamics were analyzed using 2-factorial analysis of variance for repeated measurements. For significant findings, post hoc t-tests were applied at the endpoint of each measurement. In case of multiple comparisons, p values were corrected according to Bonferroni. Fisher’s exact
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NOTE. Data are mean ⫾ SD. Abbreviations: MCI, manually controlled infusion, TCI, target-controlled infusion; LVEF, left ventricular ejection fraction; LVEDP, left ventricular end-diastolic pressure; NYHA, New York Heart Association. *1- or 2-chamber cardioverter-defibrillator. †Time from stopping propofol/remifentanil infusion until extubation. ‡p ⬍ 0.05 different from the other group.
test, chi-squared test, Mann-Whitney U-test, and nonpaired t-test were also used when appropriate; p values ⬍ 0.05 were considered significant. RESULTS
There were no significant differences between the 2 groups with respect to demographic and perioperative data (Table 1). All patients were classified as American Society of Anesthesiologists class IV. Left ventricular function was severely reduced in both groups (MCI, LVEF, 22.6 ⫾ 3.4%; TCI, LVEF, 22.6 ⫾ 7.4%). Duration of anesthesia and duration of surgery did not differ between the 2 groups (Table 1). After stopping the infusion of propofol and remifentanil, the patients of the MCI group opened their eyes in 9.3 ⫾ 3.4 minutes (TCI group, 12.6 ⫾ 5.4 minutes; p ⬍ 0.05). MCI patients were extubated significantly earlier (11.9 ⫾ 2.4 minutes) than TCI patients. (15.6 ⫾ 6.8 minutes). Postoperative analgesia was adequately provided by infiltration of the wound with local anesthetics by the surgeon. In both groups, only 3 patients needed additional piritramide, up to 15 mg (analgesic potency in comparison with morphine [⫽ 1] is 0.7) during the first postoperative night. No patient complained about pain after the first night. In both groups, no patient reported awareness during anesthesia. Of patients in both groups, 80% would like the same type of anesthesia next time. TCI patients received twice as much propofol as MCI patients (mean dose, MCI, 3.0 ⫾ 0.4 mg/kg/hr; TCI, 6.0 ⫾ 1.0 mg/kg/hr; p ⬍ 0.05 [Fig 1]; total dose per patient, MCI, 584 ⫾ 251 mg; TCI, 1011 ⫾ 237 mg; p ⬍ 0.05). The dose of remifentanil did not differ between the 2 groups (mean dose, MCI, 0.27 ⫾ 0.05 g/kg/min; TCI, 0.27 ⫾ 0.08 g/kg/min). Hemodynamics were not significantly different at any time between the 2 groups (Table 2). Heart rate dropped significantly during anesthesia in both groups. Mean arterial pressure
TARGET-CONTROLLED VERSUS MANUALLY CONTROLLED PROPOFOL INFUSION
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was significantly reduced at T2, T3, and T4 (MCI) and T2 and T3 (TCI). The lowest observed mean arterial pressure did not differ between the 2 groups (MCI, 58 ⫾ 8 mmHg; TCI, 57 ⫾ 7 mmHg). The lowest mean arterial pressure always occurred during induction of anesthesia. There were no differences in crystalloid (MCI, 960 ⫾ 286 mL; TCI, 1060 ⫾ 205 mL) or colloid (MCI, 430 ⫾ 340 mL; TCI, 295 ⫾ 261 mL) volume replacement. Four patients of the MCI group needed a continuous infusion of dobutamine (mean dose, 1.0 ⫾ 1.4 g/kg/min), whereas 8 of the TCI group patients needed dobutamine (mean dose, 2.2 ⫾ 1.9 g/kg/min; p ⬍ 0.05) (Table 3). Bolus administration of epinephrine was necessary in 2 MCI and 4 TCI patients, whereas norepinephrine was used in 3 MCI and 2 TCI patients. No continuous infusion of epinephrine or norepinephrine was necessary in any of the patients. TCI anesthesia ($44.76) was significantly more expensive per patient than MCI anesthesia ($34.73) (Table 4). The costs
Fig 1. Dose of propofol used. Mean (SD). MCI, manually controlled infusion of propofol; TCI, target-controlled infusion of propofol. *p < 0.05 between the 2 groups.
Table 2. Hemodynamic Data T1
61 ⫾ 14* 60 ⫾ 13*
92 ⫾ 14 88 ⫾ 11
T3
T4
T5
T6
58 ⫾ 12* 59 ⫾ 14*
59 ⫾ 11* 68 ⫾ 17
63 ⫾ 9* 66 ⫾ 16
86 ⫾ 19 89 ⫾ 15
60 ⫾ 9* 63 ⫾ 8*
70 ⫾ 9* 73 ⫾ 14*
74 ⫾ 12* 76 ⫾ 13
77 ⫾ 12 77 ⫾ 10
96 ⫾ 14 98 ⫾ 15
29.4 ⫾ 8.1 30.5 ⫾ 9.1
21.4 ⫾ 9.3 23.8 ⫾ 7.9
26.0 ⫾ 7.0 27.9 ⫾ 10.4
25.4 ⫾ 5.1 26.9 ⫾ 6.0
26.3 ⫾ 6.5 26.3 ⫾ 6.1
41.6 ⫾ 10 40.1 ⫾ 7.4
7.5 ⫾ 4.9 8.5 ⫾ 6.1
8.5 ⫾ 4.5 9.6 ⫾ 4.6
11.7 ⫾ 4.0 12.0 ⫾ 4.9
11.3 ⫾ 4.8 11.5 ⫾ 4.5
10.8 ⫾ 4.8 11.1 ⫾ 4.5
13 ⫾ 4.5 12.9 ⫾ 4.3
18.4 ⫾ 11.8 19.7 ⫾ 7.5
13.4 ⫾ 9.1 14.8 ⫾ 6.3
16.6 ⫾ 6.8 18.9 ⫾ 7.8
16.3 ⫾ 7.0 17.1 ⫾ 3.1
16.6 ⫾ 7.5 15.3 ⫾ 2.9
23.4 ⫾ 9.7 23.4 ⫾ 8.3
2.6 ⫾ 0.5 2.6 ⫾ 0.3
2.5 ⫾ 0.6 2.3 ⫾ 0.4
2.2 ⫾ 0.6 2.3 ⫾ 0.5
2.1 ⫾ 0.4 2.6 ⫾ 0.6
2.2 ⫾ 0.3 2.5 ⫾ 0.6
2.8 ⫾ 0.6 2.5 ⫾ 0.6
1341 ⫾ 269 1340 ⫾ 252
913 ⫾ 349 949 ⫾ 256
1116 ⫾ 257 1079 ⫾ 256
1216 ⫾ 363 1078 ⫾ 267
1206 ⫾ 277 1151 ⫾ 302
1258 ⫾ 277 1360 ⫾ 369
160 ⫾ 51 168 ⫾ 65
147 ⫾ 52 160 ⫾ 65
154 ⫾ 29 156 ⫾ 57
162 ⫾ 63 156 ⫾ 47
178 ⫾ 57 188 ⫾ 59
245 ⫾ 94 268 ⫾ 79
32.5 ⫾ 11.0 31.6 ⫾ 12.9
25.7 ⫾ 8.0 24.7 ⫾ 5.6
28.0 ⫾ 8.0 29.5 ⫾ 9.4
27.3 ⫾ 7.5 31.0 ⫾ 10.4
29.0 ⫾ 7.2 31.5 ⫾ 8.6
32.9 ⫾ 9.1 31.0 ⫾ 14.2
9.0 ⫾ 4.0 9.8 ⫾ 3.3
7.4 ⫾ 2.2 7.5 ⫾ 2.4
8.3 ⫾ 2.4 9.4 ⫾ 3.3
7.1 ⫾ 1.6 8.0 ⫾ 1.8
7.7 ⫾ 1.6 8.4 ⫾ 2.7
13.7 ⫾ 4.6 10.9 ⫾ 3.1
70 ⫾ 6 71 ⫾ 4
77 ⫾ 4 78 ⫾ 4
72 ⫾ 6 75 ⫾ 5
70 ⫾ 5 74 ⫾ 5
70 ⫾ 6 73 ⫾ 6
68 ⫾ 10 63 ⫾ 11
AC
83 ⫾ 18 76 ⫾ 15
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HR (beats/min) MCI TCI MAP (mmHg) MCI TCI MPAP (mmHg) MCI TCI CVP (mmHg) MCI TCI PCWP (mmHg) MCI TCI CI (L/min/m2) MCI TCI SVR (dyne/sec/cm⫺5) MCI TCI PVR (dyne/sec/cm⫺5) MCI TCI LVSWI (g/m/m2/beat) MCI TCI RVSWI (g/m/m2/beat) MCI TCI SvO2 (%) MCI TCI
T2
Abbreviations: T1, before induction of anesthesia; T2, after intubation; T3, at skin incision; T4, after first defibrillation; T5, after third defibrillation; T6, after extubation; MCI, manually controlled infusion of propofol; TCI, target-controlled infusion of propofol; HR, heart rate; MAP, mean arterial pressure, MPAP, mean pulmonary arterial pressure; CVP, central venous pressure; PCWP, pulmonary capillary wedge pressure; CI, cardiac index; SVR, systemic vascular resistance; PVR, pulmonary vascular resistance; LVSWI, left ventricular stroke work index; RVSWI, right ventricular stroke work index; SvO2, mixed venous oxygen saturation. *p ⬍ 0.05 different from baseline value.
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Table 3. Use of Catecholamines
Dobutamine Patients (n) Range (g/kg/min) Epinephrine Patients (n) Range (g) Norepinephrine Patients (n) Range (g)
MCI
TCI
4 2.0-2.9
8* 2.8-4.8
2 5-10
4 5-15
3 10-20
2 10-20
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NOTE. Dobutamine was given as continuous infusion, whereas epinephrine and norepinephrine were given as boli. Abbreviations: MCI, manually controlled infusion of propofol; TCI: target-controlled infusion of propofol. *p ⬍ 0.05 different from the other group.
for muscular relaxation and fluid replacement were not analyzed because they did not differ between the 2 groups. DISCUSSION
manual induction and significantly higher maintenance levels with TCI. In the present study, TCI nearly doubled the dose of propofol used compared with MCI. Whether TCI of propofol improves quality of anesthesia compared with MCI is controversial. In a multicenter study, most anesthesiologists expressed an overall preference for TCI (93%) and found it easier to use (76%) than MCI.5 In 160 patients breathing spontaneously via laryngeal mask airway, Russell et al28 showed that induction of anesthesia and positioning of laryngeal mask were faster and safer in TCI patients compared with MCI patients. These investigators showed fewer movements of TCI patients at skin incision and during surgery. Recovery times were most likely prolonged because the amount of propofol was significantly higher in TCI patients. Hunt-Smith et al26 did not find different recovery times from anesthesia comparing TCI with MCI anesthesia. Recovery times in the present study were significantly longer in TCI than in MCI patients. No patient of any group complained about awareness or intraoperative recall postoperatively, and the acceptance for TCI or MCI was similar. Hemodynamic data from this study suggest that both techniques of propofol anesthesia provided stable hemodynamics in this patient population. Significantly more patients in the TCI group than in the MCI group needed inotropic support with dobutamine, however. The higher doses of propofol in the TCI group appear to be the reason why more inotropic support in the patients with severely reduced left ventricular function in this study was required to maintain a cardiac index ⬎2.0 L/min/m2. In a study in dogs with dilated cardiomyopathy,29
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General and local anesthesia are used for implantation of ICDs.7-12 Anesthetic techniques using deep sedation without adequate monitoring in a group of high-risk patients cannot be recommended because of safety reasons.8,11 There are many possible complications (eg, pneumothorax, hemothorax, rupture of subclavian vein, hematoma, and failure of successful defibrillation by the ICD requiring external defibrillation).12-16 General anesthesia is commonly used for implantation of ICDs. The hemodynamic consequences of propofol were shown in several studies.17-20 In cardiac surgery, total intravenous anesthesia with propofol combined with an opioid is commonly used,17,18 especially for fast-track procedures.18,19 Total intravenous anesthesia has been used for patients with reduced left ventricular function.7,20 Combination with an opioid (eg, remifentanil) allows dose reduction of propofol, providing better hemodynamic stability.18,21 Recommended calculated plasma concentrations of propofol vary from 4 to 6 g/mL for induction of anesthesia in healthy, unpremedicated patients scheduled for minor orthopedic surgery.22 For maintenance of anesthesia, adequate target plasma concentration was reported to vary between 3.5 and 4.5 g/mL in patients undergoing major surgery,23 and between 4 and 6 g/mL in orthopedic surgery patients.24 Elderly patients needed lower propofol target concentrations compared with younger patients.23 Olivier et al18 reported use of TCI of propofol combined with remifentanil in 50 patients undergoing cardiac surgery with cardiopulmonary bypass. Because of the combination with remifentanil (0.25 to 1.0 g/kg/min), they reduced the calculated plasma concentration of propofol to 1.5 to 2.0 g/mL,18 which is lower than the dose used in the patients in the present study (2.0 to 3.0 g/mL), most likely because of higher doses of remifentanil. Different studies comparing TCI with MCI of propofol showed that induction doses of TCI-based anesthesia are lower than with MCI. During maintenance of anesthesia, however, TCI delivers significantly higher doses of propofol than MCI.5,6,26,27 Using computer simulations, Struys et al27 showed an overshoot in propofol blood and effect-site concentrations with
Table 4. Cost Analysis MCI
TCI
Propofol Used (total) Wasted (total) Costs (total) Costs (per patient) Remifentanil Used (total) Wasted (total) Costs (total) Costs (per patient) Dobutamine Used and wasted (total) Costs (total) Costs (per patient) Epinephrine Used and wasted (total) Costs (total) Costs (per patient) Norepinephrine Used and wasted (total) Costs (total) Costs (per patient)
10 patients 5837 mg 1663 mg $118.60 $11.86 10 patients 29,780 mg 20,220 mg $220.64 $22.06 4 patients 1000 mg $6.43 $0.64 2 patients 2 mg $0.72 $0.07 3 patients 3 mg $0.99 $0.1
10 patients 10114 mg* 3386 mg* $213.49* $21.35* 10 patients 27,060 mg 22,940 mg $220.64 $22.06 8 patients* 2000 mg* $12.86* $1.28* 4 patients 4 mg $1.43 $0.14 2 patients 2 mg $0.66 $0.07
Total costs per patient
$34.73
$44.76*
Abbreviations: MCI, manually controlled infusion of propofol; TCI, target-controlled infusion of propofol. *p ⬍ 0.05 different from the other group.
TARGET-CONTROLLED VERSUS MANUALLY CONTROLLED PROPOFOL INFUSION
complained about pain at a median time of 21 minutes after surgery. ICD implantation is not harmful and painful.36 Postoperative pain can be compared with that of pacemaker implantation. Postoperative analgesia in the patients in this study could easily be provided by infiltration of the wound by local anesthetics and, if necessary, by moderate doses of an opioid. It is difficult to compare cost analysis from other studies because of the different acquisition costs of anesthetic drugs, which vary widely from area to area and may rapidly change. In high-risk patients, a tremendous cost reduction is possible if postoperative treatment in an intensive care unit can be avoided. None of the patients in this study had severe complications, and no patient needed sustained postoperative inotropic or ventilatory support. TCI anesthesia required more anesthetic drugs and more inotropic support than MCI. In conclusion, MCI and TCI of propofol in combination with remifentanil in patients with severely reduced left ventricular function showed similar hemodynamics, were well controllable, and allowed early extubation after implantation of ICDs. TCI doubled the dose of propofol used compared with MCI, resulting in higher costs. This increased dose was associated with a greater need for inotropic support in these high-risk patients and slightly delayed emergence from anesthesia compared with patients with MCI-based anesthesia technique.
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propofol reduced left ventricular preload, afterload, and regional chamber stiffness; caused direct negative inotropic effects; and impaired early diastolic left ventricular filling. Because many patients receiving an ICD suffer from dilated cardiomyopathy, this animal model may represent the hemodynamic situation of these patients. Izquierdo et al30 reported that 25% of their ICD patients “required dobutamine for sustained hypotension.” Hachenberg et al31 needed a positive inotropic intervention in 40% of their patients receiving an ICD. In patients with dilated cardiomyopathy, total extracellular fluid volume was elevated.32 Propofol is mostly eliminated by the liver, but there is an extensive uptake and first-pass elimination in the lungs.33 The augmented extracellular fluid volume and chronic congestion of the lungs in patients with chronic heart failure might alter pharmacokinetics of propofol so that the pharmacokinetic parameters used for the TCI pumps do not predict the actual plasma concentrations in these patients well. Bailey et al34 showed that pharmacokinetics of propofol in adult patients undergoing cardiac surgery with extracorporeal circulation were dissimilar from those reported for other adult patients. One of the major disadvantages of remifentanil is the rapid disappearance of any analgesic effect in the postoperative period. Dershwitz et al35 reported that 92% of their patients
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